Background

Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders. Dissatisfaction with medications prescribed to treat FC may lead patients to seek alternative treatments. Numerous systematic reviews (SRs) examining the use of acupuncture to treat FC have reported inconsistent results, and the quality of these studies has not been fully evaluated.

Objective

In this overview, we evaluated and summarized clinical evidence on the effectiveness and safety of acupuncture for treating FC and evaluated the quality and bias of the SRs we reviewed.

Search strategy

The search strategy was structured by medical subject headings and search terms such as “acupuncture therapy” and “functional constipation.” Electronic searches were conducted in eight databases from their inception to September 2020.

Inclusion criteria

SRs that investigated the effectiveness and safety of acupuncture for managing FC were included.

Data extraction and analysis

Two authors independently extracted information and appraised the methodology, reporting accuracy, quality of evidence, and risk of bias using the following critical appraisal tools: (1) A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2); (2) Risk of Bias in Systematic Reviews (ROBIS); (3) Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A); and (4) the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A κ index was used to score the level of agreement between the 2 reviewers.

Results

Thirteen SRs that examined the clinical utility of acupuncture for treating FC were identified. Using the AMSTAR 2 tool, we rated 92.3% (12/13) of the SRs as “critically low” confidence and one study as “low” confidence. Using the ROBIS criteria, 38.5% (5/13) of the SRs were considered to have “low risk” of bias. Based on PRISMA-A, 76.9% (10/13) of the SRs had over 70% compliance with reporting standards. The inter-rater agreement was good for AMSTAR 2, ROBIS, and PRISMA-A. Using the GRADE tool, we classified 22.5% (9/40) of the measured outcomes as “moderate” quality, 57.5% (23/40) as “low” quality, and 20.0% (8/40) as “very low” quality. The inter-rater agreement was moderate when using GRADE. Descriptive analyses indicated that acupuncture was more efficacious than sham acupuncture for improving weekly complete spontaneous bowel movements (CSBMs) and for raising the Bristol Stool Form Scale (BSFS) score. Acupuncture appeared to be superior to anti-constipation drugs for improving weekly spontaneous bowel movements, the total effective rate, and the Patient Assessment of Constipation Quality of Life score. Although ten SRs mentioned the occurrence of adverse events, serious adverse events were not associated with acupuncture treatment.

Conclusion

Acupuncture may be more efficacious than sham acupuncture for improving CSBMs and BSFS scores and may be superior to anti-constipation drugs for improving bowel movement frequency, as well as quality of life. Limitations to current studies and inconsistent evidence suggest a need for more rigorous and methodologically sound SRs to draw definitive conclusions.

Systematic review registration

PROSPERO CRD42020189173.

Objective

We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience, psychology, physiology, traditional Chinese medicine (CM), modern practice of CM, and oncology to explore the effect of patients’ repression of negative emotions and traumatic events on breast cancer (BC) pathogenesis.

Methods

BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology (from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions. 

Results

A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26–79; 95% were mothers; 28% had estrogen receptor (ER)-negative BC, 52% had progesterone receptor (PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20% was reported for 52% of tumors. Statistically significant associations were found between the emotional markers (sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm (i.e., “high-lipid Qi-like microscopic phlegm”), avoidance behavior which unconsciously uses “high-lipid Qi-like microscopic phlegm” in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67. Patients with higher levels of “high-lipid Qi-like microscopic phlegm” were more likely to have tumors with worse prognosis (PR-negative, higher grade, and higher Ki-67). 

Conclusion

We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice. 

Artemisia annua and its phytocompounds have a rich history in the research and treatment of malaria, rheumatoid arthritis, systemic lupus erythematosus, and other diseases. Currently, the World Health Organization recommends artemisinin-based combination therapy as the first-line treatment for multi-drug-resistant malaria. Due to the various research articles on the use of antimalarial drugs to treat coronaviruses, a question is raised: do A. annua and its compounds provide anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) properties. PubMed/MEDLINE, Scopus, and Google Scholar were searched for peer-reviewed articles that investigated the antiviral effects and mechanisms of A. annua and its phytochemicals against SARS-CoVs. Particularly, articles that studied the herb’s role in inhibiting the coronavirus-host proteins were favored. Nineteen studies were retrieved. From these, fourteen in silico molecular docking studies demonstrated potential inhibitory properties of artemisinins against coronavirus-host proteins, including 3CLPRO, S protein, N protein, E protein, cathepsin-L, helicase protein, nsp3, nsp10, nsp14, nsp15, and GRP78 receptor. Collectively, A. annua constituents may impede the SARS-CoV-2 attachment, membrane fusion, and internalization into the host cells, and hinder the viral replication and transcription process. This is the first comprehensive overview of the application of compounds from A. annua against SARS-CoV-2/coronavirus disease 2019 (COVID-19) describing all target proteins. A. annua’s biological properties, the signaling pathways implicated in the COVID-19, and the advantages and disadvantages for repurposing of A. annuacompounds are discussed. The combination of A. annua’s biological properties, action on different signaling pathways and target proteins, and a multi-drug combined-therapy approach may synergistically inhibit SARS-CoV-2 and assist in the COVID-19 treatment. Also, A. annua may modulate the host immune response to better fight the infection. 

Background

Sleep disorders are common in older adults and have a negative influence on their physical and mental health. General aerobic exercises (GAEs) have long been used in the treatment of sleep disorders as a non-pharmacological measure. However, there is no consensus on the efficacy of traditional Chinese exercises (TCEs) for treating sleep disorders in older adults and the difference between TCEs and GAEs.

Objective

This study assessed the effects of TCEs and GAEs on the sleep quality of older adults and the differences between these two interventions.

Search strategy

PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, China Science Journal Database and Wanfang Data were searched from their inception to August 2020. 

Inclusion criteria

Randomized controlled trials (RCTs) that evaluated the effects of TCEs and GAEs on older adults with sleep disorders were included. 

Data extraction and analysis

Data were extracted by two researchers working independently. The risk bias of included studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and the quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. The Pittsburgh Sleep Quality Index (PSQI) was used to estimate sleep quality. Meta-analyses were performed to assess the total PSQI score of the exercise intervention as the primary outcome, and the scores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction were assessed as secondary outcomes. Subgroup, sensitivity, and meta-regression analyses were conducted to assess the contribution of covariables to heterogeneity.

Results

A total of 22 RCTs (including 1747 participants) were included in the meta-analysis. The results indicated that TCEs (weighted mean difference [WMD] = –2.14, 95% confidence interval [CI] [–2.82, –1.46], P < 0.001; heterogeneity: P < 0.001, I² = 82%; 15 studies, n = 1063) and GAEs (WMD = –2.88, 95% CI [–5.22, –0.55], P  < 0.001; heterogeneity: P  < 0.001, I2 = 98%; 5 studies, n = 500) significantly improved total sleep quality, having favorable effects on subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction. Subgroup analysis showed that TCEs demonstrated superiority after 12 weeks (WMD = –2.77, 95% CI [–4.26, –1.28], P  < 0.001; heterogeneity: P  < 0.001, I² = 85%; 5 studies, n = 420) and Qigong had a greater intervention effect for improving the sleep quality of older adults than Tai Chi (WMD = –3.37, 95% CI [–4.38, –2.35], P  < 0.001; heterogeneity: P  = 0.04, I² = 63%; 4 studies, n = 321). Meta-regression revealed that the year of publication, sample size, mean age of participants, and percentage of females in the primary studies did not account for the overall heterogeneity.

Conclusion

Current evidence shows that both TCEs and GAEs, as complementary and non-pharmacological approaches, help to improve the sleep quality in older adults with potentially clinical implications; however, there was not enough evidence to conclude the difference between them. More rigorous and high-quality RCTs are needed to arrive at reliable conclusions.

Metabolic syndrome (MS) involves people with the following risk factors: obesity, hypertension, high glucose level and hyperlipidemia. It can increase the risk of heart disease, stroke and type 2 diabetes mellitus. The prevalence of MS in the world’s adult population is about 20%–25%. Today, there is much care to use medicinal plants. Turmeric (Curcuma longa) as well as curcumin which is derived from the rhizome of the plant, has been shown beneficial effects on different components of MS. Thus, the purpose of this manuscript was to introduce different in vitro, in vivo and human studies regarding the effect of turmeric and its constituent on MS. Moreover, different mechanisms of action by which this plant overcomes MS have been introduced. Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivo, in vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in MS. However, more clinical trials should be done to confirm these effects. 

Objective
The coronavirus disease 2019 (COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge. Currently, some COVID-19 vaccines are being developed and applied on general population; however, whether cancer patients should take COVID-19 vaccine remains unknown. Our study aimed to explore the knowledge, attitude, acceptance, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China.

Methods
A cross-sectional study was conducted in Eastern China from June 17th to September 3rd, 2021. Patients were selected using a convenience sampling method. A self-report questionnaire was developed to assess knowledge about the COVID-19 vaccine, attitude towards the vaccine and acceptance of the vaccine; following a review of similar studies previously published in the scientific literature, multivariate logistic regression analysis was used to determine the predictors associated with COVID-19 vaccine acceptance.

