轻稀土化合物抑癌作用及机制的研究

目的在探讨稀土与肿瘤关系的基础上进一步证明稀土的抑癌作用及探讨作用机制,最终的目标是为稀土在医药保健事业方面开创一个新领域.提供确定、可靠的科学依据.方法通过动物实验及细胞培养,采用生化、免疫、分子生物学等方面的规范方法及高新技术的应用,如用电子顺磁共振(FSR)自旋扑获技术测定自由基、Northern杂交技术分析稀土元素对抑癌基因的表达等.此外,还对接触稀土人群进行了10年的动态观察和肿瘤流行病学回顾性的队列调查等.结果①整体抑癌实验按卫生部颁发的药效实验规程,给小鼠腋下种瘤株,腹腔注射ReNO3、ReCl3等,剂量在32及64 mg/kg时对S180肉瘤生长的抑制率分别为39.87%及27.34%、Lewis肺癌生长抑制率分别为36.82%及29.55%均有明显的统计学意义.给AMAE小鼠腹腔注射氨基甲酸乙酯的肺癌剂同时饮用ReCl3(0.062 5%、0.25%、1.0%)120 d时其肿瘤发生率分别为75%、61.8%、79.6%,而未给稀土组为90.0%,表明稀土对化学致肺腺癌小鼠亦具有明显抑制作用.②体外抑癌试验对人白血病细胞(K562)在ReNO3浓度为0.032～0.5 mg/ml时,生长的抑制率为15.8%～34%,在ReCl3浓度为0.01～0.5 mmol/L时其细胞生长抑制率为18%～68%,而对正常人羊膜细胞(FL)起促生长作用;对胃癌细胞(PAMC82)经ReCl31 mmol/L处理14～28 d时,其细胞形态发生明显变化,用免疫荧光染色观察细胞骨架微管和微丝的结构,多数癌细胞内出现近似正常细胞的微管网架;PAMC82细胞在软琼脂中生长良好,经ReCl3处理后,细胞生长极慢,平均每皿集落数由18.7降至4.以上结果表明,癌细胞经稀土处理后,其恶性程度降低,分化程度升高.③抑癌机制研究从免疫、生化及分子生物学等方面探讨其作用机制.A对正常小鼠腹腔隔日注射(共5次)的ReNO3(32 mg/kg)及给化学致癌剂(氨基甲酸乙酯)后饮ReCl3水溶液120 d的小鼠,取其脾脏测定NK细胞活力(%).结果均有明显激活作用.B.采用Balb/c小鼠腹腔巨噬细胞(MΦ)培养及孔雀绿显色法,以ReNO3浓度为16～250 μg/ml与MΦ培养,测得其吞噬强度范围(1.12～1.35),明显地高于非稀土培养的吞噬强度(0.88),表明稀土有促进巨噬细胞特异的吞噬功能.C利用电子顺磁共振技术EPR 300型波谱仪测得20 mg温石棉在磷酸盐缓冲液中产生的羟自由基(*OH)信号谱峰高为4.6 cm,当其分别给与2～20 mg ReCl3或ReNO3混合后,产生的*OH信号几乎消失或明显减弱;经温石棉诱导,用ReCl3处理的肺巨噬细胞,其*OH强度和超氧阴离子(O-*)2)的浓度明显受抑制;经氨基甲酸乙酯诱癌的小鼠,饮ReCl3溶液120 d后,其体内超氧化物歧化酶(SOD)显著高于未饮稀土组,脂质过氧化物代谢产物丙二醛(MDA)明显低于饮稀土组.以上结果表明稀土可抑制温石棉产生*OH和O-)/(*)2,增强SOD活性,降低膜脂质过氧化.D对肿瘤相关基因表达的研究;用Northern杂交分析方法,结果表明抑癌基因P53和P21表达水平低下的人胃癌细胞PAMC82,经1.5 mmol/L laCl3或0.75 mmol/L的CaeCl3(ReCl3)处理后,其P53和P16基因表达明显增强;而变化最明显的是抑癌基因P21的表达.④肿瘤流行病学调查对我国最大的甘肃稀土公司,进行了肿瘤回顾性的队列调查,其结果稀土组和对照组死亡率分别为19.675 2/105和87.948 4/105,RR为0.223 7(P＜0.05),稀土组和对照组的肺癌死亡率分别为0/105与40.923 0/105(P＜0.05),此结果表明稀土有控制肿瘤发生的趋势.结论从微观到宏观,从动物实验到人群流调,均证明了稀土有抑癌作用.从抑癌机制的研究表明,经稀土处理的人胃癌细胞P21、P16、P53的基因表达均有明显增强,提示其抑癌作用可能是通过稀土使癌细胞恶性程度降低,分化程度升高,增强抑癌基因表达实现的.还表明稀土在直接作用于细胞的同时,还能改善和提高机体的抗肿瘤免疫及清除体内垃圾的抗氧化功能等方面的综合性防癌作用.     

