Diarrhea-predominant irritable bowel syndrome （IBS-D） is a common digestive system disease with high prevalence and recurrence rates for years， high treatment costs， and serious impacts on patients' quality of life and economic burden. Therefore， it is important to explore new and safe treatment methods. The pathogenesis of IBS-D is complex， in which the gut-brain axis is a key factor. The gut-brain axis， a bidirectional signaling pathway connecting the gastrointestinal tract and the central nervous system， regulates gastrointestinal motility， secretion， and immune responses， playing a key role in the occurrence and development of IBS-D. Up to now， antidiarrheal agents， probiotics， and neurotransmitter modulators are the main methods for the clinical treatment of IBS-D. Although they can partially curb the progression of this disease， the therapeutic effects remain to be improved. Studies have confirmed that traditional Chinese medicine （TCM） has significant advantages in the treatment of IBS-D since it can regulate the gut-brain axis via multiple pathways and targets to improve the gastrointestinal motility and strengthen immune defenses. However， there is a lack of systematic reviews on the regulation of the gut-brain axis by TCM in the treatment of IBS-D. Based on the review of IBS-D-related articles published in recent years， this paper systematically summarized the relationship between the gut-brain axis and IBS-D and the role of TCM in the treatment， providing new ideas for the treatment of IBS-D.

Objective     To evaluate the risk factors for postoperative in-hospital mortality in elderly patients receiving cardiac valvular surgery, and develop a new prediction models using the least absolute shrinkage and selection operator (LASSO)-logistic regression. Methods     The patients≥65 years who underwent cardiac valvular surgery from 2016 to 2018 were collected from the Chinese Cardiac Surgery Registry (CCSR). The patients who received the surgery from January 2016 to June 2018 were allocated to a training set, and the patients who received the surgery from July to December 2018 were allocated to a testing set. The risk factors for postoperative mortality were analyzed and a LASSO-logistic regression prediction model was developed and compared with the EuroSCOREⅡ. Results     A total of 7 163 patients were collected in this study, including 3 939 males and 3 224 females, with a mean age of 69.8±4.5 years. There were 5 774 patients in the training set and 1 389 patients in the testing set. Overall, the in-hospital mortality was 4.0% (290/7 163). The final LASSO-logistic regression model included 7 risk factors: age, preoperative left ventricular ejection fraction, combined coronary artery bypass grafting, creatinine clearance rate, cardiopulmonary bypass time, New York Heart Association cardiac classification. LASSO-logistic regression had a satisfying discrimination and calibration in both training [area under the curve (AUC)=0.785, 0.627] and testing cohorts (AUC=0.739, 0.642), which was superior to EuroSCOREⅡ. Conclusion     The mortality rate for elderly patients undergoing cardiac valvular surgery is relatively high. LASSO-logistic regression model can predict the risk of in-hospital mortality in elderly patients receiving cardiac valvular surgery.

Objective To explore the phenotypic conversion of regulatory T cells (Tregs) in the lungs of mice with bronchopulmonary dysplasia (BPD)-affected mice. Methods A total of 20 newborn C57BL/6 mice were divided into air group and hyperoxia group, with 10 mice in each group. The BPD model was established by exposing the newborn mice to hyperoxia. Lung tissues from five mice in each group were collected on postnatal days 7 and 14, respectively. Histopathological changes of the lung tissues was detected by HE staining. The expression level of surfactant protein C (SP-C) in the lung tissues was examined by Western blot analysis. Flow cytometry was performed to assess the proportion of FOXP3⁺ Tregs and RORγt⁺FOXP3⁺ Tregs in CD4⁺ lymphocytes. The concentrations of interleukin-17A (IL-17A) and IL-6 in lung homogenate were measured by using ELISA. Spearman correlation analysis was used to analyze the correlation between FOXP3⁺Treg and the expression of SP-C and the correlation between RORγt⁺FOXP3⁺ Tregs and the content of IL-17A and IL-6. Results The hyperoxia group exhibited significantly decreased levels of SP-C and radical alveolar counts in comparison to the control group. The proportion of FOXP3⁺Tregs was reduced and that of RORγt⁺FOXP3⁺Tregs was increased. IL-17A and IL-6 concentrations were significantly increased. SP-C was positively correlated with the expression level of RORγt⁺FOXP3⁺ Tregs. RORγt⁺FOXP3⁺ Tregs and IL-17A and IL-6 concentrations were also positively correlated. Conclusion The number of FOXP3⁺ Tregs in lung tissue of BPD mice is decreased and converted to RORγt⁺ FOXP3⁺ Tregs, which may be involved in hyperoxy-induced lung injury.
Animals ; Mice ; Mice, Inbred C57BL ; Bronchopulmonary Dysplasia ; T-Lymphocytes, Regulatory ; Interleukin-17 ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Hyperoxia ; Interleukin-6 ; Forkhead Transcription Factors ; Lung

