超敏C反应蛋白、类风湿因子、抗环瓜氨酸肽抗体联合血清淀粉样蛋白A检测在类风湿性关节炎诊断中的应用价值

目的探讨超敏C反应蛋白(hs-CRP)、类风湿因子(RF)、抗环瓜氨酸肽抗体(抗CCP抗体)联合血清淀粉样蛋白A(SAA)检测诊断类风湿性关节炎的价值。方法以该院2018年1月至2018年12月收治的102例类风湿性关节炎患者作为实验组,同期82例健康体检者作为对照组,使用特种蛋白分析仪OTTMAN-1及配套试剂盒检测全血hs-CRP和SAA,使用日立7600生化分析仪及配套试剂检测抗CCP抗体及RF,比较四项指标水平。结果实验组患者的hs-CRP、RF、抗CCP抗体和SAA平均水平均明显高于对照组(P<0.05);实验组患者hs-CRP、RF、抗CCP抗体和SAA阳性检出率分别为88.24%、91.18%、81.37%和91.18%,高于对照组的1.22%、0.00%、57.32%和0.00%(P<0.05);实验组患者hs-CRP、RF、抗CCP抗体联合SAA检测阳性检出率为98.04%,高于单一指标检出率(P<0.05)。结论hs-CRP、RF、抗CCP抗体联合SAA检测有利于提高类风湿性关节炎诊断准确性。     

如意珍宝丸对偏头痛大鼠下行痛觉调节通道的影响

目的:研究藏药如意珍宝丸对硝酸甘油致偏头痛模型大鼠下行痛觉调制通道中心区域中脑导水管内神经生长因子(Nerve Growth Factor,NGF)、酪氨酸激酶A(Tyrosine Kinase A,TrkA)、瞬时感受器电位香草酸受体1(Transient Receptor Potential Vanilloid Receptor 1,TRPV1)的表达影响,探究该药干预神经源炎性痛敏性偏头痛的作用机制。方法:以颈部皮下注射硝酸甘油方法复制大鼠偏头痛模型,以如意珍宝丸为药物实验组,琥珀酸舒马普坦为阳性对照组,采用ELISA和Real-Time PCR法检测外周血清及中脑组织NGF、TrkA、TRPV1蛋白及基因表达水平,观察藏药如意珍宝丸对硝酸甘油致偏头痛模型大鼠下行痛觉调制系统的影响。结果:与空白组比较,模型组血清NGF、TrkA、TRPV1蛋白表达显著上升(P0.05);中脑NGF、TrkA、TRPV1基因表达差异性升高(P0.05)。与模型组比较,如意珍宝丸预防组可降低NGF、TRPV1蛋白表达(P0.05);如意珍宝丸观察组能使NGF、TrkA蛋白表达和NGF、TrkA、TRPV1 mRNA表达均降低(P0.05或P0.01)。结论:NGF、TrkA共同参与了下行疼痛调控中TRPV1介导的偏头痛发生;藏药如意珍宝丸可降低NGF、TrkA对TRPV1的上调作用,起到抑制神经源炎性痛敏性偏头痛的作用。     

SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7

Solute carrier family 12 member 5 (SLC12A5) has an oncogenic role in bladder urothelial carcinoma. The present study aimed to characterize the molecular mechanisms of SLC12A5 in bladder urothelial carcinoma pathogenesis. Functional assays identified that in bladder urothelial carcinoma SLC12A5 interacts with and stabilizes SOX18, and then upregulates matrix metalloproteinase 7 (MMP7). In vivo and in vitro assays were performed to confirm the effect of SLC12A5’s interaction with SOX18 on MMP7‐mediated bladder urothelial carcinoma progression. SLC12A5 was upregulated in human bladder tumors, and correlated with the poor survival of patients with bladder urothelial carcinoma tumor invasion and metastasis, promoted by SLC12A5 overexpression. We demonstrated that SLC12A5 interacted with SOX18, and then upregulated MMP7, thus enhancing tumor progression. Importantly, SLC12A5 expression correlated positively with SOX18 and MMP7 expression in bladder urothelial carcinoma. Furthermore, SLC12A5 expression was suppressed by miR‐133a‐3p. Ectopic expression of SLC12A5 partly abolished miR‐133a‐3p‐mediated suppression of cell migration. SLC12A5‐SOX18 complex‐mediated upregulation on MMP7 was important in bladder urothelial carcinoma progression. The miR‐133a‐3p/SLC12A5/SOX18/MMP7 signaling axis was critical for progression, and provided an effective therapeutic approach against bladder urothelial carcinoma.     

