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.     

In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus

Zika virus (ZIKV) causes significant human diseases without specific therapy. Previously we found erythrosin B, an FDA-approved food additive, inhibited viral NS2B−NS3 interactions, leading to inhibition of ZIKV infection in cell culture. In this study, we performed pharmacokinetic and in vivo studies to demonstrate the efficacy of erythrosin B against ZIKV in 3D mini-brain organoid and mouse models. Our results showed that erythrosin B is very effective in abolishing ZIKV replication in the 3D organoid model. Although pharmacokinetics studies indicated that erythrosin B had a low absorption profile, mice challenged by a lethal dose of ZIKV showed a significantly improved survival rate upon oral administration of erythrosin B, compared to vehicle control. Limited structure−activity relationship studies indicated that most analogs of erythrosin B with modifications on the xanthene ring led to loss or reduction of inhibitory activities towards viral NS2B−NS3 interactions, protease activity and antiviral efficacy. In contrast, introducing chlorine substitutions on the isobenzofuran ring led to slightly increased activities, suggesting that the isobenzofuran ring is well tolerated for modifications. Cytotoxicity studies indicated that all derivatives are nontoxic to human cells. Overall, our studies demonstrated erythrosin B is an effective antiviral against ZIKV both in vitro and in vivo.KEY WORDS: Flavivirus, Zika virus, Dengue virus, Antiviral, Protease inhibitor, Erythrosin B     

Self-assembled sonogels formed from 1,4-naphthalenedicarbonyldinicotinic acid hydrazide

In this paper, we report self-assembled sonogels formed from 1,4-naphthalenedicarbonyldinicotinic acid hydrazide (NDC-NN3) in some liquids including ethanol, tetrahydrofuran (THF), 1,4-dioxane, n-propanol, n-butanol and n-pentanol. When the clear solution of NDC-NN3 in the selected liquids mentioned above at a suitable concentration was irradiated with ultrasound waves at room temperature, a sonogel was formed. Upon heating, the sonogel dissolved gradually and finally became a clear solution again. Upon cooling the hot solution to room temperature, the solution state did not change even after standing for a few days. Nevertheless, if the solution underwent sonication for a certain time, a stable gel was obtained again. The critical gelation concentrations (CGCs) of NDC-NN3 in ethanol, THF, 1,4-dioxane, n-propanol, n-butanol and n-pentanol are 10, 8, 6, 8, 6 and 8 mg mL⁻¹, respectively. The obtained sonogels display excellent mechanical properties. The crystal structure of NDC-NN3 suggests that the naphthalene ring, hydrazide group and the position of N in the pyridine ring mediate the self-assembly process. Upon sonication, the formation of suitable π–π stacking and intermolecular hydrogen bonding drives the gelator molecules to self-assemble into fibers, spheres and micro-burdock-shaped balls in various solvents, which ultimately confine the liquids.

Ultrasound-induced gelation of a novel type of gelator, 1,4-naphthalenedicarbonyl- dinicotinic acid hydrazide, is reported. The gelator self-assembled into various architectures in different solvents.     

Diagnostic significance of long non-coding RNAs expression in tuberculosis patients: A systematic review and meta-analysis

Objectives:It is crucial to identify effective diagnostic biosignatures of tuberculosis (TB) to optimize its treatment. Herein, we conducted a systematic review to elucidate the diagnostic efficacy of long noncoding RNA (lncRNAs) as TB biomarkers.Methods:We searched Medline, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, VIP, and China Biology Medicine disc databases up to February 18, 2020. These studies focusing on lncRNAs as diagnosis markers of TB were collected. STATA 12.0 and Meta-disc1.4 software were used to analyze the data extracted from eligible studies.Results:We included 8 articles with 1058 TB patients, and 1896 healthy controls in our study. The values of pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.63, 0.86, 4.48, 0.43, and 10.31, respectively. Additionally, we plotted the summary receiver operating characteristic curve to evaluate the diagnostic accuracy, and the area under the curve was 0.80.Conclusion:The present study is the first meta-analysis to assess the diagnostic accuracy of lncRNAs in TB patients. We found that lncRNAs might constitute potential biomarkers for the diagnosis of TB patients. More population-based high-quality research should be conducted to validate the efficacy lncRNAs in TB patients.     

