西尼必利联合胃复春片治疗慢性萎缩性胃炎的临床研究

目的 探讨酒石酸西尼必利片联合胃复春片治疗慢性萎缩性胃炎的临床疗效。方法 选取2018年1月—2019年3月天津中医药大学第一附属医院收治的120例慢性萎缩性胃炎患者作为研究对象,按照随机数字表法将所有患者分为对照组和治疗组,每组各60例。对照组口服胃复春片,4片/次,3次/d。治疗组在对照组的基础上饭前15 min口服酒石酸西尼必利片,1 mg/次,3次/d。两组患者连续治疗12周。观察两组临床疗效,比较两组的临床症状评分、胃黏膜炎症病理评分、胃泌素（GAS）、胃动素（MTL）及谷胱甘肽过氧化物酶（GSH-Px）、前列腺素E₂（PGE₂）。结果 治疗后,治疗组的临床总有效率为93.33%,明显高于对照组80.00%,差异具有统计学意义（P<0.05）。治疗后,两组患者胃脘疼痛评分、胃中嘈杂评分、嗳气泛酸评分、胃黏膜炎症病理评分均较治疗前明显降低（P<0.05）;并且治疗后治疗组患者临床症状评分、胃黏膜炎症病理评分均明显低于对照组（P<0.05）。治疗后,两组患者GAS、MTL水平均较治疗前明显降低,GSH-Px、PGE₂水平较治疗前明显升高（P<0.05）;治疗后,治疗组患者GAS、MTL水平明显低于对照组,GSH-Px、PGE₂水平明显高于对照组（P<0.05）。结论 酒石酸西尼必利片联合胃复春片治疗慢性萎缩性胃炎的疗效确切,能有效改善临床症状、减轻胃黏膜炎症。     

Hydrogen attenuates radiation-induced intestinal damage by reducing oxidative stress and inflammatory response

The small intestine is known to be particularly sensitive to radiation, and the major limiting factor of radiotherapy is the gastrointestinal syndrome that subsequently develops after its administration. The detrimental effects of radiation are mostly mediated via the overproduction of reactive oxygen species (ROS), especially the hydroxyl radical (·OH). Because hydrogen is a selective ·OH scavenger, we hypothesized that hydrogen might exert a protective effect against radiation-induced intestinal damage. Herein, radiation models were built both in mice and in an intestinal crypt epithelial cell (IEC-6) line. In the animal experiment, we demonstrated that hydrogen-rich saline significantly reduced radiation-induced intestinal mucosal damage, improved intestinal function, and increased the survival rate. In addition, radiation-induced oxidative stress damage and systemic inflammatory response were also mitigated by hydrogen treatment. Moreover, hydrogen treatment decreased cell apoptosis and maintained intestinal epithelial cell proliferation in mice. In vitro experiments using the IEC-6 cell line showed that hydrogen-rich medium significantly inhibited ROS formation, maintained cell viability, and inhibited cell apoptosis. Importantly, hydrogen treatment prevented mitochondrial depolarization, cytochrome c release, and activity of caspase-3, caspase-9, and PARP. Moreover, the decreased expression of Bcl-xl and Bcl-2 and the increased expression of Bax protein were also blocked by hydrogen treatment. In conclusion, our study concurrently demonstrated that hydrogen provides an obviously protective effect on radiation-induced intestinal and cell injuries. Our work demonstrated that this protective effect might be due to the blockage of the mitochondrial apoptotic pathway.     

Effects of catalase and 1400W on the number of interleukin-4 and interferon-γ secreting spleen cells in mice injected with ovalbumin and alum

Context: Alum is thought to induce inflammation resulting in the release of danger signals such as uric acid (UA) which in turn enhances the immune response to an antigen. Hydrogen peroxide (H₂O₂) is produced as a byproduct in the purine catabolic pathway that leads to the production of UA. In addition, serum nitric oxide (NO) levels are increased in inflammation.

Objective: To further explore the mechanism of action of alum, this study was designed to determine the effects of catalase and 1400W on the number of interleukin-4 (IL-4) and interferon-γ (IFN-γ) secreting spleen cells in mice given ovalbumin (OVA) with alum.

Materials and methods: Groups of BALB/c mice were injected intraperitoneally with alum + OVA, alum, OVA, catalase, or 1400W. Other groups were treated with catalase or 1400W and given alum + OVA. The number of IL-4 and IFN-γ secreting spleen cells were determined at days 4 and 7 postinjection by enzyme-linked immunosorbent spot (ELISPOT).

Results: Catalase and 1400W caused a decrease in the number of IL-4 secreting spleen cells induced by alum + OVA. 1400W caused a decline in the IFN-γ secreting spleen cells induced by alum + OVA. Catalase caused an increase in IFN-γ secreting spleen cells.

