Plasma exchange treats severe intrahepatic cholestasis caused by dacomitinib: A case report

Rationale:Dacomitinib-induced liver injury is often manifested by mild elevations of transaminases and bilirubin, and severe intrahepatic cholestasis caused by dacomitinib for simultaneous taking orally cytochrome P450 2D6 (CYP2D6) competitive substrates has been rarely reported.Patient concerns:The patient was a 69-year-old woman with non–small cell lung cancer (NSCLC) who was prescribed oral dacomitinib for a month; she was given oral loratadine due to “allergic rhinitis” and metoprolol extended action tablets due to “tachycardia” separately for a few days during the course of dacomitinib treatment. The patient developed liver damage, increased fatigue, yellow urine, and pruritus, with significantly elevated serum levels of bilirubin and glutamyltranspetidase.Diagnosis:Intrahepatic cholestasis, drug-induced liver injury, and NSCLC.Interventions:After admission, the patient was prescribed adenosylmethionine, acetylcysteine, ursodeoxycholic acid capsule, methylprednisolone and fenofibrate for a month, with progressive elevation of liver biochemical parameters. Through drug enzyme gene assays in the liver tissue after percutaneous liver biopsy, we found both CYP2D6*10/*10 and ATP-binding cassette subfamily B member 1 GG variants (rs1045642) positive. After the poor response to the conventional medication, the patient underwent plasma exchange.Outcomes:The patient was discharged after her liver parameters improved; the parameters remained normal at several follow-up visits, and she renewed the NSCLC regimens without dacomitinib after being evaluated by oncologists.Lessons:Dacomitinib can induce severe intrahepatic cholestasis. It is considered that patients with intermediate metabolic CYP2D6 are susceptible to drug-induced liver injury caused by dacomitinib; plasma exchange may be an effective treatment.     

选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。     

两种培养基对贯叶连翘愈伤组织形成影响的研究

目的观察贯叶连翘叶片外植体在两种培养基中发生的结构变化。方法利用形态学手段,研究不同培养基对愈伤组织诱导过程中细胞结构变化的不同。结果不同点主要集中于叶绿体及淀粉粒的变化。发现两种培养基在诱导愈伤组织过程中在淀粉粒出现膨大的时间、淀粉粒变化趋势、叶绿体外形变化以及出愈伤时间上有不同之处。结论两种培养基下脱分化之所以会有不同是不同激素产生不同作用的结果。     

天麻镇静催眠作用研究进展

睡眠障碍是现代社会普遍存在的神经类疾病,严重影响患者的生活质量,对人类健康造成巨大威胁。天麻Gastrodiae Rhizoma是一种药食同源物质,是我国名贵中药,具有一定的镇静催眠作用,被广泛应用于改善患者的睡眠问题。通过对天麻中的天麻素、天麻苷元、腺苷、N⁶-(4-羟基苄基)嘌呤核糖及其类似物等活性成分改善睡眠的作用及其作用机制进行阐述,并对具有镇静催眠的天麻保健食品的剂型、配伍、适应人群、功能效果等进行统计分析,为天麻镇静催眠产品的研究开发提供参考。     

IL‐27 improves adoptive CD8+ T cells’ antitumor activity via enhancing cell survival and memory T cell differentiation

IL‐27 is an anti‐inflammatory cytokine that triggers enhanced antitumor immunity, particularly cytotoxic T lymphocyte responses. In the present study, we sought to develop IL‐27 into a therapeutic adjutant for adoptive T cell therapy using our well‐established models. We have found that IL‐27 directly improved the survival status and cytotoxicity of adoptive OT‐1 CD8⁺ T cells in vitro and in vivo. Meanwhile, IL‐27 treatment programs memory T cell differentiation in CD8⁺ T cells, characterized by upregulation of genes associated with T cell memory differentiation (T‐bet, Eomes, Blimp1, and Ly6C). Additionally, we engineered the adoptive OT‐1 CD8⁺ T cells to deliver IL‐27. In mice, the established tumors treated with OT‐1 CD8⁺ T‐IL‐27 were completely rejected, which demonstrated that IL‐27 delivered via tumor antigen–specific T cells enhances adoptive T cells’ cancer immunity. To our knowledge, this is the first application of CD8⁺ T cells as a vehicle to deliver IL‐27 to treat tumors. Thus, this study demonstrates IL‐27 is a feasible approach for enhancing CD8⁺ T cells’ antitumor immunity and can be used as a therapeutic adjutant for T cell adoptive transfer to treat cancer.     

