Objective: To investigate the microbial mechanisms of Banxia Xiexin Decoction (半夏泻心汤, BXXXD) in the treatment of esophageal precancerous lesions. Methods: A total of 30 specific pathogen-free (SPF) grade female C57BL/6J mice were randomly assigned to a control group (n = 6) and a 4-nitroquinoline 1-oxide (4-NQO)-exposed group (n = 24). Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water (100 μg/mL) for 17 consecutive weeks, whereas control group received sterile drinking water. After model establishment, the mice in 4-NQO-exposed group were further randomized into model group and three BXXXD-treated groups: low-dose (BXXXD-L, 3.7 g/kg), medium-dose (BXXXD-M, 7.4 g/kg), and high-dose (BXXXD-H, 14.8 g/kg) groups (n = 6 per group). During the subsequent intervention period, mice in control and model groups were gavaged with sterile water, while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks. Histopathological changes in esophageal tissues were observed by hematoxylin and eosin (HE) staining. The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity, community structure, and co-occurrence networks. BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry (UHPLC-QE-MS). Serum short-chain fatty acids (SCFA) level was quantified by targeted metabolomics using gas chromatography-mass spectrometry (GC-MS). Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles. Results: Compared with model group, BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement, with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups (P < 0.01). Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus. In the gut, BXXXD elevated the relative abundance of beneficial taxa, including Lactobacillus, Dubosiella, Bacteroides, and Faecalibacterium. Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level (P < 0.01). Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression, migration, and invasion of esophageal cancer, which were identified as kallikrein-related peptidase 6 (Klk6), defensin beta 4 (Defb4), family with sequence similarity 3 member B (Fam3b), carboxypeptidase A4 (Cpa4), serum amyloid A1 (Saa1), and chitinase-like 1 (Chil1) (P < 0.05). Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.

Background The association between occupational physical activity (OPA) and cardiometabolic risk factors remains controversial, potentially due to differences in the associations between OPA and various cardiometabolic indicators, as well as the lack of a clearly defined optimal OPA range for multiple-indicator synergistic benefits. Objective To investigate the relationship between OPA and cardiometabolic risk factors in individuals at high risk of cardiovascular disease (CVD) in Hubei Province, and to explore an optimal OPA range for multi-indicator improvements. Methods Data were derived from the Hubei Province dataset of the China Health Evaluation And Risk Reduction Through Nationwide Teamwork from 2015 to 2023, including 19028 high-risk CVD individuals. OPA (metabolic equivalent·h·d⁻¹, MET·h·d⁻¹) was assessed using the China Kadoorie Biobank physical activity questionnaire, anthropometric measurements (height, weight, waist circumference) and cardiometabolic indicators (blood pressure, fasting blood glucose, lipid profiles) were measured. Multivariate logistic regression was used to analyze the association between logOPA quartiles (Q1-Q4) and abnormal cardiometabolic indicators, while restricted cubic spline (RCS) models were employed to explore their dose-response relationships. Subgroup and interaction analyses were also conducted by gender. Results The median OPA of all participants was 12.86 MET·h·d⁻¹ (male: 14.40 MET·h·d⁻¹, female: 11.14 MET·h·d⁻¹). After adjusting for confounders, compared with the Q1 group, logOPA in the Q4 group was associated with 20% (OR=0.80, 95%CI: 0.72, 0.89), 14% (OR=0.86, 95%CI: 0.78, 0.96), and 13% (OR=0.87, 95%CI: 0.79, 0.95) reduction in the risk of abdominal obesity, low high-density lipoprotein cholesterol (HDL-C), and metabolic syndrome (MS), respectively, and 33% (OR=1.33, 95%CI: 1.18, 1.49), 33% (OR=1.33, 95%CI: 1.18, 1.50), and 38% (OR=1.38, 95%CI: 1.21, 1.57) increase in the risk of high total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), and high non-HDL-C, respectively. Similar trends were observed in males and females, with significant positive associations of logOPA with high TC and high non-HDL-C in males (P_interaction<0.05). The risk of low HDL-C decreased rapidly when logOPA was more than 2.213 (OPA>9.14 MET·h·d⁻¹), showing an inverted L-shaped trend. The risk of high TC, high LDL-C, and high non-HDL-C increased beyond logOPA thresholds of 3.244, 2.476, and 3.377 (OPA >25.64, 11.89, and 29.28 MET·h·d⁻¹), respectively, showing a J-shaped trend. However, logOPA exhibited a U-shaped nonlinear dose-response relationship with blood pressure and fasting blood glucose abnormalities (P_non-linear<0.05) , with minimal risks at logOPA 2.969 and 2.372 (OPA of 19.47 and 10.72 MET·h·d⁻¹). Conclusion OPA exhibits heterogeneous dose-response patterns across cardiometabolic indicators. Integrating the inverted L-, J-, and U-shaped association patterns, we suggest an optimal OPA range of 9.14−25.64 MET·h·d⁻¹ for multiple cardiometabolic indicators in total individuals at high-risk of CVD, with ranges of 9.61−31.34 MET·h·d⁻¹ for males and 8.97−22.87 MET·h·d⁻¹ for females. These findings provide critical evidence for developing OPA interventions strategies targeting high-risk population for CVD.

