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Objective: To assess whether cumulative exposure of unhealthy lifestyles is associated with HTH in Chinese adults and to explore the combination of unhealthy lifestyles. Methods: This study combined a community-based cross-sectional study with a 1:1 matched case-control study using propensity scores among adults in six randomly selected districts from Hunan Province, China. We recruited 5,258 people, of whom 4,012 met the criteria. Lifestyles and personal characteristics were collected by a questionnaire. Lifestyle score was calculated using cigarette smoking, heavy alcohol consumption, inactive exercise, unhealthy diet and abnormal BMI. HTH was defined as having a diagnosis of essential hypertension with Hcy ≥ 15 umol/L. Logistic regression models and multivariate analyses were used to explore the associations. We calculated odds ratios (ORs) and attributable risk proportion (ARP) for the association of HTH with lifestyle score. The dose-response relationship was evaluated using restricted cubic splines method. Results: Of the 4,012 adults, 793 had HTH, with a population prevalence of 19.8%. In the propensity-score-matched case-control study, 1,228 (614 cases and 614 controls) were included, and those with at least four unhealthy lifestyle factors had a higher risk of HTH than those with 0 unhealthy lifestyle factor (adjusted OR = 2.60, 95%CI:1.42-4.78), with an ARP of the cumulative exposure of unhealthy lifestyle was 28.23% (95% CI: 6.34-37.86%). For three unhealthy lifestyles group, the combination of heavy alcohol consumption, unhealthy diet and BMI ≥24 Kg/m2 was most associated with HTH (OR = 7.49, 95%CI: 1.12-50.08). For four unhealthy lifestyles group, the combination of smoking, heavy alcohol consumption, unhealthy diet and BMI ≥24 Kg/m2 had the greatest correlation with HTH (OR = 3.75, 95%CI: 1.24-7.38). Notably, there was a monotonically increasing curve (J-shaped) relationship between unhealthy lifestyles and the risk of HTH (p = 0.014). Conclusion: Our findings suggest that there was a significant cumulative exposure effect of unhealthy lifestyles on the risk of HTH, with the largest effect combination being heavy alcohol consumption, unhealthy diet and BMI ≥24 Kg/m2. Targeted interventions that reducing heavy alcohol consumption, quitting smoking, promoting physical activity and a healthy diet, and keep a normal BMI could substantially reduce the burden of HTH.
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RNA-binding proteins (RBPs) regulate totipotency, pluripotency maintenance, and induction. The intricacies of how they modulate these processes through their interaction with RNAs remain to be elucidated. Here we employed Targets of RBPs Identified By Editing (TRIBE) with single-cell resolution (scTRIBE) to profile the mRNA targets of the key pluripotency regulator LIN28A in mouse embryonic stem cells (ESCs), 2-cell embryo-like cells (2CLCs) and somatic cell reprogramming. LIN28A is known to act by controlling the maturation of the let-7 microRNA but, in addition, it binds to multiple mRNAs and influences their stability and translation efficiency. However, the mRNA targets of LIN28A in 2CLCs and reprogramming are unclear. Through quantitative single-cell analysis of the scTRIBE dataset, we observed a marked increase in the binding of LIN28A to mRNAs of ribosome biogenesis factors and a selected group of totipotency factors in 2CLCs within ESC cultures. Our results suggest that LIN28A extends the half-life of at least some of these mRNAs, providing new insights into its role in the totipotent state. We also uncovered the distinct trajectory-specific LIN28A-mRNA networks in reprogramming, helping explain how LIN28A facilitates the mesenchymal-to-epithelial transition and pluripotency acquisition. Our study not only clarifies the multifunctional role of LIN28A in these processes but also highlights the importance of decoding RNA-protein interactions at the single-cell level.
