广州地区不育男性Y染色体无精子因子微缺失的筛查

目的探讨Y染色体无精子因子(azoospermia factor,AZF)区域微缺失与原发无精、严重少精症之间的关系。方法采用多重聚合酶链反应技术对广州地区103例原发无精子症、72例原发严重少精症患者及60名正常生育男性进行AZFa、AZFb、AZFc3个区域微缺失分析。结果60名正常生育男性未发现Y染色体AZF区域微缺失,175例生精障碍患者中发现AZF微缺失19例,总缺失率为10.9%。其中11例无精症患者和4例少精症患者的缺失发生在AZFc区域,缺失率为8.6%;1例无精症患者和2例少精症患者发生AZFb、AZFc双重缺失,缺失率为1.7%;1例无精症患者发生AZFa、b、c3个区域同时微缺失,缺失率0.6%。生精障碍组与正常生育男性组比较Y染色体AZF区域微缺失率差异具有统计学意义(P<0.01)。结论Y染色体AZF区域微缺失是引起男性无精、少精子症的重要原因之一,对原发无精、少精子症患者在单精子注射之前进行微缺失筛查是必要的。     

特发性无精症与严重少精症患者DAZ基因缺失的研究

目的：探讨无精子缺失（deleted in azoospermia，DAZ）基因与精子发生的关系，以及特发性无精症与严重少精症患者DAZ基因缺失的发生率。方法：应用聚合酶链反应对特发性无精症或严重少精症患者DAZ基因进行检测，并结合患者的生殖激素水平及临床表型进行分析。结果：38例特发性无精症或严重少精症患者中有3例DAZ基因缺失，缺失率为7.9%，3名患者的血清FSH水平均升高。20名精子计数正常、有生育能力的男性无DAZ基因缺失。结论：DAZ基因可能与精子发生相关，DAZ的微缺失可能是造成男性不育的原因之一。     

精浆miR-122-3p和miR-141-Sp的稳定性及对于特发性弱精症的诊断价值SeminalplasmamiR-122·-3pandmiR-141·。5pstabilityanditsdiagnosisvalueforidiopathicasthenospermia北大核心CSCD

目的探讨精浆游离miR-122—3p和miR-141—5p的稳定性及其对特发性弱精症的诊断价值。方法分析不同的室温孵育时间、反复冻融次数、4℃放置时间下精浆游离miR-122-3p和miR-141—5p的稳定性。应用实时荧光定量聚合酶链反应（real-time fluorescence guantitative-polymerase chain reaction,RT—PCR）检测实验组和对照组精浆miR-122—3p和miR-141—5p的含量,以U6snRNA作为内参。相对定量采用2^-ΔΔCt帕法。将特发性弱精症组按精子前向运动百分比分为a组（0～20％）和b组（21％～32％）,比较两组精浆miR-122—3p和miR-141—5p的含量差异。结果在不同的室温孵育时间、4℃放置时间下,精浆miR-122—3p和miR-141-5p含量无明显变化。在反复冻融的条件下,精浆miR-122-3p和miR-141—5p随着冻融次数的增加而减少。RT-PCR结果表明,特发性弱精症组的精浆游离miR-122-3p含量低于对照组,差异有统计学意义（P〈0．05）,miR-141-5p含量高于对照组,差异有统计学意义（P〈0．05）。精浆游离miR-122—3p和miR-141—5p含量在特发性弱精症a组和b组之间均有显著性差异（P〈O．05）。ROC曲线结果显示,miRq22—3p曲线下面积为0．88,当以1．02为最佳截断值时,敏感度为83％,特异度为84％。miR-141—5p的曲线下面积为0．88,当以2．95为最佳截断值时,敏感度为84％,特异度为70％。结论精浆中游离miR-122-3p和miR-141—5p可稳定存在,其在特发性弱精症中的差异表达对特发性弱精症的诊断有一定的应用价值。     

