ObjectiveTo systematically quantify the multidimensional effect of virtual reality-based exergaming (VREG) on health outcomes among individuals with cognitive impairment under the framework of the International Classification of Functioning, Disability and Health (ICF). MethodsMeta-analysis was conducted in accordance with the PRISMA statement. PubMed, Cochrane Library, Embase, Scopus, Web of Science, CNKI, Wanfang Data and VIP were researched for randomized controlled trials (RCTs) investigating VREG for cognitive impairment, with the search deadline set on February 1, 2026. The Cochrane Risk of Bias 2.0 tool was adopted to evaluate the methodological quality of included studies. A three-level meta-analytic model was implemented with R 4.4.2. The GRADE framework was further used to rate the certainty of pooled evidence. ResultsA total of 22 RCTs were included. VREG might improve global cognitive function (SMD = 0.69, 95%CI 0.11 to 1.28, P = 0.022), memory (SMD = 0.47, 95%CI 0.07 to 0.87, P = 0.023), attention (SMD = 0.62, 95%CI 0.23 to 1.01, P = 0.004), executive function (SMD = 0.42, 95%CI 0.09 to 0.75, P = 0.013), balance (SMD = 0.54, 95%CI 0.07 to 1.00, P = 0.027), muscle strength (SMD = 0.63, 95%CI 0.37 to 0.88, P = 0.001), mobility (SMD = 0.29, 95%CI 0.04 to 0.54, P = 0.024) and quality of life (SMD = 0.29, 95%CI 0.03 to 0.56, P = 0.029). No significant effect was observed for depressive symptoms, comprehensive physical fitness and fall risk (all P > 0.05). Subgroup and meta-regression analyses indicated that session duration < 45 minutes produced the largest improvement in attention (SMD = 0.95, 95%CI 0.55 to 1.34, P < 0.001); intervention cycles of twelve to 24 weeks were optimal for mobility (SMD = 0.85, 95%CI 0.44 to 1.25, P < 0.001); age negatively correlated to balance improvement (β = -0.11, 95%CI -0.20 to -0.02, P = 0.020), suggesting less intervention benefits among older participants. ConclusionVREG is an effective non-pharmacological intervention to improve multidimensional physical and mental health in people with cognitive impairment. Protocols featuring short single sessions with long-term duration should be prioritized.

AIM To investigate the ameliorative effects of Compound Fufangteng Mixture(CFM)on cyclophosphamide(CTX)-induced immunosuppression in mice.METHODS Forty-eight male C57BL/6J mice were randomly divided into the blank control group,the model group,the levamisole hydrochloride group(40 mg/kg)and the low-dose,medium-dose and high-dose CFM groups(3.75,7.5,10 g/kg),with 8 mice in each group,and given respective intervention orally once daily for 14 days.On the 5th to 7th day of administration,with the blank control group given normal saline intraperitoneally,the other groups underwent intraperitoneal CTX injections(80 mg/kg).24 hours after the last administration,organ indices of thymus and spleen were calculated;splenic histopathological alterations were assessed by HE staining;serum levels of IL-2,IL-6 and IgG were quantified using ELISA;splenic CD4+,CD8+T lymphocytes,alongside CD86+and CD206+macrophages populations were analyzed by flow cytometry;and splenic expression of CD4,CD8 and F4/80 was evaluated by immunohistochemical staining.RESULTS In CTX-treated mice,CFM administration mitigated body weight loss;enhanced thymus weight and thymic index;ameliorated splenic immune cell populations,elevated serum levels of cytokines IL-2,IL-6 and IgG in serum;and upregulated splenic levels of CD45+CD3+T lymphocytes and F4/80+CD11b+macrophages,alongside increasing the expression of CD4,CD8 and F4/80 surface markers.CONCLUSION CFM alleviates CTX-induced immunosuppression state in mice by modulating immune cells,restoring immune function and enhancing anti-inflammatory and tissue repair capabilities.

