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Breast cancer, the most common malignant tumor in the world, seriously threatens human life and health. Early diagnosis of breast cancer may help enhance the survival rate. In this work, a colorimetric and fluorescent dual-mode biosensor based on the CRISPR-Cas12a system was constructed to detect the breast cancer biomarker BRCA1. The intact G4 DNA, with the assistance of K+ and hemin, catalyses the oxidation of o-phenylenediamine (OPD) with the assistance of hydrogen peroxide (H2O2), generating the oxidation product 2,3-diaminophenazine (DAP), which has distinct absorption and fluorescence peaks. The presence of the target BRCA1 activates the trans-cleavage activity of CRISPR-Cas12a, leading to the cleavage of G4 DNA and inhibiting the catalytic oxidation of OPD. Target BRCA1 was quantitatively determined by measuring both the absorbance and fluorescence intensity of DAP. The detection limits were calculated to be 0.615 nM for the colorimetric method and 0.289 nM for the fluorescence method. The dual-mode biosensor showed good selectivity and reliability for BRCA1 and can resist interference from complex substrates, and it has great potential in biomedical detection.
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COVID-19 , Complicações Pós-Operatórias , SARS-CoV-2 , Procedimentos Cirúrgicos Torácicos , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Estudos Retrospectivos , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/epidemiologia , Feminino , Masculino , Procedimentos Cirúrgicos Torácicos/mortalidade , Pessoa de Meia-Idade , Idoso , Infecção Hospitalar/mortalidade , Infecção Hospitalar/epidemiologiaRESUMO
BACKGROUND: Antiangiogenic treatment and immunochemotherapy effectively treat patients with advanced esophageal cancer. However, there remains a dearth of studies concerning neoadjuvant therapy for resectable esophageal cancer. METHODS: The study focused on patients with T2-4NxM0 resectable esophageal carcinoma. Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for antiangiogenesis and sintilimab (200 mg) and chemotherapy for three cycles. Surgical treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) and safety. RESULTS: Out of the 34 screened patients, 17 were successfully enrolled in the study, and 14 completed the entire treatment process. The pCR was 35.3% (6/17). However, two patients experienced mortality. The occurring rate of grade 3 or higher complications after the surgery was 78.6% (11/14) according to Clavien-Dindo classification. Specifically, anastomotic leakage was observed in 57.1% (8/14) of the patients. CONCLUSION: Compared to neoadjuvant chemotherapy, the current regimen demonstrated improved pCR. However, it did not show significant improvement compared to immunochemotherapy. It is essential to exercise caution when using this treatment approach in patients with esophageal cancer as it might increase postoperative complications, especially anastomotic leakage.
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Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Indóis , Terapia Neoadjuvante , Quinolinas , Humanos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Masculino , Terapia Neoadjuvante/métodos , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Indóis/uso terapêutico , Indóis/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , AdultoRESUMO
OBJECTIVES: To assess the dynamics of the anti-SARS-CoV-2 IgG antibody levels and their efficacy against COVID-19. METHODS: We conducted a longitudinal serological analysis of 852 breakthrough COVID-19 infections among the community-based population in Yichang, China. Anti-SARS-CoV-2 IgG levels were measured by chemiluminescence at approximately 3, 4, and 9 months after infection. A linear mixed model predicted IgG antibody decline over 18 months. The effectiveness of antibodies in preventing symptomatic and severe infections was determined using an existing meta-regression model. RESULTS: IgG antibodies slowly declined after breakthrough infections. Initially high at around 3 months (339.44 AU/mL, IQR: 262.78-382.95 AU/mL), levels remained significant at 9 months (297.74 AU/mL, IQR: 213.22-360.62 AU/mL). The elderly (≥60 years) had lower antibody levels compared to the young (<20 years) (P < 0.001). The protective efficacy of antibodies against symptomatic and severe infections was lower in the elderly (≥60 years) (78.34% and 86.33%) compared to the young (<20 years) (96.56% and 98.75%) after 1 year. CONCLUSION: The study indicated a slow decline in anti-SARS-CoV-2 IgG antibodies, maintaining considerable efficacy for over 1 year. However, lower levels in the elderly suggest reduced protective effects, underscoring the need for age-specific vaccination strategies.
