Background/Aims: Data from Asia regarding the short-term and long-term outcomes for acute severe ulcerative colitis (ASUC) are limited. We assessed the outcomes of ASUC, identified the risk factors for colectomy, and compared colectomy rates between the pre-biologics and post-biologics eras in Taiwan. Methods: The patients with an ASUC diagnosis between January 2013 and March 2022 at 5 tertiary medical centers were retrospectively analyzed. Results: In total, 98 patients were enrolled, with 68.4% diagnosed in the post-biologics era. In 78.6% of the ASUC patients initially received intravenous steroid therapy, for which the success rate was 74.1%. As for rescue therapy, 15 patients (93.8%) received biologics and 1 (6.3%) received cyclosporin. Biologics rescue therapy had a 93.3% success rate. One (1%) mortality due to septic shock occurred. The colectomy rate for index ASUC admission was 11.2%. Patients receiving colectomy were predominantly male (P= 0.012) and at older age (P= 0.016). Higher C-reactive protein (P= 0.035), lower albumin (P= 0.017), and hemoglobin (P= 0.023) levels were associated with colectomy risk. During a median follow-up of 24 months, 13 patients (15.1%) had recurrent ASUC and 23.1% of patients received colectomy. The accumulated colectomy rate at 3 years did not differ between the pre- and post-biologics eras (16.1% vs. 13.4%, P= 0.270). Conclusions This is the first Asian study on ASUC to compare colectomy rates between the prebiologics and post-biologics eras, revealing no significant difference. The recurrent ASUC had a higher colectomy rate than the index ASUC.

Ulcerative colitis（UC） is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa， and its complex pathogenesis involves immune abnormality， oxidative stress and other factors. The nuclear transcription factor E₂-related factor 2（Nrf2）， encoded by the Nfe212 gene， plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1（HO-1） and quinone oxidoreductase 1（NQO1）， but also enhances the activity of glutathione-S-transferase（GST） and superoxide dismutase 1（SOD1）， effectively eliminating reactive oxygen species（ROS） accumulated in the body， and mitigating oxidative stress-induced damage to intestinal mucosa. In addition， Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response， cell apoptosis and autophagy pathways， thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this， this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2， the molecular mechanism of activation， the protective effect in the pathological process of UC， and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory， promoting autophagy， inhibiting apoptosis， protecting the intestinal mucosal barrier， and promoting intestinal mucosal repair， providing new ideas and methods for the multi-faceted treatment of UC.

Objective To investigate the effects of varying durations of overwork on cardiomyocyte pyroptosis in mice.Methods A total of 24 SPF KM mice were randomly divided into four groups(n=6)using a random number table:control group,2-week overwork(W2)group,4-week overwork(W4)group,and 6-week overwork(W6)group.Mice in control group were normally raised,while those in W2,W4,and W6 groups were forced to stand in water for 8 h and then restrained for 3 h daily for 2,4,6 weeks,respectively.The general condition and weekly weight changes of the mice were observed.After modeling,blood samples were collected,and hearts were excised.Myocardial histopathological changes were assessed using hematoxylin and eosin(HE)staining.The localization of gasdermin D(GSDMD)protein in myocardial tissue was detected through immunohistochemical staining,and the expression levels of pyroptosis-related proteins[NOD-like protein receptor 3(NLRP3),Caspase-1,GSDMD]in myocardial tissue were analyzed using Western blotting.The contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in serum and myocardial tissues were measured using ELISA.Results(1)The weight of control group mice increased steadily within 2 weeks.In W2 group,there was no significant weight change within 2 weeks,while in W4 and W6 groups,the body weights were higher than their initial values from the 2nd to 6th week.Compared with control group,the body weights of W2,W4,and W6 groups were lower than those of control group in the 1st and 2nd week,with statistically significant differences(P<0.05).The activity levels of the mice in W2,W4,and W6 groups initially increased and then decreased,with their fur becoming dull and falling out,and their mental state deteriorating.(2)In control group,cardiomyocytes were neatly arranged,and the nuclear morphology was normal.Compared with control group,in W2 group,cardiomyocyte arrangement was less regular,and capillary congestion was increased.In W4 group,the vascular congestion in the myocardium was significantly increased,the interstitial tissue was hyperplastic,and vacuolization appeared around the nuclei.In W6 group,the myocardial interstitium was loose,fat infiltration was increased,vacuolization around the nuclei was increased,and myocardial fibers were swollen,and the arrangement was disordered.(3)GSDMD was mainly located in the cytoplasm of cardiomyocytes.Compared with control group,the expression levels of NLRP3,Caspase-1,and GSDMD proteins in W2,W4,and W6 groups were significantly increased,and the expression levels were in the order of W6 group>W4 group>W2 group,with significant differences(P<0.05).(4)Compared to control group,the levels of IL-1β in serum and myocardial tissues of W2,W4,and W6 groups were significantly increased.In serum,the level of IL-1β in W6 group was higher than those in W2 and W4 groups,and in myocardial tissue,the levels in W4 and W6 groups were higher than those in the W2 group,with significant differences(P<0.05).There were no significant differences in IL-1β levels in serum among W2 and W4 groups,nor were there significant differences in myocardial tissue between W4 and W6 groups(P>0.05).Compared with control group,the levels of IL-18 in serum and myocardial tissue of W4 and W6 groups were significantly increased(P<0.05).In serum,the levels of IL-18 in W4 and W6 groups were higher than that in W2 group,and in myocardial tissue,the level in W6 group was higher than those in W2 and W4 groups,with the differences being statistically significant(P<0.05).Conclusions Overwork can cause structural damage to mouse myocardial tissue,increase the expression of pyroptosis proteins NLRP3,Caspase-1,GSDMD,and aggravate myocardial inflammatory responses in overworked mice.Cardiomyocyte pyroptosis may be one of the factors contributing to sudden cardiac death induced by overwork.

