The prognostic value of the neutrophil/lymphocyte ratio in patients with snake bites for clinical outcomes and complications

IntroductionSnake bites have cardiotoxicity, neurotoxic, myotoxic, nephrotoxic, and hemotoxic features. The neutrophil/lymphocyte ratio (NLR) provides valuable information for the determination of the diagnosis and prognosis of various diseases. In this study, we aimed to investigate the relationship between NLR with the development of complications and duration of hospital stay in snakebite cases.MethodIn this study, 107 patients with snakebite complaints that applied to a tertiary care university hospital between 2011 and 2014 were retrospectively reviewed. The control group compromised of 107 age-and gender-matched healthy subjects. These patients were examined using their previous laboratory results, bite areas pictures, geographic location, and analysis of complications that developed during the hospitalization.ResultsPatients in our snake bites group (n = 107), included males (64%) and females (36%). When NLR1–NLR2, NLR1–NLR3, and NLR2–NLR3 were compared, a statistically significant difference was found (p < 0.001). No mortality was observed in our patients. In cases of snakebites, 4.67% of the patients underwent finger amputation. Compartment syndrome occurred in 3.73% of patients. In one case that developed compartment syndrome, a finger amputation was made. When 8 patients with a complication were compared with patients having snakebite but no complication, the initial NLR was found to be higher and statistically significant (p = 0.042). The average length of stay of patients in the hospital was 9 days. In the analysis of the correlation between the duration of hospitalization and NLR, the patients with a high level of NLR were found to have a longer hospital stay compared to lower NLR levels (p = 0.012).ConclusionNLR was significantly increased in patients that developed complications and needed a longer stay in the hospital.     

Proteasome Inhibitor PS-341 Effectively Blocks Infection by the Severe Fever with Thrombocytopenia Syndrome Virus

Severe fever with thrombocytopenia syndrome(SFTS) is an emerging hemorrhagic fever disease caused by SFTSV, a newly discovered phlebovirus that is named after the disease. Currently, no effective vaccines or drugs are available for use against SFTSV infection, as our understanding of the viral pathogenesis is limited. Bortezomib(PS-341), a dipeptideboronic acid analog, is the first clinically approved proteasome inhibitor for use in humans. In this study, the antiviral efficacy of PS-341 against SFTSV infection was tested in human embryonic kidney HEK293 T(293 T) cells. We employed four different assays to analyze the antiviral ability of PS-341 and determined that PS-341 inhibited the proliferation of SFTSV in 293 T cells under various treatment conditions. Although PS-341 did not affect the virus absorption, PS-341 treatment within a non-toxic concentration range resulted in a significant reduction of progeny viral titers in infected cells.Dual-luciferase reporter assays and Western blot analysis revealed that PS-341 could reverse the SFTSV-encoded nonstructural protein(NS) mediated degradation of retinoic acid-inducible gene-1(RIG-I), thereby antagonizing the inhibitory effect of NSs on interferons and blocking virus replication. In addition, we observed that inhibition of apoptosis promotes virus replication. These results indicate that targeting of cellular interferon pathways and apoptosis during acute infection might serve as the bases of future therapeutics for the treatment of SFTSV infections.     

多囊卵巢综合征肥胖患者血清维生素D、铁蛋白水平、sICAM-1与胰岛素抵抗、糖脂代谢指标的相关性

摘要 目的：探讨多囊卵巢综合征（PCOS）肥胖患者血清维生素D、铁蛋白、可溶性细胞间粘附分子-1（sICAM-1）水平与胰岛素抵抗、糖脂代谢指标的相关性。方法：2018年8月到2021年11月,选择在本院妇科诊治的PCOS患者65例作为研究对象,分为PCOS肥胖组（n=30,体重指数＜28 kg/m²）和PCOS非肥胖组（n=35,体重指数<28 kg/m²）。检测与计算两组清维生素D、铁蛋白、sICAM-1、胰岛素抵抗、糖脂代谢指标并进行相关性分析。结果：两组的血清甲状腺素（T4）、促甲状腺激素（TSH）与泌乳素（PRL）对比差异无统计学意义（P>0.05）,肥胖组的血清促黄体生成素（LH）、促卵泡生成素（FSH）、睾酮（T）水平高于非肥胖组（P<0.05）。肥胖组的血清铁蛋白、sICAM-1水平高于非肥胖组,血清维生素D水平低于非肥胖组（P<0.05）。肥胖组的胰岛素抵抗指数（HOMA-IR）、胰岛素水平（FINS）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）较非肥胖组,高密度脂蛋白胆固醇（HDL-C）低于非肥胖组（P<0.05）。在PCOS肥胖患者中,Pearson分析显示血清维生素D、铁蛋白、sICAM-1与胰岛素抵抗、糖脂代谢指标都存在相关性（P<0.05）。结论：PCOS肥胖患者与非肥胖患者的血清维生素D、铁蛋白、sICAM-1、胰岛素抵抗、糖脂代谢指标水平存在差异,血清维生素D、铁蛋白、sICAM-1水平与胰岛素抵抗、糖脂代谢指标存在相关性。     

