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Efficient electrocatalysts capable of operating continuously at industrial ampere-level current densities are crucial for large-scale applications of electrocatalytic water decomposition for hydrogen production. However, long-term industrial overall water splitting using a single electrocatalyst remains a major challenge. Here, bimetallic polyphthalocyanine (FeCoPPc)-anchored Ru nanoclusters, an innovative electrocatalyst comprising the hydrogen evolution reaction (HER) active Ru and the oxygen evolution reaction (OER) active FeCoPPc, engineered for efficient overall water splitting are demonstrated. By density functional theory calculations and systematic experiments, the electrocatalytic coenhancement effect resulting from unique charge redistribution, which synergistically boosts the HER activity of Ru and the OER activity of FeCoPPc by optimizing the adsorption energy of intermediates, is unveiled. As a result, even at a large current density of 2.0 A cm-2 , the catalyst exhibits low overpotentials of 220 and 308 mV, respectively, for HER and OER. It exhibits excellent stability, requiring only 1.88 V of cell voltage to achieve a current density of 2.0 A cm-2 in a 6.0 m KOH electrolyte at 70 °C, with a remarkable operational stability of over 100 h. This work provides a new electrocatalytic coenhancement strategy for the design and synthesis of electrocatalyst, paving the way for industrial-scale overall water splitting applications.
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Ultrathin 2D porous carbon-based materials offer numerous fascinating electrical, catalytic, and mechanical properties, which hold great promise in various applications. However, it remains a formidable challenge to fabricate these materials with tunable morphology and composition by a simple synthesis strategy. Here, a facile one-step self-flowering method without purification and harsh conditions is reported for large-scale fabrication of high-quality ultrathin (≈1.5 nm) N-doped porous carbon nanosheets (NPC) and their composites. It is demonstrated that the layered tannic/oxamide (TA/oxamide) hybrid is spontaneously blown, exfoliated, bloomed, in situ pore-formed, and aromatized during pyrolysis to form flower-like aggregated NPC. This universal one-step self-flowering system is compatible with various precursors to construct multiscale NPC-based composites (Ru@NPC, ZnO@NPC, MoS2 @NPC, Co@NPC, rGO@NPC, etc.). Notably, the programmable architecture enables NPC-based materials with excellent multifunctional performances, such as microwave absorption and hydrogen evolution. This work provides a facile, universal, scalable, and eco-friendly avenue to fabricate functional ultrathin porous carbon-based materials with programmability.
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Chinese guidelines prioritize the use of Azvudine and nirmatrelvir-ritonavir in COVID-19 patients. Nevertheless, the real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir is still lacking, despite clinical trials showing their effectiveness compared with matched controls. To compare the effectiveness of Azvudine versus nirmatrelvir-ritonavir treatments in real-world clinical practice, we identified 2118 hospitalized COVID-19 patients, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 281 Azvudine recipients and 281 nirmatrelvir-ritonavir recipients who did not receive oxygen therapy at admission. The lower crude incidence rate of composite disease progression outcome (7.83 vs. 14.83 per 1000 person-days, p = 0.026) and all-cause death (2.05 vs. 5.78 per 1000 person-days, p = 0.052) were observed among Azvudine recipients. Azvudine was associated with lower risks of composite disease progression outcome (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.32-0.94) and all-cause death (HR: 0.40; 95% CI: 0.16-1.04). In subgroup analyses, the results of composite outcome retained significance among patients aged <65 years, those having a history of disease, those with severe COVID-19 at admission, and those receiving antibiotics. These findings suggest that Azvudine treatment showed effectiveness in hospitalized COVID-19 patients compared with nirmatrelvir-ritonavir in terms of composite disease progression outcome.
