Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

ObjectiveTo analyze the research hotspots and development trends in the field of spinal cord stimulation (SCS) for spinal cord injury (SCI). MethodsLiterature about SCS for SCI was retrieve from the Web of Science (WOS) Core Collection database, with a time range from January, 1999 to July, 2025. VOSviewer 1.6.20 and CiteSpace 6.4.R2 were used to analyze the annual publication volume, countries, authors, institutions, journals and keywords. ResultsA total of 636 literatures were included. From 1999 to 2025, the overall publication trend in this field showed an upward trajectory, with recent years fluctuating but tending to stabilize. The country with the most publications was the United States (429 papers), followed by Russia (98 papers) and China (70 papers). The institution with the highest number of publications was the University of California, Los Angeles (76 papers), the author with the most publications was V. Reggie Edgerton (70 papers), and the journal with the most publications was Journal of Clinical Medicine (31 papers). The most frequently cited study focused on exploring the combination of epidural spinal cord stimulation with task-specific training to restore motor function in patients with complete SCI. Keyword analysis showed that the research hotspots in this field were mainly focused on neuroregulation mechanisms, recovery of motor and autonomic nervous dysfunction, artificial intelligence, closed-loop stimulation and brain-computer interface technology innovations. In recent years, the research focus gradually shifted from basic mechanisms to personalized and precise multifunctional rehabilitation strategies. ConclusionThe field of SCS for SCI has undergone phases of basic mechanism exploration and clinical application expansion. Current research hotspots and future trends focus primarily on the development of new stimulation paradigms and combined innovative technologies.

Background Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents. Current research suggests that environmental factors, such as per- and polyfluoroalkyl substances (PFAS), may be associated with an increased risk of ADHD in offspring. However, most epidemiological evidence originates from non-Chinese populations, with limited research investigating the association between prenatal PFAS and ADHD-like symptoms in Chinese school-aged children. Objective To examine the association between prenatal PFAS exposure and ADHD-like symptoms in 7-year-old children. Methods Based on the Shanghai Birth Cohort, this study included 488 mother-child pairs. PFAS were measured in maternal serum during the second trimester using ultra-performance liquid chromatography-tandem mass spectrometry. The analysis focused on eight specific compounds from three PFAS categories [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS)]. The hyperactivity subscale of the Strengths and Difficulties Questionnaire (SDQ) was used to assess ADHD-like symptoms in children at age 7. Basic demographic information was collected via questionnaires and medical records. Negative binomial regression models were used to evaluate the relationship between individual exposures to the three typical PFAS categories (PFOA, PFOS, and PFHxS) and children's ADHD-like symptoms, while the bayesian kernel machine regression (BKMR) mixture model was employed to assess the overall effect of PFAS mixture exposure on ADHD-like symptoms. Results The detection rates of the eight target PFAS in maternal second-trimester serum were all above 85%, with PFOA exhibiting the highest median concentration (10.21 ng·mL⁻¹). Overall, 14.75% of the children exhibited ADHD-like symptoms. Results from the negative binomial regression models showed that second-trimester exposures to PFOA (IRR=1.15, 95%CI: 1.05, 1.26), n-PFOS (IRR=1.08, 95%CI: 1.01, 1.15), 6m-PFOS (IRR=1.13, 95%CI: 1.05, 1.21), and 1m-PFOS (IRR=1.11, 95%CI: 1.03, 1.18) were associated with an increased risk of ADHD-like symptoms in 7-year-old children. Stratified analyses suggested potentially statistically significant associations in girls [e.g., for PFOA, boys vs. girls: 1.09 (0.96, 1.23) vs. 1.25 (1.09, 1.44), P-int=0.31]. The BKMR mixture model indicated that the risk of ADHD-like symptoms trended upward with increasing PFAS mixture concentrations, although this association was statistically significant only among girls (P < 0.05). Conclusion Prenatal PFAS exposure may be associated with an increased risk of ADHD-like symptoms in 7-year-old children, and this adverse association appears to be more prominent in girls.

