Cholestatic liver disease （CLD） is closely associated with bile acid homeostasis imbalance， oxidative stress， inflammatory responses， mitochondrial damage， and hepatic fibrosis. Nuclear factor-erythroid 2-related factor 2 （Nrf2） can regulate molecules related to antioxidation， detoxification， and bile acid transport， and together with signaling pathways such as farnesoid X receptor （FXR）， silent information regulator 1/AMP-activated protein kinase， and nuclear factor-κB， participates in the development and progression of CLD. This review summarizes the role of Nrf2 in the development and progression of CLD， as well as the research progress on traditional Chinese medicine （TCM） active constituents and formulas/Chinese patent medicine in regulating Nrf2 for the intervention of CLD. The results indicate that TCM active constituents such as terpenoids， saponins， flavonoids， and polysaccharides， as well as formulas/Chinese patent medicine with the effects of heat-clearing and dampness-draining， liver-soothing and choleretic-promoting， and body-strengthening and liver-protecting， can improve bile acid metabolism and transport and alleviate oxidative stress， inflammatory responses， and hepatic fibrosis by regulating Nrf2-related signaling pathways. However， existing studies still primarily judge based on Nrf2 expression， nuclear translocation， and downstream molecular expression changes， and the understanding of the regulatory relationship between Nrf2 and signaling pathways such as FXR， as well as the synergistic mechanisms of multiple constituents in formulas， remains insufficient. Future studies can strengthen gene intervention and functional validation， utilize liver or bile duct organoids， co-culture systems， and other approaches， and combine bile acid profiling and multi-omics analysis to further elucidate the mechanism by which TCM regulates Nrf2 to ameliorate CLD.

Objective: To investigate the dynamic influence mechanism of the interaction between physical exercise and pre-sleep screen time on sleep quality among college students, so as to provide a theoretical basis for sleep health interventions in the population. Methods: From March to April 2025, a convenience sample of 2 075 students was recruited from eight universities in Jiangsu Province to participate in an online survey. Physical exercise was assessed using the Physical Activity Rating Scale-3 (PARS-3), sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI), and pre-sleep screen time behaviors were recorded using a self-designed structured questionnaire. Binary Logistic regression was used to examine the independent associations of physical activity level and pre-sleep screen time with sleep disorders. An interaction effect model was then applied to plot the dose-response relationship among the three variables. Results: The overall prevalence of sleep disorder among college students was 50.3%. Significant differences in the prevalence of sleep disorder were observed across groups of sex, academic discipline, grade, pre-sleep screen time, and physical exercise ( χ 2=42.45, 14.81, 18.99, 113.23, 40.61, all P <0.05). Binary Logistic regression showed that pre-sleep screen time was associated with the risk of sleep disorders (≤15 min: OR =1.70; 16- 30 min : OR =1.91; 31-60 min: OR =3.31; >60 min: OR =5.32), while both moderate ( OR =0.44) and high ( OR =0.57) physical exercise were associated with a reduced risk (all P <0.05). The interaction effect was statistically significant (Wald χ 2= 6.82 , P <0.01). The dose-response curves revealed that, in the low-exercise group, sleep quality deteriorated sharply with increasing screen time (the predicted mean dropped to 28% at the >60 min threshold, P <0.01); in the moderate exercise group, an inverted U-shaped trend was observed, with an optimal window of 16-30 min; and in the high exercise group, a significant buffering effect was found, with the predicted mean remaining at 43% even under >60 min screen exposure, representing a decrease of only 4% compared with the no-screen use group ( P >0.05). Conclusions High screen exposure combined with low physical exercise represents the primary behavioral pattern associated with a high prevalence of sleep disorders. Regular physical exercise can partially offset the negative effects of excessive screen time on sleep.

