目的:研究人参皂苷Rg1通过Wnt3aβ-catenin信号通路影响糖尿病大鼠肾损伤的机制.方法:将60只SD大鼠随机分为对照组、模型组、厄贝沙坦组、人参皂苷Rg1组.模型组、厄贝沙坦组、人参皂苷Rg1组经腹腔注射链脲佐菌素建立糖尿病模型,给予对照组、模型组生理盐水灌胃,厄贝沙坦组接受厄贝沙坦干预,人参皂苷Rg1组接受人参皂苷Rg1干预,各组均连续干预8周.比较各组大鼠血糖血脂水平、Wnt3a/β-catenin表达、肾损伤及肾脏炎症指标.结果:与对照组相比,人参皂苷Rg1组、厄贝沙坦组、模型组空腹血糖、总胆固醇、甘油三酯水平依次升高(P＜0.05).与对照组相比,人参皂苷Rg1组、厄贝沙坦组、模型组Wnt3a、β-catenin表达水平依次升高(P＜0.05).与对照组相比,人参皂苷Rg1组、厄贝沙坦组、模型组血肌酐、尿素氮、24h尿蛋白水平依次升高(P＜0.05).与对照组相比,人参皂苷Rg1组、厄贝沙坦组、模型组C反应蛋白、单核细胞趋化蛋白-1、肿瘤坏死因子-α水平依次升高(P＜0.05).结论:人参皂苷Rg1可有效调节糖尿病大鼠血糖血脂水平,抑制肾脏炎症反应,缓解肾损伤,调控Wnt3a/β-catenin信号通路可能是其发挥作用的重要机制.

目的:探讨多囊卵巢综合征(PCOS)患者妊娠期体内维生素D水平与血脂代谢以及妊娠结局的关系,从而为患者的临床诊疗提供指导.方法:选取接受治疗的50例妊娠期患有PCOS的妇女作为观察组,并选取同期接受产检的50例正常妊娠期孕妇作为对照组.①记录并比较两组血清维生素D水平;②对两组血脂代谢相关指标进行比较,主要包括甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)以及高密度脂蛋白胆固醇(HDL-C);③分析血清维生素D水平与血脂代谢之间的相关性;④比较两组对象分娩情况,主要包括早产、剖宫产、羊水过多、羊水过少、胎盘早破、产后出血等;⑤比较两组胎儿预后情况,包括新生儿窒息、新生儿畸形、巨大儿、新生儿低血糖、低体重儿等.结果:①与对照组相比,观察组患者体内TG、TC水平明显较高,观察组患者体内维生素D、LDL-C以及HDL-C水平低于对照组,且组间差异具有统计学意义(均P<0.05);②Pearson相关分析显示,研究对象TG水平与维生素D水平呈负相关(r=-0.443,P=0.000),TC水平与维生素D水平呈负相关(r=-0.233,P=0.019),LDL-C以及HDL-C水平与维生素D水平无相关性(均P>0.05);③观察组患者剖宫产、羊水过多、羊水过少以及胎盘早破的发生率均高于对照组,但组间差异无统计学意义(均P>0.05),与对照组相比,观察组患者早产和产后出血的发生率较高,且组间差异具有统计学意义(P<0.05);④观察组患者新生儿窒息、新生儿畸形、巨大儿、新生儿低血糖等发生例数均高于对照组,但组间差异无统计学意义(均P>0.05),与对照组相比,观察组患者低体重儿例数较高,且组间差异具有统计学意义(P<0.05).结论:与正常处于妊娠期的孕妇相比,患PCOS的妊娠期妇女体内维生素D水平明显降低,加重了患者自身的血脂代谢紊乱,且对孕妇的分娩情况以及胎儿预后情况具有一定影响.

