Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective To establish a homozygous zebrafish map3k15 knockout line using CRISPR/Cas9 gene editing technology so to provide an animal model for investigation of potential role of map3k15 in renal diseases.Methods 1)Analyzing the expression pattern of map3k15 in zebrafish;2)Establishing a homozygous map3k15 knockout zebrafish line using CRISPR/Cas9;3)Observing the phenotypic effects of map3k15 deficiency in ze-brafish.Results 1)map3k15 was expressed in the zebrafish pronephros,and map3k15/map3k15 protein was found highly conserved across species;2)map3k15-/-mutant zebrafish model was constructed with+2 bp mutation and+1 bp mutation;3)map3k15 mutant zebrafish exhibited edema in yolk sac,pericardium and head during embryonic development.Conclusions A homozygous zebrafish map3k15 knockout line is successfully developed which may provide an important model for future research on the role of map3k15 in renal development and disease.

Objective: To investigate the prevalence and associated factors of depressive symptoms among middle and high school students in Zhejiang Province, so as to provide scientific basis for the implementation of depressive intervention. Methods: Based on the health status and associated factors of middle and high school students in the project "Monitoring of Common Diseases and Health Influencing Factors of Students" during 2018 to 2021, a total of 73 309 students including middle school, ordinary high school and vocational high school surveyed in 11 cities of Zhejiang Province were selected by multi stage stratified cluster random sampling method. From 2018 to 2021, there were 6 008, 21 917, 23 712 and 21 672 students, respectively. The Chi square test and Logistic regression model were used to analyze the influencing factors of depressive symptoms in middle and high school students. Results: From 2018 to 2021, depressive symptoms detection rate of middle school students was 14.8%, with higher rate in girls (17.1%) than in boys (12.7%), higher rate in high school (17.1% in ordinary high school, 17.6% in vocational high school) than middle school (12.5%)( χ 2=278.77, 327.22, P <0.05). Univariate analysis showed that there were statistically significant differences in depressive symptoms detection rate among middle school students with different years (2018: 16.7%，2019: 17.9% , 2020: 13.1%, 2021: 13.0%), residence (yes: 16.3%, no:13.5%), body mass index classification (not overweight or obesity: 14.8%, overweight: 14.2%, Obesity: 15.7%), weekly exercise days (0-2 d: 17.1%, 3-5 d: 12.5%, 6-7 d: 13.1%) and bullying (yes: 35.5%, no: 10.7%) ( χ 2=293.40, 118.35, 7.83, 287.24, 4 978.84, P <0.05). Multivariate Logistic regression analysis showed that female students, ordinary high schools, vocational high schools, obesity, school bullying were positively correlated with depression ( OR =1.65, 1.70, 1.60, 1.12, 5.21), exercise 3 to 5 days per week, exercise 6 to 7 days per week were negatively correlated with depression ( OR=0.77, 0.81, P <0.01). Conclusions Depressive symptoms among middle and high school students in Zhejiang Province are prominent. Strengthening mental health education for students and providing attention and support from families, schools, and society are essential steps to reduce the occurrence of depressive symptoms among these students.