颈动脉内膜剥脱术在颈动脉狭窄患者中的应用

目的探讨颈动脉内膜剥除术（CEA）在颈动脉狭窄患者中的治疗效果。方法回顾分析我院2009～2013年,12例颈动脉粥样硬化伴狭窄的患者,通过术前颈动脉B超、CTA检查明确诊断,探讨相关手术适应证、手术方法、术后处理及治疗效果。结果患者均治愈出院,无死亡病例,所有患者均在全麻下行CEA,5例放置颈动脉转流管,7例未放置;头晕及TIA症状明显改善者8例;5例术后出现高血压、头痛;3例术后6h发生切口渗血,1例术后朐闷不适,冠脉CTA提示左前降支病变狭窄（85％）。结论CEA在治疗颈动脉粥样硬化伴狭窄中效果良好,需严格把握适应证,做好围手术期准备,合理使用转流管。     

脂蛋白脂酶活化剂NO-1886抑制糖尿病兔动脉粥样硬化的形成

目的　合成化合物NO 1886 ,一种脂蛋白脂酶活化观察脂蛋白脂酶活化剂是否降低高脂 /高蔗糖饲料诱发的糖尿病新西兰兔的血浆葡萄糖并减轻其动脉粥样硬化。方法　给予高脂 /高蔗糖饲料升高新西兰兔血浆总胆固醇 ,甘油三酯和葡萄糖及降低高密度脂蛋白胆固醇而导致动脉粥样硬化。饲料中加入 1 0 %NO 1886进行治疗观察。分别在 0、4、8、12、16、2 0及 2 4wk从禁食过夜的兔耳静脉抽取血样测定葡萄糖和脂质水平。第 2 4周末 ,处死动物 ,分离主动脉 ,经苏丹Ⅳ染色固定脂质后 ,计算脂纹病变面积。结果　应用NO 1886后 ,实验动物血浆葡萄糖 ,总胆固醇和甘油三酯降低 ,高密度脂蛋白胆固醇增加。对动脉粥样硬化的发展具有抑制作用。结论　NO 1886不仅可改善脂质紊乱 ,而且可降低血浆葡萄糖 ,减轻糖尿病兔动脉粥样硬化     

Mechanisms underlying vasorelaxant action of astragaloside IV in isolated rat aortic rings

1. Astragaloside IV is a component from the widely used traditional Chinese herb Astragalus membranaceus and its effect on rat aortic ring contraction and relaxation were investigated. 2. The aorta from male Sprague-Dawley rats was isolated in an organ bath and ring tension was recorded with or without endothelium. Cumulative effects of astragaloside IV on vessel contraction and relaxation were observed in the presence of various antagonists related to vessel activity. 3. Astragaloside IV showed concentration-dependent inhibition of vessel contraction induced by phenylephrine and potassium chloride. The amount of calcium released from intracellular stores sensitive to phenylephrine was also markedly reduced by astragaloside IV. There was dose-dependent vasorelaxation in endothelium-intact rings, which was partly inhibited by pre-incubation with nitric oxide (NO) synthase (NOS) Nomega-nitro-L-arginine methyl ester and guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Astragaloside IV also induced a significant increase in aortic tissue content of guanosine 3",5"-cyclic monophosphate (cGMP) both in vivo and in vitro. Endothelial NOS inhibitor Nomega-nitro-L-arginine prevented vasodilatation, whereas neuronal NOS inhibitor 7-nitroindazole did not show significant influence on the vessel relaxation of astragaloside IV. 4. In conclusion, astragaloside IV inhibited vessel contraction through blocking calcium influx and intracellular calcium release. The endothelium-dependent vessel dilation of astragaloside IV was attributed mainly to the endothelium-dependent NO-cGMP pathway.     

