SDF-1/CXCR4激活ERK和PI3K/AKT通路介导髓核致炎根性疼痛

目的探讨基质细胞衍生因子1/趋化因子CXC受体4（SDF-1/CXCR4）通路在髓核致炎根性疼痛中的作用及机制。方法分为三部分：① 26只大鼠随机分为假手术组和模型组，分别行假手术或髓核自体移植。Von Frey 纤维丝测量大鼠机械撤足阈值（PWT）的变化； Western blot法检测大鼠脊髓中SDF-1、CXCR4，磷酸化细胞外信号调节激酶（pERK）和磷酸化蛋白激酶B（pAKT）表达水平；免疫荧光染色定位SDF-1、CXCR4的表达细胞。② 54只大鼠随机分为假手术组、模型组、溶剂组、AMD3100组、SDF-1中和抗体组、对照Ig G组。鞘内注射相应药物，测量大鼠PWT的变化和大鼠脊髓中pERK和pAKT的表达变化。③ 18只大鼠随机分为溶剂组、U0126组、LY294002组，鞘内注射相应药物，测量大鼠PWT的变化。结果① 髓核自体移植使大鼠PWT下降（P＜0.001），脊髓中SDF-1、CXCR4、pERK，pAKT表达上调（P＜0.05），SDF-1主要与脊髓中神经元共表达，CXCR4 与神经元和星形胶质细胞共表达。② 鞘内注射SDF-1中和抗体或CXCR4抑制剂AMD3100升高髓核自体移植大鼠的PWT（P＜0.05），并使髓核自体移植大鼠脊髓中pERK和pAKT表达下调（P＜0.05）。③ 鞘内给予MEK抑制剂U0126或PI3K抑制剂LY294002可升高髓核自体移植大鼠PWT（P＜0.05）。结论SDF-1/CXCR4通过激活ERK和PI3K/AKT通路介导髓核致炎根性疼痛

基于血清代谢组学研究黄芪甲苷抑制高脂喂养的<italic>Apc^Min/+</italic>小鼠结肠腺瘤性息肉形成

目的探究黄芪甲苷（ASIV）对高脂喂养（HF）的腺瘤性息肉病基因突变（Apc Min/+）小鼠结肠腺瘤性息肉（CAP）形成的预防作用及对血清代谢物紊乱的调控机制。方法将Apc Min/+小鼠分成对照组（Con）、高脂喂养组（HF）、黄芪甲苷治疗组（HF-ASIV），每组8只。HF组和HF-ASIV组喂养高脂饲料8周，HF-ASIV组同时每两天给予ASIV （50 mg/kg） 灌胃。记录小鼠每日饮水量、进食量和体质量变化。8周末收集小鼠血清，取小肠末端及近端结肠记录CAP个数和病理观察 （HE）； 免疫组化（IHC）检测各组小鼠CAP周围肠壁COX2水平；qRT-PCR检测肠壁IL-1 β和TNFα表达水平；液相质谱技术对小鼠肠道进行非靶向代谢轮廓分析， 筛选差异代谢物并进行功能富集。结果实验期间各组小鼠无死亡，HF-ASIV组与HF组相比肠息肉总数减少，以中腺瘤（直径1～3 mm）、大腺瘤（直径&gt;3 mm）减少为主。HF-ASIV组小鼠肠壁的杯状细胞及潘氏细胞数量较HF组增加；肠壁COX2、IL-1 β和TNFα表达水平下降。组间两两比较的代谢物OPLS-DA评分差异显著 （P &lt; 0.001； P = 0.02）。与HF组比较，HF-ASIV组血清中有13种差异代谢物发生显著回调，其中正负离子模式下功能富集到N-乙酰-α-D-氨基葡萄糖基-二磷酸的代谢物水平均显著提高 （P &lt; 0.05），并与腺瘤数量呈负相关 （P &lt; 0.01）。结论ASIV可减少高脂喂养Apc Min/+小鼠结肠腺瘤性息肉的数量，与降低肠壁炎症、调节血清代谢产物N-乙酰-α-D-氨基葡萄糖基-二磷酸水平密切相关

