ObjectiveTo study the clinical characteristics and influencing factors of rheumatoid arthritis （RA） in the patients with cold dampness obstruction syndrome. MethodsThe RA patients treated in the Department of Traditional Chinese Medicine and Rheumatology of the China-Japan Friendship Hospital from August 2022 to June 2024 were selected. The demographic information， clinical data， laboratory test results， and traditional Chinese medicine （TCM） symptom information were collected for syndrome differentiation， on the basis of which the characteristics and influencing factors of cold dampness obstruction syndrome were analyzed. ResultsA total of 258 RA patients were selected in this study， including 88 （34.1%） patients with cold dampness obstruction syndrome， 53 （20.5%） patients with dampness and heat obstruction syndrome， 31 （12.0%） patients with wind dampness obstruction syndrome， 29 （11.2%） patients with liver-kidney deficiency syndrome， 19 （7.4%） patients with Qi-blood deficiency syndrome， 14 （5.4%） patients with phlegm-stasis obstruction syndrome， 15 （5.8%） patients with stasis obstructing collateral syndrome and 9 （3.5%） patients with Qi-Yin deficiency syndrome. The patients were assigned into two groups of cold dampness obstruction syndrome and other syndromes. The group of cold dampness obstruction syndrome had lower joint fever， 28-tender joint count （TJC28）， and 28-joint disease activity score （DAS28）-C-reactive protein （CRP） and higher central sensitization， cold feeling of joints， fear of wind and cold， cold limbs， and abdominal distention than the group of other syndromes （P<0.05）. The binary logistic regression analysis showed that central sensitization （OR 5.749， 95%CI 2.116-15.616， P<0.001） and DAS28-CRP （OR 0.600， 95% CI 0.418-0.862， P=0.006） were the independent factors influencing cold dampness obstruction syndrome in RA. ConclusionCold dampness obstruction syndrome is a common syndrome in RA patients. It is associated with central sensitization， cold feeling of joints， abdominal distension and may be a clinical syndrome associated with central sensitization.

[摘 要] 嵌合抗原受体基因修饰T细胞（CAR-T细胞）疗法是一种肿瘤免疫治疗方法：来自人体的T细胞在体外经遗传学修饰、表达特异性嵌合抗原受体（CAR），然后将其回输入患者体内，用于靶向识别和消除肿瘤细胞。尽管CAR-T细胞疗法在血液系统肿瘤治疗中取得了较为显著的成功，其在实体瘤治疗中仍面临障碍。细胞因子释放综合征（CRS）等免疫相关不良反应（irAE）制约了CAR-T细胞的安全应用，肿瘤相关抗原（TAA）的异质性限制了单一CAR-T细胞的广谱适用性，也制约了其通用型开发。鉴于此，要使CAR-T细胞疗法在实体瘤临床治疗中得到应用，还需开展进一步的改良与提升研究。本文围绕实体瘤中CAR-T细胞疗法，从“CAR基因修饰策略”、“通用免疫受体的再靶向策略”及“抗原通用性‘赋靶’策略”三个方面对CAR-T细胞领域中为提高安全性和通用性所进行的探索进行述评，系统剖析各策略的研究路径、优势及局限性，并展望未来发展方向。通过综述CAR-T细胞安全性和普适性设计策略的进展，本文旨在为实体瘤的CAR-T细胞疗法研发提供创新思路。

AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People's Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study. Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality. Further stratification was performed according to preoperative deviation angles [>35 prism diopters(PD)vs ≤35 PD] and age(≥18 years adult group vs <18 years adolescent group). The baseline patient characteristics were collected, deviation angles at multiple timepoints before and after treatment were measured, and stereopsis test results were documented. Through comparative analysis of therapeutic outcomes across subgroups, we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included. At the final follow-up, both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001). Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05). For patients with deviations >35 PD, surgery yielded significantly better outcomes than injection therapy in postoperative angle, success rate, and stereopsis recovery(P<0.05). Similarly, in patients aged ≥18 years, surgical treatment was superior to injections in reducing strabismus angle, improving success rates, and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE. Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy, particularly in patients with deviations >35 PD and those aged ≥18 years. For patients with angles ≤35 PD or under 18 years, BTXA injection remains a viable treatment option.