Increasing nodal vulnerability and nodal efficiency implied recovery time prolonging in patients with supplementary motor area syndrome

Supplementary motor area (SMA) syndrome is a surgery‐related complication that commonly occurs after removing SMA glioma, and needs weeks to recover. However, susceptible factors of patients suffering from SMA syndrome remain unknown. Graphic theory was applied to reveal topological properties of sensorimotor network (SMN) by processing resting‐state functional magnetic resonance images in 66 patients with SMA gliomas. Patients were classified into SMA and non‐SMA groups based on whether they suffered from SMA syndrome. We collected recovery time and used causal mediation analysis to find association between topological properties and recovery time. Compared with the non‐SMA group, higher vulnerability (left: p = .0018; right: p = .0033) and lower fault tolerance (left: p = .0022; right: p = .0248) of the whole SMN were found in the SMA group. Moreover, higher nodal properties of lesional‐hemispheric cingulate cortex (nodal efficiency: left, p = .0389; right, p = .0169; nodal vulnerability: left, p = .0185; right, p = .0085) and upper limb region of primary motor cortex (PMC; nodal efficiency: left, p = .0132; right, p = .0001; nodal vulnerability: left, p = .0091; right, p = .0209) were found in the SMA group. Nodal efficiency and nodal vulnerability of cingulate cortex and upper limb region of PMC were important predictors for SMA syndrome occurring and recovery time prolonging. Neurosurgeons should carefully deal with upper limb region of PMC and cingulate cortex, and protect them if these two region were unnecessary to damage during SMA glioma resection.     

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma: clinical outcomes and patterns of failure

The objective of the study was to report clinical outcomes and patterns of failure for these patients with cervical esophageal squamous cell carcinoma (CESCC) treated with intensity-modulated radiotherapy (IMRT). A total of 64 patients with CESCC treated with definitive IMRT from May 2005 to March 2012 in our center were analyzed. Forty-two patients received radiotherapy alone and 22 patients received concurrent chemoradiotherapy. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. For all patients, the overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 74.5, 88.0, 66.6 and 42.5 %, respectively. Twenty-eight patients had developed treatment failure. Of the 28 patients, 14, 5, and 18 had developed local failure, regional failure, and distant metastasis, respectively. All of the 14 local failures were considered in-field failures. Of the five regional failures, three were considered in-field failures and two were marginal failures. The most frequently observed acute toxicity was mainly Grade 1 or 2. The incidence of acute Grade 3 mucositis (including pharyngitis), skin reaction, and leukopenia was 4.7, 12.5 and 10.9 %, respectively. IMRT provides satisfactory locoregional control for CESCC. Distant metastasis remains the predominate pattern of failure and the predominate pattern of locoregional failures is in-field failure.     

面神经水平段梳理术治疗半面痉挛

半面痉挛（HFS）病因机理不清，有神经冲动短路、局部癫痛、微血管压迫学说，尚无特效药物治疗。本文报告经鼓室探查术进路行面神经水平段减压术治疗HFS6例，平均随访1.2年，显效4例，复发2例，但程度减轻。5例术中未分离砧镫关节，听力不变。HFS行水平段神经梳理术不复杂，安全有效，是多种手术疗法中可取的一种。作者介绍提高手术效果的几点经验：①鼓室探查术外耳道鼓膜皮瓣比常现大一点，有利于暴露面神经水平段；②镫骨上层结构及砧镫关节是定位面神经骨管的重要标志；③为保持听力，一般不要分离砧镫关节；④面神经水平段骨管近卵圆窗缘较薄，可用细钩针挑开；⑤根据面痉挛病程和痉挛程度的不同，进行不同强度的梳理；⑥对病情顽固者，可行第二次梳理术。