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Background: Prophylactic vancomycin treatment decreases the prevalence of surgical site and deep infections by >70% in diabetic patients undergoing reconstructive foot and ankle surgery. Thus, determining whether clinically relevant local vancomycin doses affect diabetic fracture healing is of medical interest. We hypothesized that application of vancomycin powder to the fracture site during surgery would not affect healing outcomes, but continuous exposure of vancomycin would inhibit differentiation of osteoblast precursor cells and their osteogenic activity in vitro. Methods: The vancomycin dose used to treat the diabetic rats was a modest increase to routine surgical site vancomycin application of 1 to 2 g for a 70-kg adult (21 mg/kg). After femur fracture in BB-Wistar type 1 diabetic rats, powdered vancomycin (25 mg/kg) was administered to the fracture site. Bone marrow and periosteal cells isolated from diabetic bones were cultured and treated with increasing levels of vancomycin (0, 5, 50, 500, or 5000 µg/mL). Results: Radiographic scoring, micro–computed tomography (µCT) analysis, and torsion mechanical testing failed to identify any statistical difference between the vancomycin-treated and the untreated fractured femurs 6 weeks postfracture. Low to moderate levels of vancomycin treatment (5 and 50 µg/mL) did not impair cell viability, osteoblast differentiation, or calcium deposition in either the periosteum or bone marrow–derived cell cultures. In contrast, high doses of vancomycin (5000 µg/mL) did impair viability, differentiation, and calcium deposition. Clinical Relevance: In this diabetic rodent fracture model, vancomycin powder application at clinically relevant doses did not affect fracture healing or osteogenesis.

Can voluntary carbon emission reduction pledges, such as the nationally determined contributions under the Paris Agreement, result in significant emission reductions? According to prominent experts such as Nordhaus (2015), Barrett (2005), and Weitzman (2019), free-riding is unavoidable in cooperative situations based on voluntary agreements. If their assessments are correct, each country’s nationally determined contribution is unreliable. Countries will strategically promise large cuts while making only minor emission reductions.

An increasing number of people are affected by overweight or obesity, and the personal and social health burden is growing rapidly. Acupuncture is gaining popularity as an alternative treatment to manage weight. This research aims to update and synthesize the evidence of acupuncture therapies from systematic reviews for treating overweight and obesity.Nine databases were searched from their inception to March 2022. Overweight or obesity was classified using standard diagnostic criteria. Published systematic reviews that included randomized controlled trials and quasi-randomized studies were eligible. Quality was assessed via the AMSTAR-2 scale and risk of bias using the ROBIS tool.Thirty-eight systematic reviews were identified. Acupuncture therapies and auricular acupoint stimulation showed benefits in terms of reducing body weight and body mass index. Catgut embedding therapy and abdominal acupuncture are currently not in widespread use with insufficient evidence. Acupuncture therapies appear to be safe. Most of the reviews were assessed as having high risk of bias and low confidence in the findings.There is a need for larger and more methodologically sound randomized controlled trials to evaluate the effectiveness of acupuncture therapies for individuals who are affected by overweight or obesity.

Objective/ background Chronic headaches and sports-related concussions are among the most common neurological morbidities in adolescents and young adults. Given that the two can overlap in presentation, studying the effects of one on another has proven difficult. In this longitudinal study, we sought to assess the relationship between chronic headaches and concussions, analyzing the role of historic concussions on chronic headaches, as well as that of premorbid headaches on future concussion incidence, severity, and recovery. Methods This multi-center, longitudinal cohort study followed 7,453 youth athletes who were administered demographic and clinical surveys as well as a total of 25,815 Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) assessments between 2009 and 2019. ImPACT was administered at baseline. Throughout the season concussions were examined by physicians and athletic trainers, followed by re-administration of ImPACT post-injury (PI), and at follow-up (FU), a median of 7 days post-concussion. Concussion incidence was calculated as the total number of concussions per patient years. Concussion severity and recovery were calculated as standardized deviations from baseline to PI and then FU in Symptom Score and the four neurocognitive composite ImPACT scores: Verbal Memory, Visual Memory, Processing Speed, and Reaction Time. Data were collected prospectively in a well-organized electronic format supervised by a national research-oriented organization with rigorous quality assurance. Analysis was preformed retrospectively. Results Of the eligible athletes, 1,147 reported chronic headaches (CH) at the start of the season and 6,306 reported no such history (NH). Median age of the cohort was 15.4 ± 1.6 years, and students were followed for an average of 1.3 ± 0.6 years. A history of concussions (OR 2.31, P r2 = 0.95) as well as concussions characterized by a loss of consciousness (P P P = 0.85). On multivariable analysis the CH cohort did have greater deviations from baseline to PI and FU in Symptom Score (PI OR per point 1.05, P = 0.01, FU OR per point 1.11, P = 0.04) and Processing Speed (OR per point 1.08, P = 0.04), suggesting greater concussion severity and impaired symptomatic recovery as compared to the NH cohort. Conclusion A history of concussions was a significant contributor to headache burden among American adolescents and young adults. However, those with chronic headaches were not more likely to be diagnosed with a concussion, despite presenting with more severe concussions that had protracted recovery. Our findings not only suggest the need for conservative management among youth athletes with chronic headaches, they also indicate a potential health care gap in this population, in that those with chronic headaches may be referred for concussion diagnosis and management at lower rates than those with no such comorbidity.

Background The State of Victoria in Australia introduced Chinese medicine practitioner registration in 2000 and issued its education guidelines in late 2002 for introduction in 2005. This study obtained practitioners' views on desired capabilities for competent Chinese medicine practice and to identify professional development needs. Methods A questionnaire, consisting of 28 predefined capabilities in four categories with a rating scale of importance from one to five, was developed and sent to all registered Chinese medicine practitioners in the State of Victoria, Australia in October, 2005. Results Two hundreds and twenty eight completed questionnaires were returned which represented a response rate of 32.5%. Of the four categories of capabilities, technical capabilities were considered to be the most important for clinical practice. Specifically, the ability to perform acupuncture treatment and/or dispense an herbal prescription was ranked the highest. In contrast, research and information management capabilities were considered the least important. The educational background of practitioners appeared to be an important factor influencing their rating of capabilities. Significantly, nearly double the number of practitioners with Australian qualifications than practitioners trained overseas valued communication as an important capability. For continuing professional education, clinical skills courses were considered as a priority while research degree studies were not. Conclusion Registered Chinese medicine practitioners viewed skills training as important but did not support the need for research and information management training. This represents a significant hurdle to developing Chinese medicine as a form of evidence-based healthcare.

The effects of locally applied zinc chloride (ZnCl

Objective: Given the existing evidence for the analgesic effect of acupuncture, the current study aimed to assess whether acupuncture could be feasible and manageable as an adjunctive therapy for cancer pain in a real-world hospital setting. Methods: Thirty patients in an Oncology department with moderate or severe pain were recruited and randomized to an adjunctive acupuncture group or control group, who received pharmacotherapy for pain management without acupuncture. The duration of the treatment course was 1 week with a 2-week follow-up. In total, four acupuncture sessions were administered, on days 1/2/4/6 of the trial. Pain intensity was measured using a numerical rating scale (NRS) and the daily opioid dose was recorded. Results: The overall trends favored acupuncture for both pain intensity and daily opioid consumption. The proportion of participants experiencing at least a 2-point reduction in the NRS at the end of the treatment was 93% (n = 14/15) for the acupuncture group and 57% (n = 8/14) for the control group (risk difference (RD) 36.1%, 95% confidence interval (CI) [7.4%–65.0%]; relative risk (RR) 1.63, 95% CI [1.02–2.62]; p = 0.04). There were no serious adverse events and no dropouts during the treatment. Conclusion: This pilot study showed that adding acupuncture to routine analgesia for patients with cancer pain was feasible and acceptable to patients. The clinical effects of adding acupuncture as an adjunctive therapy need to be further evaluated. Clinical trial registration number: ChiCTR1800017023 (Chinese Clinical Trial Registry)

