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1.
iScience ; 24(11): 103305, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34765923

RESUMO

HIV-1 infects blood CD4 T cells through the use of CD4 and CXCR4 or CCR5 receptors, which can be targeted through blocking viral binding to CD4/CXCR4/CCR5 or virus-cell fusion. Here we describe a novel mechanism by which HIV-1 nuclear entry can also be blocked through targeting a non-entry receptor, CD2. Cluster of differentiation 2 (CD2) is an adhesion molecule highly expressed on human blood CD4, particularly, memory CD4 T cells. We found that CD2 ligation with its cell-free ligand LFA-3 or anti-CD2 antibodies rendered blood resting CD4 T cells highly resistant to HIV-1 infection. We further demonstrate that mechanistically, CD2 binding initiates competitive signaling leading to cofilin activation and localized actin polymerization around CD2, which spatially inhibits HIV-1-initiated local actin polymerization needed for viral nuclear migration. Our study identifies CD2 as a novel target to block HIV-1 infection of blood resting T cells.

2.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5117-5122, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738409

RESUMO

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.


Assuntos
COVID-19/terapia , China , Medicina Baseada em Evidências , Humanos , Medicina Tradicional Chinesa , Guias de Prática Clínica como Assunto , SARS-CoV-2
3.
Chin Med J (Engl) ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759226

RESUMO

ABSTRACT: In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

5.
J Med Internet Res ; 23(10): e28508, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34698651

RESUMO

BACKGROUND: HIV self-testing (HIVST) kits are common in key sexually active populations. Direct secondary distribution of HIVST kits (DSDHK) is effective in improving the uptake of HIVST. However, there are concerns about the various limitations of DSDHK, including limited geographic reach, payment problems, and need for face-to-face interactions. OBJECTIVE: In this study, we aim to evaluate the feasibility and characteristics of indirect secondary distribution of HIVST kits (ISDHK) via WeChat (distributing HIVST application links and follow-up HIVST kits to partners) among men who have sex with men (MSM). METHODS: From October 2017 to September 2019, an HIVST recruitment advertisement was disseminated on the WeChat social media platform to invite MSM to apply for the HIVST kits (referred to as index participants [IPs]). All MSM participants were encouraged to distribute the HIVST application link to their friends and sexual partners (referred to as alters) through their social networks. All the alters were further encouraged to continue distributing the HIVST application link. All participants paid a deposit (US $7), which was refundable upon completion of the questionnaire, and uploaded the test results via a web-based survey system. RESULTS: A total of 2263 MSM met the criteria and successfully applied for HIVST. Of these, 1816 participants returned their HIVST results, including 1422 (88.3%) IPs and 394 (21.7%) alters. More alters had condomless anal intercourse, a higher proportion of them had never previously tested for HIV, and they showed a greater willingness to distribute HIVST kits to their sexual partners (P=.002) than the IPs. After controlling for age, education, and income, the alters had a greater proportion of MSM who had never tested for HIV before (adjusted odds ratio [aOR] 1.29, 95% CI 1.00-1.68), were more willing to distribute the HIVST application link (aOR 1.71, 95% CI 1.21-2.40), had a lower number of sexual partners (aOR 0.71, 95% CI 0.57-0.90), and were less likely to search for sexual partners on the web (aOR 0.78, 95% CI 0.60-1.02) than IPs. In comparison, the rates of reactive HIVST results, conducting HIV confirmatory tests, HIV seropositivity, and initiation of HIV antiretroviral therapy were similar for IPs and alters. CONCLUSIONS: The ISDHK model of distributing HIVST application links among the MSM population via social media is feasible. The ISDHK model should be used to supplement the DSDHK model to enable a greater proportion of the MSM population to know their HIV infection status.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , China , Estudos Transversais , Estudos de Viabilidade , Infecções por HIV/diagnóstico , Homossexualidade Masculina , Humanos , Masculino , Autoteste
6.
Dalton Trans ; 50(43): 15849-15854, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34708848

RESUMO

Uniform lithium deposition is a benefit to achieving high-energy-density lithium metal batteries. There are many effective methods to suppress the dendritic growth of metallic lithium and promote the application of the lithium anode. However, the designation of lithiophilic sites at the atomic level remains a huge challenge. Herein, a two-dimensional porous conjugated porphyrin polymer linked by two acetylenic linkages from an in situ coupling reaction has been prepared on copper foil and employed as the lithiophilic host. The four electron-rich pyrrolic nitrogen atoms in the porphyrin building block and the linkage electron-rich sp-hybridized carbon atoms were regarded as precise lithiophilic sites, resulting in a decreased nucleation overpotential and dendrite free morphology. With uniform lithium deposition, the electrochemical performance of the electrode was significantly improved in regard to the overpotential, coulombic efficiency and lifespan. This work expands the precise construction of lithiophilic sites at the atomic level and benefits to further development of high-energy density lithium metal batteries.

