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1.
BMC Infect Dis ; 24(1): 565, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844855

RESUMO

BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).


Assuntos
Amidas , Fármacos Anti-HIV , Combinação de Medicamentos , Emtricitabina , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Profilaxia Pós-Exposição , Piridonas , Tenofovir , Humanos , Infecções por HIV/prevenção & controle , Estudos Prospectivos , Masculino , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagem , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , China , Adulto , Feminino , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Amidas/uso terapêutico , Amidas/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Pessoa de Meia-Idade , Profilaxia Pós-Exposição/métodos , Adesão à Medicação/estatística & dados numéricos , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Alanina/uso terapêutico , Alanina/administração & dosagem , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/administração & dosagem , Adulto Jovem , Piperazinas
2.
Artigo em Inglês | MEDLINE | ID: mdl-38753724

RESUMO

In China, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are integral to the antiretroviral therapy (ART) regimen for persons living with HIV (PWH), comprising over 80% of such treatments. To broaden treatment options and improve therapeutic effectiveness, Ainuovirine (ANV), a new NNRTI, was authorized for ART in 2021. Nevertheless, the clinical efficacy of ANV and its impact on blood biochemical markers remain somewhat underexplored. This study seeks to evaluate ANV's clinical performance in ART and its influence on relevant treatment parameters. A retrospective analysis was performed on 208 patients treated with an ANV-based regimen from July 2021 to July 2023, monitoring indicator changes from baseline to week 24. The primary endpoint was the proportion of participants achieving HIV-1 RNA levels of less than 50 copies/mL by week 24. Secondary endpoints involved assessing variations in CD4+ T cell counts and blood biochemical markers from baseline. These outcomes were also compared with data from 241 patients treated with an Efavirenz (EFV)-based regimen in the same time frame. The findings suggest that the ANV-based regimen is as effective as the EFV-based regimen in viral suppression (p > .05) and offers superior improvements in lipid profiles, liver function, and immune system indicators, alongside fewer adverse reactions. These results affirm ANV's efficacy and safety as an antiretroviral therapy option, offering Acquired Immune Deficiency Syndrome patients a wider array of treatment possibilities and the potential for better treatment outcomes.

3.
Immun Inflamm Dis ; 12(4): e1217, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38578026

RESUMO

INTRODUCTION: The efficacy and safety of ainuovirine+lamivudine+tenofovir (ANV+3TC+TDF) and efavirenz+lamivudine+tenofovir (EFV+3TC+TDF) have been confirmed in previous clinical trials; however, there are no related studies on patient-reported outcomes. This study aimed to evaluate the effectiveness and safety of these 2 antiretroviral therapy regimens and to understand the patient's symptom experience and subjective experience of sleep quality through patient-reported outcomes. METHODS: This is a single-center prospective cohort study with 243 patients evaluated from October 1, 2021 to June 30, 2022. Virological effectiveness and patient-reported outcomes results were analyzed. The primary endpoint was the proportion of HIV viral load <50 copies/mL (virological suppression rate) at 48 weeks and the changes in the HIV symptom index and Pittsburgh sleep quality index. RESULTS: The virological suppression rates in the ANV+3TC+TDF and EFV+3TC+TDF groups were 83.6% (102/122) and 87.6% (106/121), respectively, at 48 weeks. In the ANV+3TC+TDF group, the scores of HIV symptom index and pittsburgh sleep quality index in the 48th week were lower than the baseline level (p < 0.05). Logistic regression results showed that the baseline regimen EFV+3TC+TDF was a risk factor for dizziness/lightheadedness (odds ratio = 3.153, 95% confidence interval: 1.473-6.748, p = 0.003), sadness/depression odds ratio = 2.404, 95% confidence interval:1.188-4.871, p = 0.015), and difficulty sleeping (odds ratio = 2.802, 95% confidence interval: 1.437-5.463, p = 0.002) at 48 weeks. CONCLUSIONS: Both regimens showed good virological effectiveness; however, compared with ANV+3TC+TDF, the EFV+3TC+TDF regimen reduced the prevalence of HIV-related symptoms.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Inibidores da Transcriptase Reversa/efeitos adversos , Lamivudina/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Estudos Prospectivos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Tenofovir/uso terapêutico
4.
Environ Toxicol ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682583

