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BACKGROUND: Concerns regarding potential toxicity and drug-drug interactions during long-term treatment with three-drug active antiretroviral therapy (ART) regimens have been attracting increasing attention. We aimed to evaluate the efficacy and safety of dolutegravir (DTG) plus lamivudine (3TC) in ART-naive adults in China. METHODS: This prospective observational cohort study enrolled HIV-naive inpatients treated with DTG + 3TC (2DR arm) or efavirenz (EFV) plus tenofovir disoproxil fumarate (TDF) and 3TC (3DR arm). There were no limits on baseline viral load. Inflammatory biomarkers were also investigated in the 2DR arm. RESULTS: Between September 2019 and January 2020, 27 patients treated with DTG + 3TC and 28 patients treated with EFV + TDF + 3TC were enrolled in the study. At week 12, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 81.5% (22/27) compared with 53.6% (15/28) in the 3DR arm (p < 0.01). At week 24, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 100% (26/26) compared with 83.3% (20/24) in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 12 were 125.46 cells/µL in the 2DR arm and 41.20 cells/µL in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 24 were 209.68 cells/µL in the 2DR arm and 73.28 cells/µL in the 3DR arm (p < 0.05). CONCLUSIONS: DTG + 3TC achieved virologic suppression more rapidly than EFV + TDF + 3TC after 12 and 24 weeks. DTG + 3TC could represent an optimal regimen for advanced patients. Clinical Trial Registration ChiCTR1900027640 (22/November/2019).
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Alquinos , Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Ciclopropanos , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos , Humanos , Lamivudine/uso terapéutico , Oxazinas , Piperazinas , Estudios Prospectivos , Piridonas , Tenofovir/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate the efficacy and mechanistic bases of the intravenous injection of arsenic trioxide at clinical-relevant doses for treating an imiquimod-induced psoriasis-like mouse model. METHODS: After inducing psoriasis-like skin lesions on the back of mice with imiquimod, mice in each group were injected with a clinical dose of arsenic trioxide through the tail vein. The changes in the gene expression, protein expression and distribution of relevant inflammatory factors were evaluated in the inflicted skin area, for mechanisms underlying the efficacy of intravenous As2O3 intervention. HaCaT cells were used to establish an in vitro psoriasis model and pcDNA3.1-NF-κB overexpression plasmid was transfected into cells to overexpress P65, which further confirmed the role of the NF-κB signaling pathway in the effectiveness of As2O3. RESULTS: Clinical dose of As2O3 can significantly improve abnormal symptoms and pathological changes in psoriasis-like skin lesions induced by IMQ in mice. While IMQ induced abnormal expression and distribution of inflammatory factors in the RIG-I pathway and the microRNA-31 (miR-31) pathway in psoriatic skin tissues, intravenous As2O3 can effectively regulate and restore the normality. The leading role of NF-κB signaling was evidenced in vivo and validated in vitro using the NF-κB-overexpressed HaCaT cell model. CONCLUSION: Clinical dosage of As2O3 may achieve effective treatment of IMQ-induced psoriatic skin lesions by modulating the NF-κB signaling pathway which regulates both the RIG-I and the miR-31 lines of action. Our data provided strong evidence supporting the claim that systemic As2O3 administration of clinical doses can be a promising treatment for psoriasis patients.
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MicroARNs , FN-kappa B , Ratones , AnimalesRESUMEN
The recently proposed L2-norm linear discriminant analysis criterion based on Bhattacharyya error bound estimation (L2BLDA) was an effective improvement over linear discriminant analysis (LDA) and was used to handle vector input samples. When faced with two-dimensional (2D) inputs, such as images, converting two-dimensional data to vectors, regardless of the inherent structure of the image, may result in some loss of useful information. In this paper, we propose a novel two-dimensional Bhattacharyya bound linear discriminant analysis (2DBLDA). 2DBLDA maximizes the matrix-based between-class distance, which is measured by the weighted pairwise distances of class means and minimizes the matrix-based within-class distance. The criterion of 2DBLDA is equivalent to optimizing the upper bound of the Bhattacharyya error. The weighting constant between the between-class and within-class terms is determined by the involved data that make the proposed 2DBLDA adaptive. The construction of 2DBLDA avoids the small sample size (SSS) problem, is robust, and can be solved through a simple standard eigenvalue decomposition problem. The experimental results on image recognition and face image reconstruction demonstrate the effectiveness of 2DBLDA.
