老年IgA肾病患者的临床病理特征及预后危险因素

目的探讨老年IgA肾病(IgAN)患者的临床病理特征及预后危险因素。方法选择2009年1月至2013年12月经本院肾脏科肾活检确诊为Ig AN的老年患者93例作为观察组,并在同时期按照1∶4比例选择确诊为Ig AN的成人非老年患者372例作为对照组,比较两组患者性别、年龄、肉眼血尿、基线血压、平均动脉压(MAP)、24 h尿蛋白定量、血清白蛋白(Alb)、血清肌酐(SCr)、血尿酸(UA)、总胆固醇(TC)和甘油三酯(TG),估算的肾小球滤过率(e GFR),分析两组患者肾活检病理检查结果及影响老年Ig AN患者预后的危险因素。结果观察组患者肾脏病病程较对照组短(P0.05),高血压发生率和MAP水平均高于对照组(均P0.05);肾活检时,观察组患者蛋白尿水平及SCr、UA、TC、TG水平均明显高于对照组(均P0.05)。观察组患者肾小球球性硬化比例、节段性肾小球硬化发生率、肾小管萎缩/间质纤维化(TAIF)发生率明显高于对照组(均P0.05)。多因素COX回归模型显示,估算的e GFR、蛋白尿水平和TAIF是患者预后的独立危险因素。结论老年Ig AN患者高血压发生率、蛋白尿水平和肾脏组织的慢性病变情况均高于非老年患者,肾活检时蛋白尿、e GFR水平和TAIF是影响老年Ig AN患者预后的危险因素。     

高尿酸血症对IgA肾病临床病理特征和疾病进展的影响

目的分析IgA肾病(IgA nephropathy, IgAN)伴高尿酸血症的临床和病理特征,并探讨高尿酸血症对IgAN进展的影响。方法以2006年1月至2016年12月福建医科大学附属第一医院行肾组织活检确诊为IgAN的患者为研究对象,根据血尿酸水平分为高尿酸血症组和尿酸正常组,比较分析两组患者临床和病理特征。以血肌酐倍增或进入终末期肾病(ESRD)或进入肾脏替代治疗为观察终点,用Kaplan-Meier法比较两组患者的肾脏生存率,并用逐步Cox回归模型分析影响IgAN进展的危险因素。结果进入终点事件或未进入观察终点但随访时间2年的231例IgAN患者纳入研究,其中伴高尿酸血症组92例(39.8%),血尿酸正常组139例(60.2%)。两组在性别、血压、血肌酐、血尿素氮、24 h尿蛋白、估算的肾小球滤过率(eGFR)、病理分级、肾小管萎缩/间质纤维化程度方面差异有统计学意义(P0.05)。29例进入终点事件,单因素COX回归分析显示肾小球硬化、肾小管萎缩/间质纤维化、24h尿蛋白定量、高尿酸血症、贫血、高血压病、血肌酐、血尿素氮在进展组与非进展组间差异有统计学意义(P0.05);Kaplan-Meier生存曲线提示,IgAN伴高尿酸血症组肾脏存活率较低。逐步校正的多因素COX回归分析显示贫血、24 h尿蛋白、肾小球硬化、血肌酐是IgAN进展的独立危险因素。结论伴高尿酸血症的IgAN患者临床表现和肾脏病理损害更重,肾小管萎缩/肾间质纤维化程度更高,肾脏存活率更低。     

