Reactive capillary hemangiomas: a novel dermatologic toxicity following anti-PD-1 treatment with SHR-1210

Objective: SHR-1210 is a new and promising anti-PD-1 agent for solid tumors. During the phase I study of SHR-1210, we encountered a novel but prevalent immune-related dermatologic toxicity: reactive capillary hemangiomas(RCHs). Thus we tried to summarize the features of RCHs and estimate their relationship with tumor response.Methods: This prospective observational study systematically enrolled 98 patients with advanced solid tumors from April 27th,2016 to June 8th, 2017 in the context of the phase I clinical study of SHR-1210. This report focused on the skin toxicities. Patients underwent entire skin inspection every two weeks while taking medication. The clinical course of RCHs was recorded and their association with tumor response was estimated. The data cut-off date was November 15th, 2017.Results: After a median follow-up of 242(range, 29–567) days, RCHs were observed in 85.7%(84/98) of patients on cutaneous/mucosal surfaces; 84.5%(71/84) of the RCHs were evaluated as grade 1 adverse events. No grade 3 or 4 RCHs were observed. The time of onset of RCHs was dose dependent and shortest in the 400 mg-dose cohort(P < 0.001). Spontaneous and complete regression of RCHs was observed both during and after treatment. The objective response rate of tumors for patients with RCHs was 28.9%(24/83). However, no responders were observed among the patients without RCHs.Conclusions: RCHs were prevalent but manageable during treatment with SHR-1210. It might add to the expanding literature regarding immune-related dermatologic adverse events.

Toxicity Study of Anti-HABs Agents on Penaeus chinensis

In order to study the effect of anti-HABs agents on Penaeus chinensis, the toxicity experiments on clay, Ca(ClO)2, FeCl3, and AlCl3 to Penaeus chinensis are carried out. The results show that: (1) the clay isn't toxic to Penaeus chinensis; (2) Ca(ClO)2 has no toxicity to Penaeus chinensis at low levels, but has acute and chronic toxicity at high levels; (3) Penaeus chinensis can accumulate Fe and Al. The toxic effect needs further study.

Antiretroviral Therpay Induced Liver Toxicity among Immunecompromised HIV Patients at Chu Brazzaville

Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different hepatic manifestations of antiretroviral therapy and the responsible molecules. Patients and Methods: This was an eight months period prospective descriptive study, from January 1st to August 31st, 2015, conducted in the Department of Gastroenterology and Internal Medicine at the Brazzaville University Teaching Hospital. Study participants were treatment-na?ve HIV patients who were initiated on ART treatment during the study period. Patients with liver disease, liver cytolysis prior to initiation of therapy, and those with alternative therapy that may cause hepatotoxicity were excluded. The sample size was 110 patients. Results: The age was ranging from 25 to 70 years with a mean age of 47.5 ± 7.5 years. During the six months of follow-up, the alarming hepatic signs were observed in 26.36% of cases (n = 29) in the 3rd month of treatment. There was no observed alarming sign in the 6th month of follow-up. The cytolytic pattern was observed in 54.55% of cases (n = 60) in the 3rd month. The cholestatic pattern was observed in 6.36% of cases (n = 7) in the 3rd month. Triple therapy combination of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most used in 57.27% (n = 63) with a statistically significant p value to the occurrence of cytolytic pattern (p Conclusion: Drug induced liver toxicity occurs in a significant number of patients starting ART. The prevalence of hepatic events was high at the third month of treatment and the triple therapy of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most incriminated.

Phytochemical Screening, Toxicity, Analgesic and Anti-Pyretic Studies of Aqueous Leaf Extract of <i>Plectranthus barbatus</i>[Andrews. Engl.] in Rats

