Objective:To investigate the anti-leukemic effects and resistance mechanisms of venetoclax in acute myeloid leukemia (AML). Genomic, transcriptomic, and clinical data from AML patients who underwent venetoclax drug sensitivity testing were downloaded from the Beat AML database. Correlation analysis was performed between these data and venetoclax sensitivity outcomes. Differentially expressed genes (DEGs) associated with venetoclax sensitivity were identified from transcriptomic data and subsequently validated using GEO database transcriptomic results and in vitro experiments (including Western blot). Functional enrichment analyses (KEGG and GSEA), transcription factor enrichment analysis (KnockTF), and data from public databases were employed to further investigate key genes and pathways influencing drug sensitivity.Results:After filtering the Beat AML cohort, data from 52 patient samples with available in vitro venetoclax sensitivity results were included for analysis. Patients with FLT3 mutations exhibited greater sensitivity to venetoclax compared to those with FLT3 wild-type. Correlation analysis between clinical information and drug sensitivity data indicated that higher peripheral blood tumor burden was associated with increased sensitivity to venetoclax. Transcriptomic analysis and in vitro experiments confirmed that venetoclax inhibits the FLT3-related signaling pathway, including downregulation of FLT3 expression and reduced phosphorylation of its downstream targets AKT and STAT5. KEGG pathway and KnockTF transcription factor enrichment analyses indicated that venetoclax resistance was associated with increased transcriptional activity of FOXM1 and STAT3. Moreover, high expression of FOXM1 and STAT3 correlated with shorter overall survival in patients.Conclusion:Venetoclax can inhibit the activation of FLT3-related signaling pathways. The activation of STAT3 and FOXM1 transcription factors is a potential key mechanism contributing to venetoclax resistance in AML.

Hyperglycemia is a primary biological characteristic of diabetes.It is well known that three key indicators are commonly used in clinical practice to measure plasma glucose levels,such as 2-hour postload glucose(2hPG),fasting plasma glucose(FPG),and glycated hemoglobin(HbA1c).However,the association between these indicators and breast cancer incidence remains unclear.This paper systematically reviews the relationship between plasma glucose levels and breast cancer based on the above three indicators,to provide a reference for the formulation of effective plasma glucose management strategies for the primary prevention of breast cancer.

Objective To evaluate the application value of fascial platform versus commercial platform in transumbilical single-port laparoscopic transabdominal preperitoneal repair(TAPP)for inguinal hernia.Methods One hundred patients with inguinal hernia admitted between January and December 2024 were prospectively enrolled and randomly assigned to either the fascial platform group(n=50)or the commercial platform group(n=50)by using a random number table.The following parameters were compared between the two groups:platform establishment time,operative time,intraoperative blood loss,incision suture time,operative difficulty score,camera manipulation difficulty score,postoperative 24-hour Visual Analogue Scale(VAS)score of pain,postoperative hospital stay,total hospitalization cost,comprehensive satisfaction score,and postoperative complications.Results The fascial platform group demonstrated significantly superior outcomes compared to the commercial platform group in platform establishment time[(3.4±1.0)min vs.(8.1±1.5)min,t=-18.389,P＜0.001],operative time[(67.5±7.9)min vs.(72.2±11.5)min,t=-2.380,P=0.019],intraoperative blood loss[(8.3±4.3)ml vs.(11.1±5.7)ml,t=-2.798,P=0.006],incision suture time[(7.0±1.4)min vs.(11.8±2.7)min,t=-11.212,P＜0.001],operative difficulty score(14.4±3.6 vs.23.1±4.1,t=-11.215,P＜0.001),camera manipulation difficulty score(11.4±2.6 vs.18.3±2.5,t=-13.370,P＜0.001),VAS score of postoperative 24-hour pain(2.4±1.0 vs.3.7±1.1,t=-6.139,P＜0.001),total hospitalization cost[(15.8±1.6)thousand yuan vs.(18.3±1.6)thousand yuan,t=-7.841,P＜0.001],and comprehensive satisfaction score(7.3±1.1 vs.6.3±1.0,t=5.271,P＜0.001).However,there were no statistically significant differences in postoperative hospital stay or postoperative complication between the two groups(P＞0.05).All the patients were followed up for 1-12 months postoperatively[(5.3±1.8)months vs.(5.7±2.0)months,t=-0.945,P=0.347],with no recurrence observed in either group.Conclusions Both fascial platform and commercial platform can be used for transumbilical single-port TAPP.The fascial platform offers advantages including shorter platform establishment time,reduced incision suture time,lower operative and camera manipulation difficulty,decreased cost,less postoperative pain,and higher patient satisfaction.

