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Three ΔI=1 bands with the πg_{9/2}âνg_{9/2} configuration have been identified in _{35}^{74}Br_{39}. Angular distribution, linear polarization, and lifetime measurements were performed to determine the multipolarity, type, mixing ratio, and absolute transition probability of the transitions. By comparing these experimental observations with the corresponding fingerprints and the quantum particle rotor model calculations, the second and third lowest bands are, respectively, suggested as the chiral partner and one-phonon wobbling excitation built on the yrast band. The evidence indicates the first chiral wobbler in nuclei.
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Objective: To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts. Methods: C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry. Results: On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant (Pï¼0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant (Pï¼0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all Pï¼0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8+ T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, Pï¼0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, Pï¼0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, Pï¼0.05]. The proportion, of CD4+ T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, Pï¼0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, Pï¼0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all Pï¼0.05). Conclusion: High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.
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Carcinoma Pulmonar de Lewis , Dieta com Restrição de Carboidratos , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Microambiente Tumoral , Animais , Carcinoma Pulmonar de Lewis/radioterapia , Carcinoma Pulmonar de Lewis/metabolismo , Camundongos , Dieta Hiperlipídica/efeitos adversos , Dieta com Restrição de Carboidratos/métodos , Carga Tumoral , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologiaRESUMO
BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH-induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone-mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage-specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment. METHODS: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and flow cytometry. By constructing myeloid-specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label-free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT-qPCR. RESULTS: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte-derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver-targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA-deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice. CONCLUSIONS: We proposed that the impaired CMA-induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH.
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Autofagia Mediada por Chaperonas , Hepatopatia Gordurosa não Alcoólica , Complexo de Proteínas Formadoras de Poros Nucleares , Animais , Camundongos , Modelos Animais de Doenças , Fibrose , Inflamação/patologia , Fígado/patologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/patologia , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismoRESUMO
Cyanobacterial harmful algal blooms (cHABs) have the potential to adversely affect public health through the production of toxins such as microcystins, which consist of numerous molecularly distinct congeners. Microcystins have been observed in the atmosphere after emission from freshwater lakes, but little is known about the health effects of inhaling microcystins and the factors contributing to microcystin aerosolization. This study quantified total microcystin concentrations in water and aerosol samples collected around Grand Lake St. Marys (GLSM), Ohio. Microcystin concentrations in water samples collected on the same day ranged from 13 to 23 µg/L, dominated by the d-Asp3-MC-RR congener. In particulate matter <2.5 µm (PM2.5), microcystin concentrations up to 156 pg/m3 were detected; the microcystins were composed primarily of d-Asp3-MC-RR, with additional congeners (d-Asp3-MC-HtyR and d-Asp3-MC-LR) observed in a sample collected prior to a storm event. The PM size fraction containing the highest aerosolized MC concentration ranged from 0.44 to 2.5 µm. Analysis of total bacteria by qPCR targeting 16S rDNA revealed concentrations up to 9.4 × 104 gc/m3 in aerosol samples (≤3 µm), while a marker specific to cyanobacteria was not detected in any aerosol samples. Concentrations of aerosolized microcystins varied even when concentrations in water were relatively constant, demonstrating the importance of meteorological conditions (wind speed and direction) and aerosol generation mechanism(s) (wave breaking, spillway, and aeration systems) when evaluating inhalation exposure to microcystins and subsequent impacts on human health.
