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AIMS: The sympathetic nervous system regulates numerous critical aspects of mitochondrial function in the heart through activation of adrenergic receptors (ARs) on cardiomyocytes. Mounting evidence suggests that α1-ARs, particularly the α1A subtype, are cardioprotective and may mitigate the deleterious effects of chronic ß-AR activation by shared ligands. The mechanisms underlying these adaptive effects remain unclear. Here, we tested the hypothesis that α1A-ARs adaptively regulate cardiomyocyte oxidative metabolism in both the uninjured and infarcted heart. METHODS: We used high resolution respirometry, fatty acid oxidation (FAO) enzyme assays, substrate-specific electron transport chain (ETC) enzyme assays, transmission electron microscopy (TEM) and proteomics to characterize mitochondrial function comprehensively in the uninjured hearts of wild type and α1A-AR knockout mice and defined the effects of chronic ß-AR activation and myocardial infarction on selected mitochondrial functions. RESULTS: We found that isolated cardiac mitochondria from α1A-KO mice had deficits in fatty acid-dependent respiration, FAO, and ETC enzyme activity. TEM revealed abnormalities of mitochondrial morphology characteristic of these functional deficits. The selective α1A-AR agonist A61603 enhanced fatty-acid dependent respiration, fatty acid oxidation, and ETC enzyme activity in isolated cardiac mitochondria. The ß-AR agonist isoproterenol enhanced oxidative stress in vitro and this adverse effect was mitigated by A61603. A61603 enhanced ETC Complex I activity and protected contractile function following myocardial infarction. CONCLUSIONS: Collectively, these novel findings position α1A-ARs as critical regulators of cardiomyocyte metabolism in the basal state and suggest that metabolic mechanisms may underlie the protective effects of α1A-AR activation in the failing heart.
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Contração Miocárdica , Infarto do Miocárdio , Animais , Camundongos , Ácidos Graxos/metabolismo , Camundongos Knockout , Mitocôndrias/metabolismo , Infarto do Miocárdio/metabolismo , Estresse Oxidativo , Receptores Adrenérgicos alfa 1/metabolismoRESUMO
Lung adenocarcinoma (LUAD) is one of the most lethal and common malignancies. The energy metabolism of LUAD is a critical factor affecting its malignant progression, and research on this topic can aid in the development of novel cancer treatment targets. Bioinformatics analysis of the expression of long non-coding RNA (lncRNA) LINC00665 in LUAD was performed. Downstream regulatory molecules of LINC00665 were predicted using the StarBase database. We used quantitative reverse transcription polymerase chain reaction and western blot to measure the expression at mRNA and protein levels, respectively. The effects of the LINC00665/let-7c-5p/HMMR axis on cell viability in vitro were tested by CCK-8 assay. The regulatory effects on glycolysis were analyzed by extracellular acidification rate, oxygen consumption rate, glucose uptake, adenosine triphosphate production, and lactate production. The predicted competitive endogenous RNA mechanism between LINC00665 and let-7c-5p/HMMR was verified by a dual-luciferase reporter gene assay. LINC00665 was upregulated in LUAD. Silencing LINC00665 inhibited tumor proliferation and reduced the glycolytic activity of tumor cells. Additionally, the expression of LINC00665 had a negative correlation with that of let-7c-5p, while the expression of HMMR was remarkably inhibited by let-7c-5p. HMMR could affect the development of LUAD by influencing glycolytic capacity. Mechanistically, LINC00665 acted as a molecular sponge to absorb let-7c-5p and targeted HMMR. Transfection of let-7c-5p inhibitor or overexpression of HMMR plasmid could reverse the inhibition in proliferation and glycolysis of LUAD cells induced by silencing of LINC00665. In summary, this study demonstrated that the LINC00665/let-7c-5p/HMMR regulatory axis promoted the tumorigenesis of LUAD by enhancing aerobic glycolysis, suggesting that this regulatory axis was an effective target for inhibiting LUAD progression and providing theoretical support for the development of new drugs for LUAD.
