ObjectiveTo develop the Evidence Grading Scale for Ancient classical prescriptions in Traditional Chinese medicine， assess its reliability and validity， and apply it in practice to provide multi-source evidence for clinical practice guidelines development. MethodsLiterature retrieval was conducted to extract and screen existing evaluation dimensions， then the initial items were summarized using thematic analysis. Experts in the clinical medicine， medical history and literature participated in the Delphi questionnaire survey to evaluate and refine the items. An expert consensus meeting was conducted to finalize the included items， refine the method for items evaluation and evidence grading. The evidence quality rating scale for ancient classical traditional Chinese medicine （TCM） prescriptions was then established and tested for reliability and validity. ResultsThrough literature review， extraction， screening and summarization， a total of 3 dimensions and 12 initial items were formed. Questionnaires were sent to 69 experts to evaluate the initial items， with a questionnaire response rate of 100% and an expert authority coefficient of 0.92. All 12 items were retained for they had importance scores above 4. The Evidence Grading Scale on Ancient classical prescriptions in Traditional Chinese medicine includes 3 dimensions with 12 items. The 3 dimensions includes ancient evidence， inheritance status， and modern application. Each dimension contains 4 items， and each item has a full score of 5 points. The evidence was rated as high-level， moderate-level， and low-level according to the final scores. The content validity index （CVI） of the 12 items was ＞0.9， the average CVI of the scale was 0.98， and the intraclass correlation coefficient （ICC） was 0.90. ConclusionThe Evidence Grading Scale on Ancient classical prescriptions in Traditional Chinese medicine has good reliability and validity， which is practical for use in the development of TCM clinical guidelines and can better support clinical decision-making.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

DNA double-strand breaks represent a common type of serious DNA damage in living organisms, causing instability of the genome and leading to cell death. Homologous recombination and non-homologous end-joining (NHEJ) are the two main ways to repair DNA double-strand breaks. The core components involved in the NHEJ pathway are highly conserved in both yeast and humans. A few bacteria such as Mycobacterium, Pseudomonas aeruginosa, and Bacillus subtilis also have the NHEJ mechanism. NHEJ plays a key role in the double strand repair of Mycobacterium in latency. This paper summarizes the mechanism and important components of NHEJ in Mycobacterium, introduces the application of NHEJ in gene editing, and reviews the research progress of the NHEJ pathway in Mycobacterium. We hope to bring new insights into the molecular mechanism and provide clues for the application of NHEJ in Mycobacterium.
DNA End-Joining Repair/physiology* ; Gene Editing/methods* ; Mycobacterium/physiology* ; DNA Breaks, Double-Stranded ; Humans

Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective To explore the relevant protective/risk factors during the development of coronary heart disease blood stasis evidence in the process of pre-existing evidence based on the macro-,meso-,and micro-health state characterization parameter system of Chinese medicine state science.Methods 253 cases of coronary heart disease to be investigated were collected from the outpatient and inpatient departments of the Department of Cardiology in the hospitals affiliated to Hunan University of Traditional Chinese Medicine,and questionnaires were formulated according to the three dimensions of macro,meso,and micro,and the collected parameters were categorized with Python software,and the patients were diagnosed as pre-coronary heart disease blood stasis evidence(150 cases)and coronary heart disease blood stasis evidence(100 cases),and statistical analyses were performed with frequency analysis,χ2 test,and Logistic regression and other methods for statistical analysis.Results ①The results of univariate analysis showed that:age,BMI,history of smoking,history of alcohol consumption,history of hypertension,history of diabetes mellitus,average monthly high temperature,air quality,season,type of occupation,social environment,coronary artery angiographic stenosis,diastolic blood pressure,systolic blood pressure,creatinine,uric acid and total cholesterol differed between patients diagnosed as pre-Coronary artery disease blood stasis evidence and those diagnosed as Coronary artery disease blood stasis evidence,and all the differences were statistically significant(P<0.05).② Binary logistic regression analysis showed that age,BMI,history of alcohol consumption,type of occupation,coronary angiographic stenosis,diastolic blood pressure,creatinine,and dark red tongue were independent risk factors.A prediction model was established:P=1/[1+exp(16.522-1.427×age-0.975×BMI-3.55×drinking history+1.982×monthly average high temperature+0.709×season-1.827×occupational type-1.1×coronary angiographic stenosis-0.072×diastolic blood pressure-0.076×creatinine+2.398×dizziness-4.108×dark red tongue+4.169×pulse asthenia)],the model prediction rate was 90.5%.Conclusion The logistic regression model of coronary heart disease with blood stasis evidence is good with clinical diagnosis,which lays the foundation for the exploration of the state between the already diseased and undiseased of coronary heart disease,and provides important basic data for the theory of subhealth.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To investigate the current situation and influence factors of prehospital thrombolysis treatment for ST segment elevation myocardial infarction (STEMI) in China, to analyze the main factors affecting prehospital thrombolysis implementation, and optimize the pre-hospital thrombolysis strategy for STEMI to reduce mortality.Methods:A multicenter cross-sectional survey was conducted. 21 cities from six major geographical regions in China were selected by using convenient sampling method. An anonymous online electronic questionnaire was used to investigate the current situation and influence factors of prehospital emergency physicians and grassroots physicians implementing prehospital thrombolysis treatment for STEMI patients. Chi-square test was used to analyze the differences in count data between groups, and multivariate logistic regression was used to analyze the factors affecting prehospital thrombolysis in STEMI.Results:A total of 5 163 prehospital emergency physicians and physicians from grassroots township health centers/community health service centers or village clinics participated in this survey. Among them, 3208 (62.13%) have never implemtent thrombolysis, and 1 955 (37.87%) have did it before. The results of the multivariate logistic regression analysis indicated that physicians with 5-10 years of experience ( OR=1.41, 95% CI: 1.18-1.69, P<0.01), 11-20 years of experience ( OR=1.25, 95% CI: 1.03-1.52, P=0.02), those working in village clinics ( OR=1.30, 95% CI: 1.05-1.61, P=0.02), those in pre-hospital emergency medical institutions/departments ( OR=3.19, 95% CI: 2.80-3.64, P<0.01), those whose units are equipped with remote ECG transmission capabilities ( OR=1.72, 95% CI: 1.50-1.96, P<0.01), or ECG AI-assisted diagnostic tools ( OR=1.31, 95% CI: 1.15-1.49, P<0.01), and those who believe that thrombolysis is highly effective and should be widely adopted ( OR=2.55, 95% CI: 2.09-3.12, P<0.01) or consider it somewhat effective but warranting caution ( OR=2.11, 95% CI: 1.73-2.59, P<0.001), were more likely to make pre-hospital thrombolysis decisions for STEMI patients. To improve the current situation of pre-hospital thrombolysis for STEMI, the top four measures prioritized by pre-hospital emergency and grassroots physicians were enhancing the rescue capabilities of primary care doctors (92.22%), strengthening guidance from higherlevel hospitals (84.99%), increasing support for information technology (83.37%), and improving public health education (74.75%). Conclusions:The implementation rate of prehospital thrombolysis for STEMI in China still needs to be improved. Optimizing the prehospital thrombolysis strategy for STEMI, strengthening the allocation of basic medical resources and information technology support, and improving the referral mechanism are conducive to the implementation of prehospital thrombolysis for STEMI.