Evaluation of renal markers of T1D in Sprague‐Dawley exposed to 2‐aminoanthracene

The incidence of type 1 diabetes (T1D) and its associated risks of chronic kidney disease or end‐stage renal disease development are on the rise. T1D is an autoimmune disease in which insulin‐producing beta cells are destroyed. Increased incidence of T1D has been suggested to be a result of environmental factors such as exposure to polycyclic aromatic hydrocarbons (PAHs). 2‐aminoanthracene (2AA) is a PAH that has been associated with the onset of early diabetic symptoms. This study was conducted to assess if 2AA dietary ingestion would induce T1D renal injuries. To accomplish study goals, Sprague‐Dawley rats were assigned into three 2AA dietary (0, 50, and 100 mg/kg‐2AA) ingestion groups for 12 weeks. Animals were evaluated for various morphometric indices, clinical markers, and gene expression. The rats in the 100 mg/kg group lost 5% less weight than the other treatment groups and converted roughly 3% more of their food intake into body mass. Renal histopathology indicated no significant difference between groups. The kidney weight per bodyweight of the 100 mg/kg treatment group was 30.1% greater than the control group. Creatinine concentration of the 100 mg/kg group was 46.2% greater than the control group. Serum glucose levels were significantly elevated in rats exposed to 2AA. On the contrary, serum albumin concentration was significantly reduced in 2AA‐treated rats. T1D and genetic markers of renal injury such as FABP1, SPP1, IL‐1B, and IL‐7 were elevated in treated groups. These results suggest that 2AA may induce the early diabetic renal injuries.     

活血通络汤治疗痰瘀阻络型缺血性脑卒中临床研究

目的:探讨活血通络汤治疗痰瘀阻络型缺血性脑卒中的临床疗效和安全性。方法:选取82例痰瘀阻络型缺血性卒中患者作为研究对象,按照其治疗方法分为对照组40例和观察组42例,对照组予以常规西药治疗,观察组患者在对照组治疗基础上予以活血通络汤治疗,两组患者均治疗2周,治疗结束后比较两组患者临床疗效、中医症候积分、神经功能、日常生活能力、血液流变学指标水平及不良反应。结果:经治疗2周后,观察组患者临床治疗总有效率为97.62%,显著高于对照组临床总有效率82.50%(P<0.05); 两组患者治疗前中医症候积分、NIHSS及BI评分比较,差异无统计学意义,治疗后两组患者中医症候积分和NIHSS评分均较治疗前下降,而BI评分显著上升,但治疗后观察组患者中医症候积分和NIHSS评分下降和BI评分上升程度均显著高于对照组患者(P<0.05); 两组患者治疗前全血高切黏度、全血低切黏度、纤维蛋白原及血浆黏度水平比较,差异无统计学意义,治疗后两组患者全血高切黏度、全血低切黏度、纤维蛋白原及血浆黏度水平均较治疗前明显下降,但治疗后观察组患者血液流变学指标水平均低于对照组患者,差异有统计学意义(P<0.05); 两组患者均未出现不良事件。结论:活血通络汤可提高痰瘀阻络型缺血性脑卒中患者临床疗效,改善其症状体征、神经功能及血液状态,提高日常活动能力。     

IGF-1R pathway activation as putative biomarker for linsitinib therapy to revert tamoxifen resistance in ER-positive breast cancer

