Since the outbreak of coronavirus disease-19 (COVID-19) in Wuhan in December 2019, it has rapidly spread to the whole country and the world, causing serious harm to the health of people and a huge social burden. However, currently, there are no clinically available drugs, except for vaccines against COVID-19 that are being evaluated. Traditional Chinese medicine (TCM) is capable of performing syndrome differentiation and treatment according to the clinical manifestations of patients, and has a better ability of epidemic prevention and control. Therefore, we comprehensively analyzed the etiology and pathogenesis of COVID-19 based on the theory of TCM, and discussed its syndrome differentiation, treatment, and prevention measures to provide strategies and reference for the prevention and treatment of COVID-19 with TCM.

Background
Zhibai Dihuang pill (ZBDH), a Chinese herbal formula, has been widely used as an adjunctive therapy to help reduce a patient's steroid dose while maintaining low disease activity in systemic lupus erythematosus (SLE).

Objective
This systematic review evaluates the therapeutic effect of modified ZBDH in reducing steroid use in patients with SLE.

Search strategy
A systematic literature search was carried out using seven databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese VIP Information and Wanfang Database, from their inception to June 1st, 2019. The search terms included “systemic lupus erythematosus,” “Chinese medicine” and “clinical trial,” and their synonyms. Subject headings matching the above terms were also used.

Inclusion criteria
This meta-analysis included randomized controlled trials that evaluated the reduction of steroid dose in patients with SLE. Traditional Chinese medicine (TCM) formulas in experimental group should be prescribed based on ZBDH and used as adjunctive therapy and the comparator should contain steroids.

Data extraction and analysis
Two authors independently conducted database searches, study selection, data extraction and quality assessment. The extracted information contained study design, sample size, recruitment mode, diagnostic criteria, inclusion and exclusion criteria, participant characteristics, TCM patterns, TCM formulas and treatment outcomes. The primary outcome was the change of steroid dose. Secondary outcomes included SLE Disease Activity Index (SLEDAI), biomarkers of disease activity and clinical response rate. STATA 15.0 was used to analyze the pooled effects reported as weighted mean difference (WMD) or odds ratio, with a 95% confidence interval (CI).

Results
In total, 20 trials involving 1470 SLE patients were included. The pooled result showed that modified ZBDH taken in combination with standard care led to a larger reduction in steroid dose, compared to standard care alone (WMD: 3.79; 95% CI: 2.58–5.01; P < 0.001). Favorable outcomes were also seen in secondary outcome criteria, such as SLEDAI and complement 3. The modified ZBDH treatments were well tolerated without increasing adverse effects.

Conclusion
The systematic review provided preliminary evidence supporting the use of ZBDH as a co-therapy to aid steroid dose reduction in patients with SLE. However, more rigorous studies should be conducted to validate these findings, and explore the mechanisms of ZBDH’s relevant bioactive constituents.

Objective
Our previous research showed that Naotaifang (a compound traditional Chinese herbal medicine) extract (NTE) has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia. In this study, we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4 (GPX4) and iron metabolism.

Methods
We established an acute brain injury model of middle cerebral artery occlusion (MCAO) in rats, in which we could observe the accumulation of iron in neurons, as detected by Perl’s staining. Using assay kits, we measured expression levels of ferroptosis biomarkers, such as iron, glutathione (GSH), reactive oxygen species (ROS) and malonaldehyde (MDA); further the expression levels of transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), solute carrier family 7 member 11 (SLC7A11) and GPX4 were determined using immunohistochemical analysis, real-time quantitative polymerase chain reaction and Western blot assays.

Results
We found that treatment with NTE reduced the expression levels of TFR1 and DMT1, reduced ROS, MDA and iron accumulation and reduced neurobehavioral scores, relative to untreated MCAO rats. Treatment with NTE increased the expression levels of SLC7A11, GPX4 and GSH, and the number of Nissl bodies in the MCAO rats.

Conclusion
Taken together, our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways.

Objective
The objective of this study was to systematically investigate the effects of TCEs on blood glucose control in patients with prediabetes.

Search strategy:
Comprehensive retrieval of randomized controlled trials (RCTs) was carried out using PubMed, Cochrane Library, EMbase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Data Knowledge Service Platform, China Biology Medicine disc, Google Scholar and Baidu academic databases. The retrieval window ranged from the establishment of the database to December 2018, and references related to the included trials were searched without language restrictions.

Inclusion criteria:
The study included RCTs with a clinical diagnosis of prediabetes that was also treated with TCEs.

Data extraction and analysis:
Literature screening, data extraction and literature quality assessment were performed independently by two researchers. In the case of disagreement, a third party was invited to negotiate and make a decision. Standardized mean difference (SMD) was used to estimate the therapeutic effect. Meta-analysis was performed using Review Manager 5.3.5 and Stata 15.0. Heterogeneity was assessed using Q test and I2, and the source of heterogeneity was determined using Galbraith diagram and sensitivity analysis. A Q test resulting in P < 0.1 and I2 > 50% indicated significant difference and random effect model analysis was performed. Otherwise, a fixed effect model was applied. Begg’s and Egger’s tests were used to assess publication bias.

Results
Nine RCTs involving 485 participants were included in this study. The results showed that TCEs could reduce fasting blood glucose (FBG), 2 h blood glucose (2hPBG) and HbA1c in patients with prediabetes. The treatment subgroup showed that an intervention of 6 months had better results, while the Gongfa subgroup showed that the TCE Baduanjin yielded better results. (1) FBG: SMD = –0.73, 95% confidence interval (CI) [–0.97, –0.50], P < 0.00001; Baduanjin: SMD = –0.83, 95% CI [–1.13, –0.53], P < 0.00001; 6 months treatment: SMD = –0.73, 95% CI [–1.20, –0.26], P = 0.002. (2) 2hPBG: SMD = –0.75, 95% CI [–0.94, –0.57], P < 0.00001; Baduanjin: SMD = –0.62, 95% CI [–0.91, –0.32], P < 0.00001; 6 months treatment: SMD = –0.91, 95% CI [–1.39, –0.44], P = 0.0002. (3) HbA1c: SMD = –0.56, 95% CI [–0.89, –0.23], P = 0.00008; Baduanjin: SMD = –0.46, 95% CI [–0.83, –0.08], P = 0.02; 6 months treatment: SMD = –0.77, 95% CI [–1.24, –0.29], P = 0.002.

Conclusion
TCEs had positive effects in improving blood glucose levels in patients with prediabetes. Hence, TCEs may be of potential therapeutic value for patients with prediabetes, as an adjuvant therapy along with other treatments. Although the evidence suggests that the intervention is effective for 6 months, the mechanism of TCEs on glycemic control, the minimum exercise dose and their safety remain to be further studied.

Background
There is currently no drug or therapy that cures COVID-19, a highly contagious and life-threatening disease.
Objective
This systematic review and meta-analysis summarized contemporary studies that report the use of Chinese herbal medicine (CHM) to treat COVID-19.
Search strategy: Six electronic databases (PubMed/MEDLINE, Cochrane Library, ScienceDirect, Google Scholar, Wanfang Data and China National Knowledge Infrastructure) were searched from their beginning to May 15, 2020 with the following search terms: traditional Chinese medicine, Chinese medicine, Chinese herbal medicine, COVID-19, new coronavirus pneumonia, SARS-CoV-2, and randomized controlled trial.
Inclusion criteria: Randomized controlled trials (RCTs) from peer-reviewed journals and non-reviewed publications were included. Further, included RCTs had a control group that was given standard care (SC; such as conventional Western medicine treatments or routine medical care), and a treatment group that was given SC plus CHM.
Data extraction and analysis: Two evaluators screened and collected literature independently; information on participants, study design, interventions, follow-up and adverse events were extracted, and risk of bias was assessed. The primary outcomes included scores that represented changes in symptoms and signs over the course of treatment. Secondary outcomes included the level of inflammatory markers, improvement of pneumonia confirmed by computed tomography (CT), and adverse events. Dichotomous data were expressed as risk ratio or hazard ratio with 95% confidence interval (CI); where time-to-event analysis was used, outcomes were expressed as odds ratio with 95% CI. Continuous data were expressed as difference in means (MD) with 95% CI, and standardized mean difference (SMD) was used when different outcome scales were pooled.
Results
Seven original studies, comprising a total of 732 adults, were included in this meta-analysis. Compared to SC alone, CHM plus SC had a superior effect on the change of symptom and sign score (–1.30 by SMD, 95% CI [–2.43, –0.16]; 3 studies; n = 261, P = 0.03), on inflammatory marker C-reactive protein (CRP, mg/L; –11.82 by MD, 95% CI [–17.95, –5.69]; 5 studies; n = 325, P = 0.0002), on number of patients with improved lung CT scans (1.34 by risk ratio, 95% CI [1.19, 1.51]; 4 studies; n = 489, P < 0.00001). No significant adverse events were recorded in the included RCTs.

Conclusion
Current evidence shows that CHM, as an adjunct treatment with standard care, helps to improve treatment outcomes in COVID-19 cases.

Objective

MicroRNAs (miRNAs) may be viable targets for treating renal interstitial fibrosis (RIF). Fuzheng Huayu recipe (FZHY), a traditional Chinese compound herbal medicine, is often used in China to treat fibrosis. This study sought to assess the mechanisms through which FZHY influences miRNAs to treat RIF.

