Brain deviations in adult obese-hyperglycemic mice (ob/ob)

In the brain of adult obese-hyperglycemic mice (ob/ob) deviations, such as reduced brain weight, diminished myelination, and reduced amount of DNA were found. These findings cannot be explained by hypothyroidism in adults since above mentioned deviations could only have been caused by a reduced thyroidal activity in the first weeks of postnatal life. Therefore, our data are in support of the earlier hypothesis of congenital hypothyroidism.     

Significance of a terminal R wave in lead V1 of the electrocardiogram.

A terminal r wave in Lead V1 lower than 0.6 mV. was studied in the ECGs of four groups: (1) 104 healthy children, (2) 207 healthy young adults, (3) 171 patients with no autopsy evidence of a cardiopulmonary disease, and (4) 1,078 autopsy patients with a cardiopulmonary disease. Cases with a complete right bundle branch block were excluded. A terminal r wave occurred in 2.9 per cent healthy children, 1.4 per cent of healthy young adults, 0.6 per cent of patients without and in 5.9 per cent of patients with autopsy evidence of a cardiopulmonary disease. The occurrence of a terminal r wave was most common in pulmonary patients (10 per cent). But it was also found in patients with an anterior or a posterior myocardial infarction and in some cases of left ventricular hypertrophy. In the autopsy series RVH occurred in 57 per cent of patients with a Qr pattern, in 30 per cent of patients with a terminal r wave higher than the initial one, and in none of the patients with a terminal r wave lower than the initial one. It is concluded that the height of the terminal r wave has clinical significance. A terminal r wave higher than the initial one in Lead V1 is associated with a cardiopulmonary disease in subjects over 30 years of age, while an r wave lower than the initial one seems to be an innocent finding.     

肝癌中iNOS与P16、Bax的表达及其与细胞凋亡关系

探讨在肝癌(HCC)中一氧化氮合酶(iNOS)的表达对P16、Bax表达的影响及其与细胞凋亡的关系。采用免疫组化方法对HBsAg均阳性的98例HCC患者的iNOS、P16、Bax表达进行分析，TUNEL法检测细胞凋亡。iNOS和加以棕黄色颗粒着色于细胞质和／或细胞膜中，细胞核阴性，间质细胞着色不明显。P16以棕黄色着色于细胞核中，细胞质中偶见。细胞凋亡为细胞核着色，细胞质阴性。P16、Bax的表达及细胞的凋亡率与iNOS的表达有关。iNOS的表达可诱导抑癌基因P16、Bax的表达和细胞凋亡的发生，从而影响Hcc分化。故在诱导Hcc中iNOS的表达，有望提高肝细胞癌的临床效果。     

Calcitonin gene-related peptide potentiates substance P-induced plasma extravasation in the rat trachea

Antidromic stimulation of vagal sensory nerves is known to produce plasma extravasation in the rat trachea. This neurogenic inflammation is thought to be mediated by substance P or other tachykinins released from sensory nerve endings. We sought to determine whether calcitonin gene-related peptide (CGRP), which is also released from sensory nerve endings, can potentiate substance P-induced plasma extravasation in the rat trachea. To accomplish this, we measured the amounts of Evans blue dye extravasated into the trachea after intravenous injections of substance P alone and combined with CGRP. We found that when substance P and CGRP were injected together, the amount of plasma extravasation produced in the trachea was substantially greater than the amount produced when substance P was injected alone. This potentiation was critically dependent on the dosage of CGRP and was not observed when relatively high dosages were used. We also found that CGRP had a potent hypotensive effect and speculate that reduced blood pressure may account for the lack of potentiation observed at the higher CGRP dosages. Based on these findings, we conclude that CGRP can potentiate substance P-induced plasma extravasation in the rat trachea and may therefore play a role in modulating neurogenic inflammation of the airways. Offprint requests to: J.J. Brokaw     

不同剂量拉莫三嗪治疗老年癫痫的比较研究

目的 探讨不同剂量拉莫三嗪治疗老年癫痫患者的临床疗效。方法 选择2014年7月—2018年2月洛阳市第三人民医院神经内科诊治的老年癫痫患者88例作为研究对象,根据拉莫三嗪使用剂量分为对照组（40例）和观察组（48例）。对照组患者给予大剂量拉莫三嗪片治疗,拉莫三嗪起始剂量25 mg/d,2周后为50 mg/d,第5周以后为目标剂量100 mg/d,维持100 mg/d治疗观察至第8周。观察组患者给予小剂量拉莫三嗪片治疗,起始剂量25 mg/d,2周后为50 mg/d,第5周以后为目标剂量50 mg/d,维持50 mg/d治疗观察至第8周。观察两组患者的临床疗效,同时比较两组患者蒙特利尔认知评估量表（MoCA）评分、P300潜伏期、波幅和不良反应情况。结果 治疗后,对照组和观察组总有效率分别为97.5%、97.9%,两组对比差异无统计学意义。治疗后,两组患者的MoCA评分均显著高于治疗前,同组治疗前后比较差异具有统计学意义（P<0.05）;且观察组治疗后的MoCA评分显著高于对照组,两组比较差异具有统计学意义（P<0.05）。治疗后,观察组的P300潜伏期显著降低,波幅明显升高,同组治疗前后比较差异具有统计学意义（P<0.05）;且观察组治疗后P300潜伏期及波幅显著优于对照组,两组比较差异具有统计学意义（P<0.05）。观察组治疗期间的不良反应发生率为6.3%,显著低于对照组的32.5%,两组比较差异具有统计学意义（P<0.05）。结论 相对于大剂量,小剂量拉莫三嗪治疗老年癫痫患者能达到很好的疗效,能减少不良反应的发生,改善患者的神经电生理功能与认知功能。     

