Objective To evaluate the efficacy of pulmonary thromboendarterectomy (PTE) in treatment of chronic thromboembolic pulmonary hypertension (CTEPH) using 99Tcm-macroaggregated albumin (99 Tcm-MAA) pulmonary perfusion tomography.Methods Sixteen patients with CTEPH underwent 99Tcm-MAA pulmonary perfusion tomography before and 6-12 months after PTE.The perfusion defects and improvement both in pulmonary lobe and segment were observed pre-and post-PTE.Percentage of perfusion defect scores (PPDs％) were calculated and the change of systolic pulmonary artery pressure (SPAP) measured by echocardiography was also recorded.Results The postoperative SPAP was significantly lower than that before surgery ([36.56±8.47] mmHg vs [90.52±14.55] mmHg,t=14.14,P＜0.001).Before PTE,perfusion abnormalities were identified in 86 (86/96,89.58％) pulmonary lobes of 16 patients.In all of the 86 abnormal lobes,21 (21/86,24.42％) became normal,and the remaining 65 (65/86,75.58％) were improved after PTE.Perfusion defects were confirmed in 230 (230/304,75.66％) pulmonary segments of 16 patients before surgery.In all of the 230 abnormal segments,73 (73/230,31.74％) became normal,74 (74/230,32.17％) were improved and 83 (83/230,36.09％) remained unchanged after PTE.The mean PPDs％ decreased from (56.79±14.54)％ pre PTE to (28.20±15.24)％ at 6 12 months after PTE.The PPDs％ was positively correlated with homochronous SPAP (r=0.68,P＜0.001).Conclusion PTE can significantly reduce SPAP and improve the pulmonary perfusion in CTEPH patients.Pulmonary perfusion imaging can evaluate the curative effect of PTE.

Objective:To explore suitable strategies for atrial 18F-FDG PET/CT imaging and analyze the characteristics of abnormal atrial uptake in patients with atrial fibrillation(AF). Methods:From August 2017 to August 2018, 69 AF patients (43 males, 26 females, age (64±11) years) in Beijing Chaoyang Hospital were prospectively enrolled and underwent dual-phase 18F-FDG PET/CT imaging (60 and 120 min postinjection). Additionally, 10 healthy controls (3 males, 7 females, age (66±4) years) were prospectively enrolled and underwent 18F-FDG PET/CT imaging (60 min postinjection). A comprehensive strategy recommended by the Society of Nuclear Medicine and Molecular Imaging/American Society of Nuclear Cardiology/Society of Cardiovascular Computed Tomography (SNMMI/ASNC/SCCT) guideline was followed to suppress myocardial uptake. Image analysis: (1) 18F-FDG uptake of left ventricle was qualitatively analyzed and classified into 3 levels: grade 0, the activity of blood pool exceeded or was equal to myocardial activity; grade 1, myocardial activity was mildly higher than blood pool activity; grade 2, myocardial activity was obviously higher than blood pool activity. 18F-FDG uptake in the left atrium(LA), left atrial appendage (LAA) and right atrium (RA) higher than that in blood pool were defined as abnormal. Paired χ2 test was used to compare the rates of abnormal uptake in atrial structures between two phases. (2) Quantitative analysis: 18F-FDG uptake in all atrial structures were quantitatively analyzed by measuring SUV max, and left atrial cavity and right atrial cavity were quantitatively analyzed by measuring SUV mean. The target to background ratio (TBR) was calculated. Differences of TBR between two phases were analyzed by Wilcoxon signed rank test. Differences of 18F-FDG uptake in atrial structures between patients with AF and healthy controls were analyzed by Mann-Whitney U test and χ2 test. Results:Most subjects (84.8%, 67/79) achieved sufficient myocardial suppression. In one patient, the interpretation of LAA was affected by left ventricle uptake. The incidence of abnormal uptake of LA, LAA and RA in delayed phase were higher than those in early phase, but only the difference of LAA was significantly different (27.9%(19/68) vs 42.6%(29/68); χ2=8.10, P=0.020). TBR of LA, LAA and RA in delayed phase were all significantly higher than those in early phase (LA: 1.1 (1.0, 1.3) vs 1.1 (1.0, 1.2); LAA: 1.2 (1.0, 1.5) vs 1.0 (0.9, 1.2); RA: 1.4 (1.1, 1.9) vs 1.3 (1.0, 1.5); z values: from -6.81 to -3.42, all P<0.05). There were 87.0%(60/69) of AF patients with abnormal atrial FDG accumulation, which was significantly higher than that of the control group (0/10; χ2=31.50, P<0.001). In LAA and RA, the incidences of abnormal accumulation were significantly higher in AF than those in the control group (LAA: 30.4%(21/69) vs 0 (0/10); χ2=4.10, P=0.042; RA: 53.6%(37/69) and 0 (0/10); χ2=8.00, P=0.001). Conclusions:Using the method recommended by the SNMMI/ASNC/SCCT guideline to suppress the physiological uptake of the left ventricle and appropriately extending the interval is conducive to observing the abnormal 18F-FDG uptake in the atrium. The uptake of 18F-FDG in the atrium of patients with AF is increased.

