A new isoquinolinone derivative with noble vasorelaxation activity

The pharmacological effects of BDPBI (7-bromo-1,4-dihydro-2-phenyl-4,4-bis(4-pyridinylmethyl)2H-isoquinolin-3-one dihydrochloride) were tested on isolated endothelium-containing or denuded aorta of the guinea pig. BDPBI with the formula C(27)H(24)BrCl(2)N(3)O was synthesized starting with 3-isochromanone. In the endothelium-containing preparations of the aortic rings, phenylephrine (PHE; 10 micromol/l) elicited contracture and acetylcholine (ACh; 10 micromol/l) or BDPBI (0.01-10 micromol/l) elicited relaxation effects on the PHE-precontracted preparations. The BDPBI-elicited effect on the PHE-precontracted aortic rings was not altered in the presence of adrenergic blockers (propranolol or yohimbine; 1 micromol/l) or pretreated preparations with aspirin, indomethacin (10 micromol/l) or L-NAME (1 mmol/l). However, the relaxation effects of BDPBI were blocked if the preparations were pretreated with diphenhydramine (10 micromol/l) or chloropheniramine maleate (10 micromol/l). In contrast to lower concentrations of atropine (1 micromol/l), higher concentrations of atropine (30 micromol/l) did block the effects of BDPBI on the PHE-precontracted aortic rings. HTMT dimaleate (0.01-10 micromol/l), a histamine H(1) receptor agonist, also elicited relaxation effects on the PHE-precontracted preparation, and the effects were blocked if the preparations were pretreated with diphenhydramine or chloropheniramine maleate. On isolated denuded aorta of the guinea pig, BDPBI did not elicit relaxation effects on the PHE-precontracted aortic rings. These results demonstrated that the vasorelaxation effect of BDPBI on PHE-precontracted aortic rings is partly dependent on the activation of a histaminergic receptor from the vascular endothelium. We suggested that BDPBI would be an effective vasorelaxant for cardiovascular systems.     

Feasibility of sentinel lymph node biopsy omission after integration of 18F-FDG dedicated lymph node PET in early breast cancer:a prospective phase Ⅱ trial

Objective:Sentinel lymph node biopsy(SLNB) is currently the standard of care in clinically node negative(cN0) breast cancer.The present study aimed to evaluate the negative predictive value(NPV) of ¹⁸F-FDG dedicated lymph node positron emission tomography(LymphPET) in cN0 patients.Methods:This was a prospective phase II trial divided into 2 stages(NCT04072653).In the first stage,cN0 patients underwent axillary LymphPET followed by SLNB.In the second stage,SLNB was omitted in patients ...     

维生素C对顺铂杀伤卵巢癌细胞的影响

目的:探讨维生素C 是否能影响顺铂杀伤卵巢癌细胞株OVCAR5、SKOV3、CAOV3,并对其作用机制进行初探。方法:使用梯度浓度维生素C及顺铂处理卵巢癌细胞株,显微镜下观测细胞的形态学变化;使用ATP-TCA方法检测细胞生长抑制情况。选择对维生素C敏感的卵巢癌细胞株。氧化敏感探针DCFH-DA标记细胞 ,检测不同浓度维生素C处理不同时间后细胞内过氧化氢(H2O2 )水平。结果:三株卵巢癌细胞维生素C处理的敏感度不同,但总体呈现出随着维生素C浓度的增加,细胞受到抑制作用增加,维生素C对于顺铂杀伤细胞的作用具有辅助加强效应,该作用呈现剂量依赖效应。其中较低浓度维生素C处理OVCAR5细胞15min各组胞内H2O2 水平相比对照组稍高,当处理浓度为5 000μmol/L时细胞H2O2 水平明显升高,达到164%。培养30min后,荧光强度显示细胞内H2O2 水平比15min时升高更明显。不同浓度组分别达到对照组的94%、106%、122%、188%,培养60min后检测荧光强度发现各给药组H2O2 水平均已低于对照组。12h后检测到细胞内的H2O2 水平处于更低水平,各组均未达到对照组的50%。结论:较高浓度维生素C能增强顺铂杀伤卵巢癌细胞株的能力,并呈现一定的剂量依赖性。该结果可能由于维生素 C通过自氧化机制产生过氧化氢促进卵巢癌细胞凋亡。     

