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.

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.

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

JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.

Methods

HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125–50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.

Results

HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).

Conclusion

JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1.

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

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.

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

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.

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
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: 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.

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.

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.

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

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.

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

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. 

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

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

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.

Acquired immune deficiency syndrome (AIDS) is a worldwide epidemic caused by human immunodeficiency virus (HIV) infection. Newer medicines for eliminating the viral reservoir and eradicating the virus are urgently needed. Attempts to locate relatively safe and non-toxic medications from natural resources are ongoing now. Natural-product-based antiviral candidates have been exploited to a limited extent. However, antiviral research is inadequate to counteract for the resistant patterns. Plant-derived bioactive compounds hold promise as powerful pharmacophore scaffolds, which have shown anti-HIV potential. This review focuses on a consideration of the virus, various possible HIV-controlling methods and the recent progress in alternative natural compounds with anti-HIV activity, with a particular emphasis on recent results from natural sources of anti-HIV agents.

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: 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.

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
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
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.

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. 

Objective

Melittin and its derivatives have been characterized to establish effective gene delivery systems. Their capability of facilitating endosomal release enhances the nanoparticles-based gene delivery. Nevertheless, little investigation has been conducted to explore its potential application in the context of viral vectors.

Methods

Various melittin-derived peptides were inserted into the loop VIII of the capsid proteins of recombinant adeno-associated virus vectors. These vectors carrying either gfp or fluc genes were subjected to qPCR assays and transduction assays of HEK293T cells to investigate the efficiency of vector production and gene delivery. In addition, the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 mice. Finally, the intricate details of the vector-mediated transduction mechanisms were revealed by specific pharmacological inhibitors of every stage of the rAAV2 intracellular life cycle.

Results

A total of 76 melittin-related peptides were compiled from existing literature. Among them, cMA2, Melt13, p5RHH and aAR3 were found to significantly enhance the gene delivery efficiency of rAAV2 vectors. The p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to rAAV. Mechanistically, bafilomycin A1, a vacuolar endosome acidification inhibitor, completely inhibited the transgene expression mediated by the p5RHH-rAAV2 vectors. Most importantly, p5RHH-rAAV8 vectors also demonstrated increased hepatic transduction in vivo in C57BL/6 mice.

Conclusion

The incorporation of melittin analogues into the rAAV capsids results in a significant improvement in rAAV-mediated transgene expression. While further modifications remain an area of interest, our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery.

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.

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: Effects of arsenic trioxide (As2O3) on hepatocellular carcinoma (HCC) has been documented widely. In addition, autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3 -induced apoptosis in liver cancer cells.
Methods: The viability of hepatoma cells was determined with MTT assay. The apoptosis of As2O3-induced liver cancer cells was evaluated by flow cytometry, Hoechst 33258 staining and TUNEL assays. The autophagy of liver cancer cell was detected by immunofluorescence, western blot assay and transmission electron microscopy.
Results: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time- and dose-dependent manner. The apoptosis rates of both liver cancer cells increased with the concentration of As2O3 as determined by Flow cytometry. Apoptosis in liver cancer cells induced by As2O3 was also demonstrated by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression. Furthermore, we also found that As2O3 treatment induced liver cancer cells autophagy, which was demonstrated by western blot, immunofluorescence of LC3-II and Beclin 1 expression and transmission electron microscopy observation. In liver cancer cells, As2O3 inhibited the PI3K/AKT/mTOR signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator, SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-MA partially reversed As2O3-induced cell viability inhibition, and enhanced autophagy with serum starvation facilitated As2O3-induced cell death.
Conclusion: As2O3 is able to induce liver cancer cells apoptosis and autophagy. Autophagy induced by As2O3 may play a proapoptotic effect in the anti-liver cancer effects. Our present study provides novel insights into the anti-liver cancer effects of As2O3.

Objective

Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis.

Methods

The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.

Results

Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0 .582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1.

Conclusion

The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.

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.

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
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.

Background
Different homeopathic approaches have been used as supportive care for coronavirus disease 2019 (COVID-19) cases, but none has been tested in a clinical trial.

Objectives
To investigate the effectiveness and safety of the homeopathic medicine, Natrum muriaticum LM2, for mild cases of COVID-19.

