经冠脉自体骨髓单个核细胞移植治疗扩张型心肌病的随机对照研究

目的采用随机、对照、前瞻性的临床试验,旨在评价经冠脉自体骨髓单个核细胞(BMMNCs)移植治疗扩张型心肌病的有效性和安全性。方法连续入选26例扩张型心肌病患者,细胞移植组(14例)行经冠脉自体BMMNCs移植联合标准药物治疗;对照组(12例)接受标准药物治疗。结果3个月后,细胞移植组的左室射血分数(LVEF)由(29.21±4.41)%提高至(31.08±4.54)%(P=0.004),与对照组比较,无统计学差异(P=0.216);PET/CT示心肌13N-NH3灌注和18F-FDG代谢显像显著改善;氮末端脑钠素前体(NT-proBNP)、6min步行试验和明尼苏达生活质量评分的改变均具有统计学意义。结论经冠脉自体BMMNCs移植治疗扩张型心肌病安全而有效,可能是通过BMMNCs转分化为心肌细胞和血管内皮细胞而改善心功能。     

使用人工补片进行食管裂孔重建的随机对照实验的Meta分析

目的通过Meta分析对使用人工补片进行食管裂孔重建的效果和安全性进行评价。方法检索Pubmed和Cochrane数据库2007年4月10日以前有关使用人工补片进行食管裂孔重建的随机对照实验,使用Cochrane图书馆提供的Review Manager4.2软件对入选实验的数据进行合并分析。主要评价指标包括术后裂孔疝发生率和由补片引起的脏器磨损。结果有7项随机对照实验,其中3项实验满足纳入标准和排除标准而入选Meta分析。共有280名研究对象纳入分析,其中使用人工补片进行裂孔重建的患者(n=137)在随访期内有8例(5.83%)发生裂孔疝,对照组(n=143)有33例(23.08%)发生裂孔疝,相对危险度RR=0.30(95%CI,0.15-0.62,P=0.001),随访期内没有观察到因补片磨损引起的脏器损伤。结论使用人工补片进行裂孔重建明显降低术后近期裂孔疝的发生危险,具有良好的应用前景,但远期效果和安全性有待长期观察的结果进一步明确。     

解郁透达化气法治疗肝郁血结型失眠症105例临床分析

目的探讨解郁透达化气法治疗肝郁血结所致失眠的临床疗效。方法对105例患者采用解郁透达化气法辨证论治,经2至4周治疗后观察临床疗效。结果105例患者中治愈11例,好转84例,未愈7例,总有效率达90.48%。结论解郁透达化气法治疗肝郁血结的失眠疗效良好。     

乐果对大鼠血清单胺类神经递质的影响

乐果是中国最常用的有机磷农药。有机磷农药在我国占目前登记的农药品种的40％（含混剂）。农药使用不当或误服使得有机磷农药急性中毒成为目前农村地区中毒死亡的主要原因,死亡率为10％左右。城市中屡见食用农药污染的蔬菜引起中毒的报道。有机磷农药污染相当严重,城市人口70％尿样中检出有机磷代谢产物。     

Association between plasma Vitamin B5 levels and all‐cause mortality: A nested case‐control study

We aimed to evaluate the prospective association of vitamin B5 with all‐cause mortality and explore its potential modifiers in Chinese adults with hypertension. A nested, case‐control study was conducted in the China Stroke Primary Prevention Trial, including 505 deaths of all causes and 505 matched controls. The median follow‐up duration was 4.5 years. The primary outcome measure in this investigation was all‐cause mortality, which encompassed deaths for any reason. The mean plasma vitamin B5 concentration for cases (43.7 ng/mL) was higher than that in controls (40.9 ng/mL) (p = .001). When vitamin B5 was further assessed as quintiles, compared with the reference group (Q1: < 33.0 ng/mL), the risk of all‐cause mortality increased by 29% (OR = 1.29, 95% CI: 0.83‐2.01) in Q2, 22% (OR = 1.22, 95% CI: 0.77‐1.94) in Q3, 62% (OR = 1.62, 95% CI: 1.00‐2.62) in Q4, and 77% (OR = 1.77, 95% CI: 1.06‐2.95) in Q5. The trend test was significant (p = .022). When Q4‐Q5 were combined, a significant 41% increment (OR = 1.41, 95% CI: 1.03‐1.95) in all‐cause death risk was found compared with Q1‐Q3. The adverse effects were more pronounced in those with normal folate levels (p‐interaction = .019) and older people (p‐interaction = .037). This study suggests that higher baseline levels of plasma vitamin B5 are a risk factor for all‐cause mortality among Chinese patients with hypertension, especially among older adults and those with adequate folate levels. The findings, if confirmed, may inform novel clinical and nutritional guidelines and interventions to optimize vitamin B5 levels.     

IL‐27 improves adoptive CD8+ T cells’ antitumor activity via enhancing cell survival and memory T cell differentiation

IL‐27 is an anti‐inflammatory cytokine that triggers enhanced antitumor immunity, particularly cytotoxic T lymphocyte responses. In the present study, we sought to develop IL‐27 into a therapeutic adjutant for adoptive T cell therapy using our well‐established models. We have found that IL‐27 directly improved the survival status and cytotoxicity of adoptive OT‐1 CD8⁺ T cells in vitro and in vivo. Meanwhile, IL‐27 treatment programs memory T cell differentiation in CD8⁺ T cells, characterized by upregulation of genes associated with T cell memory differentiation (T‐bet, Eomes, Blimp1, and Ly6C). Additionally, we engineered the adoptive OT‐1 CD8⁺ T cells to deliver IL‐27. In mice, the established tumors treated with OT‐1 CD8⁺ T‐IL‐27 were completely rejected, which demonstrated that IL‐27 delivered via tumor antigen–specific T cells enhances adoptive T cells’ cancer immunity. To our knowledge, this is the first application of CD8⁺ T cells as a vehicle to deliver IL‐27 to treat tumors. Thus, this study demonstrates IL‐27 is a feasible approach for enhancing CD8⁺ T cells’ antitumor immunity and can be used as a therapeutic adjutant for T cell adoptive transfer to treat cancer.     

