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OBJECTIVES: To explore parameters that may determine the improvement in C-peptide levels in patients with type 2 diabetes (T2D) receiving continuous subcutaneous insulin infusion (CSII) therapy. METHODS: The trial included a lead-in period for collecting baseline parameters and correcting hyperglycemia, a 4-day CGM period, and a 2-3 weeks treatment period. After screening, patients were hospitalized and randomized to the metformin add-on NovoRapid group or the Prandilin group. Once the glycemic target was reached, all patients underwent a 4-day CGM, with treatments maintained for 2-3 weeks. OGTTs were performed at baseline and endpoint. The primary endpoint was identifying factors contributing to better ß-cell function recovery after CSII therapy. RESULTS: A total of 99 recruited patients were admitted as inpatients and achieved glycemic control within 3.8 ± 1.1 days. Of these, 83 (84 %) patients showed improvement in C-peptide levels, while 16 (16 %) did not show any change in C-peptide levels at the endpoint. Pearson analysis showed a negative correlation between the incremental AUC of glucose concentration (from 0700 to 1000) and the increase in incremental AUC of C-peptide levels (r = -0.199, P < 0.05). CONCLUSIONS: Drug-naïve T2D patients with lower postprandial glucose concentration during CSII therapy exhibit better ß-cell function recovery.
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BACKGROUND: Changes in the oxidative stress and lipid metabolism (OSLM) pathways play important roles in polycystic ovarian syndrome (PCOS) pathogenesis and development. Consequently, a systematic analysis of genes related to OSLM was conducted to identify molecular clusters and explore new biomarkers that are helpful for the diagnostic of PCOS. METHODS: Gene expression and clinical data from 22 PCOS women and 14 normal women were obtained from the GEO database (GSE34526, GSE95728, and GSE106724). Consensus clustering identified OSLM-related molecular clusters, and WGCNA revealed co-expression patterns. The immune microenvironment was quantitatively assessed utilizing the CIBERSORT algorithm. Multiple machine learning models and connectivity map analyses were subsequently applied to explore potential biomarkers for PCOS, and nomograms were employed to develop a predictive multigene model of PCOS. Finally, the OSLM status of PCOS and the hub genes expression profiles were preliminarily verified using TUNEL, qRTâPCR, western blot, and IHC assays in a PCOS mouse model. RESULTS: 19 differential expression genes (DEGs) related to OSLM were identified. Based on 19 DEGs that were strongly influenced by OSLM, PCOS patients were stratified into two distinct clusters, designated Cluster 1 and Cluster 2. Distinct differences in the immune cell proportions existed in normal and two PCOS clusters. The random forest showed the best results, with the least cross-entropy and the utmost AUC (cross-entropy: 0.111 AUC: 0.960). Among the 19 OSLM-related genes, CXCR1, ACP5, CEACAM3, S1PR4, and TCF7 were identified by a Bayesian network and had a good fit with PCOS disease risk by the nomogram (AUC: 0.990 CI: 0.968-1.000). TUNEL assays revealed more severe DNA damage within the ovarian granule cells of PCOS mice than in those of normal mice (P < 0.001). The RNA and protein expression levels of the five hub genes were significantly elevated in PCOS mice, which was consistent with the results of the bioinformatics analyses. CONCLUSION: A novel predictive model was constructed for PCOS patients and five hub genes were identified as potential biomarkers to offer novel insights into clinical diagnostic strategies for PCOS.
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Metabolismo dos Lipídeos , Estresse Oxidativo , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/imunologia , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Estresse Oxidativo/genética , Camundongos , Animais , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Regulação da Expressão Gênica , Biomarcadores/metabolismo , Modelos Animais de Doenças , NomogramasRESUMO
Large prospective studies are required to better elucidate the associations of physical activity, sedentary behaviors (SBs), and sleep with overall cancer and site-specific cancer risk, accounting for the interactions with genetic predisposition. The study included 360,271 individuals in UK Biobank. After a median follow-up of 12.52 years, we found higher total physical activity (TPA) level and higher sleep scores were related to reduced risk of cancer while higher SB level showed a positive association with cancer. Compared with high TPA-healthy sleep group and low SB-healthy sleep group, low TPA-poor sleep group and high SB-poor sleep group had the highest risk for overall cancer, breast cancer, and lung cancer. Adherence to a more active exercise pattern was associated with a lower risk of cancer irrespective of genetic risk. Our study suggests that improving the quality of sleep and developing physical activity habits might yield benefits in mitigating the cancer risk.