Methods

RIF was induced in rats by mercury chloride and treated with FZHY. Hydroxyproline content, Masson’s staining and type I collagen expression were used to evaluate renal collagen deposition. Renal miRNA profiles were evaluated using a miRNA microarray. Those miRNAs that were differentially expressed following FZHY treatment were identified and subjected to bioinformatic analyses. The miR-21 target gene phosphatase and tensin homolog (PTEN) expression and AKT phosphorylation in kidney tissues were assessed via Western blotting. In addition, HK-2 human proximal tubule epithelial cells were treated using angiotensin II (Ang-II) to induce epithelial-to-mesenchymal transition (EMT), followed by FZHY exposure. miR-21 and PTEN expressions were evaluated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), while E-cadherin and α-smooth muscle actin (α-SMA) expressions were assessed by immunofluorescent staining and qRT-PCR. Western blotting was used to assess PTEN and AKT phosphorylation.

Results

FZHY significantly decreased kidney collagen deposition, hydroxyproline content and type I collagen level. The miRNA microarray identified 20 miRNAs that were differentially expressed in response to FZHY treatment. Subsequent bioinformatic analyses found that miR-21 was the key fibrosis-related miRNA regulated by FZHY. FZHY also decreased PTEN expression and AKT phosphorylation in fibrotic kidneys. Results from in vitro tests also suggested that FZHY promoted E-cadherin upregulation and inhibited α-SMA expression in Ang-II-treated HK-2 cells, effectively reversing Ang-II-mediated EMT. We also determined that FZHY reduced miR-21 expression, increased PTEN expression and decreased AKT phosphorylation in these cells.

Conclusion

miR-21 is the key fibrosis-related miRNA regulated by FZHY. The ability of FZHY to modulate miR-21/PTEN/AKT signaling may be a viable approach for treating RIF.

Objective

To understand the protective effects of Ganoderma terpenoid extract (GTE) against Plasmodium berghei-malarial infection in mice, the present study was carried out to evaluate the effects of GTE in combination with chloroquine disulphate (CQ) on erythrocyte-selected inflammatory markers and antioxidant defense status in P. berghei-infected mice. 

Methods

P. berghei-infected mice were divided into six groups: infected control (IC) group, administered 1 mL Tween 20; GTE100 and GTE250 groups, administered 100 and 250 mg/kg GTE, respectively; GT100 + CQ and GT250 + CQ groups, co-administered 100 and 250 mg/kg GTE plus 30 mg/kg CQ, respectively; and CQ group, administered 30 mg/kg CQ. A separate group of non-infected mice were given 1 mL Tween 20, and served as a normal control group (NC). Extract and drug were dissolved in Tween 20 and administered orally once daily for 12 consecutive days. At the end of the treatment period, mice were anesthetized with chloroform and sacrificed by cervical dislocation. Plasma was prepared from blood obtained from each mouse. Parameters evaluated at the end of the treatment period include parasitemia, red blood cell count, hematocrit, malondialdehyde (MDA), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10). 

Results

Infected mice treated with a combination of GTE and CQ (GT100 + CQ and GT250 + CQ groups) showed significantly reduced parasitemia levels (P < 0.05) compared to those administered GTE alone as well as IC. Significant improvement in body weight (P < 0.05) was also observed in infected mice treated with a combination of GTE and CQ (GT100 + CQ and GT250 + CQ groups), compared to mice receiving GTE alone (GTE100 and GTE250 groups). Plasma MDA and TNF-α concentrations were significantly lowered, and IL-10 concentration was significantly increased in GT100 + CQ and GT250 + CQ groups, relative to the IC group (P < 0.05). GSH concentration and SOD, CAT and GPx activities were significantly higher in GT100 + CQ and GT250 + CQ groups compared to the GTE100, GTE250, IC and NC groups (P < 0.05). 

Conclusion

Data generated in this study showed that GTE enhanced the anti-plasmodial action of CQ in mice through its anti-inflammatory and antioxidant activities.

After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient’s condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.

Objective
To investigate the effects of Aurantii Fructus Immaturus (Zhishi, ZS) and Atractylodis Macrocephalae Rhizoma (Baizhu, BZ)-containing serum on glutamate-induced autophagy in rat colonic interstitial cells of Cajal (ICCs) and to analyze the underlying mechanism.

Methods
Rat colonic ICCs cultured in vitro were identified by fluorescence and then stimulated with glutamic acid (5 mmol/L) for 24 h to establish a cell model of autophagy. The cells were then treated with different concentrations of ZSBZ-containing serum or rat serum. The viability of the ICCs was detected with cell counting kit-8 assays, and cell apoptosis rates were examined with flow cytometry. The ultrastructure and autophagosomes in the ICCs were observed using transmission electron microscopy. The effects of ZSBZ-containing serum on apoptosis-associated mediators were assessed by Western blotting and real-time quantitative polymerase chain reaction. In addition, microtubule-associated protein light chain 3 (LC3), p-phosphoinositide 3-kinase (p-PI3K), p-Akt and p-mammalian target of rapamycin (p-mTOR) expression was detected via Western blotting analysis.

Results
Compared to those in the model group, ICC viability and apoptosis rates were significantly increased by ZSBZ-containing serum (P < 0.05). In addition, the expression levels of Beclin-1, LC3, p-PI3K, p-Akt and p-mTOR were significantly lower (P < 0.05) and Bcl-2 expression was higher in the ZSBZ-containing serum treatment groups than in the model group (P < 0.05).

Conclusion
Our findings demonstrated that ZSBZ protects glutamic acid-stimulated ICCs, and this beneficial effect may be mediated by a reduction in autophagy via inhibition of the PI3K/Akt/mTOR pathway.

Objective
Metabolic syndrome is a complex medical condition that has become an alarming epidemic, but an effective therapy for this disease is still lacking. The use of the herbal formula Huangqisan (HQS) to treat diabetes is documented in the Chinese medical literature as early as 1117 A.D.; however, its therapeutic effects and underlying mechanisms remain elusive.

Methods
To investigate the beneficial effects of HQS on metabolic disorders, high-fat diet-induced obesity (DIO), leptin receptor dysfunction (db/db) and low-density lipoprotein receptor-knockout (LDLR-/-) mice were used. Obese mice were treated with either HQS or vehicle. Blood, liver tissue, white fat tissue and brown adipose tissue were harvested at the end of the treatment. Metabolic disease-related parameters were evaluated to test HQS’s effects against diabetes, obesity and hyperlipidemia. Aortic arches from LDLR-/- mice were analyzed to investigate the effects of HQS on atherosclerosis. RNA-sequence, quantitative real-time polymerase chain reaction and Western blot were performed to investigate the mechanisms of HQS against metabolic disorder.

Results
HQS lowered body weight, fasting blood glucose and serum lipid levels and improved glucose tolerance and insulin sensitivity in DIO mice and db/db mice (P < 0.05). HQS also blocked atherosclerotic plaque formation in LDLR-/- mice. HQS suppressed de novo lipid synthesis by reducing the expression of messenger RNA for sterol regulatory element-binding factor 1, stearyl coenzyme A desaturase 1 and fatty acid synthase, and enhancing adenosine 5'-monophosphate-activated protein kinase signaling in both in vivo and in vitro experiments, indicating potential mechanisms for HQS’s activity against diabetes.

Conclusion
HQS is effective for reversing metabolic disorder and has the potential to be used as therapy for metabolic syndrome.

Worldwide, colorectal cancer (CRC) is one of the most common malignant tumors, leading to immense social and economic burdens. Currently, the main treatments for CRC include surgery, chemotherapy, radiotherapy and immunotherapy. Despite advances in the diagnosis and treatment of CRC, the prognosis for CRC patients remains poor. Furthermore, the occurrence of side effects and toxicities severely limits the clinical use of these therapies. Therefore, alternative medications with high efficacy but few side effects are needed. An increasing number of modern pharmacological studies and clinical trials have supported the effectiveness of Chinese herbal medicines (CHMs) for the prevention and treatment of CRC. CHMs may be able to effectively reduce the risk of CRC, alleviate the adverse reactions caused by chemotherapy, and prolong the survival time of patients with advanced CRC. Studies of molecular mechanisms have provided deeper insight into the roles of molecules from CHMs in treating CRC. This paper summarizes the current understanding of the use of CHMs for the prevention and treatment of CRC, the main molecular mechanisms involved in these processes, the role of CHMs in modulating chemotherapy-induced adverse reactions, and CHM’s potential role in epigenetic regulation of CRC. The current study provides beneficial information on the use of CHMs for the prevention and treatment of CRC in the clinic, and suggests novel directions for new drug discovery against CRC.

Objective

oronavirus disease 2019 (COVID-19) has raised concern around the world as an epidemic or pandemic. As data on COVID-19 has grown, it has become clear that older adults have a disproportionately high rate of death from COVID-19. This study describes the early clinical characteristics of COVID-19 in patients with more than 80 years of age.

Methods

Epidemiological, clinical, laboratory, radiological, and treatment data from 17 patients diagnosed with COVID-19 between January 20 and February 20, 2020 were collected and analyzed retrospectively. Treatment outcomes among subgroups of patients with non-severe and severe symptoms of COVID-19 were compared.

