慢性移植物抗宿主病狼疮肾炎模型的建立和淋巴细胞功能的变化

目的:探讨慢性移植物抗宿主病(cGVHI))狼疮小鼠肾炎模型方法的建立及其T、B淋巴细胞功能的变化,为进一步探讨狼疮肾炎发病机制奠定基础.方法:(1)将亲代BALB/C小鼠淋巴细胞经静脉途径输入(BALB/C×C57 BL/6)F1代小鼠体内诱导狼疮小鼠模型;(2)测定血清中抗核抗体(ANA)及肾脏病理以检测模型是否成功;(3)用ConA刺激脾和胸腺T细胞,采用MTT法检测成熟与未成熟T细胞对于丝裂原增殖转化能力.结果:(1)模型组血清中ANA均为阳性,而对照组均为阴性;(2)模型小鼠的肾脏有免疫复合物沉积,肾脏有明显的病理损害;(3)模型组成熟T细胞(脾脏细胞)和未成熟T细胞(胸腺细胞)经ConA刺激后增殖能力较对照组减弱.结论:运用cGVHD方法诱导的狼疮肾炎模型,小鼠发病迅速,病理及临床表现与人狼疮肾炎相似,并且存在T、B淋巴细胞功能异常,为应用此模型研究狼疮肾炎提供了理论依据.     

Th1 polarization in murine IgA nephropathy directed by bone marrow-derived cells

IgA nephropathy is the most common form of progressive glomerulonephritis although the pathophysiology of this nephropathy is unclear. The ddY mouse is a spontaneous animal model with variable incidence and extent of glomerular injury mimicking human IgA nephropathy. Here, we transplanted bone marrow cells from 20-week-old ddY mice with beginning or quiescent IgA nephropathy into irradiated similar ddY mice, C57Bl/6 (Th1 prone) mice, or BALB/c (Th2 prone) mice. Serum IgA/IgG complex and Th1/Th2 polarization of spleen cells was determined by enzyme-linked immunosorbent assay and confirmed by fluorescent cytometric analysis. The ddY mice with commencing IgA nephropathy demonstrated strong polarization toward Th1, while those with quiescent disease were Th2 polarized. Serum levels of IgA/IgG2a immune complex significantly correlated with the severity of the glomerular lesions. Bone marrow taken from mice with commencing IgA nephropathy conferred IgA nephropathy with Th1 polarization in recipient-quiescent mice, while transplantation from the quiescent mice ablated glomerular injury and mesangial IgA/IgG deposition in those commencing IgA disease. However, adoptive transfer of CD4(+) T cells from those whose disease began failed to induce any IgA deposition or renal injury. Our study suggests that bone marrow cells, presuming IgA producing cells, may initiate this disease. Th1 cells may be involved in the pathophysiology of the disease after glomerular IgA deposition.     

Muscle weakness,spasticity and disuse contribute to demineralization and geometric changes in the radius following chronic stroke

Summary Bone health status of the radius in individuals with chronic stroke was evaluated using peripheral quantitative computed tomography. Bone mineral density and cortical thickness on the affected side were compromised when compared with the unaffected side. Muscle weakness, spasticity, and disuse were identified as contributing factors to such changes. Introduction Following a stroke, demineralization and geometric changes occur in bone as a result of disuse and residual impairments, and these can contribute to an increased risk of fragility fractures. Methods This study used peripheral quantitative computed tomography (pQCT) to evaluate volumetric bone mineral density and geometry at the midshaft radius in people living with chronic stroke. Older individuals with chronic stroke were recruited. Each subject underwent a pQCT scan of the midshaft radius at the 30% site on both upper limbs. Muscle strength, motor function, spasticity, and chronic disuse were also evaluated. Data from 47 subjects (19 women) were assessed. Results A significant difference was found between the two limbs for cortical bone mineral content, cortical bone mineral density, cortical thickness, and polar stress-strain index. There was no significant side-to-side difference in total bone area. Percent side-to-side difference in muscle strength, spasticity, and chronic disuse were significant determinants of percent side-to-side difference in cortical bone mineral content and cortical thickness. Conclusions The findings suggest that following chronic stroke, endosteal resorption of the midshaft radius occurred with a preservation of total bone area. Muscle weakness, spasticity, chronic disuse significantly contributed to demineralization and geometric changes in the radius following chronic stroke.     

