[Network Meta-analysis of Chinese patent medicines in treatment of coronary heart disease complicated with heart failure].

The efficacy and safety of different Chinese patent medicines in the treatment of coronary heart disease complicated with heart failure were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for coronary heart disease complicated with heart failure was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to July 5, 2023. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool, and a network Meta-analysis was performed in Stata 16.0. Finally, a total of 82 RCTs were included, involving 9 298 patients and 11 Chinese patent medicines. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of improving the clinical response rate, the top three interventions were Qishen Yiqi Dripping Pills + conventional western medicine, Zhenyuan Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(2) In terms of increasing left ventricular ejection fraction(LVEF), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Compound Danshen Dripping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(3) In terms of reducing left ventricular end-diastolic diameter(LVEDD), the top three interventions were Shexiang Tongxin Dripping Pills + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(4) In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Qi-shen Yiqi Dripping Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(5) In terms of reducing hyper-sensitive C-reactive protein(hs-CRP), the top three interventions were Naoxintong Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(6) In terms of increasing the distance of the six-minute walking trail(6MWT), the top three interventions were Zhen-yuan Capsules + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Qishen Yiqi Dripping Pills + conventional western medicine. The results showed that Chinese patent medicines combined with conventional western medicine can effectively improve the clinical response rate, LVEF, and 6MWT and reduce LVEDD, NT-proBNP, and hs-CRP. However, due to the overall low quality of the articles included and the few articles of some Chinese patent medicines, direct comparison between diffe-rent Chinese patent medicines remains to be carried out and the results need to be further verified.

Phototherapy techniques for the management of musculoskeletal disorders: strategies and recent advances.

Musculoskeletal disorders (MSDs), which include a range of pathologies affecting bones, cartilage, muscles, tendons, and ligaments, account for a significant portion of the global burden of disease. While pharmaceutical and surgical interventions represent conventional approaches for treating MSDs, their efficacy is constrained and frequently accompanied by adverse reactions. Considering the rising incidence of MSDs, there is an urgent demand for effective treatment modalities to alter the current landscape. Phototherapy, as a controllable and non-invasive technique, has been shown to directly regulate bone, cartilage, and muscle regeneration by modulating cellular behavior. Moreover, phototherapy presents controlled ablation of tumor cells, bacteria, and aberrantly activated inflammatory cells, demonstrating therapeutic potential in conditions such as bone tumors, bone infection, and arthritis. By constructing light-responsive nanosystems, controlled drug delivery can be achieved to enable precise treatment of MSDs. Notably, various phototherapy nanoplatforms with integrated imaging capabilities have been utilized for early diagnosis, guided therapy, and prognostic assessment of MSDs, further improving the management of these disorders. This review provides a comprehensive overview of the strategies and recent advances in the application of phototherapy for the treatment of MSDs, discusses the challenges and prospects of phototherapy, and aims to promote further research and application of phototherapy techniques.

Integrative analysis of microbiota and metabolomics in chromium-exposed silkworm (Bombyx mori) midguts based on 16S rDNA sequencing and LC/MS metabolomics.

The gut microbiota, a complex ecosystem integral to host wellbeing, is modulated by environmental triggers, including exposure to heavy metals such as chromium. This study aims to comprehensively explore chromium-induced gut microbiota and metabolomic shifts in the quintessential lepidopteran model organism, the silkworm (Bombyx mori). The research deployed 16S rDNA sequence analysis and LC/MS metabolomics in its experimental design, encompassing a control group alongside low (12 g/kg) and high (24 g/kg) feeding chromium dosing regimens. Considerable heterogeneity in microbial diversity resulted between groups. Weissella emerged as potentially resilient to chromium stress, while elevated Propionibacterium was noted in the high chromium treatment group. Differential analysis tools LEfSe and random forest estimation identified key species like like Cupriavidus and unspecified Myxococcales, offering potential avenues for bioremediation. An examination of gut functionality revealed alterations in the KEGG pathways correlated with biosynthesis and degradation, suggesting an adaptive metabolic response to chromium-mediated stress. Further results indicated consequential fallout in the context of metabolomic alterations. These included an uptick in histidine and dihydropyrimidine levels under moderate-dose exposure and a surge of gentisic acid with high-dose chromium exposure. These are critical players in diverse biological processes ranging from energy metabolism and stress response to immune regulation and antioxidative mechanisms. Correlative analyses between bacterial abundance and metabolites mapped noteworthy relationships between marker bacterial species, such as Weissella and Pelomonas, and specific metabolites, emphasizing their roles in enzyme regulation, synaptic processes, and lipid metabolism. Probiotic bacteria showed robust correlations with metabolites implicated in stress response, lipid metabolism, and antioxidant processes. Our study reaffirms the intricate ties between gut microbiota and metabolite profiles and decodes some systemic adaptations under heavy-metal stress. It provides valuable insights into ecological and toxicological aspects of chromium exposure that can potentially influence silkworm resilience.

