p21WAF1 modulates drug-induced apoptosis and cell cycle arrest in B-cell precursor acute lymphoblastic leukemia

p21^WAF1 is a well-characterized mediator of cell cycle arrest and may also modulate chemotherapy-induced cell death. The role of p21^WAF1 in drug-induced cell cycle arrest and apoptosis of acute lymphoblastic leukemia (ALL) cells was investigated using p53-functional patient-derived xenografts (PDXs), in which p21^WAF1 was epigenetically silenced in T-cell ALL (T-ALL), but not in B-cell precursor (BCP)-ALL PDXs. Upon exposure to diverse cytotoxic drugs, T-ALL PDX cells exhibited markedly increased caspase-3/7 activity and phosphatidylserine (PS) externalization on the plasma membrane compared with BCP-ALL cells. Despite dramatic differences in apoptotic characteristics between T-ALL and BCP-ALL PDXs, both ALL subtypes exhibited similar cell death kinetics and were equally sensitive to p53-inducing drugs in vitro, although T-ALL PDXs were significantly more sensitive to the histone deacetylase inhibitor vorinostat. Transient siRNA suppression of p21^WAF1 in the BCP-ALL 697 cell line resulted in a moderate depletion of the cell fraction in G1 phase and marked increase in PS externalization following exposure to etoposide. Furthermore, stable lentiviral p21^WAF1 silencing in the BCP-ALL Nalm-6 cell line accelerated PS externalization and cell death following exposure to etoposide and vorinostat, supporting previous findings. Finally, the Sp1 inhibitor, terameprocol, inhibited p21^WAF1 expression in Nalm-6 cells exposed to vorinostat and also partially augmented vorinostat-induced cell death. Taken together, these findings demonstrate that p21^WAF1 regulates the early stages of drug-induced apoptosis in ALL cells and significantly modulates their sensitivity to vorinostat.     

Protocol for Development of American Association of Clinical Endocrinology Clinical Practice Guidelines and Consensus Statements: Summary of Methodology,Process, and Policy – 2023 Update

ObjectiveThis 2023 updated protocol summarizes the American Association of Clinical Endocrinology’s (AACE’s) new framework for the development of clinical practice guidelines and other guidance documents that includes changes to methodology, processes, and policies.MethodsAACE has critically reviewed its development processes for guidance documents over the last several years against the National Academy of Medicine Standards for Developing Trustworthy Clinical Practice Guidelines and the Council of Medical Specialty Societies Principles for Development of Specialty Society Clinical Guidelines to determine areas for improvement.ResultsThe new AACE framework for development of guidance documents incorporates many changes, including a revised conflicts of interest (COI) policy; strengthened commitment to collection of disclosures and management of relevant COI during development; open calls to membership for authors; new requirements for authors; new diversity, equity, and inclusion (DEI) policy; new empanelment process that incorporates consideration of DEI; and adoption of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to increase the quality of evidence assessment and standardize recommendation grades and statements, among other improvements.ConclusionsAACE has revised its policies and adopted a completely new methodology for guideline development in support of the mission to elevate the practice of clinical endocrinology to improve patient care. With the use of an evidence-based medicine framework and by continually assessing and improving its processes for development of guidance, AACE strives to deliver trustworthy, unbiased, and up-to-date information that ensures clinician and patient confidence in AACE content. Further, AACE hopes that these enhancements foster a more collaborative approach to development and increase engagement with the worldwide medical community to improve global health.     

Atypical lipomatous tumour/well-differentiated liposarcoma found in the buccal mucosa: A rare case report

Oral liposarcomas are uncommon diseases, the most predominant histopathological subtype being atypical lipomatous tumour/well-differentiated liposarcoma. In regard to its clinical aspects in the oral cavity, it is challenging to confirm a diagnosis and develop a treatment plan. In this case report, we present a rare case of atypical lipomatous tumour/well-differentiated liposarcoma in the right cheek of a 77-year-old male patient. Conservative surgery was performed considering the histopathological subtype of the neoplasm. Knowledge of the clinical and histopathological characteristics of this rare disease is essential to maintaining function and aesthetics through conservative treatment in older patients.     