Objective·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated(GelMA)hydrogel scaffolds loaded with tauroursodeoxycholic acid(TUDCA)on cartilage defects in rabbit knee joints.Methods·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method.The physicochemical properties of GelMA hydrogel scaffolds were characterized,and the cumulative release rate of TUDCA was determined.A rabbit knee cartilage defect model was established,and 18 rabbits were randomly assigned into three groups,with six rabbits in each group:the control group(no treatment was applied to the cartilage defect),the GelMA group(the cartilage defect was filled with GelMA hydrogel scaffold),and the GelMA+TUDCA group(the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA).At 12 weeks postoperatively,the concentrations of two inflammatory factors in synovial fluid,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),were detected by enzyme-linked immunosorbent assay(ELISA).After euthanasia,knee cartilage samples were harvested for gross observation,safranin O-fast green staining,and toluidine blue staining.The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society(ICRS)and Modified O'Driscoll Score(MODS)systems.Immunohistochemical staining was performed to detect type Ⅱ collagen(COL-Ⅱ)protein in the cartilage tissue,and Western blotting was used to assess the protein levels of aggrecan(ACAN)and COL-Ⅱ.Results·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation,along with an suitable mass swelling ratio and compressive modulus.The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release,achieving a cumulative release rate of 90.2%±2.5%within 28 d.ELISA results showed that compared to the control and GelMA groups,the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced(P<0.001).In the GelMA+TUDCA group,the cartilage defects were nearly fully repaired,with a smooth surface and good integration with the surrounding tissue.The number of newly formed chondrocytes increased,displaying orderly alignment,and the neocartilage exhibited excellent formation.Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups(P<0.001).Additionally,the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups(P<0.001).Conclusion·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.

Alzheimer's disease(AD)is a typical progressive neurodegenerative disease,mainly manifesting as severe cognitive dysfunction,and involving memory,thought processes,and emotion.The kynurenine pathway(KP)is one of the main metabolic pathways of tryptophan,which can be divided into neurotoxicity and neuroprotective branches.Increasing evidence has suggested that KP is involved in the pathogenesis of AD.This review considers the role of KP in the pathogenesis of AD,with reference to the relevant literature on KP interventions in AD in the PubMed database.The result will provide an important reference for the use of KP as a target for AD drug development.

Objective:To clarify the content on exercise training in patients with connective tissue disease-associated pulmonary arterial hypertension through a scoping review.Methods:Using the scoping review methodological framework proposed by Arksey and O'Malley as a guide, Chinese and English databases such as PubMed, Embase, Wanfang Data, and China National Knowledge Infrastructure were searched to screen the literature on exercise training for patients with connective tissue disease-associated pulmonary arterial hypertension. The search period was from database establishment to April 30, 2024. Two researchers extracted basic information of the included literature, content of the pre-exercise training assessment, exercise training program, and outcome indicators.Results:A total of 13 articles were included. The content of the pre-exercise training assessment in patients with connective tissue disease-associated pulmonary arterial hypertension was not standardized. The type of exercise training was based on aerobic, resistance and respiratory training, with a focus on home exercise. The main outcome indicators included the 6-minute walk distance, cardiopulmonary function, quality of life, and muscle strength.Conclusions:There are various types of exercise training for patients with connective tissue disease-associated pulmonary arterial hypertension, which are safe and feasible. Future research should focus on conducting home-based exercise training programs and constructing core outcome indicators to assess the effectiveness of exercise training.

Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

Objective:To evaluate the long-term effectiveness of lingual mucosal graft ureteroplasty (LMGU) for managing long-segment (≥5 cm) ureteral strictures in a multi-institutional cohort of patients.Methods:A multi-center retrospective case series study was conducted on clinical data from 42 patients undergoing LMGU for long-segment ureteral strictures (≥5 cm) across five institutions between February 2017 and June 2024. The cohort comprised 31 males and 11 females, with an age of (43.4±12.0) years (range: 15 to 64 years) and a body mass index of (24.6±2.6) kg/m2 (range: 16.0 to 30.0 kg/m2). Strictures involved the left ureter in 24 cases and right ureter in 18 cases, demonstrating a stricture length of (6.4±1.5) cm (range: 5.0 to 11.5 cm). Surgical interventions included either onlay ureteroplasty or augmented anastomotic ureteroplasty, selected according to intraoperative findings. Intraoperative parameters, postoperative complications, and follow-up outcomes were analyzed.Results:Laparoscopic surgery was performed in 22 cases and robot-assisted surgery in 20 cases. Among the 42 patients, 22 underwent onlay ureteroplasty while 20 received augmented anastomotic ureteroplasty. The graft length was (5.9±1.8) cm (range: 3.0 to 12.0 cm), operative time (191.5±55.6) minutes (range: 105.0 to 350.0 minutes), and intraoperative estimated blood loss (86.7±73.6) ml (range: 10.0 to 400.0 ml). All procedures were successfully completed without conversion to open surgery. The postoperative hospital stay was (7.6±2.0) days (range: 4.0 to 15.0 days), with double-J stent removal at 6 to 8 weeks postoperatively. During a follow-up of (49.1±25.0) months (range: 12.0 to 99.0 months), no stricture recurrence was observed in any patient.Conclusion:LMGU is a safe, feasible, and effective long-term technique for managing long-segment (≥5 cm) ureteral strictures.