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Anticorpos Antivirais , COVID-19 , Imunoglobulina G , SARS-CoV-2 , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , China/epidemiologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Estudos Longitudinais , Masculino , Adulto , Feminino , Adulto Jovem , Idoso , Adolescente , Infecções IrruptivasRESUMO
BACKGROUND: The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within the tumor microenvironment (TME). Unveiling the immune landscape of ESCC in the context of NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. METHODS: We analyzed single cells from 22 baseline and 24 post-NAT treatment samples of stage II/III ESCC patients to explore the association between the immune landscape and pathological response to neoadjuvant anti-PD-1 combination therapy, including pathological complete response (pCR), major pathological response (MPR), and incomplete pathological response (IPR). RESULTS: Single-cell profiling identified 14 major cell subsets of cancer, immune, and stromal cells. Trajectory analysis unveiled an interesting link between cancer cell differentiation and pathological response to NAT. ESCC tumors enriched with less differentiated cancer cells exhibited a potentially favorable pathological response to NAT, while tumors enriched with clusters of more differentiated cancer cells may resist treatment. Deconvolution of transcriptomes in pre-treatment tumors identified gene signatures in response to NAT contributed by specific immune cell populations. Upregulated genes associated with better pathological responses in CD8 + effector T cells primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, and negative regulation of the T cell apoptotic process, whereas downregulated genes were dominated by those in the immune response-activating cell surface receptor signaling pathway. Natural killer cells in pre-treatment tumors from pCR patients showed a similar upregulation of gene expression in response to IFNγ but a downregulation of genes in the neutrophil-mediated immunity pathways. A decreased cellular contexture of regulatory T cells in ESCC TME indicated a potentially favorable pathological response to NAT. Cell-cell communication analysis revealed extensive interactions between CCL5 and its receptor CCR5 in various immune cells of baseline pCR tumors. Immune checkpoint interaction pairs, including CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, and TNFSF4-TNFRSF4, might serve as additional therapeutic targets for ICI therapy in ESCC. CONCLUSIONS: This pioneering study unveiled an intriguing association between cancer cell differentiation and pathological response in esophageal cancer patients, revealing distinct subgroups of tumors for which neoadjuvant chemo-immunotherapy might be effective. We also delineated the immune landscape of ESCC tumors in the context of clinical response to NAT, which provides clinical insights for better understanding how patients respond to the treatment and further identifying novel therapeutic targets for ESCC patients in the future.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/terapia , Terapia Neoadjuvante , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Imunoterapia , Terapia Combinada , Microambiente Tumoral , Ligante OX40RESUMO
BACKGROUND: Previous studies usually focused on the separate association of metabolism or genetic factors with lung cancer risk and have largely ignored their combined effect. We aimed to examine the associations between serum lipid levels, genetic risk, and lung cancer risk. METHODS: A total of 426,524 participants of the UK Biobank were included. The Cox proportional hazards models and restricted cubic splines were performed to assess the association between serum lipid and lung cancer risk. Polygenic risk score (PRS) was constructed to assess its joint effect and interaction with serum lipid on lung cancer risk. RESULTS: Higher level of apolipoprotein A was significantly correlated with lower lung cancer risk. An inverse-J-shaped relationship between high-density lipoprotein (HDL) and incident lung cancer was found. Individuals with low total cholesterol, HDL, low-density lipoprotein (LDL), apolipoprotein A, and apolipoprotein B, combined with high PRS, showed significantly elevated lung cancer risks. Compared to those with low PRS and low triglycerides, participants with high PRS and elevated triglyceride levels had a notably higher risk. The interaction effect of high PRS and low LDL [relative excess risk due to the interaction (RERI): 0.25, 95% confidence interval, 0.04-0.46], as well as the interaction effect of high PRS and low apolipoprotein B (RERI: 0.28, 95% confidence interval, 0.07-0.48), were both greater than the sum of their individual effects on lung cancer risk. CONCLUSIONS: Serum lipids were associated with lung cancer risk. LDL or apolipoprotein B interacting with genetic risk may affect lung cancer risk. IMPACT: Our findings emphasize the need for individuals with heightened genetic risk should pay more attention to their lipid levels to reduce lung cancer risk.
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Lipídeos , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/epidemiologia , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Incidência , Lipídeos/sangue , Fatores de Risco , Predisposição Genética para Doença , Idoso , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. METHODS: The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. RESULTS: Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). CONCLUSIONS: This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.