Plectranthus barbatus is a popular tropical perennial plant with a wide variety of traditional medicinal uses in tropical Africa, Hindu, Ayurvedic and traditional medicines of Brazil and China. The whole plant and the leaves have many folkloric uses for diverse ailments including pain, heart disease, convulsions, coughs and colds, asthma, bronchitis and tonsillitis among others. This study investigated the phytochemical components, acute toxicity, analgesic and anti-pyretic activities of the aqueous leaf extract of Plectranthus barbatus locally known as Ekizeera in Uganda. The plant leaves were authenticated, collected and decoction was done according to local method. Phytochemical screening was conducted using methods outlined by Trease and Evans and Harborne to determine the components of the extract. Acute toxicity tests were conducted in rats using modified Lorke’s method to determine the safety of the plant material. Analgesic studies were carried out using both a mechanical method (thermally induced pain by tail-flick) and a chemical method (formalin induced pain) in rats by administering extracts orally at 100, 200 and 400 mg/kg of body weight. The method of Al-Ghamdi, modified for local laboratory setting by Adzu was adopted and used for anti-pyretic test. Decoction yielded 9.9% extract. Phytochemical screening confirmed presence of saponins, tannins, alkaloids, terpenoids and essential oils. Acute toxicity tests revealed no deaths in rats after oral treatment with up to 10,000 mg/kg of extract. Tail-flick test was non-significant (p > 0.05) while formalin-induced pain test demonstrated significant activity (p -tests. Anti-pyretic activity was non-significant (p > 0.05) with student t-test. These results suggest that the aqueous leaf extract of Plectranthus barbatus contains specific phytochemicals, has a potent dose dependent analgesic activity, no anti-pyretic activity and can be regarded as a safe medicinal plant to use traditionally, which might further be developed for conventional medical practice.

Safety and in Vivo Anti-Inflammatory Activity of Ethanolic Extract of Ficus umbellata (Vahl.) Leaves

Toxicity is the totality of adverse effects, which can be functional and morphological lesions in a living organism, caused by a substance introduced in relatively high single doses or in small, repeated doses. The aim of this study was to assess the OECD-recommended acute oral toxicity and anti-inflammatory activity of ethanolic extract of Ficus umbellata leaves. Animals were given a single oral dose of 1000, 3000 and 5000 mg/Kg body weight (BW) of the extract. For the anti-inflammatory activity test, rats were given the ethanolic extract of F. umbellata leaves at doses of 100, 300 and 500 mg/Kg or aspirin® at a concentration of 100 mg/Kg PC orally, one hour before injection of 0.05 ml of 1% formalin under the plantar fascia of the rat’s right hind paw. Paw volume measurements were taken one, two and three hours after formalin injection, using an electronic caliper. After 14 days of observation, no deaths were observed in treated rats. The LD50 of ethanolic extract of Ficus umbellata leaf powder is greater than 5000 mg/Kg body weight. This extract has no significant effects on hematological parameters and on the main markers of nephrotoxicity and hepatotoxicity for a single dose of less than 5000 mg/Kg PC. It reduces formalin-induced edema. Evaluation of the percentage inhibition showed that the extract had greater anti-inflammatory activity at 3 hours after the start of the experiment. However, better inhibition of inflammatory oedema of the paw of rats treated with 500 mg/Kg was observed at 5 hours after the start of the experiment, with a percentage inhibition of 69.23 ± 1.02, compared with the reference group treated with aspirin® 100 mg/Kg, which showed an inhibition of 63.50 ± 0.98. These results show that F. umbellata leaves possess anti-inflammatory activity, which would justify their use in traditional African medicine to prevent or treat inflammation.

肖天保教授辨治结直肠癌术后肿瘤标志物异常经验

结直肠癌是转移率、复发率较高的恶性肿瘤,手术切除是主要治疗手段,术后常需多次化疗,但化疗后不良反应多,会加剧人体正气亏虚,影响生存质量,单纯现代医学治疗长期效果欠佳。中医药具有扶正祛邪、调节免疫、抗肿瘤的功能,且较化疗不良反应少,并可改善化疗后相关症状,弥补了单纯现代医学治疗的不足。肖天保教授辨证论治结直肠癌经验丰富,故整理其经验,附自拟攻毒抑癌方结合化疗治疗直肠癌术后肿瘤标志物异常1例,以供参考。