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COVID-19 , Humanos , Tratamento Farmacológico da COVID-19 , Estudos Retrospectivos , Ritonavir/uso terapêutico , Progressão da Doença , Antivirais/uso terapêuticoRESUMO
To summarize the clinical characteristics and explore the role of treatment types in outcomes among psoriasis patients with coronavirus disease 2019 (COVID-19). The principal summary measures were pooled prevalence and risk ratio (RR) with 95% confidential interval (CI). R statistic software was used for all the analysis. A total of 19 studies including 4073 psoriasis patients with COVID-19 were eligible for the meta-analysis. The overall hospitalization rate is about 20.2% (95% CI: 12.7%-28.7%), and changed to be 18.0% (95% CI: 9.9%-27.6%) or 14.1% (95% CI: 5.9%-24.6%) after systemic or biologic treatment. Moreover, the overall fatality rate is 1.5% (95% CI: 0.4%-3.0%), and turned to be 0.7% (95% CI: 0%-2.0%) or 0.5% (95% CI: 0%-2.2%) after systemic or biologic therapy. Notably, a lower hospitalization RR was found in patients receiving biologic therapy than those receiving other treatments (RR = 0.62, 95% CI: 0.42-0.94). The results were consistent after sensitivity analysis and trim-and-fill analysis. Systemic, especially biologic therapy could lessen the clinical severity in psoriasis patients with COVID-19. Our finding will help to guide current recommendations and provide a reference for clinical decision-making.
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Produtos Biológicos , COVID-19 , Psoríase , Produtos Biológicos/uso terapêutico , Humanos , Psoríase/complicações , Psoríase/tratamento farmacológico , Psoríase/epidemiologiaRESUMO
BACKGROUND: Autophagy, a highly conserved lysosomal degradation pathway, is associated with the prognosis of melanoma. However, prognostic prediction models based on autophagy related genes (ARGs) have never been recognized in melanoma. In the present study, we aimed to establish a novel nomogram to predict the prognosis of melanoma based on ARGs signature and clinical parameters. METHODS: Data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were extracted to identify the differentially expressed ARGs. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate analysis were used to select the prognostic ARGs. ARGs signature, age and stage were then enrolled to establish a nomogram to predict the survival probabilities of melanoma. The nomogram was evaluated by concordance index (C-index), receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis (DCA) was performed to assess the clinical benefits of the nomogram and TNM stage model. The nomogram was validated in GEO cohorts. RESULTS: Five prognostic ARGs were selected to construct ARGs signature model and validated in the GEO cohort. Kaplan-Meier survival analysis suggested that patients in high-risk group had significantly worse overall survival than those in low-risk group in TCGA cohort (P = 5.859 × 10-9) and GEO cohort (P = 3.075 × 10-9). We then established and validated a novel promising prognostic nomogram through combining ARGs signature and clinical parameters. The C-index of the nomogram was 0.717 in TCGA training cohort and 0.738 in GEO validation cohort. TCGA/GEO-based ROC curve and decision curve analysis (DCA) demonstrated that the nomogram was better than traditional TNM staging system for melanoma prognosis. CONCLUSION: We firstly developed and validated an ARGs signature based-nomogram for individualized prognosis prediction in melanoma patients, which could assist with decision making for clinicians.
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Autofagia/genética , Melanoma/genética , Melanoma/mortalidade , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Fatores Etários , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Melanoma/patologia , Estadiamento de Neoplasias , Curva ROC , Análise de Regressão , Reprodutibilidade dos Testes , Neoplasias Cutâneas/patologiaRESUMO
MiR-122-5p serves as a novel biomarker for drug-induced liver injury (DILI), but its function in DILI remains unclear. The present study, therefore, explored the function and potential mechanism of miR-122-5p in DILI. Sprague-Dawley (SD) rats were treated with miR-122-5p antagomir, and then DILI was induced in the rats by acetaminophen (APAP). To determine the effect of miR-122-5p on DILI in vivo, liver injury was examined by HE staining and TUNEL assays, and the levels of serum ALT and AST were determined using an automated clinical chemistry analyzer. To further reveal the mechanism of miR-122-5p in DILI, THLE-2 (normal liver cell line) cells were transfected with miR-122-5p mimic and inhibitor, NDRG3, and siNDRG3, and then injured by APAP. The relationship between miR-122-5p and NDRG3 was determined by TargetScan, luciferase reporter assay, and Western blot. The viability and apoptosis of THLE-2 cells were detected by CCK-8 and flow cytometry, respectively. The levels of mRNA and protein in vivo and in vitro were measured by qRT-PCR and Western blot, respectively. APAP induced liver injury and increased the levels of ALT, AST, and miR-122-5p in DILI rats. However, these effects of APAP were attenuated by miR-122-5p antagomir. MiR-122-5p negatively regulated NDRG3 expression. APAP decreased cell viability, apoptosis resistance, and Bcl-w and Bcl-2 levels whereas increased Bax level in THLE-2 cells. However, these effects of APAP on THLE-2 cells were promoted by miR-122-5p up-regulation but inhibited by miR-122-5p knockdown. MiR-122-5p knockdown protects against APAP-mediated liver injury through up-regulating NDRG3.