RESUMO

BACKGROUND: Diabetes mellitus (DM) is a prevalent chronic disease marked by significant metabolic dysfunctions. Understanding its molecular mechanisms is vital for early diagnosis and treatment strategies. METHODS: We used datasets GSE7014, GSE25724, and GSE156248 from the GEO database to build a diagnostic model for DM using Random Forest (RF) and LASSO regression models. GSE20966 served as a validation cohort. DM patients were classified into two subtypes for functional enrichment analysis. Expression levels of key diagnostic genes were validated using quantitative real-time PCR (qRT-PCR) on Peripheral Blood Mononuclear Cells (PBMCs) from DM patients and healthy controls, focusing on CXCL12 and PPP1R12B with GAPDH as the internal control. RESULTS: After de-batching the datasets, we identified 131 differentially expressed genes (DEGs) between DM and control groups, with 70 up-regulated and 61 down-regulated. Enrichment analysis revealed significant down-regulation in the IL-12 signaling pathway, JAK signaling post-IL-12 stimulation, and the ferroptosis pathway in DM. Five genes (CXCL12, MXRA5, UCHL1, PPP1R12B, and C7) were identified as having diagnostic value. The diagnostic model showed high accuracy in both the training and validation cohorts. The gene set also enabled the subclassification of DM patients into groups with distinct functional traits. qRT-PCR results confirmed the bioinformatics findings, particularly the up-regulation of CXCL12 and PPP1R12B in DM patients. CONCLUSION: Our study pinpointed seven energy metabolism-related genes differentially expressed in DM and controls, with five holding diagnostic value. Our model accurately diagnosed DM and facilitated patient subclassification, offering new insights into DM pathogenesis.

5.
Antimicrob Agents Chemother ; 68(4): e0166823, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38483175

RESUMO

Ainuovirine (ANV), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), was approved in China in 2021. In a previous randomized phase 3 trial, ANV demonstrated non-inferior efficacy relative to efavirenz (EFV) and was associated with lower rates of dyslipidemia. In this study, we aimed to explore lipid changes in treatment-experienced people with human immunodeficiency virus (HIV)-1 (PWH) switching to ANV from EFV in real world. At week 24, 96.65% of patients in the ANV group and 93.25% in the EFV group had HIV-1 RNA levels below the limit of quantification (LOQ). Median changes from baseline in CD4 +T cell counts (37.0 vs 36.0 cells/µL, P = 0.886) and CD4+/CD8 +ratio (0.03 vs 0.10, P = 0.360) were similar between the two groups. The ANV group was superior to the EFV group in mean changes in total cholesterol (TC, -0.06 vs 0.26 mmol/L, P = 0.006), triglyceride (TG, -0.6 vs 0.14 mmol/L, P < 0.001), high-density lipoprotein cholesterol (HDL-C, 0.09 vs 0.08 mmol/L, P = 0.006), and low-density lipoprotein cholesterol (LDL-C, -0.18 vs 0.29 mmol/L, P < 0.001) at week 24. We also observed that a higher proportion of patients demonstrated improved TC (13.55% vs 4.45%, P = 0.015) or LDL-C (12.93% vs 6.89%, P = 0.017), and a lower proportion of patients showed worsened LDL-C (5.57% vs 13.52%, P = 0.017) with ANV than with EFV at week 24. In conclusion, we observed good efficacy and favorable changes in lipids in switching to ANV from EFV in treatment-experienced PWH in real world, indicating a promising switching option for PWH who may be more prone to metabolic or cardiovascular diseases.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Infecções por HIV/tratamento farmacológico , Estudos Retrospectivos , LDL-Colesterol , Benzoxazinas/uso terapêutico , Benzoxazinas/farmacologia , Alcinos/farmacologia , Alcinos/uso terapêutico , Ciclopropanos/farmacologia , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia
6.
Environ Res ; 247: 118392, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38307178