3种非甾体抗炎药对Q67的联合毒性效应及作用机理

随着非甾体抗炎药(NSAIDs)在环境中频繁检出,其对生物体的毒性效应成为研究的热点。文章以双氯芬酸钠(DIC)、布洛芬钠(IBU)、萘普生钠(NAP)等常见NSAIDs为目标污染物,以淡水发光菌青海弧菌Vibrio cyanobacteria sp.-Q67(Q67)为受试生物,采用直接均分和均匀设计射线法分别设计了3个二元混合物体系和1个三元混合物体系。采用浓度加和和绝对残差2种模型定性和定量分析混合物的毒性相互作用,并结合热图法分析其变化规律,用剂量减小指数(DRI)来评估混合物中各组分对整体毒性的贡献,同步测定Q67在实验暴露终点时的生理生化指标,以及扫描电镜观察NSAIDs及其混合物作用前后Q67细胞结构和形态的变化。结果表明,3种NSAIDs及其混合物对Q67的毒性具有一定的浓度和时间依赖性,浓度-效应曲线呈现为“S”型,3种NSAIDs在暴露时间12 h的毒性强弱的排序均为DIC>NAP>IBU,而混合物的毒性与各组分在混合体系中的浓度比密切相关,即混合物表现出组分比依赖的毒性。除少部分射线呈部分协同和加和作用外,其余混合射线均呈现出时间依赖性拮抗作用,最强的拮抗作用出现在暴露时间为12 h时的DIC-IBU-R1射线,d CA值为0.58。依据DRI,DIC、IBU和NAP三个组分对拮抗作用的贡献度可能为NAP>IBU>DIC。在NSAIDs及其代表性混合物的作用下,Q67细胞出现表面皱缩、黏连甚至破裂的现象,并且相较于单一药物,混合物对细胞结构的破坏程度更为明显。污染物通过诱导细胞内过氧化物的过量累积,过氧化物进一步导致细胞膜脂质过氧化,进而破坏生物膜的完整性,细胞内电导液外泄和蛋白质溶出量增加加剧了细胞损伤,最终引导致细胞死亡。

Analgesic,anti-inflammatory and anti-diarrheal activities of ethanolic leaf extract of Typhonium trilobatum L.Schott

Objective:To explore the efficacy of ethanolic leaf extract of Typhonium trilobatum L.Schott in treating diarrhea,pain and inflammation using experimental models.Methods:In the present study,acetic acid-induced writhing,xylene-induced ear edema and castor oil-imluced diarrlieal model were used to evaluate the analgesic,anti-inflammatory and anti-diarrheal activities,respectively.Acute toxicity test was carried out to fix the safe doses of the plant extract.Results:The plant extract demonstrated a significant inhibition of writhing(P<0.01)compared with the control group in acetic acid-induced writhing test in mice.The extract also significantly inhibited the xylene induced ear edema formation(P<0.05).In anti-diarrheal test,the extract significantly decreased the frequency of defecation and increased the mean latent period(P<0.0l)in castor oil-induced diarrheal model mice at the doses of 250 and 500 mg/kg body weight.Conclusions:These results suggest that the extract possesses significant analgesic,anti-inflammatory and anti-diarrheal activities that support to the ethnopharmacologicl uses of this plant.

Alleviation of Al Toxicity in Barley by Addition of Calcium

The potential mechanism by which Ca alleviates Al toxicity was investigated in barley seedlings. It was found that 100 Al-alone treatment inhibited barley plant growth and thereby reduced shoot height and root length, and dry weights of root, shoot and leaf; promoted Al accumulation but inhibited Ca absorption in plant tissues; and induced an increase in the activities of superoxide dismutase （SOD）, catalase （CAT）, and peroxidase （POD） and in the level of lipid peroxidation （MDA content） in leaves. Except for the increase in Ca concentration in plant tissues, treatment with 0.5 mM Ca in the absence of Al had less effect on the above-mentioned parameters, compared with the control. Addition of Ca efficiently reduced Al toxicity, which is reflected by the promotion of plant growth, reduction in Al concentration and MDA content, increase in Ca concentration and in SOD, POD, and CAT activities compared with the Al-alone-treatment; with increase in Ca level （3.0 raM）, the ameliorative effect became more dominant. This indicated that the alleviation of aluminum toxicity in barley seedlings with Ca supplementation could be associated with less absorption of Al and the enhancement of the protective ability of the cell because of increased activity of the antioxidative enzyme.

Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis

AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.