Antibiotics are chemicals with bactericidal or bacteriostatic activity produced by microorganisms and artificially synthesized. Since the discovery of penicillin by Alexander Fleming in 1928, antibiotics have been widely used in clinical treatments as well as in the animal husbandry and aquaculture, leading to antibiotic residues in soil, water, food and other environments. At the same time, antibiotic resistance is increasingly serious, which necessitates the discovery of novel antibiotics. In recent years, with the development of synthetic biology, researchers have developed a variety of whole-cell biosensors that can respond to antibiotics. These whole-cell biosensors use microbial cells to convert antibiotic signals into readable signals, which can not only perform dynamic detection of antibiotics simply, quickly, sensitively and accurately but also effectively discover novel antibiotics. This review comprehensively summarizes the reported whole-cell biosensors for antibiotics, classifies them into two types (specific and general), and elaborates on the design principles and applications of the two types of antibiotic biosensors. This review will provide reference for the construction and application of other whole-cell biosensors for antibiotics.
Biosensing Techniques/methods* ; Anti-Bacterial Agents/pharmacology*

This study summarizes Professor Qin Zhenhua's clinical experience in treating cutaneous pruritus using a modified self-prescribed formula,Yinqiao Xingzi Decoction.Following the viewpoints from the classical Chinese medical literature and after years of clinical practice,Professor Qin proposes that the onset of cutaneous pruritus is often associated with the attack of exogenous pathogens,disharmony of qi and blood,or debility due to prolonged illness.The disease primarily involves the skin,with the fundamental pathogenesis of pathogens stagnating in the muscular superficies.Clinically,the treatment is frequently conducted from the perspective of fire-heat syndrome,and the therapeutic methods of clearing heat and removing toxins,releasing muscles and dispersing pathogens from the superficies,and dispelling wind to relieve itching are utilized.The approaches aim to cool heat in the blood,expel pathogens from the muscular layer,eliminate heat for stopping itching,and extinguish wind for calming the skin.The basic prescription,Yinqiao Xingzi Decoction(composed of Lonicerae Japonicae Flos,Forsythiae Fructus,Armeniacae Semen Amarum,Arnebiae Radix,Tribuli Fructus,Dictamni Cortex,Kochiae Fructus,and Glycyrrhizae Radix et Rhizoma),is used by modification depending on the predominance of pathogenic factors of wind,heat,dryness,or dampness-toxins,and according to the various syndromes like blood-heat,yin deficiency,or qi-blood deficiency.Yinqiao Xingzi Decoction is applicable to cutaneous pruritus with the most of clinical common syndrome types,but it is unsuitable for cases caused by yang deficiency or qi stagnation with blood stasis.

