Cholinergic hyperactivity in patients with myasthenia gravis with MuSK antibodies: A neurophysiological study

ObjectivePatients with myasthenia gravis associated with muscle-specific tyrosine kinase antibodies (MuSK-MG) often manifest signs of cholinergic hyperactivity with standard doses of acetylcholinesterase inhibitors (AChE-Is). Aim of the study was to investigate whether repetitive compound muscle action potential (R-CMAP), the neurophysiological correlate of cholinergic hyperactivity, was present in MuSK-MG irrespective of AChE-I treatment.MethodsPatients with confirmed diagnosis of MuSK-MG were consecutively enrolled during follow-up visits, from January 2019 to April 2020. All these subjects underwent the same neurophysiological protocol, including motor nerve conduction studies and repetitive nerve stimulation. In patients taking pyridostigmine, neurophysiological testing was performed at least 12 hours after the last dose. For comparison, the presence of R-CMAP was investigated in 20 consecutive acetylcholine receptor antibody positive myasthenia gravis (AChR-MG) patients.ResultsWe enrolled 25 MuSK-MG patients (20 females), aged 16–79 years at the study time, with disease duration ranging 0.6–48.8 years (median: 17.7 years). R-CMAP was detected in 12/25 (48%) MuSK-MG cases and in none of the AChR-MG controls (p = 0.0003). In the MuSK-MG population, a history of muscle cramps and fasciculations, during low-dose pyridostigmine therapy, was significantly more frequent in R-CMAP positive than in R-CMAP negative patients (100% vs 31%, p = 0.001). At the time of the study, the proportion of patients still symptomatic for MG was higher among R-CMAP positive cases (92% vs 23%, p = 0.0005).ConclusionsCholinergic hyperactivity is a relatively common finding in MuSK-MG patients, independent of AChE-I treatment, and may constitute an intrinsic feature of the disease.SignificanceR-CMAP detection can represent a useful diagnostic clue for MuSK-MG and predicts poor tolerance to AChE-Is.     

Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver

ABSTRACT— To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%, HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.     

加用复方龙星片治疗感冒后咳嗽的临床研究

[目的] 通过用复方甲氧那敏胶囊和加用复方龙星片的方法分别治疗感冒后咳嗽,观察两组的临床疗效。[方法] 将符合入组条件的80例患者在服用复方甲氧那敏胶囊(商品名:诺尔彤)的基础上,采用随机数字表法随机分为常规治疗组(对照组)40例,加用复方龙星片组(治疗组)40例,服药14 d为1个疗程。[结果] 治疗组临床总有效率为90.00%,对照组为80.00%,两组在总体疗效上差异有统计学意义(P<0.05);治疗组在日间咳嗽、夜间咳嗽、咳痰量、咽痒、喘息的改善情况要好于对照组,差异有统计学意义(P<0.01);而两组在气短的症状改善上差异无统计学意义(P>0.05);治疗组的起效时间快于对照组;治疗后两组的生活质量评分比治疗前都有了很大的提高,而治疗组提高明显高于对照组,两组间的差异有统计学意义(P<0.05)。[结论] 经加用复方龙星片治疗感冒后咳嗽疗效明显优于对照组。     

复方川芎滴丸制备工艺再探讨

目的优选复方川芎滴丸的最佳制备工艺。方法以药物与基质的配比、滴制温度、冷却液的温度为考察因素,采用正交试验设计,以滴丸的圆整度、丸重差异、溶散时限、外观质量的综合评分为评价指标,优选滴丸的成型工艺;以滴距、滴速为考察因素,优选最佳滴制工艺。结果滴丸制备的最佳条件为药物中间体与基质配比12,滴制温度80℃,冷却剂温度15~20℃,滴距5cm,滴速40gtt/min。结论该制备工艺合理,简便,易于控制,适用于本制剂的制备。     

