Effect of ethanol addition on the physicochemical, structural and in vitro digestive properties of Tartary buckwheat starch-quercetin/rutin complexes.

The effects of ethanol on the physicochemical, structural and in vitro digestive properties of Tartary buckwheat starch-quercetin/rutin complexes (e-TBSQ and e-TBSR) were investigated. Ethanol restricted the gelatinization of Tartary buckwheat starch (TBS), which resulted an increase in ∆H, G' and G" as well as a decrease in apparent viscosity of e-TBSQ and e-TBSR. The particle size, scanning electron microscopy and X-ray diffraction results showed that ethanol influenced the morphological structure of TBS granules and the starch crystalline structure in e-TBSQ and e-TBSR changed from B-type to V-type when the ethanol concentration was 25%. Saturation transfer difference-nuclear magnetic resonance results revealed that ethanol weakened the binding ability of quercetin/rutin to TBS in e-TBSQ and e-TBSR, leading to a change in the binding site on the quercetin structural unit. The residual ungelatinized TBS granules in e-TBSQ and e-TBSR induced a high slowly digestible starch content, and thus displayed a "resistant-to-digestion".

The association between Helicobacter pylori infection and the risk for gout in hyperuricemia patients in China - A cross-sectional study.

PURPOSE: Helicobacter pylori (H. pylori) infection has been reported to be associated with multiple metabolic diseases. However, the connection between H. pylori infection and gout has not been explored previously. Our study aimed to investigate the association of gout and H. pylori infection in hyperuricemia population in China. PATIENTS AND METHODS: This cross-sectional study was performed among the subjects who underwent health checkup in our health promotion center from January 1, 2020 to December 31, 2021. A total of 53,629 subjects with a mean age of 44.2 years were included in this study. H. pylori infection was defined as a positive [13]C-urea breath test. The effect of H. pylori infection on gout was assessed by multiple logistic regression analysis. RESULTS: 720 subjects with gout and 15,077 subjects with asymptomatic hyperuricemia (> 420 µmol/L in male and > 360 µmol/L in female) were enrolled. The prevalence rates of H. pylori infection, hyperuricemia and gout were 26.3%, 29.5%, 1.3%, respectively. The prevalence rate of H. pylori infection was significantly higher in subjects with gout than in those with asymptomatic hyperuricemia (35.0% vs. 27.2%; P<0.001). Multiple logistic regression analysis showed that H. pylori infection was associated with an increased risk of gout independent of serum uric acid level in hyperuricemia population (odds ratio [OR]: 1.320, 95% confidence interval [CI]: 1.124-1.550, P = 0.001). CONCLUSION: H. pylori infection is positively associated with higher risk of gout in hyperuricemia population. The causal relationship and potential mechanism between H. pylori infection and gout warrants further investigation.

Oral administration of grape-derived nanovesicles for protection against LPS/D-GalN-induced acute liver failure.

Although the exploration of the molecular mechanisms of Acute liver failure (ALF) is supported by a growing number of studies, the lack of effective therapeutic agents and measures indicates an urgent clinical need for the development of new drugs and treatment strategies. Herein, we focused on the treatment of ALF with grape-derived nanovesicles (GDNVs), and assessed its protective effects and molecular mechanisms against liver injury. In the mice model of ALF, prophylactic administration for three consecutive days and treatment with GDNVs after successful induction of ALF showed a significant reduction of ALT and AST activity in mouse serum, as well as a blockade of the release of inflammatory cytokines IL6, IL-1ß and TNF-α. Treatment with GDNVs significantly prevented the massive apoptosis of hepatocytes caused by LPS/D-GalN and down-regulated the activation and expression of the mitochondrial apoptosis-related proteins p53, Caspase 9, Caspase 8, Caspase 3 and Bax. GDNVs downregulated the release of chemokines during the inflammatory eruption in mice and inhibited the infiltration of peripheral monocytes into the liver by inhibiting CCR2/CCR5. Moreover, the pro-inflammatory phenotype of macrophages in the liver was reversed by GDNVs. GDNVs further reduced the activation of NLRP3-related pathways, and treatment with GDNVs activated the expression of autophagy-related proteins Foxo3a, Sirt1 and LC3-II in the damaged mouse liver, inducing autophagy to occur. GDNVs could exert hepatoprotective and inflammatory suppressive functions by increasing nuclear translocation of Nrf2 and upregulating HO-1 expression against exogenous toxin-induced oxidative stress in the liver. In conclusion, these results demonstrate that GDNVs alleviate LPS/D-GalN-induced ALF and have the potential to be used as a novel hepatoprotective agent for clinical treatment.