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Adenocarcinoma , MicroRNAs , Humanos , Glicólise , Metabolismo Energético , Sobrevivência Celular , Pulmão , MicroRNAs/genética , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
PURPOSE: This study aims to evaluate the risk factors of treatment-related pneumonitis (TRP) following thoracic radiotherapy/chemoradiotherapy combined with anti-PD1 monoclonal antibodies (mAbs) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively reviewed 97 patients with advanced ESCC who were treated with thoracic radiotherapy/chemoradiotherapy combined with anti-PD1 mAbs. Among them, 56 patients received concurrent radiotherapy with anti-PD1 mAbs and 41 patients received sequential radiotherapy with anti-PD1 mAbs. The median prescribed planning target volume (PTV) dose was 59.4â¯Gy (range from 50.4 to 66â¯Gy, 1.8-2.2â¯Gy/fraction). Clinical characteristics, the percentage of lung volume receiving more than 5-50â¯Gy in increments of 5â¯Gy (V5-V50, respectively) and the mean lung dose (MLD) were analyzed as potential risk factors for TRP. RESULTS: 46.4% (45/97), 20.6% (20/97), 20.6% (20/97), 4.1% (4/97), and 1.0% (1/97) of the patients developed any grade of TRP, grade 1 TRP, grade 2 TRP, grade 3 TRP, and fatal (grade 5) TRP, respectively. Anti-PD1 mAbs administered concurrently with radiotherapy, V5, V10, V15, V25, V30, V35, V40 and MLD were associated with the occurrence of grade 2 or higher TRP. Concurrent therapy (Pâ¯= 0.010, ORâ¯= 3.990) and V5 (Pâ¯= 0.001, ORâ¯= 1.126) were independent risk factors for grade 2 or higher TRP. According to the receiver operating characteristic (ROC) curve analysis, the optimal V5 threshold for predicting grade 2 or higher TRP was 55.7%. CONCLUSION: The combination of thoracic radiotherapy/chemoradiotherapy with anti-PD1 mAbs displayed a tolerable pulmonary safety profile. Although the incidence of TRP was high, grade 1-2 TRP accounted for the majority. Anti-PD1 mAbs administered concurrently with radiotherapy and the lung V5 were significantly associated with the occurrence of grade 2 or higher TRP. Therefore, it seems safer to control V5 below 55% in clinical, especially for the high-risk populations receiving concurrent therapy.
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KEY MESSAGE: We identified a SbPLSH1gene conferring purple leaf sheath in sorghum (sorghumbicolor(L.) Moench)and developed a functional markerfor it. The purple leaf sheath of sorghum, a trait mostly related to anthocyanin deposition, is a visually distinguishable morphological marker widely used to evaluate the purity of crop hybrids. We aimed to dissect the genetic mechanism for leaf sheath color to mine the genes regulating this trait. In this study, two F2 populations were constructed by crossing a purple leaf sheath inbred line (Gaoliangzhe) with two green leaf sheath inbred lines (BTx623 and Silimei). Based on the results of bulked-segregant analysis sequencing, bulk-segregant RNA sequencing, and map-based cloning, SbPLSH1 (Sobic.006G175700), which encodes a bHLH transcription factor on chromosome 6, was identified as the candidate gene for purple leaf sheath in sorghum. Genetic analysis demonstrated that overexpression of SbPLSH1 in Arabidopsis resulted in anthocyanin deposition and purple petiole, while two single-nucleotide polymorphism (SNP) variants on the exon 6 resulted in loss of function. Further haplotype analysis revealed that there were two missense mutations and one cis-acting element mutation in SbPLSH1, which are closely associated with leaf sheath color in sorghum. Based on the variations, a functional marker (LSC4-2) for marker-assisted selection was developed, which has a broad-spectrum capability of distinguishing leaf sheath color in natural variants. In summary, this study lays a foundation for analyzing the genetic mechanism for sorghum leaf sheath color.
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Antocianinas , Folhas de Planta , Polimorfismo de Nucleotídeo Único , Sorghum , Sorghum/genética , Sorghum/crescimento & desenvolvimento , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Antocianinas/metabolismo , Marcadores Genéticos , Fenótipo , Pigmentação/genética , Mapeamento Cromossômico , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Genes de Plantas , Plantas Geneticamente Modificadas/genética , Haplótipos , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.
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Genótipo , Papillomaviridae , Infecções por Papillomavirus , Humanos , Feminino , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , China/epidemiologia , Adulto , Prevalência , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem , Papillomaviridae/genética , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Adolescente , Idoso , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia , DNA Viral/genética , Colo do Útero/virologiaRESUMO
Coronary angioplasty in patients with a right-sided heart may be difficult due to challenges in engaging the coronary arteries, interpreting angiogram, and further delivering intracoronary therapies. We present our experience of percutaneous coronary intervention in two cases and propose a practical algorithm to approach cardiac catheterization in these patients.
