ObjectiveTo systematically compare the effects of diverse electromagnetic stimulation protocols on hand function and activities of daily living (ADL) in stroke patients using network meta-analysis (NMA), and screen the optimal stimulation strategy for post-stroke hand dysfunction rehabilitation. MethodsNMA was performed in accordance with the PRISMA-NMA statement. Databases of CNKI, Wanfang data, VIP, CBM, PubMed, Web of Science and Embase were searched from database inception to April, 2026 for eligible randomized controlled trials (RCTs) comparing different electromagnetic stimulation protocols for post-stroke hand impairment. The Cochrane Risk of Bias tool and PEDro scale were used to assess methodological quality of included studies, while the GRADE system was adopted to grade evidence quality of primary outcomes of Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI). After literature screening, data extraction and bias evaluation, RevMan 5.4 and Stata 17.0 were used for meta-analysis and NMA. ResultsA total of 22 RCT involving 17 electromagnetic stimulation protocols were finally included. The PEDro scores ranged from six to ten. The top five protocols for improving FMA-UE score were repetitive peripheral magnetic stimulation (rPMS) + repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS) + rPMS, iTBS + transcranial direct current stimulation (tDCS), transcutaneous electrical acupoint stimulation (TEAS) and contralaterally controlled functional electrical stimulation (CCFES). tDCS was the most effective on MBI, followed by TEAS and iTBS+rPMS. Evidence quality for FMA-UE and MBI was moderate. Funnel plots suggested low risk of publication bias, and consistency tests verified good coherence between direct and indirect comparisons in network models. ConclusionElectromagnetic stimulation significantly facilitates upper limb and hand functional recovery, and improves ADL in stroke patients. The combined central-peripheral magnetic stimulation protocol may be the most effective on motor rehabilitation, whereas tDCS on ADL.

Objective: To explore new therapeutic strategies for periodontitis, this study prepared extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) loaded with saikosaponin D (SSD) and evaluated their efficacy in a mouse model of periodontitis. Methods: This study was approved by the Medical Ethics Committee and the Laboratory Animal Ethics Committee of the unit. hUC-MSCs at logarithmic growth phase were seeded into 96 well plates and then treated with various concentrations of SSD for 24 hours. The CCK-8 assay was used to determine the SSD concentration that preserves hUC-MSC viability. Flow cytometry (FCM) assessed SSD-induced apoptosis in hUC-MSCs and determined drug loading and loading efficiency. Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) characterized the morphology and size of hUC-MSCs-EVs and hUC-MSCs-SSD-EVs. C57BL/6J mice were divided into five groups with six mice per group: control group, periodontitis model group (PD), PD+SSD group (2 mg/kg), PD+hUC-MSCs-EVs group (10 μg/μL) and PD+hUC-MSCs-SSD-EVs group (10 μg/μL). Administration was performed 3 times a week for 4 consecutive weeks. Micro-CT and hematoxylin-eosin (HE) staining evaluated alveolar bone resorption in periodontal tissues of a mouse model of periodontitis. RT-qPCR measured inflammatory cytokine expression in periodontal tissues of a mouse model of periodontitis. Immunofluorescence analyzed macrophage M1/M2 polarization and runt-related transcription factor 2 (RUNX2) protein expression in periodontal tissues of a mouse model of periodontitis. Results: The CCK-8 assay showed that 10 μmol/L SSD had little effect on hUC-MSCs viability (P>0.05). FCM confirmed the successful loading of SSD into EVs with a loading efficiency of 11.40%. TEM and NTA revealed that hUC-MSCs-SSD-EVs presented round or oval membranous structures with diameters ranging from 200 to 300 nm. Micro CT and HE staining showed that, compared with the PD group, the distance from cementoenamel junction to alveolar bone crest (CEJ-ABC) was markedly shortened (P<0.01）.The alveolar bone of periodontitis‑model bone volume fraction (BV/TV) and trabecular number (Tb.N) were significantly elevated in the PD+hUC-MSCs-SSD-EVs group (P<0.01). RT-qPCR and IF results showed that hUC-MSCs-SSD-EVs in periodontal tissues markedly downregulated the expression of pro-inflammatory cytokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, interleukin-12 and interleukin-22 (P<0.01), upregulated the expression of the anti-inflammatory factor interleukin-10 (P<0.01), promoted the polarization of macrophages from the M1 phenotype to the M2 phenotype, and elevated the protein expression level of RUNX2 (P<0.01). Conclusion hUC-MSC-SSD-EVs effectively alleviated inflammatory responses in a mouse model of maxillary periodontitis and reduced alveolar bone loss, providing a new idea for the treatment of periodontitis.