RESUMO

Intensive anthropogenic activities have led to drastic changes in land use/land cover (LULC) and impacted the carbon storage in high-groundwater coal basins. In this paper, we conduct a case study on the Yanzhou Coalfield in Shandong Province of China. We further classify waterbodies by using the Google Earth Engine (GEE) to better investigate the process of LULC transformation and the forces driving it in four periods from 1985 to 2020 (i.e., 1985-1995, 1995-2005, 2005-2015, and 2015-2020). We modeled the spatiotemporal dynamics of carbon storage by using InVEST based on the transformation in LULC and its drivers, including mining (M), reclamation (R), urbanization and village relocation (U), and ecological restoration (E). The results indicate that carbon storage had depleted by 19.69 % (321099.06 Mg) owing to intensive transformations in LULC. The area of cropland shrank with the expansion of built-up land and waterbodies, and 56.31 % of the study area underwent transitions in land use in the study period. U was the primary driver of carbon loss while E was the leading driver of carbon gain. While the direct impact of M on carbon loss accounted for only 5.23 % of the total, it affected urbanization and led to village relocation. R led to the recovery of cropland and the reclamation of water for aquaculture, which in turn improved the efficiency of land use. However, it contributed only 2.09 % to the total increase in carbon storage. Numerous complicated and intertwined processes (211) drove the changes in carbon storage in the study area. The work here provides valuable information for decision-makers as well as people involved in reclamation and ecological restoration to better understand the link between carbon storage and the forces influencing it. The results can be used to integrate the goals of carbon sequestration into measures for land management.


Assuntos
Minas de Carvão , Água Subterrânea , Humanos , Carbono , China , Carvão Mineral , Ecossistema , Conservação dos Recursos Naturais
7.
Sci Rep ; 14(1): 3361, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336909

RESUMO

Based on the whole life cycle theory, the carbon effect of three different sizes of high-standard basic farmland construction projects is measured and analysed. The results show that the carbon emissions generated during the construction of high-standard basic farmland projects and the carbon absorption capacity at the later stage are different for projects of different sizes. The carbon emissions of different scales of high-standard basic farmland projects will increase during the construction stage. The results of carbon effect changes in the later operation and management stage show that the high-standard basic farmland construction projects will help reduce the carbon emissions of the field ecosystem where the farmland is located and increase its carbon sink capacity after the completion of construction, which is more obvious in larger projects. The emission reduction and carbon sequestration capacity of the farmland after remediation are improved to different degrees, which is more conducive to the ecological development of agricultural production and ecological environmental protection in the relevant areas. The study contributes to the green development of farmland, which is of some significance for the sustainable development of agriculture in Tianjin and the whole country.

8.
Clin Cosmet Investig Dermatol ; 17: 167-171, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38283797

RESUMO

Toxic epidermal necrolysis (TEN) is a type of drug eruption in dermatology emergencies that is rare in clinical practice but has a high mortality rate. The main causes are drug and viral infections. Unfortunately, no expert consensus on treating this disease exists, and a standard therapy is absent. Up to now, glucocorticoids combined with gamma globulin are commonly used in clinical practice, but their efficacy is highly controversial. This study reports on a 7-year-old girl with TEN who did not respond to traditional therapy, such as methylprednisolone combined with gamma globulin, but was finally cured with an additional low-dose etanercept. The results showed that etanercept therapy in paediatric TEN is safe, reliable and worth recommending.

9.
Technol Health Care ; 32(2): 511-523, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37483035

RESUMO

BACKGROUND: Radical resection of lung cancer and chemotherapy are the main methods for the treatment of early lung cancer, but surgical treatment is still the key and preferred method. OBJECTIVE: To evaluate the efficacy and safety of robotic-assisted thoracic surgery (RATS) and video assisted thoracic surgery (VATS) for non-small cell lung cancer (NSCLC). METHODS: The clinical cohort studies on the comparison of the effects of RATS and VATS in the treatment of NSCLC published in Web of Science, PubMed, The National Library of Medicine (NLM), China National Knowledge Infrastructure (CNKI) and Wanfang database from January 1, 2015 to December 31, 2022 were searched. Two researchers independently screened the literature, extracted the data, such as operation time, intraoperative conversion rate, intraoperative blood loss, number of lymph nodes dissected, and evaluated the quality of the included literature based on the Newcastle-Ottawa Scale (NOS). RevMan 5.3 software was used for Meat analysis. RESULTS: A total of 18 articles and 21,802 subjects were included. The results of the meta-analysis showed that the intraoperative blood loss of RATS was significantly less than that of VAS, and the difference was statistically significant [MD =-38.43 (95% CI: -57.71, -19.15, P< 0.001)]. Compared with VATS, the number of lymph nodes dissected in RATS was significantly higher [MD = 2.61 (95% CI: 0.47, 4.76, P= 0.02)]. The rate of conversion to thoracotomy in RATS was lower, and the difference was statistically significant [OR = 0.59 (95% CI: 0.50, 0.70, P< 0.001)]. There was no significant difference between RATS and VATS in operation time [MD =-9.34 (95% CI: -28.72, 10.04, P= 0.34)], postoperative thoracic drainage time [MD =-0.08 (95% CI: -0.42, 0.26, P= 0.64)], postoperative hospital stay [MD =-0.05 (95% CI: -0.19, 0.08, P= 0.42)], postoperative mortality [OR = 0.88 (95% CI: 0.56, 1.36, P= 0.56)] and postoperative complications [OR = 1.03 (95% CI: 0.93, 1.13, P= 0.57)]. CONCLUSION: Compared with VATS, the number of lymph nodes dissected in RATS was significantly more, and the removal of lesions and lymph nodes was more thorough and accurate. More flexible and precise operation avoids the injury of important blood vessels during operation, effectively reduces the amount of blood loss during operation, shortens the indwelling time of thoracic drainage tube, and is conducive to postoperative rehabilitation of patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Robótica , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Cirurgia Torácica Vídeoassistida/métodos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos
10.
Expert Rev Anti Infect Ther ; 22(4): 211-217, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38058002