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Angioplastia Coronária com Balão , Dextrocardia , Intervenção Coronária Percutânea , Humanos , Resultado do Tratamento , Intervenção Coronária Percutânea/efeitos adversos , Angiografia CoronáriaRESUMO
In this study, [1+2+2] cyclization of tryptamine-derived isocyanides with 3-ylideneoxindoles was systematically investigated. A series of structurally complex spiro-oxindole derivatives were obtained. Characteristic dynamic covalent chemistry was observed and confirmed by experiments and density functional theory calculation. Through the regulation of the solvent, temperature, and time, the precise and stereodivergent synthesis of spiro-oxindoles was achieved.
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Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Quimiocina CCL20 , Neoplasias Pulmonares , NF-kappa B , Proteína 2 Ligante de Morte Celular Programada 1 , Linfócitos T Reguladores , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Humanos , NF-kappa B/metabolismo , Animais , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/genética , Quimiocina CCL20/metabolismo , Quimiocina CCL20/genética , Camundongos , Fumar Tabaco/efeitos adversos , Transdução de Sinais , Linhagem Celular Tumoral , Masculino , FemininoRESUMO
BACKGROUND: Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection. CASE PRESENTATION: A 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged. CONCLUSION: To our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia.
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Bacteriemia , Infecções por Fusobacterium , Herpes Simples , Herpesvirus Humano 1 , Feminino , Humanos , Pessoa de Meia-Idade , Porphyromonas gingivalis , Fusobacterium nucleatum , Herpesvirus Humano 1/genética , Composição de Bases , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Herpes Simples/complicações , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Bacteriemia/complicações , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Infecções por Fusobacterium/complicações , Infecções por Fusobacterium/diagnóstico , Infecções por Fusobacterium/tratamento farmacológicoRESUMO
Cisplatin (DDP) resistance, often leading to first-line chemotherapy failure in non-small cell lung cancer (NSCLC), poses a significant challenge. MiR-219a-5p has been reported to enhance the sensitivity of human NSCLC to DDP. However, free miR-219a-5p is prone to degradation by nucleases in the bloodstream, rendering it unstable. In light of this, our study developed an efficient nanodrug delivery system that achieved targeted delivery of DDP and miR-219a-5p by modifying liposomes with folate (FA). Based on the results of material characterization, we successfully constructed a well-dispersed and uniformly sized (approximately 135.8 nm) Lipo@DDP@miR-219a-5p@FA nanodrug. Agarose gel electrophoresis experiments demonstrated that Lipo@DDP@miR-219a-5p@FA exhibited good stability in serum, effectively protecting miR-219a-5p from degradation. Immunofluorescence and flow cytometry experiments revealed that, due to FA modification, Lipo@DDP@miR-219a-5p@FA could specifically bind to FA receptors on the surface of tumor cells (A549), thus enhancing drug internalization efficiency. Safety evaluations conducted in vitro demonstrated that Lipo@DDP@miR-219a-5p@FA exhibited no significant toxicity to non-cancer cells (BEAS-2B) and displayed excellent blood compatibility. Cellular functional experiments, apoptosis assays, and western blot demonstrated that Lipo@DDP@miR-219a-5p@FA effectively reversed DDP resistance in A549 cells, inhibited cell proliferation and migration, and further promoted apoptosis. In summary, the Lipo@DDP@miR-219a-5p@FA nanodrug, through specific targeting of cancer cells and reducing their resistance to DDP, significantly enhanced the anti-NSCLC effects of DDP in vitro, providing a promising therapeutic option for the clinical treatment of NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Lipossomos/uso terapêutico , MicroRNAs/genética , MicroRNAs/metabolismo , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
The emergence of covalent adaptable networks (CANs) based on dynamic covalent bonds (DCBs) presents a promising avenue for achieving resource recovery and utilization. In this study, we discovered a dynamic covalent bond called selenacetal, which is obtained through a double click reaction between selenol and activated alkynes. Density functional theory (DFT) calculations demonstrated that the ΔG for the formation of selenoacetals ranges from 12 to 18â kJ mol-1, suggesting its potential for dynamic reversibility. Dynamic exchange experiments involving small molecules and polymers provide substantial evidence supporting the dynamic exchange properties of selenoacetals. By utilizing this highly efficient click reaction, we successfully synthesized dynamic materials based on selenoacetal with remarkable reprocessing capabilities without any catalysts. These materials exhibit chemical recycling under alkaline conditions, wherein selenoacetal (SA) can decompose into active enone selenide (ES) and diselenides. Reintroducing selenol initiates a renewed reaction with the enone selenide, facilitating material recycling and yielding a newly developed dynamic material exhibiting both photo- and thermal responsiveness. The results underscore the potential of selenoacetal polymers in terms of recyclability and selective degradation, making them a valuable addition to conventional covalent adaptable networks.
