Objective:To explore the incidence of Crohn's disease-like pouch (CDP) after ileal pouch-anal anastomosis (IPAA) and analyze the clinical characteristics and risk factors in ulcerative colitis (UC) patients.Methods:A retrospective cohort study was conducted. One hundred and eighty-two UC patients undergoing IPAA at Jinling Hospital affiliated to Nanjing University from November 2003 to November 2024 were enrolled. Patients were categorized into CDP and non-CDP groups. Clinical features and prognosis were compared, and multivariate Cox regression was performed to identify risk factors for CDP.Results:A total of 182 UC patients were included, with a median follow-up time of 45.00 (30.00, 75.25) months. The patients were divided into two groups based on the diagnosis of CDP, with 23 patients (12.64%) in the CDP group and 159 patients (87.30%) in the non-CDP group. Compared to the non-CDP group, patients in the CDP group had a lower body mass index (BMI) ( Z=-2.87, P=0.004), and were more likely to develop early postoperative pouchitis (χ 2=4.50, P=0.034). The median time from ileostomy closure to the development of CDP was 12 .00 (6.00, 28.00) months. Cox regression analysis showed that a preoperative BMI<18.5 kg/m 2 ( HR=2.84, 95% CI: 1.24~6.49, P=0.013) and early postoperative pouchitis ( HR=3.11, 95% CI: 1.22~7.93, P=0.018) were associated with an increased risk of CDP. Conclusions:Preoperative low BMI and pouchitis occurring within 3 months postoperatively are significant risk factors for CDP. Close monitoring and early intervention are recommended for high-risk patients.

Objective Cigarette smoke(CS)exposure combined with Klebsiella pneumoniae(KP)infection in mice was used to establish a model of chronic obstructive pulmonary disease(COPD)to investigate the mechanism of airway remodeling.Methods Male BALB/c mice were randomly divided into a Control group,CS group,KP group,and CS+KP group.The mice were exposed to CS,KP,and CS+KP from weeks 1 to 8,and were sacrificed in weeks 4,8,16,and 24.MV,Penh,MLI,MAN,and changes in lung pathological structure were detected.The expression levels of IL-1β and TNF-α in lung tissue were detected by ELISA.Collagen deposition was observed by Masson staining and immunohistochemistry.α-SMA and TGF-β1 expression in lung tissue was detected by immunofluorescence.Human bronchial epithelioid cells(16HBE)were also stimulated by CS and lipopolysaccharide(LPS)in vitro,and the expression levels of airway epithelial junction proteins,autophagy-related protein,and mTOR signaling proteins were detected.Results Compared with the Control group,the CS+KP group mice had significantly decreased MV from weeks 4 to 24(P＜0.05 or P＜0.01)and significantly increased Penh from weeks 8 to 24(P＜0.05 or P＜0.01);while the CS group had markedly decreased MV and markedly increased Penh from weeks 8 to 16(P＜0.05 or P＜0.01).Compared with the Control group,massive inflammatory cell infiltration,alveolar wall thickening,alveolar rupture and fusion,and airway wall thickening were observed by HE staining in CS+KP group from weeks 4 to 24.The CS+KP group mice had significantly decreased MAN and significantly increased MLI,IL-1β and TNF-α in their lung tissue from weeks 4 to 24(P＜0.05 or P＜0.01).The aforementioned inflammation and tissue damage were observed in the CS group and the KP group from week 8 to 16.Compared with the Control group,COL Ⅰ,COL Ⅲ,α-SMA,and TGF-β1 were significantly increased in lung tissue of mice in the CS+KP group from weeks 8 to 16(P＜0.01);COL Ⅰ was significantly increased in the CS group and KP group from weeks 8 to 16(P＜0.01).In addition,increased E-cad and decreased N-cad(P＜0.05);significantly decreased LC3B and Beclin-1(P＜0.05);and significantly increased p-mTORC1,p-P70-S6K,and p-4E-BP1 expression were observed in 16HBE cells exposed to CS and LPS(P＜0.05 or P＜0.01).Conclusion Pulmonary functional decline,pathological changes in lung tissue,and airway remodeling appeared to occur early and persist in COPD mice induced by CS and KP.The mechanisms may be related to the activation of mTORC1 signaling pathway and subsequent inhibition of autophagy.