Utilidad y seguridad de los ingresos directos a una unidad hospitalaria de agudos de un servicio de geriatría valorados por atención geriátrica en residencias

Background and objectiveMore than half of institutionalized older people need a emergency department visit annually, with high resources consumption and higher risk of adverse events, due to high complexity. Direct admission to Acute Geriatric Unit (AGU), after geriatric consultant and nursing home medical team assessment, could be a safety and effective alternative to emergency department (ED) admission.MethodsRetrospective observational study of AGU patients admitted by Nursing Home Geriatric Team between January, 1st and December, 31st, 2021. Planned admissions and SARS-CoV-2 positive patients were excluded. Medical (sociodemographic, clinical, functional and cognitive) records and outcomes data (inpatient mortality, hospital and ED lenght of stay, transfer to ED and delirium within 48 h after admission, hospital discharge location) were collected.ResultsTwo hundred and six patients directly admitted, 101 through ED (N 307). 62.5% with Barthel index <40, 65% with dementia, 56.4% with Charlson index ≥3. Inpatient mortality was 14.6% in direct admission, 20.8% in ED referral group, p = 0.14. Hospital lenght of stay was 9.61 ± 6.01 days in direct admission, 11.22 ± 5.36 days in ED group, p = 0.02. 27.7% of patients with delirium in direct admission and 36.6% in ED group; only one patient was transferred to ED, within 48 h after admission.ConclusionsDirect admission is a safety and effective alternative to ED referral in institutionalized older people after geriatric assessment, due to no increased mortality, shorter length of stay and hospital cost reduction.     

八段锦联合抗阻运动对老年2型糖尿病患者糖脂代谢、氧化应激及生活质量的影响

摘要 目的：探讨八段锦联合抗阻运动对老年2型糖尿病（T2DM）患者糖脂代谢、氧化应激及生活质量的影响。方法：选取2021年4月~2022年5月期间在我院接受治疗的老年T2DM患者238例。按照随机数字表法分为对照组（在常规治疗的基础上,接受抗阻运动干预,119例）和联合组（在对照组的基础上,接受八段锦干预,119例）。观察两组糖脂代谢、氧化应激及生活质量的改善情况。结果：干预12周后,联合组体质量指数、腰臀比低于对照组（P<0.05）。干预12周后,联合组空腹血糖（FBG）、餐后2 h血糖（2hPG）、糖化血红蛋白（HbAlc）低于对照组（P<0.05）。干预12周后,联合组高密度脂蛋白胆固醇（HDL-C）高于对照组（P<0.05）,低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、甘油三酯（TG）低于对照组。干预12周后,联合组丙二醛（MDA）低于对照组,超氧化物歧化酶（SOD）、过氧化氢酶（CAT）高于对照组（P<0.05）。干预12周后,联合组的健康调查简表（SF-36）各维度评分均高于对照组（P<0.05）。结论：八段锦联合抗阻运动用于老年T2DM患者中,可有效改善患者的氧化应激、糖脂代谢,并提高患者的生活质量。     