Apelin和APJ在IgA肾病中的表达及与肾间质纤维化相关性研究

目的探讨多肽Apelin及其受体APJ在IgA肾病(IgAN)患者血浆及肾组织中的表达情况,分析其与患者临床指标及肾间质纤维化程度之间的相关关系。方法选取2018年1月至2018年12月在北京友谊医院经肾活检确诊的原发性IgAN患者56例,按2009年IgAN牛津病理分型中的肾小管萎缩/肾间质纤维化程度标准,将患者分为3组:T0组(20例)、Tl组(17例)和T2组(19例);选取同期该院肾活检确诊的微小病变性肾病(MCD)患者20例作为对照。收集患者一般资料和常规临床指标,留取血浆和肾组织标本,采用酶联免疫吸附法检测血浆Apelin-12水平,免疫组织化学法观察肾脏APJ受体的表达。对各组指标进行比较,Pearson和Spearman相关分析明确IgAN患者肾组织APJ的表达量与血浆Apelin-12、肾间质纤维化面积及常规临床指标的相关性;多元线性回归分析影响IgAN患者肾组织APJ表达的相关因素。结果 T0组、T1组和T2组血浆Apelin-12和肾组织APJ表达量的差异有统计学意义(均P<0.05),随着肾间质纤维化程度的加重,血浆Apelin-12的浓度逐渐降低,肾脏APJ的表达逐渐增加(均P<0.05)。相关分析显示:IgAN患者肾脏APJ的表达量与肾间质纤维化面积(r=0.930, P<0.001)、血肌酐(r=0.739, P<0.001)、尿素氮水平(r=0.659, P<0.001)呈正相关,与血浆Apelin-12水平(r=-0.712, P<0.001)和估算肾小球滤过率(eGFR)(r=-0.882, P<0.001)呈负相关。多元线性回归分析显示:IgAN患者肾脏APJ的表达量与肾间质纤维化面积呈正相关(β=0.749, P<0.001)。结论 IgAN患者血浆Apelin水平降低,机体上调肾组织APJ受体表达,且APJ的表达量与肾间质纤维化程度呈正相关。提示在IgAN肾间质纤维化的病理过程中,内源性Apelin/APJ系统发挥一定的自身调节作用。     

代谢综合征对肾癌术后肾脏功能和病理改变的影响

目的:探讨代谢综合征(MS)对肾癌患者术后肾脏功能及肾脏病理改变的影响。方法:回顾分析2012年12月至2017年1月期间于福建医科大学福总临床医学院肾癌根治术后病理确诊为肾透明细胞癌合并MS患者的病理资料及术后随访的临床资料。结果:两组患者术后估算的肾小球滤过率(eGFR)均较术前显著下降(P0.001),术后1周两组间eGFR值无差异(P=0.232),随访中,两组间各时间点eGFR值差异逐渐增大存在统计学差异(P0.05)。随访中,MS组CKD3a期及以上的患者数多于非MS组(P=0.048)。MS组癌旁肾组织脏病理可见肾小球球性硬化、肾小管萎缩及肾间质纤维化等改变。结论:MS可导致肾小球硬化及肾小管萎缩、肾间质纤维化等病变,可影响单侧根治性肾切除术后健侧肾功能的代偿,术后应密切随访患者肾功能的变化。     

肥胖相关性肾病的远期预后及危险因素分析

目的:研究肥胖相关性肾病(ORG)患者长期预后及相关危险因素。方法:选取东部战区总医院国家肾脏疾病临床医学研究中心ORG随访登记数据库,分析2003年1月至2015年12月经肾活检确诊为ORG患者的随访资料。利用Kaplan-Meier法计算肾脏累积生存率,并利用COX回归模型分析预后危险因素。结果:共227例患者纳入本研究,中位随访时间61月,随访期间37例(16. 3%)新发糖尿病,14例(6. 2%)进展至终末期肾病(ESRD),18例(7. 9%)患者发生终点事件[估算的肾小球滤过率(e GFR)下降50%或进入ESED]。患者肾活检后5年、10年累积肾脏生存率分别为93. 6%和89. 9%。多因素COX回归分析结果表明活检时肾功能不全(HR=6. 140,P=0. 001)、重度间质纤维化(HR=9. 102,P=0. 045)和时间平均蛋白尿(HR=1. 578,P=0. 000)是肾脏预后的独立危险因素。调整活检时肾功能不全、时间平均蛋白尿后,重度间质纤维化较无间质纤维化,终点事件风险增加9. 102倍(P=0. 045)。结论:本研究结果表明ORG患者5年、10年肾脏累积生存率分别为93. 6%和89. 9%。活检时肾功能不全、重度间质纤维化、时间平均蛋白尿是ORG患者预后的独立危险因素。     