HPLC测定复方氨肽素片中氨茶碱与马来酸氯苯那敏的含量及含量均匀度

目的 建立HPLC测定复方氨肽素片中氨茶碱与马来酸氯苯那敏的含量及含量均匀度。方法 色谱柱为YMC Hydrosphere C₁₈(4.6 mm×250 mm,5 μm),流动相为乙腈-0.5%磷酸溶液(用三乙胺调pH值至2.2)(10∶90),流速为1.0 mL·min^-1,柱温为30 ℃,检测波长为262 nm。结果 茶碱和马来酸氯苯那敏分别在0.06~0.58 mg·mL^-1和2.2~20.0 μg·mL^-1内线性关系良好,回收率分别为100.4%和101.2%,RSD分别为0.74%和1.40%(n=9)。结论 方法快速准确,重复性好,结果可靠,可同时测定氨茶碱及马来酸氯苯那敏,为产品质量标准提高提供基础。     

复方九节茶乳膏的质量标准研究

目的：建立复方九节茶乳膏质量标准。方法采用薄层色谱法对九节茶和冰片进行鉴别;HPLC 双波长法测定复方九节茶乳膏中反丁烯二酸与迷迭香酸含量。采用 Kromasil C18色谱柱（250 mm ×4．6 mm,5μm）,流动相为0．1％甲酸乙腈溶液（B）—0．1％甲酸水溶液（D）,梯度洗脱[0～10 min,5％ B→20％ B;10～25 min,20％ B;25～30 min,20％ B→5％ B;30～35 min,5％ B],流速为1．0 mL·min －1,检测波长为210 nm 和330 nm,柱温为30℃。结果薄层鉴别斑点清晰,阴性无干扰;反丁烯二酸和迷迭香酸线性范围分别为6．53～65．28 mg·L －1（r ＝0．9999）和4．26～42．64 mg·L －1（r ＝0．9995）;平均加样回收率分别为98．3％（RSD ＝0．82％）和100．9％（RSD ＝0．63％）。结论该方法简单、准确、重复性好,能有效的控制该制剂的质量。     

复方丹参滴丸治疗糖尿病肾病疗效及安全性的Meta分析

目的：评价复方丹参滴丸治疗糖尿病肾病的疗效及安全性。方法计算机检索2006年9月至2014年9月,全面检索万方数据库、维普数据库、中国学术期刊全文数据库、中国生物医学文献数据库、Pubmed数据库,收集复方丹参滴丸治疗糖尿病肾病的试验,根据纳入和排除标准共纳入14项研究,1051例患者,选用空腹血糖、餐后2 h血糖、血肌酐、尿素氮、尿β2微球蛋白、尿微量白蛋白排泄率作为效应指标,使用RevMan5．0软件进行meta分析。结果（1）空腹血糖[WMD＝－0．15,95％的CI为（－0．38,0．09）,P＝0．22],差异无显著性;餐后两小时血糖[WMD＝－0．49,95％的CI为（－0．90,－0．08）,P＝0．02],差异具有统计学意义,治疗组均优于对照组（2）血肌酐[WMD＝－1．74,95％的CI为（－5．40,1．92）,P＝0．35],差异无显著性;尿素氮[WMD＝0．07,95％的CI为（－0．18,0．32）,P＝0．59],差异无显著性。（3）尿微量白蛋白排泄率[WMD＝－11．95,95％的CI为（－16．27,－7．64）,P＜0．00001],差异具有统计学意义,治疗组均优于对照组。结论证据表明,复方丹参滴丸治疗糖尿病肾病疗效性、安全性较高。     

The role of E255K/V-inclusive mutations in a Philadelphia-positive acute lymphoblastic leukemia with mutation evolution during sequential TKIs therapies: A case report