Discussion and conclusion: It appears that H₂O₂ and NO are needed for alum-induced production of a T-helper 2 cytokine. NO also appears to be needed, whereas H₂O₂ appeared to inhibit an alum-induced production of a T-helper 1 cytokine. These results might explain why alum is mainly a promoter of a T-helper 2 response.     

Just an additional hydrogen bond can dramatically reduce the catalytic activity of Bacillus subtilis lipase A I12T mutant: An integration of computational modeling and experimental analysis

Understanding the structural basis and energetic property of hydrogen bonding and its effects on enzymatic activity is fundamentally important for the rational design of specific enzymes with desired biological functions. In the current study, site-directed mutagenesis analysis preliminarily revealed that the amino acid substitution of Ile12 with Thr12 (I12T) dramatically reduced the hydrolytic activity of Bacillus subtilis lipase A. A further computational investigation proposed that the I12T mutation would establish a geometrically perfect hydrogen bond between the mutated Thr12 and catalytic Ser77 of lipase A, which considerably impaired the catalytic capability of lipase A through two distinct but complementary approaches: rigidizing the enzyme active site and lowering the nucleophilic ability of the catalytic residue Ser77. To verify this hypothesis, a homogenous mutation I12S serving as the control to the I12T mutation was created to examine the hydrogen bonding effect on enzymatic activity. It was found that the I12S mutant only suffered from a slight damage in its hydrolytic ability due to absence of the hydrogen bond originally present at the Thr12–Ser77 interface in the I12T mutant, which was further characterized systematically by quantum mechanics/molecular mechanics (QM/MM) modeling, atom-in-molecules (AIM) analysis and molecular dynamics (MD) simulation. It is suggested that the hydrogen bond arising from the I12T mutation in lipase A can considerably reduce the flexibility and mobility of the enzyme active site, thus impairing the catalytic activity of the lipase A I12T mutant remarkably; the activity loss can be, however, largely recovered by replacing Thr residue at the 12th position of I12T mutant with its analog Ser, which is chemically similar to Thr but cannot form effective hydrogen bonding with Ser77.     

左卡尼汀通过抑制钙/钙调素依赖蛋白激酶Ⅱ信号通路抑制过氧化氢诱导的大鼠心肌细胞凋亡

 目的： 观察左卡尼汀对过氧化氢（H2O2）诱导的大鼠心肌细胞凋亡的保护作用及其机制。方法：利用200 μmol/L H2O2刺激12 h,建立体外原代培养新生乳鼠心肌细胞凋亡模型。Ca2+螯合剂1,2-双(2-氨基苯氧基)乙烷-N, N, N′, N′-四乙酸(BAPTA)、钙调素依赖蛋白激酶II (CaMKII)特异性抑制剂KN93及左卡尼汀分别于加入H2O2前30 min或1 h加入,以检测这3种药物对H2O2刺激下心肌细胞活力、细胞凋亡、细胞内静息钙浓度（［Ca2+］i）及磷酸化CaMKII (p-CaMKII)表达的影响。利用MTT比色法检测心肌细胞活力;流式细胞仪检测细胞凋亡率;利用激光共聚焦扫描检测［Ca2+］i;蛋白质免疫印迹法检测cleaved caspase-3及p-CaMKII的表达。结果：模型组经200 μmol/L H2O2作用12 h后,细胞活力显著下降,细胞凋亡率显著增加。BAPTA、KN93及左卡尼汀预处理显著抑制上述细胞损伤。进一步研究发现,H2O2 诱导的 ［Ca2+］i水平升高、cleaved caspase-3及p-CaMKII的表达增加均可被上述3种药物不同程度地抑制。结论：左卡尼汀可抑制H2O2所致的心肌细胞凋亡,该心肌保护作用可能与其抑制Ca2+/CaMKⅡ信号通路有关。     

液体复苏联合氢气吸入对脓毒性休克大鼠肺脏的作用

 目的：研究早期液体复苏联合氢气吸入对脓毒性休克大鼠肺脏凋亡蛋白和炎症介质表达的影响。方法：60只Wistar大鼠随机分成4组：正常对照组（A组）、休克对照组（B组）、液体复苏组（C组）和液体复苏联合氢气吸入组（D组）,每组15只大鼠。 所有大鼠给予经口气管插管机械通气,呼吸机模式及参数相同。LPS静脉注射建立脓毒性休克模型,A、B和C组吸入气体为空气,D组吸入气体为2%氢空混合气。C和D组给予相同的液体复苏方案。2 h后处死大鼠,HE染色观察肺组织形态学变化,ELISA检测支气管肺泡灌洗液（BALF）中炎症介质的表达,免疫组化和Westen blotting检测肺组织中Fas及Bcl-2的表达。结果：D组与C组比较,BALF中促炎介质水平明显降低（P<0.05）,Fas表达明显减弱（P<0.05）,Bcl-2表达明显增强（P<0.01）。结论：联合氢气吸入的液体复苏方案与单纯液体复苏比较,可通过降低炎症介质水平及减少肺脏细胞凋亡而保护肺功能。     