血清miR-155、miR-23b在特发性肉芽肿乳腺炎和乳腺癌中的差异性表达及意义

目的 探讨miR-155、miR-23b在特发性肉芽肿乳腺炎（IGM）和乳腺癌（BC）鉴别诊断中的作用。方法 选取2018年10月至2021年11月我院收治的32例IGM患者（ICM组）和40例BC患者（BC组）,所有患者均经活检确诊。另外纳入33例健康女性作为对照组。比较患者的临床资料。采用实时荧光定量PCR检测血清miRNAs表达水平。采用受试者工作特征（ROC）曲线评估血清miR-155、miR-23b对IGM和BC的诊断价值。采用Pearson相关系数法评估相关性。结果 3组CRP、WBC、Hb、Hct、CA19-9、CA15-3、CA125水平比较,差异有统计学意义（P<0.05）。IGM组患者血清miR-155、miR-16-5p、miR-21-5p、miR-210-3p、miR-222-3p、miR-29c-3p表达水平较对照组升高（P<0.001）,血清miR-23b表达水平低于对照组（P<0.001）;BC组患者血清中以上miRNAs表达水平均高于对照组（P<0.001）。BC组患者血清miR-155表达水平低于IGM组（P<0.001）...     

类风湿关节炎患者外周血miR-146a、miR-155、Ets-1以及IRAK1的表达及临床意义

为探讨类风湿关节炎(rheumatoid arthritis,RA)患者PBMC中miR-146a、miR-155、Ets-1和IRAK1的表达水平及与病情活动度的相关性,收集RA高活动期患者23例、低活动期患者21例和健康志愿者22例,采用qRT-PCR检测PBMC中miR-146a、miR-155、Ets-1、IRAK1的相对表达水平,同时分析其与临床及实验室指标的相关性。RA患者PBMC的miR-146a、miR-155相对表达量显著高于健康对照组(P<0.05),高活动组高于低活动组(P<0.05)、低活动组与健康对照组差异无统计学意义(P>0.05);RA患者PBMC的Ets-1表达水平与健康对照组差异无统计学意义,高活动组显著低于低活动组和健康对照组(P<0.05)、低活动组与健康对照组差异无统计学意义(P>0.05);RA患者PBMC的IRAK1表达水平显著低于健康对照组(P<0.05),高活动组显著低于健康对照组(P<0.01)、低活动组显著低于健康对照组(P<0.05),而高活动组与低活动组间无统计学差异(P>0.05)。在RA患者中miR-155表达水平与血沉正相关(r=0.319,P=0.042)而与血红蛋白负相关(r=-0.386,P=0.017);Ets-1与CRP负相关(r=-0.408,P=0.007);IRAK1与RF、DAS 28、总补体负相关(r=-0.513,P=0.001;r=-0.332,P=0.029;r=-0.49,P=0.015)。研究结果显示,RA高活动组患者PBMC中miR-146a、miR-155表达升高,Ets-1、IRAK1表达降低,可能参与了RA发病过程的调控;但本研究样本量有限,miR-146a、miR-155和Ets-1、IRAK1参与RA发病的关系有待后续大样本研究证实,且相关调控机制仍需进一步深入研究。     

精液的流变特性研究

目的 :研究精液的流变特性。方法 :用旋转式粘度计检测 18例生育男性、16例少精症病人及 17例弱精症病人精液粘度 ,分析精液中精浆粘度及精液的理化指标对精液流变特性的影响。结果 :精液粘度表现为随切变率升高而降低的一条非直线 ;弱精症病人精液粘度与生育组比较没有统计学差异 (P >0 .0 5 ) ,少精症病人精液粘度与生育组比较有统计学差异 (P <0 .0 5 ) ;三组间精浆粘度无统计学差异 ;精液粘度与精子密度有微弱的正相关 ,与精浆粘度有显著性正相关 ,精液粘度与正常的精液液化时间、精子活率、及精浆果糖、酸性磷酸酶、α 葡萄糖苷酶浓度无明显相关关系。结论 :精液为非牛顿液体 ,具有非牛顿液体的流变特性 ;精液粘度主要受精浆粘度的影响 ,精液中精子数量对精液粘度有一定的影响 ;精液粘度的高低在男性生育中的意义须进一步研究。     

