Dendrobium huoshanense in the treatment of ulcerative colitis: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium huoshanense C. Z. Tang et S. J. Cheng (DH) is a traditional medicinal herb with a long history of medicinal use. DH has been recorded as protecting the gastrointestinal function. Modern pharmacology research shows that DH regulates intestinal flora, intestinal mucosal immunity, gastrointestinal peristalsis and secretion of digestive juices. At the same time, some studies have shown that DH has a good therapeutic effect on ulcerative colitis, but its mechanism of action has not been fully elucidated. AIMS OF THIS STUDY: To investigate the mechanism and effect of Dendrobium huoshanense C. Z. Tang et S. J. Cheng (DH) in the treatment of ulcerative colitis (UC) by combining network pharmacology and in vivo experimental validation. METHODS: A network pharmacology approach was used to perform component screening, target prediction, PPI network interaction analysis, GO and KEGG enrichment analysis to initially predict the mechanism of DH treatment for UC. Then, the mechanism was validated with the UC mouse model induced by 3% DSS. RESULTS: Based on the network pharmacological analysis, a comprehensive of 101 active components were identified, with 19 of them potentially serving as the crucial elements in DH's effectiveness against UC treatment. Additionally, the study revealed 314 potential core therapeutic targets along with the top 5 key targets: SRC, STAT3, AKT1, HSP90AA1, and PIK3CA. In experiments conducted on live mice with UC, DH was found to decrease the levels of IL-6 and TNF-α in the blood, while increasing the levels of IL-10 and TGF-ß. This led to notable improvements in colon length, injury severity, and an up-regulation of SRC, STAT3, HSP90AA1, PIK3CA, p-AKT1 and PI3K/AKT signaling pathway expression in the colon tissue. CONCLUSIONS: In this study, the active components and main targets of DH for UC treatment were initially forecasted, and the potential mechanism was investigated through network pharmacology. These findings offer an experimental foundation for the clinical utilization of DH.

Characterization and quality evaluation of QiXueShuFu Decoction based on fingerprint and ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry.

QiXueShuFu Decoction (QXSFD) modified from the Bazhen Decoction which was originally from the classic Ming Dynasty is a traditional folk formula that boosts the body's immune system. However, its ambiguous chemical components limited its quality control evaluation. In this study, ultra-performance liquid chromatography (UPLC) fingerprint combined with multivariate analysis was used to evaluate the quality of 15 batches of QXSFD, and UPLC quadrupole-orbitrap mass spectrometry was used to further examine the chemical components in QXSFD, after which representative compounds from each disassembled prescription were selected for comparison. Fifteen batches of samples had 33 common peaks in which 11 differential components could be used as a reference for subsequent quality control. One hundred forty-three components were identified from QXSFD. Saponins were mainly derived from the monarch, terpenes from the minister, and polysaccharides and glycosides from the assistant. In addition, quantitative assay revealed that the content of ferulic acid, chlorogenic acid, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside and 3,6'-disinapoyl sucrose in the whole prescription were higher than the contents of each disassembled prescription. This is the first comprehensive quality report on the chemical components of QXSFD, which is important for pharmacodynamic material basis and quality control.

Management of chronic pain associated with temporomandibular disorders: a clinical practice guideline.

