OBJECTIVE To observe the clinical efficacy of mycophenolate mofetil （MMF） combined with Budesonide enteric capsules in the treatment of high-risk progressive immunoglobulin A nephropathy （IgAN）. METHODS A total of 150 adult patients with high-risk progressive IgAN who attended the Department of Nephrology， Chongqing University Three Gorges Hospital， between August 1， 2024 and March 1， 2025 were enrolled in this study. The control group （ n ＝94） received MMF combined with glucocorticoid， while the observation group （ n ＝56） received MMF combined with Budesonide enteric capsules. The 24-hour urine protein （24 h UP）， estimated glomerular filtration rate （eGFR）， and albumin （ALB） levels of patients in both groups were compared at 1， 2， 3， and 6 months post-treatment. The complete response （CR） rate and overall response rate were calculated for both groups at 1， 2， 3， and 6 months post-treatment. Adverse reactions occurring during treatment were compared between the two groups. RESULTS Compared with before treatment， 24 h UP decreased significantly in both groups at different time points after treatment （ P ＜0.05）， and ALB increased significantly （ P ＜0.05）. However， there was no significant change in eGFR （ P ＞0.05）. The 24 h UP in the observation group at 1， 2， and 3 months after treatment was significantly lower than that of the control group （ P ＜0.05）， while the ALB level was significan tly higher （ P ＜0.05）. However， at 6 months after treatment， there was no statistically significant difference in these two indicators between the two groups （ P ＞0.05）. There was no statistically significant difference in eGFR between the two groups at different time points after treatment （ P ＞0.05）. The overall response rates in the observation group at 1 and 2 months after treatment were significantly higher than those in the control group （ P ＜0.05）. There was no statistically significant difference in the overall response rate at the remaining treatment time points and the CR rate at all time points between the two groups （ P ＞0.05）. Patients in the observation group had significantly lower rates of skin abnormalities， elevated blood glucose， and overall adverse reactions compared with the control group （ P ＜0.05）. CONCLUSIONS Compared with MMF combined with glucocorticoids， MMF combined with Budesonide enteric capsules for the treatment of high-risk progressive IgAN patients can reduce proteinuria and improve serum ALB levels more quickly， significantly increase the early overall response rate， and significantly reduce glucocorticoid-related skin adverse reactions， blood glucose elevation， and the overall incidence of adverse reactions， demonstrating a better short-term benefits.

Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

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: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult