蒙药那如-3对大鼠三种脏器中NO含量的影响

目的探讨蒙药那如-3对大鼠心脏、肝脏和肾脏中一氧化氮(NO)含量的影响.方法采用改良的Griess法测定心、肝和肾匀浆中NO含量. 结果大鼠肾匀浆NO含量(9.76±1.24μmol/g)显著高于对照组(6.23±0.69μmol/g,P<0.05).心匀浆和肝匀浆NO含量(9.85±1.52μmol/g,7.36±0.78μmol/g)与对照组(7.09±0.85μmol/g,6.95±0.71μmol/g;P>0.05)相比无统计学意义. 结论蒙药那如-3对大鼠肾脏NO含量有一定影响.     

2015—2019年恩平市农村饮用水水质卫生监测结果分析

目的了解恩平市农村生活饮用水水质卫生状况,为改善农村水质安全提供科学依据。方法2015年3月—2019年3月对恩平市的乡镇水源水、出厂水进行检测。结果2015年3月—2019年3月度共检测水样3424份,水质总的合格率为56.45%,出厂水的平均合格率为34.7%,末梢水的平均合格率为61.30%,水源水平均合格率达84.6%。各类监测指标中,不合格指标有游离余氯、菌落总数、总大肠菌群、浑浊度、pH值、铝、锌、铁、锰。结论恩平市农村生活饮用水水质合格率偏低,需要改进设备;加强水源保护、消毒净化;并积极引导农民减肥增效生产;进行卫生宣传及管理,保障饮用水质量。     

褐云玛瑙螺中枢内支配大触角肌肉神经元的分布

实验用荧光素Ｂｂ逆行追踪方法，研究了褐云玛瑙螺支配大触角肌肉活动的神经元在中枢的分布，结果表明，Ｂｂ标记神经元大多分布于同侧脑节，少量分布于侧脑节，同侧口球节，足节和侧节，Ｂｂ标记神经元大多为中小型神经元，个别属于大型神经元。     

顺铂诱导人卵巢癌COC_1、COC_1/DDP细胞凋亡的研究

目的：探讨顺铂作用于卵巢癌细胞的作用机理。方法：通过电镜、光镜、流式细胞仪等方法观察顺铂诱导人亲代和耐药卵巢癌细胞ＣＯＣ１ 、ＣＯＣ１／ＤＤＰ凋亡,进行细胞周期分析及计算凋亡率。结果：顺铂引起细胞Ｓ期增多、Ｓ期细胞凋亡,ＣＯＣ１ 、ＣＯＣ１／ＤＤＰ细胞凋亡率不同。结论：顺铂药理机制之一是诱导细胞凋亡,耐药与凋亡减少有关。     

狼疮性肾炎病人血浆内皮素级意义

①目的 探讨狼疮性肾炎（ＬＮ）病人血浆内皮素级意义。②方法 采用放射免疫分析法,对２０例正常人和２７例ＬＮ病人的血浆内皮素（ＥＴ－１）含量进行了测定。③结果 ＬＮ病人血浆ＥＴ－１水平高于正常人,而伴有肾功能损害和高血压的ＬＮ病人血浆ＥＴ－１水平高于ＬＮ组和正常人（Ｆ＝５．２８,ｑ＝７．５６￣１１．１０,Ｐ〈０．０５）。ＬＮ病人血浆ＥＴ－１水平与血尿素氮、肌酐呈正相关（ｒ＝０．４１２,０．５０８,Ｐ     

乙状窦后进路桥小脑角区手术并发症分析

目的总结乙状窦后进路桥小脑角区手术并发症的临床表现和发病机理,为临床医生提供相关观察指征和处理方法.方法回顾性分析1993年6月至2001年12月间进行的639例乙状窦后进路桥小脑角区手术的临床资料.结果639例患者中,出现的一般并发症有:眩晕、耳鸣、术侧唇部带状疱疹、暂时性面神经麻痹、皮下明胶海绵液化、伤口感染、眼睑下垂、脑脊液耳鼻漏等;严重并发症有:脑膜炎症22例,蛛网膜下腔出血3例,迟发性小脑血肿2例,化学性脑膜炎3例,应激性胃溃疡1例,脑血管意外致死亡1例.严重并发症发生率5.01%(32/639),经积极治疗,除死亡1例,其余均治愈出院.结论乙状窦后进路是切口小,难度大的手术,熟练的手术技巧是减少手术并发症的关键,及时发现和治疗是减少并发症死亡率的保证,了解并发症的类型和发病机理对预防和处理并发症是非常重要的.     