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Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Regulação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/antagonistas & inibidores , Analgésicos não Narcóticos/toxicidade , Animais , Apoptose , Sobrevivência Celular , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , MicroRNAs/genética , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Coronavirus disease 2019 (COVID-19) has brought great challenges to global public health. However, a comprehensive analysis of the relationship between liver biochemical parameters and COVID-19 mortality is quite limited. METHODS: We searched the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science, Scopus, Wanfang and China National Knowledge Infrastructure database until May 5, 2020. STATA software was used for the statistical analyses. RESULTS: A total of 25 studies involving 5971 COVID-19 patients were included in our analysis. Compared with non-survivors, survivors had lower levels of aspartate aminotransferase (AST) (weighted mean difference [WMD]=-16.71U/L, 95%CI=[-21.03,-12.40], P<0.001), alanine transaminase (ALT) (WMD=-5.20U/L, 95%CI=[-8.00,-2.41], P<0.001), total bilirubin (TBIL) (WMD=4.40µmol/L, 95%CI=[-5.11,-3.70], P<0.001) and lactic dehydrogenase (LDH) (WMD=-252.44U/L, 95%CI=[-289.57,-215.30], P<0.001), and higher albumin (ALB) level (WMD=4.47g/L, 95%CI=[3.47,5.47], P<0.001). Besides, survivors had lower proportions of these abnormally increased parameters (AST: OR=0.25, 95%CI=[0.15,0.41], P<0.001; ALT: OR=0.49, 95%CI=[0.37,0.64], P<0.001; TBIL: (OR=0.20, 95%CI=[0.12,0.34], P<0.001; LDH, OR=0.09, 95%CI=[0.06,0.14], P<0.001), and lower proportion of abnormally decreased ALB (OR=0.16, 95%CI=[0.07,0.38], P<0.001). Meta-analysis based on standard mean difference and sensitivity analysis did not change the conclusions. Egger test did not detect the presence of publication bias. CONCLUSIONS: Liver biochemical parameters were strongly correlated with COVID-19 mortality. Measurement of these liver biochemical parameters might assist clinicians to evaluate the prognosis of COVID-19.
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Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , COVID-19/mortalidade , Prognóstico , SARS-CoV-2 , Biomarcadores/sangue , COVID-19/enzimologia , Saúde Global , Humanos , Pandemias , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Studies have suggested that patients with inflammatory bowel disease (IBD) have an increased risk of rheumatoid arthritis (RA). However, the available data on this association are inconsistent. This meta-analysis aimed to determine the association between IBD and the risk of RA. METHODS: Observational studies investigating the RA risk among patients with IBD (Crohn disease (CD) and/or ulcerative colitis (UC)) were searched in PubMed, Embase, and Web of Science from the date of inception to December 2019. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Relative risks (RRs) and corresponding 95% confidential intervals (CIs) were pooled with a random-effects model. Heterogeneity was evaluated using I2 statistics while publication bias was determined using Begg's and Egger's tests. Subgroup and sensitivity analyses were performed. RESULTS: A total of three cohort studies, three cross-sectional studies, and two case-control studies were included in the meta-analyses. Compared to the non-IBD control or general population, there was a significantly higher risk of RA among patients with IBD (RR = 2.59; 95% CI: 1.93-3.48). Moreover, both CD (RR = 3.14; 95% CI: 2.46-4.01) and UC (RR = 2.29; 95% CI: 1.76-2.97) were associated with a significantly increased risk of RA. However, heterogeneity was substantial across studies and the subgroup analyses failed to identify the potential source of heterogeneity. CONCLUSIONS: Patients with IBD have a greater risk of developing RA. Rheumatologists should be consulted when patients with IBD present with undifferentiated joint complaints. However, more prospective cohort studies are needed to validate these results.