Results

Of the 17 hospitalized patients with COVID-19, the median age was 88.0 years (interquartile range, 86.6–90.0 years; range, 80.0–100.0 years) and 12 (70.6%) were men. The age distribution of patients was not significantly different between non-severe group and severe group. All patients had chronic pre-existing conditions. Hypertension and cardiovascular diseases were the most common chronic conditions in both subgroups. The most common symptoms at the onset of COVID-19 were fever (n = 13; 76.5%), fatigue (n = 11; 64.7%), and cough (n = 5; 29.4%). Lymphopenia was observed in all patients, and lymphopenia was significantly more severe in the severe group than that in non-severe group (0.4 × 109/L vs 1.2 × 109/L, P = 0.014). The level of serum creatinine was higher in the severe group than in the non-severe group (99.0 μmol/L vs 62.5 μmol/L, P = 0.038). The most common features of chest computed tomography (CT) images were nodular foci in 10 (58.8%) patients and pleural thickening in 7 (41.2%) patients. All patients received antiviral therapy, while some patients also received intravenous antibiotics therapy (76.5%), Chinese medicinal preparation therapy (Lianhuaqingwen capsule, 64.7%), corticosteroids (35.3%) or immunoglobin (29.4%). Eight patients (47.1%) were transferred to the intensive care unit because of complications. Ten patients (58.8%) received intranasal oxygen, while 3 (17.6%) received non-invasive mechanical ventilation, and 4 (23.5%) received high-?ow oxygen. As of June 20, 7 (41.2%) patients had been discharged and 10 (58.8% of this cohort, 77.8% of severe patients) had died.

Conclusion

The mortality of patients aged 80 years and older with severe COVID-19 symptoms was high. Lymphopenia was a characteristic laboratory result in these patients, and the severity of lymphopenia was indicative of the severity of COVID-19. However, the majority of patients with COVID-19 in this age cohort had atypical symptoms, and early diagnosis depends on prompt use of a viral nucleic acid test.

Objective

Prolonged use of nonsteroidal anti-inflammatory drugs is associated with severe side effects and toxicity. Therefore, we studied the anti-inflammatory role of Calcarea carbonica which had minimal toxicity at the low doses. 

Methods

THP-1 human mononuclear cells were treated with C. carbonica to evaluate the 50% cytotoxicity concentration (CC50) and 50% effective concentration (EC50). Cell survival was evaluated in lipopolysaccharide-stimulated C. carbonica-treated cells. Nitric oxide (NO) and tumor necrosis factor-α (TNF-α) were measured to evaluate the anti-inflammatory activity of C. carbonica. Cyclooxygenase-2 (COX-2) protein expression was determined by Western blotting analysis, and the interaction of C. carbonica with the COX-2 protein was evaluated using molecular docking simulation. 

Results

The CC50 and EC50 of C. carbonica were found to be 43.26 and 11.99 μg/mL, respectively. The cell survival assay showed a 1.192-fold (P = 0.0129), 1.443-fold (P = 0.0009) and 1.605-fold (P = 0.0004) increase in cell survival at 24, 48 and 72 h after initiating C. carbonica treatment, respectively. C. carbonica-treated cells showed a reduction in NO levels by 2.355 folds (P = 0.0001), 2.181 folds (P = 0.0001) and 2.071 folds (P = 0.0001) at 24, 48 and 72 h, respectively. The treated cells also showed a reduction in TNF-α levels by 1.395 folds (P = 0.0013), 1.541 folds (P = 0.0005) and 1.550 folds (P = 0.0005) at 24, 48 and 72 h, respectively. In addition, a 1.193-fold reduction (P = 0.0126) in COX-2 protein expression was found in C. carbonica-treated cells. The simulated molecular docking showed interaction of C. carbonica with the phenylalanine 367 residue present in COX-2’s active site. 

Conclusion

C. carbonica exhibited anti-inflammatory properties in lipopolysaccharide-stimulated cells by significantly reducing NO production and TNF-α level through downregulation of the COX-2 protein. This effect is probably mediated through interaction of C. carbonica with the phenylalanine 367 residue present in COX-2’s active site.

Objective

The drug sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma (HCC). Chinese herbal medicine has also been used to manage advanced HCC. The present work evaluates the effectiveness and safety of Jiedu (JD) granules, a compound of traditional Chinese herbal medicines, side-by-side with sorafenib for the treatment of advance HCC.

Methods

Patients with advanced HCC were enrolled in this study during December 2014 and March 2018. Study patients were elected to receive treatment with JD granules or sorafenib. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and safety. Propensity score matching (PSM) analysis was used to control for possible selection bias from the study group allocation process.

Results

Of the 325 patients included in this study, 161 received JD granules and 164 received sorafenib. No significant differences were found in OS or PFS among patients receiving JD granules compared to sorafenib (P > 0.05). Median OS of the two study groups was 6.83 months (95% confidence interval [CI]: 5.83–9.47) in the group receiving JD granules and 8 months (95% CI: 6.67–9.80) in the group receiving sorafenib, with half-, 1-, and 2- year survival rates of 53.6%, 31.2% and 13.2% vs 60.1%, 35.5% and 14.2%, respectively. Even after PSM, the median survival time did not differ between the JD granules group (9.03 months; 95% CI: 6.37–14.2) and the sorafenib group (7.93 months; 95% CI: 6.5–9.97), with comparable half-, 1- and 2-year survival rates. The most common adverse events (AEs) were diarrhea (13.7%) and fatigue (5.6%) in the JD granules group, and hand-foot skin reaction (46.3%) and diarrhea (36.6%) in the sorafenib group. The JD granules was more cost-effective than sorafenib treatment for advanced HCC.

Conclusion

Compared to sorafenib, JD granules provided a comparable treatment for HCC that was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC. 

Objective
To evaluate the cytotoxic, apoptotic, mutagenic and immunomodulatory activities of Kaempferia galanga Linn. (KG) extract and ethyl-p-methoxycinnamate (EPMC) in vitro.

Methods
The present study investigated the cytotoxic [using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide test], apoptotic (using a mitochondrial membrane potential assay), mutagenic (using a micronucleus test) and immunomodulatory (using flow cytometry) activities of the ethanolic extract of KG and its bioactive component, EPMC, against two cholangiocarcinoma (CCA) cell lines, CL-6 and HuCCT1, and one normal human cell line, OUMS-36T-1F.

Results
Both KG extract and EPMC exhibited moderate cytotoxic activity against both CCA cells. The cytotoxic activity was supported by their concentration-dependent induction of apoptosis. CL-6 was most sensitive (3–4 fold) and selective to 5-fluorouracil (5-FU), compared with KG extract and EPMC [median half inhibiting concentration (IC₅₀) and selectivity index (SI) were 23.01 μg/mL and 17.32; 78.41 μg/mL and 4.44; 100.76 μg/mL and 2.20, respectively for 5-FU vs. KG extract vs. EPMC]. HuCCT1 was relatively more sensitive and selective to 5-FU and EPMC than KG extract [median IC₅₀ and SI were 66.03 μg/mL and 6.04; 60.90 μg/mL and 3.65; 156.60 μg/mL and 2.23, respectively for 5-FU vs. EPMC vs. KG extract]. EPMC produced relatively potent cytotoxic activity against polymorphonuclear cells (IC₅₀ = 92.20 μg/mL). KG extract and EPMC exhibited concentration-dependent mutagenic activity, as well as inhibition of tumor necrosis factor-α and interleukin-6.

Conclusion
Considering cytotoxic, apoptotic, immunomodulatory and mutagenic activities, further development of KG as a drug candidate is likely to focus on the oral pharmaceutical formulation of a standardized KG extract rather than isolated compounds.

Critical effective constituents were identified from Bufei Yishen formula (BYF), a traditional herbal compound and combined as effective-constituent compatibility (ECC) of BYF I, which may have potential bioactive equivalence to BYF.

Methods

Results

Conclusion

Objective
Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19.

Methods
A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored.

Results
COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3⁺ T cells increased in the treatment group compared to the control group ([317.09 ± 274.39] vs. [175.02 ± 239.95] counts/μL, P = 0.030). No statistically significant differences were detected in the median improvement in levels of CD4⁺ T cells (173 vs. 107 counts/μL, P = 0.208) and CD45⁺ T cells (366 vs. 141 counts/μL, P = 0.117) between the treatment and control groups.

Conclusion
Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3⁺ T cells.

Pregnancy is a period of major transformations in a woman’s life; increased stress, and mood and sleep disorders are frequent. This review evaluates mindfulness interventions during pregnancy and their ability to help manage stress, anxiety, depression, emotional regulation, level of mindfulness and sleep quality. A search of English language scientific literature relevant to mindfulness interventions for pregnant women was conducted using PubMed, Scopus and Web of Science, without restriction on publication date. Inclusion criteria were randomized clinical trials with pregnant women, using mindfulness as an intervention for at least three weeks, in one of our main areas of interest, and using only validated scales to measure outcomes. Two hundred and thirty studies were identified in our searches of research databases, and thirteen were included in our analysis. We found a large diversity of mindfulness programs, heterogeneity among the instruments used to evaluate outcomes, and inconsistency in the gestational periods used in the studies. Mindfulness interventions were beneficial for stress, anxiety and depression. Mindfulness was also effective when applied in pregnant women with a history of depression or experiencing depression. Considering emotional regulation and the level of mindfulness, there were signs of improvement, but more studies are needed. None of the studies evaluated sleep quality. Our review provides information about current mindfulness programs, an overview of the effects of mindfulness interventions, a description of the measurements used so far, and recommendations for developing high-quality mindfulness protocols for pregnant women.

