Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway

Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma,causing endocrine disorder,reproductive dysfunction,and primary ovarian insufficiency(POI).Recent studies have suggested that extracellular vesicles(EVs)secreted from mesenchymal stem cells(MSCs)exert therapeutic effects in various degenerative diseases.In this study,transplantation of EVs from human induced pluripotent stem cell-derived MSCs(iPSC-MSC-EVs)resulted in significant restoration of ovarian follicle numbers,improved granulosa cell proliferation,and inhibition of apoptosis in chemotherapy-damaged granulosa cells,cultured ovaries,and in vivo ovaries in mice.Mechanistically,treatment with i PSC-MSC-EVs resulted in up-regulation of the integrinlinked kinase(ILK)-PI3K/AKT pathway,which is suppressed during chemotherapy,most likely through the transfer of regulatory microRNAs(miRNAs)targeting ILK pathway genes.This work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients.

High expression of the circadian clock gene NPAS2 is associated with progression and poor prognosis of gastric cancer:A singlecenter study

BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively.Immunohistochemical staining(IHC)was used to detect the expression of NPAS2 protein in GC and adjacent tissues.Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC,and a nomogram prediction model was established.The receiver operating characteristic(ROC)curve,the ROC area under the curve,the calibration curve,and C-index were used to evaluate the predictive effectiveness of the model.Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%,which was significantly higher than 30.69%in adjacent tissues.The high expression of NPAS2 was correlated with tumor-node-metastasis(TNM)stage(P<0.05),pN stage(P<0.05),metastasis(P<0.05),venous invasion(P<0.05),lymphatic invasion(P<0.05),and lymph node positive(P<0.05)of GC.Kaplan Meier survival analysis showed that the 3-year overall survival(OS)of patients with high NPAS2 expression was significantly shortened(P<0.0001).Univariate and multivariate COX regression analysis showed that TNM stage(P=0.009),metastasis(P=0.009),and NPAS2 expression(P=0.020)were independent prognostic factors of OS in GC patients for 3 years.The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740(95%CI:0.713-0.767).Furthermore,subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group(P<0.0001).CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients.Therefore,the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation.Notably,the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease

BACKGROUND Growth differentiation factor 15(GDF-15)has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events.This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality,considering traditional risk factors and other biomarkers.METHODS A prospective study was conducted and 3699 patients with stable coronary artery disease(CAD)were enrolled into the research.Baseline GDF-15 levels were measured.Median follow-up was 3.1 years during the study.We analyzed clinical variables and several biomarkers.Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction(MI),heart failure,stroke,cardiovascular death,and non-cardiovascular death.RESULTS Baseline GDF-15 levels for 3699 patients were grouped by quartile(≤1153,1153-1888,1888-3043,>3043 ng/L).Higher GDF-15 levels were associated with older age,male gender,history of hypertension,and elevated levels of N-terminal pro Btype natriuretic peptide(NT-pro BNP),soluble suppression of tumorigenesis-2(sST2),and creatine(each with P<0.001).Adjusting for established risk factors and biomarkers in Cox proportional hazards models,a 1 standard deviation(SD)increase in GDF-15 was associated with elevated risk of clinical events[hazard ratio(HR)=2.18,95%confidence interval(CI):(1.52-3.11)],including:MI[HR=2.8395%CI:(1.03-7.74)],heart failure[HR=2.7195%CI:(1.18-6.23)],cardiovascular and non-cardiovascular death[HR=2.48,95%CI(1.49-4.11)]during the median follow up of 3.1 years.CONCLUSIONS Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death,independent of clinical risk factors and other biomarkers.GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

FHL2在消化系统恶性肿瘤中的研究进展

FHL2是一种参与信号转导和基因转录的支架蛋白,具有FHL蛋白典型的结构特征.FHL2含有四个半LIM结构域,不同的LIM结构域可以与不同的蛋白质结合,从而激活或者抑制转录因子如P53、血清应答因子等的活性,进而影响肿瘤的发生发展.既往研究发现,FHL2在肿瘤发生发展中具有复杂的生物学作用,在不同类型肿瘤中发挥促癌或抑癌的作用.本文就FHL2在消化系统恶性肿瘤中的研究进展作一概述.