Objective To explore the anti-inflammatory mechanism of Tong-Xie-Yao-Fang's intervention on irritable bowel syndrome with diarrhea(IBS-D),the effects of Tong-Xie-Yao-Fang on farnesol receptor(FXR),nuclear factor-κB(NF-κB)and inflammatory factors in IBS-D model rats were observed.Methods Healthy SD rats were randomly divided into blank group(Control group),model group(Model group),low-dose group of Tong-Xie-Yao-Fang(TXYF-L group,4.977 g/kg),middle-dose group of Tong-Xie-Yao-Fang(TXYF-M group,9.954 g/kg),and high-dose group of Tong-Xie-Yao-Fang(TXYF-H group,19.908 g/kg),Pivium bromide group(PWXA group,0.018 g/kg),with 10 rats in each group.Except for the blank group,the IBS-D rat models of liver depression and spleen deficiency were established by chronic restraint stress and senna intragastric administration.After the model was successfully established,the intervention was continued for 14 days according to the corresponding group treatment method.The general situation,diarrhea rate,fecal moisture content,water injection when abdominal wall retraction reflex reaches 3 scores,sugar water preference rate and serum D-xylose level were observed.The morphological and structural changes of rat colon were observed by HE staining.The expression of FXR gene in colon tissue was detected by real-time fluorescence quantitative PCR,the expression of FXR protein and NF-κB protein in colon tissue was detected by protein Western blot,and the levels of serum IL-6,IL-8 and TNF-α were detected by ELISA.Results After the treatment of Tong-Xie-Yao-Fang,the weight of each dosage group of Tong-Xie-Yao-Fang increased,the fecal water content decreased,the sugar water preference rate increased,the water injection volume increased when the rats reached the third grade of abdominal retraction reflex score,the serum D-xylose content increased and the food intake increased.HE staining showed that villous or finger-like structures appeared in the mucosal epithelium of model group,and inflammatory cells infiltrated in the upper mucosa.After treatment,the mucosal epithelium in TXYF-M group was smooth,villous or finger-like structures disappeared,and the infiltration degree of inflammatory cells decreased.Compared with the model group,the expression of FXR mRNA and FXR protein in the colon tissue of rats in the high-dose group of Tong-Xie-Yao-Fang increased significantly,while the concentration of IL-6,IL-8 and TNF-α in serum and the expression of NF-κB protein in the colon tissue of rats in the high-dose group of Tong-Xie-Yao-Fang decreased.Conclusion The mechanism of Tong-Xie-Yao-Fang in treating low-grade inflammation of IBS-D intestinal mucosa may be related to activating the expression of FXR in colon,inhibiting the expression of NF-κB in colon tissue,and then reducing the concentration of pro-inflammatory factors IL-6,IL-8 and TNF-α in serum.

Objective:To explore the incidence of Crohn's disease-like pouch (CDP) after ileal pouch-anal anastomosis (IPAA) and analyze the clinical characteristics and risk factors in ulcerative colitis (UC) patients.Methods:A retrospective cohort study was conducted. One hundred and eighty-two UC patients undergoing IPAA at Jinling Hospital affiliated to Nanjing University from November 2003 to November 2024 were enrolled. Patients were categorized into CDP and non-CDP groups. Clinical features and prognosis were compared, and multivariate Cox regression was performed to identify risk factors for CDP.Results:A total of 182 UC patients were included, with a median follow-up time of 45.00 (30.00, 75.25) months. The patients were divided into two groups based on the diagnosis of CDP, with 23 patients (12.64%) in the CDP group and 159 patients (87.30%) in the non-CDP group. Compared to the non-CDP group, patients in the CDP group had a lower body mass index (BMI) ( Z=-2.87, P=0.004), and were more likely to develop early postoperative pouchitis (χ 2=4.50, P=0.034). The median time from ileostomy closure to the development of CDP was 12 .00 (6.00, 28.00) months. Cox regression analysis showed that a preoperative BMI<18.5 kg/m 2 ( HR=2.84, 95% CI: 1.24~6.49, P=0.013) and early postoperative pouchitis ( HR=3.11, 95% CI: 1.22~7.93, P=0.018) were associated with an increased risk of CDP. Conclusions:Preoperative low BMI and pouchitis occurring within 3 months postoperatively are significant risk factors for CDP. Close monitoring and early intervention are recommended for high-risk patients.

