经重睑切口的上睑旋转皮瓣矫正轻中度内眦赘皮疗效观察

目的探讨重睑术中采用经重睑切口的上睑旋转皮瓣矫正轻、中度内眦赘皮的疗效。方法回顾分析 2016 年 7 月—2017 年 10 月，重睑术中采用经重睑切口的上睑旋转皮瓣矫正轻、中度睑板型内眦赘皮合并单睑的 34 例患者（试验组）临床资料；以同期 38 例接受传统“Z”成形内眦开大术联合重睑术患者为对照（对照组）。两组患者年龄及内侧赘皮分度比较，差异无统计学意义（P>0.05）。于术前及术后 6 d、6 个月测量眼裂长度，计算眼裂长度改善程度；参照内眦赘皮矫正标准评价手术疗效。 结果两组患者切口均Ⅰ期愈合，并获随访 6 个月。两组内眦赘皮明显矫正。试验组内眦处无切口；对照组遗留瘢痕，其中 6 例增生明显。术后 6 d 试验组及对照组眼裂长度改善程度分别为 3.63%±0.07%、3.70%±0.05%；术后 6 个月分别为 4.64%±0.09%、4.46%±0.10%；两组比较差异均无统计学意义（t=0.005，P=0.996；t=0.287，P=0.871）。术后 6 个月疗效评价，试验组优 20 例、良 12 例、差 2 例，优良率 94.12%；对照组优 16 例、良 16 例、差 6 例，优良率 84.21%；差异无统计学意义（χ²=0.796，P=0.372）。 结论经重睑切口的上睑旋转皮瓣矫正轻、中度内眦赘皮手术操作简便、效果满意，内眦处无瘢痕形成。     

Extracellular vesicles transmitted miR-31-5p promotes sorafenib resistance by targeting MLH1 in renal cell carcinoma

Sorafenib provides survival benefits in patients with advanced renal cell carcinoma (RCC), but its use is hampered by acquired drug resistance. It is important to fully clarify the molecular mechanisms of sorafenib resistance, which can help to avoid, delay or reverse drug resistance. Extracellular vesicles (EVs) can mediate intercellular communication by delivering effector molecules between cells. Here, we studied whether EVs are involved in sorafenib resistance of RCC and its possible molecular mechanisms. Using differential centrifugation, EVs were isolated from established sorafenib-resistant RCC cells (786-0 and ACHN), and EVs derived from sorafenib-resistant cells were uptaken by sensitive parental RCC cells and thus promoted drug resistance. Elevated exogenous miR-31-5p within EVs effectively downregulated MutL homolog 1 (MLH1) expression and thus promoted sorafenib resistance in vitro. Mice experiments also confirmed that miR-31-5p could mediate drug sensitivity in vivo. In addition, low expression of MLH1 was observed in sorafenib-resistant RCC cells and upregulation of MLH1 expression restored the sensitivity of resistant cell lines to sorafenib. Finally, miR-31-5p level in circulating EVs of RCC patients with progressive disease (PD) during sorafenib therapy was higher when compared to that in the pretherapy status. In conclusion, EVs shuttled miR-31-5p can transfer resistance information from sorafenib-resistant cells to sensitive cells by directly targeting MLH1, and thus magnify the drug resistance information to the whole tumor. Furthermore, miR-31-5p and MLH1 could be promising predictive biomarkers and therapeutic targets to prevent sorafenib resistance.     

Perioperative management of diabetes

Diabetes is a complex, chronic metabolic disorder affecting approximately 9.3% of the adult population with the estimated number of adults with diabetes worldwide having more than tripled since 2000. This increase has largely been attributed to global urbanization and lifestyle changes. Diabetes affects 10–15% of the surgical population. These patients are frequently elderly, have complex medical co-morbidities and present for both high-risk elective and emergency surgery. This multisystem disease poses a significant challenge to both anaesthesia and surgery with patients with diabetes demonstrating higher morbidity and mortality rates compared to their non-diabetic counterparts. It is crucial that good glycaemic control is maintained throughout the perioperative period as this has been shown to correlate with positive patient outcomes. It is well-recognized that a co-ordinated, multidisciplinary approach aimed at optimizing every point in the patient pathway from GP referral to post-discharge care is required to obtain the best outcomes for the surgical patient with diabetes. The anaesthetist has a key role in the perioperative diabetes multidisciplinary team. Patients themselves are well experienced in manging their own diabetes and should be involved in doing so whenever possible.     