Background Anxiety and depression are common perinatal mental health issues that often occur together and can have serious negative effects on both maternal and infant health. Objective To examine the relationships between lifestyle factors and comorbid anxiety and depression (CAD) among pregnant women in Shanghai. Methods The study estimated the prevalence of CAD during the first, second, and third trimesters of pregnancy using the Self-rating Anxiety Scale (SAS) and Center for Epidemiological Studies-Depression (CES-D) based on data from the China National Birth Cohort (CNBC) embryonic-derived diseases with assisted reproductive technology (ART) sub-cohort. Information on demographics, sleep status, nutritional intake, and exercise during each trimester was collected through self-made questionnaires, the Pittsburgh Sleep Quality Index (PSQI), and the Food Frequency Questionnaire (FFQ). Lifestyle factors (such as sleep status, nutritional intake, and exercise during each trimester) were analyzed using logistic regression and generalized linear mixed models (GLMM) to determine their impacts on the prevalence of CAD (yes or no) among pregnant women. Results A total of 2876 pregnant women were included in this study. The prevalence of CAD was 10.6% (305), 3.6% (103), and 5.5% (159) in the first, second, and third trimesters of pregnancy, respectively. The logistic regression analysis revealed that poor sleep quality throughout the entire pregnancy were statistically associated with an increased prevalence of CAD, and the odds ratios (OR) with 95% confidence intervals (CI) were 2.817 (1.845, 4.301), 2.840 (1.855, 4.347), and 9.316 (5.835, 14.876) for the first, second, and third trimesters, respectively, when compared to good sleep quality. Additionally, compared to an intake frequency of 7 times per week, the frequency of egg intake ≤3 times per week in the first trimester (OR=2.025, 95%CI: 1.197, 3.425) and the frequency of egg intake of 4–6 times per week (OR=1.896, 95%CI: 1.117, 3.216) or ≤3 times per week (OR=1.906, 95%CI: 1.082, 3.357) in the third trimester were associated with an increased risk of CAD (P<0.05). Moreover, when compared to a frequency of exercise >3 times per week, never or almost never exercising in the second trimester (OR=2.218, 95%CI: 1.220, 4.035) was associated with an increased risk of CAD (P<0.05). The GLMM analysis also demonstrated a significant association between poor sleep quality, lower exercise frequency, or lower intake frequency of vegetables, eggs, or milk and an increased risk of CAD (P<0.05). Conclusion The prevalence of CAD among pregnant women in Shanghai follows a U-shaped distribution, with the highest rate occurring in early pregnancy and the lowest rate in mid-pregnancy. Factors such as poor sleep quality, inadequate intake of vegetables, eggs, or milk, and lack of exercise during pregnancy may increase the risk of CAD. Implementing lifestyle interventions during pregnancy could potentially reduce the risk of mental health problems and improve the overall health of both mothers and babies.

Background Shoemaking industry workers are prone to work-related musculoskeletal disorders (WMSDs) due to long-term awkward postures during the work process. There is little research on the prevalence and influencing factors of WMSDs in the knee region of this industry, and it should be taken seriously. Objective To estimate the prevalence of work-related knee pain among shoemaking workers and analyze the related influencing factors. Methods A total of 6982 shoemaking workers were selected from 26 shoemaking factories in Guangdong, Hubei, Fujian, Chongqing, Shandong, Zhejiang, and Jingxi by convenience sampling. Prevalence of work-related knee pain in past year, demographic characteristics, occupational related factors, and work posture were collected by a cross-sectional survey using the electronic version of Musculoskeletal Disorder Questionnaire. Logistic regression analysis was used to analyze the influencing factors that may lead to work-related knee pain. Results This survey collected 6982 valid questionnaires with a recovery rate of 98.3%. The prevalence of work-related knee pain of shoemaking workers in the past 12 months was 13.0% (908/6982). According to the results of logistic regression analysis, compared with workers with less than 5 years of service, workers with 5-10 years of service (OR=1.21, 95%CI: 1.02, 1.45) and more than 10 years (1.53, 95%CI: 1.27, 1.83) showed a higher risk of knee WMSDs; sometimes, often and very frequent (reference : rarely or never) long-term standing (OR=1.33, 95%CI: 1.08, 1.64; OR=2.67, 95%CI: 2.10, 3.39; OR=2.75, 95%CI: 2.08, 3.63) and sometimes, often and very frequent (reference: rarely or never) long-term squatting or kneeling (OR=1.80, 95%CI: 1.47, 2.21; OR=2.43, 95%CI: 1.58, 3.75; OR=3.22, 95%CI: 1.66, 6.24) increased the risk of knee pain: long-term bending (OR=1.59, 95%CI: 1.34, 1.89) and often repeated movement of lower limbs and ankles (OR=1.48, 95%CI: 1.25, 1.75) were also risk factors for knee WMSDs among shoemaking industry workers (P<0.05). Adequate rest time (OR=0.58, 95%CI: 0.49, 0.68) and able to stretch or change leg posture (OR=0.75, 95%CI: 0.64, 0.88) reduced the risk of knee WMSDs (P<0.05). Conclusion In the shoemaking industry, length of service and awkward postures are risk factors for knee pain. The shoemaking enterprises should ensure that workers have sufficient rest time, reduce long-term standing, squatting, kneeling, and bending postures, as well as lower limbs repetition in order to reduce the occurrence of knee WMSDs of workers.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.