CLINICAL QUESTION: What is the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)? CURRENT PRACTICE: TMD are the second most common musculoskeletal chronic pain disorder after low back pain, affecting 6-9% of adults globally. TMD are associated with pain affecting the jaw and associated structures and may present with headaches, earache, clicking, popping, or crackling sounds in the temporomandibular joint, and impaired mandibular function. Current clinical practice guidelines are largely consensus-based and provide inconsistent recommendations. RECOMMENDATIONS: For patients living with chronic pain (≥3 months) associated with TMD, and compared with placebo or sham procedures, the guideline panel issued: (1) strong recommendations in favour of cognitive behavioural therapy (CBT) with or without biofeedback or relaxation therapy, therapist-assisted mobilisation, manual trigger point therapy, supervised postural exercise, supervised jaw exercise and stretching with or without manual trigger point therapy, and usual care (such as home exercises, stretching, reassurance, and education); (2) conditional recommendations in favour of manipulation, supervised jaw exercise with mobilisation, CBT with non-steroidal anti-inflammatory drugs (NSAIDS), manipulation with postural exercise, and acupuncture; (3) conditional recommendations against reversible occlusal splints (alone or in combination with other interventions), arthrocentesis (alone or in combination with other interventions), cartilage supplement with or without hyaluronic acid injection, low level laser therapy (alone or in combination with other interventions), transcutaneous electrical nerve stimulation, gabapentin, botulinum toxin injection, hyaluronic acid injection, relaxation therapy, trigger point injection, acetaminophen (with or without muscle relaxants or NSAIDS), topical capsaicin, biofeedback, corticosteroid injection (with or without NSAIDS), benzodiazepines, and ß blockers; and (4) strong recommendations against irreversible oral splints, discectomy, and NSAIDS with opioids. HOW THIS GUIDELINE WAS CREATED: An international guideline development panel including patients, clinicians with content expertise, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel approached the formulation of recommendations from the perspective of patients, rather than a population or health system perspective. THE EVIDENCE: Recommendations are informed by a linked systematic review and network meta-analysis summarising the current body of evidence for benefits and harms of conservative, pharmacologic, and invasive interventions for chronic pain secondary to TMD. UNDERSTANDING THE RECOMMENDATION: These recommendations apply to patients living with chronic pain (≥3 months duration) associated with TMD as a group of conditions, and do not apply to the management of acute TMD pain. When considering management options, clinicians and patients should first consider strongly recommended interventions, then those conditionally recommended in favour, then conditionally against. In doing so, shared decision making is essential to ensure patients make choices that reflect their values and preference, availability of interventions, and what they may have already tried. Further research is warranted and may alter recommendations in the future.

Acupuncture for post-stroke depression: a systematic review and network meta-analysis.

BACKGROUND: Patients with post-stroke depression (PSD) usually experience anxiety, hopelessness, and insomnia, which have a negative impact on their daily activities and post-stroke rehabilitation. Acupuncture (AC), as a minimally invasive technique, has become a popular choice for improving depression symptoms. However, it is still unclear which therapy is associated with the best outcomes for PSD. In this review, we aimed to explore the impact of AC in alleviating symptoms of PSD and to evaluate the difference in effectiveness between AC combined with pharmacotherapies and various non-pharmacotherapies. METHODS: Six databases and three clinical trials registration platforms were searched from inception to March 2023. Randomized clinical trial comparing needle-based AC with pharmacotherapy, and other non-pharmacotherapy or invalid group were included. Two independent reviewers identified eligible studies, and collected data using a pre-made form. A Bayesian network meta-analysis was conducted to assess and compare different techniques using RStudio 3.6.0 with the package 'GEMTC' V.0.8.1. The primary outcome was the efficacy for PSD assessed by scales measuring depressive symptoms. The secondary outcomes were effectiveness for neurological function and the quality of life. The ranking probabilities for all treatment interventions was performed using the Surface Under the Cumulative Ranking curve (SUCRA). The risk of bias was assessed by using the Revised Cochrane Risk of Bias tool 2. RESULTS: Sixty-two studies, involving 5308 participants published from 2003 to 2022, were included. The results showed that compared with western medicine (WM) (defined as pharmacotherapy for PSD), AC alone or with repetitive transcranial magnetic stimulation (RTMS), Traditional Chinese medicine (TCM) alone or with WM, were superior for alleviating depression symptoms. Compared to Usual Care, AC alone or plus other therapies could significantly decrease scores on the Hamilton Depression Rating scale. According to result of SUCRA, AC plus RTMS had the highest probability of improving depressive symptoms with a probability of 49.43%. CONCLUSIONS: The results of this study indicate that AC alone or combined with other therapies appears to be effective in improving depression symptoms of stroke survivors. Moreover, in comparison to WM, AC alone or plus RTMS, TCM, TCM with WM, or WM, were more effective in improving depression symptoms of PSD. Also, AC with RTMS seems to be the most effective with the highest probability. REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database in November 2020 and updated in July 2021. The registration number is CRD42020218752.

