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Asian Journal of Andrology 2024年第2期26卷 183-188页

作者： Huan Jiang Chu-Jie Huang department of reproductive endocrinology Longgang District Maternity&Child Healthcare Hospital of Shenzhen City(Longgang Maternity and Child Institute of Shantou University Medical College)Shenzhen 518172China Institute of reproductive Immunology College of Life Science and TechnologyJinan UniversityGuangzhou 510632China

Aberrant sperm protamination is linked to sperm dysmorphology and nuclear chromatin condensation.Yet,its effects on sperm cytoplasmic maturation remain largely unexplored.The relationships of protamines,sperm morphology,DNA damage,and cytoplasmic remodeling were illustrated in this study to provide fresh perspectives on the mechanisms of male infertility.A total of 205 infertile males were allocated into 5 groups according to the percentage of spermatozoa exhibiting abnormal morphology within their samples.Sperm concentration,motility,abnormal sperm morphology,cytoplasmic droplets(CDs),and excess residual cytoplasm(ERC)were analyzed according to the World Health Organization manual(2010).Sperm nuclear vacuoles(NVs)were determined by propidium iodide(PI)staining.Sperm protamine expressions(P1 and P2)were detected by western blot.DNA damage was measured by acridine orange test(AOT)to calculate the proportion of sperm with single-strand DNA breaks(SSBs).Our data showed that sperm concentration and motility in infertile males significantly decreased with the severity of abnormal sperm morphology(both P<0.01).P1 level,P1/P2 ratio,and SSB rate increased with the severity of sperm dysmorphology,whilst the P2 level decreased(all P

关键词： abnormal sperm morphology excess residual cytoplasm male infertility protamines sperm DNA damage sperm nuclear vacuoles

Effect of SARS-CoV-2 infection on semenparameters in sperm bank volunteers with normalsperm concentration

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Asian Journal of Andrology 2024年第3期26卷 328-332页

作者： Li Wang Wen-Kai Han Xiao-Hui Song Qi-Lin Zhang An-Quan Guan Yuan Gao Jin-Long Ma Center for reproductive Medicine Shandong UniversityJinan 250001China State Key Laboratory of reproductive Medicine and Offspring Health ShandongUniversityJinan 250001China Key Laboratory of reproductive endocrinology of Ministry of Education Shandong UniversityJinan 250001China Shandong KeyLaboratory of reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250001China Shandong Provincial ClinicalResearch Center for reproductive Health Jinan 250001China Shandong Technology Innovation Center for reproductive Health Jinan 250001China NationalResearch Center for Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250001China Research Unit of Gametogenesis andHealth of ART-Offspring Chinese Academy of Medical Sciences(No.2021RU001)Jinan 250001China.

In this study,we aimed to assess the effect of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection on semenparameters.The study comprised 110 sperm volunteers who self-reported SARS-CoV-2 infection from the Human Sperm Bank ofthe Center for reproductive Medicine,Shandong University(Jinan,China).The volunteers had normal sperm concentration beforeinfection.Each volunteer provided semen samples before and after infection.We selected 90 days after infection as the cutoff point.Semen parameters within 90 days after infection of 109 volunteers(group A)were compared with semen parameters before infection.Moreover,semen parameters on or after 90 days after infection of 36 volunteers(group B)were compared with semen parameters beforeinfection.Furthermore,based on whether the volunteers had completed the three-dose SARS-CoV-2 vaccination booster,volunteersin group A and B were further divided into two subgroups separately.Semen parameters were compared before and after infection ineach subgroup.Our results showed that in this cohort population,the semen quality in volunteers with normal sperm concentrationsbefore infection decreased after SARS-CoV-2 infection within 90 days,while the semen quality returned to preinfection levels after 90days.The completion of a three-dose SARS-CoV-2 vaccination booster may exert a protective effect on semen quality after infection.

关键词： SARS-CoV-2 SARS-CoV-2 vaccination semen quality sperm donation sperm parameters

Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

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Neural Regeneration Research 2024年第4期19卷 923-928页

作者： Xiangjun Li Chunyan Li Hai Huang Dan Bai Jingyi Wang Anqi Chen Yu Gong Ying Leng department of Ophthalmology Affiliated Hospital of Beihua University department of endocrinology Affiliated Hospital of Beihua University

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.

