A Robust Approach for Blind Detection of Balanced Chromosomal Rearrangements with Whole‐Genome Low‐Coverage Sequencing

Balanced chromosomal rearrangement (or balanced chromosome abnormality, BCA) is a common chromosomal structural variation. Next‐generation sequencing has been reported to detect BCA‐associated breakpoints with the aid of karyotyping. However, the complications associated with this approach and the requirement for cytogenetics information has limited its application. Here, we provide a whole‐genome low‐coverage sequencing approach to detect BCA events independent of knowing the affected regions and with low false positives. First, six samples containing BCAs were used to establish a detection protocol and assess the efficacy of different library construction approaches. By clustering anomalous read pairs and filtering out the false‐positive results with a control cohort and the concomitant mapping information, we could directly detect BCA events for each sample. Through optimizing the read depth, BCAs in all samples could be blindly detected with only 120 million read pairs per sample for data from a small‐insert library and 30 million per sample for data from nonsize‐selected mate‐pair library. This approach was further validated using another 13 samples that contained BCAs. Our approach advances the application of high‐throughput whole‐genome low‐coverage analysis for robust BCA detection—especially for clinical samples—without the need for karyotyping.     

老年高血压病患者血浆β2微球蛋白及踝臂指数与血压变异性的关系

目的　探讨老年高血压病患者血浆β2微球蛋白（β2-MG）、踝臂指数（ABI）与血压变异性（BPV）的关系。方法　选取原发性老年高血压病患者269例,中年高血压病患者186例,分别与178例老年健康体检者进行对照,采用方差分析观察各组间血压变异性与血浆β2-MG情况。老年高血压病组按ABI分为两个亚组：ABI＜0.9组74例,ABI≥0.9组195例,比较两组间的血压变异性和血浆β2-MG等。结果　老年高血压病组24　h收缩压变异性（24hSBPV）、24　h舒张压变异性（24hDBPV）较老年对照组（21.50%±4.01%比15.16%±5.17%、15.99%±4.28%比11.24%±3.83%）和中年高血压病组（21.50%±4.01%比19.34%±6.28%、15.99%±4.28%比13.91%±5.43%）均显著增高（P<0.05）。ABI＜0.9亚组24hSBPV、24hDBPV、血浆β2-MG均显著高于ABI≥0.9亚组（P<0.05）。结论　老年高血压病患者血压变异性、血浆β2-MG水平均增高;ABI＜0.9的老年高血压病患者血压变异性、血浆β2-MG水平增高更明显。     

Label‐free molecular probe based on G‐quadruplex and strand displacement for sensitive and selective detection and naked eye discrimination of exon 2 deletion of AIMP2

Exon 2 deletion of aminoacyl tRNA synthetase complex‐interacting multifunctional protein 2 (AIMP2) is a genetic deletion related to various cancers, for instance ovarian and lung cancers. It can be worked as an indicator of cancer for diagnosis of diseases. Here, we developed a label‐free method based on the formation of split G‐quadruplex in the presence of target DNA combined with strand displacement to detect exon 2 deletion of AIMP2 (DE2) sensitively and selectively. This method is easy‐operating and cost‐saving. Moreover, it has observed discrimination of gene deletion from wild‐types by naked eyes. The results demonstrate that this strategy can be further used for the detection of different gene deletions to achieve early diagnosis of diseases and allow better prognosis.     

双腔前视胃镜治疗毕Ⅱ式胃空肠吻合术后胆胰疾病的临床观察

目的评价使用双腔前视胃镜对毕Ⅱ式胃空肠吻合术后胆胰疾病患者进行经内镜逆行胰胆管造影术（ERCP）治疗的疗效及安全性。方法回顾性总结46例使用双腔前视胃镜进行ERCP治疗的毕Ⅱ式胃空肠吻合术后胆胰疾病患者的临床资料,统计十二指肠乳头插管成功率、并发症发生情况和治疗情况。结果十二指肠乳头插管成功率为82．6％（38／46）,8例失败,其中6例因双腔前视胃镜无法进入输入袢找到十二指肠乳头而失败,2例因乳头插管困难而失败。38例插管成功者中,3l例胆管结石者均成功取出结石,4例胆总管下端恶性梗阻者均成功置入胆管金属支架,3例十二指肠乳头良性狭窄者经气囊扩张后均成功置入鼻胆引流管;所有患者术后恢复良好,无一例发生出血、穿孔和术后胰腺炎等严重并发症。结论使用双腔前视胃镜对毕Ⅱ式胃空肠吻合术后胆胰疾病患者进行ERCP治疗,插管成功率较高,可顺利完成后续ERCP相关治疗,并且不会明显增加并发症发生率,具有较好的临床应用价值。     