[Outcome indicators in clinical trials on traditional Chinese medicine treatment of microvascular angina].

This study reviewed the current status of the use of outcome indicators in randomized controlled trial(RCT) on traditional Chinese medicine(TCM) treatment of microvascular angina(MVA) and analyzed the existing problems and possible solutions, aiming to provide a basis for the design of high-quality RCT and the establishment of core outcome sets for MVA. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries were searched for the RCT on TCM treatment of MVA according to pre-defined criteria. The Cochrane's risk of bias assessment tool was used to evaluate the methodological quality of the included RCT and the use of outcome indicators was summarized. A total of 69 RCTs were included, from which 100 outcome indicators were extracted, with the frequency of 430. The extracted outcome indicators belonged to 8 domains: response rate, symptoms and signs, physical and chemical examinations, TCM efficacy, safety, quality of life, economic evaluation, and long-term prognosis. The indicators of physical and chemical examinations were the most(70 indicators with the frequency of 211), followed by those of response rate(7 indicators with the frequency of 73) and symptoms and signs(7 indicators with the frequency of 54). The outcome indicators with higher frequency were adverse reactions, angina attack frequency, clinical efficacy, endothelin-1, total duration of treadmill exercise, and hypersensitive C-reactive protein. The RCT on TCM treatment of MVA had the following problems: irregular reporting of adverse reactions, diverse indicators with low frequency, lack of attention to the application of endpoint indicators, insufficient use of TCM differentiation and efficacy indicators, non-standard evaluation criteria and failure to reflect the basic characteristics of TCM. A unified MVA syndrome differentiation standard should be established, on the basis of which an MVA treatment efficacy evaluation system and core outcome indicator set that highlights the characteristics of TCM with patient-reported outcomes as the starting point should be established to improve the clinical research and research value.

Association between serum-free thyroxine level and all-cause mortality in critically ill patients: a retrospective study from MIMIC-IV.

Background: Low thyroxine (T4) levels have been observed in critically ill patients; however, controversial results regarding T4 supplemental therapy are reported. The association between serum free T4 (FT4) levels and mortality in critically ill patients has not been fully established and needs to be clarified. Methods: Data from the Medical Information Mart for Intensive Care (MIMIC)-IV were collected and analyzed. The association between FT4 level and 30-day mortality after ICU admission was analyzed using Kaplan-Meier curves, spline smoothing fitting, martingale residuals of the null Cox model, and restricted cubic spline (RCS). Logistic regression, Cox regression, and receiver operating characteristic curve (ROC) were used to uncover the relationship and predictive value of serum FT4 and 30-day mortality in critically ill patients. Results: In the final analysis, 888 patients were enrolled, and the serum FT4 levels were divided into four groups. A significant difference in 30-day mortality was observed between the four groups. Kaplan-Meier curves also presented significantly higher 30-day mortality in groups 1 and 2 (p < 0.0001). Further multivariance logistic regression showed that group 1 with FT4 levels lower than 0.7 µg/dl can predict 30-day mortality (odds ratio (OR) = 3.30, 95% confidence interval (CI) = 1.04-11.31). Spline smoothing fitting analysis showed a "V"-shaped line between 30-day mortality and FT4 level within 0-3 µg/dl. Further RCS analysis showed that the risk of death decreased rapidly as FT4 levels increased when serum FT4 levels were lower than 1.2 µg/dl and started to become flat afterward. The area under the ROC of the lower FT4 level to predict 30-day mortality was 0.833 (95% CI = 0.788-0.878). Both multivariant Cox regression and logistic regression showed that FT4 levels lower than 1.2 µg/dl can independently predict 30-day mortality when adjusted for other potential confounders (HR = 0.34, 95% CI = 0.14-0.82; OR = 0.21, 95% CI = 0.06-0.79, respectively), but its predictive power disappeared when adjusted for T3 or total T4. Conclusion: Serum FT4 levels were significantly negatively associated with 30-day mortality when they were lower than 1.2 µg/dl and could predict the risk of 30-day mortality. A higher FT4 level is potentially related to increased 30-day mortality.

Construction and validation of nomograms to reduce completion thyroidectomy by predicting lymph node metastasis in low-risk papillary thyroid carcinoma.