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Background and importance: Explore the techniques, advantages and disadvantages of 3D Slicer reconstruction combined with transcranial neuroendoscopy in cerebrospinal fluid rhinorrhea surgery. Clinical presentation: We collected complete clinical data of two patients with cerebrospinal fluid rhinorrhea who underwent minimally invasive surgery using 3D Slicer reconstruction combined with transcranial neuroendoscopy through the supraorbital eyebrow arch keyhole approach in our hospital from June 2022 to May 2023. The patients were one male and one female, aged 50 and 63 years old. At the same time, a retrospective summary of relevant literature at home and abroad in recent years was conducted. 1 case had spontaneous cerebrospinal fluid rhinorrhea with secondary cribriform plate lesion, and the other 1 case had traumatic cerebrospinal fluid rhinorrhea. Both 2 patients were ineffective after long-term conservative treatment, and ultimately recovered after detailed preoperative evaluation and preparation and surgical treatment. Conclusion: Cerebrospinal fluid rhinorrhea is a challenging disease in neurosurgery, and improper management can lead to serious complications such as meningitis. Our team used 3D Slicer reconstruction combined with transcranial endoscopic minimally invasive keyhole surgery to treat cerebrospinal fluid rhinorrhea, achieving good results, proving that this combined technology has certain advantages and is a new surgical technique worth promoting. However, the widespread application and promotion of this technology in anterior skull base surgery still require comprehensive and reliable prospective clinical studies to test.
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BACKGROUND: Coronary heart disease and type 2 diabetes mellitus (T2DM) frequently coexist, creating a complex and challenging clinical scenario, particularly when complicated with acute myocardial infarction (AMI). AIM: To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion. METHODS: In total, 98 patients were categorized into control (n = 47) and observation (n = 51) groups. The control group received noxital, while the observation group was treated with dapagliflozin combined with noxital for 6 months. Changes in myocardial microperfusion, blood glucose level, cardiac function, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, growth differentiation factor-15 (GDF-15) level, and other related factors were compared between the two groups. Additionally, the incidence of major adverse cardiovascular events (MACE) and adverse reactions were calculated. RESULTS: After treatment, in the observation and control groups, the corrected thrombolysis in myocardial infarction frame counts were 37.12 ± 5.02 and 48.23 ± 4.66, respectively. The NT-proBNP levels were 1502.65 ± 255.87 and 2015.23 ± 286.31 pg/mL, the N-terminal pro-atrial natriuretic peptide (NT-proANP) levels were 1415.69 ± 213.05 and 1875.52 ± 241.02 ng/mL, the GDF-15 levels were 0.87 ± 0.43 and 1.21 ± 0.56 g/L, and the high-sensitivity C-reactive protein (hs-CRP) levels were 6.54 ± 1.56 and 8.77 ± 1.94 mg/L, respectively, with statistically significant differences (P < 0.05). The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group (P < 0.05). The incidence of adverse reactions was 13.73% (7/51) in the observation group and 10.64% (5/47) in the control group, with no statistically significant difference (P > 0.05). CONCLUSION: Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM. The underlying mechanism may be related to the reduction in the expression levels of NT-proANP, GDF-15, and hs-CRP.
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BACKGROUND: This paper reports a rare presentation of multiple pulp stones (PSs) emerging in all teeth during mixed dentition. It offers valuable insights into the clinical diagnosis, treatment, and prognosis of multiple PSs, shedding light on their occurrence during the mixed dentition period. CASE SUMMARY: A 10-year-old girl presented with repeated pain in the mandibular right posterior teeth. Intraoral examination revealed carious lesions, abnormal tooth shapes, and anomalies in tooth number. Radiographic examinations showed multiple PSs with diverse shapes, sizes, and quantities in all teeth, alongside anomalies in tooth shape and number. Root canal therapy was initiated, but the patient initially lacked timely follow-up. Upon return for treatment completion, an extracted tooth revealed irregular calculus within the pulp cavity. CONCLUSION: This case underscores the importance of considering multiple PSs in mixed dentition, necessitating comprehensive evaluation and management strategies.