奥氮平连续处理后大鼠中缝背核组织差异表达蛋白的生物信息学分析

目的 分析奥氮平连续处理的大鼠中缝背核蛋白的差异表达,探究奥氮平使用早期导致代谢障碍可能的中枢5-HT机制。方法 将40只SD大鼠随机分配到奥氮平组[灌胃奥氮平1.2 mg/(kg·d）]和对照组（灌胃等量0.9%氯化钠溶液）,两组各分配10只雌性大鼠、10只雄性大鼠。给药1次/d,连续28 d。最后一次给药1 h后处理大鼠,并取大脑中缝背核样本。利用绝对和相对定量同位素标记技术联合液相色谱-串联质谱技术对大鼠中缝背核组织进行蛋白质组学分析,进一步对差异表达蛋白进行GO、KEGG通路、COG、蛋白互作网络分析。另将24只大鼠随机分为4组：2个奥氮平组和2个对照组（6只/组）,类似方法得到大鼠中缝背核样本,根据蛋白质组学数据选择目标基因的表达进行qRT-PCR和Western blot验证。结果 筛选出奥氮平组与对照组大鼠中缝背核差异表达蛋白有72种上调、142种下调。GO注释分析显示,涉及奥氮平的差异表达蛋白参与细胞过程、生物调节、代谢过程、应激反应、多细胞生物过程以及结合、催化活性、分子功能调节、转录调节活性等分子功能。KEGG富集分析显示,涉及奥氮平的差异表达蛋白主要参与流体剪切应...     

Association of HLA-DQ Heterodimer Residues −18β and β57 With Progression From Islet Autoimmunity to Diabetes in the Diabetes Prevention Trial–Type 1

OBJECTIVEThe purpose was to test the hypothesis that the HLA-DQαβ heterodimer structure is related to the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).RESEARCH DESIGN AND METHODSNext-generation targeted sequencing was used to genotype HLA-DQA1-B1 class II genes in 670 subjects in the Diabetes Prevention Trial–Type 1 (DPT-1). Coding sequences were translated into DQ α- and β-chain amino acid residues and used in hierarchically organized haplotype (HOH) association analysis to identify motifs associated with diabetes onset.RESULTSThe opposite diabetes risks were confirmed for HLA DQA1*03:01-B1*03:02 (hazard ratio [HR] 1.36; P = 2.01 ∗ 10⁻³) and DQA1*03:03-B1*03:01 (HR 0.62; P = 0.037). The HOH analysis uncovered residue −18β in the signal peptide and β57 in the β-chain to form six motifs. DQ*VA was associated with faster (HR 1.49; P = 6.36 ∗ 10⁻⁴) and DQ*AD with slower (HR 0.64; P = 0.020) progression to diabetes onset. VA/VA, representing DQA1*03:01-B1*03:02 (DQ8/8), had a greater HR of 1.98 (P = 2.80 ∗ 10⁻³). The DQ*VA motif was associated with both islet cell antibodies (P = 0.023) and insulin autoantibodies (IAAs) (P = 3.34 ∗ 10⁻³), while the DQ*AD motif was associated with a decreased IAA frequency (P = 0.015). Subjects with DQ*VA and DQ*AD experienced, respectively, increasing and decreasing trends of HbA_1c levels throughout the follow-up.CONCLUSIONSHLA-DQ structural motifs appear to modulate progression from islet autoimmunity to diabetes among at-risk relatives with islet autoantibodies. Residue −18β within the signal peptide may be related to levels of protein synthesis and β57 to stability of the peptide-DQab trimolecular complex.     

Spleen stiffness-spleen size-to-platelet ratio risk score as noninvasive predictors of esophageal varices in patients with hepatitis B virus-related cirrhosis

This study was conducted to evaluate the predictive value of spleen stiffness-spleen size-to-platelet ratio risk score (SSPS) as a noninvasive predictor of esophageal varices (EVs) and to compare it with others.In this retrospective study, from April 2017 to October 2018, a total of 65 patients with hepatitis B virus-related cirrhosis who underwent the liver and spleen stiffness (LS, and SS) measurements by 2 dimensional-shear wave elastography and endoscopic evaluation for EVs were enrolled. Liver stiffness-spleen size-to-platelet ratio risk score (LSPS) and SSPS were calculated. The prognostic values were assessed by the area under the receiver operating characteristic curve (AUC).Twenty-six patients had no EV on endoscopy. Among 39 patients who had EVs, 12 patients had high risk EVs. The AUCs of the LS value, SS value, LSPS, and SSPS for predicting EVs were 0.72, 0.77, 0.80, and 0.85, respectively. The AUCs of the LS value, SS value, LSPS, and SSPS for predicting high-risk EVs were 0.55, 0.78, 0.67, and 0.80, respectively. SSPS had the highest specificity, at 96.15%, for predicting EVs.SSPS may be beneficial to exclude from having EVs and it is expected that the frequency of performing endoscopies for screening EVs can be reduced.