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Artrite Reumatoide/etiologia , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Doenças Inflamatórias Intestinais/complicações , Adolescente , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Compared with open gastrectomy (OG), laparoscopic gastrectomy (LG) for gastric cancer has achieved rapid development and popularities in the past decades. However, lack of comprehensive analysis in long-term oncological outcomes such as recurrence and mortality hinder its full support as a valid procedure. Therefore, there are still debates on whether one of these options is superior. AIM: To evaluate the primary and secondary outcomes of laparoscopic versus open gastrectomy for gastric cancer patients METHODS: Two authors independently extracted study data. Risk ratio (RR) with 95% confidence interval (CI) was calculated for binary outcomes, mean difference (MD) or the standardized mean difference (SMD) with 95% CI for continuous outcomes, and the hazard ratio (HR) for time-to-event outcomes. Review Manager 5.3 and STATA software were used for the meta-analysis. RESULTS: Seventeen randomized controlled trials (RCTs) involving 5204 participants were included in this meta-analysis. There were no differences in the primary outcomes including the number of lymph nodes harvested during operation, severe complications, short-term and long-term recurrence, and mortality. As for secondary outcomes, compared with the OG group, longer operative time was required for patients in the LG group (MD = 58.80 min, 95% CI = [45.80, 71.81], P < 0.001), but there were less intraoperative blood loss (MD = - 54.93 ml, 95% CI = [- 81.60, - 28.26], P < 0.001), less analgesic administration (frequency: MD = - 1.73, 95% CI = [- 2.21, - 1.24], P < 0.001; duration: MD = - 1.26 days, 95% CI = [- 1.40, - 1.12], P < 0.001), shorter hospital stay (MD = - 1.37 days, 95% CI = [- 2.05, - 0.70], P < 0.001), shorter time to first flatus (MD = - 0.58 days, 95% CI = [- 0.79, - 0.37], P < 0.001), ambulation (MD = - 0.50 days, 95% CI = [- 0.90, - 0.09], P = 0.02) and oral intake (MD = - 0.64 days, 95% CI = [- 1.24, - 0.03], P < 0.04), and less total complications (RR = 0.81, 95% CI = [0.71, 0.93], P = 0.003) in the OG group. There was no difference in blood transfusions (number, quantity) between these two groups. Subgroup analysis, sensitivity analysis, and the adjustment of Duval's trim and fill methods for publication bias did not change the conclusions. CONCLUSION: LG was comparable to OG in the primary outcomes and had some advantages in secondary outcomes for gastric cancer patients. LG is superior to OG for gastric cancer patients.
