达格列净对2型糖尿病患者血、尿电解质的影响

目的 观察单用二甲双胍血糖控制不佳（糖化血红蛋白,HbA1c＞7.5%）的2型糖尿病（T2DM）患者,应用达格列净后对血电解质（血钠、血钾、血钙）、尿电解质（24小时尿钠、24小时尿钾、24小时尿钙）、尿渗透浓度及其他代谢指标的影响,评估用药后的安全性。方法 选取在2017年9月至2019年4月期间,于沧州市人民医院本部院区内分泌门诊及住院部就诊的103例T2DM患者,按照随机抽样法分成对照组（55例）和试验组（48例）。对照组给予二甲双胍治疗,试验组给予二甲双胍联合达格列净治疗。观察用药24周后患者血电解质、尿电解质、尿渗透浓度及其他代谢指标较基线和对照组的变化以及评估用药的安全性。结果 治疗24周后,试验组的尿电解质、尿渗透浓度水平较基线及对照组均有所升高,差异有统计学意义(P＜0.05);试验组的血糖参数、总胆固醇（TC）、甘油三酯（TG）、24小时尿蛋白、体重指数（BMI）、体重水平较基线及对照组降低,差异存在统计学意义(P＜0.05);血电解质、尿pH、低密度脂蛋白胆固醇（LDL C）、高密度脂蛋白胆固醇（HDL C）、估算的肾小球滤过率（eGFR）水平较基线及对照组无明显变化,差异无统计学意义(P＞0.05)。结论 在单用二甲双胍控制不佳的T2DM患者中联合应用达格列净治疗,可有降低血糖、改善血脂、减轻体重、减少尿蛋白等多重获益,虽然会引起尿电解质增多及尿渗透浓度升高,但血电解质水平无明显改变,无严重不良事件发生,使用上更安全。     

产前筛查在胎儿先天性心脏病中的诊断价值

目的：探讨产前筛查在胎儿先天性心脏病中的诊断价值.材料与方法：分析2700例自2011年1月——2012年12月期间到我院行产前超声系统筛查的中晚期孕妇,入选孕周18-42周.结果：受检者中,胎儿先天性心脏病共27例,其中：室间隔缺损5例;法洛氏四联症4例;三尖瓣闭锁3例（2例合并房间隔缺损及单脐动脉,1例合并肺动脉狭窄）;三尖瓣下移畸形、单房单室、完全型大动脉转位各2例;矫正型大动脉转位1例;完全型心内膜垫缺损、部分型心内膜垫缺损、肺静脉导位引流、永存动脉干、左室发育不全各1例;漏诊3例.结论：产前筛查在胎儿先天性心脏畸形中具有较高的临床价值.     

Diagnostic Value of Automated 3D Ultrasound for Incisional Hernia

The automated volume scanning system (AVSS) has been applied in breast diseases, but its use in incisional hernias has not been reported. In this study, conventional handheld B-mode ultrasound (HHUS) and AVSS examined a total of 122 hernia defects in 78 patients. The results from two modalities were then compared with surgical findings for the purpose of assessing the diagnostic value of AVSS. Statistics showed that surgeries identified 38 small, 23 medium and 17 large incisional hernias. The results of AVSS completely agreed with surgical findings; however, HHUS misidentified nine large hernias as medium and seven medium hernias as large. AVSS proved to be more accurate than HHUS in measuring the length and width of the hernia. It also outperformed HHUS in both detecting the incisional hernias (91.8% vs. 78.7%, p = 0.00) and determining hernia contents (89.3% vs. 68.0%, p = 0.00). Moreover, the coronal images AVSS obtained clearly displayed the shapes of the hernias, with 46 being regular and 32 irregular. Overall, AVSS can be used as a promising diagnostic modality for incisional hernias.     

Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway.     

Silicon-Carbon bond cleavage reactions of Ansa tungstenocene compounds: the [Me2Si] bridge as a site for metallocene functionalization