患儿,男,14岁,因进行性面容畸形、发育迟缓2年于2018年11月5日入院.患儿于2年前发现面容畸形,右侧颅骨畸形生长,颞骨稍外凸,于外院行头颅CT考虑骨纤维异常增殖症,未进一步诊治.之后病变部位缓慢进行性生长,右侧颞骨及右额部骨质外凸明显,并逐渐出现听力减退,视物模糊,同时家长发现患儿生殖器较同龄儿小,无腋毛、阴毛,无喉结、变声.查性激素提示泌乳素( PRL)>200 ng/ml,睾酮、促黄体生成素及卵泡刺激素明显减低,遂就诊于我院.查体:身高178 cm,体质量83 kg,颜面可见牛奶咖啡斑.右颞侧及右额部头骨局限性膨出,无压痛.右侧听力明显下降,无第二性征发育,声音偏细,生殖器偏幼稚型,未见阴毛分布,阴茎长约3. 2 cm,周径1. 8 cm,睾丸容积左右侧均约6 ml,无压痛.生长激素40. 00 ng/ml,胰岛素样生长因子1 (IGF-1)1138. 00 ng/ml;促卵泡生成素1. 03 mIU/ml,促黄体生成素<0. 10 mIU/ml,雌二醇<5. 00 pg/ml,睾酮3. 21 ng/dl,孕酮0. 241 ng/ml,催乳素454. 00 ng/ml.垂体 MR 示垂体侵袭性肿瘤,自鼻窦至颅内大面积软组织样占位,内可见骨质结构(图1A、B).临床诊断为"McCune Albright综合征:骨纤维异常增殖症(多骨性) ,垂体生长激素—泌乳素瘤,巨人症".后复查GnRH兴奋试验无反应,诊断为"垂体性因素导致低促性腺激素性性腺功能减退".因垂体腺瘤已累及视力、听力,遂于2019年4月在外院行经鼻蝶窦腺瘤切除术,术后病理证实生长激素—泌乳素瘤.术后身高呈缓慢进行性增长,仍无明显第二性征出现.2020年5月出现头痛,头部MR示垂体瘤术后改变,无复发迹象,生长激素仍持续过度分泌.先后5次给予长效醋酸奥曲肽缓释剂型联合溴隐亭以抑制肿瘤,治疗过程顺利.院外口服十一酸睾酮软胶囊.治疗后生长因子、IGF-1较前明显减低,身高、体质量增长速度较前减慢,阴茎长度、周径较前增加,睾丸容积较前增加,仍无阴毛分布.

Objective:To investigate the effects of sitagliptin and gliclazide sustained-release tablets on blood glucose, blood lipids and islet β-cell function in patients with type 2 diabetes (T2DM) .Methods:Eighty-eight patients with T2DM admitted to our hospital between October 2017 and October 2019 were randomly divided into the control group and study group ( n=44 each) . The control group was treated with gliclazide sustained-release tablets. In addition, the study group was treated with sitagliptin. The levels of blood glucose, glycated hemoglobin (HbA1c) , fasting insulin (FINS) , blood lipids, and serum glucose transporter 4 (GLUT4) were recorded at baseline and at 16 weeks after the treatment in the two groups. The changes in islet β cell function and vascular endothelial function were examined in the two groups. Results:After the treatment, the levels of fasting plasma glucose (FPG) , postprandial 2 h plasma glucose (2hPG) and HbA1c in the two groups decreased compared with those at baseline, whereas the FINS increased compared with that at baseline (all P<0.05) ; the levels of plasma triglyceride (TG) , total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the two groups decreased compared with those at baseline, whereas the level of plasma high-density lipoprotein cholesterol (HDL-C) increased compared with that at baseline (all P<0.05) ; the homeostasis model assessment for β cell function (HOMA-β) index in the two groups increased compared with that at baseline, whereas the homeostasis model assessment for insulin resistance (HOMA-IR) index decreased compared with that at baseline (both P<0.05) ; the serum GLUT4 level was higher than that at baseline in the study group, and the endothelium-dependent dilation function (EDD) significantly increased compared with that at baseline in the two groups; and the indicators in the study group were significantly better than those in the control group (all P<0.05) . Conclusion:Sitagliptin and gliclazide sustained-release tablets in the treatment of T2DM may significantly reduce blood glucose level, improve dyslipidemia and islet β-cell function, and repair the damage of vascular endothelial function, with significantly clinical effect.

目的:研究丹参川芎嗪联合贝前列素钠片对早期糖尿病肾病(DN)的治疗效果及对患者血清胱抑素C(CysC)、鸢尾素(Irisin)水平的影响.方法:将早期DN患者180例,按照随机数字法分为对照组和观察组,各90例.对照组给予贝前列素钠片,观察组在对照组的基础上给予丹参川芎嗪注射液.比较两组的治疗效果,以及治疗前后两组患者CysC、Irisin、肾功能和血糖指标变化.结果:观察组的治疗有效率明显高于对照组(P<0.05).治疗后,两组CysC水平明显降低,Irisin水平明显增加,其中观察组CysC、Irisin水平变化明显优于对照组(P<0.05).治疗后,与治疗前相比,对照组和观察组尿微量白蛋白、空腹血糖和糖化血红蛋白水平均明显降低(P<0.05),其中观察组尿微量白蛋白、空腹血糖和糖化血红蛋白水平明显低于对照组(P<0.05).结论:丹参川芎嗪联合贝前列素钠片对早期DN治疗效果好,有助于改善患者肾功能以及血糖指标,调节CysC、Irisin水平,关于二者联合应用对早期DN的疗效发生机理还需进行更为深入的研究.