Adult-onset Still’s disease (AOSD) is a rare but clinically well-known, polygenic, and systemic autoinflammatory disease, which is characterized by spiking fever, evanescent skin rash, arthralgia, and sore throat. The application of non-steroidal anti-inflammatory drugs and glucocorticoids, which are first-line therapies of AOSD, is limited due to their side effects such as liver injury or disorder of blood glucose. Therefore, patients who suffer from systemic diseases in China prefer to seek help from Chinese herbal medicine (CHM), which is an important part of complementary and alternative medicine. In this case, we report a 28-year-old male badminton coach presenting with a 15-day history of fever and skin rash, accompanied by sore throat, fatigue, myalgia and chills. Additionally, hepatosplenomegaly, multiple lymphadenopathies, aminotransferase abnormality, and elevated inflammatory factor levels were observed during hospitalization. Infectious diseases, solid tumors, hematological diseases, and common autoimmune diseases were excluded. Not benefitting from antibiotic therapy, the patient was finally diagnosed with AOSD, after a careful examination, then showed rapid remission after a six-week treatment with CHM granules based on Xiaochaihu Decoction and Yinqiao Powder. After stopping the treatment, there was no relapse within a 15-month follow-up period. To the best of our knowledge, this is the first well-documented case of this successful treatment. The present case report suggests that CHM is a reliable choice for complementary and alternative therapy for AOSD, but confirming the utility of CHM for AOSD requires further support from prospective studies.

Costochondritis (ChC), especially chronic ChC, typically manifests as spontaneous vague pain in anterior chest area and often occurs in adolescents for unknown reasons; it has prevented many collegiate athletes from participating in physical training and competitions. A 21-year-old female collegiate taekwondo athlete suffering from chronic chest pain was sent by her coaches for diagnosis and treatment. Seated motion palpation was used to identify spontaneous and motion-involved pain areas. Palpation in the supine position was used to initially rule out breast diseases. X-ray, electrocardiogram, and cardiac Doppler ultrasound were used in conjunction with myocardial enzyme testing to rule out lung and cardiovascular diseases. The patient was treated using herbal medicines applied via an external patch. The medicine was comprised of Rhizoma Corydalis and borneol, and the treatment lasted for seven weeks. For five weeks patches were applied at a frequency of two or three times per day, followed by a two-week period of once per day. The patient reported that the pain was relieved after two weeks of external herb use, and the autonomic chest pain had resolved. Re-examination after one month showed that her upper limb range of motion was close to normal, and her psychological burden had almost disappeared. It is possible to seek more active medicinal treatment and more practical external products for young athletes who is suffering chronic ChC that affects the sport training and competitive performances.

Background

Hemorrhoids are one of the most common conditions that lead to surgery, and until now surgical hemorrhoidectomy has been the major effective treatment. Post-operative pain from hemorrhoidectomy has been experienced by thousands of patients and remains a major inconvenience of the operation.

Objective

This study evaluates the clinical efficacy of the pestle needle therapy, an acupoint stimulation method, for relief of post-hemorrhoidectomy pain.

Design, setting, participants and interventions

This was a single-center, patient-assessor-blinded and randomized controlled trial with 154 patients receiving Milligan hemorrhoidectomy surgery. Eligible patients were randomly assigned to either a treatment group or a control group at a ratio of 1:1. The treatment group received the pestle needle therapy, with manual stimulation at Yaoshu (DU2), Mingmen (DU4), Changqiang (DU1), Chengshan (BL57), Erbai (EX-UE2) and the perianal points (1, 3, 5, 7, 9, and 11 o’clock around the lesion); while the control group received a sham treatment with very light pressure. Three sessions of treatment were performed at 30 min, 4 h and 12 h after the surgery, and each lasted for 15 min.

Main outcome measures

The primary outcome was post-operative pain measured with the visual analogue scale (VAS) at 12 h after surgery. The secondary outcomes included the VAS scores measured at 0.5, 2, 4, 6, 8, 24 and 48 h after surgery, the analgesic dose, the time and the VAS score of the patients’ first defecation after surgery, as well as the Hamilton Rating Scale for Anxiety (HAMA) evaluated before discharge.

Results: The mean pain score of the treatment group was significantly lower than that of the control group (3.10 ± 1.27 vs 4.82 ± 1.29; P < 0.001) at 12 h after surgery. Compared with the control group, patients in the treatment group needed a smaller dose of analgesic within the first 24 hours after surgery (P = 0.002); and their HAMA scores before discharge were lower (4.07 ± 2.40 vs 5.10 ± 2.45, P = 0.009). Compared to the treatment group, patients in the control group had a greater time to the first defecation after surgery ([52.34 ± 15.72] h vs [27.08 ± 13.68] h; P < 0.001), but there was no difference in their VAS scores at the first defecation (P = 0.092).

Conclusion

The pestle needle therapy was effective for relieving pain, reducing anxiety and improving bowel function after hemorrhoidectomy, and it is worthy of clinical application.

Trial registration

Chinese Clinical Trial Registry (ChiCTR1900022329).

Objective
Barriers to healthcare in Ghana are multifaceted. Many people, including patients and providers, face them at different levels. To address these barriers, there is a need to explore the role of an intercultural healthcare system. This paper explores and provides the first evidence on ways through which an intercultural healthcare system can reduce the sociocultural and economic barriers to healthcare in Ghana.

Methods
Focus group discussions with 35 participants comprising 17 healthcare users, 11 formal healthcare providers and 7 alternative healthcare providers were conducted to gather data. Thematic analyses were performed on the transcribed data and presented based on a posteriori inductive reduction approach.

Results
Findings reveal that an intercultural healthcare system in Ghana can help reduce barriers to healthcare, especially cultural, social and economic barriers, by fostering an enhanced relationship between culture and healthcare, promoting affordable healthcare and promoting effective communication between healthcare providers and users. Weak institutional support, lack of strong political will and commitment, lack of training to meet standards of practice, poor registration and regulatory measures, inadequate general acceptance by biomedical providers and a perceived negative perception of the intercultural healthcare policy inhibit implementation of an intercultural healthcare system in Ghana.

Conclusion
The support for intercultural healthcare system and the agreement on its perceived ability to reduce social, cultural and economic healthcare barriers for service users offer an opportunity for policy makers to demonstrate a stronger political will and improved political commitment for effective education and training, enforcement of regulatory measures, improved alternative medical literacy through the inclusion of intercultural healthcare medical school curricula across the country, and ensure increased community engagement.

Objective
This meta-analysis was performed to assess the effects of L-arginine supplementation on indices of glycemic control, including fasting blood glucose (FBG), hemoglobin A1c (HbA1c), serum insulin and homeostatic model assessment of insulin resistance (HOMA-IR) levels in randomized controlled trials (RCTs).

Search strategy
This study conducted a systematic review of RCTs published in PubMed, Scopus, Web of Science, Cochrane Library and Embase, up to 5 May, 2018.

Inclusion criteria
Studies were included in this meta-analysis if they were RCTs with parallel design and reported sufficient data on participants before and after intervention, and outcomes of glycemic profile parameters in both the arginine supplementation and control groups.

Data extraction and analysis
The screening of titles and abstracts was performed independently by two reviewers. Selected articles were considered if they met the study’s inclusion criteria. The quality of included studies was assessed by using the Cochrane Collaboration modified tool. From 710 articles retrieved in the initial search, only 10 trials were suitable for pooling the effects of arginine supplementation on serum glucose, insulin, HOMA-IR and HbA1c levels, with effect sizes of nine, eight, five and five, respectively.

Conclusion
Although the results of this study confirmed that supplementation with L-arginine could have significant effects on some glycemic profile indices of participants in clinical trials, the clinical importance of this reduction may not be meaningful.

Results
Pooled random-effect analysis revealed that L-arginine supplementation could significantly decrease FBG level (weighted mean difference [WMD]: 3.35 mg/dL; 95% confidence interval [CI] = [–06.55, –00.16]; P = 0.04) and serum insulin level (WMD: –2.19 μIU/mL; 95% CI = [–3.70, –0.67]; P = 0.005). However, the effects of L-arginine supplementation on HOMA-IR and HbA1c were not significant. Results of subgroup analysis showed that supplementation with L-arginine could significantly decrease serum insulin levels when the dosage of L-arginine is > 6.5 g/d (WMD: –3.49 μIU/mL; 95% CI= [–5.59, –1.38]; P = 0.001), when the duration of supplementation is ≤ 12.8 weeks (WMD: –3.76; 95% CI = [–6.50, –0.98]; P= 0.008), when the participants are not diabetic patients (WMD: –2.54 μIU/mL; 95% CI= [–4.50, –0.50]; P= 0.01) and when the baseline serum level of insulin was > 20 μIU/mL (WMD: –3.98; 95% CI = [–6.31, –1.65]; P = 0.001).

Objective
To compare differences in self-reported musculoskeletal pain before and after receiving rapid acupuncture for pain at an outpatient emergency department.

Methods
Exactly 102 patients presenting to the emergency room of the Hospital Servidor Publico Estadual in Sao Paulo, Brazil, participated in this before-and-after study. All participants had musculoskeletal pain and were treated with the technique proposed by Marques Filho. This emergency acupuncture involved inserting a needle at a point defined by traditional Chinese medicine and applying intense stimulation for 10 s; no more than two points were used on any individual patient. Pain was measured using a numerical visual scale before and immediately after the procedure.

