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Background: Many observational studies have investigated the link between the gut microbiota and Alzheimer's disease (AD), but the causality remains uncertain. Objective: This study aimed to evaluate the causal impact of gut microbiota on AD. Methods: A two-sample Mendelian randomization (MR) study was conducted employing summary data. Summary statistics for AD were from the latest genome-wide association study (cases and proxy cases: 85,934; controls: 401,577). Summary data for gut microbiota were acquired from MiBioGen consortium. Causal effect estimations primarily relied on the inverse variance weighting method along with the sensitivity analyses for testing for pleiotropy and heterogeneity. Additionally, reverse MR analyses were performed to examine potential reverse causality. Results: Seven gut microbiota were identified as associated with AD risk. Order Selenomonadales (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.03-1.24, pâ=â0.01), Family Pasteurellaceae (OR 1.07, 95% CI 1.01-1.13, pâ=â0.01), and Genus Methanobrevibacter (OR 1.07, 95% CI 1.00-1.13, pâ=â0.04) were correlated with an elevated likelihood of AD, while Class Mollicutes (OR 0.87, 95% CI 0.79-0.95, pâ=â0.00), Genus Ruminiclostridium9 (OR 0.87, 95% CI 0.78-0.97, pâ=â0.01), Genus Clostridiuminnocuumgroup (OR 0.94, 95% CI 0.89-0.99, pâ=â0.03), and Genus Eggerthella (OR 0.94, 95% CI 0.89-1.00, pâ=â0.04) exerted beneficial impact in mitigating AD. No statistically significant reverse causality was found between AD and each of these seven specific gut microbiota species. Conclusions: This study unveiled a causal link between certain gut microbiota and AD, offering new insights for advancing clinical treatments.
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In the deep-ultraviolet (DUV) region, nonlinear optical (NLO) crystals must meet stringent requirements, including a large optical band gap and sufficient second harmonic generation (SHG) response. Typically, these criteria are fulfilled by borates, carbonates and nitrates containing π-conjugated groups. In contrast, sulfates and phosphates, with polarizabilities significantly smaller than those of π-conjugated groups, struggle to achieve similar performance. Here, we present the discovery of Mg2PO4Cl, a magnesium-based phosphate, identified from over 10,000 phosphates based on a polar-axial-symmetry screening strategy, which exhibits the highest SHG response (5.2 × KH2PO4 (KDP)) with phase-matching ability among non-π-conjugated DUV transparent NLO crystals. This compound belongs to the Pna21 space group, with [PO4] units consistently aligned along the 21 screw axis and glide planes throughout its crystal structure. Theoretical calculations attribute its remarkable SHG effect to the orderly arrangement of heteroanionic [MgO5Cl] and [MgO4Cl2] polyhedra alongside isolated [PO4] tetrahedra, supported by Berry phase analysis. Furthermore, a crystallographic structure analysis of phosphates and sulfates with significant SHG effects validates the effectiveness of our screening strategy. These findings offer valuable insights into the origins of NLO effects in non-π-conjugated compounds from both a material design and structural chemistry perspective, inspiring future efforts to revitalize DUV phosphates.
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Platensilin, platensimycin, and platencin are potent inhibitors of ß-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC80 = 0.0625 µg/mL) against S. aureus compared to platensimycin.
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Adamantano , Aminobenzoatos , Aminofenóis , Anilidas , Compostos Policíclicos , Aminofenóis/química , Aminofenóis/farmacologia , Aminofenóis/síntese química , Compostos Policíclicos/química , Compostos Policíclicos/farmacologia , Compostos Policíclicos/síntese química , Adamantano/química , Adamantano/farmacologia , Adamantano/síntese química , Adamantano/análogos & derivados , Anilidas/farmacologia , Anilidas/química , Anilidas/síntese química , Aminobenzoatos/farmacologia , Aminobenzoatos/química , Aminobenzoatos/síntese química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Staphylococcus aureus/efeitos dos fármacos , Estrutura Molecular , Reação de Cicloadição , Testes de Sensibilidade Microbiana , Estereoisomerismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/químicaRESUMO
Hypersecretion of airway mucus caused by goblet cell metaplasia is a characteristic of chronic pulmonary inflammatory diseases including asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD). Goblet cells originate from airway progenitor club cells. However, the molecular mechanisms and features of goblet cell metaplasia in lung disease are poorly understood. Herein, public single-cell RNA sequencing datasets of human lungs were reanalyzed to explore the transitional phase as club cells differentiate into goblet cells in asthma, CF, and COPD. We found that changes in club and goblet cells during pathogenesis and cellular transition were associated with signalling pathways related to immune response, oxidative stress, and apoptosis. Moreover, other key drivers of goblet cell specification appeared to be pathologically specific, with interleukin (IL)-13 and hypoxia inducible factor 1 (HIF-1)-induced genetic changes in asthma, cystic fibrosis transmembrane conductance regulator (CFTR) mutation being present in CF, and interactions with CD8+ T cells, mitophagy, and mitochondria-induced apoptosis in COPD. In conclusion, this study revealed the similarities and differences in goblet cell metaplasia in asthma, CF, and COPD at the transcriptome level, thereby providing insights into possible novel therapeutic approaches for these diseases.