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BACKGROUND: Most acute cerebral infarctions (ACI) may develop vascular dementia (VD), which involves almost all types of cognitive impairment. Unfortunately, there is currently no effective treatment for VD. Most patients exhibit mild cognitive impairment (MCI) before the development of VD. N-butyl-phthalide (NBP) is used to treat ACI and improve cognitive function. The oxygen and glucose deprivation (OGD) model of neurons is an in vitro model of ischemia, hypoxia, and cognitive dysfunction. METHODS: We conducted clinical studies and in vitro experiments to investigate the clinical efficacy and mechanism of action of NBP for treating ACI-induced MCI. Patients with ACI-induced MCI were randomly divided into control (Ctrl) and NBP groups. We assessed various indicators, such as clinical efficacy, montreal cognitive assessment scale (MOCA), activities of daily living (ADL), and cerebral infarct size in both groups before and after treatment. We observed the morphology of neurons and detected the survival rate, action potentials (APs), expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and the interaction between TLR4 and HMGB1. RESULTS: The MOCA and ADL scores increased significantly after treatment in the NBP group. A OGD model of neurons was established, and the neurons were divided into Ctrl and NBP groups. We observed that the survival rate and APs amplitude of the neurons were significantly increased in the NBP group, whereas TNF-α expression was decreased. Furthermore, the interaction between TLR4 and HMGB1 decreased in the NBP group. CONCLUSION: NBP plays a neuroprotective role by inhibiting the TLR4/HMGB1 pathway and ameliorating ACI-induced MCI.
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Benzofuranos , Infarto Cerebral , Disfunção Cognitiva , Proteína HMGB1 , Fármacos Neuroprotetores , Receptor 4 Toll-Like , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Proteína HMGB1/metabolismo , Proteína HMGB1/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Benzofuranos/farmacologia , Benzofuranos/administração & dosagem , Humanos , Infarto Cerebral/tratamento farmacológico , Masculino , Idoso , Animais , Feminino , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Mitochondrial proteins assume a pivotal role in the onset and progression of diverse diseases. Nonetheless, the causal interconnections with sensorineural hearing loss (SNHL) demand meticulous exploration. Mendelian randomization analysis is a method used in observational epidemiological studies to predict the relationship between exposure factors and outcomes using genetic variants as instrumental variables. In this study, we applied this analytical approach to two distinct samples to predict the causal impact of mitochondrial proteins on SNHL. METHODS: Two-sample Mendelian randomization analyses were executed to scrutinize the predicted associations between 63 mitochondrial proteins (nuclear-encoded) and SNHL, utilizing summary statistics derived from genome-wide association studies. Assessments of pleiotropy and heterogeneity were carried out to gauge the robustness of the obtained findings. RESULTS: Four mitochondrial proteins exhibited a suggestive causal relationship with the susceptibility to SNHL. Dihydrolipoamide dehydrogenase (DLD; OR = 0.9706, 95% CI = 0.9382-0.9953, p = 0.0230) was linked to a diminished risk of SNHL. Conversely, elevated levels of mitochondrial ribosomal protein L34 (MRPL34; OR = 1.0458, 95% CI = 1.0029-1.0906, p = 0.0362), single-pass membrane protein with aspartate-rich tail 1 (SMDT1; OR = 1.0619, 95% CI = 1.0142-1.1119, p = 0.0104), and superoxide dismutase 2 (SOD2; OR = 1.0323, 95% CI = 1.0020-1.0634, p = 0.0364) were associated with an elevated risk of SNHL. CONCLUSION: This research utilized Mendelian randomization analysis to predict the relationship between mitochondrial proteins and SNHL. It provides a potential viewpoint on the etiology and diagnosis.
