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Low-molecular-weight heparin and preeclampsia—does the sword cut both ways?Three case reports and review of literature

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World Journal of Clinical Cases 2024年第9期12卷 1634-1643页

作者： Dan Shan Tao Li Xi Tan Ya-Yi Hu Department of Obstetrics and Gynecology West China Second University HospitalSichuan UniversityChengdu 610000Sichuan ProvinceChina key laboratory of birth defects and related diseases of women and children Sichuan UniversityMinistry of EducationChengdu 610000SichuanChina

BACKGROUND Low-molecular-weight heparins(LMWH)are the most commonly used anticoagulants during pregnancy.It is considered to be the drug of choice due to its safety in not crossing placenta.Considering the beneficial effect in the improvement of microcirculation,prophylactic application of LMWH in patients with preeclampsia became a trend.However,the bleeding risk related with LMWH in preeclampsia patients has seldomly been evaluated.This current study aimed to identify the potential risks regarding LMWH application in patients with preeclampsia.CASE SUMMARY Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during pregnancy.All the cases experienced catastrophic hemorrhagic events.After reviewing the twenty-one meta-analyses,the bleeding risk related with LMWH seems ignorable.Only one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving LMWH.Other studies reported minor bleeding risks,none of these were serious enough to stop LMWH treatment.Possibilities of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be ignored.Intensive management of blood pressure even after delivery and homeostasis suture in surgery are crucial.CONCLUSION Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.

关键词： Pregnancy Preeclampsia Low-molecular-weight heparin Hemorrhage Case report

Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer

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Genes & diseases 2024年第3期11卷 400-416页

作者： Meijia Yu Yiming Wu Qingfang Li Weiqi Hong Yang Yang Xiaoyi Hu Yanfei Yang Tianqi Lu Xia Zhao Xiawei Wei laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Gynecology and Obstetrics Development and Related Disease of Women and Children Key Laboratory of Sichuan ProvinceKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenMinistry of EducationWest China Second HospitalSichuan UniversityChengduSichuan 610041China Department of Obstetrics and Gynecology The First Affiliated HospitalArmy Medical UniversityChongqing 400038China

Ovarian cancer is the tumor with the highest mortality among gynecological malig-nancies.Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the microenvironment.Colony-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid tumors.There are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor microenvironment.Here,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian cancer.We found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor prognosis.Treatment by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in vivo.Blockade of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.

关键词： CSF-1R Ovariancancer Paclitaxel PLX3397 Targeted therapy Tumor-associated macrophages

Clinical characteristics and treatment of splenic infarction in children with systemic lupus erythematosus

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World Journal of Pediatrics 2024年第5期20卷 525-531页

作者： Yan Li Yu-Rong Piao Tong-Xin Han Hua-Wei Mao Department of Immunology Ministry of Education Key Laboratory of Major Diseases in ChildrenBeijing Key Laboratory for Genetics of Birth DefectsNational Center for Children’s HealthBeijing Children’s HospitalCapital Medical UniversityNo.56 Nan Li Shi LuBeijing100045China

Splenic infarction(SI)is a rare clinical phenomenon that occurs when the blood supply to the spleen is interrupted,resulting in tissue ischemia and necrosis[1].There are many causes of SI;in adult patients,cardioembolism,hematological malignancy,and infectious disease are the most common[2].Rheumatic diseases,especially systemic lupus erythematosus(SLE)and granulomatosis with polyangitis,can also lead to SI[3];however,only a few cases have been reported.There are currently no statistically meaningful data on the etiology of SI in children.Although most patients with SI can recover after conservative treatment,a small number of patients develop complications,such as splenic abscess,splenic rupture,splenic hemorrhage,and hemoperitoneum,and may even undergo splenectomy in severe cases.

关键词： erythematosus lupus treatment

Pathological BBB Crossing Melanin-Like Nanoparticles as Metal-Ion Chelators and Neuroinflammation Regulators against Alzheimer’s Disease

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Research 2024年第1期6卷 687-706页

作者： Qianqian Huang Chaoqing Jiang Xue Xia Yufan Wang Chenxing Yan Xiaorong Wang Ting Lei Xiaotong Yang Wenqin Yang Guo Cheng Huile Gao key laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041P.R.China laboratory of Molecular Translational Medicine Center for Translational MedicineKey Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationDepartment of PediatricsWest China Second University HospitalSichuan UniversityChengdu 610041P.R.China

Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intricate pathogenesis causes severe impairment of neurons,which,in turn,exacerbates Aβaggregation and facilitates AD progression.Herein,multifunctional melanin-like metal ion chelators and neuroinflammation regulators(named PDA@K)were constructed for targeted treatment of AD.In this platform,intrinsically bioactive material polydopamine nanoparticles(PDA)with potent metal ion chelating and ROS scavenging effects were decorated with the KLVFF peptide,endowing the system with the capacity of enhanced pathological blood–brain barrier(BBB)crossing and lesion site accumulation via Aβhitchhiking.In vitro and in vivo experiment revealed that PDA@K had high affinity toward Aβand were able to hitch a ride on Aβto achieve increased pathological BBB crossing.The engineered PDA@K effectively mitigated Aβaggregate and alleviated neuroinflammation.

