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LRP1B suppresses HCC progression through the NCSTN/PI3K/AKT signaling axis and affects doxorubicin resistance

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Genes & Diseases 2023年第5期10卷 2082-2096页

作者： Xiangyu Zhai Zhijia Xia Gang Du Xinlu Zhang Tong Xia Delin Ma Xiaosong Li Bin Jin Hao Zhang Department of Hepatobiliary Surgery The Second Hospital of Shandong UniversityJinanShandong 250033China Department of General Visceraland Transplant SurgeryLudwig-Maximilians-University MunichMunich 81377Germany Department of reproductive Medicine Central Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250013China Organ Transplant Department Qilu Hospital of Shandong UniversityJinanShandong 250012China clinical Molecular Medicine Testing center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

Accumulating evidence supports the association of somatic mutations with tumor occurrence and development.We aimed to identify somatic mutations with important implications in hepatocellular carcinoma(HCC)and explore their possible mechanisms.The gene mutation profiles of HCC patients were assessed,and the tumor mutation burden was calculated.Gene mutations closely associated with tumor mutation burden and patient overall survival were identified.In vivo and in vitro experiments were performed to verify the effects of putative genes on proliferation,invasion,drug resistance,and other malignant biological behaviors of tumor cells.Fourteen genes with a high mutation frequency were identified.The mutation status of 12 of these genes was closely related to the mutation burden.Among these 12 genes,LRP1B mutation was closely associated with patient prognosis.Nine genes were associated with immune cell infiltration.The results of in vivo and in vitro experiments showed that the knockdown of LRP1B promotes tumor cell proliferation and migration and enhances the resistance of tumor cells to liposomal doxorubicin.LRP1B could directly bind to NCSTN and affect its protein expression level,thereby regulating the PI3K/AKT pathway.Our mutational analysis revealed complex and orchestrated liposomal alterations linked to doxorubicin resistance that may also render cancers less susceptible to immunotherapy and also provides new treatment alternatives.

关键词： Doxorubicin Hepatocellular carcinoma LRP1B PI3K/AKT pathway Tumor mutation burden

A homozygous frameshift mutation in ADAD2 causes male infertility with spermatogenic impairments

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Journal of Genetics and Genomics 2023年第4期50卷 284-288页

作者： Shixiong Tian Ziqi Wang Liting Liu Yiling Zhou Yue Lv Dongdong Tang Jiaxiong Wang Jing Jiang Huan Wu Shuyan Tang Guanxiong Wang Hao Geng Fangbiao Tao Hongbin Liu Xiaojin He Feng Zhang Jinsong Li Li Jin Tao Huang Chunyu Liu Yunxia Cao Institute of Metabolism and Integrative Biology State Key Laboratory of Genetic EngineeringHuman Phenome InstituteObstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key Laboratory of Female reproductive Endocrine Related Diseases Institute of Reproduction and DevelopmentFudan UniversityShanghai 200011China center for reproductive Medicine Shandong UniversityJinanShandong 250012China Key Laboratory of reproductive Endocrinology of Ministry of Education Shandong UniversityJinanShandong 250012China reproductive Medicine center Department of Obstetrics and GynecologyThe First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China NHC Key Laboratory of Study on Abnormal Gametes and reproductive Tract(Anhui Medical University) HefeiAnhui 230032China shandong Key Laboratory of reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong250012China Key Laboratory of Population health Across Life Cycle(Anhui Medical University) Ministry of Education of the People's Republic of ChinaHefeiAnhui 230032China center for Reproduction and Genetics State Key Laboratory of Reproductive MedicineThe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalSuzhouJiangsu 215002China Genome Tagging Project(GTP)center Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China reproductive Medicine center Department of Obstetrics and GynecologyThe First Affliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China

Male infertility is a complex reproductive disorder that impedes a huge number of couples from having children naturally in the world(Agarwal et al.,2021).As an important pathogenic factor of male infertility,spermatogenic impairments are mainly characterized by impaired male gamete production,reduced sperm quality,or function(Tournaye et al.,2017).Spermatogenesis is a delicate and complex biological process that requires the collaboration of a large number of proteins performing different biological functions(Liu et al.,2021).