Background: Chinese medicine (CM) has been widely used for women's health, including those with early breast cancer. Contemporary literature varies in descriptions of the CM syndromes that are critical for determining CM treatment options for breast cancer patients. However, the corresponding syndromes have not been standardized to align with the conventional medicine treatment stages. This review aimed to address this knowledge gap to enhance the quality and consistency of CM interventions for early breast cancer patients. Methods: In total, eight Chinese and English language databases were searched, and textbooks and clinical care documents were gathered. Sources were classified according to five treatment stages: preoperative, postoperative, chemotherapy, radiation therapy, and endocrine therapy. Descriptive statistics were used to examine the syndromes, and hierarchical cluster analysis was conducted to investigate clusters of signs and symptoms. Results: The CM syndrome of dual deficiency of qi and Blood was one of the most common syndromes across all treatment stages, whereas lack of strength and lassitude were the most common clinical presentations throughout all stages, except the preoperative stage. Cluster analyses identify three or four syndromes in each treatment stage. Cluster results for the preoperative stage were: Blood stasis, Liver depression and qi stagnation, and Kidney yin deficiency. Dual deficiency of qi and Blood existed at different stages except for the preoperative stage. In the postoperative stage and chemotherapy stages, some symptoms were categorized into clusters that related to the Spleen and Stomach. Syndromes such as yin deficiency with fire toxin and yin deficiency with fluid depletion were unique to the radiation therapy stage. Clusters for endocrine therapy stage included the dual deficiency of Spleen and Kidney, Liver depression and qi stagnation, and Kidney yin deficiency. Conclusions: Systematic review of the contemporary literature for early breast cancer revealed that the most frequently seen CM syndromes and cluster results have some similarities but some important distinctions. Clinical data are needed to confirm whether the syndromes described in contemporary literature reflect those seen in women with early breast cancer.

This systematic review aims to assess the effects and safety of Chinese herbal medicines (CHMs) in the management of rhinosinusitis (RS); inform clinicians of the current state of the evidence; identify the best available evidence; and suggest further directions for research. Five English and four Chinese language databases, and four clinical trial registries were searched. Eligible studies were randomised controlled trials (RCTs). Participants were diagnosed with RS based on established criteria. Test interventions were CHMs administered orally and/or nasally, excluding injections and displacement techniques. Control interventions included placebos, no additional treatment, and conventional non-invasive treatments including pharmacotherapies and/or nasal irrigation, and/or inhalations. Polyposis and post-surgical recovery were excluded. Outcomes were Sino-Nasal Outcome Test (SNOT), visual analogue scales (VAS), Lund-Mackay computed tomography score (LM), Lund-Kennedy Endoscopic score (LK), Mucociliary transport time (MTT), Mucociliary transport rate (MTR), quality of life and adverse events (AEs). Risk of bias used the Cochrane tool. Meta-analysis in Review Manager 5.4.1 used random effects for mean difference (MD) or risk ratio (RR) with 95% confidence intervals. Heterogeneity was assessed as I2. Thirty-four RCTs were included, 30 of chronic RS (CRS) and four of acute RS (ARS). These enrolled 3,752 participants. Five RCTs blinded participants. For CRS, comparisons with placebo showed greater improvements in the CHM groups for SNOT-20 and VAS-TNS (total nasal symptoms). Blinded comparisons with pharmacotherapies showed no differences between groups in the degree of improvement for SNOT-20, VAS-TNS, and LM, suggesting these CHMs had similar effects, at least in the short term. In ARS, pooled results found improved scores on VAS-TNS and LK suggesting a benefit for combining these CHMs with pharmacotherapies. Limitations included inadequacies in study design and methodological reporting, and insufficient reporting of AEs. Heterogeneity in some pooled results precluded strong conclusions. Further well-designed studies are needed to test whether the results are replicable. Systematic review registration number: PROSPERO (CRD42019119586).

Background: Treatment effect of current pharmacotherapies for migraine is unsatisfying. Discovering new anti-migraine natural products and nutraceuticals from large collections of Chinese medicine classical literature may assist to address this gap.Methods: We conducted a comprehensive search in the Encyclopedia of Traditional Chinese Medicine (version 5.0) to obtain migraine-related citations, then screened and scored these citations to identify clinical management of migraine using oral herbal medicine in history. Information of formulae, herbs and symptoms were further extracted. After standardisation, these data were analysed using frequency analysis and the Apriori algorithm. Anti-migraine effects and mechanisms of actions of the main herbs and formula were summarised.Results: Among 614 eligible citations, the most frequently used formula was chuan xiong cha tiao san (CXCTS), and the most frequently used herb was chuan xiong. Dietary medicinal herbs including gan cao, bai zhi, bo he, tian ma and sheng jiang were identified. Strong associations were constructed among the herb ingredients of CXCTS formula. Symptoms of chronic duration and unilateral headache were closely related with herbs of chuan xiong, gan cao, fang feng, qiang huo and cha. Symptoms of vomiting and nausea were specifically related to herbs of sheng jiang and ban xia.Conclusion: The herb ingredients of CXCTS which presented anti-migraine effects with reliable evidence of anti-migraine actions can be selected as potential drug discovery candidates, while dietary medicinal herbs including sheng jiang, bo he, cha, bai zhi, tian ma, and gan cao can be further explored as nutraceuticals for migraine.

BackgroundChinese medicine (CM) syndrome differentiation is one of the fundamental principles that guide the practice of Chinese herbal medicine (CHM). CHM has been widely used among breast cancer patients. Contemporary literature varies in syndrome diagnosis, and there is a need to standardize syndrome differentiation according to the different stages of breast cancer treatment. This multicenter clinical study aims to identify the CM syndromes and the clinical signs and symptoms in women with early breast cancer.MethodsParticipants who met the inclusion and exclusion criteria were interviewed during the five treatment stages: preoperative, postoperative, chemotherapy, radiation therapy, and endocrine therapy. Patient demographic data and CM syndrome (as recorded by the treating CM clinicians in medical records) were gathered. Signs and symptoms were analyzed using descriptive statistics to derive the standardized CM syndromes using hierarchical cluster analysis.ResultsThe analysis included 964 interviews with 620 participants enrolled between April 29, 2020 and May 30, 2021 from eight participating hospitals in China. The two most frequent syndromes recorded in medical records were dual deficiency of qi and blood, and dual deficiency of qi and yin during all but the preoperative stage. The symptoms of lassitude, lack of strength, and insomnia were common in all but the preoperative stage. Cluster analysis identified two clusters in the preoperative stage that most closely resembled the syndrome diagnoses of liver stagnation with congealing phlegm, and dual deficiency of the liver and kidney. Two clusters—dual deficiency of qi and blood, and dual deficiency of qi and yin—were common to multiple treatment stages. The syndrome cluster of spleen and stomach disharmony existed in both the postoperative and chemotherapy stages. Cluster analysis of the radiation therapy stage identified the unique syndrome of yin deficiency with fire toxin, while the endocrine therapy included the syndromes of liver depression and kidney deficiency.ConclusionsThis multicenter clinical study showed consistency between results from cluster analysis and the most common syndromes recorded in the medical records. Findings from this clinical study will be further validated in a Delphi study to standardize CM syndromes for various stages of breast cancer treatment.Clinical Trial Registrationwww.chictr.org.cn/index.aspx, identifier ChiCTR2000032497.

BackgroundMigraine is a prevalent headache disorder with significant impacts on patients' quality of life and economic burden. Chinese herbal medicine (CHM) is commonly prescribed for migraine in China. This review aimed to provide a rigorous evaluation of evidence on the efficacy of oral CHM for migraine and explore the correlation between its effect size and treatment duration.MethodsWe searched nine digital databases (PubMed, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, AMED, BioMedical Literature, CNKI, CQVIP, and Wanfang Data) from their inceptions to May 2021, with the language being restricted to Chinese and English. Randomized, placebo-controlled trials using oral CHM to treat adult migraine were included. Data screening and extraction were conducted by two independent reviewers. The methodological quality of randomized controlled trials (RCTs) was assessed using the Cochrane Risk of Bias tool. Meta-analyses were conducted to estimate the effect size using a random effect model, and a robust variance estimation (RVE) model was constructed to explore the correlation between treatment effects and treatment duration. The certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation. Publication bias was tested using a funnel plot and Egger's test.ResultsA total of 18 RCTs involving 3,015 participants were included. Results of the meta-analyses showed that, at the end of the treatment phase, CHM was more efficacious than placebo in reducing migraine frequency, migraine days, and pain severity, and increasing response rate. Additionally, CHM showed superior effects to placebo in lowering migraine frequency and pain severity at the end of the 4-week follow-up. The RVE model suggested that the benefits of CHM for migraine frequency and pain intensity increased as treatment duration extended. The number of adverse events reported by the CHM and placebo groups was comparable. The certainty of the evidence was graded as “moderate.” No publication bias was detected.ConclusionOral CHM appeared to be more efficacious than placebo for reducing migraine frequency and pain severity. Greater treatment effects were associated with longer treatment duration. The oral CHM was well tolerated.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42021270719.