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Aeromonas dhakensis is an important ubiquitous Gram-negative and freshwater bacterium detected in different reservoirs. It can cause invasive diseases in humans. Herein, we report the first case in Mainland China of a fulminant death of a 29-year-old man as a result of a new, unexpected association between septicemic A. dhakensis and hepatitis B viral infection (HBV). Herein, the patient died from multiple organ failure 5 d postadmission after the ingestion of Snakehead Fish meal. The isolated bacterium was initially misidentified as Aeromonas hydrophila using VITEK-2, while whole-genome sequencing (WGS) revealed that the isolate is A. dhakensis. WGS revealed the occurrence of three antimicrobial genes of resistance: imiH, cphA2, and blaOXA-12; besides, major virulence factors were detected. In silico, multilocus sequence typing (MLST) showed that our A. dhakensis 17FW001 belonged to a novel sequence type (ST557). A comparative genomic analysis of our isolate with nine selected Aeromonas species was done, which elucidated the pathogenicity of our A. dhakensis. In conclusion, we reported for the first time the association between A. dhakensis and HBV in Mainland China. We revealed that septicemic A. dhakensis could result in severe adverse clinical outcomes that end up with unexpected fulminant death especially when it is accompanied with HBV and sheds light on the virulence of A. dhakensis and the high rate of its misdiagnosis that requires to urgently consider screening of all cases of A. dhakensis for HBV in the future. Besides, caution should be taken while dealing with snakeheads which act as a vector for A. dhakensis.
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Aeromonas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/mortalidad , Hepatitis B/complicaciones , Sepsis/microbiología , Adulto , Aeromonas/clasificación , Animales , Técnicas de Tipificación Bacteriana , China , Farmacorresistencia Bacteriana/genética , Resultado Fatal , Peces , Contaminación de Alimentos , Microbiología de Alimentos , Genes Bacterianos , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Masculino , Tipificación de Secuencias Multilocus , Sepsis/mortalidad , Factores de Virulencia/genéticaRESUMEN
As a new member of persistent organic pollutants, the potent neurotoxicity of perfluorooctane sulfonates (PFOS) found in epidemiological studies and laboratory research has drawn increasing attention around the world. Previous studies showed that apoptosis driven by oxidative stress and autophagy were both observed in PFOS-induced toxicity. Taurine has been demonstrated to exert potent protections against oxidative stress as an efficient antioxidant. Whether taurine could protect against the PFOS neurotoxicity is not known. In the present study, PC12 cells were treated with several concentrations of PFOS (31.25, 250 µM) for 24 h. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was applied to assess the cell viability. DCFH-DA detector was used to explore the production of ROS. Caspase 3 activity was used to reflect the possible apoptosis pathway. The lyso-tracker red dying was invited to evaluate the autophagy. Our data showed that taurine could significantly reverse the decreased viability and the increased ROS production in PC12 cells treated with PFOS. Moreover, the increased autophagy and apoptosis elicited by PFOS in PC12 cells could also be attenuated by taurine. Collectively, our results indicate that taurine may be an effective antioxidant in fighting against PFOS cytotoxicity and therefore could potentially serve as a preventative and therapeutic agent for environmental pollution-related toxicities.
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Ácidos Alcanesulfónicos/toxicidad , Antioxidantes/farmacología , Fluorocarburos/toxicidad , Neuronas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Taurina/farmacología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Neuronas/patología , Células PC12 , RatasRESUMEN
Polybrominated diphenyl ethers (PBDEs) are globally dispersed throughout the environment, and the levels of some PBDEs in the environment may still be increasing. Previous studies showed that BDE 209 exerted neurodevelopmental and neurobehavioral effects in humans and animals. Oxidative stress is a common mechanism reported in PBDEs-induced neurotoxicity. Taurine, as an antioxidant, whether it is effective in alleviating BDE 209-induced neurotoxicity is still unknown. PC12 cells were exposed to various concentrations of BDE 209 (6.25, 12.5, 25, 50, and 100 µM). 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to assess the cell viability. 2',7'-Dichlorofluorescin diacetate (DCFH-DA) detector was used to explore the production of ROS. Acridine orange was used to reflect the permeation of lysosomal membrane. Rhodamine 123 was used to reflect the permeation of mitochondrial membrane. Lactate dehydrogenase and catalase in PC12 cells exposed to BDE 209 were examined by kits. The results showed that taurine could significantly reverse the decreased viability, the serious oxidative stress and abnormal autophagy in PC12 cells exposed to BDE 209. Collectively, our results indicated that taurine could protect PC12 cells from BDE 209-induced neurotoxicity by alleviating oxidative stress.