Results
A total of 2158 cancer patients were enrolled in this study. The rate of vaccine hesitancy was 24.05% (519/2158); further, among the participants of vaccine acceptance, 767 had taken COVID-19 vaccine (35.54%), and 872 were willing to get vaccinated (40.01%). A total of 24 variables including demographic characteristics, clinical status of cancer, impact of COVID-19 pandemic on study participants, patients’ knowledge about the COVID-19 vaccine, and attitude towards the vaccine, had significant differences between the “vaccine hesitancy” population and “vaccine acceptance” population. Multivariate logistic regression analysis indicated that parameters including alcohol consumption (odds ratio [OR] = 1.849; 95% confidence interval [CI]: 1.375–2.488; P-Ref < 0.001 vs non-drinkers), income impacted by COVID-19 pandemic (OR = 1.930, 2.037 and 2.688 for mild, moderate, and severe impact, respectively; all P-Ref < 0.01 vs no impact), knowledge of how the vaccine was developed (OR = 1.616; 95% CI: 1.126–2.318; P-Ref = 0.009 vs unknown), believing in the safety of the vaccine (OR = 1.502; 95% CI: 1.024–2.203; P-Ref = 0.038 vs denying the safety of vaccine), willingness to pay for the vaccine (OR = 3.042; 95% CI: 2.376–3.894; P-Ref < 0.001 vs unwilling), and willingness to recommend families and friends to get vaccinated (OR = 2.744; 95% CI: 1.759–4.280; P-Ref < 0.001 vs do not recommend) were contributors to vaccine acceptance. While such as being retired (OR = 0.586; 95% CI: 0.438–0.784; P-Ref < 0.001 vs unemployed), undergoing multiple therapies of cancer (OR = 0.408; 95% CI: 0.221–0.753; P-Ref = 0.004 vs no ongoing treatment), and worrying that the vaccine might deteriorate the prognosis of cancer (OR = 0.393; 95% CI: 0.307–0.504; P-Ref < 0.001 vs might not) were contributors to vaccine hesitancy.

Conclusion
This study provided preliminary estimates of the rates of vaccine acceptance and vaccine hesitancy among cancer patients in Eastern China. The intention to receive the COVID-19 vaccine was impacted by factors such as patient occupation, alcohol consumption, and some parts of knowledge about and attitude towards COVID-19 vaccine. It is recommended to develop individualized vaccination plans that meet the healthcare needs of cancer patients.

Objective
Some epidemic diseases such as coronavirus disease 2019 (COVID-19) have caused many physical, psychological, and social challenges, despite the existence of treatment strategies. Many people are looking for complementary and alternative medicine (CAM) to prevent such diseases. The present study was performed to determine how some types of CAM were being used during the COVID-19 epidemic in Iran.

Methods
The present study had a cross-sectional descriptive correlational design. All Iranian residents above 17 years old were eligible to participate in the study. A total of 782 participants completed a demographic information questionnaire, a questionnaire about their use of CAMs and a questionnaire about their satisfaction with the CAMs they used. Web-based sampling was conducted from 20 April 2020 to 20 August 2020.

Results
Of the participants, 84% used at least one type of CAM during the COVID-19 outbreak. The most used CAMs were dietary supplements (61.3%), prayer (57.9%), and herbal medicines (48.8%). The majority of the participants (50%–66%) have used CAMs to prevent the transmission of COVID-19 or to reduce anxiety caused by the COVID-19 pandemic. CAM use was associated with sex, having children, place of residence, COVID-19 status, and source of gathering information about CAM (P < 0.05). All 32 participants who had been infected with COVID-19 used at least one type of CAM for treatment or alleviation of the disease symptoms.

Conclusion
During the COVID-19 outbreak, some types of CAM, particularly nutritional supplements, medicinal herbs, and prayer, were commonly used to prevent COVID-19 and reduce pandemic-related anxiety.

Objective

Carpobrotus edulis (L.) N.E.Br. is a succulent perennial plant native to South Africa and grows invasively in the Mediterranean basin. It is commonly used for the treatment of various diseases, including skin wound healing and regeneration, for which experimental validation is lacking. We therefore evaluated the skin healing properties of C. edulis by testing an C. edulis aqueous leaf extract (CAE) on cell cultures and in enzymatic assays.

Methods

Micro-morphological analysis of leaves was carried out using scanning electron microscopy and epifluorescence microscopy. Phytochemical features and antioxidant activity of CAE were evaluated by reversed-phase liquid chromatography coupled with diode array detection and electrospray ion trap mass spectrometry (RP-LC-DAD-ESI-MS), and in vitro cell-free assays. Biological activities were evaluated using keratinocytes and fibroblasts, as well as elastase, collagenase, and hyaluronidase.

Results

CAE showed high carbohydrates (28.59% ± 0.68%), total phenols ([101.9 ± 6.0] g gallic acid equivalents/kg dry extract [DE]), and flavonoids ([545.9 ± 26.0] g rutin equivalents/kg DE). RP-LC-DAD-ESI-MS revealed the predominant presence of hydroxycinnamic acids (51.96%), followed by tannins (14.82%) and flavonols (11.32%). The extract was not cytotoxic, had a strong and dose-dependent antioxidant activity, and inhibited collagenase (> 90% at 500 μg/mL) and hyaluronidase (100% at 1000 μg/mL). In cell culture experiments, CAE increased wound closure and collagen production, which was consistent with its high polyphenol content. 

Conclusion

Our data support the use of the C. edulis for skin care and the treatment of skin problems. Moreover, use of C. edulis for skin care purposes could be an eco-friendly solution to reduce its invasiveness in the environment.

Objective
The prevalence of complementary and alternative medicine (CAM) usage among patients with type 2 diabetes mellitus (T2DM) in Indonesia is high. However, to date, little is known about why Indonesian T2DM patients choose CAM therapies, how their knowledge, attitude and practice (KAP) of CAM affects their choices, or how demographics correlate with patient choices. Therefore, this study aimed to investigate the KAP and predictors of CAM usage in T2DM patients in Indonesia.

Methods
This was an observational, cross-sectional study. Patients were interviewed using a questionnaire. Chi-square tests or Fisher’s exact tests were used to compare demographic and clinical data, as well as KAP assessments, between T2DM patients who use and do not use CAM. Multivariate logistic regression analyses were used to investigate predictors of CAM usage.

Results
A total of 628 T2DM patients were enrolled in the study. CAM therapies were used by 341 patients (54.3%). The most common therapies were herbs and spiritual healing, used by 100.0% and 68.3% of CAM-using patients, respectively. CAM therapies were frequently recommended by family members (91.5%), and CAM users had significantly more knowledge and more positive attitudes toward CAM therapies than nonusers. Among users, 66% said they would not follow their healthcare providers’ instructions to not use CAM therapies, and 69.5% said they would not disclose their plan to use CAM therapies with their healthcare provider. Neither demographic nor clinical characteristics were associated with CAM use. The factors that best predicted the use of CAM therapies were their availability and low cost (odds ratio [OR] = 4.59; 95% confidence interval [CI]: 3.01–7.01), the belief that CAM therapies were safe (OR = 2.04; 95% CI: 1.40–2.95), the belief that CAM therapies could help with diabetes control (OR = 1.75; 95% CI: 1.15–2.66), and the belief that CAM therapies could help maintain physical health (OR = 1.68; 95% CI: 1.13–2.49).

Conclusion
CAM therapy users were more knowledgeable and had more positive attitudes toward CAM, but most of them chose not to disclose their CAM use to their healthcare providers. CAM use in Indonesia was associated with its accessibility, affordability, safety and effectivity, but not with any demographic or clinical characteristics. This study provided new evidence and insights for nurses and physicians in Indonesia that will help to design educational programs about the safety and efficacy of CAM therapies.

Objective: Ipomoea batatas (L.) Lam. is a food plant used in African traditional medicine to treat cardiovascular diseases and related conditions. We assessed the hypolipidemic and anti-atherosclerogenic properties of the aqueous extract of I. batatas leaves in a rat model of diet-induced hypercholesterolemia.
Methods: Hypercholesterolemia was induced in male Wistar rats by exclusive feeding with a cholesterol-enriched (1%) standard diet for four weeks. Then, rats were treated once daily (per os) with I. batatas extract at doses of 400, 500 and 600 mg/kg or with atorvastatin (2 mg/kg), for four weeks. Following treatment, animals were observed for another four weeks and then sacrificed. Aortas were excised and processed for histopathological studies, and blood glucose level and lipid profile were measured.
Results: Hypercholesterolemic animals experienced a 21.5% faster increase in body weight, significant increases in blood glucose and blood lipids (148.94% triglycerides, 196.97% high-density lipoprotein cholesterol, 773.04% low-density lipoprotein cholesterol, 148.93% very low-density lipoprotein cholesterol and 210.42% total cholesterol), and increases in aorta thickness and atherosclerotic plaque sizes compared to rats fed standard diet. Treatment of hypercholesterolemic rats with the extract mitigated these alterations and restored blood glucose and blood lipid levels to normocholesterolemic values.
Conclusion: Our findings suggest that I. batatas leaves have hypolipidemic and anti-atherosclerogenic properties and justify their use in traditional medicine.

