Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

Background:Due to the outbreak and rapid spread of coronavirus disease 2019(COVID-19),more than 160 million patients have become convalescents worldwide to date.Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19.However,it is unknown whether their characteristics return to normal after the 1-year recovery.Methods:We recruited 35 confirmed patients to provide specimens at discharge and 1 year later,as well as 160healthy controls.A total of 497 samples were prospectively collected,including 219 tongue-coating,129 stool and 149 plasma samples.Tongue-coating and stool samples were subjected to 16S rRNA sequencing,and plasma samples were subjected to untargeted metabolomics testing.Results:The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal.In the recovery process,the microbial diversity gradually increased.Butyric acid-producing microbes and Bifidobacterium gradually increased,whereas lipopolysaccharideproducing microbes gradually decreased.In addition,sphingosine-1-phosphate,which is closely related to the inflammatory factor storm of COVID-19,increased significantly during the recovery process.Moreover,the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later.Conclusions:This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19.The key microbiome and metabolites in the process of recovery were identified,and provided new treatment ideas for accelerating recovery.And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.

Alterations in the human oral microbiome in cholangiocarcinoma

Dear Editor,Alterations in the human microbiome are closely related to various hepatobiliary diseases.Gut microbial dysbiosis has been found in patients with cholangiocarcinoma(CCA)[1].However,the characteristics of oral microbiome in patients with CCA have not been studied.

Prognosis of gestational choriocarcinoma diagnosed incidentally during laparoscopy for a presumed cornual pregnancy:a report of five cases

The clinical presentations of gestational choriocarcinoma vary markedly, and a misdiagnosis could be made in atypical patients if simply relying on clinical features. Laparoscopic resection of uterine mass lesion is rarely used in gestational choriocarcinoma diagnosis because of the fear of heavy blood loss and distant metastasis. Five patients who were preoperatively diagnosed as having cornual pregnancy underwent laparoscopic resection of mass lesion and then proved to have gestational choriocarcinoma based on pathological examinations. Chemotherapy was started within two days after surgery, and the rate of complete remission was 100%. The mean follow-up time was 29.8±19.1 months, and no patient showed signs of relapse. Laparoscopic resection of uterine mass followed by timely postoperative chemotherapy may be an effective and safe way to obtain pathologic results in patients with suspected gestational choriocarcinoma.

Intracranial hemangiopericytoma with right-sided aortic arch: a case report and summary of experience

Hemangiopericytoma is clinically rare and easily confused with meningioma.Right-sided aortic arch is also a rare disease of congenital cardiovascular variability.The intracranial hemangiopericytoma associated with the right-sided aortic arch has not been reported in the literature.We are here to register a case of right aortic arch concurrent with intracranial hemangiopericytoma;the patient was initially thought to be a simple meningioma,but he was eventually diagnosed as a hemangiopericytoma with right aortic arch and multiple intracranial vascular stenosis and malformation.Whether there was a genetic correlation between the two provides a potential research direction for us.Therefore,the diagnosis and treatment of some rare diseases should be a more comprehensive analysis and evaluation.Adequate examination and accurate diagnosis are crucial,which will directly affect the efficacy of surgery and the prognosis of patients.

Themis suppresses the effector function of CD8^(+)T cells in acute viral infection

CD8^(+)T cells play a central role in antiviral immune responses.Upon infection,naive CD8^(+)T cells differentiate into effector cells to eliminate virus-infected cells,and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is resolved.Although extensively investigated,the underlying mechanisms of CD+T-cell differentiation remain incompletely understood.Themis is a T-cell-specific protein that plays critical roles in T-cell development.Recent studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8^(+)T-cell homeostasis,cytokine responsiveness,and antibacterial responses.In this study,we used LCMV Armstrong infection as a probe to explore the role of Themis in viral infection.We found that preexisting CD8^(+)T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout mice.Further analyses showed that in the primary immune response,Themis deficiency promoted the differentiation of CD8^(+)effector cells and increased their TNF and IFNy production.Moreover,Themis deficiency impaired memory precursor cell(MPEC)differentiation but promoted short-lived effector cell(SLEC)differentiation.Themis deficiency also enhanced effector cytokine production in memory CD8^(+)T cells while impairing central memory CD8^(+)T-cell formation.Mechanistically,we found that Themis mediates PD-1 expression and its signaling in effector CD8^(+)T cells,which explains the elevated cytokine production in these cells when Themis is disrupted.