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Cianobactérias , Proliferação Nociva de Algas , Humanos , Microcistinas/análise , Toxinas de Cianobactérias , Lagos/análise , Lagos/microbiologia , Aerossóis , Água , Atmosfera/análiseRESUMO
Objective: To perform a health economic evaluation of telemedicine diabetic retinopathy (DR) examination with a non-mydriatic fundus camera in China and to investigate the optimal examination interval. Methods: Based on 18 peer-reviewed articles related to epidemiology, clinical trial, and health economic evaluation of DR, surveys from 9 ophthalmologists in 3 tertiary hospitals in China, price lists for medical services in each province, and the negotiated price in 2021, a Markov model was conducted to evaluate the cost utility of telemedicine eye examination for diabetes mellitus patients aged 45 and older from the health system perspective. Separate analyses were performed for no examination and for examination intervals of every 1 to 5 years to predict the lifetime health gain, including cumulative days of blindness, cumulative life years, and quality-adjusted life years (QALYs), and costs for unilateral and bilateral direct medication with a 3.5% discount rate. Results: The cumulative days of blindness in the absence of a DR screening were 2 375.00 days, and ranged from 701.00 to 738.00 days for five different DR screening interval programs. The cumulative life years for no screening and five DR screening programs ranged from 27.120 34 to 28.005 00 years, with QALYs ranging from 9.502 96 to 9.875 02. The direct medication costs in the absence of a DR screening program were 72 785.00 yuan for both unilateral and bilateral scenarios. For the five DR screening intervals, the direct medication costs ranged from 52 065.00 to 52 408.00 yuan for unilateral and 79 100.00 to 79 603.00 yuan for bilateral. Comparing the incremental cost-effectiveness ratios between the DR screening intervals and no screening, the 1-to 5-year intervals were dominant in the unilateral scenario (between -56 368.54 and -55 523.75 yuan/QALY). In the bilateral scenario, the ratios ranged from 17 469.07 to 18 325.15 yuan/QALY. Using a willingness-to-pay threshold equal to the per capita GDP (80 976 yuan/QALY), the 1-year DR screening interval had an 85.9% probability of being cost-effective and a 55.2% probability of being dominant in the unilateral scenario. In the bilateral scenario, the 2-year interval held a 61.4% probability of being cost-effective. Conclusions: Analyses on the remote fundus consultation in diabetic patients and health economics based on the Markov model indicate that telemedicine DR examination through a non-mydriatic fundus camera can be effectively employed for diabetes mellitus patients in China. DR examination every two years is recommended for general diabetic patients, and DR examination every year may be chosen in developed areas.
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Diabetes Mellitus , Retinopatia Diabética , Telemedicina , Humanos , Análise Custo-Benefício , Retinopatia Diabética/diagnóstico , Programas de Rastreamento , Cegueira , ChinaRESUMO
We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.
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Eletricidade , ElétronsRESUMO
A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+Aâν+A) and DM-nucleus 3â2 scattering (χ+χ+AâÏ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3â2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.
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Núcleo Celular , FótonsRESUMO
BACKGROUND: Recent improvement in treatment and patient survival has opened the eligibility of kidney transplantation to patients who developed end-stage kidney disease (ESKD) from plasma cell dyscrasias (PCDs). Data on clinical outcomes in this population are lacking. METHODS: We conducted a retrospective study of United Network for Organ Sharing/Organ Procurement and Transplantation Network dataset (2006-2018) to compare patient and graft outcomes of kidney transplant recipients with ESKD due to PCD versus other causes. RESULTS: Among 168 369 adult first kidney transplant recipients, 0.22-0.43% per year had PCD as the cause of ESKD. The PCD group had worse survival than the non-PCD group for both living and deceased donor types {adjusted hazard ratio [aHR] 2.24 [95% confidence interval (CI) 1.67-2.99] and aHR 1.40 [95% CI 1.08-1.83], respectively}. The PCD group had worse survival than the diabetes group, but only among living donors [aHR 1.87 (95% CI 1.37-2.53) versus aHR 1.16 (95% CI 0.89-1.2)]. Graft survival in patients with PCD were worse than non-PCD in both living and deceased donors [aHR 1.72 (95% CI 1.91-2.56) and aHR 1.30 (95% CI 1.03-1.66)]. Patient and graft survival were worse in amyloidosis but not statistically different in multiple myeloma compared with the non-PCD group. CONCLUSION: The study data are crucial when determining kidney transplant eligibility and when discussing transplant risks in patients with PCD.