经房间隔穿刺途径消融左心室起源的室性心律失常

目的 经主动脉逆行法是消融左心室起源室性心律失常的常规路径,但部分患者因合并禁忌证而无法应用或应用此法时导管难以到位.本研究旨在观察通过穿刺房间隔途径消融左心室起源室性心律失常的安全性和有效性.方法 自2011年10月至2013年12月在阜外心血管病医院共入选13例合并主动脉逆行法禁忌证或既往经主动脉逆行法消融失败的左心室起源室性心律失常患者,应用Agilis鞘穿刺房间隔实施导管消融术并随访.结果 13例患者,其中5例室性早搏（室早）,8例室性心动过速（室速）.2例为左后分支起源的室速,1例为左前分支起源的室速,其余均为游离壁起源.术中均达到消融终点,无并发症发生.中位手术时间53 （40～ 72） min,X线曝光时间20（9～25） min.随访至术后4（1～23）个月,1例室速患者复发,再次经房间隔穿刺途径消融成功,另12例患者均无复发.结论 应用Agilis鞘穿刺房间隔消融左心室起源的室性心律失常安全有效,是主动脉逆行法的重要补充.     

Alteration of fecal tryptophan metabolism correlates with shifted microbiota and may be involved in pathogenesis of colorectal cancer

BACKGROUNDGut tryptophan (Trp) metabolites are produced by microbiota and/or host metabolism. Some of them have been proven to promote or inhibit colorectal cancer (CRC) in vitro and animal models. We hypothesized that there is an alteration of gut Trp metabolism mediated by microbiota and that it might be involved in the pathogenesis of cancer in patients with CRC.AIMTo investigate the features of Trp metabolism in CRC and the correlation between fecal Trp metabolites and gut microbiota.METHODSSeventy-nine patients with colorectal neoplastic lesions (33 with colon adenoma and 46 with sporadic CRC) and 38 healthy controls (HCs) meeting the inclusion and exclusion criteria were included in the study. Their demographic and clinical features were collected. Fecal Trp, kynurenine (KYN), and indoles (metabolites of Trp metabolized by gut microbiota) were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry. Gut barrier marker and indoleamine 2,3-dioxygenase 1 (IDO1) mRNA were analyzed by quantitative real-time polymerase chain reaction. Zonula occludens-1 (ZO-1) protein expression was analyzed by immunohistochemistry. The gut microbiota was detected by 16S ribosomal RNA gene sequencing. Correlations between fecal metabolites and other parameters were examined in all patients.RESULTSThe absolute concentration of KYN [1.51 (0.70, 3.46) nmol/g vs 0.81 (0.64, 1.57) nmol/g, P = 0.036] and the ratio of KYN to Trp [7.39 (4.12, 11.72) × 10^-3 vs 5.23 (1.86, 7.99) × 10^-3, P = 0.032] were increased in the feces of patients with CRC compared to HCs, while the indoles to Trp ratio was decreased [1.34 (0.70, 2.63) vs 2.46 (1.25, 4.10), P = 0.029]. The relative ZO-1 mRNA levels in patients with CRC (0.27 ± 0.24) were significantly lower than those in HCs (1.00 ± 0.31) (P < 0.001), and the relative IDO1 mRNA levels in patients with CRC [1.65 (0.47-2.46)] were increased (P = 0.035). IDO1 mRNA levels were positively associated with the KYN/Trp ratio (r = 0.327, P = 0.003). ZO-1 mRNA and protein levels were positively correlated with the indoles/Trp ratio (P = 0.035 and P = 0.009, respectively). In addition, the genera Asaccharobacter (Actinobacteria) and Parabacteroides (Bacteroidetes), and members of the phylum Firmicutes (Clostridium XlVb, Fusicatenibacter, Anaerofilum, and Anaerostipes) decreased in CRC and exhibited a positive correlation with indoles in all subjects.CONCLUSIONAlteration of fecal Trp metabolism mediated by microbiota is associated with intestinal barrier function and tissue Trp metabolism, and may be involved in the pathogenesis of CRC.     