Preclinical studies indicate that activated IGF-1R can drive endocrine resistance in ER-positive (ER+) breast cancer, but its clinical relevance is unknown. We studied the effect of IGF-1R signaling on tamoxifen benefit in patients and we searched for approaches to overcome IGF-1R-mediated tamoxifen failure in cell lines. Primary tumor blocks from postmenopausal ER+ breast cancer patients randomized between adjuvant tamoxifen versus nil were recollected. Immunohistochemistry for IGF-1R, p-IGF-1R/InsR, p-ERα(Ser118), p-ERα(Ser167) and PI3K/MAPK pathway proteins was performed. Multivariate Cox models were employed to assess tamoxifen efficacy. The association between p-IGF-1R/InsR and PI3K/MAPK pathway activation in MCF-7 and T47D cells was analyzed with Western blots. Cell proliferation experiments were performed under various growth-stimulating and -inhibiting conditions. Patients with ER+, IGF-1R-positive breast cancer without p-IGF-1R/InsR staining (n = 242) had tamoxifen benefit (HR 0.41, p = 0.0038), while the results for p-IGF-1R/InsR-positive patients (n = 125) were not significant (HR 0.95, p = 0.3). High p-ERα(Ser118) or p-ERα(Ser167) expression was associated with less tamoxifen benefit. In MCF-7 cells, IGF-1R stimulation increased phosphorylation of PI3K/MAPK proteins and ERα(Ser167) regardless of IGF-1R overexpression. This could be abrogated by the dual IGF-1R/InsR inhibitor linsitinib, but not by the IGF-IR-selective antibody 1H7. In MCF-7 and T47D cells, stimulation of the IGF-1R/InsR pathway resulted in cell proliferation regardless of tamoxifen. Abrogation of cell growth was regained by addition of linsitinib. In conclusion, p-IGF-1R/InsR positivity in ER+ breast cancer is associated with reduced benefit from adjuvant tamoxifen in postmenopausal patients. In cell lines, stimulation rather than overexpression of IGF-1R is driving tamoxifen resistance to be abrogated by linsitinib.     

基于BGP、TGF-β1的表达探究蛇床子素对去卵巢致骨质疏松大鼠的作用

目的观察蛇床子素对去卵巢致骨质疏松大鼠的影响。方法选取3月龄雌性SD大鼠30只,随机分为蛇床子素组(A组)、模型对照组(B组)、假手术组(C组),各10只。A、B 2组摘除卵巢构建去势大鼠骨质疏松模型,C组仅进行手术、不摘除卵巢。造模成功后,分别给予相应药物灌胃,连续给药12周,处死。然后测量骨密度,检测治疗后血清BGP、TGF-β1、钙指标。结果B组大鼠股骨骨密度较C组明显降低(P<0.05);经12周治疗,A组股骨骨密度较B组明显升高(P<0.05)。与C组比较,B组大鼠血清中BGP含量升高、TGF-β1降低(P<0.05);与B组比较,A组大鼠血清中BGP降低、TGF-β1含量升高(P<0.05)。与C组比较,B组大鼠血清Ca水平明显降低(P<0.05);与B组比较,A组大鼠血清Ca水平明显升高(P<0.05)。差异均有统计学意义。结论蛇床子素能够有效通过调节大鼠体内激素分泌改善去卵巢大鼠的骨代谢异常,提高骨密度,对骨质疏松症起到一定的防治作用。     

中西医结合诊治新型冠状病毒肺炎的几点思考

结合病案1则,探讨中西医结合诊疗新型冠状病毒肺炎的几个共性问题。认为本病患者除呼吸道表现外,消化道症状同样较为突出。早期诊断及治疗评价将肺部CT检查和病毒核酸检查综合分析;中期着重毒痰瘀,用药防肝损;晚期应肺肠同治;恢复期多健脾益肺,活血化瘀。     

加味黄芪建中汤治疗脾阳虚型胃肠功能紊乱临床研究

目的:观察加味黄芪建中汤治疗脾阳虚型功能性胃肠功能紊乱的临床疗效。方法:将患者随机分成2组,对照组用枸橼酸莫沙比利治疗,治疗组运用枸橼酸莫沙比利治疗的基础上加用加味黄芪建中汤治疗,均治疗共4疗程。观察临床疗效及中医症状评分情况。结果:对照组有5例患者失访,疗效结束后显效率治疗组36.0%,对照组20.0%,2组比较,差异有统计学意义(P<0.05);治疗后2组胃脘痞满、食欲减退、神疲乏力评分与治疗前比较,差异有统计学意义(P<0.05),2组胃脘痞满、食欲减退以及神疲乏力等评分分别比较,差异均有统计学意义(P<0.01)。结论:加味黄芪建中汤能改善脾阳虚型胃肠功能紊乱的症状,有良好的临床疗效,优于单纯使用枸橼酸莫沙必利治疗。     