关键词： oxidative aggregation chelating

Normal sperm head morphometric reference valuesin fertile Asian males

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Asian Journal of Andrology 2024年第3期26卷 315-320页

作者： Ye-Lin Jia Ying-Bi Wu Lin Yu Yan Zheng Ting-Ting Yang Yan-Yun Wang Bin Zhou Lin Zhang Fu-Ping Li laboratory of Andrology West China Second University Hospital Human Sperm BankChengdu 610000China laboratory of Molecular Translational Medicine Center for Translational MedicineChengdu 610061China key laboratory of birth defects and related diseases of women and children(Sichuan University) Ministry of EducationChengdu 610061China NHC key laboratory of Chronobiology West China Second University HospitalSichuan UniversityChengdu 610000China

Sperm head morphology is crucial for male factor infertility diagnosis and assessment of male reproductive potential.Severalcriteria are available to analyze sperm head morphology,but they are limited by poor methodology comparability and populationapplicability.This study aimed to explore comprehensive and new normal morphometric reference values for spermatozoa heads infertile Asian males.An automated sperm morphology analysis system captured 23152 stained spermatozoa from confirmed fertilemales.Of these samples,1856 sperm head images were annotated by three experienced laboratory technicians as“normal”.Weemployed 14 novel morphometric features to describe sperm head size(head length,head width,length/width ratio,and girth),shape(ellipse intersection over union,girth intersection over union,short-axis symmetry,and long-axis symmetry),area(head,acrosome,postacrosomal areas,and acrosome area ratio),and degrees of acrosome and nuclear uniformity.This straight-forwardmethod for the morphometric analysis of sperm by accurate visual measurements is clinically applicable.The measured parameterspresent valuable information to establish morphometric reference intervals for normal sperm heads in fertile Asian males.Thepresented detailed measurement data will be valuable for interlaboratory comparisons and technician training.In vitro fertilizationand andrology laboratory technicians can use these parameters to perform objective morphology evaluation when assessing malefertilization potential.

关键词： fertile Asian males head morphometric reference value normal spermatozoa

Cluster analysis reveals a homogeneous subgroup of PCOS women with metabolic disturbance associated with adverse reproductive outcomes

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Chinese Medical Journal 2024年第5期137卷 604-612页

作者： Hanxiao Chen Rujun Zeng Xun Zeng Lang Qin The Reproductive Medical Center Department of Obstetrics and GynecologyWest China Second University HospitalSichuan UniversityChengduSichuan 610041China key laboratory of birth defects and related of women and children of Ministry of Education West China Second University HospitalSichuan UniversityChengduSichuan 610041China

Background:Polycystic ovarian syndrome(PCOS)is a heterogeneous and complex reproductive endocrinological disease that could lead to infertility.There were many attempts to classify PCOS but it remains unclear whether there is a specific subgroup of PCOS that is associated with the best or worst reproductive outcomes of assisted reproductive techniques(ART).Methods:Infertile PCOS patients who underwent their first cycle of in vitro fertilization(IVF)in West China Second University Hospital,Sichuan University from January 2019 to December 2021 were included.Basic clinical and laboratory information of each individual were extracted.Unsupervised cluster analysis was performed.Controlled ovarian stimulation parameters and reproductive outcomes were collected and compared between the different clusters of PCOS.Results:Our analysis clustered women with PCOS into"reproductive","metabolic",and"balanced"clusters based on nine traits.Reproductive group was characterized by high levels of testosterone(T),sex hormone-binding globulin(SHBG),follicular stimulation hormone(FSH),luteinizing hormone(LH),and anti-Müllerian hormone(AMH).Metabolic group was characterized by high levels of body mass index(BMI),fasting insulin,and fasting glucose.Balanced group was characterized by low levels of the aforementioned reproductive and metabolic parameters,except for SHBG.Compared with PCOS patients in reproductive and balanced clusters,those in metabolic cluster had lower rates of good quality day 3 embryo and blastocyst formation.Moreover,PCOS patients in the reproductive cluster had greater fresh embryo transfer(ET)cancelation rate and clinical pregnancy rate after fresh ET than metabolic cluster(odds ratio[OR]=3.37,95%confidence interval[CI]:1.77-6.44,and OR=6.19,95%CI:1.58-24.24,respectively).And compared with PCOS of metabolic cluster,PCOS of balanced cluster also had higher chance for fresh ET cancelation(OR=2.83,95%CI:1.26-6.35).Conclusion:Our study suggested that PCOS patients in metabolic cluster may be associated with adverse re

关键词： Polycystic ovarian syndrome Assisted reproductive techniques Clustering analysis Metabolic disturbance Clinical pregnancy

Exosomal let-7a-5p derived from human umbilical cord mesenchymal stem cells alleviates coxsackievirus B3-induced cardiomyocyte ferroptosis via the SMAD2/ZFP36 signal axis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第5期25卷 422-437页