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The Lys-Asp-Glu-Leu receptor (KDELR) family genes play critical roles in a variety of biological processes in different tumors. Our study aimed to provide a comprehensive analysis of the potential roles of KDELRs in lung adenocarcinoma (LUAD). Utilizing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, as well as clinical samples, we conducted a series of analyses and validations using R software tools and various online resources. The results showed that KDELR family genes and proteins were highly expressed and associated with a poor prognosis of LUAD. Promoter hypomethylation and the competing endogenous RNA (ceRNA) network of PCAT6/hsa-miR-326/KDELR1 might be potential causes of aberrant KDELR1 overexpression in LUAD. Three key Transcription factors (TFs) (SPI1, EP300, and MAZ) and a TFs-miRNAs-KDELRs network (involving 11 TFs) might be involved in modulating KDELRs expression abnormalities. Gene Set Enrichment Analysis (GSEA) indicated enrichment of genes highly expressing KDELR1, KDELR2, and KDELR3 in MTORC1_SIGNALING, P53_PATHWAY, and ANGIOGENESIS. Negative correlations between KDELRs expression and CD8 + T cell infiltration, as well as CTLA-4 expression. Our multiple analyses suggested that the KDELRs are important signaling molecules in LUAD. These results provided novel insights for developing prognostic markers and novel therapies of LUAD.
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Adenocarcinoma de Pulmão , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Biomarcadores Tumorais/genética , Redes Reguladoras de Genes , Metilação de DNA , Perfilação da Expressão Gênica , MicroRNAs/genéticaRESUMO
We present a space-angle dual multiplexing holographic recording system for realizing single-exposure multi-wavelength optical diffraction tomographic (ODT) imaging. This system is achieved by combining the principle of single-exposure multi-wavelength holographic imaging technique based on angle-division multiplexing with the principle of single-exposure ODT imaging technique based on microlens array multi-angle illuminations and space-division multiplexing. Compared with the existing multi-wavelength ODT imaging methods, it enables the holographic recording of all the diffraction tomography information of a measured specimen at multiple illumination wavelengths in a single camera exposure without any scan mechanism. Using our proposed data processing method, the multi-wavelength three-dimensional (3D) refractive index tomograms of a specimen can be eventually reconstructed from single recorded multiplexing hologram. Experimental results of a static polystyrene bead and a living C. elegans worm demonstrate the feasibility of this system.
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T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN. From this pool, various bispecific antibodies (BsAbs) were assembled. Notably, MSLN490 with its IgG-[L]-scFv structure displayed remarkable anti-tumor activity against MSLN-expressing tumors (EC50: 0.16 pM in HT-29-hMSLN cells). Furthermore, MSLN490 remained effective even in the presence of non-membrane-anchored MSLN (soluble MSLN). Moreover, the anti-tumor activity of MSLN490 was enhanced when combined with either Atezolizumab or TAA × CD28 BsAbs. Notably, a synergistic effect was observed between MSLN490 and paclitaxel, as paclitaxel disrupted the immunosuppressive microenvironment within solid tumors, enhancing immune cells infiltration and improved anti-tumor efficacy. Overall, MSLN490 exhibits robust anti-tumor activity, resilience to soluble MSLN interference, and enhanced anti-tumor effects when combined with other therapies, offering a promising future for the treatment of a variety of solid tumors. This study provides a strong foundation for further exploration of MSLN490's clinical potential.
