伊贝母异甾体生物碱通过Wnt/β-catenin信号通路调节哮喘大鼠气道炎症和气道重塑机制的研究

目的 探讨伊贝母异甾体生物碱对哮喘大鼠气道炎症、气道重塑及Wnt/β-catenin信号通路的影响。方法 本研究采用吸入卵清蛋白（OVA）致敏和激发的方法建立大鼠哮喘模型，连续给予药物7天；抽取支气管肺泡灌洗液（BALF）进行白细胞分类计数，酶联免疫吸附法（ELISA）检测BALF中白介素4（IL-4）、白介素5（IL-5）和白介素13（IL-13）的水平；取肺组织进行苏木精-伊红（HE）染色，观察药物对哮喘大鼠气道重塑的影响；采用Western blot技术考察异甾体生物碱对Wnt/β-catenin信号通路上Wnt5a、Wnt7b和β-catenin蛋白的调节作用。结果 与模型组比较，异甾体生物碱组大鼠肺泡间质炎性细胞浸润和支气管管腔狭窄均显著改善，支气管壁厚度和平滑肌厚度均明显降低；Western blot结果显示异甾体生物碱对于哮喘大鼠Wnt/β-catenin通路上的Wnt5a、Wnt7b和β-catenin蛋白表达均有显著的调节作用。结论 异甾体生物碱对于哮喘相关的病理变化-炎症和气道重塑均有一定的治疗作用，且该治疗作用与Wnt/β-catenin信号通路有关。     

Functional characterization of 21 CYP3A4 variants on amiodarone metabolism in vitro

1. Cytochrome P450 3A4 (CYP3A4) is an important member of the cytochrome P450 enzyme superfamily, with 33 allelic variants reported previously. Genetic polymorphisms of CYP3A4 can produce a significant effect on the efficacy and safety of some drugs, so the purpose of this study was to clarify the catalytic characteristics of 22 CYP3A4 allelic isoforms, including 6 novel variants in Han Chinese population, on the oxidative metabolism of amiodarone in vitro.

2. Wild-type CYP3A4*1 and other variants expressed by insect cells system were incubated respectively with 10–500?μM substrate for 40?min at 37?°C and terminated at ?80?°C immediately. Then these samples were treated as required and detected with ultra-performance liquid chromatography-tandem mass spectrometry used to analyze its major metabolite desethylamiodarone.

3. Among the 21 CYP3A4 variants, compared with the wild-type, the intrinsic clearance values (V_max/K_m) of two variants were apparently decreased (11.07 and 2.67% relative clearance) while twelve variants revealed markedly increased values (155.20～435.96%), and the remaining of seven variants exhibited no significant changes in enzyme activity.

4. This is the first time report describing all these infrequent alleles for amiodarone metabolism, which can provide fundamental data for further clinical studies on CYP3A4 alleles.     

壮药材滇桂艾纳香及其易混品种东风草和高艾纳香比较研究

目的： 建立壮药材滇桂艾纳香专属性检验方法。方法： 采用基原鉴别、性状鉴别、显微鉴别、薄层鉴别、分子生物学及特征图谱等方法对滇桂艾纳香及其易混品种东风草和高艾纳香进行对比研究。结果： 三者的根、茎、叶性状基本相同，区别点在于滇桂艾纳香头状花序小（直径0.5~0.8 cm），东风草头状花序大（直径1.5~2 cm），高艾纳香头状花序具密集的长绒毛；三者的根、茎横切面，粉末显微特征基本相同，高艾纳香具基部膨大的非腺毛；薄层鉴别（1）中高艾纳香比滇桂艾纳香和东风草少1个斑点；薄层鉴别（2）中滇桂艾纳香比东风草和高艾纳香少1个特征斑点；ITS2序列N-J树聚类分析显示三者具有良好的单系性，三者种间最小遗传距离均大于种内最大遗传距离；与滇桂艾纳香对照图谱相比，东风草平均相似度为0.962，高艾纳香平均相似度仅为0.789。结论： 高艾纳香与滇桂艾纳香区别较大，不宜混用，在日常使用中应注意甄别；东风草与滇桂艾纳香在性状、显微、薄层、分子生物学、特征图谱等方面相似度较高，在对二者进行充分的药理活性以及临床试验等基础上，可考虑作为滇桂艾纳香的替代品使用，以缓解药用资源不足的问题。     

急性胰腺炎伤寒六经平脉辨证体系探索

急性胰腺炎中医病因病机复杂,临床表现烦冗多变,传统中医辨证分型粗略,尚不能精准指导急性胰腺炎的中医药治疗。本文基于急性胰腺炎"热病观"和相关指南共识,结合八纲辨证和伤寒六经,拟建立急性胰腺炎的六经平脉辨证体系,以期促进急性胰腺炎的中医药治疗。     