去整合素-金属蛋白酶17在消化系统恶性肿瘤中的研究现状

去整合素-金属蛋白酶17(a disintegrin and metalloproteinase 17,ADAM17)即肿瘤坏死因子α转换酶,在哺乳动物细胞中广泛分布,与细胞黏附、细胞迁移、白细胞募集、蛋白水解等功能密切相关.ADAM17在恶性肿瘤发生发展中起重要作用,一方面通过介导膜蛋白脱落激活信号通路,参与细胞增殖、血管生成等;另一方面,通过降解细胞基底膜和细胞外基质,在肿瘤的侵袭和转移中发挥重要作用.因此,ADAM17可能作为肿瘤治疗的潜在靶点,本文就ADAM17在消化系统恶性肿瘤中的相关研究进行综述.

Role of Kupffer cells in acute hemorrhagic necrotizing pancreatitis-associated lung injury of rats

瞄准：在尖锐的出血性的引起坏死的联系胰腺炎的肺损害(AHNP-LI ) 调查 Kupffer 房间(KC ) 的角色。方法：42 只老鼠被分配到四个组[假冒的操作， AHNP 模型，金轧氯化物(GdCl3 ) 预告的处理， GdCl3 控制] 。在 GdCl3 预告的处理组， GdCl3 被尾的静脉注射 24 h 在 AHNP 模型正式就职前管理。从从胰和肺的肠骨的动脉，牙槽的巨噬细胞和纸巾的血，在尖锐胰腺炎以后每组 3 和 6 h 在六个动物被收集感应。TNF-alpha，浆液的 IL-1，肺织物的 myeloperoxidase (军邮局) ，牙槽的巨噬细胞的 NF-kappaB 激活被检测。在假冒的操作组和 GdCl3 控制组的浆液著名计算机生产厂商和中高音被测试。另外，胰和肺的组织病理学说的变化在轻显微镜下面被观察。结果：肺织物和 TNF-alpha 的军邮局，浆液的 IL-1 层次都在 AHNP 组(P【0.01 ) 与那些相比在 GdCl3 预告的处理组显著地被减少。牙槽的巨噬细胞的 NF-kappaB 激活也在 AHNP 组(P【0.01 ) 与那相比在 GdCl3 预告的处理组显著地被稀释。肺的病理学的损害在 AHNP 组与那相比在 GdCl3 预告的处理组显然被改善。不过，浆液淀粉酶水平没减少，胰的损害没在 GdCl3 预告的处理组被阻止。结论：AHNP 导致的肺的损害被 KC 激活调停， AHNP-LI 能被预告的处理显著地与 GdCl3 改善， KC 在 AHNP-LI 起一个重要作用。

Novel biomarkers for cardiovascular risk prediction

心血管的疾病(CVD ) 是死亡和世界范围的残疾的领先的原因。CVD 的主要预防依赖于在公开事件的发展前长识别高风险的个人的能力。这为精确风险层化加亮需要。越来越多的新奇 biomarkers 被识别了预言心血管的事件。Biomarkers 玩在关于心血管的事件的管理的定义，预知，和决策的一个关键角色。这评论集中于许多有希望的 biomarkers 提供诊断、预示的信息。心肌的织物特定的 biomarker 心脏的 troponin，为心脏的 troponin 的高敏感的试金，和心类型丰满的酸绑定 proteinall 帮助在跟随症状的早小时诊断心肌的梗塞(MI ) 。象生长区别 factor-15，高敏感的 C 反应的蛋白质，纤维蛋白原，和尿酸那样的煽动性的标记预言 MI 和死亡。联系怀孕的血浆蛋白质 A， myeloperoxidase，和矩阵 metalloproteinases 预言急性冠的症候群的风险。联系脂蛋白的 phospholipase A2 和能分泌的 phospholipase A2 预言事件和周期性的心血管的事件。最后，提高了肽， ST2， endothelin-1， mid-regional-pro-adrenomedullin， copeptin，和 galectin-3 都是的 natriuretic 很好验证了预言跟随 MI 的死亡和心失败并且为心失败提供风险层化信息。很快发展中的新区域例如对 micro-RNA 的评价，也被探索。所有 biomarkers 反映动脉粥样硬化的发展的不同方面。