MOB1A regulates glucose deprivation-induced autophagy via IL6-STAT3 pathway in gallbladder carcinoma

MOB kinase activator 1A (MOB1A) plays an important role in many diseases and cancers. Here, we observed that MOB1A was substantially overexpressed in gallbladder carcinoma (GBC) tissues compared with nontumor tissues. The high expression of MOB1A was closely associated with poor survival in patients with GBC at advanced TNM stages. Furthermore, our study indicated that MOB1A promoted autophagy by activating the IL6/STAT3 signaling pathway and regulating the chemosensitivity to gemcitabine under glucose deprivation conditions both in vitro and in vivo. In conclusion, these findings suggested that MOB1A is critical for the development of GBC via the MOB1A-IL6/STAT3-autophagy axis.     

Frequency and Correlation of Common Genes Copy Number Alterations in Childhood Acute Lymphoblastic Leukemia with Prognosis

Objective: It was shown by genomic profiling that despite no detectable chromosomal abnormalities a proportion of children with pre-B acute lymphoblastic leukemia harbors copy number alterations (CNA) of genes playing role in B-cell development and function. The aim of the study was to determine the frequency of CNA in pediatric acute lymphoblastic leukemia and correlate these findings with clinical outcome. Methods: DNA extracted from peripheral blood or bone marrow at diagnosis/relapse of fifty newly diagnosed children with precursor B-cell acute lymphoblastic leukemia was analyzed for CNA with multiplex ligation-dependent probe amplification. Results: The analysis revealed 76 CNA in 24 patients most frequently found in PAR1 (17%), CDKN2A/B (15.7%) and PAX5 (14.4%) genes. There were significant CNA co-occurrences between PAX5, CDKN2A/B, BTG1, ETV6, PAR1 or XP22 genes, (p <0.020) and the high-risk group. There was a significant correlation between EBF1, RB1, and IKZF1 alterations and bone marrow relapse. Patients with CNA in screened genes are more likely to succumb to their disease except for those with PAR1 or XP22 genes (p <0.050). Conclusion: The multiplex ligation-dependent probe amplification could be considered as an independent diagnostic tool allowing prompt identification of patients at high risk of treatment failure and, subsequently, a more adequate treatment approach.     

Coronavirus disease 2019-associated immunoglobulin A vasculitis/Henoch–Schönlein purpura: A case report and review

Immunoglobulin A (IgA) vasculitis or Henoch–Schönlein purpura is a predominantly pediatric disease occurring after a triggering viral or bacterial infection. Conversely, drug exposure is the most common inciting event in adult cases of IgA vasculitis. Recently, data has suggested a temporal association between coronavirus disease 2019 (COVID-19) and the development of IgA vasculitis in children and adults. Here, we describe a case of IgA vasculitis with nephritis in a 70-year-old man with COVID-19 and perform a comprehensive review of eight reported cases of suspected COVID-19-associated IgA vasculitis. When compared to classical IgA vasculitis, COVID-19-associated IgA vasculitis exclusively affects males (p < 0.00002) and is more common in adults (p < 0.005). Among cases of COVID-19-associated IgA vasculitis, adult cases were associated with significantly more arthralgia than pediatric cases (p = 0.04). In cases where skin biopsy was obtained, direct immunofluorescence (DIF) was negative for IgA in 50% of cases; thereafter, kidney biopsy DIF was positive for IgA in all cases. With this study, we provide support for an association between IgA vasculitis and severe acute respiratory syndrome coronavirus 2 infection and provide clinical information differentiating its manifestations from classical IgA vasculitis.     

基于HPLC指纹图谱、多指标成分含量测定及化学计量学的湿热痹片质量评价

目的 建立指纹图谱和多指标定量与化学计量学相结合的湿热痹片质量评价方法。方法 采用Waters Symmetry C₁₈色谱柱（250 mm×4.6 mm，5 μm），柱温30℃；检测波长分别为303 nm（检测桑皮苷A、桑皮苷F、桑辛素M）和270 nm（检测连翘酯苷B、连翘酯苷A、连翘苷、苍术素醇、白术内酯II、苍术素）；流动相为乙腈-0.2%磷酸水溶液，梯度洗脱，体积流量1.0 mL/min。利用中药色谱指纹图谱相似度评价系统（2012.130723版）建立湿热痹片的HPLC指纹图谱，确定共有峰并进行相似度评价；并对桑皮苷A、桑皮苷F、桑辛素M、连翘酯苷B、连翘酯苷A、连翘苷、苍术素醇、白术内酯II、苍术素的含量测定方法进行方法学验证；基于指纹图谱共有峰峰面积测定结果，采用聚类分析和主成分分析等化学计量学方法对不同批次的湿热痹片进行质量评价。结果 湿热痹片HPLC指纹图谱确认了16个共有峰，指认9个共有峰，10批湿热痹片样品相似度均大于0.95，相似度良好；9种成分在各自的质量浓度范围内线性关系良好（r² ≥ 0.999 1），平均加样回收率分别为98.87%、97.44%、97.94%、98.39%、100.13%、99.06%、96.80%、98.44%、99.15%，RSD分别为1.42%、1.17%、1.30%、0.91%、0.86%、1.23%、1.08%、1.37%、0.79%；10批次样品中桑皮苷A、桑皮苷F、桑辛素M、连翘酯苷B、连翘酯苷A、连翘苷、苍术素醇、白术内酯II、苍术素的质量浓度分别在0.192~0.289、0.057~0.095、0.113~0.158、0.309~0.375、1.537~1.916、0.478~0.596、0.049~0.072、0.279~0.354、0.629~0.759 mg/g。10批湿热痹片聚为2类；主成分1~6是影响湿热痹片质量评价的主要因子。结论 所建立的方法操作便捷、结果准确、重复性好，可用于湿热痹片的质量控制和评价。     

