The third-generation retinoid adapalene triggered DNA damage to induce S-phase arrest in HaCat cells

Epidermal proliferative diseases consisted of a series of common skin diseases, most of which were recurrent chronic skin diseases, and had greatly negative influence on the life quality of patient. Retinoids exhibited vital roles in the treatment of many skin diseases. Our recent study demonstrated that adapalene significantly inhibited the growth of HaCat cells, and the inhibitory activity was stronger than other retinoids, such as all-trans-retinoic acid, acitretin, isotretinoin, tazarotene, and bexarotene. Further study showed that adapalene suppressed the colony formation of HaCat cells, and it dramatically triggered S-phase arrest and apoptosis, rather than G1 phase arrest which was reported in other retinoids in several studies. Additionally, adapalene treatment greatly upregulated the protein expression of DNA damage marker γ-H2AX, which was in accord with the results of the elongation of tail moment by comet electrophoresis analysis. Moreover, DNA damage was triggered and DNA repair was suppressed synchronously with adapalene treatment, which accounted for the mechanism of S-phase arrest induced by adapalene. In summary, our recent work demonstrated that adapalene showed strong anti-proliferation activity in HaCat cells and could be an alternative agent for the epidermal proliferative disease.     

男性类风湿关节炎患者骨量减低的相关研究

目的探讨男性类风湿关节炎(rheumatoid arthriti,RA)患者骨量减低的相关情况及合并骨质疏松的危险因素。方法收集2013年8月至2019年5月在苏州大学附属常州市肿瘤医院诊治的男性类风湿关节炎患者38例,年龄(64. 39±9. 44)岁,对照组为40例健康正常人群,年龄(63. 53±8. 14)岁。通过双光能X线骨密度仪测定正位腰椎(L1～4)及左侧股骨近端(包括FN、Troch、Ward、Total)骨密度;运用电化学发光免疫分析法检测BAP、BGP、CTX;记录RA患者的ESR、CRP、关节肿胀及压痛数、RF以及CCP等情况。分析比较两组骨密度及骨生化指标的差异,并采用单因素分析和多因素Logistic回归分析调查类风湿关节炎患者合并骨质疏松的危险因素。结果两组间年龄、体质量指数(body mass index,BMI)差异无统计学意义(P0. 05)。类风湿关节炎组左侧股骨颈、整体髋骨BMD测量值较对照组减低(P0. 05);且类风湿关节炎组骨量减少、骨质疏松发生率较对照组显著增高(P0. 05);在骨生化指标方面,类风湿关节炎组CTX水平高于对照组(P0. 05)。单因素分析显示BMI、CRP、DAS28-ESR及CTX与男性类风湿关节炎患者继发骨质疏松相关(P0. 05);多因素Logistic回归分析显示,BMI 18. 5 kg/m2(OR=0. 014),DAS28-ESR5. 1(OR=21. 433)及CTX0. 7 ng/m L(OR=25. 875)是男性类风湿关节炎继发骨质疏松的独立危险因素(P0. 05)。结论男性类风湿关节炎患者同样易合并骨质疏松的发生,BMI、DAS28及CTX等危险因素应高度重视。     

丹白颗粒联合阿奇霉素治疗慢性盆腔炎的疗效分析

目的：探究丹白颗粒联合阿奇霉素对慢性盆腔炎的治疗效果。方法：选取2018年12月至2019年2月山东省日照市人民医院收治的支原体感染导致的慢性盆腔炎患者110例作为研究对象，按照随机数字表法分为对照组和观察组，每组55例。对照组患者单纯给予阿奇霉素治疗，观察组患者在对照组基础上加用丹白颗粒治疗。观察2组患者治疗期间的显效时间、临床疗效、不良反应和复发率发生情况。治疗前、治疗后子宫低切全血黏度、高切全血黏度、血浆黏度、红细胞聚集指数、红细胞压积（%）、红细胞沉降率和纤维蛋白原血流动力学指标的变化情况以及TNF-α、IL-8和IL-10的水平变化情况。结果观察组显效时间显著低于对照组；观察组总有效率为98.2%，显著高于对照组的90.9%；观察组的不良反应的复发率发生情况同样显著低于对照组；2组患者血流动力学各项指标与组内治疗前比较，差异均有统计学意义（P均＜0.05）；治疗后观察组患者血流变学各项指标与对照组比较，差异均有统计学意义（P均＜0.05）；2组患者治疗后TNF-α、IL-8和IL-10水平均比组内治疗前显著降低；与对照组比较，观察组TNF-α、IL-8和IL-10水平下降更明显，差异均有统计学意义（P均＜0.05）。结论：丹白颗粒联阿奇霉素治疗慢性盆腔炎可能是通过影响患者血液中TNF-α、IL-8和IL-10表达水平来改善其子宫血流动力学指标，最终提高治疗，降低复发率和不良反应发生率。     

