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1.
Comput Intell Neurosci ; 2021: 4123254, 2021.
Article in English | MEDLINE | ID: mdl-35003243

ABSTRACT

The assessment of teaching quality is a very complex and fuzzy nonlinear process, which involves many factors and variables, so the establishment of the mathematical model is complicated, and the traditional evaluation method of teaching quality is no longer fully competent. In order to evaluate teaching quality effectively and accurately, an optimized GA-BPNN algorithm based on genetic algorithm (GA) and backpropagation neural network (BPNN) is proposed. Firstly, an index system of teaching quality evaluation is established, and a questionnaire is designed according to the index system to collect data. Then, an English teaching quality evaluation system is established by optimizing model parameters. The simulation shows that the average evaluation accuracy of the GA-BPNN algorithm is 98.56%, which is 13.23% and 5.85% higher than those of the BPNN model and the optimized BPNN model, respectively. The comparison results show that the GA-BPNN algorithm in teaching quality evaluation can make reasonable and scientific results.


Subject(s)
Models, Theoretical , Neural Networks, Computer , Algorithms , Computer Simulation
2.
Ann Clin Microbiol Antimicrob ; 20(1): 83, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34911528

ABSTRACT

BACKGROUND: Solid transplant patients are susceptible to Pneumocystis jirovecii pneumonia (PJP). While the vast majority of PJP cases occur within the first 6 months after transplantation, very few PJP cases are seen beyond 1 year post-transplantation (late-onset PJP). PJP and coronavirus disease 2019 (COVID-19, caused by infection with SARS-CoV-2) share quite a few common clinical manifestations and imaging findings, making the diagnosis of PJP often underappreciated during the current COVID-19 pandemic. To date, only 1 case of kidney transplantation who developed COVID-19 and late-onset PJP has been reported, but this patient also suffered from many other infections and died from respiratory failure and multiple organ dysfunction syndrome. A successful treatment of kidney patients with COVID-19 and late-onset PJP has not been reported. CASE PRESENTATION: We present a case of a 55-year-old male kidney transplant patient with COVID-19 who also developed late-onset PJP. He received a combined treatment strategy, including specific anti-pneumocystis therapy, symptomatic supportive therapy, adjusted immunosuppressive therapy, and use of antiviral drugs/antibiotics, ending with a favorable outcome. CONCLUSIONS: This case highlights the importance of prompt and differential diagnosis of PJP in kidney transplant patients with SARS-CoV-2 infection. Further studies are required to clarify if kidney transplant patients with COVID-19 could be prone to develop late-onset PJP and how these patients should be treated.


Subject(s)
COVID-19 , Kidney Transplantation , Pneumonia, Pneumocystis , COVID-19/complications , COVID-19/drug therapy , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/drug therapy
3.
Aging (Albany NY) ; 13(17): 20906-20914, 2021 09 09.
Article in English | MEDLINE | ID: mdl-34499050

ABSTRACT

BACKGROUND: Cardiac injury is common and associated with poor clinical outcomes in COVID-19. Data are lacking whether high-dose intravenous vitamin C (HIVC) could help to ameliorate myocardial injury in the pandemic. METHODS: The retrospective cohort study included consecutive severe and critically ill COVID-19 patients with cardiac injury receiving symptomatic supportive treatments alone or together with HIVC. Troponin I and inflammatory markers were collected at admission and day 21 during hospitalization from the electronic medical records. RESULTS: The patients (n = 113) were categorized into the ameliorated cardiac injury (ACI) group (n = 70) and the non-ameliorated cardiac injury (NACI) group (n = 43). Overall, fifty-one (45.1%) patients were administered with HIVC, the percentages of patients with HIVC were higher in the ACI group than those in the NACI group. Logistic regression analysis revealed that HIVC was independently associated with the improvement of myocardial injury. Further analysis showed that inflammatory markers levels significantly decreased at day 21 during hospitalization in patients with HIVC therapy compared to those administered with symptomatic supportive treatments alone. Meanwhile, similar results were also observed regarding changes in inflammatory markers levels from baseline to day 21 during hospitalization in the patients treated with HIVC. CONCLUSIONS: HIVC can ameliorate cardiac injury through alleviating hyperinflammation in severe and critically ill patients with COVID-19.