IgA肾病肾组织诱骗受体2表达变化与肾小管、间质损伤的相关性分析

目的 观察诱骗受体2（DcR2）在IgA肾病患者肾组织的表达及其与肾组织损伤程度的相关性.方法 选取2013年1月～ 2013年9月我院肾内科肾活检证实为IgA肾病患者39例,根据IgAN牛津病理评分肾小管萎缩/间质纤维化评分将患者分为3组,同时选取13例肾错构瘤患者作为对照组.收集各组患者人口学资料、临床数据,免疫组化法检测肾组织DcR2的表达情况,并与肾脏病理损伤评分进行相关分析.结果 DcR2在IgA肾病肾小管上皮细胞表达,其表达水平随着肾脏损伤加重而逐渐增加,与肾小球硬化、肾小管萎缩、间质纤维化呈正相关.结论 DcR2可能以调控肾小管上皮细胞凋亡导致肾间质纤维化,并在IgA肾病进展中发挥重要作用.     

IgA肾病预后不良因素与肾血管病变相关性分析

目的：探讨IgA肾病（IgAN）肾血管病变的危险因素。方法选择宁夏人民医院肾脏内科2010年10月至2013年7月经肾活检确诊的原发性IgAN患者100例,并将其分为肾血管病变组和无肾血管病变组,进行对照研究,比较肾血管病变与各项临床指标、病理改变之间的关系。结果100例IgAN患者中有肾血管病变者70例（70%）,无肾血管病变者30例（30%）。单因素分析结果表明,肾血管病变组24h尿蛋白、血尿酸、血肌酐均高于无肾血管病变组（P＜0.05）,血清白蛋白低于无肾血管病变组（P＜0.05）;病理学检查显示肾小球硬化、肾间质纤维化、新月体形成、炎性细胞浸润、肾小管萎缩严重病理表现发生率,肾血管病变组明显高于无肾血管病变组（P＜0.05）。多因素非条件logistic回归分析结果表明,高血压（OR＝7.728,95%CI 1.708～34.964）、24h尿蛋白定量（OR＝20.022,95%CI 3.869～103.623）、肾小球硬化（OR＝12.093,95%CI 2.431～60.149）、肾间质纤维化（OR＝8.511,95%CI 1.332～54.396）是IgAN肾血管病变加重的危险因素。结论 IgAN预后不良因素为高血压、24h尿蛋白定量、肾小球硬化、肾间质纤维化,上述指标与IgAN肾血管病变密切相关,进一步证实了肾血管病变可作为判断预后的一项重要病理指标。     

青年特发性膜性肾病临床病理特征

目的:探讨青年特发性膜性肾病(IMN)患者临床病理特征及其预后。方法:回顾性分析2010-01-01日至2017-12-31日在福建医科大学附属第一医院确诊为IMN的118例患者的临床病理资料,按年龄分为青年组(46例)和中老年组(72例)。采用Kaplan-Meier法绘制生存曲线;分析影响IMN患者预后的危险因素。结果:与中老年组相比,青年组患者合并高血压的比例低,血红蛋白、估算的肾小球滤过率(eGFR)更高,肾间质纤维化、肾小球球性硬化、血管病变比例低(P均0.05)。中位随访36(6～99)月,青年组患者肾脏累计生存率高于中老年组(χ~2=5.034,P=0.015)。多因素COX比例风险模型分析显示,合并新月体形成(HR=10.377,P0.001)、起病时eGFR(HR=0.932,P0.001)、早期尿蛋白缓解(HR=0.359,P=0.002)是影响IMN患者肾脏预后的独立危险因素。结论:与中老年患者相比,青年IMN患者的临床病理表现相对较轻,肾脏预后相对较好。     