Objective To analyze the main factors influencing the management effect of rural epilepsy prevention and control projects in Hubei Province, and to provide reference for further improving the management effect. Methods According to the phenobarbital treatment and management plan of the rural epilepsy project, the target population was screened and reviewed, and patients who met the inclusion criteria were enrolled into the project management. Regular follow-up visits, free drug treatment, health education and other measures were carried out, and all relevant information was collected and integrated into the survey data. After the data was reviewed level by level, SPSS20.0 software was used for statistical analysis. Results From January 1, 2015 to December 31, 2020, among patients treated and managed with phenobarbital in 6 project counties, 1430 patients were treated and managed for more than 1 year, of whom 1119 (78.25%) had no seizures or had more than 75% reduction in the number of seizures during the observation period. Compared with other age groups, the age group of 65 years and above had the highest markedly effective/effective ratio (95.77%). From the point of follow-up, the markedly effective/effective ratio of 5 years and above was the highest (91.51%). Compared with those who received no treatment prior to enrollment and those who received regular treatment, the patients receiving informal treatment had the lowest markedly effective/effective ratio (82.43%). 1213 cases (84.83%) had good compliance during the observation period, of whom 1062 cases (87.55%) had a reduction in the number of seizures by more than 50% compared with that before treatment. Univariate analysis showed that the age of patients, the length of follow-up, the treatment status before enrollment, the average daily dose of phenobarbital and the compliance of patients all had an impact on the management effect, and the difference was statistically significant (P<0.05). Multivariate analysis showed that the markedly effective/effective rate of patients in the age group of 65 years and above was 6.749 times that of the younger age group. Receiving informal treatment prior to enrollment was a risk factor for difficult-to-control epilepsy. The markedly effective/effective rate of patients receiving informal treatment was 0.29 times that of patients never receiving treatment. Good compliance was a protective factor for epilepsy control, and the markedly effective/effective rate of patients with good compliance was 2.058 times that of patients with poor compliance. Conclusion The epilepsy prevention and management project in rural areas has a significant effect on seizure control. Early treatment, standardized treatment, and improvement of treatment compliance are effective ways to improve the management effect of epilepsy patients.

Objective To establish a quality control method for monitoring the blood concentrations of cyclosporin A and tacrolimus by HPLC-MS/MS,and to evaluate the quality control samples using the Westgard multi-rule theory.Methods HPLC-MS/MS was used to determine the concentration of cyclosporin A and tacrolimus in human whole blood.The quality control samples of low,medium and high concentration levels in the therapeutic drug monitoring process were statistically analyzed,Levery-Jennings and Z-score quality control charts were drawn,and the Westgard multi-rule theory was applied for in-house quality control evaluation.Results The established method was fully validated with linear ranges of 10.40-1 040.00 ng·mL-1 and 0.50-49.50 ng·mL-1,the quantification limits were 10.40 and 0.50 ng·mL-1,respectively.The extraction recoveries were 108.61％-113.24％and 101.99％-109.37％,respectively.The matrix factors normalized by internal standard were 106.68％-111.27％and 95.70％-97.81％for cyclosporin A and tacrolimus,respectively.The intra-day and inter-day accuracy and precision were less than 15.0％.Other parameters were also validated and met the acceptance criteria.Levery-Jennings and Z-score quality control charts showed that there were 4 warnings(violation of the 12s rule)in the results of the 26 groups of quality control samples in the third quarter of 2022,and no phenomenon was observed to be out of control.Conclusion The established in-house quality control system for therapeutic drug monitoring of cyclosporin A and tacrolimus can effectively ensure the accuracy of blood drug concentration detection.

[Objective]People infected with Hepatitis B are often divided into hepatitis B carriers and hepatitis B patients based on whether ALT is normal or not,and ALT ≥ 2UNL is one of the indications for clinical antiviral treatment,but no sufficient evidence to justify this. In order to explore the theoretical basis,the paper investigated the effects of hepatitis B virus(HBV) on hepatic stellate cells(HSCs).[Methods]A total of 132 chronic hepatitis B patients with different viral loads and ALT levels were randomly selected as the study subjects. Of these patients,those with ALT≥2UNL were treated with antiviral therapy and followed up for 24 weeks. The effects of HBV on HSCs before and after the treatment were compared and analyzed. HSCs proliferation was detected by MTT method,HSCs cell cycle by flow cytometry,and expression of TGF-β1,Smad3,Smad7,α-SMA,collagen Ⅰ,collgen Ⅲ mRNAs and corresponding proteins by RT-PCR and Western blotting,respectively.[Results]At the normal ALT level,HBV with different viral loads had no significant effect on the proliferation,cell cycle and cell secretion of the HSCs. At the abnormal ALT level,especially when ALT ≥ 2UNL,with the increase of virus loads,HSCs proliferation accelerated;cells in the G0/G1 phase decreased significantly and cells in the S and G2/M phases increased significantly;the expression of TGF-β1,Smad3,α-SMA,collagen Ⅰ,collgen Ⅲ mRNAs and corresponding proteins increased significantly,but Smad7 mRNA and protein expression decreased significantly,the differences were statistically significant. HBV showed a significantly lower effect on HSCs after the antiviral therapy than before.[Conclusions]This paper reveals the differential effects of HBV on HSCs at different ALT levels and presents a comparative analysis of the effects before and after the antiviral therapy,which provides a theroretical basis for identifying the ALT level as an indication for HBV antiviral therapy.

