Efficacy of Chinese Medicine Treatment Based on Syndrome Differentiation for Primary Insomnia: A Randomized Placebo Controlled Triple-Blinded Trial.

OBJECTIVE: To assess efficacy of Chinese medicine (CM) on insomnia considering characteristics of treatment based on syndrome differentiation. METHODS: A total of 116 participants aged 18 to 65 years with moderate and severe primary insomnia were randomized to the placebo (n=20) or the CM group (n=96) for a 4-week treatment and a 4-week follow-up. Three CM clinicians independently prescribed treatments for each patient based on syndromes differentiation. The primary outcome was change in total sleep time (TST) from baseline. Secondary endpoints included sleep onset latency (SOL), wake time after sleep onset (WASO), sleep efficiency, Pittsburgh Sleep Quality Index (PSQI) and CM symptoms. RESULTS: The CM group had an average 0.6 h more (95% confidence interval (CI): 0.3-0.9, P<0.001) TST and 34.1% (10.3%-58.0%, P=0.005) more patients beyond 0.5 h TST increment than that of the placebo group. PSQI was changed -3.3 (-3.8 to -2.7) in the CM group, a -2.0 (-3.2 to -0.8, P<0.001) difference from the placebo group. The CM symptom score in the CM group decreased -2.0 (-3.3 to -0.7, P=0.003) more than the placebo group. SOL and WASO changes were not significantly different between groups. The analysis of prescriptions by these clinicians revealed blood deficiency and Liver stagnation as the most common syndromes. Prescriptions for these clinicians displayed relative stability, while the herbs varied. All adverse events were mild and were not related to study treatment. CONCLUSION: CM treatment based on syndrome differentiation can increase TST and improve sleep quality of primary insomnia. It is effective and safe for primary insomnia. In future studies, the long-term efficacy validation and the exploratory of eutherapeutic clinicians' fixed herb formulas should be addressed (Registration No. NCT01613183).

Dipeptidyl peptidase-4 inhibitors and the risk of infection: A systematic review and meta-analysis of cardiovascular outcome trials.

BACKGROUND: Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy. AIM: To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. METHODS: Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context. RESULTS: The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)]. CONCLUSION: This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

Triceps skinfold thickness trajectories and the risk of all-cause mortality: A prospective cohort study.

BACKGROUND: The measurement of triceps skinfold (TSF) thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution. Despite its clinical utility, the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated. AIM: To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality. METHODS: This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey. Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness. Subjects were classified into subgroups reflective of their respective TSF thickness trajectory. We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality, including contributory factors. RESULTS: Upon adjustment for multiple confounding factors, we discerned that males in the 'Class 2: Thin-stable' and 'Class 3: Thin-moderate' TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the 'Class 1: Extremely thin' subgroup. In the mediation analyses, the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality. For females, a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort. CONCLUSION: In males and non-elderly females, lower TSF thickness trajectories are significantly predictive of heightened mortality risk, independent of single-point TSF thickness, body mass index, and waist circumference.

Impact of a dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: A systematic review and pairwise and network meta-analysis.