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Renal ischemiaâreperfusion injury (IRI) is one of the main causes of acute kidney injury (AKI), which is a potentially life-threatening condition with a high mortality rate. IRI is a complex process involving multiple underlying mechanisms and pathways of cell injury and dysfunction. Additionally, various types of cell death have been linked to IRI, including necroptosis, apoptosis, pyroptosis, and ferroptosis. These processes operate differently and to varying degrees in different patients, but each plays a role in the various pathological conditions of AKI. Advances in understanding the underlying pathophysiology will lead to the development of new therapeutic approaches that hold promise for improving outcomes for patients with AKI. This review provides an overview of the recent research on the molecular mechanisms and pathways underlying IRI-AKI, with a focus on regulated cell death (RCD) forms such as necroptosis, pyroptosis, and ferroptosis. Overall, targeting RCD shows promise as a potential approach to treating IRI-AKI.
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CONTEXT: Sepsis-induced acute lung injury (ALI) is associated with high morbidity and mortality. Rhodiola rosea L. (Crassulaceae) (RR) and its extracts have shown anti-inflammatory, antioxidant, immunomodulatory, and lung-protective effects. OBJECTIVE: This study elucidates the molecular mechanisms of RR against sepsis-induced ALI. MATERIALS AND METHODS: The pivotal targets of RR against sepsis-induced ALI and underlying mechanisms were revealed by network pharmacology and molecular docking. Human umbilical vein endothelial cells (HUVECs) were stimulated by 1 µg/mL lipopolysaccharide for 0.5 h and treated with 6.3, 12.5, 25, 50, 100, and 200 µg/mL RR for 24 h. Then, the lipopolysaccharide-stimulated HUVECs were subjected to cell counting kit-8 (CCK-8), enzyme-linked immunosorbent, apoptosis, and Western blot analyses. C57BL/6 mice were divided into sham, model, low-dose (40 mg/kg), mid-dose (80 mg/kg), and high-dose (160 mg/kg) RR groups. The mouse model was constructed through caecal ligation and puncture, and histological, apoptosis, and Western blot analyses were performed for further validation. RESULTS: We identified six hub targets (MPO, HRAS, PPARG, FGF2, JUN, and IL6), and the PI3K-AKT pathway was the core pathway. CCK-8 assays showed that RR promoted the viability of the lipopolysaccharide-stimulated HUVECs [median effective dose (ED50) = 18.98 µg/mL]. Furthermore, RR inhibited inflammation, oxidative stress, cell apoptosis, and PI3K-AKT activation in lipopolysaccharide-stimulated HUVECs and ALI mice, which was consistent with the network pharmacology results. DISCUSSION AND CONCLUSION: This study provides foundational knowledge of the effective components, potential targets, and molecular mechanisms of RR against ALI, which could be critical for developing targeted therapeutic strategies for sepsis-induced ALI.
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Lesão Pulmonar Aguda , Rhodiola , Sepse , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Lipopolissacarídeos/toxicidade , Simulação de Acoplamento Molecular , Farmacologia em Rede , Estresse Oxidativo , Sepse/complicações , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Células Endoteliais da Veia Umbilical HumanaRESUMO
Aims: This study investigated the nonlinear associations between neutrophil-to-lymphocyte (NLR)/platelet-to-lymphocyte (PLR) and recovery rates in sudden sensorineural hearing loss (SSNHL). Methods: Total of 244 SSNHL patients were included. The primary outcome was recovery rate. Results: A nonlinear association was detected between NLR and recovery rate using the LOWESS method, with a knot of 3. Patients with NLR ≥3 had a higher recovery rate than NLR <3. Using the linear-spline function, NLR was significantly associated with high recovery rate when NLR was <3. However, when NLR was ≥3, this association became nonsignificant. The trend test showed a similar result. PLR was not associated with recovery rate. Conclusion: The association between NLR and recovery rate is nonlinear, with a knot of around three. PLR is not associated with recovery rate.