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Diabetes Mellitus , Retinopatia Diabética , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Estudos Transversais , Inquéritos Nutricionais , Retinopatia Diabética/genética , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Fatores de Risco , Estudo de Associação Genômica AmplaRESUMO
A novel and efficient regioselective annulation of phosphinyl allenes with 2-bromophenol or 1-bromo-2-naphthol is achieved by palladium catalysis. The divergent pathway delivers structurally diverse polyarylfurans and 2H-chromene skeletons via two different Heck-type annulations. This protocol represents regioselectivity-tunable transformation of allenes into functionalized O-containing heterocycles with excellent group compatibility.
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The survival outcomes of patients with chest wall sarcomas (CWS) were evaluated after receiving wide excision and chest wall reconstruction by using three-dimensional printed (3DP) implants. The survival outcomes evaluating the effect of 3DP implants for chest wall reconstruction is lacking. Here, forty-nine patients with CWS underwent radical wide excision and chest wall reconstruction using 3DP implants. The surgical data and long-term survival outcomes were collected and analyzed. With a median follow-up of 36 months, the disease-free survival (DFS) and overall survival (OS) were 31.7% and 58.5%, respectively. In addition, the 3-year DFS and OS can be significantly differentiated using the classification criteria of tumor grade, tumor size tumor area. Hence, wide excision and chest wall reconstruction using three-dimensional printed implants are a safe and effective treatment for chest wall sarcoma. The novel classification criteria of tumor size and area have the potential to predict the prognosis of CWS.
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BACKGROUND: The significance of long non-coding RNAs (lncRNAs) as pivotal mediators of histone acetylation and their influential role in predicting the prognosis of lung adenocarcinoma (LUAD) has been increasingly recognized. However, there remains uncertainty regarding the potential utility of acetylation-related lncRNAs (ARLs) in prognosticating the overall survival (OS) of LUAD specimens. METHODS: The RNA-Seq and clinical information were downloaded from The Cancer Genome Atlas (TCGA). Through the differential analysis, weighted correlation network analysis (WGCNA), Pearson correlation test and univariate Cox regression, we found out the prognosis associated ARLs and divided LUAD specimens into two molecular subclasses. The ARLs were employed to construct a unique signature through the implementation of the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. Subsequently, the predictive performance was evaluated using ROC analysis and Kaplan-Meier survival curve analysis. Finally, ARL expression in LUAD was confirmed by quantitative real-time PCR (qRT-PCR). RESULTS: We triumphantly built a ARLs prognostic model with excellent predictive accuracy for LUAD. Univariate and multivariate Cox analysis illustrated that risk model served as an independent predictor for influencing the overall survival OS of LUAD. Furthermore, a nomogram exhibited strong prognostic validity. Additionally, variations were observed among subgroups in the field of immunity, biological functions, drug sensitivity and gene mutations within the field. CONCLUSIONS: Nine ARLs were identified as promising indicators of personalized prognosis and drug selection for people suffering with LUAD.
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Adenocarcinoma , RNA Longo não Codificante , Humanos , Acetilação , RNA Longo não Codificante/genética , Algoritmos , PulmãoRESUMO
The tumor microenvironment (TME) is a heterogeneous ecosystem containing cancer cells, immune cells, stromal cells, cytokines, and chemokines which together govern tumor progression and response to immunotherapies. Methyltransferase-like 3 (METTL3), a core catalytic subunit for RNA N6-methyladenosine (m6A) modification, plays a crucial role in regulating various physiological and pathological processes. Whether and how METTL3 regulates the TME and anti-tumor immunity in non-small-cell lung cancer (NSCLC) remain poorly understood. Here, we report that METTL3 elevates expression of pro-tumorigenic chemokines including CXCL1, CXCL5, and CCL20, and destabilizes PD-L1 mRNA in an m6A-dependent manner, thereby shaping a non-inflamed TME. Thus, inhibiting METTL3 reprograms a more inflamed TME that renders anti-PD-1 therapy more effective in several murine lung tumor models. Clinically, NSCLC patients who exhibit low-METTL3 expression have a better prognosis when receiving anti-PD-1 therapy. Collectively, our study highlights targeting METTL3 as a promising strategy to improve immunotherapy in NSCLC patients.
