腹腔镜下胆囊切除术患者预防应激性溃疡的必要性研究

目的:评价非高危因素的腹腔镜下胆囊切除术(LC)患者预防应激性溃疡(SU)的必要性,为临床合理用药提供参考。方法:将90例非高危因素的腹腔镜下胆囊切除术患者按1:2的比例随机分为未用药组和用药组,并进行回顾性分析:术后SU的发生率;住院时间、住院费用、药品费用和原有疾病治愈率;不良反应发生率。其中未用药组30例,不进行SU的预防;用药组60例,使用抑酸药(ASD)预防SU。结果:未用药组与用药组均未出现术后SU和严重不良反应;二者在住院时间、住院费用、药品费用和原有疾病治愈率上的差异均无统计学意义;未用药组平均住院费用和平均药品费用均低于用药组。结论:对于不存在高危因素的LC患者,预防应激性溃疡是没有必要的。     

Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy

Parkin, an E3 ubiquitin ligase, plays a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy. Accumulating evidence suggests that the acetylation modification of the key mitophagy machinery influences mitophagy level, but the underlying mechanism is poorly understood. Here, our study demonstrated that inhibition of histone deacetylase (HDAC) by treatment of HDACis activates mitophagy through mediating Parkin acetylation, leading to inhibition of cervical cancer cell proliferation. Bioinformatics analysis shows that Parkin expression is inversely correlated with HDAC2 expression in human cervical cancer, indicating the low acetylation level of Parkin. Using mass spectrometry, Parkin is identified to interact with two upstream molecules, acetylase acetyl-CoA acetyltransferase 1 (ACAT1) and deacetylase HDAC2. Under treatment of suberoylanilide hydroxamic acid (SAHA), Parkin is acetylated at lysine residues 129, 220 and 349, located in different domains of Parkin protein. In in vitro experiments, combined mutation of Parkin largely attenuate the interaction of Parkin with PTEN induced putative kinase 1 (PINK1) and the function of Parkin in mitophagy induction and tumor suppression. In tumor xenografts, the expression of mutant Parkin impairs the tumor suppressive effect of Parkin and decreases the anticancer activity of SAHA. Our results reveal an acetylation-dependent regulatory mechanism governing Parkin in mitophagy and cervical carcinogenesis, which offers a new mitophagy modulation strategy for cancer therapy.     

高温致金黄地鼠神经管畸形的上调表达基因筛选及其鉴定

目的:筛选高温致金黄地鼠神经管畸形的上调表达基因,探讨其分子生物学机制。方法:通过抑制性消减杂交技术获得消减产物,转化大肠杆菌DH5α,构建高温致金黄地鼠胚胎神经管畸形的消减cDNA文库;联合蓝白斑和菌落PCR方法筛选含插入片段的阳性克隆,进行测序和同源性分析,并经Northern杂交技术检测基因的表达。结果:成功构建高温致金黄地鼠胚胎神经管畸形的消减cDNA文库,其中2个克隆插入片段的基因序列与小鼠磷酸甘油酸酯激酶(Pgk-1)同源。Northern杂交证实该基因在高温致畸胚胎神经管的表达较其在同龄正常胚胎神经管明显升高。结论:Pgk-1的上调表达可能与高温致神经管畸形密切相关。     

青春双歧杆菌对环磷酰胺免疫抑制小鼠的免疫功能的影响

目的研究青春双歧杆菌(BFA)对免疫抑制小鼠模型的体内免疫调节作用。方法采用环磷酰胺腹腔注射法制作免疫抑制小鼠模型,分别用3种不同浓度的BFA菌液连续干预免疫抑制小鼠14d,同时设黄芪治疗组,正常生理盐水对照组和单纯免疫抑制组。干预过程中,每天测定各组小鼠的各项指标,包括小鼠血中IL-2含量,胸腺、脾脏、肝脏指数,小鼠体重增长曲线,粪便BFA菌落计数和血白细胞数。采用SPSS12.0统计软件包进行数据处理分析。结果随着BFA干预天数的增加,BFA摄入量的增多,粪便中BFA菌落数逐渐减少,BFA干预组和对照组相比差异有显著性(P<0.05);肝、脾、胸腺指数的比较结果表明,BFA干预组与其他各组差异有显著性(P<0.05);血IL-2,白细胞含量比较,BFA高剂量干预组最高,与对照组和其它剂量干预组相比差异有显著性(P<0.05);BFA高剂量干预组体重增加明显,体重曲线表现出BFA干预对免疫抑制小鼠体重的明显促进作用,与对照组相比差异有显著性(P<0.05)。结论BFA对环磷酰胺免疫抑制小鼠的免疫功能有一定的恢复和增强作用。     