The relationship of publication language, study population, risk of bias, and treatment effects in acupuncture related systematic reviews: a meta-epidemiologic study.

BACKGROUND: There are debates in acupuncture related systematic reviews and meta-analyses on whether searching Chinese databases to get more Chinese-language studies may increase the risk of bias and overestimate the effect size, and whether the treatment effects of acupuncture differ between Chinese and non-Chinese populations. METHODS: In this meta-epidemiological study, we searched the Cochrane library from its inception until December 2021, and identified systematic reviews and meta-analyses with acupuncture as one of the interventions. Paired reviewers independently screened the reviews and extracted the information. We repeated the meta-analysis of the selected outcomes to separately pool the results of Chinese- and non-Chinese-language acupuncture studies and presented the pooled estimates as odds ratios (OR) with 95% confidence interval (CI). We calculated the Ratio of ORs (ROR) by dividing the OR of the Chinese-language trials by the OR of the non-Chinese-language trials, and the ROR by dividing the OR of trials addressing Chinese population by the OR of trials addressing non-Chinese population. We explored whether the impact of a high risk of bias on the effect size differed between studies published in Chinese- and in non-Chinese-language, and whether the treatment effects of acupuncture differed between Chinese and non-Chinese population. RESULTS: We identified 84 Cochrane acupuncture reviews involving 33 Cochrane groups, of which 31 reviews (37%) searched Chinese databases. Searching versus not searching Chinese databases significantly increased the contribution of Chinese-language literature both to the total number of included trials (54% vs. 15%) and the sample size (40% vs. 15%). When compared with non-Chinese-language trials, Chinese-language trials were associated with a larger effect size (pooled ROR 0.51, 95% CI 0.29 to 0.91). We also observed a higher risk of bias in Chinese-language trials in blinding of participants and personnel (97% vs. 51%) and blinding of outcome assessment (93% vs. 47%). The higher risk of bias was associated with a larger effect estimate in both Chinese-language (allocation concealment: high/unclear risk vs. low risk, ROR 0.43, 95% CI 0.21 to 0.87) and non-Chinese-language studies (blinding of participants and personnel: high/unclear risk vs. low risk, ROR 0.41, 95% CI 0.23 to 0.74). However, we found no evidence that the higher risk of bias would increase the effect size of acupuncture in Chinese-language studies more often than in non-Chinese-language studies (the confidence intervals of all ROR in the high-risk group included 1, Table 3). We further found acupuncture appeared to be more effective in Chinese than in non-Chinese population (Table 4). CONCLUSIONS: The findings of this study suggest the higher risk of bias may lead to an overestimation of the treatment effects of acupuncture but would not increase the treatment effects in Chinese-language studies more often than in other language studies. The difference in treatment effects of acupuncture was probably associated with differences in population characteristics. TRIAL REGISTRATION: We registered our protocol on the Open Science Framework (OSF) ( https://doi.org/10.17605/OSF.IO/PZ6XR ).

Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review.  OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence).   For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence).  AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.

STandards for Reporting Interventions in Clinical Trials Of Tuina/Massage (STRICTOTM): Extending the CONSORT statement.