OBJECTIVE To investigate trends in the prevalence of hypertension and dyslipidaemia in incident type 2 diabetes (T2DM), time to antihypertensive (AHT) and lipid-lowering therapy (LLT), and the association with systolic blood pressure (SBP) and lipid control. RESEARCH DESIGN AND METHODS Using The Health Improvement Network UK primary care database, 254 925 people with incident T2DM and existing dyslipidaemia or hypertension were identified. Among those without atherosclerotic cardiovascular disease (ASCVD) history and not on AHT or LLT at diagnosis, the adjusted median months to initiating an AHT or an LLT, and the probabilities of high SBP or lipid levels over 2 years in people initiating therapy within or after 1 year were evaluated according to high and low ASCVD risk status. RESULTS At diabetes diagnosis, 66% and 66% had dyslipidaemia and hypertension, respectively. During 2005 to 2016, dyslipidaemia prevalence increased by 10% in people aged

Introduction. Herbal medicine is commonly used by patients with chronic cough, but the role of herbal medicine for cough variant asthma (CVA) has not yet been clearly defined. For the first time, we performed a meta-analysis to integrate the current evidence of randomized controlled trials (RCTs) on this topic and assess the efficacy of herbal medicine in adults with CVA. Methods. A comprehensive search was conducted in electronic databases to identify RCTs of herbal medicine for adult CVA. Cochrane systematic review methods were followed, and the Grading of Recommendations Assessment, Development, and Evaluation was performed to evaluate the quality of evidence. Results. Twenty-eight RCTs were included. Compared with placebo, moderate-quality evidence from two studies showed that herbal medicine was associated with reduced cough symptom score (CSS) (MD −1.15 points; 95% CI, −1.67 to −0.63) and visual analogue scale (VAS) (MD −1.76 points; 95% CI, −2.66 to −0.86). Compared with montelukast, low- to moderate-quality evidence from 11 studies indicated that herbal medicine was associated with improved Leicester Cough Questionnaire (LCQ) (MD 2.38 points; 95% CI, 1.32 to 3.44), reduced CSS (SMD −0.81 points; 95% CI, −1.09 to −0.53), and VAS (MD −1.34 points; 95% CI, −1.82 to −0.86). There were no significant differences between herbal medicine and ICS plus bronchodilator. Conclusions. In adults with CVA, herbal medicine may result in improved quality of life and reduced cough frequency and severity scores compared with placebo or montelukast. Herbal medicine was not better than ICS plus a bronchodilator but the evidence is very uncertain.

Context People with spasticity that occurred between 30 days and one year after stroke onset with a baseline Modified Ashworth Scale (MAS) ≥1. Objectives To determine the practicality of a pragmatic parallel-group open-labeled randomized controlled trial and to collect preliminary data of effectiveness and safety of electroacupuncture (EA) for poststroke spasticity. Methods Eligible participants were randomly allocated to the intervention group (EA plus usual care) or the control group (usual care alone) at a 1:1 ratio with block sizes of six. Participants received EA three times a week for four weeks, then were followed up for another four weeks. Participants' retention and adherence in the trial were assessed to determine the practicality of trial design. Clinical outcome measures were the change scores of MAS, Fugl-Meyer Assessment of motor performance and Barthel Index, and adverse events. Results Seventy-two people were screened for eligibility, and 30 of them were recruited and randomized. At the end, 25 participants followed the trial protocol and were included in our final data analyses using an intention-to-treat approach. No significant between-group difference was detected for the change scores of MAS, Fugl-Meyer Assessment, or Barthel Index at the end of treatment or end of follow-up. Eighteen participants reported 37 adverse events, but none of the participants was deemed related to EA. Conclusion It is feasible to conduct a full-scale trial to precisely evaluate the effectiveness and safety of EA for treating poststroke spasticity; however, longer treatment and follow-up phases should be considered in the full-scale trial.

The effects of naproxen, a nonsteroidal anti-inflammatory drug (NSAID), on articular cartilage degeneration in female Sprague-Dawley rats was examined. Osteoarthritis (OA) was induced by destabilization of the medial meniscus (DMM) in each knee. Rats were treated with acetaminophen (60 mg/kg), naproxen (8 mg/kg), or 1% carboxymethylcellulose (placebo) by oral gavage twice daily for 3 weeks, beginning 2 weeks after surgery. OA severity was assessed by histological Osteoarthritis Research Society International (OARSI) scoring and by measuring proximal tibia cartilage depth using contrast enhanced µCT (n = 6 per group) in specimens collected at 2, 5, and 7 weeks after surgery as well as on pristine knees. Medial cartilage OARSI scores from the DMM knees of naproxen-treated rats were statistically lower (i.e., better) than the medial cartilage OARSI scores from the DMM knees of placebo-treated rats at 5-weeks (8.7 ± 3.6 vs. 13.2 ± 2.4, p = 0.025) and 7-weeks (9.5 ± 1.2 vs. 12.5 ± 2.5, p = 0.024) after surgery. At 5 weeks after DMM surgery, medial articular cartilage depth in the proximal tibia specimens was significantly greater in the naproxen (1.78 ± 0.26 mm, p = 0.005) and acetaminophen (1.94 ± 0.12 mm, p < 0.001) treated rats as compared with placebo-treated rats (1.34 ± 0.24 mm). However, at 7 weeks (2 weeks after drug withdrawal), medial articular cartilage depth for acetaminophen-treated rats (1.36 ± 0.29 mm) was significantly reduced compared with specimens from the naproxen-treated rats (1.88 ± 0.14 mm; p = 0.004). The results indicate that naproxen treatment reduced articular cartilage degradation in the rat DMM model during and after naproxen treatment.

Background Poria cocos (Schw.) Wolf or Fuling is one of the top 10 most frequently prescribed herbs in China for the treatment of type 2 diabetes mellitus (T2DM). Objective The purpose of this systematic review is to determine the additional benefit of Fuling formulae use in addition to hypoglycaemic agents for T2DM in randomised clinical trials. Methods English (5) and Chinese (4) medical databases were searched from their inception to August 2021. RCTs that included Fuling in herbal formulae for T2DM were included. Risk of bias were assessed using the Cochrane Collaboration’s procedures. Stata software (13.0) was used for data analysis. Results Seventy-three RCTs (6,489 participants) with herbal formulae containing Fuling were included. Most studies were at risk of bias and strength of the evidence were low to moderate. Meta-analysis findings showed that the addition of formulae containing Fuling to hypoglycaemic agent-treatments could benefit people with T2DM by reducing fasting blood glucose (MD -0.82 [-0.93, -0.71]; I2 = 79.6%, P = 0.00), 2-hour postprandial blood glucose (MD-1.15 [-1.31, -0.98], I2 = 80%, P = 0.00) and haemoglobin A1c (MD-0.64 [-0.75, -0.53], I2 = 84.7%, P = 0.00). Adverse events were also significantly lower in the integrative group than in the hypoglycaemic alone group (RR 0.99 [0.93, 1.06], P = 0.87). Conclusion Evidence from this study supports the use of Fuling formulae combined with hypoglycaemic agents for T2DM. The combined therapies appear to be well tolerated. Trail registration This review is registered with the PROSPERO international prospective register of systematic reviews (CRD42020214635).

