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STUDY OBJECTIVE: Hyperlipidemia and postoperative delirium (POD) significantly affect patients' quality of life; however, the question of whether hyperlipidemia constitutes a risk factor for POD remain unclear. This study aimed to investigate whether patients with hyperlipidemia face elevated risks of developing POD and to identify potential causes for this increased risk. DESIGN: A prospective cohort study. SETTING: Operating room. PATIENTS: Patients were adults scheduled for colorectal cancer surgery in 2023. EXPOSURES: The exposure factor was hyperlipidemia, and the patients were divided into hyperlipidemia group and non-hyperlipidemia group. MEASUREMENTS: POD occurrence within three days post-surgery was assessed using the 3-Minute Diagnostic Interview for Confusion Assessment Method. Over one year, these patients were monitored through telephone to evaluate their survival and cognitive function. Logistic regression analysis was performed to evaluate the risk factors for POD development in patients with hyperlipidemia and to construct a clinical prediction model. MAIN RESULTS: This study included 555 patients. POD incidence was 21.6% in the hyperlipidemia group and 12.7% in the non-hyperlipidemia group. One year following surgery, patients with hyperlipidemia and POD exhibited significantly higher rates of mortality and cognitive decline than did those without POD (p < 0.001). A multifactorial logistic clinical prediction model was constructed from seven independent risk factors for POD development in patients with hyperlipidemia, including education, preoperative total cholesterol (TC), preoperative triglyceride (TG), diet, history of hypertension, Sedation-Agitation Scale, and postoperative trimethylamine N-oxide expression level, and it had the highest predictive value for POD development in patients with hyperlipidemia. CONCLUSIONS: Compared with those without hyperlipidemia, patients with hyperlipidemia had higher POD incidence. Elevated serum TC and TG levels are independent risk factors for POD in patients with hyperlipidemia. The study's findings could help develop strategies for improving POD and hyperlipidemia treatment.
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OBJECTIVE: With the improvement of medical level, the number of elderly patients is increasing, and the postoperative outcome of the patients cannot be ignored. However, there have been no studies on the relationship between preoperative heart rate variability (HRV) and Perioperative Neurocognitive Disorders (PND). The purpose of this study was to explore the correlation between (HRV) and (PND), postoperative intensive care unit (ICU), and hospital stay in patients undergoing non-cardiac surgery. METHOD: This retrospective analysis included 687 inpatients who underwent 24-hour dynamic electrocardiogram examination in our six departments from January 2021 to January 2022. Patients were divided into two groups based on heart rate variability (HRV): high and low. Possible risk factors of perioperative outcomes were screened using univariate analysis, and risk factors were included in multivariate logistic regression to screen for independent risk factors. The subgroup analysis was carried out to evaluate the robustness of the results. The nomogram of PND multi-factor logistic prediction model was constructed. The receiver operating characteristic (ROC) curve was drawn, and the calibration curve was drawn by bootstrap resampling 1000 times for internal verification to evaluate the prediction ability of nomogram. RESULT: A total of 687 eligible patients were included. The incidence of low HRV was 36.7% and the incidence of PND was 7.6%. The incidence of PND in the low HRV group was higher than that in the high HRV group (11.8% vs 5.2%), the postoperative ICU transfer rate was higher (15.9% than 9.3%P = 0.009), and the hospital stay was longer [15 (11, 19) vs (13), 0.015]. The multivariable logistic regression analysis showed that after adjusting for other factors, decreased low HRV was identified as an independent risk factor for the occurrence of PND (Adjusted Odds Ratio = 2.095; 95% Confidence Interval: 1.160-3.784; P = 0.014) and postoperative ICU admission (Adjusted Odds Ratio = 1.925; 95% Confidence Interval: 1.128-3.286; P = 0.016). This study drew a nomogram column chart for a multivariate logistic regression model, incorporating age and HRV. The calibration curve shows that the predicted value of the model for the occurrence of cardio-cerebrovascular events is in good agreement with the actual observed value, with C-index of 0.696 (95% CI: 0.626 ~ 0.766). Subgroup analysis showed that low HRV was an independent risk factor for PND in patients with gastrointestinal surgery and ASA â ¢, aged ≥ 65 years. CONCLUSION: In patients undergoing non-cardiac surgery, the low HRV was an independent risk factor for PND and postoperative transfer to the ICU, and the hospitalization time of patients with low HRV was prolonged. Through establishing a risk prediction model for the occurrence of PND, high-risk patients can be identified during the perioperative period for early intervention.