关键词： choroidal thickness diabetic macular edema laser photocoagulation retinal ganglion cell-inner plexiform layer thickness retinal ganglion cells retinal nerve fiber layer thickness thickness of the macular area vascular endothelial growth factor visual acuity

Allelic reprogramming of chromatin states in human early embryos

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National Science Review 2024年第3期11卷 58-71页

作者： Shenli Yuan Lei Gao Wenrong Tao Jianhong Zhan Gang Lu Jingye Zhang Chuanxin Zhang Lizhi Yi Zhenbo Liu Zhenzhen Hou Min Dai Han Zhao Zi-Jiang Chen Jiang Liu Keliang Wu Center for reproductive Medicine Shandong University CAS Key Laboratory of Genome Sciences and Information Collaborative Innovation Center of Genetics and Development Beijing Institute of Genomicsand China National Center for BioinformationChinese Academy of Sciences University of Chinese Academy of Sciences CUHK-SDU Joint Laboratory on reproductive Genetics School of Biomedical Sciences the Chinese University of Hong Kong Key Laboratory of reproductive endocrinology of the Ministry of Education Shandong University Center for reproductive Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University CAS Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here,we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. Human embryos have a larger portion of genome with parentally specific epigenetic states than mouse embryos.The allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K27me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K27me3-dependent imprinting is not observed in human early embryos.Collectively, allele-specific epigenomic reprogramming is different in humans and mice.

关键词： human embryo epigenetics reprogramming DNA methylation H3K27me3 chromatin accessibility

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy:A Multicenter Double-Blind Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2024年第3期30卷 195-202页

作者： HUANG Hao-yue LIN Yu-ping WEI Hua FU Yu ZHOU Yue-hong FANG Zhao-hui QIU Xiao-tang WANG Mei LI Qing-bo LI Shan-shan WANG Shi-dong DAI Fang LIU Zhen-jie ZHAO Ling WEN Jian-xuan WU Li-yan ZENG Hui-yan ZHANG Jin-ming LU Qi-yun HE Liu SONG Wei SUN Lu LUO Lu-lu HE Jia-li XIE Wen-wen LIANG Qing-shun HUANG Yuan ZHU Sheng-ling LONG Jie-er GAO Zhi-juan WEN Ze-huai LI Chun-ji OUYANG Wen-wei LI Geng WU Ming-hui LI An-xiang HUANG Jin-zhu Sanjoy K Paul TANG Xian-yu FAN Guan-jie department of endocrinology Guangdong Provincial Hospital of Chinese MedicineGuangzhou510120China The Second Clinical College of Guangzhou University of Chinese Medicine Guangzhou510120China department of endocrinology The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou510120China Guangdong Provincial Academy of Chinese Medical Sciences Guangzhou510120China department of endocrinology The First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China department of endocrinology Liuyang Hospital of Chinese MedicineChangsha410000China department of endocrinology The First Affiliated Hospital of Anhui University of Chinese MedicineHefei230000China department of endocrinology Hainan Provincial Hospital of Traditional Chinese MedicineHaikou570100China department of endocrinology The Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang110000China department of Geriatric Luoyang No.1 Hospital of Traditional Chinese MedicineLuoyangHenan Province471000China department of endocrinology The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550000China department of endocrinology Beijing University of Chinese Medicine Affiliated Dongzhimen HospitalBeijing100000China department of endocrinology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550000China Melbourne EpiCentre The University of Melbourne and Melbourne HealthMelbourne3013Australia

Objective:To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction(TW)in treating patients with diabetic peripheral neuropathy(DPN).Methods:It is a multicenter double-blinded randomized controlled trial.Participants with DPN were recruited between November 18,2016 and May 30,2018 from 8 hospitals in China.All patients received basic treatments for glycemic management.Patients received foot baths with TW herbal granules either 66.9 g(intervention group)or 6.69 g(control group)for 30 min once a day for 2 weeks and followed by a 2-week rest,as a therapeutic course.If the Toronto Clinical Scoring System total score(TCSS-TS)6 points,the patients received a total of 3 therapeutic courses(for 12 weeks)and were followed up for 12 weeks.The primary outcome was change in TCSS-TS score at 12 and 24 weeks.Secondary outcomes included changes in bilateral motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV)of the median and common peroneal nerve.Safety was also assessed.Results:Totally 632 patients were enrolled,and 317 and 315 were randomized to the intervention and control groups,respectively.After the 12-week intervention,patients in both groups showed significant declines in TCSSTS scores,and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment(P0.05),and no serious adverse event was related with treatment.Conclusion:Treatment of TW foot baths was safe and significantly benefitted patients with DPN.A low dose of TW appeared to be more effective than a high dose.(Registry No.Chi CTR-IOR-16009331)

关键词： diabetic peripheral neuropathy herbal medicine foot baths Chinese medicine randomized controlled trial Tangbi Waixi Decoction

Identification of two compound heterozygous GNRHR mutations in two siblings with congenital hypogonadotropic hypogonadism

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Asian Journal of Andrology 2024年第1期26卷 120-122页

