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.

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.

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

Objective:To elucidate the inhibitory effect of interferon-γ(IFN-γ)on the proliferation of neuroblastoma cells and the protentral gene signature of IFN-γ and the relationship between the expression of gene signature of IFN-γ in the neuroblastoma cells and its adverse prognosis,and to clarify the effect of IFN-γ and its gene signture in the neuroblastoma.Methods:The SK-N-BE(2)(proto-oncogene N-MYC amplification type)and SH-SY5Y(proto-oncogene N-MYC non-amplification type)neuroblastoma cells were selected and treated with different concentrations(0,500,750,1 000 and 1 500 μg·L-1)of IFN-γ for 24 h,followed by cell proliferation assays using cell counting kit-8(CCK-8).Transcriptome sequencing was then performed to identify the gene signature of IFN-γ.Additionally,the tissue microarrays from 23 cases of neuroblastoma and 6 cases of normal adrenal gland samples were collected,immunohistochemistry(IHC)analysis was used to to detect the expression of gene signature of IFN-γ.Based on the expression levels of gene signature of IFN-γ,the samples were divided into SULT2B1 low and high expression groups.The correlation between the expression of gene signature of IFN-γ and poor prognosis of the patients was analyzed.Results:The CCK-8 assay results showed that as IFN-γconcentration increased,the proliferation of SK-N-BE(2)cells was significantly inhibited(P＜0.01),with inhibitory rates of SK-N-BE(2)cells in four groups were 6.73％,6.77％,7.67％,and 9.19％,respectively.In contrast,the proliferation rate of SH-SY5Y cells were significantly increased with the increase of IFN-γ concentrations(P＜0.01),and the proliferation rates of SH-SY5Y cells in four groups were 46.80％,79.19％,70.30％,and 72.33％,respectively.Transcrip tome sequencing identified hydroxysteroid sulfotransferase 2B1(SULT2B1)as a potential gene signature of IFN-γ.The IHC analysis results showed the expression amount of SULT2B1 protein in neuroblastoma tissues was increased.The clinical data analysis results revealed significant differences in age(Z=-2.618,P=0.018),lymphnode metastasis(x2=4.439,P=0.035),and distant metastasis(x2=5.856,P=0.016)between low and high SULT2B1 expression groups.Conclusion:IFN-γ can inhibit the proliferation of SK-N-BE(2)cells while promoting the proliferation of SH-SY5Y cells.SULT2B1 is a potential gene signature of IFN-γ,and its expression is upregulated in neuroblastoma tissue.SULT2B1 high expression is significantly associated with poor prognosis in the neuroblastoma patients.

With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.