Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)₂-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)₂-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)₂-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)₂-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)₂-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.

Objective To observe the clinical efficacy of traditional Chinese medicine(TCM)sequential therapy in treating patients with psoriasis vulgaris in Shenzhen,and to explore the syndrome differentiation and treatment for the patients with psoriasis vulgaris in Shenzhen region.Methods From January 2019 to February 2024,70 cases of psoriasis vulgaris admitted to Shenzhen Bao'an Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine(Shenzhen Bao'an Traditional Chinese Medicine Hospital Group)were retrospectively analyzed.The patients were divided into the observation group(39 cases)and the control group(31 cases)according to the treatment plans.In the control group,only topical application of Calcipotriol Ointment was given throughout the treatment,while in the observation group the patients were treated with TCM sequential therapy according to the illness stage on the basis of treatment for the control group,i.e.,internal administration of modified Shuiniujiao Huanglian Decoction was given in the acute stage and modified Sijunzi Shuiniujiao Decoction was given in the remission stage.Both groups were treated for 3 months.Before and after the treatment,the changes of Psoriasis Area and Severity Index(PASI)scores,Dermatology Life Quality Index(DLQI)scores and TCM syndrome scores in the two groups were observed.After treatment,the clinical efficacy and drug safety of the two groups were evaluated.Results(1)After 3 months of treatment,the total effective rate of the observation group was 89.74%(35/39),and that of the control group was 74.19%(23/31).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the PASI scores for evaluating the severity of skin lesions in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the DLQI scores for evaluating the quality of life in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the scores of TCM syndromes such as erythema,itching,vexation and dry mouth in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(5)During the treatment period,no obvious adverse reactions occurred in the two groups of patients,with high safety.Conclusion On the basis of conventional western medicine treatment,application of TCM sequential therapy exerts certain clinical efficacy in treating patients with psoriasis vulgaris in Shenzhen region,and the combined therapy is effective on controlling the patients'illness conditions,significantly alleviating the symptoms and improving the quality of life of the patients.

Fresh Chinese herbal medicine,being distinct from the dried herbs,is one of the therapies of traditional Chinese medicine(TCM)widely used in dermatology.It is employed to treat various skin diseases,namely herpes simplex,herpes zoster,common warts,flat warts,boils,carbuncles,erysipelas,acne vulgaris,fungal skin diseases,psoriasis,contact dermatitis,insect bite dermatitis,and eczema.The commonly-used fresh herbs for skin diseases are fresh Portulacae Herba,fresh Houttuyniae Herba,fresh Rubiae Radix,fresh Lygodii Spora,fresh Patriniae Herba,fresh Aloe,fresh Plataginis Herba,fresh Pinelliae Rhizoma,and fresh Taraxaci Herba.These herbs usually have the actions of clearing heat,detoxifying,and cooling blood.For the treatment of skin diseases,fresh herbal medicine can be administered orally or applied topically,with a predominant use of topical application or a combination of oral and topical administration.Due to the rapid development of modern society,the supply and standardization of fresh herbs fail in meeting the demands of a large population of the patients,leading to their gradual decline in use.However,the efficacy of fresh herbs cannot be entirely replaced by that of the dried herbs.This article reviewed the advances in the modern application of fresh Chinese herbal medicine in dermatology,aiming to promote further research and expand its clinical application in treating skin diseases.

ObjectiveTo investigate the ability of the modified albumin-bilirubin （mALBI） grade in predicting the prognosis of patients with Child-Pugh A unresectable hepatocellular carcinoma （uHCC） after transcatheter arterial chemoembolization （TACE） combined with immunotherapy and anti-angiogenic drugs （hereafter referred to as targeted immunotherapy）. MethodsA retrospective analysis was performed for the data of 76 patients with Child-Pugh A uHCC who met the inclusion criteria and underwent TACE combined with targeted immunotherapy in The First Affiliated Hospital of Soochow University from January 2020 to January 2023， and according to the mALBI grade， they were divided into mALBI 1/2a group with 38 patients and mALBI 2b group with 38 patients. The primary endpoint was overall survival （OS）， and the secondary endpoints were progression-free survival （PFS）， objective response rate （ORR）， and disease control rate （DCR）. Evaluation criteria included complete remission， partial remission， stable disease， and progressive disease. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical variables between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of median OS （mOS） and median PFS （mPFS） between groups. The univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors for prognosis. ResultsThere were significant differences in albumin and tumor burden between the two groups （both P<0.05）. The 76 patients had an mOS of 25.2 months （95% confidence interval ［CI］： 18.4 — 32.0）， an mPFS of 9.4 months （95%CI： 7.1 — 11.7）， an ORR of 63.2%， and a DCR of 82.9%. The mOS was 30.1 months （95%CI： 19.8 — 40.4） in the mALBI 1/2a group and 19.5 months （95%CI： 7.1 — 31.9） in the mALBI 2b group， and there was a significant difference in mOS between the two groups （χ²=4.490， P=0.034）. The mALBI 1/2a group had an mPFS of 10.2 months （95%CI： 8.4 — 12.0）， an ORR of 71.1%， and a DCR of 86.8%， while the mALBI 2b group had an mPFS of 7.6 months （95%CI： 4.6 — 10.6）， an ORR of 55.3%， and a DCR of 78.9%； there were no significant differences in mPFS， ORR， and DCR between the two groups （all P>0.05）. ECOG status， tumor burden， mALBI grade， portal vein invasion， and extrahepatic metastasis were independent risk factors for mOS in patients undergoing TACE combined with targeted immunotherapy （all P<0.05）. There were no treatment-related deaths. ConclusionThe mALBI grade has a good value in predicting the survival of patients with Child-Pugh A uHCC undergoing TACE combined with targeted immunotherapy.

