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...     

格列喹酮与格列齐特的临床疗效及不良反应比较

目的回顾性分析对比格列喹酮与格列齐特的临床疗效及不良反应。方法将丽水市中心医院内分泌科用过格列喹酮和格列齐特两种药物3个月以上的门诊和住院患者129例的病历资料及化验单进行统计分析,比较用药后空腹血糖、餐后2 h血糖及肝肾功能等指标。结果两组治疗3个月后空腹血糖均明显下降(P<0.05),格列齐特降空腹血糖效果优于格列喹酮,格列喹酮降餐后2 h血糖作用优于格列齐特;两组肝肾功能各项指标无大的波动,不良反应发生率无显著性差异。结论格列喹酮和格列齐特都有一定的降血糖疗效,格列喹酮不良反应较格列齐特少,且对肾功能具有一定的保护作用。     

反相高效液相色谱法测定苯磺酸氨氯地平胶囊的含量和有关物质

目的建立测定苯磺酸氨氯地平胶囊中苯磺酸氨氯地平含量及有关物质的反相高效液相色谱(RP-HPLC)法。方法采用HypersilBDS柱(200 mm×4.6 mm,5μm),以0.01 mol/L磷酸氢二钾溶液(含0.7%三乙胺,磷酸调pH=4.0±0.1)-乙腈(70∶30)为流动相,流速为1.0 mL/min,柱温为30℃,检测波长237 nm。结果苯磺酸氨氯地平峰和相邻杂质峰可达到有效分离(R>1.5)。苯磺酸氨氯地平质量浓度在5.0～50.0μg/mL范围内与峰面积线性关系良好(r=0.999 9,n=5);低、中、高3种质量浓度的平均回收率分别为99.17%,100.03%,99.85%,RSD分别为1.21%,0.87%,1.06%(n=3);方法的精密度和重复性良好,RSD均小于2%。结论该方法准确、简便、快速,适用于苯磺酸氨氯地平胶囊的质量控制。     

Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy

Parkin, an E3 ubiquitin ligase, plays a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy. Accumulating evidence suggests that the acetylation modification of the key mitophagy machinery influences mitophagy level, but the underlying mechanism is poorly understood. Here, our study demonstrated that inhibition of histone deacetylase (HDAC) by treatment of HDACis activates mitophagy through mediating Parkin acetylation, leading to inhibition of cervical cancer cell proliferation. Bioinformatics analysis shows that Parkin expression is inversely correlated with HDAC2 expression in human cervical cancer, indicating the low acetylation level of Parkin. Using mass spectrometry, Parkin is identified to interact with two upstream molecules, acetylase acetyl-CoA acetyltransferase 1 (ACAT1) and deacetylase HDAC2. Under treatment of suberoylanilide hydroxamic acid (SAHA), Parkin is acetylated at lysine residues 129, 220 and 349, located in different domains of Parkin protein. In in vitro experiments, combined mutation of Parkin largely attenuate the interaction of Parkin with PTEN induced putative kinase 1 (PINK1) and the function of Parkin in mitophagy induction and tumor suppression. In tumor xenografts, the expression of mutant Parkin impairs the tumor suppressive effect of Parkin and decreases the anticancer activity of SAHA. Our results reveal an acetylation-dependent regulatory mechanism governing Parkin in mitophagy and cervical carcinogenesis, which offers a new mitophagy modulation strategy for cancer therapy.     

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury–repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300–β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.     

Preclinical evaluation and pilot clinical study of [18F]AlF-labeled FAPI-tracer for PET imaging of cancer associated fibroblasts

In recent years, fibroblast activation protein (FAP) has emerged as an attractive target for the diagnosis and radiotherapy of cancers using FAP-specific radioligands. Herein, we aimed to design a novel ¹⁸F-labeled FAP tracer ([¹⁸F]AlF-P-FAPI) for FAP imaging and evaluated its potential for clinical application. The [¹⁸F]AlF-P-FAPI novel tracer was prepared in an automated manner within 42 min with a non-decay corrected radiochemical yield of 32 ± 6% (n = 8). Among A549-FAP cells, [¹⁸F]AlF-P-FAPI demonstrated specific uptake, rapid internalization, and low cellular efflux. Compared to the patent tracer [¹⁸F]FAPI-42, [¹⁸F]AlF-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo. Micro-PET imaging in the A549-FAP tumor model indicated higher specific tumor uptake of [¹⁸F]AlF-P-FAPI (7.0 ± 1.0% ID/g) compared to patent tracers [¹⁸F]FAPI-42 (3.2 ± 0.6% ID/g) and [⁶⁸Ga]Ga-FAPI-04 (2.7 ± 0.5% ID/g). Furthermore, in an initial diagnostic application in a patient with nasopharyngeal cancer, [¹⁸F]AlF-P-FAPI and [¹⁸F]FDG PET/CT showed comparable results for both primary tumors and lymph node metastases. These results suggest that [¹⁸F]AlF-P-FAPI can be conveniently prepared, with promising characteristics in the preclinical evaluation. The feasibility of FAP imaging was demonstrated using PET studies.     

Bond Properties of Magnesium Phosphate Cement-Based Engineered Cementitious Composite with Ordinary Concrete

A magnesium phosphate cement-based engineered cementitious composite (MPC-ECC) was developed using polyvinyl alcohol (PVA) fibers and fly ash. In this study, the bond behavior of MPC-ECC with ordinary concrete was evaluated through single and double shear bond strength tests. The effects of the water to solid mass ratio (W/S), the sand to binder mass ratio (S/B), the molar ratio of MgO to KH2PO4 (M/P), the fly ash content (F), the borax dosage (B), the volume fraction of PVA fibers (Vf), and curing age on the bond behavior of MPC-ECC with ordinary concrete were examined. The results showed that as the W/S increased, the single and double shear bond strengths were gradually reduced. As the S/B increased, the double shear bond strength increased; the single shear bond strength first decreased up to an S/B of 0.1 and then increased. With the increase of M/P, the single and double shear bond strengths increased. With the increase of F, the single shear bond strength first increased up to an F of 30% and then decreased; the double shear bond strength decreased. With the increase of B, the single and double shear bond strengths increased first and then decreased, and their strength reached its maximum at a B of 6%. The increase of Vf improved the single and double shear bond strengths. The research results can provide some technical guidance for repairing concrete structures with MPC-ECC.     

原发性膀胱颈梗阻/原发性膀胱颈协同失调的诊断与治疗现状

原发性膀胱颈梗阻(primary bladder neck obstruction,PBNO)/原发性膀胱颈协同失调(primary bladder neck dyssynergia,PBND)是一组病因不明的膀胱颈梗阻综合征,临床表现为排尿期症状(排尿费力、尿踌躇、尿流变细、排空不全等)、储尿期症状(尿频、尿急、尿失禁、夜尿等)或两者同时存在。影像尿动力检查(video-urodynamic study,VUDS)是诊断PBNO/PBND的金标准,PBNO/PBND特征为高压低流的排尿模式,在影像透视下可见膀胱颈未开放或开放不全。轻症患者可采取观察、药物治疗及间歇清洁自家导尿等措施进行保守治疗,保守治疗无效的患者应行经尿道膀胱颈电切术。为进一步了解PBNO/PBND及其进展,本文就相关研究进展进行综述。