Objective To investigate plasma protein expression changes in heatstroke patients using proteomics technology and to identify reliable prognostic biomarkers.Methods A retrospective analysis was conducted on 20 heatstroke patients hospitalized at the 908th Hospital of the Chinese PLA Joint Logistics Support Force from July 2022 to February 2024.Patients were divided into survival(n=16)and death groups(n=4)based on 28-day outcomes.Fasting venous blood samples were collected from both groups for proteomic analysis.Liquid chromatography-mass spectrometry(LC-MS/MS)was used to identify and screen differentially expressed proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses were performed.LASSO regression was applied to screen key prognostic biomarkers,and receiver operating characteristic(ROC)curve analysis was used to evaluate their predictive value.Results A total of 27 upregulated and 90 downregulated proteins were identified between the two groups.These proteins were primarily involved in biological processes such as immune responses,complement activation,and metabolic processes.LASSO regression analysis indicated that actin-related protein 2(ARP2),cysteine-rich scavenger receptor type 1 M130(CD163),and catalase(CAT)could serve as effective biomarkers for evaluating heatstroke prognosis.ROC curve analysis demonstrated that ARP2 had higher diagnostic efficacy(AUC=0.98,sensitivity=0.80,specificity=1.00)compared to CD163(AUC=0.94,sensitivity=0.76,specificity=1.00),CAT(AUC=0.96,sensitivity=0.67,specificity=1.00),and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score(AUC=0.79,sensitivity=0.44,specificity=1.00).Conclusion Elevated plasma ARP2 level has good clinical value for predicting poor prognosis in heatstroke patients.

Objective : To investigate the protective effect of total glucosides of paeony ( TGP) on dexamethasone(DEX) ⁃induced liver injury in rats. Methods: Thirty SD rats were randomly divided into normal ( N) , DEX ,DEX + TGP (50 mg/kg) , DEX + TGP ( 100 mg/kg) , and DEX + TGP (200 mg/kg) groups , with 6 rats in each group. A rat model of liver injury was established by intraperitoneal injection of DEX ( 17. 5 mg/kg) . Serum levels of alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , and alkaline phosphatase ( ALP) were measured , and the liver⁃to⁃body weight ratio was calculated. HE staining was performed to observe histopathological changes in the liver. The contents of malondialdehyde ( MDA) , superoxide dismutase ( SOD) , and glutathione (GSH) in liver tissues were determined. Western blot analysis was conducted to detect the expression levels of NADPH oxidase 4 ( NOX4 ) and endoplasmic reticulum stress⁃related proteins : glucose regulatory protein 94 homologous protein (CHOP) expression level in liver tissues. Results: Compared with the normal group , the DEX group exhibited significantly elevated serum levels of ALT , AST , ALP and liver⁃to⁃body weight ratio ( t = 14. 96 ,ing, degeneration , and necrosis ( t = 15. 49 , P < 0. 01) . Compared with the DEX group , there was no significant change in liver function biochemical indexes and liver histopathology in the TGP (50 mg/kg) treatment group. TGP treatment at 100 mg/kg and 200 mg/kg significantly attenuated these effects : both doses reduced ALT , AST , ALP and liver⁃to⁃body weight ratio( t = 3. 30 , 4. 13 , 7. 45 , 2. 97 , P < 0. 05 ; t = 8. 92 , 6. 45 , 8. 65 , 7. 47 , P < 0. 01) ,vealed that DEX administration significantly increased hepatic MDA levels ( t = 7. 06 , P < 0. 01) and NOX4 ex⁃pression ( t = 4. 23 , P < 0. 01) , whereas SOD activity ( t = 7. 78 , P < 0. 01) and GSH content ( t = 7. 92 , P <0. 01) were markedly suppressed. There was no significant change in the TGP (50 mg/kg) treatment group , TGP intervention at 100 mg/kg and 200 mg/kg effectively reversed these changes , lowering MDA and NOX4 levels( t = 3. 35 , 4. 30 , P < 0. 05 ; t = 5. 44 , 7. 44 , P < 0. 01) , while restoring SOD ( t200 mg/kg = 4. 04 , P < 0. 05) and GSH ( t = 4. 70 , P < 0. 05 ; t = 5. 50 , P < 0. 01) . Endoplasmic reticulum stress markers , including GRP94、GRP78、p- elF2α、CHOP ( t = 3. 31 , 6. 53 , 5. 18 , 3. 09 ; P < 0. 05 , 0. 01 , 0. 01 , 0. 05 ) , were significantly upregulated in the DEX group compared to the normal group. However, TGP treatment at 100 mg/kg and 200 mg/kg dose-dependent- ly suppressed the expression of GRP94、GRP78、p-elF2α、CHOP ( t = 3. 14 ,4. 95 , 3. 13 ,4. 25 , P < 0. 05 ; t = 4. 03 , 7. 48 ,4. 68 ,5. 10 ,P < 0. 01) expression levels were significantly reduced compared to the DEX group , and there was no significant change in the TGP (50 mg/kg) treatment group. Conclusion TGP exerts protective effects a- gainst DEX-induced liver injury , and its mechanism is likely mediated by suppressing hepatic oxidative stress and endoplasmic reticulum stress triggered by DEX in rats.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

