模拟定位导向Max—Core活检针经皮肺活检临床评价

目的 探讨模拟定位机下经皮穿刺肺活检对周围性肿块的临床诊断价值。方法 采用模拟定位机导向对47例肺周围性肿块进行模拟定位导向，经皮肺活检后作病理诊断。结果 肺癌43例，结核2例，炎性假瘤2例，阳性率93％．且并发症少．操作简便、快捷、安全。结论 模拟定位导向经皮穿刺肺活检对肺部周围性肿块是一种较为安全有效的诊断技术。     

紫外线致皮肤光老化及光癌变机制的研究进展

日光的累计照射可加速皮肤老化与癌变,使皮肤的生物学及临床反应发生改变,包括急性损伤(日晒伤)和慢性损伤(光老化、光癌变或色素沉着等)。文章概述了近年来紫外线对皮肤光老化及光癌变影响的研究进展,揭示光老化和光致癌机制是通过紫外线照射产生活性氧和DNA损伤,以及由此引起的细胞损伤、炎症、免疫抑制、细胞外基质重塑及血管生成改变所致,为临床防治光老化和光癌变提供帮助。     

Phase I and scintigraphy studies to evaluate safety,tolerability, pharmacokinetics,and lung deposition of inhaled GDC‐0214 in healthy volunteers

Several inflammatory cytokines that promote inflammation and pathogenesis in asthma signal through the Janus kinase 1 (JAK1) pathway. This phase I, randomized, placebo‐controlled trial assessed the pharmacokinetics and safety of single and multiple ascending doses up to 15 mg twice daily for 14 days of a JAK1 inhibitor, GDC‐0214, in healthy volunteers (HVs; n = 66). Doses were administered with a dry powder, capsule‐based inhaler. An accompanying open‐label gamma scintigraphy study in HVs examined the lung deposition of a single dose of inhaled Technetium‐99m (^99mTc)‐radiolabeled GDC‐0214. GDC‐0214 plasma concentrations were linear and approximately dose‐proportional after both single and multiple doses. Peak plasma concentrations occurred at 15–30 min after dosing. The mean apparent elimination half‐life ranged from 32 to 56 h across all single and multiple dose cohorts. After single and multiple doses, all adverse events were mild or moderate, and none led to treatment withdrawal. There was no clear evidence of systemic toxicity due to JAK1 inhibition, and systemic exposure was low, with plasma concentrations at least 15‐fold less than the plasma protein binding‐corrected IC50 of JAK1 at the highest dose. Scintigraphy showed that approximately 50% of the emitted dose of radiolabeled GDC‐0214 was deposited in the lungs and was distributed well to the peripheral airways. ^99mTc‐radiolabeled GDC‐0214 (1 mg) exhibited a mean plasma C_max similar to that observed in phase I at the same dose level. Overall, inhaled GDC‐0214 exhibited pharmacokinetic properties favorable for inhaled administration.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Many factors drive asthma pathogenesis, including several cytokines that signal through the Janus kinase 1 (JAK1) pathway. Inhibition of JAK1 is a possible target for asthma treatments, but previous studies show oral JAK1 inhibitors lead to increased risk of severe infections, malignancy and cardiovascular events.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study investigated the safety, pharmacokinetics, and lung deposition of GDC‐0214, an inhaled JAK1 inhibitor designed to target the lungs.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Inhaled delivery of a JAK inhibitor for 14 days exhibited low systemic exposure, leading to few adverse events and limited systemic toxicity, while demonstrating high deposition in the lungs.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Local pulmonary application of JAK inhibitors may be an effective treatment for asthma with limited systemic risks.     

乳酸脱氢酶同工酶C_4与男性不育的关系

用自制的抗人乳酸脱氢酶同工酶C_4(LDH-C_4)单克隆抗体(McAb),以免疫荧光、BA-ELISA及聚丙烯酰胺凝胶电泳(PAGE)等方法,测定了110例正常及各种不育症患者精子及精浆中LDH-C_4的含量。结果表明:不明原因性不育症、少精症及无精症患者精液中LDH-C_4的含量明显低于正常对照组,与正常组比较P值均<0.001,有极显著性差异;免疫荧光还发现不育症组伴有各种畸形精子。LDH-C_4含量的明显降低可能与男性不育有关。     

血糖紊乱与胰腺癌患者生存时间相关性的研究

目的:探讨血糖紊乱与胰腺癌患者生存时间的关系。方法:回顾性分析44例胰腺癌患者的临床资料,根据血糖水平分成血糖正常组、糖尿病前期组及糖尿病组,观察各组患者的年龄分布、通过随访了解糖代谢紊乱与胰腺癌患者生存时间的关系。结果:本组胰腺癌患者伴糖尿病前期的比例为27.27%,胰腺癌伴糖尿病的比例为31.84%,胰腺癌患者伴有糖耐量异常患者生存时间长于胰腺癌合并糖尿病患者(P<0.05),胰腺癌患者不伴有糖耐量异常的生存时间长于合并糖尿病患者(P<0.05)。结论:胰腺癌患者出现糖代谢紊乱的比例较高,糖代谢紊乱的胰腺癌患者生存时间明显短于无糖代谢异常的患者。     

Conversional synthesis and cytotoxic evaluation of novel taxoid analogs

Four novel taxoid analogs were conversionally synthesized from the C₁₉-diterpenoid alkaloid deltaline, and their cytotoxic activities were evaluated against a small panel of cancer cell lines.     