Progressive exercise for anabolism in kidney disease (PEAK): a randomized, controlled trial of resistance training during hemodialysis

Skeletal muscle wasting is common and insidious in patients who receive maintenance hemodialysis treatment for the management of ESRD. The objective of this study was to determine whether 12 wk of high-intensity, progressive resistance training (PRT) administered during routine hemodialysis treatment could improve skeletal muscle quantity and quality versus usual care. Forty-nine patients (62.6 +/- 14.2 yr; 0.3 to 16.7 yr on dialysis) were recruited from the outpatient hemodialysis unit of the St. George Public Hospital (Sydney, Australia). Patients were randomized to PRT + usual care (n = 24) or usual care control only (n = 25). The PRT group performed two sets of 10 exercises at a high intensity (15 to 17/20 on the Borg Scale) using free weights, three times per week for 12 wk during routine hemodialysis treatment. Primary outcomes included thigh muscle quantity (cross-sectional area [CSA]) and quality (intramuscular lipid content via attenuation) evaluated by computed tomography scan. Secondary outcomes included muscle strength, exercise capacity, body circumference measures, proinflammatory cytokine C-reactive protein, and quality of life. There was no statistically significant difference in muscle CSA change between groups. However, there were statistically significant improvements in muscle attenuation, muscle strength, mid-thigh and mid-arm circumference, body weight, and C-reactive protein in the PRT group relative to the nonexercising control group. These findings suggest that patients with ESRD can improve skeletal muscle quality and derive other health-related adaptations solely by engaging in a 12-wk high-intensity PRT regimen during routine hemodialysis treatment sessions. Longer training durations or more sensitive analysis techniques may be required to document alterations in muscle CSA.     

Proteomic analysis of rat penile tissue in a model of erectile dysfunction after radical prostatectomy

OBJECTIVE: To identify differential protein expression in penile tissue in a rat model of erectile dysfunction (ED) at an early stage after bilateral cavernosal nerve (CN) neurectomy, using proteomic techniques. MATERIALS AND METHODS: Twelve male adult Sprague-Dawley rats were randomly divided into two equal groups, one having bilateral CN resection and one a control group. The penises were harvested 7 days after CN resection. Total protein was separated into >1250 protein spots by two-dimensional electrophoresis using pH 3-10 nonlinear immobilized pH gradient strips. Differential expression of proteins was analysed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and database searching. RESULTS: Thirty-two proteins were significantly changed in the denervated penis, of which 25 (including nine up-regulated and 16 down-regulated) with cytoskeletal functions, and pathophysiological functions related to energy metabolism and oxidative stress, were identified. Examples include transgelin, creatine kinase B, annexin-1 and galactin-7. CONCLUSIONS: The expression of several important proteins participating in pathophysiological processes of penile tissue are changed early after bilateral CN neurectomy. These changes might give new insights into the cellular and molecular mechanisms involved in neurogenic ED development, and indicate potential therapeutic targets.     

A comparison of polysomnography and the WatchPAT in the diagnosis of obstructive sleep apnea.

OBJECTIVE: Our goal was to validate the WatchPAT in the diagnosis of obstructive sleep apnea. STUDY DESIGN: We conducted a prospective, blinded, nonrandomized clinical trial. METHODS: Patients with suspected obstructive sleep apnea scheduled for an overnight level I polysomnogram were offered enrollment in a study to compare the WatchPAT (Itamar Ltd, Israel) device with polysomnography. Patients wore the WatchPAT device simultaneously while undergoing polysomnography during evaluation in the sleep lab. RESULTS: Thirty-seven patients participated in the study. They had a mean age of 50.1 years (range, 31-73 years) and mean body mass index of 34.6 kg/m(2) (range, 21.2-46.8 kg/m(2)). There was high correlation between the polysomnogram and WatchPAT apnea-hypopnea index (r = 0.9288; 95% confidence interval = 0.8579-0.9650, P < 0.0001). The lowest oxygen saturation also showed high correlation (r = 0.989; 95% confidence interval = 0.9773-0.9947, P < 0.0001). The overall polysomnogram and WatchPAT sleep times revealed a correlation of r = 0.5815 (P = 0.005). CONCLUSION: The WatchPAT showed a high correlation with the polysomnogram in apnea-hypopnea index, lowest oxygen saturation, and sleep time. SIGNIFICANCE: It's use as a reliable tool in the diagnosis of Obstructive Sleep Apnea.     

Differential retention of alpha-vitamin E is correlated with its transporter gene expression and growth inhibition efficacy in prostate cancer cells

BACKGROUND: Epidemiological studies showed Vit E has protective effects against prostate cancer (PCa). Interestingly, different prostate cancer cells have different sensitivity to alpha-Vit E or VES treatment. The goal of this study is to determine whether cellular Vit E bioavailability and its transport proteins are important contributing factors. METHODS: alpha-Vit E and its ester form, VES, were used to treat prostate cancer LNCaP, PC3, and DU145 cells, and their growth rates were determined by MTT assay. Cellular levels of Vit E were quantified using HPLC as the index of bioavailability. The expression levels of Vit E transport proteins were determined by real-time PCR. RESULTS: Among these PCa cells, only LNCaP cells were sensitive to 20 microM alpha-Vit E treatment, while both LNCaP and PC3 cells were sensitive to 20 microM VES treatment. Coordinately, cellular levels of alpha-Vit E and VES positively correlated to their inhibitory effects. Further study found expression levels of Vit E transport proteins, including tocopherol associated protein (TAP), scavenger receptor class B type I (SR-BI), alpha-tocopherol transfer protein (TTP), and ATP binding cassette transporter A1 (ABCA1), were different in various PCa cells, which may contribute to cellular Vit E bioavailability. This notion is further supported by the findings that overexpression or knockdown of TTP could coordinately alter cellular alpha-Vit E levels in PCa cells. CONCLUSION: Antiproliferative efficacy of alpha-Vit E is correlated with its cellular bioavailability in PCa cells. Modulating the expression of the efflux or influx transporters could sensitize the growth inhibition efficacy of Vit E in prostate cancer cells.     