This document is the revised edition of the previously issued Shanghai Expert Consensus on Clinical Protocol for Traditional Chinese Medicine Treatment of COVID-19 among the Elderly Population. Based on the clinical experience and the Protocol for Diagnosis and Treatment of COVID-19 (Trial 9th Edition), this revised edition provides treatment approaches and recommendations to proactively cope with Omicron variant and increase the therapeutic efficacy for coronavirus disease 2019 among the elderly population in Shanghai, China.

Background

Core muscle functional strength training (CMFST) has been reported to reduce injuries to the lower extremity. However, no study has confirmed whether CMFST can reduce the risk of low-back pain (LBP).

Objective

This study identified the effects of CMFST on the incidence of LBP in military recruits.

Design, setting, participants and intervention

We performed a prospective, open-label, randomized, controlled study in a population of young healthy male naval recruits from a Chinese basic combat training program. Participants were randomly assigned to either the core group or the control group. In additional to normal basic combat training, recruits in the core group underwent a CMFST program for 12 weeks, while recruits in the control group received no extra training.

Main outcome measures

At the beginning of the study and at the 12th week, the number of participants with LBP was counted, and lumbar muscle endurance was measured. In addition, when participants complained of LBP, they were assessed using the visual analog scale (VAS) and Roland Morris Disability Questionnaire (RMDQ).

Results: A total of 588 participants were included in the final analysis (295 in the core group and 293 in the control group). The incidence of LBP in the control group was about twice that of the core group over the 12-week study (20.8% vs 10.8%, odds ratio: 2.161–2.159, P < 0.001). The core group had better lumbar muscle endurance at 12 weeks than the control group ([200.80 ± 92.98] s vs [147.00 ± 84.51] s, P < 0.01). There was no significant difference in VAS score between groups, but the core group had a significantly lower RMDQ score at week 12 than the control group (3.33 ± 0.58 vs 5.47 ± 4.41, P < 0.05).
Conclusion: This study demonstrated that the CMFST effectively reduced the incidence of LBP, improved lumbar muscle endurance, and relieved the dysfunction of LBP during basic military training.

Trial registration

Chinese Clinical Trial Registry (ChiCTR-POC-14005550).

Objective

Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI.

Methods

A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function.

Results

The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. 

Conclusion

This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.

Objective

High-fat diet (HFD) and inflammation are two key contributors to nonalcoholic fatty liver disease (NAFLD). Shenling Baizhu powder (SLBZP), a classical herbal compound, has been successfully used to alleviate NAFLD. However, its specific mechanisms are not fully understood. In this study, we assess the anti-NAFLD effect of SLBZP in vivo.

Methods

Rats were fed an HFD with or without SLBZP or with probiotics. At the end of week 16, an echo magnetic resonance imaging (EchoMRI) body composition analyser was used to quantitatively analyse body composition; a micro-computed tomography (micro-CT) imaging system was used to evaluate whole body and liver fat; and the Moor full-field laser perfusion imager 2 was used to assess liver microcirculation, after which, all rats were sacrificed. Then, biochemical indicators in the blood and the ultrastructure of rat livers were evaluated. Protein expression related to the liver Toll-like receptor 4 (TLR4)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) signalling pathway was assessed using Western blot analysis. Further, high-throughput screening of 29 related inflammatory factors in liver tissue was performed using a cytokine array. 

Results

SLBZP supplementation reduced body weight, serum free fatty acid, and insulin resistance index (P < 0.05). It also ameliorated liver microcirculation and ultrastructural abnormalities. EchoMRI and micro-CT quantitative analyses showed that treatment with SLBZP reduced fat mass and visceral fat (P < 0.05 and P < 0.01, respectively). In addition, SLBZP decreased the expression of lipopolysaccharide (LPS)-activated TLR4/NLRP3 signalling pathway-related proteins and altered the expression levels of some inflammatory cytokines in liver tissues.

Conclusion

SLBZP can inhibit NLRP3 inflammasome activation and interleukin-1β release by suppressing LPS-induced TLR4 expression in rats with HFD-induced NAFLD. Thus, SLBZP may be beneficial for the prevention and treatment of inflammatory damage and associated diseases. 

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease. It results from the death of dopaminergic neurons. The pathophysiological mechanisms in idiopathic PD include the production of α-synuclein and mitochondrial respiratory function-affecting complex I, caused by reactive oxygen species. Therefore, the use of natural antioxidants in PD may provide an alternative therapy that prevents oxidative stress and reduces disease progression. In this review, the effects of hydroxytyrosol, Ginkgo biloba, Withania somnifera, curcumin, green tea, and Hypericum perforatum in PD animal and cell line models are compared and discussed. The reviewed antioxidants show evidence of protecting neural cells from oxidative stress in animal 
and cell models of PD. However, the clinical efficacy of these phytochemicals needs to be optimised and further investigated.

Objective

To investigate effects of berberine (BBR) on cholesterol synthesis in HepG2 cells with free fatty acid (FFA)-induced steatosis and to explore the underlying mechanisms.

Methods

A steatosis cell model was induced in HepG2 cell line fed with FFA (0.5 mmol/L, oleic acid:palmitic acid = 2:1), and then treated with three concentrations of BBR; cell viability was assessed with cell counting kit-8 assays. Lipid accumulation in cells was observed through oil red O staining and total cholesterol (TC) content was detected by TC assay. The effects of BBR on cholesterol synthesis mediators were assessed by Western blotting and quantitative polymerase chain reaction. In addition, both silent information regulator 1 (SIRT1) and forkhead box transcription factor O1 (FoxO1) inhibitors were employed for validation. 

Results

FFA-induced steatosis was successfully established in HepG2 cells. Lipid accumulation and TC content in BBR groups were significantly lower (P < 0.05, P < 0.01), associated with significantly higher mRNA and protein levels of SIRT1(P < 0.05, P < 0.01), significantly lower sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy 3-methylglutaryl-CoA reductase levels (P < 0.05, P < 0.01), as well as higher Acetyl-FoxO1 protein level (P < 0.05, P < 0.01) compared to the FFA only group. Both SIRT1 inhibitor SIRT1-IN-1 and FoxO1 inhibitor AS1842856 blocked the BBR-mediated therapeutic effects. Immunofluorescence showed that the increased SIRT1 expression increased FoxO1 deacetylation, and promoted its nuclear translocation.

Conclusion

BBR can mitigate FFA-induced steatosis in HepG2 cells by activating SIRT1-FoxO1-SREBP2 signal pathway. BBR may emerge as a potential drug candidate for treating nonalcoholic hepatic steatosis. 

Background

Filiform needle acupuncture (FNA), the most classical and widely applied acupuncture method based on traditional Chinese medicine theory, has shown a promising effect in the treatment of allergic rhinitis (AR).

Objective

We aim to comprehensively evaluate the efficacy, safety, cost-effectiveness, and patient preference of FNA in the treatment of AR by comparing FNA with sham acupuncture, no treatment, and conventional medication.

Search strategy

Eight electronic databases were systematically searched from inception to October 14, 2021. Additional studies were acquired from clinical trial registration platforms and reference lists.

Inclusion criteria

RCTs were included if they compared FNA with either sham acupuncture, no treatment, or conventional medications for AR.

Data extraction and analysis

Two researchers extracted data independently of each other using a predesigned data acquisition form, and results were cross-checked after completion. The primary outcome was symptom score (Total Nasal Symptom Score or Visual Analog Scale), and the secondary outcomes were the AR control questionnaire, quality of life (QoL) score (Different versions of Rhinoconjunctivitis Quality of Life Questionnaires), medication score (use of rescue medication), mental health score, total IgE, adverse event rate, clinical economic indicators, and patient satisfaction score. Standardized mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CIs) was used to calculate the effect size for continuous data, while risk ratio with 95% Cis was used for dichotomous data.

Results

Thirty studies were included in this review. Compared with sham acupuncture, FNA significantly reduced the symptom score (SMD: –0.29 [–0.43, –0.15]), AR’s impact on QoL (SMD: –0.23 [–0.37, –0.08]) and medication score (SMD: –0.3 [–0.49, –0.11]). Compared with no treatment, FNA dramatically reduced the symptom score (SMD: –0.8 [–1.2, –0.39]) and AR’s impact on QoL (SMD: –0.82 [–1.13, –0.52]). There were no increased rates of adverse event with FNA compared to sham acupuncture and no treatment. FNA increased patient satisfaction and may be cost-effective. Most pieces of evidence from the above two comparisons were of high confidence. Moreover, FNA significantly outperformed conventional medication in reducing the symptom score (SMD: –0.48 [–0.85, –0.1]) and displayed a lower rate of adverse events, but the quality of evidence was very low.

Conclusion

FNA is an effective and safe intervention for AR and can help with symptom relief, QoL improvement, reducing medication usage, and increasing patient satisfaction. Further studies are needed to verify its cost-effectiveness and superiority over conventional medication and the best therapeutic strategies.

Objective

Numerous studies have demonstrated the close relationship between chronic stress and blood pressure (BP). Hypertensive subjects exhibit exaggerated reactions to stress, especially higher BP. The mechanisms by which stress affects pre-existing hypertension still need to be explored. Danzhi Xiaoyao Powder (DP), a historical traditional Chinese medicine formula, is a promising treatment for BP control in hypertensive patients under stress. The present study investigated the metabolomic disruption caused by chronic stress and the treatment effect and mechanism of DP.

