RESUMO
Conventionally, women are perceived to feel colder than men, but controlled comparisons are sparse. We measured the response of healthy, lean, young women and men to a range of ambient temperatures typical of the daily environment (17 to 31 °C). The Scholander model of thermoregulation defines the lower critical temperature as threshold of the thermoneutral zone, below which additional heat production is required to defend core body temperature. This parameter can be used to characterize the thermoregulatory phenotypes of endotherms on a spectrum from "arctic" to "tropical." We found that women had a cooler lower critical temperature (mean ± SD: 21.9 ± 1.3 °C vs. 22.9 ± 1.2 °C, P = 0.047), resembling an "arctic" shift compared to men. The more arctic profile of women was predominantly driven by higher insulation associated with more body fat compared to men, countering the lower basal metabolic rate associated with their smaller body size, which typically favors a "tropical" shift. We did not detect sex-based differences in secondary measures of thermoregulation including brown adipose tissue glucose uptake, muscle electrical activity, skin temperatures, cold-induced thermogenesis, or self-reported thermal comfort. In conclusion, the principal contributors to individual differences in human thermoregulation are physical attributes, including body size and composition, which may be partly mediated by sex.
Assuntos
Regulação da Temperatura Corporal , Humanos , Feminino , Masculino , Regulação da Temperatura Corporal/fisiologia , Adulto , Regiões Árticas , Adulto Jovem , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Marrom/metabolismo , Caracteres Sexuais , Fatores Sexuais , Temperatura Corporal/fisiologia , Termogênese/fisiologia , Metabolismo Basal/fisiologiaRESUMO
BACKGROUND: The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression-free survival of 7.5 months in a phase Ib trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial. PATIENTS AND METHODS: This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations. RESULTS: Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders. CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.
Assuntos
Anticorpos Monoclonais Humanizados , Melanoma , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axitinibe/efeitos adversos , Axitinibe/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/cirurgia , Terapia Neoadjuvante/métodos , Estadiamento de NeoplasiasRESUMO
BACKGROUND: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD). OBJECTIVE: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG). METHODS: A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson's Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity. RESULTS: A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups. CONCLUSIONS: An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease. TRIAL REGISTRATION: Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 - Sept 13, 2022.
Assuntos
Dieta Cetogênica , Doença de Parkinson , Humanos , Estudos de Viabilidade , Levodopa , Triglicerídeos , Método Duplo-CegoRESUMO
OBJECTIVES: Low social standing and teasing are independently associated with increased body mass index (BMI) and overeating in children. However, children with low social status may be vulnerable to teasing. METHODS: We tested the statistical interaction of subjective social status (SSS) and subjective socioeconomic status (SSES) and teasing distress on BMI, fat mass index (FMI), and eating in the absence of hunger (EAH) in children (Mage = 13.09 years, SD = 2.50 years; 27.8% overweight/obese). Multiple linear regressions identified the main effects of self-reported SSS (compared to peers in school), distress due to teasing, and theirâ¯interaction on BMI (n = 115), FMI (n = 114), and child- (n = 100) and parent-reported (n = 97) EAH. RESULTS: Teasing distress was associated with greater BMI, FMI, and child-reported EAH due to negative affect (a subscale of EAH) and total EAH scores. There were no associations of SSS with these outcomes. However, there was an interaction between SSS and teasing distress for BMI, FMI, and EAH from negative affect such that lower SSS was associated with higher BMI, FMI, and EAH from negative affect in the presence of teasing distress. However, there were no main effects or interactions (with teasing distress) of SSES on the outcomes. CONCLUSIONS: These findings suggest that the relationship between lower SSS and increased adiposity and overeating behaviors may be exacerbated by other threats to social standing, such as teasing. Children exposed to multiple social threats may be more susceptible to eating beyond physiological need and obesity than those who experience a single form of perceived social disadvantage.