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Antioxidantes/farmacología , Éteres Difenilos Halogenados/toxicidad , Neuronas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Taurina/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Neuronas/patología , Células PC12 , RatasRESUMEN
AIMS: This study aimed to investigate miR-106a expression in peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B (CHB) patients and to analyze the function of miR-106a. MATERIALS AND METHODS: miR-106a expression levels in PBMCs from 40 healthy controls and 56 CHB patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The luciferase activity assays were used to determine whether miR-106a binds to 3'UTR of IL-8. miR-106a mimics and inhibitors were transfected into healthy PBMCs. IL-8 mRNA and protein levels were detected and determined by qRT-PCR and ELISA, respectively. RESULTS: The qRT-PCR results suggested that the PBMC miR-106a levels were decreased in CHB patients. IL-8 was augmented in CHB patients and was inversely correlated with miR-106a levels. The luciferase activity assays indicated that IL-8 is a target of miR-106a. Exogenous expression of miR-106a could significantly repress IL-8 expression at both mRNA and protein levels in PBMCs, whereas miR-106a inhibitor had the opposite effects. CONCLUSIONS: This study suggested that miR-106a is downregulated in PBMCs of CHB patients and that miR-106a may play an important role in CHB by targeting IL-8.
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Hepatitis B Crónica/sangre , Hepatitis B Crónica/metabolismo , Interleucina-8/sangre , Interleucina-8/metabolismo , Leucocitos Mononucleares/metabolismo , MicroARNs/sangre , MicroARNs/metabolismo , Adulto , Femenino , Humanos , Interleucina-8/genética , MasculinoRESUMEN
Weil's disease, an icterohemorrhagic infection, is the most severe and fatal form of leptospirosis and is characterized by jaundice, renal dysfunction, and hemorrhagic predisposition. Weil's disease with HIV infection has rarely been reported. A 68-year-old male with HIV infection presented to our hospital with fever and dyspnea that progressed to severe hemoptysis and systemic multiple organ failure, necessitating a tracheal intubation ventilator. A diagnosis of Weil's disease was made after Leptospira interrogans was identified via metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF). After immediately receiving supportive therapy and targeted antimicrobial agents, the patient achieved complete recovery upon discharge. The co-infection of HIV infection and leptospirosis resulting in systemic multi-organ failure is rare, but awareness should be raised of the differential diagnosis. mNGS can help identify pathogens and facilitate the use of targeted and efficacious antimicrobial therapy in unusual clinical environments.
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BACKGROUND: Wogonin, a flavone isolated from Scutellaria baicalensis Georgi, is a commonly used phytochemical with anti-inflammatory and antitumor properties. However, the antiviral activity of wogonin against human immunodeficiency virus type 1 (HIV-1) has not been reported. PURPOSE: The current study aimed to explore whether wogonin can suppress latent HIV-1 reactivation and the mechanism of wogonin in inhibiting proviral HIV-1 transcription. METHODS: We assessed the effects of wogonin on HIV-1 reactivation using flow cytometry, cytotoxicity assay, quantitative PCR (qPCR), viral quality assurance (VQA), and western blot analysis. RESULTS: Wogonin, a flavone isolated from S. baicalensis, significantly inhibited the reactivation of latent HIV-1 in cellular models and in primary CD4+ T cells from antiretroviral therapy (ART)-suppressed individuals ex vivo. Wogonin exhibited low cytotoxicity and long-lasting inhibition of HIV-1 transcription. Triptolide is a latency-promoting agent (LPA) that inhibits HIV-1 transcription and replication; wogonin had a stronger ability to inhibit HIV-1 latent reactivation than triptolide. Mechanistically, wogonin inhibited the reactivation of latent HIV-1 by inhibiting the expression of p300, a histone acetyltransferase, and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. CONCLUSION: Our study found that wogonin is a novel LPA that can inhibit HIV-1 transcription by HIV-1 epigenetic silencing, which could bear promising significance for future applications of HIV-1 functional cure.