关键词： impaired impairment infertility

Outcomes of 13 ICSI-PGD cycles with ejaculated spermatozoa in patients with Klinefelter syndrome

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Asian Journal of Andrology 2016年第3期18卷 498-499页

作者： Tian-Xiang Ni Jun-Hao Yan Bo Wang Yue-Ting Zhu Hong-Chang Li Hong-Qiang Xie Wen-Jie Jiang Zi-Jiang Chen center for reproductive Medicine Shandong Provincial Hospital Affiliatedto Shandong University Shandong Provincial Key Laboratory of Reproductive Medicine Jinan 250021 China National research center for Assisted reproductive Technology and reproductive Genetics Jinan 250021 China The Key Laboratory for reproductive Endocrinology of Ministry of Education Jinan 250021 China Department of Anesthesiology Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021 China.

Dear Editor, Klinefelter syndrome （KS） is the most frequent genetic cause of infertility in men. Paternity can be achieved through intracytoplasmic sperm injection （ICSI） with spermatozoa recovered from ejaculated... 详细信息

关键词： INTRACYTOPLASMIC INJECTION TESTICULAR SPERMATOZOA BIRTH

Trends in point-of-care ultrasound protocols in the emergency department and intensive care unit:a review

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Emergency and Critical Care Medicine 2023年第2期3卷 64-69页

作者： Xinhui Fan Yuan Bian Guoying Wang Weikang Liu Luyao Gao Yuhui Pan Shengchuan Cao Qiuhuan Yuan Shujian Wei Feng Xu Yuguo Chen Department of Emergency and Chest Pain center Shandong Provincial Clinical Research Center for Emergency and Critical Care MedicineInstitute of Emergency and Critical Care Medicine of Shandong UniversityKey Laboratory of Emergency and Critical Care Medicine of Shandong ProvinceKey Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceQilu Hospital of Shandong UniversityJinanChina.

Together with the development of the focused assessment with sonography for trauma protocol for ultrasound in trauma patients,point-of-care ultrasound is widely used in the field of emergency and critical care medicine.researchers have established several classic operating protocols for different diseases,such as acute respiratory failure,shock,and cardiac arrest,in the emergency department and intensive care unit.With further development in the portability and popularity of ultrasonic equipment,it is expected to be used as a new type of technology for physical examination,including inspection,palpation,percussion,auscultation,and insonation,which will improve the clinical medicine practice in the future.

关键词： Auscultation and insonation Inspection Palpation Percussion Point-of-care ultrasound Protocol Seven-point and nineplane protocol

Decidualization and Related Pregnancy Complications

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Maternal-Fetal Medicine 2022年第1期4卷 24-35页

作者： Jing Tong Shijian Lv Jieqiong Yang Hongwanyu Li Weiya Li Cong Zhang center for reproductive Medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200135China Shanghai Key Laboratory for Assisted Reproduction and reproductive Genetics Shanghai200135China shandong provincial Key Laboratory of Animal Resistance Biology College of Life SciencesShandong Normal UniversityJinanShandong 250014China

Decidualization is the differentiation of endometrial stromal cells into secretory decidual stromal cells.Human decidualization involves some amount of signaling molecules and pathways as well as genetic reprogramming,which is driven by the postovulatory rise in progesterone levels and local cyclic adenosine monophosphate production.Decidualization extends from the primary decidual zone to the secondary decidual zone,and then exits through apoptosis.Evidences support that decidual fibroblasts function as the pool of decidual stromal cells during pregnancy.Decidualization undergoes an acute inflammatory phase,an anti-inflammatory secretory phase to the final recession phase.The decidualization of the inner layer of endometrium,termed decidua,is the most critical determinant of pregnancy success,which can promote placenta formation,modulate immune tolerance,foster resistance to oxidative stress,sense embryo quality,and control labor.Failure to adequate decidualization in terms of hormones,biochemistry,and immunology leads to adverse pregnancy outcomes,including diseases such as preeclampsia,miscarriage,premature labor,repeated implantation failures,and some age-related decline in reproductive capacity.The development of animal models and in vitro culture systems combined with emerging technologies provides a powerful system to explore the mechanism of decidualization.However,decidualization is a dynamic,multi-step process,and translating of current research progress into disease predictions and interventions for pregnancy complications remains to be achieved.The study of periodic regeneration and spontaneous decidualization of the endometrium will be beneficial to the diagnosis and treatment of pregnancy diseases.