Design, setting, participants, and interventions
A randomized, double-blind, two‐armed, parallel, single-center, placebo-controlled clinical trial was conducted from June 2020 to April 2021 in S?o-Carlos, Brazil. Participants aged > 18 years, with influenza-like symptoms and positive result from a real-time polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 were recruited and randomized (1:1) into two groups that received different treatments during a period of at-home-isolation. One group received the homeopathic medicine Natrum muriaticum, prepared with the second degree of the fifty-millesimal dynamization (LM2; Natrum muriaticum LM2), while the other group received a placebo.

Outcome measures
The primary endpoint was time until recovery from COVID-19 influenza-like symptoms. Secondary measures included a survival analysis of the number and severity of COVID-19 symptoms (influenza-like symptoms plus anosmia and ageusia) from a symptom grading scale that was informed by the participant, hospital admissions, and adverse events. Kaplan-Meier curves were used to estimate time-to-event (survival) measures.

Results
Data from 86 participants were analyzed (homeopathy, n = 42; placebo, n = 44). There was no difference in time to recovery between two groups among participants who were reporting influenza-like symptoms at the beginning of monitoring (homeopathy, n = 41; placebo, n = 41; P = 0.56), nor in a sub-group that had at least 5 moderate to severe influenza-like symptoms at the beginning of monitoring (homeopathy, n = 15; placebo, n = 17; P = 0.06). Secondary outcomes indicated that a 50% reduction in symptom score was achieved significantly earlier in the homeopathy group (homeopathy, n = 24; placebo, n = 25; P = 0.04), among the participants with a basal symptom score ≥ 5. Moreover, values of restricted mean survival time indicated that patients receiving homeopathy might have improved 0.9 days faster during the first five days of follow-up (P = 0.022). Hospitalization rates were 2.4% in the homeopathy group and 6.8% in the placebo group (P = 0.62). Participants reported 3 adverse events in the homeopathy group and 6 in the placebo group.

Conclusion
Results showed that Natrum muriaticum LM2 was safe to use for COVID-19, but there was no statistically significant difference in the primary endpoints of Natrum muriaticum LM2 and placebo for mild COVID-19 cases. Although some secondary measures do not support the null hypothesis, the wide confidence intervals suggest that further studies with larger sample sizes and more symptomatic participants are needed to test the effectiveness of homeopathic Natrum muriaticum LM2 for COVID-19.

Trial registration
UMIN Clinical Trials Registry ID: JPRN-UMIN000040602.

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
This study aimed to develop expert fuzzy logic model to assist physicians in the prediction of postoperative complications of prostatic hyperplasia before surgery.

Methods
A method for classification of surgical risks was developed. The effect of rotation of the current-voltage characteristics at biologically active points (acupuncture points) was used for the formation of classifier descriptors. The effect determined reversible and non-reversible changes in electrical resistance at acupuncture points with periodic exposure to a sawtooth probe current. Then, the developed method was tested on the prediction of the success of surgical treatment of benign prostatic hyperplasia.

Results
Input descriptors were obtained from collected data including current-voltage characteristics of 5 acupuncture points and composed of 27 arrays feeding in the model. The maximum diagnostic sensitivity of the classifier for the success of a surgical operation in the control sample was 88% and for testing data set prediction accuracy was 97%.

Conclusion
The use of tuples of current-voltage characteristic descriptors of acupuncture points in the classifiers could be used to predict the success of surgical treatment with satisfactory accuracy. The model can be a valuable tool to support physicians' diagnosis.

Objective: Severe cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology.
Methods: Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets.
Results: Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase.
Conclusion: Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.

Music therapy is an integrative oncology practice that has been rapidly emerging, over the past two decades, as a field of its own, clinically and academically. The randomized controlled trials that evaluate the clinical impact of music therapy are growing in number, and at the same time, there has been progress in understanding the neurobiological mechanisms that underly the beneficial effects of music therapy. Cultural background and autobiographical memories may uniquely influence music perception and cognition. It is vital to personalize music therapy because music preferences are unique; one size does not fit all. Cognitive music science studies and clinical music therapy trials that study individualized music choices will serve as a vital step forward in providing patient-directed personalized integrative cancer care. The field of music therapy is advancing, and its ability to improve a patient’s quality of life can be understood only through robust, personalized, evidence-based initiatives that focus on research, advocacy, education, and delivery of care.

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.