AIM To investigate the protective effects of kaempferide on hyperuricemic nephropathy(HN)in mice.METHODS Sixty Kunming mice were randomly divided into the control group,the model group,the allopurinol group(5 mg/kg),the kaempferol group(50 mg/kg),and the low-dose and high-dose kaempferide groups(25,50 mg/kg).HN mouse models were established by administering potassium oxyzinate(300 mg/kg)and hypoxanthine(500 mg/kg)in combination for 21 days,concurrently with the test drug.Following treatment administration,serum uric acid(SUA),serum creatinine(SCr),24-hour urinary protein(24 h UTP),and hepatic xanthine oxidase(XOD)levels were measured.Renal tissue pathology was assessed using HE staining and Masson staining.Apoptosis in renal tissue was evaluated via TUNEL staining.The expressions of NLRP3 inflammasome and apoptosis-associated proteins in renal tissues were analyzed by immunohistochemistry and Western blot.RESULTS Compared to the control group,the model group demonstrated elevated levels of SUA,SCr,24 h UTP,and hepatic XOD activity(P＜0.01);marked renal damage,and increased area of renal interstitial fibrosis and apoptosis rate(P＜0.01);and increased protein expressions of NLRP3,ASC,Caspase-1,cleaved-Caspase-1,pro-IL-1β,IL-1β,Caspase-3 and cleaved-Caspase-3 in renal tissue(P＜0.05,P＜0.01).Compared to the model group,the groups treated with allopurinol,kaempferol,or kaempferid showed reduced levels of SUA,SCr,24 h UTP,and hepatic XOD activity(P＜0.05,P＜0.01);improved renal pathological injury with reduced renal interstitial fibrosis area and apoptosis rate of renal tissue(P＜0.01);and downregulated protein expressions ofNLRP3,ASC,Caspase-1,cleaved-Caspase-1,pro-IL-1β,IL-1β,Caspase-3 and cleaved-Caspase-3 in renal tissue as well(P＜0.05,P＜0.01).CONCLUSION Kaempferide improves renal function while attenuating inflammation,fibrosis,and apoptosis in the kidneys of HN mice.This nephroprotective effect may stem from its dual action in inhibiting hepatic XOD to reduce uric acid synthesis and blocking NLRP3 inflammasome activation.

Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer. Computational methods have been widely explored and have become increasingly accurate in recent years. However, the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients. We present a novel disentangled synthesis transfer network (DiSyn) for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients. DiSyn uses a domain separation network (DSN) to disentangle drug response related features, employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement. DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets, The Cancer Genome Atlas (TCGA), Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2 (I-SPY2) and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia (NIBR PDXE), achieving competitive performance with the state-of-the-art methods on cancer patients and mice. Furthermore, the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

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Objective To investigate the early predictive value of combined detection of serum sodium,heparin-binding protein-to-albumin ratio(HBP/ALB)and interleukin-10(IL-10)in Ka-wasaki disease shock syndrome(KDSS)caused by Kawasaki disease in children.Methods A total of 105 children with KDSS caused by Kawasaki disease(KDSS group)and 105 children with Kawasa-ki disease(control group)were selected as study subjects.Clinical data,serum sodium levels,HBP/ALB and IL-10 levels were compared between the two groups.Multivariate logistic regression a-nalysis was used to screen the influencing factors of KDSS caused by Kawasaki disease in children a-mong serum sodium,HBP/ALB and IL-10.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate the predictive value of traditional prediction schemes(coronary artery dam-age and IVIG resistance)and new prediction schemes(serum sodium and HBP/ALB,IL-10)for KDSS caused by Kawasaki disease in children.Results The proportion of patients with coronary ar-tery damage and IVIG resistance was significantly higher in the KDSS group than those in the control group(P＜0.05).Serum sodium levels were lower,while HBP/ALB and IL-10 levels were higher in the KDSS group compared to the control group(P＜0.05).Multivariate logistic regression analysis showed that serum sodium,BP/ALB and IL-10 were influencing factors of KDSS caused by Kawasaki diseasein children(P＜0.05).For traditional prediction schemes,the areas under the curves(AUCs)for coronary artery damage,IVIG resistance and their combination in predicting KDSS caused by Kawasaki disease were 0.795,0.676 and 0.873,respectively(P＜0.05);for new prediction schemes,the AUCs for serum sodium,HBP/ALB,IL-10 and their combination in predicting KDSS were 0.767,0.824,0.760 and 0.945,respectively(P＜0.05).The AUC for the combination of serum sodium,HBP/ALB and IL-10 was greater than that for the combination of coronary artery dam-age and IVIG resistance(P＜0.05).Conclusion Decreased serum sodium,elevated HBP/ALB and elevated IL-10 are associated with KDSS caused by Kawasaki disease in children.Combined prediction using serum sodium,HBP/ALB and IL-10 has a high predictive value for KDSS caused by Kawasaki disease in children.

Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P₂₅, P₇₅)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.