7.
PLoS One ; 16(10): e0258517, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34653189

RESUMO

Depression is associated with poorer outcomes in a wide spectrum of surgeries but the specific effects of depression in patients undergoing cervical spine surgery are unknown. This study aimed to evaluate the prevalence and impact of pre-surgical clinical depression on pain and other outcomes after surgery for cervical degenerative disc disease using a national representative database. Data of patients with cervical myelopathy and radiculopathy were extracted from the 2005-2014 US Nationwide Inpatient Sample (NIS) database. Included patients underwent anterior discectomy and fusion (ACDF). Acute or chronic post-surgical pain, postoperative complications, unfavorable discharge, length of stay (LOS) and hospital costs were evaluated. Totally 215,684 patients were included. Pre-surgical depression was found in 29,889 (13.86%) patients, with a prevalence nearly doubled during 2005-2014 in the US. Depression was independently associated with acute or chronic post-surgical pain (aOR: 1.432), unfavorable discharge (aOR: 1.311), prolonged LOS (aOR: 1.152), any complication (aOR: 1.232), respiratory complications/pneumonia (aOR: 1.153), dysphagia (aOR: 1.105), bleeding (aOR: 1.085), infection/sepsis (aOR: 1.529), and higher hospital costs (beta: 1080.640) compared to non-depression. No significant risk of delirium or venous thrombotic events was observed in patients with depression as compared to non-depression. Among patients receiving primary surgery, depression was independently associated with prolonged LOS (aOR: 1.150), any complication (aOR:1.233) and postoperative pain (aOR:1.927). In revision surgery, no significant associations were found for prolonged LOS, any complication or pain. In conclusion, in the US patients undergoing ACDF, pre-surgical clinical depression predicts post-surgical acute or chronic pain, a slightly prolonged LOS and the presence of any complication. Awareness of these associations may help clinicians stratify risk preoperatively and optimize patient care.

8.
Front Endocrinol (Lausanne) ; 12: 721198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552561

RESUMO

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer's disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review.

9.
Lancet Reg Health West Pac ; 16: 100269, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34590068

RESUMO

Background: Most existing prognostic models for people living with HIV/AIDS (PLWHA) were derived from cohorts in high-income settings established a decade ago and may not be applicable for contemporary patients, especially for patients in developing settings. The aim of this study was to develop and externally validate a prognostic model for survival in PLWHA initiating ART based on a large population-based cohort in China. Methods: We obtained data for patients from the Chinese National Free Antiretroviral Treatment Program database. The derivation cohort consisted of PLWHA treated between February 2004 and December 2019 in a tertiary center in Guangzhou, South China, and validation cohort of patients treated between February 2004 to December 2018 in another tertiary hospital in Shenyang, Northeast China. We included ART-naive patients aged above 16 who initiated a combination ART regimen containing at least three drugs and had at least one follow-up record. We assessed 20 candidate predictors including patient characteristics, disease characteristics, and laboratory tests for an endpoint of death from all causes. The prognostic model was developed from a multivariable cox regression model with predictors selected using the least absolute shrinkage and selection operator (Lasso). To assess the model's predictive ability, we quantified the discriminative power using the concordance (C) statistic and calibration accuracy by comparing predicted survival probabilities with observed survival probabilities estimated with the Kaplan-Meier method. Findings: The derivation cohort included 16481 patients with a median follow-up of 3·41 years, among whom 735 died. The external validation cohort comprised 5751 participants with a median follow-up of 2·71 years, of whom 185 died. The final model included 10 predictors: age, body mass index, route of HIV acquisition, coinfection with tuberculosis, coinfection with hepatitis C virus, haemoglobin, CD4 cell count, platelet count, aspartate transaminase, and plasma glucose. The C-statistic was 0·84 (95% confidence interval 0·82-0·85) in internal validation after adjustment of optimism and 0·84 (0·82-0·87) in external validation, which remained consistently above 0·75 in all landmark time points within five years of follow up when using time-updated laboratory measurements. The calibration accuracy was satisfactory in both derivation and validation cohorts. Interpretation: We have developed and externally validated a model to predict long-term survival in PLWHA on ART. This model could be applied to individualized patient counseling and management during treatment, and future innovative trial design. Funding: Natural Science Foundation of China Excellent Young Scientists Fund, Natural Science Foundation of China International/Regional Research Collaboration Project, Natural Science Foundation of China Young Scientist Fund, the National Science and Technology Major Project of China,National Special Research Program of China for Important Infectious Diseases, 13th Five-Year Key Special Project of Ministry of Science and Technology, and the Joint-innovation Program in Healthcare for Special Scientific Research Projects of Guangzhou.