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Estudo de Associação Genômica Ampla , Perda Auditiva Neurossensorial , Análise da Randomização Mendeliana , Proteínas Mitocondriais , Humanos , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/epidemiologia , Proteínas Mitocondriais/genética , Predisposição Genética para Doença , Superóxido Dismutase/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells to those observed in vivo further underscores its potential as a research tool. Notably, teratomas derived from human naïve (pre-implantation epiblast-like) pluripotent stem cells (PSCs) have larger embryonic cell diversity and contain extraembryonic lineages, making them more suitable to study developmental processes. However, the cell type-specific epigenetic profiles of naïve PSC teratomas have not been yet characterized. Using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we analyzed 66,384 cell profiles from five teratomas derived from human naïve PSCs and their post-implantation epiblast-like (primed) counterparts. We observed 17 distinct cell types from both embryonic and extraembryonic lineages, resembling the corresponding cell types in human fetal tissues. Additionally, we identified key transcription factors specific to different cell types. Our dataset provides a resource for investigating gene regulatory programs in a relevant model of human embryonic development.
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Cromatina , Células-Tronco Pluripotentes , Análise de Célula Única , Teratoma , Humanos , Teratoma/genética , Teratoma/patologia , Células-Tronco Pluripotentes/metabolismo , Linhagem da Célula , Fatores de Transcrição/genéticaRESUMO
Doping transition metal oxide spinels with metal ions represents a significant strategy for optimizing the electronic structure of electrocatalysts. Herein, a bimetallic Fe and Ru doping strategy to fine-tune the crystal structure of CoV2O4 spinel for highly enhanced oxygen evolution reaction (OER) is presented performance. The incorporation of Fe and Ru is observed at octahedral sites within the CoV2O4 structure, effectively modulating the electronic configuration of Co. Density functional theory calculations have confirmed that Fe acts as a novel reactive site, replacing V. Additionally, the synergistic effect of Fe, Co, and Ru effectively optimizes the Gibbs free energy of the intermediate species, reduces the reaction energy barrier, and accelerates the kinetics toward OER. As expected, the best-performing CoVFe0.5Ru0.5O4 displays a low overpotential of 240 mV (@10 mA cm-2) and a remarkably low Tafel slope of 38.9 mV dec-1, surpassing that of commercial RuO2. Moreover, it demonstrates outstanding long-term durability lasting for 72 h. This study provides valuable insights for the design of highly active polymetallic spinel electrocatalysts for energy conversion applications.
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Objective: Brucellosis has a considerable impact on human health and the economy in developing countries. In China, the biggest developing country, brucellosis shifted spread of the epidemic from northern to southern regions. Understanding the transmission characteristic of brucellosis on Hunan province, located in central China, is of great significance for successful control. Methods: We developed a multi-population and multi-route dynamic model (MPMRDM), which is an animal-human-environment coupled model. The model is an extension of the SEIR model, taking into account direct transmission and indirect transmission. We used the model to explore the spread of brucellosis and evaluate the effectiveness of various intervention strategies. Results: The animal-to-animal transmission rate was the highest at 5.14 × 10-8, while the environment-to-person transmission rate was the lowest at 9.49 × 10-12. The mean R0 was 1.51. The most effective intervention was taking personal protection, followed by shortening the infection period. Shortening the infection period combined with personal protection is the most effective two-combined intervention strategy. After any comprehensive intervention strategy was implemented, TAR dropped by 90% or more. Conclusion: The results demonstrate that animal transmission route is essential for controlling human brucellosis. Strengthening personal protection, early detection, and early treatment can effectively control the trend of brucellosis. These results can provide an important reference for optimizing brucellosis intervention plans.
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BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.