通心络胶囊联合阿托伐他汀及氯吡格雷治疗冠心病心绞痛临床研究

目的:观察通心络胶囊联合阿托伐他汀、氯吡格雷治疗冠心病心绞痛的临床疗效。方法:选取84例冠心病心绞痛患者,按随机数字表法分为观察组与对照组,对照组40例给予阿托伐他汀联合氯吡格雷治疗,观察组44例在对照组基础上给予通心络胶囊治疗,3个月后比较2组临床疗效。结果:观察组总有效率(93.18%)显著高于对照组(70.00%),差异有统计学意义(P<0.05)。治疗前,2组心绞痛的持续时间、心绞痛发作次数、心功能指标、血管内皮功能指标比较,差异无统计学意义(P>0.05)。治疗后,2组心绞痛持续时间、心绞痛发作次数较治疗前明显降低,观察组心绞痛持续时间、心绞痛发作次数显著低于对照组(P<0.05);2组心功能指标包括心输出量(CO)、心博出量(SV)、心脏指数(CI)及射血分数(EF)均较治疗前明显上升,且观察组各项心功能指标明显高于对照组(P<0.05);2组内皮功能指标内皮素(ET)、血栓素B2(TXB2)水平较治疗前明显降低,一氧化氮(NO)水平较治疗前明显上升(P<0.05),观察组ET、TXB2水平明显低于对照组,NO水平明显高于对照组(P<0.05)。结论:对冠心病心绞痛患者给予通心络胶囊联合阿托伐他汀、氯吡格雷治疗疗效显著,可有效降低心绞痛持续时间和发作次数,改善患者心功能和内皮功能,值得临床推广应用。     

PRKAA1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells Through Activating JNK1 and Akt Pathways

PRKAA1 (protein kinase AMP-activated catalytic subunit 1) is a catalytic subunit of AMP-activated protein kinase (AMPK), which plays a key role in regulating cellular energy metabolism through phosphorylation, and genetic variations in the PRKAA1 have been found to be associated with gastric cancer risk. However, the effect and underlying molecular mechanism of PRKAA1 on gastric cancer tumorigenesis, especially the proliferation and apoptosis, are not fully understood. Our data showed that PRKAA1 is highly expressed in BGC- 823 and MKN45 cells and is expressed low in SGC-7901 and MGC-803 cells in comparison with the other gastric cancer cells. PRKAA1 downregulation by shRNA or treatment of AMPK inhibitor compound C significantly inhibited proliferation as well as promoted cell cycle arrest and apoptosis of BGC-823 and MKN45 cells. Moreover, the expression of PCNA and Bcl-2 and the activity of JNK1 and Akt signaling were also reduced in BGC-823 and MKN45 cells after PRKAA1 downregulation. In vivo experiments demonstrated that tumor growth in nude mice was significantly inhibited after PRKAA1 silencing. Importantly, inactivation of JNK1 or Akt signaling pathway significantly inhibited PRKAA1 overexpression-induced increased cell proliferation and decreased cell apoptosis in MGC-803 cells. In conclusion, our findings suggest that PRKAA1 increases proliferation and restrains apoptosis of gastric cancer cells through activating JNK1 and Akt pathways.     

IMRT联合TP方案治疗晚期食管鳞癌的临床疗效及对患者血清MMP2、TIMP2、nm23-H1及不良反应的影响

目的分析调强放射治疗(IMRT)联合TP方案治疗晚期食管鳞癌的临床疗效及对患者血清基质金属蛋白酶2(MMP2)、组织金属蛋白酶抑制剂2(TIMP2)、nm23-H1及不良反应的影响。方法选取晚期食管鳞癌患者80例为研究对象,按随机数字表法将其分为观察组(n=40,采用IMRT联合TP方案化疗)、对照组(n=40,单纯采用IMRT治疗),比较2组临床疗效、治疗前后血清MMP2、TIMP2、nm23-H1表达阳性率、局控率与生存情况及不良反应。结果观察组治疗有效率(85.00%)明显高于对照组(65.00%)(P<0.05)。治疗后2组血清MMP2表达阳性率下降,而TIMP2、nm23-H1表达阳性率上升,且观察组治疗后血清MMP2表达阳性率低于对照组,而TIMP2、nm23-H1表达阳性率高于对照组(P<0.05)。观察组治疗后1年、2年局控率高于对照组,但2组治疗后1年、2年生存率差异无统计学意义(P>0.05)。观察组白细胞减少、放射性食管炎发生率高于对照组(P<0.05),2组其他不良反应发生率差异无统计学意义(P>0.05)。结论晚期食管癌患者采用IMRT联合TP方案治疗可获得较好的疗效,对患者血清MMP2、TIMP2、nm23-H1有明显改善,但可能会较单纯IMRT治疗具有更多不良反应,需加以监测。