Objective The aim of this study is to systematically analyze the therapeutic mechanisms of Wuzi Yuye Decoction in diabetic oligoasthenozoospermia based on network pharmacology and animal experiments.Methods Active components and therapeutic targets of Wuzi Yuye Decoction were screened by integrating multiple databases,and their inter-section with diabetic oligoasthenozoospermia-related targets was obtained.Common targets were identified using the Venny platform,and protein-protein interaction(PPI)networks were constructed via the STRING database.And key targets were screened through topological analysis with Cytoscape.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed using the DAVID platform.A mouse model of diabetic oligoasthenozoospermia was established by high-fat diet combined with streptozotocin induction,followed by intervention with Wuzi Yuye Decoction.Body weight,testicular index,and sperm quality were assessed,while histopathological changes were evaluated by HE staining and transmission electron microscopy(TEM).In addition,ELISA,oxidative stress assays and Western blot were used to verify the changes in key pathway-related proteins.Results A total of 36 common targets were identified,including key nodes such as TNF,IL6 and IL1B.Enrichment analysis indicated that these targets were sig-nificantly involved in inflammatory responses,oxidative stress,autophagy-apoptosis regulation and reproduction-related pathways.Animal experiments confirmed that Wuzi Yuye Decoction markedly improved testicular mass and sperm motility in diabetic mice,reduced the levels of AGE,TNF-α,IL-6 and IL-1β in testicular tissues,alleviated oxidative stress damage,and restored autophagic flux and blood-testis barrier function by inhibiting the RAGE/NF-κB/mTOR signaling axis.Conclusion Wuzi Yuye Decoction improves the pathological progression of diabetic oligoasthenozoospermia by synergistically modulating multiple targets,including inflammation inhibition,antioxidant effects,autophagy regulation,and related pathways.

Human epidermal growth factor receptor 2 (HER2) is a key therapeutic target for breast cancer. With the wide application of anti-HER2 and HER2 antibody-drug conjugates such as trastuzumab, pertuzumab, trastuzumab emtansine, and trastuzumab deruxtecan, the survival of patients with advanced HER2-positive breast cancers have been significantly improved. However, the subsequent drug-induced interstitial lung disease (DILD) has gradually become an important complication affecting the therapeutic effect and safety. However, the clinical understanding of interstitial lung disease (ILD) caused by this type of drugs is still insufficient, the management lacks unified standards, and the molecular mechanism has not been fully clarified. This study, through two clinical cases of severe DILD, explores the pathogenesis, treatment strategies, risk factors and follow-up monitoring requirements of ILD caused by HER2-targeted drugs, providing a scientific basis for optimizing the clinical diagnosis and treatment plan.

Objective To investigate the relationship between the expression of serum microRNA(miR)-488 and miR-184 and the occurrence of preeclampsia in patients with gestational hypertension.Methods A to-tal of 128 patients with gestational hypertension admitted to a hospital from June 2022 to March 2023 were se-lected and divided into the simple gestational hypertension group(55 cases)and the combined with pre-eclampsia group(73 cases)according to whether they developed preeclampsia.Another 46 healthy pregnant women in the same period were selected as the control group.Real-time fluorescence quantitative polymerase chain reaction was used to detect miR-488 and miR-184 expression in each group,and multiple Logistic regres-sion was used to analyze the influencing factors of the occurrence of preeclampsia in patients with gestational hypertension.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of each influencing factor in the occurrence of preeclampsia in patients with gestational hypertension,and Pearson cor-relation was used to analyze the correlation between serum miR-488,miR-184 and placental growth factor.Re-sults Compared with the control group,the expressions of serum miR-488 and miR-184 were increased in the simple pregnancy hypertension group and the combined with preeclampsia group,and the differences were sta-tistically significant(P<0.05).Compared with mild preeclampsia group,serum miR-488 and miR-184 ex-pressions were increased in severe preeclampsia group,and the difference was statistically significant(P<0.05).There were significant differences in gravida and parity,systolic blood pressure,diastolic blood pres-sure,urinary protein quantity and placental growth factor levels between the combined with preeclampsia group and the simple pregnancy hypertension group(P<0.05).Multiple Logistic regression analysis showed that gravida and parity,systolic blood pressure,diastolic blood pressure,urinary protein quantity,miR-488 and miR-184 were risk factors for preeclampsia in patients with gestational hypertension(P<0.05),and placental growth factor was protective factor for preeclampsia in patients with gestational hypertension(P<0.05).ROC curve analysis showed that the prediction efficiency of miR-488+miR-184 was significantly better than that of serum miR-488(Z=2.530,P=0.011)and miR-184(Z=2.437,P=0.015)alone.Serum miR-488 and miR-184 were negatively correlated with placental growth factor(r=-4.361,-4.288,P<0.05).Con-clusion Serum miR-488 and miR-184 have predictive value in the occurrence of preeclampsia in patients with gestational hypertension.