10.
Lancet Reg Health West Pac ; 12: 100171, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34527967

RESUMO

Background: Assisted partner notification (PN) is an effective approach for increasing HIV testing among heterosexual partners. There is sparse evidence on its effect among sexual partners of men who have sex with men (MSM). Methods: A randomized controlled trial was conducted to compare the effect of assisted PN and passive PN interventions on uptake of HIV testing among male and female sexual partners of newly HIV-diagnosed MSM. In the passive PN group, participants were encouraged to disclose their HIV status and refer and persuade sexual partners to access HIV testing services (HTS). In the assisted PN group, participants were further provided with HIV self-testing kits for sexual partners to take a test at home or allow a community health worker from MSM-serving community-based organization (CBO) to anonymously refer and persuade their sexual partners to access HTS. The primary outcome was the proportion of index cases who had any sexual partner accessing HTS within four months after randomization. This trial is registered with chictr.org.cn, ChiCTR1800017813. Findings: Between August 2017 and January 2019, 187 MSM newly diagnosed with HIV in a large city Shenyang in northern China were enrolled in the study and randomly assigned to either passive PN (n=90) or assisted PN (n=97) study groups. The proportion of index cases who disclosed their HIV status to any sexual partners within three months of randomization was similar between passive PN (57%, 95% confidence interval [CI]: 46-67%) and assisted PN groups (58%, 95% CI: 48-68%). During four months of follow-up, the number of sexual partners named, referred to HTS, tested and testing positive per index case was 3•2, 0•7, 0•2 and 0•03 in the passive PN group, and 4•0, 1•0, 0•5 and 0•10 in the assisted PN group. Thirty-five percent of index cases in the assisted PN group had any sexual partners accessing HIV testing compared to 17% in the passive PN group (P = 0•004); 49% sexual partners who were disclosed by index cases in the assisted PN group had access HTS compared to 28% in the passive PN group (P = 0•007). Interpretation: The assisted PN strategy incorporating HIV self-testing and CBO outreach can increase uptake of HIV testing among sexual partners of MSM who were recently diagnosed with HIV. Funding: National Science and Technology Major Project of China, National Natural Science Foundation of China, and Project for Overseas Visiting Research of Liaoning Province.

11.
Clin Chem Lab Med ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34533003

RESUMO

OBJECTIVES: Peripheral blood lymphocyte subsets are important parameters for monitoring immune status; however, lymphocyte subset detection is time-consuming and error-prone. This study aimed to explore a highly efficient and clinically useful autoverification system for lymphocyte subset assays performed on the flow cytometry platform. METHODS: A total of 94,402 lymphocyte subset test results were collected. To establish the limited-range rules, 80,427 results were first used (69,135 T lymphocyte subset tests and 11,292 NK, B, T lymphocyte tests), of which 15,000 T lymphocyte subset tests from human immunodeficiency virus (HIV) infected patients were used to set customized limited-range rules for HIV infected patients. Subsequently, 13,975 results were used for historical data validation and online test validation. RESULTS: Three key autoverification rules were established, including limited-range, delta-check, and logical rules. Guidelines for addressing the issues that trigger these rules were summarized. The historical data during the validation phase showed that the total autoverification passing rate of lymphocyte subset assays was 69.65% (6,941/9,966), with a 67.93% (5,268/7,755) passing rate for T lymphocyte subset tests and 75.67% (1,673/2,211) for NK, B, T lymphocyte tests. For online test validation, the total autoverification passing rate was 75.26% (3,017/4,009), with 73.23% (2,191/2,992) for the T lymphocyte subset test and 81.22% (826/1,017) for the NK, B, T lymphocyte test. The turnaround time (TAT) was reduced from 228 to 167 min using the autoverification system. CONCLUSIONS: The autoverification system based on the laboratory information system for lymphocyte subset assays reduced TAT and the number of error reports and helped in the identification of abnormal cell populations that may offer clues for clinical interventions.