OBJECTIVES: Massage is a common therapy of nonpharmacological treatments, particularly in Tuina (Chinese massage) as its most common style, detailed guidance in reporting the intervention is warranted for its evaluation and replication. Based on the CONSORT (Consolidated Standards of Reporting Trials), we aimed to develop an Extension for Tuina/Massage, namely "The STandards for Reporting Interventions in Clinical Trials Of Tuina/Massage (STRICTOTM)." METHODS: A group of professional clinicians, trialists, methodologists, developers of reporting guidelines, epidemiologists, statisticians, and editors has developed this STRICTOTM checklist through a standard methodology process recommended by the EQUATOR (Enhancing the QUAlity and Transparency of Health Research) Network, including prospective registration, literature review, draft of the initial items, three rounds of the Delphi survey, consensus meeting, pilot test, and finalization of the guideline. RESULTS: A checklist of seven items (namely Tuina/Massage rationale, details of Tuina/Massage, intervention regimen, other components of the intervention, Tuina/Massage provider background, control or comparator interventions, and precaution measures), and 16 subitems were developed. Explanations and examples (E&E) for each item are also provided. CONCLUSIONS: The working group hopes that the STRICTOTM, in conjunction with both the CONSORT statement and extension for nonpharmacologic treatment, can improve the reporting quality and transparency of Tuina/Massage clinical research.

Protective effects of Dendrobium huoshanense polysaccharide on D-gal induced PC12 cells and aging mice, in vitro and in vivo studies.

Dendrobium huoshanense C. Z. Tang et S. J. Cheng polysaccharide (DHP) is the essential active ingredient of D.huoshanense and has high medicinal value. A high dose of D-galactose (D-gal) is commonly utilized in the aging model establishment. In this study, we explored whether DHP shields PC12 cells and aging mice from D-gal caused damage and the possible mechanism. In vitro experiments, D-gal induced PC12 cells were used to investigate, and then DHP was used for treatment. In vivo experiments, 72 SPF ICR male mice were randomly divided into six groups (control: normal saline; model: D-gal (400 mg/kg); VE group: VE (50 µg/ml); DHP groups: D-gal + DHP (15.6 mg/ml; 31.2 mg/ml; 62.4 mg/ml)). The results showed that DHP could enhance the viability of D-gal injured PC12 cells and prevent cell apoptosis. DHP effectively promoted the transition from phase G0/G1 to phase S and inhibited cell cycle arrest. DHP has a potential neuroprotective effect on D-gal caused cognitive and memory disorders in mice. On the one hand, DHP protects the antioxidant enzymes SOD, GSH-PX, and CAT from excessive ROS buildup. On the other hand, DHP was demonstrated to block the expression of the P53/P21 signaling pathway-related proteins P53, P21, and P16. These results imply that DHP could be a potential neuroprotective agent against aging. PRACTICAL APPLICATIONS: Cognitive and memory decline caused by aging problems has become a problem in recent years. There are many theories about aging, among which oxidative stress is considered to be one of the important pathophysiological parts of various diseases in the aging process. In this study, DHP could not only improve the damage of D-Gal to PC12 cells, but also improve the cognitive and memory impairment caused by D-Gal in mice. In conclusion, this study verified the anti-aging effect of DHP from in vitro and in vivo experiments, and its mechanism may involve the P53/P21 pathway. Therefore, this study indicated that polysaccharides from Dendrobium huoshanense, a traditional Chinese medicine of homologous medicine and food, had potential and industrial value as potential anti-aging drugs.

Qualitative Proteome-Wide Analysis Reveals the Diverse Functions of Lysine Crotonylation in Dendrobium huoshanense.

The lysine crotonylation of histone proteins is a newly identified posttranslational modification with diversified cellular functions. However, there are few reports on lysine crotonylation of non-histone proteins in medicinal plant cells. By using high-resolution liquid chromatography-mass spectrometry (LC-MS) coupled with highly sensitive-specific immune-affinity antibody analysis, a whole crotonylation proteome analysis of Dendrobium huoshanense was performed. In total, 1,591 proteins with 4,726 lysine crotonylation sites were identified; among them, 11 conserved motifs were identified. Bioinformatic analyses linked crotonylated proteins to the drought stress response and multiple metabolic pathways, including secondary metabolite biosynthesis, transport and catabolism, energy production and conversion, carbohydrate transport and metabolism, translation, and ribosomal structure and biogenesis. This study contributes toward understanding the regulatory mechanism of polysaccharide biosynthesis at the crotonylation level even under abiotic stress.

