Ductular reaction （DR） refers to the adaptive pathological changes that occur after hepatobiliary injury， and it is essentially a repair response involving the proliferation， fibrosis， and inflammation of biliary epithelial cell （BEC）. With the understanding of the biological function of BEC， the potential value of DR in disease prognosis and treatment has gradually become a research hotspot. This article systematically reviews the molecular mechanism of DR， its potential as a therapeutic target， and future development directions， as well as novel therapies suggested by targeting these molecular mechanisms， in order to provide a new direction for overcoming current bottlenecks in the treatment of bile duct diseases.

Animal model research on spleen and stomach diseases in traditional Chinese medicine （TCM） is of great significance for elucidating the nature of diseases and syndromes and for revealing the mechanisms of action of Chinese herbal medicinals. At present， studies on classical TCM syndrome models of spleen and stomach diseases mainly focus on spleen deficiency syndrome， liver constraint syndrome， and damp-heat syndrome. Model construction is mostly based on the etiological and pathophysiological characteristics of syndrome， and model evaluation primarily involves macroscopic manifestations and physicochemical indicators. This paper summarizes the current research status of animal models integrating disease and syndrome for seven common spleen and stomach diseases， including chronic gastritis and gastric precancerous lesions， gastroesophageal reflux disease， functional dyspepsia， inflammatory bowel disease， irritable bowel syndrome， functional constipation， and functional diarrhea. The modeling methods and characteristics of disease-syndrome combined animal models for each disease are analyzed. It is proposed that future research on disease-syndrome integration in spleen and stomach diseases should move toward syste-matic， precise， and integrative development， and that interdisciplinary and cross-disciplinary research approaches should be adopted to enhance the predictive value and application efficiency of disease-syndrome combined animal models.

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

Hepatolenticular degeneration, also known as Wilson disease (WD), is a type of copper metabolism disorder caused by an ATP7B gene variant, which is manifested by the abnormal accumulation of copper in the liver and other organs, resulting in multisystem damage. This article summarizes the latest research progress, with an emphasis on clinical characteristics, analysis of the optimization of diagnostic technology, and the clinical application of novel copper chelator therapy, as well as the development status and future prospects of gene therapy for WD. Future research should focus on the in-depth analysis of the mechanism, the application of multidimensional precision diagnosis technology, the development of individualized treatment plans, and the development of multicenter clinical trials in order to improve the comprehensive treatment effects and quality of life for patients with WD.

Wilson disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive inherited disorder of copper metabolism that primarily affects the liver, brain, and other organs. The diagnostic criteria include clinical features, biochemical tests (plasma ceruloplasmin, 24-hour urinary copper, liver copper content), and molecular genetic analysis. The Leipzig scoring system, supplemented by the use of exchangeable copper, is recommended for diagnosis. Pharmacotherapy mainly includes chelating agents (such as penicillamine and trientine) and zinc salts. Chelating agent therapy is recommended only for patients with severe liver disease. Patient monitoring is primarily based on clinical symptoms, liver biochemical indices, and copper metabolism parameters (such as 24-hour urinary copper and exchangeable copper) to identify poor adherence as well as over-treatment or under-treatment situations. The diagnosis and treatment of acute liver failure with WD is extremely challenging, as the diagnosis is difficult and medical treatment cannot save life. The role of liver transplantation has been clearly recognized in the treatment of acute liver failure with WD, and it may also be considered in cases with neurological involvement.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Objective:To establish a Zika virus-infected suckling SD rat model with type Ⅰ interferon receptor deficiency（SD-Ifnar1 -/-［cc］）and provide a novel animal model for investigating Zika virus pathogenesis and developing therapeutic strategies. Methods:Seventeen-day-old male SD-Ifnar1 -/-［cc］rat pups were randomly divided into experimental and control groups（ n=6）. The experimental group received an intraperitoneal injection of Zika virus strain SZ-wiv01（5×10 4 PFU/rat，200 μl），while the control group received an equal volume of phosphate-buffered saline（PBS）. Animals were euthanized via CO 2 asphyxiation on days 12 and 15 post-infection（dpi），and brain，spleen，liver，and testis tissues were harvested. Viral loads and cytokine expression levels were quantified using quantitative real-time PCR qRT-PCR），and histopathological evaluation was performed via HE staining. Results:qRT-PCR analysis revealed no detectable Zika virus RNA（Ct >35）in control tissues. In the experimental group，viral RNA（Ct <35）was detected in the brain，spleen，liver，and testis by day 12，with stable viral loads across tissues by day 15（ P>0.05）. Cytokine profiling demonstrated significant upregulation in the brain at day 12：IFN-β（5.58-fold， P<0.01），IL-6（7.11-fold， P<0.01），and CCL5（3.79-fold， P<0.01）. By day 15，these levels remained elevated（IFN-β：3.07-fold；IL-6：4.04-fold；CCL5：5.22-fold；all P<0.01）. In the liver，IFN-β mRNA decreased to 20% of the control level by day 15（ P<0.05），while IL-6 declined to 24% and CCL5 mRNA dropped to 38% by day 12. No significant cytokine changes were observed in the spleen（ P>0.05）. Testicular tissues exhibited reduced IFN-β mRNA levels（43% of control at day 12，31% at day 15； P<0.05）. Histopathological analysis revealed marked splenomegaly with disrupted splenic corpuscle architecture and lymphocyte depletion，significant inflammatory cell infiltration in hepatic portal areas，and testicular structural disorganization with inflammatory infiltration in Zika-infected rats. Conclusions:The SD-Ifnar1 -/-［cc］suckling rat model is successfully established and validated. This model recapitulates systemic Zika virus infection，tissue-specific pathology，and immune response dynamics，providing a robust platform for elucidating viral pathogenesis and advancing antiviral drug development.