Results
Participants in this study were mostly women (78%), had a college degree (47%) and were below the age of 60 (56%). The most common region of pain was the lower back (31%), and the most common type of pain was acute and exacerbated chronic pain. The meridians most commonly involved were the eight extra meridians (40%), and the points most often used for treatment were Houxi (SI3), Shenmai (BL62) and Zulinqi (GB41). Almost all participants reported a decrease in pain intensity, independent of sex, education level, pain site and pain type (acute/chronic; P < 0.05). At the end of the session, only 4% of the participants reported a desire for allopathic medication.

Conclusion
This emergency acupuncture technique for analgesia appears to reduce musculoskeletal pain.

Qi, often translated as “vital energy,” is a central concept in tai chi and qigong that has puzzled physicians, scientists, and people in the West. To date, qi is not falsifiable by the scientific method and thus cannot be subject to scientific inquiry, leading many to criticize it as “pseudoscientific.” Even as medical research reveals the health benefits of tai chi and qigong, many wonder how to treat this seemingly outdated concept when promoting these meditative practices. While some tai chi and qigong practitioners insist on the existence of qi, more skeptical thinkers suggest that a scientific understanding should replace this “superstitious” idea. Integrative health professionals must be equipped to discuss this concept intelligently by considering a couple of subtle and clarifying points that often miss from discussion. First, science’s inability to verify qi’s existence does not affirm its nonexistence. In fact, under the philosophical system of idealism, qi might not be said to be less real than things that are verifiable by science. Similarly, under the instrumental and pragmatic view of science, health professionals should be cautious not to declare what is metaphysically real or unreal but instead what is useful and not useful. Second, even though qi may be pseudoscientific, it remains useful and indispensable to the correct practice of tai chi and qigong. Tai chi and qigong practitioners routinely visualize and perceive the flow of qi to guide their movements, breathing, and mental activity. As such, qi and related metaphysical concepts serve as a useful mental model during practice, and belief in them may be viewed as an “expedient means” to achieve one’s health goals.

Background

Obesity is a major public health problem and its occurrence is markedly increasing in developed and developing countries. However, few studies have investigated the use of natural products to treat obesity. The effects of taking a combination of oxymel and Zataria multiflora Boiss. (ZM), herein referred to as Zataria oxymel (ZO), on obesity, lipid profile and insulin resistance have not yet been studied.

Objective

This study evaluates the effects of oxymel and ZO on obesity, lipid profile and insulin resistance.

Design, setting, participants and interventions
In this randomized, controlled, triple-blind trial, overweight patients were randomly divided into three groups and received doses of study compounds twice per day for twelve weeks. Group A received 0.75 g ZM in 10 mL oxymel in each treatment; group B received 1.5 g ZM in 10 mL of oxymel in each treatment and group C (control) only received 10 mL of oxymel in each treatment.

Main outcome measures
Anthropometric parameters, including body mass index (BMI), waist circumference and hip circumference, were measured at the time of registration. Blood tests were carried out at the beginning and once again at end of the study. Blood parameters included fasting blood sugar (FBS), insulin levels, serum lipid profile (total cholesterol, triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol) and liver enzymes (aspartate transaminase and alanine transaminase). Serum creatinine was also measured at the beginning of the project and in monthly intervals for three months. The homeostasis model assessment index was calculated as fasting insulin (μIU/mL) × FBS (mg/dL)/405.

Results
The results showed that patients receiving ZO experienced significant reduction in waist circumference in groups A, B and C, respectively (P < 0.001) but no significant change in BMI. Group A also experienced reduction in hip circumference (P = 0.01). Groups B and C had reduction in the homeostatic model assessment of insulin resistance (P = 0.05 and P = 0.01, respectively), with no significant reduction in FBS. No effect on lipid profile, liver enzymes or serum creatinine was observed in the three groups.

Conclusion
In this study, treatment with ZO and oxymel reduced insulin resistance, and waist and hip circumferences in overweight patients. Nonetheless, the traditional Persian use of ZO as a beverage to improve the anthropometric indices in overweight individuals still requires further research with a larger sample size.

Objective: Few studies to date have measured the real-time effects of consumption of common and commercially available Cannabisproducts for the treatment of headache and migraine under naturalistic conditions. This study examines, for the first time, the effectiveness of using dried Cannabis flower, the most widely used type of Cannabis product in the United States, in actual time for treatment of headache- and migraine-related pain and the associations between different product characteristics and changes in symptom intensity following Cannabis use.
Methods: Between 06/10/2016 and 02/12/2019, 699 people used the Releaf Application to record real-time details of their Cannabisuse, including product characteristics and symptom intensity levels prior to and following self-administration; data included 1910 session-level attempts to treat headache- (1328 sessions) or migraine-related pain (582 sessions). Changes in headache- or migraine-related pain intensity were measured on a 0-10 scale prior to, and immediately, following Cannabis consumption.
Results: Ninety-four percent of users experienced symptom relief within a two-hour observation window. The average symptom intensity reduction was 3.3 points on a 0-10 scale (standard deviation = 2.28, Cohen’s d = 1.58), with males experiencing greater relief than females (P < 0.001) and a trend that younger users (< 35 years) experience greater relief than older users (P = 0.08). Mixed effects regression models showed that, among the known (i.e., labeled) product characteristics, tetrahydrocannabinol levels 10% and higher are the strongest independent predictors of symptom relief, and this effect is particularly prominent in headache rather than migraine sufferers (P < 0.05), females (P < 0.05) and younger users (P < 0.001). Females and younger users also appear to gain greater symptom relief from flower labeled as “C. indica” rather than “C. sativa” or other hybrid strains. 
Conclusion: These results suggest that whole dried Cannabis flower may be an effective medication for treatment of migraine- and headache-related pain, but the effectiveness differs according to characteristics of the Cannabis plant, the combustion methods, and the age and gender of the patient. 

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
Herbal medicine is an important therapeutic option for benign prostatic hyperplasia (BPH), a common disease in older men that can seriously affect their quality of life. Currently, it is crucial to develop agents with strong efficacy and few side effects. Herein we investigated the effects of the extract of Rauwolfia vomitoria, a shrub grown in West Africa, on BPH.
Methods
Rats with testosterone-induced BPH were treated with R. vomitoria. Prostates were histologically analyzed by hematoxylin and eosin staining. Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting. Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction. The sperm count and body weight of rats were also measured.
Results
The oral administration of R. vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats, supported by the decreased thickness of the prostate epithelial layer and increased lumen size. Similar effects were observed in the BPH rats treated with the reference drug, finasteride. R. vomitoria extract significantly reduced the testosterone-induced proliferation markers, including proliferating cell nuclear antigen and cyclin D1, in the prostate glands of BPH rats; it also reduced levels of androgen receptor, its associated protein steroid 5α-reductase 1 and its downstream target genes (FK506-binding protein 5 and matrix metalloproteinase 2). Notably, compared with the finasteride group, R. vomitoria extract did not significantly reduce sperm count. 
Conclusion
R. vomitoria suppresses testosterone-induced BPH development. Due to its milder side effects, R. vomitoria could be a promising therapeutic agent for BPH.

Objective

Osteoarthritis is a degenerative disease that affects synovial joints. Micro-injuries of articular structures initiate inflammatory processes, leading to persistent pain. Due to various risk factors, osteoarthritis is often diagnosed in multimorbid patients. This makes pain management one of the key challenges, with a consistent need for new therapeutic strategies. Hence, complementary and integrative methods such as hirudotherapy have become increasingly important, even though their mechanisms of action are not entirely understood.

Methods

We retrospectively analyzed the longitudinal effect of a single leech application on osteoarthritic joints in a heterogenic cohort of 24 cases with various chronic pain syndromes. We assessed articular pain intensity ratings and movability of the treated joint after one-time leeching for up to 12 months. We further investigated the effect of hirudotherapy on the systemic pain status and multimodal treatment strategies of the patients.

Results

There was a significant reduction in pain intensity ratings at the joint of leech application for up to 12 months after treatment. The improvements in pain intensities were independent of the form of osteoarthritis treated. In addition, we saw a considerable enhancement in local movability of the treated joint. Hirudotherapy did not seem to influence the systemic pain status as well as the previously established individualized multimodal treatment model of the patients. 

Conclusion

Leeching as an adjuvant therapy has a great potential especially in terms of safety and long-term outcome.

Background
Major depressive disorder (MDD) accompanied by anxious distress is a chronic and disabling disorder. Its conventional drug therapies often have low patient compliance due to drug-related side effects. In Persian medicine, lavender-dodder syrup is one formula often recommended for such disorders.

Objective
This study compares the effects of lavender-dodder syrup to the standard drug, citalopram, for treating MDD with anxious distress.

Design, setting, participants and intervention
This six-week, double-blind, randomized, clinical trial was carried out in a psychiatric outpatient clinic. During the six-week intervention period, patients in citalopram group received citalopram tablets 20 mg/d plus 5 mL placebo syrup every 12 h; patients in group B received placebo tablets once daily plus 5 mL of lavender-dodder herbal syrup every 12 h.

Main outcome measures
Primary outcome measures, depression and anxiety, were evaluated using the Hamilton Depression/Anxiety Rating Scales, and were scored at the beginning of the study and at weeks three and six. Secondary outcome measures including response to treatment and remission rates were also compared between the two groups.

Results
Fifty-six participants with MDD and anxious distress were randomly assigned to two groups. Mean depression scores significantly decreased in citalopram and herbal groups at weeks three and six (time effect: P < 0.001), although the observed changes were not significantly different between the groups (intervention effect: P = 0.61). Mean anxiety scores were not significantly different between the two groups at week three (P = 0.75). However, at the end of week six, the observed decrease was significantly higher in the herbal syrup group than the citalopram group (intervention effect: P = 0.007).

