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 investigate whether patients with pulmonary hypertension (PH) develop abnormal fibroblast activation protein (FAP) inhibitor (FAPI) uptake in the left ventricular free wall and to analyze its characteristics and significance.Methods:Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-FAPI-04 PET/CT images of 51 patients diagnosed with PH (24 males, 27 females; age: (48±21) years) and 10 healthy volunteers (4 males, 6 females; age: (59±12) years) from Beijing Chaoyang Hospital of Capital Medical University between February 2021 and January 2024 were retrospectively analyzed. Higher FAPI uptake in the left ventricular free wall than that in blood pool was defined as abnormal and SUV max, SUV mean, and total lesion FAP activity were quantitatively measured. Associated factors with FAPI uptake in the left ventricle were analyzed, and differences of clinical parameters between patients with and without abnormal left ventricular uptake were compared. Independent-sample t test and Mann-Whitney U test were used to compare differences between groups. Spearman rank correlation analysis was used for correlation analysis. Results:Abnormal FAPI uptake that was diffusely distributed in the left ventricular free wall was observed in 19 patients with PH. Total lesion FAP activity was positively correlated with peak mitral late-diastolic inflow velocity ( A) ( rs=0.696, P=0.001) and negatively correlated with peak mitral early-diastolic inflow velocity ( E)/ A and pulmonary vascular resistance (PVR) ( rs values: -0.629, -0.540, P values: 0.004, 0.017). Significant differences in E/ A (0.8(0.6, 1.1) vs 0.9(0.8, 1.4); z=-2.33, P=0.020), left ventricular end-systolic internal diameter ((25.7±2.6) vs (27.8±4.2) mm; t=-2.22, P=0.031), and left ventricular end-systolic volume ((26.7±7.3) vs (32.5±9.9) ml; t=-2.26, P=0.028) were found between patients with and without abnormal FAPI uptake in the left ventricle. Conclusion:In patients with PH, the left ventricular free wall develops diffuse abnormal uptake of FAPI, the extent of which is related to impaired left ventricular diastolic function.

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 analyze the influence factors on the efficacy of immunosuppression therapy (IST) combined with eltrombopag and IST alone in the treatment of childhood severe aplastic anemia (SAA).Methods:A retrospective cohort study. A total of 124 children with SAA who were initially treated with IST at Beijing Children′s Hospital from March 2017 to May 2020 were enrolled. Clinical characteristics, laboratory examination and prognosis data were collected at the time of enrollment. According to the treatment plan, the children were divided into the eltrombopag combined with IST group (eltrombopag group) and the IST group. Binary Logistic regression model was used to analyze the factors affecting the efficacy of the two groups at 6 months of treatment, and the factors affecting the efficacy of the eltrombopag group at the end of follow-up.Results:There were 75 cases (45 males and 30 females) in the eltrombopag group. The age of diagnosis was 5.9 (3.5, 8.5) years. There were 49 patients in the IST group, including 23 males and 26 females, whose age at diagnosis was 6.2 (4.4, 8.8) years. The absolute lymphocyte count before treatment in the eltrombopag group was significantly lower than that in the IST group (1.1 (0.4, 1.6)×10 9vs. 2.1 (1.4, 2.8)×10 9/L). Absolute reticulocyte count in the eltrombopag group was significantly higher than that of IST group (26.9 (8.7, 54.2)×10 9vs. 9.5 (4.0, 19.0)×10 9/L) (both P<0.05). Influencing factors of 6-month response: a comparison between response and un-response groups in the eltrombopag treated patients showed that, before treatment, hemoglobin (69 (61, 78) vs. 64 (59, 68) g/L), platelet (10 (6, 16)×10 9vs. 6 (3, 8)×10 9/L), absolute reticulocyte count (ARC) (34.0 (15.8, 57.3)×10 9vs. 6.5 (4.6, 16.8)×10 9/L) and the response rate to granulocyte colony stimulating factor (G-CSF) after treatment (82.4% (47/57) vs. 9/18) were significantly different (all P<0.05). Logistic regression model analysis showed that ARC ( OR=1.09, 95% CI 1.02-1.18) and absolute neutrophil count were independent influencing factors of 6-month response rate in the eltrombopag group ( OR=0.00, 95% CI 0.00-0.89). ARC was also the independent influencing factors of the end of follow-up response rate in the eltrombopag group ( OR=1.04, 95% CI 1.01-1.07). Conclusions:Pre-treatment blood count and response to G-CSF were predictors of overall response to eltrombopag combined with IST. The higher the ARC before treatment, the higher the total response rate and complete response.

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.

Objective:To summarize and analyze of the clinical and genetic characteristics of children with nonmuscle myosin heavy chain 9 (MYH9)-related disease (MYH9-RD).Methods:To screen the patients who were first diagnosed as "chronic/refractory immune thrombocytopenia (ITP) " from April 2016 to May 2019 in Beijing Children′s Hospital by genetic and clinical examinations, then the clinical manifestation, laboratory examination and genetics results of 7 children diagnosed with MYH9-RD were collected and summarized retrospectively.Results:Among 7 children diagnosed with MYH9-RD, 3 were males and 4 females. The age of onset was 1.25 (0.41-6.16) years. The course of disease was 2.16 (0.41-8.59) years. The automatic platelet count was (9 (5-30))×10 9/L. All the cases were found with giant platelets under microscope,and the manual platelet count was (70 (30-100))×10 9/L. Four cases had skin hemorrhage or epistaxis and 3 cases had no bleeding. All 7 patients had received first-or second-line therapy of ITP, of whom 1 case received splenic embolization, and all the treatments mentioned above were ineffective. Finally, it was confirmed that all 7 patients had heterozygous missense mutations of MYH9 gene by next generation sequencing (NGS), including 2 pedigrees and 5 sporadic cases. Four sporadic mutations occurred in N-terminal globular head domain (HD), and 1 sporadic case with p.D1424N mutations occurred in the C-terminal tail domain (TD). One of the pedigrees also had p.D1424N mutation. The other familial case had a novel variant with one missense variant p.A44D caused by the c.131C>A transition. One of the two p.R702 mutations had kidney damage, and several relatives of the new p.A44D mutations had deafness. Conclusions:In this study, the spontaneous mutations of seven MYH9-RD were common, and all patients were misdiagnosed as ITP, whereas the bleeding was mild and immunotherapy was ineffective. The suspected disease can be identified earlier by manual visual platelet volume and count, which can be confirmed by genetic testing. It is more important to monitor the development of other organs damage instead of thrombocytopenia. For cases with p.R702 mutations the doctor should be aware of kidney damage, and for the cases with novel mutations p.A44D the doctor should be aware of hearing loss.

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