BackgroundMigraine is a chronic neurological disease causing significant socioeconomic burden and impaired quality of life. Chinese medicine is commonly used for migraine in China. Clinical trials have generated evidence of the effectiveness of Chinese medicine therapies for migraine. However, little is known about how to use these therapies to treat migraine in real-world clinical settings.MethodsIn this retrospective study, we analyzed data from the electronic medical records (EMRs) of 2,023 migraine patients who attended the Guangdong Provincial Hospital of Chinese Medicine (GPHCM) between July 2018 and July 2020.ResultsMore than three-quarters (77.21%) of the patients were female. Most (78.20%) of the patients were aged between 18 and 50 years, 18.49% were aged above 50 years, and the remaining 3.31% were under 18 years. Sleep disorders were the most documented comorbidity occurring in 27.29% of patients, and more common in females (29.77%) than male (18.87%). Fatigue was the most frequently reported trigger of migraine attacks among all patients (9.39%), while menstruation was the most common trigger for female patients (10.24%). Less than a quarter of patients (21.01%) reported a history of taking analgesic medication for their migraine. The median treatment duration reported by the patients was 10 days. Chinese herbal medicine (CHM) was the predominant treatment for migraine at the hospital (88.48%), while pharmacotherapies were prescribed to 28.97% of the patients. CHM was prescribed more often as a sole treatment (53.58% of patients) than combined with pharmacotherapies (27.39% of patients). Among patients who reported improvements after taking CHM, the most frequently used herbs were fu ling and chuan xiong, the most frequent patented CHM product was tong tian oral solution, and the main herbal formulae were chuan xiong cha tiao san and yi qi cong ming tang.ConclusionCHM formulae, such as chuan xiong cha tiao san and yi qi cong ming tang, patented CHM product tong tian oral solution, and some herbs are potentially effective treatments for migraine. As such, CHM can be used as an alternative to conventional pharmacotherapies for migraine and is worth further evaluation in randomized controlled trials.

Low-dose carbon monoxide (CO) is under investigation in clinical trials to treat non-cancerous diseases and has an excellent safety profile. Due to early detection and cancer awareness, an increasing number of cancer patients are diagnosed at early stages, when potentially curative surgical resection can be done. However, many patients ultimately experience recurrence. Here, we evaluate the therapeutic effect of CO on metastatic cancer progression. We show that 250 ppm CO inhibits the migration of multiple types of cancer cell lines, including breast, pancreatic, colon, prostate, liver, and lung cancer and reduces the ability to adhere to fibronectin. We demonstrate that in mouse models, 250 ppm inhaled CO inhibits lung metastasis of breast cancer and liver metastasis of pancreatic cancer. Moreover, low-dose CO suppresses recurrence and increases survival after surgical removal of primary pancreatic cancer in mice. Mechanistically, low-dose CO blocks transcription of heme importers, leading to diminished intracellular heme levels and a heme-regulated enzyme, cytochrome P4501B1 (CYP1B1). Either supplementing heme or overexpressing CYP1B1 reverses the anti-migration effect of low-dose CO. Taken together, low-dose CO therapy inhibits cell migration, reduces adhesion to fibronectin, prevents disseminated cancer cells from expanding into gross metastases, and improves survival in pre-clinical mouse models of metastasis.

Background Increasing antibiotic resistance has motivated interest in non-antibiotic prophylaxis of recurrent urinary tract infections (rUTI). Objectives To conduct a systematic review of the current state of evidence of acupuncture for uncomplicated rUTI in women. Search strategy Nine databases (PubMed, Embase, CENTRAL, CINAHL, AMED, CBM, CNKI, CQVIP, Wanfang) were searched from inception to February 2019. Selection criteria Randomised controlled trials (RCTs) evaluating the effects of acupuncture and related therapies for prophylaxis or treatment of uncomplicated rUTI in women were included. Data collection and analysis Risk of bias was assessed, and the quality and strength of evidence evaluated using the GRADE framework. Results were reported as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). Main results Five RCTs involving 341 participants were included. Methodological quality of studies and strength of the evidence were low to moderate. The chance of achieving a composite cure with acupuncture therapies was greater than that with antibiotics (three studies, 170 participants, RR 1.92, 95% CI 1.31-2.81, I2 = 38%). The risk of UTI recurrence was lower with acupuncture than with no treatment (two studies, 135 participants, RR 0.39, 95% CI 0.26-0.58, I2 = 0%) and sham acupuncture (one study, 53 participants, RR 0.45, 95% CI 0.22-0.92). Conclusions Acupuncture appeared to be beneficial for treatment and prophylaxis of rUTIs, noting the limitations of the current evidence. Given the growing challenge of antibiotic resistance, there is a need for high-quality RCTs of non-pharmacological interventions such as acupuncture. Tweetable abstract This review found that acupuncture may improve treatment and prevent recurrence of urinary tract infection in women.

ObjectiveDetermine if deep learning detects sepsis earlier and more accurately than other models. To evaluate model performance using implementation-oriented metrics that simulate clinical practice.Materials and MethodsWe trained internally and temporally validated a deep learning model (multi-output Gaussian process and recurrent neural network [MGP–RNN]) to detect sepsis using encounters from adult hospitalized patients at a large tertiary academic center. Sepsis was defined as the presence of 2 or more systemic inflammatory response syndrome (SIRS) criteria, a blood culture order, and at least one element of end-organ failure. The training dataset included demographics, comorbidities, vital signs, medication administrations, and labs from October 1, 2014 to December 1, 2015, while the temporal validation dataset was from March 1, 2018 to August 31, 2018. Comparisons were made to 3 machine learning methods, random forest (RF), Cox regression (CR), and penalized logistic regression (PLR), and 3 clinical scores used to detect sepsis, SIRS, quick Sequential Organ Failure Assessment (qSOFA), and National Early Warning Score (NEWS). Traditional discrimination statistics such as the C-statistic as well as metrics aligned with operational implementation were assessed.ResultsThe training set and internal validation included 42 979 encounters, while the temporal validation set included 39 786 encounters. The C-statistic for predicting sepsis within 4 h of onset was 0.88 for the MGP–RNN compared to 0.836 for RF, 0.849 for CR, 0.822 for PLR, 0.756 for SIRS, 0.619 for NEWS, and 0.481 for qSOFA. MGP–RNN detected sepsis a median of 5 h in advance. Temporal validation assessment continued to show the MGP–RNN outperform all 7 clinical risk score and machine learning comparisons.ConclusionsWe developed and validated a novel deep learning model to detect sepsis. Using our data elements and feature set, our modeling approach outperformed other machine learning methods and clinical scores.

Yuanbin Chen,1,* Lin Lin,1,* Lei Wu,1 Yinji Xu,1 Johannah L Shergis,2 Anthony L Zhang,2 Zehuai Wen,1 Christopher Worsnop,3 Cliff Da Costa,4 Frank Thien,5 Charlie C Xue1,2 1The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, People’s Republic of China; 2School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia; 3Institute of Breathing and Sleep, Austin Health, Heidelberg, Victoria, Australia; 4School of Science, RMIT University, Bundoora, Victoria, Australia; 5Department of Respiratory Medicine, Eastern Health, Victoria, Australia, and Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia*These authors contributed equally to this workCorrespondence: Charlie C XueSchool of Health and Biomedical Sciences, PO BOX 71, Bundoora, Victoria 3083, AustraliaTel +61 3 99257360Fax +61 3 99256539Email charlie.xue@rmit.edu.auPurpose: Herbal medicines are commonly used by people with chronic obstructive pulmonary disease (COPD) but high quality randomized controlled trials are limited. This study evaluated the therapeutic value of ginseng capsules in reducing acute exacerbations and improving the quality of life in people with COPD.Patients and Methods: This randomized, double-blind and placebo-controlled trial assessed ginseng’s effects on 200 patients with moderate to very severe COPD. Ginseng capsules (200 mg, twice per day) were compared to placebo over 24 weeks. Patients were followed up for a further 24 weeks after the treatment period. The primary outcome measure was acute COPD exacerbation rate over 12 months. Secondary outcome measures were health-related quality of life, including the St George’s Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT) and the Short Form 36 Health Survey (SF-36). We also assessed lung function, walking distance and use of relief medication.Results: Baseline characteristics were balanced between groups. The rate of COPD exacerbations was not statistically significant between groups after 1 year (62 participants in the ginseng group and 63 in the placebo group). Secondary outcome measures showed improvements after ginseng and placebo but results were not clinically significant. The incidence of adverse events in the two groups was similar and events were unrelated to the intervention.Conclusion: Compared with placebo, ginseng did not reduce the rate of acute COPD exacerbations over 12 months. It was safe and well tolerated by people with moderate to very severe COPD.Keywords: COPD, ginseng, exacerbation, quality of life, randomized controlled trial

Objectives: Bupleurum chinense (BC; Radix Bupleuri) formulae are widely used in herbal medicine clinical practice for major depressive disorder (MDD). This study provides an up-to-date and comprehe...