依达拉奉右莰醇联合丁苯酞治疗对老年大动脉粥样硬化型脑卒中患者血清PTX3、lp-PLA2以及MES的影响

摘要 目的：探讨依达拉奉右莰醇联合丁苯酞对老年大动脉粥样硬化（LAA）型脑卒中患者血清五聚素3（PTX3）、脂蛋白相关磷脂酶A2（Lp-PLA2）以及微栓子信号（MES）的影响。方法：回顾性选取2021年9月-2022年9月在本院收治的120例老年LAA型脑卒中患者,根据其不同治疗方案分为对照组（56例）,采用依达拉奉右莰醇单独治疗,和观察组（64例）,采用依达拉奉右莰醇联合丁苯酞治疗。观察两组患者的临床疗效;对比两组患者治疗前后神经功能[脑卒中量表（NIHSS）及中枢神经特异性蛋白（S-100β）、神经元特异性烯醇化酶（NSE）]状态、炎症因子[血清五聚素3（PTX3）、脂蛋白相关磷脂酶A2（Lp-PLA2）]水平及脑血流微栓子信号（MES）阳性率变化。记录不良反应发生情况。结果：观察组患者治疗有效率为95.31%,高于对照组的78.57%（χ²=7.653 ,P=0.006）;治疗后,观察组患者NIHSS评分、S-100β及NSE水平低于对照组（P＜0.05）;观察组PTX3、Lp-PLA2水平及MES阳性率低于对照组（P<0.05）。观察组与对照组总不良反应发生率比较无差异（6.25 % vs 5.36 %）（Fisher=1.000）。结论：依达拉奉右莰醇联合丁苯酞可有效提高临床疗效,促进老年LAA型患者神经功能恢复,降低PTX3、lp-PLA2水平及MES阳性率,控制病情发展,且安全性较好。     

超声引导下神经阻滞麻醉联合全身麻醉对股骨头置换老年患者麻醉效果及术后认知功能的影响

摘要 目的：研究超声引导神经阻滞麻醉联合全身麻醉对股骨头置换老年患者的麻醉效果及对术后认知功能的影响。方法：选取2019年1月至2021年12月期间我院收治的150例拟行股骨头置换术的老年患者,随机分为对照组和观察组,各75例。对照组患者行常规全身麻醉,观察组在对照组的基础上行超声引导下神经阻滞麻醉,比较两组患者的血流动力学指标,拔管时间、苏醒时间和复苏室停留时间,苏醒后疼痛,术后认知功能及不良反应的发生率。结果：观察组患者各时间点的心率（HR）和平均动脉压（MAP）均较对照组低（P＜0.05）。观察组拔管时间、苏醒时间和复苏室停留时间均较对照组短（P＜0.05）。观察组患者术后视觉模拟评分（VAS）均低于同一时间点的对照组（P＜0.05）。与对照组相比,观察组患者术后1 h、12 h和24 h的简易智力状态检查（MMSE）评分均较高（P＜0.05）,观察组术后1 h、12 h和24 h术后认知功能障碍（POCD）发生率较对照组低（P＜0.05）。两组患者不良反应发生率无差异（P＞0.05）。结论：超声引导神经阻滞麻醉可稳定血流动力学,缩短拔管、苏醒及复苏室停留时间,减轻术后疼痛,改善术后认知功能,减少POCD的发生,值得临床推广。     

血清IL-4、IL-6、IL-33与老年重症肺炎患者肠道菌群的相关性分析及对预后的影响

摘要 目的：探究老年重症肺炎患者血清白介素（IL）-4、IL-6、IL-33与肠道菌群变化的相关性及预后影响因素。方法：选取我院2020年1月-2022年1月期间收治的老年重症肺炎患者中筛选82例纳入重症组,从同期老年健康体检志愿者中选取50例纳入正常组。对比两组的IL-4、IL-6、IL-33与肠道菌群水平差异,Pearson相关系数分析肠道菌群与IL-4、IL-6、IL-33水平相关性,根据重症组随访6个月的预后情况分为生存组55例、死亡组27例,对比生存组、死亡组的临床因素差异,多因素Logistic回归模型分析重症肺炎死亡的影响因素。结果：（1）对比正常组,重症组的IL-4、IL-6、IL-33水平均明显升高（P<0.05）;（2）对比正常组,重症组的大肠埃希菌水平均明显升高且双歧杆菌水平明显降低（P<0.05）;（3）大肠埃希菌与IL-4、IL-6、IL-33均呈正相关,双歧杆菌与IL-4、IL-6、IL-33均呈负相关;（4）对比生存组,死亡组年龄、急性生理和慢性健康（APACHE-Ⅱ）评分、IL-4、IL-6、IL-33、大肠埃希菌、机械通气比例、餐后2 h平卧比例均明显更高且双歧杆菌明显更低（P<0.05）;（5）重症肺炎死亡的独立危险因素包括年龄增加、APACHE-Ⅱ评分升高、IL-4升高、IL-6升高、IL-33升高、大肠埃希菌升高、机械通气、餐后2 h平卧且独立保护因素是双歧杆菌升高。结论：老年重症肺炎患者存在明显的炎症反应与肠道菌群失衡,患者的IL-4、IL-6、IL-33、大肠埃希菌、双歧杆菌异常变化并且存在密切关系,老年重症肺炎患者的年龄、机械通气、餐后体位等因素均会影响其预后生存结局。     