Methods

Spontaneously hypertensive rats (SHRs) were subjected to chronic restraint stress (CRS) for 4 weeks. BP was measured via the tail-cuff method, and anxiety-like behavior was quantified using the elevated-plus-maze test. Meanwhile, DP was administered intragastrically, and its effects were observed. Global metabolomic analysis was performed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis to detect differential metabolites and pathways.

Results

DP alleviated the CRS-induced increase in BP and anxiety-like behavior. Systematic metabolic di?erences were found among the three study groups. A total of 29 differential plasma metabolites were identified in both positive- and negative-ion modes. These metabolites were involved in triglyceride metabolism, amino acid (phenylalanine, tryptophan, and glycine) metabolism, and steroid hormone pathways.

Conclusion

These findings expose the metabolomic disturbances induced by chronic stress in SHRs and suggest an innovative treatment for this disorder.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare adverse cutaneous reaction with a low incidence and high mortality. Despite posing a serious threat to patients’ health and lives, there is no high-quality evidence for a standard treatment regimen. Here we report the case of a 62-year-old man with stage IV pancreatic cancer who experienced immunotherapy-induced SJS/TEN. After consensus-based regular treatments at a local hospital, his symptoms became worse. Thus, he consented to receive Chinese herbal medicine (CHM) therapy. The affected parts of the patient were treated with the CHM Pi-Yan-Ning which was applied externally for 20 min twice a day. After 7 days of treatment, the dead skin began peeling away from the former lesions that had covered his hands, feet, and lips, indicating that skin had regenerated. After 12 days of treatment, the patient’s skin was completely recovered. In this case, SJS/TEN was successfully treated with Pi-Yan-Ning, suggesting that there might be tremendous potential for the use of Pi-Yan-Ning in the treatment of severe skin reactions to drug treatments. Further basic investigations and clinical trials to explore the mechanism and efficacy are needed.

Objective
To investigate the changes in the functional connectivity (FC) in the right insula between migraine without aura (MWoA) and healthy controls by using resting-state functional magnetic resonance imaging (rs-fMRI), and to observe the instant alteration of FC in MWoA during electroacupuncture (EA) stimulation at Shuaigu (GB8).

Methods
A total of 30 patients with MWoA (PM group) and 30 healthy controls (HC group) underwent rs-fMRI scans. The PM group underwent a second rs-fMRI scan while receiving EA at GB8. The right insula subregions, including the ventral anterior insula (vAI), dorsal anterior insula (dAI) and posterior insula (PI), were selected as the seed points for FC analysis.

Results
Aberrant FC, including dAI with right postcentral gyrus, PI with left precuneus, was found among PM before EA (PMa), PM during EA (PMb) and HC. Meanwhile, decreased FC between dAI and the right postcentral gyrus was found in the PMa compared to the HC and PMb. Increased FC between the PI and left precuneus was found in the PMa compared to the HC and PMb. Correlation analysis showed that the FC value of the right postcentral gyrus in PMa was negatively correlated with the scores of Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety. The FC value of the left precuneus in PMa was positively correlated with the visual analogue scale score.

Conclusion
The alteration of FC between the right insula subregions and multiple brain regions may be an important index for MWoA. EA at GB8 was able to adjust the FC between the right insula subregions and parietal lobe, namely, the right dAI and right postcentral gyrus, and the right PI and left precuneus, thereby rendering an instant effect in the management of MWoA.

Objective

Complementary and alternative medicine use and type of use may be influenced by sociodemographic and economic determinants through which we could identify characteristics of patients with greater trend to use it. This paper aims to describe the changes in the consumption of homeopathic and natural remedies in Spain for three time points in order to discern changes in rate of consumption, associated factors and whether their use has been affected by a period of economic recession. 

Methods

This study utilized 2006, 2011 and 2017 cross-sectional data from the Spanish National Health Survey, a nationally representative survey of the population aged more than 15 years old and resident in Spain. Independent bivariate and multivariate descriptive analyses for each of the 3 years studied were performed.

Results

The rate of consumption of both homeopathic and natural remedies has decreased over the periods studied. In spite of this decrease, the consumer profile appears to remain stable over the three periods. The sociodemographic factors associated with their consumption were being female, being 30–64 years old, being separated/divorced, having higher education qualifications, being employed and belonging to a higher social class. Psychiatric morbidity, chronic health problems such as pain, mental health problems or malignant tumors, and absence of major cardiovascular events were the clinical factors associated. 

Conclusion

It can be concluded that beyond the economic situation, the use of homeopathic and natural remedies obeys to the needs of the patients related to their state of health and the response they receive from the health system. It may be that women have different needs and expectations of the healthcare system and, given this breach of expectations, seek remedy to alleviate their needs outside the system and conventional medicine.

Background

Acupuncture has been widely used to relieve migraine-related symptoms. However, the findings of previous systematic reviews (SRs) and meta-analyses (MAs) are still not completely consistent. Their quality is also unknown, so a comprehensive study is needed.

Objective
To evaluate the reporting and methodological quality of these MAs concerning acupuncture for migraine, and summarize evidence about the efficacy and safety of acupuncture for migraine.

Search strategy
PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Databases, Wanfang Data, and VIP databases were searched from inception to September 2020, with a comprehensive search strategy.

Inclusion criteria
The pairwise MAs of randomized controlled trials (RCTs) concerning migraine treated by acupuncture or acupuncture-based therapies, with a control group that received sham acupuncture, medication, no treatment, or acupuncture at different acupoints were included.

Data extraction and analysis
Two independent investigators screened studies, extracted relevant data, and assessed reporting and methodological quality using PRISMA 2009 and AMSTAR 2, then all results were cross-checked. Spearman correlation test was used to evaluate the correlation between reporting and methodological quality scores.

Results
A total of 20 MAs were included in this study. The included MAs indicated that acupuncture was efficacious and safe in preventing and treating migraine when compared with control intervention. There was a high correlation between reporting and methodological quality scores (rs = 0.87, P < 0.001). The quality of the included SRs needs to be improved mainly with regard to protocol and prospective registration, using a comprehensive search strategy, summarizing the strength of evidence body for key outcomes, a full list of excluded studies with reasons for exclusion, reporting of RCTs’ funding sources, and assessing the potential impact of risk of bias in RCTs on MA results.

Conclusion
Acupuncture is an effective and safe intervention for preventing and treating migraine, and could be considered as a good option for patients with migraine. However, the reporting and methodological quality of MAs included in this overview is suboptimal. In the future, AMSTAR 2 and PRISMA tools should be followed when making and reporting an SR with MA.

Aconitum heterophyllum (Patrees) is a critically endangered medicinal herb of the northwestern Himalayas and has enormous pharmacological potential. It is the only nonpoisonous member of the genus Aconitum, and has been used as a medicinal herb since ancient times. A. heterophyllum is an important ingredient in many traditional systems of medicine. Mostly, it is harvested for its roots, and its medicinal properties are due to the presence of diverse bioactive secondary metabolites, commonly known as aconites. Our understanding of the pharmacological properties of this intriguing genus is continuously growing due to its broad chemical diversity. The therapeutic uses identified by traditional medicinal practice are receiving extensive study. Multiple in vitro experimental investigations of A. heterophyllum have reported the analgesic, anti-inflammatory, antiarrhythmic, antiparasitic and anticancer properties, as well as its effects on the central nervous system. In this review, we highlight the classification, distribution, commerce, traditional uses, phytochemistry, pharmacology and conservation measures relevant to this species. Additionally, this review includes the biosynthetic pathways of A. heterophyllum’s key constituents, which could be targeted to enhance the expression levels of desired metabolites via genetic interventions. Studying the genomics, transcriptomics, proteomics and metabolomic aspects of this species would be helpful in developing highly designed genotypes and chemotypes of this species to be used in commercial production.

Background

Conscious patients admitted to intensive care units (ICUs) suffer from pain for various reasons, which can affect their recovery process. 

Objective

The present study compared the effects of aromatherapy with Citrus aurantium and lavender essential oils against placebo for reducing pain in conscious intensive care patients.

Design, setting, participants and interventions

This study was a parallel randomized placebo-controlled trial. The ICUs of two educational hospitals in Kerman in Southeastern Iran were the study setting. One hundred and fifty conscious intensive care patients were randomly divided into three groups using a stratified block randomization method. Two groups received aromatherapy with essential oils: one with lavender and the other with C. aurantium; these patients received a 30-minute therapy session using their assigned essential oil on the second day of their intensive care stay. The placebo group used 5 drops of normal saline instead of essential oil during their session. 

Main outcome measures

Patient’s pain was assessed using a visual analog scale before the aromatherapy intervention, as well as immediately after and one and three hours after intervention. 

Results

The mean pain score of the lavender group was 40.01 before the aromatherapy intervention and fell to 39.40, 30.60 and 23.68 immediately after the intervention, and at hour one and three post-intervention, respectively. The mean pain score of the C. aurantium group was 45.48 before the intervention and was reduced to 32.34 at three hours after the intervention. The mean pain of the placebo group decreased from 42.80 before the intervention to 35.20 at three hours after the intervention. Pain scores of all groups decreased during the study (P < 0.001). The mean pain of the lavender group was significantly lower than that of the placebo group at three hours after the intervention. 

Conclusion

The results of this study showed that aromatherapy with lavender essential oil reduced pain in conscious ICU patients. Our data could not justify the use of C. aurantium for reducing pain in this population.