Assuntos
Adiposidade , Índice de Massa Corporal , Autorrelato , Humanos , Feminino , Masculino , Adolescente , Adiposidade/fisiologia , Criança , Bullying/psicologia , Status Social , Fome , Obesidade Infantil/psicologia , Comportamento Alimentar/psicologia , Afeto , Angústia PsicológicaRESUMO
Objective: To analyze the clinical characteristics of patients with common cardiovascular diseases (CVD, including hypertension, coronary heart disease, atrial fibrillation, and heart failure) combined with mild cognitive impairment (MCI) and explore the potential risk factors of MCI in patients with CVD. Methods: A total of 2 294 patients with common cardiovascular diseases who met the criteria at Cardiology Medical Center in Beijing Anzhen Hospital, Capital Medical University, from June 1, 2021, to January 5, 2022, were retrospectively included. The patients were divided into the normal cognitive function group (1 107 cases) and the MCI group (1 187 cases). Demographic information and CVD status were collected. The information of cognitive function were collected using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) scales. The difference between normal cognitive function and MCI were compared and analyzed. The logistic regression analysis was used to explored risk factors of MCI in CVD patients. Results: A total of 2 294 patients aged (60.6±10.4) years were included, among whom there were 29.99% (688 cases) females. Compared with patients in the normal cognitive function group, patients in the MCI group were older [ (57.9±11.4) vs (63.1±8.9) years old, P<0.001], with a higher proportion of women [26.47% (293 cases) vs 33.28% (395 cases), P<0.001]; there was a higher proportion of patients suffering from hypertension in the MCI group [59.62% (660 cases) vs 64.62% (767 cases), P=0.014ï¼½, and more components of CVD [(1.68±0.62) vs (1.74±0.65) components, P=0.017]. The risk factors of MCI in patients with common CVD were increased age, increased depression score, combined with hypertension, and ≥3 common components of CVD, with OR (95%CI) of 1.043 (1.032-1.054), 1.021 (1.004-1.037), 1.151 (1.142-3.439), and 1.137 (1.023-1.797), respectively (all P values <0.05). Increasing education level was observed to be associated with reduced risk of MCI with OR (95%CI) of 0.319 (0.271-0.378) (P<0.05). Conclusions: The incidence of MCI was high in CVD patients. The risk factors of MCI in CVD patients included hypertension and≥3 common components of CVD.
Assuntos
Doenças Cardiovasculares , Disfunção Cognitiva , Hipertensão , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Hipertensão/epidemiologia , CogniçãoRESUMO
Benign tracheal stenosis (BTS) is a refractory disease with a complex pathogenesis and limited therapeutic drug effects. The management of benign tracheal stenosis remains a major challenge for the interventional physiologist. In recent years, the role of infection in the occurrence and development of tracheal stenosis has attracted some attention, but there is still some controversy. A clear understanding of the relationship between infection and tracheal stenosis is essential to elucidate the pathogenic mechanism of BTS, and then to improve early prevention and management of BTS. This article reviewed the research progress on BTS associated with infection to explore new effective interventions that can reduce the BTS.
Assuntos
Infecções , Estenose Traqueal , Humanos , Estenose Traqueal/etiologia , Infecções/complicaçõesRESUMO
Objective: This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB). Methods: The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications. Results: A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines. Conclusion: The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.
Assuntos
Antivirais , Hepatite B Crônica , Guias de Prática Clínica como Assunto , Organização Mundial da Saúde , Humanos , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Adulto , Feminino , Masculino , China/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Idoso , População do Leste AsiáticoRESUMO
BACKGROUND & AIMS: Hepatic energy metabolism is a dynamic process modulated by multiple stimuli. In nonalcoholic fatty liver disease (NAFLD), human studies typically focus on the static fasting state. We hypothesized that unique postprandial alterations in hepatic lipid metabolism are present in NAFLD. METHODS: In a prospective clinical study, 37 patients with NAFLD and 10 healthy control subjects ingested a standardized liquid meal with pre- and postprandial blood sampling. Postprandial plasma lipid kinetics were characterized at the molecular lipid species level by untargeted lipidomics, cluster analysis, and lipid particle isolation, then confirmed in a mouse model. RESULTS: There was a specific increase of multiple plasma diacylglycerol (DAG) species at 4 hours postprandially in patients with NAFLD but not in controls. This was replicated in a nonalcoholic steatohepatitis mouse model, where postprandial DAGs increased in plasma and concomitantly decreased in the liver. The increase in plasma DAGs appears early in the disease course, is dissociated from NAFLD severity and obesity, and correlates with postprandial insulin levels. Immunocapture isolation of very low density lipoprotein in human samples and stable isotope tracer studies in mice revealed that elevated postprandial plasma DAGs reflect hepatic secretion of endogenous, rather than meal-derived lipids. CONCLUSIONS: We identified a selective insulin-related increase in hepatic secretion of endogenously derived DAGs after a mixed meal as a unique feature of NAFLD. DAGs are known to be lipotoxic and associated with atherosclerosis. Although it is still unknown whether the increased exposure to hepatic DAGs contributes to extrahepatic manifestations and cardiovascular risk in NAFLD, our study highlights the importance of extending NAFLD research beyond the fasting state.