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Neurocognitive Disorders , Nomograms , Aged , Humans , Retrospective Studies , Heart Rate , Risk FactorsABSTRACT
BACKGROUND: Vaccination has been proven effective against infection with enterovirus A71 (EV-A71) in clinical trials, but vaccine effectiveness in real-world situations remains incompletely understood. Furthermore, it is not clear whether previous vaccination will result in symptom attenuation among post-vaccinated cases. METHODS: Based on long-term data extracted from the only designed referral hospital for infectious diseases, we used a test-negative case-control design and multivariate logistic regression models to analyze the effectiveness of EV-A71 vaccine against hand, foot and mouth disease (HFMD). And then, generalized linear regression models were used to evaluate the associations between prior vaccination and disease profiles. RESULTS: We selected 4883 inpatients for vaccine efficacy estimations and 2188 inpatients for disease profile comparisons. Vaccine effectiveness against EV-A71-induced HFMD for complete vaccination was 63.4 % and 51.7 % for partial vaccination. The vaccine effectiveness was higher among cases received the first dose within 12 months. No protection was observed against coxsackievirus (CV) A6-, CV-A10- or CV-A16-associated HFMD among children regardless of vaccination status. Completely vaccinated cases had shorter hospital stay and disease course compared to unvaccinated cases (P < 0.05). CONCLUSIONS: These findings reiterate the need to continue the development of a multivalent vaccine or combined vaccines, and have implications for introducing optimized vaccination strategies.
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Communicable Diseases , Enterovirus A, Human , Enterovirus Infections , Enterovirus , Hand, Foot and Mouth Disease , Viral Vaccines , Child , Humans , Hand, Foot and Mouth Disease/prevention & control , Enterovirus Infections/prevention & control , Vaccination , Antibodies, Viral , Antigens, Viral , Vaccines, Combined , ChinaABSTRACT
OBJECTIVE: To screen the independent influencing factors of restoration of spontaneous circulation (ROSC) in patients after cardiopulmonary resuscitation (CPR) and establish a predictive model, and explore its clinical value. METHODS: A retrospective case control study was conducted. The clinical data of cardiac arrest patients admitted to the emergency department of Tangdu Hospital of Air Force Military Medical University and received CPR from January to July 2023 were analyzed, including general information, blood biochemical indicators, main cause of cardiac arrest, whether it was defibrillation rhythm, duration from admission to CPR, and whether ROSC was achieved. The clinical data between the patients whether achieved ROSC or not were compared. The binary multivariate Logistic regression analysis was used to screen the independent influencing factors of ROSC in in-hospital CPR patients. According to the above influencing factors, the ROSC prediction model was established, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of the model for ROSC. RESULTS: A total of 235 patients who received CPR in the emergency department were enrolled, including 153 cases (65.11%) of in-hospital CPR and 82 cases (34.89%) of out-of-hospital CPR. The ROSC ratio was 30.21% (71/235). Among all patients, the majority were aged 61-80 years [40.43% (95/235)], and cardiogenic disease was the main cause of cardiac arrest [32.77% (77/235)]. Among 153 patients with in-hospital CPR, 89 were non-ROSC and 64 were ROSC with ROSC rate of 41.83%. Compared with the non-ROSC group, the patients in the ROSC group had lower blood lactic acid (Lac), N-terminal pro-brain natriuretic peptide (NT-proBNP), Lac/albumin (Alb) ratio (LAR), and ratio of non-defibrillation rhythm [Lac (mmol/L): 5.50 (2.33, 9.65) vs. 7.10 (3.50, 13.35), NT-proBNP (µg/L): 0.87 (0.20, 8.68) vs. 3.00 (0.58, 20.17), LAR: 0.14 (0.07, 0.29) vs. 0.19 (0.10, 0.43), non-defibrillation rhythm ratio: 68.75% (44/64) vs. 93.26% (83/89)], higher actual base excess (ABE) and Alb [ABE (mmol/L): -3.95 (-12.75, 0.23) vs. -7.50 (-13.50, -3.35), Alb (g/L): 38.13±7.03 vs. 34.09±7.81], and shorter duration from admission to CPR [hours: 3.25 (1.00, 14.00) vs. 8.00 (2.00, 27.50)], the differences were statistically significant (all P < 0.05). Binary multivariate Logistic regression analysis showed that LAR [odds ratio (OR) = 0.037, 95% confidence interval (95%CI) was 0.005-0.287], non-defibrillation rhythm (OR = 0.145, 95%CI was 0.049-0.426), and duration from admission to CPR (OR = 0.984, 95%CI was 0.972-0.997) were independent influencing factors for ROSC in hospitalized CPR patients (all P < 0.05). Based on the above influencing factors, a ROSC prediction model was constructed through regression analysis results. The ROC curve analysis showed that the area under the ROC curve (AUC) for predicting ROSC in in-hospital CPR patients was 0.757 (95%CI was 0.680-0.834), Yoden index was 0.429, sensitivity was 76.6%, and specificity was 66.3. CONCLUSIONS: LAR, non-defibrillation rhythm and duration from admission to CPR were independent influencing factors for ROSC in patients with in-hospital CPR. The ROSC prediction model established based on the above influencing factors has a good predictive value for ROSC of CPR patients in hospital, and can guide clinicians to evaluate the prognosis of patients through relevant indicators as early as possible.
Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Humans , Cardiopulmonary Resuscitation/methods , Retrospective Studies , Case-Control Studies , Heart Arrest/therapy , Emergency Service, Hospital , Hospitals , AlbuminsABSTRACT
BACKGROUND: This study explored the specific relationship between different lipid indicators and cognitive impairment and aimed to provide a reference for implementing targeted lipid regulation measures to prevent and alleviate cognitive impairment. METHODS: We searched three databases (PubMed, Embase, and Web of Science) for literature related to hyperlipidaemia, lipid levels, and cognitive impairment, and used the Newcastle-Ottawa Scale to evaluate the quality of the identified literature. A meta-analysis was performed using RevMan 5.4, and the combined effect size ratio using a random-effects model (odds ratio [OR] and 95% confidence interval [CI]) was used to evaluate the association between dyslipidaemia and cognitive impairment. RESULTS: Among initially identified 2247 papers, we ultimately included 18 studies involving a total of 758,074 patients. The results of the meta-analysis revealed that patients with hyperlipidaemia had a 1.23-fold higher risk of cognitive impairment than those with normal lipid levels (OR = 1.23, 95% CI: 1.04-1.47, p = 0.02). Further subgroup analysis showed that elevated total cholesterol (TC) levels increased the risk of cognitive impairment by 1.59-fold (OR = 1.59, 95% CI: 1.27-2.01, p < 0.0001) and were more significant in older or male patients. Moreover, elevated triglyceride levels were inversely correlated with cognitive disorders, whereas elevated low-density lipoprotein cholesterol levels were unrelated to cognitive impairment risk. CONCLUSIONS: Dyslipidaemia was strongly associated with cognitive impairment, and elevated TC levels were a risk factor for cognitive impairment. Furthermore, the damaging effects of elevated TC levels on cognition were more pronounced in older and male populations.
Subject(s)
Cognitive Dysfunction , Dyslipidemias , Humans , Cognitive Dysfunction/etiology , Case-Control Studies , Cohort StudiesABSTRACT
Excessive ultraviolet B ray (UVB) exposure to sunlight results in skin photoageing. Our previous research showed that a Q-switched 1064 nm Nd: YAG laser can alleviate skin barrier damage through miR-24-3p. However, the role of autophagy in the laser treatment of skin photoageing is still unclear. This study aims to investigate whether autophagy is involved in the mechanism of Q-switched 1064 nm Nd: YAG in the treatment of skin ageing. In vitro, primary human dermal fibroblast (HDF) cells were irradiated with different doses of UVB to establish a cell model of skin photoageing. In vivo, SKH-1 hairless mice were irradiated with UVB to establish a skin photoageing mouse model and irradiated with laser. The oxidative stress and autophagy levels were detected by western blot, immunofluorescence and flow cytometer. String was used to predict the interaction protein of TGF-ß1, and CO-IP and GST-pull down were used to detect the binding relationship between TGFß1 and ITGB1. In vitro, UVB irradiation reduced HDF cell viability, arrested cell cycle, induced cell senescence and oxidative stress compared with the control group. Laser treatment reversed cell viability, senescence and oxidative stress induced by UVB irradiation and activated autophagy. Autophagy agonists or inhibitors can enhance or attenuate the changes induced by laser treatment, respectively. In vivo, UVB irradiation caused hyperkeratosis, dermis destruction, collagen fibres reduction, increased cellular senescence and activation of oxidative stress in hairless mice. Laser treatment thinned the stratum corneum of skin tissue, increased collagen synthesis and autophagy in the dermis, and decreased the level of oxidative stress. Autophagy agonist rapamycin and autophagy inhibitor 3-methyladenine (3-MA) can enhance or attenuate the effects of laser treatment on the skin, respectively. Also, we identified a direct interaction between TGFB1 and ITGB1 and participated in laser irradiation-activated autophagy, thereby inhibiting UVB-mediated oxidative stress further reducing skin ageing. Q-switched 1064 nm Nd: YAG laser treatment inhibited UVB-induced oxidative stress and restored skin photoageing by activating autophagy, and TGFß1 and ITGB1 directly incorporated and participated in this process.