RESUMO

BACKGROUND: This study aimed to evaluate the therapeutic effect and tolerance of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) use for 24 weeks in anti-retroviral therapy (ART)-naïve patients in China. METHODS: This single-center retrospective cohort study included ART-naïve patients who received BIC/FTC/TAF from July 2021 to April 2022. The proportion of patients with HIV RNA < 50 copies/mL at the end point of 24 weeks (virological suppression rate) was the primary outcome, and the changes in CD4 cell count, CD4/CD8 ratio, weight, blood lipid, and safety were secondary outcomes. RESULTS: A total of 80 ART-naïve patients were enrolled. The virological suppression rate was 86.3% at 24 weeks. The median CD4 cell count increased from 212 cells/µL (interquartile range [IQR]: 90.3-398.3) at baseline to 348 cells/µL (IQR: 219.8-541.0) at 24 weeks. The median CD4/CD8 ratio increased from 0.25 (IQR: 0.13-0.37) at baseline to 0.40 (IQR: 0.26-0.66) at 24 weeks. During the follow-up of 80 ART-naïve patients using BIC/FTC/TAF, 16 participants had adverse events; however, these events did not lead to drug withdrawal. CONCLUSION: This real-world cohort study showed that BIC/FTC/TAF could achieve good immunological and virological responses in ART-naïve patients. In addition, this study also shows good safety.


Assuntos
Adenina/análogos & derivados , Alanina , Amidas , Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Piperazinas , Piridonas , Tenofovir/análogos & derivados , Adulto , Humanos , Estudos Retrospectivos , Estudos de Coortes , Emtricitabina/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Infecções por HIV/tratamento farmacológico , Combinação de Medicamentos , Fármacos Anti-HIV/uso terapêutico
11.
J Sep Sci ; 47(1): e2300562, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37906087

RESUMO

Loxoprofen sodium is a chiral drug with two chiral centers. In our previous work, we found that the elimination of its four isomers showed stereospecificity in rats, while how the stereospecific behavior occurred in vivo was unclear. To clarify this issue, each single isomer of loxoprofen sodium was prepared by a chiral semi-preparative high-performance liquid chromatography (HPLC) and then administered to rats. By analysis of each isomer in rat plasma utilizing an analytical chiral HPLC, it was discovered that the chiral inversion occurred only to its (2R)-isomers, one from (1'S,2R)- to (1'S,2S)-isomer and the other from (1'R,2R)- to (1'R,2S)-isomer. The reduction of α-substituted cyclopentanone occurred only to its (1'R)-isomers, with (1'R,2R)-isomer reduced to (2'S,1'R,2R)-trans-alcohol and (1'R,2S)- to (2'S,1'R,2S)-trans-alcohol. Interestingly, both the inversion and the reduction reaction occurred to its (1'R,2R)-isomer due to the special stereo-structure with both (2R)- and (1'R)-configuration, and conversely, neither of them occurred to its (1'S,2S)-isomer, which caused the significantly different elimination rate in vivo. These new findings were meaningful for evaluation of the safety and efficacy of chiral drugs.