Subject(s)
Ascorbic Acid/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Heart Injuries/drug therapy , Pandemics , Aged , Biomarkers/blood , COVID-19/blood , Dose-Response Relationship, Drug , Female , Hospitalization , Humans , Inflammation/pathology , Inflammation Mediators/blood , Male , Middle Aged , Retrospective Studies , Troponin I/metabolism
4.
Front Immunol ; 12: 658843, 2021.
Article in English | MEDLINE | ID: mdl-34276653

ABSTRACT

Background: Easily accessible tools that reliably stratify Mycobacterium tuberculosis (MTB) infection are needed to facilitate the improvement of clinical management. The current study attempts to reveal lymphocyte-related immune characteristics of active tuberculosis (ATB) patients and establish immunodiagnostic model for discriminating ATB from latent tuberculosis infection (LTBI) and healthy controls (HC). Methods: A total of 171 subjects consisted of 54 ATB, 57 LTBI, and 60 HC were consecutively recruited at Tongji hospital from January 2019 to January 2021. All participants were tested for lymphocyte subsets, phenotype, and function. Other examination including T-SPOT and microbiological detection for MTB were performed simultaneously. Results: Compared with LTBI and HC, ATB patients exhibited significantly lower number and function of lymphocytes including CD4+ T cells, CD8+ T cells and NK cells, and significantly higher T cell activation represented by HLA-DR and proportion of immunosuppressive cells represented by Treg. An immunodiagnostic model based on the combination of NK cell number, HLA-DR+CD3+ T cells, Treg, CD4+ T cell function, and NK cell function was built using logistic regression. Based on receiver operating characteristic curve analysis, the area under the curve (AUC) of the diagnostic model was 0.920 (95% CI, 0.867-0.973) in distinguishing ATB from LTBI, while the cut-off value of 0.676 produced a sensitivity of 81.48% (95% CI, 69.16%-89.62%) and specificity of 91.23% (95% CI, 81.06%-96.20%). Meanwhile, AUC analysis between ATB and HC according to the diagnostic model was 0.911 (95% CI, 0.855-0.967), with a sensitivity of 81.48% (95% CI, 69.16%-89.62%) and a specificity of 90.00% (95% CI, 79.85%-95.34%). Conclusions: Our study demonstrated that the immunodiagnostic model established by the combination of lymphocyte-related indicators could facilitate the status differentiation of MTB infection.


Subject(s)
Host-Pathogen Interactions/immunology , Lymphocytes/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis/immunology , Tuberculosis/microbiology , Biomarkers , Humans , Immunophenotyping , Latent Tuberculosis , Lymphocyte Activation/immunology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Lymphocytes/metabolism , ROC Curve , Tuberculosis/diagnosis
5.
Front Immunol ; 12: 652383, 2021.
Article in English | MEDLINE | ID: mdl-33912176

ABSTRACT

Background: Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in immunocompromised patients. The accurate prediction of PJP development in patients undergoing immunosuppressive therapy remains challenge. Methods: Patients undergoing immunosuppressive treatment and with confirmed pneumocystis jiroveci infection were enrolled. Another group of matched patients with immunosuppressant treatment but without signs of infectious diseases were enrolled to control group. Results: A total of 80 (40 PJP, 40 non-PJP) participants were enrolled from Tongji Hospital. None of the patients were HIV positive. The routine laboratory indicators, such as LYM, MON, RBC, TP, and ALB, were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH in PJP patients was significantly higher than in non-PJP controls. For immunological indicators, the numbers of T, B, and NK cells were all remarkably lower in PJP patients than in non-PJP controls, whereas the functional markers such as HLA-DR, CD45RO and CD28 expressed on CD4+ or CD8+ T cells had no statistical difference between these two groups. Cluster analysis showing that decrease of host immunity markers including CD3+, CD4+ and CD8+ T cells, and increase of tissue damage marker LDH were the most typical characteristics of PJP patients. A further established model based on combination of CD8+ T cells and LDH showed prominent value in distinguishing PJP from non-PJP, with AUC of 0.941 (95% CI, 0.892-0.990). Conclusions: A model based on combination of routine laboratory and immunological indicators shows prominent value for predicting the development of PJP in HIV-negative patients undergoing immunosuppressive therapy.