Objective To explore the role of secreted phosphoprotein 1(SPP1)and myeloid differentiation primary response 88(MYD88)in morphine-induced cardiomyocyte apoptosis.Methods A morphine addiction model was established in Sprague-Dawley(SD)rats.Twelve SD rats were randomly assigned to the normal saline(NS)group or the morphine-dependent(DAM)group.Histopathological analysis was employed to observe and compare myocardial tissue morphology between the two groups.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining was performed to assess the number of apoptotic cells in each group.The expression levels of SPP1 and MYD88 were evaluated using immunohistochemistry.Quantitative real-time poly merase chain reaction(RT-qPCR)and Western blot were used to detect the mRNA and protein expression of SPP1,MYD88,Bax,Bcl2,Caspase-3,and Caspase-9.Simultaneously,Western blot analysis was used to detected the expression of Cleaved Caspase-3 and Cleaved Caspase-9 proteins.In vitro,SPP1 expression was knocked down in primary neonatal rat cardiomyocytes(NRCMs),and cells were divided into three groups:control(CON),morphine treated(DA),and shSPP1#3+DA.Cell viability was assessed using the CCK-8 assay,and apoptosis rates were determined by flow cytometry.Results HE and TUNEL staining of myocardial tissues from morphine-addicted SD rats revealed that,compared with the NS group,myofibrils in the DAM group exhibited partial disruption and a significant increase in apoptotic cells(P<0.05).Western blot and RT-qPCR analyses demonstrated that,relative to the NS group,the mRNA and protein levels of SPP1,MYD88,Bax,Caspase-3,and Caspase-9 were significantly upregulated in the DAM group(P<0.05),whereas Bcl2 expression was significantly downregulated at both mRNA and protein levels(P<0.05),and the protein expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 were also increased.with all differences being statistically significant.In NRCMs following morphine intervention,cell viability in the DA group was markedly reduced compared to the CON group(P<0.05),accompanied by a signifi-cant increase in apoptosis rate(P<0.05).Consistently,Western blot and RT-qPCR results showed elevated mRNA and protein expression of SPP1,MYD88,Bax,Caspase-3,and Caspase-9 in the DA group(P<0.05),along with decreased Bcl2 expression(P<0.05).The protein expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 were elevated simultaneously.In contrast,the shSPP1#3+DA group exhibited opposing trends compared to the DA group,with statistically sig nificant differences(P<0.05).Conclusion SPP1 and MYD88 play critical roles in mediating morphine-induced cardiomyocyte apoptosis,and silencing SPP1 has been shown to significantly reduce the extent of cardiomyocyte apoptosis following morphine exposure.

Objective·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated(GelMA)hydrogel scaffolds loaded with tauroursodeoxycholic acid(TUDCA)on cartilage defects in rabbit knee joints.Methods·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method.The physicochemical properties of GelMA hydrogel scaffolds were characterized,and the cumulative release rate of TUDCA was determined.A rabbit knee cartilage defect model was established,and 18 rabbits were randomly assigned into three groups,with six rabbits in each group:the control group(no treatment was applied to the cartilage defect),the GelMA group(the cartilage defect was filled with GelMA hydrogel scaffold),and the GelMA+TUDCA group(the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA).At 12 weeks postoperatively,the concentrations of two inflammatory factors in synovial fluid,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),were detected by enzyme-linked immunosorbent assay(ELISA).After euthanasia,knee cartilage samples were harvested for gross observation,safranin O-fast green staining,and toluidine blue staining.The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society(ICRS)and Modified O'Driscoll Score(MODS)systems.Immunohistochemical staining was performed to detect type Ⅱ collagen(COL-Ⅱ)protein in the cartilage tissue,and Western blotting was used to assess the protein levels of aggrecan(ACAN)and COL-Ⅱ.Results·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation,along with an suitable mass swelling ratio and compressive modulus.The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release,achieving a cumulative release rate of 90.2%±2.5%within 28 d.ELISA results showed that compared to the control and GelMA groups,the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced(P<0.001).In the GelMA+TUDCA group,the cartilage defects were nearly fully repaired,with a smooth surface and good integration with the surrounding tissue.The number of newly formed chondrocytes increased,displaying orderly alignment,and the neocartilage exhibited excellent formation.Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups(P<0.001).Additionally,the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups(P<0.001).Conclusion·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.