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Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Neutrófilos , Prognóstico , Contagem de Linfócitos , Estudos Retrospectivos , Linfócitos , PlaquetasRESUMO
Rhizoma Dioscoreae Nipponicae (RDN) is a traditional Chinese medicine that widely applied in the treatment of human diseases. This study aims to explore the therapeutic potential of RDN in asthma and the underlying mechanisms. A mouse model of asthma was established by the stimulation of ovalbumin (OVA). HE staining was performed to detect the pathological injuries of tracheal tissues. The protein expression of collagen I, FN1, α-SMA (airway remodeling markers), and p-p38 (a marker of the p38 MAPK pathway) were detected by Western blot. Eosinophils were then isolated from the model mice. Cell viability and ROS level were measured by CCK-8 and Flow cytometry, respectively. The mRNA expression of GPX4 and ACSL4 (ferroptosis markers) in eosinophils were measured by qRT-PCR. RDN significantly reduced the numbers of total cells and eosnophils in bronchoalveolar lavage fluid (BALF), inhibited inflammatory cell infiltration, and down-regulated remodeling markers (Collagen I, FN1, and α-SMA) in OVA-induced mice. The p38 MAPK pathway was blocked by the intervention of RDN in the model mice, and its blocking weakens the poor manifestations of OVA-induced asthma. In addition, RDN induced the ferroptosis of eosnophils both in vitro and in vivo. Blocking of the p38 MAPK pathway also enhanced the ferroptosis of eosnophils in vitro, evidenced by the decreased cell viability and GPX4 expression, and increased ROS level and ACSL4 expression. RDN induced the ferroptosis of eosinophils through inhibiting the p38 MAPK pathway, contributing to the remission of asthma.
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Asma , Ferroptose , Animais , Humanos , Camundongos , Asma/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças , Eosinófilos/metabolismo , Pulmão/patologia , Ovalbumina/efeitos adversos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
Background: Multiple myeloma (MM) is the second most common haematologic malignancy, presenting a great disease burden on the general population; however, the quality of care of MM is overlooked. We therefore assessed gains and disparity in quality of care worldwide from 1990 to 2019 based on a novel summary indicator - the quality of care index (QCI) - and examined its potential for improvement. Methods: Using the Global Burden of Disease 2019 data set, we calculated the QCI of MM for 195 countries and territories. We used the principal component analysis to extract the first principal component of ratios with the combinations of mortality to incidence, prevalence to incidence, disability-adjusted life years to prevalence, and years of life lost to years lived with disability as QCI. We also conducted a series of descriptive and comparative analyses of QCI disparities with age, gender, period, geographies, and sociodemographic development, and compared the QCI among countries with similar socio-demographic index (SDI) through frontier analysis. Results: The age-standardised rates of MM were 1.92 (95% uncertainty interval (UI) = 1.68, 2.12) in incidence and 1.42 (95% UI = 1.24, 1.52) in deaths per 100 000 population in 2019, and were predicted to increase in the future. The global age-standardised QCI increased from 51.31 in 1990 to 64.28 in 2019. In 2019, New Zealand had the highest QCI at 99.29 and the Central African Republic had the lowest QCI at 10.74. The gender disparity of QCI was reduced over the years, with the largest being observed in the sub-Saharan region. Regarding age, QCI maintained a decreasing trend in patients aged >60 in SDI quintiles. Generally, QCI improved with the SDI increase. Results of frontier analysis suggested that there is a potential to improve the quality of care across all levels of development spectrum. Conclusions: Quality of care of MM improved during the past three decades, yet disparities in MM care remain across different countries, age groups, and genders. It is crucial to establish local objectives aimed at enhancing MM care and closing the gap in health care inequality.