Conclusion
The herbal syrup is an effective and tolerable supplement for treating MDD with anxious distress.

Objective
Duranta repens is reported to contain a wide array of secondary metabolites, including α-amylase and α-glucosidase inhibitors, and it has potent antioxidant activity. The present study evaluated the network pharmacology of D. repens (whole plant) with targets related to diabetes mellitus and assessed its outcome by evaluating the effects of the hydroalcoholic extract of D. repens in streptozotocin-nicotinamide-induced diabetes mellitus.

Methods
Phytoconstituents of D. repens were retrieved from an open-source database and published literature, and their targets were predicted for diabetes mellitus using BindingDB and the therapeutic target database. Protein-protein interaction was predicted using STRING, and pathways involved in diabetes mellitus were identified using the Kyoto Encyclopedia of Genes and Genomes pathway browser. Druglikeness, ADMET profile (absorption, distribution, metabolism, excretion and toxicity) and cytotoxicity of compounds modulating proteins involved in diabetes were predicted using MolSoft, admetSAR2.0 and CLC-Pred, respectively. The interaction network among phytoconstituents, proteins and pathways was constructed using Cytoscape, and the docking study was performed using autodock4.0. The hydroalcoholic extract of D. repens was evaluated using streptozotocin-nicotinamide-induced diabetes mellitus animal model for 28 d, followed by an oral glucose tolerance test. At the end of the study, biochemical parameters like glycogen content, hepatic enzymes, antioxidant biomarkers and lipid profiles were quantified. Further, the liver and pancreas were collected for a histopathology study.

Results
Thirty-six different secondary metabolites from D. repens were identified to regulate thirty-one targets involved in diabetes mellitus, in which protein-tyrosine phosphatase 1B (PTP1B) was primarily targeted. Enrichment analysis of modulated proteins identified 12 different pathways in diabetic pathogenesis in which the phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway was chiefly regulated. The docking study found that durantanin I possessed the highest binding affinity (–8.9 kcal/mol) with PTP1B. Similarly, ADMET profiling showed that the majority of bioactive constituents from D. repens had higher human intestinal absorptivity and minimal cytotoxicity to normal cell lines, than tumor cell lines. Further, an in vivo animal study reflected the efficacy of the hydroalcoholic extract of D. repens to lower the elevated blood glucose level by stimulating insulin secretion, maintaining pancreatic β cell mass, regulating glycolysis/gluconeogenesis and upregulating the glucose uptake in skeletal muscles.

Conclusion
The present study reflected the probable network interaction of bioactive constituents from D. repens, their targets and modulated pathways, which identified the prime regulation of the PI3K-Akt signaling pathway and PTP1B protein. Modulation of PTP1B protein and PI3K-Akt signaling pathway could contribute to enhancing glucose uptake, insulin production and glycolysis and decreasing gluconeogenesis in diabetes, which was evaluated via the experimental study.

On May 15, 2020, the Lancet published an article titled Use of Herbal Drugs to Treat COVID-19 Should be with Caution. While this is true of all drugs, herbal and otherwise, the data may be biased and deserve a scientific response. We believe these types of reports will unfairly and negatively impact the field of integrative medicine as a whole, and must be answered with facts and statistics that more accurately represent the current situation.

Objective
Hepatic veno-occlusive disease (HVOD) has attracted increasing attention in recent years due to its relationship with ingestion of Gynura segetum. The mortality of severe HVOD remains high due to the lack of specific therapies. The aim of the study was to delineate the clinical characteristics and outcomes and explore the potential prognostic factors of HVOD.

Methods
This was a single-center retrospective study. Eighty-nine HVOD patients were screened from the First Affiliated Hospital of Zhejiang University with an ingestion history of G. segetum before developing symptoms from January 2009 to May 2018. The enrolled patients were divided into the survivor and death groups according to the clinical follow-up that ended on September 1, 2019. The demographic variables and clinical data of the patients were recorded. A binary logistic regression analysis and receiver operating characteristic curve were conducted to identify the prognostic factors and assess the prognostic value for predicting death, and a survival analysis was performed to evaluate the clinical outcomes.

Results
Sixty-four patients were eligible for further analysis. Most patients showed abdominal distension and were positive for migrating dullness in the abdomen (P = 0.740 and P = 0.732, respectively). The patients who died had higher levels of model for end-stage liver disease score, and higher prothrombin time than those who survived (both P < 0.001). All HVOD patients in both the survival and death groups showed ascites with abnormal imaging presentations of the liver parenchyma and hepatic blood vessels. Unexpectedly, we found that hydrothorax was detected in 21 (65.63%) patients in the death group and 19 (59.38%) patients in the survivor group during hospitalization, which was rarely mentioned in previous studies. Furthermore, international normalized ratio (INR) and creatinine are found to be potential independent prognostic factors for predicting death. Six severe patients achieved clinical improvements and survived after liver transplantation.

Conclusion
HVOD can be induced by the ingestion of G. segetum, and INR combined with creatinine has prognostic value for predicting death. Liver transplantation may be an effective treatment option for severe HVOD patients.

Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease involving exocrine glands. Current studies have found that the occurrence of the disease is closely related to genetic, environmental and neuroendocrine factors, as well as abnormal activation of T and B lymphocytes. The etiology and pathogenesis of pSS is complex, and there is a lack of specific targeted drugs. Traditional Chinese medicines (TCMs) have been comprehensively investigated for their treatment effects on pSS. Through a systematic review of the literature, we summarized the TCMs used to treat pSS, and find that there are four major ways that TCMs are used, including upregulation of aquaporin proteins, suppression of cell apoptosis, suppression of the abnormal activation of B lymphocytes and suppression of the abnormal activation of T lymphocytes (balancing T helper type [Th]1/Th2 & Th17/Treg and suppressing follicular helper T [Tfh] cells). However, there are not enough data about the active constituents, quality control, pharmacokinetics, toxicity and modern preparations of these TCMs; therefore, more investigations are needed. This paper highlights the importance of TCMs for treating pSS and provides guidance for future investigations.

The processing of Chinese herbal medicine is a form of pharmaceutical technology developed over thousands of years, in order to increase efficiency and decrease toxicity of herbs in traditional Chinese medicine (TCM). Herbal processing is essential for safe and effective application of TCM in clinical practice, as it alters the active chemical components and therefore the functions of herbal medicines. Alkaloid-rich herbal medicines in TCM are commonly processed by cleansing, cutting, processing by dry stir-frying, stir-frying with liquid adjuvants, and processing by water decoction. In addition, commonly used adjuvants for processing alkaloid-rich herbal medicines are river sand, wine, vinegar, brine, honey and herbal juice. For alkaloid-rich herbal medicines, the main chemical reactions that occur during processing include hydrolysis, oxidation, replacement, decomposition and condensation. This paper aimed to summarize the processing methods and mechanisms for alkaloid-rich Chinese herbal medicines, and provide much-needed theoretical support and scientific evidence for understanding those mechanisms and effects. Information on processing methods for alkaloid-rich herbal medicines was collected from classic books of herbal medicine, PhD and MSc dissertations, online scientific databases including PubMed, SciFinder, Scopus, Web of Science, Baidu Scholar and Google Scholar. This paper should help to advance our knowledge of the processing mechanisms and aid in the development of processing methods for alkaloid-rich Chinese herbal medicines.

Objective
Patients who are involuntarily committed to a psychiatric facility often experience anxiety or increased anxiety in response to being placed in the institutional environment. The weighted blanket introduced a proactive treatment option. The purpose of this study was to evaluate patients' anxiety symptoms before and after weighted blanket, compared to a group that did not use a weighted blanket to control anxiety.

Methods
This study was conducted in an inpatient mental health facility from June 10, 2019, through November 7, 2019, with psychiatric patients who were not actively psychotic. Participants were offered the choice of weighted or unweighted blankets for a 20-minute intervention. The treatment group was comprised of individuals who had opted to use a 14-pound weighted blanket, 20-pound weighted blanket or 5-pound weighted lap pad. Participants in the comparison group had selected an un-weighted blanket. Before application of the blankets, pulse rate was measured using a pulse oximeter, and anxiety was measured using the Spielberger State-Trait Anxiety Inventory shortened form (STAI: Y-6). Both measures were taken again after the intervention. A two-way mixed analysis of variance (ANOVA) was run to examine the interaction effects between time (pre/post) and group (comparison/weighted blanket). Simple main effects were then further examined for the comparison/weighted blanket groups using a repeated measures ANOVA. Within the weighted blanket group, additional two-way mixed ANOVA was run to determine if gender or blanket weight made a statistically significant difference.

Results
There was a statistically significant difference (P < 0.05) among those who used weighted blankets (n = 61) and those who did not (n = 61) based on the pre/post data for both the STAI: Y-6 inventory and the patients’ pulse rates. The results of two-way ANOVA indicated a significant interaction effect between intervention time and group (P < 0.001). Repeated measures ANOVA indicated a change between pre/post for the weighted blanket group only, and showed significant reductions in both the STAI: Y-6 (P < 0.001) and pulse rates (P = 0.040). Within the weighted blanket group, additional two-way mixed ANOVA showed that neither gender nor blanket weight had significant difference for either the STAI: Y-6 or the pulse measures.

