Diabetic kidney disease （DKD） stands as one of the most prevalent microvascular complications of diabetes，noted for its concealed onset and tendency to evolve into end-stage renal disease，profoundly impacting patients' life expectancy and quality of life. Epithelial-to-mesenchymal transition （EMT） is a central pathological process in the initiation and progression of DKD，facilitating disease advancement and renal fibrosis，thus representing a crucial focus of research into the pathological mechanisms of DKD. EMT is driven by the abnormal activation of signaling pathways，including transforming growth factor-β （TGF-β）/Smad，secreted glycoprotein/β-catenin，Notch，tumor necrosis factor-α （TNF-α）/nuclear factor-κB （NF-κB），and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR），leading to renal cellular injury and subsequently accelerating renal fibrosis and the progression of DKD. Traditional Chinese medicine （TCM），characterized by its multi-target and multi-pathway therapeutic approach，demonstrates unique advantages in addressing DKD and EMT. Recent research has shown that active ingredients in TCM，including glycosides，flavonoids，and polyphenols，as well as TCM formulas，can precisely target these relevant signaling pathways，effectively inhibiting cellular injury in DKD and intervening in the EMT process. These findings not only underscore the potential of TCM monomers and formulas in treating DKD and EMT but also pave new directions for research in this field within TCM. This paper systematically reviewed the signaling pathways associated with EMT and provided an in-depth analysis of the research achievements and underlying mechanisms of TCM monomers and formulas in treating DKD and intervening in EMT，aiming to offer new insights and directions for TCM in the treatment of DKD and research on EMT，thereby further promoting the modernization and development of TCM.

OBJECTIVE: To investigate the effects of liriodendrin on the intestinal flora and the ferroptosis signaling pathway in renal tissue of rats with sepsis-induced acute kidney injury (AKI). METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), sepsis model induced by cecal ligation and puncture group (CLP group), and liriodendrin intervention group (CLP+LIR group), with 10 rats in each group. The CLP+LIR group was given 0.2 mL of 100 mg/kg liriodendrin by gavage 2 hours before modeling; Sham group and CLP group were given the same volume of normal saline by gavage. The samples were collected after anesthesia 24 hours after modeling. The pathological changes of renal tissue were observed by hematoxylin-eosin (HE) staining. The levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukins (IL-1β, IL-6) were detected by enzyme linked immunosorbent assay (ELISA). The levels of renal function indicators such as creatinine (Cr), and urea nitrogen (UREA) in peripheral blood, and the content of malondialdehyde (MDA) and Fe²⁺ in renal tissue were detected. Western blotting was used to detect the expressions of nuclear factor E2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) in renal tissues. The changes of intestinal flora were detected by 16S rDNA high-throughput sequencing. RESULTS: Compared with the Sham group, the CLP group showed significantly enlarged glomeruli, noticeable renal interstitial edema, disorganized kidney tissue, and significantly increased pathological scores. The contents of TNF-α, IL-1β, IL-6, Cr, and UREA in peripheral blood and the levels of MDA and Fe²⁺ in renal tissue were significantly increased. The protein expressions of Nrf2, GPX4, and HO-1 in renal tissue were significantly down-regulated. The species richness of intestinal flora decreased significantly, and the relative abundances of pathogenic bacteria such as Morganella, Citrobacter, Proteus, Klebsiella, Shigella, Aggregatibacter, and Enterococcus increased significantly, while the relative abundances of beneficial bacteria such as Butyricimonas, Veillonella, Prevotella, Lactobacillus, Bifidobacterium, and Ruminococcus decreased significantly. Compared with the CLP group, CLP+LIR group could significantly reduce the pathological damage of renal tissue, the pathological score significantly decreased (1.80±0.84 vs. 4.20±1.30, P < 0.05), and improve the composition of intestinal flora, reduce the relative abundances of pathogenic bacteria such as Proteus, Klebsiella, Shigella, Aggregatibacter, and Enterococcus, and significantly increase the relative abundances of Lactobacillus, Bifidobacterium, and Ruminococcus, significantly reduce the contents of TNF-α, IL-1β, IL-6, Cr, and UREA in peripheral blood and the levels of MDA and Fe²⁺ in renal tissue [blood TNF-α (ng/L): 191.31±7.23 vs. 254.90±47.89, blood IL-1β (ng/L): 11.15±4.04 vs. 23.06±1.67, blood IL-6 (ng/L): 163.20±17.83 vs. 267.69±20.92, blood Cr (μmol/L): 24.14±4.25 vs. 41.17±5.43, blood UREA (mmol/L): 4.59±0.90 vs. 8.01±1.07, renal MDA (μmol/g): 9.67±0.46 vs. 16.05±0.88, renal Fe²⁺ (mg/g): 0.71±0.07 vs. 0.93±0.04, all P < 0.05], and increase the protein expressions of Nrf2, GPX4, and HO-1 (Nrf2/GAPDH: 1.21±0.01 vs. 0.39±0.01, GPX4/GAPDH: 0.74±0.04 vs. 0.48±0.04, HO-1/GAPDH: 0.91±0.01 vs. 0.41±0.02, all P < 0.05). CONCLUSIONS Liriodendrin has an obvious protective effect on sepsis-induced AKI. The mechanism may involve regulating the intestinal flora, increasing the activation of the Nrf2/HO-1/GPX4 signaling pathway in renal tissue, and reducing ferroptosis.
