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 improve the underwater technique during the start phase of breaststroke swimmers through swimming flume training and assess its effectiveness in enhancing competitive performance.Methods The participants were 14 male swimmers in the short-distance Level 4 category from the Shanghai Swimming Team,and they were randomly divided into the experimental group(n=7)and control group(n=7).The experimental group underwent swimming flume start training,while the control group underwent regular pool start training,and both groups received the training twice a week for 16 weeks.Before and after the 16-week training,a 15-m breaststroke start test was conducted.Repeated measures analysis of variance and paired t-tests were used to compare the changes in kinematic parameters(time,speed,and entry angle)between and within groups.Results After 16 weeks of specialized training,the 15-m performance at the start for the experimental group and control group(F(1,12)=6.52,P＜0.05,η2=0.39)showed an interaction,with the experimental group performing better after training compared to the control group before training(P＜0.05).In the experimental group,the duration of the pull-out phase(F(1,12)=10.28,P＜0.01,η2=0.46)and the second sliding phase(F(1,12)=4.81,P＜0.05,η2=0.22)was improved;the distance of the pull-out phase(F(1,12)=4.71,P＜0.05,η2=0.21)and the second sliding phase(F(1,12)=4.90,P＜0.05,η2=0.21)was improved;the speed of the pull-out phase(F(1,12)=4.77,P＜0.05,72=0.20)was significantl improved.The within-group statistics showed that the experimental group significantly improved their exit speed(P＜0.05).The hand entry angle was optimized(P＜0.05),while changes in other joint angles were not significant.Conclusions Swimming flume training reduced the time spent in the pull-out and second gliding phases during the breaststroke start,effectively preventing the speed loss during underwater gliding.This provides an experimental evidence for enhancing start performance and optimizing training method for breaststroke swimmers.

Sleep disorders is one of the most frequent and severe complications in patients with tinnitus and is highly correlated with the severity of tinnitus.Sleep disorders and tinnitus influence each other,forming a vicious circle.While in-terventions have been developed to alleviate tinnitus distress,these interventions are usually not effective in improving sleep in patients with tinnitus and sleep disorders.Helping tinnitus patients to resolve sleep disorders is the key to breaking the cycle and improving their quality of life.In this narrative review,we studyed the current state of research on sleep disorders in patients with tinnitus through three aspects:epidemiology,physiological and psychological mechanisms,and existing psychological,physical,and pharmacological interventions,and to provide a basis for further research on the relationship between tinnitus and sleep disorders and the precise treatment of tinnitus.

AIM:To investigate the role of SET and MYND domain-containing protein 3(SMYD3)-mediated histone H3 lysine 4 trimethylation(H3K4me3)dysregulation in pulmonary vascular remodeling in a rat model of pulmo-nary arterial hypertension associated with atrial septal defect(PAH-ASD).METHODS:The PAH-ASD rat model was created using transseptal puncture and radiofrequency ablation techniques.The rats were randomly assigned to 5 groups:normal,sham,PAH-ASD,PAH-ASD+vehicle(Veh),and PAH-ASD+BCI-121(SMYD3 inhibitor).Four weeks after modeling,lung tissues and pulmonary vessels were harvested for subsequent analysis.Western blot analysis was conducted to evaluate the protein levels of SMYD3,H3K4me3,transforming growth faction-β1(TGF-β1),and collagen type Ⅲ(Col Ⅲ).The mRNA expression of TGF-β1 was quantified using RT-qPCR.Histological assessment of pulmonary vascu-lar fibrosis,vascular wall thickness and smooth muscle proliferation was executed through Masson's trichrome and HE staining.Co-immunoprecipitation(Co-IP)assay was performed to investigate the interactions among SMYD3,H3K4me3,and TGF-β1.Hemodynamic parameters,including mean pulmonary artery pressure(mPAP),were quantified using a computerized physiological signal acquisition system.RESULTS:The Western blot analysis indicated a significant in-crease in the protein levels of SMYD3,TGF-β1,Col Ⅲ,and H3K4me3 in the PAH-ASD group compared with the sham group(P<0.05).RT-qPCR corroborated the elevation of TGF-β1 mRNA expression in the PAH-ASD group(P<0.05).Furthermore,Masson's trichrome and HE staining techniques revealed more pronounced pulmonary vascular fibrosis,an augmented vascular wall area,and an elevated vascular area index within the PAH-ASD group(P<0.05).Additionally,the right ventricular hypertrophy index(RVHI)and mPAP were significantly elevated in the PAH-ASD group(P<0.05).The administration of BCI-121 resulted in a significant reduction of SMYD3,TGF-β1,Col Ⅲ,and H3K4me3 levels(P<0.05),while also mitigating pulmonary vascular fibrosis,RVHI,mPAP,pulmonary vascular area,and area index(P<0.05).Co-IP confirmed direct interactions among SMYD3,H3K4me3,and TGF-β1.CONCLUSION:Histone methyl-transferase SMYD3-mediated histone H3K4me3 modification plays a role in the pulmonary vascular remodeling of PAH-ASD model rats.The underlying mechanism may involve the regulation of pulmonary vascular proliferation and fibrosis me-diated by the overexpression of TGF-β1 and Col Ⅲ.