12.
World J Gastroenterol ; 27(31): 5232-5246, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34497447

RESUMO

BACKGROUND: Artificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice. AIM: To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies. METHODS: With high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital. RESULTS: The CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time (P = 0.32; P = 0.16, respectively). CONCLUSION: CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted.


Assuntos
Pólipos do Colo , Aprendizado Profundo , Inteligência Artificial , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Computadores , Humanos
13.
J Integr Med ; 19(5): 389-394, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34384714

RESUMO

Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndrome- set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.


Assuntos
Medicina Tradicional Chinesa , Projetos de Pesquisa , Estudos Transversais , Técnica Delfos , Determinação de Ponto Final , Resultado do Tratamento
14.
J Med Internet Res ; 23(8): e23978, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34448709

RESUMO

BACKGROUND: Routine HIV testing accompanied with pre-exposure prophylaxis (PrEP) requires innovative support in a real-world setting. OBJECTIVE: This study aimed to determine the usage of HIV self-testing (HIVST) kits and their secondary distribution to partners among men who have sex with men (MSM) in China, who use PrEP, in an observational study between 2018 and 2019. METHODS: In 4 major cities in China, we prospectively followed-up MSM from the China Real-world oral PrEP demonstration study, which provides daily or on-demand PrEP for 12 months, to assess the usage and secondary distribution of HIVST on quarterly follow-ups. Half of the PrEP users were randomized to receive 2 HIVSTs per month in addition to quarterly facility-based HIV testing. We evaluated the feasibility of providing HIVST to PrEP users. RESULTS: We recruited 939 MSM and randomized 471 to receive HIVST, among whom 235 (49.9%) were daily and 236 (50.1%) were on-demand PrEP users. At baseline, the median age was 29 years, 390 (82.0%) men had at least college-level education, and 119 (25.3%) had never undergone facility-based HIV testing before. Three months after PrEP initiation, 341 (74.5%) men had used the HIVST provided to them and found it very easy to use. Among them, 180 of 341 (52.8%) men had distributed the HIVST kits it to other MSM, and 132 (51.6%) among the 256 men who returned HIVST results reported that used it with their sexual partners at the onset of intercourse. Participants on daily PrEP were more likely to use HIVST (adjusted hazard ratio=1.3, 95% CI 1.0-1.6) and distribute HIVST kits (adjusted hazard ratio=1.3, 95% CI 1.1-1.7) than those using on-demand PrEP. CONCLUSIONS: MSM who used PrEP had a high rate of usage and secondary distribution of HIVST kits, especially among those on daily PrEP, which suggested high feasibility and necessity for HIVST after PrEP initiation. Assuming that fourth-generation HIVST kits are available, HIVST may be able to replace facility-based HIV testing to a certain extent. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800020374; https://www.chictr.org.cn/showprojen.aspx?proj=32481. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-036231.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Adulto , China , Estudos de Coortes , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Internet , Masculino , Estudos Prospectivos , Autoteste
15.
Front Immunol ; 12: 656663, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447368

RESUMO

A major barrier to HIV eradication is the persistence of viral reservoirs. Resting CD4+ T cells are thought to be one of the major viral reservoirs, However, the underlying mechanism regulating HIV infection and the establishment of viral reservoir in T cells remain poorly understood. We have investigated the role of IP-10 in the establishment of HIV reservoirs in CD4+ T cells, and found that in HIV-infected individuals, plasma IP-10 was elevated, and positively correlated with HIV viral load and viral reservoir size. In addition, we found that binding of IP-10 to CXCR3 enhanced HIV latent infection of resting CD4+ T cells in vitro. Mechanistically, IP-10 stimulation promoted cofilin activity and actin dynamics, facilitating HIV entry and DNA integration. Moreover, treatment of resting CD4+ T cells with a LIM kinase inhibitor R10015 blocked cofilin phosphorylation and abrogated IP-10-mediated enhancement of HIV latent infection. These results suggest that IP-10 is a critical factor involved in HIV latent infection, and that therapeutic targeting of IP-10 may be a potential strategy for inhibiting HIV latent infection.