Animals ; Acute Kidney Injury/microbiology* ; Rats, Sprague-Dawley ; Sepsis/complications* ; Male ; Ferroptosis/drug effects* ; Gastrointestinal Microbiome/drug effects* ; Rats ; Signal Transduction ; Kidney/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Objective:To discuss the effect of microRNA-34a-5p(miR-34a-5p)on the neuron apoptosis in hippocampus tissue of the rats with temporal lobe epilepsy,and to clarify its mechanism.Methods:Fifty-two male SD rats were randomly divided into control group,model group,miR-34a-5p inhibitor group,and inhibitor negative control group,and there were 13 rats in each group.The PONEMAH 6.X experimental animal telemetry platform was used to record the electroencephalogram(EEG)of the rats in various groups;real-time fluorescence quantitative PCR(RT-qPCR)was used to detect the expression levels of miR-34a-5p in hippocampus tissue of the rats in various groups;HE staining was used to observe the morphology of hippocampus tissue of the rats in various groups;TUNEL method was used to detect the apoptotic rates of neurons in hippocampus tissue of the rats in various groups;immunohistochemistry method was used to determine the positive expression rates of CDK6,p-Rb,and E2F1 proteins in hippocampus tissue of the rats in various group;Western blotting method was used to detect the expression levels of cyclin-dependent protein kinase 6(CDK6),phosphorylated retinoblastoma protein(p-Rb),and E2F transcription factor 1(E2F1)proteins in hippocampus tissue of the rats in various groups.Results:No abnormalities were observed in the rats in control group;the rats in model group,miR-34a-5p inhibitor group,and inhibitor negative control group exhibited varying degrees of drooling,trembling,bloody tears,staring,chewing tremors,followed by nodding and blinking,and finally forelimb convulsions,standing upright,and falling.Compared with control group,the total duration of epileptic seizures of the rats in model group was significantly prolonged(P<0.01);compared with model group,the total duration of epileptic seizures of the rats in miR-34a-5p inhibitor group was shortened(P<0.01);compared with miR-34a-5p inhibitor group,the total duration of epileptic seizures of the rats in inhibitor negative control group was prolonged(P<0.01).The RT-qPCR results showed that compared with control group,the expression level of miR-34a-5p in hippocampus tissue of the rats in model group was increased(P<0.01);compared with model group,the expression level of miR-34a-5p in hippocampus tissue of the rats in miR-34a-5p inhibitor group was increased(P<0.05);compared with miR-34a-5p inhibitor group,the expression level of miR-34a-5p in hippocampus tissue of the rats in inhibitor negative control group was increased(P<0.01).The HE staining results showed that compared with control group,the cell arrangement in model group was disordered;compared with model group,the cell arrangement in miR-34a-5p inhibitor group was orderly;compared with miR-34a-5p inhibitor group,the cell morphology in inhibitor negative control group was irregular.The TUNEL staining results showed that compared with control group,the apoptotic rate of neurons in CA1 region of hippocampus tissue of the rats in model group was increased(P<0.01);compared with model group,the apoptotic rate of neurons in CA1 region of hippocampus tissue of the rats in miR-34a-5p inhibitor group was decreased(P<0.05);compared with miR-34a-5p inhibitor group,the apoptotic rate of neurons in CA1 region of hippocampus tissue of the rats in inhibitor negative control group was increased(P<0.05).The immunohistochemistry results showed that compared with control group,the positive expression rates of CDK6,p-Rb and E2F1 proteins in hippocampus tissue of the rats model group were increased(P<0.05 or P<0.01);compared with model group,the positive expression rates of CDK6,p-Rb and E2F1 proteins in hippocampus tissue of the rats in miR-34a-5p inhibitor group were decreased(P<0.05);compared with miR-34a-5p inhibitor group,the positive expression rates of CDK6,p-Rb and E2F1 proteins in hippocampus tissue of the rats in inhibitor negative group were increased(P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of CDK6,p-Rb,and E2F1 proteins in hippocampus tissue of the rats in model group were increased(P<0.01);compared with model group,the expression levels of CDK6,p-Rb,and E2F1 proteins in hippocampus tissue of the rats in miR-34a-5p inhibitor group were decreased(P<0.05 or P<0.01);compared with miR-34a-5p antagomir group,the expression levels of CDK6,p-Rb,and E2F1 proteins in hippocampus tissue of the rats in inhibitor negative control group were increased(P<0.05 or P<0.01).Conclusion:The expression of miR-34a-5p is upregulated in the hippocampal tissue of temporal lobe epilepsy rats,and hippocampal neuron apoptosis is increased.Inhibition of miR-34a-5p expression can reduce the hippocampal neuron apoptotic rate,and its mechanism may be related to the regulation of CDK6,p-Rb,and E2F1 protein expressions in the hippocampus tissue by miR-34a-5p.

