加贝酯联合奥曲肽对急性胰腺炎患者胃肠功能、免疫功能及炎性因子水平的影响

目的:探讨加贝酯联合奥曲肽对急性胰腺炎(AP)患者胃肠功能、血清炎性因子及免疫功能的影响。方法:选取2014年1月到2018年6月在我院接受治疗的AP患者100例,采用随机数字表法将所有患者分为对照组和观察组各50例。对照组给予注射用醋酸奥曲肽治疗,观察组在对照组的基础上给予注射用甲磺酸加贝酯治疗。对比两组患者治疗后临床疗效、胃肠功能恢复情况、血清炎性因子水平及免疫球蛋白lgG、lgM、lgA的变化情况。结果:治疗后观察组总有效率为83.24%,高于对照组的67.03%(P0.05)。治疗后观察组排气恢复时间、排便恢复时间、肠鸣音消失时间、腹胀缓解时间、腹痛缓解时间均显著短于对照组(P0.05)。治疗后两组肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)、白细胞介素-6(IL-6)及白细胞介素-8(IL-8)水平较治疗前均明显下降(P0.05),且治疗后观察组的TNF-α、CRP、IL-6及IL-8水平低于对照组(P0.05)。治疗后两组的lgG、lgM、lgA水平均较治疗前均明显升高(P0.05),治疗后观察组的lgG、lgM水平高于对照组(P0.05)。结论:加贝酯联合奥曲肽治疗AP不仅能够有效抑制患者的炎症反应,改善其免疫功能,还能够促进患者胃肠功能恢复,提高临床疗效。     

丹红注射液治疗急性脑梗死的临床疗效分析

目的:探讨丹红注射液治疗急性脑梗死的临床疗效。方法:选择2016年1月至2017年6月来我院进行治疗急性脑梗死疾病患者70例作为本研究的对象,采用随机数字表法均分为研究组和对照组。对照组采用常规抗血小板聚集、降低颅内压、营养脑细胞等治疗,研究组在对照组的基础上采用丹红注射液治疗,对比两组患者的疗效、治疗前后的神经功能缺损评分、日常生活活动能力评分、全血黏度和红细胞比积的变化。结果:治疗后,对照组患者的治疗有效率(82.86%)显著低于研究组(94.29%)(P0.05),研究组患者日常生活活动能力评分显著高于对照组(P0.05),神经功能缺损评分、全血黏度、红细胞比积均显著低于对照组(P0.05)。结论:丹红注射液用于治疗急性脑梗死可显著提高其临床疗效,明显提高患者日常生活能力,改善神经功能和血液流变学。     

奥曲肽辅助十二指肠镜治疗急性水肿型胆源性胰腺炎疗效及对炎症反应的影响

目的:探讨奥曲肽辅助十二指肠镜治疗急性水肿型胆源性胰腺炎疗效及对炎症反应的影响。方法:选择急性水肿型胆源性胰腺炎患者100例,随机分为研究组与对照组各50例,两组患者均给予禁食、抗感染、营养支持、酶抑制剂治疗,对照组同期给予十二指肠镜治疗,研究组同期给予奥曲肽辅助十二指肠镜治疗,比较两组腹痛缓解时间,白细胞(WBC)、体温恢复正常时间,治疗前(T0)、治疗3d(T1)、治疗7d(T2)血、尿淀粉酶水平与炎症因子CRP、IL-6、TNF-α水平的变化。结果:(1)研究组腹痛缓解时间、WBC、体温恢复正常时间均较对照组明显缩短(P0.05);(2)两组患者T1、T2血、尿淀粉酶水平均较T0明显降低,且T2血、尿淀粉酶水平低于T1(P0.05),研究组T1、T2血、尿淀粉酶水平均低于对照组(P0.05);(3)两组T1、T2血清CRP、IL-6、TNF-α水平均较T0明显降低,且T2低于T1(P0.05),研究组T1、T2时血清CRP、IL-6、TNF-α水平均低于对照组(P0.05)。结论:奥曲肽辅助十二指肠镜治疗急性水肿型胆源性胰腺炎可提高早期治疗效果,减轻炎症反应。     

乌司他丁辅助治疗急性重症胰腺炎的疗效及对occludin、CRPI、IL-6水平的影响

目的:研究乌司他丁辅助治疗急性重症胰腺炎的疗效及对咬合蛋白(Occludin)、C反应蛋白(快速)(CRPI)、白细胞介素6(IL-6)水平的影响。方法:选择2014年12月至2016年11月在我院进行治疗的118例急性重症胰腺炎患者,随机将其均分为观察组(59例)和对照组(59例),对照组给予常规治疗,观察组患者则在对照组治疗方案的基础上增加乌司他丁辅助治疗,两组患者的治疗疗程均为两周,记录并比较两组患者治疗前后的血清occludin、CRPI、IL-6水平,治疗后腹胀、腹痛、恶性呕吐及腹膜刺激征等体征消失时间及临床疗效。结果:治疗后,观察组和对照组患者的总有效率分别是88.1%、69.5%,观察组总有效率显著高于对照组(P0.05);观察组患者治疗后的血清occludin水平较对照组患者显著升高(P0.05),血清IL-6及CRPI水平显著低于对照组,且腹胀、腹痛、恶性呕吐、腹膜刺激征等体征消失时间显著短于对照组(P0.05)。结论:乌司他丁辅助治疗重症急性胰腺炎的临床疗效显著优于常规治疗,不仅能改善腹胀、腹痛、恶性呕吐及腹膜刺激征,而且可有效降低患者血清CRPI、IL-6水平和提高occludin水平。     