不同基原土牛膝的性状显微比较研究

目的 建立3种不同基原的土牛膝的性状及显微鉴别方法。方法 在植物分类学鉴定基础上，对不同基原的土牛膝进行鉴定，并使用性状和显微研究方法，对采集的土牛膝进行比较分析。结果 通过研究发现，3种土牛膝可以通过横切面显微特征区分，粉末显微特征区别不明显。结论 土牛膝不同基原可以通过性状、显微进行鉴别,通过对二者性状、显微的细致研究，为相关的标准修订与提高提供依据。     

Expression and effect of sodium-potassium-chloride cotransporter on dorsal root ganglion neurons in a rat model of chronic constriction injury

Sodium-potassium-chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) are associated with the transmission of peripheral pain.We investigated whether the increase of NKCC1 and KCC2 is associated with peripheral pain transmission in dorsal root ganglion neurons.To this aim,rats with persistent hyperalgesia were randomly divided into four groups.Rats in the control group received no treatment,and the rat sciatic nerve was only exposed in the sham group.Rats in the chronic constriction injury group were established into chronic constriction injury models by ligating sciatic nerve and rats were given bumetanide,an inhibitor of NKCC1,based on chronic constriction injury modeling in the chronic constriction injury + bumetanide group.In the experiment measuring thermal withdrawal latency,bumetanide (15 mg/kg) was intravenously administered.In the patch clamp experiment,bumetanide (10 μg/μL) and acutely isolated dorsal root ganglion neurons (on day 14) were incubated for 1 hour,or bumetanide (5 μg/μL) was intrathecally injected.The Hargreaves test was conducted to detect changes in thermal hyperalgesia in rats.We found that the thermal withdrawal latency of rats was significantly decreased on days 7,14,and 21 after model establishment.After intravenous injection of bumetanide,the reduction in thermal retraction latency caused by model establishment was significantly inhibited.Immunohistochemistry and western blot assay results revealed that the immune response and protein expression of NKCC1 in dorsal root ganglion neurons of the chronic constriction injury group increased significantly on days 7,14,and 21 after model establishment.No immune response or protein expression of KCC2 was observed in dorsal root ganglion neurons before and after model establishment.The Cl^– (chloride ion) fluorescent probe technique was used to evaluate the change of Cl^– concentration in dorsal root ganglion neurons of chronic constriction injury model rats.We found that the relative optical density of N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (a Cl^– fluorescent probe whose fluorescence Cenintensity decreases as Cl– concentration increases) in the dorsal root ganglion neurons of the chronic constriction injury group was significantly decreased on days 7 and 14 after model establishment.The whole-cell patch clamp technique revealed that the resting potential and action potential frequency of dorsal root ganglion neurons increased,and the threshold and rheobase of action potentials decreased in the chronic constriction injury group on day 14 after model establishment.After bumetanide administration,the above indicators were significantly suppressed.These results confirm that CCI can induce abnormal overexpression of NKCC1,thereby increasing the Cl^– concentration in dorsal root ganglion neurons;this then enhances the excitability of dorsal root ganglion neurons and ultimately promotes hyperalgesia and allodynia.In addition,bumetanide can achieve analgesic effects.All experiments were approved by the Institutional Ethics Review Board at the First Affiliated Hospital,College of Medicine,Shihezi University,China on February 22,2017 (approval No.A2017-169-01).     