Subject(s)
Biomarkers , Immunocompromised Host , Opportunistic Infections , Pneumocystis carinii , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/etiology , Adult , Aged , Computational Biology/methods , Disease Susceptibility , Female , Humans , Immunophenotyping , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Pneumocystis carinii/immunology , Prognosis , ROC Curve , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
6.
Front Cell Infect Microbiol ; 11: 650163, 2021.
Article in English | MEDLINE | ID: mdl-33816355

ABSTRACT

Background: The prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting. Methods: 28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT.TB. We analyzed specimen types' effect on these assays' performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections. Results: Sputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB+/Xpert+ and 6/7 of AFB+/Xpert- cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB+ or Xpert+. However, T-SPOTMDC (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of Mycobacterium tuberculosis-specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT.TB assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB-/Xpert- patients. Conclusions: Concurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOTMDC and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB-/Xpert- patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers' decisions regarding prevention and control of TB in a high burden setting.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Adult , Algorithms , Big Data , China , Humans , Leukocytes, Mononuclear , Retrospective Studies , Sensitivity and Specificity , Sputum
7.
Am J Med Sci ; 361(6): 718-724, 2021 06.
Article in English | MEDLINE | ID: mdl-33582156

ABSTRACT

BACKGROUND: Inflammation can facilitate development of coronavirus disease 2019 (COVID-19) and cardiac injury is associated with worse clinical outcomes. However, data are relatively scarce on the association between hyper-inflammatory response and cardiac injury among COVID-19 patients. METHODS: The study was designed based on severe and critically ill patients with COVID-19. Information on clinical characteristics and laboratory examinations was collected from the electronic medical records and analyzed. RESULTS: There were 32.4% (n = 107) of patients with cardiac injury. The median age was 67 years, and 48.8% (n = 161) of patients were men. Hypertension was the most common in 161 (48.8%) patients, followed by diabetes (16.7%, n = 55) and coronary heart disease (13.3%, n = 44). Compared to cases without cardiac injury, those with cardiac injury were older, had higher proportions of coronary heart disease, and leukocyte counts, significantly elevated concentrations of N-terminal pro-B-Type natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6, and IL-8, but lower lymphocyte counts. A significant positive correlation was observed between high-sensitivity troponin I and inflammatory cytokines. Logistic regression analysis showed that hs-CRP, TNF-α and IL-6 were independent risk factors for cardiac injury. CONCLUSIONS: Cardiac injury was associated with elevated levels of inflammatory cytokines among severe and critically ill patients with COVID-19, suggesting that hyper-inflammatory response may involve in cardiac injury.


Subject(s)
COVID-19 , Heart Diseases , SARS-CoV-2 , Troponin I/blood , Aged , C-Reactive Protein/analysis , COVID-19/immunology , COVID-19/physiopathology , COVID-19/therapy , Cardiometabolic Risk Factors , China/epidemiology , Critical Illness/epidemiology , Critical Illness/therapy , Diabetes Mellitus/epidemiology , Female , Heart Diseases/diagnosis , Heart Diseases/immunology , Heart Diseases/virology , Humans , Hypertension/epidemiology , Interleukin-6/blood , Male , Risk Assessment , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/virology , Tumor Necrosis Factor-alpha/blood
8.
Ann Med ; 53(1): 257-266, 2021 12.
Article in English | MEDLINE | ID: mdl-33410720