Maligned non-steroidal anti-inflammatory drugs:Misunderstanding of their safety profile in patients with renal insufficiency

Non-steroidal anti-inflammatory drugs have a fundamental and pivotal position in management of many of the disorders managed by rheumatologists.Promulgation of a false perspective of their toxicity has compromised our ability to advise our patients and participate in the management of their disorders. The literature sources, from which the false perspective derives, do not accurately reflect safety and fail to address the value of appropriate drug use monitoring.We, as rheumatologists, must stand up and proactively address engrained misconceptions-if we are to be able to continue to provide safe, effective care for our patients.

萃取/反萃取-电感耦合等离子体发射光谱(ICP-OES)法测定肥料样品中铅、镉、汞、铊、锑、砷

为保障农产品的质量与安全,肥料中的有毒有害物质,尤其是重金属含量被严格限制。为提高肥料中有毒有害物质检测的效率,利用铅、镉、汞、铊、锑、砷在盐酸介质中形成稳定的碘络合物的特性,采用甲基异丁基酮(MIBK)萃取、硝酸溶液反萃取的方法实现肥料样品中基质与待测元素的分离,通过电感耦合等离子体发射光谱法测定肥料样品中的6种重金属元素。通过考察萃取条件及残余基体对分析结果的影响,结果证实,在6 mol/L的盐酸萃取体系中加入5 mL碘化铵(30%)溶液,采用10 mL的MIBK萃取2~3次即可使样品中的铅、镉、汞、铊、锑、砷等被完全萃取,通过萃取/反萃取的方法实现了样品的分离富集,方法的检出限(3σ)为铅0.042 mg/kg、镉0.005 mg/kg、汞0.059 mg/kg、铊0.026 mg/kg、锑0.024 mg/kg、砷0.052 mg/kg,加标回收率在90.1%~108%,可以满足不同肥料样品的质量控制要求。按照实验方法测定6种不同肥料样品中的重金属含量,并采用标准方法进行方法比对,结果表明两种方法的测定结果基本一致。

基于炎症大鼠代谢组学的马钱子炮制减毒存效机制研究

运用动物模型、血浆药物化学及代谢组学方法,探讨马钱子炮制前后干预炎症大鼠作用机制。按不同剂量灌胃小鼠,以死亡率初步考察炮制前后毒性;建立大鼠蛋清性足跖肿胀模型,通过肿胀率和炎性因子水平评价炮制前后抗炎效果;采用高分辨质谱结合多元统计学,鉴定入血后的移行成分及相应的代谢产物;比较分析各实验组代谢轮廓及差异生物标志物,并构建其代谢通路。结果显示,高剂量下马钱子砂烫品的毒性要明显低于生品。生品和砂烫品均能显著降低大鼠足肿胀率和肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)的水平,炮制前后在抗炎效果上差异无统计学意义(P>0.05)。通过血浆药物分析,鉴定出了12个移行成分,以及相应60个代谢产物,S-plot鉴定出10个差异性化合物。代谢组学实验共发现10个内源性代谢物含量发生显著变化(P<0.05),生物标志物主要涉及苯丙氨酸代谢、甘油磷脂代谢、谷氨酸及谷氨酰胺循环、精氨酸和脯氨酸代谢等途径。通过本研究确证马钱子生品和砂烫品均有较好抗炎治疗作用,高温炮制可以降低马钱子毒性;入血后有效成分应多为生物碱,经过I相反应就容易被体内清除;马钱子炮制抗炎、镇痛、减毒机制主要与氨基酸和脂质代谢相关。该实验结果进一步阐明了起效物质基础及体内作用机制,为后续炮制工艺改进和新药研发等提供科学支撑。

TERATOGENIC EFFECT OF ANTI-HBs-A CONCURRENT COHORT STUDY

One thousand, five hundred and seventy six pregnant women were followed upprospectively from early pregnancy to investigate the relation or Anti-HBs and other 10 risk factors from pregnant women with the congenital malformation of newborn. The results confirmed the teratogenic effect of Anti-HBs. The monofactorial analysis showed that the newborn congenital malformationincidence in Anti-HBs positive mothers was higher than that in Anti-HBs negative mothers (x2=6. 0274,P = 0.0141). The multifactorial analysis by using unconditional Logistic Repression model confirmed that Anti-HBs had a teratogenic effect (OR=5. 30952, P=0. 000302). The possibleteratogenic mechanism of Anti-HBs is discussed. It is important to further study the teratogenic effect of Anti-HBs in eugenics. Anti-HBc may have prevention effect on congenital malformation development (OR= 0. 27110, P= 0. 004515). In addition, exposure to toxicants during pregnancy is one of the risk factors causing congenital malformation (OR= 8. 17080, P=0. 001780).

