TNF-α和低氧对胰腺癌细胞表达VEGF-A、C的调节

目的:探讨细胞活素肿瘤坏死因子-α(TNF-α)、SNAP(S-Nitroso-Nacetyl-penicillamine)对胰腺癌细胞产生血管内皮生长因子A、C(VEGF-A、C)的调节.方法:用Northern杂交和Western杂交法分析6种人胰腺癌细胞株中VEGF-A、C基因和蛋白的表达;以TNF-α或SNAP刺激其中两个细胞株后用逆转录-聚合酶链式反应技术(RT-PCR)分析其VEGF-A、C基因的表达.结果:Northern杂交法显示这6种胰腺癌细胞株均有4.1kb VEGF-A基因和2.4kb VEGF-C基因的表达;Western杂交法显示它们均有分子量为43kD的VEGF-A蛋白质和分子量为55kD的VEGF-C蛋白质的表达.RT-PCR分析法显示:TNF-α使细胞株COLO-357产生VEGF-A、VEGF-C mRNA分别减少约1～2.5倍、1～2倍,使细胞株CAPAN-1产生VEGF-A、VEGF-C mRNA分别减少约1倍、1.6～2.5倍;而SNAP刺激细胞株COLO-357产生VEGF-A mRNA增加约5倍,刺激细胞株CAPAN-1产生VEGF-A mRNA增加约4倍,但对这两种细胞株产生VEGF-C mRNA均无明显刺激作用.结论:细胞活素TNF-α和低氧通过调节血管内皮生长因子A、C的表达而影响胰腺癌细胞的生物学特性,抑制癌细胞的增殖,促进其凋亡、死亡或进展、恶化.     

Transient retrograde interfragmentary compression technique in AO/OTA type 33-C distal femur fractures: A surgical technique and short-term radiographic follow up results

Surgical treatment of AO/OTA type 33-C fractures is a therapeutic challenge despite advances in surgical instruments and techniques. We introduce a novel surgical technique named transient retrograde interfragmentary compression (TRIC) to help intraarticular fragment reduction in AO/OTA type 33-C fracture. We inserted a partial threaded 7.0-cannulated screw with a washer along the transepicondylar axis from the medial femoral epicondyle during the articular block reduction process of AO/OTA type 33-C fractures to strengthen the compressive force between the condylar fragments and to enhance the handling of the articular block fragment in the alignmental correction stage. Following the provisional reduction and fixation using lateral distal femur locking compression plate, TRIC screw was removed. Fifteen AO/OTA type 33-C distal femoral intraarticular fractures of thirteen patients were surgically treated using the TRIC technique. We analyzed the radiographic result of the patients by measuring the horizontal gap and vertical step-off in the postoperative radiographs. Mean horizontal fracture gap was 0.34 mm and mean vertical step-off between bicondylar fragments was 0.63 mm. The median value of the horizontal fracture gap and vertical step off was 0 and 0.46 mm, respectively. Mean time to union in the bicondylar fracture fragment was 9 week. TRIC is considered to be a valuable surgical reduction technique in the treatment of the AO/OTA 33-C type fractures.     

Effect of Atrial Natriuretic Factor [ANF (arg 101–Tyr 126)] on Kallikrein and Cyclic GMP in the Renovascular Hypertensive Rat

The intravenous injection of an ED₅₀ natriuretic dose (1 μg) of synthetic ANF decreases blood pressure by 61 ± 6 mmHg in 2-K, 1-C, and of 45 ± 6 mmHg in 1-K, 1-C hypertensive rats, which was positively correlated with its initial level only in the 2-K, 1-C group. The hypotensive response lasted longer in the latter (> 40 min) than in normotensive sham-operated rats. No difference in duration was seen between 1-K, 1-C hypertensive and its uninephrectomized normotensive controls. The diuretic response to ANF was higher in 2-K, 1-C rats. No hematocrit changes were observed in any group. ANF induced a rise in urinary kallikrein in all groups but the 1-K, 1-C. Urinary kallikrein excretion was positively correlated with natriuresis in normotensive but not in hypertensive groups. ANF induced an increase in urinary cGMP excretion in all groups but the 1-K, 1-C, and an increase in plasma cGMP in the normotensive sham-operated animals.

