Subclinical Pulmonary Congestion and Abnormal Hemodynamics in Heart Failure With Preserved Ejection Fraction

ObjectivesThe authors hypothesized that quantitative computed tomography (QCT) imaging would reveal subclinical increases in lung congestion in patients with heart failure and preserved ejection fraction (HFpEF) and that this would be related to pulmonary vascular hemodynamic abnormalities.BackgroundGross evidence of lung congestion on physical examination, laboratory tests, and radiography is typically absent among compensated ambulatory patients with HFpEF. However, pulmonary gas transfer abnormalities are commonly observed and associated with poor outcomes.MethodsPatients referred for invasive hemodynamic exercise testing who had undergone chest computed tomography imaging within 1 month were identified (N = 137). A novel artificial intelligence QCT algorithm was used to measure pulmonary fluid content.ResultsCompared with control subjects with noncardiac dyspnea, patients with HFpEF displayed increased mean lung density (–758 HU [–793, –709 HU] vs –787 HU [–828, –747 HU]; P = 0.002) and a higher ratio of extravascular lung water to total lung volume (EVLWV/TLV) (1.25 [0.80, 1.76] vs 0.66 [0.01, 1.03]; P < 0.0001) by QCT imaging, indicating greater lung congestion. EVLWV/TLV was directly correlated with pulmonary vascular pressures at rest, with stronger correlations observed during exercise. Patients with increasing tertiles of EVLWV/TLV demonstrated higher mean pulmonary artery pressures at rest (34 ± 11 mm Hg vs 39 ± 14 mm Hg vs 45 ± 17 mm Hg; P = 0.0003) and during exercise (55 ± 17 mm Hg vs 59 ± 17 mm Hg vs 69 ± 22 mm Hg; P = 0.0003).ConclusionsQCT imaging identifies subclinical lung congestion in HFpEF that is not clinically apparent but is related to abnormalities in pulmonary vascular hemodynamics. These data provide new insight into the long-term effects of altered hemodynamics on pulmonary structure and function in HFpEF.     

84例产褥感染的临床特点及常见致病微生物耐药性分析

目的 研究产褥感染的危险因素及常见致病微生物耐药情况，为临床治疗提供参考。方法 回顾性分析我院2017 年1 月～2019 年12 月发生的84 例产褥感染病例的临床资料，与同时期未发生产褥感染的200 例产妇进行对照研究，分析产褥感染的影响因素，并对分离获得的致病微生物进行耐药性分析。结果 感染组妊娠糖尿病、产钳助产、宫口开全后中转剖宫产患者的分布率高于对照组，差异有统计学意义（P＜0.05）；经多因素Logistic 回归分析，妊娠糖尿病是产褥感染的独立影响因素（P＜0.05）。本研究中共检出致病微生物40 株，其中革兰阴性菌13 株（占32.50%），革兰阳性菌10 株（占25.00%），支原体16 株（占40.00%），衣原体1 株（占2.50%），革兰阴性菌中以大肠埃希菌最常见，对二代头孢菌素类抗生素耐药率20%。革兰阳性菌以金黄色葡萄球菌最常见，对青霉素及头孢菌素耐药率高，未发现对亚胺培南及万古霉素耐药。结论 产钳助产、妊娠糖尿病、宫口开全后中转剖宫产是产褥感染可能的危险因素，其中，妊娠糖尿病是产褥感染的独立危险因素。目前临床常见致病微生物谱及耐药率未发生明显变化。     

Design,synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure–activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.     

基于预测剂量引导的宫颈癌自动计划研究

目的:使用机器学习方法建立宫颈癌计划剂量预测回归模型，并将预测剂量引导生成Monaco 计划系统（TPS）可调用 的优化模板文件，实现宫颈癌的自动计划设计。方法:对50例宫颈癌术后调强治疗计划中的危及器官采集基于重叠体积直 方图的几何特征值和基于剂量直方图的剂量目标值，建模后将模型预测剂量结果自动生成Monaco TPS模板文件，进而由TPS 调用优化。使用该方法对另外10例未参与模型训练的测试病例进行自动计划设计，并和人工设计的计划进行对比分析。 结果:自动计划比手动计划的平均设计时间减少了40 min（P<0.05），且平均调优次数降低了3次（P<0.05），剂量学指标和计 划执行效率上两者无明显差异（P>0.05）。结论:基于预测剂量引导的宫颈癌自动计划可以达到临床要求，并且提高了计划 设计效率。     

Regional volume changes of the brain in migraine chronification

The pathophysiology of migraine is complex.Neuroimaging studies reveal functional and structural changes in the brains of migraine patients.We sought to explore regional volume differences in intracranial structures in patients with episodic and chronic migraine.Sixteen episodic migraine patients,16 chronic migraine patients,and 24 normal controls were recruited and underwent 3.0 T MRI scanning.The volumes of 142 brain regions were calculated by an automatic volumetric algorithm and compared with clinical variables.Results demonstrated that the volumes of specific regions in the frontal and occipital lobes,and the right putamen,were increased and the volume of the fourth ventricle was decreased in the episodic migraine patients compared with controls.The volumes of the left basal forebrain,optic chiasm,and,the fourth ventricle were decreased in the chronic migraine patients,while the occipital cortex and the right putamen were larger.Compared to episodic migraine patiants,chronic migraine patients displayed larger left thalamus and smaller frontal regions.Correlation analysis showed that headache frequency was negatively correlated with the volume of the right frontal pole,right lateral orbital gyrus,and medial frontal lobes and positively correlated with the volume of the left thalamus.The sleep disturbance score was negatively correlated with the volume of the left basal forebrain.This suggests that migraine patients have structural changes in regions associated with pain processing and modulation,affective and cognitive processing,and visual perception.The remodeling of selective intracranial structures may be involved in migraine attacks.This study was approved by the Ethics Committee of Chinese PLA General Hospital(approval No.S2018-027-02)on May 31,2018.     