关键词： Decidua Decidualization Decidual stromal cells Endometrial stromal cells Pregnancy complications

Integrating polygenic and clinical risks to improve stroke risk stratification in prospective Chinese cohorts

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Science China(Life Sciences) 2023年第7期66卷 1626-1635页

作者： Qingmei Cui Fangchao Liu Jianxin Li Xiaoge Niu Zhongying Liu Chong Shen Dongsheng Hu Keyong Huang Shufeng Chen Jie Cao Xiaoqing Liu Ling Yu Fanghong Lu Xianping Wu Liancheng Zhao Jianfeng Huang Ying Li Zhibin Hu Hongbing Shen Dongfeng Gu Xiangfeng Lu Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100037China Key Laboratory of Cardiovascular Epidemiology Chinese Academy of Medical SciencesBeijing100037China Department of Nephrology Henan Provincial Key Laboratory of Kidney Disease and ImmunologyHenan Provincial Clinical Research Center for Kidney DiseaseHenan Provincial People’s Hospital and People’s Hospital of Zhengzhou UniversityZhengzhou450053China Department of Epidemiology and Biostatistics Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing211166China Department of Epidemiology and health Statistics College of Public HealthZhengzhou UniversityZhengzhou450001China Department of Prevention Medicine Shenzhen University School of MedicineShenzhen518060China Division of Epidemiology Guangdong Provincial People’s Hospital and Cardiovascular InstituteGuangzhou510080China Department of Cardiology Fujian Provincial People’s HospitalFuzhou350014China Cardio-Cerebrovascular Control and research center Institute of Basic MedicineShandong Academy of Medical SciencesJinan250062China Sichuan center for Disease Control and Prevention Chengdu610041China research Units of Cohort Study on Cardiovascular Diseases and Cancers Chinese Academy of Medical SciencesBeijing100730China School of Medicine Southern University of Science and TechnologyShenzhen518055China

The utility of the polygenic risk score(PRS)to identify individuals at higher risk of stroke beyond clinical risk remains unclear,and we clarified this using Chinese population-based prospective cohorts.Cox proportional hazards models were used to estimate the 10-year risk,and Fine and Gray’s models were used for hazard ratios(HRs),their 95%confidence intervals(CIs),and the lifetime risk according to PRS and clinical risk categories.A total of 41,006 individuals aged 30–75 years with a mean follow-up of 9.0 years were included.Comparing the top versus bottom 5%of the PRS,the HR was 3.01(95%CI 2.03–4.45)in the total population,and similar findings were observed within clinical risk strata.Marked gradients in the 10-year and lifetime risk across PRS categories were also found within clinical risk categories.Notably,among individuals with intermediate clinical risk,the 10-year risk for those in the top 5%of the PRS(7.3%,95%CI 7.1%–7.5%)reached the threshold of high clinical risk(≥7.0%)for initiating preventive treatment,and this effect of the PRS on refining risk stratification was evident for ischemic stroke.Even among those in the top 10%and 20%of the PRS,the 10-year risk would also exceed this level when aged≥50 and≥60 years,respectively.Overall,the combination of the PRS with the clinical risk score improved the risk stratification within clinical risk strata and distinguished actual high-risk individuals with intermediate clinical risk.

关键词： stroke polygenic risk score clinical risk score utility stratification

Mutational analysis of the GATA4 gene in Chinese men with nonobstructive azoospermia

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Asian Journal of Andrology 2021年第2期23卷 205-210页

作者： Xu Zhang Tai-Jian Zhang Wen Liu Yun-Na Ning Yue-Hong Bian Yong-Zhi Cao Hong-Bin Liu Jin-Long Ma Hao-Bo Zhang center for reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250012China National research Centre for Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250012China shandong provincial Key Laboratory of Animal Cells and Developmental Biology School of Life SciencesShandong UniversityQingdao 266237China

As a crucial transcription factor for spermatogenesis,GATA-binding protein 4(GATA4)plays important roles in the functioning of Sertoli and Leydig cells.Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility.However,whether GATA4 is associated with human azoospermia has not been reported.Herein,we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia(NOA).We identified a missense mutation(c.191G>A,p.G64E),nine single-nucleotide polymorphisms(SNPs),and one rare variant(c.^(*)84C>T)in the 3′untranslated region(UTR).Functional studies demonstrated that the p.G64E mutation did not affect transactivation ability of GATA4 for spermatogenesis-related genes(claudin-11 and steroidogenic acute regulatory protein,Star),and the 3′UTR rare variant c.^(*)84C>T did not generate microRNA-binding sites to repress GATA4 expression.To our knowledge,this is the first report to investigate the association between GATA4 and azoospermia;our results indicate that mutations in GATA4 may not be pathogenic for NOA in Chinese men.

