真武汤合苓桂术甘汤改善心肾综合征大鼠模型水钠潴留的作用机制研究

[目的]研究真武汤合苓桂术甘汤对心肾综合征大鼠模型水钠潴留的作用机制。[方法]将60只雄性SD大鼠随机分为两组,即空白组与手术组,空白组大鼠常规饲养,手术组大鼠经5/6肾切除联合异丙肾上腺素皮下注射制备心肾综合征模型,剔除死亡大鼠后,将手术组剩余成模大鼠按体质量分层随机分为空白组、中药组、常规治疗组。中药组给予真武汤合苓桂术甘汤灌胃,给药量为7.29 g生药/(kg·d);常规治疗组给予贝那普利(0.45 mg/kg)+呋塞米(1.8m g/kg);空白组予以等容积生理盐水灌胃,每日1次,连续6周。观察实验过程中各组大鼠的精神状态、活动情况、灵敏度、毛发情况、食欲、大小便等一般情况及死亡情况,比较各组灌胃前、灌胃6周后的血清脑钠肽(BNP)、血肌酐(Scr)、血尿素氮(BUN)、尿水通道蛋白2(AQP2)的前后差值情况。[结果]灌胃6周后,中药组大鼠一般情况较灌胃前改善、喘息不明显,常规治疗组一般情况同样较灌胃前改善。通过比较治疗前后各组大鼠实验室指标差值发现,中药组与常规治疗组BNP均下降,中药改善大鼠心力衰竭情况接近常规治疗组水平,两组下降水平无统计学差异(P0.05);中药组Scr水平较前下降,常规治疗组Scr水平升高;中药组尿AQP2水平较前略增高,与空白组尿AQP2水平无统计学差异(P0.05),常规治疗组尿AQP2水平较前明显升高。[结论]心肾综合征大鼠尿AQP2的表达主要由肾脏调控,AQP2可作为心肾综合征水钠潴留状态的参考指标,真武汤合苓桂术甘汤改善心肾综合征大鼠水钠潴留状态的作用机制可能是通过抑制大鼠肾脏AQP2过度表达,减少水的重吸收,改善了水钠潴留状态。     

Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma development and growth in vivo

Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for Braf^V600E‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (Tyr^CreERT2/+; Braf^{LSL‐V600E/+}; Pten^flox/flox) to Sirt5^?/? knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5^?/? mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for Braf^V600E‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.     

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。     

Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma

Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings.     

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。     

Translocation between chromosome 5q35 and chromosome 11q13 – an unusual cytogenetic finding in a primary refractory acute myeloid leukemia

Cytogenetic abnormalities are observed in approximately two‐thirds of patients with acute myeloid leukemia (AML). Chromosome rearrangements are associated with specific subtypes of AML and associated prognosis. We report a patient with AML, M2, who was primarily refractory to standard induction chemotherapy with idarubicin and cytarabine. Flow cytometry of a bone marrow aspirate showed aberrant expression of B‐cell markers including CD19. Cytogenetic studies disclosed a translocation between 5q35 and 11q13. Fluorescence in situ hybridization analyses demonstrated that neither the NSD1 nor MLL genes were involved in this case. Further study is required to define conclusively the genes involved and their contribution to pathogenesis in this case.     

Photodynamic therapy in Argentina

The use of endogenous Protoporphyrin IX generated through the heme biosynthetic pathway after administration of 5-aminolevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). In Buenos Aires, Argentina, the Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), reported for the first time, in 1975, porphyrin synthesis from ALA in highly dividing plant tissues. Increased porphyrin synthesis in tumours as well as cell photosensitisation was reported soon after. Our group is also interested in studying the use of new synthetic lipophilic derivatives of ALA as well as ALA delivery in liposomes. We have elucidated the mechanism of ALA transport in mammalian and yeast cells. The interactions between ALA-PDT and nitric oxide were investigated in three murine adenocarcinoma cell lines. In the National University of Río Cuarto, Córdoba, a group is devoted to the synthesis of new porphyrin-derived photosensitisers to study their effects on photoinactivation of bacterial and mammalian cells death by PDT. At the Centre of Electron Microscopy of the Cordoba National University, a prototype of a 630 nm noncoherent light source was designed and constructed. Cost of the light source and scarce knowledge of the benefits of PDT by physicians limit the spread of the treatment throughout the country.