Y型聚乙二醇干扰素琢-2b注射液治疗HCV基因2/3型慢性丙型肝炎患者疗效和安全性的多中心随机对照试验研究

目的以标准剂量的聚乙二醇干扰素(Peg IFN)α-2a联合利巴韦林作为阳性对照,评价新型试验药物Y型Peg IFNα-2b注射液联合利巴韦林治疗2型/3型慢性丙型肝炎(CHC)患者的疗效和安全性。方法采用多中心、随机开放、阳性药对照的Ⅲ期临床试验,筛选符合要求的2型/3型CHC患者,按照2:1的比例随机分配到Y型Peg IFNα-2b组和Peg IFNα-2a组,同时口服利巴韦林,疗程24 w,停药随访24 w。采用Abbott Real Time HCV Genotype II检测HCV基因型,采用Cobas Taq Man实时定量PCR法检测血清HCV RNA水平。详细记录不良事件。主要疗效指标为持续病毒学应答(SVR),并进行非劣效检验。结果本试验实际入组2型/3型CHC患者255例,实际治疗241例。全分析集(FAS)数据显示,158例试验组和83例对照组患者SVR分别为85.4%(95%CI 79.94%~90.94%)和79.5%(95%CI 70.84%~88.20%,P=0.2402);对符合方案分析集(PPS)人群分析显示,试验组和对照组患者SVR分别为87.9%(95%CI 82.45%~93.27%)和85.9%(95%CI 77.82%~94.01%,P=0.7060),率差的95%可置信区间均符合非劣效标准;对PPS人群分析显示,85.8%受试者获得了早期病毒学应答(RVR),RVR的阳性预测值为90.1%;试验组和对照组不良事件发生率相似,分别为95.6%和95.2%,严重不良事件发生率分别为3.8%和3.6%。结论应用Peg IFNα联合利巴韦林治疗2型/3型CHC患者,新型试验药物Y型Peg IFNα-2b具有与对照药物Peg IFNα-2a相似的疗效和安全性。国家科技部“十二五”重大专项(编号:2012ZX10002-003)；“重大新药创制”十二五科技重大专项(编号:2012ZX09303019)

NO吸入对肝移植急性肺损伤大鼠肺组织iNOS?IL-1β及IL-6的影响

【目的】 观察一氧化氮(NO)吸入对肝移植急性肺损伤大鼠肺组织诱导型NO合酶(iNOS)?白细胞介素-1β(IL-1β)?白细胞介素-6(IL-6)水平的影响与意义?【方法】 选用SD大鼠24只,按随机数字表法分为对照组(C组)?自体原位肝移植组(M组)和NO吸入组(T组),每组8只?对照组开腹游离肝叶后即关腹,后两组行大鼠自体原位肝移植?对照组及自体原位肝移植组术后于室内吸空气,NO吸入组术后即放入特制的密封盒内(NO体积分数为20 × 10-6)?手术结束后8 h行肺脏病理检查,测定肺组织干湿质量比(W/D),并检测iNOS?IL-1β?IL-6水平?【结果】 ① C组肺组织结构基本正常,M组肺组织炎症损伤明显,T组肺组织炎症损伤较M组明显减轻?②M组肺组织W/D明显高于对照组,T组则低于M组,但仍高于对照组?③M组iNOS活性及蛋白表达?IL-1β?IL-6水平较C组明显升高,T组则较M组降低,但仍高于C组?【结论】 肝移植术后NO吸入可抑制肺组织iNOS活性及蛋白表达,降低IL-1β?IL-6水平,肺组织病理损伤减轻,干湿质量比下降

融合蛋白TAT-RabGEF1原核表达载体的构建及蛋白表达

： 【目的】构建PET28a-TAT-RabGEF1重组质粒载体，在E.coli Rosetta（DE3）菌株中高效表达并纯化融合 蛋白，研究TAT-RabGEF1融合蛋白对肥大细胞的跨膜转导活性。【方法】以小鼠组织cDNA为模板，设计上游和下游 含有限制性酶切位点和TAT序列的引物，PCR扩增目的片段TAT-RabGEF1，并通过双酶切构建PET28a-TAT-Rab? GEF1重组质粒载体，在E.coli Rosetta（DE3）大肠杆菌中诱导表达融合蛋白，产物用亲和层析柱纯化后测量浓度及 鉴定。CCK-8检测融合蛋白的细胞毒性，并用荧光显微镜及荧光分光光度计定性定量观察其对小鼠肥大细胞瘤细 胞P815的转导活性。【结果】成功构建了PET28a-TAT-RabGEF1重组载体，高效表达了具有较高特异性，相对分子 质量约为57 ku的融合蛋白TAT-RabGEF1，0.1、1、10 μmol/L浓度的TAT-RabGEF1蛋白对细胞无明显毒性，荧光显 微镜显示1 μmol/L浓度的融合蛋白TAT-RabGEF1具有快速转导进入P815细胞内的能力，且为进入细胞的饱和浓 度。【结论】通过TAT-RabGEF1的原核表达和蛋白纯化分析，证实了TAT-PTD的跨膜转导活性，为研究RabGEF1在 肥大细胞激活途径中的作用提供了物质基础

Prediction of Energy Resolution in the JUNO Experiment

International audienceThis paper presents the energy resolution study in the JUNO experiment, incorporating the latest knowledge acquired during the detector construction phase. The determination of neutrino mass ordering in JUNO requires an exceptional energy resolution better than 3% at 1 MeV. To achieve this ambitious goal, significant efforts have been undertaken in the design and production of the key components of the JUNO detector. Various factors affecting the detection of inverse beta decay signals have an impact on the energy resolution, extending beyond the statistical fluctuations of the detected number of photons, such as the properties of liquid scintillator, performance of photomultiplier tubes, and the energy reconstruction algorithm. To account for these effects, a full JUNO simulation and reconstruction approach is employed. This enables the modeling of all relevant effects and the evaluation of associated inputs to accurately estimate the energy resolution. The study reveals an energy resolution of 2.95% at 1 MeV. Furthermore, the study assesses the contribution of major effects to the overall energy resolution budget. This analysis serves as a reference for interpreting future measurements of energy resolution during JUNO data taking. Moreover, it provides a guideline in comprehending the energy resolution characteristics of liquid scintillator-based detectors

Measurement of integrated luminosity of data collected at 3.773 GeV by BESIII from 2021 to 2024

We present a measurement of the integrated luminosity e+e- of collision data collected by the BESIII detector at the BEPCII collider at a center-of-mass energy of Ecm = 3.773 GeV. The integrated luminosities of the datasets taken from December 2021 to June 2022, from November 2022 to June 2023, and from October 2023 to February 2024 were determined to be 4.995±0.019 fb-1, 8.157±0.031 fb-1, and 4.191±0.016 fb-1, respectively, by analyzing large angle Bhabha scattering events. The uncertainties are dominated by systematic effects, and the statistical uncertainties are negligible. Our results provide essential input for future analyses and precision measurements

Determination of the number of ψ(3686) events taken at BESIII

The number of ψ(3686) events collected by the BESIII detector during the 2021 run period is determined to be (2259.3±11.1)×106 by counting inclusive ψ(3686) hadronic events. The uncertainty is systematic and the statistical uncertainty is negligible. Meanwhile, the numbers of ψ(3686) events collected during the 2009 and 2012 run periods are updated to be (107.7±0.6)×106 and (345.4±2.6)×106, respectively. Both numbers are consistent with the previous measurements within one standard deviation. The total number of ψ(3686) events in the three data samples is (2712.4±14.3)×10^