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BACKGROUND: The purpose of this study was to investigate the role of hsa_circRNA_102051 in colorectal cancer (CRC) and its effect on the stemness of tumor cells. METHODS: CircRNA microarray was under analysis to screen differentially expressed novel circRNAs in the pathology of CRC. Quantitative real-time PCR was used to detect the relative RNA expression in CRC cells and samples. The effects of hsa_circRNA_102051 on biological functions in CRC cells were accessed both in vitro and in vivo. FISH, RIP and luciferase reporter assay were conducted to confirm the regulatory correlations between hsa_circRNA_102051 and miR-203a, as well as miR-203a and BPTF. Xenograft models were applied to further verify the impacts and fluctuations of hsa_circRNA_102051/miR-203a/BPTF. Moreover, the mechanism how hsa_circRNA_102051 affected the Notch signals was also elucidated. RESULTS: Hsa_circRNA_102051 was up-regulated in CRC tissues and cell lines, capable to promote the growth and invasion of CRC. In addition, hsa_circRNA_102051 could enhance stemness of CRC cells. BPTF was identified as downstream factors of hsa_circRNA_102051, and miR-203a was determined directly targeting both hsa_circRNA_102051 and BPTF as an intermediate regulator. Hsa_circRNA_102051 in CRC could block miR-203a expression, and subsequently activated BPTF. Hsa_circRNA_102051/miR-203a/BPTF axis modulated stemness of CRC cells by affecting Notch pathway. CONCLUSIONS: Our findings provided new clues that hsa_circRNA_102051 might be a potential predictive or prognostic factor in CRC, which induced the fluctuation of downstream miR-203a/BPTF, and subsequently influenced tumor growth, activities and stemness. Thereinto, the Notch signals were also involved. Hence, the hsa_circRNA_102051/miR-203a/BPTF axis could be further explored as a therapeutic target for anti-metastatic therapy in CRC patients.
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Background Since the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies. Methods We searched all the relevant studies in PubMed, Embase and Cochrane Library databases. We also reviewed abstracts of relevant conferences, to prevent omissions. The meta-analysis was performed using Stata version 16.0. Results Chemoradiotherapy combined with immunotherapy can improve PFS (HR: 0.60, 95%CI :0.55-0.60) and OS (HR: 0.59, 95%CI :0.53-0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5%-52.7%) and 71.3% (95% CI, 67.3%-75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95%CI, 51.0%-70.3%) and 77.4% (95%CI, 73.2%-81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95%CI, 31.3%-39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95%CI, 31.9%-51.9%). The pooled rate of pneumonitis ≥ grade 3 was 6.7% (95%CI, 5.0%-8.5%). The incidence of pneumonitis ≥ grade 3 after 1 year of immunotherapy is 4.8% (95%CI, 3.1%-6.5%). The incidence of pneumonitis ≥ grade 3 after 2 years of immunotherapy is 5.1% (95%CI, 2.9%-7.3%). Conclusions Prolonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit.
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BACKGROUND: The purpose of this study was to explore the risk factors for postoperative infection in patients with primary hepatic carcinoma (PHC), build a nomogram prediction model, and verify the model to provide a better reference for disease prevention, diagnosis and treatment. METHODS: This single-center study included 555 patients who underwent hepatobiliary surgery in the Department of Hepatobiliary Surgery of Tianjin Third Central Hospital from January 2014 to December 2021, and 32 clinical indicators were selected for statistical analysis. In this study, Lasso logistic regression was used to determine the risk factors for infection after liver cancer resection, establish a predictive model, and construct a visual nomogram. The consistency index (C-index), calibration curve, and receiver operating characteristic (ROC) curve were used for internal validation, and decision curve analysis (DCA) was used to analyze the clinical applicability of the predictive model. The bootstrap method was used for intramodel validation, and the C-index was calculated to assess the model discrimination. RESULTS: Among the 555 patients, 279 patients met the inclusion criteria, of whom 48 had a postoperative infection, with an incidence rate of 17.2%. Body mass index (BMI) (P = 0.022), alpha-fetoprotein (P = 0.023), total bilirubin (P = 0.016), intraoperative blood loss (P < 0.001), and bile leakage (P < 0.001) were independent risk factors for infection after liver cancer surgery. The nomogram was constructed and verified to have good discriminative and predictive ability. DCA showed that the model had good clinical applicability. The C-index value verified internally by the bootstrap method results was 0.818. CONCLUSION: Postoperative infection in patients undergoing hepatectomy may be related to risk factors such as BMI, preoperative AFP level, TBIL level, intraoperative blood loss and bile leakage. The prediction model of the postoperative infection nomogram established in this study can better predict and estimate the risk of postoperative infection in patients undergoing hepatectomy.