Objective:To evaluate the application of modular teaching program in the clinical competence training for community general practitioners.Methods:This was a cross-sectional study. A 140 teaching hour-modular training program was designed by the authors on the basis of the previous training experience and conducted in clinical competence training for 20 general practitioners (study group) from all 10 community health service centers in Shanghai Huangpu district between September 2022 and April 2023; and 26 general practitioners who planned to participate in the next batch of training courses were enrolled as the control group. The clinical competence assessment was conducted in May 2023, including knowledge level tests and clinical skill assessment. By comparing the scores of clinical competence assessment and satisfaction survey between two groups, the training effectiveness was evaluated.Results:Among the 46 general practitioners, 33 (71.7%) were female, aged 27 to 47 (37±6), working in general practice for 2 to 25 (9.4±5.5) years, 31 (67.4%) had participated in standardized residency training for general practice and 31 (67.4%) were contracted family doctors. The total score of 46 general practitioners was 69.7±9.6, and 68.9±8.6 for knowledge level and 69.8±10.6 for clinical skills. The total scores and single scores of trained participants were all significantly higher than those of untrained(all P<0.05). The multiple linear regression model showed that after controlling for gender, age, educational background, professional title, years of working in general practice, participation in standardized residency training, and status as a contracted family doctor, the trained participants had significantly higher scores in history collection, pediatric reception, indwelling gastric tube and abdominal puncture (all P<0.05). There was no statistically significant difference in the scores in knowledge level test, nervous system physical examination, SOAP medical record writing, and tutorium between the trained and untrained groups (all P>0.05). Among 20 general practitioners who completed training, the overall satisfaction score of the training program was 4.3±0.7 points, including 4.3±0.6 for the training course, 4.3±0.7 for teachers, and 4.3±0.7 for the organization and arrangement; 85% of the participants considered the training to be very helpful or helpful for improving their competence, and 90% considered the training to be very helpful or helpful for their future work. Conclusion:Modular teaching program is helpful to improve the clinical competence of community general practitioners, especially in clinical skills.

Objective:To investigate the efficacy of pungent-heat-dampness-drying method combined with methotrexate in the treatment of rheumatoid arthritis with cold-dampness blockage syndrome and its effect on knee joint function.Methods:A randomized controlled study was conducted on 120 patients with rheumatoid arthritis exhibiting cold-dampness blockage syndrome, who were admitted to the Quzhou Municipal Hospital of Traditional Chinese Medicine between July 2020 and October 2022. Using the random number table method, these patients were randomly assigned to either the control group ( n = 60) or the observation group ( n = 60). The control group received methotrexate tablets exclusively, while the observation group received a combined therapy of pungent-heat-dampness-drying method along with methotrexate. All patients were treated for 4 weeks. At the end of the treatment period, improvements in clinical indices and knee joint function were compared between the two groups. Results:After 4 weeks of treatment, the activity pain time [(0.95 ± 0.05) hours], rest pain time [(0.62 ± 0.08) hours], morning stiffness duration [(0.65 ± 0.02) hours], and pain paralysis duration [(0.52 ± 0.083) hours] in the observation group were significantly lower than those in the control group [(2.13 ± 0.15) hours, (1.36 ± 0.14) hours, (1.23 ± 0.63) hours and (1.02 ± 0.52) hours, respectively] ( t = 57.81, 35.55, 7.13, 7.44; all P < 0.001). The Knee Society Score in the observation group was (35.42 ± 8.26) points, which was significantly higher than that in the control group [(20.23 ± 5.75) points, t = -11.69, P < 0.001]. Additionally, levels of alanine aminotransferase, aspartate aminotransferase, erythrocyte sedimentation rate, and C-reactive protein were significantly lower in the observation group compared to the control group ( t = 26.96, 57.72, 19.44, 12.61, 17.37; all P < 0.05). The knee joint function score in the observation group was (75.42 ± 5.26) points, which was significantly higher than that in the control group [(62.23 ± 5.65) points, t = -13.24, P < 0.05]. Conclusion:The combination of the pungent-heat-dampness-drying method with methotrexate for the treatment of rheumatoid arthritis with cold-dampness blockage syndrome not only effectively improves clinical indices but also significantly reduces knee joint pain and improves knee joint function.