Instability in a carbon pool driven by multiple dissolved organic matter sources in a eutrophic lake basin: Potential factors for increased greenhouse gas emissions.

Lakes serve as vital reservoirs of dissolved organic matter (DOM) and play pivotal roles in biogeochemical carbon cycles. However, the sources and compositions of DOM in freshwater lakes and their potential effects on lake sediment carbon pools remain unclear. In this study, seven inflowing rivers in the Lake Taihu basin were selected to explore the potential effects of multi-source DOM inputs on the stability of the lake sediment carbon pool. The results showed the high concentrations of dissolved organic carbon in the Lake Taihu basin, accompanied by a high complexity level. Lignins constituted the majority of DOM compounds, surpassing 40% of the total, while the organic carbon content was predominantly composed of humic acids (1.02-3.01 g kg-1). The high amounts of lignin oxidative cleavage led to CHO being the main molecular structure in the DOM of the seven rivers. The carbon constituents within the sediment carbon reservoir exhibited a positive correlation with dissolved CH4 and CO2, with a notable emphasis on humic acid and dissolved CH4 (R2 = 0.86). The elevated concentration of DOM, coupled with its intricate composition, contributed to the increases in dissolved greenhouse gases (GHGs). Experiments showed that the mixing of multi-source DOM can accelerate the organic carbon mineralization processes. The unit carbon emission efficiency was highest in the mixed group, reaching reached 160.9 µmol∙Cg-1, which also exhibited a significantly different carbon pool. The mixed decomposition of DOM from different sources influenced the roles of the lake carbon pool as source and sink, indicating that the multi-source DOM of this lake basin was a potential driving factor for increased carbon emissions. These findings have improved our understanding of the sources and compositions of DOM in lake basins and revealed their impacts on carbon emissions, thereby providing a theoretical basis for improving assessments of lake carbon emissions.

The application of 5E rehabilitation management mode in the nursing of patients with aortic dissection complicated by obstructive sleep apnea.

OBJECTIVE: This study was designed to explore the effect of 5E rehabilitation mode (encouragement, education, exercise, employment, and evaluation) in patients with aortic dissection (AD) complicated by obstructive sleep apnea (OSA). METHODS: Patients with Stanford type B AD (TBAD) complicated by OSA were admitted to Guangdong Provincial People's Hospital from January 2019 to December 2020. They were randomly divided into an experimental group and a control group. After discharge, patients in the control group were given routine nursing and follow-up education, whereas patients in the experimental group were given 5E rehabilitation management mode-based nursing and follow-up education. Upon the nursing intervention, the differences in polysomnography (PSG) parameters, medication adherence, quality of life, blood pressure, and heart rate of patients between the two groups were compared. Logistic regression analysis was performed to evaluate the risk factors for the occurrence of adverse aortic events. RESULTS: A total of 89 patients were enrolled, 49 in the experimental group and 40 in the control group. After the intervention, the control of heart rate, systolic blood pressure, medication adherence, PSG parameters, and quality of life scores in the experimental group were significantly better than those in the control group (P<0.05). The incidence of adverse aortic events including aortic rupture and progressive aortic dilation in the experimental group was significantly lower than that in the control group (P < 0.05). Logistic regression analysis revealed that acute TBAD [odds ratio (OR) = 15.069; 95%confidence interval (CI), 1.738-130.652; P=0.014], history of chronic kidney disease (OR=10.342; 95%CI, 1.056-101.287; P=0.045), and apnea hypopnea index (AHI) ≥ 30 (OR=2.880; 95%CI, 1.081-9.51; P=0.036) were adverse factors affecting adverse aortic events; while 5E rehabilitation management mode (OR=0.063; 95%CI, 0.008-0.513; P=0.010) was a favorable factor for occurrence of adverse aortic events. CONCLUSION: The findings suggest that continuous nursing based on information carrier 5E rehabilitation management significantly enhanced medication adherence, improved patients' overall quality of life, and decreased the incidence of adverse aortic events in patients TBAD patients and OSA.