Assuntos
Insulinas , Hepatopatia Gordurosa não Alcoólica , Animais , Diglicerídeos/metabolismo , Humanos , Insulinas/metabolismo , Lipidômica , Fígado/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estudos ProspectivosRESUMO
OBJECTIVES: This study aimed to identify and evaluate the short-term and lag effects of environmental factors on asthma hospitalizations in different regions. STUDY DESIGN: The ecological study on asthma is performed in three regions of Guangxi, China, that are distinctly different in geography and climate. METHODS: We used distributed lag non-linear models to investigate the exposure-response-lag relationship between meteorological factors, air pollutants, and asthma hospital admissions across the three regions during 2015 (January 1 to December 31). RESULTS: Cold was an important meteorological factor affecting asthma. At lag 0, the relative risk (RR; 23°C as reference) of cold in the Northwest, Northeast, and South was 1.10 (10°C), 1.14 (8°C), and 1.30 (11°C), respectively. NO2 was identified as the most important air pollutant affecting asthma. The RR of asthma hospitalization increased by 10.9% (at lag 4), 8.1% (at lag 0), and 4.2% (at lag 2) for every 10 µg/m3 increase in NO2 concentration in the Northwest, Northeast, and South, respectively. CONCLUSIONS: In the three regions of Guangxi, there were differences in the dominant factors affecting asthma hospitalizations. Differences in geography can inform governments as to how to prepare the healthcare system to meet the expected peaks.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Humanos , Dióxido de Nitrogênio/efeitos adversos , China/epidemiologia , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Asma/epidemiologia , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Hospitalização , Conceitos Meteorológicos , Material Particulado/análiseRESUMO
Upper eyelid aging with lateral hooding is common among Asian women older than 40 years. Since Asians tend to develop more visible scars than White people, we used an extended upper blepharoplasty technique to correct lateral hooding and conceal the scar, combined with the removal of the thick subbrow skin for women over 60 years of age, to achieve a stable, improved outcome. An extended cutaneous scalpel-shaped excision was designed and hid the extended part of the excision in the patient's upward crow's feet to address the redundant skin of lateral hooding. For patients older than 60 years, we used a crescent-shaped excision and simultaneously removed the thick skin under the eyebrow to reduce the likelihood of long-term postoperative pseudoexcess. A retrospective study was conducted on 40 Asian women who underwent upper eyelid rejuvenation surgery with the above methods from July 2020 to March 2021 (follow-up, 12-15 mo). Extended blepharoplasty notably corrected the lateral hooding and achieved a natural double eyelid. The postoperative scar was inconspicuous. For patients older than 60 years, the long-term rejuvenation outcome was stable when associated with subbrow skin removal. However, two patients older than 60 years in whom the subbrow skin was not removed developed pseudoexcess of the upper eyelid 1 year postoperatively. Extended blepharoplasty is a simple and effective technique for improving periorbital aging in Asian women, and the postoperative scarring was inconspicuous. For patients older than 60 years, we recommend removal of the thick subbrow skin to avoid long-term postoperative pseudoexcess.
Assuntos
Blefaroplastia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Blefaroplastia/métodos , Cicatriz/cirurgia , Pálpebras/cirurgia , Estudos Retrospectivos , Povo AsiáticoRESUMO
Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.
Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/patologia , Células HeLa , Fibronectinas/metabolismo , Meios de Cultivo Condicionados , Carcinoma de Células Escamosas/metabolismo , Caderinas/metabolismo , RNA Mensageiro/metabolismo , Movimento Celular , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Proliferação de Células , Proteína A7 Ligante de Cálcio S100/metabolismoRESUMO
Objective: To investigate the clinicopathological characteristics, immunohistochemical profiles, molecular features, and prognosis of subungual melanoma in situ (SMIS). Methods: Thirty cases of SMIS were collected in Fudan University Shanghai Cancer Center, Shanghai, China from 2018 to 2022. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. By using Vysis melanoma fluorescence in situ hybridization (FISH) probe kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed. Results: There were 8 males and 22 females. The patients' ages ranged from 22 to 65 years (median 48 years). All patients presented with longitudinal melanonychia involving a single digit. Thumb was the most commonly affected digit (16/30, 53.3%). 56.7% (17/30) of the cases presented with Hutchinson's sign. Microscopically, melanocytes proliferated along the dermo-epithelial junction. Hyperchromatism and nuclear pleomorphism were two of the most common histological features. The melanocyte count ranged from 30 to 185. Most cases showed small to medium nuclear enlargement (29/30, 96.7%). Pagetoid spread was seen in all cases. Intra-epithelial mitoses were identified in 56.7% (17/30) of the cases. Involvement of nailfold was found in 19 cases, 4 of which were accompanied by cutaneous adnexal extension. The positive rates of SOX10, PNL2, Melan A, HMB45, S-100, and PRAME were 100.0%, 100.0%, 96.0%, 95.0%, 76.9%, and 83.3%, respectively. FISH analysis was positive in 6/9 of the cases. Follow-up data were available in 28 patients, and all of them were alive without disease. Conclusions: SMIS mainly shows small to medium-sized cells. High melanocyte count, hyperchromatism, nuclear pleomorphism, Pagetoid spreading, intra-epithelial mitosis, nailfold involvement, and cutaneous adnexal extension are important diagnostic hallmarks. Immunohistochemistry including SOX10 and PRAME, combined with FISH analysis, is valuable for the diagnosis of SMIS.
Assuntos
Melanoma , Doenças da Unha , Neoplasias Cutâneas , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Cutâneas/patologia , Prognóstico , Estudos Retrospectivos , Hibridização in Situ Fluorescente , China , Melanoma/diagnóstico , Doenças da Unha/cirurgia , Doenças da Unha/diagnóstico , Doenças da Unha/patologia , Antígenos de NeoplasiasRESUMO
Objective: To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods: A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results: A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion: In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.
Assuntos
Hepatite B Crônica , Humanos , Adulto , Hepatite B Crônica/complicações , Estudos Retrospectivos , Estudos Transversais , Antígenos E da Hepatite B , DNA Viral , Antivirais/uso terapêutico , Vírus da Hepatite B/genética , DemografiaRESUMO
Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.
Assuntos
Hepatite A , Hepatite B Crônica , Hepatite B , Humanos , Masculino , Feminino , Adulto , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Antígenos E da Hepatite B , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B , Cirrose Hepática/tratamento farmacológico , China/epidemiologia , Sistema de Registros , Vírus da Hepatite B/genética , DNA ViralRESUMO
Objective: To investigate the characteristics of spontaneous brain activity in children with congenital cortical cataract amblyopia. Methods: A cross-sectional study was conducted. Twenty cases of unilateral congenital cortical cataract amblyopia (unilateral amblyopia group) and 14 cases of bilateral congenital cortical cataract amblyopia (bilateral amblyopia group) were enrolled from January 2022 to December 2022 at the First Affiliated Hospital of Zhengzhou University. Seventeen age and gender matched children with normal visual acuity were recruited as the healthy control group. Resting-state functional MRI (fMRI) was performed on all participants, and the amplitude of low-frequency fluctuations (ALFF) technique was used to analyze their spontaneous brain activities. The original ALFF value of each voxel was divided by the average ALFF value of the whole brain to obtain the standardized ALFF value (referred to as ALFF value), which reflected the intensity of spontaneous brain activity in different brain regions. General demographic data were compared using one-way analysis of variance, Kruskal-Wallis test, and chi-square test. Comparison of ALFF values was conducted using one-way analysis of variance. Results: There were no significant differences in age, gender, distribution of amblyopic eye or non-dominant eye, and degree of refractive error among the three groups (all P>0.05). Compared to the healthy control group, the unilateral amblyopia group showed higher ALFF values in the right posterior lobe of the cerebellum (67 