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BACKGROUND: No studies to date have focused on the timing of pulmonary resection in patients with previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present study, the authors analyzed the surgical outcomes and evaluated the optimal time point of pulmonary resection surgery following SARS-CoV-2 infection. MATERIALS AND METHODS: In this multicenter retrospective cohort study, patients were divided into different groups according to the time interval between SARS-CoV-2 diagnosis and pulmonary resection. The primary outcome measure was postoperative complications within 30 days after surgery, which was investigated to determine the optimal time point of pulmonary resection. Logistic regression models were used to calculate the risk factors for postoperative complications. RESULTS: In total, 400 patients were enrolled, and the postoperative pathologic examination of 322 (80.5%) patients showed lung cancer. As the interval between SARS-CoV-2 infection and pulmonary resection increased, the incidence of complications gradually decreased in each group. The incidence of grade ≥II complications was higher in the ≤2-week and 2-week to 4-week groups than in the 4-week to 6-week, 6-week to 8-week and >8-week groups [3 (21.4%), 17 (20.2%), 10 (10.6%), 13 (7.9%), and 3 (6.5%), respectively] ( P <0.05). Multiclassification regression analysis showed that the risk of grade ≥II complications in the ≤2-week and 2-week to 4-week groups was significantly higher than that in the >8-week group [odds ratio (95% CI), 3.937 (1.072-14.459), P =0.039 and 3.069 (1.232-6.863), P =0.015]. The logistic regression analysis suggested that underlying disease, persistent SARS-CoV-2 symptoms, and surgical timing (≤4 weeks) were independent risk factors for complications of pulmonary resection after SARS-CoV-2 infection. CONCLUSION: Pulmonary resection should be delayed for at least 4 weeks following SARS-CoV-2 infection to reduce the risk of postoperative complications.
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COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , Teste para COVID-19 , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
IMPORTANCE: In this study, we have found that the existence of Smyd3 promoted the replication of SCRV. Additionally, we report that Smyd3 negatively regulates the NF-κB and IRF3 signaling pathway by facilitating the degradation of TAK1 in fish. Our findings suggest that Smyd3 interacts with TAK1. Further investigations have revealed that Smyd3 specifically mediates K48-linked ubiquitination of TAK1 and enhances TAK1 degradation, resulting in a significant inhibition of the NF-κB and IRF3 signaling pathway. These results not only contribute to the advancement of fish anti-viral immunity but also provide new evidence for understanding the mechanism of TAK1 in mammals.
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Doenças dos Peixes , Fator Regulador 3 de Interferon , MAP Quinase Quinase Quinases , NF-kappa B , Transdução de Sinais , Animais , MAP Quinase Quinase Quinases/metabolismo , NF-kappa B/metabolismo , Ubiquitinação , Doenças dos Peixes/virologia , Peixes , Rhabdoviridae , Fator Regulador 3 de Interferon/metabolismoRESUMO
Background: Evidence for the effects of immunotherapy in non-small cell lung cancer (NSCLC) patients with distant organ metastasis is insufficient, and the predictive efficacy of established markers in tissue and blood is elusive. Our study aimed to determine the prognostic factors and develop a survival prognosis model for these patients. Methods: A total of 100 advanced NSCLC patients with distant organ metastases, who received single or combination immune checkpoint inhibitors (ICIs) in Xijing Hospital between June 2018 and June 2021, were enrolled for retrospective analysis. The major clinicopathological parameters were collected, and associated survival outcomes were followed up by telephone or inpatient follow-up for nearly 3 years to assess prognoses. The survival prognosis model was established based on univariate and multivariate Cox regression analyses to determine the candidate prognostic factors. Results: From the start of immunotherapy to the last follow-up, 77 patients progressed and 42 patients died, with a median follow-up of 18 months [95% confidence interval (CI): 15-19.9]. The median progression-free survival (PFS) and overall survival (OS) were 8 months (95% CI: 5.6-10.4) and 21 months (95% CI: 8.9-33.1), respectively. Multivariate Cox proportional hazards analysis showed Eastern Cooperative Oncology Group performance status (ECOG PS), body mass index (BMI), age-adjusted Charlson comorbidity index (ACCI), lactate dehydrogenase (LDH), and absolute neutrophil count (ANC) were correlated significantly with OS. Based on these five predictive factors, a nomogram and corresponding dynamic web page were constructed with a concordance index (C-index) of 0.81 and a 95% CI of 0.778-0.842. Additionally, the calibration plot and time-receiver operating characteristic (ROC) curve validated the precision of the model at 6-, 12-, and 18-month area under the curves (AUCs) reached 0.934, 0.829, and 0.846, respectively. According to the critical point of the model, patients were further divided into a high-risk total point score (TPS) >258, middle-risk (204< TPS ≤258), and low-risk group (TPS ≤204), and significant OS differences were observed among the three subgroups (median OS: 4.8 vs. 13.0 vs. 32.9 months). Conclusions: A feasible and practical model based on clinical characteristics has been developed to predict the prognosis of NSCLC patients with distant organ metastasis undergoing immunotherapy.