CONTEXT: More than 5 central lymph nodes metastases (CLNM) or lateral lymph node metastasis (LLNM) indicates a higher risk of recurrence in low-risk papillary thyroid carcinoma (PTC) and may lead to completion thyroidectomy (CTx) in patients initially undergoing lobectomy. OBJECTIVE: To screen potentially high-risk patients from low-risk patients by using preoperative and intraoperative clinicopathological features to predict lymph node status. METHODS: A retrospective analysis of 8301 PTC patients in Wuhan Union Hospital database (2009-2021) was performed according to the 2015 American Thyroid Association (ATA) and 2021 National Comprehensive Cancer Network (NCCN) guidelines, respectively. Logistic regression and best subsets regression were used to identify risk factors. Nomograms were established and externally validated using the Differentiated Thyroid Cancer in China cohort. RESULTS: More than 5 CLNM or LLNM was detected in 1648 (19.9%) patients. Two predictive models containing age, gender, maximum tumor size, free thyroxine (FT4) and palpable node (all p < 0.05) were established. The nomogram based on NCCN criteria showed better discriminative power and consistency with a specificity of 0.706 and a sensitivity of 0.725, and external validation indicated that 76% of potentially high-risk patients could achieve preoperative conversion of surgical strategy. CONCLUSIONS: Models based on large cohorts with good predictive performance were constructed and validated. Preoperative low-risk (T1-2N0M0) patients with age younger than 40 years, male gender, large tumor size, low FT4 and palpable nodes may be at high risk of LLNM or more than 5 CLNM, and they should receive more aggressive initial therapy to reduce CTx.

[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.

Development of a core outcome set in the clinical trials of traditional Chinese medicine for diabetic foot: A study protocol.

Background: Diabetic Foot (DF) is one of the most common complications of diabetes, and it is characterized by high morbidity, disability, lethality and low cure rate. Traditional Chinese medicine treatment has certain characteristics and advantages in diabetic foot. Due to selective reporting bias and heterogeneity of research results, on the one hand, relevant clinical studies are of low quality and poor practicability, and on the other hand, similar studies cannot be included in meta-analysis to form high-quality evidence-based evidence and evaluate the value of studies. Therefore, the development of a core set of outcomes (COS-TCM-DF) for traditional Chinese medicine for the treatment of diabetic foot is an important way to address these issues. Methods: The COS-TCM-DF project will refer to the developed COS methodology and the steps are divided into four stages: (1) a scoping review and analysis of enrolled research protocols to collect and analyze all existing outcomes that have been used in trials on the prevention or treatment of diabetic foot with Chinese Medicine; (2) qualitative interviews with Diabetic foot patient and attendants to Collect additional outcomes related to them; (3) Gather opinionest and obtain initial consensus from key stakeholders, including patients, clinicians, researchers, and pharmaceutical company staff, through a Delphi survey; (4) a consensus meeting was held to develop the final COS-TCM-DF. Discussion: Currently, there is no COS on measuring or monitoring diabetic foot with TCM in trials or clinical practice. The COS-TCM-DF will be developed to advance the synthesis of evidence regarding the prevention and treatment of diabetic foot in TCM and to promote the standardized and consistent application of results in future studies in this field. Trial registration: Registered with the Core Outcome Measures in Effectiveness Trials (COMET) database, December 2019 https://www.comet-initiative.org/Studies/Details/1553.

Abundant and diverse endophytic bacteria associated with medicinal plant Arctium lappa L. and their potential for host plant growth promoting.

Arctium lappa L. is one of the medicinal and food homologous plants in China, which is rich in nutrients and medicinal ingredients. The use of plant growth-promoting (PGP) endophytic bacteria is an alternative to reducing chemical fertilizers in agricultural production. The aim of this study was to analyze the diversity of endophytic bacteria in different cultivars of A. lappa L. collected from two geographical locations in China and evaluate PGP traits of the isolates and their potential PGP ability in greenhouse condition. Endophytic bacterial community was investigated by culture-dependent and culture-independent methods. Isolates were screened and investigated for multiple PGP traits, and representative strains were inoculated host seedlings to evaluate the growth promoting effect. A total of 348 endophytic bacteria were obtained and they were distributed into 4 phyla and 30 genera. In addition, high throughput sequencing revealed more abundant bacterial community, including 17 bacterial phyla and 207 genera. A high proportion of PGP traits were detected, including production of indole acetic acid, siderophore, ammonia and phosphate solubilization. Four representative strains with multiple PGP traits of the most dominant genera (Bacillus, Pantoea, Microbacterium and Pseudomonas) were further selected for host inoculation and growth promoting evaluation, and they significantly increase seedlings length, root length and fresh weight. This study demonstrated that A. lappa L. harbors abundant endophytic bacteria, and some endophytic bacteria showed good potential for the development of microbial fertilizer in the future.