Extracellular ATP promotes angiogenesis and adhesion of TNBC cells to endothelial cells via upregulation of CTGF

Our previous works have indicated that extracellular ATP is an important prometastasis factor. However, the molecular mechanism involved needs to be further studied. We demonstrated that extracellular ATP treatment could upregulate the expression of connective tissue growth factor (CTGF) in both triple‐negative breast cancer (TNBC) cells and endothelial cells (ECs). Extracellular ATP stimulated the migration of TNBC cells and ECs, and angiogenesis of ECs via the P2Y2––YAP‐CTGF axis. Furthermore, we demonstrated that adenosine triphosphate (ATP) stimulated TNBC cell adhesion to ECs and transmigration through the EC layer via CTGF by upregulation of integrin β1 on TNBC cells and VCAM‐1 on ECs. Both apyrase (ATP‐diphosphohydrolase) and CTGF shRNA treatments could inhibit the metastasis of inoculated tumors to lung and liver in a mouse model, and these treated tumors had fewer blood vessels. Collectively, our data indicated that extracellular ATP promotes tumor angiogenesis and the interactions between TNBC cells and ECs through upregulation of CTGF, thereby stimulating TNBC metastasis. The pleiotropic effects of ATP in angiogenesis and cell adhesion suggest that extracellular ATP or CTGF could be an effective target for TNBC therapy.     

Clinical application of metagenomic next‐generation sequencing technology in the diagnosis and treatment of pulmonary infection pathogens: A prospective single‐center study of 138 patients

IntroductionRapid and accurate pathogen identification is essential for the treatment of pneumonia. Metagenomic next‐generation sequencing (mNGS) is a newly developed technology to obtain microbial nucleic acid sequence information quickly, efficiently, and without bias.MethodsWe performed shotgun metagenomic next‐generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) for pathogen identification in pneumonia in a prospective study with 138 patients from a single center. We compared the results of mNGS with standard methods including culture, staining, and targeted PCR and evaluated the clinical applicability of mNGS.ResultsMost of the patients (128/138, 92.75%) were cured or improved. One patient (1/138, 0.72%) died because of acute gastrointestinal bleeding, and 9 patients (9/138, 6.52%) showed no improvement. mNGS identified more bacteria (53 versus 27), fewer fungi (8 versus 31), and more viruses (16 versus 1) than standard methods. In total, treatment in 34 out of 138 cases (24.64%) was adjusted and optimized because of mNGS results. Positive mNGS results contributed to a definitive diagnosis in 23 cases (16.67%), which helped guide treatment decision by either adjusting the antibiotics without de‐escalation or continuing the empirical treatment. mNGS also confirmed no active infection in 11 cases (7.97%) allowed for antibiotic de‐escalation.ConclusionThis prospective clinical study evaluated the clinical utility of mNGS for the diagnosis of pneumonia and showed that mNGS of BALF provides valuable information for effective treatment.     

Trappin-2对HaCaT细胞及银屑病跨膜模型增殖的抑制作用

目的 构建Trappin-2的真核表达体系,初步探讨Trappin-2对HaCaT细胞及银屑病跨膜模型增殖的影响.方法 采用DNA重组技术构建Trappin-2的表达载体pIRES2-EGFP-Trappin-2,通过脂质体法转染入宫颈癌HeLa细胞.将Trappin-2高表达上清加入HaCaT细胞及银屑病跨膜模型中,通过3H-TdR掺入法、MTT法、流式细胞术及组化染色Ki67检测对增殖的影响.结果 Trappin-2作用后MTY和cpm值变化率显示Trappin-2可抑制HaCaT细胞的代谢与DNA合成,同时可使HaCaT细胞G2 S期细胞比例下降,而G1期细胞比例增加.Trappin-2可下调银屑病皮损Ki67表达水平.结论 成功将Trappin-2基因转染HeLa细胞,并进行有效表达,初步证实Trappin-2具有抑制HaCaT细胞及银屑病跨膜模型增殖的特性.     

开腹胆囊切除术372例报告

目的探讨开腹胆囊切除术的手术治疗方法及其并发症的防范措施。方法对本院1995年1月-2007年1月行开腹胆囊切除术372例的临床资料进行回顾性分析。结果本组病例均痊愈出院。无医源性胆道损伤、出血及胆漏等并发症发生。结论若能准确把握开腹胆囊切除术的适应证及手术时机,规范手术操作,医源性胆道损伤是可以避免的。