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Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Gastrectomia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the social support level and its influencial factors in patients with systemic lupus erythematosus (SLE), and to develop the management strategies for chronic disease.â© Methods: Patients with SLE were investigated by Social Support Rating Scale (SSRS), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), 36-Item Short-Form Health Survey (SF-36) and Visual Analogue Scale (VAS) of fatigue. The demographic and clinical data of SLE patients were recorded. SLE disease activity and damage severity were assessed by SLE Disease Activity Index (SLEDAI) and SLE Damage Index (SDI), respectively. Influencial factors for social support were analyzed.â© Results: A total of 246 patients were included. Social support scores for these patients were 40.76±7.93 and the scores showed no significant difference with the national norm (P>0.05). Patients who were younger than 18, single, unemployed or damaged by disease showed lower level of social support (P<0.05). Compared with the high social support group, patients in the low social support group experienced more severe depression or anxiety, and scored lower on mental component summary scale (vitality, social functioning, emotional role and mental health perception) and physical role of SF-36 (P<0.05).â© Conclusion: Social support levels for patients with SLE are closely related to the quality of life, and influenced by age, marital status, professional condition, and disease damage. Health education for patients and their families should be strengthened in chronic disease management to enhance social support and finally, improve their quality of life.
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Lúpus Eritematoso Sistêmico , Qualidade de Vida , Doença Crônica , Nível de Saúde , Humanos , Índice de Gravidade de Doença , Apoio Social , Inquéritos e QuestionáriosRESUMO
A novel postpolymerization modification methodology is demonstrated to achieve selective functionalization of hyperbranched polymer (HBP). Terminal and internal acrylates of HBP derived from cross-metathesis polymerization (CMP) are functionalized in a chemoselective fashion using the thiol-Michael chemistries. Model reactions between different thiols (benzyl mercaptan and methyl thioglycolate) and acrylates (n-hexyl acrylate and ethyl trans-2-decenoate) by using dimethylphenylphosphine or amylamine as the catalyst are investigated to optimize the modification protocol for HBP. High-molecular-weight HBP P0 is generated through CMP of AB2 monomer 2, a compound containing one α-olefin and two acrylate metathetically polymerizable groups. CMP kinetics is monitored by NMR and gel permeation chromatography (GPC). Accordingly, microstructural analysis is conducted in detail, and CMP procedure is optimized. Postpolymerization modification of HBP P0 is performed via two distinguished strategies, namely one-step complete modification and sequential modification, to generate terminally and/or internally functionalized HBPs P1-P3 in a chemoselective fashion by using phosphine-initiated and/or base-catalyzed thiol-Michael chemistries. Finally, thermal stability and glass transition behaviors of HBPs P0-P3 are studied by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC), respectively.
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Acrilatos/química , Poliésteres/química , Polimerização , Compostos de Sulfidrila/química , Alcenos/química , Varredura Diferencial de Calorimetria , Catálise , Técnicas de Química Sintética , Modelos Químicos , Estrutura Molecular , Poliésteres/síntese química , TermogravimetriaRESUMO
Precise structure-property relation of a biodegradable polymer (e.g., aliphatic polyester) is anticipated only if monomer units and chiral centers are arranged in a defined primary sequence as a biomacromolecule. An emerging synthetic methodology, namely segmer assembly polymerization (SAP), is introduced in this paper to reveal the latest progress in polyester synthesis. Almost any periodic polyester envisioned can be synthesized via SAP using a programed linear or cyclic monomer. In this context, the macroscopic properties of a biodegradable polymer are fundamentally determined by microstructural information through a bottom-up approach. It can be highlighted that SAP ideally combines the precision of organic synthesis and the high efficiency of a polymerization reaction. Previously reported strategies including nucleophilic displacement, polyesterification, cross-metathesis polymerization (CMP), ring-opening polymerization (ROP), ring-opening metathesis polymerization (ROMP) and entropy-driven ring-opening metathesis polymerization (ED-ROMP) are critically reviewed in this paper to shed light on precision synthesis of aliphatic polyesters via SAP. Emerging yet challenging, SAP is a paradigm which reflects the convergence of organic and polymer chemistries and is also an efficient pathway to microstructural control. The current status, future challenges and promising trends in this realm are analyzed and discussed in this overview of the state-of-the-art.