Assuntos
Fenilpropionatos , Sódio , Ratos , Animais , Cromatografia Líquida de Alta Pressão , Estereoisomerismo , Biotransformação
12.
Expert Rev Anti Infect Ther ; : 1-8, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37927079

RESUMO

BACKGROUND: The efficacy and safety of dolutegravir+lamivudine (DTG +3TC) and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) have been demonstrated in clinical trials of treatment-naïve therapy. However, real-life data are lacking. We investigated and compared the virological outcomes and safety of DTG + 3TC with BIC/FTC/TAF in an adult cohort of people living with HIV (PLWH). RESEARCH DESIGN AND METHODS: We performed a retrospective cohort analysis of PLWH who were naïve to antiretroviral therapy and initiated the antiretroviral regimen of DTG + 3TC or BIC/FTC/TAF from January 2020 to March 2022. Treatment effectiveness, defined as the capability of treatment to achieve viral suppression (viral load < 50 copies/mL), was analyzed. Changes in immunology, metabolism, liver and renal function after 48 weeks of treatment were evaluated. RESULTS: At 48 weeks, both groups showed high viral suppression, with 82.4% (108/131) and 89% (129/145) of the patients in the BIC/FTC/TAF and DTG + 3TC groups, respectively, having viral suppression (OR = 0.58, 95% CI: 0.29-1.15, P = 0.3). No differences existed in immunology, metabolism, liver and renal function; however, BIC/FTC/TAF led to greater weight gain. CONCLUSIONS: Both optimization strategies showed high tolerability in antiretroviral therapy-naïve patients, with no differences in virological efficacy; however, BIC/FTC/TAF may be related to the risk of weight gain risk. Further research is required to evaluate this problem.

13.
Heliyon ; 9(11): e22385, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38034667

RESUMO

Promoting green production behavior among farmers is crucial for enhancing income, improving industrial efficiency, and ensuring ecological security. This study analyzes the determinants of green production behavior among farmers in Cheifeng, China, Using a binary logistic model on a sample of 860 microdata. The result of empirical analysis pointed out that the implementation rate of rural households was low at 54.5 %, highlighting the need for intervention. The results suggest that age, party members, total income, total area, irrigation conditions, market, policy, social factors, and knowledge transfer ability significantly influence green production behavior. Among these factors, age, party member, total area, irrigation conditions, and knowledge transfer ability have negative effects, while other factors positively affect green production. To promote green production behavior, this study recommends improving access to information, developing a training system, enhancing quality and safety information disclosure, establishing traceability mechanisms, and providing policy subsidies. This stud also highlights the need to strengthen publicity, technical guidance, and media persuasion for promoting the green production of Chinese medicinal materials.

14.
Infect Dis Ther ; 12(10): 2457-2469, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37787861

RESUMO

INTRODUCTION: Ainuovirine/lamivudine/tenofovir is a novel antiretroviral therapy regimen used to treat human immunodeficiency virus-1 (HIV-1) infection. This study aimed to compare the pharmacokinetics of ainuovirine/lamivudine/tenofovir in HIV-1-infected patients aged ≥ 65 (elderly patients) and ≤ 40 years (young patients). METHODS: This prospective, open-label, parallel controlled clinical study included 15 young and 15 elderly patients. Blood (1 mL) was collected 30 min before dosing and at 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, and 24 h after dosing, to measure the plasma concentrations of ainuovirine/lamivudine/tenofovir. Safety was assessed by monitoring the adverse events, physical examinations, and clinical laboratory tests. RESULTS: Plasma concentrations of each ainuovirine/lamivudine/tenofovir component reached peak levels 1-4 h after dosing and gradually decreased during the remaining observation period. Compared with the young group, ainuovirine had significantly higher T1/2Ke, AUC0-24, and AUC0-inf (all P < 0.05) in the elderly group, whereas Ke (P = 0.002) was significantly lower. However, the Cmax and Tmax of ainuovirine did not differ significantly. Lamivudine and tenofovir also had a significantly higher Cmax (p = 0.004 and p = 0.008, respectively) and AUC0-inf (P = 0.014 and P = 0.006, respectively) in the elderly group, whereas there was no significant difference in Tmax, Ke, and T1/2Ke. Ainuovirine/lamivudine/tenofovir was well tolerated in both the young and elderly groups. CONCLUSION: This study suggests that the ainuovirine/lamivudine/tenofovir regimen might be an effective and safe treatment regimen for HIV-1-infected patients aged ≥ 65 years and ≤ 40 years. Further studies are needed to confirm these results and develop optimal dosing regimens for elderly HIV-1-infected patients.

