A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Loss of epithelial integrity resulting from E-cadherin dysfunction predisposes airway epithelial cells to adenoviral infection

Epithelial intercellular adhesion is fundamental to the formation of the airway epithelial protective barrier. In this respect, cadherins are important because these adhesion molecules regulate formation and maintenance of epithelial intercellular junctions. To study the importance of airway epithelial integrity in determining susceptibility to virus infection, we used a replication-incompetent adenovirus, RAd35, and an E-cadherin specific function-blocking antibody, SHE78-7, to disrupt intercellular contacts in human bronchial epithelial cell line 16HBE14o- and primary bronchial epithelial cells. After exposure of 16HBE14o- cell cultures to SHE78-7, disruption of the transepithelial permeability barrier was indicated by a loss of transepithelial electrical resistance and an associated increase of mannitol, inulin, and dextran paracellular flux. Subsequent exposure of SHE78-7-treated cell cultures to RAd35 showed a remarkable increase in adenoviral infection as assessed by beta-galactosidase reporter gene expression. In cultures exposed to SHE78-7, disruption of E-cadherin function resulted in infection equivalent to that in control cultures using 16-fold lower viral titers. These studies show that manipulation of E-cadherin function provides a specific means of altering epithelial integrity that in turn determines resistance of airway epithelia to adenoviral infection.     

Pentasomy 8q in therapy-related myelodysplastic syndrome due to cyclophosphamide therapy for fibrosing alveolitis

Trisomy 8/8q is a common cytogenetic event in myelocytic malignancies, ranging from myelodysplastic syndrome (MDS) to acute myelocytic leukemia (AML) to blastic transformation of chronic myelocytic leukemia. Isochromosome 8q results in the same gene dosage effect. Duplication of i(8q), resulting in pentasomy 8q, has been reported only in two cases of AML. A patient with fibrosing alveolitis on prolonged cyclophosphamide treatment developed therapy-related MDS. Karyotyping, FISH, and CGH analysis showed a duplicated i(8q) among other complex abnormalities. The clinical features of 11 cases of myelocytic leukemia with pentasomy and hexasomy 8/8q were summarized. Compared with trisomy and tetrasomy 8, significant features included reduced median survival (90 days), treatment refractoriness (even with transplantation), monocytic differentiation, trilineage dysplasia, and radiation or toxin exposure. Increasing copy numbers of chromosome 8/8q may therefore be a marker of advanced leukemic evolution, exposure to toxins, underlying myelodysplasia, and an overall poor prognosis.     

Genomic Surveillance of SARS-CoV-2: Distribution of Clades in the Republic of Korea in 2020

Since a novel beta-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019, there has been a rapid global spread of the virus. Genomic surveillance was conducted on samples isolated from infected individuals to monitor the spread of genetic variants of SARS-CoV-2 in Korea. The Korea Disease Control and Prevention Agency performed whole genome sequencing of SARS-CoV-2 in Korea for 1 year (January 2020 to January 2021). A total of 2,488 SARS-CoV-2 cases were sequenced (including 648 cases from abroad). Initially, the prevalent clades of SARS-CoV-2 were the S and V clades, however, by March 2020, GH clade was the most dominant. Only international travelers were identified as having G or GR clades, and since the first variant 501Y.V1 was identified (from a traveler from the United Kingdom on December 22^nd, 2020), a total of 27 variants of 501Y.V1, 501Y.V2, and 484K.V2 have been classified (as of January 25^th, 2021). The results in this study indicated that quarantining of travelers entering Korea successfully prevented dissemination of the SARS-CoV-2 variants in Korea.     

芜湖市2015-2018年幼托儿童健康状况分析

7岁以下儿童健康状况是反映经济社会发展重要指标之一,一直受到社会关注.为了解芜湖市托幼机构儿童健康状况,提高芜湖市托幼机构卫生保健质量,芜湖市各县区妇幼保健机构每年对辖区内的托幼机构儿童进行1次健康检查,现将2015-2018年芜湖市托幼机构健康检查结果分析如下.     

Territorywide Study of Early Coronavirus Disease Outbreak,Hong Kong,China

Initial cases of coronavirus disease in Hong Kong were imported from mainland China. A dramatic increase in case numbers was seen in February 2020. Most case-patients had no recent travel history, suggesting the presence of transmission chains in the local community. We collected demographic, clinical, and epidemiologic data from 50 patients, who accounted for 53.8% of total reported case-patients as of February 28, 2020. We performed whole-genome sequencing to determine phylogenetic relationship and transmission dynamics of severe acute respiratory syndrome coronavirus 2 infections. By using phylogenetic analysis, we attributed the community outbreak to 2 lineages; 1 harbored a common mutation, Orf3a-G251V, and accounted for 88.0% of the cases in our study. The estimated time to the most recent common ancestor of local coronavirus disease outbreak was December 24, 2019, with an evolutionary rate of 3.04 × 10⁻³ substitutions/site/year. The reproduction number was 1.84, indicating ongoing community spread.     