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Carga Global da Doença , Mieloma Múltiplo , Humanos , Masculino , Feminino , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Efeitos Psicossociais da Doença , Prevalência , Incidência , Qualidade da Assistência à Saúde , Saúde GlobalRESUMO
As an inexpensive industrial chemical, chlorodifluoromethane (Freon-22), despite its relatively low reactivity, can serve as a practical CF2 source for the construction of gem-difluorinated ring structures. Here, we develop a protocol for the efficient assembly of valuable fluorinated 2,3-dihydrobenzofurans from the [4 + 1] annulation in good yields under basic conditions. The reliable practicability and scalability of the process have also been demonstrated by preparation at the multigram scale, late-stage modifications of pharmaceutical molecules, and potential antitumor potency.
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Benzofuranos , Clorofluorcarbonetos de Metano , Clorofluorcarbonetos , Hidrocarbonetos FluoradosRESUMO
BACKGROUND: Both genetic and dietary factors play significant roles in the etiology of colorectal cancer (CRC). To evaluate the relationship between certain food exposures and the risk of CRC, we carried out a large-scale association analysis in the UK Biobank. METHODS: The associations of 139 foods and nutrients' intake with CRC risk were assessed among 118,210 participants. A polygenic risk score (PRS) of CRC was created to explore any interaction between dietary factors and genetic susceptibility in CRC risk. The hazard ratio (HR) and 95% confidence interval (CI) of CRC risk linked to dietary variables and PRS were estimated using Cox regression models. Multiple comparisons were corrected using the error discovery rate (FDR). RESULTS: During a mean follow-up of 12.8 years, 1466 incidents of CRC were identified. In the UK Biobank, alcohol and white bread were associated with increased CRC risk, and their HRs were 1.08 (95% CI: 1.03-1.14; FDRP = 0.028) and 1.10 (95% CI: 1.05-1.16; FDRP = 0.003), whereas dietary fiber, calcium, magnesium, phosphorus, and manganese intakes were inversely associated. We found no evidence of any PRS-nutrient interaction relationship in relation to CRC risk. CONCLUSIONS: Our results show that higher intakes of alcohol and white bread are associated with increased CRC risk, whilst dietary fiber, calcium, magnesium, phosphorus, and manganese are inversely associated.
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Cálcio , Neoplasias Colorretais , Humanos , Estudos Prospectivos , Magnésio , Manganês , Predisposição Genética para Doença , Dieta/efeitos adversos , Fatores de Risco , Fibras na Dieta , Cálcio da Dieta , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , FósforoRESUMO
Background: Due to their known variation by geography and economic development, we aimed to evaluate the incidence and mortality of colorectal cancer (CRC) in China over the past decades and identify factors associated with CRC among the Chinese population to provide targeted information on disease prevention. Methods: We conducted a systemic review and meta-analysis of epidemiolocal studies on the incidence, mortality, and associated factors of CRC among the Chinese population, extracting and synthesising data from eligible studies retrieved from seven global and Chinese databases. We pooled age-standardised incidence rates (ASIRs) and mortality rates (ASMRs) for each province, subregion, and the whole of China, and applied a joinpoint regression model and annual per cent changes (APCs) to estimate the trends of CRC incidence and mortality. We conducted random-effects meta-analyses to assess the effect estimates of identified associated risk factors. Results: We included 493 articles; 271 provided data on CRC incidence or mortality, and 222 on associated risk factors. Overall, the ASIR of CRC in China increased from 2.75 to 19.39 (per 100 000 person-years) between 1972 and 2019 with a slowed-down growth rate (APC1 = 5.75, APC2 = 0.42), while the ASMR of CRC decreased from 12.00 to 7.95 (per 100 000 person-years) between 1974 and 2020 with a slight downward trend (APC = -0.89). We analysed 62 risk factors with synthesized data; 16 belonging to the categories of anthropometrics factors, lifestyle factors, dietary factors, personal histories and mental health conditions were graded to be associated with CRC risk among the Chinese population in the meta-analysis limited to the high-quality studies. Conclusions: We found substantial variation of CRC burden across regions and provinces of China and identified several associated risk factors for CRC, which could help to guide the formulation of targeted disease prevention and control strategies. Registration: PROSPERO: CRD42022346558.
