Plasmacytoid variant urothelial bladder cancer: Is it time to update the treatment paradigm?

ObjectivesPlasmacytoid variant (PCV) urothelial cancer (UC) of the bladder is rare, with poor clinical outcomes. We sought to identify factors that may better inform expectations of tumor behavior and improve management options in patients with PCV UC.Materials and methodsA retrospective analysis of the Indiana University Bladder Cancer Database between January 2008 and June 2013 was performed comparing 30 patients with PCV UC at cystectomy to 278 patients with nonvariant (NV) UC at cystectomy who underwent surgery for muscle-invasive disease. Multivariable logistic regression was used to assess precystectomy variables associated with non–organ-confined disease at cystectomy and Cox regression analysis to assess variables associated with mortality.ResultsPatients with PCV UC who were diagnosed with a higher stage at cystectomy (73% pT3-4 vs. 40%, P = 0.001) were more likely to have lymph node involvement (70% vs. 25%, P<0.001), and positive surgical margins were found in 40% of patients with PCV UC vs. 10% of patients with NV UC (P<0.001). Median overall survival and disease-specific survival were 19 and 22 months for PCV, respectively. Median overall survival and disease-specific survival had not been reached for NV at 68 months (P<0.001). Presence of PCV UC on transurethral resection of bladder tumor was associated with non–organ-confined disease (odds ratio = 4.02; 95% CI: 1.06–15.22; P = 0.040), and PCV at cystectomy was associated with increased adjusted risk of mortality (hazard ratio = 2.1; 95% CI: 1.2–3.8; P = 0.016).ConclusionsPCV is an aggressive UC variant, predicting non–organ-confined disease and poor survival. Differentiating between non–muscle- and muscle-invasive disease in patients with PCV UC seems less important than the aggressive nature of this disease. Instead, any evidence of PCV on transurethral resection of bladder tumor may warrant aggressive therapy.     

变异性鼻炎应用通窍鼻炎片联合糠酸莫米松鼻喷雾剂治疗的效果观察

目的探究变异性鼻炎应用通窍鼻炎片联合糠酸莫米松鼻喷雾剂治疗的效果。方法本次研究资料选取时间段为2019年8月至2020年8月,患者为我院诊治的96例变异性鼻炎患者。经随机数字表法予以分组,其中参照组(48例)行糠酸莫米松鼻喷雾剂治疗,观察组(48例)行通窍鼻炎片联合糠酸莫米松鼻喷雾剂治疗。比较两组临床疗效及症状、体征情况与不良反应发生情况等。结果相较参照组,观察组治疗总有效率更高,不良反应发生率更低(P<0.05)。两组治疗后临床症状、体征评分均比治疗前低,且观察组比参照组低(P<0.05)。结论变异性鼻炎患者应用通窍鼻炎片联合糠酸莫米松鼻喷雾剂治疗效果确切,利于患者疗效提高、症状改善及不良反应发生率降低,可行推广。     

中国7个地区诺如病毒G II．4／Sydney 2012变异株分析

目的　分析2012--2013年冬季中国地区诺如病毒新流行株GII．4／Sydney 2012的衣壳蛋白区核苷酸与氨基酸变异特点。方法　对已获得的22份2012--2013年冬季北京地区GⅡ．4／Sydney2012株进行全衣壳蛋白区基因扩增。从GenBank检索中国其他地区的GⅡ．4／Sydney 2012株衣壳蛋白区核苷酸序列。对获得的GII．4／Sydney 2012株的衣壳蛋白区核苷酸及氨基酸序列与往年GⅡ．4流行株进行系谱分析。结果　获得中国7个地区（北京、上海、江苏、湖州、荆州、香港和台湾）的GⅡ．4／Sydney 2012株资料共38份（至少包含完整VPl核苷酸序列）。GH．4／Sydney 2012株之间VPl核苷酸差异为0．1％～3．3％,氨基酸差异为0～3．1％。系谱分析发现GⅡ．4／Sydney2012株与Apeldoorn 2008和NewOrleans 2009起自共同的分支。中国和悉尼GH．4／Sydney 2012代表株的A、D、E抗原表位氨基酸序列组合有两种：TSRN-GTT-SNT和TSRN-STT-SNT。结论　G II．4／Sydney 2012株已在中国多个地区出现,各地区病毒株同源性较高。G H．4／Sydney 2012株的抗原表位氨基酸组合发生明显改变。     

东莞地区16182名个体18个耳聋易感基因100个变异位点的测序筛查

目的确定东莞地区耳聋基因的变异类型和携带率。方法收集新生儿及门诊筛查的16182名个体,新生儿采集足跟血片,非新生儿采集外周静脉血样,对18个耳聋易感基因的100种变异进行检测。结果共检出1631例耳聋基因变异,总体检出率为10.08%,其中5例为纯合变异。SLC26A4基因变异的检出率最高(5.22%),共845例,其余依次为GJB2(673例,4.16%)、GJB3(100例,0.62%)、TMC1(12例,0.07%)、MYO15A(1例,0.01%)。GJB2基因c.235delC变异检出率最高(3.24%),共524例,其次为SLC26A4基因IVS7-2A>G变异(270例,1.67%)。33名个体(0.20%)同时携带两个变异,其中7例(0.04%)携带同一基因的复合杂合变异。结论扩大耳聋易感基因变异的筛查范围有助于了解携带情况及耳聋的遗传因素,对提早发现先天性耳聋、对受检者提供干预和遗传咨询具有重要的价值。     

Booster BNT162b2 COVID-19 Vaccination Increases Neutralizing Antibody Titers Against the SARS-CoV-2 Omicron Variant in Both Young and Elderly Adults

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND₅₀) titers in serum samples. ND₅₀ titers against the omicron variant (median [interquartile range], 5.3 [< 5.0–12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7–294.0]) and delta (24.3 [14.3–81.1]) variants. Furthermore, 19/30 participants (63.3%) displayed lower ND₅₀ titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND₅₀ titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.     