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Plásticos Biodegradáveis/síntese química , Lactonas/síntese química , Poliésteres/síntese química , Polimerização , Plásticos Biodegradáveis/química , Catálise , Lactonas/química , Poliésteres/química , Polímeros/química , Relação Estrutura-AtividadeRESUMO
Sequence-regulated polymerization is realized upon sequential cross-metathesis polymerization (CMP) and exhaustive hydrogenation to afford precision aliphatic polyesters with alternating sequences. This strategy is particularly suitable for the arrangement of well-known monomer units including glycolic acid, lactic acid, and caprolactic acid on polymer chain in a predetermined sequence. First of all, structurally asymmetric monomers bearing acrylate and α-olefin terminuses are generated in an efficient and straightforward fashion. Subsequently, cross-metathesis (co)polymerization of M1 and M2 using the Hoveyda-Grubbs second-generation catalyst (HG-II) furnishes P1-P3, respectively. Finally, hydrogenation yields the desired saturated polyesters HP1-HP3. It is noteworthy that the ε-caprolactone-derived unit is generated in situ rather than introduced to tailor-made monomers prior to CMP. NMR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) results verify the microstructural periodicity of these precision polyesters. Differential scanning calorimetry (DSC) results reflect that polyesters without methyl side groups exhibit crystallinity, and unsaturated polyester samples show higher glass transition temperatures than their hydrogenated counterparts owing to structural rigidity.
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Poliésteres/síntese química , Polimerização , Varredura Diferencial de Calorimetria , Caproatos , Lactonas , Poliésteres/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Since objects above absolute zero agree with the Plank law, the objects' temperature is reflected by the infrared radiation. With fast response and high resolution, temperature estimation based on mid-wave infrared remote sensing could realize the temperature measurement for small, high-speed and touch-free objects. A new optical system for infrared (IR) image-spectrum integration remote sensing was used to acquire infrared emission spectra from different temperatures of metal. With this basis, we extracted four appropriate spectral features which were the center of gravity position, peak position, the value of wavelength λ1 and the value of wavelength λ2 from the training samples. The relationship between temperature and these features was studied. A multiple linear regression model was established to estimate the temperatures from the spectra. The experimental results showed that, the method could distinguish hot objects with obvious temperature differences. The absolute error was less than 30 â in the experimental temperature range. The accuracy was 98% in the range that the measurement error was less than 20 â, which was better than the 2% precision of the general system with the complex strict emissivity, atmospheric transmittance, environmental equivalent radiation temperature and some other parameters. This method could measure the temperature of the remote objects in a simple and effective way, and so could expand the application field of temperature estimation based on infrared remote sensing.
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Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Complicações Infecciosas na Gravidez , COVID-19 , Feminino , Humanos , Fígado , Gravidez , SARS-CoV-2Assuntos
Betacoronavirus , Infecções por Coronavirus , Pneumonia Viral , COVID-19 , Humanos , Pandemias , SARS-CoV-2RESUMO
Patients with metastatic uveal melanoma (mUM) have a poor prognosis, and few appropriate medications are available. Tebentafusp is approved by the Food and Drug Administration for mUM recently. However, the real efficacy and safety of tebentafusp are still unclear. We searched PubMed, Embase, and Cochrane Library from inception to March 20, 2024. The research was reported based on the preferred reporting items for systematic reviews and meta-analysis guidelines. We used random effects models to aggregate data on the response rates and adverse events of tebentafusp therapy. Six studies met the inclusion criteria with a total sample of 589 participants. The pooled objective response rate was 0.08 (95% CI: 0.05-0.12), and pooled disease control rate was 0.51 (95% CI: 0.44-0.57). The overall incidence was 0.99 (95% CI: 0.95-1.00) for any grade adverse events, 0.50 (95% CI: 0.41-0.59) for grade 3-4 adverse events, and 0.01 (95% CI: 0-0.03) for discontinuation due to adverse events. Tebentafusp exhibits promising treatment outcomes for mUM patients. Although accompanied with a common occurrence of adverse events, which can typically be managed and controlled. Future research is necessary for substantiating these findings and refining guidelines for management of mUM.
