1.Research progress on antibody-drug conjugates in the treatment of triple-negative breast cancer
Danna LIU ; Shuangshuang SONG ; Lu CHEN ; Yongqiang SUN ; Bo SUN ; Hanli ZHOU ; Xiaoli ZHAO ; Tiandong KONG
China Pharmacy 2026;37(1):124-129
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.
2.Correlation between environmental factors and pediatric respiratory disease visits in a central hospital of Shanghai
ZHOU Shuangshuang, CAI Yizhou, MIAO Xueqin, ZHANG Lili, ZHOU Yibin, HE Dandan, LIU Jie, HU Yanqi
Chinese Journal of School Health 2025;46(5):708-711
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.
3.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
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.
4.Advances in the Application of Forensic Microbiome Analysis in Tissue Source Inference
Hewen YAO ; Chaoran SUN ; Shuangshuang WANG ; Yuxiang ZHOU ; Zhirui ZHANG ; Feng SONG ; Haibo LUO
Journal of Sichuan University (Medical Sciences) 2025;56(5):1419-1426
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.
5.The Association between Ophthalmic Artery Doppler Variables and the Severi-ty of Pre-eclampsia:a Meta-analysis
Li DAI ; Xiaohong WEI ; Lingyun LIAO ; Yangxue YIN ; Qin XU ; Shuangshuang XIE ; Rong ZHOU
Journal of Practical Obstetrics and Gynecology 2024;40(2):153-158
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.
6.Correlation Between TyG Index,MHR and Coronary Lesions,Myocardial Ischemia in Patients with Coronary Heart Disease,and the Value of Combined Detection
Shuangshuang XU ; Wei ZHAO ; Lei JIANG ; Huajiang LIU ; Fang WANG ; Zhisheng TAN ; Likun ZHOU
Journal of Kunming Medical University 2024;45(3):65-71
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.
7.Perioperative care of a patient implanted left ventricular assist device combined with cryoablation
Si PENG ; Xia ZHANG ; Lin ZHOU ; Shuangshuang LIU ; Xinmin ZHOU ; Jianming LI
Chinese Journal of Nursing 2024;59(22):2785-2789
To summarize the nursing experience of a patient with cardiac resynchronization therapy defibrillator(CRT-D)implantation who was about to deplete battery due to repeated discharge after implantation and underwent left ventricular assist device implantation combined with cryoablation.Key points of care were as follows.To begin with,we actively managed arrhythmias and electric storm.Secondly,we carried refined capacity management to avoid water and sodium retention.Thirdly,we formulated personalized anticoagulation programs to reduce the risk of bleeding and thrombosis.Then,the pump line infection should be prevented as early as possible.At the whole stage,we provided psychological counseling to improve emotional state.After discharge,regular follow-up was carried out through online and offline method to ensure quality of life in the long term.After careful treatment and nursing care,23 days after surgery,the patient was discharged smoothly,and good follow-up after discharge.
8.Research progress on the role of remnant lipoprotein and inflammation in atherosclerotic cardiovascular disease
Die YU ; Jihua ZHOU ; Shuangshuang CHEN ; Zhanke WANG
International Journal of Laboratory Medicine 2024;45(24):3039-3044
Remnant lipoprotein cholesterol(RLP-C)are composed of very low-density lipoprotein 3 cho-lesterol(VLDL3-C)and intermediate density lipoprotein cholesterol(IDL-C),which are the remnants produced by the hydrolysis of triglyceride-rich lipoproteins(TRLs).RLP-C levels are significantly related to the occur-rence of atherosclerotic cardiovascular disease(ASCVD)and are the remaining risk factors for ASCVD other than low-density lipoprotein cholesterol(LDL-C).Subintimal accumulation of atherogenic lipoprotein particles causes chronic inflammatory responses,including innate immune responses and adaptive immune responses.Unlike LDL-C,RLP-C is more likely to remain under the arterial endothelium and is directly phagocytosed by macrophages without oxidative modification,leading to the formation of foam cells and inflammatory reaction in the arterial wall endothelium,thereby forming atherosclerotic plaques.This review summarizes the concept of RLP-C,the relationship and quantitative detection method of RLP-C and ASCVD,and the mechanism of in-flammatory in ASCVD caused by RLP-C.