Trial registration

No. IRCT20170116031972N9 (https://en.irct.ir/trial/40827).

Objective
To evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics, yeast β-glucans, minerals and silymarin (Silybum marianum), on lipid metabolism and inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese mice.

Methods
After an acclimation period, 32 male C57BL/6 mice were divided into the following groups: nonfat diet (NFD) vehicle, NFD supplemented, high-fat diet (HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet (28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of mice.

Results
After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia, fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-α, AMP-activated protein kinase-1α, peroxisome proliferator-activated receptor γ co-activator 1-α, and mitochondrial transcription factor A expression levels were augmented; however, levels of IκB kinase α and p65 nuclear factor-κB expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic-pituitary-adrenal axis immune interface status, was found to be modulated by the supplement.

Conclusion
We found that the novel supplement modified different antioxidant, metabolic and inflammatory pathways, improved energy homeostasis and the inflammatory state, and consequently alleviated hepatic steatosis.

Background
Patients commonly develop postoperative pain after total knee arthroplasty (TKA). Acupuncture-related techniques and low-level laser therapy could be beneficial for pain management for older individuals.

Objective
To examine the effect of low-level laser acupuncture (LA) in reducing postoperative pain, pain-related interference in daily life, morphine consumption, and morphine-related side effects in older patients with knee osteoarthritis who underwent TKA.

Design, setting, participants and intervention
A single-blind randomized placebo-controlled trial was conducted. Patients (N = 82) were recruited and randomly assigned via a computer-generated list to the LA group or a placebo group. The LA group received low-level laser therapy at Sanyinjiao (SP6), Taixi (KI3), Kunlun (BL60), Fengshi (GB31), Futu (ST32) and Neiguan (PC6) after TKA, while the placebo acupuncture group received the same treatment procedure without laser energy output.

Main outcome measures
The primary outcome was postoperative pain intensity, and it was measured at baseline and hours 2, 6, 10, 24, 48 and 72 after TKA. The secondary outcomes, including relative pain, postoperative pain-related interference in daily life and morphine consumption, were measured at hours 24, 48 and 72 after TKA.

Results
Generalized estimating equations revealed significant between-group differences in pain intensity (P = 0.01), and trend differences in pain intensity for the LA group starting at hours 10 to 72 (P < 0.05) and morphine consumption at hours 48 and 72 (P < 0.05). The changes in pain-related interference in daily life were significant (P < 0.05) at 72 h, with the exception of the parameters for worst pain, mood, and sleep. Nausea and vomiting side effects from morphine had significant between-group differences at hours 10 and 24 (P < 0.05).

Conclusion

Low-level LA gradually reduced older patients’ postoperative pain intensity and morphine consumption within the first 72 h after their TKA for osteoarthritis. Low-level LA may have benefits as an adjuvant pain management technique for clinical care.

Trial registration

ClinicalTrials.gov registration number NCT03995446.

Objective: The present study evaluated the antinociceptive activity of Calendula officinalis L. (Ca) cream on inflammatory hypernociception.
Methods: Creams with different Ca concentrations were tested for their ability to ameliorate pain-related behavior and edema in rats using formalin test, carrageenan (Cg)-induced acute inflammation model, bradykinin (BK)-induced acute inflammation model, and complete Freund’s adjuvant (CFA)-induced chronic inflammation model. Using the formalin test, we also examined the implication of peripheral opioid receptors in the antinociceptive mechanisms of Ca cream, by means of Q-naloxone, a peripherally acting nonselective opioid antagonist. Furthermore, the effects of Ca cream compared with diclofenac on BK-induced edema were examined when the kininase II in tissue was preserved or inhibited by captopril. The local production of redox biomarkers in formalin model, tumor necrosis factor-α (TNF-α) in Cg model and histopathological changes in CFA model were also evaluated.
Results: A single application of Ca cream at a dose of 10% or 30% (w/w) decreased the formalin-induced licking/biting behavior during both phases of this test in a Q-naloxone-sensitive manner. This effect was associated with the reduction of oxidative stress in the injured paw and the edema associated with the later phase of formalin-induced pain. A single application of Ca cream (10% or 30%) reduced paw edema and thermal hypernociception in Cg-induced acute inflammation, corresponding with a local decrease in TNF-α. Ca cream also inhibited BK-induced spontaneous nociceptive behavior and paw inflammation in both paradigms studied. Repeated applications of Ca cream also decreased CFA-induced chronic inflammation, mechanical hypernociception and histopathological changes in the paw.
Conclusion: These results reveal the topical antinociceptive and antiedematogenic effects of Ca cream. A modulatory action on peripheral opioid receptors associated with its antioxidant mechanism may be involved, at least in part, in its analgesic effects. These findings may have an impact on the clinical management of painful inflammatory diseases.

Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndromes set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.

Objective

The chemo-preventative and therapeutic properties of selenium nanoparticles (SeNPs) have been documented over recent decades and suggest the potential uses of SeNPs in medicine. Biogenic SeNPs have higher biocompatibility and stability than chemically synthesized nanoparticles, which enhances their medical applications, especially in the field of cancer therapy. This study evaluated the potential of green-synthetized SeNPs by using berberine (Ber) as an antitumor agent and elucidated the mechanism by which these molecules combat Ehrlich solid tumors (ESTs).

Methods

SeNPs containing Ber (SeNPs-Ber) were synthesized using Ber and Na2SeO3 and characterized with Fourier transform infrared spectroscopy. Sixty male Swiss albino mice were then acclimatized for one week, injected with Ehrlich ascites tumor cells, and divided into four groups: EST, EST + cisplatin (5 mg/kg), EST + Ber (20 mg/kg), and EST+ SeNPs-Ber (0.5 mg/kg). At the end of a 16-day observation period, 12 mice from each group were euthanized to analyze differences in the body weight, tumor size, gene expression, and oxidative stress markers in the four groups. Three mice from each group were kept alive to compare the survival rates.

Results

Treatment with SeNPs-Ber significantly improved the survival rate and decreased the body weight and tumor size, compared to the EST group. SeNPs-Ber reduced oxidative stress in tumor tissue, as indicated by a decrease in the lipid peroxidation and nitric oxide levels and an increase in the glutathione levels. Moreover, SeNPs-Ber activated an apoptotic cascade in the tumor cells by upregulating the Bcl-2-associated X protein and caspase-3 expression rates and downregulating the B-cell lymphoma 2 expression rate. SeNPs-Ber also considerably improved the histopathological alterations in the developed tumor tissue, compared to the EST group. 

Conclusion

Our study provides a new insight into the potential role of green-synthesized SeNPs by using Ber as a promising anticancer agent, these molecules could be used alone or as supplementary medication during chemotherapy.

Objective

By optimizing the extreme learning machine network with particle swarm optimization, we established a syndrome classification and prediction model for primary liver cancer (PLC), classified and predicted the syndrome diagnosis of medical record data for PLC and compared and analyzed the prediction results with different algorithms and the clinical diagnosis results. This paper provides modern technical support for clinical diagnosis and treatment, and improves the objectivity, accuracy and rigor of the classification of traditional Chinese medicine (TCM) syndromes.

Methods

From three top-level TCM hospitals in Nanchang, 10,602 electronic medical records from patients with PLC were collected, dating from January 2009 to May 2020. We removed the electronic medical records of 542 cases of syndromes and adopted the cross-validation method in the remaining 10,060 electronic medical records, which were randomly divided into a training set and a test set. Based on fuzzy mathematics theory, we quantified the syndrome-related factors of TCM symptoms and signs, and information from the TCM four diagnostic methods. Next, using an extreme learning machine network with particle swarm optimization, we constructed a neural network syndrome classification and prediction model that used “TCM symptoms + signs + tongue diagnosis information + pulse diagnosis information” as input, and PLC syndrome as output. This approach was used to mine the nonlinear relationship between clinical data in electronic medical records and different syndrome types. The accuracy rate of classification was used to compare this model to other machine learning classification models.

Results

The classification accuracy rate of the model developed here was 86.26%. The classification accuracy rates of models using support vector machine and Bayesian networks were 82.79% and 85.84%, respectively. The classification accuracy rates of the models for all syndromes in this paper were between 82.15% and 93.82%.

Conclusion

Compared with the case of data processed using traditional binary inputs, the experiment shows that the medical record data processed by fuzzy mathematics was more accurate, and closer to clinical findings. In addition, the model developed here was more refined, more accurate, and quicker than other classification models. This model provides reliable diagnosis for clinical treatment of PLC and a method to study of the rules of syndrome differentiation and treatment in TCM.