Aripiprazole versus other atypical antipsychotics for schizophrenia

BACKGROUND: In most western industrialised countries, second generation (atypical) antipsychotics are recommended as first line drug treatments for people with schizophrenia. In this review we specifically examine how the efficacy and tolerability of one such agent - aripiprazole - differs from that of other comparable second generation antipsychotics. OBJECTIVES: To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (November 2011), inspected references of all identified studies for further trials, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised clinical trials (RCTs) comparing aripiprazole (oral) with oral and parenteral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We assessed risk of bias for each included study. MAIN RESULTS: We included 12 trials involving 6389 patients. Aripiprazole was compared to olanzapine, risperidone and ziprasidone. All trials were sponsored by an interested drug manufacturer. The overall number of participants leaving studies early was 30% to 40%, limiting validity (no differences between groups).When compared with olanzapine no differences were apparent for global state (no clinically important change: n = 703, 1 RCT, RR short-term 1.00 95% CI 0.81 to 1.22; n = 317, 1 RCT, RR medium-term 1.08 95% CI 0.95 to 1.22) but mental state tended to favour olanzapine (n = 1360, 3 RCTs, MD total Positive and Negative Syndrome Scale (PANSS) 4.68 95% CI 2.21 to 7.16). There was no significant difference in extrapyramidal symptoms (n = 529, 2 RCTs, RR 0.99 95% CI 0.62 to 1.59) but fewer in the aripiprazole group had increased cholesterol levels (n = 223, 1 RCT, RR 0.32 95% CI 0.19 to 0.54) or weight gain of 7% or more of total body weight (n = 1095, 3 RCTs, RR 0.39 95% CI 0.28 to 0.54).When compared with risperidone, aripiprazole showed no advantage in terms of global state (n = 384, 2 RCTs, RR no important improvement 1.14 95% CI 0.81 to 1.60) or mental state (n = 372, 2 RCTs, MD total PANSS 1.50 95% CI -2.96 to 5.96).One study compared aripiprazole with ziprasidone (n = 247) and both the groups reported similar change in the global state (n = 247, 1 RCT, MD average change in Clinical Global Impression-Severity (CGI-S) score -0.03 95% CI -0.28 to 0.22) and mental state (n = 247, 1 RCT, MD change PANSS -3.00 95% CI -7.29 to 1.29).When compared with any one of several new generation antipsychotic drugs the aripiprazole group showed improvement in global state in energy (n = 523, 1 RCT, RR 0.69 95% CI 0.56 to 0.84), mood (n = 523, 1 RCT, RR 0.77 95% CI 0.65 to 0.92), negative symptoms (n = 523, 1 RCT, RR 0.82 95% CI 0.68 to 0.99), somnolence (n = 523, 1 RCT, RR 0.80 95% CI 0.69 to 0.93) and weight gain (n = 523, 1 RCT, RR 0.84 95% CI 0.76 to 0.94). Significantly more people given aripiprazole reported symptoms of nausea (n = 2881, 3 RCTs, RR 3.13 95% CI 2.12 to 4.61) but weight gain (7% or more of total body weight) was less common in people allocated aripiprazole (n = 330, 1 RCT, RR 0.35 95% CI 0.19 to 0.64). Aripiprazole may have value in aggression but data are limited. This will be the focus of another review. AUTHORS' CONCLUSIONS: Information on all comparisons are of limited quality, are incomplete and problematic to apply clinically. Aripiprazole is an antipsychotic drug with a variant but not absent adverse effect profile. Long-term data are sparse and there is considerable scope for another update of this review as new data emerges from the many Chinese studies as well as from ongoing larger, independent pragmatic trials

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^