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Amiloidose , Falência Renal Crônica , Transplante de Rim , Mieloma Múltiplo , Adulto , Humanos , Estados Unidos/epidemiologia , Transplante de Rim/efeitos adversos , Mieloma Múltiplo/complicações , Estudos Retrospectivos , Sobrevivência de Enxerto , Doadores Vivos , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Amiloidose/complicações , Amiloidose/cirurgia , Resultado do Tratamento , Rejeição de Enxerto/epidemiologiaRESUMO
Objective: To investigate the molecular characteristics of ciprofloxacin-cefotaxime-azithromycin co-resistant Salmonella enterica serovar Thompson (S. Thompson) isolates from sporadic cases of foodborne diseases and aquatic foods in Hunan province. Methods: Ciprofloxacin-cefotaxime-azithromycin co-resistant S. Thompson isolates were selected from samples, and broth microdilution method was used to determine the resistance to 11 antibiotics of these isolates in vitro. Whole genome sequencing was used for investigating antimicrobial resistance gene patterns and phylogenetic relationships of strains. Results: Nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates were recovered from 19 S. Thompson isolates. Among nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates, eight of them harbored IncC plasmids, simultaneously carrying plasmid-mediated quinolone resistance (PMQR) genes qepA and qnrS1, ß-lactamase resistance gene blaCMY-2, azithromycin resistance gene mph(A), and one isolate harbored IncR plasmid, and carried PMQR genes qnrB4 and aac(6')-Ib-cr, blaOXA-10 and mph(A). Genetic environment analysis showed that qnrS1, qepA, mph(A) and blaCMY-2 genes might be integrated on genomes of strains by ISKra4, IS91, IS6100 and ISEcp1, respectively. Phylogenetic core genome comparisons demonstrated that ciprofloxacin-cefotaxime-azithromycin co-resistant isolates from patients and aquatic foods were genetically similar and clustered together. Conclusion: Ciprofloxacin-cefotaxime-azithromycin co-resistant S. Thompson isolates have been isolated from both human and aquatic food samples, suggesting that the spread of multidrug resistant Salmonella between human and aquatic animals.
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Doenças Transmitidas por Alimentos , Quinolonas , Salmonella enterica , Animais , Humanos , Ciprofloxacina , Cefotaxima , Azitromicina , Sorogrupo , Filogenia , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Salmonella , Plasmídeos , Testes de Sensibilidade MicrobianaRESUMO
Objective: To analyze the clinical characteristics of patients with Möbius syndrome (MBS) and to explore likely pathogenic genes. Methods: Cross-sectional study. The study enrolled 18 sporadic MBS patients who visited the Eye Center of Beijing Tongren Hospital Affiliated to Capital Medical University from July 2018 to December 2021. All patients completed the general information questionnaire and underwent detailed ophthalmic examinations and general physical examinations. Seventeen patients received MRI examination of cranial nerves and the orbit. The peripheral venous blood of all patients and their nuclear family members was collected, the genomic DNA was extracted, and the pathogenic gene variations that may lead to MBS were identified by whole exome sequencing and bioinformatics analysis. Results: Among the 18 patients, there were 8 males and 10 females, and the age was (4.5±4.0) years (range, 8 months to 17 years). All patients showed congenital, bilateral or unilateral abduction deficit and facial weakness, which met the minimum diagnostic criteria of MBS. Among them, bilateral abduction deficit (16/18) and bilateral facial weakness (15/18) were more common. Nine patients were orthotopic in primary position, eight presented with esotropia, and one showed hypotropia. All patients had ametropia, of which 4 patients were diagnosed as amblyopia. Fifteen patients were also accompanied by other multiple congenital malformations, mainly characterized by abnormal development of glossopharynx (14/18) and limbs (5/18), and 7 patients were also accompanied by motor retardation. In addition, 9 patients had intrauterine exposure to adverse factors. Among the 17 patients who underwent MRI, 15 patients had bilateral hypoplasia of the abducens nerve, two had unilateral hypoplasia of the abducens nerve, 14 showed bilateral hypoplasia of the facial nerve, and three showed hypoplasia of the left facial nerve. Besides, some patients were also accompanied by hypoplasia of other cranial nerves, mainly the glossopharyngeal nerve and the hypoglossal nerve. No definite pathogenic variations were found by whole exome sequencing and bioinformatics analysis. Conclusions: The main clinical features of MBS were congenital abduction deficit and facial weakness, with complicated manifestations and variable severity. MRI showed absence or thinning of the abducens nerve and the facial nerve. The results of MRI can be used as a supplement to the diagnostic criteria of MBS. The mutation detection rate of MBS was low, and half of patients had exposure to adverse factors during pregnancy, suggesting that there was a multifactorial pathogenic mechanism in MBS.