[Me(2)Si(Cp(Me(2)))(2)]W(H)Cl is obtained via reaction of WCl(6) with a mixture of [Me(2)Si(Cp(Me(2)))(2)]Li(2) and NaBH(4), from which the dichloride [Me(2)Si(Cp(Me(2)))(2)]WCl(2) is obtained via treatment with CHCl(3). [Me(2)Si(Cp(Me(2)))(2)]WCl(2) provides a means to access other ansa tungstenocene compounds, such as [Me(2)Si(Cp(Me(2)))(2)]WH(2), [Me(2)Si(Cp(Me(2)))(2)]WMe(2), and [Me(2)Si(Cp(Me(2)))(2)]WCO. Of most interest, the reactions of [Me(2)Si(Cp(Me(2)))(2)]W(H)Cl with organolithium reagents do not yield simple ansa tungstenocene derivatives. Specifically, the reactions of [Me(2)Si(Cp(Me(2)))(2)]W(H)Cl with MeLi, Bu(n)Li, or PhLi result in the formation of mixed-ring tungstenocene compounds resulting from C-Si cleavage and functionalization of the ansa bridge, namely (Cp(Me(2)))(eta(5),kappa(1)-C(5)H(2)Me(2)SiMe(2)CH(2))WH, (Cp(Me(2)))[eta(5),kappa(1)-C(5)H(2)Me(2)Si(Me)(Bu(n))CH(2)]WH, and (Cp(Me(2)))[eta(5),kappa(1)-C(5)H(2)Me(2)SiMe(2)(C(6)H(4))]WH, respectively. In contrast to the C-Si cleavage achieved by MeLi, Bu(n)Li, and PhLi, the ansa bridge of [Me(2)Si(Cp(Me(2)))(2)]W(H)Cl is inert to Bu(t)Li and the product obtained is the fulvene ("tuck-in") complex [Me(2)Si(Cp(Me(2)))(eta(6)-C(5)MeH(2)CH(2))]WH derived from dehydrohalogenation.     

Cell-surface expression, progestin binding, and rapid nongenomic signaling of zebrafish membrane progestin receptors alpha and beta in transfected cells

Recently, a unique family of membrane progestin receptors (mPRalpha, mPRbeta, and mPRgamma) was identified, which may be responsible for mediating rapid, nongenomic actions of progestins in a variety of target tissues. In this study, the mPRalpha and mPRbeta isoforms from zebrafish were shown to be rapidly and specifically activated by the maturation-inducing steroid (MIS) of this species, 4-pregnen-17,20beta-diol-3-one (17,20beta-DHP). The zebrafish mPRalpha and a previously uncharacterized mPRbeta isoform were stably expressed in nuclear progesterone receptor-deficient mammalian breast cancer cells, MDA-MB-231. Expression and surface localization of the receptors were verified by flow cytometry, biotin surface labeling, and Western blotting. Plasma membrane proteins from mPRalpha- or mPRbeta-transfected cells showed high affinity (mPRalpha, K(d) 7 nM; mPRbeta, K(d) 12 nM), saturable, displaceable, single-binding sites specific for 17,20beta-DHP, whereas negligible specific 17,20beta-DHP binding was observed in nontransfected cells. Progestin treatment caused significant activation of mitogen-activated protein kinase (MAPK) within 5 min in cells transfected with either of the receptors as measured by western blotting and flow cytometry. The rank order of the potencies of several progestins in activating MAPK via mPRalpha and mPRbeta was the same (17,20beta-DHP>progesterone >4-pregnen-17,20beta,21-triol-3-one). Interestingly, the MIS in zebrafish, 17,20beta-DHP, was also the most potent inhibitor, among the progestins tested, of adenylyl cyclase activity in cells transfected with either of the receptors. This progestin significantly decreased cAMP levels in both mPRalpha- and mPRbeta-transfected cells in a dose-responsive and time-dependent manner. In addition, signaling of the zebrafish mPRalpha was blocked by pertussis toxin, implying activation of a G(i) protein, while sensitivity to pertussis or cholera toxin was not shown with mPRbeta-mediated signaling, possibly indicating that this receptor activates a different pertussis toxin-insensitive G protein. The results of this study suggest that zebrafish mPRalpha and mPRbeta signal similarly upon progestin binding resulting in rapid activation of MAPK and downregulation of adenylyl cyclase activity.     

肝纤维化的干细胞治疗进展

近年来国内外研究表明,在个体发育的不同阶段及不同成体组织中均存在着干细胞.肝脏内不仅存在肝源性干细胞,还存在其他组织来源的干细胞(如骨髓干细胞,胰腺干细胞等),这些干细胞最终可以分化为成熟的肝样细胞.因此,干细胞的替代疗法为终末期肝病患者的肝纤维化治疗提供了新的思路.本文就近年来干细胞治疗肝纤维化方面的相关研究进展作一综述.     

糖尿病大鼠心力衰竭时心肌细胞凋亡的研究

目的探讨糖尿病大鼠心力衰竭时是否存在心肌细胞凋亡.方法建立STZ糖尿病大鼠模型,饲养12周,经心功能检测后确认为糖尿病心力衰竭的大鼠,采用TUNEL法及TEM法,检测糖尿病大鼠左室心肌的凋亡细胞.结果 糖尿病大鼠出现心功能异常并可见凋亡的心肌细胞,而对照组左室心肌组织中未见心肌细胞凋亡.结论心肌细胞凋亡与糖尿病大鼠心力衰竭密切相关.