利用DNA序列对错义突变的致病性进行预测

错义突变的致病性预测在基因组学和临床研究中有重要作用,其中基于计算方法的预测工具已经取得较大进展。现有的工具大多根据功能影响、保守性来对错义突变的致病性进行预测,从DNA序列出发进行错义突变致病性预测的工具较少。随着自然语言处理技术在多个生物序列领域的迁移学习和应用,将DNA序列作为一种生物语言进行处理并进行基因突变的致病性预测越来越值得探索。该文提出了一个基于预训练的自然语言模型DNABert和DNA突变序列对错义突变致病性进行预测的深度学习模型MissenseBert,并且在多个数据集上对MissenseBert进行了训练和测试,测试结果说明MissenseBert取得了较好的预测效果,证明了利用DNA序列预测错义突变的致病性具有可行性。     

An Outbreak of Breakthrough Infections by the SARS-CoV-2 Delta Variant in a Psychiatric Closed Ward

BackgroundA rapid decline in immunity and low neutralizing activity against the delta variant in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinees has been observed. This study describes an outbreak of coronavirus disease 2019 (COVID-19) breakthrough infections caused by the SARS-CoV-2 delta variant in a psychiatric closed ward.MethodsData from epidemic intelligence service officers were utilized to obtain information regarding demographic, vaccination history, and clinical data along with SARS-CoV-2 PCR test results for a COVID-19 outbreak that occurred in a closed psychiatric ward.ResultsAmong the 164 residents, 144 (87.8%) received two doses of vaccines and 137 (95.1%) of them received ChAdOx1 nCoV-19 vaccine. The mean interval between the second vaccination and COVID-19 diagnosis was 132.77 ± 40.68 days. At the time of detection of the index case, SARS-CoV-2 had spread throughout the ward, infecting 162 of 164 residents. The case-fatality ratio was lower than that in the previously reported outbreak before the vaccination (1.2%, 2/162 vs. 6.9%, P = 0.030). Prolonged hospitalization occurred in 17 patients (11.1%) and was less prevalent in the vaccinated group than in the unvaccinated group (8.5% vs. 25.0%, P = 0.040).ConclusionThe findings of this study highlight that while vaccination can reduce mortality and the duration of hospitalization, it is not sufficient to prevent an outbreak of the SARS-CoV-2 delta variant in the present psychiatric hospital setting.     

呼吸道合胞病毒融合蛋白变异及其对抗体和药物效果的影响

呼吸道合胞病毒(respiratory syncytial virus,RSV)是造成婴幼儿与老年人下呼吸道感染和住院的主要原因之一.目前开发疫苗、抗体及药物成为防控RSV的热点,其主要靶点是融合蛋白(fusion glyco-protein,F).本文分析了现有RSV病毒株融合蛋白的变异情况,剖析了融合蛋白的结构特点...     

疏肝解郁方加减治疗胸闷变异性哮喘临床经验总结

胸闷变异性哮喘(Chest Tightness Variant Asthma,CTVA)属于支气管哮喘类型中少见的一种特殊哮喘,其症状主要表现为胸闷,而无咳嗽、气喘、气促、喉中哮鸣声等典型哮喘表现,故临床常被误诊.西医治疗主要是吸入糖皮质激素,但临床应用效果差,其原因考虑CTVA与过敏无明显关系,主要与患者的情志有很大...     

PIGA related disorder as a range of phenotypes rather than two distinct subtypes

Patients with germline phosphatidylinositol glycan biosynthesis class A (PIGA) related disorder have historically been categorized into one of two distinct subtypes: a severe form which is often fatal, and a less severe form. However, the increasing number of cases with features indicative of both subtypes raise the possibility of a phenotypic spectrum associated with PIGA disorder.In order to further characterize this phenotypic spectrum, we present two patients with features of both the severe and less severe subtypes with a review of phenotypes reported to date in the literature. In eight year old patient 1, a maternally inherited PIGA likely pathogenic variant was discovered using exome sequencing. He presented with myoclonic epilepsy, mild intellectual disability, spastic diplegia, developmental motor delay, and autism spectrum disorder. Patient 2 is a 13 year old with focal epilepsy, profound developmental delay, coarse facial features, severe intellectual disability and autism spectrum disorder. A de novo PIGA likely pathogenic variant was found through exome sequencing. Both patients had normal alkaline phosphatase levels and are without related organ abnormalities. We conclude that pathogenic PIGA variants cause a spectrum of phenotypes rather than the categories of “severe” and “less severe” as previously posited.