σFactor SigW/Anti-σFactor RsiW参与东湖假单胞菌HYS对秀丽隐杆线虫毒性作用

东湖假单胞菌HYS对秀丽隐杆线虫具有较强毒性,但机制尚不完全了解。本研究旨在探究东湖假单胞菌HYS中σ因子SigW与反σ因子RsiW在其对秀丽隐杆线虫毒性中的作用。通过对东湖假单胞菌HYS减毒突变株突变位点序列进行生物信息分析,构建目的基因敲除突变株,借助酵母双杂交、荧光定量PCR以及假单胞菌-秀丽隐杆线虫互作等研究方法进行相关基因蛋白功能验证。结果发现:(1)基因rsiW与东湖假单胞菌HYS菌株对秀丽隐杆线虫毒性相关;(2)RsiW与基因组上邻近的SigW(σ24)是一对σ因子与反σ因子,在蛋白水平存在互作;(3)RsiW与SigW互作参与东湖假单胞菌HYS对秀丽隐杆线虫毒性作用且存在一定的剂量效应,即SigW表达相对较强时,存在减毒效应。该研究发现一对σ因子与反σ因子(SigW/RsiW)参与东湖假单胞菌HYS对秀丽隐杆线虫的毒性作用,为深入探讨假单胞菌毒力因子调控机制提供了新线索和思路。

Anti-Inflammatory and Antioxidant Properties of the Aqueous Extracts of the Leaves of Opilia amentacea (Opiliaceae)

Opilia amentacea (Opiliaceae) is a woody plant with multiple medicinal claimed effects. The present study aimed to assess the anti-inflammatory and antioxidant activities of the decoction and macerate extracts from the leaves of Opilia amentacea. Moreover, acute toxicity and phytochemical analysis were performed. The acute toxicity was evaluated on NMRI mice at 2000 mg/kg bw. The anti-inflammatory activity was studied using the carrageenan-induced mouse paw edema and the lipoxygenase inhibition assay. The radical scavenging (DPPH and ABTS), ferric-reducing antioxidant power (FRAP), and lipid peroxidation (LPO) assays were used to measure the antioxidant capacity of the extracts. Qualitative and quantitative methods served for identifying and quantifying the extract’s phytoconstituents. The decoction demonstrated low acute toxicity;the lethal dose was therefore estimated to be superior to 2000 mg/kg bw. The extracts significantly reduced the mouse paw’s thickness at 600 mg/kg bw. The extracts developed weak radical scavenging and lipid peroxidation inhibitory effects. However, the macerate showed a high ability (664.90 ± 0.71 mol Ascorbic Acid Equivalent/g dry extract) to reduce the ferric ions. Saponins, sterols, triterpenes, and flavonoids were qualitatively detected in the two extracts. Total phenolics (TP) and total flavonoids (TF) were found abundant in the extracts, especially the decoction (TP content (TPC) = 94.03 ± 2.66 mg GAE/g;TF content (TFC) = 35.05 ± 0.32 mg QE/g). Strong positive correlations existed between ferric-reducing capacity and TPC (r = 0.959) for the macerate, while TFC was mainly involved in the DPPH radical scavenging of the two extracts. Instead, most correlations were negative between the polyphenol compounds and the anti-inflammatory assays. The results indicate potent in vivo anti-inflammatory and in vitro antioxidant effects of the aqueous extracts from the leaves of Opilia amentacea. Further studies are needed to find the anti-inflammatory and antioxidant effects mechanism.

