利用虚拟仿真技术开展侧颅底教学改革探讨

侧颅底位置深在,解剖关系复杂,传统手术死亡率高,曾被认为是手术禁区。近年来随着相关学科的发展,侧颅底外科的诊疗技术取得很大进步。文章介绍了在临床教学实践中引入虚拟仿真技术,进行教学改革,达到虚拟手术切除,显示重要器官结构相对毗邻关系的做法。     

Discovery of Cobimetinib as a novel A-FABP inhibitor using machine learning and molecular docking-based virtual screening

Adipocyte fatty acid-binding protein (A-FABP, also called FABP4, aP2) is an adipokine identified as a critical regulator of metabolic function due to its dual functions of fatty acid transport and pro-inflammation. Because of the high therapeutic potential of A-FABP inhibition for the treatment of metabolic diseases and related vascular complications, numerous inhibitors have been developed against A-FABP. However, none of these inhibitors have been approved for use in patients due to severe side effects. Here, we used a virtual screening (VS) strategy to identify potential inhibitors of A-FABP in the latest FDA-approved drug library (∼2600 compounds), aiming to explore the existing drugs with proven safety profiles. We firstly combined ligand-based machine learning and structure-based molecular docking to develop a screening pipeline for identifying A-FABP inhibitors. The screening of FDA-approved drugs identified four compounds (Cobimetinib, Larotrectinib, Pantoprazole, and Vildagliptin) with the highest scores, whose inhibitory effects on A-FABP were further assessed in cellular assays. Among the selected compounds, Cobimetinib significantly inhibited the activation of the JNK/c-Jun signaling pathway by A-FABP in mouse macrophages without causing obvious cytotoxicity. In summary, we present an integrated VS pipeline for A-FABP inhibitor screening, and identified Cobimetinib as a novel A-FABP inhibitor that may be repurposed for the treatment of metabolic diseases and associated vascular complications.

The integrated virtual screening pipeline was constructed to identify potential inhibitors of A-FABP in the latest FDA-approved drug library, aiming to explore the existing drugs with proven safety profiles.     

Therapeutic Effectiveness of Sustained Low‐Efficiency Hemodialysis Plus Hemoperfusion and Continuous Hemofiltration Plus Hemoperfusion for Acute Severe Organophosphate Poisoning

There is no report on the effects of sustained low‐efficiency dialysis (SLED) plus hemoperfusion (HP) (SLED + HP) in patients with acute severe organophosphate (OP) poisoning (ASOPP). This study was designed to compare the therapeutic effectiveness between SLED + HP and continuous hemofiltration (CHF) plus HP (CHF + HP) in patients with ASOPP. In order to assess the two treatment methods, 56 patients with ASOPP were divided into CHF + HP group and SLED + HP group. The biochemical indicators, in‐hospital duration, hemodynamic parameters, Acute Physiology, and Chronic Health Evaluation (APACHE II) score, and survival and mortality rates were compared. In both groups after treatment, the levels of serum creatine kinase isozyme MB, creatine kinase, creatinine, glutamic‐oxalacetic transaminease, and glutamate‐pyruvate transaminase, and the APACHE II scores on the first, second, and seventh day decreased (P < 0.05), whereas the levels of serum acetylcholinesterase increased. The two groups showed no statistical differences in in‐hospital duration, biochemical indicators, APACHE II score, hemodynamic parameters, survival rate, or the mortality rate (P > 0.05). In conclusion, SLED has similar hemodynamic stability to CHF and the two treatment methods have similar effects on ASOPP patients. More importantly, SLED plus HP is relatively economical and convenient for patients with ASOPP in clinical practice.     

Single-Incision Laparoscopic Common Bile Duct Exploration with Conventional Instruments: an Innovative Technique and a Comparative Study

Background

Single-incision laparoscopic surgery developed rapidly in recent years. We introduce an innovative technique: single-incision laparoscopic common bile duct exploration (SILCBDE) with conventional instruments. A retrospective comparison between SILCBDE and standard laparoscopic common bile duct exploration (LCBDE) was analyzed.

Methods

Thirty-four patients who underwent LCBDE for choledocholithiasis in a period of 17 months were enrolled. Seventeen standard LCBDEs and 17 SILCBDEs were attempted. Simultaneous cholecystectomies were performed.

Results

The stone clearance rate was 94.1 % (16 patients) in the standard LCBDE group and 100 % in the SILCBDE group. There was no statistical difference in demographic distribution, clinical presentations, and operative results between the two groups, except the SILCBDE group had a higher rate of acute cholecystitis than the standard LCBDE group (76.5 vs. 35.3 %; p?<?0.05). One procedure (5.9 %) in the SILCBDE group was converted to a four-incision transcystic LCBDE. The complication rate was 11.8 % (two patients) in the standard LCBDE group and 5.9 % (one patient) in the SILCBDE group. The average follow-up period was 4.2 months.