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Infecciones por VIH , VIH-1 , Humanos , Histonas/metabolismo , VIH-1/fisiología , Latencia del Virus/fisiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Linfocitos T CD4-PositivosRESUMEN
Whether hypervariable region 1 (HVR1)-targeting antibodies elicited during natural hepatitis C virus (HCV) infection contribute to virus clearance and what is the mechanism underlying remain unclear. Here, we demonstrated that treatment of HCV-infected hepatoma Huh7.5 cells with the IgGs purified from 2 of 28 (7.1%) chronic hepatitis C (CHC) patients efficiently controlled the infection, for which genotype 1b HVR1 (1bHVR1)-binding antibody was critical. Moreover, we found that 1bHVR1 peptide was superior to 2aHVR1 in rabbit immunization to elicit antibodies neutralizing genotypes 1a, 2a, 3a, and 4a. The neutralization effect of 1bHVR1 IgG could be augmented by HH-1, an antibody constructed from CHC memory B cells but without binding to HVR1 peptide. Mechanistic studies showed that 1bHVR1 antisera and IgGs disrupted the interaction of E2-SR-B1 receptor. This study highlights the neutralizing activity of HVR1 antibody elicited by CHC patients and generated by HVR1-immunization against the established infections of multiple HCV genotypes.
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Recent advances show that two-dimensional linear discriminant analysis (2DLDA) is a successful matrix based dimensionality reduction method. However, 2DLDA may encounter the singularity issue theoretically, and also is sensitive to outliers. In this paper, a generalized Lp-norm 2DLDA framework with regularization for an arbitrary p>0 is proposed, named G2DLDA. There are mainly two contributions of G2DLDA: one is G2DLDA model uses an arbitrary Lp-norm to measure the between-class and within-class scatter, and hence a proper p can be selected to achieve robustness. The other one is that the introduced regularization term makes G2DLDA enjoy better generalization performance and avoid singularity. In addition, an effective learning algorithm is designed for G2LDA, which can be solved through a series of convex problems with closed-form solutions. Its convergence can be guaranteed theoretically when 1≤p≤2. Preliminary experimental results on three contaminated human face databases show the effectiveness of the proposed G2DLDA.
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Algoritmos , Cara , Bases de Datos Factuales , Análisis Discriminante , Generalización Psicológica , HumanosRESUMEN
In this article, we propose a general model for plane-based clustering. The general model reveals the relationship between cluster assignment and cluster updating during clustering implementation, and it contains many existing plane-based clustering methods, e.g., k-plane clustering, proximal plane clustering, twin support vector clustering, and their extensions. Under this general model, one may obtain an appropriate clustering method for a specific purpose. The general model is a procedure corresponding to an optimization problem, which minimizes the total loss of the samples. Thereinto, the loss of a sample derives from both within-cluster and between-cluster information. We discuss the theoretical termination conditions and prove that the general model terminates in a finite number of steps at a local or weak local solution. Furthermore, we propose a distribution loss function that fluctuates with the input data and introduce it into the general model to obtain a plane-based clustering method (DPC). DPC can capture the data distribution precisely because of its statistical characteristics, and its termination that finitely terminates at a weak local solution is given immediately based on the general model. The experimental results show that our DPC outperforms the state-of-the-art plane-based clustering methods on many synthetic and benchmark data sets.