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Paralisia Facial , Síndrome de Möbius , Estrabismo , Estudos Transversais , Paralisia Facial/congênito , Feminino , Humanos , Lactente , Masculino , Síndrome de Möbius/genética , Sequenciamento do ExomaRESUMO
RATIONALE & OBJECTIVE: Outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) are not well understood. The goal of this study was to investigate the survival and kidney outcomes of these patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients (aged≥18 years) hospitalized with COVID-19 at 13 hospitals in metropolitan New York between March 1, 2020, and April 27, 2020, followed up until hospital discharge. EXPOSURE: AKI. OUTCOMES: Primary outcome: in-hospital death. SECONDARY OUTCOMES: requiring dialysis at discharge, recovery of kidney function. ANALYTICAL APPROACH: Univariable and multivariable time-to-event analysis and logistic regression. RESULTS: Among 9,657 patients admitted with COVID-19, the AKI incidence rate was 38.4/1,000 patient-days. Incidence rates of in-hospital death among patients without AKI, with AKI not requiring dialysis (AKI stages 1-3), and with AKI receiving dialysis (AKI 3D) were 10.8, 31.1, and 37.5/1,000 patient-days, respectively. Taking those without AKI as the reference group, we observed greater risks for in-hospital death for patients with AKI 1-3 and AKI 3D (HRs of 5.6 [95% CI, 5.0-6.3] and 11.3 [95% CI, 9.6-13.1], respectively). After adjusting for demographics, comorbid conditions, and illness severity, the risk for death remained higher among those with AKI 1-3 (adjusted HR, 3.4 [95% CI, 3.0-3.9]) and AKI 3D (adjusted HR, 6.4 [95% CI, 5.5-7.6]) compared with those without AKI. Among patients with AKI 1-3 who survived, 74.1% achieved kidney recovery by the time of discharge. Among those with AKI 3D who survived, 30.6% remained on dialysis at discharge, and prehospitalization chronic kidney disease was the only independent risk factor associated with needing dialysis at discharge (adjusted OR, 9.3 [95% CI, 2.3-37.8]). LIMITATIONS: Observational retrospective study, limited to the NY metropolitan area during the peak of the COVID-19 pandemic. CONCLUSIONS: AKI in hospitalized patients with COVID-19 was associated with significant risk for death.
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Injúria Renal Aguda , COVID-19 , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Diálise Renal , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/terapia , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/fisiopatologia , COVID-19/terapia , Feminino , Humanos , Incidência , Testes de Função Renal/métodos , Testes de Função Renal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Análise de SobrevidaRESUMO
We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.
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We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032+4127 and the other mainly with a pulsar wind nebula PWN G75.2+0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.