Objective To explore the role of resilience and stress in childhood maltreatment and adolescent depression and anxiety symptoms, and to provide a basis for adolescent psychological intervention. Methods From September to October 2022, a total of 11 217 students from four middle schools in Changsha were selected by multistage stratified sampling, and the Childhood Trauma Questionnaire, Depression–Anxiety–Stress Scales and the Resilience Scale for Chinese Adolescents were used to carry out online questionnaire survey. Results The detection rate of depressive symptoms and anxiety symptoms in adolescent was 19.43% (2 179) and 28.7% (3 224). The direct effect of childhood maltreatment on depressive symptoms was significant (β =0.09), Childhood maltreatment is a negative prediction of resilience (β = -0.57) and a positive prediction of pressure (β =0.06); Resilience can negatively predict stress (β = -0.61) and depressive symptoms (β = -0.25) (all P values <0.001); The direct effect of childhood maltreatment on anxiety symptoms was significant (β =0.03), resilience negatively predicts anxiety symptoms (β = -0.08) (all P values <0.01). Resilience and stress have a partially mediating role between childhood maltreatment and depressive symptoms, the mediation effect value was 0.39, accounting for 81.25% of the total effect. The effect values of the three pathways accounted for 29.17%, 8.33% and 43.75% of the total effect, respectively. Resilience and stress have a partial mediating effect between childhood abuse and anxiety symptoms, and the mediating effect was 0.36, accounting for 92.31% of the total effect, and the effect values of the three pathways accounted for 12.82%, 10.26% and 69.23% of the total effect, respectively. Conclusion Childhood maltreatment could affect adolescents’ depression and anxiety through the chain mediating effect of resilience and stress.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Combined vaccines can simplify the vaccination process, improve coverage rates, reduce the risk of adverse events following immunization, lower social costs, and improve the timeliness of childhood vaccination. This article focuses on multi-component vaccines based on the diphtheria-tetanus-pertussis containing vaccine. Globally, multiple combined vaccines have been developed and marketed, but the development of combined vaccine is still in its infancy stage in China, with limited vaccine types and doses available. The research, development, and application of combined vaccines still face numerous challenges in China, including technical challenges in research and development, as well as insufficient motivation for research and development. Additionally, the high cost of existing combined vaccines, coupled with low public awareness and weak vaccination intentions, significantly hinders their widespread application, China should continue to rigorously implement the Vaccine Administration Law of the People's Republic of China, promote innovative development of combined vaccines, increase public awareness, strengthen child guardians' confidence in vaccination, and improve the accessibility and affordability of combined vaccines to protect public health across all life stages.

Objective:To analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021, and to explore the effects of age, period, and cohort on pancreatic cancer incidence and mortality.Methods:Data from the Global Burden of Disease Study (GBD) 2021 database were used to analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021. The Joinpoint software was applied to analyze the time trends of standardized incidence and mortality rates, and to calculate the average annual percentage change. An age-period-cohort model was constructed to analyze the effects of age, period, and birth cohort on the trends of pancreatic cancer incidence and mortality. The disease burden of pancreatic cancer deaths attributed to risk factors such as hyperglycemia and smoking was analyzed.Results:In 2021, the incidence of pancreatic cancer in China was 8.34/100 000, and the mortality rate was 8.41/100 000, representing increases of 150.45% and 145.19%, respectively, compared to 1992 (3.33/100 000 and 3.43/100 000) . By sex, the incidence (9.93/100 000) and mortality (9.91/100 000) rates in males in 2021 were higher than those in females (6.68/100 000 and 6.83/100 000) . From 1992 to 2021, the standardized incidence and mortality rates of pancreatic cancer in China showed upward trends, with average annual increases of 0.80% and 0.62%, respectively, both of which were statistically significant (both P<0.001) . Age effect results indicated a general increasing trend in pancreatic cancer incidence, with a steady rise in the 15-49 age group, a sharp increase after the age of 50, and a peak in the over 85 age group at 68.64/100 000. The mortality rate showed a slow increase in the 15-79 age group, with a marked rise and peak in the 80-84 age group at 196.51/100 000. Period effect results showed an overall upward trend in the period relative risk ( RR) for pancreatic cancer incidence, with the highest risk in 2017-2021 ( RR=1.09, 95% CI: 1.05-1.13, P=0.012) , compared to the reference period 2002-2006 ( RR=1) . The RR for pancreatic cancer mortality showed a fluctuating trend, with the highest risk in 2012-2016 ( RR=1.60, 95% CI: 1.07-2.38, P=0.021) , compared to the reference period 2002-2006 ( RR=1) . The results of cohort effect showed that the incidence and mortality risk of pancreatic cancer in China generally increased with the increase of years. With the 1952-1956 birth cohort as the reference cohort ( RR=1) , the incidence ( RR=1.18, 95% CI: 0.99-1.40, P=0.032) and mortality ( RR=1.63, 95% CI: 0.12-11.53, P=0.042) risk of pancreatic cancer were the highest in the 1987-1991 birth cohort, and showed decreasing trends after the 1992-1996 birth cohort. The proportion of pancreatic cancer deaths attributable to high blood glucose showed an increasing trend, while those attributable to smoking showed a decreasing trend. Conclusions:From 1992 to 2021, the standardized incidence and mortality rates of pancreatic cancer in China have continued to rise, with males having higher incidence and mortality rates than females. Age, period, and cohort all significantly influence the trends in pancreatic cancer incidence and mortality. The trend in pancreatic cancer deaths attributable to high blood glucose is increasing.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry， in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry， this study introduced the standardized assessment and precautions before issuing long-term prescriptions， the formulation and adjustment of the drug list， as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions， a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors， pharmacological treatment plans and other non-pharmacological therapies， physical illnesses. Additionally， healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments， and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore， measures such as adding special identifiers to long-term prescriptions， providing patients with reminders about （No.YGLX202537） prescription expiration， or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently， the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration， incomplete coverage of diagnostic categories， poor patient adherence， and the risk of deviation in clinical assessments. In this regard， measures such as collaborating with multiple departments to strengthen long-term prescription information management， providing matching pharmaceutical services， ensuring the quality and rationality of long-term prescription implementation， and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.