Objective To explore the correlation between central venous oxygen saturation(ScvO2)-re-lated indexes at different time points and the occurrence of low cardiac output syndrome(LCOS)after con-genital heart disease(CHD)correction surgery.Methods A total of 73 children who underwent CHD correc-tion surgery in this hospital from July 1st,2021 to July 1st,2024 were selected as the research subjects.The clinical data,preoperative conditions,and postoperative conditions of the children were collected.The ScvO2 and arterial lactate(Lac)levels of the children at different time points(the 1st,6th,12th,and 24th hours after surgery)were monitored,and the ScvO2/Lac at different time points and the change rate of ScvO2 in different time periods were calculated.The correlation between ScvO2-related indexes and LCOS after CHD correction surgery was analyzed.Results ScvO2 at the 6th hour after surgery,ScvO2 at the 12th hour after surgery,Sc-vO2/Lac at the 12th hour after surgery,the change rate of ScvO2 from the 1st to the 24th hour after surgery,the change rate of ScvO2 from the 6th to the 12th hour after surgery,and the change rate of ScvO2 from the 12th to the 24th hour after surgery were independent influencing factors of LCOS occurrence after CHD cor-rection surgery(P＜0.05).There was a negative correlation between ScvO2 at the 12th hour after surgery,ScvO2/Lac and LCOS occurrence after CHD correction surgery(r=-0.543,-0.523,P＜0.05).The area under the curve(AUC)of ScvO2 at the 12th hour after surgery for predicting LCOS occurrence after CHD correction surgery was 0.938(95％CI:0.865-1.000);the AUC of ScvO2/Lac at the 12th hour after surgery for predicting LCOS occurrence after CHD correction surgery was 0.922(95％CI:0.851-0.994).Conclusion ScvO2 and ScvO2/Lac at the 12th hour after surgery have good predictive potential for LCOS occurrence af-ter CHD correction surgery.

OBJECTIVE: To observe the neuroprotective effect of 6-shogaol (6-SH) in global cerebral ischemia/reperfusion injury (CIRI) following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in rats. METHODS: Computer-aided molecular docking was used to determine whether 6-SH could spontaneously bind to death-associated protein kinase 1 (DAPK1). SPF-grade male SD rats were randomly divided into a sham group (n = 5), a CPR group (n = 7), and a CPR+6-SH group (n = 7). The CPR group and CPR+6-SH group were further divided into 12-, 24-, and 48-hour subgroups based on observation time points. A rat model of global CIRI after CA-CPR was established by asphyxiation. In the sham group, only tracheal and vascular intubation was performed without asphyxia and CPR induction. The CPR group was intraperitoneally injected with 1 mL of normal saline immediately after successful modeling. The CPR+6-SH group received an intraperitoneal injection of 20 mg/kg 6-SH (1 mL) immediately after successful modeling, followed by administration every 12 hours until the endpoint. Neurological Deficit Score (NDS) was recorded at each time point after modeling. After completion of observation at each time point, rats were anesthetized and sacrificed, and brain tissue specimens were collected. Histopathological changes of neurons were observed under light microscopy after hematoxylin-eosin (HE) staining. Ultrastructural changes of hippocampal neurons and autophagy were observed by transmission electron microscopy (TEM). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA expression levels of DAPK1, vacuolar protein sorting 34 (VPS34), Beclin1, and microtubule-associated protein 1 light chain 3 (LC3) in brain tissues. Western blotting was used to detect protein expression levels of DAPK1, phosphorylated DAPK1 at serine 308 (p-DAPK1 ser308), VPS34, Beclin1, and LC3. Immunofluorescence was used to observe Beclin1 and LC3 expression in brain tissues under a fluorescence microscope. RESULTS: Molecular docking results indicated that 6-SH could spontaneously bind to DAPK1. Compared with the sham group, the NDS scores of the CPR group rats were significantly increased at all modeling time points; under light microscopy, disordered cell arrangement, widened intercellular