Objective:To investigate the diagnostic potential of serum Dickkopf-related protein 3(Dkk3)as a novel biomarker for sarcopenia in an elderly Chinese population by examining its correlation with muscle mass, muscle strength, and physical function.Methods:The study included elderly individuals aged ≥60 years from the Health Examination Center of Jiangsu Provincial Hospital between 2021 and 2022, who had independent mobility and were free from acute diseases.Fat and muscle mass were measured using Dual-energy X-ray Absorptiometry(DXA). Grip strength and chair stand test times were employed to assess upper and lower limb muscle strength, respectively.Physical function was evaluated using the Short Physical Performance Battery(SPPB). Serum Dkk3 concentration was measured using a human Dkk3 enzyme-linked immunosorbent assay(ELISA)kit.Results:A total of 108 elderly participants(83 males)were included in the study, with an age range of 60 to 97 years(mean age: 70.6±10.8). Serum Dkk3 concentration was found to be negatively correlated with the skeletal muscle mass index(SMI)( R=-0.292, P=0.002), lower limb muscle mass( R=-0.320, P<0.001), upper limb muscle mass( R=-0.222, P=0.020), and hip muscle mass( R=-0.261, P=0.006). Functional assessments revealed negative correlations with grip strength( R=-0.204, P=0.035), 4-meter walking speed( R=-0.195, P=0.043), the three-position balance test( R=-0.245, P=0.011), and the SPPB score( R=-0.196, P=0.043). Regression analysis indicated that, after adjusting for age, sex, body mass index(BMI), and comorbidities, Dkk3 remained negatively associated with lower limb muscle mass( β=-0.197, P=0.012), hip muscle mass( β=-0.156, P=0.029), and the SPPB score( β=-0.001, P=0.013). The sarcopenia group exhibited a 55.6% higher serum Dkk3 level compared to the control group(76.68±37.62 ng/ml vs.49.27±25.88 ng/ml, P<0.001). Receiver Operating Characteristic(ROC)curve analysis determined the optimal diagnostic threshold to be 80.08 ng/ml, with an area under the curve of 0.726, a sensitivity of 41.98%, and a specificity of 96.30% for detecting sarcopenia. Conclusions:Serum Dkk3 is closely associated with reduced muscle mass in the lower limbs and hips, as well as a decline in physical function, in elderly individuals with sarcopenia.Given its cost-effectiveness and clinical utility, serum Dkk3 shows potential as a meaningful biomarker for diagnosing sarcopenia in the elderly.

Objective:To explore the correlation between hyperuricemia (HUA) and chronic kidney disease (CKD) in the individuals undergoing physical examinations.Methods:It was a retrospective cohort study. The study selected 6 910 individuals who received health check-ups at the Xiangya Hospital Health Management Center of Central South University in 2012 and 2022, with none of them having developed CKD in 2012. Using the presence of HUA in 2012 as the independent variable and the occurrence of CKD in 2022 as the outcome variable, four Cox proportional hazards regression models were constructed, with baseline age, gender, body mass index, waist circumference, glomerular filtration rate, presence of hypertension, presence of diabetes, presence of dyslipidemia, white blood cell count, hemoglobin level, direct bilirubin level, alanine aminotransferase level, and blood uric acid level in 2013 as confounding variables. These models were used to analyze the correlation between HUA and CKD, and sensitivity analyses were conducted. The percentile bootstrap method was employed to conduct mediation effect testing, analyzing the intermediary risk factors that influence the correlation between HUA and CKD.Results:Among the 6 910 participants included in the study, the overall baseline detection rate of HUA was 8.78% (607/6 910). In 2022, the incidence of CKD was 7.2% (498/6 910). Cox regression analysis showed a positive correlation between HUA and the occurrence of CKD in the overall population ( HR=1.586, 95% CI: 1.224-2.055). However, after gradually adjusting for confounding factors, the correlation between HUA and CKD was not statistically significant. Stratified by gender, the occurrence of HUA was positively correlated with the incidence of CKD in women ( HR=2.599, 95% CI: 1.069-6.316), but the correlation became non-significant after adjusting for confounding factors. In contrast, there was no significant correlation between HUA and CKD in men. In sensitivity analysis, When uric acid levels were analyzed by grouping participants into two categories based on thresholds of>420 μmol/L for men and>360 μmol/L for women, or as a continuous variable, the results showed a positive correlation between HUA and CKD in the overall population and in women, the HR (95% CI) value was 1.627 (1.282-2.064), 2.465 (1.552-3.914), 1.004 (1.003-1.005) and 1.006 (1.004-1.008), respectively. However, after adjusting for confounding factors, the correlation between HUA and CKD became non-significant in both cases. In the males, there was no correlation between uric acid and the occurrence of CKD, regardless of whether uric acid was treated as a categorical or continuous variable. Mediation analysis revealed that diabetes and hypertension were full mediators between HUA/blood uric acid levels and CKD in the overall population. Among males, diabetes and hypertension were full mediators between blood uric acid levels and CKD. In females, hypertension was a full mediator between HUA/blood uric acid levels and CKD, with an effect proportion of 100%. Conclusion:HUA is positively correlated with the risk of CKD, particularly in females, but HUA is not an independent predictor of CKD. HUA influences the occurrence of CKD through conditions such as diabetes and hypertension.