Objective To conduct an in-depth analysis and feature extraction of the transcriptomics data of 10 types of cancers in order to realize the staging diagnosis of cancer samples.Methods The transcriptomics data of the top 10 cancers having the highest incidence were amassed from the UCSC Xena website,which comprised 4 938 samples and 59 428 genes.With the aid of variational autoencoder,we developed an incremental feature ranking and selection variational autoencoder(IFRSVAE)based on feature importance ranking and incorporating the masking algorithm and the Incremental Feature Selection(IFS).Subsequently,the performance efficiency of our IFRSVAE model was evaluated in conjunction with Random Forest(RF),Support Vector Machine(SVM),and eXtreme Gradient Boosting(XGboost),and it was also compared with other methods.Results Our research extracted 21 features for the ensuing classification.In comparison to the conventional variational autoencoder,recursive feature elimination,and Lasso regression models,the IFRSVAE model attained more favorable performance across all 3 classifiers(highest AUC value,and well performed other indicators).Notably,the IFRSVAE-RF exhibited the most outstanding performance,with an AUC value reaching 85.49%(95%CI:83.24%～87.74%).Moreover,Shapley additive explanations(SHAP)interpretable model illustrated well contributions of the features in our model.Conclusion Our developed IFRSVAE shows certain effectiveness in feature extraction.The constructed IFRSVAE-RF model demonstrates relatively good performance in the task of cancer staging diagnosis,which providing a new and referable idea for research orientation of deep-learning-based diagnostic methods for cancer staging.

Objective:To discuss the ameliorative effect of a novel antiepileptic drug Q808 on neuronal injury in temporal lobe epilepsy(TLE)rats,and to clarify its mechanism of action.Methods:TLE rat model was prepared by intraperitoneal injection of the innovative antiepileptic drug candidate 6-(4-chlorophenoxy)-tetrazolo(5,1-a)phthalazine(Q808).Forty-five successfully modeled rats were randomly divided into model group,low dose of Q808 group,and high dose of Q808 group,and there were 15 rats in each group.The rats in low dose of Q808 group and high dose of Q808 group were gavaged with 20 and 80 mg·kg-1 Q808,respectively,and the rats in model group were gavaged with an equal amount of 0.3％sodium carboxymethyl cellulose.Another 15 healthy SD rats were selected as control group.After 4 weeks of continuous gavage treatment,the morphology of the rats in varioius groups was observed;PONEMAH 6.X experimental animal telemetry platform was used to record the electroencephalogram of the rats in various groups;Golgi staining was used to observe the morphology of dendritic and dendritic spine density of hippocampal CA1 neurons of the rats in various groups;Western blotting method was used to detect the expression levels of synaptic plasticity-specific protein calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)in hippocampus tissue of the rats in various groups.Results:The rats in control group showed normal activity without convulsions or other abnormal manifestations.The rats in model group,low dose of Q808 group,and high dose of Q808 group showed varying degrees of reduced activity,trembling and nodding,loss of balance,muscle rigidity and forelimb convulsions,gradually transforming into whole-body muscle rigidity and standing,followed by falling backwards,and there were no convulsions during the interictal period.Compared with control group,the total durations of epileptic seizures of the rats in model group,low dose of Q808 group,and high dose of Q808 group were significantly prolonged(P＜0.01).Compared with model group,the total durations of epileptic seizures in low dose of Q808 group and high dose of Q808 group were significantly shortened(P＜0.01).The hippocampal CA1 neurons of the rats in control group showed regular distribution of dendrites with dense and orderly dendritic networks.The hippocampal CA1 neurons of the rats in model group showed disordered arrangement of dendrites with massive dendritic entanglement,forming thicker nerve fiber bundles.Compared with model group,the dendritic networks of hippocampal CA1 neurons of the rats in low dose of Q808 group and high dose of Q808 group were partially recovered with relatively regular arrangement.Compared with control group,the dendritic spine density of hippocampal CA1 neurons of the rats in model group was significantly decreased(P＜0.01).Compared with model group,the dendritic spine densities of hippocampal