Pulmonary manifestations of POEM syndrome: a retrospective analysis of 282 cases.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystemic clonal plasma cell disorder. Pulmonary involvement is frequently found in patients with POEMS syndrome, manifesting various clinical features. Therefore, to improve diagnostic accuracy and provide treatment strategies, a comprehensive analysis of pulmonary manifestations of POEMS syndrome is needed. METHODS: This retrospective study included patients with POEMS syndrome at Peking Union Medical College Hospital, a major referral medical center in China, between June 1, 2013, and June 1, 2023. Demographic data, laboratory findings, pulmonary function test results, echocardiograms, and chest imaging data were extracted. Continuous variables were compared using the t-test or Mann-Whitney method. Pearson's chi-square test or Fisher's exact test was conducted to compare categorical data. RESULTS: Overall, 282 individuals diagnosed with POEMS syndrome were included in this study, of which 56% were male with an average age of 48.7 years. Respiratory symptoms were found in 40.1% of the patients, with dyspnea as the most common symptom (34.4%). Chest computed tomography and echocardiography findings showed that 56.4% of patients exhibited pleural effusion, 62.8% displayed mediastinal or hilar lymphadenopathy, 46.5% presented pleural thickening, 27.3% demonstrated bone lesions of the ribs or thoracic vertebra, 7.8% showed lung interstitial abnormalities, and 35.5% had pulmonary hypertension. Decreased diffuse capacity and restrictive ventilatory patterns were identified in 85.2% (115 cases) and 47.4% (64 cases) of patients, respectively. Patients with respiratory symptoms exhibited higher declined lung function measures than those having no respiratory symptoms. High-risk patients with poor prognosis showed more pulmonary function abnormalities. CONCLUSION: Abnormalities in pulmonary manifestations constitute the significant features of POEMS syndrome. Several patients with POEMS syndrome presented with respiratory symptoms at the initial evaluation. These findings underscore the importance of early identification and accurate diagnosis of POEMS syndrome by clinicians, particularly in cases involving lung and multisystem.

Garlic-derived exosome-like nanovesicles as a hepatoprotective agent alleviating acute liver failure by inhibiting CCR2/CCR5 signaling and inflammation.

Acute liver failure (ALF) is a life-threatening clinical syndrome mostly induced by viral infections or drug abuse. As a novel therapeutic adjuvant or delivery vehicle, plant-derived exosome-like nanovesicles (PELNVs) have been extensively studied in recent years. This study aimed to develop garlic-derived exosome-like nanovesicles (GaELNVs) in order to ameliorate liver injury induced by LPS/D-GalN in mice, inhibit inflammatory eruption and reduce inflammatory cells infiltration. The results showed that treatment with GaELNVs improved liver pathology and reduced the levels of soluble inflammatory mediators IL-6, IL-1ß and TNF-α in the serum of ALF mice. GaELNVs reversed the upregulation of Cleaved Caspase-9, Cleaved Caspase-3, p53 and Bax expression and decreased Bcl2 activation caused by D-GalN/LPS, and inhibited NF-κB p65 expression and translocation to the nucleus. Meanwhile, treatment with GaELNVs resulted significant reduction in NLRP3 activation and Caspase-1 maturation, as well as decrease in the release of the inflammatory mediator IL-18. Additionally, an upregulation of the expression of proteins related to energy metabolism and autophagy occurrence including Foxo3a, Sirt1, and LC3-II was detected in the liver. Oral administration of GaELNVs also led to significant alteration in the expression of F4/80 and CD11b in the liver. Furthermore, the detection of chemokines in mouse liver tissue revealed that GaELNVs exhibited minimal reduction in the expression of CCL2, CCL3, CCL5 and CCL8. The decreased expression of CCR2 and CCR5 in the liver suggests that GaELNVs have the ability to decrease the recruitment of monocytes from the circulation to the liver. A reduction in the infiltration of F4/80loCD11bhi monocyte-derived macrophages into the liver was also observed. This study provides novel evidence that GaELNVs can ameliorate inflammatory eruptions and hinder the migration of circulating monocytes to the liver, as well as decrease macrophage infiltration by inhibiting CCR2/CCR5 signaling. Consequently, GaELNVs hold promise as a novel therapeutic agent for clinical management of liver disease.

Cardiovascular disease and all-cause mortality associated with individual and combined cardiometabolic risk factors.

