Differential Expression of PD-L1 Between Sporadic and VHL-Associated Hereditary Clear-Cell Renal Cell Carcinoma and Its Correlation With Clinicopathological Features

Background

Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel–Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear.

The PROFILE of assessment program for internal medicine internship of Sun Yat-Sen University

Objective: To reflectively look at the present methods by which the clinical competence of 5th-year medical students (i.e. interns) in Sun Yat-Sen University (SYSU) are assessed upon finishing internship rotation in internal medicine (IM).

Methods: Current procedures for the competence assessment of end-of-rotation IM interns in the First Affiliated Hospital of SYSU were reviewed, along with a point-by-point appraisal based on the PROFILE approach to structured assessment, and, whenever possible, suggestions for future improvement.

Results and discussions: On a scale of 1–10, with 10 being the best or the most ideal, our marks for current methods to assess end-of-rotation IM interns in terms of being Programmatic, Real-World, Outcome-based, Formative, Impactful, Learner-engaged, and Evaluation-guaranteed were 7, 9, 3, 4, 6, 8, and 1, respectively. The strengths, weaknesses as well as potential solutions in each of the seven aspects are also discussed separately.

Conclusions: Current assessment program for IM internship is strong in being programmatic, real-world, educationally impactful and learner engaged, and has room for further improvement in its time-based arrangements, relative shortage of feedback provision, as well as a systematic lack of quality control measures.     

氯氮平片辅助治疗PD合并精神障碍患者的有效性及不良反应研究

目的:对氯氮平片在帕金森病(Parkinson’s disease,PD)合并精神障碍辅助治疗中的应用价值予以探讨。方法:选取50例我院2013年1月1日—2019年6月30日接诊的PD合并精神障碍患者进行研究,按照随机数表法分为对照组和观察组。对照组用多巴丝肼,观察组联合氯氮平片,对比治疗效果。结果:观察组疾病治疗总有效率96.00%(24/25)高于对照组68.00%(17/25),差异有统计学意义(P<0.05),不良反应发生率8.00%(2/25)与对照组20.00%(5/25)差异无统计学意义(P>0.05);观察组UPDRD评分、VGI-S评分和BPRS评分明显低于对照组,差异有统计学意义(P<0.05)。结论:氯氮平片辅助治疗PD合并精神障碍患者,既可提高临床疗效,也不会增加用药后不良反应,安全性高,值得推广。     

The role of lncRNA MSC-AS1/miR-29b-3p axis-mediated CDK14 modulation in pancreatic cancer proliferation and Gemcitabine-induced apoptosis

Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related death due to the failure of traditional therapies. In the present study, we attempted to construct a lncRNA-miRNA-mRNA network which may modulate PDAC cell proliferation and Gemcitabine-induced cell apoptosis starting from CDK14, a new member of the CDK family and an oncogene in many cancers. Based on TCGA data, a significant positive correlation was observed between lncRNA MSC-AS1 and CDK14. Moreover, MSC-AS1 expression was upregulated in PDAC tissues. Higher MSC-AS1 expression was correlated with poorer prognosis in patients with PDAC. MSC-AS1 knockdown in Panc-1 and BxPC-3 cells significantly inhibited the cell proliferation. Moreover, miR-29b-3p, which has been reported to act as a tumor suppressor, was predicted to bind to both MSC-AS1 and CDK14. Contrary to MSC-AS1, higher miR-29b-3p expression was correlated to better prognosis in patients with PDAC. In both PDAC cell lines, miR-29b-3p negatively regulated MSC-AS1 and CDK14. As confirmed using luciferase reporter gene and RIP assays, MSC-AS1 served as a ceRNA for miR-29b-3p to counteract miR-29b-mediated CDK14 repression. MSC-AS1 knockdown inhibited CDK14 protein levels and PDAC proliferation and enhanced gemcitabine-induced cell death and apoptosis while miR-29b-3p inhibition exerted an opposing effect; the effect of MSC-AS1 knockdown was partially attenuated by miR-29b-3p inhibition. Taken together, we demonstrated that MSC-AS1/miR-29b-3p axis modulates the cell proliferation and GEM-induced cell apoptosis in PDAC cell lines through CDK14. We provided a novel experimental basis for PDAC treatment from the perspective of lncRNA-miRNA-mRNA network.     

Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma

Background Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC).Methods We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance.Results ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens.Conclusions F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.Subject terms: Tumour biomarkers, Oesophageal cancer     

Pediatric Wilson disease presenting as acute liver failure: Prognostic indices

BACKGROUNDAcute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable. AIMTo determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.METHODSWe reviewed the medical records of our pediatric WDALF patients (n = 41 over 6-years-old, single-center retrospective study) and compared seven prognostic models (King’s College Hospital Criteria, model for end-stage liver disease/pediatric end-stage liver disease scoring systems, Liver Injury Unit [LIU] using prothrombin time [PT] or international normalized ratio [INR], admission LIU using PT or INR, and Devarbhavi model) with one another.RESULTSAmong the 41 Han Chinese patients with ALF, WD was established by demonstrating ATP7B variants in 36. In 5 others, Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis. Three died during hospitalization and three underwent liver transplantation (LT) within 1 mo of presentation and survived (7.3% each); 35 (85.4%) survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis. Parameters significantly correlated with mortality included encephalopathy, coagulopathy, and gamma-glutamyl transpeptidase activity, bilirubin, ammonia, and serum sodium levels. Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.CONCLUSIONWDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis, even after enlisting for LT.     

Qianzheng powder for the treatment of primary Hemifacial spasm: A protocol for systematic reviews and meta-analysis

Background:Hemifacial spasm (HFS) is a clinical common neurological disease, its main performance for 1 side or 2 sides muscles (the orbicularis oculi muscle, expression, orbicularisoris muscles) recurrent paroxysmal, involuntary twitching, aggravating when excited or nervous, more severe cases of the disease may include difficulty in opening the eyes, crooked corners of the mouth, and twitching noises in the ears, etc.^[1] Early manifestations of the disease are intermittent mild convulsions of the orbicularis oculi muscle, and then gradually spread to 1 side of the facial muscles, such as frowning muscles, nasal muscles, buccinalis muscles, etc, especially the most obvious spasms of the oral muscles, which can involve the ipsilateral platysma muscle in severe cases, with each twitch for a few seconds to a few minutes. The disease will affect the quality of life such as speaking, eating, seeing and so on, and even cause psychological effects such as inferiority, anxiety and depression. At present, the incidence of the disease in China is 11 per 1.1 million, females are more common than males. There are many ways to treat HFS, but the Qianzheng powder has a unique advantage in treating this disease. Therefore, our systematic review aims to evaluate the efficacy and safety of Qianzheng powder in the treatment of Primary Hemifacial spasm, and to provide a reliable basis for clinical decision makers.Methods:From its inception until April 2021, we will search electronic databases, including PubMed, Embase, Cochrane Library, China Biomedical Literature Database, China Knowledge Infrastructure, Wanfang Database, and China Scientific Journals Database. The authors will independently sift through studies, extract data information, and assess methodological quality using the Cochrane Risk of Bias tool. The RevManV. 5.3 software will be used for statistical analysis.Results:The results of this study, which will be published in a peerreviewed journal, will evaluate the efficacy and safety of Qianzheng powder in the treatment of primary Hemifacial spasm.Conclusion:This systematic review will provide reliable evidence-based basis for treating primary Hemifacial spasm with Qianzheng powder.INPLASY Registration number:INPLASY202130037.