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Antibacterianos , Infecções Comunitárias Adquiridas , Levofloxacino , Quinolonas , Humanos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Levofloxacino/uso terapêutico , Levofloxacino/efeitos adversos , Levofloxacino/administração & dosagem , Método Duplo-Cego , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Adulto , Idoso , Resultado do Tratamento , Quinolonas/uso terapêutico , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Administração Intravenosa , Infusões Intravenosas , Adulto Jovem , Pneumonia/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Idoso de 80 Anos ou maisRESUMO
Perforation of the tympanic membrane (TM) is a common condition that often requires a scaffold as a support for surgery. However, because of the external environment of the auditory canal, the scaffold could become bacterially infected and prevent the TM from healing. As a result, the perfect scaffold should have both antibacterial and biomimetic qualities. In this study, the biodegradable biomaterial poly(1,4-butylene carbonate) (PBC) films containing levofloxacin (LEV) was successfully prepared for the first time. The results showed that the hydrophilicity of the LEV/PBC film was improved after the addition of LEV, and the tensile strength was also complied with the requirements of the standard. The created antibacterial film demonstrated excellent antibacterial properties. In vitro hemolysis experiments revealed no risk of hemolysis for the new material, and the cytotoxicity study further confirmed its non-cytotoxic nature. Overall, LEV was a good component of PBC/LEV film, which is expected to be used for TM repair in the future.
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Malignant tumors and central nervous system (CNS) disorders are intricately linked to a process known as "aberrant cell cycle re-entry," which plays a critical role in the progression of these diseases. Addressing the dysregulation in cell cycles offers a promising therapeutic approach for cancers and CNS disorders. MicroRNAs (miRNAs) play a crucial role as regulators of gene expression in cell cycle transitions, presenting a promising therapeutic avenue for treating these disorders and their comorbidities. This review consolidates the progress made in the last three years regarding miRNA-based treatments for diseases associated with aberrant cell cycle re-entry. It encompasses exploring fundamental mechanisms and signaling pathways influenced by miRNAs in cancers and CNS disorders, particularly focusing on the therapeutic effects of exosome-derived miRNAs. The review also identifies specific miRNAs implicated in comorbidity of cancers and CNS disorders, discusses the future potential of miRNA reagents in managing cell cycle-related diseases.
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Ciclo Celular , Doenças do Sistema Nervoso Central , Comorbidade , MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , Neoplasias/genética , Neoplasias/terapia , Neoplasias/patologia , Animais , Ciclo Celular/genética , Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/terapia , Transdução de SinaisRESUMO
Background: Tinnitus can severely impair people's quality of life. Stress has been involved in the pathogenesis of multiform mental disorders. Tinnitus-related annoying symptoms have a negative effect on the life quality of tinnitus sufferers. Objectives: The aim of this study is to explore the association between stress and the symptomatic tinnitus. Methods: A total of 183 participants were categorized into 3 groups, depending on the presence of tinnitus-related symptoms. All participants underwent audiological examination, and their demographic data were collected via a questionnaire. Furthermore, the Social Readjustment Rating Scale (SRRS), the Tinnitus Handicapped Inventory (THI), and Tinnitus Questionnaire were filled by tinnitus patients. Results: The mean SRRS score in symptomatic (tinnitus-related symptoms) group was higher than that in asymptomatic group and the control group (P < .001), meanwhile no difference in this score was reported between asymptomatic group and control group. SRRS score (Grade 2) is an independent risk factor for symptomatic tinnitus. The SRRS score were positively correlated with THI scores. Conclusions and Significance: Stress is related to the occurrence of symptomatic tinnitus.
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BACKGROUND: According to the latest report, colorectal cancer is still one of the most prevalent cancers, with the third highest incidence and mortality worldwide. Treatment of advanced rectal cancer with distant metastases is usually unsatisfactory, especially for mismatch repair proficient (pMMR) rectal cancer, which leads to poor prognosis and recurrence. CASE SUMMARY: We report a case of a pMMR rectal adenocarcinoma with metastases of multiple lymph nodes, including the left supraclavicular lymph node, before treatment in a 70-year-old man. He received full courses of chemoradiotherapy (CRT) followed by 4 cycles of programmed death 1 inhibitor Tislelizumab, and a pathologic complete response (pCR) was achieved, and the lesion of the left supraclavicular lymph node also disappeared. CONCLUSION: pMMR advanced rectal cancer with preserved intact distant metastatic lymph nodes may benefit from full-course CRT combined with immunotherapy.
