论灵活配伍乌头治诸痛

[目的]探析乌头止痛功效与其峻烈药性之间的辩证关系,总结乌头的不同配伍在痛证治疗方面的应用,为临床灵活运用乌头拓展思路。[方法]通过查阅历代文献医籍,搜集部分医家的学术观点及相关用药经验,从痛证的不同病因病机探讨乌头的配伍应用,并结合现代药理学研究,总结一般规律。[结果]在风、寒、湿、瘀等以实邪结聚,阻滞经络为主要病机的痛证中,多取用乌头辛热发散之药性祛除病因,同时消除湿浊、瘀血、痰饮等病理产物来达到止痛目的;热痛虽为邪实疼痛,但其病机与乌头大辛大热之性不相适宜,治疗应配伍石膏、知母、白芍等与之药性相反的药物,起到"去性存用"的效果;虚痛的治疗应以标本兼治为原则,在补虚扶正的基础上保留或增强乌头的止痛作用",减毒增效"成为其应用的关键;在外伤、麻醉、癌痛等各类杂痛中,重视对乌头药理活性成分及其抗炎镇痛效应的现代研究,并结合历代医家方药,侧重于发挥乌头"对症治疗"的作用。[结论]乌头为止痛之要药,通过准确辨证,合理配伍,各类痛证均可大胆用之。     

Obstetric emergencies

For more than 60 years the Confidential Enquiry into Maternal Deaths triennial reports and later reports from Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK) have helped build a picture of maternity care within the UK highlighting not only our successes but failures in caring for women within the puerperal period. Despite most obstetric emergencies being well described and having clear management strategies and guidance, there continues to be substandard management with poor outcomes recorded. This article describes some common obstetric emergencies with which the anaesthetist will become involved. It emphasizes management related to some deficiencies identified in the MBRRACE-UK report as well as highlighting a multidisciplinary approach throughout. Good communication between team members is paramount in all aspects of medical care but this approach should be fostered routinely to ensure that rapid and appropriate decisions are made in a safe and timely manner.     

含贝达喹啉方案治疗耐药肺结核的不良反应分析

目的: 分析贝达喹啉联合常规抗结核药物治疗耐药肺结核过程中产生的不良反应,为贝达喹啉的安全使用与监测提供依据。方法: 采用回顾性研究的方法,搜集2018年11月至2020年12月于山东省公共卫生临床中心耐药结核病房完成了24周治疗及随访的127例耐多药肺结核、准广泛耐药肺结核、广泛耐药肺结核及利福平耐药肺结核患者作为研究对象,其中,使用含贝达喹啉方案治疗的66例患者作为观察组,使用不含贝达喹啉治疗方案的61例患者作为对照组。收集研究对象的临床资料,包括年龄、性别、耐药诊断类型、是否合并糖尿病、是否合用其他导致QTc间期延长的药物等。监测两组研究对象在治疗过程中药物不良反应的发生情况,分析观察组患者发生QTc间期延长(>450ms)的影响因素。结果: 观察组QTc间期延长发生率为48.5%(32/66),明显高于对照组的26.2%(16/61),差异有统计学意义(χ²=6.678,P=0.001);观察组与对照组发生QTc间期>500ms者分别有3例(4.5%)和1例(1.6%),差异无统计学意义(Fisher精确概率法,P=0.143)。两组其他药物不良反应发生情况未见差异。观察组QTc间期随着含贝达喹啉治疗方案使用时间增加逐渐增大,第4周末QTc间期为(435.1±28.8)ms,明显高于基线期QTc间期[(419.0±23.2)ms],差异有统计学意义(t=3.477,P=0.001);在第12周末达峰值[(439.5±30.7)ms]。多因素分析显示,年龄≥45岁的患者使用含贝达喹啉方案治疗时出现QTc间期延长的风险是年龄18~45岁者的9.027倍(95%CI:1.033~78.859);合并使用其他可导致QTc间期延长的药物亦是导致患者发生QTc间期延长的独立危险因素[OR(95%CI)=9.033(1.042~78.326)]。结论: 耐药肺结核患者应用含贝达喹啉方案治疗后QTc间期延长的发生率增高,但未见严重的心脏不良事件;其他系统不良事件发生率未见增加。高龄患者是QTc间期延长发生的高危人群。     

Review of the environmental prenatal exposome and its relationship to maternal and fetal health

Environmental chemicals comprise a major portion of the human exposome, with some shown to impact the health of susceptible populations, including pregnant women and developing fetuses. The placenta and cord blood serve as important biological windows into the maternal and fetal environments. In this article we review how environmental chemicals (defined here to include man-made chemicals [e.g., flame retardants, pesticides/herbicides, per- and polyfluoroalkyl substances], toxins, metals, and other xenobiotic compounds) contribute to the prenatal exposome and highlight future directions to advance this research field. Our findings from a survey of recent literature indicate the need to better understand the breadth of environmental chemicals that reach the placenta and cord blood, as well as the linkages between prenatal exposures, mechanisms of toxicity, and subsequent health outcomes. Research efforts tailored towards addressing these needs will provide a more comprehensive understanding of how environmental chemicals impact maternal and fetal health.     

Acute toxicity of chlorpyrifos to the non-target organism Cnesterodon decemmaculatus

Chlorpyrifos is the most used insecticide in Argentina. Cnesterodon decemmaculatus is a widely distributed, endemic fish from Neotropical America. It attains high densities in the shallow water assemblages of Argentina and Brazil. The aim of this study was to assess the acute toxicity of chlorpyrifos to C. decemmaculatus. The mean 96-h LC₅₀ of three independent determinations was 105.3 (±?3.1) μg/L. Sublethal effects were observed. Swimming behavioral changes at each chlorpyrifos exposure concentration were reported. C. decemmaculatus represents a good model for ecotoxicological risk assessment.     

Metabolomic Study of Biochemical Changes related to toxicity induced by bupleurotoxin Using LC-MSCoupled with a Pattern Recognition Approach

The purpose of this study was to detect changes in urine of mice and to clarify the toxicity induced by bupleurotoxin (BETX) using liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). A procedure for urine analysis using pattern recognition was proposed to evaluate the toxicity induced by BETX in male BALB/c mice. BETX at 2.5 mg/kg was administered intraperitoneally (i.p.), and urine samples for the metabolomic study were collected from control and BETX experimental groups. Changes in the concentrations of some urine metabolites were detected exclusively in the experimental group. All results suggested that exposure to BETX might cause a disturbance in fatty acid metabolism and the oxidative stress system. These results may not only clarify the underlying mechanism of diverse intoxication effects of BETX but also provide the guidance in preclinical toxicity screening for new drugs.     

Protective effects of pharmacological therapies in animal models of multiple sclerosis: a review of studies 2014–2019

Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.     

Gambogic acid causes fin developmental defect in zebrafish embryo partially via retinoic acid signaling

Gambogic acid (GA), the major active ingredient of gamboge, has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients due to its strong anticancer activity. However, our previous research showed that GA was teratogenic against zebrafish fin development. To explore the teratogenicity and the underlying mechanisms, zebrafish (Danio rerio) embryos were used. The morphological observations revealed that GA caused fin defects in zebrafish embryos in a concentration-dependent manner. The critical exposure time of GA to reveal teratogenicity was before 8 hpf (hours post fertilization). LC/MS/MS analysis revealed that a maximum bioconcentration of GA was occurred at 4 hpf. Q-PCR data showed that GA treatment resulted in significant inactivation of RA signaling which could be partially rescued by the exogenous supply of RA. These results indicate the potential teratogenicity of GA and provide evidence for a caution in its future clinic use.