Assuntos
Fatores de Despolimerização de Actina/metabolismo , Linfócitos T CD4-Positivos/virologia , Quimiocina CXCL10/farmacologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/fisiologia , Quinases Lim/metabolismo , Latência Viral/efeitos dos fármacos , Adulto , Biomarcadores , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Feminino , Infecções por HIV/imunologia , HIV-1/classificação , HIV-1/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Memória Imunológica , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Provírus/genética , Transdução de Sinais , Carga Viral , Replicação Viral , Adulto Jovem
17.
Contrast Media Mol Imaging ; 2021: 5545178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366725

RESUMO

Objective: Pre-eclampsia (PE) can cause brain development delay in infants. This work aims to characterize the pattern differences of brain white matter development in premature infants under PE conditions and those without. Methods: Eighty preterm infants delivered by women with PE were selected as the PE group, and ninety-six preterm infants of the same period born to women without high-risk perinatal factors were used as control. All infants underwent diffusion tensor imaging (DTI) examination. The fractional anisotropy (FA) was measured in five regions of interests (ROIs), including posterior limbs of internal capsule (PLIC), splenium of the corpus callosum (SCC), superior frontal gyrus (SFG), superior parietal lobule (SPL), and superior occipital gyrus (SOG). The relationship between the FA values and postmenstrual age (PMA) was analyzed. Results: After adjusting for the birth weight and gestational ages, in the SCC and PLIC, the PMA and FA values showed a low-to-medium intensity positive correlation in the control group (r = 0.30, p=0.003; r = 0.53, p < 0.0001), while no positive relevance was detected in the PE group (r = 0.08, p=0.47; r = 0.19, p < 0.08). In the PE and control groups, in the SPL and SOG, the PMA and FA values showed a near-consistent positive correlation (r = 0.57, r = 0.55 vs. r = 0.31, r = 0.55; all p < 0.05). In the control group, in SFG, the PMA and FA values had a medium intensity positive correlation (r = 0.47, p < 0.0001), but there was no statistical difference in correlation in PE (r = 0.10, p=0.39). Conclusion: PE may cause lagging brain development in the SCC, PLIC, and SFG during infancy. DTI may be an effective and sensitive detection tool.

18.
Front Immunol ; 12: 712802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367176

RESUMO

Background: In the "treat all" era, there are few data on the nature of HIV clinical progression in middle-income countries. The aim of the current study was to prospectively analyze the clinical progression of HIV and its indicators among men in China with acute HIV who have sex with men. Methods: From 2009-2014 a total of 400 men with acute HIV infection (AHI) were identified among 7,893 men who have sex with men via periodic pooled nucleic acid amplification testing, and they were assigned to an AHI prospective cohort in Beijing and Shenyang, China. Rapid progression was defined as two consecutive CD4+ T cell counts < 350/µL within 3-24 months post-infection. Kaplan-Meier and Cox-regression analyses were conducted to identify predictors of rapid progression. Results: Among 400 men with AHI 46.5% were rapid progressors, 35.1% reached rapid progressor status by 12 months post-infection, and 63.9% reached rapid progressor status by 24 months. Rapid progression was associated with herpes simplex-2 virus coinfection (adjusted hazard ratio [aHR] 1.7, 95% confidence interval [CI] 1.2-2.3], depression (aHR 1.9, 95% CI 1.5-2.6), baseline CD4+ T cell count < 500/µL (aHR 3.5, 95% CI 2.4-5.1), higher baseline HIV viral load (aHR 1.6, 95% CI 1.2-2.3), acute symptoms lasting ≥ 2 weeks (aHR 1.6, 95% CI 1.1-2.2), higher body mass index (aHR 0.9, 95% CI 0.9-1.0), higher HIV viral load (aHR 1.7, 95% CI 1.4-2.1), set point viral load at 3 months (aHR 2.0, 95% CI 1.6-2.5), each 100-cell/µL decrease in CD4+ T cell count at 3 months (aHR 2.2, 95% CI 1.9-2.5), and baseline routine blood tests including white blood cell count < 5.32, hemoglobin ≥ 151, mean corpuscular hemoglobin ≥ 30.5, hemoglobin concentration ≥ 342, mean platelet count ≥ 342, lymphocytes ≥ 1.98, and mixed cell count ≥ 0.4 (all p < 0.05). Conclusion: Almost half of the patients underwent rapid clinical progression within 2 years after HIV infection. A treat-all policy is necessary and should be strengthened globally. Rapid progression was correlated with herpes simplex-2 virus coinfection, depression, low CD4+ T cell counts, and high set point viral load in acute infection stage. Rapid progression can be identified via simple indicators such as body mass index and routine blood test parameters in low and middle-income countries.