Prenatal diagnosis and molecular cytogenetic characterization of a de novo proximal interstitial deletion of chromosome 4p (4p15.2→p14)

We present prenatal diagnosis of de novo proximal interstitial deletion of chromosome 4p (4p15.2→p14) and molecular cytogenetic characterization of the deletion using uncultured amniocytes. We review the phenotypic abnormalities of previously reported patients with similar proximal interstitial 4p deletions, and we discuss the functions of the genes of RBPJ, CCKAR, STIM2, PCDH7 and ARAP2 that are deleted within this region.     

DNA repair mechanisms in dividing and non-dividing cells

DNA damage created by endogenous or exogenous genotoxic agents can exist in multiple forms, and if allowed to persist, can promote genome instability and directly lead to various human diseases, particularly cancer, neurological abnormalities, immunodeficiency and premature aging. To avoid such deleterious outcomes, cells have evolved an array of DNA repair pathways, which carry out what is typically a multiple-step process to resolve specific DNA lesions and maintain genome integrity. To fully appreciate the biological contributions of the different DNA repair systems, one must keep in mind the cellular context within which they operate. For example, the human body is composed of non-dividing and dividing cell types, including, in the brain, neurons and glial cells. We describe herein the molecular mechanisms of the different DNA repair pathways, and review their roles in non-dividing and dividing cells, with an eye toward how these pathways may regulate the development of neurological disease.     

MLH1 constitutional and somatic methylation in patients with MLH1 negative tumors fulfilling the revised Bethesda criteria

Lynch syndrome (LS) is a tumor predisposing condition caused by constitutional defects in genes coding for components of the mismatch repair (MMR) apparatus. While hypermethylation of the promoter of the MMR gene MLH1 occurs in about 15% of colorectal cancer samples, it has also been observed as a constitutional alteration, in the absence of DNA sequence mutations, in a small number of LS patients. In order to obtain further insights on the phenotypic characteristics of MLH1 epimutation carriers, we investigated the somatic and constitutional MLH1 methylation status of 14 unrelated subjects with a suspicion of LS who were negative for MMR gene constitutional mutations and whose tumors did not express the MLH1 protein. A novel case of constitutional MLH1 epimutation was identified. This patient was affected with multiple primary tumors, including breast cancer, diagnosed starting from the age of 55 y. Investigation of her offspring by allele specific expression revealed that the epimutation was not stable across generations. We also found MLH1 hypermethylation in cancer samples from 4 additional patients who did not have evidence of constitutional defects. These patients had some characteristics of LS, namely early age at onset and/or positive family history, raising the possibility of genetic influences in the establishment of somatic MLH1 methylation.     

肺炎克雷伯菌致肝脓肿侵袭综合征3例临床分析及文献复习

为提高对肺炎克雷伯菌感染所致肝脓肿侵袭综合征的临床表现及其危害的认识,回顾性分析3例确诊为肺炎克雷伯菌感染所致肝脓肿患者的临床经过、治疗反应及转归。结果发现3例患者均有肝外播散性病灶,符合肝脓肿侵袭综合征的临床特征。这3例患者为社区获得性感染,均有肝脓肿,其中2例合并眼内炎并造成失明,1例合并腰椎感染、腹主动脉感染及感染性心内膜炎。2例有糖尿病病史,1例免疫正常。结合文献复习,发现肺炎克雷伯菌感染引起肝脓肿及肝外播散性病灶,临床上称为肝脓肿侵袭综合征,大多由高毒力肺炎克雷伯菌引起,好发于糖尿病及免疫缺陷人群,也可发生于免疫正常人群,治疗困难,临床危害严重,需引起重视。