Plasma microRNA profiling in nasopharyngeal carcinoma patients revealsmiR-548q andmiR-483-5p as potential biomarkers

MicroRNAs （miRNAs）, which play a role in tumorigenesis, may also serve as diagnostic or prognostic biomarkers. However, studies on human miRNA profiles in plasma from nasopharyngeal carcinoma （NPC） patients are in their infancy. Here, we used microarrays to perform systematic profiling of human miRNAs in plasma from NPC patients. We subsequently used realtime quantitative polymerase chain reaction （Q-PCR） to validate miRNAs with aberrant expression that could serve as potential biomarkers. By comparing the plasma miRNA profiles of 31 NPC patients and 19 controls, 39 of 887 human miRNAs were found to be aberrantly expressed. Considering the fold change and P value, miR-548q and miR-483- 5p were validated in 132 samples from 82 NPC patients and 50 controls. Moreover, high expression of miR-548q and miR483-5p was further found in 3 NPC cell lines and clinical biopsy tissues from 54 NPC patients and 22 controls. Our results revealed that miR-548q and miR-483-5p are potential biomarkers of NPC. Combining the receiver operating characteristic （ROC） analyses of these 2 miRNAs, an area under the ROC curve （AUC） of 0.737 with 67.1% sensitivity and 68.0% specificity were obtained, showing the preliminary diagnostic value of plasma miRNAs. Moreover, most NPC patients with a poor outcome exhibited high expression （〉 median） of miR548q （70.6%） and miR-483-5p （64.7%） in tissue samples, indicating their prognostic value. The high expression levels of miR-548q and miR-483-5p in plasma, cell lines, and clinical tissues of NPC patients indicate that their roles in NPC should be explored in the future.     

The Chinese Journal of Cancer is indexed in Science Citation Index （SCI） Expanded

On July 22, 2014, the Chinese Journal of Cancer （CJC） received a notification from Thomson Reuters that the publications of our journal starting from 2012 have been accepted for coverage in Science Citation Index Expanded, available at the Web of Science, Core Collection, Biological Abstracts, and Biosis Previews. What this means in practical terms is that CJC will receive its first official impact factor （IF） in 2015. This is an important milestone in the history of CJC.     

Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non-high-grade serous ovarian carcinomas

The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision-making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high-grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non-HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high-grade endometrioid (3/20; 15%), low-grade endometrioid (1/40; 2.5%), low-grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re-evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight ‘anomalous’ cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first ‘anomalous’ non-HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53-abnormal high-grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53-wildtype low-grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non-causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high-grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype-directed sequencing. Furthermore, in-depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2-related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.     

淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达及临床意义

本研究旨在检测淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达,分析其与临床特征的相关性并探讨其在淋巴瘤诊断、评价疗效及预后方面的作用。运用RT-PCR方法检测淋巴瘤患者(55例)、淋巴结炎性肿大患者(10例)和正常对照(27名)血浆中miR-21、miR-155、miR-210的表达。结果表明,淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达量均明显高于正常对照及淋巴结炎性肿大患者(P<0.05),淋巴结炎性肿大患者血浆中miR-21、miR-210的表达量与正常对照无显著差异。淋巴瘤患者血浆中miR-21的表达随血清乳酸脱氢酶水平增高而增高。初治淋巴瘤患者血浆中miR-21、miR-210的表达量明显高于6个疗程以上患者的表达量(P<0.05)。miR-21、miR-155、miR-210用于淋巴瘤的诊断准确度分别可达56.4%、65.3%、47.6%,三者联合诊断率可达82.7%。结论:淋巴瘤血浆中miR-21、miR-155、miR-210的表达量增高,检测三者在血浆中的表达量有助于临床淋巴瘤的诊断及疗效、预后的判断。     

骨髓间接Coombs试验方法的应用及其对免疫相关性全血细胞减少症患者的临床诊断意义

本研究旨在应用骨髓间接Coombs试验方法,并探讨其对免疫相关性全血细胞减少症(IRP)患者的临床诊断意义。实验组选取30例全血细胞减少患者〔IRP 22例,意义未明血细胞减少患者(ICUS)8例〕骨髓上清液和15名缺铁性贫血对照者骨髓有核细胞孵育,对照组选取15名缺铁性贫血患者自身骨髓有核细胞与骨髓上清液孵育。应用流式细胞术(FCM)检测孵育45 min后骨髓造血细胞(CD15+、GlyCoA+和CD34+细胞)膜抗体阳性率,并与其临床指标进行相关性分析。结果显示:30例患者中(骨髓直接Coombs试验16例阳性,14例阴性),骨髓间接Coombs试验阳性者共16例,阳性率53.33%;其中8例ICUS患者中4例骨髓膜抗体出现阳性,阳性率50%。实验组CD15+IgM中位阳性率为0.34%,明显高于对照组0.20%(P<0.05);CD34+IgG、IgM中位阳性率分别为0.64%,0.21%,明显高于对照组0.00%(P<0.05)、0.00%(P<0.05);GlyCoA+IgG、IgM阳性率分别为(0.83±0.75)%,(2.12±1.98)%,明显高于对照组(0.47±0.43)%(P<0.05)、(0.68±0.64)%(P<0.01)。CD15+IgG、IgM阳性率分别与CD5+B细胞比例呈显著正相关,与其他临床指标均无相关性;GlyCoA+IgG、IgM阳性率分别与患者入院时血红蛋白水平、网织红细胞百分率、骨髓红系比例及树突细胞亚群比例(DC1/DC2)呈明显负相关,与CD5+B细胞比例和间接胆红素水平呈显著正相关。结论:部分IRP及ICUS患者骨髓上清液中存在针对骨髓造血细胞的抗体(IgG或IgM),且阳性率的高低与疾病的进展呈一定相关性;部分抗体可作用于正常骨髓有核细胞膜蛋白成分。     