Objective:To investigate the accuracy of free-breathing CT in evaluating the volume and shape of epicardial adipose tissue (EAT), and further explore the characteristics of EAT volume and activity in patients with atrial fibrillation using 18F-FDG PET/CT " one-stop" imaging. Methods:(1) Retrospective analysis was performed on 20 patients (16 males, 4 females, age: 33-86 (61.1±14.2) years) who underwent 18F-FDG PET/CT imaging and without obvious diseases affecting the images of the heart and surrounding lungs between March 2020 and May 2020 in Beijing Chaoyang Hospital. Free-breathing CT and breath-hold high resolution CT (HRCT) images were reviewed. Spearman rank correlation analysis, Bland-Altman consistency analysis and intraclass correlation coefficient (ICC) were used to evaluate the correlation and consistency of the EAT volume and shape, as well as the repeatability of the two operators′ measurements. (2) Prospective analysis was conducted to compare the differences in EAT volume and 18F-FDG uptake values between 20 patients (6 males, 14 females, age: 52-76 (66.0±6.4) years) with atrial fibrillation and 10 healthy controls (3 males, 7 females, age: 59-69 (66.0±3.6) years) collected between August 2017 and August 2018 in Beijing Chaoyang Hospital. Mann-Whitney U test was used to compare the differences in EAT volume and 18F-FDG SUV max between patients with atrial fibrillation and healthy controls. EAT volume measurement was conducted by the combination of Mimics Research 21.0 software and manual analysis. The shape of EAT was automatically calculated by the same software to obtain the maximum length of the projection of the three-dimensional (3D) model on the reference axes ( x, y, z). SUV max of EAT was manually measured. Results:The measurements of EAT volume had good repeatability (intra-operator ICC=0.999; inter-operator ICC=0.997). There was a good correlation and a good consistency between EAT volumes measured by free-breathing CT and breath-hold HRCT (96.6 (79.9, 136.4) vs 96.2 (80.9, 135.8) ml; rs=0.929, P<0.001); data of 19 cases were within 95% limits of agreement (95% LoA). The maximum projection length of EAT 3D model on the reference coordinate axis also showed good correlation and consistency ( x axis: rs=0.869, P<0.001, data of 19 cases were within 95% LoA; y axis: rs=0.854, P<0.001, data of 18 cases were within 95% LoA; z axis: rs=0.586, P=0.007, data of 20 cases were within 95% LoA). EAT volume of atrial fibrillation group was higher than those of healthy control group (137.2 (113.9, 202.9) vs 94.4 (76.6, 134.4) ml; z=-2.11, P=0.035) and SUV max of EAT in the atrial fibrillation group was higher than that in healthy control group (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2); z=-2.14, P=0.035). Conclusions:Free-breathing CT and breath-hold HRCT have good correlation, consistency and repeatability in measurement of EAT volume and shape. 18F-FDG PET/CT can be a " one-stop" imaging strategy for the evaluation of EAT volume and activity.

Objective:To investigate the related factors of the serum sickness morbidity in the treatment of children with acquired aplastic anemia (AA) by rabbit antithymosinglobulin (ATG), summarize the clinical characte-ristics of serum sickness and evaluate the influence of serum sickness on the prognosis of AA.Methods:The data of patients diagnosed as AA after treated with immunosuppressive therapy (IST) in Beijing Children′s Hospital, Capital Medical University, from March 2016 to December 2018 were collected, and the onset time, clinical manifestations, treatment, and prognosis of serum sickness were analyzed.Results:A total of 48 cases were enrolled, with the median age of 5 years and 5 months (ranging from 2 years and 1 month to 15 years and 6 months), and the proportion of male to female was 1.4∶1.0, 75.0% of the patients(36/48 cases) developed serum sickness.The median onset time was the 11 th day and 72.2% of the patients (26/48 cases) occurred from the 7 th to the 14 th day during IST.The 3 main clinical manifestations included arthralgia (63.9%, 23 cases), fever (52.7%, 19 cases) and rash (52.7%, 19 cases). There was no significant difference in peripheral blood leukocytes, neutrophils and lymphocytes between the patients with serum sickness and patients without serum sickness before IST and during serum sickness (all P>0.05). The incidence of serum sickness in children who received continuous glucocorticoid prophylaxis after IST (2/12 cases, 16.6%) was lower than that of those who did not (34/36 cases, 94.4%), and the difference was significant ( χ2=29.037, P<0.001). The symptoms of serum sickness improved after glucocorticoid therapy [Methylprednisolone 2-4 mg/(kg·d)]. Among 37 children who were followed up for 6 months or more after IST treatment, 25 patients had serum sickness and 12 patients did not have serum sickness.Nineteen patients with serum sickness and 10 patients without serum sickness were cured or markedly improved; 6 patients with serum sickness and 2 patients without serum sickness were not cured.No significant difference in the prognosis between 2 groups was observed ( P>0.05). Conclusion:Children with AA are prone to develop serum sickness after IST treatment.The peak period of incidence of serum sickness is the second week during IST, and the main clinical manifestations of serum sickness include arthralgia, fever, and rash.There is no correlation between the incidence of serum sickness and the blood routine test before IST and during serum sickness.The incidence of serum sickness can be reduced by giving glucocorticoid prophylaxis, and glucocorticoid is still effective after the onset of the serum sickness.There is no correlation between the morbidity of serum sickness and the prognosis of AA treated with IST.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins