Modifying effects of disulfiram on DNA adduct formation and persistence of benzaldehyde in N-nitroso-N-methyl-benzylamine-induced carcinogenesis in rats

Summary Whereas disulfiram (DSF) is known to inhibit tumor formation resulting from a number of chemical carcinogens, such inhibition does not apply to nitrosamines. In the present study, biochemical and morphological findings were examined to elucidate the effect of DSF on long-term application of N-nitroso-N-methylbenzylamine (NMBA). HPLC and fluorescence detection were used to determine O⁶-methylguanine (O⁶-MG) in DNA obtained from the respiratory tract of rats subjected to long-term simultaneous application of DSF and NMBA. After 2 days of treatment, more O⁶-MG was detected in the proximal portion of the respiratory tract, including the trachea and main bronchi, than in the distal portion. The findings were reversed after 10 and 30 days, at which time formation of the DNA adduct was substantially higher in the distal portion of the respiratory tract, despite increases in both portions. The biochemical results corresponded to morphological findings. Initially, mereased numbers of metabolizing goblet cells appeared in mucous cell hyperplasia in the proximal respiratory tract. Subsequently, the hyperplasia migrated to distal regions of the respiratory tract; at this stage, the goblet cells disappeared from the proximal portion, which now revealed toxic degeneration, atrophy and subsequent squamous metaplasia of the mucous lining and squamous papillomas.At various times during a 40-day period, 2 to 7 times more O⁶-MG in pulmonary DNA was detected in rats treated with DSF and NMBA, than with NMBA alone, whereby distinct amounts of O⁶-MG were found in the latter animals. In contrast to the above-mentioned morphological findings, no morphological alterations occurred in the respiratory tract of the animals treated with NMBA alone. It is therefore conceivable that the above pathological lesions resulted not merely from the presence of DNA adducts, but also from an additional, previously unspecified effect.As benzaldehyde (BA) is formed in equimolar amounts in NMBA metabolism and DSF has been demonstrated to inhibit aldehyde metabolism, this aldehyde is a possible candidate for such an effect. In the present study, rats were therefore treated with BA, DSF, or NMBA, or combinations thereof. Histomorphological evaluation of these experiments revealed that long-term application of BA alone led to the following alterations in the respiratory tract: goblet cell hyperplasia, hyperplasia of the peribronchial lymphatic system, mucous epithelial atrophy and accompanying peerivasculitis — the same alterations seen under long-term application of NMBA and DSF. Furthermore, these changes were most pronounced in the group with concomitant application of NMBA, DSF, and BA. It is therefore conceivable that BA plays a role in pathological changes observed under the influence of NMBA.Presented at the SEK workshop DNA Adducts and Chemical Carcinogenesis, Tübingen, February 28–March 1, 1986Supported by Breuninger Stiftung, D-7000 Stuttgart; AWG-Analysen-Geräte GmbH, D-7970 Leutkirch, FRG; Asta-Werke AG, D-6000 Frankfurt am Main. FRG; Cyanamid GmbH, D-8190 Wolfratshausen, FRG, Farmitalia Carlo Erba GmbH, D-7800 Freiburg i Br., FRG     