Subject(s)
Integrin beta1 , Lasers, Solid-State , Skin Aging , Transforming Growth Factor beta1 , Animals , Humans , Mice , Autophagy , Collagen , Lasers, Solid-State/therapeutic use , Mice, Hairless , Transforming Growth Factor beta1/genetics , Integrin beta1/geneticsABSTRACT
CONTEXT: Volatile organic compounds (VOCs) are pervasive environmental pollutants that have been linked to various adverse health effects. However, the effect of ambient VOCs, whether individually or in mixtures, on diabetes remains uncertain and requires further investigation. OBJECTIVE: This study investigates the effects of ambient VOCs exposure, whether single or mixed, on diabetes mellitus and glucose homeostasis in the general population. METHODS: Urinary concentrations of VOC metabolites were obtained from the National Health and Nutrition Examination Survey. Survey-weighted logistic regression and generalized linear regression were used to explore the associations between individual VOC exposure and diabetes risk and glucose homeostasis indicators, respectively. Weighted quantile sum (WQS) regression models were applied to assess the combined effects of VOC mixtures. RESULTS: Out of 8468 participants, 1504 had diabetes mellitus. Eight VOC metabolites showed positive associations with diabetes mellitus (OR, 1.15-1.43; all P < .05), insulin resistance (IR) (OR, 1.02-1.06; P < .05), and other glucose homeostasis indicators (ß, 0.04-2.32; all P < .05). Mixed VOC models revealed positive correlations between the WQS indices and diabetes risk (OR = 1.52; 95% CI, 1.29-1.81), IR (OR = 1.36; 95% CI, 1.14-1.62), and other glucose homeostasis indicators (ß, 0.17-2.22; all P < .05). CONCLUSION: Urinary metabolites of ambient VOCs are significantly associated with an increased diabetes risk and impaired glucose homeostasis. Thus, primary prevention policies aimed at reducing ambient VOCs could attenuate diabetes burden.
Subject(s)
Diabetes Mellitus , Insulin Resistance , Volatile Organic Compounds , Humans , Environmental Monitoring , Nutrition Surveys , Diabetes Mellitus/epidemiology , GlucoseABSTRACT
BACKGROUND: Previous studies have shown that patients with cerebrovascular disease (CVD) have a significantly increased risk of cognitive decline or dementia; however, the association between preoperative CVD and perioperative neurocognitive disorders (PNDs) remains unclear. This study aimed to explore the correlation between preoperative CVD and PNDs, as well as combine logistic regression and receiver operating characteristic (ROC) curves to construct a clinical prediction PND model. MATERIALS AND METHODS: This retrospective cohort study evaluated 13 899 surgical patients of a large-scale comprehensive hospital between January 2021 and January 2022 to explore the association between preoperative CVD and PNDs, with follow-up to monitor postoperative survival until 28 February 2023, unless the patient died. The study participants comprised all inpatients from the Bone and Joint Surgery, Spine Surgery, Urology, Hepatobiliary Surgery, Gastrointestinal Surgery, and Thoracic Surgery departments. Patients were classified into two groups: the CVD group with a confirmed diagnosis and the noncerebrovascular disease group. The incidence of PNDs was measured, and potential associations between patient demographic information, preoperative comorbidities, and CVD, as well as the correlation between preoperative CVD and PNDs, were investigated by multivariate logistic regression analysis. Next, the authors constructed a clinical prediction PND model by drawing the ROC curve. The postoperative survival of all patients was tracked, and a survival curve was constructed and incorporated into the Cox proportional hazard regression model to analyze the relationship between preoperative CVD and the overall postoperative survival rate. RESULTS: Of the included 13 899 patients, propensity score matching yielded 1006 patient pairs. Multivariate logistic regression analysis revealed that CVD was an independent risk factor for PNDs [odds ratio: 10.193; 95% CI: 7.454-13.938; P <0.001]. Subsequently, the authors developed a clinical prediction model for PNDs by multivariate logistic regression analysis. The area under the ROC curve was 0.798 (95% CI: 0.765-0.830). The survival of 11 702 patients was followed up. Multivariate Cox hazard ratio regression analysis revealed that CVD affected the overall postoperative survival rate (hazard ratio, 1.398; 95% CI: 1.112-1.758; P <0.001). CONCLUSION: CVD was an independent risk factor for PNDs and affected the overall postoperative survival rate of surgical patients with preoperative CVD.