Would integrated Western and traditional Chinese medicine have more benefits for stroke rehabilitation? A systematic review and meta-analysis.

BACKGROUND: Stroke is a major cause of death or long-term disability worldwide. Many patients with stroke receive integrative therapy consisting of Western medicine (WM) and routine rehabilitation in conjunction with Chinese medicine (CM), such as acupuncture and Chinese herbal medicine. However, there is no available evidence on the effectiveness of the combined use of WM and CM interventions in stroke rehabilitation. AIMS: The purpose of this meta-analysis is to evaluate the results of all individual studies to assess the combined use of CM and WM in stroke rehabilitation compared with WM only. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. MEDLINE, EMBASE, Cochrane and China National Knowledge Infrastructure (CNKI) were searched. The included outcomes were dependency, motor function, depression and swallowing function. Subgroup analysis was performed, and publication bias was assessed using funnel plots. SUMMARY OF REVIEW: 58 studies and 6339 patients were included in the meta-analysis. Subgroup analysis revealed that combined therapy comprising both acupuncture and WM had a superior effect on improving dependency and swallowing function compared with standard WM therapy alone. Potential superiority of combined therapy comprising CM and WM in improving depression compared with standard WM therapy was also found. CONCLUSIONS: Our results indicate that the combined use of CM and WM could be more efficacious in stroke rehabilitation compared with the use of WM therapy alone. However, most studies were short in duration (2 to 4 weeks) and prone to different types of biases, which prevents making any conclusion regarding the long-term effects and raises concerns regarding true efficacy in context of high likelihood of Hawthorn bias. So, more randomised controlled trials with more rigorous design and longer duration of treatment and follow-up need to be conducted to compare WM alone versus WM and CM combined. PROSPERO REGISTRATION NUMBER: CRD42020152050.

Prophylaxis against covid-19: living systematic review and network meta-analysis.

UPDATES: This is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version number and date of access for clarity. OBJECTIVE: To determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis (NMA). DATA SOURCES: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022. STUDY SELECTION: Randomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. RESULTS: The second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation­risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence. CONCLUSIONS: Much of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a supplement. FUNDING: This study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).

Discovery and evaluation on the antibacterial and cytotoxic activities of a novel antifungalmycin N2 produced from Streptomyces sp. strain N2.

Antifungalmycin N2 (3-methyl-3,5-amino-4-vinyl-2-pyrone, C6H7O2N) was a novel metabolite produced from Streptomyces sp. strain N2, and the present study aimed to evaluate its antibacterial and cytotoxic properties. By using Oxford cup method, the obtained results revealed that antifungalmycin N2 exhibited a significant antibacterial activity against the pathogenic bacteria such as Staphylococcus aureus, Escherichia coli, and Micrococcus kristinae, especially the Gram-positive S. aureus. Meanwhile, the MTT assay showed that antifungalmycin N2 could exert a marked inhibitory action on tumor cell lines, such as the cell lines of BEL-7402 (human hepatocellular carcinoma), Hela (human cervical carcinoma), HCT116 (human colon cancer), and SW620 (human colon cancer). And the IC50 values antifungalmycin N2 against the above cell lines ranged from 11.23 to 15.37 µg/mL. In conclusion, the antibacterial and cytotoxic activities suggested that the novel antifungalmycin N2 was a promising active structure to be developed as new drug for treating infectious diseases and cancers.

PRISMA extension for moxibustion 2020: recommendations, explanation, and elaboration.