BACKGROUND:It is known that N6-methyladenosine(m6A)plays a role in the pathogenesis of various diseases and studies have suggested its involvement in the pathologic changes of steroid-induced femoral head necrosis(SNFH).However,research on m6A methylation modifications in steroid-induced femoral head necrosis is limited. OBJECTIVE:Using bioinformatics methods to identify the differential expression of m6A-related genes in steroid-induced femoral head necrosis and to predict miRNAs associated with these genes to further elucidate the role and mechanism of m6A methylation in steroid-induced femoral head necrosis. METHODS:Differential gene expression between steroid-induced femoral head necrosis and control groups was analyzed using GSE123568 gene expression data and identified using the"limma"package in R.Functional enrichment analysis was performed on the differentially expressed genes.Differential analysis of the related genes was carried out using the"ggstatsplot"package in R.The differential genes were cross-validated using the GSE74089 dataset.An mRNA-miRNA regulatory network was constructed,and co-expression analysis was performed on the module genes followed by enrichment analysis.Differences in immune cell infiltration between steroid-induced femoral head necrosis and control groups were quantified using the ssGSEA method. RESULTS AND CONCLUSION:Correlation analysis revealed 13 m6A-related genes,and further analysis through the protein-protein interaction network identification and receiver operating characteristic curve analysis showed that YTHDF2 was expected to be a core differential gene as a potential early biomarker.Enrichment analysis indicated that differentially expressed genes were mainly involved in inflammation and immune response and were closely related to osteoclasts.Cross-validation analysis showed that differential gene expression results between the two datasets were consistent.mRNA-miRNA regulatory network analysis revealed that YTHDF2 was negatively correlated with miRNA-27a.Immune infiltration analysis revealed an increase in immune cell infiltration in steroid-induced femoral head necrosis,and YTHDF2 was positively correlated with the infiltration of CD4+T cells.To conclude,m6A-related gene YTHDF2 can serve as a potential biomarker of steroid-induced femoral head necrosis and is valuable for the early clinical diagnosis and treatment of steroid-induced femoral head necrosis.The negative correlation between YTHDF2 and mir-27a and the positive correlation between YTHDF2 and CD4+T cell infiltration provide new insights into the early diagnosis and treatment of steroid-induced femoral head necrosis and shed light on the mechanism of m6A in steroid-induced femoral head necrosis.

Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

Objective:To investigate the correlation between blood uric acid level and body composition, exercise capacity, and cardiopulmonary function in medical examination population.Methods:In this cross-sectional study, 83 individuals who underwent physical examinations at Peking University Third Hospital from June 1, 2023, to October 1, 2023, and met the inclusion criteria were included. According to whether they had hyperuricemia (HUA), the participants were divided into HUA group (53 cases) and non-HUA group (30 cases). Body composition parameters, such as body mass index and visceral fat area, were measured with a body composition analyzer. Exercise capacity indicators, including grip strength, vertical jump, back strength, and sit-and-reach test, were measured using specific monitoring devices. Cardiopulmonary function was assessed using the stair index test. The clinical characteristics of the two groups were compared with t-tests or chi-square tests, and the correlation between uric acid levels and body composition, exercise capacity, and cardiopulmonary function was analyzed. Results:The HUA group had significantly higher skeletal muscle mass, body fat mass, body mass index, and visceral fat area when compared with the non-HUA group [(31.92±5.60) vs (26.11±6.19) kg, (23.66±9.33) vs (17.19±5.00) kg, (26.53±3.68) vs (23.27±3.59) kg/m2, 91.20 (74.25, 123.90) vs 68.25 (56.25, 90.48) cm 2, respectively] (all P<0.05). The grip strength, vertical jump, and back pull strength were all lower in the HUA group [32.70 (25.25, 40.30) vs 42.35 (35.95, 48.10) kg, 30.30 (24.10, 36.48) vs 40.55 (33.06, 45.10) kg, 24.20(20.60, 32.23) vs 29.90 (25.20, 35.50) cm, 65.60 (51.75, 78.00) vs 91.00 (67.25, 111.50) kg, respectivley] (all P<0.05). The increased step index was positively correlated with reduced risk of hyperuricemia ( OR=0.875, 95% CI: 0.793-0.966) ( P<0.05). Conclusions:Blood uric acid level is correlated with cardiopulmonary function in medical examination population. Individuals with better cardiopulmonary function have a lower risk of developing HUA. However, the relationship between blood uric acid level and body composition and exercise capacity is not clear.