20(S)-ginsenoside Rh1 alleviates T2DM induced liver injury via the Akt/FOXO1 pathway.

Diabetes-associated liver injury becomes a dominant hepatopathy, leading to hepatic failure worldwide. The current study was designed to evaluate the ameliorative effects of ginsenoside Rh1 (G-Rh1) on liver injury induced by T2DM. A T2DM model was established using C57BL/6 mice through feeding with HFD followed by injection with streptozotocin at 100 mg·kg-1.. Then the mice were continuously administered with G-Rh1 (5 and 10 mg·kg-1), to explore the protective effects of G-Rh1 against liver injury. Results showed that G-Rh1 exerted significant effects on maintaining the levels of FBG and insulin, and ameliorated the increased levels of TG, TC and LDL-C induced by T2DM. Moreover, apoptosis in liver tissue was relieved by G-Rh1, according to histological analysis. Particularly, in diabetic mice, it was observed that not only the increased secretion of G6Pase and PEPCK in the gluconeogenesis pathway, but also inflammatory factors including NF-κB and NLRP3 were suppressed by G-Rh1 treatment. Furthermore, the underlying mechanisms by which G-Rh1 exhibited ameliorative effects was associated with its capacity to inhibit the activation of the Akt/FoxO1 signaling pathway induced by T2DM. Taken together, our preliminary study demonstrated the potential mechnism of G-Rh1 in protecting the liver against T2DM-induced damage.

Quality Evaluation and Reporting Specification for Real-World Studies of Traditional Chinese Medicine.

In recent years, the real-world studies (RWS) have attracted extensive attention, and the real-world evidence (RWE) has been accepted to support the drug development in China and abroad. However, there is still a lack of standards for the evaluation of the quality of RWE. It is necessary to formulate a quality evaluation and reporting specification for RWE especially in traditional Chinese medicine (TCM). To this end, under the guidance of China Association of Chinese Medicine, the Quality Evaluation and Reporting Specification for Real-World Evidence of Traditional Chinese Medicine (QUERST) Group, including 24 experts (clinical epidemiologists, clinicians, pharmacologists, ethical reviewer and statisticians), was established to develop the specification. This specification contains the listing of classification of RWS design and RWE, the general principles and methods of RWE quality evaluation (26 tools or scales), 25 types of bias in RWS, the special considerations in evaluating the quality of RWE of TCM, and the 19 reporting standards of RWE. This specification aims to propose the quality evaluation principles and key points of RWE, and provide guidance for the proper use of RWE in the development of TCM new drugs.

[Acupoint application for exogenous fever: a multi-central retrospective cohort study].

OBJECTIVE: To explore the effectiveness on exogenous fever and the characteristics of effective population, as well as the specialties of prescription of acupoint application. METHODS: Using the internet electronic diagnosis and treatment platform (Spring Broadcast Wanxiangyun Clinic Database, and the main TCM suitable technology promoted by this platform is acupoint application therapy), from August 24, 2020 to November 5, 2020, the patients complained with fever and diagnosed as common cold, with a record of initial visit and at least one return visit, were included as the subjects. According to whether acupoint application therapy was received or not, the subjects were divided into an exposure group (with acupoint application therapy, 26 664 cases) and a non-exposure group (without acupoint application therapy, 515 cases). Using the propensity score, the mixed factors, e.g. age and sex, were matched between the two groups. The disappearance rate of fever (within 2 days) and the time for the first fever disappearance were taken as the effect indexes. The association rules extraction was adopted to analyze the characteristics of effective population and acupoint application prescription in treatment of exogenous fever. RESULTS: After propensity score matching, there were 1 229 cases in the application group and 423 cases in the non-application group. The disappearance rate of fever in the application group was 1.82 times as high as that in the non-application group (P<0.05). The time for the first fever disappearance in the application group was shorter than the non-application group (P<0.01). A total of 5 370 cases were effective with acupoint application therapy, of which, the median age was 2 years old and the proportion of children patients under 6 years old was relatively high. In the effective crowd, the most commonly-used acupoints were Shenque (CV 8), Dazhui (GV 14), Yongquan (KI 1) and Tiantu (CV 22), etc. Shenque (CV 8) and Dazhui (GV 14) were highly associated and the support was 62.57%. The most common herbal materials in the acupoint application therapy included Radix et Rhizoma Rhei, Natrii Sulfas, Radix Scutellariae, Herba Ephedrae and Radix Bupleuri, etc. Radix et Rhizoma Rhei and Natrii Sulfas were most commonly used at Shenque (CV 8) and the supports were 57.49% and 57.21% respectively. Herba Ephedrae was most commonly applied to Shenque (CV 8) and Dazhui (GV 14) and the supports were 48.21% and 43.91% respectively. Radix Bupleuri was the most common herb at Dazhui (GV 14) with the support of 46.61%. Besides, the most commonly combined western drugs included cefixime and keteling in the acupoint application therapy and the supports were 13.07% and 12.72% respectively. CONCLUSION: Acupoint application is effective on exogenous fever. The common therapy refers to Radix et Rhizoma Rhei and Natrii Sulfas plaster at Shenque (CV 8), while Herba Ephedrae and Radix Bupleuri at Dazhui (GV 14).

