Antibody-drug conjugates （ADCs） are a novel class of anti-tumor agents composed of a targeted monoclonal antibody， a cytotoxic drug， and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer （TNBC） is characterized by high aggressiveness， elevated risks of recurrence and metastasis， and poor prognosis， largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 （such as trastuzumab deruxtecan）， trophoblast cell surface antigen 2 （such as sacituzumab govitecan and datopotamab deruxtecan）， zinc transporter LIV-1 （such as ladiratuzumab vedotin）， HER-3 （such as patritumab deruxtecan）， epidermal growth factor receptor （such as AVID100）， and glycoprotein non-metastatic melanoma protein B （such as glembatumumab vedotin） have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities， ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.

Forensic microbiology,a pivotal discipline within forensic science,focuses on microorganisms as the primary subject of study and applies life science technologies to analyze microbial evidence in criminal and civil investigations.Tissue source inference plays a crucial role in forensic investigations,facilitating case assessment and crime scene reconstruction.The application of microbiome analysis in tissue source inference benefits from the tissue specificity and spatiotemporal stability of human microbial communities.This article provides a systematic review of recent advances in tissue source inference based on microbiome analysis,covering technological development,research trends,and practical applications.Finally,the challenges confronted in practice in forensic microbiology and the future prospects for its development are summarized.

Objective:To analyze the association between physical activity levels and all-cause mortality risk in patients with diabetic kidney disease (DKD) and to investigate the mediating effect of inflammation.Methods:Based on National Health and Nutrition Examination Survey of America data matched with the National Death Index of America, a prospective cohort was formed, including 59 482 participants from six cycles between 2007 and 2018. After applying inclusion and exclusion criteria, 2 214 DKD patients were selected for the study. Cox proportional hazard regression models were used to analyze the impact of physical activity levels on all-cause mortality risk. The mediating effect of inflammatory markers in the association between physical activity and all-cause mortality risk was explored.Results:There were statistically significant differences in survival curves among different physical activity level groups ( P<0.001). As physical activity levels increased, the risk of mortality decreased. Patients in the high physical activity group had a lower mortality risk compared to those in the inactive group ( HR=0.64, 95% CI: 0.53-0.78), with a statistically significant difference ( P<0.001). Patients with higher physical activity levels had lower levels of inflammation (white blood cell, neutrophil, and C-reactive protein) ( P<0.001). White blood cell, neutrophil, C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR), and the systemic inflammation index (SII) were independent risk factors for mortality in DKD patients ( HR>1.00), with higher risk effects observed for the combined indicator lgNLR ( HR=2.06, 95% CI: 1.76-2.41) and lgSII ( HR=1.44, 95% CI: 1.26-1.64). Mediation analysis showed that physical activity had an indirect effect on all-cause mortality risk through neutrophil, with an effect size of -0.033 (95% CI: -0.052 - -0.002), which was statistically significant ( P<0.05), with a mediation effect proportion of 9.75%. Conclusion:Physical activity is a protective factor against all-cause mortality risk in DKD patients, partly through reducing neutrophil levels.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective: To explore the correlation and lag effects of environmental factors on pediatric respiratory disease visits at hospital, so as to provide scientific basis for disease prediction and optimizing clinical diagnosis and treatment. Methods: Data from 503 889 pediatric respiratory disease outpatient and emergency visits a central hospital in Minhang District of Shanghai between 2017 and 2019, along with concurrent meteorological data were collected. A distributed lag non-linear models (DLNM) was constructed to explore the specific relationship between pediatric respiratory disease consultations and various environmental factors and to quantify the cumulative lag effects of environmental factors on respiratory disease consultations. Results: Among the environmental factors, temperature, fine particulate matter (PM 2.5 ), inhalable particulate matter (PM 10 ), nitrogen dioxide (NO 2), and sulfur dioxide (SO 2) were associated with pediatric respiratory disease visits. After adjusting for temperature, PM 2.5 and PM 10 concentrations did not show significant immediate or lag effects. The relative risk (RR) of pediatric respiratory disease visits increased with rising NO 2 concentrations. When NO 2 concentration ≥55 μg/m 3, significant immediate and lagged effects (lag 3, 5, and 7 days) were observed. The RR values were 1.05, 1.13, 1.17, and 1.21( P <0.05). The RR values showed an inverted “U” shaped relationship with SO 2 concentrations. When SO 2 concentration ≥5 μg/m 3, significant lagged effects (lag 3, 5, and 7 days) were observed. The RR values were 1.03 , 1.03, and 1.04 ( P <0.05). Conclusion High concentrations of NO 2 and SO 2 increase the risk of pediatric respiratory disease visits, with observable lag effects.

