Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Objective : To investigate the effect of long non-coding RNA LUCAT1 (lncRNA LUCAT1) on the biological behavior of MIA PaCa-2 in human pancreatic cancer cells , and to explore the potential role of LUCAT1 in the malignant progression of pancreatic cancer. Methods : The mutation and expression of LUCAT1 in pancreatic cancer were analyzed by GEPIA , the expression levels of LUCAT1 in human pancreatic ductal cells HPNE and hu- man pancreatic cancer cells were detected by q-PCR , and the expression and distribution of LUCAT1 in human pancreatic cancer tissues were detected by FISH . CCK-8 assay and Transwell assay were used to detect the effects of LUCAT1 on the proliferation , apoptosis , drug resistance , and migration of MIA PaCa-2 cells . Gene ensemble enrichment analysis was performed to compare the related signaling pathways involved in LUCAT1 , and Western blot assay was used to verify the protein expression level . Results : The results of GEPIA analysis showed that the expression level of LUCAT1 in human pancreatic cancer tissues was up-regulated , and the expression of LUCAT1 in human pancreatic cancer cells was significantly higher ( P < 0. 05 ) . Knockdown and overexpression of LUCAT1 could affect the proliferation , apoptosis , gemcitabine resistance , migration and invasion of pancreatic cancer cells , and the differences were statistically significant (P < 0. 05) . In addition , LUCAT1 affected p-Akt expression levels in pancreatic cancer and was inhibited after treatment with Akt inhibitor MK-2206 . Conclusion LUCAT1 regulates the malignant progression of MIA PaCa-2 in pancreatic cancer cells through the PI3K-Akt signaling pathway.

A patient with osteomyelitis who developed a rash after previous treatment with vancomycin was admitted to the hospital due to a recurrence of osteomyelitis.After admission,the orthopedic doctor intended to perform a"calcium sulfate vancomycin implantation surgery"on him.Clinical pharmacist identified the patient's previous rash reaction as red man syndrome(RMS)rather than genuine drug allergy.At the same time,in response to the clinical doubt of whether patients with previous RMS can undergo"calcium sulfate vancomycin implantation surgery",clinical pharmacists reviewed and analyzed the literature,and suggested that the surgery can continue under close monitoring.The patient did not experience RMS or allergic reactions after surgery,and the condition improved.In this paper,the clinical pharmacists started with the identification of RMS and rapid allergic reactions,reviewed the literature on the local use of vancomycin and the risk of RMS,and provide suggestions for subsequent treatment,and also provide references for clinical safe drug use and treatment of similar diseases.

Objective:To construct an index system for including ideological and political education elements and cases in the Health Assessment course, and to provide a reference for the evaluation of ideological and political teaching of the Health Assessment course.Methods:By using literature analysis, the nominal group method, and the Delphi expert consultation method, we determined indicators for ideological and political elements and case inclusion criteria for the undergraduate nursing course Health Assessment. The analytic hierarchy method was applied to quantify the items and determine the final weights of the indicators at each level.Results:The response rates of two rounds of expert consultation were both 100%. The authority coefficient of the experts was 0.880. For the second-round consultation on the system of ideological and political elements, the coefficient of variation was 0.078, and the Kendall's coefficient of concordance was 0.334. For the second-round consultation on the inclusion criteria for ideological and political cases, the coefficient of variation was 0.075, and the Kendall's coefficient of concordance was 0.312. Finally, we determined 6 first-level indicators and 30 second-level indicators for the ideological and political elements of the Health Assessment course, and 9 indicators for the inclusion of ideological and political cases for the Health Assessment course.Conclusions:The established index system for the ideological and political elements and cases of the Health Assessment course for nursing undergraduates is reasonable, scientific, and reliable, which can provide a reference for subsequent construction of the ideological and political teaching system for the Health Assessment course.

Purpose To analyze the gene subtypes and characteristics of human papilloma virus(HPV)infection among women attending outpatient and physical examination centers at our hospital.Methods We utilized Polymerase Chain Reaction(PCR)combined with reverse dot hybridization to detect 28 HPV gene subtypes.Results HPV infection rate among the women was 24.15％.The five most prevalent high-risk(HR)and low-risk(LR)HPV gene subtypes were HPV 52,16,53,58,39,and HPV 61,81,54,42,44,respectively.Single and double infections accounted for 68.97％and 20.72％,with no signifi-cant difference found in the combination of multiple infection types.When stratified by age,the highest HPV infection rate was found among the group aged ≤25 years,followed by the group aged ≥66 years and then the group aged 56-65 years.This pattern of HPV infection rates across age groups revealed an approximate U-shaped curve.Conclusion The majority of female HPV in-fections in Huadu district are single infections,primarily affecting young and middle-aged women.HPV gene subtypes exhibit the characteristics of population or region-specific distribution.The overall infection rate of HPV is 24.15％,with the most common types being 52,16,and 53.The three peak age groups for HPV infection ranges are ≤25 years,56-65 years,and ≥66 years.