作者： Xiao-Bin Wang Ping Chen Xue-Er Yu Zu-Liang Yao Ting-Chao Guo Bo-Chen Pan Center for reproductive Medicine Department of Obstetrics and GynecologyShengjing Hospital of China Medical UniversityShenyang 110004China NuProbe Shanghai 200433China Urology Surgery of The Affiliated reproductive Hospital of China Medical University and Liaoning Key Laboratory of reproductive Health Liaoning Research Institute of Family Planning(The Affiliated Reproductive Hospital of China Medical University)Shenyang 110031China NHC Key Laboratory of reproductive Health and Medical Genetics China Medical UniversityShenyang 110122China

DearEditor,Congenital hypogonadotropic hypogonadism(CHH)is a rare genetic disease characterized by gonadotropin-releasing hormone(GnRH)deficiency or insufficiency and normal hypothalamic-pituitary structures,resulting in defective sexual maturation or/and infertility.!CHH presents as a variety of nonreproductive phenotypes,such as renal hypoplasia,dental hypoplasia,or oculomotor abnormalities.

关键词： pogon compound ism

Genetic lineage tracing identifies adaptive mechanisms of pancreatic islet β cells in various mouse models of diabetes with distinct age of initiation

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Science China(Life Sciences) 2024年第3期67卷 504-517页

作者： Qi Fu Yu Qian Hemin Jiang Yunqiang He Hao Dai Yang Chen Zhiqing Xia Yucheng Liang Yuncai Zhou Rui Gao Shuai Zheng Hui Lv Min Sun Kuanfeng Xu Tao Yang department of endocrinology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

During the pathogenesis of type 1 diabetes(T1D) and type 2 diabetes(T2D), pancreatic islets, especially the β cells, face significant challenges. These insulin-producing cells adopt a regeneration strategy to compensate for the shortage of insulin, but the exact mechanism needs to be defined. High-fat diet(HFD) and streptozotocin(STZ) treatment are well-established models to study islet damage in T2D and T1D respectively. Therefore, we applied these two diabetic mouse models, triggered at different ages, to pursue the cell fate transition of isletβ cells. Cre-LoxP systems were used to generate islet cell type-specific(α, β, or δ) green fluorescent protein(GFP)-labeled mice for genetic lineage tracing, thereinto β-cell GFP-labeled mice were tamoxifen induced. Single-cell RNA sequencing(scRNA-seq) was used to investigate the evolutionary trajectories and molecular mechanisms of the GFP-labeled β cells in STZ-treated mice. STZ-induced diabetes caused extensive dedifferentiation of β cells and some of which transdifferentiated into α or δ cells in both youth-and adulthood-initiated mice while this phenomenon was barely observed in HFD models. β cells in HFD mice were expanded via self-replication rather than via transdifferentiation from α or δ cells, in contrast, α or δ cells were induced to transdifferentiate into β cells in STZ-treated mice(both youthand adulthood-initiated). In addition to the re-dedifferentiation of β cells, it is also highly likely that these “α or δ” cells transdifferentiated from pre-existing β cells could also re-trans-differentiate into insulin-producing β cells and be beneficial to islet recovery. The analysis of ScRNA-seq revealed that several pathways including mitochondrial function, chromatin modification, and remodeling are crucial in the dynamic transition of β cells. Our findings shed light on how islet β cells overcome the deficit of insulin and the molecular mechanism of islet recovery in T1D and T2D pathogenesis.

关键词： islet regeneration lineage tracing high fat diet(HFD) streptozotocin(STZ)

Neferine inhibits the progression of diabetic nephropathy by modulating the miR-17-5p/nuclear factor E2-related factor 2 axis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 44-53页

作者： HUANG Hongmei YANG Maojun LI Ting WANG Dandan LI Ying TANG Xiaochi YUAN Lu GU Shi XU Yong department of endocrinology Chengdu Shuangliu District First People's Hospital(West China Airport of Sichuan University)Chengdu 610200China department of endocrinology Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