spaces, and edema were observed in brain tissues, with pyknotic and necrotic nuclei in some areas; under TEM, mitochondria were markedly swollen with intact membranes, dissolved matrix, reduced or disappeared cristae, vacuolization, and increased autophagosomes. Compared with the CPR group, the NDS scores of the CPR+6-SH group rats were significantly decreased at all modeling time points; under light microscopy, local neuronal edema and widened perinuclear space were observed; under TEM, mitochondria were mostly mildly swollen with intact membranes, fewer autophagosomes, and alleviated injury. RT-qPCR results showed that compared with the sham group, mRNA expression levels of DAPK1, VPS34, Beclin1, and LC3 in brain tissues were significantly upregulated in all CPR subgroups, with the most pronounced changes at 24 hours. Compared with the CPR group, the CPR+6-SH group showed significantly lower mRNA expression of the above indicators at each time point [24 hours post-modeling (relative expression): DAPK1 mRNA: 3.41±0.68 vs. 4.48±0.62; VPS34 mRNA: 3.63±0.49 vs. 4.66±1.18; Beclin1 mRNA: 3.08±0.49 vs. 4.04±0.22; LC3 mRNA: 2.60±0.36 vs. 3.67±0.62; all P < 0.05]. Western blotting results showed that compared with the sham group, the protein expression levels of DAPK1, VPS34, Beclin1, and LC3 in all CPR subgroups were significantly increased, while the expression of p-DAPK1 ser308 was significantly decreased, with the most pronounced changes observed in the CPR 24-hour subgroup. Compared with the CPR group, the CPR+6-SH subgroups exhibited significantly reduced protein expression of DAPK1, VPS34, Beclin1, and LC3 [24-hour post-modeling: DAPK1/β-actin: 1.88±0.22 vs. 2.47±0.22; VPS34/β-actin: 2.55±0.06 vs. 3.46±0.05; Beclin1/β-actin: 2.12±0.03 vs. 2.87±0.03; LC3/β-actin: 2.03±0.24 vs. 3.17±0.23; all P < 0.05]. Conversely, the expression of p-DAPK1 ser308 was significantly upregulated in the CPR+6-SH group compared to the CPR group [24-hour post-modeling: p-DAPK1 ser308/β-actin: 0.40±0.02 vs. 0.20±0.07, P < 0.05]. Under the fluorescence microscope, fluorescence intensities of Beclin1 and LC3 in the CPR 24-hour group were significantly higher than those in the sham 24-hour group; compared with the CPR 24-hour group, the CPR+6-SH 24-hour group showed significantly reduced fluorescence intensities of Beclin1 and LC3. CONCLUSION 6-SH inhibited the expression of DAPK1, alleviated excessive autophagy after global CIRI following CA-CPR in rats, and exerted neuroprotective effects. The mechanism may be related to phosphorylation at the DAPK1 ser308 site.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; Cardiopulmonary Resuscitation ; Autophagy/drug effects* ; Heart Arrest/therapy* ; Death-Associated Protein Kinases/metabolism* ; Reperfusion Injury/metabolism* ; Disease Models, Animal ; Neuroprotective Agents/pharmacology* ; Brain Ischemia/metabolism*

Objective Cigarette smoke(CS)exposure combined with Klebsiella pneumoniae(KP)infection in mice was used to establish a model of chronic obstructive pulmonary disease(COPD)to investigate the mechanism of airway remodeling.Methods Male BALB/c mice were randomly divided into a Control group,CS group,KP group,and CS+KP group.The mice were exposed to CS,KP,and CS+KP from weeks 1 to 8,and were sacrificed in weeks 4,8,16,and 24.MV,Penh,MLI,MAN,and changes in lung pathological structure were detected.The expression levels of IL-1β and TNF-α in lung tissue were detected by ELISA.Collagen deposition was observed by Masson staining and immunohistochemistry.