Orally Administrated Ascorbic Acid Suppresses Neuronal Damage and Modifies Expression of SVCT2 and GLUT1 in the Brain of Diabetic Rats with Cerebral Ischemia-Reperfusion

Diabetes mellitus is known to exacerbate cerebral ischemic injury. In the present study, we investigated antiapoptotic and anti-inflammatory effects of oral supplementation of ascorbic acid (AA) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. We also evaluated the effects of AA on expression of sodium-dependent vitamin C transporter 2 (SVCT2) and glucose transporter 1 (GLUT1) after MCAO/Re in the brain. The diabetic state markedly aggravated MCAO/Re-induced cerebral damage, as assessed by infarct volume and edema. Pretreatment with AA (100 mg/kg, p.o.) for two weeks significantly suppressed the exacerbation of damage in the brain of diabetic rats. AA also suppressed the production of superoxide radical, activation of caspase-3, and expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in the ischemic penumbra. Immunohistochemical staining revealed that expression of SVCT2 was upregulated primarily in neurons and capillary endothelial cells after MCAO/Re in the nondiabetic cortex, accompanied by an increase in total AA (AA + dehydroascorbic acid) in the tissue, and that these responses were suppressed in the diabetic rats. AA supplementation to the diabetic rats restored these responses to the levels of the nondiabetic rats. Furthermore, AA markedly upregulated the basal expression of GLUT1 in endothelial cells of nondiabetic and diabetic cortex, which did not affect total AA levels in the cortex. These results suggest that daily intake of AA attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-apoptotic and anti-inflammatory effects via the improvement of augmented oxidative stress in the brain. AA supplementation may protect endothelial function against the exacerbated ischemic oxidative injury in the diabetic state and improve AA transport through SVCT2 in the cortex.     

Safety and effectiveness of combined scoring balloon and paclitaxel-coated balloon angioplasty for stenosis in the hemodialysis access circuit

Purpose

To evaluate the safety and effectiveness of combined scoring balloon (SB) and paclitaxel-coated balloon (PCB) angioplasty for stenosis in the dysfunctional hemodialysis access circuit.

Evolutionarily related small viral fusogens hijack distinct but modular actin nucleation pathways to drive cell-cell fusion

Fusion-associated small transmembrane (FAST) proteins are a diverse family of nonstructural viral proteins. Once expressed on the plasma membrane of infected cells, they drive fusion with neighboring cells, increasing viral spread and pathogenicity. Unlike viral fusogens with tall ectodomains that pull two membranes together through conformational changes, FAST proteins have short fusogenic ectodomains that cannot bridge the intermembrane gap between neighboring cells. One orthoreovirus FAST protein, p14, has been shown to hijack the actin cytoskeleton to drive cell-cell fusion, but the actin adaptor-binding motif identified in p14 is not found in any other FAST protein. Here, we report that an evolutionarily divergent FAST protein, p22 from aquareovirus, also hijacks the actin cytoskeleton but does so through different adaptor proteins, Intersectin-1 and Cdc42, that trigger N-WASP–mediated branched actin assembly. We show that despite using different pathways, the cytoplasmic tail of p22 can replace that of p14 to create a potent chimeric fusogen, suggesting they are modular and play similar functional roles. When we directly couple p22 with the parallel filament nucleator formin instead of the branched actin nucleation promoting factor N-WASP, its ability to drive fusion is maintained, suggesting that localized mechanical pressure on the plasma membrane coupled to a membrane-disruptive ectodomain is sufficient to drive cell-cell fusion. This work points to a common biophysical strategy used by FAST proteins to push rather than pull membranes together to drive fusion, one that may be harnessed by other short fusogens responsible for physiological cell-cell fusion.