Objective To explore the efficacy of ranibizumab combined with retinal laser photocoagulation in patients with macular edema secondary to branch retinal vein occlusion(BRVO)and its impact on best-corrected visual acuity(BCVA)and central macular thickness(CMT).Methods A prospective analysis was conducted on 70 patients with secondary macular edema caused by BRVO who were admitted to the 901th Hospital of Joint Logistics Support Force from March 2019 to March 2023.According to the random number table method,the patients were assigned into study group or control group,with 35 cases in each group.The control group was treated with ranibizumab,while the study group was treated with ranibizumab and retinal laser photocoagulation.The efficacy,BCVA,CMT,intraocular pressure,adverse reactions,and 36-item short form health survey(SF-36)score were compared between the two groups.Results There was a significant difference in the efficacy between the two groups(Z=2.272,P<0.05),and the total effective rate of the study group was higher than that of the control group(P<0.05).The results of repeated measure ANOVA showed that CMT and intraocular pressure decreased significantly,while BCVA increased significantly in both groups after 3 months,6 months,and 12 months of treatment(P<0.05);moreover,these parameters in the study group were superior to those in the control group(P<0.05).There were no significant differences in the incidence of cataracts,transient intraocular pressure elevation,subconjunctival hemorrhage,retinal detachment,or the total incidence of adverse reactions between the two groups(P>0.05).After 12 months of treatment,the total score of SF-36 increased in both groups(P<0.05),and the difference value of total score of SF-36 in the study group was superior to that in the control group(P<0.05).Conclusion The combination of ranibizumab and retinal laser photocoagulation can achieve a good therapeutic effect on macular edema caused by BRVO.It can effectively improve BCVA,CMT and intraocular pressure,reduce the risk of adverse reactions,and enhance the quality of life.

Objective To investigate gender differences and age-related changes in body composition(BC)among Miao adults in Rongshui,Guangxi Province,and to provide the basis for assessing nutritional status and health.Methods With informed consent,630 Miao adults(218 males,412 females)were randomly selected for this study.Body composition was assessed using bioelectrical impedance analysis(BIA).Results Weight,fat-free mass,muscle mass,trunk muscle mass,limb muscle mass,waist-to-hip ratio(WHR),body water,presumtion of bone mass and protein were significantly higher in males than in females.And the fat mass,trunk fat mass,limb fat mass,visceral fat content,subcutaneous fat content and percentage of body fat were significantly higher in females than in males.According to the evaluation of body mass index(BMI)and WHR,the proportion of overweight and obesity of Miao adults was higher than the average level of Miao residents,and their obesity was characterized by central obesity.With age,weight,fat mass,muscle mass,fat-free mass,limb muscle mass,limb fat mass,subcutaneous fat content,percentage of body fat,body water,presumtion of bone mass,and protein of Rongshui Miao adults showed a gradual decreasing trend,while visceral fat content and WHR increased progressively.BMI in male Miao adults,along with BMI,fat mass,trunk fat mass,subcutaneous fat content,percentage of body fat,and body water in female Miao adults,showed a trend of increasing followed by decreasing,peaking at the age of 40-49 years.Conclusion The body composition of Miao adults in Rongshui,Guangxi,exhibits significant gender differences and age-related variation change patterns,which may increase the risk of sarcopenia and metabolic diseases with aging.