ObjectiveTo investigate the mechanism of action of Huangqi Guizhi Wuwutang （HGWT） against cerebral ischemia-reperfusion injury （CIRI） based on bioinformatics and experimental validation. MethodsBiological informatics methods were used to screen for active components of HGWT and their targets. The GEO database was utilized to obtain CIRI-related differentially expressed genes （DEGs）， and platforms such as GeneCards were used to identify disease targets. Venn diagram analysis was conducted to identify overlapping targets， followed by protein-protein interaction （PPI）， gene ontology （GO）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis， as well as immune infiltration and immune cell differential analysis. Core genes （Hub genes） were screened using LASSO regression and ROC curves， and molecular docking was used to validate the binding efficiency between the active components of the drug and the core targets. A rat CIRI model was established， with rats randomly divided into five groups （n=10）： Sham surgery group （Sham）， model group （MG）， and low-dose （LD，5.3 g·kg^-1）， medium-dose （MD，10.6 g·kg^-1）， and high-dose （HD，21.2 g·kg^-1） HGWT groups. From 3 days before modeling to 7 days after surgery， oral administration was performed daily： Sham and MG groups received physiological saline， while each drug group received the corresponding dose of HGWT. Hematoxylin-eosin （HE） staining， Nissl staining， and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL staining） were used to assess the repair effects of HGWT on neural damage. Western blot analysis was used to detect B-cell lymphoma-2 protein （Bcl-2）， Bcl-2-associated X protein （Bax）， signal transducer and activator of transcription 3 （STAT3）， phosphorylated STAT3 ［p-STAT3 （Tyr705）］， protein kinase B1 （Akt1）， and phosphorylated Akt1 ［p-Akt1 （Ser473）］， among other target proteins. ResultsAfter screening， 56 common target points of DEGs-disease-drug were obtained. GO and KEGG analyses indicated that HGWT primarily functions in pathways such as apoptosis， oxidative stress， and inflammatory responses. Immune infiltration analysis revealed a significant association between HGWT's anti-CIRI activity and immune cells such as Th17 cells and myeloid-derived suppressor cells （MDSCs） （P0.01）. LASSO-ROC analysis identified Akt1， Caspase-3， glycogen synthase kinase-3β （GSK-3β）， and STAT3 as core genes. Molecular docking confirmed that Hub genes exhibit significant binding affinity with the active components of HGWT （binding energy ≤ -5 kJ·mol^-1）（1 cal≈4.186 J）. Animal experiment results showed that compared with the sham group， the MG group exhibited significant neuronal necrosis， nuclear condensation， and vacuolar degeneration in rat brains， with a significant decrease in Nissl body density （P0.01） and increased neuronal apoptosis in rat brains as indicated by TUNEL staining （P0.01）. Compared with the MG， the LD， MD， and HD groups showed reduced neuronal necrosis， nuclear condensation， and vacuolar degeneration in rat brain neurons， increased Nissl body density， and reduced apoptosis （P0.01）， with significant differences among the drug groups （P0.01）. Western blot results showed that compared with the sham group， the MG group had reduced Bcl-2 and p-Akt1 （P0.01） and increased Bax and p-STAT3 （P0.01）. Compared with the MG group， the drug groups showed increased Bcl-2 and p-Akt1 （P0.01） and decreased Bax and p-STAT3 （P0.01）. There were no significant changes in total Akt1 and STAT3 protein levels among the groups. ConclusionBased on network pharmacology and experimental verification， HGWT may exert its neuroprotective effects by regulating the phosphorylation levels of Akt1 and STAT3， thereby alleviating cell apoptosis， inflammatory responses， and oxidative stress in rat brain tissue following CIRI. This provides theoretical support for the clinical treatment of CIRI.