Dasatinib and interferon alpha synergistically induce pyroptosis-like cell death in philadelphia chromosome positive acute lymphoblastic leukemia

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is a high-risk disease subtype with a dismal prognosis. Inhibiting BCR-ABL kinase alone is insufficient to eradicate Ph+ALL clones, and alternative BCR-ABL-dependent and -independent pathways need to be targeted as an effective strategy. Our study revealed that the combination of dasatinib and interferon-α showed synergistic activity against Ph+ALL, inducing mitochondrial dysfunction and causing necrosis-like cell lysis. Mechanistic studies showed that the induced cell death was caspase-3-independent. Canonical necroptosis signals, such as RIP1 and MLKL, were not activated; instead, the pyroptosis executor Gasdermin D was upregulated expression and activated. The expression levels of extracellular ATP and IL-1β were also upregulated, both of which are markers of pyroptotic cell death. In a murine Ph+ALL model, the dual drug treatment prolonged the survival of tumor-bearing mice. More importantly, we incorporated the dual drugs to maintenance therapy in 39 patients who were unfit for allogeneic stem cell transplantation (allo-HSCT). The median follow-up was 28.5 months, the 4-year disease-free survival and overall survival rates were 52.2% and 65.2%, respectively. Our data suggest that the combination of dasatinib and interferon-α has potential synergistic activity against Ph+ALL and shows promise as a maintenance therapy for Ph+ALL patients who are unfit for allo-HSCT.     

Pre-attack and pre-episode symptoms in cluster headache: a multicenter cross-sectional study of 327 Chinese patients

BackgroundThere have been a few studies regarding the pre-attack symptoms (PAS) and pre-episode symptoms (PES) of cluster headache (CH), but none have been conducted in the Chinese population. The purpose of this study was to identify the prevalence and features of PAS and PES in Chinese patients, as well as to investigate their relationships with pertinent factors.MethodsThe study included patients who visited a tertiary headache center and nine other headache clinics between January 2019 and September 2021. A questionnaire was used to collect general data and information about PAS and PES.ResultsAmong the 327 patients who met the CH criteria (International Classification of Headache Disorders, 3rd edition), 269 (82.3%) patients experienced at least one PAS. The most common PAS were head and facial discomfort (74.4%). Multivariable logistic regression analysis depicted that the number of triggers (OR = 1.798, p = 0.001), and smoking history (OR = 2.067, p = 0.026) were correlated with increased odds of PAS. In total, 68 (20.8%) patients had PES. The most common symptoms were head and facial discomfort (23, 33.8%). Multivariable logistic regression analysis showed that the number of triggers were associated with increased odds of PES (OR = 1.372, p = 0.005).ConclusionsPAS are quite common in CH patients, demonstrating that CH attacks are not comprised of a pain phase alone; investigations of PAS and PES could help researchers better understand the pathophysiology of CH.     

热毒宁口服液质量标准研究

目的 建立热毒宁口服液的薄层鉴别方法及含量测定的高效液相色谱法.方法 采用薄层鉴别法对金银花、大青叶、柴胡和甘草进行定性鉴别.采用高效液相色谱法测定连翘苷含量,色谱柱为岛津Wonda Cract ODS-2柱(250 mm×4.6 mm,5μm),流动相为乙腈-水(30:70,V/V),流速为1 mL/min,柱温为3...     

直腰旋转平推法治疗腰椎间盘突出症效果分析

目的:观察直腰旋转平推法治疗腰椎间盘突出症的临床疗效。方法:569例腰椎间盘突出症患者,随机分为直腰旋转平推法治疗组301例,常规推拿治疗组268例。两组均每日治疗一次,10次为一疗程,1个疗程后进行临床疗效观察。结果:治疗组疗效明显优于对照组(P<0.05)。结论:直腰旋转平推法治疗腰椎间盘突出症疗效确切,优于常规推拿治疗。     

CSCO guidelines for colorectal cancer version 2022: Updates and discussions

<正>Colorectal cancer(CRC) is the third most common cancer worldwide and the second most common in tumor-related mortality by Global Cancer Statistics 2020(1). Recent data show that the incidence and mortality of CRC in China are increasing(2-4), with the number of new cases and deaths reaching 607,900 and 261,777 in 2019.     

青少年多囊卵巢综合征与其父母代谢综合征的相关性研究

目的探讨青少年多囊卵巢综合征（PCOS）与其父母代谢综合征（MBS）的相关性。方法选择2004年3月—2007年3月在浙江省慈溪市妇幼保健院与慈溪市人民医院的36例PCOS青少年患者（11～16岁）及其父母（35例母亲,19例父亲）、21例正常青少年（女,11～16岁）,进行其体质量指数（BMI）、腰围、血压测量,并检测其血清胆固醇（TC）、三酰甘油（TG）、雄性激素水平,同时进行糖耐量测定（OGTT）及超声检查多囊卵巢情况。结果①PCOS患者的父亲94%肥胖或超重,79%患有MBS。②PCOS患者的母亲停经前36%患MBS,明显高于患PCOS者（≤20%）。③PCOS患者的多囊卵巢特征极少数遗传于母亲,其主要遗传于父亲的MBS因素（P=0.008）。④PCOS患者中28%患有MBS。结论青少年PCOS在根本上是由其父亲患有MBS遗传因素所致。     

不同频率神经肌肉电刺激对ARDS相关性ICU-AW小鼠肌肉萎缩防治及临床意义

目的 不同频率下神经肌肉电刺激(neuromuscular electrical stimulation,NMES)在ARDS相关性ICU获得性衰弱(ICU-acquired weakness,ICU-AW)中的作用及机制。方法 健康雄性C57BL/6小鼠88只随机分为11组,每组8只。分为:空白对照组(C1)、气管内注入无菌水组(C2)、ICU-AW模型组(ICU-AW)、ICU-AW+AMPK激动剂A-769662组(ICU-AW-A)、ICU-AW+A-769662溶剂对照组(ICU-AWV)、NMES 20 Hz组(ICU-AW-20)、NMES 40 Hz组(ICU-AW-40)、NMES 60 Hz组(ICU-AW-60)、NMES80 Hz组(ICU-AW-80)、ICU-AW-40+AMPK抑制剂Compound C组(ICU-AW-40-C)、ICU-AW-40+Compound C溶剂对照组(ICU-AW-40-V)。检测小鼠四肢抓力和存活状态,7 d后收集小鼠肺组织和腓肠肌标本,采用HE染色观察肺和肌肉病理学变化,采用western blot以及qRT-PCR的方...     

小剂量利妥昔单抗联合糖皮质激素治疗儿童落叶型天疱疮一例疗效观察

患儿男,9岁,头皮红斑、糜烂伴瘙痒1个月,泛发全身1周。皮损组织病理：表皮内颗粒层下方水疱形成,疱内见大量棘层松解细胞,真皮浅层小血管周围淋巴细胞及嗜酸性粒细胞浸润。直接免疫荧光检查示表皮细胞间IgG、补体C3呈网状沉积,IgM、IgA阴性。酶联免疫吸附实验检测血清抗Dsg1抗体阳性（157.00 U/ml）。诊断：落...