中药代谢分析研究进展＊

中药具有多成分、多靶点的特性，药效物质基础及药物代谢途径不明确严重制约中药的发展。中药小分子经过体内代谢后转化成代谢物发挥药效或者清除。近年来随着MS技术的飞速发展，通过LC-MS技术进行精准定性定量分析，以阐明中药代谢物与机体生理及病理相关变化的关系，从而明确中药的药效物质基础及体内代谢路径。本文从中药代谢研究思路、研究方法、影响因素以及应用等方面，就近年来中药代谢分析领域的研究进展进行综述。     

桑叶中降糖活性成分筛选及其药效学研究

目的:筛选桑叶中α-葡萄糖苷酶(α-GS苷酶)抑制活性最佳组分,并进行体内降糖活性研究。方法:采用柱层析法对桑叶水提物进行分离,利用体外细胞实验筛选出α-葡萄糖苷酶抑制活性最佳组分,并采用链脲霉素诱导的大鼠高血糖动物模型进行跟踪验证。结果:细胞实验结果表明,桑叶提取物中生物碱的α-葡萄糖苷酶抑制活性最强。体内试验中,与模型组比较,生物碱给药组糖尿病大鼠的血糖有明显降低。结论:桑叶中的生物碱具有显著的降血糖的作用(P0.05)。     

一氧化氮和水杨酸依次介导内生真菌诱导子促进苍术细胞中苍术素生物合成的信号转导

目的 研究介导内生真菌诱导子促进苍术悬浮细胞中苍术素生物合成的信号分子及信号转导途径,并探讨诱导子对苍术素合成途径关键酶活性的影响。方法 采用植物细胞悬浮培养法,考察内生真菌诱导子处理下苍术细胞中一氧化氮（NO）、水杨酸（SA）及苍术素量的变化。结果 内生真菌诱导子通过诱导苍术细胞中一氧化氮合酶（NOS）、苯丙氨酸解氨酶（PAL）以及乙酰辅酶A羧化酶（ACC）的活性,显著促进苍术细胞的NO迸发、SA和苍术素的合成。NOS抑制剂PBITU可以阻断诱导子对NO、SA和苍术素合成的促进作用,外源NO供体SNP及外源SA单独处理也能促进苍术素的合成,说明NO和SA是参与苍术素合成的信号分子,且NOS是参与诱导子诱发苍术细胞NO迸发的主要途径。NO猝灭剂cPITO可以有效清除诱导子诱发苍术细胞的NO迸发,显著阻断诱导子对苍术细胞中SA和苍术素合成的促进作用,外源SNP可以逆转cPITO对PAL、ACC活性以及SA、苍术素合成的抑制作用,表明NO是介导内生真菌诱导子诱发苍术细胞中苍术素和SA生物合成所必需的上游信号分子。结论 NO主要通过SA信号途径介导内生真菌诱导子激活ACC,显著促进苍术细胞中苍术素的生物合成。     

Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway

ContextAsthma is a common respiratory system disease. Louki Zupa decoction (LKZP), a traditional Chinese medicine, presents a promising efficacy against lung diseases.ObjectiveTo investigate the pathogenic mechanism of asthma and reveal the intervention mechanism of LKZP.Materials and methodsForty-eight female Balb/c mice were randomly divided into 6 groups: normal control group (NC), ovalbumin (OVA)/saline asthma model group, OVA/LL group, OVA/LM group, OVA/LH group and OVA/DEX group (n = 8 per group). The asthmatic mice were modelled through intraperitoneal injecting and neutralizing OVA. LKZP decoction was administrated by gavage at the challenge stage for seven consecutive days (2.1, 4.2 and 8.4 g/kg/day). We investigated the change in lung function, airway inflammation, mucus secretion and TH-1/TH-2-related cytokines. We further verify the activated status of the IL-33/ST2/NF-κB/GSK3β/mTOR signalling pathway.ResultsLKZP was proved to improve asthmatic symptoms, as evidenced by the down-regulated airway resistance by 36%, 58% and 53% (p < 0.01, p < 0.001 vs. OVA/saline group), up-regulated lung compliance by 102%, 114% and 111%, decreased airway inflammation and mucus secretion by 33%, 40% and 33% (p < 0.001 vs. OVA/saline group). Moreover, the content of cytokines in BALF related to airway allergy (such as IgE) and T helper 1/T helper 2 cells (like IL-2, IL-4, IL-5, IL-13, TNF-α and IFN-γ), were also markedly reduced by 13–65% on LKZP intervention groups compared with model group. Mechanistic research revealed that the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway was activated in the OVA/saline group and LKZP significantly down-regulated this pathway.Discussion and conclusionLKZP improves lung function, airway inflammation, mucus secretion and correct immune imbalance by intervening with the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway, presenting a promising therapeutic choice for asthma.     