Objective To investigate the dynamic change of nutritional risk and malnutrition before op-eration and chemotherapy beginning and at the chemotherapy end in the patients with gastrointestinal malig-nant tumors.Methods The patients receiving gastrointestinal malignant tumors operation in Zhejiang Provin-cial Tongde Hospital from January 2017 to December 2022 were selected as the study subjects.The anthropo-metric measurement data,Karnofsky functional status(KPS)score change were recorded before operation and chemotherapy beginning and at the chemotherapeutic end.The nutritional risk screening 2002(NRS2002)and Global Leadership Initiative Consensus on Diagnostic Criteria for Malnutrition(GLIM)were adopted to evalu-ate the nutritional status of the patients.Results A total of 239 patients were included,there were 221 cases(92.47％)of nutritional risk before the chemotherapeutic beginning,206 cases(86.19％)of GLIM standard malnutrition,71 cases(29.70％)of moderate malnutrition and 135 cases(56.49％)of severe malnutrition in GLIM classification evaluation.At the chemotherapeutic end,there were 182 cases(76.15％)of nutritional risk,181 cases(73.75％)of GLIM standard malnutrition,52 cases(21.76％)of moderate malnutrition and 129 cases(53.97％)of severe malnutrition in GLIM classification evaluation.The screening rate of nutritional risk and malnutrition at the chemotherapeutic end were significant higher than those before operation and the difference was statistically significant(P＜0.001).The levels of total protein,albumin,leukocyte count,neu-trophile granulocyte,hemoglobin and platelet count at the chemotherapeutic end were decreased compared with those before operation with statistical difference(P＜0.05).Conclusion The nutritional risk and malnu-trition incidence rate in the patients with gastrointestinal malignant tumors are high,moreover which at the chemotherapeutic end are higher than those before operation.

Objective To explore the value of preoperative nutritional risk screening and malnutrition on postoperative prediction in the patients with gastrointestinal tract malignant tumor.Methods A total of 428 patients with gastrointestinal tract malignant tumors receiving elective operation in the gastrointestinal surgery department and proctology department of this hospital from January 2017 to October 2023 were se-lected as the study subjects.The patients were classified by postoperative complications Clavien-Dindo classifi-cation and divided into non-complication group(n=288)and complication group(n=140)according to whether or not having complications.The Nutritional Risk Screening 2002(NRS2002)and Global Leadership Initiative on Malnutrition(GLIM)were adopted to evaluate the nutritional status of the patients.The postop-erative complications during the hospitalization period,hospitalization duration,hospitalization expenses,30 d and 60 d non-planed readmission were recorded.Results Compared with the non-complication group,the age,complications ≥2,NRS2002 score ≥3 points,severe malnutrition proportion,urea level,hospitalization dura-tion,hospitalization expenses,ICU admission ratio,30 d and 60 d non-planned readmission rate in the compli-cation group were higher,BMI,KPS score,albumin,total calcium,low density lipoprotein,RBC count,Hb and HCT level were lower,and the differences were statistically significant(P＜0.05).The logistic regression a-nalysis results showed that after adjusting the relevant confounding factors,nutritional risk in NRS2002 screening,malnutrition in GLIM assessment and moderate to severe malnutrition in GLIM classification were all risk factors for postoperative complications occurrence in the patients with gastrointestinal malignant tumors(P＜0.05).None of them were the risk factors for unplanned readmission on 30,60 d(P＞0.05).The receiver operating characteristic(ROC)curve analysis results showed that the arae under the curve(AUC)of NRS2002 was greater than that of GLIM(0.733 vs.0.704),and the difference was statistically significant(P＜0.05).There was no statistically significant difference in the comparison among the GLIM grading(0.710)in NRS2002 and GLIM(P＞0.05).Conclusion The predictive ability of NRS2002 for postoperative complications in the patients with gastrointestinal tract maliganat tumors is slightly superior to that of GLIM.

Objective To determine whether four-and-a-half LIM-only protein 2(FHL2)can affect macrophage foa-ming by regulating nuclear factor kappa-B(NF-κB)signaling pathway.Methods FHL2 over-expression plasmids and siRNA of FHL2 were constructed and transfected into human monocyte/macrophages cell line THP-1.Western blot was used to detect the expression of FHL2.The cells were stimulated with oxidized low density lipoprotein(ox-LDL)and the expression of IL-6,IL-1β,TNF-α and other cytokines were detected by ELISA.Oil red O staining was used to detect the degree of cell foaming.The protein expression of NF-κB signaling pathway was detected by Western blot.Results The expression of FHL2 increased after transfected with FHL2 over-expression plasmids while decreased in si-FLH2 transfected cells.FHL2 down-regulated secretion of inflammatory cytokines.Down-regulation of FHL2 allevi-ated THP-1 macrophage foaming.The down-regulation of FHL2 inhibited activation of NF-κB signaling pathway,while the over-expression FHL2 showed an opposite trend.Conclusions FHL2 down-regulation inhibits the activation of NF-κB signaling pathway,reduces the secretion of inflammatory cytokines and alleviates foaming of macrophages.