Objective:To evaluate the role of IL-12 and CpG as adjuvants to promote the differentiation of antigen-specific CD4~+T cells in vivo.Methods:Naive OVA-TCR-Tg CD4~+T cells were isolated from spleens and lymph nodes of DO11.10 mice.The cells were labeled with CFSE in vitro and then were adoptively transferred into normal mice.One day after transfer,mice were immunized i.v.either with OVA,OVA+IL-12 or OVA+CpG.3 days post transfer,single cell suspensions were prepared from spleens,lymph nodes and lungs.The proliferation and IFN-? expression of transferred CD4~+T cells in different tissues were assessed by FACS.Results:No proliferation of antigen-specific CD4~+T cells was observed in the absence of immunization.After immunization with OVA for 3 days,cells were proliferated.The frequency of IFN-? producing cells in spleens,lymph nodes and lungs was at a range of 0.93%～2.17%.IL-12 promoted IFN-?~+ cells(4.53%～26.79%);Moreover,CpG enhanced the frequency of IFN-?-producing cells(3.84%) by the cells only from lymph nodes.In consistent with the results reported previously,cells divided 3-5 times revealed higher frequency of IFN-?-producing cells than the rest of them.Conclusion:IL-12 and CpG as adjuvants can promote the differentiation and expression of IFN-? by antigen-specific CD4~+T cells,and thus mediate cellular immune responses.

Objective:Understanding of subset、memory cell generation、effector function and organ distribution of Th1 cells in vitro and in vivo.Methods:Different stages of polarized Th1 cells are generated from antigen-specific CD4 +T cells.The expression of cell surface markers and intracellular cytokines(IL-2、IFN-? and IL-4) is determined at a single cell level by FACS. Equal numbers of CFSF-labeled naive CD4 +T cells and different stages of Th1 cells are adoptively transferred into mouse.The production of IFN-? and distribution of Th1 memory cells in lymphoid and non-lymphoid organs are measured. Results:Th1 cell populations can be subdivided into several subsets based upon the production of IL-2 and IFN-?. The percentage of IFN-?-producing cells is increased and IL-2-producing cells is decreased following repeatedly stimulation under Th1 culture condition. Moreover,the expression of CD62L on Th1 cells is reduced after activation and differentiation of CD4 +T cells. 2 weeks post-transfer,the frequency of naive CD4 +T cells is comparable from lymph nodes、spleens and lungs,whereas memory Th1 cells are preferentially detected in spleens and lungs and rapidly produce IFN-? following re-exposure to the same antigen.Conclusion:Th1 cell population is composed of distinct subsets of cells. In comparson with naive CD4 +T cells,memory Th1 cells reveal the changes of surface molecule expression、biologic function and distribution in tissues.

Objective:To investigate the correlation between CD4+T cell division and surface molecule expression or cytokine production after stimulation with antigen.Methods:Isolation of CD4+T cells from spleens and lymph nodes of OVA-T cell-receptor transgenic mouse (TCR-Tg ). After stimulation with OVA peptide antigen in the presence of antigen-presenting cells, CD4+T cell division, surface molecule expression and intracellular cytokine production are determined in flow cytometry.Results:CD4+T cells are divided 1-5 times after stimulation for 3 days with antigen. The cell division is associated with both up- and down-regulation of surface molecules such as CD25, CD44, CD62L and CD69 and of cytokines such as IFN-?, IL-4 and IL-10.IL-12 promotes cell division and enhances IFN-? but inhibits IL-4 and IL-10 production.Conclusion:After stimulation with antigen, CD4+T cells are divided in association with the quantitative and qualitative changes of surface molecules and cytokine production.

Objective: IFN-y is produced by both activated T and NK cells in response to mitogen or antigen and has a broad range of immunoregulatory activity. IL-12 has been described as a strong inducer of IFN-?production and promotes the differentiation of naive CD4+T cells toward the Th1 phenotype, priming them for IFN-?production, and consequent induction of cell-mediated immunity. Aim is to know endogenous production of IL,12 from PBMC inducing production of IFN-?in vitro, which is involving in mechanism of T cells to be activated. Methods: Induced IFT-? secretion from human PBMC by stimulated with anti-CD3 , PHA, anti-CD3 plus anti-CD28 and antigen(MLC) Also inhibited IFN-?production by neutralizing antibodies to IL-12 and IL-12R?1 significantly. Results: IFN-?secretion from human activated PBMC is endogenous IL-12dependent, and activated T cells induce the production of IL-12 from APC by a mechanism involving the interaction between CD40L on T cells and CD40 on APC. Conclusion: These results suggest that endogenous IL-12 plays an important role in the normal host defense against infection by a variety of intracellular pathogens and also plays a central role in the genesis of some forms of immunopathology including autoimmune diseases and transplantation rejections.

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.

BACKGROUND:Micro-robots have the characteristics of small size,flexibility,and strong targeting,and can complete complex tasks in a single or clustered manner in a narrow environment.With the continuous optimization of materials,preparation processes,and driving approaches,they have shown increasingly important application value in the field of biomedicine. OBJECTIVE:To analyze the application of field-driven micro-robots in medical field and to look forward to their application prospect. METHODS:Using"microrobots,nanorobots,drivers,biomedical,medical"as Chinese keywords and"microrobots,micro-robots,nanorobots,micromachine,microswimmer,medical"as English keywords,WanFang Data and PubMed databases were searched,respectively.The search time range was from January 2010 to January 2024,and a small number of long-term articles were included.Through reading the titles and preliminarily screening the abstracts,the repetitive studies,low-quality journals,and irrelevant literature were excluded.After reading the entire text,66 papers were finally included for review. RESULTS AND CONCLUSION:Field-driven medical micro-robots mainly include magnetic,optical,thermal,ultrasonic,and multi-mixed factor-driven robots.Field-driven robots have been used in intestinal diagnosis,drug targeting therapy,and stem cell therapy.Medical micro-robots are currently only used in a small number of clinical applications,but most of which are still in the theoretical and experimental stages.Medical micro-robots will face many challenges in future,such as large-scale preparation,precise control of micro-robots,recycling or degradation in vivo,whether the materials used will cause adverse reactions to the human body,and the related minimally invasive medical procedures.

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.

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.