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Dog roundworm (Toxocara canis) is the major causative agent of toxocarosis, a parasitic disease of both veterinary and medical importance. Knowledge gaps in fundamental and applied aspects hinder the control of this important zoonotic disease. To have a better understanding of Toxocara infection and host immune responses, mouse macrophages were exposed to excretory/secretory (ES) proteins released by adult worms of T. canis in vitro. The messenger RNA transcription and protein expression of nucleotide-binding oligomerization domain-containing protein 1 (NOD1), receptor interacting protein 2 (RIP2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in macrophages were analysed using quantitative real-time PCR (qRT-PCR) and Western blot. The levels of tumour necrosis factor alpha (TNF-É), interleukin-1 beta (IL-1ß) and IL-6 released by the stimulated macrophages were analysed using enzyme-linked immunosorbent assay. It was found that 20 µg/mL ES proteins of adult T. canis induced the expression of NOD1, RIP2 and NF-κB in mouse macrophages at both transcriptional and translational levels after 9 h of incubation in vitro. Incubation with 20 µg/mL ES proteins also modulated the production of pro-inflammatory cytokines TNF-É, IL-1ß and IL-6 by the macrophages. Taken together, ES proteins of adult T. canis appeared to be able to affect the macrophage NOD1-RIP2-NF-κB signalling pathway, which might play a role in regulating the production of proinflammatory cytokines. Further investigation of these aspects should lead to a better understanding of immune recognition of and modulation by Toxocara canis in host animals.
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Citocinas/biossíntese , Proteínas de Helminto/metabolismo , Macrófagos Peritoneais/metabolismo , Toxocara canis/metabolismo , Animais , Western Blotting , Sobrevivência Celular , Citocinas/metabolismo , Cães , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Helminto/farmacologia , Interleucina-1beta/biossíntese , Interleucina-1beta/metabolismo , Interleucina-6/biossíntese , Interleucina-6/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Toxocara canis/química , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Objective: To evaluate the relationship between serum folate and the prognosis of cervical intraepithelial neoplasia grade I (CIN1) and the interaction between folate and high risk human papillomavirus (HR-HPV) infection. Methods: From a community-based married women cohort established in Jiexiu and Yangqu County of Shanxi Province from June to December 2014, a total of 564 eligible women with CIN1 by pathologically diagnosed were recruited. The pathological examination was performed again 12 months later. According to the prognosis of CIN1, participants were divided into CIN1 regression group, persistence and progression group, respectively. Nested case-control study was used to explore the relationship between serum folate and CIN1 prognosis, and additive model was used to analyze the interaction between serum folate and HR-HPV infection. Results: Among 564 CIN1 patients, 479 cases underwent pathological examination again, 331 were divided in CIN1 regression group and other 148 in persistence and progression group. The levels of serum folate in CIN1 regression group and persistence and progression group were (18.890±8.360) and (15.640±5.550) nmol/L, respectively, and the difference was statistically significant (Z=-6.937, P<0.001). HPV infection was detected in 154 patients, including 148 cases of HR-HPV infection and 6 cases of low risk human papillomavirus (LR-HPV) infection. Univariate analysis showed that there were significant differences in the age, passive smoking, frequency of pudendal cleaning, frequency of cleaning after sex, frequency of changing underwear, serum folate and HR-HPV infection between regression group and persistence and progression group (P<0.05). Multivariate logistic regression analysis showed that the frequency of pudendal cleaning (OR=0.422, 95%CI: 0.238-0.750), frequency of changing underwear (OR=0.574, 95%CI: 0.355-0.928), serum folate (13.06-16.78nmol/L: OR=4.806, 95%CI: 2.355-9.810; ≤13.05nmol/L: OR=8.378, 95%CI: 4.024-17.445), HR-HPV infection (OR=1.852, 95%CI: 1.170-2.933) were the independent influencing factors of CIN1 prognosis. Interaction analysis showed that the relative excess risk of low serum folate level and HR-HPV infection for the CIN1 persistence and progression was 4.992 (95%CI: 0.189-9.796), attributable proportion due to interaction was 0.552 (95%CI: 0.279-0.824), synergy index was 2.632 (95%CI: 1.239-5.588), aOR of serum folate≤16.78 nmol/L and HR-HPV infection positive was 9.055 (95%CI: 4.878-16.807). Conclusion: Low serum folate level could increase the risk of CIN1 persistence and progression, and might enhance the risk when combined with HR-HPV infection.