Systematic Review and Meta-analysis of Laparoscopic Versus Open Distal Gastrectomy

Background

Laparoscopic distal gastrectomy has been increasingly utilized in the treatment of gastric adenocarcinoma. This study aims to compare the morbidity/mortality and postoperative outcomes of laparoscopic-assisted versus open distal gastrectomy since 2000.

Methods

A comprehensive search of MEDLINE and EMBASE was conducted including studies published between 2000 and present.

Results

Seventeen studies with a total of 7,109 distal gastrectomies (3,496 lap vs 3,613 open) were included. Across all studies, postoperative morbidity rates for laparoscopic gastrectomy were lower than that of open [median (range) 10 (0–36)?% vs 17 (0–43)?%]. Meta-analysis of postoperative morbidity rates in prospective studies only yielded pooled odds ratio of 0.52 (95 % CI 0.33–0.81) (P?=?0.004). In-hospital mortality rates were comparable between the two (range: laparoscopic 0–3.3 vs open 0–6.7 %). The long-term oncological outcomes of resection were difficult to analyze given variable reporting but appeared similar between the two. Meta-analysis of prospective studies showed that laparoscopic-assisted distal gastrectomy was associated with significantly shorter hospital length of stay [standard mean difference (SMD)?=??0.78 (95 % CI?=??1.0 to ?0.56)], comparable intraoperative bleeding [SMD?=?0.64 (95 % CI?=??1.3–0.0430) P?=?0.066] and longer operative time compared to open gastrectomy [1.9 (95 % CI 0.05–3.8) P?=?0.045, with P?<?0.001].

Conclusion

This study supports the use of laparoscopic-assisted distal gastrectomy for treatment of gastric adenocarcinoma with evidence of comparable, if not better, short-term postoperative parameters when compared to open distal gastrectomy. The long-term oncological outcomes appear similar but may require more evaluation.     

诺帝-褐藻酸钠微球血管内介入治疗兔VX2肝癌

目的探讨诺帝-褐藻酸钠微球(KMG)血管内介入治疗兔VX2肝癌的效果。方法将50只VX2肝癌模型兔随机分为5组(n=10),于DSA引导下行靶血管灌注:A组灌注生理盐水,B组诺帝,C组KMG,D组5-氟尿嘧啶+KMG,E组诺帝-KMG。术前1天及术后2周行增强CT扫描,比较各组肿瘤体积及体积增长率。采用免疫组织化学方法检测肿瘤组织血管内皮生长因子(VEGF)表达,计数肿瘤微血管密度(MVD)。结果术前1天各组肿瘤体积差异无统计学意义(P均0.05);术后2周,A、B组肿瘤体积及体积增长率均大于C、D、E组(P均0.05)。5组间VEGF阳性率及MVD差异均有统计学意义(P均0.01),E组VEGF阳性率及MVD均低于其他各组(P均0.05)。结论诺帝-KMG血管内介入治疗兔VX2肝癌效果较好。     

血浆脂蛋白相关磷脂酶A2与急性心肌梗死患者心功能的相关性研究

目的：研究急性心肌梗死患者血浆脂蛋白相关磷脂酶A2（Lp?PLA2）浓度变化情况及其与心肌梗死后心功能的相关性。方法：连续入选急性心肌梗死患者90例,测定患者入院即刻（T0）、入院次日（T1）、入院第3天（T2）和入院第7天（T3）血浆Lp?PLA2及心梗后1个月（T4）N端前体脑钠肽（NT?proBNP）水平,并采用二维心脏超声测定T1和T4患者左室射血分数（LVEF）,Pearson相关分析Lp?PLA2与LVEF及NT?proBNP的相关性。以43例同期入院稳定性心绞痛患者和48例健康体检者作为对照。结果：急性心肌梗死患者血浆Lp?PLA2水平呈动态改变,心梗发作时显著增高,而入院第7天后基本降至对照组水平［（61.42±36.99）mg/L vs.（49.83±27.17）mg/L,P > 0.05］。相关性分析显示入院即刻（T0）血浆Lp?PLA2水平与C反应蛋白水平（r=0.06,P > 0.05）及血浆肌钙蛋白T水平（r=-0.07,P > 0.05）均无显著相关性。进一步研究发现入院时（T0）血浆Lp?PLA2水平与T4血浆NT?proBNP水平（P=0.16,P > 0.05）、左室射血分数（LVEF）（r=-0.09,P > 0.05）及T4与T1 LVEF差值（ΔLVEF）（r=0.04,P > 0.05）均无显著相关性。结论：血浆Lp?PLA2水平反映了急性心肌梗死动脉斑块不稳定状态,但与急性心肌梗死患者梗死后心功能恢复情况无关。