Subject(s)
Cardiovascular Diseases , Cerebrovascular Disorders , Humans , Prognosis , Retrospective Studies , Models, Statistical , Risk Factors , Cardiovascular Diseases/complications , Cerebrovascular Disorders/complications , Neurocognitive DisordersABSTRACT
AIMS: There is limited research on the relationship between food insecurity and mortality among individuals with diabetes. This study aims to investigate the impact of food insecurity on all-cause and cause-specific mortality in adults with diabetes. RESEARCH DESIGN AND METHODS: This study included 5749 adults with diabetes from the National Health and Nutrition Examination Survey cycles 2003-2018 and followed up until 31 December 2019. Food insecurity was measured by the Food Security Survey Module. Cox proportional hazard models were employed to estimate hazard ratios (HRs) and 95% confidence intervals for both all-cause mortality and cause-specific mortality. RESULTS: The weighted prevalence of full food security, marginal food security, low food security, and very low food security was 70.8%, 11.0%, 10.4%, and 7.8%, respectively. Food insecurity demonstrated a significant correlation with diminished diet quality and reduced consumption of healthy foods. Over the course of 42,272.0 person-years of follow-up, we documented 1091 deaths, of which 370 were attributed to cardiovascular disease and 180 to cancer. After adjusting for multiple variables, food insecurity scores were significantly and linearly associated with increased all-cause mortality. Comparing to full food security, participants experiencing very low food security had a multivariate-adjusted HR of 1.48 (1.12, 1.95) for all-cause mortality (ptrend = 0.010). CONCLUSIONS: Food insecurity was associated with increased all-cause mortality and compromised diet quality, especially in individuals experiencing very low food security. Future strategies may necessitate the monitoring of and interventions for food insecurity among individuals with diabetes.
Subject(s)
Diabetes Mellitus , Food Supply , Adult , Humans , Nutrition Surveys , Retrospective Studies , Diabetes Mellitus/epidemiology , Food InsecurityABSTRACT
OBJECTIVES: The study aimed to extend original research and identify operational and space-related requirements for specialization from the perspectives of nursing behavior and process. BACKGROUND: Studies related to the specialty of different nursing units have been widely conducted in nursing science, while few studies have explored the specialized requirements for the physical environments of nursing units in different departments. METHOD: Questionnaire survey data were collected from 125 nurses in 11 clinical departments, and nurse shadowing (approximately 68 hr) was conducted in four clinical departments. RESULTS: The questionnaire survey showed that satisfaction with care activity, visibility, and physical environment within the existing nursing unit environment was rated differently among different departments of nursing units. However, nurses in different groups of age, education, work experience, and position indicated no statistically significant difference. Behavioral observations demonstrated that the spatial and temporal distributions of activities, spatial linkages, and communication patterns varied in distinct departments. CONCLUSION: This research found that nurses in different departments had different evaluations of satisfaction and environmental characteristics. It also explains the differences in nursing work behaviors and processes found in various departments and sheds light on specialized requirements from the behavior perspective. The findings could help optimize the design of efficient and satisfactory nursing units in different departments.
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BACKGROUND: Gastric carcinoma (GC) treatment needs to be developed rapidly. Compound Kushen Injection (CKI), a formula from traditional Chinese medicine, has been used clinically in combination with chemotherapy to treat GC with satisfactory results. However, the molecular mechanism by which CKI acts to cure GC is still unclear. METHODS: In the present study, in vivo and in vitro experiments were used to assess the efficacy of CKI. Using ceRNA microarray and TMT technologies, the molecular mechanism of CKI was further investigated at the transcriptional and protein levels, and a bioinformatics approach was employed to investigate and functionally validate key CKI targets in GC. RESULTS: When combined with cisplatin (DDP), CKI significantly increased its efficacy in preventing the proliferation and metastasis of GC cells and malignant-looking tumors in mice. High-throughput sequencing data and bioinformatics analysis showed that CKI regulated the TNF signaling pathway, epithelial-mesenchymal transition (EMT), with VCAM1 as a key target. The transcription factors CEBPB, JUN, RELA, NFKB1, the EMT mesenchymal-like cell markers N-cadherin and vimentin, as well as the expression of VCAM1 and its upstream signaling driver TNF, were all downregulated by CKI. In contrast, the expression of the EMT epithelial-like cell marker E-cadherin was upregulated. CONCLUSION: CKI can effectively inhibit GC growth and metastasis, improve body's immunity, and protect normal tissues from damage. The molecular mechanism by which CKI inhibits metastasis of GC is by regulating VCAM1 induced by the TNF signaling pathway to inhibit EMT of GC. Our results provide an important clue to clarify precisely the multi-scale molecular mechanism of CKI in the treatment of GC.