在胃的癌症的帮助 laparoscopy 对开的激进的 gastrectomy 的短期的功效

AIM:To investigate the short-term benefits of laparoscopic radical gastrectomy(LARG)and open radical gastrectomy(ORG)in patients with gastric cancer.METHODS:A total of 400 patients with gastric cancer aged≤65 years who were treated at General Hospital of Lanzhou Military Region were enrolled.Among these,200 patients underwent LARG between October2008 and August 2012(LARG group);and 200 patients underwent ORG between March 2000 and September2008(ORG group).The short-term therapeutic benefits between the two groups were analyzed.RESULTS:The LARG procedure offered significantly better benefits to the patients compared to the ORG procedure,including less intraoperative blood loss(103.1±19.5 mL vs 163.0±32.9 mL,P【0.0001),shorter postoperative hospital stay(6.8±1.2 d vs 9.5±1.6 d,P【0.0001),less frequent occurrence of postoperative complications(6.5%vs 13.5%,P=0.02),shorter time to mobilization(1.0±0.3 vs 3.3±0.4 d,P【0.0001),shorter time to bowel opening(3.3±0.7 d vs 4.5±0.7 d,P【0.0001),and shorter time to normal diet(3.0±0.4 vs d 3.8±0.5 d,P【0.0001).However,LARG required a longer time to complete than the ORG procedure(192.3±20.9 min vs 180.0±26.9 min,P【0.0001).CONCLUSION:Compared to ORG,LARG is safer,more effective,and less invasive for treating gastric cancer,with better short-term efficacy.

Sphingosine 1 phosphate receptor-1 （S1PR1） signaling protects cardiac function by inhibiting cardiomyocyte autophagy

ObjectiveTo 在 cardiomyocyte autophagy， cardiomyocyte 肥大和心脏的 function.MethodsCardiomyocytes 调查 sphingosine-1-phosphate (S1P ) 和它的受体的角色从新生的远景老鼠被孤立。分别地， cardiomyocytes 的 Autophagy 和肥大经由饥饿文化和 phenylephrine (PE ) 被导致， S1P 被用来对待 cardiomyocytes。cardiomyocyte autophagy 上的 S1P 的效果被 autophagosomes， autophagy 相关的蛋白质的表示和 autophagic 标记基因的数字在 cardiomyocytes 评估。cardiomyocyte 肥大上的 S1P 的效果被检验 cardiomyocytes 和 hypertrophic 基因的表示的表面区域评估。随后，不同小介入 RNA (siRNAs ) 习惯于击倒三的表示在 cardiomyocytes 上 S1P 受体打字，那调停分析受体的类型 S1P 在 cardiomyocytes 发信号。最后，鞘氨醇 1 磷酸盐 receptor-1 (S1PR1 ) 在用 Cas9 技术的老鼠 cardiomyocytes 是猛烈的。心脏的 autophagy 和心脏的肥大上的 S1PR1 的效果被估计 cardiomyocyte autophagy， cardiomyocyte 肥大和心脏的导致 function.ResultsStarvation 的 cardiomyocyte autophagy 检验，导致 PE 的 cardiomyocyte 肥大被 S1P 显著地稀释。结果证明 autophagosomes 的形成被减少，联系 autophagy 的蛋白质 LC3II/I 和 autophagic 标记基因 Atg5， Atg12， Beclin1 和 LC3B 的表示在 S1P 处理以后减少了。cardiomyocytes 的表面区域被减少，并且 hypertrophic 基因，包括的 atrial natriuretic 因素(ANF ) ，骨胳的肌肉和心脏的肌动朊(SKA ) 的表示，肌浆球蛋白重链(-MHC) 和大脑 natriuretic 肽(BNP ) 都在 S1P 处理以后被减少。在 S1PR1 组合式的组的 cardiomyocytes 的 autophagy 和肥大显著地在控制组， S1PR2 和 S1PR3 与那些相比被增加组合式的组。在 vivo，在 cardiomyocytes 的 S1PR1 的大美人加重了导致压力的心脏的 autophagy，心脏的肥大和心脏的 function.ConclusionS1P 的缺陷能禁止 cardiomyocyte autophagy，从而禁止 cardiomyocyte 肥大并且保护由激活在在鼠标的过载压力的 cardiomyocytes 的 S1PR1 的心脏的功能。

Should atrial fibrillation patients with hypertension as an additional risk factor of the CHA2DS2-VASc score receive oral anticoagulation？

高血压被发现了被增加在 atrial 纤维性颤动(AF ) 的击的风险。欧洲人和美国指南倡导 CHA 2 DS 2-VASc (充血的心失败，高血压，年龄 > 75 年，糖尿病 mellitus， stroke/transient ischemic 攻击，脉管的疾病，年龄 65-74 年，性别范畴) 为风险层化的计划。尽管维生素 K 对手是比在阻止 ischaemic 击的 acetylsalicylic 酸更有效的，它的利益是由增加的出血风险的 offs。在有 AF 和 CHA 2 1 的 DS 2-VASc 分数被认为是低风险并且不能被期望得益于 anticoagulation 治疗。然而，高血压带 ischemic 击的增加的风险它也是为在 AF 的出血的一个清楚的风险因素。因此，最佳的 antithrombotic 管理特别与一个仅仅风险因素与 AF 在病人被加亮高血压。