[Influence of acupoint application on clinical use of antibiotics: a real world study of 1.23 million primary clinic patients].

OBJECTIVE: To observe the influence of acupoint application on the use of antibiotics in primary clinic practice, and explore the effect of acupoint application and its influence on the use of antibiotics based on common diseases in primary clinic (fever, cough, diarrhea, sore throat). METHODS: With the help of the internet electronic diagnosis and treatment platform (the main TCM suitable technology promoted by this platform is acupoint application therapy), the diagnosis and treatment data of 1.23 million patients in 2 000 primary clinics from August 24, 2020 to March 31, 2021 were collected. The patients were divided into an application group (acupoint application treatment) and a non-application group (non-acupoint application treatment), and the proportion of antibiotic use in the two groups was compared. The propensity score was used to match age, gender, concomitant symptoms, diagnosed diseases and other confounding factors of treatment, and the disappearance rate of symptoms (fever, cough, diarrhea, sore throat) and the time to first disappearance of symptoms were compared between the two groups. RESULTS: A total of 1 230 923 patients were analyzed, including 1 048 382 cases in the application group, accounting for 85.2%; 182 541 cases in the non-application group, accounting for 14.8%. The most patients who used acupoint application treatment were 0-2 years old, followed by 3-6 years old, and the patients over 15 years old who did not use acupoint application treatment were the most. The proportion of antibiotic use in the application group was 2.4%, lower than that in the non-application group (44.2%, P<0.001). The proportion of antibiotic use in all ages of patients in the application group was lower than that in the non-application group (P<0.001). Among the common diseases in primary clinic (fever, cough, diarrhea and sore throat), the proportion of antibiotic use in the application group was lower than that in the non-application group (P<0.01); the disappearance rate of symptoms in the application group was higher than that in the non-application group, and the time to first disappearance of symptoms was shorter than that in the non-application group (P<0.001). CONCLUSION: Acupoint application has a certain influence on the use of antibiotics in primary clinic patients. In the treatment of common diseases, patients treated with acupoint application have better curative effect and lower proportion of antibiotic use.

Using Structural Equation Modeling to Untangle Pathways of Risk Factors Associated with Incident Type 2 Diabetes: the Lifelines Cohort Study.

Risk factors for type 2 diabetes are multifaceted and interrelated. Unraveling the complex pathways of modifiable risk factors related to incident type 2 diabetes will help prioritize prevention targets. The current analysis extended a previously proposed conceptual model by Bardenheier et al. (Diabetes Care, 36(9), 2655-2662, 2013) on prediabetes with a cross-sectional design. The model described the pathways of four aspects of modifiable risk factors in relation to incident type 2 diabetes, including socioeconomic status (income and education); lifestyle behaviors (diet quality, physical activity, TV watching, smoking, risk drinking, and unhealthy sleep duration); clinical markers (HDL-cholesterol, triglycerides, BMI, and waist circumference); and blood pressure. We performed structural equation modeling to test this conceptual model using a prospective population-based sample of 68,649 participants (35-80 years) from the Lifelines cohort study. During a median follow-up of 41 months, 1124 new cases of type 2 diabetes were identified (incidence 1.6%). The best-fitting model indicated that among all modifiable risk factors included, waist circumference had the biggest direct effect on type 2 diabetes (standardized ß-coefficient 0.214), followed by HDL-cholesterol (standardized ß-coefficient - 0.134). Less TV watching and more physical activity were found to play an important role in improving clinical markers that were directly associated with type 2 diabetes. Education had the biggest positive effects on all lifestyle behaviors except for unhealthy sleep duration. Our analysis provides evidence to support that structural equation modeling enables a holistic assessment of the interplay of type 2 diabetes risk factors, which not only allows the estimation of their total effects but also prioritization of prevention targets. Regarding the current guideline for diabetes prevention, waist management in addition to BMI control (clinical level), as well as less TV watching in addition to more physical activity (behavioral level), may provide additional public health benefits. Better education would be the main societal goal for the prevention of type 2 diabetes.