ABSTRACT

OBJECTIVES: To appraise effective predictors for COVID-19 mortality in a retrospective cohort study. METHODS: A total of 1270 COVID-19 patients, including 984 admitted in Sino French New City Branch (training and internal validation sets randomly split at 7:3 ratio) and 286 admitted in Optical Valley Branch (external validation set) of Wuhan Tongji hospital, were included in this study. Forty-eight clinical and laboratory features were screened with LASSO method. Further multi-tree extreme gradient boosting (XGBoost) machine learning-based model was used to rank importance of features selected from LASSO and subsequently constructed death risk prediction model with simple-tree XGBoost model. Performances of models were evaluated by AUC, prediction accuracy, precision, and F1 scores. RESULTS: Six features, including disease severity, age, levels of high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), ferritin, and interleukin-10 (IL-10), were selected as predictors for COVID-19 mortality. Simple-tree XGBoost model conducted by these features can predict death risk accurately with >90% precision and >85% sensitivity, as well as F1 scores >0.90 in training and validation sets. CONCLUSION: We proposed the disease severity, age, serum levels of hs-CRP, LDH, ferritin, and IL-10 as significant predictors for death risk of COVID-19, which may help to identify the high-risk COVID-19 cases. KEY MESSAGES A machine learning method is used to build death risk model for COVID-19 patients. Disease severity, age, hs-CRP, LDH, ferritin, and IL-10 are death risk factors. These findings may help to identify the high-risk COVID-19 cases.


Subject(s)
COVID-19/mortality , Clinical Decision Rules , Hospitalization , Machine Learning , Adult , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/physiopathology , Cardiovascular Diseases/epidemiology , China/epidemiology , Cohort Studies , Comorbidity , Diabetes Mellitus/epidemiology , Female , Ferritins/metabolism , Humans , Hypertension/epidemiology , Interleukin-10/metabolism , L-Lactate Dehydrogenase/metabolism , Male , Middle Aged , Prognosis , Reproducibility of Results , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
9.
Hematology ; 25(1): 484-488, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33295842

ABSTRACT

OBJECTIVES: Hemophilia B (HB, OMIM: 300746) is one of the most common bleeding disorders with an X-linked recessive inheritance pattern, caused by the deficiency of coagulation factor IX (FIX). FIX is encoded by the F9 gene located on Xq27.1. Diagnosis of HB is primarily suspected by prolonged activated partial thromboplastin time (APTT), decreased FIX activity (FIX:C) or genetic test of the F9 gene. We herein described a Chinese family with patients of mild HB. METHODS: Sanger sequencing of the F9 gene was applied to identify mutation. Coagulation tests were performed. RESULTS: The proband was a 5-year-old boy. He suffered prolonged bleeding after tonsillectomy recently and circumcision last year as well. His grandfather experienced prolonged bleeding after gastric surgery. Both patients showed normal APTT, though they had significantly decreased FIX:C. Sanger sequencing of the F9 gene revealed a novel hemizygous F9 c.639C > A (p.Asn213Lys) missense mutation in both patients. The proband's mother carried heterozygous mutation. This mutation was located in the activation peptide domain of FIX. CONCLUSION: In conclusion, we confirmed that APTT could be normal in mild HB patients. Highly sensitive APTT for mild HB and molecular genetic test could confirm the diagnosis of mild HB.