Probiotics improve survival of septic rats by suppressing conditioned pathogens in ascites

AIM: To investigate the benefits of probiotics treatment in septic rats. METHODS: The septic rats were induced by cecal ligation and puncture. The animals of control, septic model and probiotics treated groups were treated with vehicle and mixed probiotics, respectively. The mixture of probiotics included Bifidobacterium longum , Lacto-bacillus bulgaricus and Streptococcus thermophilus . We observed the survival of septic rats using different amounts of mixed probiotics. We also detected the bacterial population in ascites and blood of experimental sepsis using cultivation and real-time polymerase chain reaction. The severity of mucosal inflammation in colonic tissues was determined. RESULTS: Probiotics treatment improved survival of the rats significantly and this effect was dose dependent. The survival rate was 30% for vehicle-treated septic model group. However, 1 and 1/4 doses of probiotics treatment increased survival rate significantly comparedwith septic model group (80% and 55% vs 30%, P < 0.05). The total viable counts of bacteria in ascites decreased significantly in probiotics treated group compared with septic model group (5.20 ± 0.57 vs 9.81 ± 0.67, P < 0.05). The total positive rate of hemoculture decreased significantly in probiotics treated group compared with septic model group (33.3% vs 100.0%, P < 0.05). The population of Escherichia coli and Staphy-lococcus aureus in ascites of probiotics treated group were decreased significantly compared with that of septic model group (3.93 ± 0.73vs 8.80 ± 0.83,P < 0.05; 2.80 ± 1.04 vs 5.39 ± 1.21, P < 0.05). With probiotics treatment, there was a decrease in the scores of inflammatory cell infiltration into the intestinal mucosa in septic animals (1.50 ± 0.25vs 2.88 ± 0.14,P < 0.01). CONCLUSION: Escherichia coli and Staphylococcus aureus may be primary pathogens in septic rats. Probiotics improve survival of septic rats by suppressing these conditioned pathogens.

Effect of Ramipril on Renin-Angiotensin-Aldosterone System of Young and Middle-Aged Patients with Hypertension

Objective:To explore the effect of Ramipril on renin-angiotensin-aldosterone system of young and middle-aged patients with hypertension.Methods 90 young and middle-aged patients with hypertension who had been seeking treatment in the hospital between August 2017 and August 2018 were selected and randomly divided into a control group and an observation group according to the random number table,with 45 cases in each group.The control group received Amlodipine for treatment,whereas the observation group was given Amlodipine combined with Ramipril for treatment.The hemodynamic indexes,blood lipid,blood pressure,angiotensinⅡ(AngⅡ),plasma renin(PRA),aldosterone(ALD)levels and incidence of adverse reactions during the medication in the two groups were compared before and after treatment.Results After treatment,thefibrinogen,plasma viscosity and whole blood viscosity in the observation group were significantly higher than those in the control group,with statistically significant difference between the two groups(P<0.05);total cholesterol(TC),triacylglycerol(TG)and low density lipoprotein cholesterin(LDL-C)in the observation group were significantly lower than those in the control group,and statistically significant difference was registered between the two groups(P<0.05);the diastolic pressure and systolic pressure in the observation group were decreased more significantly compared with the control group,with statistically significant difference shown between the two groups(P<0.05);the AngⅡ,ALD and PRA levels in the observation group were significantly lower than the control group,and the difference between two groups were statistically significant(P<0.05);during the medication,no significant bleeding or liver and kidney function damages occurred in the two groups.Conclusions For young and middle-aged patients with hypertension,the treatment with Ramipril,which is of high safety,can effectively improve the activity of their renin-angiotensin-aldosterone system,reduce the level of blood pressure and AngⅡ,ALD and PRA levels.