健康教育在针灸减肥中的应用

目的探讨健康教育在针灸减肥中的应用效果。方法对122例单纯性肥胖症病人,采用穴位针刺电针、穴位埋线、耳穴贴压等减肥治疗,30 d为1个疗程,共3个疗程,针灸期间同时实施相关减肥知识教育。观察治疗3个疗程后病人治疗的效果。结果本组122例单纯性肥胖症病人显效77例(63.1%),有效36例(29.5%),无效9例(7.4%),总有效率为92.6%。结论健康教育在针灸减肥中起着重要作用,可提高减肥效果,值得临床推广应用。     

Endoplasmic reticulum stress is involved in podocyte apoptosis induced by saturated fatty acid palmitate

Background  Podocyte apoptosis is recently indicated as an early phenomenon of diabetic nephropathy. Pancreatic b-cells exposed to saturated free fatty acid palmitate undergo irreversible endoplasmic reticulum (ER) stress and consequent apoptosis, contributing to the onset of diabetes. We hypothesized that palmitate could induce podocyte apoptosis via ER stress, which initiates or aggravates proteinuria in diabetic nephropathy.

Methods  Podocyte apoptosis was detected by 4¢,6-diamidio-2-phenylindole (DAPI) stained apoptotic cell count and Annexin V-PI stain. The expressions of ER molecule chaperone glucose-regulated protein 78 (GRP78), indicators of ER-associated apoptosis C/EBP homologous protein (CHOP), and Bcl-2 were assayed by Western blotting and real-time PCR. GRP78 and synaptopodin were co-localized by immunofluorescence stain.

Results  Palmitate significantly increased the percentage of cultured apoptotic murine podocytes time-dependently when loading 0.75 mmol/L (10 hours, 13 hours, and 15 hours compared with 0 hour, P <0.001) and dose-dependently when loading palmitate ranging from 0.25 to 1.00 mmol/L for 15 hours (compared to control, P <0.001). Palmitate time-dependently and dose-dependently increased the protein expression of GRP78 and CHOP, and decreased that of Bcl-2. Palmitate loading ranging from 0.5 to 1.0 mmol/L for 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to control (P <0.001), with the maximum concentration being 0.75 mmol/L. Palmitate 0.5 mmol/L loading for 3 hours, 8 hours, and 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to 0 hour (P <0.001), with the maximum effect at 3 hours. Confocal microscopy demonstrated that GRP78 expression was significantly increased when exposed to 0.5 mmol/L of palmitate for 8 hours compared to control.

Conclusion  Palmitate could induce podocyte apoptosis via ER stress, suggesting podocyte apoptosis and consequent proteinuria caused by lipotoxic free fatty acid could be ameliorated by relief of ER stress.

     

Recombinant adeno-associated virus delivered human thioredoxin-PR39 prevents hypoxia-induced apoptosis of ECV304 cells

Human thioredoxin and antibacterial peptide, PR39, have been shown to have potent antioxidant effects that may prolong survival of cells during hypoxia. The pSSCMV/human thioredoxin-PR39 vector was successfully constructed in this study and used to infect ECV304 cells. Transfected ECV304 cells were incubated at 1%, 5% hypoxic, and normal oxygen conditions. We found that the number of apoptotic cells after transfection with recombinant adeno-associated virus-human thioredoxin -PR39 was significantly lower than controls, suggesting a protective effect of the recombinant human thioredoxin-PR39 protein on hypoxic cells.     

Transanal endorectal pull-through for Hirschsprung's disease using long cuff dissection and short V-shaped partially resected cuff anastomosis: early and late outcomes

Background  

Transanal endorectal pull-through was described by De la Torre-Mondragon’s technique. In the original transanal pull-through procedure, a long rectal muscular cuff was dissected and left for anocolic anastomosis, which would sometimes lead to postoperative obstructive symptoms and enterocolitis. While a modified short mucosal dissection may increase the risk of injury to pelvic and perirectal nerves and other structures when dissected on the outside of the rectum deep in the pelvis. We report early and late results of the modified transanal procedure for Hirschsprung’s disease (HD) over 8 years.     

Duodenal heterotopic pancreas in a child

Background  Heterotopic pancreas is characterized by pancreatic tissue outside the pancreatic bed. However, duodenal heterotopic pancreas in children is rarely reported so far. We describe herein duodenal heterotopic pancreas in a child who suffered from chronic abdominal pain. Methods  An 8-year-old boy presented with upper abdominal pain and intermittent vomiting, without a history of melena, hematochezia, hematemesis, claycolored stools, jaundice, hepatitis or dyscrasia. No specific medication or change in position relieved the pain. Based on the elevated serum amylase levels, and the findings of CT, barium meal X-ray examination, magnetic resonance imaging, and upper gastrointestinal endoscopy, a duodenal mass was diagnosed initiatively. Intraoperative frozen section analysis was performed for the diagnosis. The mass was dissected. Results  Intraoperative frozen section analysis and routine pathological examination confirmed the diagnosis of duodenal heterotopic pancreas. The patient had an uneventful recovery and remained asymptomatic postoperatively during a follow-up period of 16 months. Conclusions  Heterotopic pancreas should be considered in children with a duodenal mass and abdominal pain. Intraoperative frozen section analysis is helpful in the diagnosis of the disease. Surgical treatment of the lesion should be performed to prevent bleeding, ulceration, outlet obstruction or malignant degeneration. Zheng LD and Tong QS contributed equally to this work