基于Raf-MEK-ERK信号通路探究梓醇对蛛网膜下腔出血大鼠脑组织损伤的影响

[目的] 通过考察梓醇对蛛网膜下腔出血（SAH）大鼠脑组织丝/苏氨酸蛋白激酶（Raf）-丝裂原活化蛋白激酶（MEK）-细胞外调节蛋白激酶（ERK）信号通路的影响,探讨其抗SAH脑损伤的作用机制。[方法] 将大鼠随机分为假手术组、SAH组、梓醇组、梓醇+U0126组（梓醇+Raf-MEK-ERK信号通路抑制剂U0126）。采用血管内穿孔法构建大鼠SAH模型,评估大鼠神经功能和SAH分级,伊文思蓝（EB）检测血脑屏障通透性,苏木素-伊红（HE）染色观察脑组织病理变化,免疫荧光染色检测神经元细胞凋亡及微管连接蛋白轻链3-Ⅱ（LC3-Ⅱ）、p-ERK阳性细胞表达,蛋白免疫印迹（Western blot）检测脑组织Raf、MEK、磷酸化（p）-MEK、ERK1/2、p-ERK1/2、B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）、自噬基因Beclin-1、LC3-Ⅱ表达。[结果] 与假手术组相比,SAH组神经元细胞排列松散,数目减少,SAH分级、脑组织含水量、EB渗出量、原位末端标（TUNEL）阳性细胞数显著增加,凋亡率、LC3-Ⅱ、p-ERK阳性表达、Bax、Beclin-1、LC3-Ⅱ、Raf、p-MEK/MEK、p-ERK1/2/ERK1/2表达显著升高,神经功能评分减少,Bcl-2蛋白表达降低（P<0.05）;与SAH组相比,梓醇组神经元损伤明显减轻,细胞死亡较少,SAH分级、脑组织含水量、EB渗出量、TUNEL阳性细胞数显著减少,凋亡率、Bax显著降低,神经功能评分、Bcl-2表达升高,LC3-Ⅱ、p-ERK阳性表达及Beclin-1、LC3-Ⅱ、Raf、p-MEK/MEK、p-ERK1/2/ERK1/2表达进一步升高（P<0.05）;Raf-MEK-ERK通路抑制剂U0126可逆转梓醇对脑组织损伤的改善作用（P<0.05）。[结论] 梓醇可能通过激活Raf-MEK-ERK信号通路,促进神经细胞自噬,改善SAH大鼠脑损伤。     

膜肾1号方对大鼠肾脏病理及PI3K/Akt/mTOR信号通路表达的影响

[目的] 观察膜肾1号方对膜性肾病大鼠肾脏病理的改善作用及其对自噬通路磷脂肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素靶蛋白（mTOR）相关蛋白表达的影响。[方法] 将大鼠随机分为对照组、模型组、膜肾1号方高剂量组、中剂量组、低剂量组,盐酸贝那普利组。采用大鼠尾静脉注射阳离子化牛血清白蛋白（C-BSA）的方法建立MN大鼠模型,灌胃、取材。苏木精-伊红（HE ）染色法观察大鼠肾脏组织病理改变;免疫球蛋白G（IgG）免疫荧光染色观察大鼠IgG沉积;蛋白免疫印迹法（Western Blot）检测PI3K/Akt/mTOR 信号通路相关蛋白及自噬相关蛋白轻链3（LC3）表达。[结果] 药物干预后,膜肾1号方组大鼠24 h尿蛋白、三酰甘油、总胆固醇、低密度脂蛋白下降且低于模型组,并具有统计学差异（P＜0.05）。光镜下观察,HE染色示正常组肾组织整体结构基本正常,膜性肾病（MN）模型组肾小球毛细血管丛充血,系膜增生,基底膜出现增厚,部分肾小管细胞空泡变、组织内可见炎症细胞浸润,可见嗜复红蛋白及IgG沉积。经膜肾1号方和盐酸贝那普利干预后,大鼠肾脏病理学改变均有所减轻。各组大鼠IgG沉积显示,与对照组比较模型组IgG沉积明显,IgG荧光表达升高,差异具有统计学意义（P＜0.05）,盐酸贝那普利组和膜肾1号方组IgG荧光表达下降且低于模型组,具有统计学差异（P＜0.05）。Western Blot检测显示,药物干预后,盐酸贝那普利组和膜肾1号方组大鼠PI3K-Akt信号通路相关蛋白表达下降,LC3 表达增加,并具有统计学差异（P＜0.05）。[结论] 膜肾1号方可改善大鼠肾脏病理损伤,膜肾1号方干预后PI3K-Akt信号通路相关蛋白磷酸化磷酸肌醇3激酶（p-PI3K）,磷酸化Akt蛋白（p-Akt）,磷酸化雷帕霉素靶蛋白（p-mTOR）表达明显降低,自噬相关蛋白LC3表达升高,其分子机制与自噬信号通路的调控有关。     