无精子因子C区部分缺失与男性不育相关性研究

目的 探讨Y染色体无精子症因子C区(azoospermia factor C,AZFc)部分缺失与男性不育的关系.方法 采用多重PCR技术对实验组453例原发不育患者(无精子症158例,严重少精子症160例,少精子症135例)和对照组236名已正常生育男性进行AZFc区部分缺失检测,并应用限制性片段长度多态性技术,对部分缺失携带者进行DAZ基因拷贝缺失分析.结果 在所发现的两种常见缺失中,少精症组和严重少精症组与正常对照组b2/b3缺失率差异均有统计学意义,而在各组中gr/gr缺失显示相似的频率.结论 Y染色体AZFc区b2/b3缺失可能是该人群生精障碍发生的风险因素,并与男性原发不育相关.     

男性不育患者精浆果糖和α-糖苷酶水平的研究

目的探讨精浆果糖、α-糖苷酶的含量与男性不育的关系。方法检测98例正常生育男性和824例不育男性患者的精液常规、精浆果糖和α-糖苷酶的浓度,并在各组之间作了比较。结果（1）精液常规分析正常组、精子密度正常组间精浆果糖和α-糖苷酶都无明显差异（P〉0.05）,而少精子组和无精子组精浆果糖比正常组、精子密度正常组显著性增高（P〈0.05）;相反,精液常规分析正常组、精子密度正常组精浆的α-糖苷酶明显高于少精组和无精（P〈0.05）。结论精浆果糖和α-糖苷酶的测定对男性的不育诊断有一定的参考意义。     

类风湿关节炎患者外周血miR-146a、miR-16的表达水平及临床指标与中医证型的关系探讨

目的研究类风湿关节炎（RA）患者外周血miR-146a、miR-16的表达及ESR、CRP、RF、抗CCP抗体与中医证型的关系,为RA辨证分型提供客观依据。方法根据《中药新药临床研究指导原则》有关RA的中医证候诊断标准,主要分为两个证型：风湿夹瘀型（n=20）和肝肾亏损型（n=16）;16名健康体检者作为健康对照组。Real-timePCR检测RA患者及健康对照组miR-146a、miR-16的表达,记录ESR、CRP、RF、抗CCP抗体等临床指标。结果风湿夹瘀型miR-146a、miR-16的表达水平高于肝肾亏损型和对照组（P均〈0.05）,肝肾亏损型miR-146a、miR-16的表达水平与健康对照组相比差异无统计学意义（P均〉0.05）,风湿夹瘀型RA患者ESR及CRP高于肝肾亏损型（P〈0.01和P〈0.05）,RF低于肝肾亏损型（P〈0.05）,抗CCP抗体在两种证型之间差异无统计学意义（P〉0.05）。结论 miR-146a、miR-16的表达水平和ESR、CRP、RF等临床指标可能为RA风湿夹瘀及肝肾亏损型的辨证分型提供参考。     

脑胶质瘤患者血清miR-128和miR-720相对表达量及临床意义

目的探讨血清miR-128和miR-720相对表达量对脑胶质瘤的诊断价值。方法采用TaqMan MicroRNA AssaysReal-time PCR技术检测62名健康对照者、54例低级别脑胶质瘤患者和57例高级别脑胶质瘤患者血清miR-128和miR-720相对表达量。结果低级别脑胶质瘤组与健康对照组比较血清miR-720相对表达量差异有统计学意义(P<0.05),高级别脑胶质瘤组miR-128和miR-720相对表达量差异均有统计学意义(P<0.05);与低级别脑胶质瘤组比较,高级别脑胶质瘤组的miR-128和miR-720相对表达量差异均有统计学意义(P<0.05)。miR-128和miR-720联合检测区分健康对照组和脑胶质瘤组的诊断灵敏性和特异性分别为92.3%和87.2%,区分低级别脑胶质瘤组和高级别脑胶质瘤组的诊断灵敏性和特异性分别为84.3%和88.9%。结论血清miR-128和miR-720相对表达量联合诊断为临床脑胶质瘤的诊断和预后提供一种辅助方法。     