克唑替尼联合PC方案治疗非小细胞肺癌的临床研究

目的 探讨克唑替尼联合PC方案治疗非小细胞肺癌的临床疗效。方法 选择2016年1月—2018年12月新疆喀什地区第二人民医院治疗的64例非小细胞肺癌患者作为研究对象。用抽签法随机将患者分为对照组和观察组,每组各32例。对照组每天静脉滴入注射用培美曲塞二钠,500 mg/m²,静滴时间超过10 min,并静脉滴入卡铂注射液,AUC5静滴时间超过30 min。观察组在对照组的基础上口服克唑替尼胶囊,250 mg/次,2次/d。1个周期为21 d,两组共治疗2个周期。观察两组患者的临床疗效,同时比较两组患者治疗前后的血清癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、人鳞状细胞癌相关抗原（SCCAg）以及细胞角蛋白19片段（Cyfra21-1）水平和Karnofsky功能状态评分量表（KPS）评分情况。结果 治疗后,观察组总有效率为81.25%,明显高于对照组的59.37%（P<0.05）。两组治疗后的NSE、CEA、SCCAg和CYFRA21-1水平均明显降低（P<0.05）,且观察组上述肿瘤标志物水平明显低于对照组（P<0.05）。治疗后,观察组的生活质量好转率明显高于对照组,恶化率明显低于对照组（P<0.05）。结论 克唑替尼联合PC方案治疗非小细胞肺癌患者的疗效显著,能明显降低肿瘤标志物水平,提高生活质量。     

Genetic insight into cytochrome P450 in Chinese from the Chinese Millionome Database

Genetic variations of cytochrome P450 (CYP) influence the inter‐individual differences in drug response. Here, we collected 8682 variants of 57 CYP genes and cytochrome P450 oxidoreductase (POR) from a large‐scale sequencing project in Chinese, Chinese Millionome Database (CMDB). In addition, 52 294 variants from the Genome Aggregation Database (gnomAD) had been simultaneously identified and analysed. Rare variants with a variant allele frequency (VAF) < 0.01 comprised 41.4% (3594/8682) of identified variations in the CMDB, while 98.1% (51 320/52 294) in the gnomAD were rare. Out of 8682 variants in the CMDB, 66.9% (5808/8682) were in introns and only 4.3% (377/8682) were missense variants. In contrast, 36.2% (18 929/52 294) variants in the gnomAD were missense. The common alleles with a VAF over 0.1 were found in CYP1A2*1C, CYP1A2*1F, CYP2C19*2, CYP2D6*2, CYP2D6*10, CYP3A5*3 and CYP4F2*3, with a VAF of 0.161, 0.6, 0.27, 0.274, 0.678, 0.92 and 0.233, respectively. The growing number of genetic variations in CYP genes as more genomes are sequenced would increase the power to predict drug metabolism and response based on the genotype of the particular individual.     

USP21 promotes cell proliferation by maintaining the EZH2 level in diffuse large B‐cell lymphoma

BackgroundDiffuse large B‐cell lymphoma (DLBCL) is the most common category of non‐Hodgkin lymphoma (NHL). However, the underlying molecular mechanism of DLBCL remains unclear.MethodsReal‐time PCR and Western blot analysis were performed to assess the expression of ubiquitin‐specific peptidase 21 (USP21) or enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2). CCK8 assay and cell death staining were carried out to examine the role of USP21 in cell proliferation and cell death, respectively.ResultsWe found that the deubiquitinase USP21 was highly expressed in the DLBCL lymphoid tissue. The expression of USP21 promoted DLBCL cell proliferation, while it had no obvious effect on cell death. In addition, we found that USP21 regulated cell proliferation via cysteine 221, the catalytic site of USP21. Furthermore, we identified that USP21 could stabilize EZH2, a protein required for germinal center formation and lymphoma formation.ConclusionThe deubiquitinase USP21 promotes cell proliferation by maintaining the EZH2 protein level in DLBCL.     

Correlations between Serum P2X7, Vitamin A, 25‐hydroxy Vitamin D,and Mycoplasma Pneumoniae Pneumonia

BackgroundIdentifying new molecular diagnostic markers for Mycoplasma Pneumoniae Pneumonia (MPP) has always been an essential topic since MPP cases have increased every year, especially among children. Here, we examined the correlation between serum level of Purinergic receptor P2X7, vitamin A, and 25‐hydroxy vitamin D (25(OH)D) and the severity of MPP, aiming to identify molecules that have the potential to become diagnostic markers.MethodsThis study was conducted on 186 cases aged 1–14 (136 MPP and 50 non‐MPP patients). Serum levels of Purinergic receptor P2X7, vitamin A, 25(OH)D, and multiple inflammatory and immune factors were measured, compared, and tested for statistical significance.ResultsSerum P2X7, tumor necrosis factor‐α (TNF‐α), and interleukin‐1β (IL‐1β) levels were significantly increased in severe MPP patients, while serum vitamin A, 25(OH)D, IgA, and IgG levels were significantly decreased.ConclusionOur results demonstrated a positive correlation between serum P2X7 level and the severity of MPP, and negative correlations between serum levels of vitamin A and 25(OH)D and the severity of MPP, suggesting that high serum levels of P2X7 and low serum levels of vitamin A and 25(OH)D may indicate relatively severer MPP.