后腹腔镜肾根治性切除术中肾标本取出方法的探索

目的探讨一次性切口保护套在后腹腔镜肾根治性切除术中的应用及标本取出效率。方法回顾性分析本院2018年12月至2019年6月接受后腹腔镜肾根治性切除术的37例肾癌患者的临床资料。根据手术后标本取出体外的方法分为观察组(18例)和对照组(19例),观察组使用一次性切口保护套,对照组则使用传统自制标本袋;观察比较两组患者标本的取出时间和置入次数等指标。结果观察组与对照组的标本取出时间分别为(225.94±47.04)、(508.84±45.81)s,差异有统计学意义(P<0.05)。观察组中有17例患者标本一次性顺利取出,1例因肿瘤较大,取出困难,经延长切口后顺利取出,所有标本完整均未破裂;对照组中有17例患者标本一次性顺利取出,另外2例患者经适当延长切口后取出,所有标本完整均未破裂。两组置入次数比较,差异无统计学意义(P>0.05)。术后随访1年发现,所有患者均未出现癌细胞经手术切口种植转移的情况。结论在后腹腔镜肾根治性切除术中运用一次性切口保护套来辅助取标本,其手术时间短、操作简单,易上手,具有实用价值,值得临床推广应用。     

First‐in‐human phase I study of E7090, a novel selective fibroblast growth factor receptor inhibitor,in patients with advanced solid tumors

Fibroblast growth factor receptors (FGFR) are a family of transmembrane receptor tyrosine kinases involved in regulating cellular processes. FGFR mutations are implicated in oncogenesis, representing therapeutic potential in the form of FGFR inhibitors. This phase I, first‐in‐human study in Japan evaluated safety and tolerability of E7090, a potent selective FGFR1‐3 inhibitor, in patients with advanced solid tumors. Dose escalation (daily oral dose of 1‐180 mg) was carried out to assess dose‐limiting toxicity (DLT), maximum tolerated dose, and pharmacokinetics. Pharmacodynamic markers (serum phosphate, fibroblast growth factor 23, and 1,25‐(OH)₂‐vitamin D) were also evaluated. A total of 24 patients refractory to standard therapy or for whom no appropriate treatment was available were enrolled. No DLT were observed up to the 140‐mg dose; one patient in the 180‐mg cohort experienced a DLT (increased aspartate aminotransferase/alanine aminotransferase, grade 3). The maximum tolerated dose was not reached. Dose‐dependent increases in the maximum concentration and area under the curve from time 0 to the last measurable concentration were observed up to 180 mg. Dose‐dependent increases were observed in all pharmacodynamic markers and plateaued at 100‐140 mg, indicating sufficient FGFR pathway inhibition at doses ≥100 mg. In conclusion, E7090 showed a manageable safety profile with no DLT at doses ≤140 mg. Maximum tolerated dose was not determined. The recommended dose for the follow‐up expansion part, restricted to patients with tumors harboring FGFR alterations, was determined as 140 mg, once daily.     

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.

Loss of GRB2 associated binding protein 1 in arteriosclerosis obliterans promotes host autophagy

Background:Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.     

Effect of different modeling time on intestinal bacteria in letrozole induced PCOS rats

Objective: The differences of ovarian morphology, reproductive hormones, glucose and lipid metabolism and intestinal bacteria in rats with polycystic ovary syndrome (PCOS) induced by triazole were compared. Method: Eighteen 21 SPF female SD rats were randomly divided into group A (3-week group), group B (5-week group) and group D (control group) by random number table.Group A received letrozole + CMC-Na mixture by gavage in the first 3 weeks and CMC-Na solution by gavage in the last 2 weeks, group B received letrozole + CMC-Na mixture by gavage for 5 weeks, and group D received CMC-Na solution by gavage for 5 weeks, and all three groups of rats were fed with normal diet.At the end of gavage, the body weight of rats in each group was observed, the histological changes of ovaries were observed by hematoxylin-eosin (HE) staining, the serum levels of estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), total cholesterol (TC), triglyceride (TG), fasting blood glucose (Glu), fasting insulin (FINS) and lipopolysaccharide (LPS) were measured by enzyme-linked immunosorbent assay (ELISA), and the LH/FSH ratio and insulin resistance index (HOMA IR) were calculated; the intestinal bacteria of rats were detected by 16S rRNA technique. Result: 1. Comparison of ovary histomorphology: Under light microscope, multiple luteum and oocytes were observed in mature follicles in group D, and granulosa cells were orderly arranged and multilayered, without cystic dilated follicles. There were no mature follicles in the ovarian tissues of group A and GROUP B. The follicles were irregular in structure and more cystic dilated follicles were visible. The number of granular cells in some follicles decreased or even disappeared. 2. Comparison of sex hormone levels: compared with group D, T level in group B was significantly increased (P < 0.001), and T level in group A had an upward trend (P > 0.05); The LH/FSH levels in group A and B were significantly increased (P < 0.001; P < 0.001). Compared with group A, E2 in group B was significantly decreased (P < 0.05) and T was significantly increased (P < 0.01). 3. Comparison of glucose and lipid metabolism levels: Compared with group D, TC levels in groups A and B were significantly increased (P < 0.01; P < 0.01). Compared with group A, TG in group B was significantly increased (P < 0.05). There were no significant differences in Glu, FINS and HOMA-IR levels among all groups. 4. Comparison of LPS levels: Compared with group D, the serum LPS levels of rats in groups A and B were significantly increased (P < 0.001; P < 0.01). 5. Intestinal flora analysis and comparison: At the phylum level, compared with group D, the abundance of Firmicutes in group B increased (P < 0.01), Firmicutes in group A showed an upward trend (P > 0.05), and the abundance of Bacteroidetes in groups A and B decreased (P < 0.05). At the genus level, compared with group D, Lactobacillus in group B increased (P < 0.01). The results of LEfSe analysis showed that there were differences in the composition of various intestinal bacteria among the three groups (LDA > 3).Conclusion: The phenotype of PCOS rats was related to the length of modeling, and the phenotypic characteristics of PCOS in rats at 5 weeks of modeling were more typical than those in rats at 3 weeks of modeling; PCOS can cause changes in intestinal flora, and the changes in the structure of intestinal flora between groups are related to different modeling duration.     