Subject(s)
Antineoplastic Agents , Carcinoma , Stomach Neoplasms , Animals , Mice , Epithelial-Mesenchymal Transition , Antineoplastic Agents/pharmacology , Signal Transduction , Stomach Neoplasms/genetics , Cadherins , Cell Line, TumorABSTRACT
Objectives: Postoperative cognitive dysfunction (POCD) is objectively measurable after anesthesia and surgery. Lower heart rate variability (HRV) is associated with poorer cognitive performance, but the relationship between HRV and POCD remains unclear. Methods: Elderly patients who underwent total hip replacement under general anesthesia from the Department of Bone and Joint Surgery, Affiliated Hospital of Southwest Medical University were enrolled. Neuropsychological tests, standard deviation of the interbeat interval (SDNN, a parameter of HRV), and plasma concentrations of glial cell line-derived neurotrophic factors (GDNF) were performed one day before (T-1) and 7 days after (T7) surgery. Results: POCD occurred in 35% of patients on 7 days after surgery. Lower SDNN(T7) (OR=.91) and longer surgery time (OR=1.33) were associated with POCD. Compared with patients without POCD, there was higher variation SDNN (Δ SDNN) and plasma GDNF (ΔGDNF) in those with POCD from T-1 to T7 period. ΔGDNF is positively correlated with ΔSDNN (r = .61, p<.001). Conclusions: Lower SDNN (T7) was associated with POCD and might be used as a warning indicator for the risk of POCD.
Subject(s)
Cognitive Dysfunction , Postoperative Cognitive Complications , Humans , Aged , Heart Rate , Postoperative Complications/psychology , Glial Cell Line-Derived Neurotrophic Factor , Neuropsychological TestsABSTRACT
Sepsis refers to host response disorders caused by infection, leading to life-threatening organ dysfunction. RNA-binding motif protein 3 (RBM3) is an important cold-shock protein that is upregulated in response to mild hypothermia or hypoxia. In this study, we aimed to investigate whether RBM3 is involved in sepsis-associated acute lung injury (ALI). Intraperitoneal injection of LPS (10 mg/kg) was performed in wild type (WT) and RBM3 knockout (KO, RBM3-/-) mice to establish an in vivo sepsis model. An NLRP3 inflammasome inhibitor, MCC950 (50 mg/kg), was injected intraperitoneally 30 min before LPS treatment. Serum, lung tissues, and BALF were collected 24 h later for further analysis. In addition, we also collected serum from sepsis patients and healthy volunteers to detect their RBM3 expression. The results showed that the expression of RBM3 in the lung tissues of LPS-induced sepsis mice and the serum of patients with sepsis was significantly increased and positively correlated with disease severity. In addition, RBM3 knockout (KO) mice had a low survival rate, and RBM3 KO mice had more severe lung damage, inflammation, lung cell apoptosis, and oxidative stress than WT mice. LPS treatment significantly increased the levels of nucleotide binding and oligomerization domain-like receptor family 3 (NLRP3) inflammasomes and mononuclear cell nuclear factor-κB (NF-κB) in the lung tissues of RBM3 KO mice. However, these levels were only slightly elevated in WT mice. Interestingly, MCC950 improved LPS-induced acute lung injury in WT and RBM3 KO mice but inhibited the expression of NLRP3, caspase-1, and IL-1ß. In conclusion, RBM3 was overexpressed in sepsis patients and LPS-induced mice. RBM3 gene deficiency aggravated sepsis-associated ALI through the NF-κB/NLRP3 pathway.