关键词： biological function GATA-binding protein 4(GATA4)mutation nonobstructive azoospermia

SUPER Score Contributes to Warning and Management in Early-Stage COVID-19

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Infectious Medicine

Infectious Medicine 2023年第4期2卷 308-314页

作者： Yuan Bian Qi Han Yue Zheng Yu Yao Xinhui Fan Ruijuan Lv Jiaojiao Pang Feng Xu Yuguo Chen Department of Emergency Medicine Qilu Hospital of Shandong UniversityJinan 250012China Chest Pain center Shandong Provincial Clinical Research Center for Emergency and Critical Care MedicineInstitute of Emergency and Critical Care Medicine of Shandong UniversityQilu Hospital of Shandong UniversityJinan 250012China Key Laboratory of Emergency and Critical Care Medicine of shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinan 250012China The Key Laboratory of Cardiovascular Remodeling and Function research Chinese Ministry of EducationChinese Ministry of Health and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu Hospital of Shandong UniversityJinan 250012China

Background:Some COVID-19 patients deteriorate to severe cases with relatively higher case-fatality rates,which increases the medical burden.This necessitates identification of patients at risk of severe disease.Early assessment plays a crucial role in identifying patients at risk of severe disease.This study is to assess the effectiveness of SUPER score as a predictor of severe COVID-19 cases.Methods:We consecutively enrolled COVID-19 patients admitted to a comprehensive medical center in Wuhan,China,and recorded clinical characteristics and laboratory indexes.The SUPER score was calculated using pa-rameters including oxygen saturation,urine volume,pulse,emotional state,and respiratory rate.In addition,the area under the receiver operating characteristic curve(AUC),specificity,and sensitivity of the SUPER score for the diagnosis of severe COVID-19 were calculated and compared with the National Early Warning Score 2(NEWS2).Results:The SUPER score at admission,with a threshold of 4,exhibited good predictive performance for early identification of severe COVID-19 cases,yielding an AUC of 0.985(95%confidence interval[CI]0.897-1.000),sensitivity of 1.00(95%CI 0.715-1.000),and specificity of 0.92(95%CI 0.775-0.982),similar to NEWS2(AUC 0.984;95%CI 0.895-1.000,sensitivity 0.91;95%CI 0.587-0.998,specificity 0.97;95%CI 0.858-0.999).Com-pared with patients with a SUPER scorehealth resources.

关键词： COVID-19 Early warning NEWS2 SUPER score

Unsatisfactory Glucose Management and Adverse Pregnancy Outcomes of Gestational Diabetes Mellitus in the Real World of clinical Practice： A Retrospective Study

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Chinese Medical Journal 2018年第9期131卷 1079-1085页

作者： Ru Feng Lu Liu Yuan-Yuan Zhang Zhong-Shang Yuan Ling Gao Chang-Ting Zuo Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong University Jinan Shandong 250021 China shandong clinical Medical center of Endocrinology and Metabolism Jinan Shandong 250021 China Institute of Endocrinology and Metabolism Shandong Academy of Clinical Medicine Jinan Shandong 250021 China Department of Obstetrics Shandong Provincial Hospital Affiliated to Shandong University Jinan Shandong 250021 China Department of Biostatistics School of Public Health Shandong University Jinan Shandong 250012 China Scientific center Shandong Provincial Hospital Affiliated to Shandong University Jinan Shandong 250021 China

Background：Facing the increasing prevalence of gestational diabetes mellitus （GDM）,this study aimed to evaluate the management of GDM and its association with adverse pregnancy outcomes.Methods：The data of 996 inpatients with GDM who terminated pregnancies in our hospital from January 2011 to December 2015 were collected.Treatments during pregnancy and the last hospital admission before delivery were analyzed.Pregnancy outcomes of the GDM patients were compared with 996 nondiabetic subjects matched by delivery year and gestational age.The association between fasting plasma glucose （FPG） and adverse pregnancy outcomes was examined by logistic regression analyses.Results：The average prevalence of GDM over the 5 years was 4.4％（1330/30,191）.Within the GDM patients,42.8％（426/996） received dietary intervention,whereas 19.1％（190/996） received insulin treatment.Adverse outcomes were more likely to occur in patients with unsatisfactory control of blood glucose such as respiratory distress syndrome （RDS,x2 =13.373,P ＜ 0.01）.Elevated FPG was identified as an independent risk factor for premature birth （odds ratio [OR] =1.460,P ＜ 0.001）,neonatal care unit admission （OR =1.284,P ＜ 0.001）,RDS （OR=1.322,P =0.001）,and stillbirth （OR =1.427,P ＜ 0.001）.Conclusions：Management of GDM in the real world of clinical practice was unsatisfactory,which might have contributed to adverse pregnancy outcomes.

关键词： Blood Glucose Disease Management Gestational Diabetes Mellitus Pregnancy Outcome Risk Factors