2011—2020年湖南省伤寒、副伤寒流行病学特征和菌株耐药分析

目的 分析2011—2020年湖南省伤寒、副伤寒流行特征和菌株耐药情况,为做好伤寒、副伤寒防控工作提供依据。方法 收集2011—2020年湖南省伤寒、副伤寒监测数据,采用描述性流行病学方法分析三间分布特征,对各市州分离上送的67株伤寒、副伤寒沙门菌采用梅里埃VITEK2 Compact 全自动细菌鉴定及药敏分析系统进行细菌鉴定和药敏分析。结果 10年间湖南省共报告伤寒、副伤寒病例9 888例,死亡0例,年均发病率1.47/10万。发病人群以农民、散居儿童、学生为主,5—9月为高发季节,主要集中在湘南和湘西地区。2011—2020年湖南省共报告4起伤寒、副伤寒暴发疫情,暴发场所均为学校,传播途径均为水型传播。67株伤寒、副伤寒菌对头孢他啶、氨曲南和厄他培南100%敏感;对哌拉西林/他唑巴坦、头孢吡肟和复方新诺明敏感率为98.5%;对氨苄西林/舒巴坦敏感率为97.0%;对头孢唑林、头孢替坦、阿米卡星、庆大霉素和妥布霉素敏感性较低（＜10%）。55.3%菌株对三类及以上抗生素耐药,发现1株同时对8种抗生素耐药。结论 湖南省伤寒、副伤寒发病呈持续低发状态,局部地区存在暴发。菌株多重耐药现象严重,应加强疫情及耐药监测。     

2008-2018年云南省人间布鲁菌病流行特征及灰色GM(1,1)模型预测

目的分析云南省布鲁菌病(简称布病)流行特征,建立灰色GM(1,1)模型,预测云南省布病病情。方法收集中国疾病预防控制信息系统和云南省统计局2008-2018年云南省布病疫情数据和人口资料,分析布病流行病学特征(包括时间、地区、人群分布),并以灰色GM(1,1)模型进行建模,预测2019、2020年云南省布病发病率。结果2008-2018年云南省共报告布病病例1216例,年均发病率为0.2374/10万,呈逐年递增趋势(χ²趋势=843.34,P<0.01)。病例报告主要集中在3-9月份,占总病例数的69.41%(844/1216)。病例报告数居前5位的州市分别为红河州(289例)、曲靖市(264例)、昆明市(258例)、大理州(160例)、玉溪市(134例),占总病例数的90.87%(1105/1216)。职业以农民为主,占79.03%(961/1216)。建立灰色GM(1,1)模型预测2019、2020年云南省布病发病率分别为0.4876/10万和0.4817/10万。结论云南省布病发病较以往上升,应对重点地区、重点人群进行针对性防控,并对预测结果进行前瞻性评价,逐步完善云南省布病预测模型。     

人SR-AI转基因小鼠模型的主要形态学特性、血液学指标和血脂水平的研究

目的明确人SR-AI转基因小鼠的一些形态、脏器、血液学和血浆脂质参数,为人SR-AI转基因小鼠模型的应用提供相关依据.方法用游标卡尺和电子称量天平测量人SR-AI转基因小鼠的吻长、眶间距、体长、尾长及12个脏器系数并与C57BL/6J小鼠进行比较分析;用SysmexK-4500型全血自动多参数血液分析仪检测其血液学指标;并用酶法分别测定血浆总胆固醇、甘油三酯和高密度脂蛋白胆固醇含量.结果人SR-AI转基因小鼠外部形态指标和脏器系数与C57BL/6J小鼠比较差异没有显著意义(P>0.05);转基因小鼠的各项血液学指标无明显改变,血脂蛋白成分的改变亦未显示统计学意义(P>0.05),甘油三酯的浓度略有增高(P<0.05).结论人SR-AI转基因小鼠的外部形态指标、脏器系数及各项血液学指标均无明显改变,适合用作动脉粥样硬化模型的研究.     

Clinical features and outcome of maintenance hemodialysis patients with COVID-19 from a tertiary nephrology care center in Romania