Study of Biological Activity and Toxicity of Thiosemicarbazides Carbohydrate Derivatives by in Silico, in Vitro and in Vivo Methods

Computer analysis of N-(β-D-galactopyranosyl)-thiosemicarbazide compounds by in silico method revealed high probability of antibacterial (antimycobacterial), anti-tuberculosis (antituberculosic), antiviral (Influenza), antitumor (antineoplastic) 9 > Pa > 0.5 and with a low probability of cytotoxic/cytostatic (cytostatic/cytotoxic) activities. An experimental study by in vitro and in vivo methods allowed us to conclude that studied new synthetic compound N-(β-D-galactopyranosyl)-thiosemicarbazide in the studied concentrations has a pronounced bactericidal and bacteriostatic effects.

黑老虎叶提取物纯化及其在化妆品原料中的应用研究

目的:探讨黑老虎叶提取物在化妆品原料开发中的潜在应用。方法:以黄酮含量为评价标准,构建了大孔吸附树脂对黑老虎叶提取物的纯化流程,并结合动物实验、细胞实验及化学实验,开展提取物的急性毒性及其功能特性研究。结果:AB-8大孔吸附树脂对黑老虎叶黄酮具有良好的吸附和解吸性能;上样条件为:总黄酮浓度1.0 mg/mL的料液调节pH 3,以3 BV/h流速上样5 BV;洗脱条件为:用80%乙醇以3 BV/h流速洗脱5 BV;动物实验表明,提取物无急性毒性;细胞实验显示,在2.5~50.0μg/mL浓度范围内,提取物能显著减少H_(2)O_(2)引起的人皮肤成纤维细胞死亡,有效降低细胞中ROS、MDA水平,增强SOD、CAT活性;在0.1~2.0 mg/mL浓度范围内,提取物能显著降低小鼠B16F10细胞中TYR活性;提取物抑制HAase的IC_(50)为4.748μg/mL。结论:利用AB-8大孔吸附树脂纯化的黑老虎叶提取物没有表现出急性毒性,同时展现了抗衰老、美白、抗过敏等功效,在作为化妆品原料应用上具有一定开发潜力。

附子药理作用机制及减毒增效技术的研究进展

附子具有回阳救逆、补火助阳、温经散寒等功效,但对心脏、肝脏等多系统具有毒性作用,如何在保证疗效的同时降低毒性值得探究。目前,对附子的药理研究主要集中在其强心、保护血管、抗肿瘤、抗炎镇痛及保护神经系统等方面,并在不断挖掘新的方向,如调节免疫及改善糖尿病等。作用机制主要为通过多成分、多靶点、多途径地调控相关信号通路、离子通道等,在生物体内发生细胞水平、组织水平和系统水平的改善。对附子的减毒增效的研究主要是在炮制方法的革新和药物配伍的作用机制等方面。随着科技发展,无胆炮制、微生物发酵技术等逐渐推广应用,不仅能在降低附子毒性的同时维持甚至提升附子的药理作用,还研发出某些疾病的专属性炮制品,对附子的毒理及配伍后药物成分研究也有了长足发展。本文对附子近年来的药理作用及减毒增效的研究进展进行综述,并总结阐述了现有研究的不足之处,以期更好地利用附子资源。

中药常山、蜀漆古今文献考证

目的探究常山、蜀漆的基原、产地、性味归经、功效、毒性特点,以期为常山、蜀漆的研究与合理应用提供参考。方法以第5版中华医典数据库、读秀数据库、中医智库在线古籍数据库为检索范围,考证常山、蜀漆的基原、产地、性味归经、功效、毒性,同时结合现代文献研究进行分析。结果发现常山、蜀漆别名较多,分布广泛,喜阴凉湿润环境,以四川产量最大,质量最优。常山的性味与归经在历代古籍中未发现明显变化,但蜀漆性味记载存在分歧,且归经论述较少,未得统一。古籍载常山、蜀漆功效多为截疟、涌吐,现代药理研究发现两者还具有抗球虫、抗肿瘤、解热、降压、抗流感病毒等药理作用。但因两者均存在一定毒性,为保证安全用药,传统多通过炮制及配伍进行减毒存效,现代多从其活性成分本身的结构修饰及致毒机理实现减毒增效。结论古今文献梳理发现常山及蜀漆,除截疟外还具有抗肿瘤等多种药理活性,研发前景良好,但囿于其存在一定的毒性,制约了其临床应用,传统临床多通过炮制、配伍减毒存效,现代学者尝试通过结构修饰和改变给药途径减毒增效,为其减毒增效提供了新的思路和方向。