AIMS: To evaluate the impact of a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide (TZP), and its potential dose-response effect, on heart rate. METHODS: Articles were searched from PubMed, Web of Science, Embase, Cochrane Library, and clinical trials registries (ClinicalTrials.gov) databases. Randomized controlled trials (RCTs) comparing TZP at doses of 5, 10 and 15 mg in adults with type 2 diabetes were included. Six study arms were summarized from original research (TZP 5, 10 and 15 mg, GLP-1 receptor agonists [GLP-1RAs], insulin, placebo). The GLP-1RA and non-GLP-1RA groups were combined to form a control group. Two reviewers independently extracted data and assessed the quality of each study. Mean differences (MDs) were calculated as effect estimates for continuous outcomes. Pairwise meta-analyses and network meta-analyses were conducted. The study protocol was prospectively registered (PROSPERO ID: CRD42023418551). RESULTS: Eight articles were included in this systematic review and meta-analysis. The mean baseline heart rate ranged from 65.2 to 75.7 beats per minute. Pairwise meta-analysis showed that, compared with combined the control group, there were significantly greater increases in heart rates in the TZP group (MD 1.82, 95% confidence interval [CI] 0.75, 2.89). Similar significant rises were identified when comparing TZP with GLP-1RAs and non-GLP-1RAs (GLP-1 RAs: MD 2.29, 95% CI 1.00, 3.59; non-GLP-1RAs: MD 1.58, 95% CI 0.26, 2.91). TZP 5 mg was associated with smaller increases in heart rates compared to TZP 10 mg and TZP 15 mg (TZP 10 mg: MD -0.97, 95% CI -1.79, -0.14; TZP 15 mg: MD -2.57, 95% CI -3.79, -1.35). TZP 10 mg increased heart rate less than TZP 15 mg (MD -1.5, 95% CI -2.38, -0.82). Network meta-analysis indicated that TZP 15 mg was associated with significant increases in heart rate compared with TZP 5 mg (MD 2.53, 95% CI 1.43, 3.62), TZP 10 mg (MD 1.44, 95% CI 0.35, 2.53), GLP-1RAs (MD 3.46, 95% CI 1.67, 5.25), insulin (MD 2.86, 95% CI 1.32, 4.41) and placebo (MD 2.96, 95% CI 1.36, 4.57). CONCLUSIONS: Our study showed not only that there was a greater increase in heart rate in the TZP group than in the control, GLP-1RA and non-GLP-1RA groups, but also that the 15-mg dose of TZP had the strongest impact on increasing heart rates compared with the other five inventions, with a TZP dose-response impact on heart rate. Further research on the effects of TZP treatment-related increases in heart rate is required.

Global, regional, and national time trends in cancer mortality attributable to high fasting plasma glucose: an age-period cohort analysis.

BACKGROUND: High fasting plasma glucose (HFPG) is the fastest-growing risk factor for cancer deaths worldwide. We reported the cancer mortality attributable to HFPG at global, regional, and national levels over the past three decades and associations with age, period, and birth cohort. METHODS: Data for this study were retrieved from the Global Burden of Disease Study 2019, and we used age-period-cohort modelling to estimate age, cohort and period effects, as well as net drift (overall annual percentage change) and local drift (annual percentage change in each age group). RESULTS: Over the past 30 years, the global age-standardized mortality rate (ASMR) attributable to HFPG has increased by 27.8%. The ASMR in 2019 was highest in the male population in high sociodemographic index (SDI) areas (8.70; 95% CI, 2.23-18.04). The net drift for mortality was highest in the female population in low SDI areas (2.33; 95% CI, 2.12-2.55). Unfavourable period and cohort effects were found across all SDI quintiles. Cancer subtypes such as "trachea, bronchus, and lung cancers", "colon and rectal cancers", "breast cancer" and "pancreatic cancer" exhibited similar trends. CONCLUSIONS: The cancer mortality attributable to HFPG has surged during the past three decades. Unfavourable age-period-cohort effects on mortality were observed across all SDI quintiles, and the cancer mortality attributable to HFPG is expected to continue to increase rapidly in the future, particularly in lower SDI locations. This is a grim global public health issue that requires immediate attention.

Development and validation of questionnaire-based machine learning models for predicting all-cause mortality in a representative population of China.

Background: Considering that the previously developed mortality prediction models have limited applications to the Chinese population, a questionnaire-based prediction model is of great importance for its accuracy and convenience in clinical practice. Methods: Two national cohort, namely, the China Health and Nutrition Survey (8,355 individual older than 18) and the China Health and Retirement Longitudinal Study (12,711 individuals older than 45) were used for model development and validation. One hundred and fifty-nine variables were compiled to generate predictions. The Cox regression model and six machine learning (ML) models were used to predict all-cause mortality. Finally, a simple questionnaire-based ML prediction model was developed using the best algorithm and validated. Results: In the internal validation set, all the ML models performed better than the traditional Cox model in predicting 6-year mortality and the random survival forest (RSF) model performed best. The questionnaire-based ML model, which only included 20 variables, achieved a C-index of 0.86 (95%CI: 0.80-0.92). On external validation, the simple questionnaire-based model achieved a C-index of 0.82 (95%CI: 0.77-0.87), 0.77 (95%CI: 0.75-0.79), and 0.79 (95%CI: 0.77-0.81), respectively, in predicting 2-, 9-, and 11-year mortality. Conclusions: In this prospective population-based study, a model based on the RSF analysis performed best among all models. Furthermore, there was no significant difference between the prediction performance of the questionnaire-based ML model, which only included 20 variables, and that of the model with all variables (including laboratory variables). The simple questionnaire-based ML prediction model, which needs to be further explored, is of great importance for its accuracy and suitability to the Chinese general population.