三氧化二砷诱导肺癌细胞凋亡及对细胞周期的影响

目的 :探讨三氧化二砷 (As2 O3 )对人肺癌细胞株 (Spc- A1)诱导凋亡的机制 ,为抗肿瘤药物的筛选和用药方式提供理论依据。方法 :体外培养 Spc- A1细胞株与不同浓度的 As2 O3 进行作用 ,应用 MTT比色法、流式细胞仪技术、电子显微镜技术观察细胞增殖率、细胞周期率、细胞凋亡率及亚细胞水平变化。结果 :As2 O3 能够抑制 Spc- A1细胞的增殖 ,且呈时间剂量依赖性 ,Spc- A1细胞凋亡率与药物浓度和时间呈依赖关系。电镜观察细胞线粒体肿胀、空泡 ,染色质浓缩、核碎裂。结论 :As2 O3 可诱导 Spc- A1细胞凋亡 ,细胞周期延长 ,线粒体变性。     

血浆内皮素和心钠素与维持性血液透析患者高血压关系的研究

目的：探讨血浆瓦皮素（ET）和心钠素（ANP）在维持性血液透析患者高血压中的作用。方法：尿毒症患者分为维持性血液透析不使用促红细胞生成素（EPO）组、维持性血液透析使用EPO组及尿毒辣症非透析组,以上3组各自分为高血压组和高血压正常组,另设健康对照组。应用放射免疫法检测血浆ET－1和ANP水平。结果：所有尿毒症患者血浆ET－1和ANP水平均高于健康对照组,维持血液透析使用EPO组血浆ET－1和ANP水平高于维持特性血液透不使用EPO组（P＜0．05）;各组中高血压亚组的血压ET－1水平及ET－1／ANP比值均高于其相应的患者的高血压同 浆ET－1水平井高升以及ET－1和ANP比值的增大有密切关系。     

Deregulated microRNA-22-3p in patients with sepsis-induced acute kidney injury serves as a new biomarker to predict disease occurrence and 28-day survival outcomes

Background

Acute kidney injury (AKI) is a common and serious complication of sepsis. MicroRNA-22-3p (miR-22-3p) has been found to be involved in septic AKI progression. The purpose of this study was to analyze both the serum and urinary expression of miR-22-3p in septic AKI patients, and evaluated the clinical value of miR-22-3p in the diagnosis and prognosis of sepsis-induced AKI.

Methods

Serum and urinary expression of miR-22-3p was examined using qRT-PCR. The risk factors related with septic AKI onset were assessed using logistic analysis. A receiver-operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of miR-22-3p, and the Kaplan–Meier survival curves and Cox regression analysis were used to evaluate the predictive value of miR-22-3p for the 28-day survival of septic AKI patients.

Results

Both serum and urinary miR-22-3p expression was decreased and negatively correlated with kidney injury biomarkers in septic AKI patients. MiR-22-3p expression was a risk factor for AKI onset and had diagnostic accuracy in septic AKI patients. The expression of both serum and urinary miR-22-3p was lower in patients who died, and served as a prognostic biomarker to predict 28-day survival in septic AKI patients.

Conclusion

Serum and urinary miR-22-3p was reduced in sepsis-induced AKI patients, and served as a biomarker to predict AKI occurrence and 28-day survival in sepsis patients.

     

Clinicopathological patterns of bladder carcinoma over 1 year: experience from University Hospital of Nepal

Purpose

To define the clinical and pathological patterns of urinary bladder carcinoma from the University Hospital of Nepal.

Methods

This is a retrospective analytical study. Patients with bladder mass who underwent surgery over 1 year and who had data record were included in the study. Demographic profile, type of surgery, findings on clinical examination, cystoscopy findings, histopathological report, tumor stage, and post-surgery adjuvant therapy were analyzed.

Results

Out of 86 patients who underwent transurethral resection of bladder tumor, 77 patients had biopsy-proven malignant bladder tumor. Urothelial cancer was present in 96.1%. Male were 78.6%. The mean age of diagnosis was 65.5?±?11.8 years. Non-muscle-invasive bladder cancer (NMIBC) was 3.7 times more common than muscle-invasive bladder cancer (MIBC). High-grade tumors (58.6%) were more common than low grade (41.4%). The detrusor muscle was present inthe biopsy specimen of 48 patients (64%). Re-TURBT within 2–6 weeks was considered based on histopathology reports for about half of the patients (45.3%). Upstaging and upgrading of the tumor was present in 5.8 and 5.8% of the patients, respectively. Residual tumor without upstaging and upgrading was present in 23.5%. One patient (1.3%) had Clavien–Dindo grade 1, three (4%) patients had grade 2 and two patients (2.7%) had grade 3b.

Conclusion

In the present study, patients with bladder cancer are younger than reported in other studies. Smokers are strongly predisposed. The histological pattern is similar to the Western and Asian populations. NMIBC and MIBC occur in proportion to that described as in other studies. We had a lower rate of recurrence, upstaging and upgrading. We had a lesser rate of acceptance for radical cystectomy in our patients.