Subject(s)
Acute Lung Injury , Sepsis , Animals , Mice , Acute Lung Injury/chemically induced , Inflammasomes/metabolism , Lipopolysaccharides , Mice, Inbred C57BL , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , RNA-Binding Proteins , Sepsis/complications , Sulfonamides , HumansABSTRACT
OBJECTIVE: To evaluate the effect of overall peripheral inflammatory levels on cognitive function, we explored the relationship between established biomarkers of peripheral inflammation (circulating C-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) and cognitive decline by performing a review of observational studies and creating an updated summary. METHODS: We included literatures exploring the relationship between peripheral levels of CRP, IL-6, and TNF-α and subsequent cognitive decline, published until July 2022, by searching the following databases: PubMed, Embase, Web of Science, the Cochrane Library, ClinicalTrials, CNKI, and VIP databases. We used random-effects models to pool the odds ratios (ORs) for the risks of subsequent cognitive decline in older adults with high levels of peripheral inflammation. We initially screened out 501 literatures, of which only 17 were ultimately eligible. Overall, there were 19,516 older individuals included in our meta-analysis, and 2134 of them experienced subsequent cognitive change. RESULTS: Individuals with high levels of peripheral inflammation may have 14% more chance to develop subsequent cognitive decline than those with low levels (OR = 1.14, 95% CI: 1.03-1.27; p < 0.00001). In the subgroup analysis, the incidence of cognitive decline was higher in individuals with high levels of IL-6. This study further demonstrates the link between systemic inflammation and cognitive status. INTERPRETATION: Detecting CRP, IL-6, and TNF-α in peripheral blood is necessary, as they may become effective indicators for forthcoming cognitive performance.
Subject(s)
Cognitive Dysfunction , Dementia , Humans , Aged , Interleukin-6 , Tumor Necrosis Factor-alpha , Inflammation , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Dementia/diagnosis , Dementia/epidemiologyABSTRACT
Background: While the community health service system was initially established in rural areas of mainland China, the utilization of community health service resources by the rural elderly population is not clear. Methods: Cross-sectional studies on the utilization of community health services by the rural elderly population in mainland China published within the last 10 years were retrieved from the China National Knowledge Infrastructure (CNKI), Wan Fang, Medline and Web of Science (WOS) databases. The quality of the article was evaluated by the Critical Appraisal Skills Programme (CASP), and obstacles to the utilization of community health services by the rural elderly population were analyzed based on the Andersen model. Results: Twenty-four studies were analyzed, and 3 gaps were found. (i) The cognition of rural elderly residents does not match the current health security system. (ii) There is a gap between the supply of health service resources in rural communities and the health needs of the elderly residents in these areas. (iii) The health services provided by rural primary health service institutions are not targeted. Conclusions: In mainland China, the provision of community health services to the rural elderly population has improved significantly. However, several factors from the individual level to the system level lead to low levels of access and utilization. This finding means that under the leadership of the government, it is necessary to integrate the strength of multiple departments to cooperate in improving the welfare system, policy publicity, health education, financial support, system guarantees and resource exchange and sharing for the elderly population in rural areas and to jointly promote community health services for the elderly population in rural areas.
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Background: Due to lack of enough specific targets and the immunosuppressive tumor microenvironment (TME) of triple-negative breast cancer (TNBC), TNBC patients often cannot benefit from a single treatment option. This study aims to explore the regulatory effects of Compound kushen injection (CKI) plus chemotherapy on the TME of TNBC from a single cell level. Methods: A mouse TNBC model in BALB/c mice was established to evaluate the antitumor efficacy and toxicity of CKI combined with chemotherapy. Flow cytometry was used to observe the influence of CKI on the lymphocyte populations in the tumor bearing mice. Both bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) were applied to portray the modulation of CKI combined with chemotherapy on the TME of TNBC mice. Results: CKI significantly enhanced the anticancer activity of chemotherapy in vivo with no obvious side effects. Flow cytometry results revealed a significantly higher activation of CD8+ T lymphocytes in the spleens and tumors of the mice with combination therapy. Bulk RNA-seq indicated that CKI could promote the cytotoxic immune cell infiltrating into tumor tissues. Meanwhile, scRNA-seq further revealed that CKI combined with chemotherapy could enhance the percentage of tumor-infiltrating CD8+ T cells, inhibit tumor-promoting signaling pathways, and promote T cell activation and positive regulation of immune response. In addition, CKI showed obvious anticancer activity against MDA-MB-231 breast tumor cells in vitro. Conclusions: The combination of CKI and chemotherapy might provide a higher efficiency and lower toxicity strategy than a single chemotherapy drug for TNBC. CKI potentiates the anti-TNBC effects of chemotherapy by activating anti-tumor immune response in mice.