Aquareovirus and orthoreovirus are two genera of the Reoviridae family of segmented double-stranded RNA viruses that form multinucleated syncytia after infection, which can increase viral spread and pathogenicity (1–4). To drive cell-cell fusion, both aquareovirus and orthoreovirus express a nonstructural, fusion-associated small transmembrane (FAST) protein on the plasma membrane of infected cells. The FAST protein is not required for viral entry, and expression of FAST protein alone is sufficient to cause cells to fuse with naïve neighboring cells, forming large multinucleated syncytium (1, 2, 5–12), confirming they are bona fide cell-cell fusogens. Although they have similar function and topology in the membrane, FAST proteins from aquareovirus and orthoreovirus share minimal sequence identity (13). Based on phylogenetic analysis, they are hypothesized to have evolved from a common, likely nonfusogenic, ancestor 510 million years ago (4, 13, 14). Separate gain-of-function events are believed to have produced fusogenic proteins in both aquareovirus and orthoreovirus, with further divergence or acquisition events resulting in the diversity of FAST proteins found in reoviruses today (13).Aquareovirus and orthoreovirus FAST proteins are single-pass membrane proteins of fewer than 200 residues comprised of a mostly disordered cytoplasmic tail, a transmembrane domain, and a small ectodomain of fewer than 40 residues (1, 2). The membrane-disruptive ectodomains of FAST proteins typically have solvent-exposed hydrophobic residues and/or myristoylation motifs that are necessary for cell-cell fusion (5, 15–17). In contrast to other cell-cell fusogens that fuse membranes by pulling them together using conformational changes in their ∼10 nm-tall ectodomains, the ectodomains of FAST proteins have minimal predicted secondary structure, are unlikely to undergo conformational changes to drive membrane fusion (1, 2), and extend only ∼1 nm above the bilayer (5, 18). How such short fusogens can overcome the ∼2 nm repulsive hydration barrier and larger barrier presented by cell surface proteins to reach and fuse with an opposing membrane (5, 18) has been a long-standing question for FAST proteins and other short cell-cell fusogens, such as myomixer and myomaker that are involved in myoblast fusion (19–22).Recently, we found that the FAST protein from reptilian orthoreovirus, p14, hijacks the host cell actin cytoskeleton to drive cell-cell fusion by forming localized branched actin networks (23). This is accomplished through a c-src phosphorylated tyrosine motif, YVNI, in p14’s disordered cytoplasmic tail that binds to a host adaptor protein, Grb2, which then binds to N-WASP and nucleates branched actin assembly. We hypothesize that this directly couples local actin-generated forces to push p14’s short, fusogenic ectodomain into the opposing cell’s plasma membrane (23). While all FAST family proteins have similarly short ectodomains, it is unclear if this is a general strategy used by other FAST proteins to drive cell-cell fusion.Here, we report that a FAST protein from the divergent aquareovirus, p22, also hijacks the host actin cytoskeleton but does so using a molecular strategy distinct from that of the orthoreovirus FAST protein p14. Instead of binding to Grb2, we find that p22 binds to Intersectin-1 through an SH3 binding motif in its cytoplasmic tail, which binds Cdc42 to activate N-WASP–mediated branched actin assembly. We show that despite minimal sequence identity, the p22 cytoplasmic tail can be functionally swapped with that of p14, suggesting that while the cytoplasmic tails of the two FAST proteins evolved independently, they serve a similar function. By directly coupling the ectodomain to a different actin nucleator, we suggest that actin’s functional role is applying mechanical pressure to a fusogenic ectodomain at the plasma membrane. This biophysical role may be shared across other members of the FAST protein family and could be more generally employed by other cell-cell fusogens.     

中西医结合治疗肺结核的临床疗效研究

目的:评价常规化疗方案联合中成药“抗痨合剂”及中医适宜技术治疗肺结核的临床疗效。方法:采用前瞻性研究的方法,连续纳入2017年1月至2019年12月浙江中医药大学附属丽水中医院结核科诊治的300例初治肺结核患者,采用随机数字表法将患者均等分成3组,即常规西药抗结核治疗组(A组)、常规西药抗结核治疗联合中成药抗痨合剂组(B组)、常规西药抗结核治疗联合中成药抗痨合剂及中医适宜技术组(C组)。剔除24例因诊断变更、中断治疗、发生药物不良反应患者后最终纳入276例患者,其中A组97例、B组93例、C组86例。观察并比较三组患者疗程末的中医症状改善情况、肺部病灶吸收情况、T淋巴细胞亚群变化及治疗转归情况。结果:治疗6个月后,B组和C组中医证状改善有效率[92.5%(86/93)和94.2%(81/86)]、肺部病灶吸收有效率[92.5%(86/93)和94.2%(81/86)]、CD3⁺T淋巴细胞百分比[(65.76±5.42)%和(67.06±5.95)%]、CD4⁺T淋巴细胞百分比[(44.97±5.35)%和(46.51±5.26)%]、治疗成功率[94.6%(88/93)和97.7%(84/86)]均明显优于A组[分别为82.5%(80/97)、76.3%(74/97)、(63.80±4.57)%、(42.72±4.82)%、80.4%(78/97)],差异均有统计学意义(χ²=2.000,P=0.046;χ²=2.999,P=0.003;χ²=2.427,P=0.015;χ²=2.886,P=0.004;t=2.699,P=0.008;t=4.186,P=0.005;t=3.048,P=0.003;t=6.428,P<0.001;χ²=2.069,P=0.039;χ²=2.192,P=0.028)。而B组和C组治疗后外周血CD8⁺T淋巴细胞百分比[(27.12±2.32)%和(26.35±3.17)%]均明显低于A组[(29.12±2.21)%],差异有统计学意义(t=5.051,P<0.001;t=9.231,P<0.001)。结论:中西药联合抗结核治疗可明显减轻肺结核患者的临床症状,促进肺部病灶吸收,提高肺结核患者免疫力,有效提高临床疗效,但中医适宜技术的应用效果未得到证实。