15.
Infect Dis Ther ; 12(11): 2581-2593, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37845566

RESUMO

INTRODUCTION: Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir plus lamivudine (DTG + 3TC) are well tolerated and effective in clinical trials. This study aimed to evaluate the safety and efficacy of these two schemes in a real-world setting and to obtain the first dataset for switching to BIC/FTC/TAF and DTG + 3TC in a Chinese population. METHODS: This retrospective single-center cohort study in China included participants who switched to DTG + 3TC or BIC/FTC/TAF between January 2020 and February 2023. The main endpoint was the proportion of participants with HIV-1 RNA levels of ≥ 50 copies/mL. Safety, tolerance, and the incidence of low-level viremia (LLV) were evaluated. RESULTS: A total of 525 participants were included, 454 of whom were included in the PP analysis. At week 48, the proportions of participants with HIV-1 RNA ≥ 50 copies/mL were 4.4% (10/225) for DTG + 3TC and 6.1% (14/229) for BIC/FTC/TAF; virological efficacy did not differ significantly between the two groups. Consistent results were obtained in an intent-to-treat (ITT) analysis. The incidences of LLV were 3.6% (7/193) and 4.9% (10/206), respectively. During the study, none of the participants stopped taking drugs because of a lack of efficacy or adverse reactions. CONCLUSIONS: Both regimens are well tolerated and effective for switching HIV-1 infection therapy. However, the detection of genotypic drug resistance should be considered when baseline virological non-suppression is observed.

16.
ACS Omega ; 8(35): 31984-31997, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37692224

RESUMO

Since the hydrogenation of imines (X) and the dehydrogenation of amines (XH2) generally involve the two hydrogen ions (H- + H+) transfer, the thermodynamic abilities of various amines releasing hydrides or two hydrogen ions as well as various imines accepting protons or two hydrogen ions are important and characteristic physical parameters. In this work, the pKa values of 84 protonated imines (XH+) in acetonitrile were predicted. Combining Gibbs free energy changes of amines releasing hydrides in acetonitrile from our previous work with the pKa(XH+) values, the Gibbs free energy changes of amines releasing two hydrogen ions and imines accepting two hydrogen ions were derived using Hess's law by constructing thermochemical cycles, and the thermodynamic evaluations of amines as hydrides or two hydrogen ions reductants and imines as protons or two hydrogen ions acceptors are well compared and discussed. Eventually, the practical application of thermodynamic data for amines and imines on hydrogenation feasibility, mechanism, and possible elementary steps was shown and discussed in this paper from the point of thermodynamics.

17.
Immun Inflamm Dis ; 11(8): e974, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37647435

RESUMO

BACKGROUND: Prospective studies examining long-term therapeutic outcomes of the Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) regimen in human immunodeficiency virus (HIV) infection remain limited. This study assessed the actual efficacy and safety of BIC/FTC/TAF in HIV-infected individuals in southwest China. METHODS: This was a single-center, prospective study enrolling ART-naïve (n = 32) and ART-experienced (n = 177) HIV-infected patients administered BIC/FTC/TAF treatment between March 2022 and August 2022. The data were collected until February 28, 2023. Virological reactions and adverse events to the treatment were recorded, and patient subjective feelings in the form of Electronic Patient Reporting Outcome (ePRO) were collected. The primary endpoint was the rate of patients with HIV viral load <50 copies/mL at Week 24. RESULTS: At Week 24, 87.5% and 95.5% of ART-naïve and ART-experienced HIV patients had a viral load <50 copies/mL, respectively. CD4 cell counts in ART-naïve and ART-experienced patients increased significantly by 163.5 cells/µL (p = .002) and 55.0 cells/µL (p = .022), respectively. By Week 24, no patients had discontinued the BIC/FTC/TAF treatment due to adverse events. Based on ePRO data, ART-naïve and ART-experienced patients at Week 24 had stable disease symptom burden, quality of life, and depression level after treatment with BIC/FTC/TAF. CONCLUSION: BIC/FTC/TAF reduces the viral load in ART-naïve patients with high viral load as well as ART-experienced patients with residual viremia. The patient's subjective experience was maintained stable after treatment with BIC/FTC/TAF. This study also revealed a very low incidence for BIC/FTC/TAF drug-related side effects.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Humanos , Estudos Prospectivos , Infecções por HIV/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento , Combinação de Medicamentos , China , Eletrônica , Emtricitabina/uso terapêutico
18.
RSC Adv ; 13(23): 16023-16033, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37260565

