Objective: To explore the clinical and chest computed tomography (CT) features and the outcome of immune checkpoint inhibitor-related pneumonitis (CIP). Methods: Clinical and chest CT data of 38 CIP patients with malignant tumors from the Cancer Hospital, Chinese Academy of Medical Sciences between August 2017 and April 2021 were retrospectively reviewed, and the outcomes of pneumonitis were followed up. Results: The median time from the administration of immune checkpoint inhibitors (ICIs) to the onset of CIP was 72.5 days in 38 patients with CIP, and 22 patients developed CIP within 3 months after the administration of ICIs. The median occurrence time of CIP in 24 lung cancer patients was 54.5 days, earlier than 119.0 days of non-lung cancer patients (P=0.138), with no significant statistical difference. 34 patients (89.5%) were accompanied by symptoms when CIP occurred. The common clinical symptoms were cough (29 cases) and dyspnea (27 cases). The distribution of CIP on chest CT was asymmetric in 31 cases and symmetrical in 7 cases. Among the 24 lung cancer patients, inflammation was mainly distributed ipsilateral to the primary lung cancer site in 16 cases and diffusely distributed throughout the lung in 8 cases. Ground glass opacities (37 cases) and consolidation (30 cases) were the common imaging manifestations, and organizing pneumonia (OP) pattern (15 cases) was the most common pattern. In 30 CIP patients who were followed up for longer than one month, 17 cases had complete absorption (complete absorption group), and 13 cases had partial absorption or kept stable (incomplete absorption group). The median occurrence time of CIP in the complete absorption group was 55 days, shorter than 128 days of the incomplete absorption group (P=0.022). Compared with the incomplete absorption group, there were less consolidation(P=0.010) and CIP were all classified as hypersensitivity pneumonitis (HP) pattern (P=0.004) in the complete absorption group. Conclusions: CIP often occurs within 3 months after ICIs treatment, and the clinical and CT findings are lack of specificity. Radiologic features may have a profound value in predicting the outcome of CIP.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Retrospective Studies ; Pneumonia/drug therapy* ; Lung Neoplasms/drug therapy* ; Tomography, X-Ray Computed/methods*

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.
Male ; Child ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Blood Coagulation ; COVID-19 ; China/epidemiology* ; Connective Tissue Diseases ; Coronary Aneurysm ; Fever ; Systemic Inflammatory Response Syndrome/therapy*

Since the end of 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has swept the world,bringing great harm to human society and significantly increasing the health burden.Due to stron-ger infectivity,faster transmission,and higher reinfection rate of the Omicron variant,it has now replaced the Delta variant as the main epidemic strain for both imported and local outbreaks in China.Chinese Diagnosis and treatment protocol for SARS-CoV-2 infection(10th trial version)emphasizes"strengthening the protection of key popula-tions,"which includes the increasing number of immunocompromised population.These people have a high inci-dence of severe diseases and a high fatality rate after infected with SARS-CoV-2,and belong to the high-risk popula-tions of severe or critical diseases.Moreover,due to underlying diseases,these people take immunosuppressants and other related drugs chronically.The interactions between anti-SARS-CoV-2 infection treatment drugs and origi-nal drugs are complicated,thus bring significant challenges to the treatment after the SARS-CoV-2 infection.Cur-rently,there is a lack of guidelines or consensus on the diagnosis and treatment of SARS-CoV-2 infection among im-munocompromised population.Therefore,the Guangzhou Institute of Respiratory Health and National Center for Respiratory Medicine organized experts from multiple disciplines(respiratory and critical care medicine,organ transplantation,rheumatology and immunology,hematology,infection,critical care medicine,etc.)in China.Af-ter multiple rounds of discussions,13 items of recommendations are made as the reference for peers based on evi-dence-based medical evidence,so as to provide a theoretical and practical reference for the diagnosis and treatment strategies of this population.

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

Renal artery thrombosis can cause acute occlusion of unilateral or bilateral renal arteries,and kidney failure would be induced if it is not diagnosed and treated in time.Therefore,rapid and correct treatment is especially important for renal artery thrombosis.Due to the lack of specificity of clinical manifestations,this disease in commonly misdiagnosed or missed and thus has a low early diagnosis rate.Here we report a case of acute renal artery thrombosis to improve the diagnosis and treatment.
Acute Disease ; Diagnostic Errors/adverse effects* ; Humans ; Renal Artery ; Renal Artery Obstruction/diagnosis* ; Thrombosis/etiology*

The present study was aimed to investigate the effects of circRNA-0028171 on the apoptosis of vascular endothelial cells induced by arsenic trioxide (As₂O₃). Human umbilical vein endothelial cells (HUVECs) were treated with 0-15 μmol/L As₂O₃ for 24 h. Then, cellular viability was measured by MTT assay. The expression levels of circRNA-0028171, Bcl-2 and Bax mRNA were detected by real-time quantitative PCR. Bcl-2/Bax protein ratio was detected by Western blot. Whether circRNA-0028171 was involved in the regulation of HUVECs by As₂O₃ was investigated by transfection with overexpression plasmid of circRNA-0028171 and siRNA. The results showed that compared with the control group, As₂O₃ group showed decreased cellular viability, reduced Bcl-2/Bax mRNA and protein ratios, and significantly lower expression of circRNA-0028171. Overexpression of circRNA-0028171 inhibited apoptosis of HUVECs induced by As₂O₃. Knockdown of circRNA-0028171 by siRNA promoted As₂O₃-induced apoptosis in HUVECs. These results suggest that circRNA-0028171 is involved in the vascular endothelial cell apoptosis induced by As₂O₃.
Humans ; Arsenic Trioxide/pharmacology* ; RNA, Circular ; bcl-2-Associated X Protein/metabolism* ; RNA, Small Interfering/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Human Umbilical Vein Endothelial Cells/metabolism* ; RNA, Messenger/metabolism*

Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.

BACKGROUND: There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China. METHODS: From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups. RESULTS: Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300). CONCLUSIONS Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.
China ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, T-Cell, Peripheral/therapy* ; Neoplasm Recurrence, Local ; Retrospective Studies ; Transplantation, Autologous ; Transplantation, Homologous ; Treatment Outcome

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER NCT03620565, https://register.clinicaltrials.gov.
China ; Female ; Gynecologic Surgical Procedures/adverse effects* ; Humans ; Pelvic Floor/surgery* ; Pelvic Organ Prolapse/surgery* ; Surgical Mesh/adverse effects* ; Treatment Outcome ; Vagina