电子线照射对小鼠胰岛素生长因子相关蛋白表达的影响

目的：探讨电子线对胰岛素生长因子-1家族蛋白表达的影响，为研究辐射对肝脏的早期损伤提供依据。方法：采用电子线照射小鼠，照射剂量为1、2、4 Gy，用Western blot法检测照射后12、48和72 h小鼠肝脏中胰岛素生长因子1受体（IGF-1R）、胰岛素生长因子结合蛋白1（IGFBP1）、胰岛素生长因子结合蛋白4（IGFBP4）和胰岛素生长因子1（IGF-1）蛋白表达水平的改变。结果：照射剂量为1 Gy时，与对照组相比，IGF-1蛋白在照射后48 h时表达增加，IGFBP1、IGFBP4和IGF1R蛋白的表达在照射后12、48和72 h均表达减少。照射剂量为2 Gy时，IGF-1和IGFBP4蛋白在照射后48 h时表达增加，其余时间点表达减少。IGFBP1蛋白在照射后12 h时表达增加，48和72 h时表达减少。IGF1R蛋白在照射后3个时间点均呈现为表达减少。照射剂量4 Gy时，肝脏中IGF-1、IGFBP1和IGFBP4蛋白均表达减少，IGF1R蛋白在照射后12 h时表达增加，48、72 h时均表达减少（均为P < 0.05）。结论：电子线照射后小鼠肝脏中胰岛素生长因子-1家族蛋白多以下调表达为主，与前期基因表达的结果相一致，有可能作为反映放射性工作人员早期肝脏损伤的生物标志物之一。     

免疫检查点抑制剂治疗少见突变非小细胞肺癌疗效的研究进展

驱动基因的发现及针对驱动基因的靶向治疗已显著提高了肺癌患者的生存质量和时间，但目前对于BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的靶向药物的选择仍然较少。近年来免疫检查点抑制剂在肺癌治疗中取得了一定的疗效，但因为少见驱动基因突变的肺癌患者本身样本量少，开展大规模临床随机对照试验尚存在一定的困难，目前此类患者接受免疫检查点抑制剂治疗的疗效情况仍不明确。本文将对目前已掌握的免疫检查点抑制剂治疗BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的临床研究结果进行综述，以期在一定程度上为临床工作提供一些依据和参考。     

Focal peritubular capillary C4d deposition in acute rejection.

BACKGROUND: Diffuse peritubular capillary (PTC) C4d deposition has been shown to be associated with relatively poor graft outcome. The significance of focal PTC C4d staining in the early post-transplant period is uncertain. METHODS: Sixty-five biopsies from 53 patients with acute rejection were graded (Banff '97 criteria), stained for C4d, monocytes and T cells, and divided into three groups according to PTC C4d: (i) focal C4d (F) (14 biopsies, 14 patients), (ii) diffuse C4d (D) (23 biopsies, 15 patients) and (iii) no C4d (N) (28 biopsies, 24 patients). The three groups were compared with respect to a variety of biopsy and clinical parameters including outcome. RESULTS: The incidence of transplant glomerulitis and glomerular monocyte infiltration were significantly greater in F (64% and 2.0+/-2.0) and D (57% and 3.4+/-2.0) than in N (11% and 0.2+/-0.2). A significantly higher proportion of F (93%) demonstrated acute cellular rejection (Banff '97 grade > or = 1A) than did D (35%). The F and D groups included significantly more females (50 and 67%, respectively) than did N (21%). The percentage of patients with a second or third transplant was higher in F (29%) and D (40%) than in N (8%) (P = 0.0589). The proportion of patients with glomerular filtration rate < 30 ml/min at 12, 24 and 48 months was higher in the D and F groups than in the N, and there was a statistically significant increasing trend in odds of this outcome occurring at 48 months across the three groups (D > F > N group) (P = 0.0416). CONCLUSION: The results suggest that the biopsy findings and clinical course in patients with focal PTC C4d staining are similar to those associated with diffuse C4d.     

表皮生长因子对牛眼小梁细胞c—fos基因表达的诱导

目的研究表皮生长因子（ｅｐｉｄｅｒｍａｌｇｒｏｗｔｈｆａｃｔｏｒ，ＥＧＦ）对小梁细胞的作用。方法应用分子杂交技术研究ＥＧＦ对体外培养的牛眼小梁细胞ｃ－ｆｏｓ基因表达的诱导和３Ｈ胸腺核苷酸（３Ｈ－ｔｈｙｍｉｄｉｎｅｉｎｃｏｒｐａｒａｔｉｏｎ，３Ｈ－ＴｄＲ）掺入法观察细胞ＤＮＡ的合成。结果小梁细胞的３Ｈ－ＴｄＲ掺入率随着ＥＧＦ浓度不同而变化，浓度为２０～１５０ｎｇ／ｍｌ时，细胞掺入率随浓度增加升高（Ｐ＜０．０１）。与对照组相比，ＥＧＦ刺激停止生长的小梁细胞０．５小时后，ｃ－ｆｏｓ基因开始表达，１小时后达高峰，至２小时后消失。不同浓度ＥＧＦ刺激小梁细胞１小时后，ｃ－ｆｏｓ基因表达呈浓度依赖性。结论实验结果表明ＥＧＦ刺激小梁细胞增殖或进入生长状态，可能与ｃ－ｆｏｓ基因产物的信号传递作用有关。     

Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

紫胡皂甙的高效液相色谱分离与测定

建立了高效液相色谱法，应用反相柱，以甲醇－水（６６∶３４）为流动相，分离了柴胡中的主要有效成分柴胡皂甙ａ、ｃ、ｄ（Ｓａｉｋｏｓａｐｏｎｉｎａ，ｃ，ｄ）并用紫外法进行含量测定。