Conclusion
The use of weighted blankets is a safe and potentially effective way to help individuals in a psychiatric facility manage anxiety. This study found a statistically significant drop in anxiety for adults at an inpatient facility, as shown by the STAI: Y-6 scores and drop in pulse rates among patients using weighted blankets. This study suggests a possible alternative to medications, seclusion and physical restraints, which are not patient- centered or trauma-supported.

Objective
This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU.

Search strategy
The search strategy looked for the presence of related keywords, such as “chronic urticaria” and “cupping therapy,” in the title and abstract of research articles indexed in major databases. Randomized controlled trials (RCTs) were selected after querying nine electronic databases from their inception to May 2019 with the above search terms.

Inclusion criteria
RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping. Publications could be written in Chinese or English.

Data extraction and analysis
Data were extracted, and the studies were assessed for the quality of their methodological design and risk of bias. Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome. Skin disease quality of life index score, recurrence rate, and adverse events were assessed as secondary outcomes. Subgroup analyses were conducted based on different interventions.

Results
Thirteen comparisons from 12 RCTs involving 842 participants were included. There were no significant differences between wet cupping and medications in total effective rate (n = 372; risk ratio [RR] = 1.10, 95% confidence interval [CI] 0.97 to 1.25; P = 0.14) or recurrence rate (n = 240; RR = 0.56, 95% CI 0.23 to 1.36; P = 0.20). Cupping therapy, in combination with antihistamine treatment was more efficacious than antihistamines alone, with a greater total effective rate (n = 342; RR = 1.18, 95% CI 1.01 to 1.39; P = 0.03) and lower recurrence rate (n = 342; RR = 0.52, 95% CI 0.32 to 0.84; P = 0.007). Cupping therapy combined with acupuncture was more effective than acupuncture alone (n = 156; RR = 1.25, 95% CI 1.07 to 1.46; P = 0.006). No serious adverse events were reported.

Conclusion
Wet cupping may be as effective as treatment with antihistamines. When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture, it may enhance the efficacy. Results drawn from these studies should be interpreted with caution and applied with care to clinical practice, because of the poor quality among the studies that were reviewed.

Cancer immunotherapy has led to a new era of cancer treatment strategies, and transforming healthcare for cancer patients. Meanwhile, reports of immune-related adverse events have been increasing, greatly hindering the use of cancer immunotherapy. Traditional Chinese medicine (TCM), which has been widely used in Asian countries for thousands of years, is known to play a complementary role in the treatment of cancer. Taken in combined with conventional modern therapies, such as resection, ablation and radiotherapy, TCM exerts its main anti-cancer effects in two ways: health-strengthening (Fu-Zheng) and pathogen-eliminating (Qu-Xie). Theoretically, pathogen-eliminating TCM can promote the release of tumor-related antigens and should be able to increase the effect of immunotherapy, while health-strengthening TCM may have immune-enhancing mechanisms that overlap with immunotherapy. In the era of cancer immunotherapy, it is important to balance the use of TCM and immunotherapy, with the goal of enhancing immune efficacy and antagonizing immune toxicity. In this article, we discuss this issue by considering the mechanism of tumor immunotherapy, alongside the theoretical basis of TCM treatment of tumors, with the aim of bringing new insights to future research in this field.

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

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

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

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

On May 25, 2019, the World Health Assembly approved the eleventh revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11), containing a chapter on traditional medicine. This means that the traditional East Asian medicine (TEAM) is now officially recognized as a part of mainstream medical practice. However, the patterns presented in the ICD-11 traditional medicine chapter are only the tip of the iceberg of TEAM clinical practice, and it will be necessary to supplement and upgrade the contents. In order to implement this, objectification and standardization of TEAM must be premised and grafting with proper modern science and technology is imperative. Pattern Identification and Prescription Expert-11 (PIPE-11), which is a TEAM clinical decision support system, adopts vastly from clinical literature on pattern identification and the prescription. By adopting the rule-based reasoning method, the way of diagnosis and prescription by a TEAM practitioner in actual clinical practice is implemented as it is. PIPE-11 could support to improve both the accuracy of medical diagnosis and the reliability of the medical treatment of TEAM in clinical practices. In the field of research, it might facilitate the usage for reliable reference for symptoms and signs retrieval and patient simulation. In the field of education, it can provide a high level of training for learning pattern identification and prescription, and further be used to reinforce skills of diagnosis and prescription by providing self-simulation methods. Therefore, PIPE-11 as a digital application is expected to support the traditional medicine chapter of ICD-11 to successfully contribute to the improvement of human health.

Background
Some depressed patients receive acupuncture as an adjunct to their conventional medications.

Objective
This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness of antidepressants for treating depression, and explore whether acupuncture can reduce the adverse reactions associated with antidepressants.

Search strategy
English and Chinese databases were searched for randomized controlled trials (RCTs) published until December 1, 2021.

Inclusion criteria
RCTs with a modified Jadad scale score ≥ 4 were included if they compared a group of participants with depression that received acupuncture combined with antidepressants with a control group that received antidepressants alone.

Data extraction and analysis
Meta-analysis was performed, and statistical heterogeneity was assessed based on Cochran’s Q statistic and its related P-value. Primary outcomes were the reduction in the severity of depression and adverse reactions associated with antidepressants, while secondary outcomes included remission rate, treatment response, social functioning, and change in antidepressant dose. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to evaluate the overall quality of evidence in the included studies.

Results
This review included 16 studies (with a total of 1958 participants). Most studies were at high risk of performance bias and at low or unclear risk of selection bias, detection bias, attrition bias, reporting bias, and other bias. Analysis of the 16 RCTs showed that, compared with antidepressants alone, acupuncture along with antidepressants reduced the Hamilton Depression Rating Scale-17 (HAMD-17) scores (standard mean difference [SMD] ?0.44, 95% confidence interval [CI] ?0.55 to ?0.33, P < 0.01; I2 = 14%), Self-rating Depression Scale (SDS) scores (SMD ?0.53, 95% CI ?0.84 to ?0.23, P < 0.01; I2 = 79%), and the Side Effect Rating Scale (SERS) scores (SMD ?1.11, 95% CI ?1.56 to ?0.66, P < 0.01; I2 = 89%). Compared with antidepressants alone, acupuncture along with antidepressants improved World Health Organization Quality of Life-BREF scores (SMD 0.31, 95% CI 0.18 to 0.44, P < 0.01; I2 = 15%), decreased the number of participants who increased their antidepressant dosages (relative risk [RR] 0.32, 95% CI 0.22 to 0.48, P < 0.01; I2 = 0%), and resulted in significantly higher remission rates (RR 1.52, 95% CI 1.26 to 1.83, P < 0.01; I2 = 0%) and treatment responses (RR 1.35, 95% CI 1.24 to 1.47, P < 0.01; I2 = 19%) in terms of HAMD-17 scores. The HAMD-17, SDS and SERS scores were assessed as low quality by GRADE and the other indices as being of moderate quality.

Conclusion
Acupuncture as an adjunct to antidepressants may enhance the therapeutic effectiveness and reduce the adverse drug reactions in patients receiving antidepressants. These findings must be interpreted with caution, as the evidence was of low or moderate quality and there was a lack of comparative data with a placebo control.

Systematic review registration: INPLASY202150008.

Objective

Pulmonary nodules (PNs) are one of the imaging manifestations of early lung cancer screening, which should receive more attention. Traditional Chinese medicine believes that voice changes occur in patients with pulmonary diseases. The purpose of this study is to explore the differences in phonetic characteristics between patients with PNs and able-bodied persons.

Methods

This study explores the phonetic characteristics of patients with PNs in order to provide a simpler and cheaper method for PN screening. It is a case-control study to explore the differences in phonetic characteristics between individuals with and without PNs. This study performed non-parametric statistics on acoustic parameters of vocalizations, collected from January 2017 to March 2018 in Shanghai, China, from these two groups; it explores the differences in third and fourth acoustic parameters between patients with PNs and a normal control group. At the same time, computed tomography (CT) scans, course of disease, combined disease and other risk factors of the patients were collected in the form of questionnaire. According to the grouping of risk factors, the phonetic characteristics of the patients with PNs were analyzed.

Results

This study was comprised of 200 patients with PNs, as confirmed by CT, and 86 healthy people that served as a control group. Among patients with PNs, 43% had ground glass opacity, 32% had nodules with a diameter ≥ 8 mm, 19% had a history of smoking and 31% had hyperlipidemia. Compared with the normal group, there were statistically significant differences in pitch, intensity and shimmer in patients with PNs. Among patients with PNs, patients with diameters ≥ 8 mm had a significantly higher third formant. There was a significant difference in intensity, fourth formant and harmonics-to-noise ratio (HNR) between smoking and non-smoking patients. Compared with non-hyperlipidemia patients, the pitch, jitter and shimmer of patients with PNs and hyperlipidemia were higher and the HNR was lower; these differences were statistically significant.

Conclusion

This measurable changes in vocalizations can be in patients with PNs. Patients with PNs had lower and weaker voices. The size of PNs had an effect on the phonetic formant. Smoking may contribute to damage to the voice and formant changes. Voice damage is more pronounced in individuals who have PNs accompanied by hyperlipidemia.