BACKGROUND: Previous studies have investigated the association between cardiometabolic risk factors and cardiovascular disease (CVD), but evidence of the attributable burden of individual and combined cardiometabolic risk factors for CVD and mortality is limited. We aimed to investigate and quantify the associations and population attributable fraction (PAF) of cardiometabolic risk factors on CVD and all-cause mortality, and calculate the loss of CVD-free years and years of life lost in relation to the presence of cardiometabolic risk factors. METHODS: Twenty-two thousand five hundred ninety-six participants aged ≥ 35 without CVD at baseline were included between October 2012 and December 2015. The outcomes were the composite of fatal and nonfatal CVD events and all-cause mortality, which were followed up in 2018 and 2019 and ascertained by hospital records and death certificates. Cox regression was applied to evaluate the association of individual and combined cardiometabolic risk factors (including hypertension, diabetes and high low-density lipoprotein cholesterol (LDL-C)) with CVD risk and all-cause mortality. We also described the PAF for CVD and reductions in CVD-free years and life expectancy associated with different combination of cardiometabolic conditions. RESULTS: During the 4.92 years of follow-up, we detected 991 CVD events and 1126 deaths. Hazard ratio were 1.59 (95% confidential interval (CI) 1.37-1.85), 1.82 (95%CI 1.49-2.24) and 2.97 (95%CI 1.85-4.75) for CVD and 1.38 (95%CI 1.20-1.58), 1.66 (95%CI 1.37-2.02) and 2.97 (95%CI 1.88-4.69) for all-cause mortality, respectively, in participants with one, two or three cardiometabolic risk factors compared with participants without diabetes, hypertension, and high LDL-C. 21.48% of CVD and 15.38% of all-cause mortality were attributable to the combined effect of diabetes and hypertension. Participants aged between 40 and 60 years old, with three cardiometabolic disorders, had approximately 4.3-year reductions life expectancy compared with participants without any abnormalities of cardiometabolic disorders. CONCLUSIONS: Cardiometabolic risk factors were associated with a multiplicative risk of CVD incidence and all-cause mortality, highlighting the importance of comprehensive management for hypertension, diabetes and dyslipidemia in the prevention of CVD.

Dual-Cross-Linked Chitosan-Based Antibacterial Hydrogels with Tough and Adhesive Properties for Wound Dressing.

Biocompatible chitosan-based hydrogels have attracted extensive attention in wound dressing due to their human skin-like tissue characteristics. However, it is a crucial challenge to fabricate chitosan-based hydrogels with versatile properties, including flexibility, stretchability, adhesivity, and antibacterial activity. In this work, a kind of chitosan-based hydrogels with integrated functionalities are facilely prepared by solution polymerization of acrylamide (AAm) and sodium p-styrene sulfonate (SS) in the presence of quaternized carboxymethyl chitosan (QCMCS). Due to the dual cross-linking between QCMCS and P(AAm-co-SS), the optimized QCMCS/P(AAm-co-SS) hydrogel exhibits tough mechanical properties (0.767 MPa tensile stress and 1100% fracture strain) and moderate tissue adhesion (11.4 kPa). Moreover, biological evaluation in vitro illustrated that as-prepared hydrogel possesses satisfactory biocompatibility, hemocompatibility, and excellent antibacterial ability (against S. aureus and E. coli are 98.8% and 97.3%, respectively). Then, the hydrogels are tested in a rat model for bacterial infection incision in vivo, and the results show that they can significantly accelerate epidermal regeneration and wound closure. This is due to their ability to reduce the inflammatory response, promote the formation of collagen deposition and granulation tissue. The proposed chitosan-based antibacterial hydrogels have the potential to be a highly effective wound dressing in clinical wound healing.

Clinical Characteristics, Drug Resistance, and Risk Factors for Death of Klebsiella pneumoniae Infection in Patients with Acute Pancreatitis: A Single-Center Retrospective Study from China.