[Re-evaluation of systematic reviews of acupuncture and moxibustion for childhood autism].

OBJECTIVE: To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment. METHODS: The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence. RESULTS: A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias. CONCLUSION: Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.

Estimates and trends of the global burden of NASH-related liver cancer attributable to high fasting plasma glucose in 1990-2019: analysis of data from the 2019 Global Burden of Disease Study.

BACKGROUND: Experimental and epidemiological studies have indicated an association between diabetes exposure and an increased risk of liver cancer due to nonalcoholic steatohepatitis (NASH). However, to date, no systematic study has specifically investigated the burden of NASH-related liver cancer due to exposure to high fasting plasma glucose (HFPG) levels worldwide. METHODS: The number and rate of deaths and disability-adjusted life years (DALYs) from HFPG-induced NASH-related liver cancer were estimated based on the results of the 2019 Global Burden of Disease Study. The estimated annual percentage changes (EAPCs) for age-standardized death or DALYs rates were calculated using a generalized linear model with a Gaussian distribution to quantify the temporal trends in the global burden of NASH-related liver cancer attributable to HFPG. The strength and direction of the association between the sociodemographic index (SDI) and death or DALY rate were measured using Spearman's rank-order correlation. RESULTS: Globally, approximately 7.59% of all DALY and 8.76% of all mortalities of NASH-related liver cancer in 2019 were due to HFPG. The age-standardized death and DALY rates of NASH-related liver cancer attributable to HFPG increased from 1990 to 2019. The corresponding EAPCs were 0.69 (95% UI 0.48-0.89), and 0.30 (95% UI 0.05-0.56), respectively. This increasing pattern was most obvious in the high- and low-SDI regions. The age-standardized mortality and DALYs rate of NASH-related liver cancer attributable to HFPG varies considerably worldwide, with the middle SDI region having the highest death and DALY rates in 2019 (DALY 0.96 [95% UI 0.23-2.18]; death 0.05 [95% UI 0.01-0.11]). CONCLUSION: The burden of NASH-related liver cancer attributable to HFPG has increased over the past three decades, particularly in regions with high and low SDI.

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS: There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

Establishment of basic principles and methods of acupuncture standardization in traditional Chinese medicine / 数字中医药（英文）

@#Standardization is the universal language of the world, and standardization of traditional Chinese medicine (TCM) is essential for its communication in China and globally. However, the principles and methods of TCM acupuncture standardization have been unclear and inadequate in the early stages. Based on an investigative approach to understanding the current status, identifying problems, and finding solutions, our team has established basic principles of TCM acupuncture that embody Chinese wisdom, evaluated the international strategic environment systematically, proposed the principle of “importance of harmony and exercise of impartiality”, and established basic working principles. A series of methods for TCM acupuncture standard development and evaluation have been constructed, including general standards for the revision of TCM acupuncture standards, the first TCM acupuncture clinical research management specification, a shared full chain technology platform, a data center, and an evaluation research base for TCM acupuncture clinical research. Evaluation criteria for ancient literature and expert experience, a recommendation method for the “three main and three auxiliaries” TCM guideline for prevention were established, and quantifiable assessment methods of TCM standard applicability were proposed. These findings provide methodological guidance for TCM acupuncture standardization.

[Stable angina pectoris of coronary heart disease treated with different acupuncture and moxibustion therapies: a network Meta-analysis].

