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。     

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     

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.     

Deletion of Krüppel-like factor-4 promotes axonal regeneration in mammals

Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01).

Chinese Library Classification No.R456; R741; Q344+.14     

A rare case of monozygotic triplets with Duchenne muscular dystrophy

Twins with Duchenne muscular dystrophy (DMD) have been widely studied. We report the first rare case of monozygotic triplets with DMD who shared consistent phenotypes, including delayed motor and language milestones, muscle wasting and weakness, joint contracture, and lumbar lordosis. Muscle magnetic resonance imaging and biopsy revealed the similar muscle injury characteristics and dystrophin absence. Short tandem repeat analysis confirmed monozygosity. A de novo mutation (exon 49–52 deletion) was found in the triplets but not in their mother. Treatment included prednisone, idebenone, and rehabilitation management. At the 2-year follow-up, motor function had deteriorated, and muscle fatty infiltration was more extensive and severe. Our case offers a unique opportunity for genetic and therapeutic research. Furthermore, it highlights the critical role of genetic factors in DMD phenotypes and provides a potential choice for treatment observations.