α-SMA and TGF-β1 expression in lung tissue was detected by immunofluorescence.Human bronchial epithelioid cells(16HBE)were also stimulated by CS and lipopolysaccharide(LPS)in vitro,and the expression levels of airway epithelial junction proteins,autophagy-related protein,and mTOR signaling proteins were detected.Results Compared with the Control group,the CS+KP group mice had significantly decreased MV from weeks 4 to 24(P＜0.05 or P＜0.01)and significantly increased Penh from weeks 8 to 24(P＜0.05 or P＜0.01);while the CS group had markedly decreased MV and markedly increased Penh from weeks 8 to 16(P＜0.05 or P＜0.01).Compared with the Control group,massive inflammatory cell infiltration,alveolar wall thickening,alveolar rupture and fusion,and airway wall thickening were observed by HE staining in CS+KP group from weeks 4 to 24.The CS+KP group mice had significantly decreased MAN and significantly increased MLI,IL-1β and TNF-α in their lung tissue from weeks 4 to 24(P＜0.05 or P＜0.01).The aforementioned inflammation and tissue damage were observed in the CS group and the KP group from week 8 to 16.Compared with the Control group,COL Ⅰ,COL Ⅲ,α-SMA,and TGF-β1 were significantly increased in lung tissue of mice in the CS+KP group from weeks 8 to 16(P＜0.01);COL Ⅰ was significantly increased in the CS group and KP group from weeks 8 to 16(P＜0.01).In addition,increased E-cad and decreased N-cad(P＜0.05);significantly decreased LC3B and Beclin-1(P＜0.05);and significantly increased p-mTORC1,p-P70-S6K,and p-4E-BP1 expression were observed in 16HBE cells exposed to CS and LPS(P＜0.05 or P＜0.01).Conclusion Pulmonary functional decline,pathological changes in lung tissue,and airway remodeling appeared to occur early and persist in COPD mice induced by CS and KP.The mechanisms may be related to the activation of mTORC1 signaling pathway and subsequent inhibition of autophagy.

Objective To explore the anti-inflammatory mechanism of Tong-Xie-Yao-Fang's intervention on irritable bowel syndrome with diarrhea(IBS-D),the effects of Tong-Xie-Yao-Fang on farnesol receptor(FXR),nuclear factor-κB(NF-κB)and inflammatory factors in IBS-D model rats were observed.Methods Healthy SD rats were randomly divided into blank group(Control group),model group(Model group),low-dose group of Tong-Xie-Yao-Fang(TXYF-L group,4.977 g/kg),middle-dose group of Tong-Xie-Yao-Fang(TXYF-M group,9.954 g/kg),and high-dose group of Tong-Xie-Yao-Fang(TXYF-H group,19.908 g/kg),Pivium bromide group(PWXA group,0.018 g/kg),with 10 rats in each group.Except for the blank group,the IBS-D rat models of liver depression and spleen deficiency were established by chronic restraint stress and senna intragastric administration.After the model was successfully established,the intervention was continued for 14 days according to the corresponding group treatment method.The general situation,diarrhea rate,fecal moisture content,water injection when abdominal wall retraction reflex reaches 3 scores,sugar water preference rate and serum D-xylose level were observed.The morphological and structural changes of rat colon were observed by HE staining.The expression of FXR gene in colon tissue was detected by real-time fluorescence quantitative PCR,the expression of FXR protein and NF-κB protein in colon tissue was detected by protein Western blot,and the levels of serum IL-6,IL-8 and TNF-α were detected by ELISA.Results After the treatment of Tong-Xie-Yao-Fang,the weight of each dosage group of Tong-Xie-Yao-Fang increased,the fecal water content decreased,the sugar water preference rate increased,the water injection volume increased when the rats reached the third grade of abdominal retraction reflex score,the serum D-xylose content increased and the food intake increased.HE staining showed that villous or finger-like structures appeared in the mucosal epithelium of model group,and inflammatory cells infiltrated in the upper mucosa.After treatment,the mucosal epithelium in TXYF-M group was smooth,villous or finger-like structures disappeared,and the infiltration degree of inflammatory cells decreased.Compared with the model group,the expression of FXR mRNA and FXR protein in the colon tissue of rats in the high-dose group of Tong-Xie-Yao-Fang increased significantly,while the concentration of IL-6,IL-8 and TNF-α in serum and the expression of NF-κB protein in the colon tissue of rats in the high-dose group of Tong-Xie-Yao-Fang decreased.Conclusion The mechanism of Tong-Xie-Yao-Fang in treating low-grade inflammation of IBS-D intestinal mucosa may be related to activating the expression of FXR in colon,inhibiting the expression of NF-κB in colon tissue,and then reducing the concentration of pro-inflammatory factors IL-6,IL-8 and TNF-α in serum.