To compare the clinical efficacy among different acupuncture and moxibustion therapies on stable angina pectoris (SAP) of coronary heart disease by means of network Meta-analysis. The articles of randomized controlled trial (RCT) for SAP of coronary heart disease treated with acupuncture and moxibustion therapies were searched from PubMed, Web of Science, Cochrane Library, CNKI, Wanfang database and VIP database from May 1, 2002 to May 1, 2022. The quality of them was assessed with the risk of bias assessment tool of Cochrane 5.3, and the network Meta-analysis was undertaken with Stata 13.1 software. A total of 29 articles were included with the acupuncture and moxibustion therapies involved, e.g. acupuncture, acupoint application and moxibustion. In comparison with the simple routine western medication, the effective rate was better on SAP treated with the combined treatments, in which, acupoint application, moxibustion, acupuncture and intradermal needling were combined with routine western medication (P<0.05). Of those combined treatments, the combination of the acupoint application with routine western medication had high probability, suggesting the optimal regimen (area under the curve [SUCRA]=0.711, P<0.05). The effective rate of acupuncture combined with routine western medication for ECG improvement was better than that of routine western medication (P<0.05), and such combined treatment was high in probability, underlying its optimal treatment (SUCRA=0.800, P<0.05). Combined with routine western medication, acupuncture, acupoint application, moxibustion and intradermal needling all improve the clinical efficacy on SAP of coronary heart disease. But, with different outcomes considered, the optimal treatments may be different. It needs more multi-central and large-sample randomized controlled trials to validate these results.

Acupuncture Case Registry Study: Rationale, Implementations, and Achievements.

The acupuncture case registry study is focusing on acupuncture therapy data from patient cases. The main objective is to collect real-world data and integrate clinically meaningful outcome evaluation indicators to uncover and evaluate real-world acupuncture efficacy and safety, explore factors affecting acupuncture efficacy, and provide real-world evidence to complement RCTs. Since the International Acupuncture Case Registry data collection system's establishment in 2017, 16 projects have been underway, including two acupuncture specialty therapies and 15 diseases. Data from 3404 patients included extensive information on the diagnosis and treatment of acupuncture and the evaluation of its efficacy. In order to serve as a guide for future studies, this article discusses the value of and rationale for establishing acupuncture case registry studies, how to distinguish them from patient registries, and crucial techniques for implementing registry studies in terms of applications, patient recruitment, costakeholder collaboration, data collection and management, study quality control, and ethics.

Occupational and domestic physical activity and diabetes risk in adults: Results from a long-term follow-up cohort.

Background: Physical activity (PA) has been associated with decreased incidence of diabetes. However, few studies have evaluated the influence of occupational and domestic PA on the risk of diabetes with a long-term follow-up. We aimed to examine the association between occupational and domestic PA and the risk of diabetes in a long-term prospective cohort of Chinese adults. Methods: A total of 10,343 adults who were followed up in the China Health and Nutrition Survey from 1997 to 2015 were included in our analysis. Occupational and domestical PA were collected with detailed seven-day data and were converted into metabolic equivalents values. Total PA included occupational, domestic, transportation, and leisure time PA. Diabetes cases were identified by self-reported doctor/health professional diagnosis of diabetes, fasting blood glucose ≥7.0 mmol/L, and glycosylated hemoglobin (HbA1c) ≥6.5%. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: During up to 18 years of follow-up (median 10 years), there were 575 diabetes cases documented. Occupational PA accounted for the majority of total PA (68%) in Chinese population, followed by domestic PA (25%). With adjustments for possible covariates, the highest quartiles of total PA (HR, 0.728 [95% CI, 0.570-0.929]) and occupational PA (HR, 0.765 [95% CI, 0.596-0.982]) were significantly associated with a lower risk of diabetes compared with lowest quartiles. The association between domestic PA and the risk of diabetes was insignificant (P >0.05). Conclusion: Higher levels of occupational PA were associated with a decreased risk of diabetes risk in the Chinese population. Domestic PA was not associated with the incidence of diabetes.

[Minimal clinically important difference of the frequency of bowel movement for patients with chronic severe functional constipation treated with acupuncture].