Potential of Baliospermum montanum against compound 48/80-induced systemic anaphylaxis

Context: Decoctions of Baliospermum montanum Müll. Arg. (Euphorbiaceae) leaves are reported to be useful in the treatment of asthma and other respiratory complications in the Ayurvedic system.

Objective: To evaluate the mast cell stabilization and antihistaminic activities of the chloroform (BMLC) and ethanol (BMLE) extracts of the leaves of Baliospermum montanum.

Materials and methods: The stabilization potential was studied on mouse peritoneal mast cells and the antihistaminic activity was carried out by determining the mortality rate of mice treated with toxicant (compound 48/80) and the effect on elevation of histamine release upon degranulation.

Results: The increased number of intact mast cells (43.640 ± 1.7% and 61.57 ± 1.79% at 200 and 400?mg/ kg, respectively) suggested that the BMLC stabilized the mast cell degranulation and showed decreased elevation of histamine.

Conclusion: BMLC extract was found to be most effective against degranulation and release of histamine from mast cells. Identifying the lead from this plant will be a definite target for treating allergic diseases.     

Intraoperative lateral rectus electromyographic recordings optimized by deep intraorbital needle electrodes

ObjectiveWe demonstrate the advantages and safety of long, intraorbitally-placed needle electrodes, compared to standard-length subdermal electrodes, when recording lateral rectus electromyography (EMG) during intracranial surgeries.MethodsInsulated 25 mm and uninsulated 13 mm needle electrodes, aimed at the lateral rectus muscle, were placed in parallel during 10 intracranial surgeries, examining spontaneous and stimulation-induced EMG activities. Postoperative complications in these patients were reviewed, alongside additional patients who underwent long electrode placement in the lateral rectus.ResultsIn 40 stimulation-induced recordings from 10 patients, the 25 mm electrodes recorded 6- to 26-fold greater amplitude EMG waveforms than the 13 mm electrodes. The 13 mm electrodes detected greater unwanted volume conduction upon facial nerve stimulation, typically exceeding the amplitude of abducens nerve stimulation. Except for one case with lateral canthus ecchymosis, no clinical or radiographic complications occurred in 36 patients (41 lateral rectus muscles) following needle placement.ConclusionsIntramuscular recordings from long electrode in the lateral rectus offers more reliable EMG monitoring than 13 mm needles, with excellent discrimination between abducens and facial nerve stimulations, and without significant complications from needle placement.SignificanceLong intramuscular electrode within the orbit for lateral rectus EMG recording is practical and reliable for abducens nerve monitoring.     

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.     

Relationships among objective measures and speech perception in adult users of the HiResolution Bionic Ear

Abstract

The purpose of this study was to describe speech recognition performance for subjects using electrically evoked stapedial reflex thresholds (eSRT) based on programs with the HiResolution Bionic Ear system. A secondary goal was to evaluate the relationship of the electrically evoked compound action potentials (eCAP) as measured with neural response imaging (NRI) relative to the subjects' most comfortable stimulation levels (M levels). M levels, eSRT and eCAP thresholds were measured in 19 postlinguistically deafened adults using either a CII or HiRes 90K cochlear implant. The results showed that eSRTs could be measured easily in a majority of subjects, whereas eCAPS were measured in all subjects. There were close agreements between eSRTs and M levels in the subjects' behaviorally based programs. In contrast, the correspondence between M levels and eCAP thresholds was not as strong. New programs were created with M levels based on the eSRTs for 11 subjects. Programs created using eSRTs as a guide for setting levels yielded better speech recognition than programs using conventional behavioural measures of M levels. These data indicate that individuals can obtain strong benefits from cochlear implants using programs with stimulation levels based on objective measures. Copyright © 2008 John Wiley & Sons, Ltd.     