m6A结合蛋白IGF2BP1在肝细胞癌中的基因调控网络分析

目的 分析m6A阅读器胰岛素样生长因子2-mRNA结合蛋白1（insulin-like growth factor 2 mRNA-binding protein 1，IGF2BP1）在肝细胞癌（hepatocellular carcinoma，HCC）中的表达水平及其对HCC患者预后的影响，并探讨IGF2BP1在HCC发生发展中的作用及其潜在机制。方法 基于5对HCC癌及相应癌旁组织mRNA-seq数据和TCGA数据库LIHC的mRNA-seq数据综合分析IGF2BP1在HCC中的表达情况，同时利用TCGA数据库中343例HCC患者的临床随访资料分析IGF2BP1表达水平对HCC患者总生存期的影响。基于TCGA数据库筛选IGF2BP1的共表达mRNA，并利用m6Avar在线网站预测mRNA的m6A位点及其RNA结合蛋白等信息，最终构建IGF2BP1的基因调控网络。结果 IGF2BP1基因在HCC中表达上调（log2FC HCC转录组数据=10.684，P<0.001；log2FC TCGA-LIHC数据集=7.032，P<0.001）。生存分析显示IGF2BP1低表达的HCC患者中位生存时间为5.84年，IGF2BP1高表达患者为4.44年，高表达患者总生存期缩短（P=0.011）。22个差异表达的mRNA与IGF2BP1存在靶向结合关系，并与其表达水平呈正相关。其中，HMGA2等15个高表达mRNA的HCC患者总生存期缩短。HMGA2、PEG10、CEP55、RHO、CDC6和KIF23基因中的潜在m6A甲基化位点位于mRNA 3'UTR端的miRNA结合区域。结论 IGF2BP1在HCC中高表达且导致患者总生存期缩短。IGF2BP1可能通过m6A甲基化及miRNA抑制作用的方式上调mRNA的表达，促进HCC发生并导致不良预后。     

Effects of Bisphenol A on expression of genes related to amino acid transporters,insulin- like growth factor,aquaporin and amino acid release by porcine trophectoderm cells

The peri-implantation period of pregnancy is critical for conceptus development, implantation, and signaling for establishment of pregnancy. This study evaluated the effects of bisphenol A (BPA) on proliferation, adhesion, and migration of porcine trophectoderm (pTr2) cells, expression of transporters of arginine and synthesis of amino acids. All concentrations of BPA decreased proliferation and adhesion of pTr2 cells after 96 h compared to the control group. Lower concentrations of BPA (1 × 10⁻⁹, 1 × 10^-8, 10^-7M) increased (P < 0.05), but higher concentrations of BPA (1 × 10^-5, 1 × 10^-4 M) decreased migration of pTr2 cells. BPA increased expression of SLC7A1 mRNA at lower concentrations (1 × 10⁻⁹ to 1 × 10^-6M) and SL7A6, another cationic acid transporter, at higher concentrations (1 × 10^-5, 1 × 10^-4 M). BPA also down-regulated the expression of IGF1 and IGF1 receptor at concentrations of 1 × 10^-7 to 1 × 10^-4 M compared to the control group. The expression of mRNAs for aquaporins (AQP) 3 and 4 were reduced at all concentrations of BPA, but at lower concentrations of BPA, (1 × 10⁻⁹ to 1 × 10^-8M) expression of AQP9 mRNA increased and the expression of AQP11 was not affected by BPA (P > 0.05). There was an inhibitory effect of BPA on the release of synthesis of asparagine, threonine, taurine, tryptophan, and ornithine into the culture medium by pTr2 cells. Collectively, BPA adversely affected the expression of transporters for cationic amino acids like arginine, as well as AQPs, IGF1, and IGF1R associated with proliferation, migration, and adhesion of pTr2 cells. Those adverse effects would likely increase pregnancy losses during the peri-implantation period of pregnancy.     

Immunogenicity of the hepatitis A vaccine 20 years after infant immunization

To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer ≥ 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.