Objective:To compare the efficacy of three-dimensional visualization-assisted intermuscular versus conventional intermuscular cervical expansive open-door laminoplasty (CEOL) in the treatment of cervical spinal cord injury without fracture or dislocation (CSCIWFD).Methods:A retrospective cohort study was conducted to analyze the clinical data of 58 patients with CSCIWFD admitted to Zhengzhou Orthopedic Hospital from October 2021 to January 2024, including 39 males and 19 females, aged 36-77 years [(52.9±8.9)years]. Among them, 26 patients were treated with three-dimensional visualization-assisted intermuscular CEOL (three-dimensional visualization group), while 32 patients were treated with conventional intermuscular CEOL (conventional intermuscular group). All patients were treated with CEOL in 4 segments (C 3-C 6), comprising 104 surgical segments in the three-dimensional visualization group and 128 in the conventional intermuscular group. The following outcomes were compared between the two groups, including the operative duration, intraoperative blood loss, accuracy rate of open-door and hinge placement at the surgical levels, visual analogue scale (VAS) of the neck and shoulder and Japanese Orthopedic Association (JOA) score preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up, American Spinal Injury Association (ASIA) impairment scale preoperatively and at the last follow-up, and postoperative complication rate. Results:All patients were followed up for 12-24 months [(17.5±3.1)months]. The operative duration and intraoperative blood loss were (117.0±12.3)minutes and (151.3±30.9)ml in the three-dimensional visualization group, which were shorter or less than (131.9±15.0)minutes and (184.7±42.9)ml in the conventional intermuscular group ( P<0.01). The accuracy rate of open-door and hinge placement at the surgical levels was 94.2% (98/104) in the three-dimensional visualization group, significantly higher than 83.6% (107/128) in the conventional intermuscular group ( P<0.05). The VAS scores of the neck and shoulder preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively, and at the last follow-up were 6.0(5.0, 7.0)points, 3.5(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.0, 3.0)points, 2.0(1.0, 2.3)points, and 2.0(1.0, 2.0)points in the three-dimensional visualization group, which were not statistically different from 5.0(4.3, 6.8)points, 4.0(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.3, 2.0)points, 2.0(1.0, 2.8)points, and 2.0(1.0, 2.0)points in the conventional intermuscular group ( P>0.05). The VAS scores of the neck and shoulder in the two groups were significantly decreased at 1 week, 1 month and 3 months postoperatively from the preoperative values ( P<0.05), while they were stabilized at 6 months postoperatively and at the last follow-up compared with those at 3 months postoperatively, with no significant difference among them ( P>0.05). The JOA scores were (8.1±2.8)points, (10.0±2.6)points, (10.5±2.6)points, (11.6±2.3)points, (12.7±2.3)points, and (13.7±2.4)points in the three-dimensional visualization group, which were not statistically different from (8.8±2.2)points, (10.3±2.1)points, (10.8±2.0)points, (12.0±2.0)points, (12.9±2.0)points, and (13.8±2.1)points in the conventional intermuscular group ( P>0.05). The JOA scores of the two groups showed continuous improvement at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up in comparison with the preoperatively values ( P<0.05). Although no significant difference was observed between the two groups in ASIA grade preoperatively and at the last follow-up ( P>0.05), the ASIA grade at the last follow-up was significantly improved compared with that before surgery in both groups ( P<0.05). The postoperative complication rate was 12% (3/26) in the three-dimensional visualization group, significantly lower than 38% (12/32) in the conventional intermuscular group ( P<0.05). Conclusion:Compared with the conventional intermuscular approach, the three-dimensional visualization-assisted intermuscular CEOL offers advantages in reducing surgical trauma, improving surgical precision, and lowering the postoperative complication rate in the treatment of CSCIWFD.

Objective:To investigate the risk factors and their predictive efficacy for postoperative premature epiphyseal closure in pediatric patients with distal tibial epiphyseal fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 216 pediatric patients with distal tibial epiphyseal fractures admitted to Zhengzhou Orthopedics Hospital from January 2018 to December 2023, including 136 males and 80 females, aged 2-16 years [11.8(9.8, 13.3)years]. Among them, 112 patients were affected on the left side and 104 on the right. According to the Salter-Harris fracture classification, the fracture was classified as type I in 14 patients, type II in 97, type III in 38, type IV in 64 and type VI in 3. According to the presence of premature epiphyseal closure after surgery, the patients were divided into premature epiphyseal closure group ( n=38) and normal epiphyseal group ( n=178). Age, gender, body mass index (BMI), injury mechanism, side of injury, Salter-Harris classification of