BACKGROUND: Moxibustion is a common intervention of Chinese medicine (CM). Systematic reviews (SRs) on moxibustion are increasing. Although the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement provides guidelines for SRs, the quality of moxibustion-related SRs is still not satisfactory. In particular, descriptions of the interventions and the rationale for using moxibustion are insufficient. To address these inadequacies, the working group developed this PRISMA extension for reporting SRs of moxibustion (PRISMA-M 2020). METHODS: A group of CM clinical professionals, methodologists of SRs, reporting guideline developers, and journal editors developed this PRISMA-M 2020 through a comprehensive process that includes registration, literature review, consensus meetings, Delphi exercises for soliciting comments, and revision, resulting in this final draft. RESULTS: Seven of the 27 PRISMA checklist items, namely title (1), rationale (3), eligibility criteria (6), data item (11), additional analyses (16), study characteristics (18), and additional analysis (23), were extended, with specific reference to the application of moxibustion. Illustrative examples and explanations for each item are provided. CONCLUSION: The PRISMA-M 2020 will help improve the reporting quality of SRs with moxibustion. SYSTEMATIC REVIEW REGISTRATION: We have registered it on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network, particularly under the item of PRISMA-TCM: http://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-systematic-reviews/#65 .

[Start-up and Optimization of Denitrifying Phosphorus Removal in ABR-MBR Coupling Process].

The feasibility of the denitrifying phosphorus removal process in the ABR-MBR system with no sludge reflux and high concentration of seeding activated sludge (25 g ·L-1, in MLSS) in the ABR was investigated. The characteristics of the microbial community in the denitrifying phosphorus removal compartment were also evaluated. The denitrifying phosphorus removal function was achieved by gradually increasing the reflux ratio (R) from 0% to 200%. During the stable operation, the average removal rates of COD, PO43--P, and TN in the system were 88.28%, 54.45%, and 61.93%, respectively. When the influent loading rate, NOx--N reflux ratio, and hydraulic retention time (HRT) of ABR and MBR were 0.8 kg ·(m3 ·d)-1, 150%, and 9 h and 3.3 h, respectively, the average VFA concentration of 80.58 mg ·L-1, ρ(NO2--N)/ρ(NO3--N) reflux ratio of 1.68, and PO43--P and TN removal rates of 64.94% and 62.95% were obtained. The short-cut nitrification denitrifying phosphorus removal was achieved in the ABR-MBR system. Batch tests showed that denitrifying phosphorus removal bacteria (DPAOs) were the main functional bacteria in the ABR, with anaerobic phosphorus release and anoxic phosphorus uptake of 3.73 mg ·L-1 and 10.22 mg ·L-1, respectively. High throughput sequencing results showed that Proteobacteria and Bacteroidetes were the dominant phyla in the phosphorus removal compartment, accounting for 23.49%-53.66% and 16.55%-21.78% of the total phyla, respectively. Thauera, Thiothrix, Pseudomonas, norank_ f_Rhodocyclaceae, and unclassification_ f_Rhodocyclaceae in Proteobacteria, and Sphingobacteriales in Bacteroidetes were the potential denitrifying phosphorus removal microorganisms.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020).

Chinese Herbal Medicines (CHM) are the most common interventions of traditional Chinese medicine (TCM), typically administered as either single herbs or formulas. Systematic reviews (SRs) are essential references for evaluating the efficacy and safety of CHM treatments accurately and reliably. Unfortunately, the reporting quality of SRs with CHM is not optimal, especially the reporting of CHM interventions and the rationale of why these interventions were selected. To address this problem, a group of TCM clinical experts, methodologists, epidemiologists, and editors has developed a PRISMA extension for CHM interventions (PRISMA-CHM) through a comprehensive process, including registration, literature review, consensus meeting, three-round Delphi survey, and finalization. The PRISMA checklist was extended by introducing the concept of TCM Pattern and the characteristics of CHM interventions. A total of twenty-four items (including sub-items) are included in the checklist, relating to title (1), structured summary (2), rationale (3), objectives (4), eligibility criteria (6), data items (11), synthesis of results (14, 21), additional analyses (16, 23), study characteristics (18), summary of evidence (24), and conclusions (26). Illustrative examples and explanations are also provided. The group hopes that PRISMA-CHM 2020 will improve the reporting quality of SRs of CHM.