CA1 neurons in low dose of Q808 group and high dose of Q808 group significantly increased(P＜0.01).Compared with control group,the expression levels of CaMKⅡ protein in hippocampus tissue of the rats in model group,low dose of Q808 group,and high dose of Q808 group were significantly decreased(P＜0.01).Compared with model group,the expression levels of CaMKⅡ protein in hippocampus tissue of the rats in low dose of Q808 group and high dose of Q808 group were significantly increased(P＜0.01).Conclusion:The novel antiepileptic drug Q808 has an ameliorating effect on the TLE model rats;its mechanism may be related to Q808's ability to reduce the dendritic lesions in hippocampal CA1 neurons and increase the expression level of synaptic plasticity-related protein CaMKⅡ protein.

Objective: To explore the relationship between physical exercise and parenting styles, and psychological resilience among college students, in order to provide guidance for improving college students physical exercise status. Methods: From September 10, 2022 to January 6, 2023, 1 227 students from three comprehensive universities in Jinan were selected for investigation using a stratified random sampling and convenient sampling method. Physical exercise was assessed using the Physical Activity Rating Scale, parenting style was evaluated with the short-Egna Minnen av Barndoms Uppfostran for Chinese (s-EMBU-C), and psychological resilience was measured by the Resilience Scale for Chinese Adolescents (RSCA). The influence of parenting style and psychological resilience on physical exercise was explored by Pearson correlation analysis, linear and Logistic regression analysis. Results: A total of 815 (66.42%) engaged in lowintensity exercise, 308 (25.10%) in moderateintensity exercise, and 104 (8.48%) in highintensity exercise. The total score on the Physical Activity Rating Scale was (22.15±0.72). Logistic regression analysis showed that gender (OR=1.58, 95%CI=1.07-2.33) and whether the student was a sports specialist (OR=1.61, 95%CI=1.17-2.22) were the related factors for college students physical exercise classification(P<0.05). Linear regression analysis showed that emotional warmth dimensions of the s-EMBU-C (mother version and father version), the total score of s-EMBU-C(mother version), positive cognition, emotional control and the total score of RSCA all affected the physical activity level of college students (β=0.29, 0.20, 0.26, 0.32, 0.15, 0.20, P<0.05). Conclusions College students physical exercise behavior is closely related to gender, sports specialization, parenting styles, and psychological resilience. Colleges and universities can promote changes in physical exercise behavior among college students through joint parental supervision and psychological counseling.

Children and adults differ significantly in physiology,biochemistry and immune function,which leads to sig-nificant differences in blood transfusion strategies between children and adults.To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children,the National Health Commission organized the formulation and re-lease of the health industry standard Guideline for Pediatric Transfusion(WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard,and explain and interpret the preparation of the"scope","general provisions"and"factors to consider"of the Standard,hoping to contribute to the understanding and implementation of the Standard.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Pyroptosis is a programmed death of inflammatory cells triggered by pathogen invasion,dependent on caspase activation,through both classical and non-classical pyroptosis pathways.Cell pyroptosis is related to the occurrence and development of a variety of animal infectious diseases caused by microbial infection.After microorganisms invading,cells are stimulated by pathology-re-lated molecular patterns,causing strong immune response,stimulating inflammatory signaling pathways,and then activating inflammasome,leading to pyroptosis.The immune system has e-volved multiple mechanisms to fight microbial infections and regulate inflammatory responses.The innate immune system,by recognizing microbial molecules in pathogens and responding quickly by producing inflammasome and activating pyroptosis,helps clear pathogens to prevent infection and maintain the normal functioning of the body.A thorough study of the pathogenesis and immune es-cape mechanism of cell pyroptosis in animal infectious diseases will provide a new direction for the treatment of animal infectious diseases.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.