fracture, initial displacement distance of the fracture end, medial malleolar involvement by the fracture line surgical fixation method, operation duration, reduction method, and reduction quality were recorded in the two groups. Univariate analysis and binary Logistic regression analysis were used to evaluate and determine the independent risk factors for postoperative premature physeal closure in pediatric patients with distal tibial epiphyseal fracture. The receiver operating characteristic (ROC) curve was plotted and area under the curve (AUC) was calculated to evaluate the predictive efficacy of each risk factor for the occurrence of premature physeal closure in pediatric patients with distal tibial epiphyseal fractures. Results:Univariate analysis showed the occurrence of postoperative premature epiphyseal closure of the distal tibia was associated with age, Salter-Harris fracture classification, medial malleolar involvement by the fracture line, surgical fixation method, reduction method, and reduction quality ( P<0.05), while it was not correlated with gender, BMI, injury mechanism, side of injury, initial displacement distance of the fracture end, and operation duration ( P>0.05). Multivariate binary Logistic regression analysis showed that medial malleolar involvement by the fracture line ( OR=0.18, 95% CI 0.04, 0.76, P<0.05) and reduction quality ( OR=43.18,95% CI 10.71, 174.05, P<0.01) were significantly correlated with the occurrence of postoperative premature epiphyseal closure of the distal tibia. The results of ROC curve analysis showed that medial malleolar involvement by the fracture line had limited predictive efficiency (AUC=0.53, 95% CI 0.43, 0.63), reduction quality had moderate predictive efficacy (AUC=0.81, 95% CI 0.72, 0.91), while their combination demonstrated even higher predictive efficacy (AUC=0.83, 95% CI 0.74, 0.91). Conclusions:Medial malleolar involvement by the fracture line and reduction quality are independent risk factors for postoperative premature epiphyseal closure in pediatric patients with distal tibial epiphyseal fractures. Reduction quality demonstrates good predictive efficacy, while medial malleolar involvement by the fracture line shows limited predictive value. The combination of both factors achieves even better predictive performance.

AIM:This study aims to investigate the protective effect of Buyang-Huanwu decoction(BYHWD)on cerebral ischemia-reperfusion injury(CIRI)in rats,focusing on its role in regulating the autophagy of cerebral micro-vascular endothelial cells(BMECs).METHODS:(1)We established a rat model of middle cerebral artery occlusion/re-perfusion(MCAO/R)and divided the subjects into four groups:sham group,model(MCAO/R)group,BYHWD group,and 3-n-butylphthalide(NBP)group.Neurological deficits were assessed using the Zea Longa score,while the volume of cerebral infarction was measured through 2,3,5-triphenyltetrazolium chloride(TTC)staining.Pathological damage in the ischemic penumbra was evaluated using HE staining,and blood-brain barrier(BBB)permeability was assessed by Evans blue(EB)staining.The ultrastructure of BMECs was analyzed by transmission electron microscopy,and the co-expres-sion and positive cell rate of microtubule-associated protein 1 light chain 3(LC3)in BMECs were determined through im-munofluorescence double staining.Additionally,the protein expression levels of ZO-1,claudin-5 and occludin in the cor-tical region of the ischemic penumbra in rats were examined using Western blot analysis.(2)A rat BMEC model of oxy-gen-glucose deprivation/reoxygenation(OGD/R)was also established.Rat BMECs were categorized into normal control(CON),OGD/R,dimethyl sulfoxide(DMSO),rapamycin and 3-methyladenine groups to observe autophagy levels by monodansylcadaverine(MDC)staining.Furthermore,rat BMECs were divided into CON,OGD/R,BYHWD-containing serum(BHDS)and NBP groups.The cell autophagy was assessed by MDC staining and Western blot,while cell viability was measured by CCK-8 assay.RESULTS:(1)The rats in MCAO/R group exhibited significantly higher neurological scores(P＜0.01)and increased cerebral infarction volumes(P＜0.01)compared with sham group.Severe damage in the ischemic penumbra was observed,characterized by disordered tissue structure,widened intercellular spaces,and compro-mised cellular integrity.The EB dye permeability was notably elevated(P＜0.01),and BMECs showed structural destruc-tion,including damaged cell membranes,swollen Golgi apparatus,dilated endoplasmic reticulum vesicles,and damaged mitochondria.The ratio of LC3+CD31+/CD31+and the protein levels of ZO-1,claudin-5 and occludin were significantly el-evated(P＜0.01).In contrast,the rats in BYHWD and NBP groups demonstrated lower neurological scores(P＜0.01)and reduced cerebral infarction volumes(P＜0.01).Furthermore,EB permeability decreased(P＜0.01),BMEC morphol-ogy improved,and the protein expression levels of ZO-1,claudin-5 and occludin increased(P＜0.05).