Conclusion

SILCBDE is as safe and efficacious as standard LCBDE in experienced hands. Choledochoscope manipulation and bile duct repair are the key skills. Long-term follow-up and further prospective randomized trials are anticipated.     

腺病毒载体介导的PML生长抑制因子对前列腺癌细胞生长和致瘤能力的抑制效果

为探讨用腺病毒载体携带ＰＭＬ（ＰｒｏｍｙｅｌｏｃｙｔｉｃＬｅｕｋｅｍｉａ）基因作为前列腺癌基因治疗的可能性，应用重组人携带ＰＭＬ基因腺病毒（ＡｄＰＭＬ）感染培养的前列腺癌细胞，观察表达ＰＭＬ蛋白的癌细胞与对照组癌细胞的体外生长和裸鼠体内致瘤能力变化，对荷瘤裸鼠瘤体周围注射ＡｄＰＭＬ，观察治疗组和对照组肿瘤生长的变化。结果显示，感染ＡｄＰＭＬ的前列腺癌细胞体外生长和裸鼠体内致瘤能力明显下降，荷瘤裸鼠瘤体周围注射ＡｄＰＭＬ后肿瘤生长速度明显减慢。证实了ＰＭＬ是一种生长抑制因子，提示其可能被应用于前列腺癌的基因治疗研究     

四生汤减轻放射反应的作用机制研究

为进一步研究四生汤减轻放射反应的作用机制,分别以＾１３７Ｇｓ－γ射线全身一次性照射造成小鼠急性辐射损伤模型及人骨髓细胞为研究对象,观察四生汤对模型动物和人骨髓细胞增殖的影响。结果表明四生汤明显提高模型动物Ｇ－ＣＦＵ和ＣＦＵ－Ｓ数量,对人骨髓Ｇ－ＣＦＵ产率也有明显的促进作用。四生汤内可能含有促进骨髓造血干细胞增殖和分化的成分。     

胰岛素对糖尿病大鼠再灌注损伤性心肌的影响及可能机制

目的 观察胰岛素对糖尿病和非糖尿病大鼠再灌注损伤性心肌的影响并探讨其可能机制.方法 复制实验性糖尿病大鼠模型,造模9周,结扎左冠状动脉前降支复制心肌缺血/再灌注模型.动物随机分为6组,糖尿病组和非糖尿病组分别给予生理盐水、胰岛素或胰岛素+渥曼青霉素.观察心肌血清酶学、心律失常评分及心肌磷酸化蛋白激酶b(p-Akt)和磷酸化Bad(p-Bad)表达.结果 与非糖尿病对照组比较,胰岛素组可以使血清肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)降低;胰岛素组心律失常评分降低;心肌组织p-Akt和p-Bad蛋白表达高于非糖尿病对照组,胰岛素的这种作用被渥曼青霉素取消.与糖尿病对照组比较,胰岛素组可以使血清CK和CK-MB降低;胰岛素组心律失常评分降低;心肌组织p-Akt和p-Bad蛋白表达增强,该变化可以被渥曼青霉素取消.胰岛素对糖尿病大鼠和非糖尿病大鼠的心肌再灌注损伤的影响的比较:糖尿病大鼠的血清CK和CK-MB高于非糖尿病大鼠;两者的心律失常评分比较无显著差异;非糖尿病胰岛素组心肌p-Akt表达高于糖尿病胰岛素组.结论 胰岛素通过PI3K/Akt信号转导途径对于非糖尿病再灌注损伤心肌具有保护作用,胰岛素对于糖尿病再灌注损伤心肌同样具有保护作用,但保护作用效果弱于非糖尿病心肌.     

长链非编码 RNALOC100288637在原发性肝癌中差异性表达的生物学意义及相关机制研究

目的：研究长链非编码 RNA （LncRNA ） LOC100288637在肝癌中的表达差异,对肝癌细胞增殖的影响及相关机制。方法分析GEO数据集GSE58043和GSE10694,得出LOC100288637及hsa‐miR‐101‐3p在肝癌组织中差异表达,RNA‐hy‐brid分析LOC100288637与hsa‐miR‐101‐3p的结合具有可能性。逆转录‐聚合酶链式反应在组织和细胞水平检测LOC100288637表达量。荧光原位杂交观察LOC100288637在细胞中的定位。敲低LOC100288637后CCK‐8检测细胞增殖情况。过表达hsa‐miR‐101‐3p后,检测 LOC100288637的变化。结果 LOC100288637在肝癌组织中的表达量高于癌旁组织（ P＜0．05）;LOC100288637在肝癌细胞系中的表达量高于肝细胞系（P＜0．05）。LOC100288637在 HepG2细胞核质均有表达,以细胞质居多。敲低LOC100288637后 HepG2细胞增殖活性降低（P＜0．01）。过表达hsa‐miR‐101‐3p后,LOC100288637表达量下降（P＜0．05）。结论 LncRNA LOC100288637可能在肝癌发生,发展过程中起重要作用并接受hsa‐miR‐101‐3p靶向调控影响肝癌细胞的增殖。