Objective:To analyze the association between physical activity levels and all-cause mortality risk in patients with diabetic kidney disease (DKD) and to investigate the mediating effect of inflammation.Methods:Based on National Health and Nutrition Examination Survey of America data matched with the National Death Index of America, a prospective cohort was formed, including 59 482 participants from six cycles between 2007 and 2018. After applying inclusion and exclusion criteria, 2 214 DKD patients were selected for the study. Cox proportional hazard regression models were used to analyze the impact of physical activity levels on all-cause mortality risk. The mediating effect of inflammatory markers in the association between physical activity and all-cause mortality risk was explored.Results:There were statistically significant differences in survival curves among different physical activity level groups ( P<0.001). As physical activity levels increased, the risk of mortality decreased. Patients in the high physical activity group had a lower mortality risk compared to those in the inactive group ( HR=0.64, 95% CI: 0.53-0.78), with a statistically significant difference ( P<0.001). Patients with higher physical activity levels had lower levels of inflammation (white blood cell, neutrophil, and C-reactive protein) ( P<0.001). White blood cell, neutrophil, C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR), and the systemic inflammation index (SII) were independent risk factors for mortality in DKD patients ( HR>1.00), with higher risk effects observed for the combined indicator lgNLR ( HR=2.06, 95% CI: 1.76-2.41) and lgSII ( HR=1.44, 95% CI: 1.26-1.64). Mediation analysis showed that physical activity had an indirect effect on all-cause mortality risk through neutrophil, with an effect size of -0.033 (95% CI: -0.052 - -0.002), which was statistically significant ( P<0.05), with a mediation effect proportion of 9.75%. Conclusion:Physical activity is a protective factor against all-cause mortality risk in DKD patients, partly through reducing neutrophil levels.

Objective:To analyze the relationship between Cardiovascular Health(CVH)and Pelvic Inflamma-tory Disease(PID)using data from the National Health and Nutrition Examination Surveys(NHANES).Meth-ods:Participants from the NHANES database were extracted based on the inclusion of PID,LE8 scores,and mul-tiple potential confounding factors,excluding those with missing variables.Multivariate Logistic regression analysis was conducted using R to assess the relationship between the CVH and the risk of PID.Additionally,subgroup a-nalysis and interaction tests were performed for age,race,poverty,marital status,education,BMI,menstrual regu-larity,and pregnancy history.Results:A total of 3934 female participants were included,with an average age of 39.95±11.42 years.Multivariable Logistic regression analysis showed that after adjusting for age,race,BMI,edu-cation level,marital status,household income,menstrual cycle,and pregnancy history,the risk of PID gradually decreased with an increase in CVH assessment metric LE8 scores(OR 0.98,95％CI 0.97-0.99,P＜0.001).Stratified analysis indicated significant interactions between age,race,and marital status in the association be-tween CVH and PID(interaction P＜0.05 for all),while household income level,education level,BMI,menstrual regularity,and pregnancy history showed no significant interactions with the CVH and PID association(P＞0.05).Conclusions:There is a significant negative relationship between CVH and PID in adult women in the United states,suggesting that better cardiovascular health may help reduce the risk of PID.

Objective:To analyze the relationship between Cardiovascular Health(CVH)and Pelvic Inflamma-tory Disease(PID)using data from the National Health and Nutrition Examination Surveys(NHANES).Meth-ods:Participants from the NHANES database were extracted based on the inclusion of PID,LE8 scores,and mul-tiple potential confounding factors,excluding those with missing variables.Multivariate Logistic regression analysis was conducted using R to assess the relationship between the CVH and the risk of PID.Additionally,subgroup a-nalysis and interaction tests were performed for age,race,poverty,marital status,education,BMI,menstrual regu-larity,and pregnancy history.Results:A total of 3934 female participants were included,with an average age of 39.95±11.42 years.Multivariable Logistic regression analysis showed that after adjusting for age,race,BMI,edu-cation level,marital status,household income,menstrual cycle,and pregnancy history,the risk of PID gradually decreased with an increase in CVH assessment metric LE8 scores(OR 0.98,95％CI 0.97-0.99,P＜0.001).Stratified analysis indicated significant interactions between age,race,and marital status in the association be-tween CVH and PID(interaction P＜0.05 for all),while household income level,education level,BMI,menstrual regularity,and pregnancy history showed no significant interactions with the CVH and PID association(P＞0.05).Conclusions:There is a significant negative relationship between CVH and PID in adult women in the United states,suggesting that better cardiovascular health may help reduce the risk of PID.