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BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) with portal-superior mesenteric vein (PV/SMV) resection and reconstruction is increasingly performed. We aimed to introduce a safe and effective surgical approach and share our clinical experience with LPD with PV/SMV resection and reconstruction. METHODS: We reviewed data for the patients undergoing LPD and open pancreaticoduodenectomy (OPD) combined with PV/SMV resection and reconstruction at the First Hospital of Jilin University between April 2021 and May 2023. The inferior-posterior "superior mesenteric artery-first" approach was used. We compared the preoperative, intraoperative, and postoperative clinicopathological data of the 2 groups to conduct a comprehensive evaluation of LPD with major vascular resection. RESULTS: A cohort of 37 patients with periampullary and pancreatic tumors underwent pancreaticoduodenectomy (PD) with major vascular resection and reconstruction, consisting of 21 LPDs and 16 OPDs. The LPD group had a longer operation time (322 vs. 235 min, P =0.039), reduced intraoperative bleeding (152 vs. 325 mL, P =0.026), and lower intraoperative blood transfusion rates (19.0% vs. 50.0%, P =0.046) compared with the OPD group. The LPD group had significantly shorter operation times in end-to-end anastomosis (26 vs. 15 min, P =0.001) and artificial grafts vascular reconstruction (44 vs. 22 min, P =0.000) compared with the OPD group. There was no significant difference in the rate of R0 resection (100% vs. 87.5%, P =0.096). The length of hospital stay and ICU stay did not show significant differences between the 2 groups (15 vs. 18 d, P =0.636 and 2.5 vs. 4.5 d, P =0.726, respectively). However, the postoperative hospital stay in the LPD group was notably shorter compared with the OPD group (11 vs. 16 d, P =0.007). Postoperative complication rates, including postoperative pancreatic fistula (POPF) Grade A/B, biliary leakage, and delayed gastric emptying (DGE), were similar between the two groups (38.1% vs. 43.8%, P =0.729). In addition, 1 patient in each group developed thrombosis, with vascular patency improving after anticoagulation treatment. CONCLUSION: LPD combined with PV/SMV resection and reconstruction can be easily and safely performed using the inferior-posterior "superior mesenteric artery-first" approach in cases of venous invasion. Further studies are required to evaluate the procedure's long-term outcomes.
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Laparoscopia , Artéria Mesentérica Superior , Veias Mesentéricas , Duração da Cirurgia , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Veia Porta , Humanos , Pancreaticoduodenectomia/métodos , Veias Mesentéricas/cirurgia , Masculino , Feminino , Laparoscopia/métodos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Veia Porta/cirurgia , Artéria Mesentérica Superior/cirurgia , Estudos Retrospectivos , Idoso , Tempo de Internação , Resultado do Tratamento , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Perda Sanguínea Cirúrgica/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Procedimentos Cirúrgicos Vasculares/métodos , Procedimentos de Cirurgia Plástica/métodosRESUMO
Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2.89, displayed a high selectivity against the target JIMT-1 breast cancer cells in vitro, as well as a slightly higher level of internalization than HER2- or HER3-monospecific ADCs. More importantly, the bispecific ADC potently inhibited the viability of MCF7, JIMT-1, BT474, BxPC-3 and SKOV-3 cancer cells in vitro. In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs.
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Anticorpos Biespecíficos , Neoplasias da Mama , Imunoconjugados , Receptor ErbB-2 , Receptor ErbB-3 , Humanos , Animais , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Feminino , Receptor ErbB-3/antagonistas & inibidores , Receptor ErbB-3/metabolismo , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Imunoconjugados/química , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Linhagem Celular Tumoral , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
BACKGROUND/AIMS: The purpose of this study is to screen the feature genes related to gut microflora and explore the role of the genes in predicting the prognosis of patients with gastric cancer. MATERIALS AND METHODS: We downloaded the gene profile of gastric cancer from the University of California Santa Cruz, the gut microflora related to gastric cancer from The Cancer Microbiome Atlas. The GSE62254 dataset was downloaded from National Center for Biotechnology Information Gene Expression Omnibus as a validation dataset. A correlation network between differentially expressed genes and gut microflora was constructed using Cytoscape. The optimized prognostic differentially expressed genes were identified through least absolute shrinkage and selection operator (LASSO) algorithm and univariate Cox regression analysis. The risk score model was established and then measured via Kaplan-Meier and area under the curve. Finally, the nomogram model was constructed according to the independent clinical factors, which was evaluated using C-index. RESULTS: A total of 754 differentially expressed genes and 8 gut microflora were screened, based on which we successfully constructed the correlation network. We obtained 9 optimized prognostic differentially expressed genes, including HSD17B3, GNG7, CHAD, ARHGAP8, NOX1, YY2, GOLGA8A, DNASE1L3, and ABCA8. Moreover, Kaplan-Meier curves indicated the risk score model correctly predicted the prognosis of gastric cancer in both University of California Santa Cruz and GSE62254 dataset (area under the curve >0.8; area under the curve >0.7). Finally, we constructed the nomogram, in which the C index of 1, 3, and 5 years was 0.824, 0.772, and 0.735 representing that the nomogram was consistent with the actual situation. CONCLUSIONS: These results indicate the 9 differentially expressed genes related to gut microflora might predict the survival time of patients with gastric cancer. Both risk signature and nomogram could effectively predict the prognosis for patients with gastric cancer.