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Neoplasias Colorretais , Humanos , Incidência , Fatores de Risco , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controleRESUMO
Alkali-activated slag (AAS) presents a promising alternative to ordinary Portland cement due to its cost effectiveness, environmental friendliness, and satisfactory durability characteristics. In this paper, cow dung waste was recycled as a renewable natural cellulose fiber, modified with alkali, and then added to AAS mortar. The physico-chemical characteristics of raw and modified cow dung fibers were determined through Fourier transform infrared (FTIR), X-ray diffraction (XRD), and Scanning electron microscope (SEM). Investigations were conducted on the dispersion of cow dung fibers in the AAS matrix, as well as the flowability, strength, and autogenous shrinkage of AAS mortar with varying cow dung fiber contents. The results indicated that modified fiber has higher crystallinity and surface roughness. The ultrasonic method showed superior effectiveness compared to pre-mixing and after-mixing methods. Compared with raw cow dung fibers, modified fibers led to an increase of 11.3% and 36.3% of the 28 d flexural strength and compressive strength of the AAS mortar, respectively. The modified cow dung fibers had a more significant inhibition on autogenous shrinkage, and the addition of 2 wt% cow dung fibers reduced the 7 d autogenous shrinkage of the AAS paste by 52.8% due to the "internal curing effect." This study provides an alternative value-added recycling option for cow dung fibers as a potential environmentally friendly and sustainable reinforcing raw material for cementitious materials, which can be used to develop low autogenous shrinkage green composites.
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OBJECTIVE: The aim of this study is to investigate potential risk factors associated with peripheral nervous system lesions in primary Sjögren's syndrome (pSS) through a retrospective analysis of clinical manifestations, examination characteristics, and clinical electrophysiological features. MATERIALS AND METHODS: A retrospective case-control study was conducted at Nanfang Hospital, including 108 patients diagnosed with pSS following the criteria revised by the American College of Rheumatology in 2016. The study spanned from January 2015 to October 2020. The patient cohort was divided into two groups, an experimental group (N = 27) consisting of patients with primary Sjögren's syndrome-peripheral nervous system lesions (pSS-PNS), and a control group (N = 81) comprising patients without peripheral neurological impairment, i.e., primary Sjögren's syndrome-non peripheral nervous system lesions (pSS-nPNS). RESULTS: The results showed a significant correlation between immunoglobulin G (IgG), α-Fodrin immunoglobulin G (α-FIgG), platelet counts (PLT), dry mouth and peripheral neuropathy of Sjogren's syndrome (p < 0.01). The research also revealed that α-FIgG (OR 2.03; 95% CI 1.14-3.64), IgG (OR 1.23; 95% CI 1.06-1.42), and PLT (OR 1.01; 95% CI 1.00-1.01) were identified as risk factors for the onset of peripheral neuropathy of Sjogren's syndrome, while dry mouth had a negative correlation (OR 0.08; 95% CI 0.02-0.40). Remarkably, the total risk assessment of the independent variables demonstrated a high AUC (95%CI) of 0.923 (0.861-0.986; p < 0.001), indicating an excellent prediction of pSS-PNS occurrence through the ROC analysis. Additionally, high platelet counts and strong positive anti-SSB antibody titer were found to be risk factors for dual motor and sensory nerve damages among pSS-PNS patients. CONCLUSION: IgG, α-FIgG, and PLT were identified as independent risk factors for patients with pSS-PNS. The likelihood of peripheral neuropathy appeared to increase in tandem with the elevated levels of above three factors. Interestingly, we found that dry mouth might play a protective role in this context. Our study further noted that both high platelet counts and strong positive anti-SSB antibody titer may be associated with increased risk of both motor and sensory nerve involvement in pSS-PNS patients. These findings have significant implications for both the etiologies and therapeutics of pSS-PNS.