HLA—DQA1,DQB1基因与特发性膜性肾病关联研究

为探讨上海地区特发性膜性肾病（ＩＭＮ）与ＨＬＡ－Ⅱ类基因的关联，本研究用聚合酶链反应（ＰＣＲ）及序列特异性寡核苷酸（ＳＳO）探针杂交方法，对３３例上海地区汉族ＩＭＮ患者及７０例同一地区 正常人作了ＨＬＡ－ＤＱＡ１、－ＤＱＢ１位点的等位基因分型，并比较其基因频率。结果表明：ＩＭＮ组ＤＯＡ１０１０１等位基因频率高于对照组，统计学处理有显著性差异（ＲＲ＝３．０４３，Ｐ＝０．００２，Ｐｃ－０．０１８）。ＤＱＢ１０６０４等位基因频率较对照组高，而ＤＱＢ１０３０１等位基因频率较对照组低，但统计学处理后差异均不显著（Ｐ＜０．０５，Ｐｃ＞０．０５），以上结果提示，１ＭＮ的发病机制可能与免疫遗传因素有关。     

Detection of miR-1246, miR-23a and miR-451 in sera of colorectal carcinoma patients: a case-control study in Cairo University hospital

BackgroundColorectal cancer (CRC) has high morbidity and mortality rates. Invasive techniques and other laboratory tests with variable sensitivity and specificity are currently used in diagnosis. Micro ribonucleic acids (miRNAs) have bio vital roles in cell proliferation and apoptosis. Dys-regulation of miRNAs is linked to tumour genesis. The objective of this study was to evaluate the specificity and sensitivity of serum non-invasive biomarkers (micro-RNAs), miR-1246, miR-23a, and miR-451in CRC patients.MethodsPeripheral expression of three miRNAs (miR-1246, miR-23a and miR-451) was investigated in sera of 37 CRC Egyptian patients and 30 healthy controls, using quantitative real-time polymerase chain reaction trying to reach the optimal non-invasive combination of miRNAs.ResultsSerum miR-1246 was up-regulated in sera of CRC patients compared to normal controls (fold change = 3.55; P<0.001) and showed 100% sensitivity and 80% specificity in diagnosis of CRC. Serum miR-451 was significantly down-regulated in CRC patients (fold change = -4.86; p= 0.014), whereas, miR-23a was down-regulated but this was not statistically significant.ConclusionUp-regulation of miR-1246 and down-regulation of miR-451 in the sera of primary CRC Egyptian patients were confirmed with high sensitivity and specificity. Large-scale studies on a wider spectrum of miRNAs in Egyptian CRC patients are needed.     

扩张-伸缩式机器人在肠道中的力学特性研究

目的肠道机器人内镜是新一代肠道疾病诊疗设备,为了提高这类设备在肠道内自主运动的效率,本文研究了机器人运动机构与肠道之间的相互作用力对设备自主运动的影响。方法针对扩张-伸缩式机器人的运动原理提出了两个模型,分别是扩张机构与肠道之间的力学模型、机器人机身与肠道之间的力学模型,并在猪体外肠道环境下开展了实验验证。结果机器人机身与肠道之间的阻力在0. 1～0. 4 N之间;扩张机构与肠道之间的阻力在0. 1～1. 8 N之间,且与扩张直径成正比。扩张机构的扩张直径大于肠道直径超过10 mm后,扩张机构受到的肠道阻力将明显大于0. 1～0. 4 N,有利于有效驻留的产生。结论这种利用腿式结构在肠道内产生力学差使机器人实现在肠道内自主运动的方式,以及腿式结构与肠道之间的力学可以为能对胃肠道机器人的设计提供参考。     

Dysregulated Serum MicroRNA Expression Profile and Potential Biomarkers in Hepatitis C Virus-infected Patients