Objective To explore the value of coronary CT angiography(CCTA)combined with serum in-terleukin(IL)-12p70,protein C(PC)and protein S(PS)in the diagnosis of coronary artery stenosis in coro-nary heart disease.Methods A total of 186 patients with coronary artery disease admitted to Wujin Hospital Affiliated to Jiangsu University(Changzhou Wujin People's Hospital)from April 2022 to April 2024 were prospectively selected as the study group,and the patients were grouped into mild,moderate and severe groups according to Gensimi scores,and another 186 patients with healthy physical examination during the same peri-od were selected as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect IL-12p70 levels.Automatic coagulation instrument was used to detect the levels of PC and PS.The influencing factors of severe coronary artery stenosis in coronary heart disease were analyzed by multivariate Logistic re-gression analysis.Receiver operating characteristic(ROC)curve was plotted to analyze the diagnostic value of CCTA parameters combined with serum IL-12p70,PC and PS in the diagnosis of severe coronary artery steno-sis in coronary heart disease.Results The serum level of IL-12p70 in the study group was greatly higher than that in the control group(P＜0.05),and the levels of PC and PS were greatly lower than those in the control group(P＜0.05).Minimum lumen diameter(MLD),minimum tubular neck area(MLA),serum PC,and PS levels were sequentially decreased in the mild,moderate,and severe groups(P＜0.05),and percentage area stenosis(％AS),percentage diameter stenosis(％DS),and serum IL-12p70 levels were sequentially increased(P＜0.05).According to multivariate Logistic regression analysis,IL-12p70 was a risk factor for severe coro-nary artery stenosis in coronary heart disease(P＜0.05),and PC and PS were protective factors(P＜0.05).According to the ROC curve,the area under the curve(AUC)of MLD,MLA,％AS,％DS,serum IL-12p70,PC,and PS for the diagnosis of severe coronary artery stenosis in coronary heart disease was 0.810,0.767,0.782,0.779,0.776,0.809,and 0.805.The AUC of combined diagnosis for severe coronary artery stenosis in coronary heart disease was 0.982,which was better than that of individual diagnosis(Zcombination vs.MLD=2.489,Zcombination vs.MLA=2.502,Zcombination vs.％AS=2.531,Zcombination vs.％DS=2.602,Zcombination vs.IL-12p70=2.643,Zcombination vs.PC=2.537,Zcombination vs.PS=2.546,all P＜0.05).Conclusion Serum IL-12p70 is greatly increased in patients with coronary heart disease,PC and PS levels are greatly reduced.CCTA combined with serum IL-12p70,PC,and PS could effectively improve their value in diagnosing degree of coronary artery stenosis in cor-onary heart disease.

Targeted protein degradation(TPD)technology is an emerging approach that utilizes intracellu-lar proteasome or lysosome systems to eliminate disease-causing proteins,providing novel strategies for dis-ease treatment.Compared with conventional therapies,TPD has advantages such as targeting"undruppable"proteins,overcoming drug resistance and high selectivity.Among them,proteolysis-targeting chimeras(PRO-TACs)and molecular gels are representative methods,which have achieved significant progress in E3 ligase expansion,linker design,and delivery systems,and are gradually entering clinical research.PROTACs and mo-lecular glues can not only target key oncoproteins and overcome resistance,but also modulate immune respon-ses for therapeutic purposes,demonstrating broad clinical application prospects.This article reviews the re-search progress of the two types of technologies and their current application status in cancer treatment,and discusses their potential and challenges in efficacy monitoring and individualized medication from the perspec-tive of laboratory medicine.

As people's attention to health continues to increase,the market demand for traditional Chinese medi-cine(TCM)is growing steadily.The quality and safety of Chinese medicinal materials have attracted unprecedent-ed social attention.In particular,the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society.The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM .This not only reflects China's high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision.Basis on this study,by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detec-tion standards in the Chinese Pharmacopoeia 2025 Edition,deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition.Moreo-ver,it interprets the future development directions of the detection of exogenous residues in TCM ,aiming to provide a reference for the formulation of TCM safety supervision policies.

As people’s attention to health continues to increase, the market demand for traditional Chinese medicine (TCM) is growing steadily. The quality and safety of Chinese medicinal materials have attracted unprecedented social attention. In particular, the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society. The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM. This not only reflects China’s high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision. Basis on this study, by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detection standards in the Chinese Pharmacopoeia 2025 Edition, deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition. Moreover, it interprets the future development directions of the detection of exogenous residues in TCM, aiming to provide a reference for the formulation of TCM safety supervision policies.