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Mucosal associated invariant T (MAIT) cells play a critical role in Helicobacter pylori (H. pylori)-induced gastritis by promoting mucosal inflammation and aggravating mucosal injuries (1, 2). However, the underlying mechanism and key molecules involved are still uncertain. Here we identified OX40, a co-stimulatory molecule mainly expressed on T cells, as a critical regulator to promote proliferation and IL-9 production by MAIT cells and facilitate mucosal inflammation in H. pylori-positive gastritis patients. Serum examination revealed an increased level of IL-9 in gastritis patients. Meanwhile, OX40 expression was increased in mucosal MAIT cells, and its ligand OX40L was also up-regulated in mucosal dendritic cells (DCs) of gastritis patients, compared with healthy controls. Further results demonstrated that activation of the OX40/OX40L pathway promoted IL-9 production by MAIT cells, and MAIT cells displayed a highly-activated phenotype after the cross-linking of OX40 and OX40L. Moreover, the level of IL-9 produced by MAIT cells was positively correlated with inflammatory indexes in the gastric mucosa, suggesting the potential role of IL-9-producing MAIT cells in mucosal inflammation. Taken together, we elucidated that OX40/OX40L axis promoted mucosal MAIT cell proliferation and IL-9 production in H. pylori-induced gastritis, which may provide potential targeting strategies for gastritis treatment.
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Mucosa Gástrica/microbiología , Gastritis/microbiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Interleucina-9/metabolismo , Células T Invariantes Asociadas a Mucosa/microbiología , Ligando OX40/metabolismo , Receptores OX40/metabolismo , Adulto , Estudios de Casos y Controles , Proliferación Celular , Células Cultivadas , Técnicas de Cocultivo , Femenino , Mucosa Gástrica/inmunología , Mucosa Gástrica/metabolismo , Gastritis/inmunología , Gastritis/metabolismo , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/inmunología , Interacciones Huésped-Patógeno , Humanos , Inmunidad Mucosa , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Células T Invariantes Asociadas a Mucosa/inmunología , Células T Invariantes Asociadas a Mucosa/metabolismo , Fenotipo , Transducción de Señal , Adulto JovenRESUMEN
Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018-2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.
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Coxiella burnetii/aislamiento & purificación , Fiebre Q/microbiología , Adulto , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/transmisión , China/epidemiología , Coxiella burnetii/clasificación , Coxiella burnetii/genética , Brotes de Enfermedades , Femenino , Enfermedades de las Cabras/epidemiología , Enfermedades de las Cabras/microbiología , Enfermedades de las Cabras/transmisión , Cabras , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Metagenómica , Persona de Mediana Edad , Filogenia , Fiebre Q/diagnóstico , Fiebre Q/epidemiología , Fiebre Q/transmisión , Adulto Joven , Zoonosis/diagnóstico , Zoonosis/epidemiología , Zoonosis/microbiología , Zoonosis/transmisiónRESUMEN
In this paper, we propose a robust linear discriminant analysis (RLDA) through Bhattacharyya error bound optimization. RLDA considers a nonconvex problem with the L1 -norm operation that makes it less sensitive to outliers and noise than the L2 -norm linear discriminant analysis (LDA). In addition, we extend our RLDA to a sparse model (RSLDA). Both RLDA and RSLDA can extract unbounded numbers of features and avoid the small sample size (SSS) problem, and an alternating direction method of multipliers (ADMM) is used to cope with the nonconvexity in the proposed formulations. Compared with the traditional LDA, our RLDA and RSLDA are more robust to outliers and noise, and RSLDA can obtain sparse discriminant directions. These findings are supported by experiments on artificial data sets as well as human face databases.
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INTRODUCTION: We analyzed the clinical characteristics of COVID-19 fecal/perianal swab nucleic acid-positive patients in our hospital and evaluated the effect of SARS-CoV-2 on the gastrointestinal tract. METHODOLOGY: Ninety-seven patients in the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, 2020 to March 2, 2020 with fecal/perianal swab samples were selected as subjects and the results of real-time fluorescence reverse transcriptase-PCR SARS-CoV-2 nucleic acid detection of fecal/perianal swabs were used to divide subjects into positive and negative groups. RESULTS: Fecal/perianal swabs of 53.61% (52/97) patients were positive including 31 males (59.62%) and 21 females (40.38%). The negative group had more females than males (P = 0.001). The distribution of case classification based on the most severe condition observed after admission was different between groups: five (5.15%) critical type patients were all from the positive group (P = 0.029). There was no statistical difference in clinical manifestations between the groups. In the positive group, the mean nucleic acid-negative conversion time was 14.13 ± 8.61 days, which was significantly later than the negative group (6.98 ± 5.16 days; P < 0.001). In the positive group, 92% (48/52) had nucleic acid-negative conversion with a mean nucleic acid-negative conversion time of 22.58 ± 10.30 days. Among them, 41 (78.85%) cases were delayed compared with pharynx/nasal swab nucleic acid-negative conversion time. CONCLUSIONS: The positive rate of fecal/perianal swab nucleic acid in male patients was higher than that in female patients. Fecal/perianal swab nucleic acid positive may be an indicator of critical conditions in those with COVID-19.