9.Study on the intestinal absorption characteristics of saikosaponins
Yazhi WANG ; Qiyi WANG ; Wenzhong FENG ; Shuangshuang CHEN ; Xinguang SUN ; Lijuan ZHOU ; Yan ZHANG ; Jianyong ZHANG ; Cancan DUAN
China Pharmacy 2023;34(14):1681-1685
OBJECTIVE To explore the intestinal absorption characteristics of saikosaponins. METHODS Based on everted intestinal sac model, using accumulative absorption amount (Q) and absorption rate constant (Ka) as indexes, UHPLC-MS/MS technique as a method, the absorption of saikosaponin A, B2, C, D and F from total saponins of Bupleurum chinense (8 g/mL, by crude drug) in the duodenum, jejunum and ileum was detected. RESULTS The correlation coefficients (r) of the regression equations for the absorption of saikosaponins A, B2, C and F in the duodenum, jejunum and ileum were all higher than 0.95, while the r of saikosaponin D in the above intestinal segments was lower than 0.95; compared with the absorption of the same composition in the duodenum, the Q and Ka of saikosaponin A and C circulating in jejunum and ileum for 120 min, as well as the Q and Ka of saikosaponin F circulating in the ileum for 120 min were significantly decreased (P<0.05). CONCLUSIONS Saikosaponin A and the other 4 saikosaponins are all absorbed in the duodenum, jejunum and ileum; among them, saikosaponin A, B2, C and F are linearly absorbed, which conforms to the zero-order absorption characteristics, but saikosaponin D shows non- linear absorption.
10.Invasive mucinous adenocarcinoma of the lungs versus mixed invasive mucinous and non-mucinous adenocarcinoma:a clinicopathological analysis
Shuangshuang PENG ; Wei LI ; Zhaoya ZHOU ; Biao ZHANG ; Chaoshan WANG ; Xiaohong PU ; Wen YANG ; Jun YANG ; Hongyan WU ; Yao FU ; Jieyu CHEN ; Xiangshan FAN
Chinese Journal of Clinical and Experimental Pathology 2023;39(11):1328-1333
Purpose To investigate the clinicopathological characteristics,diagnosis,and differential diagnosis of invasive mucinous adenocarcinoma(IMA)and mixed invasive mucinous and non-mucinous adenocarcinoma(mIMA).Methods The clinical data were collected in 36 patients with primary IMA and 17 patients with mIMA,and the expression of TTF-1,CK7,CK20,SATB2,CDX2,EGFR,HNF4a,etc.was detected by immunohistochemical EnVision two-step method.The Sanger se-quencing and the FISH were used for KRAS mutation and NRG1 gene rearrangement detection.The clinicopathological character-istics were analyzed with review of relevant literature.Results There were 9 cases(25.0%)and 3(8.3%)cases of papillary and micropapillary structures in IMA,while 13 cases(76.5%)(P<0.001)and 9 cases(52.9%)(P=0.001)were present in mIMA.There were 5 cases(13.9%)of high nuclear grade of IMA and 10 cases(58.8%)of high nuclear grade of mIMA(P=0.002).TTF-1 had a positive rate of 37.5%in IMA,but 60.0%and 80.0%in the mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA(P=0.021),respectively.The positive rates of CK7,CK20,and CDX2 in IMA were 90.6%,21.9%,and 9.4%,and the positive rates in mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA were 100%,20%,20%and 100%,6.7%,6.7%,respectively and no SATB2 expression was found in all cases.There was no significant difference in the expres-sion of total EGFR and two EGFR mutation-specific antibodies(L858R,DEL19)between IMA and mIMA.There were 3 cases of mucinous adenocarcinoma with L858R positive in mIMA,and 2 of them were negative for non-mueinous adenocarcinoma.In another case,the non-mueinous adenocarcinoma component of mIMA expressed DEL19,but the mucinous adenocarcinoma component was not expressed.The positive rate of HNF4a in IMA was 72.0%(18/25),and those of HNF4a in mucinous adenocarcinoma and non-mucinous adenocarcinoma in mIMA were 41.7%(5/12)and 33.3%(4/12),respectively(P=0.048).KRAS gene sequencing was carried out in 19 cases of IMA,among which 9 cases(47.4%)had mutations,G12D and G12V were most commonly detected,and 4 cases of mIMA were sequenced,but none of them showed KRAS mutations.FISH detection showed that 2 cases(7.1%)IMAs had NRG1 translocation rearrangement.Conclusion Pulmonary mIMA is more aggressive than IMA.For example,mIMA has significantly more papillary structure,micropapillary structure,and high nu-clear grade cases than IMA.The differences in immunohisto-chemical expression and KRAS mutation between the two are sta-tistically significant.


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