Artificial intelligence:A new budding star in gastric cancer

The pursuit of health has always been the driving force for the advancement of human society,and social development will be profoundly affected by every breakthrough in the medical industry.With the arrival of the information technology revolution era,artificial intelligence(AI)technology has been rapidly developed.AI has been combined with medicine but it has been less studied with gastric cancer(GC).AI is a new budding star in GC,and its contribution to GC is mainly focused on diagnosis and treatment.For early GC,AI’s impact is not only reflected in its high accuracy but also its ability to quickly train primary doctors,improve the diagnosis rate of early GC,and reduce missed cases.At the same time,it will also reduce the possibility of missed diagnosis of advanced GC in cardia.Furthermore,it is used to assist imaging doctors to determine the location of lymph nodes and,more importantly,it can more effectively judge the lymph node metastasis of GC,which is conducive to the prognosis of patients.In surgical treatment of GC,it also has great potential.Robotic surgery is the latest technology in GC surgery.It is a bright star for minimally invasive treatment of GC,and together with laparoscopic surgery,it has become a common treatment for GC.Through machine learning,robotic systems can reduce operator errors and trauma of patients,and can predict the prognosis of GC patients.Throughout the centuries of development of surgery,the history gradually changes from traumatic to minimally invasive.In the future,AI will help GC patients reduce surgical trauma and further improve the efficiency of minimally invasive treatment of GC.

Risk of cardiac rupture after acute myocardial infarction is related to a risk of hemorrhage

Although cardiac rupture (CR) is a fatal mechanical complication of acute myocardial infarction (AMI), to date no predictive model for CR has been described. CR has common pathological characteristics with major bleeding. We aimed to investigate the relationship between the risk factors of major bleeding and CR. A total of 10 202 consecutive AMI patients were recruited, and mechanical complications occurred in 72 patients. AMI patients without CR were chosen as control group. Clinical characteristics including bleeding-related factors were compared between the groups. The incidences of free wall rupture (FWR), ventricular septal rupture (VSR), and papillary muscle rupture (PMR) were 0.39%, 0.21%, and 0.09%, respectively, and the hospital mortalities were 92.5%, 45.5%, and 10.0%, respectively. Female proportion and average age were significantly higher in the groups of FWR and VSR than in the control group (P<0.01); higher white blood cell count and lower hemoglobin were found in all CR groups (P<0.01). Compared to the control group, patients with CR were more likely to receive an administration of thrombolysis [26.39% vs. 13.19%, P<0.05], and were less likely to be treated with primary percutaneous coronary intervention (PCI) [41.67% vs. 81.60%, P<0.05]. The major bleeding scores (integer scores) of FWR, VSR, and PMR were (17.70±7.24), (21.91±8.33), and (18.60±7.88), respectively, and were significantly higher than that of the control group (11.72±7.71) (P<0.05). A regression analysis identified age, increased heart rate, anemia, higher white blood cell count, and thrombolysis as independent risk factors of CR, most of which were major bleeding-related factors. The patients with CR have a significantly higher risk of hemorrhage compared to the group without CR. Risk of CR after AMI is related to the risk of hemorrhage.

A new TEX11 mutation causes azoospermia and testicular meiotic arrest

There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men.Here,we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del(p.D51fs)frame-shift mutation in exon 3 of the testis expressed 11(TEX11)gene in one patient.Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation.Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes.In contrast,testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression.Western blotting of human embryonic kidney(HEK293)cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression.In conclusion,we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient,emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.

子宫内膜不典型增生或复杂性增生不孕患者孕激素和IVF后的妊娠结局分析（英文）

本回顾性队列研究包括了年龄在45岁以下被诊断为伴有或不伴有不典型增生的子宫内膜复杂性增生患者,对孕激素治疗后的临床结局及妊娠结局进行了比较。结果表明,伴有或不伴有不典型增生的子宫内膜复杂性增生接受孕激素治疗后,其临床及妊娠结局并没有显著差异。我们认为对于这些患者,在短暂的孕激素治疗控制病情后,尽快施行体外受精-胚胎移植治疗(IVF)将有利于改善其妊娠结局。

Significance and interaction of bonding parameters with bonding ratio in press bonding of TC4 alloy

The variation of bonding ratio in the press bonding of TC4 alloy at temperatures from 850 to 900℃,pressures from 10 to 30 MPa,and time from 5 to 15 min was investigated.The bonding ratio increases with the increase of temperature,time and pressure.The maximum bonding ratio,i.e.98 %,can be obtained at 900℃,30 MPa and 15 min.The significance and interaction of bonding parameters with the bonding ratio were investigated.The results demonstrate that the effect of pressure on the bonding ratio is the most effective and the effect of temperature is secondary,while the effect of time is not very powerful.The interaction of bonding parameter on the bonding ratio exists but that is distinguishing in different bonding parameter ranges.It is concluded that increasing pressure can be considered as the primary method to increase the bonding ratio.

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

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.