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BACKGROUND AND OBJECTIVES: Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications. METHODS AND STUDY DESIGN: We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment. RESULTS: The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05). CONCLUSIONS: Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.
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Recém-Nascido Prematuro , Fentolamina , Complexo Vitamínico B , Feminino , Humanos , Recém-Nascido , Masculino , Intolerância Alimentar , Gastroenteropatias/tratamento farmacológico , Fentolamina/administração & dosagem , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/uso terapêuticoRESUMO
BACKGROUND AND AIMS: Although the life expectancy of women systematically and robustly exceeds that of men, specific differences and molecular mechanisms of sex in influencing longevity phenotypes remain largely unknown. Therefore, we performed transcriptome sequencing of peripheral blood samples to explore regulatory mechanisms of healthy longevity by incorporating sex data. METHODS: We selected 34 exceptional longevity (age: 98.26 ± 2.45 years) and 16 controls (age: 52.81 ± 9.78) without advanced outcomes from 1363 longevity and 692 controls recruited from Nanning of Guangxi for RNA sequencing 1. The transcriptome sequencing 1 data of 50 samples were compared by longevity and sex to screen differentially expressed genes (DEGs). Then, 121 aging samples (40-110 years old) without advanced outcomes from 355 longevity and 294 controls recruited from Dongxing of Guangxi were selected for RNA sequencing 2. The genes associated with aging from the transcriptome sequencing 2 of 121 aging samples were filtered out. Finally, the gender-related longevity candidate genes and their possible metabolic pathways were verified by cell model of aging and a real-time polymerase chain reaction (RT-PCR). RESULTS: Metabolism differs between male and female and plays a key role in longevity. Moreover, the principal findings of this study revealed a novel key gene, UGT2B11, that plays an important role in regulating lipid metabolism through the peroxisome proliferator activated receptor gamma (PPARG) signalling pathway and ultimately improving lifespan, particularly in females. CONCLUSION: The findings suggest specific differences in metabolism affecting exceptional longevity phenotypes between the sexes and offer novel therapeutic targets to extend lifespan by regulating lipid homeostasis.
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Longevidade , Fenótipo , Humanos , Masculino , Feminino , Longevidade/genética , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto , Transcriptoma , Estudos de Casos e Controles , Prognóstico , Seguimentos , Perfilação da Expressão Gênica , Biomarcadores/análise , Fatores Sexuais , Envelhecimento/genéticaRESUMO
This study aims to examine the development trend of COVID-19 in China and propose a model to assess the impacts of various prevention and control measures in combating the COVID-19 pandemic. Using COVID-19 cases reported by the National Health Commission of China from January 2, 2020, to January 2, 2022, we established a Susceptible-Exposed-Infected-Asymptomatic-Quarantined-Vaccinated-Hospitalized-Removed (SEIAQVHR) model to calculate the COVID-19 transmission rate and Rt effective reproduction number, and assess prevention and control measures. Additionally, we built a stochastic model to explore the development of the COVID-19 epidemic. We modeled the incidence trends in five outbreaks between 2020 and 2022. Some important features of the COVID-19 epidemic are mirrored in the estimates based on our SEIAQVHR model. Our model indicates that an infected index case entering the community has a 50%-60% chance to cause a COVID-19 outbreak. Wearing masks and getting vaccinated were the most effective measures among all the prevention and control measures. Specifically targeting asymptomatic individuals had no significant impact on the spread of COVID-19. By adjusting prevention and control parameters, we suggest that increasing the rates of effective vaccination and mask-wearing can significantly reduce COVID-19 cases in China. Our stochastic model analysis provides a useful tool for understanding the COVID-19 epidemic in China.