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Diabetic foot ulcer often leads to amputation, and both nutritional status and immune function have been associated with this process. We aimed to investigate the risk factors of diabetic ulcer-related amputation including the Controlling Nutritional Status score and neutrophil-to-lymphocyte ratio biomarker. We evaluated data from hospital in patients with diabetic foot ulcer, performing univariate and multivariate analyses to screen for high-risk factors and Kaplan-Meier analysis to correlate high-risk factors with amputation-free survival. Overall, 389 patients underwent 247 amputations over the follow-up period. After correction to relevant variables, we identified five independent risk factors for diabetic ulcer-related amputation: ulcer severity, ulcer site, peripheral arterial disease, neutrophil-to-lymphocyte ratio and nutritional status. Amputation-free survival was lower for the moderate-to-severe versus mild cases, for the plantar forefoot versus hindfoot location, for the concomitant peripheral artery disease versus without and in the high versus low neutrophil-to-lymphocyte ratio (all p < 0.01). The results showed that ulcer severity (p < 0.01), ulcer site (p < 0.01), peripheral artery disease (p < 0.01), neutrophil-to-lymphocyte ratio (p < 0.01) and Controlling Nutritional Status score (p < 0.05) were independent risk factors for amputation in diabetic foot ulcer patients and have predictive values for diabetic foot ulcer progression to amputation.
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Diabetes Mellitus , Pé Diabético , Doença Arterial Periférica , Humanos , Pé Diabético/complicações , Estado Nutricional , Neutrófilos , Fatores de Risco , Linfócitos , Amputação Cirúrgica , Doença Arterial Periférica/complicações , Estudos RetrospectivosRESUMO
Objective: To investigate the feasibility of multimodal regimen by paracetamol, gabapentin, ketamine, lidocaine, dexmedetomidine and sufentanil among cardiac surgery patients, and compare the analgesia efficacy with conventional sufentanil-based regimen. Design: A single-center, prospective, randomized, controlled clinical trial. Setting: One participating center, the cardiovascular center of the major integrated teaching hospital. Participants: A total of 115 patients were assessed for eligibility: 108 patients were randomized, 7 cases were excluded. Interventions: The control group (group T) received conventional anesthesia management. Interventions in the multimodal group (group M) were as follows in addition to the standard of care: gabapentin and acetaminophen 1 hour before surgery; ketamine for induction and to maintain anesthesia with lidocaine and dexmedetomide. Ketamine, lidocaine, and dexmedetomidine were added to routine sedatives postoperatively in group M. Measurements and Main Results: The incidence of moderate-to-severe pain on coughing made no significant difference (68.5% vs 64.8%, P=0.683). Group M had significantly less sufentanil use (135.72µg vs 94.85µg, P=0.000) and lower rescue analgesia rate (31.5% vs 57.4%, P=0.007). There was no significant difference in the incidence of chronic pain, PONV, dizziness, inflammation index, mechanical ventilation time, length of stay, and complications between the two groups. Conclusion: Our multimodal regimen in cardiac surgery is feasible, but was not superior to traditional sufentanil-based regimen in the aspects of analgesia effects; however, it did reduce perioperative opioid consumption along with rescue analgesia rate. Moreover, it showed the same length of stay and the incidences of postoperative complications.