古草生机汤对H22荷瘤小鼠体内抑瘤及免疫调节作用的初步研究

目的：探究古草生机汤对H22荷瘤小鼠体内实体瘤的抑瘤功效和对机体的免疫调节作用机制。方法：本研究采用H22实体瘤动物模型,随机分为空白组、模型组、阳性药组、古草生机汤低、高剂量组,灌胃给药7 d,计算各组小鼠的体质量增长率、肿瘤抑制率、胸腺及脾指数,小鼠实体瘤病理切片苏木精-伊红（HE）染色观察瘤体组织和细胞形态,酶联免疫吸附试验法检测小鼠血清中γ干扰素（IFN-γ）、肿瘤坏死因子-α(TNF-α)、白细胞介素-2（IL-2）、Fas、Fas配体、天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）的含量,实时荧光定量PCR测量小鼠瘤组织中Bax和Bcl-2mRNA的相对表达量。结果：古草生机汤有促进H22荷瘤小鼠体质量增长、抑制体内实体瘤增长和促进肿瘤凋亡坏死的作用,可提高小鼠的胸腺指数同时降低脾脏指数,可显著提高小鼠血清中IFN-γ、TNF-α、IL-2的含量并降低Fas、Fas配体、AST、ALT的含量（均P<0.01）,能够上调小鼠瘤组织中Bax mRNA的表达并下调Bcl-2mRNA的表达。结论：古草生机汤具有明显的体内抗肝肿瘤药效,在抑制肿瘤生长、促进肿瘤细胞凋亡、调节机体免疫方面有一定作用。     

补阳还五汤治疗慢性脑供血不足疗效观察及对血流动力学、认知功能的影响

目的：观察补阳还五汤治疗慢性脑供血不足（CCCI） 的临床疗效及对脑部血流动力学、认知功能 的影响。方法：选取82 例CCCI 患者的临床资料作回顾性分析,根据不同治疗方式分为对照组和观察组各 41 例。对照组给予常规西药治疗,观察组在常规西药治疗基础上加用补阳还五汤治疗。治疗1 个月后比较 2 组临床疗效,治疗前后临床症状评分、基底动脉（BA）、左椎动脉（LVA）、右椎动脉（RVA）、左大脑中动 脉（LMCA）、右大脑中动脉（RMCA） 的平均血流速度（Vm） 及认知功能［蒙特利尔认知评估量表（MoCA）、 简易智力状态检查量表（MMSE）、长谷川痴呆量表（HDS）］ 评分,血浆一氧化氮（NO）、内皮素-1（ET-1） 水平,血清超敏C-反应蛋白（hs-CRP）、白细胞介素-6（IL-6） 水平。结果：观察组总有效率为95.12%,对 照组为80.49%,2 组比较,差异有统计学意义（P＜0.05）。治疗后,2 组头痛、眩晕、失眠、健忘等症状评分 均较治疗前降低（P＜0.05）,且观察组上述各项评分均低于对照组（P＜0.05）。治疗后,2 组BA、LVA、 RVA、LMCA、RMCA 的Vm 值均较治疗前升高（P＜0.05）,且观察组上述各项指标均高于对照组（P＜ 0.05）。治疗后,2 组MoCA、MMSE、HDS 评分均较治疗前升高（P＜0.05）,且观察组上述各项评分均高于对 照组（P＜0.05）。治疗后,2 组血浆ET-1 及血清hs-CRP、IL-6 水平均较治疗前降低（P＜0.05）,血浆NO 水 平较治疗前升高（P＜0.05）;且观察组ET-1、hs-CRP、IL-6 水平均低于对照组（P＜0.05）,NO 水平高于对 照组（P＜0.05）。结论：补阳还五汤治疗CCCI 可缓解临床症状,有效改善患者认知功能、血管内皮功能及血 流动力学状态,抑制机体炎症反应,提高临床治疗效果。     

胆总管囊肿胆管穿孔引流术后二次腹腔镜根治术体会

目的 探讨胆总管囊肿胆管穿孔引流术后采取二次腹腔镜行胆总管囊肿根治术的可行性。方法 回顾性分析徐州医科大学附属徐州儿童医院2012年2月至2020年2月收治的10例胆总管囊肿并胆管穿孔行外引流术、并再次行腹腔镜胆总管囊肿根治术的患儿临床资料,分析术前及术中注意事项,总结相关经验。二次手术采用四孔法,其中脐部及右侧腹切口选择原切口,没有额外增加切口;囊肿分离采取囊肿横断切除法,避免损伤门静脉和肝动脉。结果 10例患儿,其中男4例,女6例;年龄9个月至8岁,平均（3.1±0.6）岁。9例患儿在腔镜下完成二次手术,手术方式为腹腔镜下胆总管囊肿切除肝管空肠Roux-en-Y吻合术。1例因纤维增生囊壁厚,腹腔镜下操作渗血多,不易止血影响操作视野,放弃腹腔镜操作中转开腹手术。所有患儿术中未发生腹腔镜手术副损伤,术后未发生胆漏、肠瘘、腹腔感染等并发症,均康复出院,住院时间7～10 d。结论 采用腹腔镜胆总管囊肿根治术治疗既往有胆管穿孔外引流手术史的患儿是安全可行的。     

