Cassane-type diterpenes from Caesalpinia minax induce apoptosis in pituitary adenoma: structure–activity relationship,ER stress and Wnt/β-catenin pathways

Plant-derived natural products have been the highly significant sources of novel antitumor agents. The cassane-type diterpenes of genus Caesalpinia have been reported to bear antiproliferative activities toward different types of cancer cells. In this study, we evaluated the antineoplasmic activities of 16 natural origin cassane-type diterpenes isolated from the CHCl₃ extract of the seeds of C. minax in pituitary adenomas cells and identified caesalpin G (CAG) showed the strongest cytotoxicity. Moreover, we further investigated the structure–activity relationship and molecular mechanism of these derivatives systematically. The results confirmed the unsaturated lactone-type ring, hydroxyl at C-7, and alkenyl at C-11 or C-14 functionality as critical for anticancer activity in this family of natural products. In addition, the mechanism experiments also demonstrated unfolded protein response and ER stress and Wnt/β-catenin pathway were involved in the CAG-induced apoptosis.     

Inversion recovery ultrashort echo time imaging of ultrashort T2 tissue components in ovine brain at 3 T: a sequential D2O exchange study

Inversion recovery ultrashort echo time (IR‐UTE) imaging holds the potential to directly characterize MR signals from ultrashort T₂ tissue components (STCs), such as collagen in cartilage and myelin in brain. The application of IR‐UTE for myelin imaging has been challenging because of the high water content in brain and the possibility that the ultrashort T₂* signals are contaminated by water protons, including those associated with myelin sheaths. This study investigated such a possibility in an ovine brain D₂O exchange model and explored the potential of IR‐UTE imaging for the quantification of ultrashort T₂* signals in both white and gray matter at 3 T. Six specimens were examined before and after sequential immersion in 99.9% D₂O. Long T₂ MR signals were measured using a clinical proton density‐weighted fast spin echo (PD‐FSE) sequence. IR‐UTE images were first acquired with different inversion times to determine the optimal inversion time to null the long T₂ signals (TI_null). Then, at this TI_null, images with echo times (TEs) of 0.01–4 ms were acquired to measure the T₂* values of STCs. The PD‐FSE signal dropped to near zero after 24 h of immersion in D₂O. A wide range of TI_null values were used at different time points (240–330 ms for white matter and 320–350 ms for gray matter at TR = 1000 ms) because the T₁ values of the long T₂ tissue components changed significantly. The T₂* values of STCs were 200–300 μs in both white and gray matter (comparable with the values obtained from myelin powder and its mixture with D₂O or H₂O), and showed minimal changes after sequential immersion. The ultrashort T₂* signals seen on IR‐UTE images are unlikely to be from water protons as they are exchangeable with deuterons in D₂O. The source is more likely to be myelin itself in white matter, and might also be associated with other membranous structures in gray matter.     

药学服务在癌痛患者门诊治疗中的作用——设组对比癌痛咨询与回访指导的效果

药师通过制定门诊癌痛患者咨询和回访指导制度，对90例患者进行随机分组和药学干预。结果显示，该制度切实可行，临床药师全程化参与门诊癌痛的治疗工作，提高了患者的疼痛缓解程度和依从性，降低了不良反应，发挥了药师在门诊癌痛治疗中的作用。     

T-cell acute lymphoblastic leukemia from miRNA perspective: Basic concepts,experimental approaches,and potential biomarkers

T-cell acute lymphoblastic leukemia (T-ALL) is a rare, aggressive and heterogeneous malignancy originating from T-cell precursors. The mechanisms of T-ALL pathogenesis related to non-protein coding part of the genome are currently intensively studied. miRNAs are short, non-coding molecules acting as negative regulators of gene expression which shape phenotype of cells in a complex and context-specific manner. miRNAs may act as oncogenes or tumor suppressors; several miRNAs have been related to drug resistance and treatment response in various malignancies.Here we present the review of the state-of-the-art knowledge on the role of miRNAs in T-ALL pathogenesis, with detailed overview of the studies reporting on miRNAs with oncogenic and tumor suppressor potential. We discuss whether miRNAs might be considered candidate biomarkers of prognosis in T-ALL and leukemia subtype-specific markers. We also describe experimental approaches and a typical workflow applied in research on the involvement of miRNAs in oncogenesis.     

Targeting P-glycoprotein expression and cancer cell energy metabolism: combination of metformin and 2-deoxyglucose reverses the multidrug resistance of K562/Dox cells to doxorubicin

P-glycoprotein (P-gp) is one of the major obstacles to efficiency of cancer chemotherapy. Here, we investigated whether combination of metformin and 2-deoxyglucose reverses the multidrug resistance (MDR) of K562/Dox cells and tried to elucidate the possible mechanisms. The combination of metformin and 2-deoxyglucose selectively enhanced the cytotoxicity of doxorubicin against K562/Dox cells. Metformin was not a substrate of P-gp but suppressed the elevated level of P-gp in K562/Dox cells. The downregulation of P-gp may be partly attributed to the inhibition of extracellular signal-regulated kinase pathway. The addition of 2-deoxyglucose to metformin initiated a strong metabolic stress in both K562 and K562/Dox cells. Combination of metformin and 2-deoxyglucose inhibited glucose uptake and lactate production in K562 and K562/Dox cells leading to a severe depletion in ATP and a enhanced autophagy. Above all, P-gp substrate selectively aggravated this ATP depletion effect and increased cell apoptosis in K562/Dox cells. In conclusion, metformin decreases P-gp expression in K562/Dox cells via blocking phosphorylation of extracellular signal-regulated kinase. P-gp substrate increases K562/Dox cell apoptosis via aggravating ATP depletion induced by combination of metformin and 2-deoxyglucose. Our observations highlight the importance of combination of metformin and 2-deoxyglucose in reversing multidrug resistance.     