Background There is limited information about the clinical characteristics, treatment and outcome of maintenance hemodialysis patients with COVID-19. Moreover, regional differences are also conceivable since the extend and severity of outbreaks varied among countries.Methods In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of 37 maintenance hemodialysis patients (median age 64 years, 51% men) hospitalized with COVID-19 from 24 March to 22 May 2020 as confirmed by real-time PCR.Results The most common symptoms at admission were fatigue (51%), fever (43%), dyspnea (38%) and cough (35%). There were 59% mild/moderate patients and 41% severe/critical patients. Patients in the severe/critical group had a significantly higher atherosclerotic burden since diabetic kidney disease and vascular nephropathies were the most common primary kidney diseases and eighty percent of them had coronary heart disease. Also, Charlson comorbidity score was higher in this group. At admission chest X-ray, 46% had ground-glass abnormalities. Overall, 60% patients received hydroxychloroquine, 22% lopinavir–ritonavir, 11% tocilizumab, 24% systemic glucocorticoids, and 54% received prophylactic anticoagulation. Seven (19%) patients died during hospitalization and 30 were discharged. The main causes of death were cardiovascular (5 patients) and respiratory distress syndrome (2 patients). In Cox regression analysis, lower oxygen saturation, anemia and hypoalbuminemia at admission were associated with increased mortality.Conclusions In conclusion, we observed a high mortality rate among maintenance hemodialysis patients hospitalized for COVID-19. Anemia, lower serum albumin and lower basal oxygen saturation at admission were factors associated with poor prognosis.     

子宫腺肌症患者临床特点回顾性分析

目的研究子宫腺肌症患者临床特点,为子宫腺肌症患者的临床管理提供理论基础。方法收集2012年3月至2015年9月于北京协和医院妇产科手术且确诊的291例子宫腺肌症患者资料,对临床检查结果进行统计学分析。结果子宫腺肌症患者发病的中位年龄为[34(29.0,40.0)]岁,确诊的中位年龄为[40(35.0,44.0)]岁。所有纳入患者中,9.3%的患者无症状,17.5%的患者因不孕症就诊,39.5%的患者发现月经异常,71.8%的患者伴疼痛症状。38.8%的患者合并子宫内膜异位症,58.1%的患者合并子宫肌瘤。72.4%的患者术前发现血清糖类抗原125(CA125)升高,超声扫描结果显示85.6%的患者子宫肌层的回声不均匀。接受子宫病灶切除术的患者208位(71.5%),接受全子宫切除伴或不伴附件切除术的患者83位(28.5%);接受经腹手术、腹腔镜手术及宫腔镜手术患者的比例分别为37.8%、59.5%和2.7%。结论子宫腺肌症患者发病年龄较轻,多伴有月经异常、疼痛及不孕症状,合并症以卵巢的子宫内膜异位症多见。因此,应根据子宫腺肌症患者的临床表现及生育要求制定个体化治疗方案。     