Additional file 1: Appendix S1. The professional field of the steering committee and the expert consensus group. Appendix S2. Details of panel members��� declarations of interests. Appendix S3. Grading the certainty of evidence and the strength of recommendations. Appendix S4. Details of patients preference and values. Appendix S5. Details of expert consensus. Appendix S6. Summary of findings table.

Introduction: Atrial fibrillation (AF) is a common arrythmia associated with high morbidity and mortality. Understanding modifiable risk factors that contribute to AF could have a broad impact on patient outcomes. While work has been done to understand the association between alcohol use and AF, there is limited understanding in the relationship between non-alcohol substance use and new-onset AF. Our study sought to investigate the associations of methamphetamine, cocaine, opiate, and cannabis use with incident AF. Methods: This is a retrospective observational study of 23,561,844 adult inpatient hospitalizations and ED visits from January 1, 2005 to September 30, 2015 in California’s Office of Statewide Health Planning and Development (OSHPD) database. International Classification of Disease (ICD) codes were used to document AF and methamphetamine, cocaine, opiate, or cannabis use disorders. All patients with prevalent AF were excluded from analysis. Results: Methamphetamine use (n=98,271), cocaine use (n=48,700), opiate use (n=10,032), and cannabis use (n=132,834) disorders were coded as part of routine clinical care. In multivariate analysis adjusting for age, race, sex, income, and cardiovascular risk factors, methamphetamine, cocaine, opiate, and cannabis use were associated with higher incidence of AF ( Table ). The cumulative probability of incident AF increased over time with all four substances ( Figure ). Conclusion: Patients with documented methamphetamine, cocaine, opiate, or cannabis use disorders had an increased risk of incident AF that was independent of the risk already portended by established cardiovascular risk factors.

Introduction: Localized studies have reported a decline in myocardial infarctions during the coronavirus disease 2019 (COVID-19) pandemic. The mechanisms underlying these observations remain unknown, but evidence that patients may avoid healthcare facilities for fear of COVID-19 infection has heightened concern that true rates of myocardial infarctions have been under-ascertained and left untreated. Methods: We analyzed data from the National Emergency Medical Services Information System (NEMSIS) and incident COVID-19 infections across the United States between January 1, 2020 to April 30, 2020. Grouping events by US Census Division, multivariable adjusted negative binomial regression models were utilized to estimate the relationship between COVID-19 and EMS activations for chest pain, non-ST-elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI), cardiac arrests, and ventricular arrhythmias. Results: After multivariable adjustment, increasing rates of COVID-19 were associated with a reduction in EMS activations for chest pain (RR 0.67, 95% CI 0.63-0.70, p < 0.001) and NSTEMIs (RR 0.16, 95% CI, 0.10-0.26; p < 0.001). Simultaneously, increasing COVID-19 was associated with a significant increase in EMS activations for cardiac arrests (RR 1.51, 95% CI 1.36-1.68, p < 0.001), ventricular fibrillation (RR 1.47, 95% CI 1.23-1.77, p < 0.001), and ventricular tachycardia (VT) episodes (RR 1.34, 95% CI 1.16-1.56, p < 0.001). These statistically significant relationships were consistently observed within each of the 9 US Census Divisions alone. Conclusions: Taken together, these data suggest that individuals are commonly delaying or avoiding care for myocardial infarction in areas with more COVID-19, leading to lethal consequences. Interventions aimed at reinforcing the need to seek appropriate care for suspected myocardial infarctions, even in the context of heightened infectious disease risks, should be pursued.

Background This study aims to develop an evidence-based clinical practice guideline of acupuncture in the treatment of patients with moderate and severe cancer pain. Methods The development of this guideline was triggered by a systematic review published in JAMA Oncology in 2020. We searched databases and websites for evidence on patient preferences and values, and other resources of using acupuncture for treatment of cancer pain. Recommendations were developed through a Delphi consensus of an international multidisciplinary panel including 13 western medicine oncologists, Chinese medicine/acupuncture clinical practitioners, and two patient representatives. The certainty of evidence, patient preferences and values, resources, and other factors were fully considered in formulating the recommendations. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the certainty of evidence and the strength of recommendations. Results The guideline proposed three recommendations: (1) a strong recommendation for the treatment of acupuncture rather than no treatment to relieve pain in patients with moderate to severe cancer pain; (2) a weak recommendation for the combination treatments with acupuncture/acupressure to reduce pain intensity, decrease the opioid dose, and alleviate opioid-related side effects in moderate to severe cancer pain patients who are using analgesics; and (3) a strong recommendation for acupuncture in breast cancer patients to relieve their aromatase inhibitor-induced arthralgia. Conclusion This proposed guideline provides recommendations for the management of patients with cancer pain. The small sample sizes of evidence limit the strength of the recommendations and highlights the need for additional research.

Introduction Migraine is a disabling, recurrent headache disorder with complex comorbidities. Conventional treatments for migraine are unsatisfactory, with side effects and limited effectiveness. Chinese herbal medicine (CHM) has been used as an alternative or complementary treatment option for migraine in China. Currently, the existing evidence of benefit of CHM for migraine has been generated from randomised clinical trials using standardised intervention with a focus on internal validity hence with limited external validity. Moreover, CHM individualised intervention design, patients’ preferences and concerns, and clinicians’ experience are critical to clinical decision making and therapeutic success. This real-world observational study aims to gather practice-based evidence of effects and safety of CHM for migraine in the context of integrating Chinese medicine diagnostic procedures, patients’ preferences and matters relevant to clinical decision making. Methods and analysis The study is being undertaken at the Guangdong Provincial Hospital of Chinese Medicine (GPHCM) from December 2020 to May 2022. We anticipate that approximately 400 adult migraineurs will be enrolled and observed on their migraine severity, analgesic consumption, quality of life, anxiety, depression and insomnia at baseline and then every four weeks over 12 weeks. Treatments, diagnostic information, and patient-reported most bothersome symptoms will be collected from patient clinical records. Patient’s demographic data, preferences and concerns on CHM treatments will also be gathered at baseline and be analysed. Factors related to clinical outcomes will be explored with multiple correlation and multivariable regression analyses. Effects of CHM will be evaluated using generalised estimated equation, based on clinical outcome data. Discussion This study will provide comprehensive evidence of CHM for migraine in the context of evidence-based practice. Trial registration number ChiCTR2000041003

IMPORTANCE: The Epic Sepsis Model (ESM), a proprietary sepsis prediction model, is implemented at hundreds of US hospitals. The ESM’s ability to identify patients with sepsis has not been adequately evaluated despite widespread use. OBJECTIVE: To externally validate the ESM in the prediction of sepsis and evaluate its potential clinical value compared with usual care. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted among 27 697 patients aged 18 years or older admitted to Michigan Medicine, the academic health system of the University of Michigan, Ann Arbor, with 38 455 hospitalizations between December 6, 2018, and October 20, 2019. EXPOSURE: The ESM score, calculated every 15 minutes. MAIN OUTCOMES AND MEASURES: Sepsis, as defined by a composite of (1) the Centers for Disease Control and Prevention surveillance criteria and (2) International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes accompanied by 2 systemic inflammatory response syndrome criteria and 1 organ dysfunction criterion within 6 hours of one another. Model discrimination was assessed using the area under the receiver operating characteristic curve at the hospitalization level and with prediction horizons of 4, 8, 12, and 24 hours. Model calibration was evaluated with calibration plots. The potential clinical benefit associated with the ESM was assessed by evaluating the added benefit of the ESM score compared with contemporary clinical practice (based on timely administration of antibiotics). Alert fatigue was evaluated by comparing the clinical value of different alerting strategies. RESULTS: We identified 27 697 patients who had 38 455 hospitalizations (21 904 women [57%]; median age, 56 years [interquartile range, 35-69 years]) meeting inclusion criteria, of whom sepsis occurred in 2552 (7%). The ESM had a hospitalization-level area under the receiver operating characteristic curve of 0.63 (95% CI, 0.62-0.64). The ESM identified 183 of 2552 patients with sepsis (7%) who did not receive timely administration of antibiotics, highlighting the low sensitivity of the ESM in comparison with contemporary clinical practice. The ESM also did not identify 1709 patients with sepsis (67%) despite generating alerts for an ESM score of 6 or higher for 6971 of all 38 455 hospitalized patients (18%), thus creating a large burden of alert fatigue. CONCLUSIONS AND RELEVANCE: This external validation cohort study suggests that the ESM has poor discrimination and calibration in predicting the onset of sepsis. The widespread adoption of the ESM despite its poor performance raises fundamental concerns about sepsis management on a national level.