Objective: To explore the relationship between sedentary behavior with cardiorespiratory fitness and executive function in adolescents, and to provide some references for sedentary behavior prevention and executive function improvement. Methods: From September to December 2022, a total of 5 018 adolescents aged 13 to 18 years were selected by stratified random sampling method in Shanghai, Suzhou, Taiyuan,Wuyuan, Xingyi, and Urumqi to conduct physical activity survey, as well as cardiorespiratory fitness and executive function assessment. Pearson s correlation was used to analyze the relationship between sedentary behavior, cardiorespiratory fitness and executive function. The mediation effect model was fitted by the bootstrap mediation procedure in the PROCESS (version 3.3 ) SPSS macro compiled by Haves, and the mediation effect of adolescents cardiorespiratory fitness in the relationship between static behavior and executive function was examined using model 4 in the PROCESS SPSS macro, where Boosrap method was used to compute the mediation effect of adolescents cardiorespiratory fitness. where the Boosrap method was used to calculate confidence intervals for the mediating effects. Results: Adolescents daily sedentary time was positively correlated with both the refreshing function (1-back and 2-back) and the switch function reaction time ( r =0.05, 0.07, 0.05, P <0.01). Adolescent VO 2max was negatively correlated with both the refreshing function (1-back,2-back) and the switching function ( r =-0.09, -0.14 , -0.11, P <0.01). Adolescents daily sedentary time was negatively correlated with VO 2max ( r =-0.04, P <0.01); cardiorespiratory fitness mediated effect values between sedentary behavior and refreshing function (1-back and 2-back) and converted function were 0.20(95% CI =0.06-0.36), 0.43(95% CI =0.14-0.74) and 0.13 (95% CI =0.04-0.22), with mediating effect shares of 6.87%, 8.33% and 8.59%, respectively. Conclusion The duration of sedentary behavior in adolescents is related to executive function performance, and cardiorespiratory fitness may serve as a mediator to mediate the association between sedentary behavior and executive function in adolescents.

Objective This study aimed to investigate the effects of P.odoratum extract on lactase activity and microflora diversity in mice with bacterial dysbacteriosis.Methods SPF male BALB/c mice were randomized into 4 groups:control,model,P.odoratum extract low dose(1.56 g·kg-1·d-1)and high dose(3.12 g·kg-1·d-1)treatment group.There were 8 mice in each group(5 in the blank group).In addition to the control group,after 7 days of intragastric administration of mixed antibiotics,the administration groups were given P.odoratum extract for 7 days,and the control group and the model group were given the same amount of sterile water.The changes of diarrhea,body weight and food intake of mice were recorded.The colon HE staining sections,ZO-1 protein,IL-6 expression,and serum LPS concentration were detected.Feces were collected for lactase activity and microbial diversity determination with 16S rRNA high-throughput sequencing technology.Results After 7 days of antibiotic intervention,compared with the control group,the mice in the model group had soft stool,weight loss,reduced food intake,and significantly reduced intestinal flora diversity.At the 14th day,in the model group,ulceration accompanied by slight interstitial congestion and edema was seen in the colon,ZO-1 expression was significantly reduced,IL-6 expression was significantly increased,serum LPS was significantly increased,lactase activity was significantly reduced,and intestinal flora diversity was still lower compared with the control group.After 7 days of administration,compared with the model group,P.odoratum reduced the diarrhea rate of mice,promoted a recovery of body weight and food intake,downregulated pathological colon tissue damage,significantly increased ZO-1 protein expression,and reduced colon factor IL-6 and serum LPS concentration.In addition,P.odoratum can significantly up-regulate lactase activity and improve the community richness and diversity of dysbacteriosis mice.It is shown that three phyla(up-regulated Firmicutes,down-regulated Proteobacteria and Bacteroidetes)and seven genera(up-regulated Rikenellaceae_RC9_gut_group,Rikenella,Colidextribacter,norank_f__Lachnospiraceae,norank_f__Oscillospiraceae,and Lachnospiraceae_NK4A136_group,down-regulated Alloprevotella),the abundance of which was significantly correlated with body weight and lactase activity,serum LPS,and colon factor IL-6.Conclusion P.odoratum can alleviate the gut barrier injury and dysfunction caused by antibiotic induced dysbiosis,and its mechanism may be achieved by regulating microflora structure.

Objective To rapidly visualize and detect the extracellular vesicles of glial cells in a simulated space environment.Methods By using 2,5 Gy irradiation and 12,24 h microgravity treatment,a damage model of glial cells was established in a simulated space environment.Exosomes extracted from conditioned media with reagent kits were transferred to neurons to elucidate the impact of glial cells on neurons.By performing live-cell fluorescence labeling of exosomes,a visualization monitoring scheme based on fluorescence intensity analysis was developed to characterize the release patterns of extracellular vesicles.The release patterns of exosomes were represented by the fluorescence intensity of the conditioned media.The effects of different storage conditions and duration on the quantity and size of exosomes were investigated.Results The exosomes released from damaged glial cells in the simulated space environment could to some extent protect neurons,with exosomes playing a decisive role in this process,and the neurosystem exosome visualization detection scheme was consistent with the traditional exosome validation scheme.An empirical curve for exosome quantity and size was established for semi-quantitative analysis,providing a new approach for rapid detection of exosomes in cell culture media.Furthermore,the optimal storage conditions for culture medium samples were clarified,laying the foundation for ground/space-based online analysis of culture medium samples after spaceflight.Conclusion Exosome rapid detection and analysis can be achieved through fluorescence labeling and utilized to investigate glial cell injury in a simulated space environment.

Objective:To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application.Methods:This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively.Results:All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] ( Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] ( Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] ( Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively ( P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] ( Z=-2.81, P=0.005). Conclusions:A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.