voxels, t=3.48) and left posterior lobe of the cerebellum (71 voxels, t=4.09), and lower ALFF values in the right postcentral gyrus (91 voxels, t=-3.91), right inferior parietal lobule (73 voxels, t=-4.88), right inferior frontal gyrus (78 voxels, t=-4.09), left inferior parietal lobule (556 voxels, t=-4.82), and left inferior frontal gyrus (122 voxels, t=-4.27) (all P<0.01). The bilateral amblyopia group showed higher ALFF values in the right insula (60 voxels, t=3.54), right Rolandic operculum (69 voxels, t=3.73), right posterior lobe of the cerebellum (54 voxels, t=3.43), and left posterior lobe of the cerebellum (143 voxels, t=3.69), and lower ALFF values in the left inferior frontal gyrus (99 voxels, t=-4.39), left postcentral gyrus (231 voxels, t=-4.28), and right inferior parietal lobule (54 voxels, t=-3.77) (all P<0.01). Compared to the unilateral amblyopia group, the bilateral amblyopia group showed higher ALFF values in the left middle frontal gyrus (52 voxels, t=3.15, P=0.029), left posterior lobe of the cerebellum (77 voxels, t=3.39, P=0.001), and right Rolandic operculum (53 voxels, t=3.59, P=0.007). Conclusion: Children with congenital cortical cataract amblyopia exhibit altered spontaneous brain activity in multiple brain regions, and there are differences in spontaneous brain activity changes between unilateral and bilateral amblyopia.
Assuntos
Ambliopia , Erros de Refração , Criança , Humanos , Encéfalo , Estudos Transversais , Imageamento por Ressonância Magnética/métodos , Masculino , FemininoRESUMO
This paper reported 1 case of poisoning caused by stramonium. Cases of Datura poisoning have been reported nationwide, Its effect on the central nervous system of patients is characterized by first excitation and then inhibition, clinical manifestations include decreased gland secretion, dilated pupils, and tachycardia, etc. Its poisoning mechanism is anticholinergic effect, the effect on Peripheral nervous system is to inhibit Parasympathetic nervous system. Hemoperfusion combined with neostigmine anticholinergic therapy at the early stage of poisoning can effectively improve the clinical symptoms of patients in a short time.
Assuntos
Datura stramonium , Intoxicação por Plantas , Intoxicação , Humanos , Intoxicação por Plantas/diagnóstico , Intoxicação por Plantas/terapia , Antagonistas Colinérgicos/uso terapêutico , Intoxicação/tratamento farmacológicoRESUMO
BACKGROUND: No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only â¼5 months after surgery alone. This phase II trial aimed to compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM. PATIENTS AND METHODS: From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 [95% confidence interval (CI) 8.31-19.02] months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms [hazard ratio (HR) 1.00; 95% CI 0.65-1.54]. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients' actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%). CONCLUSIONS: Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.
Assuntos
Melanoma , Recidiva Local de Neoplasia , Anticorpos Monoclonais Humanizados , Humanos , Interferon alfa-2/uso terapêutico , Interferon-alfa/efeitos adversos , Melanoma/patologia , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
BACKGROUND/OBJECTIVES: Previous research indicates that youth with obesity exhibit deficits in executive functioning (EF), which often take the form of impaired response inhibition. One aspect of EF not previously studied in obesity is the adaptive process known as retrieval-induced forgetting (RIF), the suppression/inhibition of intrusive or non-target items by the retrieval of specific items from memory. The present study investigated if child or adolescent obesity disrupts the ability to inhibit retrieval of intrusive memories. SUBJECTS/METHODS: We compared the manifestation of RIF in children (ages 8-12) and adolescents (ages 13-18) as a function of their weight status and sex. We also evaluated the effects of these variables on simple recall of items from episodic memory under conditions where competition from intrusive items was reduced. RESULTS: Children with obesity did not demonstrate significant RIF, whereas RIF was exhibited by preteens without obesity and by teenage participants with- and without obesity (Weight Status × Age Group interaction p = 0.028). This pattern of results did not differ as a function of sex for either age group. No differences in episodic memory were found. Additional analyses using Age as continuous covariate (and not as a nominal group) comparing participants who exhibited RIF with those who did not, found that the no RIF group consumed fast-food meals more frequently (p = 0.024) and had higher percentages of total body adiposity and android fat compared to the RIF group (p's < 0.05). CONCLUSIONS: The findings expand what is known about the effects of childhood obesity on cognitive functioning, identify impaired RIF with specific behavioral and dietary factors and increased adiposity, and suggest the possibility that impairments in the ability to inhibit intrusive memories of food and eating may contribute to poor early-life weight control.