Background: Psoriasis vulgaris and chronic urticaria are common skin conditions with a significant health burden. Achieving long-term control remains a challenge, and some patients choose Chinese herbal medicine (CHM) to meet this need. Little is known about the motivators and experiences of using CHM for these skin conditions.Objectives: To determine the motivators for choosing CHM, and experience of using CHM for psoriasis vulgaris and chronic urticaria.Methods: We conducted semi-structured interviews with participants who had previously used CHM for these conditions. Interviews were transcribed for data analysis.Results: Twenty participants completed the interviews in Guangzhou (n = 16), China, and Melbourne (n = 4), Australia. Motivators included wanting an alternative to conventional medicine, beliefs about CHM and previous experience. Participants expected that CHM would be safer and could prevent relapse; this expectation was met for some participants. Preparing CHM decoctions was onerous, and CHM granules were more convenient.Conclusion: Beliefs, previous experience of using CHM, desire to prevent relapse, and safety are important motivators for choosing CHM in people with psoriasis vulgaris and chronic urticaria. Further clinical evidence is required to enable patients to make informed clinical decisions. Patient preferences should be considered in the context of available evidence when prescribing CHM.

Background: Mild cognitive impairment (MCI) prevalence is estimated at 6%-12% of the population. It is possible that early treatment at the MCI stage could reduce progression to more severe cognitive impairment. The Montreal Cognitive Assessment (MoCA) is a sensitive measure used to assess changes in cognitive function. Various Chinese herbal medicines (CHMs) have been tested for effects on MCI using MoCA. Objectives: To evaluate the clinical evidence for CHMs on MoCA scores in MCI. Design: Five biomedical databases in English and Chinese language were searched for randomized controlled trials that compared orally administered CHMs with a control group and assessed changes in cognition using MoCA. Analyses were based on the comparison, control intervention, and study duration. Mean differences and 95% confidence intervals were calculated to evaluate treatment effects. For each study, risk of bias was assessed according to the Cochrane tool. Results: Nineteen studies were included with 16 contributing to the data analyses. Three studies were placebo controlled. Nine compared a CHM with a pharmacotherapy, three combined a CHM with a pharmacotherapy, and one combined CHM with cognitive training. In the two placebo-controlled studies of 24-week duration, results favored the CHMs at end of treatment. Conclusions: The systematic review suggests that the oral application of certain CHMs improved scores on MoCA by 1.76-2.34 points compared with placebo in people with MCI after 24 weeks of treatment. However, these two studies used different CHM formulations. Two studies that tested the same CHM formulation, Bu Yang Huan Wu Tang, in combination with donepezil, reported improvement in the integrative groups, but the studies were not blind and the durations were only 8-12 weeks. Overall, methodological weaknesses limited the strength of the evidence. The herbal formulae included ingredients that have received considerable research attention for their effects on memory and cognition. PROSPERO international prospective register of systematic reviews protocol registration number: CRD42018099650.

BackgroundPanax ginseng (ginseng) is a therapeutic herb which might be beneficial in COPD. The study investigated if ginseng, compared with placebo, is effective and safe for people with moderate COPD.MethodsThis multicentre, randomised, double-blind, placebo-controlled trial compared 24 weeks of ginseng capsules (100 mg twice daily) with placebo. Participants were followed up for a further 24 weeks. Participants were aged 40 years and over and had airflow limitation in the moderate (Global Initiative for Chronic Obstructive Lung Disease 2) COPD range. The coprimary endpoints were the St George’s Respiratory Questionnaire, the COPD Assessment Test and the Short Form Health Survey. Secondary outcomes included lung function, exacerbation rate and use of relief medication.Findings168 participants were randomised 1:1 from five centres in Australia and China. Baseline characteristics were balanced between groups. There were no significant differences between ginseng and placebo, with overall results improving in both groups. Ginseng seemed safe for, and well tolerated by, people with COPD.InterpretationThere was no significant difference in improvement in health-related quality of life (primary outcome) between the ginseng and placebo groups.Trial registration numberACTRN12610000768099.

Background The World Health Organization (WHO) reported that colorectal cancer (CRC) was the third most common cancer in men and the second in women, worldwide. Our previous meta-analysis found Sophora flavescens increased tumour response rate in randomised controlled trials of CRC. We hypothesised that its principal constituent matrine had exerted anti-tumour effects. Purpose To elucidate its mechanisms of action we investigated the dose-related anti-tumour effects of matrine on four human CRC cell-lines: LS174T, Caco-2, SW1116 and RKO. In a LS174T xenografted tumour model in nude mice we assessed the effects of matrine and oxaliplatin on tumour volume, weight and morphology. Computer simulated dockings for target proteins were also conducted. Methods and design Cell viability, cell cycle and apoptosis were measured by Cell Counting Kit-8 and flow cytometry, and Annexin V-FITC/PI double staining assay respectively. Western blot was performed to examine the expression of Bax, Bcl-2 and caspase-3 in the cells. The xenograft model and immunohistochemistry were used to investigate the effect of matrine in vivo. Oxaliplatin was set as positive control. Molecular docking was performed to predict the binding modes of matrine and oxaliplatin with target proteins using CDOCKER algorithm. Results Matrine inhibited proliferation of cancer cells in a dose- and time-dependent manner. Matrine induced cell-cycle arrest at G1/G0 phase, induced apoptosis and reduced expression of Bcl-2 and caspase-3 while up-regulating Bax and cleaved caspase-3 in the four CRC cells. In vivo, matrine significantly inhibited tumour growth without side effects on physical health compared to the negative (vehicle) control group. Mice in the oxaliplatin group lost vigour, became frail and lost weight. Expression of Bcl-2 in tumour tissue was lower and Bax expression was higher in the matrine-treated groups compared to the negative control. In computer-simulated docking, matrine successfully docked into active sites of Bcl-2 and caspase-3. Conclusion Matrine inhibited growth of colorectal cancer cells in vitro and in vivo. A molecular mechanism was apoptosis induction via effects on Bcl-2, Bax and caspase-3. Moreover, matrine showed minimum side effects and may provide a candidate for the development of new therapies for colorectal cancer.

Background Electroacupuncture (EA) is a modern form of acupuncture therapy where stainless steel acupuncture needles are used as percutaneous electrodes to apply electrical stimulation. The concern about electrolytic corrosion of needles during EA has not been conclusively addressed. Aim To examine whether corrosion of stainless steel acupuncture needles occurs after EA to establish the safety profile of this therapy. Methods The study comprised four EA sessions on healthy participants mimicking a common clinical practice, with needle surface examinations conducted immediately after each session. Used acupuncture needles that did not undergo electrical stimulation and unused needles taken from the original package were also examined as control comparisons. Two commonly used types of single-use, silicone-coated, stainless steel needles were selected for the experiment. The ES-160 digital acupunctoscope (a charge-balanced electric stimulator) was used to deliver electrical stimulation, and an oscilloscope was used to record the waveforms and electric currents. All needles were sterilised before examination by a scanning electron microscope (SEM), where images of needle tips and shafts were taken for further analysis. Results and conclusions 32 needles were examined under the SEM. As the main findings, the SEM images showed the surface finish, burr attachments and surface characteristics of needle samples. No evidence of electrolytic corrosion was detected on any needle that underwent electrical stimulation for 30 min delivered by a charge-balanced acupunctoscope in healthy participants. The choice of a charge-balanced acupunctoscope is recommended to avoid any potential corrosion of needles in EA clinical practice.