Objective To investigate the value of 4D-CTA combined with SDF-1a/CXCR4 signaling pathway in evaluating the risk of intracranial aneurysm rupture.Methods Fifty patients with unruptured intracranial posterior communicating aneurysms and 50 patients with ruptured intracranial posterior communicating aneurysms were divided into unruptured group 1 and ruptured group 1.All patients underwent 4D-CTA examination and serumSDF-1alevel was detected.Non-ruptured group 1 was followed up for 12 months(After conservative treatment),on this basis,patients with ruptured posterior communicating aneurysms were included in ruptured group 2,and patients with unruptured posterior communicating aneurysms were included in non-ruptured group 2.Results The AUC values of Wn,AR,L,SR,SDF-1a and their combinations in diagnosing ruptured intracranial posterior communicating aneurysms were all greater than 0.70.The AUC values of Wn,AR,L,SR,SDF-1a and their combinations in predicting ruptured intracranial posterior communicating aneurysms in ruptured group 2 were all greater than 0.70.Conclusion 4D-CTA combined with SDF-1acan effectively distinguish ruptured intracranial posterior communicating aneurysms and predict the risk of rupture.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Objective:To explore the predictive value of lipoproteins on the progression of critically ill patients to chronic critical illness (CCI).Methods:A retrospective cohort study was conducted to analyze clinical data of patients admitted to the intensive care unit (ICU) of Nanjing Drum Tower Hospital from January 1, 2020, to December 31, 2022. The levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and apolipoproteins (ApoA-Ⅰ, ApoB) at 1, 3, 7, 14 and 21 days after admission to ICU were collected. The progression to CCI was recorded. CCI was defined as the length of ICU stay ≥14 days with sustained organ dysfunction [sequential organ failure assessment (SOFA) score ≥2]. Differences in lipoprotein levels between the patients with and without CCI were compared. Multivariate Logistic regression was used to analyze risk factors for critically ill patients progressing to CCI. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of lipoproteins on critically ill patients progressing to CCI.Results:A total of 200 patients were enrolled in the final analysis. 137 patients (68.5%) progressed to CCI, and 63 patients (31.5%) did not. The lipoprotein indicators in the CCI group showed a decrease after the acute phase, while the lipoprotein indicators in the non-CCI group showed an increase. The levels of HDL, LDL, ApoA-Ⅰ, and ApoB at various time points in the CCI group were significantly lower than those in the non-CCI group. HDL at 7 days in the CCI group was significantly lower than that in the non-CCI group [mmol/L: 0.44 (0.31, 0.61) vs. 0.67 (0.49, 0.75), P < 0.01]. Multivariate Logistic regression analysis showed that 7-day HDL was an independent risk factor for critically ill patients progressing to CCI [odds ratio ( OR) = 0.033, 95% confidence interval (95% CI) was 0.004-0.282, P = 0.002]. ROC curve analysis showed that the area under the ROC curve (AUC) of 7-day HDL for predicting critically ill patients progressing to CCI was 0.702, with a 95% CI of 0.625-0.779, P < 0.001. When the optimal cut-off value was 0.59 mmol/L, the sensitivity was 69.8%, and the specificity was 72.4%. Conclusions:The low level of lipoproteins is closely related to the progression of critically ill patients, and 7-day HDL has a certain predictive value for critically ill patients progressing to CCI. Continuously observation of the change trend of lipoprotein level is helpful to judge the progression of CCI in critically ill patients.