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IMPORTANCE: The expression of circVPS13D was upregulated with SCRV invasion, which proved that circVPS13D was involved in the regulation of the antiviral immune response. Our study revealed that the existence of circVPS13D promoted the replication of SCRV. Functionally, circVPS13D negatively regulates the antiviral responses of fish. Mechanistically, we confirmed that circVPS13D inhibited RLRs antiviral signaling pathway via the encoded protein VPS13D-170aa by targeting MAVS. Our study provided novel insights into the roles of protein-coding circRNAs and supported VPS13D-170aa as a negative regulator in the antiviral immune responses of teleost fish.
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Proteínas de Peixes , RNA Circular , Proteínas de Transporte Vesicular , Viroses , Animais , Proteínas de Peixes/genética , Peixes/imunologia , Peixes/virologia , Imunidade Inata , RNA Circular/metabolismo , Transdução de Sinais , Proteínas de Transporte Vesicular/genética , Viroses/imunologia , Viroses/metabolismo , Viroses/veterinária , Viroses/virologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/metabolismo , Doenças dos Peixes/virologiaRESUMO
PURPOSE: To assess the effectiveness and safety of combining intravitreal endothelial growth factor inhibitor (anti-VEGF) and ocular corticosteroids for diabetic macular edema (DME). METHODS: Articles concentrating on the efficacy and safety of combining anti-VEGF and ocular corticosteroids therapy for DME versus anti-VEGF monotherapy was screened systematically. Meta-analysis was conducted on the basis of a protocol registered in the PROSPERO (CRD42023408338) and performed on the extracted continuous variables and dichotomous variables. The outcome was expressed as weighted mean difference (MD) and risk ratio (RR). RESULTS: Add up to 21 studies including 1468 eyes were enrolled in this study. The MD for best-corrected visual acuity (BCVA) improvement at 1/3/6/12-month between the combination therapy group and monotherapy group were 2.56 (95% CI [0.43, 4.70]), 2.46 (95% CI [-0.40, 5.32]), - 1.76 (95% CI [-3.18, -0.34]), - 1.94 (95% CI [-3.87, 0.00]), respectively. The MD for central retinal thickness (CMT) reduction at 1/3/6/12-month between two groups were - 66.27 (95% CI [-101.08, -31.47]), - 33.62 (95% CI [-57.55, -9.70]), - 4.54 (95% CI [-16.84, 7.76]), - 26.67 (95% CI [-41.52, -11.82]), respectively. Additionally, the combination group had higher relative risk of high intraocular pressure and cataract progression events. CONCLUSIONS: Anti-VEGF combined with ocular corticosteroids had a significant advantage over anti-VEGF monotherapy within 3 months of DME treatment, which reached the maximum with increasing anti-VEGF injection times to 3. However, with the prolongation of the treatment cycle, the effect of combined therapy after 6 months was no better than monotherapy, and the side effects of combined therapy were more severe.
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Importance: The benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) remains unknown. Objective: To assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC. Design, Setting, and Participants: In this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022. Interventions: Patients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2, and platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m2]) or chemotherapy alone, followed by surgery after 4 to 6 weeks. Main Outcomes and Measures: The primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis. Results: Ninety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported. Conclusions and Relevance: This randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04338620.
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OBJECTIVES: To estimate the prevalence of influenza coinfection in COVID-19 patients and investigate its association with severe clinical outcomes. METHODS: We systematically searched the Web of Science, PubMed, Scopus, Embase, The Cochrane Library, and CNKI for studies published between January 01, 2020, and May 31, 2023. Meta-analysis was performed to estimate the pooled prevalence of coinfection and the impact on clinical outcomes. Systematic review registered in PROSPERO (CRD42023423113). RESULTS: A total of 95 studies involving 62,107 COVID-19 patients were included. The pooled prevalence of coinfection with influenza virus was 2.45% (95% confidence interval [CI]: 1.67-3.58%), with a high proportion of influenza A. Compared with mono-infected patients (COVID-19 only), the odds ratio (OR) for severe outcomes (including intensive care unit admission [OR = 2.20, 95% CI: 1.68-2.87, P < 0.001], mechanical ventilation support [OR = 2.73, 95% CI: 1.46-5.10, P = 0.002], and mortality [OR = 2.92, 95% CI: 1.16-7.30, P = 0.022]) was significantly higher among patients coinfected influenza A. CONCLUSION: Although the prevalence of coinfection is low, coinfected patients are at higher risk of severe outcomes. Enhanced identification of both viruses, as well as individualized treatment protocols for coinfection, are recommended to reduce the occurrence of serious disease outcomes in the future.