Background Mild‐moderate psoriasis vulgaris is a common dermatological autoimmune condition with limited conventional therapeutic options. Safe and effective adjunct therapies to topical non‐steroidal antipsoriatic therapy are needed. The oral Chinese herbal medicine (CHM) formula PSORI‐CM01 has been evidenced potential antipsoriatic pharmacological activity. This article reports a pilot study which was designed as a double‐blinded, placebo‐controlled randomized controlled trial (RCT) evaluating the effects of PSORI‐CM01 when added to topical calcipotriol cream. Methods People with moderate psoriasis vulgaris were randomized to receive oral PSORI‐CM01 or placebo administered for 12 weeks in combination with calcipotriol. The primary clinical outcome was the change of psoriasis area severity index (PASI) score at week 12 and week 24. Secondary clinical outcomes were PASI75, PASI50, relapse rate, change in body surface area, dermatology life quality index and Skindex29, and adverse events (AEs). Participants’ satisfaction and willingness to repeat were also assessed. Results The pilot study was conducted in Australia and China, 29 participants were randomized with 26 completed the treatment and follow‐up. Participants’ baseline basic characteristics were comparable. No between‐group statistical significance was found on pre‐defined clinical outcome measures, although there seemed a trend of treatment effects favoring the combination of PSORI‐CM01 with calcipotriol. Frequency and severity of AEs were similar between two groups, with no severe AEs reported. Conclusions The design and duration of the study appears feasible. A proper powered RCT with slight adjustments in the methods is needed to reveal the add‐on effects of oral CHM PSORI‐CM01. The experience and results from this pilot study will contribute to the refine of objectives and design of a future study, and assist the sample size calculation for the full‐scale RCT.

Background and purpose Chinese medicine is increasingly used by women with postpartum depression (PPD). We systematically analyzed randomized controlled trials of acupuncture and Chinese herbal medicine (CHM) for PPD. Methods Studies were retrieved from English and Chinese databases. The Cochrane risk of bias tool was used to assess methodological quality. Results Fifteen CHM, and three acupuncture studies were included. Low quality evidence suggested that CHM alone or combined with antidepressants as add-on therapy may reduce symptoms of depression compared to placebo or antidepressants on the Edinburgh Postnatal Depression Scale (EPDS). There was no statistically significant difference between acupuncture and antidepressants. Adverse events were rare. Conclusions CHM reduced PPD symptoms greater than placebo or antidepressants. Acupuncture was neither superior nor inferior to antidepressants. More rigorously designed studies are required to confirm the effect of CHM and acupuncture for PPD.

Background An ideal placebo design in clinical research should resemble the intervention under investigation to facilitate blinding, yet remain clinically inert. With regard to physical interventions such as acupuncture, a true placebo device has not been developed and validated. Since 1998, researchers have designed several placebo acupuncture devices (PADs). The three most widely used PADs are the Streitberger, the Park and the Takakura device. Aim This review focuses on evaluating studies of these devices, in the context of credibility of blinding (COB), assessment of penetrating pain or sensation, and de qi sensation. Methods Electronic database searches were conducted in four English and two Chinese databases from their inception until November 2016. All studies included in the review were conducted on healthy participants and compared verum manual acupuncture with any of the aforementioned PADs with respect to one or more of the above three outcomes related to blinding effect. Results The synthesised analyses of the 15 included studies showed that the Streitberger and Park placebo devices may not blind participants successfully when tested at a sensitive acupuncture point (LI4). In terms of penetrating sensation, there were significant differences between these two placebo devices and verum acupuncture when applied at this point. The Takakura device was the only PAD that had the potential to blind the acupuncturist. However, the blinding analyses of all outcome measures were inconsistent. Conclusion Overall, there were insufficient data to confirm the blinding effects of these skin-contact PADs as each device was associated with limitations that warrant further design improvements.

Acne vulgaris is a common inflammatory skin condition characterized by comedones. Current pharmacotherapies are effective but are associated with adverse events (AEs) such as mood disorders and antibiotic resistance. The Eriobotrya japonica Formula (EJF) contains six herbs commonly used in traditional Chinese medicine clinical practice. This paper evaluates the experimental evidence and clinical efficacy of EJF for acne vulgaris. Searches of 11 English and Chinese databases were conducted to identify eligible randomized controlled trials (RCTs). PubMed was searched for experimental evidence of herbs included in EJF. Meta-analyses were performed to analyse the clinical effects of EJF compared to pharmacotherapies. Ingredients in EJF were reported to have an effect on inhibiting TNF-α, PPAR-γ and IL-6 cytokines. Some also inhibited P. acnes and had anti-androgenic and anti-lipogenic effects. There were 15 RCTs included in the clinical review. The number of people achieving a clinical improvement based on lesion count was higher with EJF than pharmacotherapies. The effective rate of EJF was greater than antibiotics and benzoyl peroxide (2 studies, RR: 1.47 [1.23, 1.77], I2 = 0%), and antibiotics with topical supplements (2 studies, RR: 1.77 [1.18, 2.67], I2 = 0%). There were 107 mild AEs reported in 7 trials, 33 in the intervention groups and 74 in the control groups. No serious AEs were reported. There is some evidence that EJF can decrease inflammatory lesions in acne vulgaris with fewer AEs in the short-term. However, due to methodological limitations of the included trials, results on clinical efficacy should be interpreted with caution.

The majority of studies of integrative treatment for colorectal cancer (CRC) have been published in Chinese journals. These studies indicate potential benefits, but concerns have been raised over the quality of trials published in Chinese journals. The CONSORT statement provides a guide for study reporting that has been endorsed by more than 400 international journals. Previous studies have used the CONSORT checklist to assess the quality of randomized controlled trials (RCTs).This study focused on RCTs of integrative and traditional medicine for CRC published in Chinese journals and assessed: (1) the overall quality of reporting with a focus on methodological aspects; (2) change over time; and (3) the influence of study funding, level of institution conducting the trial, rank of the journal, and the length of the article.Searches of seven databases identified RCTs. Quality was assessed using CONSORT 2010 with adaptations to facilitate scoring. Additional codes were added for publication year, hospital rank, report length, and status of the journal. Scores of each checklist item, total scores, and scores for eight items associated with RCT methodology were calculated.Eighty-one studies were included in the main analyses. The RCT methodology subgroup scores were significantly higher in studies: with public funding, conducted by authors from university hospitals, published in higher ranked journals, and in longer articles.Few Chinese journals mention CONSORT in their author guidelines. In these RCTs on CRC better reporting of RCT methodology was associated with ranking of the journal as "core," public funding of the RCT, and first or correspondent author from a university hospital but the quality of reporting had not significantly improved in 15 years. As the volume of scientific information produced in China grows, it is imperative that there is growth in the quality of this information.

Pancreatic cancer has the lowest survival rate in all types of cancer. Pancreatic cancer patients are often diagnosed at advanced stages. A better therapeutic development for this devastating disease is urgently needed. Receptor for hyaluronan-mediated motility (RHAMM), not expressed in adult normal pancreas, has been suggested as a prognostic factor and a potential therapeutic target for pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumor (PNET). In this study, we initially sought to determine whether genetic deletion of RHAMM would slow down pancreatic cancer progression using Rhamm−/− mice. However, we found that Rhamm−/− mice expressed a N-terminal RHAMM protein. While N-terminal RHAMM did not enable malignant progression of pancreatic intraepithelial neoplasia in p48-Cre; LSL-KRASG12D mice, it accelerated the formation of invasive PDAC and shortened the survival of p48-Cre; LSL-KRASG12D mice with heterozygous p53 knockout. KrasG12D PDAC mice with homozygous p53 knockout mice died around 10 weeks, and the effect of N-terminal RHAMM was not apparent in these mice with short life span. In addition, N-terminal RHAMM shortened the survival of PNET-bearing RIP-Tag mice, which had inactivated p53. In our analysis of TCGA dataset, pancreatic cancer patients with mutant TP53 or loss of one copy of TP53 had higher RHAMM expression, which, combined, predicted worse outcomes. Taken together, by collaborating with dysfunctional p53, N-terminal RHAMM that lacks the centrosome targeting domain and degrons for interaction with the Anaphase-Promoting Complex (APC) accelerated pancreatic cancer progression. Citation Format: Anthony Lin, Jennifer Feng, Xiang Chen, Dunrui Wang, Megan Wong, George Zhang, Joseph Na, Tiantian Zhang, Zhengming Chen, Yao-Tseng Chen, Yi-Chieh Nancy Du. N-terminal RHAMM cooperates with dysfunctional p53 to accelerate the progression of pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-060.