Mechanism of Sanhua Decoction in the Treatment of Ischemic Stroke Based on Network Pharmacology Methods and Experimental Verification.

OBJECTIVE: The mechanism of action of Sanhua Decoction (SHD) in the treatment of ischemic stroke (IS) was analyzed based on the network pharmacology technology, and the pharmacodynamics and key targets were verified using the rat middle cerebral artery occlusion (MCAO) model. METHODS: The GEO database was used to collect IS-related gene set S D , and DrugBank and TTD databases were used to obtain the therapeutic drug target set S T . IS disease gene set S I was collected from DisGeNET, GeneCards, and OMIM databases. These three different gene sets obtained from various sources were merged, duplicates were removed, and the resulting IS disease gene set S IS was imported into the STRING database to establish the protein-protein interaction (PPI) network. Two methods were used to screen the key targets of IS disease based on the PPI network analysis. The TCMSP database and PubChem were applied to retrieve the main chemical components of SHD, and the ACD/Labs software and the SwissADME online system were utilized for ADMET screening. HitPick, SEA, and SwissTarget Prediction online systems were used to predict the set of potential targets for SHD to treat IS. The predicted set of potential targets and the IS disease gene set were intersected. Subsequently, the set of potential targets for SHD treatment of IS was identified, the target information was confirmed through the UniProt database, and finally, the component-target data set for SHD treatment of IS was obtained. clusterProfiler was used for GO function annotation and KEGG pathway enrichment analysis on the target set of SHD active ingredients. A rat MCAO model was established to evaluate the pharmacodynamics of SHD in the treatment of IS, and Western blot analysis assessed the level of proteins in the related pathways. RESULTS: This study obtained 1,009 IS disease gene sets. PPI network analysis identified 12 key targets: AGT, SAA1, KNG1, APP, GNB3, C3, CXCR4, CXCL12, CXCL8, CXCL1, F2, and EDN1. Database analyses retrieved 40 active ingredients and 47 target genes in SHD. The network proximity algorithm was used to optimize the six key components in SHD. KEGG enrichment showed that the signaling pathways related to IS were endocrine resistance, estrogen, TNF signal pathway, and AGEs/RAGE. Compound-disease-target regulatory network analysis showed that AKT1, IL-6, TNF-α, TP53, VEGFA, and APP were related to the treatment of IS with SHD. Animal experiments demonstrated that SHD significantly reduces the neurological function of rat defect symptoms (P < 0.05), the area of cerebral avascular necrosis, and neuronal necrosis while increasing the levels of IL-6 and APP proteins (P < 0.05) and reducing the levels of AKT1 and VEGFA proteins (P < 0.05). CONCLUSION: The effective components of SHD may regulate multiple signaling pathways through IL-6, APP, AKT1, and VEGFA to reduce brain damage and inflammatory damage and exert a neuroprotective role in the treatment of IS diseases. Thus, this study provides a feasible method to study the pharmacological mechanism of traditional Chinese medicine compound prescriptions and a theoretical basis for the development of SHD into a new drug for IS treatment.

Cardioprotective effect of ethanol extracts of Sugemule-3 decoction on isoproterenol-induced heart failure in Wistar rats through regulation of mitochondrial dynamics.