作者： Xin LI Yanan HU Yueting WU Zuocheng YANG Yang LIU Hanmin LIU Department of Pediatric Pulmonology and Immunology West China Second University HospitalSichuan UniversityChengdu 610041China key laboratory of birth defects and related diseases of women and children(Sichuan University) Ministry of EducationChengdu 610041China NHC key laboratory of Chronobiology(Sichuan University) Chengdu 610041China The Joint laboratory for Lung Development and related diseases of West China Second University Hospital Sichuan University and School of Life Sciences of Fudan UniversityWest China Institute of Women and Children's HealthWest China Second University HospitalSichuan UniversityChengdu 610041China Sichuan birth defects Clinical Research Center West China Second University HospitalSichuan UniversityChengdu 610041China Department of Pediatrics the Third Xiangya HospitalCentral South UniversityChangsha 410013China

Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and teenagers.However,its pathogenesis is still unclear,and effective treatments are lacking.This study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular model.Cardiac echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac function.In CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione) peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 stimulation.Let-7a-5p was enriched in hucMSCs-exo,and the inhibitory ffect of hucMSCs-exoa-ie-pmimo on CVB3-induced ferroptosis was higher than that of hucMSCs-exommie N(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)decreased.Let-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 protein.Silencing SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related indicators.Meanwhile,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe^(2+)increased.In conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 expression.Exo-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.

关键词： Exosome Let-7a-5p Mothers against decapentaplegic homolog 2(SMAD2) Coxsackievirus B3(CVB3) Ferroptosis

Association of interpregnancy interval and risk of adverse pregnancy outcomes in woman by different previous gestational ages

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Chinese Medical Journal 2024年第1期137卷 87-96页

作者： Peiran Chen Yi Mu Zheng Liu Yanping Wang Xiaohong Li Li Dai Qi Li Mingrong Li Yanxia Xie Juan Liang Jun Zhu National Office for Maternal and Child Health Surveillance of China West China Second University HospitalSichuan UniversityChengduSichuan 610066China Department of Obstetrics West China Second University HospitalSichuan UniversityChengduSichuan 610066China key laboratory of birth defects and related diseases of women and children Ministry of EducationSichuan UniversityChengduSichuan 610066China

Background:With an increasing proportion of multiparas,proper interpregnancy intervals(IPIs)are urgently needed.However,the association between IPIs and adverse perinatal outcomes has always been debated.This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages.Methods:We used individual data from China’s National Maternal Near Miss Surveillance System between 2014 and 2019.Multivariable Poisson models with restricted cubic splines were used.Each adverse outcome was analyzed separately in the overall model and stratified models.The stratified models included different categories of fertility policy periods(2014-2015,2016-2017,and 2018-2019)and infant gestational age in previous pregnancy(birth(OR[95%CI]:1.63[1.55,1.71]for vaginal delivery[VD]and 1.10[1.03,1.19]for cesarean section[CS]),low Apgar scores and small for gestational age(SGA),and a decreased risk of diabetes mellitus in pregnancy,preeclampsia or eclampsia,and gestational hypertension.A long IPI(≥60 months)was associated with an increased risk of preterm birth(OR[95%CI]:1.18[1.11,1.26]for VD and 1.39[1.32,1.47]for CS),placenta previa,postpartum hemorrhage,diabetes mellitus in pregnancy,preeclampsia or eclampsia,and gestational hypertension.Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes.The estimated risk of preterm birth,low Apgar scores,SGA,diabetes mellitus in pregnancy,and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss.Conclusion:For pregnant women with shorter or longer IPIs,more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

关键词： Interpregnancy interval Fertility policy Gestational age Preterm birth Gestational hypertension Diabetes mellitus in pregnancy

Precise genome-editing in human diseases:mechanisms,strategies and applications

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1065-1085页

作者： Yanjiang Zheng Yifei Li Kaiyu Zhou Tiange Li Nathan J.VanDusen Yimin Hua key laboratory of birth defects and related diseases of women and children of MOE Department of PediatricsWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Department of Cardiovascular Surgery West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pediatrics Herman B Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisIN 46202USA

Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and substitutions.The continuous enhancement of these tools has led to a revolution in the life sciences,which promises to deliver novel therapies for genetic disease.Precise genome-editing can be traced back to the 1950s with the discovery of DNA’s doublehelix and,after 70 years of development,has evolved from crude in vitro applications to a wide range of sophisticated capabilities,including in vivo applications.Nonetheless,precise genome-editing faces constraints such as modest efficiency,delivery challenges,and off-target effects.In this review,we explore precise genome-editing,with a focus on introduction of the landmark events in its history,various platforms,delivery systems,and applications.First,we discuss the landmark events in the history of precise genome-editing.Second,we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human genome.Third,we introduce the current delivery systems used to deploy precise genome-editing components through DNA,RNA,and RNPs.Finally,we summarize the current applications of precise genome-editing in labeling endogenous genes,screening genetic variants,molecular recording,generating disease models,and gene therapy,including ex vivo therapy and in vivo therapy,and discuss potential future advances.

关键词： precise generating editing