淋巴细胞/单核细胞比值对急性脑梗死患者预后的预测价值研究

目的:探讨淋巴细胞/单核细胞比值(LMR)对急性脑梗死预后的预测价值。方法:回顾性分析急性脑梗死患者242例的临床资料,根据发病90天改良m RS评分分为预后良好组(163例,m RS 0-2分)和预后不良组(79例,m RS 3-6分),比较其入院时一般人口学资料、美国国立卫生研究院卒中量表评分(NIHSS评分)、血常规、血生化、C反应蛋白(CRP)等资料,根据入院时淋巴细胞与单核细胞计数计算出LMR值,采用logistics回归分析评估LMR与急性脑梗死预后的关系。采用受试者工作特征(ROC)曲线评价入院时LMR水平对急性脑梗预后的预测价值。结果:与预后良好组相比,预后不良组年龄、入院时NIHSS评分、伴随房颤、尿素氮、白细胞、CRP较高,而LMR水平较低,组间差异具有统计学意义(P0.05)。预后不良组LMR水平较预后良好组明显降低(3.48±2.23 vs. 4.39±1.84,P0.05),入院时NIHSS评分增高与低水平LMR是预后不良的独立危险因素(OR值分别为2.066、0.835,95%可信区间为1.668-2.559、0.759-0.946,P0.05)。入院时LMR水平ROC曲线下面积为0.762(95%CI 0.692-0.832),Youden法计算出LMR低于2.633(最佳临界值)预示预后不良,敏感性为86.9%,特异性为47%。结论:入院时LMR水平与急性脑梗死预后不良负相关,低水平LMR对预测急性脑梗死患者预后不良具有一定的参考价值。     

依达拉奉联合克林澳对急性脑梗死患者血清MMP-3、MMP-9、TIMP-1、EPCs的影响及疗效观察

目的:研究依达拉奉联合克林澳对急性脑梗死患者血清MMP-3(基质金属蛋白酶-3)、MMP-9(基质金属蛋白酶-9)、TIMP-1(组织基质金属蛋白酶抑制剂1)、EPCs(内皮祖细胞)的影响及疗效观察。方法:选取我院收治的114例急性脑梗死患者,按照随机数表法分为联合治疗组(n=57)和单独治疗组(n=57)。单独治疗组仅应用依达拉奉治疗,联合治疗组则联合克林澳治疗。观察并比较两组患者临床治疗效果、NIHSS(美国国立卫生研究院卒中量表)评分变化情况、实验室指标水平变化情况、血脂水平变化情况以及不良反应发生情况。结果:治疗后,联合治疗组基本痊愈和显著进步的患者达到49例,其总有效率为85.96%,而单独治疗组基本痊愈和显著进步的患者仅为39例,其总有效率为68.42%,两组比较差异显著(P0.05)。治疗14 d和28 d后,患者的评分均较治疗前有明显下降,同时,联合治疗组下降水平明显优于单独治疗组(P0.05)。两组患者MMP3和MMP9水平较治疗前显著下降,而TIMP-1和EPCs水平则明显上升,且联合治疗组MMP3和MMP9水平下降情况和TIMP-1和EPCs水平上升情况均明显优于单独治疗组(P0.05)。治疗14 d和28 d后,患者血脂各指标水平均较前一次测量有明显下降,且单独治疗组较联合治疗组下降更为明显(P0.05)。联合治疗组不良反应发生率为5.26%;单独治疗组不良反应发生率为10.53%,不良反应发生率比较无统计学意义(P0.05)。结论:依达拉奉联合克林澳应用于治疗急性脑梗死患者疗效确切,有效改善血清MMP-3、MMP-9、TIMP-1、EPCs以及患者血脂异常情况,促进血管新生,保护患者脑组织。     

Synthesis and characterization of amino acid substituted sunitinib analogues for the treatment of AML

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Sunitinib, a multikinase inhibitor, was the first Fms-like tyrosine kinase 3 (FLT3) inhibitor clinically used against AML. Off-target effects are a major concern for multikinase inhibitors. As targeted delivery may reduce such undesired side effects, our goal was to develop novel amino acid substituted derivatives of sunitinib which are potent candidates to be used conjugated with antibodies and peptides. In the current paper we present the synthesis, physicochemical and in vitro characterization of sixty two Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutant kinase inhibitors, bearing amino acid moieties, fit to be conjugated with peptide-based delivery systems via their carboxyl group. We determined the solubility, pK_a, CHI and LogP values of the compounds along with their inhibition potential against FLT3-ITD mutant kinase and on MV4-11 cell line. The ester derivatives of the compounds inhibit the growth of the MV4-11 leukemia cell line at submicromolar concentration.     