Subject(s)
Blood Coagulation , Hemophilia B/blood , Hemophilia B/diagnosis , Partial Thromboplastin Time , Alleles , Amino Acid Substitution , Blood Coagulation Tests , Child, Preschool , DNA Mutational Analysis , Factor IX/genetics , Genotype , Hemophilia B/etiology , Humans , Male , Middle Aged , Mutation , Mutation, Missense , Pedigree , Severity of Illness Index
11.
Mol Carcinog ; 59(8): 980-988, 2020 08.
Article in English | MEDLINE | ID: mdl-32484301

ABSTRACT

Nonreceptor protein tyrosine phosphatases (NRPTPs) are reported to be associated with several human cancers, but their roles in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. Here, we integrated bioinformatics tools, population association analyses, and biological assays to systematically screen for potentially functional single nucleotide polymorphisms (SNPs) within the 17 NRPTPs genes and evaluate the effects of candidate SNPs on the risk of HCC or persistent HBV infection. A total of 790 HBV-related HCC cases and 1454 cancer-free controls were enrolled. Controls included 711 HBV persistent carriers and 743 spontaneously recovered subjects. Results demonstrated that PTPN4 rs9308777 (odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.06-1.49, P = .009) and PTPN12 rs350050 (OR = 1.26, 95% CI = 1.10-1.45, P = .001), were significantly associated with HCC risk, but not with persistent HBV infection risk. The cumulative risk effect of these two SNPs was more significantly increased the susceptibility to HCC (OR = 1.27, 95% CI = 1.14-1.41, P = 2.40 × 10-5 ). Subsequent biological assays further revealed the potential pathogenesis that PTPN4 rs9308777 might decrease the gene expression, and PTPN12 rs3750050 might promote cell proliferation by attenuating PTPN12's inhibitory activity on EGFR/ERK pathway. In summary, our integrative study highlights that PTPN4 and PTPN12 are significantly associated with HBV-related HCC risk, but do not influence persistent HBV infection. These findings shed light on the importance of the synergistic effects of regulatory and missense variants on the risk for HCC, and provide data to support personalized cancer medicine in the future.


Subject(s)
/genetics , Carcinoma, Hepatocellular/epidemiology , Hepatitis B virus/isolation & purification , Hepatitis B/complications , Polymorphism, Single Nucleotide , Protein Tyrosine Phosphatase, Non-Receptor Type 12/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 4/genetics , Biomarkers, Tumor , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Case-Control Studies , China/epidemiology , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Hepatitis B/virology , Humans , Incidence , Liver Neoplasms/epidemiology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/virology , Male , Middle Aged , Prognosis , Risk Factors
12.
JCI Insight ; 5(10)2020 05 21.
Article in English | MEDLINE | ID: mdl-32352933

ABSTRACT

BACKGROUNDThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a novel viral pneumonia (COVID-19), which is rapidly spreading throughout the world. The positive result of nucleic acid test is a golden criterion to confirm SARS-CoV-2 infection, but the detection features remain unclear.METHODSWe performed a retrospective analysis in 5630 high-risk individuals receiving SARS-CoV-2 nucleic acid tests in Wuhan, China, and investigated their characteristics and diagnosis rates.RESULTSThe overall diagnosis rate was 34.7% (1952/5630). Male (P = 0.025) and older populations (P = 2.525 × 10-39) were at significantly higher risk of SARS-CoV-2 infection. People were generally susceptible, and most cases concentrated in people of 30-79 years. Furthermore, we investigated the association between diagnosis rate and the amount of testing in 501 subjects. Results revealed a 1.27-fold improvement (from 27.9% to 35.5%) of diagnosis rate from testing once to twice (P = 5.847 × 10-9) and a 1.43-fold improvement (from 27.9% to 39.9%) from testing once to 3 times (P = 7.797 × 10-14). More than 3 testing administrations was not helpful for further improvement. However, this improvement was not observed in subjects with pneumonia (P = 0.097).CONCLUSIONAll populations are susceptible to SARS-CoV-2 infection, and male and older-aged populations are at significantly higher risk. Increasing the amount of testing could significantly improve diagnosis rates, except for subjects with pneumonia. It is recommended to test twice in those high-risk individuals whose results are negative the first time, and performing 3 tests is better, if possible.FUNDINGThis work was supported by National Mega Project on Major Infectious Disease Prevention (no. 2017ZX10103005-007) and National Key Research and Development Program of China (no. 2018YFE0204500).