兔肝VX_2肿瘤模型的建立及生物学特性

目的探讨采用瘤块种植制备兔肝VX2肿瘤模型的可行性并研究其生物学特性。方法采用VX2肿瘤组织块制备兔肝肿瘤模型,观察谷丙转氨酶(ALT)、体温、体质量、体液免疫球蛋白、肿瘤的增长、脏器转移及组织病理学改变等。结果兔肝VX2肿瘤原位移植模型的移植成功率为100%,6周肝内转移率为100%,6周肺转移率为80%。随着瘤体体积的增长,体温及ALT逐渐升高,体质量逐渐减轻,免疫球蛋白则呈下降趋势。超声检查显示肝脏有结节样增强回声。肿瘤呈灰白色,质硬,光镜下可见癌细胞核大,深染伴核异型。结论采用瘤块种植制备兔肝VX2肿瘤模型,具有容易制备、生长周期短、成功率高及模型稳定等特点,是一种较理想的肝肿瘤实验动物模型。     

冬虫夏草子囊孢子的弹射

在四川康定和西藏那曲两地,对虫草子座的光照强度处理,结果表明：两地的虫草子囊孢子弹射时间有差异;光照强度不同,子囊孢子弹射的数量,时间和萌发率均不同。要使冬虫夏草子囊孢子正常弹射和提高萌发率,必须满足温度、湿度和日照三个基本条件。本结果为人工培植冬虫夏草奠定基础。     

正常青春期少女及特发性中枢性性早熟女孩生长激素结合蛋白、性激素与生长

本文对41例青春期女孩及30例特发性中枢性性早熟(ICPP)女孩。观察其身高、体重、身高增长速度、骨龄与生长激素结合蛋白(GHBP)、雌二醇(E_2)的相关关系,结果示GHBP在青春各期间无显著差异,GHBP与身高生长速度(GV)、身高标准差分(HtsDs)、体重指数(BMI)呈正相关,GHBP与E_2、年龄(CA)、骨龄(BA)无相关关系。正常青春少女与ICPP女孩相应青春期血清GHBP无明显差异,ICPP女孩GHBP与HtsDs及BMI呈正相关关系,与E_2、CA及BA无相关关系。提示正常青春少女及ICPP女孩的生长,在GH轴调控途径上,至少在生长激素受体(GHR)/GHBP水平是相同的。GHBP受营养的正性影响,不受年龄、骨龄影响。     

Hypertension and diabetes synergistically strengthen the association with cataracts among Chinese

AIM: To examine the relationship between age-related cataracts (ARC) and comorbid hypertension and diabetes. METHODS: We analyzed the administrative records of 6,467 patients aged 50 years and older admitted to the ophthalmological department of a tertiary hospital from January 1st, 2011 to May 20th, 2017. With either eye considered, an ARC (n=3,343) was defined as the presence of lens opacity or previous cataract surgery without evidence of trauma, congenital anomalies or using certain medications. Patients admitted to the same department during the same period due to ocular traumas without clinical evidence of cataracts (n=379) were recruited as the cataract-free controls. Unconditional logistic regressions were obtained the odds ratio (OR) of hypertension and diabetes among ARC patients adjusted for age, sex and health care accessibility. RESULTS: Hypertension was diagnosed in 29.54% of men with any type of cataracts, in 30.12% of men with an ARC, and 10.82% of men of cataract-free controls. Diabetes was diagnosed in 16.64% of men with any type of cataracts, in 16.48% of men with ARC and 4.22% of men of cataract-free controls. Similar patterns were observed among women. After adjusting for age, sex, and health care accessibility, hypertension was weakly [OR=1.83 (95%CI: 1.23, 2.74)] and diabetes was strongly [3.38 (1.86, 6.15)] associated with ARCs. The adjusted OR of comorbid hypertension and diabetes among adults with ARC was 18.20 (4.38, 75.59). CONCLUSION: Hypertension and diabetes were independently associated with ARC. Hypertension and diabetes, if co-existing, multiplicatively strengthened the association with ARC.     