Objectives:To evaluate and predict the risk for in-hospital mortality in elderly patients receiving cardiac valvular surgery preferably,we developed a new prediction model using machine learning. Methods:Clinical data including baseline characteristics,peri-operative data and primary endpoint of 7 163 elderly patients aged 65 years or older undergoing cardiac valvular surgery from January 2016 to December 2018 from 87 hospitals were collected from the Chinese Cardiac Surgery Registry(CCSR).Patients from January 2016 to June 2018 were assigened to the training cohort(n=5 774)and patients from July to December 2018 were assigened to the validation cohort(n=1 389).The primary endpoint was in-hospital mortality.Machine learning algorithms were used to analyze risk factors and develop prediction model. Results:Overall in-hospital mortality was 4.1%.Linear discriminant analysis(LDA),support vector classification(SVC)and logistic regression(LR)models in the training cohort all have high AUCs and low Brier scores,with good discrimination and calibration.In validation cohort,the AUC of LDA,SVC and LR were 0.744,0.744 and 0.746 respectively,which were significantly better than that of 0.642 using the European System for Cardiac Operative Risk Evaluation II(EuroSCORE II)model(P<0.05). Conclusions:The mortality rate for elderly patients undergoing cardiac valvular surgery is relatively high.LDA,SVC and LR can predict the risk for in-hospital mortality in elderly patients receiving cardiac valvular surgery with high accuracy.

Objective To investigate the mechanism by which conbercept reverses transforming growth factor-β2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(HLECs).Methods Cultured HLEC SRA01/04 cells were treated with TGF-β2,conbercept,or both,and the changes in cell proliferation,apoptosis,and migration were observed using MTT assay,flow cytometry,scratch assay,and Transwell assay.Western blotting and qRT-PCR were used to detect the changes in the expression of EMT-related epithelial cell markers(E-Cadherin,α-SMA,and Snail),extracellular matrix components,and genes related to the TGF-β/Smad signaling pathway.Results Conbercept significantly reduced TGF-β2-induced EMT of SRA01/04 cells,decreased the expression levels of mesenchymal and extracellular matrix markers α-SMA,Snail,collagen I,collagen IV,and FN1,and upregulated the protein and mRNA expressions of E-cadherin(P<0.05).Transwell assay showed significantly lower cell migration ability in TGF-β2+conbercept group than in TGF-β2 group(P<0.05).Conbercept also inhibited the increase in Smad2/3 phosphorylation levels in HLEC-SRA01/04 cells with TGF-β2-induced EMT(P<0.01).Conclusion Conbercept inhibits TGF-β2 induced EMT by downregulating the expression of pSmad2/3 in TGF-β/Smad signaling pathway,indicating a potential therapeutic strategy against visual loss induced by posterior capsule opacification.

Aim To explore the effect of Pueraria Lobata Flowers Extract(PFE)on lipid accumulation in mac-rophage-derived foam cells.Methods The concentration of PFE in THP-1-derived foam cells was screened by MTT,intracellular lipid accumulation was detected by oil red O staining and cholesterol detection kit,intracellular cholesterol ef-flux levels were detected by cholesterol efflux assay kit,RT-qPCR and Western blot were used to analyze mRNA and pro-tein expression.Results PFE significantly reduced lipid accumulation in THP-1-derived foam cells.PFE did not affect the mRNA expression of CD36,scavenger receptor-A Ⅰ(SR-A Ⅰ),sterol regulatory element-binding protein 2(SREBP2),3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR),but it could upregulate the mRNA and protein expres-sion levels of ATP-binding cassette transporter A1(ABCA1)(P＜0.05),and promote the intracellular cholesterol efflux of macrophage-derived foam cells(P＜0.01).PFE could activate the activity of peroxisome proliferator-activated receptor y(PPARγ)(P＜0.01)and upregulate the mRNA and protein expression levels of PPARγ(P＜0.05).Compared with the PFE control group,the expression of PPARγ and ABCA1 proteins decreased and cholesterol efflux decreased after GW9662 treatment(all P＜0.01).Conclusion PFE could significantly prevent the lipid accumulation in THP-1-derived foam cells and inhibit the formation of foam cells by upregulating ABCA1 expression and cholesterol efflux mediated by PPARγ.

