基于TNF/NF-κB信号通路探讨枳实薤白桂枝汤减轻心肌梗死大鼠心肌损伤的作用机制

目的 从肿瘤坏死因子/核转录因子-κB（TNF/NF-κB）信号通路探讨枳实薤白桂枝汤（ZXGT）对异丙肾上腺素（ISO）诱导的大鼠心肌梗死（MI）的影响。方法 将48只SD大鼠随机分为空白组、模型组、培哚普利组（4 mg·kg^-1）、ZXGT组（24.4 g·kg^-1）、ZXGT+抑制剂组（ZXGT,24.4 g·kg^-1;TNF-α受体抑制剂R7050,5 mg·kg^-1）、抑制剂组（R7050,5 mg·kg^-1）,每组8只;各组大鼠预防性灌胃给药7 d,且ZXGT+抑制剂组、抑制剂组在第6、第7天给予腹腔注射抑制剂R7050 5 mg·kg^-1,除空白组外其余各组腹腔注射ISO,连续2 d,诱导大鼠MI模型;于实验第7天注射ISO 30 min后麻醉大鼠,检测心电图（ECG）观察ST段抬高值;采用小动物超声心动图检测大鼠心脏整体轴向应变（GLS）和心脏同步性;腹主动脉取血测定血清心肌肌钙蛋白T（cTnT）、肌酸激酶MB同工酶（CK-MB）、乳酸脱氢酶（LDH）水平及炎症因子TNF-α、白细胞介素-1β（IL-1β）水平;苏木素-伊红（HE）染色观察心肌组织病理变化;免疫组化（IHC）法检测心脏组织TNF-α、NF-κB p65、磷酸化（p）-NF-κB p65蛋白表达;蛋白免疫印迹法（Western blot）检测心脏组织肿瘤坏死因子受体1（TNFR1）、肿瘤坏死因子受体相关因子2（TRAF2）、转化生长因子激酶1（TAK1）、NF-κB抑制蛋白α（IκBα）、p-IκBα、NF-κB p65、p-NF-κB p65蛋白表达。结果 与空白组比较,模型组大鼠ECG ST段显著抬高（P<0.01）,超声心动图中GLS增大及同步性显著降低（P<0.01）,病理组织学显示心肌大面积坏死,血清cTnT、CK-MB、LDH、TNF-α、IL-1β水平显著升高（P<0.01）,心肌组织中的TNF-α、TNFR1、TRAF2、TAK1、p-IκBα、p-NF-κB p65蛋白表达水平显著升高（P<0.01）,IκBα蛋白表达水平显著降低（P<0.01）;与模型组比较,培哚普利组、ZXGT组、ZXGT+抑制剂组和抑制剂组大鼠的ECG ST段抬高值明显降低（P<0.05,P<0.01）,GLS和心脏同步性改善（P<0.05,P<0.01）,心肌坏死面积减小,血清cTnT、CK-MB、LDH、TNF-α、IL-1β水平均下调（P<0.01）,且ZXGT组、ZXGT+抑制剂组和抑制剂组均下调模型大鼠升高的TNF-α、TNFR1、TRAF2、TAK1、p-IκBα、p-NF-κB p65蛋白表达水平和上调IκBα的表达水平（P<0.05,P<0.01）;与ZXGT组比较,ZXGT+抑制剂组和抑制剂组差异无统计学意义。结论 ZXGT能保护ISO诱导的大鼠MI损伤,改善心脏功能,其作用机制可能与调控TNF/NF-κB信号通路有关。     

A Multidisciplinary,Community-Based Program to Reduce Unplanned Hospital Admissions

ObjectivesTo evaluate the effect of Hospital Admission Risk Program (HARP) on unplanned hospitalization, bed days, and mortality of enrolled individuals and to evaluate the cost-effectiveness of HARP.DesignA retrospective longitudinal analysis of hospital administrative data.InterventionIndividuals at risk of hospitalization were provided with multidisciplinary, community-based care support managed by care coordinators including integrated care planning, education, monitoring, service linkages, and general practitioner liaison over 6-9 months.Setting and ParticipantsIndividuals who were enrolled into 1 of 8 HARP chronic disease management programs between July 1, 2017, and June 30, 2018, at the Royal Melbourne Hospital, Australia.MethodsHospital admissions between 18 months before and 18 months after HARP enrollment were analyzed. Total hospital costs were compared between 18 months before and 12 months after HARP enrollment.ResultsA total of 1553 individuals with a median age of 71 years (interquartile range 60-81), 63.4% males, were admitted to HARP. Both unplanned hospitalizations and bed days were reduced during the HARP intervention compared to within 3 months before enrollment in each of the HARP management programs. After the HARP intervention, cardiac coach, cardiac heart failure, chronic respiratory, diabetes comanagement, and medication management programs had higher hospitalizations and bed days than individuals’ baseline of at least 3 months before HARP enrollment. Individuals in cardiac heart failure and chronic respiratory management programs had a higher mortality rate than other HARP chronic disease management programs. Individuals in cardiac coach, diabetes comanagement, and medication management programs had lower hospital costs during the HARP intervention compared to within 3 months before HARP enrollment.Conclusions and ImplicationsHARP reduced unplanned hospitalization and bed days but did not return individuals’ hospital use to baseline before the intervention. The variations in mortality between HARP chronic disease management programs implies that condition-specific goals between programs is preferable.     

Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection

We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.     

血肿穿刺抽吸治疗对高血压性脑出血患者血糖及按期预后的影响

目的：探讨治疗创伤对高血压性脑出血患者血糖及按期预后的影响。方法：采用局麻血肿穿刺抽吸治疗（治疗组32例）及全麻外科手术血肿清除治疗（对照组30例）,比较术后的血糖变化,结果：治疗组血肿穿刺抽吸后血糖高峰值水平显著低于对照组（P＜0．01）,而治疗后第1,2,周血糖降至正常者治疗组显著高于对照组（P＜0．05）,病死率治疗组6．25％,对照组26．7％）,两组比较差异显著（P＜0．05）,结论：高血压性脑出血患者血肿穿刺抽吸治疗较外科手术血肿清除治疗有血糖峰值低,恢复正常的速度快,病死率低,对脑组织的损伤小等优点,值得临床推广。     

细胞因子激活骨髓免疫细胞的实验研究

目的：通过对骨髓单个核细胞在体外与不同细胞因子培养,了解不同细胞因子对骨髓淋巴细胞的激活能力和对骨髓干祖细胞的损伤情况。方法：将IL-1、IL-2、γ-IFN、CD3单抗进行不同组合后,在体外与骨髓单个核细胞分成对照组、IL-2组、CD3-AK、CIK组进行培养。培养过程中观察细胞形态和数量的变化,并在培养后检测免疫活性细胞的细胞毒性和造血干细胞的保存情况。结果：培养过程中对照组细胞数量减少;IL-2组细胞数量变化不明显;CD3-AK组、CIK组细胞数量显著增多,并出现较多的集聚成簇的淋巴样细胞,培养后其细胞毒性明显强于对照组及IL-2组,但细胞数量增加和细胞毒性无明性差异,培养后各组造血干细胞保存情况约16%～87%。结论：IL-2、CD3单抗在体外与骨髓单个核细胞培养后,即能激活免疫细胞增殖,又能保留足够的造血干细胞。     

夹竹桃水提物灭螺活性研究

目的 研究夹竹桃水提物的灭螺活性。方法 测试水提物作用后钉螺的死亡率,用直线回归法进行量效和时效分析。结果 夹竹桃水提物灭螺的量效和时效关系分别为Y＝95．4378D－21．2478和Y＝21．32T－3．96,pH从5．5到8．5的范围内其活性随pH上升略有下降,室内贮存1年及100℃加热2h其活性基本不变。结论 夹竹桃水提物具有很强的灭螺活性。     

功能性鼻窦内窥镜手术100例疗效观察

目的：功能性鼻窦内窥镜手术的长期疗效。方法：采用Messerklinger术式为100例患者手术;并以传统术式治疗100例作对照。结果：内窥镜组临床治愈率81％,总有效率95％,明显优于传统手术组（P＜0．05）,手术并发症发生率为6％,明显低于传统组（P＜0．05）。结论：内窥镜手术长期疗效可靠,并发症少,复发率低。     

X线下带膜支架治疗食管气管瘘10例分析

目的　探讨X线下用带膜支架治疗食管气管瘘的方法。方法　在X线监视下以导丝引导 ,用支架推送器将带膜食管支架送入患者有食管气管瘘的食道段内 ,达到堵瘘目的。结果　 10例患者全部一次堵瘘成功 ,当天即可正常进食 ,无 1例出现严重并发症。结论　在X线下带膜支架治疗食管气管瘘是一种很好的方法。     

2型糖尿病患者血浆NO和vWF水平的变化

目的　探讨 2型糖尿病患者血浆一氧化氮 (NO)和血管性假血友病因子 (v WF)的变化 ,了解其在血管病变中的意义。　方法　采用硝酸还原酶法和酶联免疫吸附双抗体夹心法 ,测定 48例糖尿病人和 32例正常人血浆 NO和 v WF水平。　结果　糖尿病人血浆 NO水平 (5 5 .6 4± 2 0 .38μmol/ L )明显低于正常人 (86 .44± 2 9.6 6μm ol/ L ,P <0 .0 1) ;糖尿病人血浆 v WF水平 (12 2 .46 %± 45 .6 5 % )明显高于正常人 (84.44 %± 16 .80 % ,P <0 .0 1)。病例组 NO与 v WF的相关系数为 - 0 .412 ,P<0 .0 1。　结论　血浆 NO水平和 v WF水平反映糖尿病血管结构和功能的改变 ,在糖尿病的发生、发展中起重要作用。血浆 v WF水平有可能是 2型糖尿病肾病发生的早期预测指标