Adult parameningial alveolar rhabdomyosarcoma: Case report and literature review

Alveolar rhabdomyosarcoma (ARMS) represents the most common childhood soft tissue sarcoma, but they are rarely seen among adults. Most of the protocols for adults are adapted from pediatric protocols. Here we report a case of a 53-year-old woman diagnosed with a nasal alveolar rhabdomyosarcoma, stage IV at diagnosis, treated by chemotherapy (a regimen inspired from the pediatric protocole pEpSSG RMS 2005) which led to partial response followed by chemo-radiotherapy. We performed a systematic review of adult head and neck ARMS and found 29 cases. Primary chemotherapy with different protocols (VAC, VAI or VIE) should be done followed by surgery and/or external beam radiotherapy (preferably with IMRT). EBRT seems beneficial to every ARMS with a dose around 50 Gy in a conventional fractionation, eventually completed with a boost on residual tumor. The target volume must be defined on pre-chemotherapy imaging. Brachytherapy and proton therapy are under evaluation.     

探讨绝经过渡期、育龄子宫肌瘤患者异常阴道出血相关因素分析

目的: 探讨育龄、绝经过渡期子宫肌瘤患者异常阴道出血危险因素，为异常阴道出血临床精准诊断、治疗提供理论依据。方法： 选取2017年06月—2020年06月于内蒙古医科大学附属医院住院行手术治疗的子宫肌瘤患者。实验组设为非月经期异常阴道出血的子宫肌瘤患者，对照组为无异常阴道流血子宫肌瘤患者。根据第9版教科书年龄18-43岁定为育龄组；44-54岁定为绝经过渡期组（我国妇女平均绝经年龄为49.5岁，80%在44-54岁之间〔1〕）。 应用Excel双录入，核对无误后进行统计分析。计数资料的比较用R×C列联表卡方检验、四格表卡方检验及两独立样本秩和检验。非条件Logistic回归模型用于子宫肌瘤阴道异常出血危险因素的分析，并分别得到OR值与相应95%的可信区间。在此模型中，OR值＞1认为是危险因素，OR值＜1认为是保护因素。统计学显著性水平设定为双侧p≤0.05，即认为差异有统计学意义。全部统计分析选用SPSS19.0软件进行统计学分析。结果：1.将与子宫肌瘤阴道异常出血相关的33项临床指标纳入单因素分析得出，月经周期异常、肌瘤位置（子宫颈肌瘤）、肌瘤直径≥9cm、血红蛋白异常、子宫内膜癌、核分裂像＞5个差异有统计学意义（P≤0.05），均是子宫肌瘤阴道异常出血的危险因素；2.子宫肌瘤异常阴道出血核分裂像＞5个与子宫内膜病理性改变和异常阴道出血差异有统计学意义（P=0.019）。结论：1. 子宫内膜发生病理改变是子宫肌瘤患者引起异常阴道出血的原因之一。2.月经周期异常、子宫颈肌瘤、肌瘤直径≥9cm、血红蛋白异常、子宫内膜病理改变均是子宫肌瘤阴道异常出血的危险因素；子宫肌瘤核分裂像＞5个是子宫平滑肌瘤出现异常阴道出血的独立高危因素；3.子宫肌瘤核分裂像＞5与阴道出血、子宫内膜病理改变有统计学意义。进行单因素分析后得知，月经周期、肌瘤位置、肌瘤大小、血红蛋白、子宫内膜病理变化均子宫肌瘤阴道异常出血的发生有关。 关键词育龄；绝经过渡期；子宫平滑肌瘤；异常阴道出血；危险因素     

Accelerated iTBS treatment applied to the left DLPFC in depressed patients results in a rapid volume increase in the left hippocampal dentate gyrus,not driven by brain perfusion

BackgroundAccelerated intermittent Theta Burst Stimulation (aiTBS) has been shown to be an effective antidepressant treatment. Although neurobiological changes shortly after this intervention have been reported, whether aiTBS results in structural brain changes must still be determined. Furthermore, it possible that rapid volumetric changes are driven by factors other than neurotrophic processes.ObjectivesWe examined whether possible grey matter volumetric (GMV) increases after aiTBS treatment could be driven by increased brain perfusion, measured by Arterial Spin Labeling (ASL).Methods46 treatment-resistant depressed patients were randomized to receive 20 sessions of active or sham iTBS applied to the left dorsolateral prefrontal cortex. All sessions were delivered over 4 days at 5 sessions per day (trial registration: http://clinicaltrials.gov/show/NCT01832805). Patients were scanned the day before starting stimulation and three days after aiTBS.ResultsThere was a significant cluster of increased left hippocampal GMV in the dentate gyrus related to HRSD changes after active aiTBS, but not after sham stimulation. These GMV increases became more pronounced when accounting for changes in cerebral perfusion.ConclusionsActive, but not sham, aiTBS, resulted in acute volumetric changes in parts of the left dentate gyrus, suggesting a connection with adult neurogenesis. Furthermore, taking cerebral perfusion measurements into account impacts on detection of the GMV changes. Whether these hippocampal volumetric changes produced by active aiTBS are necessary for long-term clinical improvement remains to be determined.