Objective

‘Multi-targeting’ drugs can prove fruitful to combat drug-resistance of multifactorial disease—cervical cancer. This study envisioned to reveal if Thuja homeopathic mother tincture (MT) and its bioactive component could combat human papillomavirus (HPV)-16-infected SiHa cervical cancer cells since it is globally acclaimed for HPV-mediated warts.

Methods

Thuja MT was studied for its antiproliferative and antimigratory properties in SiHa cells followed by microscopic determination of reactive oxygen species (ROS) generation by 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) staining and loss in mitochondrial membrane potential (MMP) by rhodamine (Rh) 123 staining. Apoptosis and autophagy inductions were studied by acridine orange (AO) ethidium bromide (EB) staining and immunoblot analyses of marker proteins. The bioactive component of Thuja MT detected by gas chromatography-mass spectrometry was studied for antiproliferative and antimigratory properties along with in silico prediction of its cellular targets by molecular docking and oral drug forming competency.

Results 

Thuja MT showed significant antiproliferative and antimigratory potential in SiHa cells at a 50% inhibitory concentration (IC50) dosage of 17.3 μL/mL. An increase in DCFDA fluorescence and loss in Rh123 fluorescence prove that Thuja MT acted through the burst of ROS and loss in MMP respectively. AO/EB-stained cells under the microscope and immunoblot analyses supported Thuja-induced cellular demise via dual pathways—apoptosis and autophagy. Immunoblots showed cleavage of caspase-3 and poly adenosine diphosphate-ribose polymerase-1 (PARP-1) along with upregulation of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B)-II, and p62 proteins. Hence, the apoptotic cascade followed a caspase-3-dependent pathway supported by PARP-1 cleavage, while autophagic death was Beclin-1-dependent and mediated by accumulation of LC3BII and p62 proteins. Thujone, detected as the bioactive principle of Thuja MT showed greater anti-proliferative and anti-migratory potential at an IC50 77 μg/mL along with excellent oral drug competency with the ability for gastrointestinal absorption and blood-brain-barrier permeation with nil toxicity. Molecular docking depicted thujone with the strongest affinity for mammalian target of rapamycin, phosphoinositide 3-kinase, and protein kinase B followed by B-cell lymphoma 2, murine double minute 2 and adenosine monophosphate-activated protein kinase, which might act as upstream triggers of apoptotic-autophagic crosstalk. 

Conclusion

Robust ‘multi-targeting’ anticancer potential of Thuja drug and thujone for HPV-infected cervical cancer ascertain its therapeutic efficacy for HPV infections. 

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.

Background

Beginning with the concepts of stress developed by Selye, an approach to stress and pain management, known as neuro-emotional technique (NET), has been developed. It is a treatment approach based on the principle that the stressor effects of dormant and/or current unresolved issues or trauma are what determine one’s bodily responses. These responses are relatively personalized to the conditioned, experiential and emotional reality of the individual.

Objective

To determine the effect of NET on patients with chronic low back pain (CLBP) over time. 

Design, setting, participants, and interventions

In a randomized, double-blinded, placebo-controlled study conducted in a single clinic, NET or control treatments were given twice weekly for 4 weeks in a population of 112 patients. 

Main outcome measures

Outcome measures, including Oswestry Disability Index, Quadruple Visual Analogue Scale, the psychoneuroimmunology markers of blood serum levels of C-reactive protein, tumour necrosis factor-α, interleukin-1 (IL-1), IL-6, and IL-10, and 10 dimensions of the Short Form Health Survey scale, were assessed at baseline and at 1, 3 and 6 months following the intervention period.

Results

Compared to placebo, NET produced clinical and statistical significance (P < 0.001) via declines of virtually all physiological, pain and disability markers, accompanied by gains in quality-of-life indicators at 0 (baseline), 1, 3 and 6 months. Reductions of the percentages of patients whose 5 biomarkers lay outside the normative range were achieved at 1, 3 and 6 months by NET but not control interventions. 

Conclusion

A randomized, controlled trial of CLBP patients indicated that 8 NET interventions, compared to placebo, produced clinically and statistically significant reductions in pain, disability and inflammatory biomarkers, and improvements in quality-of-life measures.

Trial Registration

The trial was registered with the Australian and New Zealand Clinical Trials Registry (No. ACTRN12608000002381).

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.