Our results suggest that the fall in blood pressure induced by synthetic ANF could be due to vasodilatation, a drop in cardiac output cannot, however, be eliminated. Whether the hypotensive effect of ANF is mediated by cGMP remains to be demonstrated.     

Impacts of Sensation,Perception, and Motor Abilities of the Ipsilesional Upper Limb on Hand Functions in Unilateral Stroke: Quantifications From Biomechanical and Functional Perspectives

Background

The presence of subtle losses in hand dexterity after stroke affects the regaining of independence with regard to activities of daily living. Therefore, awareness of ipsilesional upper extremity (UE) function may be of importance when developing a comprehensive rehabilitation program. However, current hand function tests seem to be unable to identify asymptomatic UE impairments.

G蛋白β3亚单位C825T基因多态性与富马酸比索洛尔降压疗效的相关性

 目的 探讨G蛋白β₃亚单位C825T基因多态性与富马酸比索洛尔降压疗效的相关性。方法 选择2018-10至2020-10在解放军总医院第一医学中心心内科住院或门诊就诊的轻、中度原发性高血压患者,均口服5 mg/d比索洛尔,进行GNβ₃-C825T基因型测定,依据基因型分为3组:CC组、CT组、TT组,每组150例,在3组受试者治疗7 d,1、3、6个月后进行随访,测定患者的富马酸比索洛尔药物代谢血药浓度;治疗前、治疗7 d,1、3、6个月后进行24 h动态血压监测,比较患者静息状态下收缩压及舒张压(SBP、DBP),24 h收缩压均数(24 h SBP)、24 h舒张压均数(24 h DBP)、白天收缩压均数(d SBP)、白天舒张压均数(d DBP)、夜间收缩压均数(n SBP)、夜间舒张压均数(n DBP)的组间差异;进行24 h动态心电图监测,比较24 h平均心率、窦性心律震荡水平。结果 治疗7 d,随访1、3、6个月TT组富马酸比索洛尔血药浓度均高于CC组及CT组,差异均有统计学意义(P＜0.05),CC组与CT组无统计学差异,3组组内不同时间血药浓度变化均无统计学差异;应用富马酸比索洛尔后,3组患者血压均有下降趋势,其中TT组降压效果＞CT组＞CC组,3组间血压下降水平有统计学差异(P＜0.05);治疗7 d后,动态心电图显示:3组患者心率有下降趋势,TT组＞CT组＞CC组,其中TT组与CT组、CC组比较有统计学差异(P＜0.05),CT组与CC组心率下降无统计学差异;TT组窦性心律震荡水平优于CT组、CC组。结论 G蛋白β₃亚单位C825T基因多态性与富马酸比索洛尔降压疗效之间具有相关性。     

CYP2C19*2/ABCB1-C3435T polymorphism and risk of cardiovascular events in coronary artery disease patients on clopidogrel: Is clinical testing helpful?

BackgroundStudies evaluating CYP2C19*2 and ABCB1-C3435T polymorphisms have shown conflicting results. We performed this meta-analysis to evaluate role of clinical testing for these polymorphisms in CAD patients on clopidogrel.Methods19,601 patients from 14 trials were analyzed. The endpoints were major adverse cardiovascular events (MACE), cardiovascular (CV) death, stent thrombosis (ST), myocardial infarction (MI), stroke and major bleeding. Combined relative risks (RR) with 95% confidence intervals (CI) were computed for each outcome by using standard methods of meta-analysis and test parameters were computed.ResultsCYP2C19*2 polymorphism was associated with higher risk of MACE [RR: 1.28, CI: 1.06–1.54; p = 0.009], CV death [RR: 3.21, CI: 1.65–6.23; p = 0.001], MI [RR: 1.36, CI: 1.12–1.65; p = 0.002], ST [RR: 2.41, CI: 1.69–3.41; p < 0.001]. No difference was seen in major bleeding events [RR: 1.02, CI: 0.86–1.20; p = 0.83]. Subgroup analysis showed similar results for elective PCI [RR: 1.34, CI: 1.01–1.76; p = 0.03], and PCI with DES [RR: 1.53, CI: 1.029–1.269; p = 0.03]. CYP2C19*2 polymorphism has very low sensitivity (28–58%), specificity (71–73%), positive predictive value (3–10%) but good negative predictive value (92–99%). ABCB1-C3435T polymorphism analysis revealed similar MACE [RR: 1.13, CI: 0.99–1.29; p = 0.06], ST [RR: 0.88, CI: 0.52–1.47; p = 0.63] and major bleeding [RR: 1.04, CI: 0.87–1.25; p = 0.62] in both groups.ConclusionIn CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events. However, due to the low positive predictive value, routine genetic testing cannot be recommended at present.     

Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8

Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of “Spice” and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥ 10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast to other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material.     

甲胎蛋白、Ⅳ型胶原蛋白、甘胆酸、GPC3在乙型肝炎肝硬化与肝癌鉴别诊断的临床价值

目的 探讨血清甲胎蛋白(AFP)、Ⅳ型胶原蛋白(Ⅳ-C)、甘胆酸(CG)、磷脂酰肌醇蛋白聚糖3(GPC-3)水平在乙型肝炎肝硬化及原发性肝癌(PHC)鉴别诊断中的应用价值.方法 采用前瞻性队列研究,选择内蒙古医科大学附属医院2018年8月至2020年3月收治的55例PHC患者(PHC组),62例乙型肝炎肝硬化患者(肝硬...     

原发性甲状腺功能减退症患者血脂谱变化的特点

目的 探讨原发性甲状腺功能减退症患者的血清脂蛋白胆固醇亚组分的变化.方法 原发性甲状腺功能减退症患者38例分为临床甲状腺功能减退组(甲减组,20例)、亚临床甲状腺功能减退组(亚甲减组,18例),另选择20例健康体检者作对照(对照组).留取患者空腹静脉血5 ml,分离血清取上清液-80℃冰箱保存,配置密度液,在不同背景密度下超速离心,采用胆固醇氧化酶法测定血清小而密低密度脂蛋白胆固醇(sdLDL-C)、高密度脂蛋白2胆固醇(HDL2-C)、高密度脂蛋白3胆固醇(HDL3-C)的水平.同时检测三碘甲状原氨酸(T3)、甲状腺素(T4)和促甲状腺素(TSH),统计分析其与血清脂蛋白胆固醇亚组分的相关性.结果①甲减组和亚甲减组患者总胆固醇、三酰甘油、LDL胆固醇水平高于对照组,HDL水平低于对照组,差异有统计学意义(P＜0.05);②甲减组和亚甲减组患者sdLDL-C水平高于对照组,差异有统计学意义(P＜0.05);甲减组和亚甲减组血清HDL2-C低于对照组,差异有统计学意义(P＜0.05);HDL3-C组间比较差异无统计学意义;甲减组与亚甲减组sdLDL-C、HDL2-C、HDL3-C比较差异无统计学意义;③原发性甲状腺功能异常发生时,sdLDL-C水平与TSH呈正相关性(r =0.287,P=0.026),与T4呈负相关性(r=-0.267,P =0.039);与T3无相关性;HDL2-C与T3、T4呈正相关性(r =0.271、0.270,P=0.036、0.037);HDL3-C与TSH、T3、T4无明显相关性.结论 甲状腺功能减退症患者的临床血脂谱及脂蛋白胆固醇亚组分产生变化,并与甲状腺功能相关.     

万氏改良推拿手法治疗C_1-C_2失稳型颈椎病的研究

目的：探索经颅多普勒（TCD）超声在万氏改良旋转复位手法治疗颈椎C1-C2失稳的诊断及疗效的评定价值。方法：按临床诊断标准收集椎动脉C1-C2失稳型颈椎病患者157例（疾病组）,对照组为年龄相近的健康人群38例。采用德国进口的DWL-X-4型彩色经颅多普勒超声仪于万氏改良推拿手法治疗C1-C2失稳型颈椎病前后对脑血管血流进行检测分析。结果：疾病组（治疗前）椎基底动脉血流速度明显低于对照组（P〈0.05）;疾病组（治疗前）TCD异常率为90.6%,治疗后椎基底动脉系血流速度明显改善（P〈0.05）与对照组相比无显著差异（P〉0.05）。结论：TCD可作为椎动脉C1-C2失稳型颈椎病患者辅助诊断及疗效评定的参考依据。