Sleep disorders is one of the most frequent and severe complications in patients with tinnitus and is highly correlated with the severity of tinnitus.Sleep disorders and tinnitus influence each other,forming a vicious circle.While in-terventions have been developed to alleviate tinnitus distress,these interventions are usually not effective in improving sleep in patients with tinnitus and sleep disorders.Helping tinnitus patients to resolve sleep disorders is the key to breaking the cycle and improving their quality of life.In this narrative review,we studyed the current state of research on sleep disorders in patients with tinnitus through three aspects:epidemiology,physiological and psychological mechanisms,and existing psychological,physical,and pharmacological interventions,and to provide a basis for further research on the relationship between tinnitus and sleep disorders and the precise treatment of tinnitus.

Objective To investigate the protective effect and mechanism of the antioxidant Lutein in a mouse model of dry age-related macular degeneration(AMD)induced by hydroquinone.Methods Twenty-four specific pathogen-free(SPF)grade male C57BL/6 mice,aged 6-8 weeks,were randomly divided into 3 groups(n=8 per group).The control group was fed a standard diet and water for 3 months.The model group and the drug intervention group received 8 g·L-1 hydroquinone in drinking water combined with a high-fat diet for 2 months to establish the dry AMD mouse model.After modeling,the model group resumed a standard diet and water for 1 month.The drug group received oral gavage daily at 8:00 AM,administered Lutein at 0.1 g per kg body weight(dissolved in distilled water),for 1 month.At the experimental endpoint,all mice were euthanized,and samples were collected for analysis.The ultrastructure of retinal pigment epithelial(RPE)cells was observed by electron microscopy.Serum activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)were measured using a microplate reader.mRNA expression levels of nuclear factor ery-throid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and glutamate-cysteine ligase(GCL)in retinal tissue were de-tected by real-time quantitative PCR.Protein expression levels of Nrf2,HO-1,and GCL in retinal tissue were determined by Western blot.Results In the model group,mitochondria and intracellular organelles in RPE cells exhibited vacuolar de-generation,with compromised structural integrity;simultaneously,microvilli were disorganized and significantly reduced in number.In the drug group,the mitochondrial structure of RPE cells was relatively well-preserved,with morphology largely normal;microvilli structure was clear,and density showed some recovery compared to the model group.Compared to the control group,serum activities of SOD,CAT,and GSH-Px were significantly decreased in the model group(all P＜0.01).Compared to the model group,serum activities of SOD,CAT,and GSH-Px were significantly increased in the drug group(all P＜0.05).Compared to the control group,retinal mRNA expression levels of Nrf2,HO-1,and GCL were significantly decreased in the model group(all P＜0.01).Compared to the model group,retinal mRNA expression levels of Nrf2,HO-1,and GCL were significantly increased in the drug group(all P＜0.01).Compared to the control group,retinal protein ex-pression levels of Nrf2,HO-1,and GCL were decreased in the model group(all P＜0.05).Compared to the model group,retinal protein expression levels of Nrf2,HO-1,and GCL were increased in the drug group(all P＜0.05).Conclusion The antioxidant Lutein promotes the expression of downstream target genes HO-1 and GCL by activating the Nrf2 signaling pathway,which not only enhances the biosynthesis levels of antioxidant enzymes(SOD,CAT,GSH Px),but also effec-tively inhibits oxidative stress response by enhancing autophagic activity.

AIM:To investigate the role of SET and MYND domain-containing protein 3(SMYD3)-mediated histone H3 lysine 4 trimethylation(H3K4me3)dysregulation in pulmonary vascular remodeling in a rat model of pulmo-nary arterial hypertension associated with atrial septal defect(PAH-ASD).METHODS:The PAH-ASD rat model was created using transseptal puncture and radiofrequency ablation techniques.The rats were randomly assigned to 5 groups:normal,sham,PAH-ASD,PAH-ASD+vehicle(Veh),and PAH-ASD+BCI-121(SMYD3 inhibitor).Four weeks after modeling,lung tissues and pulmonary vessels were harvested for subsequent analysis.Western blot analysis was conducted to evaluate the protein levels of SMYD3,H3K4me3,transforming growth faction-β1(TGF-β1),and collagen type Ⅲ(Col Ⅲ).The mRNA expression of TGF-β1 was quantified using RT-qPCR.Histological assessment of pulmonary vascu-lar fibrosis,vascular wall thickness and smooth muscle proliferation was executed through Masson's trichrome and HE staining.Co-immunoprecipitation(Co-IP)assay was performed to investigate the interactions among SMYD3,H3K4me3,and TGF-β1.Hemodynamic parameters,including mean pulmonary artery pressure(mPAP),were quantified using a computerized physiological signal acquisition system.RESULTS:The Western blot analysis indicated a significant in-crease in the protein levels of SMYD3,TGF-β1,Col Ⅲ,and H3K4me3 in the PAH-ASD group compared with the sham group(P<0.05).RT-qPCR corroborated the elevation of TGF-β1 mRNA expression in the PAH-ASD group(P<0.05).Furthermore,Masson's trichrome and HE staining techniques revealed more pronounced pulmonary vascular fibrosis,an augmented vascular wall area,and an elevated vascular area index within the PAH-ASD group(P<0.05).Additionally,the right ventricular hypertrophy index(RVHI)and mPAP were significantly elevated in the PAH-ASD group(P<0.05).The administration of BCI-121 resulted in a significant reduction of SMYD3,TGF-β1,Col Ⅲ,and H3K4me3 levels(P<0.05),while also mitigating pulmonary vascular fibrosis,RVHI,mPAP,pulmonary vascular area,and area index(P<0.05).Co-IP confirmed direct interactions among SMYD3,H3K4me3,and TGF-β1.CONCLUSION:Histone methyl-transferase SMYD3-mediated histone H3K4me3 modification plays a role in the pulmonary vascular remodeling of PAH-ASD model rats.The underlying mechanism may involve the regulation of pulmonary vascular proliferation and fibrosis me-diated by the overexpression of TGF-β1 and Col Ⅲ.