B7-H4及Fas、FasL与宫颈癌免疫逃逸机制的关系

目的:检测免疫共刺激分子B7-H4及Fas、FasL在不同宫颈组织中的表达，研究三者的异常表达与宫颈癌免疫逃逸机制的关系。方法:选择陕西省肿瘤医院病理科2014-2018年的石蜡包埋标本162例，采用免疫组织化学方法检测20例正常宫颈、30例宫颈上皮内瘤变(CIN)和112例I期-IV期宫颈癌组织中B7-H4及Fas、FasL的表达水平。结果:B7-H4在正常宫颈组、CIN组、宫颈癌组的阳性表达率分别为0、20.0%、47.32%，两两相比，具有显著性差异（P<0.05）。在112例宫颈癌病例中FIGO临床分期I期至IV期各期别宫颈癌组织B7-H4的阳表达率分别为16.67%、43.18%、70.83%、85.71%，各组间相比差异具有统计学意义。正常对照组Fas的阳性表达率是85.00％，CIN组43.33％，宫颈癌组41.96％，正常组与CIN、正常组与宫颈癌组相比差异均具有统计学意义（P<0.05），CIN组与宫颈癌组相比，无明显差异（P>0.05）。FasL的阳性表达率在正常组为20.00%，CIN组为50.00%，宫颈癌组为56.25%，正常组与CIN、宫颈癌组比较，差异具有统计学意义(P<0.05)，CIN组与宫颈癌组比较无显著差异;B7-H4阳性宫颈癌组Fas阳性表达率28.30%明显较B7-H4阴性宫颈癌组Fas阳性表达率54.24%低，差异具有统计学意义（P<0.05）；而B7-H4阳性宫颈癌组FasL阳性表达率79.25%明显高于B7-H4阴性宫颈癌组FasL阳性表达率35.59%，差异具有统计学意义（P<0.05）。结论:负性免疫共刺激分子B7-H4和Fas、FasL凋亡蛋白在宫颈癌的发生、进展中起到了重要作用，其协同作用可能为宫颈癌细胞逃逸机体免疫的机制之一。     

Plastin 1 drives metastasis of colorectal cancer through the IQGAP1/Rac1/ERK pathway

Tumor metastasis is the dominant cause of death in colorectal cancer (CRC) patients, and it often involves dysregulation of various cytoskeletal proteins. Plastin 1 (PLS1) is an actin‐bundling protein that has been implicated in the structure of intestinal epithelial microvilli; however, its role in CRC metastasis has not yet been determined. In this study, we demonstrated that PLS1 is highly expressed in 33.3% (45/135) of CRC patients and is correlated with lymph node metastasis and poor survival. In in vitro and in vivo experiments, PLS1 induced the migration and invasion of CRC cells and the metastases to the liver and lung in mice. Moreover, the expressions of key factors for CRC metastases, matrix metalloproteinase (MMP) 9 and 2, were enhanced by PLS1, which was dependent on phosphorylating ERK1/2 activated by IQGAP1/Rac1 signaling. The connection between these signals and PLS1 was further confirmed in CRC tissues of patients and the metastatic nodules from a mouse model. These findings suggest that PLS1 promotes CRC metastasis through the IQGAP1/Rac1/ERK pathway. Targeting PLS1 may provide a potential approach to inhibit the metastasis of CRC cells.     

煮炸鹿茸加工过程中晚期糖基化终产物生成规律及动力学分析

目的研究煮炸鹿茸加工过程中晚期糖基化终产物的生成规律及动力学参数。方法通过构建葡萄糖与赖氨酸模拟煮炸鹿茸加工过程美拉德(Maillard)反应体系,分别采用紫外-可见分光光度法和UPLC-MS/MS法测定体系褐变指数和典型晚期糖基化终产物(羧甲基赖氨酸和羧乙基赖氨酸)含量变化,探讨晚期糖基化终产物的生成规律和动力学参数。结果鹿茸加工过程中煮炸时发生褐变反应,生成羧甲基赖氨酸和羧乙基赖氨酸反应的活化能分别为5.07、40.44、78.47 kJ/mol,且均为零级反应;烘烤时相应反应的活化能分别为6.72、89.34、164.77 kJ/mol,也均为零级反应。相对于生成羧甲基赖氨酸而言,生成羧乙基赖氨酸所需能量更高,反应更难发生。结论烘烤过程温度变化对晚期糖基化终产物的动力学参数影响显著高于煮炸过程,长时间较高温度的烘烤使鹿茸中产生了较多的晚期糖基化终产物,这些结果为鹿茸加工过程中晚期糖基化终产物的阻断、抑制策略提供了理论基础,对生产绿色安全的鹿茸及加强中药安全具有重要意义。     

基于文献计量学骶髂关节半脱位影像学诊断标准的探讨

目的:基于文献计量学方法,探讨分析骶髂关节半脱位的影像学诊断标准。方法:回顾2017年5月30日前有关骶髂关节半脱位的中文文献,对文献中骶髂关节半脱位的病因及影像学诊断标准进行归纳分析。结果:共纳入283篇符合要求的文献,167篇有影像学诊断标准,骨盆X线正位片和斜位片是最常用的诊断方法,骶髂关节间隙增宽或狭窄、双侧髂嵴不等高、骶髂关节密度增高或粗糙和骶髂关节间隙模糊是报道最多的几种影像学依据,文献中的骶髂关节间隙变化和髂嵴高度异常标准不统一。结论:骶髂关节半脱位的影像学诊断依据混乱,关节间隙和髂嵴高度差异等可能的依据也常见于强直性脊柱炎等疾病,以上标准仍存在一些问题。