The feasibility of quantitative MRI of extra‐ocular muscles in myasthenia gravis and Graves' orbitopathy

Although quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra‐ocular muscles (EOM), acquisition can be challenging as EOM are small and prone to eye‐motion artefacts. We explored the feasibility of assessing fat fractions (FF), muscle volumes and water T2 (T2_water) of EOM in healthy controls (HC), myasthenia gravis (MG) and Graves' orbitopathy (GO) patients. FF, EOM volumes and T2_water values were determined in 12 HC (aged 22‐65 years), 11 MG (aged 28‐71 years) and six GO (aged 28‐64 years) patients at 7 T using Dixon and multi‐echo spin‐echo sequences. The EOM were semi‐automatically 3D‐segmented by two independent observers. MANOVA and t‐tests were used to assess differences in FF, T2_water and volume of EOM between groups (P < .05). Bland–Altman limits of agreement (LoA) were used to assess the reproducibility of segmentations and Dixon scans. The scans were well tolerated by all subjects. The bias in FF between the repeated Dixon scans was ?0.7% (LoA: ±2.1%) for the different observers; the bias in FF was ?0.3% (LoA: ±2.8%) and 0.03 cm³ (LoA: ± 0.36 cm³) for volume. Mean FF of EOM in MG (14.1% ± 1.6%) was higher than in HC (10.4% ± 2.5%). Mean muscle volume was higher in both GO (1.2 ± 0.4 cm³) and MG (0.8 ± 0.2 cm³) compared with HC (0.6 ± 0.2 cm³). The average T2_water for all EOM was 24.6 ± 4.0 ms for HC, 24.0 ± 4.7 ms for MG patients and 27.4 ± 4.2 ms for the GO patient. Quantitative MRI at 7 T is feasible for measuring FF and muscle volumes of EOM in HC, MG and GO patients. The measured T2_water was on average comparable with skeletal muscle, although with higher variation between subjects. The increased FF in the EOM in MG patients suggests that EOM involvement in MG is accompanied by fat replacement. The unexpected EOM volume increase in MG may provide novel insights into underlying pathophysiological processes.     

双侧深低温停循环顺行性脑灌注对主动脉弓替换术患者脑损伤的影响

目的 探讨双侧深低温停循环(Deep hypothermia and circulatory arrest,DHCA)+顺行性脑灌注(Anterograde cerebral perfusion,ACP)对主动脉弓替换术患者脑损伤的影响。方法 选择2018年1月-2020年1月本院实施主动脉弓替换术的DebakeyⅠ型主动脉夹层患者96例,根据不同的脑保护技术将患者分为单侧ACP组和双侧ACP组,各48例; 2组均进行DHCA,单侧ACP组经右侧腋动脉进行单侧ACP,双侧ACP组经右侧腋动脉和左颈总动脉进行双侧ACP。结果 全部患者痊愈出院,出院前CT复查显示主动脉弓和升主动脉的人工血管血流畅通,无人工血管扭曲和造影剂渗漏等状况。双侧ACP组术后短暂性脑损伤发生率为2.08%(1/48),明显低于单侧ACP组的16.67%(8/48)(P<0.05)。双侧ACP组术后苏醒时间为(13.18±3.42)h,明显短于单侧ACP组的(16.98±4.18)h(P<0.05)。体外循环开始后2组血清神经元特异性烯醇化酶(Neuron-specific enolase,NSE)、中枢神经特异性蛋白 100-β亚型(Specific protein 100-β,S100-β)水平均逐渐升高,且在体外循环结束时达到峰值,随后开始降低; 脑灌注5min后双侧ACP组血清NSE,S-100β水平明显低于单侧ACP组(P<0.05)。结论 双侧深低温停循环顺行性脑灌注对主动脉弓替换术患者脑损伤的影响程度更小,其机制可能是通过降低血清NSE,S-100β水平,进而有效保护脑组织。