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Carcinoma , Neoplasias Hepáticas , Humanos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Nomogramas , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
PURPOSE OF REVIEW: Clonal hematopoiesis (CH) refers to the expansion of hematopoietic stem cell clones and their cellular progeny due to somatic mutations, mosaic chromosomal alterations (mCAs), or copy number variants which naturally accumulate with age. CH has been linked to increased risk of blood cancers, but CH has also been linked to adverse cardiovascular outcomes. RECENT FINDINGS: A combination of clinical outcome studies and mouse models have offered strong evidence that CH mutations either correlate with or cause atherosclerosis, diabetes mellitus, chronic kidney disease, heart failure, pulmonary hypertension, aortic aneurysm, myocardial infarction, stroke, aortic stenosis, poor outcomes following transcatheter aortic valve replacement (TAVR) or orthotopic heart transplant, death or need of renal replacement therapy secondary to cardiogenic shock, death from cardiovascular causes at large, and enhance anthracycline cardiac toxicity. Mechanistically, some adverse outcomes are caused by macrophage secretion of IL-1ß and IL-6, neutrophil invasion of injured myocardium, and T-cell skewing towards inflammatory phenotypes. CH mutations lead to harmful inflammation and arterial wall invasion by bone marrow-derived cells resulting in poor cardiovascular health and outcomes. Blockade of IL-1ß or JAK2 signaling are potential avenues for preventing CH-caused cardiovascular morbidity and mortality.
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Aterosclerose , Insuficiência Cardíaca , Camundongos , Animais , Humanos , Hematopoiese Clonal/genética , Hematopoese/genética , Células-Tronco Hematopoéticas/metabolismo , MutaçãoRESUMO
AIM: The use of magnetic carbon nanotubes for multi-modal cancer treatment, incorporating both hyperthermia and drug delivery functions, has drawn substantial interest. Yet, the present method of regulating hyperthermia temperature involves manually adjusting the magnetic field intensity, adding to the complexity and difficulty of clinical applications. This study seeks to design novel magnetic carbon nanotubes capable of self-temperature regulation, and investigate their drug loading and release characteristics. METHODS: Using the co-precipitation method, we synthesized magnetic carbon nanotubes with a Curie temperature of 43 °C. A comprehensive investigation was conducted to analyze their morphology, crystal structure, and magnetic characteristics. To enhance their functionality, chitosan and sodium alginate modifications were introduced, enabling the loading of the antitumor drug doxorubicin hydrochloride (DOX) into these magnetic carbon nanotubes. Subsequently, the loading and release properties of DOX were investigated within the modified magnetic nanotubes. RESULTS: Under alternating magnetic field, magnetic carbon nanotubes exhibit self-regulating properties by undergoing a magnetic phase transition, maintaining temperatures around 43 °C as required for hyperthermia. On the other hand, during magnetic induction heating, the release percentage of DOX reached 23.5% within 2 h and 71.7% within 70 h at tumor pH conditions, indicating their potential for sustained drug release. CONCLUSIONS: The prepared magnetic carbon nanotubes can effectively regulate the temperature during hyperthermia treatment while ensuring controlled drug release, which presents a promising method for preparing nanomaterials that synergistically enhance magnetic hyperthermia and chemotherapy drugs.
