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.     

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。     

表格式管理集束化护理用于糖尿病视网膜病变术后患者的价值

目的　分析表格式管理集束化护理在糖尿病视网膜病变（DR）术后患者中的应用价值。方法　回顾性分析2019年3月至2021年6月济南市第二人民医院收治的89例DR患者的临床资料，使用电脑进行随机编号，单数者为对照组44例（患眼59只），双数者为观察组45例（患眼65只）。对照组男21例，女23例，年龄（42.18±10.27）岁；观察组男23例，女22例，年龄（42.39±10.52）岁。对照组予以DR术后常规护理，观察组在对照组基础上予以表格式管理集束化护理干预，两组患者均干预1个月。干预前后使用自我护理能力测定量表（ESCA）和视功能损害眼病患者生存质量问卷（SQOL-DVI）评定患者的自护能力和生活质量；使用简易疾病感知问卷（BIPQ）评定两组患者疾病认知情况；比较两组患者术后并发症（角膜水肿、视网膜脱离和玻璃体出血）的发生情况。计量资料采用t检验，计数资料采用χ²检验，等级资料采用Mann-Whitney U检验。结果　干预后，观察组患者ESCA总分高于对照组［（110.19±13.59）分比（96.59±12.47）分］，差异有统计学意义（t=4.916，P<0.001）；BIPQ等级改善程度优于对照组（U=2.520，P=0.012）；观察组并发症总发生率低于对照组［4.44%（2/45）比18.18%（8/44）］，差异有统计学意义（χ²=4.210，P=0.040）；干预后，观察组SQOL-DVI总分高于对照组［（87.59±12.64）分比（75.52±11.77）分］，差异有统计学意义（t=4.660，P<0.001）。结论　表格式管理集束化护理可以提高DR术后患者的疾病自护能力和疾病认知水平，降低患者并发症的发生率，提高患者的生存质量。     

THE STUDY APPLIED ON BA IN PATIENTS WITH EPILEPSY

目的：探讨脑电地形图在癫癎病人中的应用价值。方法：脑电地形图在132例原发性癫癎和18例继发性癫癎病人中被检查了。结果：在这些病人中脑电地形图的改变是明显的。结论：脑电地形图在癫癎诊断和鉴别诊断中有重要的应用价值。     

痘病毒载体艾滋病疫苗研究进展

艾滋病是一种传染性强、传播速度快、传播范围广、病死率高的传染病.抗逆转录病毒药物可以抑制感染者体内病毒的复制,但不能将其完全清除.研究显示,以痘病毒为载体,经过局部基因修饰后研制的预防性艾滋病疫苗具有较好安全性和一定免疫原性.此文对痘病毒载体艾滋病疫苗的研究进展进行综述.     

Acute drug toxicity related to drinking herbal tea in a kidney transplant recipient

Calcineurin and mTOR inhibitors are commonly used immunosuppressive agents with narrow therapeutic range. As the drugs are mainly metabolized by the P450 cytochrome system, the interaction between food and herbs are also commonly seen and affect the drug levels. We present a case of a kidney transplant recipient with toxic therapeutic levels of cyclosporine A and sirolimus due to interaction between the immunosuppressive agents and Chinese herbal tea. Ingredients within the herbal tea were reported to have inhibitory effect on cytochrome CYP3A4 in-vitro studies. Transplant recipients should be alert that there may be potent interaction between the immunosuppressive drugs and herbs resulting in adverse effect on allograft function.