不同剂量右美托咪定联合超声引导下多点髂筋膜间隙阻滞在老年全髋关节置换术中的应用效果分析

摘要 目的：探讨超声引导下多点髂筋膜间隙阻滞联合不同剂量右美托咪定在老年全髋关节置换术（THA）中的应用效果。方法：选取2019年11月-2022年12月北京积水潭医院贵州医院择期行THA的老年患者120例,按照随机数字表法分为A组（n=40）、B组（n=40）、C组（n=40）,三组均接受超声引导下多点髂筋膜间隙阻滞治疗,在此基础上,A组、B组、C组分别给予0.5 μg/kg、1.0 μg/kg、1.5 μg/kg右美托咪定注射液。对比三组临床指标、血流动力学指标、应激反应指标、脑神经损伤情况,观察三组围术期间不良反应发生情况。结果：B组、C组的阻滞消退时间、拔管时间长于A组,首次下床时间短于A组（P<0.05）。B组、C组的阻滞消退时间、拔管时间、首次下床时间对比无差异（P>0.05）。三组麻醉诱导后即刻（T1）~手术结束时（T3）时间点心率（HR）、平均动脉压（MAP）升高后降低（P<0.05）。B组、C组的T1~T3时间点HR、MAP均低于A组,且B组低于C组（P<0.05）。三组T3时间点皮质醇（Cor）、白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）升高（P<0.05）。B组、C组的T3时间点Cor、IL-6、TNF-α均低于A组,且B组低于C组（P<0.05）。B组、C组的T3时间点中枢神经特异性蛋白（S100β）均低于A组,且B组低于C组（P<0.05）。B组、C组的T3时间点脑源性神经生长因子（BDNF）均高于A组,且B组高于C组（P<0.05）。三组不良反应发生率组间对比无差异（P>0.05）。结论：超声引导下多点髂筋膜间隙阻滞联合1.0 μg/kg右美托咪定在THA中具有更好的麻醉效果,可缩短首次下床时间,减轻机体应激反应、血流动力学波动以及脑部神经损伤。     

髓内固定对老年股骨转子间骨折患者关节功能的影响

摘要 目的：研究髓内固定对老年股骨转子间骨折患者关节功能的影响。方法：选取2016年9月~2019年9月我院收治的股骨转子间骨折的老年患者80例为研究对象,采用随机数字表法将其分为两组,每组各40例。对照组患者采用Gamma钉进行治疗,观察组患者采用股骨近端防旋髓内钉固定治疗。比较两组患者的围术期相关指标、骨折愈合时间、Harris评分、临床治疗效果及并发症的发生情况。结果：观察组患者的手术时间、切口长度、术中出血量、术后引流量、住院时间及骨折愈合时间均显著少于或短于对照组(P＜0.05)。术前,两组患者的Harris评分比较无统计学差异(P＞0.05);术后6个月及术后12个月,两组患者的Harris评分均较术前显著升高,且观察组显著高于对照组(P＜0.05)。观察组患者的治疗优良率为92.50 %,显著高于对照组(75.00 %,P＜0.05)。两组患者深静脉血栓、感染、褥疮、固定松动、股骨头坏死及严重疼痛的发生率比较无统计学差异(P＞0.05)。结论：股骨近端防旋髓内钉固定治疗老年股骨转子间骨折效果明显优于Gamma钉治疗,可有效缩短骨折愈合时间,提高髋关节功能。