Objective:To investigate the effect of microwave on human adenovirus type 2 (HAdV-2) capsid protein in simulated infectious wastes.Methods:Droplets of HAdV-2 virus suspension were added to medical disposable gloves to simulate infectious waste, irradiated under different microwave conditions, the temperature change was recorded, and the irradiated viral supernatant was treated with Dnase I and detected by PCR and qPCR to determine the effect of microwave on the integrity of the viral capsid. ELISA was used to detect the effect of microwave irradiation on the structure of viral hexon protein. The virus was treated alone at the highest temperature during microwave irradiation to investigate whether there were non-thermal effects during microwave disinfection.Results:The maximum temperature during microwave irradiation was 76 ℃, and the PCR and qPCR result showed that Dnase I could significantly damage the viral nucleic acid after microwave irradiation, while the virus control group and heat treatment group were not significantly affected, indicating that microwave irradiation could destroy the integrity of the viral capsid. The result of ELISA showed that microwave irradiation could significantly weaken the binding ability of Hexon protein and antibody, and the result of heat treatment group were similar.Conclusions:Microwave irradiation can destroy the integrity of the HAdV-2 capsid and the structure of Hexon protein, in which the damage to the integrity of the capsid is mainly due to non-thermal effects, and the structural changes of hexon protein are mainly due to thermal effects.

Objective:To evaluate the morphological and functional changes of the heart during second trimester fetuses with ventricular septal defect (VSD) using fetal heart quantification (fetal HQ) technology.Methods:A prospective study was conducted from July 2022 to January 2024 at Chengdu Women′s and Children′s Central Hospital, collecting 91 singleton fetuses diagnosed with isolated VSD (VSD group) and 91 normal fetuses matched for gestational age (control group). Fetal HQ technology was used to measure the length and width of the four-chamber view of the fetal heart, obtaining the global sphericity index (GSI). Speckle tracking technology was used to track the endocardial motion trajectories of the left and right ventricles during diastole and systole, obtaining parameters such as left and right ventricular global longitudinal strain (LV-GLS and RV-GLS), end-diastolic diameter (EDD), 24-segment sphericity index (SI), 24-segment fraction of shortening (FS), left ventricular ejection fraction (LV-EF), fraction of area change (FAC), left ventricular stroke volume (LV-SV), and left ventricular cardiac output (LV-CO).The differences between groups were compared, and the correlations between the values of VSD and GSI, GLS, and FAC were evaluated.Results:The EDD of the left ventricular segments 20-23 in the VSD group was lower, while the SI value of the right ventricular segments 1-4 in the VSD group was higher than that in the control group (all P<0.05). There was no statistically significant difference in GSI between the two groups ( P>0.05). LV-GLS in the VSD group was lower than that in the control group ( P<0.05). There was no statistically significant difference in RV-GLS ( P>0.05). Values of LV-FAC, LV-EF, LV-SV, and LV-CO in the VSD group were significantly lower than those in the control group (all P<0.05). The FS value of left ventricular segments 1-10 in the VSD group presented lower, but the FS value of right ventricular segments 7-21 higher compared to controls(all P<0.05). LV-GLS and LV-FAC absolute values were negatively correlated with the size of VSD ( r=-0.309, P=0.004; r=-0.264, P=0.015), while GSI, RV-GLS, and RV-FAC showed no significant correlation with the size of VSD (all P>0.05). Conclusions:The overall sphericity index of second trimester VSD fetuses is normal, but there are changes in the shape of the left ventricular apical segments and the right ventricular basal segments, with the left heart chamber tending to be flatter and the right heart chamber more fusiform. The left ventricular systolic function of VSD fetuses is significantly reduced, the local systolic function of right ventricular increases while the global systolic function shows no significant change. The absolute values of LV-GLS and LV-FAC in VSD fetuses are negatively correlated with the size of VSD.