Among adolescents, the incidence of type 2 diabetes mellitus (T2DM) has recently increased. A 12-year-old Chinese boy with a one-year history of hyperphagia presented to our clinic. The patient was diagnosed with T2DM one month prior to visiting the clinic and reported undergoing no pharmacologic treatment. Using an integrative medicine approach, including Chinese herbal decoction, berberine hydrochloride tablets, physical exercise and diet control, the patient’s fasting blood glucose (FBG) decreased from 8.3 mmol/L to 5.5 mmol/L. Additionally, his glycated haemoglobin decreased from 12.9% to 6.1%, indicating that without any Western medicine intervention his diabetes has been reversed after six months of treatment. His FBG remained normal, and nine months after completion of treatment it was 4.9 mmol/L. A potential mechanism in this response may be related to improved insulin resistance and β-cell function, as indicated by observed changes in homeostasis model assessment of insulin resistance and β-cell function. Further, weight loss may also have contributed to the effectiveness of the treatment. This case study is the first to present the innovative approach of integrative medicine to achieve remission of new-onset adolescent T2DM.

Objective
The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu).
Methods
Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing.
Results
Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and β-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.
Conclusion
Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.

Objective 

High-fat diet is one of the main risk factors that disrupt the balance of gut microbiota, which eventually will induce colorectal cancer (CRC). Evodiamine (EVO) is a wildly used multifunctional traditional Chinese medicine extract. In this study, we investigated the role of gut microbiota in high-fat diet-propelled CRC and the potential of EVO for CRC chemoprevention.

Methods

Gut microbiota, serum D-lactic acid and endotoxin from 38 patients with colon cancer and 18 healthy subjects were detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). In addition, body mass index, phospho-signal transducer and activator of transcription 3 (p-STAT3) expression in cancer tissues and paracancerous tissues were detected by immunohistochemistry. A mouse intestinal inflammatory tumor model was established by azomethane/sodium dextran sulfate, followed by treatment with EVO and 5-aminosalicylic acid (ASA). Gut microbiota and inflammatory factors were detected by quantitative polymerase chain reaction, while serum D-lactic acid and endotoxin were detected by ELISA. Furthermore, cell proliferation, cell apoptosis, and interleukin (IL)-6/STAT3/P65 pathway were evaluated by 5-ethynyl-2′-deoxyuridine, terminal-deoxynucleotidyl transferase-mediated nick-end labeling, and Western blot assays.

Results

In patients with colon cancer, the numbers of Enterococcus faecalis and Escherichia coli were increased, while those of Bifidobacterium, Campylobacter and Lactobacillus were decreased. Serum endotoxin and D-lactic acid levels and p-STAT3 levels were significantly increased. In the mouse model, both EVO and ASA inhibited tumor formation, decreased the proliferation of tumor cells, and induced apoptosis of tumor cells. Compared with the control group, the numbers of E. faecalis and E. coli were decreased, while Bifidobacterium, Campylobacter and Lactobacillus numbers were increased. In the EVO group, serum endotoxin and D-lactic acid levels and inflammatory factors were significantly decreased. Further, the IL6/STAT3/P65 signaling pathway was inhibited in the EVO group.

Conclusion

EVO may inhibit the occurrence of colon cancer by regulating gut microbiota and inhibiting intestinal inflammation. The potential mechanism involves inhibition of the IL6/STAT3/P65 signaling pathway, revealing its potential therapeutic significance in clinical applications.

Objective
This study tests whether long-term intake of Allium tuberosum (AT) can alleviate pulmonary inflammation in ovalbumin (OVA)-induced asthmatic mice and evaluates its effect on the intestinal microbiota and innate lymphoid cells (ILCs).

Methods
BALB/c mice were divided into three groups: phosphate buffer saline, OVA and OVA + AT. The asthmatic murine model was established by sensitization and challenge of OVA in the OVA and OVA + AT groups. AT was given to the OVA + AT group by oral gavage from day 0 to day 27. On day 28, mice were sacrificed. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin, and periodic acid-Schiff staining. The levels of IgE in serum, interleukin-5 (IL-5) and IL-13 from bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The ILCs from the lung and gut were detected by flow cytometry. 16S ribosomal DNA sequencing was used to analyze the differences in colon microbiota among treatment groups.

Results
We found that long-term intake of AT decreased the number of inflammatory cells from BALF, reduced the levels of IL-5 and IL-13 in BALF, and IgE level in serum, and rescued pulmonary histopathology with less mucus secretion in asthmatic mice. 16S ribosomal DNA sequencing results showed that AT strongly affected the colonic bacteria community structure in asthmatic mice, although it had no significant effect on the abundance and diversity of the microbiota. Ruminococcaceae and Desulfovibrionaceae were identified as two biomarkers of the treatment effect of AT. Moreover, AT decreased the numbers of ILCs in both the lung and gut of asthmatic mice.

Conclusion
The results indicate that AT inhibits pulmonary inflammation, possibly by impeding the activation of ILCs and adjusting the homeostasis of gut microbiota in asthmatic mice.

Metabolic syndrome (MS) is associated with a sedentary and stressful lifestyle and affects underactive people disproportionately. Yoga is considered to be a low-impact mind-body stress-relieving exercise, and researchers are increasing their focus on the benefits of yoga for managing metabolic disorders. It is also important for physicians and health care professionals to understand the therapeutic efficacy of yoga intervention, in terms of its type, duration and frequency on various MS risk factors. The present review summarizes the current scientific understanding of the effects of yoga on MS risk factors such as glucose homeostasis markers, lipid profile, adipocytokines and cardiovascular risk factors, and discusses the possible mechanisms of action. MEDLINE, PubMed, Scopus and Cochrane Library were searched from their inception up to December 2019, using the keywords “metabolic syndrome,” “diabetes,” “cardiovascular diseases,” “obesity” and “yoga.” The literature summarized in this review have shown mixed effects of yoga on MS risk factors and do not provide robust evidence for its efficacy. More rigorous research and well‐designed trials that have a higher standard of methodology and evaluate yoga’s long-term impacts on MS are needed. Understanding yoga’s biochemical and molecular mechanisms of action on various metabolic pathways is also needed.

Background
Acupuncture therapy has shown promise for effectively relieving preoperative anxiety. Nevertheless, previous findings from randomized controlled trials (RCTs) are inconsistent and must be examined in detail.

Objective
This study systematically evaluates the efficacy and safety of acupuncture therapy for preoperative anxiety as well as the quality of evidence supporting this application.

Search strategy
The China National Knowledge Infrastructure Database, Wanfang Data Journal Database, Chinese Biomedical Literature Database, Chongqing VIP, Embase, PubMed and Cochrane Library Databases were queried from their inception to 19, February 2020, using keywords such as “acupuncture therapy,” “preoperative” and “anxioty.” Manual searches expanded the search breadth and included conference abstracts and other reference lists.

Inclusion criteria
RCTs were included in the current study if they contained a comparison between a group of anxiety patients that received acupuncture therapy and a control group that received sham acupuncture.

Data extraction and analysis
Literature was reviewed, and various articles were selected using the NoteExpress 3.2.0 software. Two researchers independently screened and extracted data and evaluated the risk of bias in the included studies. The RevMan 5.3 software was used for data aggregation and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) assessment was used to evaluate the quality of the study outcomes.

Results
Twelve studies were included in the review, containing a total of 916 patients. Meta-analysis showed that, compared with the control group, patients who received acupuncture therapy had reduced State-Trait Anxiety Inventory Scale (STAI-S) score (mean difference [MD] = –9.07, 95% confidence interval [CI] [–13.19 to –4.96], P < 0.0001) and Visual Analogue Scale (VAS) score (MD = –1.37, 95% CI [–2.29 to –0.45], P = 0.003). However, for the Hamilton Anxiety Scale (HAMA) score, there was no difference between the two groups (MD = –3.98, 95% CI [–12.89 to 4.92], P = 0.38). Further, the GRADE assessment demonstrated that the STAI-S was of moderate quality, the VAS of low quality and the HAMA of very low quality.

Conclusion
Acupuncture therapy may be able to decrease anxiety in preoperative patients, but the results need to be further verified due to the small sample sizes and the low quality of evidence to date.

Objective

Traditional Chinese medicine (TCM) has been widely used throughout China to prevent and cure diseases for thousands of years, and now it is a part of the integrative medicine field that is available in Western societies. To ensure the safety and quality of the herbal medicines that are a major part of the TCM tradition, they must be held to modern pharmaceutical standards. Erzhi pill (EZP) is a Chinese Pharmacopeia-listed herbal preparation that is used in the long-term clinical management of post-menopausal symptoms, osteoporosis and menstrual disorders. Until now, whether the drug release mechanism of EZP is in line with its intended TCM usage has not been studied.

Methods

The release of specnuezhenide from three EZPs (self-made, Leiyunshang and Renhe) in simulated gastric fluid (SGF), acetate buffer (pH 4.5 buffer) and simulated intestinal fluid (SIF) was investigated in a dissolution test. The water uptake capacity and erosion extent of the three EZPs were investigated using swelling and erosion studies. The drug release mechanism was further assessed through statistical model fitting, using DDSolver software.

Results

The release of specnuezhenide from all three EZPs in SGF was less than 50% within a 4 h period. However, over 70% of the specnuezhenide was released from each EZP in both pH 4.5 buffer and SIF in the same time. Analysis of the swelling and erosion behaviors and the drug release mechanism of the three EZPs confirmed that the release rate from EZP followed a sustained release profile, which was an interactive combination of swelling and erosion. 

Conclusion

This study showed that the release pattern from the pills was in line with the intended TCM use of EZP. TCM had not only theoretically considered sustained release from the pills, but also formulated them to achieve this release pattern. When establishing quality control standards for pills, the theoretical TCM usage and the actual release patterns need to be considered.