2020年全国社区医院建设追踪监测分析

背景　社区医院建设是新时期满足群众基本医疗卫生服务需求的重要举措，是推动构建优质高效医疗卫生服务体系的关键环节。自2019年开展社区医院试点工作以来，国家紧密出台相关政策文件推动其发展。截至2020年底，我国已成功创建1 410家社区医院，对其建设情况进行监测、分析十分必要。目的　分析2020年全国社区医院监测数据，针对社区医院建设推进过程中存在的问题与困难，提出进一步推动社区医院建设相关政策建议。方法　利用课题组于2020年12月开展的社区医院追踪监测数据，从社区医院达到推荐标准、业务用房建筑面积、实际开放床位数、科室设置、全科医生配置等方面进行分析，梳理各省份2020年社区医院建设工作进展。结果　截至2020年12月，全国创建社区医院1 410个，73.12%（1 023/1 399）的社区医院达到“优质服务基层行”推荐标准，山西省等9个省份的社区医院全部达到推荐标准。2020年，全国已建成的社区医院平均业务用房面积6 822 m2，较2019年增加347 m2，达到“业务用房面积≥3 000 m2”标准的社区医院占比为96.07%（1 343/1 398）；社区医院平均实际开放床位数为91张，较2019年增加3张，达到“实际开放床位数≥30张”标准的社区医院占比为97.13%（1 355/1 395）；社区医院临床科室设置逐渐齐全，除全科医疗科、康复医学科、中医科外达到“其他10个临床专业科室数≥5个”标准的社区医院占比为89.15%（1 241/1 392），2020年新增临床科室占比较多的依次为发热门诊（18.95%，260/1 372）、康复医学科（9.10%，126/1 384）、精神/心理科（6.55%，89/1 358）；社区医院平均配置全科医生16.15人，较2019年增加1.16人。结论　社区医院推进工作进展顺利，数量翻番，基础设施设备加强，临床科室不断增加，服务能力进一步提升；但各省份社区医院建设数量差距较大，部分省份社区医院对标不够，配套政策应持续完善，人才队伍建设是关键环节。社区医院建设应与各地“十四五”规划相衔接，稳步推进；多部门协同配合，强化社区医院政策保障，推动社区医院高质量发展。     

Novel Linker Variants of Antileishmanial/Antitubercular 7-Substituted 2-Nitroimidazooxazines Offer Enhanced Solubility

Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, culminating in a new clinical investigational drug for visceral leishmaniasis (DNDI-0690). To offset development risks, we continued to seek further leads with divergent candidate profiles, especially analogues possessing greater aqueous solubility. Starting from an efficacious monoaryl derivative, replacement of the side chain ether linkage by novel amine, amide, and urea functionality was first explored; the former substitution was well-tolerated in vitro and in vivo but elicited marginal alterations to solubility (except through a less stable benzylamine), whereas the latter groups resulted in significant solubility improvements (up to 53-fold) but an antileishmanial potency reduction of at least 10-fold. Ultimately, we discovered that O-carbamate 66 offered a more optimal balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).     

Severe Mitral Regurgitation Caused by Perivalvular Abnormal Communication of the Mitral Valve Due to Blunt Chest Trauma

Perivalvular leaks are usually caused by suture interruption in prosthetic valves or infective endocarditis. Traumatic mitral annular dehiscence is a very uncommon event. We present a rare case of severe mitral regurgitation secondary to perivalvular abnormal communication in a 35‐year‐old man with a history of blunt chest trauma. He presented with symptoms of cough and chest tightness for 3 months. Preoperative two‐dimensional and real time three‐dimensional transesophageal echocardiography clearly showed the position and size of the perivalvular abnormal communication and the incident damage of the left ventricular wall. The patient finally underwent successful surgical repair.     

142例老年骨质疏松的临床护理体会

目的:研究分析老年骨质疏松患者的临床护理措施和护理效果。方法:回顾性分析2010年5月-2012年10月期间,我院收治的142例老年骨质疏松患者的临床资料,按照患者入院治疗的先后顺序和采用的临床干预措施不同,将142例患者分为两组,对照组患者71例,采用一般护理措施干预治疗,观察组患者71例,加强临床针对性护理。结果:观察组患者的临床疗效和护理满意度均明显优于对照组,两组比较差异明显,具有统计学意义,(P0.05)。结论:加强老年骨质疏松患者的临床针对性护理能够有效的改善患者的临床症状,提高护理满意度。