ObjectiveTo evaluate the efficacy and safety of first-line transcatheter arterial chemoembolization （TACE） combined with targeted therapy and immunotherapy in the treatment of patients with stage Ⅱb/Ⅲa hepatocellular carcinoma （HCC） based on China Liver Cancer Staging （CNLC）. MethodsA total of 198 patients who received first-line TACE combined with targeted therapy and immunotherapy or received TACE alone from January 2015 to December 2022 in the First Affiliated Hospital of Soochow University were enrolled in this study， and after propensity score matching， there were 50 patients in combination group and 50 patients in TACE group. The Kaplan-Meier method was used to calculate median overall survival （mOS） and median progression-free survival （mPFS）. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate objective response rate （ORR） and disease control rate （DCR）， and Common Terminology Criteria for Adverse Events v5.0 was used to evaluate adverse events. The chi-square test was used for comparison of categorical data between two groups； the t-test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to estimate survival time and calculate 95% confidence interval （CI）， and the Log-rank test was used for comparison of mOS and mPFS between two groups. ResultsThe combination group had an mOS of 30.1 months （95%CI： 21.9‍ ‍—‍ ‍38.3）， and the TACE group had an mOS of 14.5 months （95%CI： 11.0 ‍—‍‍ ‍18.0）， with a significant difference between the two groups （χ²=17.8， P<0.001）； the combination group had an mPFS of 10.3 months （95%CI： 8.8‍ ‍—‍ ‍11.8）， and the TACE group had an mPFS of 7.1 months （95%CI： 5.8‍ — ‍8.4）， with a significant difference between the two groups （χ²=10.4， P<0.001）. There were significant differences between the combination group and the TACE group in ORR （84% vs 58%， P<0.05） and DCR （94% vs 80%， P<0.05）. There was no significant difference between the combination group and the TACE group in the incidence rate of adverse events （24% vs 16%， P=0.317）， and no adverse event-related deaths were observed in either group. ConclusionCompared with TACE alone， TACE combined with targeted therapy and immunotherapy has a better efficacy in the treatment of patients with CNLC stage Ⅱb/Ⅲa HCC， without increasing the incidence rate of severe adverse events.

Objective:To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene.Methods:This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation.Results:All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days.Conclusions:The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.

Objective:To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene.Methods:This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation.Results:All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days.Conclusions:The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.

Objective:To investigate the relationship between triglyceride glucose index (TyG) and body inflammation.Methods:The data were obtained from a baseline survey in population in Xi'an in natural population cohort study in northwest China established in 2018-2019. Based on TG and FPG, TyG/TyG-BMI was constructed to reflect insulin resistance (IR) in the body, and systemic immune-inflammation index (SII) reflecting inflammation in the body was constructed using neutrophil, lymphocyte, and platelet counts. A logistic regression model was used to explore the relationship between the TyG and the SII.Results:A total of 11 491 subjects were included in the analysis. After adjusting for covariates, each unit increase in the TyG increased the risk of high SII by 21% ( OR=1.21, 95% CI:1.12-1.30). The risk of high SII in the group with the TyG in Q4 was 1.34 times higher than that in the group Q1 ( OR=1.34, 95% CI:1.18-1.52). Both sensitivity analysis and subgroup analysis further confirmed the stability of the association between the TyG and the SII. In the population with a BMI ranging from 18.5 to 23.9 kg/m 2, for every unit increase in the TyG as a continuous variable, the risk for high SII increased by 31% ( OR=1.31, 95% CI:1.18-1.45). As a categorical variable, the risk for high SII in the Q4 group was 1.52 times higher than that in the Q1 group ( OR=1.52, 95% CI:1.27-1.83). In a population with BMIs ranging from 24.0 to 27.9 kg/m 2, for every unit increase in the TyG as a continuous variable, the risk for high SII increased by 20% ( OR=1.20, 95% CI:1.07-1.35), and there was no significant difference when it was a categorical variable. Conclusions:The increase in IR is closely related to the development of inflammation in the body, and BMI may regulate their relationship. Early prevention of elevated IR levels before overweight or obesity may have a positive effect on the control of inflammation in the body.

Cohort study is one of the important research methods in analytical epidemiology because of its clear time sequence relationship, which is better than other observational studies in demonstrating causal association. However, screening diagnosis or other methods are often used to exclude the individuals with outcome events during the enrollment process of the subjects in cohort studies. The accuracy of screening diagnosis and the effectiveness of exclusion will affect the accuracy of the baseline status assessment of the subjects included in the study, which may lead to the causal time sequence reversal of exposure-outcome in the estimation of causal effect. Landmark analysis can be used to control reverse causality by excluding subjects with potentially unknown expose-outcome timing. In this paper, we describe the basic principles and analytical steps of landmark analysis, and use data from the Chinese Longitudinal Healthy Longevity Survey to explore the relationship between physical activity and frailty, and introduce the specific application of landmark analysis for the purpose of facilitating its application and inferring causal effects more accurately in cohort studies.

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.