Objective
It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury, but the optimized parameters and effective mechanism were unclear. In the present study, we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury (SNI).
Methods
Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups: sham group, SNI group, SNI + A-1 mm group, SNI + A-2 mm group, and SNI + A-4 mm group (A refers to the amplitude; n = 10 per group). Starting on the 7th day after model initiation, local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1, 2 or 4 mm for 5 min. The sciatic function index (SFI) was assessed before surgery and on the 7th, 14th, 21st and 28th days after surgery. Tissues were harvested on the 28th day after surgery for morphological, immunofluorescence and Western blot analysis.
Results
Compared with the SNI group, on the 28th day after surgery, the SFIs of the treatment groups were increased; the difference in the SNI + A-2 mm group was the most obvious (95% confidence interval [CI]: [5.86, 27.09], P < 0.001), and the cross-sectional areas of myocytes in all of the treatment groups were improved. The G-ratios in the SNI + A-1 mm group and SNI + A-2 mm group were reduced significantly (95% CI: [?0.12, ?0.02], P = 0.007; 95% CI: [?0.15, ?0.06], P < 0.001). In addition, the expressions of S100 and nerve growth factor proteins in the treatment groups were increased; the phosphorylation expressions of ERK1/2 protein in the SNI + A-2 mm group and SNI + A-4 mm group were upregulated (95% CI: [0.03, 0.96], P = 0.038; 95% CI: [0.01, 0.94], P = 0.047, respectively), and the phosphorylation expression of Akt in the SNI + A-1 mm group was upregulated (95% CI: [0.11, 2.07], P = 0.031).
Conclusion
Local vibration therapy, especially with medium amplitude, was able to promote the recovery of nerve function in rats with SNI; this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 and Akt signaling pathways.

Background
The therapeutic evidence collected from well-designed studies is needed to help manage the global pandemic of the coronavirus disease 2019 (COVID-19). Evaluating the quality of therapeutic data collected during this most recent pandemic is important for improving future clinical research under similar circumstances.

Objective
To assess the methodological quality and variability in implementation of randomized controlled trials (RCTs) for treating COVID-19, and to analyze the support that should be provided to improve data collected during an urgent pandemic situation.

Search strategy
PubMed, Excerpta Medica Database, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP, and the preprint repositories including Social Science Research Network and MedRxiv were systematically searched, up to September 30, 2020, using the keywords “coronavirus disease 2019 (COVID-19),” “2019 novel coronavirus (2019-nCoV),” “severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2),” “novel coronavirus pneumonia (NCP),” “randomized controlled trial (RCT)” and “random.”

Inclusion criteria
RCTs studying the treatment of COVID-19 were eligible for inclusion. 

Data extraction and analysis
Screening of published RCTs for inclusion and data extraction were each conducted by two researchers. Analysis of general information on COVID-19 RCTs was done using descriptive statistics. Methodological quality was assessed using the risk-of-bias tools in the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0). Variability in implementation was assessed by comparing consistency between RCT reports and registration information. 

Results
A total of 5886 COVID-19 RCTs were identified. Eighty-one RCTs were finally included, of which, 45 had registration information. Methodological quality of the RTCs was not optimal due to deficiencies in five main domains: allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. Comparisons of consistency between published protocols and registration information showed that the 45 RCTs with registration information had common deviations in seven items: inclusion and exclusion criteria, sample size, outcomes, research sites of recruitment, interventions, and blinding.

Conclusion
The methodological quality of COVID-19 RCTs conducted in early to mid 2020 was consistently low and variability in implementation was common. More support for implementing high-quality methodology is needed to obtain the quality of therapeutic evidence needed to provide positive guidance for clinical care. We make an urgent appeal for accelerating the construction of a collaborative sharing platform and preparing multidisciplinary talent and professional teams to conduct excellent clinical research when faced with epidemic diseases of the future. Further, variability in RCT implementation should be clearly reported and interpreted to improve the utility of data resulting from those trials.

Cupping therapy has historical, traditional and religious value. It is increasingly popular in the field of complementary, alternative and integrative medicine. However, standards for safety and quality of service are absent. Although it is generally considered safe, cupping therapy can cause adverse events. Most of these events are predictable and preventable. A comprehensive approach to patient eligibility and therapist selection, along with compliance with standard operational procedures is essential to regulate the safety of the practice. Here we discuss a model framework for standardizing safety and quality of care. We recommend that this model be used routinely by cupping therapists and their associations on a nation-wide scale.

Background
Constipation is a common chronic bowel disorder with an incidence of more than 50% in the elderly population. Complementary and alternative medicine is a cost-effective and satisfactory treatment for constipation used widely by the elderly.

Objective
This study evaluates the efficacy of an herbal formula made from Foeniculum vulgare Mill. and Rosa damascena for the treatment of constipation in an elderly population and consequent changes to their quality of life.

Design, setting, participants and intervention
This double-blind randomized active controlled clinical trial, with parallel group allocation ratio of 1:1, was conducted in a referral clinic in Afzalipour Hospital, affiliated to Kerman University of Medical Sciences in Kerman, Southeastern Iran. Individuals over 60 years of age, diagnosed with functional constipation (based on the Rome IV criteria), were included in this study. Participants received a sachet of 10 g F. vulgare and R. damascena (herbal formula group) or polyethylene glycol 4000 (PEG 4000 group) with a glass of warm water two times a day for 4 weeks and were followed up for 4 additional weeks.

Main outcome measures
Constipation severity, stool consistency, and the quality of life were used as the primary outcomes. Drug side effects were used as a secondary outcome. The outcomes were assessed using the Constipation Assessment Scale, the Bristol Stool Form Scale, and the Patient Assessment of Constipation Quality of Life questionnaire.

Results
A total of 25 participants in each group completed the four-week treatment cycle and the eight-week follow-up. At the end of the four-week treatment cycle, all clinical outcomes had significant improvements in both groups (P < 0.05). The analysis of constipation severity (P < 0.001), stool consistency (P < 0.001), and the quality of life (P < 0.001) showed significant improvements with fewer side effects (mild diarrhea) and a longer duration of symptom relief in the herbal formula group compared to the PEG 4000 group.

Conclusion
Although both interventions significantly improved the treatment outcomes, constipation severity, stool consistency and the quality of life were improved more effectively by the herbal formula than by PEG 4000; however, the mechanism of action is not yet understood.

Trial registration
This trial was registered in the Iranian Registry of Clinical Trials (IRCTID: IRCT20200108046056N1).

Background
High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown.

Objective
The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated.

Design, participants and intervention
This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone.

Main outcome measures
The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3.

Results
A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups.

Conclusion
STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.

Objective

Bufalin is an effective drug for the treatment of liver cancer. But its high toxicity, poor water-solubility, fast metabolism and short elimination half-life limit its use in tumor treatment. How to make the drug accumulate in the tumor and reduce side effects while maintaining its efficacy are urgent problems to be solved. The goal of this study is to solve these problems.

Methods

A copolymer with tunable poly-N-isopropylacrylamide and polylactic acid was designed and synthesized. The corresponding dual targeting immunomicelles (DTIs) loaded with bufalin (DTIs-BF) were synthesized by copolymer self-assembly in an aqueous solution. The size and structure of DTIs-BF were determined by ZetaSizer Nano-ZS and transmission electron microscopy. Then, its temperature sensitivity, serum stability, critical micelle concentration (CMC), entrapment efficiency (EE), drug release and non-cytotoxicity of blank block copolymer micelles (BCMs) were evaluated. Next, the effects of DTIs-BF on cellular uptake, cytotoxicity, and tumor cell inhibition were evaluated. Finally, the accumulation of DTIs-fluorescein isothiocyanate (FITC) and the in vivo anti-tumor effect were observed using an interactive video information system. 

Results

DTIs-BF had a small size, spherical shape, good temperature sensitivity, high serum stability, low CMC, high EE, and slow drug release. The blank BCMs had very low cytotoxicity. Compared with free bufalin, the in vitro cellular internalization and cytotoxicity of DTIs-BF against SMMC-7721 cells were significantly enhanced, and the effects were obviously better at 40 ℃ than 37 ℃. In addition, the therapeutic effect on SMMC-7721 cells was further enhanced by the programmed cell death specifically caused by bufalin. When DTIs-FITC were injected intravenously in BALB/c nude mice bearing liver cancer, the accumulation of FITC was significantly increased in tumors.

Conclusion

DTIs-BF is a potentially effective nano-formulation and has broad prospects in the clinical treatment of liver cancer.

Objective
Exercise, as a common non-drug intervention, is one of several lifestyle choices known to reduce the risk of cancer. Mitochondrial division has been reported to play a key role in the occurrence and transformation of hepatocellular carcinoma (HCC). This study investigated whether exercise could regulate the occurrence and development of HCC through mitosis.
Methods
Bioinformatics technology was used to analyze the expression level of dynamin-related protein 1 (DRP1), a key protein of mitochondrial division. The effects of DRP1 and DRP1 inhibitor (mdivi-1) on the proliferation and migration of liver cancer cells BEL-7402 were observed using cell counting kit-8, plate colony formation, transwell cell migration, and scratch experiments. Enzyme-linked immunosorbent assay, Western blot and real-time polymerase chain reaction were used to detect the expression of DRP1 and its downstream phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. A treadmill exercise intervention was tested in a nude mouse human liver cancer subcutaneous tumor model expressing different levels of DRP1. The size and weight of subcutaneous tumors in mice were detected before and after exercise.
Results
The expression of DRP1 in liver cancer tissues was significantly upregulated compared with normal liver tissues (P < 0.001). The proliferation rate and the migration of BEL-7402 cells in the DRP1 over-expression group were higher than that in the control group. The mdivi-1 group showed an inhibitory effect on the proliferation and migration of BEL-7402 cells at 50 μmol/L. Aerobic exercise was able to inhibit the expression of DRP1 and decrease the size and weight of subcutaneous tumors. Moreover, the expression of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) decreased in the exercise group. However, exercise could not change p-PI3K and p-AKT levels after knocking down DRP1 or using mdivi-1 on subcutaneous tumor.
Conclusion
Aerobic exercise can suppress the development of tumors partially by regulating DRP1 through PI3K/AKT pathway.