葡萄糖转运蛋白1和波形蛋白在肺癌胸水中的应用价值

目的:采用免疫细胞化学技术测定葡萄糖转运蛋白1(GLUT1)及波形蛋白(VM)在癌细胞中的定位表达,探讨GLUT1和VM在肺癌胸水中的应用价值。方法:以肺癌患者为研究对象,以肺癌性胸水为检测基础,收集胸水沉淀细胞,制成石蜡切块,采用免疫组化技术-链霉菌抗生物素-过氧化物霉法检测30例肺癌胸水和20例良性胸水中GLUT1和VM蛋白表达,统计单个及联合应用价值。结果:30例肺癌胸水中,GLUT1表达阳性的有25例(86.7%),良性胸水中间皮细胞VM表达阳性的有18例(90.0%),两种不同性质的胸水GLUT1和VM的阳性率表达均有差异(P<0.05),GLUT1和VM在肺癌胸水中表达呈负相关(P<0.05),两者联合诊断灵敏度为90%。结论:应用免疫组化方法检测肺癌胸水中GLUT1和VM蛋白表达,可提高肺癌早期诊断的灵敏度。     

Therapeutic efficacy of arthroscopy-assisted transosseous fixation with the Versalok suture anchor for tibial eminence fractures in adults

To investigate the clinical outcomes of arthroscopy-assisted transosseous fixation of tibial eminence fractures with the Versalok suture anchor in adults.A total of 23 adult cases of tibial eminence fractures treated between June 2016 and March 2019 were retrospectively analyzed. The results of the preoperative drawer test and Lachman test were positive. Radiography and computed tomography were performed before and after the procedure. Magnetic resonance imaging was performed in every patient after admission. Arthroscopy-assisted fracture reduction and Orthocord high-strength suture fixation with two Versalok anchors were performed in all the patients. The International Knee Documentation Committee scale and the Lysholm Knee Scoring Scale were used to evaluate outcomes during the follow-up period. Additionally, the KT-2000 knee stability test was performed.At the final follow-up, all the fractures had proceeded to bony union and no wound infection was observed. The average Lysholm Knee Score of the affected knees was 93.1 (range, 90–98), which was not significantly different from that of the healthy knees (t = 0.732, P = .132). Based on the International Knee Documentation Committee scale results, 21 patients were graded as normal and the other 2 patients were graded as nearly normal. The KT-2000 test showed that the anterior displacement of the affected side and the healthy side was less than 3.6 mm in all cases.The outcomes indicated firm fixation and good fracture healing with minimal trauma. Thus, arthroscopy-assisted transosseous fixation with Versalok suture anchors for adult tibial eminence fractures seems to have satisfactory clinical outcomes.     

基于深度学习的FFRCT在可疑冠心病病人中的应用

目的 探讨基于深度学习的CT血流储备分数（FFR_CT）在可疑冠心病病人中应用的可行性,分析缺血性病变（FFR_CT≤0.80）的预测因素及对治疗决策的影响。方法 回顾性纳入因疑似冠心病行冠状动脉CT血管成像（CCTA）的病人292例,其中男187例,女105例,平均年龄（65.8±10.3）岁。利用CCTA影像将狭窄程度分为轻度 （≥25%且<50%）、中度（≥50%且<70%）和重度（≥70%且<99%）。采用基于深度学习的FFR_CT软件对病人的CCTA数据进行测量。根据FFR_CT数值范围将病人分为阳性组（FFR_CT≤0.80,102例）和阴性组（FFR_CT>0.80,190例）。2组病人的一般资料、CCTA上的血管特征及血运重建,以及基于FFR_CT与CCTA制定的治疗策略的比较采用Mann-Whitney U 检验、t检验及卡方检验。采用Logistic回归分析FFR_CT≤0.80的独立预测因素。结果 阳性组病人的年龄更大,男性更多,高血压、糖尿病和吸烟的比例均高于阴性组（均P<0.05）。阳性组较阴性组病人更多的表现为中重度狭窄（分别为80.4%和28.4%）,更多的病人行血运重建术（分别为56.8%和11.1%）,均P<0.05。74例病人（25.3%）基于FFR_CT的结果治疗决策发生改变。多因素Logsitic回归分析显示,高血压（OR=2.245）、糖尿病（OR=2.238）及中重度狭窄（OR=8.837）是FFR_CT≤0.80的独立预测因素（均P<0.05）。结论 基于深度学习的FFR_CT技术在可疑冠心病病人中的应用是可行的,高血压、糖尿病及中重度狭窄是FFR_CT≤0.80的独立预测因素,FFR_CT可能影响病人的治疗决策。     

Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line

Interferon alfa (IFN-alpha)-based treatment is the only therapeutic option for chronic hepatitis C viral infection. However, the molecular mechanisms of IFN-alpha antiviral activity are not completely understood. The recent development of an HCV replicon cell culture system provides a feasible experimental model to investigate the molecular details of IFN-induced direct antiviral activity in hepatocytes. In this report, we show that IFN-alpha can effectively inhibit HCV subgenomic RNA replication and suppress viral nonstructural protein synthesis. Using cDNA microarray analysis, we also show that the replicon cells have different gene expression profile compared with the parental hepatoma cells (Huh7). IFN-alpha can induce a number of responsive genes in the replicon cells. One of the genes, 6-16 (G1P3), can enhance IFN-alpha antiviral efficacy. In addition, we demonstrate that IFN-alpha can significantly activate STAT3 in hepatoma cells, suggesting that this pathway plays a role in IFN-alpha signaling. In conclusion, our results indicate that IFN-alpha antiviral activity is associated with activation of STAT3-signaling pathway and intracellular gene activation. Our results also suggest that IFN-alpha-induced target genes may play an important role in IFN-alpha anti-HCV activity.