OBJECTIVE:To investigate the effect of Neferine(Nef)on diabetic nephropathy(DN)and to explore the mechanism of Nef in DN based on miRNA regulation theory.METHODS:A DN mouse model was constructed and treated with Nef.Serum creatinine(Crea),blood urea(UREA)and urinary albumin were measured in mice by kits,and renal histopathological changes and fibrosis were observed by hematoxylin-eosin staining and Masson staining.Renal tissue superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-Px)activities were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)signaling pathway-related proteins in kidney tissues.Quantitative reverse transcription-polymerase chain reaction(q RT-PCR)was used to detect the expression of miR-17-5p in kidney tissues.Subsequently,a DN in vitro model was constructed by high glucose culture of human mesangial cells(HMCs),cells were transfected with miR-17-5p mimic and/or treated with Nef,and we used q RTPCR to detect cellular miR-17 expression,flow cytometry to detect apoptosis,ELISAs to detect cellular SOD,MDA,and GSH-Px activities,Western blots to detect Nrf2/HO-1 signaling pathway-related protein expression,and dual luciferase reporter gene assays to verify the targeting relationship between Nrf2 and miR-17-5p.RESULTS:Administration of Nef significantly reduced the levels of blood glucose,Crea,and UREA and the expression of miR-17-5p,improved renal histopathology and fibrosis,significantly reduced MDA levels,elevated SOD and GSH-Px activities,and activated Nrf2 expression in kidney tissues from mice with DN.Nrf2 is a post-transcriptional target of miR-17-5p.In HMCs transfected with miR-17-5p mimics,the m RNA and protein levels of Nrf2 were significantly suppressed.Furthermore,miR-17-5p overexpression and Nef intervention resulted in a significant increase in high glucose-induced apoptosis and MDA levels in HMCs and a significant decrease in the protein expr

关键词： diabetic nephropathies neferine miR-17-5p NF-E2-related factor 2 oxidative stress

Cellular atlases of ovarian microenvironment alterations by diet and genetically-induced obesity

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Science China(Life Sciences) 2024年第1期67卷 51-66页

作者： Yonghui Jiang Xueying Gao Yue Liu Xueqi Yan Huangcong Shi Rusong Zhao Zi-Jiang Chen Fei Gao Han Zhao Shigang Zhao Center for reproductive Medicine Shandong UniversityJinan 250012China Research Unit of Gametogenesis and Health of ART-Offspring Chinese Academy of Medical Sciences(No.2021RU001)Jinan 250012China Key Laboratory of reproductive endocrinology of Ministry of Education Shandong UniversityJinan 250012China Shandong Key Laboratory of reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250012China Shandong Provincial Clinical Research Center for reproductive Health Jinan 250012China National Research Center of Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250012China The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215000China Center for reproductive medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Shanghai Key Laboratory for Assisted Reproduction and reproductive Genetics Shanghai 200127China State Key Laboratory of Stem Cell and reproductive Biology Institute of ZoologyChinese Academy of ScienceBeijing 100101China

Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive system.The ovary,as one of the primary regulators of female fertility,is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment(OME).Despite its importance,the effect of obesity on the entire ovary remains poorly documented.In this study,we performed ovary single-cell and nanoscale spatial RNA sequencing to investigate how the OME changed under different kinds of obesity,including high-fat diet(HFD)induced obesity and Leptin ablation induced obesity(OB).Our results demonstrate that OB,but not HFD,dramatically altered the proportion of ovarian granulosa cells,theca-interstitial cells,luteal cells,and endothelial cells.Furthermore,based on the spatial dynamics of follicular development,we defined four subpopulations of granulosa cell and found that obesity drastically disrupted the differentiation of mural granulosa cells from small to large antral follicles.Functionally,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular development.These differences can be explained by the differential expression pattern of the transcription factor Foxo1.Overall,our study provides a powerful and high-resolution resource for profiling obesity-induced OME and offers insights into the diverse effects of obesity on female reproductive disorders.

关键词： obesity ovarian microenvironment snRNA-seq Stereo-seq Foxo1

Targeting nuclear receptors for NASH/MASH:From bench to bedside

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Liver Research 2024年第1期8卷 34-45页

作者： Rohit A.Sinha department of endocrinology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia

The onset of metabolic dysfunction-associated steatohepatitis(MASH)or non-alcoholic steatohepatitis(NASH)represents a tipping point leading to liver injury and subsequent hepatic complications in the natural progression of what is now termed metabolic dysfunction-associated steatotic liver diseases(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD).With no pharmacological treat-ment currently available for MASH/NASH,the race is on to develop drugs targeting multiple facets of hepatic metabolism,inflammation,and pro-fibrotic events,which are major drivers of MASH.Nuclear receptors(NRs)regulate genomic transcription upon binding to lipophilic ligands and govern multiple aspects of liver metabolism and inflammation.Ligands of NRs may include hormones,lipids,bile acids,and synthetic ligands,which upon binding to NRs regulate the transcriptional activities of target genes.NR ligands are presently the most promising drug candidates expected to receive approval from the United States Food and Drug Administration as a pharmacological treatment for MASH.This review aims to cover the current understanding of NRs,including nuclear hormone receptors,non-steroid hormone receptors,circadian NRs,and orphan NRs,which are currently undergoing clinical trials for MASH treatment,along with NRs that have shown promising results in preclinical studies.

关键词： Nuclear receptor(NR) Metabolic dysfunction-associated steatohepatitis(MASH) Metabolic dysfunction-associated steatotic liver disease(MASLD) Transcription factor Liver Drug