卡托普利防治腹主动脉狭窄性高血压大鼠心肌肥厚的形态定量研究

方法选用腹主动脉狭窄的大鼠实验性心肌肥厚模型,采用光镜、电镜形态计量手段,定量观察了血管紧张素转换酶抑制剂卡托普利防治心肌肥厚的作用,并比较了倍他乐克对心肌肥厚的作用。结果卡托普利组大鼠的全心／体重比、心肌组织／间质比、心肌细胞横径及心肌细胞线粒体体密度与对照组类似（p＞0．05）,明显不同于心肌肥厚组（p＜0．05）,而倍他乐克组上述多指标与心肌肥厚组相似（p＞0．05）。本实验表明卡托普利通过保护心肌细胞及间质而使心肌组织免遭损伤因素刺激发生肥厚的作用,即对大鼠高血压性。心肌肥厚具有良好的防治作用。     

Analgesic and anti-arthritic effects of Lingzhi and San Miao San supplementation in a rat model of arthritis induced by Freund's complete adjuvant

Aim of study

In this study, we have investigated the analgesic and anti-arthritic effects of a traditional Chinese medicine (TCM) combination of Lingzhi and San Miao San (SMS) in a rat model of arthritis induced by Freund's complete adjuvant (FCA).

Materials and methods

Sprague–Dawley rats were induced with monoarthritis by single unilateral injection of FCA into the knee joint. The TCM combination was administered to the rats daily by intraperitoneal injection (50 mg/(kg day)) or via oral administration (500 mg/(kg day)) for 7 days before induction of arthritis and 7 days after. Extension angle that provoked struggling behavior, and size and blood flow of the rat knees were measured to give indexes of allodynia, edema, and hyperemia, respectively. The extent of cell infiltration, tissue proliferation, and erosions of joint cartilage provided additional indexes of the arthritis condition.

Results

FCA injection produced significant allodynia, edema, hyperemia, immune cell infiltration, synovial tissue proliferation, and erosions of joint cartilage in the ipsilateral knees compared with the contralateral saline-injected knees. Intraperitoneal injection of the TCM combination (50 mg/(kg day)) suppressed allodynia, edema, and hyperemia in the inflamed knees, and oral administration (500 mg/(kg day)) suppressed edema and hyperemia. Histological examination showed that the TCM administered by either route reduced immune cell infiltration and erosion of joint cartilage.

Conclusions

These findings suggest the Lingzhi and SMS formulation has analgesic and anti-inflammatory effects in arthritic rat knees, and concur to previous clinical studies that showed the TCM combination reduced pain in rheumatoid arthritis patients, and extends its possible benefit to suppression of inflammatory symptoms in these patients.     

细胞周期调控基因p21和p27单核苷酸多态性与卵巢上皮性癌的关系

目的 探讨细胞周期调控基因p21和p27的单核苷酸多态性(SNP)与卵巢上皮性癌(卵巢癌)发病风险的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测234例卵巢癌患者(卵巢癌组)和284例健康妇女(对照组)p21基因C/T和p27基因V/G SNP位点基因型和等位基因的频率分布.结果 (1)对照组妇女p21基因的C/C、C/T和T/T基因型频率分别为34.2%、49.6%和16.2%,C和T等位基因频率分别为59.0%和41.0%;卵巢癌组患者3种基因型频率分别为28.2%、53.0%和18.8%,C和T等位基因频率分别为54.7%和45.3%.两组基因型频率和等位基因频率分别比较,差异均无统计学意义(P＞0.05).3种基因型频率在4种病理类型的卵巢癌中的分布有明显差异(P=0.02),C/C基因型降低子宫内膜样癌的发病风险(OR为0.56,95%CI为0.32～0.98).(2)对照组妇女p27基因V/V、V/G和G/G基因型频率分别为88.4%、10.9%租0.7%,V和G等位基因频率分别为93.8%和6.2%;卵巢癌组患者的基因型频率分别为93.6%、5.1%和1.3%,V和G等位基因频率分别为96.2%和3.8%.两组基因型频率分布比较,差异有统计学意义(P=0.04),等位基因频率分布比较,差异则无统计学意义(P=0.09).与V/G和G/G基因型比较,V/V基因型增加卵巢癌的发病风险(OR为1.92,95%CI为1.02～3.63).结论 p21基因C/T多态性的C/C基因型可能降低子宫内膜样癌的发病风险,p27基因的V/V基因型可能是卵巢癌发病的潜在危险因素.     