Traditional medicine systems around the globe, like Unani, Ayurveda and traditional Chinese medicine, include a number of sugar-based formulations, which contain a large amount of saccharide-containing sweetener, such as honey, sucrose or jaggery. With pervasive lifestyle disorders throughout the world, there have been discussions to consider alternative sweetening agents. Here, from the perspective of Unani medicine, we discuss how the saccharide-based sweeteners may be an essential component of these traditional preparations, like electuaries, which may be deprived of their bioactivities without these saccharides. With contemporary researches, it is known that apart from their own therapeutic effects, saccharides also form deep eutectic solvents which help in enhancing the bioactivity of other ingredients present in crude drugs. In addition, they provide energy for fermentation which is essential for biotransformation of compounds. Interestingly, the sugars also increase the shelf-life of these compound drugs and act as natural preservatives. On the basis of this review, we strongly believe that saccharide-based sweeteners are an essential component of traditional medicines and not merely an excipient.

Background
Traditional Chinese medicine (TCM) is becoming a popular complementary approach in pediatric oncology. However, few or no meta-analyses have focused on clinical studies of the use of TCM in pediatric oncology.

Objective
We explored the patterns of TCM use and its efficacy in children with cancer, using a systematic review, meta-analysis and data mining study.

Search strategy
We conducted a search of five English (Allied and Complementary Medicine Database, Embase, PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and four Chinese databases (Wanfang Data, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and VIP Chinese Science and Technology Periodicals Database) for clinical studies published before October 2021, using keywords related to “pediatric,” “cancer,” and “TCM.”

Inclusion criteria
We included studies which were randomized controlled trials (RCTs) or observational clinical studies, focused on patients aged < 19 years old who had been diagnosed with cancer, and included at least one group of subjects receiving TCM treatment.

Data extraction and analysis
The methodological quality of RCTs and observational studies was assessed using the six-item Jadad scale and the Effective Public Healthcare Panacea Project Quality Assessment Tool, respectively. Meta-analysis was used to evaluate the efficacy of combining TCM with chemotherapy. Study outcomes included the treatment response rate and occurrence of cancer-related symptoms. Association rule mining (ARM) was used to investigate the associations among medicinal herbs and patient symptoms.

Results
The fifty-four studies included in this analysis were comprised of RCTs (63.0%) and observational studies (37.0%). Most RCTs focused on hematological malignancies (41.2%). The study outcomes included chemotherapy-induced toxicities (76.5%), infection rate (35.3%), and response, survival or relapse rate (23.5%). The methodological quality of most of the RCTs (82.4%) and observational studies (80.0%) was rated as “moderate.” In studies of leukemia patients, adding TCM to conventional treatment significantly improved the clinical response rate (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.49–4.36), lowered infection rate (OR = 0.23; 95% CI = 0.13–0.40), and reduced nausea and vomiting (OR = 0.13; 95% CI = 0.08–0.23). ARM showed that Radix Astragali, the most commonly used medicinal herb (58.0%), was associated with treating myelosuppression, gastrointestinal complications, and infection.

Conclusion
There is growing evidence that TCM is an effective adjuvant therapy for children with cancer. We proposed a checklist to improve the quality of TCM trials in pediatric oncology. Future work will examine the use of ARM techniques on real-world data to evaluate the efficacy of medicinal herbs and drug-herb interactions in children receiving TCM as a part of integrated cancer therapy.

Objective

The present study investigated antiglycation and antioxidant activities of crude dry extract and saponin fraction of Tribulus terrestris. It also developed a method of microencapsulation and evaluated antiglycation and antioxidant activities of crude dry extract and saponin fraction before and after microcapsules release. 

Methods

Antiglycation activity was determined by relative electrophoretic mobility (REM), free amino groups and inhibition of advanced glycation end-product (AGE) formation. Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric ion reducing antioxidant power (FRAP), nitric oxide (NO) and thiobarbituric acid reactive species (TBARS) tests. Microcapsules were prepared using maltodextrin as wall material and freeze-drying as encapsulation technique. Morphological characterization of microcapsules was evaluated by scanning electron microscopy, and encapsulation efficiency and microcapsules release were determined by total saponins released. Antiglycation and antioxidant assays were performed using crude dry extract and saponin fraction of T. terrestris before and after release.

Results

Saponin fraction showed an increase of 32.8% total saponins. High-performance liquid chromatography-mass spectrometry analysis showed the presence of saponins in the obtained fraction. Antiglycation evaluation by REM demonstrated that samples before and after release present antiglycation activity similar to bovine serum albumin treated with aminoguanidine. Additionally, samples inhibited AGEs formation, highlighting treatment with saponins fraction after release (89.89%). Antioxidant tests demonstrated antioxidant activity of the samples. Crude dry extract before encapsulation presented the highest activities in DPPH (92.00%) and TBARS (32.49%) assays. Saponins fraction before encapsulation in FRAP test (499 μmol Trolox equivalent per gram of dry sample) and NO test (15.13 μmol nitrite formed per gram of extract) presented the highest activities. 

Conclusion

This study presented antiglycation activity of crude dry extract and saponins fraction of T. terrestris, besides it demonstrated promising antioxidant properties. It also showed that the encapsulation method was efficient and maintained biological activity of bioactive compounds after microcapsules release. These results provide information for further studies on antidiabetic and antiaging potential, and data for new herbal medicine and food supplement formulations containing microcapsules with crude extract and/or saponins fraction of T. terrestris.

Background

Coronavirus disease 2019 (COVID-19) has become a worldwide life-threatening pandemic. Lianhua Qingwen is believed to possess the ability to treat or significantly improve the symptoms of COVID-19. These claims make it important to systematically evaluate the effects of using Lianhua Qingwen with Western medicine to treat COVID-19.

Objective

To evaluate the safety and efficacy of combination therapy, employing Lianhua Qingwen with Western medicine, to treat COVID-19, using a meta-analysis approach.

Search strategy

China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Embase, and Cochrane Library databases were searched for studies evaluating the effect of Lianhua Qingwen-Western medicine combination therapy in the treatment of COVID-19.

Inclusion criteria

(1) Research object: hospitalized patients meeting the diagnostic criteria of COVID-19 were included. (2) Intervention measures: patients in the treatment group received Lianhua Qingwen treatment combined with Western medicine, while the control group received either Western medicine or Chinese medicine treatment. (3) Research type: randomized controlled trials and retrospective study were included.

Data extraction and analysis

Two researchers extracted the first author, the proportion of males and females, age, body temperature, course of treatment, rate of disappearance of main symptoms, duration of fever, adverse reactions, and total effectiveness from the literature. Odds ratio (OR) and 95% confidence interval (CI) were used as the effect value for count data, and mean difference (MD) and 95% CI were used as the effect value for measurement data.

Results

Six articles met the inclusion criteria, including a total of 856 COVID-19 patients. The meta-analysis showed that Lianhua Qingwen combination therapy achieved higher rates of fever reduction (OR = 3.43, 95% CI [1.78, 6.59], P = 0.0002), cough reduction (OR = 3.39, 95% CI [1.85, 6.23], P < 0.0001), recovery from shortness of breath (OR = 10.62, 95% CI [3.71, 30.40], P < 0.0001) and recovery from fatigue (OR = 2.82, 95% CI [1.44, 5.53], P = 0.003), higher total effectiveness rate (OR = 2.51, 95% CI [1.73, 3.64], P< 0.00001), and shorter time to recovery from fever (MD = –1.00, 95% CI [–1.04, 0.96], P < 0.00001), and did not increase the adverse reaction rate (OR = 0.65, 95% CI [0.42, 1.01], P = 0.06), compared to the single medication control. 

Conclusion

The Lianhua Qingwen and Western medicine combination therapy is highly effective for COVID-19 patients and has good clinical safety. As only a small number of studies and patients were included in this review, more high-quality, multicenter, large-sample-size, randomized, double-blind, controlled trials are still needed for verification.

Angiotensin-converting enzyme (ACE) inhibitors are antihypertensive medications often used in the treatment of diabetes-related complications. Synthetic ACE inhibitors are known to cause serious side effects like hypotension, renal insufficiency, and hyperkalaemia. Therefore, there has been an intensifying search for natural ACE inhibitors. Many plants or plant-based extracts are known to possess ACE-inhibitory activity. In this review, articles focusing on the natural ACE inhibitors extracted from plants were retrieved from databases like Google Scholar, PubMed, Scopus, and Web of Science. We have found more than 50 plant species with ACE-inhibitory activity. Among them, Angelica keiskei, Momordica charantia, Muntingia calabura, Prunus domestica, and Peperomia pellucida were the most potent, showing comparatively lower half-maximal inhibitory concentration values. Among the bioactive metabolites, peptides (e.g., Tyr-Glu-Pro, Met-Arg-Trp, and Gln-Phe-Tyr-Ala-Val), phenolics (e.g., cyanidin-3-O-sambubioside and delphinidin-3-O-sambubioside), flavonoids ([-]-epicatechin, astilbin, and eupatorin), terpenoids (ursolic acid and oleanolic acid) and alkaloids (berberine and harmaline) isolated from several plant and fungi species were found to possess significant ACE-inhibitory activity. These were also known to possess promising antioxidant, antidiabetic, antihyperlipidemic and anti-inflammatory activities. Considering the minimal side effects and lower toxicity of herbal compounds, development of antihypertensive drugs from these plant extracts or phytocompounds for the treatment of diabetes-associated complications is an important endeavour. This review, therefore, focuses on the ACE inhibitors extracted from different plant sources, their possible mechanisms of action, present status, and any safety concerns.

