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.

Pathological classification and prognosis of renal damage caused by antineutrophil cytoplasmic antibody associated vasculitis

Objective To analyze the pathological characteristics and prognostic factors of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods A retrospective analysis of AAV patients with renal biopsy results admitted to Kidney Disease Center of the First Affiliated Hospital from January 2004 to February 2017 was performed. The patients were divided into 4 types according to Berden classification, and their clinical, pathological characteristics and prognosis were compared. The survival curves of each type of patients were plotted by Kaplan-Meier method, and the difference of survival curves was compared using Log-rank test. With entering the maintenance dialysis as the endpoint, Cox regression was used to analyze the prognostic factors. Results A total of 175 patients with AAV, including 59 cases (33.7%) of focal type, 39 cases (22.3%) of crescent type, 32 cases (18.3%) of sclerosis type, 45 cases (25.7%) of mixed type. The basal serum creatinine levels in crescent type group and sclerosis type group were significantly higher than those in the focal type group or mixed type group (all P＜0.05), and loop necrosis rate in sclerosis type group was significantly lower than chat in the focal type group or crescent type group (both P＜0.05). The median follow-up period was 11.8 (0.5-86.7) months. The event-free survival rates were 83.1%, 77.8%, 64.1% and 50.0% in the focal type, mixed type, crescent type and sclerotic type groups (Log-rank χ2=11.537, P=0.009). Cox regression analysis showed higher parathyroid hormone (HR=1.013, 95%CI 1.007-1.019, P＜0.001), glomerular sclerosis ≥50% (HR=10.532, 95%CI 2.903-38.203, P＜0.001) were independent risk factors for AAV patients entering maintenance dialysis, and higher estimated glomerular filtration rate (HR=0.943, 95%CI 0.896-0.993, P=0.025) was protective factor. Conclusion The prognosis of AAV renal damage is worsened according to focal, mixed, crescent and sclerosis types. Lower estimated glomerular filtration rate, higher parathyroid hormone and glomerular sclerosis ≥50% are independent risk factors for AAV patients entering maintenance dialysis.     

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     

Assessing the CT findings and clinical course of ED patients with first-time versus recurrent acute pancreatitis

Study objectives

The primary objective of this study was to compare Emergency Department patients with first-time versus recurrent acute pancreatitis.

高危原发前列腺胃肠道外间质瘤诊疗体会及文献复习

目的探讨前列腺原发胃肠道外间质瘤诊治要点。 方法回顾性分析我院2017年9月诊治的1例高危原发性前列腺胃肠道外间质瘤临床病理特征资料、随访情况，总结现有文献讨论总结本病诊治心得。 结果65岁男性，因"前列腺电切术后2年，反复血尿3个月余"入院。术前MRI考虑为来源不清的盆腔巨大实性占位（115 mm×105 mm×85 mm），经直肠穿刺诊断为梭形细胞来源的肿瘤。行盆腔肿瘤切除+膀胱前列腺腺切除+盆腔淋巴结清扫术+Bricker术。术后病理提示为前列腺原发胃肠道外间质瘤[CD117（+）；Dog1（+）；CD34（+）；PSA（+）；AR（+）；P504s（+）；Ki-67（2%）]。术后肿瘤组织全外显子测序提示为C-Kit基因（Exon 11 p.Q556-V560del）存在明显临床意义突变，筛选靶向药物甲磺酸伊马替尼+比卡鲁胺（PSA平稳后停用）口服，术后随访18个月无肿瘤复发及不良并发症。 结论前列腺原发胃肠道外间质瘤罕见，需与前列腺其他良恶性肿瘤相鉴别诊断。全外显子测序了解其发病高危基因，同时筛选药物辅助治疗可使患者生存获益。     

Dehydroascorbic Acid and pGPMA Dual Modified pH-Sensitive Polymeric Micelles for Target Treatment of Liver Cancer

In clinical therapy, the poor prognosis of hepatocellular carcinoma (HCC) is mainly attributed to the failure of chemotherapeutical agents to accumulate in tumor as well as lack of potency of tumor penetration. In this work, we developed actively tumor-targeting micelles with pH-sensitive linker as a novel nanocarrier for HCC therapy. These micelles comprised biodegradable poly(ethylene glycol)-poly(aspartate) polymers, in which paclitaxel can be covalently conjugated to pAsp via an acid-labile acetal bond to form pH-responsive structures. In vitro drug release studies showed that these structures were stable in physiological condition, whereas collapsed once internalized into cells due to the mildly acidic environment in endo/lysosomes, resulting in facilitated intracellular paclitaxel release. In addition, dehydroascorbic acid and guanidinopropyl methacrylamide polymers were decorated on the surface of micelles to achieve specific tumor accumulation and tumor penetration. Cellular uptake and in vivo imaging studies proved that these micelles had remarkable targeting property toward hepatocarcinoma cells and tumor. Enhanced anti-HCC efficacy of the micelles was also confirmed both in vitro and in vivo. Therefore, this micellar system may be a potential platform of chemotherapeutics delivery for HCC therapy.     

Two new saponins from the leaves of Panax notoginseng

Two new saponins, notoginsenosides Ng1 (1) and Ng2 (2), together with seven known compounds (3–9), were isolated from the leaves of Panax notoginseng. Their structures were elucidated by UV, IR, HRESIMS, and NMR experiments. Compounds 6 and 7 showed moderate cytotoxic activities against HCT-116, with IC₅₀ values of 4.98 and 0.64 μmol/L, respectively.     

mTOR and ERK regulate VKORC1 expression in both hepatoma cells and hepatocytes which influence blood coagulation

Clinical and Experimental Medicine - Deficiency of γ-glutamyl carboxylation of coagulation factors, as evidenced by the elevated level of Des-γ-carboxyl prothrombin (DCP), is a common...