ObjectiveTo investigate the differential expression of integrin alpha-6（ITGA6） in abdominal wall endometriosis （AWE） tissues and its molecular mechanisms in regulating AWE. Methods36 AWE lesions were designated as the experimental group， while 36 cases of normal endometrial tissues served as the controls. Differential expression of ITGA6 between the two groups was assessed through immunohistochemical （IHC） staining. Human ITGA6 gene-specific interference sequences were designed， synthesized， and packaged into lentiviral vectors to establish the Ishikawa cell line with ITGA6-knockdown. Similarly， the ITGA6-overexpression cell line was constructed using the coding sequence （CDS） of the gene. Real-time PCR and Western blot were performed to detect changes in epithelial-mesenchymal transition（EMT）-related markers and angiogenesis-related indicators. Cell invasion and migration capabilities were assessed by Cell Scratch and Transwell assays. Furthermore， Western blot was conducted to profile PI3K/AKT pathway dynamics. ResultsEctopic endometrial tissues exhibited a marked increase in the number of ITGA6-positive cells and their expression intensity compared to eutopic endometrium （each P < 0.001）. Compared with the NC group， the ITGA6-knockdown group showed significantly reduced expression of N-cadherin， VEGF， and TGF-β1 （all P < 0.01）， while E-cadherin expression was markedly increased （P < 0.01）. Concomitantly， the invasion and migration capacities of ITGA6-low expression were significantly impaired （P < 0.001 for both）， accompanied by a marked reduction in AKT and phosphorylated AKT（p-AKT） levels （P < 0.001）. Conversely， overexpressing ITGA6 resulted in opposite effects. ConclusionITGA6 modulates EMT and angiogenesis in Ishikawa cells via the PI3K/AKT signaling pathway， thereby enhancing cell invasion and migration capabilities， which contributes to the pathogenesis of AWE.

Drug resistance is one of the key factors affecting the effectiveness of cancer treatment methods, including chemotherapy, radiotherapy, and immunotherapy. Its occurrence is related to factors such as mRNA expression and methylation within cancer cells. If drug resistance in patients can be accurately identified early, doctors can devise more effective treatment plans, which is of great significance for improving patients' survival rates and quality of life. Cancer drug resistance prediction based on artificial intelligence (AI) technology has emerged as a current research hotspot, demonstrating promising application prospects in guiding clinical individualized and precise medication for cancer patients. This review aims to comprehensively summarize the research progress in utilizing AI algorithms to analyze multi-omics data including genomics, transcriptomics, epigenomics, proteomics, metabolomics, radiomics, and histopathology, for predicting cancer drug resistance. It provides a detailed exposition of the processes involved in data processing and model construction, examines the current challenges faced in this field and future development directions, with the aim of better advancing the progress of precision medicine.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Glioma is the most common primary tumor of the central nervous system,with glio-blastoma multiforme of World Health Organization grade Ⅳ exhibiting the highest malignancy and worst prognosis.Long non-coding RNA(lncRNA)is a type of regulatory RNA without protein-coding ability,which can promote the malignant phenotypic evolution of glioma cells and induce therapeutic resistance by reprogramming glycolytic metabolism,playing a crucial role in the malignant progression and prognosis of glioma.This paper mainly introduced the role of lncRNA in regulating the biological behavior of glioma cells and aerobic glycolysis,and proposed a new paradigm of combined therapy based on the aerobic glycolysis metabolism-epigenetic network,providing new ideas for the discovery of diagnostic biomarkers and the development of novel therapeutic strategies for glioma.

Parkinson's disease(PD)is the second most prevalent neurodegenerative disorder globally,and its pathogenesis remains incompletely understood.Mitochondrial dysfunction in micro-glia serves as a crucial factor in the onset and progression of PD,with studies on mitochondrial disor-ders playing a vital role in elucidating the pathogenesis of PD.A profound understanding of the rela-tionship between mitochondrial dysfunction and microglia activation in PD is of great significance for unraveling the pathogenesis,diagnosis,and treatment of PD.This review summarized the research progress on the roles of mitochondrial energy metabolism disorders,dynamic imbalance,autophagy defects,and mitochondrial transfer in the activation of microglia in PD.