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Analgesia , Procedimentos Cirúrgicos Cardíacos , Dor Crônica , Dexmedetomidina , Ketamina , Humanos , Sufentanil , Gabapentina , Estudos Prospectivos , Lidocaína , AcetaminofenRESUMO
Previous studies reported human immunodeficiency virus (HIV) could enhance human papillomavirus (HPV)-induced cervical cancer. Therefore, the burden of cervical cancer associated with HIV across different regions and time periods need to be assessed. We aim to investigate the global burden of cervical cancer associated with HIV infection. Age standardized rates (ASRs) of cervical cancer disability-adjusted life-years (DALYs) in females (≥15 years old) were calculated by standardization, according the age-specific DALYs numbers extracted from GBD data set 2019. Population attributable fractions was calculated by combining the published risk ratio, with the HIV prevalence (≥15 years old) from Joint United Nations Programme on HIV and AIDS (UNAIDS), and transferred to estimate the HIV-associated cervical cancer burden. Expected annual percentage changes (EAPCs) was calculated to describe the temporal trend of ASR from 1990 to 2019. Pearson correlation analysis were conducted to assess the correlation between the ASR or EAPCs and the socio-demographic index. The worldwide DALYs ASR caused by HIV-associated cervical cancer rose from 3.78 (95% confidence interval [CI]: 2.19-5.56) in 1990 to 9.50 (95% CI: 5.66-13.79) in 2019 per 100k population. In 2019, the region with the greatest burden was Eastern and Southern Africa, with the highest DALYs of 273 900 (95% CI: 149 100-476 400) and ASR of 254.44 per 100k population (95% CI: 168.86-329.28). Notably, the Eastern Europe and Central Asia regions had the highest EAPC (14.07%) of HIV-associated DALYs ASR. Women in Eastern and Southern Africa experience the greatest burden of HIV-associated cervical cancer, while the Eastern Europe and Central Asia regions had witnessed the largest increase over the last 30 years. Prioritize the promotion of HPV vaccination and cervical cancer screening for women living with HIV were crucial in these regions.
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Infecções por HIV , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Adolescente , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Carga Global da Doença , Detecção Precoce de Câncer , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , HIV , Saúde GlobalRESUMO
BACKGROUND: Previous studies of the relationships between traits have focused on the natural growth conditions of wild plants. Urban garden plants exhibit some differences in plant traits due to environmental interference. It is unknown whether the relationships between the leaf traits of urban garden plants differ under distinct climates. In this study, we revealed the variation characteristics of the leaf functional traits of trees, shrubs, and vines in two urban locations. Two-way ANOVA was used to reveal the response of plant leaf traits to climate and life forms. Pearson correlation analysis and principal component analysis were used to calculate the correlation coefficient between the leaf functional traits of plants at the two locations. RESULTS: Leaf dry matter content (LDMC) and vein density (VD) of different life forms in Mudanjiang were higher than those in Bozhou (P < 0.05), and the relative water content (RWC) in Bozhou was higher, whereas vein density (VD) of trees and shrubs in the two urban locations was significant (P < 0.05), but the vines were not significant. The photosynthetic pigments of tree and shrub species were larger in Mudanjiang, but the opposite was true for the vines. Both leaf vein density (VD) and stomatal density (SD) showed a very significant positive correlation in the two urban locations (P < 0.01), and both were significantly positively correlated with specific leaf area (SLA) (P < 0.05); and negatively correlated with leaf thickness (LT), and the relationship between pigment content were closer. CONCLUSION: The response to climate showed obvious differences in leaf traits of different life forms species in urban area, but the correlations between the traits showed convergence, which reflects that the adaptation strategies of garden plant leaves to different habitats are both coordinated and relatively independent.
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Aclimatação , Jardins , Árvores , China , Folhas de PlantaRESUMO
Artificial intelligence has quickly integrated into human society and its moral decision-making has also begun to slowly seep into our lives. The significance of moral judgment research on artificial intelligence behavior is becoming increasingly prominent. The present research aims at examining how people make moral judgments about the behavior of artificial intelligence agents in a trolley dilemma where people are usually driven by controlled cognitive processes, and in a footbridge dilemma where people are usually driven by automatic emotional responses. Through three experiments (n = 626), we found that in the trolley dilemma (Experiment 1), the agent type rather than the actual action influenced people's moral judgments. Specifically, participants rated AI agents' behavior as more immoral and deserving of more blame than humans' behavior. Conversely, in the footbridge dilemma (Experiment 2), the actual action rather than the agent type influenced people's moral judgments. Specifically, participants rated action (a utilitarian act) as less moral and permissible and more morally wrong and blameworthy than inaction (a deontological act). A mixed-design experiment provided a pattern of results consistent with Experiment 1 and Experiment 2 (Experiment 3). This suggests that in different types of moral dilemmas, people adapt different modes of moral judgment to artificial intelligence, this may be explained by that when people make moral judgments in different types of moral dilemmas, they are engaging different processing systems.