Objective To analyze the correlation between tongue image features and the risk levels of disease in patients with idiopathic membranous nephropathy(IMN).Methods Based on IMN clinical research electronic data acquisition system,a cross-sectional study method was used to analyze the clinical diagnosis and treatment data of 135 IMN patients from Guangdong Provincial Hospital of Chinese Medicine.The patients were grouped according to the risk levels of disease,and then the correlation between the risk levels of disease and tongue image features was analyzed.During the description of tongue image features,TB is for tongue body,TC is for tongue coating,L is for luminance,a is for red-green axis,G is for the value of green,B is for the value of blue,and AUT is for the value of autocorrelation.Results The comparison of tongue image feature indicators of patients with different risk levels of IMN showed that:(1)the higher the level of disease risk of IMN patients,the greater the values of TB-L,TB-G and TB-B(P<0.05 or P<0.01).The values of tongue image indicator TB-a and TC-a of the patients with different risk levels of IMN were shown in decreasing sequence:low-risk group>high-risk group>middle-risk group>extremely-high-risk group(P<0.05).(2)Linear regression analysis showed that TB-L,TB-G,and TB-B were significantly increased in the high-risk group compared with those in the middle-and low-risk groups(P<0.05 or P<0.01),whereas there were no significant differences between the middle-risk group and low-risk group(P>0.05).(3)The results of correlation analysis showed that there was a positive correlation among most of the tongue image feature indicators(including TB-L,TB-G,TB-B,TB-AUT,TC-L,TC-G,and TC-B,etc.)and the risk level of disease,while TB-a was negatively correlated with the risk level of disease,and the differences were all statistically significant(P<0.05 or P<0.01).(4)All patients were treated with Chinese medicine and/or Chinese patent medicine,and 46.7%of patients were given hormones and immunosuppressants,and there was no statistically significant difference in the the use of hormones and immunosuppressants among various groups(P=0.637).Conclusion There is a correlation between the tongue image features of IMN patients and the risk level of disease,and the results will provide an objective reference for the assessment of illness state and traditional Chinese medicine(TCM)syndrome differentiation of IMN patients.With reference to the changes in the tongue image features,the illness state can be precisely identified,which is more accurate than the inspection of four diagnostic methods of TCM.

Objective To observe the clinical efficacy of toripalimab combined with bronchial ar-terial chemoembolization(BACE)and intensity-modulated radiotherapy(IMRT)in advanced lung cancer.Methods A prospective single-arm trial was conducted in 104 patients with programmed death-ligand 1(PD-L1)-positive,driver gene-negative non-small cell lung cancer(NSCLC)in stages of Ⅲ B to Ⅳ admitted to the First People's Hospital of Guangyuan City of Sichuan Province.All patients received toripalimab combined with BACE and IMRT.Clinical efficacy,symptom improve-ment time,tumor biomarker levels[carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199),cytokeratin 19 fragment(CYFRA21-1),neuron-specific enolase(NSE)],T-lymphocyte subsets(CD3+,CD4+,CD4+/CD8+),survival outcomes,and adverse events were analyzed.Results Among 102 patients,the objective response rate(ORR)was 75.49％,disease control rate(DCR)was 90.20％,survival rate was 68.63％,and 12-month progression-free survival rate was 62.75％.The overall incidence of adverse events of any grade was 72.55％.Post-BACE,post-IMRT,and post-toripalimab treatment levels of CEA,CYFRA21-1,CA199,and NSE were significantly lower than baseline data(P＜0.05),with the lowest levels observed after toripalimab treatment compared to post-BACE and post-IMRT(P＜0.05).CD3+,CD4+,and CD4+/CD8+decreased after BACE,IMRT and toripalimab therapy,but they were increased following toripalimab therapy compared with the other two therapies(P＜0.05).Conclusion Toripalimab combined with BACE and IMRT demonstrates significant clinical efficacy and acceptable tolerability in PD-L1-positive,driver gene-negative NSCLC in stages of ⅢB to Ⅳ,serving as a preferred consolidation regimen after unresect-able chemoradiotherapy.