Subject(s)
Antineoplastic Agents , Triple Negative Breast Neoplasms , Humans , Mice , Animals , CD8-Positive T-Lymphocytes/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , RNA , Tumor MicroenvironmentABSTRACT
In order to investigate the solubility behavior of lignin in formic acid (FA) solution Phragmites australis biomass was subjected to a sequential two-step formosolv fractionation using 88% FA followed by 70% FA to obtain four specific lignin fractions, designated as IFL-88%, IFSL-70%, IFIL-70% and IFL-EtAc. The structures of the four isolated lignin fractions were successfully characterized by gel permeation chromatography (GPC), Fourier transform infrared (FTIR) spectroscopy, two-dimensional heteronuclear single quantum coherence nuclear magnetic resonance spectroscopy (2D-HSQC NMR), thermogravimetric analysis (TGA), and gas chromatography-mass spectroscopy (GC/MS). Furthermore, the total phenolic content of the four isolated lignin samples was assessed by Folin-Ciocalteu analysis. The data from structural properties revealed that depolymerization of the isolated lignin fractions occurred via ß-O-4 cleavage, accompanied by competitive condensation reaction. Interestingly, 70% aqueous FA could separate specific lignin fractions with different antioxidant capacities of ABTSË+ and DPPH radical scavenging activity. Due to the high total phenolic hydroxyl content (25%) and low molecular weight (Mw = 2760 Da) and polydispersity index (PDI = 1.5), IFL-EtAc lignin showed excellent antioxidant activity at the same concentration of 2.0 mg mL-1 in comparison with three other isolated lignin fractions, and it was even equal to that of commercial antioxidant butylated hydroxytoluene (BHT). These findings are helpful to separate specific lignins with higher value as potential antioxidants by sequential two-step formosolv fractionation in lignin chemistry.
ABSTRACT
Three inactivated enterovirus A71 (EV-A71) vaccines have been widely vaccinated among children in the targeted age group in mainland China since mid-2016. However, comprehensive virological surveillance of hand, foot and mouth disease (HFMD) over multiple years after the use of EV-A71 vaccines has rarely been conducted. Using long-term data extracted from the Public Health and Clinical Center of Chengdu, we described the clinical, aetiological, and epidemiological characteristics of HFMD inpatients after the use of EV-A71 vaccines from 2017 through 2022. A total of 5115 patients were selected for analysis with a male-to-female ratio of 1.63:1 and were mostly under 5 years of age (97.6%). Among these cases, 4.3% presented with severe symptoms, and 4.1% of severe cases experienced significant complications. EV-A71 was no longer the major serotype for laboratory-confirmed HFMD, responsible for 15.6% of severe cases and 1.2% of mild cases. A significant downwards trend of EV-A71 infections was observed after the use of EV-A71 vaccines (P for trend < 0.001). Coxsackievirus A6 was the predominant pathogen, accounting for 63.5% of mild cases and 36.2% of severe cases. Coxsackievirus A10 (CV-A10) and A16 were sporadically detected, and an upwards trend was observed in the proportion of CV-A10 infections. This study provides baseline molecular epidemiology for the evaluation of EV-A71 vaccination impact and potential serotype replacement based on HFMD inpatients. Additional nationwide and population-based epidemiologic and serologic studies are essential to elucidate HFMD dynamics after the use of EV-A71 vaccines, and to inform public health authorities to introduce optimized intervention strategies.
Subject(s)
AIDS Vaccines , Enterovirus A, Human , Enterovirus Infections , Enterovirus , Hand, Foot and Mouth Disease , Influenza Vaccines , Papillomavirus Vaccines , Respiratory Syncytial Virus Vaccines , SAIDS Vaccines , Child , Humans , Male , Female , Enterovirus/genetics , Hand, Foot and Mouth Disease/epidemiology , Hand, Foot and Mouth Disease/prevention & control , Hand, Foot and Mouth Disease/complications , Diphtheria-Tetanus-Pertussis Vaccine , Molecular Epidemiology , BCG Vaccine , Measles-Mumps-Rubella Vaccine , Enterovirus Infections/epidemiology , Enterovirus Infections/prevention & control , Enterovirus Infections/diagnosis , China/epidemiology , Vaccines, Inactivated , Antigens, Viral , Hospitalization , Enterovirus A, Human/geneticsABSTRACT
Nucleophilic recyclization of pyridinium salts involving a CCN interchange ring transformation for the synthesis of 2-methylnicotinonitrile derivatives was herein developed. 3-Aminocrotononitrile (3-ACN) produced in situ from CH3CN acted as a C-nucleophile, as well as the source of CH3 and CN groups, which was supported by isotope-labeling and control experiments.