The effectiveness and safety of acupuncture for depression: An overview of meta-analyses.

PURPOSE: To provide an overview of existing meta-analysis (MAs) on the efficacy and safety of acupuncture for depression, and assess the methodological quality and the strength of evidence of the included MAs. METHODS: We searched MAs of randomized trials that have evaluated the effects of acupuncture on depression in three international and three Chinese databases from their inception until August 2019. The methodological quality of included MAs was evaluated with the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), and the strength of evidence with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). We used the intra-class correlation coefficient (ICC) to assess reviewer agreement in the pre-experiment. RESULTS: We included 31 MAs and 59 RCTs. The results of included MAs were conflicting, our meta-analyses found that acupuncture may confer small benefit in reducing the severity of depression by end of treatment than no treatment/wait list/treatment as usual(SMD -0.74, 95% CI -1.06 to -0.41, eight trials, 624 participants), control acupuncture (invasive, non-invasive sham controls) (SMD 0.27, 95% CI -0.51 to -0.04, 20 trials, 1055 participants), antidepressants(Selective serotonin reuptake inhibitors (SSRI)/ Tetracyclic antidepressants(TCAs)) (SMD -0.28, 95% CI -0.46 to -0.10, 30 trials, 3068 participants), acupuncture plus antidepressants versus antidepressants(SSRI/TCAs) (SMD -0.99, 95% CI -1.37 to -0.61, 17 trials, 1110 participants). Subgroup analyses showed that there was no difference between electro-acupuncture and invasive control (P = 0.37), electro-acupuncture and non-invasive control (P = 0.90), manual acupuncture and Tetracyclic antidepressants (P = 0.57), electro-acupuncture and Tetracyclic antidepressants (P = 0.07). Six MAs concluded that acupuncture reduced the incidence of adverse events compared with antidepressants. The evaluation with AMSTAR-2 showed that the quality of included MAs was low or critically low. The results of the GRADE evaluation showed that the strength of evidence was low to very low for most outcomes. CONCLUSIONS: Although acupuncture appears to be more effective and safer than no treatment, control acupuncture and antidepressants, the quality of the available evidence was very low. Further methodologically rigorous and adequately powered primary studies are needed to confirm the effectiveness of acupuncture for depression.

The effectiveness of acupuncture for Parkinson's disease: An overview of systematic reviews.

OBJECTIVES: Acupuncture is an alternative therapy for Parkinson's disease (PD), but its efficacy and safety are controversial. This overview aimed to summarize the existing evidence from systematic reviews (SRs) and meta-analyses (MAs) in order to assess the effectiveness of acupuncture as a treatment for PD. METHODS: Seven electronic databases were searched from their inception until July 2019. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklists were used to assess evidence quality and methodological quality, respectively. The outcomes of study were calculated using mean differences (MDs) and risk ratios (RRs) with 95 % confidence intervals (CIs). A meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 12 SRs/MAs were included. All 12 SRs/MAs had more than one critical weakness in AMSTAR 2 and were considered of critically low methodological quality. The quality of evidence was unsatisfactory according to the GRADE checklist. Meta-analyses showed that acupuncture combined with drug for the treatment of PD can significantly improve the total effectiveness rate compared with drug alone (RR = 1.25, 95 % CI 1.16-1.34, P < 0.001). It was also found that acupuncture combined with drug significantly improved the UPDRS I-IV total summed scores (WMD=-6.18, 95 % CI -10.32 to -2.04, P < 0.001) and Webster scores (WMD=-4.20, 95 % CI -7.59 to -0.81, P < 0.001). CONCLUSION: Acupuncture might improve the UPDRS score, Webster score, and total effective rate in treatment of PD. It might be a safe and useful adjunctive treatment for patients with PD. However, we should interpret the findings of these reviews with caution, considering the overall limited methodological and reporting quality.

Traditional Chinese medicine clinical records classification with BERT and domain specific corpora.