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Microbioma Gastrointestinal , Neoplasias Gástricas , Humanos , Prognóstico , Microbioma Gastrointestinal/genética , Neoplasias Gástricas/genética , Nomogramas , Algoritmos , Fatores de Transcrição , Proteínas Ativadoras de GTPaseRESUMO
According to statistics, the incidence of liver cancer is increasing yearly, and effective treatment of liver cancer is imminent. For early liver cancer, resection surgery is currently the most effective treatment. However, resection does not treat the disease in advanced patients, so finding a method with a better prognosis is necessary. In recent years, ferroptosis and cuproptosis have been gradually defined, and related studies have proved that they show excellent results in the therapy of liver cancer. Cuproptosis is a new form of cell death, and the use of cuproptosis combined with ferroptosis to inhibit the production of hepatocellular carcinoma cells has good development prospects and is worthy of in-depth discussion by researchers. In this review, we summarize the research progress on cuproptosis combined with ferroptosis in treating liver cancer, analyze the value of cuproptosis and ferroptosis in the immune of liver cancer, and propose potential pathways in oncotherapy with the combination of cuproptosis and ferroptosis, which can provide background knowledge for subsequent related research.
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BACKGROUND: The association of atherosclerotic cardiovascular disease (ASCVD) with cancer occurrence is not well examined, and the impact of common risk factors on the risk of cancer in ASCVD patients is not known. This study aimed to explore the effect and possible causes of ASCVD on cancer risk through a cohort study. METHODS: A total of 14,665 age- and sex-matched pairs of participants were recruited from the Kailuan cohort (ASCVD vs non-ASCVD). A competing risk model was used to calculate the risk of cancer after ASCVD. RESULTS: A total of 1124 cancers occurred after 5.80 (3.05-9.44) years of follow-up. The ASCVD group had a reduced risk of cancer (hazard ratio 0.74; 95% confidence interval, 0.65-0.85). Also, the risk of cancer in the digestive system, respiratory system, urinary system, and reproductive system was reduced by 17%, 16%, 14%, and 52%, respectively. According to the status of systolic and diastolic blood pressure, fasting blood glucose, high-sensitivity C-reactive protein and body mass index after ASCVD, the risk of overall cancer and digestive system cancer decreased with the increase in the number of ideal indicators (P for trend < .01). With the increase of follow-up time, the risk of cancer and the 5 site-specific cancers gradually decreased. CONCLUSIONS: Cancer risk can be reduced by controlling for common risk factors after ASCVD event. This risk reduction is site-specific-, time-, and the number of ideal indicator-dependent.
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Aterosclerose , Doenças Cardiovasculares , Neoplasias , Humanos , Estudos de Coortes , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Medição de Risco , Fatores de Risco , Aterosclerose/epidemiologia , Aterosclerose/prevenção & controle , Neoplasias/epidemiologia , Neoplasias/prevenção & controleRESUMO
BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. METHODS: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis. RESULTS: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. CONCLUSIONS: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. TRIAL REGISTRATION: ChiCTR2200057685 was registered on March 15th, 2022.
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Treinamento Resistido , Humanos , Suplementos Nutricionais , Unidades de Terapia Intensiva , Força Muscular , Músculo Esquelético/fisiologia , Alta do Paciente , Qualidade de Vida , Método Simples-Cego , AdultoRESUMO
Purpose: Given the limited research on health care utilization among transgender women in China, we described the use of primary health care and gender-affirming health care, and the associations between utilization of gender-affirming health care and depression and sexual risk behaviors. Methods: We conducted a cross-sectional survey in 2017 among a purposive sample of transgender women in Shanghai, China (N=199). We examined correlates of health care utilization and its association with depression and sexual risk behaviors with Chi-square (χ2), Fisher's exact tests, and analysis of variance. Results: The majority of the sample (78.5%) only had physician appointments when having an illness, while about one-fifth of the sample had physician appointments for yearly checkups. Nineteen out of 199 participants (9.5%) received gender-affirming surgery, among which only five used hormone therapy prescribed by a doctor (26.3%). Receiving some form of gender-affirming surgery was associated with higher depression scores [Welch's F(2, 12.22)=4.16, p=0.04], engagement in sex work (p=0.001), having 7 or more male sexual partners in the last 30 days (p=0.003), lifetime unprotected sex with a man (p=0.050), and unprotected sex with a main partner (p=0.043). Compared with transgender women who received both breast augmentation and vulvo-vaginoplasty (mean=5.86), those who received breast augmentation only (mean=12.33) scored higher on depression (p=0.04). Conclusions: Access to gender-affirming health care is low among transgender women in this study. The utilization of gender-affirming surgery is associated with depression and sexual risk behaviors. Findings suggest China should establish national guidelines on transgender-related health care and set up more clinics to provide consultation and services for the transgender population in China.