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Canal Anal/virología , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Heces/virología , Neumonía Viral/virología , ARN Viral/análisis , Adulto , Anciano , COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2RESUMEN
BACKGROUND: A cluster of pneumonia cases were reported by Wuhan Municipal Health Commission, China in December 2019. A novel coronavirus was eventually identified, and became the COVID-19 epidemic that affected public health and life. We investigated the psychological status and behavior changes of the general public in China from January 30 to February 3, 2020. METHODS: Respondents were recruited via social media (WeChat) and completed an online questionnaire. We used the State-Trait Anxiety Inventory, Self-rating Depression Scale, and Symptom Checklist-90 to evaluate psychological status. We also investigated respondents' behavior changes. Quantitative data were analyzed by t-tests or analysis of variance, and classified data were analyzed with chi-square tests. RESULTS: In total, 608 valid questionnaires were obtained. More respondents had state anxiety than trait anxiety (15.8% vs 4.0%). Depression was found among 27.1% of respondents and 7.7% had psychological abnormalities. About 10.1% of respondents suffered from phobia. Our analysis of the relationship between subgroup characteristics and psychological status showed that age, gender, knowledge about COVID-19, degree of worry about epidemiological infection, and confidence about overcoming the outbreak significantly influenced psychological status. Around 93.3% of respondents avoided going to public places and almost all respondents reduced Spring Festival-related activities. At least 70.9% of respondents chose to take three or more preventive measures to avoid infection. The three most commonly used prevention measures were making fewer trips outside and avoiding contact (98.0%), wearing a mask (83.7%), and hand hygiene (82.4%). CONCLUSIONS: We need to pay more attention to public psychological stress, especially among young people, as they are likely to experience anxiety, depression, and psychological abnormalities. Different psychological interventions could be formulated according to the psychological characteristics of different gender and age groups. The majority of respondents followed specific behaviors required by the authorities, but it will take time to observe the effects of these behaviors on the epidemic.
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Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/psicología , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/psicología , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Adolescente , Adulto , Anciano , Betacoronavirus , COVID-19 , China/epidemiología , Infecciones por Coronavirus/prevención & control , Estudios Transversales , Depresión/epidemiología , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Trastornos Fóbicos/epidemiología , Trastornos Fóbicos/psicología , Neumonía Viral/prevención & control , SARS-CoV-2 , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Corona Virus Disease 2019 (COVID-19) due to the 2019 novel coronavirus (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China. We aimed to compare arbidol and lopinavir/ritonavir(LPV/r) treatment for patients with COVID-19 with LPV/r only. METHODS: In this retrospective cohort study, we included adults (age≥18years) with laboratory-confirmed COVID-19 without Invasive ventilation, diagnosed between Jan 17, 2020, and Feb 13, 2020. Patients, diagnosed after Jan 17, 2020, were given oral arbidol and LPV/r in the combination group and oral LPV/r only in the monotherapy group for 5-21 days. The primary endpoint was a negative conversion rate of coronavirus from the date of COVID-19 diagnosis(day7, day14), and assessed whether the pneumonia was progressing or improving by chest CT (day7). RESULTS: We analyzed 16 patients who received oral arbidol and LPV/r in the combination group and 17 who oral LPV/r only in the monotherapy group, and both initiated after diagnosis. Baseline clinical, laboratory, and chest CT characteristics were similar between groups. The SARS-CoV-2 could not be detected for 12(75%) of 16 patients' nasopharyngeal specimens in the combination group after seven days, compared with 6 (35%) of 17 in the monotherapy group (p < 0·05). After 14 days, 15 (94%) of 16 and 9 (52·9%) of 17, respectively, SARS-CoV-2 could not be detected (p < 0·05). The chest CT scans were improving for 11(69%) of 16 patients in the combination group after seven days, compared with 5(29%) of 17 in the monotherapy group (p < 0·05). CONCLUSION: In patients with COVID-19, the apparent favorable clinical response with arbidol and LPV/r supports further LPV/r only.