(2)Rat BMECs in OGD/R group had a significantly elevated autophagy level compared with CON group(P＜0.01),with increased expres-sion of LC3 and beclin-1 proteins and decreased level of P62 protein(P＜0.05).Notably,the cells in BHDS and NBP groups displayed decreased autophagy level compared with OGD/R group,with increased cell viability(P＜0.01),re-duced LC3 and beclin-1 protein expression,and increased P62 protein expression(P＜0.05).CONCLUSION:Buyang-Huanwu decoction alleviates cerebral ischemia-reperfusion injury in rats by inhibiting the autophagy of cerebral microvas-cular endothelial cells.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective:To explore the efficacy of percutaneous vertebroplasty (PVP) using the partition injection technique in the treatment of Kümmell’s disease of stages Ⅰ and Ⅱ.Methods:A retrospective study was conducted of the 30 patients with stage Ⅰ or Ⅱ Kümmell’s disease (the partition group) who had been treated by PVP using the partition injection technique at Department of Spinal Surgery, Zhengzhou Orthopedic Hospital from January 2020 to January 2022. The data of another 30 patients who had been treated at the same department and the same period using conventional PVP for stage Ⅰ or Ⅱ Kümmell's disease were selected as the conventional group. In the partition group, there were 13 males and 17 females, with an age of (72.3±10.1) years and disease duration of (3.1±1.5) months. Seventeen thoracic and 13 lumbar vertebrae were affected. In the conventional group, there were 11 males and 19 females, with an age of (75.5±12.7) years and disease duration of (3.5±1.8) months. Eighteen thoracic and 12 lumbar vertebrae were affected. Surgical time, volume of bone cement injected, bone cement leakage, and bone cement distribution were compared between the 2 groups. The heights of the anterior and middle vertebral bodies, kyphotic Cobb angle, visual analog scale (VAS) pain score, and Oswestry disability index (ODI) were assessed postoperatively at 1 day, 6 months, and the last follow-up and compared between the 2 groups.Results:No significant differences were found in the baseline data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (17.3±3.1) months. There were no significant differences in the surgical time or bone cement leakage between the 2 groups ( P>0.05). The volume of bone cement injected in the partition group was significantly higher [(6.3±1.5) mL] than that in the conventional group [(4.9±1.0) mL] ( P<0.05). Bone cement distribution was significantly better in the partition group than that in the conventional group ( P<0.05). At postoperative 1 day, 6 months, and the last follow-up, the partition group was significantly better than the conventional group in anterior vertebral body height, middle vertebral body height, and kyphotic Cobb angle ( P<0.05). At the 6-month and the last follow-ups, the partition group was also significantly better than the conventional group in VAS pain score and ODI ( P<0.05). Conclusion:In the treatment of Kümmell’s disease of stages Ⅰ and Ⅱ, compared with conventional PVP, PVP using the partition injection technique may lead to better long-term outcomes due to its better bone cement distribution, more adequate cement injection, and better restoration of vertebral body heights and correction of local deformity.

Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

Objective : To analyze the epidemiological characteristics and spatial clustering of brucellosis in Shanxi Province from 2019 to 2023, so as to provide a reference for formulating prevention and control measures of brucellosis. Methods: The case data of brucellosis in Shanxi Province from 2019 to 2023 were collected through the Infectious Disease Surveillance System of the Chinese Disease Prevention and Control Information System. The seasonal distribution, population distribution, and region distribution of brucellosis cases were described. Spatial autocorrelation analysis was applied to explore the spatial clustering characteristics of brucellosis. Results: A total of 21 241 human brucellosis cases were reported in Shanxi Province from 2019 to 2023, with an average annual reported incidence of 11.87/100 000, showing an upward trend (P<0.05). The peak incidence period was from March to August, with 14 163 cases reported cumulatively, accounting for 66.68% of the total. There were 16 336 male cases and 4 905 female cases, with a male-to-female ratio of 3.33:1. The high-incidence age group was 40-<70 years, with 15 675 cases accounting for 73.80%. The majority of patients were farmers, with 17 926 cases accounting for 84.39%. Spatial autocorrelation analysis showed that there was spatial clustering in the incidence of brucellosis from 2019 to 2023 (all Moran's I>0, P<0.05). The high-high clustering areas were mainly Datong City, and Shuozhou City in northern Shanxi, and Linfen City in the southern Shanxi. The low-low clustering areas were mainly Taiyuan City and Yangquan City in central Shanxi, and Changzhi City and Jincheng City in southeastern Shanxi. Conclusions From 2019 to 2023, the reported incidence of brucellosis in Shanxi Province showed an upward trend. The incidence peaked from March to August, and males, middle-aged and elderly people and farmers were the high-risk groups. There was spatial clustering and the high-high clustering areas gradually expanded from northern Shanxi to southern Shanxi.