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The exploitation of highly active and stable catalysts for reduction of CO2 and water oxidation is one of the approaches to facilitate scalable and sustainable CO2 reduction potentially at the industrial scale. Herein, a feasible strategy to rationally build an overall CO2 + H2O electrocatalytic reaction device is the preparation and matchup of a high-performance CO2 reduction catalyst and low-cost and highly active oxygen anode catalyst. A heterostructured nanosheet, γ-NiOOH/NiCO3/Ni(HCOO)2, exhibited superior catalytic activity in the oxygen evolution reaction, and was integrated with CoPc/Fe-N-C to build an overall CO2 + H2O cell with a current density of 10 mA cm-2 at a very low cell voltage of 1.97 V, and the faradaic deficiency of CO2 to CO was maintained at greater than 90% at 1.9 V.
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BACKGROUND: Lung adenocarcinoma (LUAD) is a fatal form of lung cancer with a poor prognosis. Coagulation system had been confirmed closely related to tumor progression and the hypercoagulable state encouraged the immune infiltration and development of tumor cells, leading to a poor prognosis in cancer patients. However, the use of the coagulation-related genes (CRGs) for prognosis in LUAD has yet to be determined. In this study, we constructed an immune-related signature (CRRS) and identified a potential coagulation-related biomarker (P2RX1). METHODS: We obtained a total of 209 CRGs based on two coagulation-related KEGG pathways, then developed the CRRS signature by using the TCGA-LUAD RNA-seq data via the procedure of LASSO-Cox regression, stepwise-Cox regression, univariate and multivariate Cox regression. Grouped by the CRRS, Kaplan-Meier survival curves and receiver operating characteristic curves were drawn for the training and validation sets, respectively. In addition, single-sample gene set enrichment analysis was exploited to explore immune infiltration level. Moreover, immunophenotypes and immunotherapy grouped by CRRS were further analyzed. RESULTS: We developed an immune-related signature (CRRS) composed of COL1A2, F2, PLAUR, C4BPA, and P2RX1 in LUAD. CRRS was an independent risk factor for overall survival and displayed stable and powerful performance. Additionally, CRRS possessed distinctly superior accuracy than traditional clinical variables and molecular features. Functional analysis indicated that the differentially high expressed genes in the low-risk group significantly enriched in T cell and B cell receptor signaling pathways. The low-risk group was sensitive to anti-PD-1/PD-L1 immunotherapy and displayed abundant immune infiltration and immune checkpoint gene expression. Finally, we identified an independent prognostic gene P2RX1. Low expression of P2RX1 associated with poor overall survival and decreased immune infiltration. CONCLUSIONS: Our study revealed a significant correlation between CRRS and immune infiltration. CRRS could serve as a promising tool to improve the clinical outcomes for individual LUAD patients.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , ImunoterapiaRESUMO
Objective: To explore the effect of esketamine nasal drops on pain in children after tonsillectomy using low-temperature plasma ablation. Methods: 76 children who underwent tonsillectomy between May 2020 and July 2021, were randomly divided into two groups of 38 cases each. Patients in the control group were treated with conventional medication, while those in the study group were treated with esketamine nasal drops, along with the routine drug treatment. Pain levels of children in the two groups were compared within 1-3 days post-surgery, and the pseudomembrane formation and shedding-off time and recovery time were statistically analyzed. Results: The pain level of children in the study group was lower than that of the control group 1-3 days post-surgery. The pseudomembrane formation and shedding-off time and recovery time in the study group were shorter than in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups, and there were no serious adverse reactions in the two groups (P > 0.05). Conclusion: It is safe to use esketamine nasal drops in children after tonsillectomy using low temperature plasma ablation, and this is found to reduce pain and shorten the recovery time.