Maximising access to and the success of fertility treatments should be a priority for global reproductive health, as should overall patient well-being. The demand for in vitro fertilization (IVF) and other assisted fertility treatments has increased over the past decade and is likely to further increase in years to come. Nevertheless, there is still considerable unmet demand for infertility support worldwide. Moreover, the high emotional, physical and financial burden experienced by individuals undergoing IVF cycles can be a risk for their mental and physical health, which in turn can influence treatment continuation and the likelihood of IVF success. Studies from various parts of the world show that most individuals undergoing IVF also use adjunct alternative medicines and procedures, the most common being traditional Chinese medicine (TCM). The complementary and synergistic role of TCM for individuals undergoing IVF is an area that merits further attention and research, both for its potential positive effects on IVF success rates and for its broader physical and mental health benefits. However, much of the existing evidence is not sufficiently robust or consistent for findings to be adopted with confidence. This commentary argues that much work must be done to understand the efficacy and clinical best practices for these integrated approaches. This can be achieved in part by developing more robust and clinically relevant randomized controlled trial protocols, collecting and triangulating evidence through a variety of study designs and methods, and strengthening the collection and pooling of clinic-level data.

Objectives

Ziyin Huatan recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC) in the clinic. However, its potential mechanism in treating GC has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo.

Methods

Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of gastric cancer in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene.

Results

The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, and migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT.

Conclusion

ZYHT can e?ectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.

Objective

In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae (RAB) and Eucommiae Cortex (EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid (GC)-induced osteoporosis (GIOP) and find its optimal dosage in zebrafish.

Methods

The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 μmol/L dexamethasone (Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase (ALP) activity. Multiple regression analysis was conducted to test the optimal dosage ratio.

Results

According to the Chinese Pharmacopoeia (2015), β-ecdysone (β-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside (PDG) is the major marker in EC extract. Both of β-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 μmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 μg/mL RAB and 50 μg/mL EC was optimal for preventing GIOP in zebrafish. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the mRNA expression of osteogenesis-related genes. A treatment of 10 μmol/L Dex decreased runt-related transcription factor 2 (Runx2), osteogenic protein-1 (OP-1), bone γ-carboxyglutamic acid-containing protein (BGLAP), and β-catenin levels. This effect was counteracted by RAB and EC co-treatment (P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the presence of GC. The best mass ratio was 1:1.

Conclusion

RAB and EC herbal pair could ameliorate GC-induced effects in zebrafish, with 1:1 as the optimal dosage ratio.

Spinal manipulation is a manual treatment technique that delivers a thrust, using specific biomechanical parameters to exert its therapeutic effects. These parameters have been shown to have a unique dose-response relationship with the physiological responses of the therapy. So far, however, there has not been a unified approach to standardize these biomechanical characteristics. In fact, it is still undetermined how they affect the observed clinical outcomes of spinal manipulation. This study, therefore, reviewed the current body of literature to explore these dosage parameters and evaluate their significance, with respect to physiological and clinical outcomes. From the experimental studies reviewed herein, it is evident that the modulation of manipulation’s biomechanical parameters elicits transient physiological responses, including changes in neuronal activity, electromyographic responses, spinal stiffness, muscle spindle responses, paraspinal muscle activity, vertebral displacement, and segmental and intersegmental acceleration responses. However, to date, there have been few clinical trials that tested the therapeutic relevance of these changes. In addition, there were some inherent limitations in both human and animal models due to the use of mechanical devices to apply the thrust. Future studies evaluating the effects of varying biomechanical parameters of spinal manipulation should include clinicians to deliver the therapy in order to explore the true clinical significance of the dose-response relationship.

Background
Propolis and honey have been studied as alternative treatments for patients with coronavirus disease 2019 (COVID-19). However, no study has yet summarized the full body of evidence for the use of propolis and honey in COVID-19 prevention and treatment.

Objective
This study systematically reviews the mechanisms of propolis and honey against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and current evidence for the use of propolis and honey in COVID-19 prevention and treatment.

Search strategy
A systematic search was conducted of electronic databases including PubMed, Scopus, ScienceDirect, and Cochrane Library from their inceptions to April 2021.

Inclusion criteria
Studies that evaluated the effect of propolis or bee products against SARS-CoV-2 using in silico methods, clinical studies, case reports and case series were included.

Data extraction and analysis
A standardized data extraction form was used, and data were extracted by two independent reviewers. Narrative synthesis was used to summarize study results concerning the use of propolis or honey in COVID-19 prevention and treatment and their potential mechanisms of action against SARS-CoV-2.

Results
A total of 15 studies were included. Nine studies were in silico studies, two studies were case reports, one study was a case series, and three studies were randomized controlled trials (RCTs). In silico studies, using molecular docking methods, showed that compounds in propolis could interact with several target proteins of SARS-CoV-2, including angiotensin-converting enzyme 2, the main protease enzyme, RNA-dependent RNA polymerase, and spike protein. Propolis may have a positive effect for clinical improvement in mild and moderate-to-severe COVID-19 patients, according to case reports and case series. The included RCTs indicated that propolis or honey could probably improve clinical symptoms and decrease viral clearance time when they were used as adjuvant therapy to standard of care.

Conclusion
In silico studies showed that compounds from propolis could interact with target proteins of SARS-CoV-2, interfering with viral entry and viral RNA replication, while clinical studies revealed that propolis and honey could probably improve clinical COVID-19 symptoms and decrease viral clearance time. However, clinical evidence is limited by the small number of studies and small sample sizes. Future clinical studies are warranted.

Objective: This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli (FZ) against type 2 diabetes mellitus (T2DM) based on network pharmacology and experimental validation.
Methods: Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry, and gas chromatography-mass spectrometry were used to identify the constituents of FZ. Next, the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases (including Gene Expression Omnibus database and Swiss Target Prediction online database), and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the pathway was verified by in vitro experiments, and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM.
Results: A total of 43 components were identified from FZ, and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM. The dug component-target network indicated that PPARA, PPARG, PIK3R3, JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM. Interestingly, the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in HepG2 cells. Moreover, FZ treatment was able to promote the AMPK and PI3K/Akt expressions in HepG2 cells.
Conclusion: Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.

The term Jingluo, translated as meridian or channel, is a core component of traditional Chinese medicine (TCM) and has played a fundamental role in guiding the clinical practice of acupuncture for thousands of years. However, the essence of the meridian remains elusive and is a source of both confusion and debate for researchers. In this study, a “4D” systemic view on the essence of the meridian, namely substantial, functional, chronological, and cultural dimensions, was proposed based on a review of the ancient medical classics, recent research developments, and results from clinical practice. Previous studies have primarily focused on the substantial dimension of the meridian system, with scant interpretation about its functional domain. Neither systemic data nor evaluations have been adequately documented. Additionally, a limited but increasing number of studies have focused on the chronological and cultural dimensions. More investigations that embody the holistic concept of TCM and integrate the systemic modes and advanced techniques with dominant diseases of TCM need to be performed to obtain a more comprehensive understanding of the essence of meridians. The goal of this study is to yield useful information in understanding the essence of meridians and provide a reference and perspective for further research.

Peperomia pellucida (L.) Kunth is a medicinal plant used to manage inflammatory illnesses such as conjunctivitis, and gastrointestinal and respiratory tract disorders in tropical and subtropical regions. However, little is known about its pharmacological mechanism of action against eye diseases. This review aims to critically discuss the phytochemistry, pharmacology and toxicology of P. pellucida as well as its roles in the treatment of cataract, glaucoma and diabetic retinopathy. Recent developments in the uses of P. pellucida for healthcare and nutraceutical products by the pharmaceutical industry are also covered in this review. For this review, a literature search was performed with PubMed, ScienceDirect, SciFinder Scholar and Scopus databases, using relevant keywords. Among the various phytochemicals identified from P. pellucida, β-caryophyllene, carotol, dillapiole, ellagic acid, pellucidin A, phytol and vitexin exhibit strong pharmacological activities within the mitogen-activated protein kinase and nuclear factor-κB signalling pathways in inflammatory eye diseases. The antihypertensive, anti-inflammatory, antioxidant, antihyperglycemic and anti-angiogenic activities displayed by P. pellucida extracts in many in vitro, in vivo and clinical studies suggest its potential role in the management of inflammatory eye diseases. P. pellucida extract was non-toxic against normal cell lines but displayed mild toxicity in animal models. The growing public interest in P. pellucida has inspired the nutraceutical and pharmaceutical industries to process the plant into health products. Although the potential pharmacological mechanisms against eye diseases have been summarized, further studies of the interactions among constituent phytochemicals from P. pellucida within various signalling pathways shall support the use of the plant as an alternative therapeutic source.