Objectives: Circulating microRNAs (miRNAs) play critical roles in pathogen-host interactions. Aberrant miRNA expression profiles might have specific characteristics for virus strains, and could serve as noninvasive biomarkers for screening and diagnosing infectious diseases. In this study, we aimed to find new potential miRNA biomarkers of hepatitis C virus (HCV) infection.Methods: Expression levels of broad-spectrum miRNAs in serum samples from 10 patients with HCV viremia and 10 healthy volunteers were analyzed using miRNA PCR arrays. Subsequently, the differential expression of four selected miRNAs (miR-122, miR-134, miR-424-3p, and miR-629-5p) was verified by qRT-PCR in the serum of 39 patients compared with that in 29 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate their potential for the diagnosis of HCV infection.Results: miRNA PCR array assays revealed differential expression of 106 miRNAs in sera of HCV patients compared with that in healthy controls. Serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p were well identified. The ROC curves showed that miR-122, miR-134, miR-424-3p, and miR-629-5p could distinguish HCV patients with preferable sensitivity and specificity. In addition, Correlation analysis indicated serum miR-122 expression was positive correlation with ALT/AST levels. Functional analysis of target proteins of these miRNAs indicated the involvement of viral replication, inflammation, and cell proliferation.Conclusion: HCV patients have a broad ''fingerprint'' profile with dysregulated serum miRNAs compared with that in healthy controls. Among these, serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p are identified as promising indication factors of the serum miRNA profile of HCV infection. Particularly, miR-122 could be one of serum biomarkers for early pathological process of HCV. However, more miRNA biomarkers and biological functions of these miRNAs require further investigation.     

系统性硬皮病患者血小板参数分析

目的观察系统性硬皮病(systemic scleroderma,SSc)患者的血小板分布宽度(platelet distribution width,PDW)、血小板计数(platelet count,PLT)、血小板平均体积(mean platelet volume,MPV)、血小板比率(platelet ratio,P-LCR)的水平,探讨PLT、PDW、MPV、P-LCR与SSc的关系。方法用全自动血液分析仪EX2100测定97例确诊的SSc患者的PLT、PDW、MPV、P-LCR参数,同等条件下与正常人作对照,并进行方差分析。结果 SSc患者治疗前PLT明显低于正常对照组(P <0.01),而PDW、MPV和P-LCR均显著高于正常对照组(P <0.01)。SSc患者治疗后的PLT与治疗前差异无统计学意义(P>0.05),而PDW、MPV和P-LCR均较治疗前显著下降(P <0.01)。结论 SSc患者治疗前PLT水平较低,PDW、MPV、P-LCR水平较高。通过SSc患者的血液常规检查有助于SSc发病机制的探讨及为临床诊治后的疗效提供实验室依据。     

帕金森病冻结步态的实时监测系统

目的由于帕金森病冻结步态的突发性,临床上对其进行评估存在一定困难,为此本文研究了一种用于实时监测冻结步态的系统。方法该系统由可穿戴设备和配套的APP两部分构成,其中设备通过惯性传感器和超声波传感器采集患者腿部运动的加速度和抬脚高度数据,并传输至APP软件中,通过软件中的冻结步态识别模型进行分析。系统为构建冻结步态识别模型,首先通过实验采集12位患者的运动数据,然后经过信号预处理、特征提取和机器学习算法训练出模型,最后通过对数据集采用十折交叉验证来评估模型的准确度和精确度。结果系统对冻结步态的识别准确率可达98.6%,精确率达97.2%。结论该系统能够实时监测帕金森病患者日常生活中的冻结步态发作情况,为医生的诊疗提供定量、可靠的参考依据。     

Low-dose prednisolone/chlorambucil therapy in patients with severe membranous glomerulonephritis

