Objective To develop a machine learning(ML)-based prediction model for assessing the therapeutic effects of resveratrol(RES)on the pathological damage of acute pancreatitis(AP),and to optimize RES administration strategies for AP through validation using an animal model.Methods AAn ML-based prediction model was constructed using published data.Interpretability analysis was applied to identify high-efficacy zones within the parameter space of administration dose and frequency,which was followed by rigorous screening to select the optimal dosing strategy that balanced therapeutic efficacy and experimental feasibility.A total of 32 C57BL/6 mice were randomly assigned to 4 groups(n=8 per group),including a control group(Ctrl),an AP model group induced by caerulein(CER)and referred to as CER-AP,a treatment group receiving RES via intraperitoneal injection(RES i.p.),and a treatment group receiving RES via intragastric gavage(RES i.g.).The Ctrl group received intraperitoneal injection of normal saline.The CER-AP and the treatment groups were induced with 10 intraperitoneal injections of CER at 50 μg/kg.RES was administered to the RES i.p.and RES i.g.groups according to the optimal dose and timing predicted by the ML model.Blood and tissue samples were collected 12 hours after the experiment started.Results The gradient boosting decision tree model,optimized via Hyperopt,yielded the best performance,predicting that the optimal dose and administration frequency were 19.992 mg/kg and 3.828 times,respectively.Accordingly,a regimen of 20 mg/kg RES,administered four times,was used in the animal experiments.Compared with the Ctrl group,the CER-AP group exhibited higher pancreatic pathology scores and elevated levels of serum amylase,lipase,pancreatic myeloperoxidase,and trypsin,with all differences reaching statistical significance(all P<0.05).The administration of 20 mg/kg RES via both intraperitoneal injection and intragastric gavage mitigated pancreatic inflammatory cell infiltration and necrosis,improved the overall pathology score,and reduced serum amylase,lipase,and pancreatic myeloperoxidase levels to varying degrees(all P<0.05).Conclusion A regimen of 20 mg/kg RES administered four times effectively alleviates the severity of CER-induced AP.The therapeutic benefits appear to arise from a multi-target regulatory network that simultaneously suppresses inflammatory cascades,mitigates oxidative stress,and reduces apoptosis,thereby reducing pancreatic tissue damage and systemic inflammatory responses.

OBJECTIVES: The 24-hour movement behaviors, comprising physical activity, sedentary behavior, and sleep, are crucial factors affecting children's mental health. This study aims to explore the longitudinal association between 24-hour movement behaviors and psychological well-being in overweight and obese children, providing empirical evidence for mental health promotion in this population. METHODS: A total of 445 overweight and obese children were recruited via stratified cluster random sampling from a provincial capital city in China and followed up for one year. Measures included objectively assessed physical activity and sleep duration using triaxial accelerometers (ActiGraph GT3X+), parent-reported sedentary screen-based time (SST), and self-reported psychological well-being. RESULTS: After one year, the proportion of children meeting all 3 movement guidelines increased from 10.11% to 11.68%, while those meeting none increased from 11.24% to 15.06%. After adjusting for relevant covariates, children who met individual guidelines for moderate-to-vigorous physical activity (MVPA) (β=0.377, 95% CI 0.209 to 0.545), sleep (β=0.187, 95% CI 0.042 to 0.332), or guideline combinations of MVPA+SST (β=0.545, 95% CI 0.377 to 0.713) and MVPA+sleep (β=0.602, 95% CI 0.449 to 0.755) showed significant improvements in psychological well-being after one year. Additionally, an increase in the number of guidelines met was significantly associated with improved well-being (β=0.113, 95% CI 0.011 to 0.214). CONCLUSIONS Adherence to any single movement guideline, especially MVPA or sleep, and combinations such as MVPA+SST or MVPA+sleep is significantly associated with enhanced psychological well-being in overweight and obese children. Integrated behaviors may be an effective strategy to improve mental well-being in this population.
Humans ; Child ; Exercise/psychology* ; Sleep ; Sedentary Behavior ; Female ; Male ; Pediatric Obesity/psychology* ; Overweight/psychology* ; Mental Health ; China ; Accelerometry ; Psychological Well-Being