儿童综合医院重症医学科护理人力资源配置现状研究

目的 调查儿童综合医院重症医学科护理工作量及护理人力资源配置现状。方法 采用护理活动评分量表,于2019年3月1日至31日连续31 d,每天3个时间点,即每班次下班时的16:00、00:00、8:00,共93个时点对当班所有患儿进行数据采集,评估住院所有患儿所有班次的护理工作量及护理人力资源配置情况。结果 共采集了2 703份护理工作量及护理人力资源配置相关数据。儿童综合医院重症医学科患儿护理活动评分量表得分平均为（58.63±10.81）分;儿童综合医院重症医学科护士总体配置上,每例患儿每班次实际配置的护士数小于理论应配置护士数,两者比较差异具有统计学意义（P<0.01）。各班次每例患儿实际配置的护士数与理论应配置护士数相比,差异具有统计学意义（P<0.01）。结论 儿童综合医院重症医学科护理人力资源配置应该与成人ICU持平或高于成人ICU。儿童综合医院重症医学科护理人力资源总体配置和各班次配置均不足,夜班护士工作负荷尤其过重。护理管理者应努力提高护理人力资源的总体配置水平和各班次配置水平,并根据白夜班护理工作量的差异,进行护理人力资源的精确配置。     

Biofluid Biomarkers of Alzheimer’s Disease: Progress,Problems, and Perspectives

Since the establishment of the biomarker-based A-T-N (Amyloid/Tau/Neurodegeneration) framework in Alzheimer’s disease (AD), the diagnosis of AD has become more precise, and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted. However, the A-T-N framework does not encompass the whole spectrum of AD pathologies, and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system. Therefore, we suggest the addition of an “X” to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD. In this review, we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework, analyze the problems, and present our perspectives on the diagnosis of AD.     

Nobiletin Inhibits Hypoxia-Induced Placental Damage via Modulating P53 Signaling Pathway

In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague–Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.     

Prevention of Gestational Diabetes Mellitus and Gestational Weight Gain Restriction in Overweight/Obese Pregnant Women: A Systematic Review and Network Meta-Analysis

Background: Overweight/obesity is associated with pregnancy-related disorders, such as gestational diabetes mellitus (GDM) and excessive gestational weight gain (GWG). Although multiple interventions have been proposed to prevent GDM and restrict GWG, our knowledge of their comparative efficacy is limited. Objective: To evaluate the effectiveness and identify the optimal intervention strategy to prevent GDM and restrict GWG among overweight/obese pregnant women. Methods: Randomized controlled trials that recruited overweight/obese pregnant women at <20 gestational week were obtained. Predictive and confidence interval plot and surface under the cumulative ranking (SUCRA) were performed using Stata statistical software to determine and compare the efficacy of interventions (diet, physical activity (PA), diet + PA intervention and medication). Results: 23 studies with a total of 8877 participants were eligible for analysis. Our results indicated that although neither PA, diet + PA, diet nor medication intervention could significantly protect overweight/obese women from the development of GDM, there was a trend that PA and diet + PA intervention were preventive factors of GDM. Of these, PA intervention (SUCRA, 82.8%) ranked as the superior strategy, and diet intervention (SUCRA, 19.7%) was the least efficacious regimen. Furthermore, interventions of diet, PA and diet + PA were significantly beneficial for GWG restriction, whereas medication intervention could not restrict GWG. In detail, diet intervention (SUCRA, 19.7%) ranked as the optimal regimen, whilst PA intervention (SUCRA, 62.3%) ranked as the least efficacious regimen. Conclusion: Although none of the interventions could offer remarkable benefit for GDM prevention, interventions of diet, PA and diet + PA were significant factors to restrict GWG. In aggregate, diet + PA intervention seemed the superior choice for the prevention of both GDM and excessive GWG. Registration: PROSPERO CRD42022313542.