ETHNOPHARMACOLOGICAL RELEVANCE: Sugemule-3 decoction (SD-3) is a commonly used prescription in Mongolian medicine which composed of the herbs Baidoukou (the fruit of Amomum compactum Sol. ex Maton), Baijusheng (the fruit of Lactuca sativa L.) and Biba (Piper longum L.). SD-3 has remarkable effect on the cardiovascular diseases, but its pharmacological mechanism has not been elucidated. AIM OF THIS STUDY: To evaluate the cardioprotective effects and the potential mechanisms of the ethanol extracts of SD-3 against isoproterenol (ISO)-induced heart failure (HF) in rats. MATERIAL AND METHODS: The ethanol extracts of SD-3 were prepared and analyzed by LC-ESI-MS/MS. One hundred male Wistar rats were randomly divided into five groups: control, ISO (HF) and different doses of SD-3 (0.4, 0.2, 0.1 g/kg/d) groups. HF model rats were established by intraperitoneal injecting of ISO. The left ventricular function was evaluated by echocardiography. Myocardial injury and fibrosis were examined by hematoxylin-eosin (HE) and Masson staining. Western-blot analysis was performed to determine the protein expression of apoptosis and mitochondrial dynamics in all the groups. Moreover, the structural changes in the mitochondria of cardiomyocytes were also observed by transmission electron microscopy. RESULTS: Fifteen compounds were detected in the ethanol extracts of SD-3, include piperine, piperanine, etc. Rats administered with ISO showed a significant decline in the left ventricular function. The cardiac histopathological changes such as local necrosis, interstitial edema, and cardiac fibrosis were also observed in the ISO group. The treatment with SD-3 significantly inhibited these effects of ISO. ISO was found to increase the protein expression of Bax, cleaved-PARP and cleaved-caspase-3, -7 -9, destroy the balance between mitochondrial fusion and fission, and alter the mitochondrial morphology. The ethanol extracts of SD-3 could rebalance mitochondrial fusion and fission, and ameliorates the morphological abnormalities induced by ISO in mitochondria. CONCLUSION: The current study demonstrated that ethanol extracts of SD-3 improved isoprenaline-induced cardiac hypertrophy and fibrosis through inhibiting cardiomyocyte apoptosis and regulating the mitochondrial dynamics.

Acupoint application for exogenous fever: a multi-central retrospective cohort study / 中国针灸

OBJECTIVE@#To explore the effectiveness on exogenous fever and the characteristics of effective population, as well as the specialties of prescription of acupoint application.@*METHODS@#Using the internet electronic diagnosis and treatment platform (Spring Broadcast Wanxiangyun Clinic Database, and the main TCM suitable technology promoted by this platform is acupoint application therapy), from August 24, 2020 to November 5, 2020, the patients complained with fever and diagnosed as common cold, with a record of initial visit and at least one return visit, were included as the subjects. According to whether acupoint application therapy was received or not, the subjects were divided into an exposure group (with acupoint application therapy, 26 664 cases) and a non-exposure group (without acupoint application therapy, 515 cases). Using the propensity score, the mixed factors, e.g. age and sex, were matched between the two groups. The disappearance rate of fever (within 2 days) and the time for the first fever disappearance were taken as the effect indexes. The association rules extraction was adopted to analyze the characteristics of effective population and acupoint application prescription in treatment of exogenous fever.@*RESULTS@#After propensity score matching, there were 1 229 cases in the application group and 423 cases in the non-application group. The disappearance rate of fever in the application group was 1.82 times as high as that in the non-application group (P<0.05). The time for the first fever disappearance in the application group was shorter than the non-application group (P<0.01). A total of 5 370 cases were effective with acupoint application therapy, of which, the median age was 2 years old and the proportion of children patients under 6 years old was relatively high. In the effective crowd, the most commonly-used acupoints were Shenque (CV 8), Dazhui (GV 14), Yongquan (KI 1) and Tiantu (CV 22), etc. Shenque (CV 8) and Dazhui (GV 14) were highly associated and the support was 62.57%. The most common herbal materials in the acupoint application therapy included Radix et Rhizoma Rhei, Natrii Sulfas, Radix Scutellariae, Herba Ephedrae and Radix Bupleuri, etc. Radix et Rhizoma Rhei and Natrii Sulfas were most commonly used at Shenque (CV 8) and the supports were 57.49% and 57.21% respectively. Herba Ephedrae was most commonly applied to Shenque (CV 8) and Dazhui (GV 14) and the supports were 48.21% and 43.91% respectively. Radix Bupleuri was the most common herb at Dazhui (GV 14) with the support of 46.61%. Besides, the most commonly combined western drugs included cefixime and keteling in the acupoint application therapy and the supports were 13.07% and 12.72% respectively.@*CONCLUSION@#Acupoint application is effective on exogenous fever. The common therapy refers to Radix et Rhizoma Rhei and Natrii Sulfas plaster at Shenque (CV 8), while Herba Ephedrae and Radix Bupleuri at Dazhui (GV 14).