Aim: This study aimed to investigate the specificity and potency of curcumin derivative 64PH in inhibiting the proliferation of HepG2 human hepatoma cells in vitro. Methods: Various concentrations of 64PH were administrated to HepG2 hepatoma cells and HL7702 hepatic cells. The viability of cells was evaluated by methyl thiazolyl tetrazolium assay. The concentration-inhibition rates in the two cell lines were calculated, and the accumulation normal distribution function was adopted to fit their rate curves. The differences of the rates between the two cells were observed on the 3rd day of 64PH treatment. The maximum difference and the 95% credibility interval of the corresponding 64PH concentration were evaluated. Results: 64PH inhibited the proliferation of HepG2 and HL7702 cells in vitro. To fit the concentration-effect curves on the 3rd day, the determination coefficients (γ2) were more than 0.99, the half maximal inhibitory concentration (IC50) was 3.07 and 4.28 μg/mL of 64PH, respectively, and their ratio was 1.39. To fit the normal distribution function of the differences of concentration-inhibition rates between HepG2 and HL7702 cells (s2 = 0.9861), the maximum difference of inhibition rates was 33.58%, and the corresponding concentration of 64PH and the 95% credibility interval were 2.65 and 3.52 μg/mL, respectively. Conclusion: In vitro, HepG2 cells are more sensitive than HL7702 cells due to the presence of 64PH. The inhibition of cell proliferation induced by 64PH is stronger in HepG2 than in HL7702 at concentrations between 2.65 and 3.52 μg/mL. 64PH has the potential to be a therapeutic approach in hepatocellular carcinoma and to achieve the desired efficacy and safety.

Objective To investigate the effects of all-trans retinioc acid (ATRA)on proliferation of rat hepatic stellate cells (HSC-T6)and expressions of collagen Ⅰ,matrix metalloproteinase-2 (MMP-2),tissue inhibitor of metalloproteinases-1 (TIMP-1 )and signal protein Smad2/3 in TGF-β1-simulated HSC-T6 so as to explore the impact and molecular mechanisms of ATRA on liver fibrosis in vitro .Methods Cultured HSC-T6s were treated with different concentrations of ATRA (0.1,1,10 μmol/L)for fixed time (12,24,48 hours).After intervention time,cell proliferation was evaluated by MTT.Meanwhile,HSC-T6s stimulated by TGF-β1 (5 ng/mL)were treated with different concentrations of ATRA for 24 h.The mRNA expressions of COL1α2,MMP-2 and TIMP-1 were quantified by RT-PCR;the expression of Smad 2/3 protein was determined by cell immunochemistry.Results The proliferation of hepatic stellate cells was inhibited by ATRA in a dose-dependent manner (P < 0.05 ).After induced by TGF-β1,the mRNA expressions of COL1α2,MMP-2 and TIMP-1 and the expression of Smad 2/3 protein were increased significantly compared with control group (P <0.05).However,ATRA could obviously reduce themRNA expressions of COL1α2,MMP-2 and TIMP-1 and the expression of Smad 2/3 protein in HSC-T6 induced by TGF-β1 (P < 0.05 ).Conclusion ATRA can inhibit the proliferation of HSC-T6s and reduce the mRNA expressions of COL1α2,MMP-2 and TIMP-1 in HSC-T6 which were induced by TGF-β1.The anti-hepatic fibrosis function of ATRA may be related to its inhibition on the expression of Smad 2/3 protein in HSC-T6 to influence TGF-β1/Smad signaling pathway.

目的:探讨姜黄素衍生物64PH的体内外抗肿瘤活性.方法:MTT法检测64PH对小鼠B16黑色素瘤细胞及人HepG2肝癌细胞的体外增殖抑制作用;采用小鼠移植性肿瘤H22观察64PH的体内抑瘤活性,HE染色观察肿瘤血管新生.结果:64PH对B16的IC50分别为10.30 μg·ml-1(24 h),3.12 μg·ml-1(48 h),2.67 μ上g·ml-1(72 h),对HepG2的IC50分别为5.60μ.g·ml-1(24 h),7.60 μg·ml-1(48 h),5.92 μg·ml-1(72 h);低剂量(100mg·kg-1)、高剂量(300mg·kg-1)64PH对小鼠H22的抑瘤率分别为26.1％,33.0％,且可明显抑制小鼠H22肿瘤的血管生成.结论:64PH在体内外均具有较好的抗肿瘤活性.

实体肿瘤的发生发展过程离不开血管新生.骨髓源性细胞(Bone marrow-derived cells,BMDCs)在肿瘤血管新生的过程中发挥十分重要的作用,其中表达雌激素受体阳性的BMDCs受到雌激素调节.雌激素又与多种女性常见肿瘤的发生发展过程密切相关,分析表明肿瘤血管新生、BMDCs、雌激素三者之间存在紧密联系.在肿瘤治疗过程中,BMDCs可作为肿瘤治疗的新靶点和药物载体,为肿瘤的治疗开辟新道路.