Subject(s)
Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19 , COVID-19 Testing , Child , Child, Preschool , China/epidemiology , Clinical Laboratory Techniques/methods , Coronavirus Infections/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Molecular Diagnostic Techniques , Pandemics , Pneumonia, Viral/epidemiology , RNA, Viral/analysis , Real-Time Polymerase Chain Reaction , Retrospective Studies , Sex Factors , Young Adult
13.
JCI Insight ; 5(10)2020 05 21.
Article in English | MEDLINE | ID: mdl-32324595

ABSTRACT

BACKGROUNDThe coronavirus disease 2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak throughout the world. The host immunity of COVID-19 patients is unknown.METHODSThe routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission.RESULTSA total of 65 SARS-CoV-2-positive patients were classified as having mild (n = 30), severe (n = 20), and extremely severe (n = 15) illness. Many routine laboratory tests, such as ferritin, lactate dehydrogenase, and D-dimer, were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells, and B cells were gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The costimulatory molecule CD28 had opposite results. The percentage of natural Tregs was decreased in extremely severe patients. The percentage of IFN-γ-producing CD8+ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-γ-producing CD4+ T cells was increased in extremely severe patients. IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients.CONCLUSIONThe number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4+ and CD8+ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection.FUNDINGThis work was funded by the National Mega Project on Major Infectious Disease Prevention (2017ZX10103005-007) and the Fundamental Research Funds for the Central Universities (2019kfyRCPY098).


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology , Betacoronavirus , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Cytokines/metabolism , Diagnostic Tests, Routine , Female , Humans , Immunity , Lymphocyte Count , Male , Middle Aged , Pandemics , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/immunology
14.
BMC Med Genet ; 21(1): 6, 2020 01 06.
Article in English | MEDLINE | ID: mdl-31906886

ABSTRACT

BACKGROUND: Thalassemia is a group of inherited hemoglobic disorders resulting from defects in the synthesis of one or more of the hemoglobin chains, which is one of the most prevalent inherited disorders in southern China. Only few studies reported the molecular characterization of α- and ß-Thalassemia in Hubei Province in the central of China. METHODS: A total of 4889 clinically suspected cases of thalassemia were analyzed by Gap-PCR, PCR-based reverse dot blot (RDB). RESULTS: 1706 (33.8%) subjects harbored thalassemia mutations, including 539 (11.0%) subjects with α-thalassemia, 1140 (23.3%) subjects with ß-thalassemia mutations, and 25 (0.51%) subjects with both α- and ß-thalassemia mutations. Seven genotypes of α-thalassemia mutations and 29 genotypes of ß-thalassemia mutations were characterized. --SEA/αα (66.05%), -α3.7/αα (24.12%), and -α4.2/αα (3.71%) accounted for 93.88% of the α-thalassemia mutations. ßIVS-II-654/ßN, ßCD41-42/ßN, ßCD17/ßN, ßCD27-28/ßN, ßCD71-72/ßN, ß - 28/ßN, ß - 29/ßN, ßCD43/ßN, ßE/ßN, accounting for 96.40% of all ß-thalassemia genotypes. Furthermore, mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) were sensitive markers for both ß-thalassemia and α-thalassemia with --SEA/αα, but not -α3.7/αα and -α4.2/αα. CONCLUSIONS: Our data indicated great heterogeneity and extensive spectrum of thalassemias in Hubei province of China.