Design and synthesis of novel senkyunolide analogues as neuroprotective agents

A class of senkyunolide analogues bearing benzofuranone fragment were designed, synthesized and evaluated for their neuroprotective effect in models of oxygen glucose deprivation (OGD) and oxidative stress. All tested compounds showed neuroprotection profile based on the cell viability assay. In particular, derivatives 1f–1i possessing furoxan-based nitric oxide releasing functionality exhibited significant biological activities in OGD models. More importantly, compound 1g containing short linker with furoxan displayed the most potent neuroprotection at the concentration of 100?μM (cell survival up to 145.2%). Besides, 1g also showed the middle level neuroprotective effect in model of oxidative stress.     

心电图ST段不同改变与急性心肌梗死患者冠脉造影病变特点及生活质量的相关性研究

目的:探讨心电图ST段不同改变与急性心肌梗死患者冠脉造影病变特点及生活质量的相关性。方法:选取选取2015年6月到2017年6月在本院接受治疗的急性心肌梗死患者208例,根据心电图ST段的改变情况将患者分为ST段抬高组(124例)、ST段压低组(64例)、ST段无偏移组(20例),所有患者进行冠脉造影检查和常规治疗,比较治疗前三组患者的冠脉造影情况和冠脉狭窄程度,比较治疗1个月后三组患者的生活质量评分。结果:在ST段抬高组中,共检测出单支血管闭塞病变99例,占79.84%,两支或两支以上血管病变25例,占20.16%,其中侧支循环开放19例,开放率为15.32%。在ST段压低组中,共检测出单支血管非闭塞病变6例,占9.38%,两支或两支以上血管非闭塞病变56例,占87.50%,单支血管闭塞病变2例,占3.13%,其中侧支循环开放34例,开放率为53.13%。在ST段无偏移组中,单支血管闭塞病变15例,占75.00%,单支或多支血管非闭塞病变5例,占25.00%,其中侧支循环开放7例,开放率为35.00%。ST段抬高组、ST段无偏移组患者的冠脉狭窄程度以重度狭窄为主,ST段压低组患者的冠脉狭窄程度以中度狭窄为主,三组患者的轻度狭窄、中度狭窄、重度狭窄整体比较存在统计学差异(P0.05)。三组患者的疼痛评分、躯体受限评分、精神及活动评分整体比较具有统计学差异(P0.05),ST段压低组的上述评分均显著高于ST段抬高组和ST段无偏移组(P0.05)。结论:心电图ST段不同改变与急性心肌梗死患者冠脉造影病变密切相关,且ST段压低患者的预后通常较好。     

Toxicological and immunological evaluation of the MHC-non-restricted cytotoxic T cell line TALL-104

 The human MHC-non-restricted cytotoxic T cell line TALL-104 has been shown to display potent antitumor effects in several animal models with spontaneous and induced malignancies. In view of its potential future use in cancer therapy, we investigated the tolerability and target-organ toxicity of these cells in various animal species. The acute toxicity of TALL-104 cell administrations was evaluated in: (a) healthy immunocompetent mice and immunodeficient (SCID) mice bearing human tumors using multiple (up to 15) intraperitoneal (i.p.) injections, and (b) healthy dogs, tumor-bearing dogs, and healthy monkeys using multiple (up to 17) intravenous (i.v.) injections. TALL-104 cells were γ-irradiated (40 Gy) prior to administration to mice and dogs, but administered without irradiation in monkeys. Cell doses ranged from 5×10⁷/kg to 10¹⁰/kg for each injection. All regimens were well tolerated, the main clinical signs observed being transient gastrointestinal effects. Moderate and transient increases in liver transaminase levels were observed in all animal species. Discrete and transient leukocytosis with neutrophilia was also noted in dogs and monkeys after i.v injections of TALL-104 cells. Histological analysis revealed foci of hepatic necrosis with lympho-/mono-/granulocytic infiltration in immunocompetent mice injected i.p. with 5×10⁹ – 10¹⁰ cells/kg. In the same mice, the colon showed an increased number of muciparous cells and alterations in the villi structure: these alterations were completely reversed by 72 h after the last injection, while liver alterations reversed more slowly (1 week). No delayed or chronic toxicity was observed in any of the animals even when non-irradiated TALL-104 cells were administered: both immunocompetent mice and healthy dogs were found to be grossly and histopathologically normal when sacrificed (1 year and 1 month after the last TALL-104 injection respectively). TALL-104 cells did not persist in these hosts. In addition, monkeys showed no molecular signs of TALL-104-cell-induced leukemia in their blood 1 year after the last cell injection. Despite immunosuppression, most of the tumor-bearing dogs as well as the healthy dogs and monkeys developed both humoral and cellular immune responses against TALL-104 cells. The data derived from these preclinical studies suggest that administration of high doses of irradiated TALL-104 cells is well tolerated and would be unlikely to induce severe toxicity if applied in clinical trials to the treatment of patients with refractory cancer. Received: 8 September 1996 / Accepted: 28 January 1997