Objective To retrospective analyze the use of inpatients taking sacubitril/valsartan in Nanjing Drum Tower Hospital,and to provide references for rational clinical application.Methods The relevant data of inpatients taking sacubitril/valsartan in our hospital were systematically collected from July 2019 to September 2021,and the rationality of drug use was eval-uated.Results A total of 2 682 cases were collected,and 868 cases(32.36%)of them involved 918 times of irrational drug use.The specific situations of irrational drug use included off-label use(182 times),irrational usage and dosage(389 times),irrational conversation of drugs(251 times),and irrational drug use for special populations(96 times).Conclusion The use of sacubitril/valsartan exists in unreasonable situations in our hospital.Clinical pharmacists should participate in medication man-agement to a certain extent,strengthen the pharmaceutical care of patients,and improve the rational rate of drug use.

Objective:To evaluate the epidemiological characteristics and explore the associated factors of breakthrough cases (BC) from Public Health Emergency Events (PHEEs) of varicella in Zhejiang Province from 2019 to 2022.Methods:Data on cases were obtained from the China Information System for Disease Control and Prevention and the PHEEs Reporting Information Database of Varicella in Zhejiang Province. History records were matched through the Zhejiang Provincial Immunization Information System. Descriptive analysis and multiple logistic regression model with a bidirectional stepwise selection method were performed to explore associated factors for BC during 2019-2022.Results:A total of 144 276 varicella cases were reported from 2019 to 2022, with the annual reported incidence of 47.35-82.80 cases per 100 000 population. Among these cases, 109 172 were non-breakthrough cases (NBC, accounting for 75.67%), 34 517 were BC (23.92%), and the rest 587 cases had unclear vaccination history on varicella (0.41%). A total of 214 PHEEs of varicella were reported, of which 99.07% occurred in school settings. The proportion of PHEEs that occurred in high school increased significantly as time went on ( χ2trend=5.742, P=0.017). Multiple logistic regression model which focused on "BC vs. NBC (as the reference)" indicated that the year of onset ( OR=1.585, 95% CI:1.343-1.878), the month of onset (taking January as the reference, OR=2.311-15.652), city (taking Hangzhou as the reference, Jiaxing OR=2.370, Jinhua OR=2.197, Lishui OR=0.134), age ( OR=0.887, 95% CI: 0.826-0.944), PHEEs setting (taking "primary school and below" as the reference, "high school and above" OR=0.516, 95% CI: 0.305-0.897), and the number of rashes ( OR=0.569, 95% CI: 0.458-0.703) were associated factors. Multiple logistic regression model which focused on "two-dose BC vs. one-dose BC (as the reference)" showed that the age of initial vaccination ( OR=0.045, 95% CI: 0.014-0.107), the time interval from onset to the last dose ( OR=0.037, 95% CI: 0.011-0.087) and the age of onset ( OR=20.724, 95% CI: 8.383-72.485) were associated factors. Conclusion:During 2019-2022, the reported high-risk group of varicella in Zhejiang Province has shifted to adolescents and young adults. Although vaccination could not completely prevent the onset of VZV, it could relieve clinical symptoms and delay the age of onset.

Diabetic cognitive dysfunction （DCD） is one of the complications of diabetes， which is characterized by impaired brain structure and progressively decreased learning and memory ability. With the increasing incidence of diabetes worldwide， DCD has become a serious medical and social problem. However， its pathophysiological mechanisms are not well understood. The occurrence and development of DCD involve multiple pathological links and mechanisms， and the prevention and treatment require multi-link and multi-target therapeutic measures. At present， there is no specific drug to prevent or improve DCD. Hypoglycemic drugs such as metformin and vigagliptin or anti-dementia drug including Donepezil are commonly used in clinical treatment to delay the occurrence and progression of cognitive dysfunction， but these drugs have a single target and obvious side effects. Traditional Chinese medicine has a long history in the prevention and treatment of diabetes and central cognitive diseases， and it has many unique advantages such as multiple components， multiple targets， side effects， and low price. A large number of studies have confirmed that traditional Chinese medicine has a significant prevention and treatment effect on DCD， which can improve insulin resistance， synaptic dysfunction， inflammation， oxidative stress， endoplasmic reticulum stress， and neuronal apoptosis by regulating phosphatidylin-ositol 3-kinase （PI3K）/protein kinase B （Akt）， advanced glycation end products （AGEs）/advanced glycation end products receptor （RAGE）/nuclear transcription factor-κB （NF-κB）， NOD-like receptor thermal protein domain associated protein 3 （NLRP3） inflammasome， and endoplasmic reticulum stress and nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathways. This article reviewed the effects and related mechanisms of traditional Chinese medicine on DCD in recent years， so as to provide a reference for the prevention and treatment of DCD by traditional Chinese medicine.