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Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Indoles/uso terapéutico , Lopinavir/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Ritonavir/uso terapéutico , Administración Oral , Adulto , Antivirales/administración & dosificación , COVID-19 , Estudios de Cohortes , Infecciones por Coronavirus/diagnóstico por imagen , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Indoles/administración & dosificación , Lopinavir/administración & dosificación , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico por imagen , Estudios Retrospectivos , Ritonavir/administración & dosificación , Tomografía Computarizada por Rayos XRESUMEN
CD103 is considered as a surface marker for the resident immune cells. However, little is known about the intrinsic function of CD103 in infection and inflammation. In this study, we found that CD103 was highly expressed in CD4+T cells of the gastric mucosa from patients with H. pylori-positive gastritis. Mucosal resident CD103+CD4+T cells exhibited an increase in the CD45RO+CCR7- effector memory phenotype and high expression of the chemokine receptors CXCR3 and CCR9 compared with those in CD103-CD4+T cells. An In vitro coculture study demonstrated that H. pylori-specific antigen CagA/VacA-primed dendritic cells (DCs) induced proliferation and IFN-γ, TNF as well as IL-17 production by CD103+CD4+T cells from patients with H. pylori-positive gastritis, while blocking CD103 with a neutralizing antibody reduced proliferation and IFN-γ, TNF, and IL-17 production by CD103+CD4+T cells cocultured with DCs. Moreover, immunoprecipitation revealed that CD103 interacted with TCR α/ß and CD3ζ, and activation of CD103 enhanced the phosphorylation of ZAP70 induced by the TCR signal. Finally, increased T-bet and Blimp1 levels were also observed in CD103+CD4+T cells, and activating CD103 increased T-bet and Blimp1 expression in CD4+T cells. Our results explored the intrinsic function of CD103 in gastric T cells from patients with H. pylori-positive gastritis, which may provide a therapeutic target for the treatment of gastritis.
Asunto(s)
Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Linfocitos T CD4-Positivos , Mucosa Gástrica , Humanos , Linfocitos TRESUMEN
Hepatitis C virus (HCV) is classified into seven major genotypes, and genotype 6 is commonly prevalent in Asia, thus reverse genetic system representing genotype 6 isolates in prevalence is required. Here, we developed an infectious clone for a Chinese HCV 6a isolate (CH6a) using a novel strategy. We determined CH6a consensus sequence from patient serum and assembled a CH6a full-length (CH6aFL) cDNA using overlapped PCR product-derived clones that shared the highest homology with the consensus. CH6aFL was non-infectious in hepatoma Huh7.5 cells. Next, we constructed recombinants containing Core-NS5A or 5'UTR-NS5A from CH6a and the remaining sequences from JFH1 (genotype 2a), and both were engineered with 7 mutations identified previously. However, they replicated inefficiently without virus spread in Huh7.5 cells. Addition of adaptive mutations from CH6a Core-NS2 recombinant, with JFH1 5'UTR and NS3-3'UTR, enhanced the viability of Core-NS5A recombinant and acquired replication-enhancing mutations. Combination of 22 mutations in CH6a recombinant with JFH1 5'UTR and 3'UTR (CH6aORF) enabled virus replication and recovered additional four mutations. Adding these four mutations, we generated two efficient recombinants containing 26 mutations (26m), CH6aORF_26m and CH6aFL_26m (designated "CH6acc"), releasing HCV of 104.3-104.5 focus-forming units (FFU)/ml in Huh7.5.1-VISI-mCherry and Huh7.5 cells. Seven newly identified mutations were important for HCV replication, assembly, and release. The CH6aORF_26m virus was inhibited in a dose- and genotype-dependent manner by direct-acting-antivirals targeting NS3/4A, NS5A, and NS5B. The CH6acc enriches the toolbox of HCV culture systems, and the strategy and mutations applied here will facilitate the culture development of other HCV isolates and related viruses.