超声引导经肩袖间隙注射治疗冻结肩的临床研究

目的探讨超声引导经肩袖间隙肩关节腔和三角肌下滑囊注药治疗冻结肩的可行性与临床疗效。 方法选取2020年3月至2021年3月于解放军总医院第一医学中心确诊的65例冻结肩患者进行超声引导经肩袖间隙肩关节腔和三角肌下滑囊注药治疗。治疗前超声检查测量肩袖间隙处肱二头肌长头肌腱至皮肤的最短距离和喙肱韧带的厚度，分别于治疗前和治疗后1周、1个月及3个月行视觉模拟量表（VAS）疼痛评分以及Constant量表和美国加利福尼亚大学（UCLA）量表肩关节功能评分。 结果治疗前测量肱二头肌长头肌腱至皮肤最短距离为（11.81±2.52）mm，喙肱韧带厚度平均为（2.69±0.42）mm。所有患者均成功进行超声引导经肩袖间隙肩关节腔和三角肌下滑囊注药治疗。与治疗前评分比较，治疗后1周、1个月和3个月的VAS疼痛评分随时间延长而降低，两两比较差异均有统计学意义（P均＜0.008）。与治疗前比较，治疗后1个月、3个月Constant量表和UCLA量表的肩关节功能评分得到改善，评分比较差异均有统计学意义（P均＜0.016）；与治疗后1个月比较，治疗后3个月Constant量表和UCLA量表的肩关节功能评分改善不明显，评分比较差异无统计学意义（P＞0.016）。与治疗前相比，治疗后1个月、3个月Constant量表中的疼痛程度、日常生活能力、肩关节活动程度和肌力均得到改善，评分比较差异均有统计学意义（P均＜0.016）；与治疗后1个月相比，治疗后3个月的疼痛程度、日常生活能力、肩关节活动度和肌力均未见进一步改善，评分差异均无统计学意义（P均＞0.016）。 结论超声引导经肩袖间隙注射可一次进针实现肩关节腔和三角肌下滑囊2个部位的注射，临床短期疗效满意，可作为冻结肩超声引导微创治疗的方案之一。     

Heparanase-1 is downregulated in chemoradiotherapy orbital rhabdomyosarcoma and relates with tumor growth as well as angiogenesis

AIM:To determine the role of heparanase-1(HPSE-1)in orbital rhabdomyosarcoma(RMS),and to investigate the feasibility of HPSE-1 targeted therapy for RMS.METHODS:Immunohistochemistry was performed to analyze HPSE-1 expression in 51 cases of orbital RMS patients(including 28 cases of embryonal RMS and 23 cases of alveolar RMS),among whom there were 27 treated and 24 untreated with preoperative chemoradiotherapy.In vitro,studies were conducted to examine the effect of HPSE-1 silencing on RMS cell proliferation and tube formation of human umbilical vein endothelial cells(HUVECs).RD cells(an RMS cell line)and HUVECs were infected with HPSE-1 sh RNA lentivirus at a multiplicity of infection(MOI)of 10 and 30 separately.Real-time PCR and Western blot were applied to detect the m RNA and protein expression levels of HPSE-1.Cell viability of treated or control RD cells was evaluated by cell counting kit-8(CCK-8)assay.Matrigel tube formation assay was used to evaluate the effect of HPSE-1 RNAi on the tube formation of HUVECs.RESULTS:Immunohistochemistry showed that the expression rate of HPSE-1 protein was 92.9%in orbital embr yonal RMS and 91.3%in orbital alveolar RMS.Tissue from alveolar orbital RMS did not show relatively stronger staining than that from the embryonal orbital RMS.However,despite the types of RMS,comparing the cases treated chemoradiotherapy with those untreated,we have observed that chemoradiotherapy resulted in weaker staining in patients’tissues.The expression levels of HPSE-1 declined significantly in both the m RNA and protein levels in HPSE-1 sh RNA transfected RD cells.The CCK-8 assay showed that lentivirus-mediated HPSE-1 silencing resulted in significantly reduced RD cells viability in vitro.Silencing HPSE-1 expression also inhibited VEGF-induced tube formation of HUVECs in Matrigel.CONCLUSION:HPSE-1 silencing may be a promising therapy for the inhibition of orbital RMS progression.     

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses

Background and aimsObservational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults.Methods and resultsThe China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]).ConclusionsThis study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.     

生物型与骨水泥型假体全髋关节置换术治疗老年移位型股骨颈骨折的疗效分析

目的 比较生物型与骨水泥型假体全髋关节置换术(THA)治疗老年移位型股骨颈骨折(DFNF)的临床疗效.方法 前瞻性纳入2015年7月—2018年6月佳木斯大学附属第一医院骨科收治的老年DFNF患者128例,男性71例,女性57例;年龄61～84岁,平均72.7岁.骨折原因:跌伤75例,撞伤32例,高处坠落伤21例.依据随机数字表法分为生物型假体THA组(BPTHA组,n=64)与骨水泥型假体THA组(CPTHA组,n=64).BPTHA组行生物型假体髋关节置换,CPTHA组行骨水泥型假体髋关节置换.观察两组术中出血量、手术时间、术后引流量等围术期指标及住院时间.比较术前及术后6、12个月髋关节功能(Harris),血清前列腺素缓激肽(BK)、5-羟色胺(5-HT)等疼痛因子水平及视觉模拟评分(VAS),血清淀粉样蛋白A(SAA)、C反应蛋白(CRP)、红细胞沉降率(ESR)等炎性反应指标水平;分析术后并发症发生情况.结果 两组术中出血量、手术时间、术后引流量差异均无统计学意义(P>0.05);BPTHA组住院时间长于CPTHA组[(19.76±2.24)d vs.(15.37±1.71)d,P<0.05].术后6个月,BPTHA组Harris评分低于CPTHA组[(81.72±8.37)分vs.(86.68±8.85)分,P<0.05];术后12个月,BPTHA组Harris评分高于CPTHA组[(95.54±9.67)分vs.(90.72±9.12)分,P<0.05].术后6个月,BPTHA组血清BK、5-HT、SAA、CRP、ESR水平及VAS均高于CPTHA组(P<0.05);术后12个月,BPTHA组血清BK、5-HT、SAA、CRP、ESR水平及VAS均低于CPTHA组(P<0.05).BPTHA组并发症发生率为3.13％,CPTHA组并发症发生率为4.69％,两组比较差异无统计学意义(P>0.05).结论 BPTHA、CPTHA均可应用于老年DFNF的临床治疗,但CPTHA近期疗效优于BPTHA,而BPTHA远期疗效优于CPTHA.