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Endoscopic biliary drainage is the main treatment for unresectable malignant hilar biliary obstruction (MHBO). Recurrent biliary obstruction (RBO) often occurs after unilateral metal stent deployment. Endoscopic reintervention can be complex for this problem, especially for drainage of the contralateral bile duct. The stent-in-stent (SIS) method is a possible solution to this problem. Our objective was to evaluate the safety and feasibility of the SIS method for endoscopic reintervention in patients with RBO due to MHBO after unilateral metal stent deployment. Eleven patients with MHBO received endoscopic reintervention using the SIS method to manage RBO after unilateral metal stent deployment. Clinical data, including technical and clinical success, procedure time, adverse events and complications, stent patency, RBO of the revisionary stent, and survival time were recorded. Nine patients (82%) achieved technical success, and all 9 of them also achieved clinical success. The 2 unsuccessful cases received percutaneous transhepatic cholangial drainage. The median procedure time was 73 minutes. The 3 adverse events were post-endoscopic retrograde cholangiopancreatography pancreatitis, cholangitis, and liver abscess. 6 patients (67%) experienced RBO of the revisionary stent, the median time to RBO of the revisionary stent was 95.5 days, the median survival time after reintervention was 111 days, and the median overall survival time was 305.5 days. Endoscopic reintervention after previous unilateral metal stent deployment using the SIS method appears to be safe and technically feasible for MHBO patients who experience RBO.
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Neoplasias dos Ductos Biliares , Colestase , Stents Metálicos Autoexpansíveis , Humanos , Stents Metálicos Autoexpansíveis/efeitos adversos , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Stents/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colestase/cirurgia , Colestase/complicações , Resultado do Tratamento , Estudos RetrospectivosRESUMO
OBJECTIVES: This study aimed to assess the association between longitudinal change in non-high-density lipoprotein cholesterol (non-HDL-C) and subsequent cardiovascular disease (CVD) risk. DESIGN: A retrospective study. SETTING: Data were obtained from the Kailuan Study, a dynamic cohort study initiated in 2006 in Tangshan, China. PARTICIPANTS: The current study included 41 085 participants (mean age 53.9±11.6 years) free of CVD events in or before 2012. The non-HDL-C trajectory was developed according to the repeated measurement during 2006-2012 surveys to predict the CVD risk from 2012 to 2020. PRIMARY OUTCOME MEASURES: CVD events included myocardial infarction and stroke. RESULTS: 3 discrete non-HDL-C trajectories were identified: low-increasing (n=20 038), moderate-increasing (n=17 987) and high-increasing (n=3060). During 8 years of follow-up, 1797 CVD events were documented. Relative to the low-increasing pattern, adjusted HRs were 1.25 (95% CI: 1.13 to 1.38) for the moderate-increasing pattern and 1.46 (95% CI: 1.24 to 1.71) for the high-increasing pattern after adjustment for potential confounders such as age, sex, education background, smoking status, drinking status, physical activity, body mass index, low-density lipoprotein cholesterol, hypertension, diabetes and lipid-lowering medications. CONCLUSIONS: Changes in non-HDL-C were significantly associated with subsequent risk of CVD events, and participants with a high-increasing pattern had a higher CVD risk. Long-term monitoring of non-HDL-C could be useful to improve the prediction of CVD risk. TRIAL REGISTRATION NUMBER: ChiCTR-TNC-1100148.
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Doenças Cardiovasculares , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Estudos Retrospectivos , Fatores de Risco , HDL-Colesterol , ColesterolRESUMO
Excessive nitric oxide (NO) is often observed in the airways of patients with severe asthma. Here, we show that the NO donor diethylamine NONOate impairs the proliferative capacity of mouse club cells and induces club cell apoptosis, cell cycle arrest, and alterations in lipid metabolism. Our data suggest that NO inhibits club cell proliferation via upregulation of Gdpd2 (glycerophosphodiester phosphodiesterase domain containing 2). During ovalbumin (OVA) challenge, apoptotic club cells are observed, but surviving club cells continue to proliferate. OVA exposure induces Gdpd2 expression; Gdpd2 knockout promotes the proliferation of club cells but inhibits goblet cell differentiation. Elimination of airway NO was found to inhibit goblet cell differentiation from club cells during OVA challenge. Our data reveal that excessive NO might be related to airway epithelial damage in severe asthma and suggest that blockade of the NO-Gdpd2 pathway may be beneficial for airway epithelial restoration.