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Nanotubos de Carbono , Humanos , Liberação Controlada de Fármacos , Calefação , Febre , Hipertermia , Campos MagnéticosRESUMO
BACKGROUND AND AIMS: The upper limits of normal serum uric acid (SUA) or the lower limits of hyperuricemia were frequently set at 420 or 360 µmol/L (7.0 or 6.0 mg/dL). We aimed to explore the association between high-normal SUA (360 ≤ SUA≤420 µmol/L) and incidence of macrovascular and renal events based on a 10-year cohort with type 2 diabetes mellitus (T2DM) to explore which cut-off was more appropriate. METHODS AND RESULTS: A total of 2988 patients with T2DM without hyperuricemia (SUA≤420 µmol/L) were included and followed up. Cox proportional hazards models and restricted cubic spline regression were used to evaluate the relationship between baseline SUA (as continuous and categorical variable) and macrovascular and renal events. Patients were grouped as low-normal (SUA<360 µmol/L) and high-normal groups based on baseline SUA, and the latter group had higher incidence of macrovascular events. Multivariate Cox regression analysis indicated that baseline levels of SUA were significantly associated with cardiovascular (HR = 1.385, 95%CI:1.190-1.613, P < 0.001) and peripheral vascular events (HR = 1.266, 95%CI:1.018-1.574, P = 0.034), and the linear association existed. Moreover, fully adjusted multivariable Cox analyses indicated high-normal SUA increased the risks of cardiovascular (HR = 1.835, 95%CI:1.319-2.554, P < 0.001) and peripheral vascular events (HR = 1.661, 95%CI:1.000-2.760, P = 0.050) compared to low-normal SUA. CONCLUSIONS: Baseline SUA levels were positively associated with cardiovascular and peripheral vascular events, and high-normal SUA increased the risks of these events in patients with T2DM even without hyperuricemia. A threshold value for SUA of 360 µmol/L should be more appropriate in terms of predicting macrovascular events risks compared to the value of 420 µmol/L.
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Diabetes Mellitus Tipo 2 , Hiperuricemia , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Ácido Úrico , Fatores de Risco , RimRESUMO
A large-scale exchange of information between media across national borders is frequently observed when a worldwide public health emergency occurs. This study investigated the global news citation network in the early stage of the COVID-19 pandemic by analysing the network structure at different levels to identify important nodes and the relationships among news organisations. The results show that COVID-19-related international news flow had a complex and unequal pattern, with a few countries and media outlets occupying a prominent place in the network and three media groups played key but different roles in disseminating the news. It was jointly influenced by national traits, the relatedness between countries, and the pandemic emergency with public health risks. From a global perspective, the media of the United States, mainland China, and the United Kingdom played the most important parts in collaboration within the world media system in the early stage of the COVID-19 pandemic.
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COVID-19 , Mídias Sociais , Humanos , Estados Unidos , COVID-19/epidemiologia , Saúde Pública , SARS-CoV-2 , Pandemias , Emergências , Disseminação de InformaçãoRESUMO
Covalent adaptable networks (CANs) possess unique properties as a result of their internal dynamic bonds, such as self-healing and reprocessing abilities. In this study, we report a thermally responsive C-Se dynamic covalent chemistry (DCC) that relies on the transalkylation exchange between selenonium salts and selenides, which undergo a fast transalkylation reaction in the absence of any catalyst. Additionally, we demonstrate the presence of a dissociative mechanism in the absence of selenide groups. After incorporation of this DCC into selenide-containing polymer materials, it was observed that the cross-linked networks display varying dynamic exchange rates when using different alkylation reagents, suggesting that the reprocessing capacity of selenide-containing materials can be regulated. Also, by incorporating selenonium salts into polymer materials, we observed that the materials exhibited good healing ability at elevated temperatures as well as excellent solvent resistance at ambient temperature. This novel dynamic covalent chemistry thus provides a straightforward method for the healing and reprocessing of selenide-containing materials.
RESUMO
In 1981, Caves pointed out that the phase sensitivity of a Mach-Zehnder interferometer with single-mode inputs is bounded by the shot-noise limit. The quantum Fisher information analysis shows that this statement holds true for the scenario where two antisymmetric phase shifts occur in two arms, but it is invalid for the scenario where an unknown phase is embedded in one of two arms. In this paper, we focus on the phase sensitivity directed against the latter scenario. The optimal single-mode input is discussed by analyzing common states, including displaced squeezed states, displaced number states, squeezed number states, Schrödinger cat states and completely mixed states. We find that the best choice is a squeezed vacuum state and show the specific measurement scheme which is capable of saturating the corresponding phase sensitivity limit. In addition, we study the effects of several realistic factors-anti-squeezing noise, photon loss and dark counts-on the phase sensitivity. Our results suggest that sub-shot-noise-limited phase sensitivity is attainable with low noise or loss, which paves the way for practical metrology.