OBJECTIVE: To estimate the minimal clinically important difference (MCID) of the frequency of bowel movement for the patients with chronic severe functional constipation treated with acupuncture so as to provide the evidence for the clinical decision. METHODS: In this study, 813 patients with chronic severe functional constipation treated with acupuncture in two previous randomized controlled trials were included. Through the anchor-based method (anchored by the item 28 "satisfaction with previous treatment" of the patient assessment of constipation-quality of life [PAC-QOL]) and the distribution-based method, the MCID of the weekly frequency of complete spontaneous bowel movement (CSBM) and spontaneous bowel movement (SBM) was analyzed statistically in the patients. RESULTS: The MCID of the mean weekly frequency of CSBM and SBM was 1.3 times and 1.6 times in patients with chronic severe functional constipation treated with acupuncture, respectively. CONCLUSION: The mean increase of the weekly CSMB is ≥ 1.3 times and that of SBM is ≥ 1.6 times after treatment when compared with the baseline respectively, suggesting the clinical significance.

Dietary patterns, oxidative Stress, inflammation and biological variation in hemoglobin A1c: Association and Mediation analysis in a rural community in north China.

OBJECTIVE: The aim is to assess the relationship between the hemoglobin glycation index(HGI) and dietary patterns, and investigates whether inflammation and oxidative stress mediate the relationship. METHODS: Cross-sectional data were collected from 453 dwellers in a Chinese rural community. Diet was assessed using 24 h food recalls. Based on the energy intake ratio from three macronutrients, dietary patterns were identified by cluster analysis. The HGI was defined as the observed HbA1c minus predicted HbA1c. Indicators of inflammation and oxidative stress were assessed. RESULT: 3 dietary patterns were clustered, namely "fat(n = 100)", "balance(n = 186)" and "carbohydrate(n = 167)". The fat dietary patterns had lower HGI than the other two dietary patterns. TNFα was higher in the carbohydrate dietary pattern. Linear regression analysis suggested that the carbohydrate dietary pattern was correlated with higher HGI levels(ß = 0.204,95 %CI(0.071,0.338)), compared with the fat dietary pattern. The relationship disappeared after accounting for biomarkers of inflammation and oxidative stress. Mediation analyses indicated that TNFα might explain for 19.15 % effects of the carbohydrate dietary pattern on HGI, compared with the fat dietary pattern. CONCLUSION: The carbohydrate dietary pattern had positive associations with HGI and TNFα. TNFα partly mediated the relationship between dietary patterns and HGI.

Postmarketing Reevaluation of Chinese Traditional Therapy Kangbingdu Oral Liquid in the Treatment of the Common Cold.

Background: Observational studies from China suggest that Kangbingdu oral liquid (KBD) may be effective in treating the common cold. Objective: Reevaluation of efficacy and safety of Kangbingdu oral liquid after marketing and expanding population. Design: Prospective, Pragmatic randomized controlled trial (Chictr.org.cn registration number: chiCTR-TRC-12002399). Setting. Eleven hospitals from 3 provinces in China. Patients were recruited through 11 centers, including 7 teaching hospitals, 2 University health services, one military clinic, and one community hospital. Patients. 2647 persons aged 18 to 75 years with Common cold. Intervention. Patients were randomly allocated to 2 groups: the treatment group Kangbingdu oral liquid (composed of 9 Chinese herbal medicines and honey) and the placebo group were divided into a standard-dose group of 10 ml every time, a middle dose group of 20 ml every time, high dose group of 30 ml every time, 3 times daily. Interventions and control were given for 5 days. Measurements. The primary outcome is the mean amount of total scores measured by the 11-primary symptoms: to observe the change of main symptoms from severe to disappear and to calculate and compare the mean amount of total scores after the periods of observation. Secondary outcomes are the disappearance rate of each symptom and the median time of body temperature returned to normal. Results: On day 5, the Kangbingdu liquid group had significant reductions in the mean amount of total scores measured by the 11-primary symptoms (7.39 [95% CI 7.26 to 7.51] compared to the placebo group (6.43 [95%: CI 6.24 to 6.62]). The Kangbingdu liquid can improve the remission rate of accompanying symptoms on day 5 including aversion to wind, aversion to cold, fever, cough, stuffy, runny nose, sore throat, muscular aches, headache, fatigue, and sweat (P < 0.0001). Significant reductions in time of body temperature to return to normal in the Kangbingdu liquid group (P50, 48.33 [95% CI 46.00 to 52.50] compared with the control group (P50, 64.59 [95% CI 51.08 to 70.50] (P=0.0022). 13 (0.7%) participants in the Kangbingdu liquid group and 1(0.2%) participants in the placebo group (P > 0.05) had treatment-related AEs, which mainly include diarrhea and dyspepsia in the Kangbingdu liquid group and constipation in the placebo group. Conclusion: The study's conclusion in this paper was based on the placebo, Kangbingdu oral liquid two groups which clinically diagnosed the common cold and flu. (1) Kangbingdu oral liquid can effectively improve the comprehensive clinical symptoms of common adult cold, also improved main symptoms, including sore throat, muscle aches, headache, and so on. (2) Kangbingdu oral liquid effectively shortens the time of body temperature to return to normal.

Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials.

OBJECTIVE: To examine the association between dipeptidyl peptidase-4 inhibitors and gallbladder or biliary diseases. DESIGN: Systematic review and pairwise and network meta-analysis. DATA SOURCES: PubMed, EMBASE, Web of Science, and CENTRAL from inception until 31 July 2021. ELIGIBILITY CRITERIA: Randomised controlled trials of adult patients with type 2 diabetes who received dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors compared with placebo or other antidiabetes drugs. MAIN OUTCOME MEASURES: Composite of gallbladder or biliary diseases, cholecystitis, cholelithiasis, and biliary diseases. DATA EXTRACTION AND DATA SYNTHESIS: Two reviewers independently extracted the data and assessed the quality of the studies. The quality of the evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework (GRADE) approach. The meta-analysis used pooled odds ratios and 95% confidence intervals. RESULTS: A total of 82 randomised controlled trials with 104 833 participants were included in the pairwise meta-analysis. Compared with placebo or non-incretin drugs, dipeptidyl peptidase-4 inhibitors were significantly associated with an increased risk of the composite of gallbladder or biliary diseases (odds ratio 1.22 (95%confidence interval 1.04 to 1.43); risk difference 11 (2 to 21) more events per 10 000 person years) and cholecystitis (odds ratio 1.43 (1.14 to 1.79); risk difference 15 (5 to 27) more events per 10 000 person years) but not with the risk of cholelithiasis and biliary diseases. The associations tended to be observed in patients with a longer duration of dipeptidyl peptidase-4 inhibitor treatment. In the network meta-analysis of 184 trials, dipeptidyl peptidase-4 inhibitors increased the risk of the composite of gallbladder or biliary diseases and cholecystitis compared with sodium-glucose cotransporter-2 inhibitors but not compared with glucagon-like peptide-1 receptor agonists. CONCLUSIONS: Dipeptidyl peptidase-4 inhibitors increased the risk of cholecystitis in randomised controlled trials, especially with a longer treatment duration, which requires more attention from physicians in clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021271647.

Efficacy Analysis of the Reinforcing and Circulation-Promoting Protocol of Acupuncture and Moxibustion in Treatment of Twenty-Four Patients with Refractory Chronic Low Back Pain.

Objectives: The purpose of this study was to observe the clinical efficacy of the reinforcing and circulation-promoting protocol of acupuncture and moxibustion in treatment of refractory chronic low back pain, analyze therapeutic principles to obtain treatment efficacy, and develop new therapeutic principles to treat chronic low back pain. Methods: Twenty-four patients from the registry of patients suffering from refractory chronic low back pain were invited to our self-controlled case series, which was conducted in "real-world" settings. We implemented the reinforcing and circulation-promoting protocol of acupuncture and moxibustion to treat these patients and used the Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) as the observation indices. Results: All 24 patients completed the treatment of acupuncture and moxibustion. The VAS of low back pain was 6.83 ± 2.18 before treatment and 2.13 ± 1.45 after treatment. The difference before and after treatment was significant (P < 0.001). The ODI was 28.21 ± 13.06 before treatment and 16.63 ± 7.20 after treatment. Their difference before and after treatment was significant (P < 0.001). Conclusion: The reinforcing and circulation-promoting protocol of acupuncture and moxibustion is effective in treating refractory chronic low back pain mainly because low back pain can be significantly relieved and motor function can be promoted. This trial was registered with AMCTR-OOO-17000045 (3 December 2016).