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Melanoma , Neoplasias Uveais , Humanos , Neoplasias Uveais/tratamento farmacológico , Melanoma/tratamento farmacológico , Resultado do Tratamento , Metástase Neoplásica , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêuticoRESUMO
The ZF2001 vaccine has demonstrated high efficacy in preventing coronavirus disease 2019 (COVID-19). However, the clinical characteristics of breakthrough infections in vaccinated individuals and the risk factors for adverse outcomes in COVID-19 patients remain unclear. We conducted a retrospective single-center cohort study at Xiangya Hospital of Central South University, including 210 fully vaccinated COVID-19 inpatients from December 5, 2022, to January 31, 2023. Data on clinical characteristics, laboratory findings, disease severity, treatment, and prognosis were collected and analyzed. Our findings revealed that COVID-19 inpatients still experienced common symptoms at the onset of illness, but most laboratory findings were within the normal range, except for white blood cell count (WBC), lymphocyte count, and lactate dehydrogenase (LDH) levels. Following standard treatment, 95.7% of patients were discharged from the hospital. We identified seven variables significantly associated with a higher risk of adverse outcomes, including age over 65, elevated WBC count, reduced lymphocyte count, higher levels of blood urea nitrogen (BUN), LDH, troponin, D-dimer, and procalcitonin. This study supports the substantial clinical benefits of the ZF2001 vaccine for COVID-19 patients. Additionally, age over 65, elevated WBC count, reduced lymphocyte count, and higher blood levels of BUN, LDH, D-dimer, and procalcitonin may be used as predictive factors for disease progression in fully vaccinated COVID-19 inpatients.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fatores de Risco , SARS-CoV-2/imunologia , Adulto , Pacientes Internados , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinação , Idoso de 80 Anos ou mais , Infecções Irruptivas , Vacinas de Subunidades AntigênicasRESUMO
BACKGROUND: Glucagon-like peptide-1 receptor (GLP1R) agonists have been approved by Food and Drug Administration for management of obesity. However, the causal relationship of GLP1R agonists (GLP1RA) with cancers still unclear. METHODS: The available cis-eQTLs for drugs target genes (GLP1R) were used as proxies for exposure to GLP1RA. Mendelian randomizations (MR) were performed to reveal the association of genetically-proxied GLP1RA with 14 common types cancer from large-scale consortia. Type 2 diabetes was used as positive control, and the GWASs data including 80 154 cases and 853 816 controls. Replicating the findings in the FinnGen study and then pooled with meta-analysis. Finally, all the related randomized controlled trails (RCTs) on GLP1RA were systematically searched from PubMed, Embase, and the Cochrane Library to comprehensively synthesize the evidence to validate any possible association with cancers. RESULT: A total of 22 significant cis-eQTL single-nucleotide polymorphisms were included as genetic instrument. The association of genetically-proxied GLP1RA with significantly decreased type 2 diabetes risk [OR (95%)=0.82 (0.79-0.86), P <0.001], which ensuring the effectiveness of identified genetic instruments. The authors found favorable evidence to support the association of GLP1RA with reduced breast cancer and basal cell carcinoma risk [0.92 (0.88-0.96), P <0.001, 0.92 (0.85-0.99), P =0.029, respectively], and with increased colorectal cancer risk [1.12 (1.07-1.18), P <0.001]. In addition, there was no suggestive evidence to support the association of GLP1RA with ovarian cancer [0.99 (0.90-1.09), P =0.827], lung cancer [1.01 (0.93-1.10), P =0760], and thyroid cancer [0.83 (0.63-1.10), P =0.187]. Our findings were consistent with the meta-analysis. Finally, 80 RCTs were included in the systematic review, with a low incidence of different kinds of cancer. CONCLUSIONS: Our study suggests that GLP1RA may decrease the risk of breast cancer and basal cell carcinoma, but increase the risk of colorectal cancer. However, according to the systematic review of RCTs, the incidence of cancer in patients treated with GLP1RA is low. Larger sample sizes of RCTs with long-term follow-up are necessary to establish the incidence of cancers and evaluate the risk-benefit ratios.