Rationale:Until recently, the survival rate in patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) was approximately 30%. Tyrosine kinase inhibitors (TKIs), which are a new class of drugs that target BCR-ABL fusion protein, have shown to be effective in treating Ph+ ALL in adults. However, the resistance mechanisms that promote the disease recurrence have altered the initial success of these revolutionary agents.Patient concerns:A 71-year-old Chinese female patient who suffered from severe shoulder and back pain for 1 week.Diagnosis:The patient was diagnosed with Ph+ ALL (B–cell) because of the following items. Complete blood count showed extremely abnormal white blood cell count (26.26×10⁹/l), hemoglobin concentration (65 g/l) and platelet count (14×10⁹/l). And because that Bone marrow aspirate showed 72.5% lymphoblasts and 59.30% lymphoblasts were confirmed by flow cytometry (FCM). At mean time, Real-time fluorescent quantitative PCR analysis confirmed that the P190 BCR/ABL fusion gene expression was 5.9%. Karyotype analysis indicated the following: 45, XX, −7, t (922) (q34; q11) [cp3].Interventions:The patient was treated with chemotherapy and different TKIs including imatinib, dasatinib, ponatinib, and bosutinib.Outcomes:The patient achieved complete remissions with different TKIs after diagnose but relapsed afterward and died of infection.Lessons:Multidrug-resistant mutations within the BCR-ABL1 kinase domain are an emerging clinical problem for patients receiving sequential TKIs therapy. Acquisition of E255K/V-inclusive mutations is usually associated with ponatinib resistance, thus it is necessary to screen out new real pan-inhibitor compounds for all BCR/ABL mutations and figure out the potential efficacy of asciminib-based drug combinations in the future.     

Deciphering Subtype-Selective Modulations in TRPA1 Biosensor Channels

The transient receptor potential (TRP) proteins are a family of ion channels that act as cellular sensors. Several members of the TRP family are sensitive to oxidative stress mediators. Among them, TRPA1 is remarkably susceptible to various oxidants, and is known to mediate neuropathic pain and respiratory, vascular and gastrointestinal functions, making TRPA1 an attractive therapeutic target. Recent studies have revealed a number of modulators (both activators and inhibitors) that act on TRPA1. Endogenous mediators of oxidative stress and exogenous electrophiles activate TRPA1 through oxidative modification of cysteine residues. Non-electrophilic compounds also activate TRPA1. Certain non-electrophilic modulators may act on critical non-cysteine sites in TRPA1. However, a method to achieve selective modulation of TRPA1 by small molecules has not yet been established. More recently, we found that a novel N-nitrosamine compound activates TRPA1 by S-nitrosylation (the addition of a nitric oxide (NO) group to cysteine thiol), and does so with significant selectivity over other NO-sensitive TRP channels. It is proposed that this subtype selectivity is conferred through synergistic effects of electrophilic cysteine transnitrosylation and molecular recognition of the non-electrophilic moiety on the N-nitrosamine. In this review, we describe the molecular pharmacology of these TRPA1 modulators and discuss their modulatory mechanisms.     

复方半枝莲防治二乙基亚硝胺诱发大鼠肝癌的研究

目的 :研究复方半枝莲 (SBC)对二乙基亚硝胺 (DEN)诱发大鼠肝癌的防治作用。方法 :利用免疫组化、流式细胞仪、血清和组织生化等检测方法 ,分别在第 14周和第 2 4周观察 SBC对 DEN诱发的肝癌形成过程的影响。结果 :中药组 14周时大鼠肝脏异型性增生灶明显较模型组少 ,2 4周时形成的肝癌结节小而少 ,模型组、中药组肝癌发生率分别为 75 .0 %、5 0 .0 % ;免疫组化显示中药组大鼠肝组织谷胱甘肽 - S-转移酶胎盘型阳性灶面积明显低于模型组 ;肝组织匀浆上清液谷胱甘肽 - S-转移酶含量以及血清 λ-谷氨酰转移酶、碱性磷酸酶、谷丙转氨酶含量也明显低于模型组 ;流式细胞仪检测结果显示 ,中药组大鼠肝细胞 G0 - G1 期比例下降 ,G2 - M期比例升高。结论 :SBC能抑制癌前病变 ,延缓肝癌的形成 ,降低肝癌发病率 ,其作用机制之一可能为阻滞 G2 - M期细胞进展 ,从而抑制DEN引起的肝细胞的去分化和恶性增殖