19.
Ann Transl Med ; 9(14): 1123, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430564

RESUMO

Background: The TWIK-related potassium channel (TREK-1) can be regulated by different stimuli. However, it is not clear whether some antiarrhythmics affect the activity of TREK-1. In the present study, the effect of bepridil on the TREK-1 currents is investigated. Methods: In a TREK-1 stably-expressed HEK-293 cell line (HEK-TREK-1), U251MG cells, and isolated mouse ventricular myocytes, the TREK-1 current and action potentials were recorded by the patch-clamp technique. The standard voltage protocol was a 200 ms constant potential at 20 mV, followed bya 500 ms ramp from -90 to +20 mV (HEK-TREK-1) or +80 mV (U251MG cells and myocytes) every 10 s. The currents at +20 mV or +80 mV were used for analysis. The docking study of bepridil's binding model in the TREK-1 channel was performed using the Swissdock web service. Results: In HEK-TREK-1 cells, BL1249 induced a significantly large outwardly rectifying current with similar baseline TREK-1 current characteristic, with a reversal potential (-70 mV). The concentration of half-maximal activation (EC50) of BL1249 was 3.45 µM. However, bepridil decreased the baseline TREK-1 currents, with a concentration of half-maximal inhibition (IC50) 0.59 µM and a Hill coefficient of 1.1. Also, bepridil inhibited BL1249-activated TREK-1 currents, with an IC50 4.08 µM and a Hill coefficient of 3.22. The outside-out patch-clamp confirmed bepridil inhibited BL1249-activated TREK-1 currents. In U251MG cells and myocytes, BL1249 activated outwardly rectifying endogenous TREK-1 currents, which could be inhibited by bepridil. BL1249 (10 µM) could decrease the peak value and reduce the duration of the action potential. Bepridil (10 µM) prolonged the duration of action potential of myocytes. The docking study revealed that bepridil might affect the K+ pore domain and the M4 modulator pocket. Conclusions: Bepridil may be a blocker for the TREK-1K+channel at a clinically therapeutic concentration, providing a new mechanism of TREK-1 regulation and bepridil's antiarrhythmic effect.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34257697

RESUMO

Background: Acupuncture is considered a complementary therapy for atopic eczema. The aim of this scoping review is to identify, examine, and summarize the potential acupoint prescriptions and outcome reporting regarding the clinical trials of acupuncture for eczema. Methods: We searched different databases from inception to September 30, 2020. The data were screened and extracted to identify the potential acupuncture prescription and examine the variation in outcome reporting, outcome measurement instruments (OMIs), and measurement time points in clinical trials of acupuncture. Results: A total of 116 clinical studies were included. The acupoint combination of LI11 and SP10 was used frequently. The core acupoint association networks were acupoints LI11, SP10, ST36, SP6, and LI4. For clinical trials of acupuncture, a total of 6 outcome distinct domains were identified in the 32 outcome measurements. The most frequently reported outcome was the eczema area, which was reported 97 times (83.6%, 97/116). Immune system outcomes were assessed in 15 outcome measurements, which totally reported 37 times. Adverse events were reported 51 times. TCM syndrome, which could reflect the characteristics of TCM, was reported 4 times. 29 outcomes (90.6%, 29/32) were provided definitions or OMIs. Among these outcomes, the outcome measurement times ranged from 0 to 34. Conclusions: This scoping review provides potential knowledge that should be considered as priority in future research of acupuncture for eczema.

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