Objective:To investigate the protective effects and mechanisms of targeted inhibition of type 3 deiodinase (Dio3) on skeletal muscle mitochondria in sepsis.Methods:① In vivo experiments: adeno-associated virus (AAV) was employed to specifically target Dio3 expression in the anterior tibial muscle of rats, and a septic rat model was generated using cecal ligation and puncture (CLP). The male Sprague-Dawley (SD) rats were divided into shNC+Sham group, shD3+Sham group, shNC+CLP group, and shD3+CLP group by random number table method, with 8 rats in each group. After CLP modeling, tibial samples were collected and Western blotting analysis was conducted to assess the protein levels of Dio3, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), and silence-regulatory protein 1 (SIRT1). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was utilized to examine mRNA expression of genes including thyroid hormone receptors (THRα, THRβ), monocarboxylate transporter 10 (MCT10), mitochondrial DNA (mtDNA), and PGC1α. Transmission electron microscopy was employed to investigate mitochondrial morphology. ② In vitro experiments: involved culturing C2C12 myoblasts, interfering with Dio3 expression using lentivirus, and constructing an endotoxin cell model by treating cells with lipopolysaccharide (LPS). C2C12 cells were divided into shNC group, shD3 group, shNC+LPS group, and shD3+LPS group. Immunofluorescence colocalization analysis was performed to determine the intracellular distribution of PGC1α. Co-immunoprecipitation assay coupled with Western blotting was carried out to evaluate the acetylation level of PGC1α. Results:① In vivo experiments: compared with the shNC+Sham group, the expression of Dio3 protein in skeletal muscle of the shNC+CLP group was significantly increased (Dio3/β-Tubulin: 3.32±0.70 vs. 1.00±0.49, P < 0.05), however, there was no significant difference in the shD3+Sham group. Dio3 expression in the shD3+CLP group was markedly reduced relative to the shNC+CLP group (Dio3/β-Tubulin: 1.42±0.54 vs. 3.32±0.70, P < 0.05). Compared with the shNC+CLP group, the expression of T3-regulated genes in the shD3+CLP group were restored [THRα mRNA (2 -ΔΔCt): 0.67±0.05 vs. 0.33±0.01, THRβ mRNA (2 -ΔΔCt): 0.94±0.05 vs. 0.67±0.02, MCT10 mRNA (2 -ΔΔCt): 0.65±0.03 vs. 0.57±0.02, all P < 0.05]. Morphology analysis by electron microscopy suggested prominent mitochondrial damage in the skeletal muscle of the shNC+CLP group, while the shD3+CLP group exhibited a marked improvement. Compared with the shNC+Sham group, the shNC+CLP group significantly reduced the number of mitochondria (cells/HP: 10.375±1.375 vs. 13.750±2.063, P < 0.05), while the shD3+CLP group significantly increased the number of mitochondria compared to the shNC+CLP group (cells/HP: 11.250±2.063 vs. 10.375±1.375, P < 0.05). The expression of mtDNA in shNC+CLP group was markedly reduced compared with shNC+Sham group (copies: 0.842±0.035 vs. 1.002±0.064, P < 0.05). Although no difference was detected in the mtDNA expression between shD3+CLP group and shNC+CLP group, but significant increase was found when compared with the shD3+Sham group (copies: 0.758±0.035 vs. 0.474±0.050, P < 0.05). In the shD3+CLP group, PGC1α expression was significantly improved at both transcriptional and protein levels relative to the shNC+CLP group [PGC1α mRNA (2 -ΔΔCt): 1.49±0.13 vs. 0.68±0.06, PGC1α/β-Tubulin: 0.76±0.02 vs. 0.62±0.04, both P < 0.05]. ② In vitro experiments: post-24-hour LPS treatment of C2C12 cells, the cellular localization of PGC1α became diffuse; interference with Dio3 expression promoted PGC1α translocation to the perinuclear region and nucleus. Moreover, the acetylated PGC1α level in the shD3+LPS group was significantly lower than that in the shNC+LPS group (acetylated PGC1α/β-Tubulin: 0.59±0.01 vs. 1.24±0.01, P < 0.05), while the expression of the deacetylating agent SIRT1 was substantially elevated following Dio3 inhibition (SIRT1/β-Tubulin: 1.04±0.04 vs. 0.58±0.03, P < 0.05). When SIRT1 activity was inhibited by using EX527, PGC1α protein expression was notably decreased compared to the shD3+LPS group (PGC1α/β-Tubulin: 0.92±0.03 vs. 1.58±0.03, P < 0.05). Conclusion:Inhibition of Dio3 in skeletal muscle reduced the acetylation of PGC1α through activating SIRT1, facilitating nuclear translocation of PGC1α, thereby offering protection against sepsis-induced skeletal muscle mitochondrial damage.