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Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Estudos de Casos e Controles , Feminino , Ácido Fólico , Humanos , Papillomaviridae/genética , PrognósticoRESUMO
DNA methylation is an essential epigenetic modification involved in numerous biological processes. Here, we present a cell-based system pLTR-Luc2P-EGFP for evaluation of DNA methylation in mammalian cells. In this system, the expression of reporter gene luciferase2P (Luc2P)-EGFP is under the control of HIV-1 promoter 5' long terminal repeat (LTR), which contains multiple CpG sites. Once these sites are methylated, the expression of Luc2P-EGFP is turned off, which may be visualized under fluorescence microscopy, with quantification performed in luciferase activity assay. As a proof of principle, pLTR-Luc2P-EGFP was methylated in vitro, and transfected into 293T cells, where the reduction of Luc2P-EGFP expression was confirmed. Premixed reporter DNA samples with the methylation levels varying from 0 to 100% were used for quantitative measurements of DNA methylation. The resulting standard curves indicated the accuracy of luciferase activity exceeding that of the Western blotting against EGFP. The Bland-Altman analysis showed that data from luciferase activity assay were in good agreement with the actual DNA methylation levels. In summary, we have established a reporter system coupled with reliable detection technique capable of efficient quantifying the changes in methylation in mammalian cells. This system may be utilized as a high throughput screening tool for identifying molecules that modulate DNA methylation.
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Metilação de DNA , Epigênese Genética , Animais , Genes Reporter , Luciferases/genética , Regiões Promotoras GenéticasRESUMO
Auditory brainstem implantation is a hearing restoration technique on the central auditory pathway, which directly stimulates neural tissues of cochlear nucleus by electrode array to produce hearing, so it will not be restricted by abnormalities of the cochlea and cochlear nerve. In the past 30 years since the birth of multi-channel ABI, its indications have expanded from patients with neurofibromatosis type 2 (NF2) to congenital deafness patients with severe inner ear and/or cochlear nerve malformations, and the age of recipients decreases from adults to young children. This article summarizes the principle, indications, surgical techniques, complications and auditory outcomes of ABI.
Assuntos
Implante Auditivo de Tronco Encefálico , Implante Coclear , Surdez , Neurofibromatose 2 , Adulto , Criança , Pré-Escolar , Surdez/cirurgia , Testes Auditivos , Humanos , Neurofibromatose 2/cirurgia , Resultado do TratamentoRESUMO
Objective: To evaluate the diagnosic performance of a novel Mycobacterium tuberculosis (MTB) specific T-cell based assay for tuberculosis, which targets the mRNA detection of interferon gamma-induced protein 10 (IP-10). Methods: Suspected tuberculosis patients were prospectively and consecutively recruited in Beijing Chest Hospital between March 2018 and November 2019, and individuals with lower risk of MTB infection were also recruited. IP-10.TB and T-SPOT.TB assays were simulataneously performed on peripheral blood samples. The diagnostic performance of IP-10.TB and T-SPOT.TB were analyzed using the receiver operating characteristic curve. Accordance of IP-10.TB and T-SPOT.TB was analyzed by Cohen's kappa test, while the correlation between the expression level of IP-10 mRNA in IP-10.TB test and the number of SFCs in T-SPOT.TB test were analyzed by Pearson correlation test. Results: A total of 235 patients with tuberculosis, 110 patients with other diseases and 153 individuals with lower risk of MTB infection were included in the final analysis. No significant difference was detected in the rate of indeterminate results between IP-10.TB assay (3/498, 0.60%) and T-SPOT.TB assay (6/498, 1.21%). The total sensitivity and specificity of IP-10.TB assay were 91.3% (95%CI 86.8%-94.6%) and 81.1% (95%CI 75.8%-85.7%). The specificity of IP-10.TB in individuals with lower risk of MTB infection was 98.0% (95%CI 94.4%-99.6%). The total sensitivity and specificity of T-SPOT.TB assay were 93.0% (95%CI 88.9%-96.0%) and 83.8% (95%CI 78.7%-88.1%). The specificity of T-SPOT.TB in individuals with lower risk of MTB infection was 100% (95%CI 97.6%-100.0%). No significant differences were detected in sensitivity and specificity between IP-10.TB and T-SPOT.TB assays (P>0.05). The positive coincidence rate of these 2 methods was 91.0% (95%CI 87.5%-94.5%), and the negative coincidence rate was 88.9% (95%CI 84.9%-92.9%) and the total coincidence rate was 90.0% (95%CI 87.3%-92.6%). The Cohen's kappa value was 0.80 (95%CI 0.75-0.85, P<0.001) between IP-10.TB and T-SPOT.TB assays. Conclusion: These results showed that the diagnostic performance of IP-10.TB was consistent with that in T-SPOT.TB, and this test could be a novel adjunctive tool for the diagnosis of tuberculosis.