RESUMO

Nitrogen-containing heterocycles are an important class of antioxidants, and their reactivity and selectivity in hydrogen atom reactions have attracted significant interest from chemists. In this work, the kinetics of hydrogen atom transfer reactions from C(sp3)-H bonds of 28 nitrogen-containing heterocycles, oxygen-containing heterocycles, alicyclic amines and cycloalkanes, which were denoted as XH, to the CumO˙ radical, were investigated. The characteristic physical parameter of the substrate, i.e., the thermo-kinetic parameter ΔG≠o(XH), was determined using the kinetic equation [ΔG≠XH/Y = ΔG≠o(XH) + ΔG≠o(Y)] to quantitatively evaluate the H-donating ability of XH. The effects of the substrate structure, substituent attached to the nitrogen atom, and ring size on the H-donating ability were discussed carefully. By comparing the H-donating abilities of cycloalkanes, alicyclic amines and nitrogen/oxygen-containing heterocycles, the influence of the introduction of N, O, or carbonyl groups in the carbon ring on the H-donating ability of C(sp3)-H bond was determined. The electronic, steric and stereo-electronic effects of the groups were also discussed. Herein, we not only quantitatively determined the H-donating ability of the substrate, but also provided ideas for the synthesis of new antioxidants.

19.
J Phys Condens Matter ; 35(27)2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37011631

RESUMO

This study is started from a photon-magnon model with a competition effect of the level attraction and repulsion, its Hermiticity is mainly decided by a phase-dependent and asymmetric coupling factor, namelyφ = 0 for Hermitian andϕ=πfor non-Hermitian. Then an extensional study predicts the quantum critical behaviors using an Hermitian and even no-Hermitian photon-spins model with an additional second-order drive. The numerical results firstly indicate that this coupling phaseφcan function the protective effect on quantum phase transitions (QPTs), and the new tricritical points can not only be modulated by this nonlinear drive, but also be influenced by the dissipation and the collective decoherence. Secondly, this competition effect can also induce a reversal of the value of order parameters between the positive and negative. This study can also bring more important results of QPTs toward the issue of symmetry breaking and non-Hermiticity.

20.
J Cardiothorac Surg ; 18(1): 54, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732810

RESUMO

BACKGROUND: Short-term and long-term comparative outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for multivessel coronary artery (MVCA) or left main coronary artery (LMCA) disease are highly debated. GOALS: We performed a meta-analysis to evaluate the difference between PCI and CABG for the treatment of patients with MVCA or LMCA in long-term follow-up. METHODS: Literatures were searched in PubMed, EMBASE and The Cochrane Library from January 1, 2000 to January 1, 2021, including RCTs and observational studies (OSs). The primary outcome was all-cause mortality at 10 years follow-up, and the secondary outcomes included cardiac mortality, repeated revascularization, myocardial infarction, and stroke. RESULTS: A total of 5 RCTs reporting data from 3013 participants and 4 OSs of 5608 participants were included for analysis. There was no significant difference between PCI and CABG in all-cause mortality (Odds Ratio (OR) 1.03 [95% confidence interval (CI) 0.89 to 1.19]), whereas PCI was associated with higher cardiac mortality (OR 0.76 [95% CI 0.65 to 0.90]) and repeated revascularization rate comparing to CABG (OR 1.77 [95% CI 1.08 to 2.89]; I2 = 94.61%). The difference between PCI and CABG in repeated revascularization in either RCTs or OSs, in myocardial infarction in either RCTs or OSs were not significant. In OSs, stroke rate in PCI group was lower than those in CABG, but not in RCTs. There was a significant increase of stroke rate in CABG comparing to PCI (OR 0.65 [95% CI 0.53 to 0.80]; I2 = 0.00%). No significant difference between PCI and CABG in myocardial infarction was not observed (OR 0.92 [95% CI 0.64 to 1.31]; I2 = 57.84%). CONCLUSION: Evidence from our study and prior studies suggested the superiority of CABG over PCI in improving 5- but not 10-year survival among patients with MVCA. In the contrast, there was no significant difference between CABG and PCI for treating patients with LMCA in either 5- or 10-year survival rate. More long-term trials are needed to better define differences of outcome between 2 techniques.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Ponte de Artéria Coronária/efeitos adversos , Infarto do Miocárdio/etiologia , Acidente Vascular Cerebral/etiologia
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