Objective To investigated the effect of tripterygium glycosides(TG)on dextran sodium sulfate(DSS)-induced colonic mucosal damage in ulcerative colitis(UC)mice and its regulatory mechanism.Methods Forty C57BL/6J mice were randomly divided into a normal group,a model group,and a tretinoin low,medium,and high dose group(administered at concentrations of 9.00mg/kg,27.03mg/kg,and 81.09mg/kg,respectively).The mice in the normal group were free to drink distilled water,and the rest of the mice drank 5％DSS to induce UC modeling.After modeling,mice in the model group were given 0.4ml of saline by gavage daily,and the rest of the mice in the treatment group were given the corresponding dose of TG for gavage intervention.The mass and disease activity index of the mice in each group were compared,and the pathological and histological damage of the colon was observed.Tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),and superoxide dismutase(SOD)levels were measured using the corresponding kits.Western blot Detection of Nur77,tumor necrosis factor receptor-associated factor 2(Traf2),nucleoporin 62(P62),autophagy protein-microtubule associated protein1 light chain 3(LC3)molecular expression.Results Compared with the blank group,the body weight,colon length,SOD,Nur77,Traf2,and LC3Ⅱ/LC3Ⅰ levels of mice in the model group were significantly decreased(P<0.05),and the DAI level,colon pathology score,TNF-α,MDA level,and P62 of the mice were significantly increased(P<0.05).Compared with mice in the UC model group,mice in the low,medium and high dose groups of tretinoin polyphenols showed significant increases in body weight,colon length,SOD,Nur77,Traf2,LC3Ⅱ/LC3Ⅰlevels(P<0.05),and mice with DAI scores,TNF-α,MDA levels in the colon,and P62 levels were significantly decreased(P<0.05).Mice in the medium and high dose groups of tretinoin polyphenols pathological scores were significantly reduced(P<0.05).Conclusion TG is able to treat ulcerative colitis through Nur77-Traf2-P62 signaling pathway.

Objective To investigate the effect and mechanism of Yiguan Decoction(YGJD)on the efficacy of M1 bone marrow-derived macrophages(M1-BMDMs)in the treatment of rats with liver cirrhosis induced by 2-AAF/CCl4.Methods BMDMs were isolated and induced into M1-BMDMs by lipopolysaccharide.A total of 50 male Wistar rats were randomly divided into normal group with 5 rats and model group with 45 rats.The rats for modeling were given subcutaneous injection of 50%CCl4 twice a week.Since week 7,the rats for modeling were randomly divided into model group(M group),YGJD group,M1-BMDM group,M1-BMDM+YGJD group,and sorafenib(SORA)group,and they were given subcutaneous injection of 30%CCl4 to maintain the progression of liver cirrhosis and intragastric administration of 2-AAF.CCR2 inhibitors were added to the drinking water,and each group was given the corresponding intervention.Related samples were collected at week 9.The rats were observed in terms of serum liver function parameters,liver pathology,hydroxyproline(Hyp)content in liver tissue,hepatic stellate cell activation,hepatic fibrosis and inflammation factors,and the expression levels of molecules associated with the Wnt signaling pathway.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the M group,the M1-BMDM+YGJD group had significant reductions in the serum levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin(TBil)(all P<0.05)and a significant increase in the content of albumin(Alb)(P<0.05),and compared with the M1-BMDM group,the M1-BMDM+YGJD group had a significant reduction in the serum level of TBil(P<0.05)and a significant increase in the serum level of Alb(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in the expression levels of CD68 and TNF-α(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in Hyp content and Sirius red positive area(P<0.05).As for the non-canonical Wnt signaling pathway molecules,compared with the M1-BMDM group,the M1-BMDM+YGJD group had significantly lower mRNA and protein expression levels of Wnt5a(P<0.05)and mRNA expression level of Fzd2(P<0.05),as well as significant reductions in the mRNA expression levels of Wnt4,Wnt5b,and Fzd3(P<0.05),while there were no significant changes in the mRNA expression levels of the canonical Wnt signaling pathway molecules β-catenin,LRP5,LRP6,Fzd5,and TCF.Conclusion YGJD can enhance the therapeutic effect of M1-BMDMs on rats with liver cirrhosis induced by 2-AAF/CCl4,possibly by inhibiting the non-canonical Wnt5a/Fzd2 signaling pathway,which provides new ideas for the synergistic effect of traditional Chinese medicine on M1-BMDMs in the treatment of liver cirrhosis.