经皮穴位电刺激不同时间对雷公藤甲素致大鼠急性肝损伤的影响

目的 观察经皮穴位电刺激（transcutanclus electrical acupoint stimulation,TEAS）不同刺激时间对雷公藤甲素致大鼠急性肝损伤的保护作用。方法 将50只SD大鼠随机分为空白组、模型组、TEAS Ⅰ组（刺激20 min）,TEAS Ⅱ组（刺激30 min）、TEAS Ⅲ组（刺激40 min）,以雷公藤甲素灌胃法复制急性肝损伤模型。TEAS各组刺激“足三里”穴,每日1次,连续5 d。观察肝脏组织形态学变化,检测血清天冬氨酸氨基转移酶（aspartate aminotransferase,AST）、丙氨酸氨基转移酶（alanine aminotransferase,ALT）及肝组织丙二醛（malondialdehyde,MDA）、肿瘤坏死因子- α（tumor necrosis factor- α,TNF- α）、白介素- 10（interleukin- 10,IL- 10）、硫化氢的含量。结果 模型组大鼠肝索排列紊乱,肝窦扩张,肝细胞水肿、脂肪变性、坏死;各TEAS组肝脏病理变化较模型组减轻。与空白组比较,模型组大鼠血清ALT、AST及肝组织MDA、TNF- α含量明显升高（P＜0.05）,硫化氢含量明显降低（P＜0.05）,肝组织IL- 10含量无明显变化（P＞0.05）。与模型组比较,TEAS Ⅰ、Ⅱ、Ⅲ组大鼠血清AST、ALT含量和肝组织MDA、TNF- α含量明显降低（P<0.05）或呈降低趋势（P>0.05）,硫化氢含量明显升高（P<0.05）。其中TEAS Ⅲ组与TEAS Ⅰ、Ⅱ组各指标比较,差异均具有统计学意义（P＜0.05）。结论 TEAS能减轻雷公藤甲素对肝组织的损伤,且较长时间（40 min）刺激的保护作用更为明显。     

经直肠腔内三维超声在肛瘘诊断中的价值

目的分析经直肠腔内三维超声对肛瘘的检出情况。方法 57例临床和术后证实的肛瘘患者,应用三维超声探查肛瘘并推注过氧化氢超声造影。结果 57例肛瘘患者,三维超声检出率100%。除去9例内盲瘘,内口检出率为33.3%(16/48),瘘道超声造影后检出率提高到60.4%(29/48);继发瘘道检出率为29.2%(14/48),继发瘘道超声造影后检出率提高到37.5%(18/48)。结论经直肠腔内三维超声结合瘘道过氧化氢超声造影可为外科手术提供更多的信息,指导手术。     

双氧水与声诺维三维输卵管超声造影对输卵管通畅度的诊断价值

目的比较双氧水与声诺维三维输卵管超声造影(3D-Hy Co Sy)对输卵管通畅度的诊断价值。方法回顾分析我院经阴道超声引导下行输卵管造影检查的24例不孕症患者(共47条输卵管)的影像资料,所有病例均行双氧水造影和3D-Hy Co Sy。3D-Hy Co Sy检查前行子宫输卵管碘油造影(HSG),以HSG检查结果作为评估输卵管通畅度的金标准,对比两种超声造影诊断输卵管通畅度的优缺点。结果 1与HSG诊断结果比较,3D-Hy Co Sy对输卵管通畅度的诊断符合率为80.9%,双氧水造影对输卵管通畅度的诊断符合率为59.6%,差异有统计学意义(P﹤0.05)。3D-Hy Co Sy的假阳性率为5.3%,低于双氧水造影(47.4%);3D-Hy Co Sy的假阴性率为14.3%,高于双氧水造影(3.6%)。23D-Hy Co Sy判断近端输卵管狭窄及梗阻部位结果与HSG高度一致(Kappa值分别为0.77、0.90),双氧水造影为基本一致(Kappa值分别为0.40、0.45)。3D-Hy Co Sy判断中远端输卵管狭窄及梗阻部位结果与HSG高度一致(Kappa值分别为0.70、0.80),双氧水造影与HSG一致性差(Kappa值分别为0.31、0.31)。结论双氧水造影与3D-Hy Co Sy检查安全无创、操作简便,但双氧水造影较3D-Hy Co Sy假阴性率低,3D-Hy Co Sy可更清晰地显示输卵管立体形态结构,准确评估输卵管的通畅度及确定梗阻部位;两者结合有望提高输卵管超声造影的诊断准确率。