Objective:To investigate the association between the Doppler variables of the ophthalmic artery with the severity of preeclampsia(PE).Methods:Systematic literature was searched between January 1995 and March 2023 in PubMed,Web of Science,Embase,and the Cochrane Library.Studies comparing ophthalmic artery Doppler variables,including peak systolic velocity(PSV),end-diastolic velocity(EDV),resistive index(Rl),pulsa-tility index(PI),and peak ratio(PR,the ratio of the flow velocity of the second peak to that of the initial peak)in patients with PE,severe preeclampsia(sPE),and healthy pregnant women were included.The random-effects model was adopted as the method of pooled analysis,and the I2value was used to assess heterogeneity.The pooled standardized mean difference(SMD)with 95％confidence interval(CI)was used to estimate the associa-tion between ophthalmic artery Doppler variables and PE patient's characteristics.Results:Eight retrospective studies were eventually included in this Meta-analysis.Our pooled results suggested that compared with PE ca-ses,sPE patients had lower PI levels(SMD-0.56,95％CI-0.92～-0.20,P=0.000),higher EDV levels(SMD 0.47,95％CI 0.12～0.83,P=0.028)and higher PR levels(SMD0.96,95％CI 0.13～1.78,P=0.023).Howev-er,there was no significant difference between PE and sPE patients about the PSV and RI(P=0.361,P=0.626).Conclusions:This review demonstrates that ophthalmic artery Doppler variables(PI,EDV and PR)could be useful for predicting PE and PE development(especially in identifying sPE),which in turn may help the practitioner in the management of these complicated cases and in taking early necessary precautions.

Objective To investigate the correlation of triacylglycerol glucose(TyG)index,monocyte to high-density lipoprotein cholesterol ratio(MHR)with coronary artery disease and myocardial ischemia degree in coronary heart disease(CHD),and to analyze the two Predictive value of coronary artery disease and myocardial ischemia degree.Methods CHD patients from the 920th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force from January 2019 to January 2022 were selected as the study group(n = 150),and healthy physical examination subjects from the same period were selected as the control group(n = 75).The TyG index and MHR of the two groups were compared and analyzed.The extent of coronary artery disease was evaluated based on the Gensini score,and the TyG index and MHR of patients with different coronary lesions and myocardial ischemia were compared,and their correlation with Gensini score and myocardial ischemia was analyzed.The predictive value of TyG index,MHR,and the combined detection of both for coronary lesions and myocardial ischemia was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC).Results The TyG index and MHR of the study group were(4.12±0.35)and(0.26±0.08)×109,respectively,which were higher than those of the control group(4.94±0.55)and(0.43±0.12)×109,and the TyG index and MHR of severe coronary artery disease>moderate coronary artery disease>mild coronary artery disease,acute myocardial infarction TyG index,MHR>unstable angina pectoris>stable angina pectoris(P<0.05);TyG index and MHR were positively correlated with Gensini score(r = 0.621,0.635,P<0.05),and positively correlated with the severity of myocardial ischemia(r = 0.617,0.642,P<0.05).The AUC of TyG index and MHR for the joint identification of mild coronary artery disease and moderate coronary artery disease was 0.917,which was greater than the AUCs of 0.749 and 0.832 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of mild to moderate coronary artery disease and severe coronary artery disease was 0.935,which was greater than the AUCs of 0.770 and 0.767 for the two conditions individually(P<0.05).The AUC of TyG index and MHR for the joint identification of stable angina pectoris and unstable angina pectoris was 0.922,which was greater than the AUCs of 0.812 and 0.824 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of stable angina pectoris,unstable angina pectoris,and acute myocardial infarction was 0.913,which was greater than the AUCs of 0.708 and 0.714 for the two conditions individually(P<0.05).Conclusions TyG index and MHR are positively correlated with Gensini score and myocardial ischemia degree.The combined detection of the two has a higher application value in the evaluation of coronary artery disease and myocardial ischemia degree.