The plant Sophora flavescens Ait. has been used in the clinical management of colorectal cancer (CRC). Its constituent compounds, notably the alkaloids matrine, oxymatrine, and sophoridine, have received considerable research attention in experimental models of CRC in vivo and in vitro. This review found that extracts of S. flavescens and/or its constituent compounds have been reported to inhibit CRC cell proliferation by inducing cell-cycle arrest at the G1 phase, inducing apoptosis via the intrinsic pathway, interfering in cancer metabolism, inhibiting metastasis and angiogenesis, regulating senescence and telomeres, regulating the tumour microenvironment and down-regulating cancer-related inflammation. In addition, matrine and oxymatrine reversed multi-drug resistance and enhanced the effects of chemotherapies. These anti-cancer effects were associated with regulation of several cellular signalling pathways including: MAPK/ERK, PI3K/AKT/mTOR, p38MAPK, NF-κB, Hippo/LATS2, TGF-β/Smad, JAK/STAT3, RhoA/ROC, and Wnt/ β-catenin pathways. These multiple actions in CRC suggest the alkaloids of S. flavescens may be therapeutic candidates for CRC management. Nevertheless, there remains considerable scope for future research into its flavonoid constituents, the effects of combinations of compounds, and the interaction between these compounds and anti-cancer drugs. In addition, more research is needed to investigate likely drug ligand-receptor interactions for each of the bioactive compounds.

ObjectiveUntil effective treatments and vaccines are made readily and widely available, preventative behavioural health measures will be central to the SARS-CoV-2 public health response. While current recommendations are grounded in general infectious disease prevention practices, it is still not entirely understood which particular behaviours or exposures meaningfully affect one’s own risk of incident SARS-CoV-2 infection. Our objective is to identify individual-level factors associated with one’s personal risk of contracting SARS-CoV-2.DesignProspective cohort study of adult participants from 26 March 2020 to 8 October 2020.SettingThe COVID-19 Citizen Science Study, an international, community and mobile-based study collecting daily, weekly and monthly surveys in a prospective and time-updated manner.ParticipantsAll adult participants over the age of 18 years were eligible for enrolment.Primary outcome measureThe primary outcome was incident SARS-CoV-2 infection confirmed via PCR or antigen testing.Results28 575 unique participants contributed 2 479 149 participant-days of data across 99 different countries. Of these participants without a history of SARS-CoV-2 infection at the time of enrolment, 112 developed an incident infection. Pooled logistic regression models showed that increased age was associated with lower risk (OR 0.98 per year, 95% CI 0.97 to 1.00, p=0.019), whereas increased number of non-household contacts (OR 1.10 per 10 contacts, 95% CI 1.01 to 1.20, p=0.024), attending events of at least 10 people (OR 1.26 per 10 events, 95% CI 1.07 to 1.50, p=0.007) and restaurant visits (OR 1.95 per 10 visits, 95% CI 1.42 to 2.68, pConclusionsOur study identified three modifiable health behaviours, namely the number of non-household contacts, attending large gatherings and restaurant visits, which may meaningfully influence individual-level risk of contracting SARS-CoV-2.

Objectives This study sought to determine the most common oral herbal formula for menopausal symptoms in classical Chinese medicine textbooks and investigate its clinical effectiveness and potential mechanisms of action. Methods The most common formula used for menopause-like symptoms in past eras was identified from the Encyclopedia of Traditional Chinese Medicine. A systematic review of randomized controlled trials (RCTs) was undertaken and findings from relevant experimental studies were summarized. Results Licorice (Glycyrrhiza spp.) and jujube (Ziziphus jujuba Mill.) formula (LJF) was used in 63 of the 175 citations (36%) in the classical literature. Evidence from four RCTs showed that while LJF may improve sleep symptoms, there is insufficient evidence to provide recommendations for clinical practice. Experimental studies showed sedative, antidepressant-like, estrogenic and antiprogestogenic actions. Conclusions LJF has a long history of use for menopause-like symptoms, but further research is needed to confirm its clinical effects and guide clinical decision-making.

Increasing placebo effect sizes over time have been reported in randomized controlled trials (RCTs) for outcomes related to psychiatric symptoms. The Neuropsychiatric Inventory (NPI) is a key outcome measure in clinical trials of the behavioral and psychological symptoms of dementia (BPSD). Accurate placebo effect size estimates for NPI are needed for sample size calculations in order to adequately power future studies. This study investigated variation in placebo effect sizes for NPI in RCTs testing oral interventions for BPSD. A search of PubMed was conducted in April 2016 for two-armed, double-blinded, placebo-controlled RCTs testing any oral intervention for management of BPSD using the NPI. Meta-analysis was conducted of baseline versus end of treatment placebo group data of included studies. Twenty-five RCTs published from 2000 to 2015 were included. Substantial variation in placebo effect sizes was detected. Participants in placebo groups showed greater improvements in recent studies compared with earlier studies. Subgroup analyses indicated robustness of this finding. From 2000 to 2008 there was no significant change in total NPI scores within placebo groups (12 studies; 1,056 participants), whereas from 2009 to 2015 there was significant improvement (mean difference: −2.68; 95% confidence interval: −4.38, −0.99; z = 3.10; p = 0.002, random effects; I 2 = 76%; 13 studies; 1,170 participants). This increase in NPI effect sizes in placebo groups has important implications for power calculations for future clinical trials of BPSD. Effect size estimates for NPI need to be based on more recent studies.

This study evaluated the effect of local vanadyl acetylacetonate (VAC), an insulin mimetic agent, upon the early and late parameters of fracture healing in rats using a standard femur fracture model. Mechanical testing, and radiographic scoring were performed, as well as histomorphometry, including percent bone, percent cartilage, and osteoclast numbers. Fractures treated with local 1.5 mg/kg VAC possessed significantly increased mechanical properties compared to controls at 6 weeks post-fracture, including increased torque to failure (15%; p = 0.046), shear modulus (89%; p = 0.043), and shear stress (81%; p = 0.009). The radiographic scoring analysis showed increased cortical bridging at 4 weeks and 6 weeks (119%; p = 0.036 and 209%; p = 0.002) in 1.5 mg/kg VAC treated groups. Histomorphometry of the fracture callus at days 10 and 14 showed increased percent cartilage (121%; p = 0.009 and 45%; p = 0.035) and percent mineralized tissue (66%; p = 0.035 and 58%; p = 0.006) with local VAC treated groups compared to control. Additionally, fewer osteoclasts were observed in the local VAC treated animals as compared to controls at day 14 (0.45% ± 0.29% vs. 0.83% ± 0.36% of callus area; p = 0.032). The results suggest local administration of VAC acts to modulate osteoclast activity and increase percentage of early callus cartilage, ultimately enhancing mechanical properties comparably to non-diabetic animals treated with local VAC. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2174-2180, 2017.

This study reviewed the biological action of key herbs and evaluated systematically the efficacy and safety of oral Gentiana formula for herpes zoster (HZ). Experimental studies relevant to HZ were identified in PubMed. Randomized controlled trials using Gentiana formula for HZ were identified from nine English and Chinese databases. The primary outcome was evaluation of pain. Potential risk of bias was assessed. Meta-analysis was conducted using mean difference or risk ratio with 95% confidence intervals. Key herbs Gentiana scabra Bunge, Gentiana triflora Pall, Scutellaria baicalensis Georgi, and Gardenia jasminoides Ellis have shown antiinflammatory actions through inhibition of inflammatory cytokines and pro-inflammatory enzymes. Twenty-six clinical studies, involving 2955 participants, were included. Modified Gentiana formula resolved pain earlier than pharmacotherapy when used alone or combined with topical Chinese herbal medicine. Incidence of postherpetic neuralgia was lower (risk ratio 0.14, 95% confidence interval 0.03 to 0.74) with modified Gentiana formula plus topical Chinese herbal medicine. Mild adverse events were reported. Antiinflammatory actions of key herbs of Gentiana formula may explain clinical benefit in hastening pain relief and decreasing postherpetic neuralgia. Few adverse events were reported. Findings were limited by study quality and diversity in intervention and comparator dosage. Copyright © 2017 John Wiley & Sons, Ltd.