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COVID-19 , Coinfecção , Influenza Humana , Humanos , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/terapia , Influenza Humana/complicações , Influenza Humana/epidemiologia , Influenza Humana/terapia , Coinfecção/epidemiologia , PrevalênciaRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a high prevalence and poor prognosis. It is an urgent problem to deeply understand the molecular mechanism of ESCC and develop effective diagnostic and prognostic methods. METHODS: Using tumor tissue and corresponding paracancerous samples from 141 resected ESCC patients, we assessed Jumonji domain-containing protein 6 (JMJD6) expression using Immunohistochemical (IHC) staining. Kaplan-Meier survival analysis and univariate or multivariate analysis were used to investigate the relationship between JMJD6 expression and clinicopathological features. The expression status and prognostic value of JMJD6 were analyzed by bioinformatics and enrichment analysis. RESULTS: The expression of JMJD6 in ESCC samples was higher than that in the corresponding paracancerous samples, and high expression of JMJD6 was positively associated with poor prognosis of ESCC patients. In addition, bioinformatics analysis of the expression and prognosis of JMJD6 in a variety of tumors showed that high expression of JMJD6 was significantly associated with poor overall survival (OS) in ESCC patients. Enrichment analysis indicated that the high expression of genes similar to JMJD6, such as Conserved oligomeric Golgi 1(COG1), Major facilitator superfamily domain 11 (MFSD11) and Death Effector Domain Containing 2 (DEDD2), was associated with poor prognosis of ESCC, suggesting that JMJD6 might be involved in the occurrence and prognosis of ESCC. CONCLUSION: Our study found that JMJD6 expression was significantly increased in ESCC patients and positively correlated with prognosis, indicating that targeting JMJD6 might be an attractive prognostic biomarker and provides a potential treatment strategy for ESCC. TRIAL REGISTRATION: The study was approved by Tangdu Hospital ethics committee (No. TDLL-202110-02).
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Oncogenes , Biologia Computacional , Complexo de Golgi , Histona Desmetilases com o Domínio JumonjiRESUMO
BACKGROUND: This study aimed to investigate the prospects of using chemotherapy in combination with atezolizumab in the neoadjuvant or conversion treatment of small cell lung cancer (SCLC). METHODS: Prior to surgery, untreated patients with limited-stage SCLC received three cycles of neoadjuvant or conversion atezolizumab combined with chemotherapy of etoposide and platinum. The primary endpoint of the trial was pathological complete response (pCR) in the per-protocol (PP) cohort. In addition, safety was assessed based on treatment-related adverse events (AEs) and postoperative complications. RESULTS: Overall, 13 of 17 patients (including 14 males and 3 females) underwent surgery. In the PP cohort, pCR and major pathological response were observed in 8 (8/13, 61.5%) and 12 (12/13, 92.3%) patients, respectively. According to the intention-to-treat (ITT) analysis, the pCR and major pathological response in the ITT cohort were 47.1% (8/17) and 70.6% (12/17), respectively. In addition, an overall response rate of 100% was recorded in the PP cohort. Moreover, 15 (15/17, 88.2%) patients and 1 (1/17, 5.9%) in the ITT cohort attained partial remission (PR), and complete remission, respectively, with an overall response rate of 94.1%. The median overall survival of the patients of pCR and the median event-free survival of the patients on surgery had not achieved. However, the median overall survival of the patients of non-pCR was 18.2 months and the median event-free survival of the nonsurgical patients was 9.5 months. During the neoadjuvant treatment, the incidence of grade 3 or higher AEs was 58.8% (10/17). Additionally, three patients (17.6%) developed immune-related adverse event (grades 1-2). CONCLUSION: In patients with SCLC, neoadjuvant or conversion atezolizumab combined with chemotherapy significantly improved pCR with manageable AEs. Therefore, this regimen may be considered a safe and effective treatment for SCLC.