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BACKGROUND: Increasingly, studies have discovered that different fatty acids (Fas) are linked to colorectal cancer (CRC) risk. METHODS: We systematically searched Embase and Medline databases to identify eligible studies that examined the associations of different types of Fas with CRC risk. The effect estimates and their 95% confidence intervals (Cis) were pooled using a random-effects model. Subgroup and sensitivity analyses were performed to examine the robustness of the study findings. RESULTS: This study evaluated the associations of 28 dietary and 18 blood Fas with CRC risk by summarizing the most updated evidence from 54 observational and four Mendelian Randomization (MR) studies. The present findings suggested that high dietary intake of eicosapentaenoic acid (EPA), docosahexanoic acid (DHA), and docosapentaenoic acid (DPA) are related to low risk of CRC, while the n-6/n-3 PUFA ratio and trans-FA are related to high risk of CRC. The summary of all cohort studies found that a high intake of SFA and DHA was a protective factor for CRC, and a high intake of the n-6/n-3 PUFA ratio was a risk factor for CRC. In the subgroup analysis of cancer subsites, we found that the dietary intake of linoleic acid (LA) and trans-FA are risk factors, while DPA is a protective factor for colon cancer. High dietary DHA intake was associated with a lower risk of rectal cancer, while the dietary n-6/n-3 PUFA ratio was associated with a higher risk of rectal cancer. Meta-analysis of blood FA levels showed a significant reverse association between blood pentadecanoic acid and CRC risk, whilst other blood Fas showed no significant association with CRC risk. All included MR studies showed that high plasma arachidonic acid (AA) is associated with increased CRC risk. CONCLUSIONS: Current evidence on the dietary intake and blood levels of Fas in relation to CRC risk is less consistent. Future studies are needed to investigate how the metabolism of Fas contributes to CRC development.
Assuntos
Neoplasias Colorretais , Ácidos Graxos Ômega-3 , Neoplasias Retais , Humanos , Ácidos Graxos , Ingestão de Alimentos , Fatores de Risco , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Estudos Observacionais como AssuntoRESUMO
AIM: The urokinase plasminogen activator receptor (uPAR) is a promising biomarker for cancer diagnosis and therapy. We herein fabricated a new type of uPAR-targeted imaging probe Al18F-NOTA-VC and preliminarily evaluated its potential application in PET imaging of the glioma model in vivo. METHODS: Peptide VC was synthesized and identified by MALDI-TOF-MS. The IC50 between VC/precursor NOTA-VC and uPAR was then determined before the synthesis and purification of Al18F-NOTA-VC, followed by further studies of in-vitro properties of Al18F-NOTA-VC. Meanwhile, the AE105-based probe followed a similar procedure in-vitro test. Finally, the PET imaging properties, including uPAR-targeting ability and the metabolism of Al18F-NOTA-VC, were investigated. RESULTS: The VC and NOTA-VC were obtained successfully and demonstrated a good affinity with uPAR. Followed by Al18F labeling successfully, excellent properties, including the serum stability, water solubility, and specificity of Al18F-NOTA-VC, were obtained in-vitro test compared with AE105 based probe. An excellent tumor uptake and renal excretion data of Al18F-NOTA-VC were acquired from in-vivo U87MG tumor model PET imaging, consistent with the subsequent biodistribution study. CONCLUSION: In addition to the excellent specificity and high tumor/normal tissue contrast for uPAR-targeted PET imaging of U87MG tumor, Al18F-NOTA-VC possessed promising clearance ability by renal system route. These excellent properties facilitated Al18F-NOTA-VC to be a promising imaging agent for uPAR high-expressing tumors and, thus, provided a paradigm for developing peptide-based probes for uPAR-associated disease diagnosis.