表麻下小切口透明晶状体吸出及人工晶状体植入术治疗高度近视

目的 :评价高度近视患者表麻下行透明晶状体吸出及人工晶状体植入术的术后效果。方法 :5 6例 10 6眼高度近视患者在表面麻醉下行小切口透明晶状体吸出及人工晶状体植入术。使用超声乳化仪 ,但未用超声能量。平均年龄 3 8 5 9± 9 44岁 ;术前裸眼视力 0 0 1～ 0 2 ,矫正视力 0 0 5～ 1 0 ;平均近视度 (-19 47± 5 41)D ,平均眼轴长(3 0 45± 1 94)mm ,平均植入人工晶状体屈光度数 ( 3 96± 4 2 7)D。术后平均随访时间 16个月。结果 :术后裸眼视力均好于或等于术前矫正视力。术后裸眼视力≥ 0 5者 79眼 (74 5 % )。术后矫正视力≥ 0 5者 99眼 (93 4% )。术后平均屈光度 (-1 49± 1 11)D。发生后囊膜混浊及玻璃体前界膜混浊 8眼 ,无视网膜脱离及黄斑囊样水肿发生。结论 :表麻下小切口透明晶状体吸出及人工晶状体植入术矫正高度近视 ,安全有效 ,预测性好 ,视力稳定。     

Ovarian hyperstimulation syndrome: a clinical retrospective study on 565 inpatients

Abstract

The aim of this study was to analyze clinical manifestations of 565 ovarian hyperstimulation syndrome (OHSS) inpatients in the largest Obstetrics and Gynecology hospital in China from year 2010 to 2017, to get more understanding of epidemiologic features of this disease, and to provide some insight on the diagnosis, treatment, and preventions of OHSS. It is a clinical retrospective study. In the 565 cases that developed OHSS over an eight-year period between 2010 and 2017 were reviewed, we assessed patients’ general characteristics, clinical manifestations, treatment, prognosis, and the relationship between different indicators and the severity of OHSS. Totally 12 kinds of ovulation induction protocols (Protocol 1: CC; Protocol 2: Gn; Protocol 3: hCG; Protocol 4: GnRh-a; Protocol 5: CC & Gn; Protocol 6: CC & hCG; Protocol 7: Gn & hCG; Protocol 8: GnRh-a & Gn; Protocol 9: CC & Gn & hCG; Protocol 10: GnRh-a & CC & Gn; Protocol 11: Letrozole & Gn & hCG; Protocol 12:GnRh-a & Letrozole & Gn) were analyzed and the Odds Ratio (OR) of each protocol were calculated. Five hundred and sixty-five patients were reviewed in our study. In all these patients, the number of hospitalizations, mean age, primary infertility rate, and pregnancy rate did not differ through the last 8?years. From which we may infer that the incidence rate of OHSS may not change over the last 8?years. Older patients tend to develop into more severe stage easily. The pregnancy rate was much lower in mild stage patients, but no difference was found between patients in moderate, severe and critical stage. Oocytes retrieval is strongly associated with severity. PCOS history, irregular menstrual cycle and infertility type do not seem to affect the severity of OHSS. Twelve kinds of ovulation induction protocols were analyzed, OR of different protocols were calculated, what is noteworthy is that patients who used GnRh easily developed more severe OHSS than the patients who received oocytes retrieval. We suggest that we may choose ovulation induction protocols according to the OR table while treating women with high-risk factors.