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Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinação , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , China/epidemiologia , Vacinação/estatística & dados numéricos , SARS-CoV-2/imunologia , Vacinas contra COVID-19/administração & dosagem , Surtos de Doenças/prevenção & controle , Incidência , Adulto , Número Básico de Reprodução , Pessoa de Meia-IdadeRESUMO
This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar HEC14028 compared to reference Trulicity® (dulaglutide) in healthy male Chinese subjects. This study was a single-center, randomized, open, single-dose, parallel-controlled comparative Phase I clinical trial, including a screening period of up to 14 days, a 17-day observation period after administration, and a 7-day safety follow-up period. A total of 68 healthy male subjects were randomly assigned (1:1) to the test group (HEC14028) and the reference group (dulaglutide) (single 0.75 mg abdominal subcutaneous dose). The primary objective was to evaluate the pharmacokinetic characteristics of HEC14028 and compare the pharmacokinetic similarities between HEC14028 and dulaglutide. The primary PK endpoints were maximum plasma concentration (Cmax) and area under the blood concentration-time curve from zero time to the estimated infinite time (AUC0-∞). The study results showed that HEC14028 and dulaglutide were pharmacokinetically equivalent: 90% confidence interval (CI) of Cmax and AUC0-∞ geometric mean ratios were 102.9%-122.0% and 97.1%-116.9%, respectively, which were both within the range of 80.00%-125.00%. No grade 3 or above treatment emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to withdrawal from the trial, or TEAEs leading to death were reported in this study. Both HEC14028 and dulaglutide showed good and similar safety profiles, and no incremental immunogenicity was observed in subjects receiving HEC14028 and dulaglutide.
Assuntos
Medicamentos Biossimilares , Peptídeos Semelhantes ao Glucagon , Voluntários Saudáveis , Fragmentos Fc das Imunoglobulinas , Proteínas Recombinantes de Fusão , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Área Sob a Curva , Povo Asiático , Medicamentos Biossimilares/farmacocinética , Medicamentos Biossimilares/administração & dosagem , Medicamentos Biossimilares/efeitos adversos , China , População do Leste Asiático , Peptídeos Semelhantes ao Glucagon/farmacocinética , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Fragmentos Fc das Imunoglobulinas/imunologia , Injeções Subcutâneas , Proteínas Recombinantes de Fusão/farmacocinética , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Equivalência TerapêuticaRESUMO
Tertiary lymphoid structure (TLS) contributes to the anti-tumor immune response, and predicts the prognosis of colorectal cancer patients. However, the potential impact of TLS in shaping the immune status of rectal adenocarcinoma, and the intrinsic relationship between TLS and neoadjuvant therapies (neoTx) remain unclear. We performed hematoxylin-eosin staining, immunohistochemical and biomolecular analyses to investigate TLS and tumor-infiltrating lymphocytes (TILs) in 221 neoTx-treated and 242 treatment-naïve locally advanced rectal cancer (LARC) patients. High TLS density was significantly associated with the absence of vascular invasion, a lower neutrophil-to-lymphocyte ratio, increased TLS maturity, a longer recurrence-free survival (RFS) (hazard ratio [HR] 0.2985 95% confidence interval [CI] 0.1894-0.4706, p < 0.0001) and enhanced infiltration of adaptive immune cells. Biomolecular analysis showed that high TLS-score was strongly associated with more infiltration of immune cells and increased activation of immune-related pathways. TLS+ tumors in pre-treatment specimens were associated with a higher proportion of good respond (62.5% vs. 29.8%, p < 0.0002) and pathological complete remission (pCR) (40.0% vs. 11.1%, p < 0.0001), and significantly increased RFS (HR 0.3574 95%CI 0.1489-0.8578 p = 0.0213) compared with TLS- tumors in the neoTx cohort, which was confirmed in GSE119409 and GSE150082. Further studies showed that neoTx significantly reduced TLS density and maturity, and abolished the prognostic value of TLS. Our study illustrates that TLS may have a key role in mediating the T-cell-inflamed tumor microenvironment, which also provides a new direction for neoTx, especially neoadjuvant immunotherapy, in LRAC patients.