Because of the high rate of spontaneous remission, treatment of membranous nephropathy with prednisolone and chlorambucil is still controversial. The aim of this study was to give this therapy only to those patients at risk of developing renal insufficiency and to test the efficacy of a low-dose therapeutic regimen. Seventeen patients with more than 10 g protein excretion per day (mean 16.9) and/or a deterioration in renal function (mean serum creatinine, 162 mol/l) were included. Serum total protein, serum lipids, proteinuria, serum creatinine, and blood pressure were measured, along with the diuretic and antihypertensive medication. The observation time before the start of treatment was 27 ± 27 months. Steroids were given during months 1, 3, and 5 (methylprednisolone 3 × 500 mg intravenously) prednisolone 0.5 mg/kgBW daily per os for 1 week, then tapered by 0.1 mg/kg BW/week for 1 month. Chlorambucil was given during months 2, 4, and 6 at a dose of 0.12 mg/kgBW daily. At the end of treatment proteinuria had significantly decreased (mean of all patients, 7.8 ± 1.4 g/d) in all patients. Six months after the end of treatment proteinuria was significantly lower than at baseline in 14 of 17 patients. Hypoproteinemia and hyperlipidemia had improved; diuretic and antihypertensive medication were reduced. Elevated serum creatinine decreased in 7 of 9 patients (pretreatment, 227 ± 39 mol/1; 6 months, 176 ± 28 mol/l). Nonresponders with respect to serum creatinine responded with respect to proteinuria. Regarding adverse effects, two patients complained of dyspepsia while taking steroids; during chlorambucil treatment two patients experienced nausea and lack of appetite, and one developed leukopenia (1600/l). Chlorambucil was stopped and cell counts normalized 2 weeks later. We conclude that low-dose prednisolone/chlorambucil is both safe and efficient in the majority of patients with severe membranous nephropathy.Abbreviations MGN membranous glomerulonephritis Correspondence to: R. Brunkhorst     

miR-200a/miR-141 and miR-205 upregulation might be associated with hormone receptor status and prognosis in endometrial carcinomas

The aim of this study was to compare the clinicopathological significance of miR-200a/miR-141 and miR-205 expression in endometrioid carcinomas (ECs) versus nonendometrioid carcinomas (NECs) and to assess their correlation with hormone receptor status. miR-200a/miR-141 and miR-205 expression in 154 endometrial cancers was determined by qRT-PCR. The status of estrogen and progesterone receptor (ER/PR) was assessed using immunohistochemistry. miR-200a/miR-141 and miR-205 increased significantly in ECs and in NECs. The expression level of miR-200a was significantly higher in NECs than in ECs (P = 0.025). Furthermore, there was a trend that NECs with worse clinicopathological variables had a higher miR-200a expression, while an inverse trend existed in ECs. miR-205 upregulation occurred frequently in NECs without lymph node metastases (P = 0.030), whereas such association was not present in ECs. Interestingly, In ECs, miR-200a/miR-141 upregulation occurred frequently in the hormone receptor positive subgroups than the negative subgroups (P < 0.05). Similarly, the expression level of miR-205 was higher in the hormone receptor positive subgroups and the association between miR-205 and PR reached statistical significance (P = 0.024). In contrast, in NECs, a negative correlation was found between miR-200a/miR-141 and ER or PR status. Meanwhile, in ECs, miR-200a upregulation correlated with prolonged survival in the ER positive subgroup (P = 0.046), whereas an inverse trend existed in the ER negative subgroup. Our findings suggest that miR-200a/miR-141 and miR-205 increased significantly in ECs and in NECs. However, they might behave differently in ECs versus NECs. miR-200a/miR-141 and miR-205 might be associated with hormone receptor status in endometrial cancer and may possess prognostic impacts.     

富含半胱氨酸蛋白61在结直肠癌中的应用

目的通过测定结直肠癌(colorectal cancer,CRC)患者血清富含半胱氨酸蛋白61(cysteine-rich Protein 61,Cyr61)水平,分析其用于结直肠癌诊断和病理评估的价值。方法用ELISA方法检测血清Cyr61浓度,再用ROC曲线计算最佳灵敏度和特异性,比较Cyr61在诊断结直肠癌的效果;分析Cyr61水平与结直肠癌TNM分期及淋巴结转移的关系,探究血清Cyr61水平与结直肠癌临床病理分期的关系。结果 CRC患者的血清Cyr61水平明显高于健康对照组(P<0.05),血清Cyr61、CEA和CA19-9检测对诊断结直肠癌的灵敏度分别为70.2%、48.2%和48.9%,Ⅲ-Ⅳ期血清Cyr61表达高于Ⅰ-Ⅱ期,有淋巴结转移的血清Cyr61表达高于无淋巴结转移。结论血清Cyr61水平可作为CRC诊断的潜在标志物,且与肿瘤分期和淋巴结转移有关,血清Cyr61水平对结直肠癌的监测有重要意义。