急性缺血性脑卒中后认知障碍患者精神行为症状的特征性分析

目的探讨急性缺血性脑卒中后认知障碍(PSCI)患者精神行为症状(BPS)发生的特征。方法纳入2018年1月~2019年5月苏北人民医院神经内科住院的急性脑梗死患者105例,PSCI患者73例分为脑卒中后痴呆(PSD)组28例和脑卒中后认知障碍非痴呆(PSCI-ND)组45例,脑卒中后非认知障碍(非PSCI)组32例。PSCI患者又分为BPS组50例和非BPS组23例。根据英国牛津郡社区脑卒中规划分型,将急性脑梗死患者分为部分前循环梗死型(PACI)、后循环梗死型和腔隙性脑梗死型(LACI)。认知功能评估采用简易智能状态检查量表(MMSE)和蒙特利尔认知评估量表(MoCA),BPS评估采用神经精神问卷(NPI)。评价患者日常生活活动能力量表(ADL),并收集相关临床资料。结果PSD组和PSCI-ND组NIHSS评分、NPI总分、BPS发生率均明显高于非PSCI组,教育年限明显低于非PSCI组(P<0.05)。PSD组年龄明显高于PSCI-ND组(P<0.05)。BPS组ADL总分、MMSE总分和MoCA总分明显低于非BPS组[(86.90±10.50)分vs(92.61±10.10)分,P=0.032;(24.39±2.13)分vs(20.36±4.27)分,P=0.000;(17.04±4.23)分vs(22.00±2.65)分,P=0.000]。与非BPS组比较,BPS组PACI发生率明显升高(52.0%vs 4.3%,P=0.000),LACI发生率明显降低(20.0%vs 56.5%,P=0.002)。PSD组和PSCI-ND组幻觉、激越、抑郁、淡漠、异常运动和睡眠行为障碍比例明显高于非PSCI组(P<0.05)。PSD组激越、抑郁、淡漠和睡眠行为障碍比例明显高于PSCI-ND组(P<0.05)。结论PSCI患者较易出现BPS,其认知水平不同BPS发生率及表现不同,揭示了PSCI的临床异质性特点,为PSCI的治疗提供临床依据。     

不同月龄、疾病严重程度的毛细支气管炎患儿血清IL-4、IL-8及外周血T淋巴细胞亚群的变化*

目的 探讨呼吸道合胞病毒感染所致的急性毛细支气管炎婴幼儿血清IL-4、IL-8和外周血T淋巴细胞亚群的变化。方法 选取2014年3月—2018年6月广西壮族自治区南溪山医院儿科呼吸道合胞病毒感染的急性毛细支气管炎患儿142例,按疾病严重程度分为轻度组、中度组和重度组,每组再分为≤6个月亚组和>6个月亚组。另选取健康婴幼儿（11例）和排除感染的住院术前准备婴幼儿（26例）共37例设为对照组。观察各组血清IL-4和IL-8的变化及外周血T淋巴细胞亚群相对比例变化情况。结果 重度组的IL-4、IL-8水平在≤6个月亚组和>6个月亚组中最高,与其他组比较,差异有统计学意义（P?<0.05）。重度组CD3+CD4+T淋巴细胞比值高于其他组,其中≤6个月亚组最高;重度组CD3+CD8+和CD3+CD56+T淋巴细胞比值低于其他组,其中≤6个月亚组最低,与其他组比较,差异有统计学意义（P?<0.05）。结论 呼吸道合胞病毒感染所致毛细支气管炎患儿月龄和疾病程度的不同,对血清IL-4和IL-8水平及外周血T淋巴细胞亚群具有影响。     

早期生理盐水复苏后脓毒症患者血清氯水平 与急性肾损伤的关系

目的 探索脓毒症患者经生理盐水复苏72 h 后血清氯离子水平与急性肾损伤（AKI）的关系。 方法 选取2015 年1 月—2019 年5 月山西医科大学第一医院重症监护室收治并用生理盐水早期复苏的200 例 脓毒症或脓毒症休克患者,按照72 h 后的血清氯,分为高氯血症组（≥ 110 mmol/L）和非高氯血症组 （<110 mmol/L）,观察其初始血清氯离子浓度及肌酐、72 h 后最高血清氯离子浓度及肌酐、基础肌酐清除率 （Ccr）、初始急性生理功能和慢性健康状况评估Ⅱ（APACHE Ⅱ）评分、机械通气、肾替代治疗等指标,并 计算72 h 后血清氯离子变化值。结果 两组患者年龄、性别、机械通气、肾替代治疗、Ccr、APACHE Ⅱ 评分、72 h 后最高血清氯离子浓度及72 h 后血清氯离子浓度变化值比较,差异有统计学意义（P <0.05）。高 氯血症组AKI 发病率较非高氯血症组高（P <0.05）。单因素Logistic 回归分析显示,72 h 后最高血清氯离子 浓度与AKI 有关（P <0.05）。72 h 后血清氯离子浓度变化值≥ 1.5 mmol/L 和72 h 后血清氯离子浓度变化 值≥ 5.5 mmol/L 与AKI 也有关（P <0.05）。多因素Logistic 回归分析显示,APACHE Ⅱ评分[Ol ^ R=2.451 （95% CI：1.961,2.880）,P =0.000]、72 h 后最高血清氯离子浓度[Ol ^ R=2.023（95% CI：1.991,3.211）,P =0.010] 和72h 后血清氯离子浓度变化值[Ol ^ R=3.211（95% CI ：2.347,3.630）,P =0.006] 是AKI 发病的危险因素。 结论 脓毒症患者经生理盐水复苏72 h 后血清高氯离子与AKI 独立相关,且72 h 后血清氯离子浓度变化值、 APACHE Ⅱ评分也与AKI 有关。