小儿复方氨基酸和锌佐治小儿难治性腹泻疗效分析

目的：探讨小儿复方氨基酸和锌佐治小儿难治性腹泻的临床效果。方法100例小儿难治性腹泻患儿，随机分为实验组与对照组，各50例。对照组患儿给予常规腹泻对症治疗，实验组患儿在对照组的基础上注射小儿复方氨基酸和口服葡萄糖酸锌口服液联合治疗，比较两组的临床疗效。结果实验组总有效率92%明显高于对照组62%，差异具有统计学意义(P<0.05)。结论小儿复方氨基酸和锌佐治小儿难治性腹泻疗效显著，具有借鉴性。     

白蚁防治中茚虫威的应用研究进展

茚虫威对白蚁来说是一种无驱避性的农药。在综述了茚虫威对白蚁的毒性、传递性、复配对其增效作用及其他特性后,提出了在白蚁防治方面可加强茚虫威的传递性、复配增效性及其在饵剂系统的应用研究。     

A HYPOTHALAMIC DIGOXIN-MEDIATED MODEL FOR AUTISM

The isoprenoid pathway and its metabolites--digoxin, dolichol, and ubiquinon--were assessed in autism. The isoprenoid pathway and digoxin status was also studied for comparison in individuals of differing hemispheric dominance to determine the role of cerebral dominance in the genesis of autism. There was an upregulation of the isoprenoid pathway as evidenced by elevated HMG CoA reductase activity in autism. Digoxin, an endogenous Na+-K+ ATPase inhibitor secreted by the hypothalamus, was found to be elevated and RBC membrane Na+-K+ ATPase activity was found to be reduced in autism. Membrane Na+-K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced magnesium levels. Hypothalamic digoxin can modulate conscious and subliminal perception and its dysfunction may lead to autism. Digoxin can also preferentially upregulate tryptophan transport over tyrosine resulting in increased levels of depolarizing tryptophan catabolites--serotonin, quinolinic acid (NMDA agonist), strychnine (blocks glycinergic inhibitory transmission), and nicotine (promotes dopamine release) and decreased levels of hyperpolarizing tyrosine catabolites--dopamine, noradrenaline, and morphine--contributing to membrane Na+-K+ ATPase inhibition. Increased nicotine levels can produce increased dopaminergic transmission in the presence of low dopamine levels. NMDA excitotoxicity could result from hypomagnesemia induced by membrane Na+K+ ATPase inhibition and quinolinic acid, an NMDA agonist acting on the NMDA receptor. Hypomagnesemia and increased dolichol level can affect glycoconjugate metabolism and membranogenesis leading on to disordered synaptic connectivity in the limbic allocortex and defective presentation of viral antigens and neuronal antigens contributing to autoimmunity and viral persistance important in the pathogenesis. Membrane Na+-K+ ATPase inhibition can produce immune activation, a component of autoimmunity. Mitochondrial dysfunction consequent to altered calcium/magnesium ratios and reduced ubiquinone levels can result in increased free radical generation and reduced free radical scavenging and defective apoptosis leading to abnormal synaptogenesis. Autism can thus be considered a syndrome of hypothalamic digoxin hypersecretion consequent to an upregulated isoprenoid pathway. The biochemical patterns including hyperdigoxinemia observed in autism correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance is a predisposing factor for autism     

A novel compound heterozygosity in Southern China: IVS-II-5 (G > C) and IVS-II-672 (A > C)

β-Thalassemia (β-thal) is a common hereditary anemia due to decreased or absent synthesis of the β-globin chains. Here, we report a patient found to be a novel compound heterozygote for the rare IVS-II-5 (G?>?C) (NG_000007.3: g.71044G?>?C) and IVS-II-672 (A?>?C) (NG_000007.3: g.71711A?>?C) mutations, which may be silent mutations that are associated with consistent residual output of β chains, normal red blood cell (RBC) indices and normal or borderline Hb A₂ levels.     

不同中药制剂治疗骨折临床观察

目的:探讨复方三七片及复方接骨片在骨折治疗中的作用。方法:选取180例门诊治疗的桡骨远端骨折患者,随机分为复方三七片组、复方接骨片组和对照组。观察3组患者消肿止痛效果、血碱性磷酸酶水平及原始骨痂出现时间。结果:止痛效果显示,复方三七片组及复方接骨片组的止痛效果优于对照组。消肿效果显示,复方三七片及复方接骨片组有效率分别达90%、80%,优于对照组的61.67%。血碱性磷酸酶水平显示,复方三七片及复方接骨片组有效率分别达86.67%、95%,优于对照组的75%。复方三七片及复方接骨片组在第2周即有原始骨痂开始出现,4周内分别有93.33%、96.67%的患者出现原始骨痂,而对照组在第3周才可见原始骨痂出现,4周内有66.67%的患者出现原始骨痂。结论:复方三七片及复方接骨片均能够减轻患部疼痛,促进患部肿胀消退,提高血碱性磷酸酶水平,促进原始骨痂形成。骨折早期(2周内)口服复方三七片有利于消肿止痛,骨折2周后口服复方接骨片有利于骨痂生长、骨折愈合。