右归丸对骨髓抑制小鼠造血功能的影响

目的：观察右归丸对骨髓抑制小鼠外周血、造血干细胞增殖能力、骨髓细胞周期和凋亡的影响,并探讨其可能作用机制。方法：小鼠48只,随机分为正常组、模型组,右归丸低、中、高剂量组和阳性对照组,每组8只。除正常组外,余五组均予造模,连续3天给予腹腔注射环磷酰胺制备骨髓抑制模型。造模后各组应用相应药物治疗7天。用全自动血细胞分析仪、白细胞计数法、造血祖细胞培养和流式细胞术（FCM）分别检测右归丸对骨髓抑制小鼠外周血、骨髓有核细胞数、体外培养各系造血祖细胞的集落数以及骨髓细胞周期和凋亡的影响。结果：右归丸中、高剂量均能明显升高外周血红细胞（RBC）、血红蛋白（Hb）、骨髓有核细胞（BMC）数,高剂量对血小板（PET）和白细胞（WBC）有明显升高作用。右归丸能明显提高体外培养各系造血祖细胞的集落数,以中、高剂量效果显著。右归丸低、高剂量均能促进骨髓G0／G1期细胞向S期细胞以及S期细胞向G2／M期细胞的转化,提高G2／M期细胞比例,增殖指数（PI）明显升高。右归丸中、低剂量组的骨髓细胞凋亡比例显著下降。结论：右归丸可能通过促进G0期造血干细胞进入细胞周期,进行增殖;加速骨髓细胞修复受损的DNA,通过GI／S和S期监测点;抑制造血细胞的凋亡;调节造血细胞增殖与凋亡之间的平衡等机制,从而促进损伤骨髓造血功能恢复。     

Predictors and consequences of HIV status disclosure to adolescents living with HIV in Eastern Cape,South Africa: a prospective cohort study

IntroductionThe World Health Organization recommends full disclosure of HIV‐positive status to adolescents who acquired HIV perinatally (APHIV) by age 12. However, even among adolescents (aged 10–19) already on antiretroviral therapy (ART), disclosure rates are low. Caregivers often report the child being too young and fear of disclosure worsening adolescents’ mental health as reasons for non‐disclosure. We aimed to identify the predictors of disclosure and the association of disclosure with adherence, viral suppression and mental health outcomes among adolescents in sub‐Saharan Africa.MethodsAnalyses included three rounds (2014–2018) of data collected among a closed cohort of adolescents living with HIV in Eastern Cape, South Africa. We used logistic regression with respondent random‐effects to identify factors associated with disclosure, and assess differences in ART adherence, viral suppression and mental health symptoms between adolescents by disclosure status. We also explored differences in the change in mental health symptoms and adherence between study rounds and disclosure groups with logistic regression.ResultsEight hundred and thirteen APHIV were interviewed at baseline, of whom 769 (94.6%) and 729 (89.7%) were interviewed at the second and third rounds, respectively. The proportion aware of their HIV‐positive status increased from 63.1% at the first round to 85.5% by the third round. Older age (adjusted odds ratio [aOR]: 1.27; 1.08–1.48) and living in an urban location (aOR: 2.85; 1.72–4.73) were associated with disclosure between interviews. There was no association between awareness of HIV‐positive status and ART adherence, viral suppression or mental health symptoms among all APHIV interviewed. However, among APHIV not aware of their status at baseline, adherence decreased at the second round among those who were disclosed to (N = 131) and increased among those not disclosed to (N = 151) (interaction aOR: 0.39; 0.19–0.80). There was no significant difference in the change in mental health symptoms between study rounds and disclosure groups.ConclusionsAwareness of HIV‐positive status was not associated with higher rates of mental health symptoms, or lower rates of viral suppression among adolescents. Disclosure was not associated with worse mental health. These findings support the recommendation for timely disclosure to APHIV; however, adherence support post‐disclosure is important.     

白消安对小鼠造血干细胞功能的损伤作用

目的检测不同给药方式对小鼠造血干细胞功能的影响。方法 C57小鼠,白消安腹腔给药,分为高剂量组(40 mg/kg)和低剂量组(20 mg/kg),低剂量组给药一次,高剂量给药组分两天给药,每天给予20 mg/kg。给药后15 d和30 d分别检测小鼠外周血和骨髓细胞计数,造血干细胞,造血祖细胞和长期造血干细胞比例,通过CFU-GM实验评价小鼠造血祖细胞增殖能力,流式分选长期造血干细胞体外培养,通过单细胞集落实验检测造血干细胞功能。结果高剂量组和低剂量组白消安均可以降低C57小鼠外周血中白细胞和血小板数目,降低造血干、祖细胞和长期造血干细胞的比例,降低CFU-GM和单细胞集落形成能力。高剂量组比低剂量组损伤作用进一步加重。小鼠体重和对照组相比差异无显著性。结论高剂量组白消安给药15 d后可以诱导造血干细胞损伤,为造血干细胞损伤机制的探讨和损伤防护的研究提供模型和基础。     

血清TGF-β1、sST2水平与胸主动脉瘤病变长度和病变程度的关系

目的探讨血清转化生长因子β1(TGF-β1)、可溶性生长刺激表达因子2蛋白(sST2)水平与胸主动脉瘤(TAA)病变长度和病变程度的关系,分析血清TGF-β1、sST2水平诊断胸主动脉瘤的价值。方法选择2018年7月—2020年12月四川大学华西广安医院收治的72例TAA患者(TAA组)和77例健康志愿者(对照组),检测血清TGF-β1、sST2、炎症因子以及纤维化指标水平,超声心动图测量胸主动脉瘤病变长度和病变程度。Pearson或Spearman相关分析TGF-β1、sST2与胸主动脉瘤病变长度和病变程度、炎症因子以及纤维化指标的相关性。Logistic回归分析胸主动脉瘤的危险因素,受试者工作特征(ROC)曲线分析TGF-β1、sST2诊断胸主动脉瘤的价值。结果 TAA组血清TGF-β1、sST2水平高于对照组(t=18.480、27.534,P<0.05)。血清TGF-β1、sST2水平与胸主动脉瘤病变长度和病变程度、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、白细胞介素33(IL-33)、透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)、层黏连蛋白(...