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Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , Interferon gama , Mycobacterium tuberculosis/genética , Sensibilidade e Especificidade , Linfócitos TRESUMO
Objective: To examine the factors influencing the false lumen remodeling of abdominal aortic segment in the midterm and longterm after thoracic endovascular aortic repair (TEVAR). Methods: The data of patients with type B aortic dissection diagnosed and underwent TEVAR at the Department of Vascular and Endovascular Surgery, the First Medical Center, People's Liberation Army General Hospital, from November 2009 to November 2019 were analyzed retrospectively. Patients of acute or subacute long segment dissection with residual tears of abdominal but no thoracic segment and follow-up for more than one year were enrolled. Patients with operation-related complications, and dissection caused by trauma and Marfan syndrome were excluded. A total of 51 patients were enrolled, including 45 males and 6 females, with an age of (49.4±10.6) years (range: 31 to 72 years). The patients included in the analysis were divided into stable and enlarged group. The criteria for inclusion in the enlarged group were any of the following: (1) the maximum growth rate of the abdominal segment false lumen was ≥3 mm/year; (2) the maximum diameter of the abdominal aorta was ≥50 mm; (3) the diameter of the abdominal segment false lumen increased more than 10 mm. χ2 test, t-test and nonparametric test were used for univariate analysis. The variables with P≤0.1 were included in the Logistic multivariate stepwise regression to analyze the independent correlation factors, and the receiver operating characteristic (ROC) curve was used to calculate the cut-off value of the quantitative data. Results: All patients were divided into stable group (n=30) and enlarged group (n=21). The follow-up time of all patients was 42(29) months (range: 12 to 115 months). There were no significant differences in baseline characteristics, endovascular treatment characteristics and postoperative medication between the two groups (P>0.05). Compared with stable group,the number of residual tears around visceral arteries was more (2(1) vs. 1(1), Z=-2.829, P=0.005) and the number of lumbar arteries originating from false lumen was more (5(6) vs. 3(5), Z=-2.025, P=0.043) early after TEVAR in enlarged group. The number of residual tears around visceral arteries (OR=3.966, 95%CI: 1.552 to 10.131, P=0.004) was found to be the independent influence factor for the poor remodeling of the abdominal false lumen in multivariate Logistic regression analysis. ROC curve analysis showed that the cut-off value of the number of residual tears around visceral arteries was 2 at least (area under curve: 0.718). Conclusion: The incidence of poor remodeling of the abdominal false lumen after TEVAR was high. The number of residual tears around visceral arteries (≥2) could be independent influence factor to predict the poor remodeling of abdominal false lumen, and the follow-up of such patients should be strengthened in clinic.
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Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Adulto , Idoso , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
With the development of endovascular technology for peripheral arterial diseases, paclitaxel drug-eluting stents and drug-coated balloons have been widely used in recent years. It has been proved that paclitaxel-coated devices have good clinical effects in reducing vascular restenosis. However, the clinical safety of paclitaxel devices has encountered challenges, some of the studies have shown that paclitaxel-coated devices may increase long-term mortality. In addition, some studies have confirmed the effectiveness and safety of paclitaxel devices, leading to this topic becoming the focus and hot spot of global attention. Whether paclitaxel-coated devices increase the risk of long-term death, whether paclitaxel doses are related to mortality, and the pharmacokinetics of paclitaxel devices should be examined.