Traditional Chinese Medicine (TCM) has been developed for several thousand years and plays a significant role in health care for Chinese people. This paper studies the problem of classifying TCM clinical records into 5 main disease categories in TCM. We explored a number of state-of-the-art deep learning models and found that the recent Bidirectional Encoder Representations from Transformers can achieve better results than other deep learning models and other state-of-the-art methods. We further utilized an unlabeled clinical corpus to fine-tune the BERT language model before training the text classifier. The method only uses Chinese characters in clinical text as input without preprocessing or feature engineering. We evaluated deep learning models and traditional text classifiers on a benchmark data set. Our method achieves a state-of-the-art accuracy 89.39% ± 0.35%, Macro F1 score 88.64% ± 0.40% and Micro F1 score 89.39% ± 0.35%. We also visualized attention weights in our method, which can reveal indicative characters in clinical text.

Reporting items for systematic reviews and meta-analyses of acupuncture: the PRISMA for acupuncture checklist.

BACKGROUND: Acupuncture is widely used worldwide, and systematic reviews on acupuncture are increasingly being published. Although acupuncture systematic reviews share several essential elements with other systematic reviews, some essential information for the application of acupuncture is not covered by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Considering this, we aimed to develop an extension of the PRISMA statement for acupuncture systematic reviews. METHODS: We used the PRISMA statement as a starting point, and conducted this study referring to the development strategy recommended by the EQUATOR network. The initial items were collected through a wide survey among evidence users and a review of relevant studies. We conducted a three-round Delphi survey and one-day face-to-face meeting to select items and formulate the checklist. After the consensus meeting, we drafted the manuscript (including the checklist) and sent it to our advisory experts for comments, following which the checklist was refined and circulated to a group of acupuncture systematic review authors for pilot test. We also selected a sample of acupuncture systematic reviews published in 2017 to test the checklist. RESULTS: A checklist of five new sub-items (including sub items) and six modified items was formulated, involving content related to title, rationale, eligibility criteria, literature search, data extraction, and study characteristics. We clarified the rationales of the items and provided examples for each item for additional guidance. CONCLUSION: The PRISMA for Acupuncture checklist is developed for improving the reporting of systematic reviews of acupuncture interventions. TRIAL REGISTRATION: We have registered the study on the EQUATOR network ( http://www.equator-network.org/library/reporting-guidelines-under-development/#91 ).

Pharmacological and non-pharmacological treatments for irritable bowel syndrome: Protocol for a systematic review and network meta-analysis.

BACKGROUND: The global prevalence of Irritable bowel syndrome (IBS) is estimated to be as high as 15% and a number of different non-pharmacological and pharmacological treatments have been used to manage IBS in clinical practice, which poses great challenges for clinicians to make appropriate decisions. Hence, a systematic review and network meta-analysis on all available pharmacological and non-pharmacological treatments for IBS is needed to provide reliable evidence. METHODS: We will search the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane IBD Group Specialized Trials Register, MEDLINE, EMBASE, and Chinese Biomedical medicine (CBM) from inception to 31, May 2019. Randomized controlled trials of pharmacological and nonpharmacological interventions for IBS will be included. Study quality will be assessed on the basis of the methodology and categories described in the Cochrane Collaboration Handbook. Primary outcomes are global or clinical improvement and quality of life. A Bayesian network meta-analysis would be performed, and relative ranking of agents would be assessed. A node splitting method will be used to examine the inconsistency between direct and indirect comparisons when a loop connecting 3 arms exists. RESULTS: Researchers will rank the effectiveness and safety of the potentials interventions for IBS according the characteristics of patients by conducting an advanced network meta-analysis based on Bayesian statistical model, and interpret the results by using GRADE approach. CONCLUSION: The conclusion of our study will provide updated evidence to rank the effectiveness and safety of pharmacological and non-pharmacological interventions for IBS. ETHICS AND DISSEMINATION: Ethical approval is not applicable since this study is a network meta-analysis based on published trials. PROTOCOL REGISTRATION NUMBER: CRD42018083844.