了解我国综合性医药卫生期刊的办到质量和学术影响力状况.本文以《中文核心期刊要目总览》(2008年版)中的24种综合性医药卫生期刊为研究对象,以2006～2010年出版的《中国科技期刊引证报告》核心版(CJCR)的数据为依据,对其中24种综合性医药卫生期刊的年载文量、总被引频次、他引率、影响因子、即年指标、被引半衰期、篇均参考文献量和基金论文比等8项指标进行了统计分析,并与CJCR中收录的全国医科大学学报类的相应数据进行了比较.结果显示,24种综合性医药卫生期刊的整体质量和学术影响力高于CJCR中医科大学学报类期刊的平均水平,但其办刊质量和学术影响力存在较大差异,其评价指标间并不都呈线性关系.因此,对于大多数学报而言,应该扬长避短,再接再厉；对于少部分学报而言,需要采取措施,及时纠正.

OBJECTIVE To investigate the anti-tumor effect of total saponins of Aralia white(TSAW) in vitro and in vivo.METHODS The cytotoxicity of TSAW to mouse B16 melanoma cells,H22 hepatoma cells and FBL3 erythroleukemia cells were tested by cell inhibitory assay.The inhibitory effect of TSAW on S180 and H22 tumor growth were observed in mice.RESULTS The proliferations of B16 cells,FBL3 cells and mice H22 cells were inhibited by TSAW in vitro.IC50 of B16 and FBL3 were 0.077 4 g·L-1and 0.199 g·L-1 respectively.The inhibitory rate of TSAW on H22 cells proliferation was more than 80% in the concentration range 0.02-3.2 g·L-1 in vitro.The inhibitory rates of TSAW on S180 tumor growth were 16.9%,37.1% and 27.0%,at 100,200 and 300 mg·kg oral dose respectively in vivo,and on H22 tumor weight were 23.7%,10% and 13.4% at the same dosage series.CONCLUSION TSAW showed anti-tumor activities in vitro in the concentration range 0.02-3.2 g·L-1 and in vivo with the oral dosage of 200-300 mg·kg-1 in mice.

Objective To observe changes of neuronal nitric oxide synthase and endothelial nitric oxide synthase levels in the physiological aging process of SD rats and investigate the possible mechanism of functional gastrointestinal disorders(FGID) in old people.Methods Twenty-four healthy SD rats were divided into four groups at the age of 3 months,9 months,18 months and 24 months,with six rats in each group.The content of neuronal and endothelial nitric oxide synthase in brain-gut axis(brain,gastric body,jejunum,ileum,sigmoid and rectum) was measured by ELISA in each group.Results Level of neuronal and endothelial nitric oxide synthase in brain-gut axis was decreased with aging,and these changes in the adult rats(9 months,18 months and 24 months old) were more significant(P0.05,P0.01).The distribution of neuronal and endothelial nitric oxide synthase in brain-gut axis was uneven,and this non-uniform distribution did not change with aging.Conclusion The content of neuronal and endothelial nitric oxide synthase in brain-gut axis of SD rats is decreased in the physiological aging process.These changes may participate in the occurrence and development of functional gastrointestinal disorders in old people.

Objective: To observe changes of intestinal sensitivity and Ghrelin levels in serum and brain-gut axis in the physiological aging process of SD rats. Methods: Twenty-four healthy SD rats were divided into four groups according to the age of three months, nine months, eighteen months and twenty-four months, respectively, with six rats in each group. Rectal saccule dilatation which can cause abdominal muscle contraction was applied. Intestinal sensitivity was estimated by the area under the curve (ANC) generated by muscle contraction. The contents of Ghrelin in serum and brain-gut axis were measured by ELISA. Results: (1) After rectal saccule dilatation, 3-month-old rats showed the smallest ANC, and the ANC was expanded with the increase of age, especially in the medium and high intensity of dilatation (all P<0.05). (2) Ghrelin level in serum was the lowest in the 3-month group and the highest in the 9-month group. After that, the serum level of Ghrelin tended to decrease, but without significant difference (P>0.05). (3) Ghrelin level in gastrointestinal tissues tended to increase gradually with age (all P<0.05), and the level in the same age group was as follows: the highest in the body of the stomach (P<0.01), followed by the jejunum and the ileum (P<0.05), and the lowest in the sigmoid colon and the rectum junction (P<0.05). Conclusion: Intestinal sensitivity of SD rats is increased in the process of physiological aging; Ghrelin level in serum is decreased and that in brain-gut axis is increased in the physiological aging process on the whole. These changes may cause gastrointestinal sensory and motor abnormalities, and are possibly involved in the occurrence and development of functional gastrointestinal disorders in old people.