Clinicopathological characteristics,prognosis, and chemosensitivity in patients with metastatic upper tract urothelial carcinoma

PurposeTo investigate the clinical characteristics, chemosensitivity, and outcome of metastatic upper tract urothelial carcinoma (UTUC).Patients and MethodsRecords of patients with metastatic UTUC since January 2005 were retrieved from a database that included clinical and survival data. Statistical analyses including survival and multivariate analyses of factors were respectively performed by the Kaplan-Meier method and Cox proportional hazard model.ResultsA total of 250 consecutive UTUC cases were evaluated. There were 56 patients (22.4%) with initially diagnosed stage IV disease. The most common metastatic sites were lung (39.6%), distant lymph nodes (39.2%), bone (19.6%), liver (18.0%), and adrenal gland (7.2%), respectively, and the local recurrence rate was 10.4%. Two hundred thirteen patients received first-line chemotherapy. The overall response rate was only 28.7% and the median progression-free survival time was only 5.0 months. The overall survival time of the cohort was 18.0 months. Multivariate analyses showed that initially diagnosed stage IV disease, number of metastatic organs ≥3, no response to chemotherapy and cycles of chemotherapy ≤2 were adverse prognosticators for overall survival.ConclusionUTUC presented to be more prone to metastasize than locally recur and thought to have low chemosensitivity. Stage IV disease at initial diagnosis, number of metastatic organs, response and cycles of chemotherapy were independent prognosticators for metastatic UTUC.     

Treatment of spinal cord compression caused by C2 osteochondroma with reconstruction and fusion after total resection: Case report and literature review

Context: Osteochondroma is the most common benign tumor of the bone, but spinal osteochondroma is rare. We report a case of cervical osteochondroma in multiple exostoses arising from the lamina of the C2 vertebra, presenting with features of compressive myelopathy in a 22-year-old male. Total resection of the tumor and atlantoaxial fixation and fusion after reconstruction of the C1 posterior arch were performed.Findings: The patient recovered significantly. He was asymptomatic and no sign of recurrence was observed after one-year follow-up.Conclusions: Osteochondroma should be considered as a rare cause of spinal cord compression. Entire removal of the tumor will result in complete decompression and can reduce the risk of recurrence. We provide a new approach to reconstruct after resection.     

Short- and Long-Term Outcome after Emergent Cardiac Surgery during Transcatheter Aortic Valve Implantation

Objective: Our study aimed to evaluate short- and long-term outcomes of patients who required emergent conversion from transcatheter aortic valve implantation (TAVI) to open surgery. Besides, the reasons and procedural settings of emergent cardiac surgery (ECS) were also reported.Methods: We retrospectively reviewed the patients who underwent TAVI in our institution between 2012 and 2019 and collected the clinical data of cases who converted from TAVI to bail-out surgery. Telephone and outpatient follow-ups were performed.Results: Of 516 TAVI patients, 20 required ECS, and the bail-out surgery occurred less frequently with the increase in TAVI volume. The most common reason for conversion was left ventricular perforation (7/20, 35.0%). Thirty-day mortality was 35.0% in ECS patients. Kaplan–Meier survival curves showed that the cumulative survival rate was 65.0% at 1 year, 50.1% at 5 years in all ECS patients, and 77.1% at 5 years in patients who survived over 30 days after conversion.Conclusion: Although the bail-out operation was performed immediately after TAVI abortion, ECS still associated with high 30-day mortality. The long-term survival benefit was seen in patients surviving from bail-out surgery. An experienced TAVI team is of crucial importance in avoiding ECS-related life-threatening complications and providing effective salvage surgery.     

The Effect of Minimally Invasive Thoracoscopic Left Atrial Appendage Excision on Cardiac Dynamic and Endocrine Function

Purpose: Left atrial appendage (LAA) isolation is an effective surgical treatment for decreasing thromboembolic risk. We sought to evaluate the short-term effect of minimally invasive surgery with LAA excision on left atrial dynamic and endocrine function in atrial fibrillation (AF) patients.Methods: A total of 52 patients with paroxysmal AF undergoing minimally invasive surgery with LAA excision in Anzhen Hospital from October 2012 to June 2014 were enrolled in the study. The natriuretic peptide plasma level was determined by enzyme-linked immunosorbent assay (ELISA), and left atrial dynamic function was measured preprocedure by real-time three-dimensional echocardiography and postprocedure after 7 days and 3 months.Results: With the exception of six recurrences, 88.5% (46/52) of the patients were prospectively followed over 3 months in terms of their sinus rhythm postprocedure. No severe operative complications or embolism events occurred within those 3 months. Echocardiography showed a 3–6% decrease in left atrial volume postprocedure, and dynamic function was largely restored by 3 months. There was no significant change in natriuretic peptide levels, although a slight decrease was detected 7 days postprocedure, which gradually recovered by 3 months (P = 0.350).Conclusions: There are no significant differences in left atrial dynamics and natriuretic peptide secretion in AF patients after minimally invasive surgery with LAA excision.