Assuntos
Memória Episódica , Obesidade Infantil , Adolescente , Criança , Função Executiva/fisiologia , Humanos , Inibição Psicológica , Rememoração Mental/fisiologia , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologiaRESUMO
Sleep has been shown to affect cognitive function in laboratory studies; however, its association to the academic performance of adolescents has largely been demonstrated using self-reported measures. Studies with objective measures of both sleep and academic performance are limited. The aim of the present study was to determine whether the free-living sleep quantity, quality, and timing of 15-year-old adolescents measured with wrist actiography are associated with their scores on national standardised examinations as an objective measure of academic achievement. We measured sleep with wrist actiography for 1 week in 253 (150 girls) Icelandic adolescents with a mean (SD) age of 15.9 (0.3) years. Multiple linear regression was used to assess associations between sleep parameters and combined standardised examination scores in mathematics, English, and Icelandic obtained from the Icelandic Directorate of Education. We found that students went to bed at 00:49 hours (± 51.8 min) and slept for a mean (SD) of 6.6 (0.7) hr/night, with a median (interquartile range) night-to-night variation in sleep duration of 1.2 (0.7) hr and an efficiency of 88.1 (5.3)%. Combined analyses adjusted for sex, demonstrated that both bedtime and night-to-night variability in total sleep time were negatively associated with the average score across all topics. Sex-specific associations did not indicate clear differences between boys and girls. These findings suggest that, in addition to appropriate sleep duration, public health guidance should also highlight the importance of early and consistent sleep schedules to academic achievement for both boys and girls.
Assuntos
Sono , Estudantes , Adolescente , Cognição , Escolaridade , Feminino , Humanos , Masculino , AutorrelatoRESUMO
BACKGROUND: Metabolic disease risk in youth is influenced by sedentary behaviors. Acute in-lab studies show that, during a single day, interrupting a sedentary period with short bouts of physical activity improves glucometabolic outcomes. OBJECTIVE: To determine if acutely improved glucose metabolism persists after multi-day interruptions of sitting with walking brief bouts. We hypothesized that children who underwent interrupting sitting on multiple days would demonstrate lower insulin area under the curve during an oral glucose tolerance test compared to uninterrupted sitting. METHODS: Healthy, normoglycemic children (N = 109) ages 7-11 years were randomized to one of two conditions: Control (3 h of daily Uninterrupted Sitting) or Interrupted Sitting (3-min of moderate-intensity walking every 30 min for 3 h daily); with dietary intake controlled through provision of foodstuffs for the entire experiment. Participants attended six consecutive daily visits at a research ambulatory unit. The primary outcome was insulin area under the curve during the oral glucose tolerance test on day 6 during interrupted or uninterrupted sitting; secondary outcomes included glucose and c-peptide area under the curve, energy intake at a buffet meal on day 6, and free-living activity. RESULTS: Among 93 children (42 uninterrupted sitting, 51 interrupted sitting), daily interrupted sitting resulted in 21% lower insulin (ß = 0.102 CI:0.032-0.172, p = 0.005) and a 10% lower C-peptide (ß = 0.043, CI:0.001-0.084, p = 0.045) area under the curve. Matsuda and Glucose Effectiveness Indices were also improved (p's < 0.05). There were no group differences in energy intake or expenditure. CONCLUSIONS: Sustained behavioral change by interrupting sedentary behaviors is a promising intervention strategy for improving metabolic risk in children.