Objective: Infection is a common complication of acute pancreatitis (AP). Klebsiella pneumoniae (KP) is one of the most common pathogens associated with nosocomial infections. Our study focuses on investigating the clinical characteristics and risk factors for death of Klebsiella pneumoniae infections in AP patients, further to quantify the prognosis of the patients, and provide evidence for guiding antibiotic use and improving prognosis. Methods: The data of epidemiology, clinical manifestations and drug resistance rate with K. pneumoniae infections in AP patients from January 1, 2012 to August 30, 2022 were retrospectively collected. Logistic regression model and Cox regression model were, respectively, used to determine the risk factors for carbapenem-resistant Klebsiella pneumoniae (CRKP) acquisition and death. The nomogram prediction model was built by RMS software package to predict the 90-day survival rate. Results: One hundred and twenty-six AP patients combined with K. pneumoniae infections, with a mortality rate of 34.9%. The most common infection sites were pancreas and peri-pancreas (54.8%), followed by lung (20.6%) and blood stream (18.3%). The resistance rate of K. pneumoniae to commonly used antibiotics in clinical practice was high, especially CRKP, which was only sensitive to sulfamethoxazole-trimethoprim (SMZ-TMP) and tigecycline (TGC) (resistance rates were 37.57% and 17.57%, respectively). Independent risk factors for CPKP acquisition were male (OR = 1.655, 95% CI 0.642-4.265, P = 0.017) and PICC/CVC implantation (OR = 3.157, 95% CI 1.223-8.147, P = 0.021). Independent risk factors for mortality included carbapenem resistance (HR = 2.556, 95% CI 1.011-6.462, P = 0.047), hemorrhage (HR = 2.392, 95% CI 1.104-5.182, P = 0.027), septic shock (HR = 3.022, 95% CI 1.312-6.959, P = 0.009), age >60 years (HR = 2.977, 95% CI 1.303-6.799, P = 0.01), creatinine >177µmol/L (HR = 2.815, 95% CI 1.075-7.369, P = 0.035). Conclusion: K. pneumoniae infection has become a serious threat for AP patients, which recommends us more attention and active new strategies seeking.

Development and validation of a fully automated system using deep learning for opportunistic osteoporosis screening using low-dose computed tomography scans.

Background: Bone density measurement is an important examination for the diagnosis and screening of osteoporosis. The aim of this study was to develop a deep learning (DL) system for automatic measurement of bone mineral density (BMD) for osteoporosis screening using low-dose computed tomography (LDCT) images. Methods: This retrospective study included 500 individuals who underwent LDCT scanning from April 2018 to July 2021. All images were manually annotated by a radiologist for the cancellous bone of target vertebrae and post-processed using quantitative computed tomography (QCT) software to identify osteoporosis. Patients were divided into the training, validation, and testing sets in a ratio of 6:2:2 using a 4-fold cross validation method. A localization model using faster region-based convolutional neural network (R-CNN) was trained to identify and locate the target vertebrae (T12-L2), then a 3-dimensional (3D) AnatomyNet was trained to finely segment the cancellous bone of target vertebrae in the localized image. A 3D DenseNet was applied for calculating BMD. The Dice coefficient was used to evaluate segmentation performance. Linear regression and Bland-Altman (BA) analyses were performed to compare the calculated BMD values using the proposed system with QCT. The diagnostic performance of the system for osteoporosis and osteopenia was evaluated with receiver operating characteristic (ROC) curve analysis. Results: Our segmentation model achieved a mean Dice coefficient of 0.95, with Dice coefficients greater than 0.9 accounting for 96.6%. The correlation coefficient (R2) and mean errors between the proposed system and QCT in the testing set were 0.967 and 2.21 mg/cm3, respectively. The area under the curve (AUC) of the ROC was 0.984 for detecting osteoporosis and 0.993 for distinguishing abnormal BMD (osteopenia and osteoporosis). Conclusions: The fully automated DL-based system is able to perform automatic BMD calculation for opportunistic osteoporosis screening with high accuracy using LDCT scans.

Effects of new hypoglycemic drugs on cardiac remodeling: a systematic review and network meta-analysis.

BACKGROUND: In recent years, the incidence of diabetes mellitus has been increasing annually, and cardiovascular complications secondary to diabetes mellitus have become the leading cause of death in diabetic patients. Considering the high incidence of type 2 diabetes (T2DM) combined with cardiovascular disease (CVD), some new hypoglycemic agents with cardiovascular protective effects have attracted extensive attention. However, the specific role of these regimens in ventricular remodeling remains unknown. The purpose of this network meta-analysis was to compare the effects of sodium glucose cotransporter type 2 inhibitor (SGLT-2i), glucagon-like peptide 1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 inhibitor (DPP-4i) on ventricular remodeling in patients with T2DM and/or CVD. METHODS: Articles published prior to 24 August 2022 were retrieved in four electronic databases: the Cochrane Library, Embase, PubMed, and Web of Science. This meta-analysis included randomized controlled trials (RCTs) and a small number of cohort studies. The differences in mean changes of left ventricular ultrasonic parameters between the treatment and control groups were compared. RESULTS: A total of 31 RCTs and 4 cohort studies involving 4322 patients were analyzed. GLP-1RA was more significantly associated with improvement in left ventricular end-systolic diameter (LVESD) [MD = -0.38 mm, 95% CI (-0.66, -0.10)] and LV mass index (LVMI) [MD = -1.07 g/m2, 95% CI (-1.71, -0.42)], but significantly decreased e' [MD = -0.43 cm/s 95% CI (-0.81, -0.04)]. DPP-4i was more strongly associated with improvement in e' [MD = 3.82 cm/s, 95% CI (2.92,4.7)] and E/e'[MD = -5.97 95% CI (-10.35, -1.59)], but significantly inhibited LV ejection fraction (LVEF) [MD = -0.89% 95% CI (-1.76, -0.03)]. SGLT-2i significantly improved LVMI [MD = -0.28 g/m2, 95% CI (-0.43, -0.12)] and LV end-diastolic diameter (LVEDD) [MD = -0.72 ml, 95% CI (-1.30, -0.14)] in the overall population, as well as E/e' and SBP in T2DM patients combined with CVD, without showing any negative effect on left ventricular function. CONCLUSION: The results of the network meta-analysis provided high certainty to suggest that SGLT-2i may be more effective in cardiac remodeling compared to GLP-1RA and DPP-4i. While GLP-1RA and DPP-4i may have a tendency to improve cardiac systolic and diastolic function respectively. SGLT-2i is the most recommended drug for reversing ventricular remodeling in this meta-analysis.