Influence of acupoint application on clinical use of antibiotics: a real world study of 1.23 million primary clinic patients / 中国针灸

OBJECTIVE@#To observe the influence of acupoint application on the use of antibiotics in primary clinic practice, and explore the effect of acupoint application and its influence on the use of antibiotics based on common diseases in primary clinic (fever, cough, diarrhea, sore throat).@*METHODS@#With the help of the internet electronic diagnosis and treatment platform (the main TCM suitable technology promoted by this platform is acupoint application therapy), the diagnosis and treatment data of 1.23 million patients in 2 000 primary clinics from August 24, 2020 to March 31, 2021 were collected. The patients were divided into an application group (acupoint application treatment) and a non-application group (non-acupoint application treatment), and the proportion of antibiotic use in the two groups was compared. The propensity score was used to match age, gender, concomitant symptoms, diagnosed diseases and other confounding factors of treatment, and the disappearance rate of symptoms (fever, cough, diarrhea, sore throat) and the time to first disappearance of symptoms were compared between the two groups.@*RESULTS@#A total of 1 230 923 patients were analyzed, including 1 048 382 cases in the application group, accounting for 85.2%; 182 541 cases in the non-application group, accounting for 14.8%. The most patients who used acupoint application treatment were 0-2 years old, followed by 3-6 years old, and the patients over 15 years old who did not use acupoint application treatment were the most. The proportion of antibiotic use in the application group was 2.4%, lower than that in the non-application group (44.2%, P<0.001). The proportion of antibiotic use in all ages of patients in the application group was lower than that in the non-application group (P<0.001). Among the common diseases in primary clinic (fever, cough, diarrhea and sore throat), the proportion of antibiotic use in the application group was lower than that in the non-application group (P<0.01); the disappearance rate of symptoms in the application group was higher than that in the non-application group, and the time to first disappearance of symptoms was shorter than that in the non-application group (P<0.001).@*CONCLUSION@#Acupoint application has a certain influence on the use of antibiotics in primary clinic patients. In the treatment of common diseases, patients treated with acupoint application have better curative effect and lower proportion of antibiotic use.

Reevaluation of Criteria and Establishment of Models for Total Thyroidectomy in Differentiated Thyroid Cancer.

INTRODUCTION: After the publication of the 2015 American Thyroid Association (ATA) guidelines, the indication for total thyroidectomy (TT) was reported to be underestimated before surgery, which may lead to a substantial rate of secondary completion thyroidectomy (CTx). METHODS AND MATERIALS: We retrospectively analyzed differentiated thyroid cancer patients from Wuhan Union Hospital (WHUH). Univariate analysis was performed to evaluate all preoperative and intraoperative factors. New models were picked out by comminating and arranging all significant factors and were compared with ATA and National Comprehensive Cancer Network (NCCN) guidelines in the multicenter prospective Differentiated Thyroid Cancer in China (DTCC) cohort. RESULTS: A total of 5,331 patients from WHUH were included. Pre- and intraoperative criteria individually identified 906 (17.0%) and 213 (4.0%) patients eligible for TT. Among all factors, age <35 years old, clinical N1, and ultrasound reported local invasion had high positive predictive value to predict patients who should undergo TT. Accordingly, we established two new models that minorly revised ATA guidelines but performed much better. Model 1 replaced "nodule size >4 cm" with "age <35 years old" and achieved significant increase in the sensitivity (WHUH, 0.711 vs. 0.484; DTCC, 0.675 vs. 0.351). Model 2 simultaneously demands the presence of "nodule size >4 cm" and "age <35 years old," which had a significant increase in the specificity (WHUH, 0.905 vs. 0.818; DTCC, 0.729 vs. 0.643). CONCLUSION: All high-risk factors had limited predictive ability. Our model added young age as a new criterion for total thyroidectomy to get a higher diagnostic value than the guidelines.

[Effects of density on growth and gene transcription characteristics of Rehmannia glutinosa].

The present study analyzed the effects of planting density on the development, quality, and gene transcription characte-ristics of Rehmannia glutinosa using 85-5 and J9 as materials with three planting densities of 5 000, 25 000, and 50 000 plants/Mu(1 Mu≈667 m~2). The agronomic characteristics of leaves and tuberous roots, the content of catalpol and acteoside, and the changes of gene expression were determined. The results showed that the leaf size, the diameter of tuberous root, leaf biomass, tuberous root number, and tuberous root biomass per plant at low density were significantly higher than those of medium and high densities. The content of catalpol and acteoside in leaves was higher at high density. The content of catalpol in tuberous roots was higher at low density, and the change trend was similar to that in leaves, while the content of acteoside in tuberous roots was higher at high density. Transcriptome analysis found that about 1/2 of the expansin genes could change regularly in response to density treatment, which was rela-ted to the development of tuberous roots. The change trend of the gene expression of multiple catalytic enzymes involved in the biosynthesis of catalpol and acteoside was consistent with that of their content, which was presumedly involved in the accumulation and regulation of density-responsive medicinal components. Based on the analysis of the development, medicinal components, and gene expression characteristics of R. glutinosa at different densities, this study is expected to provide an important basis for regulating the quality and yield of medicinal materials of R. glutinosa by managing the planting density.