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

Chronic hepatitis B（CHB）is one of the major challenges in the global public health field. As of 2022，approximately 254 million people worldwide were infected with the hepatitis B virus（HBV）. CHB is one of the main causes of liver cirrhosis and hepatocellular carcinoma（HCC）. Nucleos（t）ide analogs（NAs）and interferon therapy can delay the progression of liver fibrosis by inhibiting viral replication，but they cannot completely avoid the problem of heterogeneous treatment responses. Some patients are in a state of low-level viremia（LLV）during treatment. The persistent LLV state can induce chronic inflammation and the progression of liver fibrosis，ultimately increase the risk of HCC. In patients with poor treatment responses，the continuous active viral replication can induce immune disorders，accelerate the evolution of fibrosis to the decompensated stage of liver cirrhosis，and increase the risk of patient death. This article aims to review the definition，mechanisms，and impact on treatment outcomes of LLV and suboptimal response based on the latest research，provide a basis for optimizing antiviral therapy for CHB.

ObjectiveTo explore the potential mechanism by which Huangqi Baijiang Yiren decoction （HBY） repairs the intestinal mucosal injury in the rat model of ulcerative colitis （UC） via the miR-21/suppressor of cytokine signaling 1 （SOCS1）/Janus kinase 1 （JAK1）/signal transducer and activator of transcription 6 （STAT6） signaling pathway. MethodsSixty SPF-grade male SD rats were randomly assigned into six groups： blank， model， low-dose （3.68 g·kg^-1） HBY， medium-dose （7.35 g·kg^-1） HBY， high-dose （14.5 g·kg^-1） HBY， and mesalazine （0.035 g·kg^-1）， with 10 rats in each group. The rat model of UC was established in other groups except the blank group by 3% dextran sulfate sodium solution. The rats were administrated with corresponding drugs once a day for 7 consecutive days since the 3th day after modeling. The histopathological changes of the colon were observed by hematoxylin-eosin staining， and the Robarts histopathology index （RHI） was scored. Enzyme-linked immunosorbent assay was employed to measure the levels of pro-inflammatory cytokines ［interleukin （IL）-6， IL-18， IL-1β， and tumor necrosis factor-α （TNF-α）］ in the serum. Real-time PCR was employed to determine the mRNA levels of miR-21， SOCS1， JAK1， and STAT6 in the colon tissue. Western blot was employed to determine the protein levels of SOCS1， JAK1， phosphorylated （p）-JAK1， STAT6， p-STAT6， Occludin， and Claudin-1 in the colon tissue. ResultsCompared with the blank group， the model group showed an increase in disease activity index （DAI） （P<0.01）， shortening of colon length （P<0.01）， severe histopathological damage in the colon tissue， and an increase in RHI， rises in serum levels of IL-6， IL-1β， IL-18， and TNF-α （P<0.01）， up-regulation in mRNA levels of miR-21， JAK1， and STAT6 and protein levels of p-JAK1 and p-STAT6 （P<0.01）， and down-regulation in mRNA and protein levels of SOCS1 and protein levels of Occludin and Claudin-1 （P<0.01）. The treatment with HBY reduced the DAI （P<0.01）， alleviated colon shortening and histopathological damage in the colon tissue， decreased the RHI （P<0.01）， lowered the serum levels of IL-6， IL-1β， IL-18， and TNF-α （P<0.01）， down-regulated the mRNA levels of miR-21， JAK1， and STAT6 （P<0.05， P<0.01）， up-regulated the mRNA level of SOCS1 （P<0.05）， up-regulated the protein levels of SOCS1， Occludin， and Claudin-1 （P<0.05， P<0.01）， and down-regulated the protein levels of p-JAK1 and p-STAT6 （P<0.05， P<0.01）. ConclusionHBY may modulate the miR-21/SOCS1/JAK1/STAT6 signaling pathway to suppress inflammatory responses and restore the intestinal mucosal barrier in UC rats.

Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.