Subject(s)
Genetics, Population , Hemoglobins/genetics , alpha-Thalassemia/genetics , beta-Thalassemia/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , China , Female , Genetic Heterogeneity , Genotype , Hemoglobins/biosynthesis , Humans , Infant , Male , Middle Aged , Mutation , Young Adult , alpha-Thalassemia/epidemiology , beta-Thalassemia/blood , beta-Thalassemia/epidemiology
15.
Front Genet ; 10: 887, 2019.
Article in English | MEDLINE | ID: mdl-31608117

ABSTRACT

Background: Aberrant hypermethylation of the Septin 9 (SEPT9) is an early event in several human cancers, and increasing studies have reported good performance of methylated SEPT9 (mSEPT9) in cancer diagnosis. Recent studies further focused on its value in cancer prognosis, but results are not clearly elucidated. Methods: A comprehensive search to identify relevant studies about the association between mSEPT9 and cancer prognosis was conducted through the EMBASE, PubMed, and Web of Science databases (up to January 2019). The main outcomes were overall survival (OS) and disease-free survival (DFS). The hazard ratio (HR) and 95% confidence interval (CI) for OS and DFS were extracted from each included study and pooled using a random-effects model. Results: Ten eligible studies comprising 1,266 cancer patients were included. Results demonstrated that mSEPT9 was associated with poor OS (HR = 2.07, 95% CI = 1.40-3.06). Specially, mSEPT9 detected in preoperative plasma predicted worse OS in cancer patients (HR = 3.25, 95% CI = 1.93-5.48). In addition, we also identified a significant association of mSEPT9 with decreased DFS of cancer (HR = 3.24, 95% CI = 1.81-5.79). Conclusion: Our meta-analysis supports that mSEPT9 is associated with reduced OS and DFS in cancer patients. Moreover, detection of mSEPT9 using plasma appears to be a convenient and promising way to predict long-term survival of cancer patients.

17.
Curr Med Sci ; 38(5): 932-936, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30341532

ABSTRACT

Oculocutaneous albinism (OCA) is an autosomal recessive pigmentation abnormality, characterized by variable hair, skin, and ocular hypopigmentation. OCA1 is the most frequent subtype of OCA, caused by mutations in the tyrosinase gene (TYR). In this study, we investigated the genetic mutation of a Chinese family with a female OCA patient who came for genetic counseling before pregnancy. Complete physical examination was performed, and DNA from blood samples was collected from the family members. Mutations of TYR, OCA2, and SLC45A2 genes were examined in the proband, and verified in her parents by Sanger sequencing. Large deletion or duplication of TYR and OCA2 genes was detected by multiplex ligation-dependent probe amplification (MLPA). A homozygous TYR c.307T>C (p.Cys103Arg) missense mutation was identified in the proband, and both parents were heterozygous carriers. No large deletion or duplication was found in the proband. This mutation was absent in 1000G, ExAC, or HGMD database, and multiple lines of in silico tools supported a deleterious effect. These results suggest that TYR c.307T>C mutation might be responsible for OCA1, and our study further expands the mutation spectrum of OCA1 in the Chinese population.


Subject(s)
Albinism, Oculocutaneous/genetics , Genetic Predisposition to Disease , Monophenol Monooxygenase/genetics , Adult , Albinism, Oculocutaneous/pathology , Computer Simulation , Female , Genotype , Homozygote , Humans , Mutation, Missense , Pedigree
18.
Int J Infect Dis ; 71: 14-19, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29428408

ABSTRACT

OBJECTIVE: Limited data on the diagnostic accuracy of the Xpert MTB/RIF assay using bronchoalveolar lavage fluid from patients with suspected pulmonary tuberculosis (PTB) have been reported in China. Therefore, a retrospective study was designed to evaluate the diagnostic accuracy of this assay. METHODS: Clinical, radiological, and microbiological characteristics of 238 patients with suspected PTB were reviewed retrospectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of active PTB were calculated for the Xpert MTB/RIF assay using TB culture or final diagnosis based on clinical and radiological evaluation as the reference standard. RESULTS: The sensitivity and specificity of the Xpert MTB/RIF assay were 84.5% and 98.9%, respectively, and those for smear microscopy were 36.2% and 100%, respectively, when compared to the culture method. However, compared with the sensitivity and specificity of final diagnosis based on clinical and radiological evaluation, the sensitivity and specificity of the assay were 72.9% and 98.7%, respectively, which were significantly higher than those for smear microscopy. CONCLUSIONS: The Xpert MTB/RIF assay on bronchoalveolar lavage fluid could serve as an additional rapid diagnostic tool for PTB in a high TB-burden country and improve the time to TB treatment initiation in patients with PTB.