尿视黄醇结合蛋白、N-乙酰-β-D-氨基葡萄糖苷酶及尿蛋白检测在IgA肾病患者肾小管间质损害中的临床意义

目的 探讨尿视黄醇结合蛋白（RBP）、N-乙酰-β-D-氨基葡萄糖苷酶（NAG）及24小时尿蛋白定量（UPE）等指标判断IgA肾病（IgAN）患者肾小管间质损害程度的临床意义.方法 收集我院2010年5月～2013年2月114例住院IgAN患者的临床及病理资料,依据Lee氏病理分级系统将患者分为Lee I～Ⅱ级27例（A组）、LeeⅢ级46例（B组）和LeeⅣ～V级41例（C组）,分析不同分级IgAN肾小管间质病变情况与尿RBP、NAG、UPE等指标之间的相关性.结果 各组间血红蛋白（Hb）、白蛋白（ALB）、前白蛋白（pre-ALB）、血肌酐（SCr）、尿素氮（BUN）、总胆固醇（TC）、UPE、尿RBP及NAG等指标比较差异有统计学意义（P＜0.01）,镜下血尿及高血压的发生率随病理程度加重而上升（P＜0.01）,肾小管萎缩、肾间质炎细胞浸润、肾间质纤维化及动脉硬化在各组间比较差异均有统计学意义（P＜0.01）,相关性分析显示尿RBP、NAG与肾小管萎缩、肾间质炎症细胞浸润、肾间质纤维化及动脉硬化程度呈正相关;UPE与肾小管萎缩程度呈负相关（r=-0.213,P＜0.05）,尿RBP、NAG水平与eGFR呈负相关.结论 IgAN患者高血压及血尿发生率、Hb、ALB、TC、肾功能、RBP、NAG、UPE等指标与肾脏病理损伤程度有关,尿RBP、NAG及UPE联合检测对判断肾小管病理损伤程度及肾功能有临床意义.     

肥大细胞在肥胖相关性肾病肾组织损伤中的作用

目的:观察肥胖相关性肾病(obesity related glomerulopathy,ORG)患者肾组织肥大细胞数量、分布特点及其与病情的关系,探讨肥大细胞与ORG肾组织损伤及病情进展之间的关系.方法:选取经肾活检确诊的ORG 39例,应用免疫组化及双重免疫荧光法检测肾组织中肥大细胞(类胰蛋白酶)和巨噬细胞(CD68)分布情况,分析两者与临床病理之间的关系.结果:ORG患者肾组织中肥大细胞数显著高于对照组(P<0.01),其主要分布在肾间质,以萎缩的肾小管和间质纤维化处更多见,并可见肾小管炎;肾小球内未见肥大细胞浸润,但球囊周围可见肥大细胞浸润;小血管周围也可见肥大细胞浸润.肾间质肥大细胞数与体质量指数(body mass index,BMI)(r=0.364,P<0.05)、收缩压(r=0.459,P<0.01)、舒张压(r=0.347,P<0.05)、尿N-乙酰-β-D-葡萄糖苷酶(NAG)(r=0.324,P<0.05)、血清肌酐SCr)水平(r=0.637,P<0.01)、肾小球球性硬化(r=0.409,P<0.01)、肾小球节段硬化(r=0.457,P<0.01)、肾小管萎缩(r=0.470,P<0.01)和肾间质纤维化(r=0.669,P<0.01)指标间成正相关,与采用MDRD公式计算的肾小球滤过率(eGFR)水平呈负相关(r＝-0.559,P<0.01).ORG患者肾组织巨噬细胞数也显著高于对照组,且主要分布在有较多炎性细胞浸润的肾间质中,肾小球内也有少量浸润.巨噬细胞数量与间质炎细胞数量呈正相关(r=0.476,P<0.01).双重免疫荧光染色提示巨噬细胞与肥大细胞在分布上有一定的一致性.多元回归分析显示肾间质肥大细胞浸润程度是影响eGFR水平的独立因素.结论:本研究证实ORG患者肾间质肥大细胞数量增多,并主要分布在肾小管周围、间质纤维化处和肾小球球囊周围,其数量与BMI、血压、肾小管损伤及肾功能进展之间存在显著的相关性,表明肥大细胞参与了ORG的发生和发展过程.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.