Objective This study aims to explore the association between non-suicidal self-injury(NSSI)and suicide attempts(SA)in adolescents and the mediating effect of cognitive flexibility.Methods A total of 218 depression patients with NSSI who met the Diagnostic and Statistical Manual of Mental Disorders,5th Edition(DSM-5)diagnostic criteria for NSSI were enrolled.Patients were divided into SA group(n=105)and non-SA group(n=113)according to the presence or absence of SA in the last one year.The adolescent non-suicidal self-injury assessment questionnaire(ANSAQ)and the Wisconsin card sorting tests(WCST)was used to assess the frequency of NSSI and cognitive flexibility,respectively.A mediation model was constructed to conduct path analysis,and the product distribution method was utilized to test the mediation effect.Results The difference between SA group and non-SA group in NSSI(20.1±10.7 vs.14.7±9.1)and WCST scores[correct responses percentage(67.3％±14.2％vs.72.9％±12.2％),error responses(39.8±20.3 vs.31.6±17.9),perseverative response(6.7±3.8 vs.5.3±2.9),and non-perseverative errors(37.6±21.0 vs.28.9±18.1)]were significant(P<0.05).Dichotomous logistic regression analysis showed that the frequency of NSSI(OR=1.051,95％CI:1.021-1.082)and the score of perseverative response(OR=1.100,95％CI:1.008-1.199)were significantly associated with suicidal behavior among adolescents with NSSI(P<0.05).Moreover,perseverative response partially mediated the association between NSSI and SA(95％CI of Za×Zb:0.0003-0.0168).Conclusion High NSSI and low cognitive flexibility are risk factors for suicide attempts in NSSI adolescents and NSSI may also affect SA indirectly by lowering cognitive flexibility.

Objective This study aims to explore the association between non-suicidal self-injury(NSSI)and suicide attempts(SA)in adolescents and the mediating effect of cognitive flexibility.Methods A total of 218 depression patients with NSSI who met the Diagnostic and Statistical Manual of Mental Disorders,5th Edition(DSM-5)diagnostic criteria for NSSI were enrolled.Patients were divided into SA group(n=105)and non-SA group(n=113)according to the presence or absence of SA in the last one year.The adolescent non-suicidal self-injury assessment questionnaire(ANSAQ)and the Wisconsin card sorting tests(WCST)was used to assess the frequency of NSSI and cognitive flexibility,respectively.A mediation model was constructed to conduct path analysis,and the product distribution method was utilized to test the mediation effect.Results The difference between SA group and non-SA group in NSSI(20.1±10.7 vs.14.7±9.1)and WCST scores[correct responses percentage(67.3％±14.2％vs.72.9％±12.2％),error responses(39.8±20.3 vs.31.6±17.9),perseverative response(6.7±3.8 vs.5.3±2.9),and non-perseverative errors(37.6±21.0 vs.28.9±18.1)]were significant(P<0.05).Dichotomous logistic regression analysis showed that the frequency of NSSI(OR=1.051,95％CI:1.021-1.082)and the score of perseverative response(OR=1.100,95％CI:1.008-1.199)were significantly associated with suicidal behavior among adolescents with NSSI(P<0.05).Moreover,perseverative response partially mediated the association between NSSI and SA(95％CI of Za×Zb:0.0003-0.0168).Conclusion High NSSI and low cognitive flexibility are risk factors for suicide attempts in NSSI adolescents and NSSI may also affect SA indirectly by lowering cognitive flexibility.

Chronic hepatitis B（CHB）is one of the major challenges in the global public health field. As of 2022，approximately 254 million people worldwide were infected with the hepatitis B virus（HBV）. CHB is one of the main causes of liver cirrhosis and hepatocellular carcinoma（HCC）. Nucleos（t）ide analogs（NAs）and interferon therapy can delay the progression of liver fibrosis by inhibiting viral replication，but they cannot completely avoid the problem of heterogeneous treatment responses. Some patients are in a state of low-level viremia（LLV）during treatment. The persistent LLV state can induce chronic inflammation and the progression of liver fibrosis，ultimately increase the risk of HCC. In patients with poor treatment responses，the continuous active viral replication can induce immune disorders，accelerate the evolution of fibrosis to the decompensated stage of liver cirrhosis，and increase the risk of patient death. This article aims to review the definition，mechanisms，and impact on treatment outcomes of LLV and suboptimal response based on the latest research，provide a basis for optimizing antiviral therapy for CHB.