New insight into the oncogenic mechanism of the retroviral oncoprotein Tax

Human T cell leukemia virus type 1(HTLV-1),an etio-logical factor that causes adult T cell leukemia and lym-phoma(ATL),infects over 20 million people worldwide.About 1 million of HTLV-1-infected patients develop ATL,a highly aggressive non-Hodgkin's lymphoma without an effective therapy.The pX region of the HTLV-1 viral genome encodes an oncogenic protein,Tax,which plays a central role in transforming CD4+ T lymphocytes by deregulating oncogenic signaling pathways and promoting cell cycle progression.Expression of Tax following viral entry is critical for promoting survival and proliferation of human T cells and is required for initiation of oncogenesis.Tax exhibits diverse functions in host cells,and this oncoprotein primarily targets IκB kinase complex in the cytoplasm,resulting in persistent activation of NF-κB and upregulation of its responsive gene expressions that are crucial for T cell survival and cell cycle progression.We here review recent advances for the pathological roles of Tax in modulating IκB kinase activity.We also discuss our recent observation that Tax connects the IκB kinase complex to autophagy pathways.Understanding Tax-mediated pathogenesis will provide insights into development of new therapeutics in controlling HTLV-1-associated diseases.

Pulmonary deportation of hydatidiform mole:a 12-year,single tertiary center experience in China

Background:Pulmonary deportation of hydatidiform mole is an exceedingly rare entity.The underlying mechanisms and proper management strategies remain unclear based on sporadic case reports over the past six decades.This study aimed to investigate the clinical features and rational treatment of patients with benign molar pregnancies with pulmonary deportation based on our experience.Methods:Medical records of 20 cases of hydatidiform mole with pulmonary deportation were retrospectively reviewed at Peking Union Medical College Hospital from November 2006 to May 2019.The detailed information of all patients was recorded and analyzed.Patients were divided into different groups according to their characteristics and Mann-Whitney U test was used to compare the duration to achieve a normal b-human chorionic gonadotrophin(b-hCG)level after the first evacuation among groups.Results:Initial pulmonary computed tomography scans showed suspected bilateral,left and right chest deportation of hydatidiform mole in 12,four,and four patients,respectively,with the maximum nodular diameter ranging from 0.6 to 1.2 cm.Ten patients achieved lesion resolution while the remaining ten patients achieved decreases in the size of their pulmonary lesions.The median duration to achieve a normal b-hCG level after the first evacuation was 15.5(13.0,21.9)weeks.There was no significant difference in the duration to achieve a normal b-hCG level after the first evacuation between two groups based on age(≥40 years vs.<40 years:15.8[12.2,21.5]weeks vs.15.5[12.9,23.0]weeks,Z=0.094,P=0.925),type of antecedent mole(partial mole vs.complete mole:15.2[12.5,27.4]weeks vs.15.9[12.9,21.5]weeks,Z=0.165,P=0.869),distribution of pulmonary nodules(bilateral lungs vs.unilateral lung:15.2[12.8,22.5]weeks vs.15.9[13.2,22.2]weeks,Z=0.386,P=0.700),maximum size of pulmonary nodules(>0.5 cm vs.
0.5 cm:13.0[11.3,17.2]weeks vs.16.0[14.5,23.8]weeks,Z=1.815,P=0.070),and number of uterine evacuations(once vs.twice or three times:15.0[13.0,16.3]weeks vs.16.0[12.8,23.9]weeks,Z=0.832,P=0.405).The post-molar cohort was followed up for 17 to 139 months,and no gestational trophoblastic neoplasia was observed.Conclusions:No surgeries other than uterine evacuation and no chemotherapy regimens are recommended for such patients if they achieve satisfactory decreases in the level of hCG and gradual decrease or disappearance of pulmonary deportation nodules.Patients should be informed about the necessity of long-term follow-up.More collaborative international studies on this exceedingly rare condition may guide decisions regarding optimal management strategies.

Sensitivity analysis of single-angle polarization reflectance observed by satellite

Two channels of the Cloud Aerosol Polarimetric Imager,onboard the TanSat-Chinese carbon dioxide observation satellite,are designed to detect the polarization state of radiation reflected by the earth-atmosphere system in a single-viewing angle.Aiming to understand how the earth and atmospheric parameters affect the polarization state of radiation,we conduct a sensitivity analysis of the polarized reflectance at the top of atmosphere(TOA)with respect to the aerosol microphysical parameters,atmospheric profiles,and surface polarization properties.It is found that(1)the TOA polarization reflectance at 0.66 lm is most sensitive to the real part of the aerosol complex refractive index,the mean radius of the fine mode aerosol particles,as well as atmospheric pressure and temperature profiles;(2)the TOA polarization reflectance at 1.64 lm is sensitive to the volume ratio between the coarse mode and fine mode particles as well,but it is not sensitive to atmospheric profiles;and(3)surface polarization properties have a relatively weak influence on the TOA polarization reflectance at both 0.66 and 1.64 lm.