中重度僵硬型颈椎后凸畸形的形态特点与手术效果

【摘要】 目的：评估中重度僵硬型颈椎后凸的矢状位形态特征与手术效果,并分析影响手术矫形效果及神经功能转归的相关因素。方法：回顾性分析2014年1月~2021年3月在我院接受手术治疗的34例中重度僵硬型颈椎后凸畸形患者临床资料,中重度后凸定义为局部后凸角≥20°,僵硬型后凸定义为过伸位X线片示后凸柔韧性＜30%或颈椎CT示后凸节段骨性强直。患者接受手术时年龄为50.1±17.6岁（14~83岁）,其中男性21例,女性13例。致畸因素包括退变性后凸18例,先天畸形5例,医源性后凸5例,强直性脊柱炎3例,创伤性后凸3例。行前路、后路或前后路联合手术分别为24例、5例及5例;其中5例行三柱截骨矫形手术。收集所有患者术前一般资料、围手术期参数和随访信息,并利用疼痛视觉模拟评分（visual analogue scale,VAS）、颈椎功能障碍指数（neck disability index,NDI）及日本骨科协会改良颈椎评分（modified Japanese Orthopaedic Association scale,mJOA）评估患者颈部疼痛和神经功能状态。通过颈椎侧位X线片测量患者术前、术后即刻及末次随访时的局部后凸角、T1倾斜角、颈椎矢状面垂直轴及颌眉垂线角,并定义畸形成角系数为局部后凸角/后凸累及节段数。根据数据分布情况选用独立样本或配对样本t检验、Mann-Whitney U检验、Wilcoxon signed-rank检验、卡方检验或Fisher精确概率检验比较上述影像学参数与评分指标在不同时间点或不同患者亚组间的分布。结果：患者局部后凸角中位数为25°（20°~100°）,畸形成角系数中位数为7.5°（5°~25°）。根据mJOA评分将患者分为两组,重度颈脊髓病组患者的畸形成角系数显著大于轻中度颈脊髓病组[9.3°（5.0°~25.0°） vs 7.0°（5.3°~10.0°）,P=0.016];手术时长277±140min,中位失血量150（20~2000）ml。局部后凸角与畸形成角系数分别由术前的31.6°±19.5°与8.8°±4.2°矫正至术后2.8°±5.7°与0.9°±1.9°,差异有统计学意义（P<0.001）;经过1.0±0.8（0.3~3.1）年的影像学随访,末次随访时局部后凸角与畸形成角系数与术后即刻相比差异均无统计学意义（P>0.05）;经过3.0±1.5年的临床随访,末次随访时患者VAS、NDI及mJOA评分分别由术前的5.3±1.8分、（27.7±16.5）%及11.9±4.3分改善至1.3±1.2分、（7.7±7.1）%及14.8±2.2分,差异有统计学意义（P<0.001）。畸形成角系数的矫形幅度与mJOA评分的改善幅度呈正相关（Spearman r=0.417,P=0.018）。共有14例患者（41.2%）术后出现早期并发症,包括10例（29.4%）神经系统并发症;共有8例患者（23.5%）出现远期并发症。发生术后早期并发症的患者病程更长,最高截骨等级>2级的比例更高,手术出血量更大（P<0.05）。结论：选择恰当的手术方式治疗中重度僵硬型颈椎后凸畸形可以获得满意的临床疗效。畸形成角系数可以作为形态学评估的重要参数,并在一定程度上预测术后神经功能改善情况。     

中国胆囊癌外科治疗现状与病理学特征多中心回顾性研究（附4345例报告）

目的 探讨中国胆囊癌病人的外科治疗模式、病理学特征和预后。方法 收集中国13个省市的26家医院自2010年1月至2017年12月收治的4345例胆囊癌病人临床资料,分析中国胆囊癌病人的地区、性别、年龄分布;基于病人的诊疗记录与检查结果对手术病人肿瘤的可切除性进行评估,分析可切除性肿瘤病人的外科治疗模式,参照术前检查、手术记录和术后病理学检查结果评估可切除性肿瘤手术治疗是否达到根治标准,分析行根治性手术胆囊癌病人的病理学特征。结果 4345例胆囊癌病人中,男性1664例（38.23%）,女性2681例（61.77%）。行外科手术治疗的病人3129例（71.01%）,其中可切除性肿瘤2074例（66.28%）。在可切除性肿瘤2074例病人中,仅1133例（54.63%）在术前即诊断为胆囊恶性肿瘤,1002例（48.31%）行根治性切除,1072例（51.69%）未达根治标准。胆囊癌根治性切除病人的病理学检查结果中,736例（73.45%）为腺癌,348例（34.73%）为低分化癌,376例（37.52%）伴肝侵犯,152例（15.17%）伴神经浸润,96例（9.58%）伴血管内癌栓,78例（7.78%）伴周围脂肪组织浸润,89例（8.88%）伴周围器官受累,328例（32.73%）活体组织病理学检查淋巴结阳性。获得生存随访资料的2357例手术治疗病人术后中位生存期为16.17个月,多因素Cox回归生存分析结果显示肿瘤TNM分期（P<0.001）、肿瘤分化程度（P<0.001）、肝脏侵犯（P<0.001）、R0切除（P=0.003）均为术后生存期的独立预后因素。结论 中国胆囊癌术前诊断率有待提高;胆囊癌外科治疗模式亟待规范;病理学检查报告中反映的多个因素与胆囊癌病人预后密切相关,其描述的规范化对指导胆囊癌病人的精准治疗有重要意义。     

基于术前MRI影像组学特征预测肝癌经肝动脉化疗栓塞治疗的反应性

目的 探索术前MRI影像组学特征预测肝细胞癌（hepatocellular carcinoma,HCC）对经肝动脉化疗栓塞（transcatheter arterial chemoembolization,TACE）治疗反应性的可行性。方法 回顾性收集2016年3月至2018年4月经临床或病理确诊、并在温州医科大学附属第五医院接受TACE治疗的中晚期HCC患者86例,采用随机数字表法分为训练组（n=59）及验证组（n=27）,基于ITK-SNAP软件在术前T2WI图像勾画肿瘤感兴趣区,使用GE AI-Kit软件提取影像特征;经最小绝对收缩与选择算子（LASSO）回归筛选最优的特征子集,并构建TACE反应性预测模型;利用受试者工作特征（ROC）曲线、校准曲线及决策曲线分析评价模型的诊断效能和临床应用价值。结果 共筛选出8个影像学特征与TACE反应性相关,并成功构建预测模型。训练组中,该模型的ROC曲线下面积（AUC）为0.838（95%CI 0.737～0.939）,灵敏度为74.1%,特异度为84.4%;在验证组中,AUC为0.794（95%CI 0.604～0.985）,灵敏度为75.0%,特异度为80.0%。校准曲线显示该模型在训练组和验证组的预测概率与实际概率拟合较好;决策曲线分析显示该模型在0.1～1.0的阈值范围内具有较高的净收益。结论 术前MRI T2WI图像影像组学特征可用于预测HCC的TACE 反应性,基于MRI T2WI图像影像特征的预测模型特异度和灵敏度较高。     

成都379例新型冠状病毒肺炎的临床分析

目的分析新型冠状病毒肺炎(COVID-19)患者的临床特征及预后。方法纳入成都市公共卫生临床医疗中心2020年1月16日至11月30日收治的379例COVID-19确诊病例,按照年龄分为老年组(42例,年龄≥60岁)和非老年组(337例,年龄<60岁),比较两组患者的流行病学、临床特征、实验室检查、治疗及预后。结果379例患者年龄2个月至87岁,平均41.2岁,其中男286例(75.5%),女93例。老年组平均年龄为69.5岁,女性更多见(占61.9%),大多为武汉输入和本土续发(占73.8%),以普通型和危重型为主(88.1%)。非老年组的平均年龄为37.8岁,男性更多见(80.1%),主要来自境外输入(75.7%),以轻型和普通型为主(95.0%)。179例患者(47.2%)合并一种或多种基础疾病,老年组以高血压病(15例,35.7%)及糖尿病(11例,26.2%)多见,而非老年组则以非酒精性脂肪性肝炎(132例,39.2%)多见。最常见的临床表现是发热(138例,36.4%)和咳嗽(129例,34.0%),但老年组的发热、咳嗽、呼吸困难及乏力等症状较非老年组更多见(P<0.05)。与非老年组相比,老年组的总淋巴细胞计数、CD4⁺及CD8⁺T淋巴细胞计数更低,而心肌损伤标志物及炎症指标更高(P<0.05)。139例患者(36.7%)的心脏彩色超声心动图异常,主要为左室舒张功能降低(22.7%)及心脏瓣膜反流(14.0%),且老年组患者的心脏彩色超声心动图异常率明显高于非老年组(85.7%vs.30.6%,P<0.05)。经治疗后,除老年组死亡3例外,其余均已治愈出院;但老年组的住院时间较非老年组更长(22.1 d vs.18.8 d,P=0.033)。结论成都老年COVID19患者主要来自武汉输入和本地续发,以普通型和危重型为主,常合并高血压或糖尿病等基础疾病;成都非老年COVID-19患者主要来自境外输入,以轻型和普通型为主,常合并非酒精性脂肪性肝炎;经治疗后,患者大多预后良好。