Subject(s)
Bronchoalveolar Lavage Fluid/microbiology , Molecular Diagnostic Techniques/methods , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , Tuberculosis, Pulmonary/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Antitubercular Agents , China , Female , Humans , Male , Middle Aged , Reference Standards , Retrospective Studies , Sensitivity and Specificity , Tuberculosis, Pulmonary/drug therapy , Young Adult
19.
Oncotarget ; 8(68): 113282-113286, 2017 Dec 22.
Article in English | MEDLINE | ID: mdl-29348906

ABSTRACT

Hereditary spherocytosis (HS) is a congenital hemolytic anemia that affects the cell membrane of red blood cells and is characterized by the presence of spherical-shaped erythrocytes in the peripheral blood film. The clinical manifestation of HS ranges from asymptomatic to severe cases that require transfusion during early childhood. HS is caused by mutations in red blood cell membrane protein encoding genes, including ANK1, EPB42, SLC4A1, SPTA1, and SPTB. Mutations of the ANK1 gene account for 75% of all HS cases, and these particular mutations are typically inherited in an autosomal dominant manner. In this study, heterozygous an ANK1 IVS3-2A>C mutation was identified in a 7-year-old girl with Coombs-negative and severe hemolytic jaundice using targeted next-generation sequencing (NGS) and Sanger sequencing. Spherocytes were observed in a peripheral smear. Osmotic fragility was increased, and glucose-6-phosphate dehydrogenase (G6PD) activity was normal. A genetic mutation screen for α- and ß-thalassemia was negative. Autoimmune antibody tests were negative. Both the girl and her affected father received a splenectomy. Patient-derived peripheral blood mononuclear cells showed skipping of exon 4 in the mRNA, which confirmed the splicing mutation effect of the ANK1 IVS3-2A>C mutation. Moreover, the anemia was ameliorated after splenectomy. Our results demonstrate that the ANK1 IVS3-2A>C mutation may lead to exon 4 skipping of the ANK1 gene and cause HS.

20.
Oncotarget ; 8(57): 96791-96797, 2017 Nov 14.
Article in English | MEDLINE | ID: mdl-29228571

ABSTRACT

Hereditary spherocytosis (HS) is an inherited heterogeneous hemolytic anemia, characterized by the presence of spherical-shaped erythrocytes on the peripheral blood smear, and the clinical manifestation ranges from asymptomatic to severely anemic, and transfusion-dependent patients. Mutations in at least five genes (ANK1, EPB42, SLC4A1, SPTA1, and SPTB) have been identified so far, and mutations of ANK1 gene are responsible for the majority of all HS cases. In this study, targeted next generation sequencing (NGS) was applied to identify a novel de novo ANK1 c.4276C>T (p.R1426*) nonsense mutation in a Chinese family with a patient of HS who was diagnosed clinically with only 10% spherical-shaped erythrocytes in the peripheral blood and received splenectomy. Sanger sequencing further confirmed that only the patient carried heterozygous ANK1 c.4276C>T nonsense mutation, while none of his parents or his young brother carried this mutation. Moreover, consistent with the genetic findings, the anemia was ameliorated after splenectomy. RBCs increased from 2.74 × 1012/L pre-surgery to 4.76 × 1012/L one month post-surgery, and hemoglobin increased from 66g/L to 126g/L respectively. This is the first report of ANK1 c.4276C>T (p.R1426*) heterozygous nonsense mutation responsible for HS. Our results also demonstrate that targeted NGS may provide a powerful approach for rapid genetic test of HS.

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