Optogenetic engineered umbilical cord MSC-derived exosomes for remodeling of the immune microenvironment in diabetic wounds and the promotion of tissue repair.

BACKGROUND: Angiogenesis and tissue repair in chronic non-healing diabetic wounds remain critical clinical problems. Engineered MSC-derived exosomes have significant potential for the promotion of wound healing. Here, we discuss the effects and mechanisms of eNOS-rich umbilical cord MSC exosomes (UCMSC-exo/eNOS) modified by genetic engineering and optogenetic techniques on diabetic chronic wound repair. METHODS: Umbilical cord mesenchymal stem cells were engineered to express two recombinant proteins. Large amounts of eNOS were loaded into UCMSC-exo using the EXPLOR system under blue light irradiation. The effects of UCMSC-exo/eNOS on the biological functions of fibroblasts and vascular endothelial cells in vitro were evaluated. Full-thickness skin wounds were constructed on the backs of diabetic mice to assess the role of UCMSC-exo/eNOS in vascular neogenesis and the immune microenvironment, and to explore the related molecular mechanisms. RESULTS: eNOS was substantially enriched in UCMSCs-exo by endogenous cellular activities under blue light irradiation. UCMSC-exo/eNOS significantly improved the biological functions of cells after high-glucose treatment and reduced the expression of inflammatory factors and apoptosis induced by oxidative stress. In vivo, UCMSC-exo/eNOS significantly improved the rate of wound closure and enhanced vascular neogenesis and matrix remodeling in diabetic mice. UCMSC-exo/eNOS also improved the inflammatory profile at the wound site and modulated the associated immune microenvironment, thus significantly promoting tissue repair. CONCLUSION: This study provides a novel therapeutic strategy based on engineered stem cell-derived exosomes for the promotion of angiogenesis and tissue repair in chronic diabetic wounds.

Comparison of the lower limit of normal to the fixed ratio method for the diagnosis of airflow obstruction at high altitudes: a large cross-sectional survey of subjects living between 3000-4700 m above sea level.

BACKGROUND: There is no general agreement on the preferential use of a fixed ratio (FR) of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.7 vs. the lower limit of normal (LLN) of FEV1/FVC to define airflow obstruction. Determining the impact of these different cut-off levels in people living at high altitudes has not been studied. We assessed the prevalence of airflow obstruction and its clinical characteristics in residents living at high altitude using a fixed ratio and the LLN of FEV1/FVC according to Global Lung Initiative 2012 (GLI) reference values. METHODS: Using a multistage stratified sampling method, 3702 participants (aged ≥ 15 years) living at an altitude of 3000-4700 m in Tibet were included. RESULTS: 11.4% and 7.7% of participants had airflow obstruction according to GLI-LLN and a fixed FEV1/FVC cut-off value, respectively. The participants in the FR-/LLN+ group were younger, predominantly female, more frequently exposed to household air pollution, and had a higher proportion of chronic obstructive pulmonary disease assessment test scores ≥ 10 than those in the FR-/LLN- group. They also had a significantly lower FEV1 and a higher frequency of small airway dysfunction. Compared with the participants of the FR+/LLN+ group, those in the FR-/LLN+ group showed no significant difference in the risk factors for airflow obstruction and respiratory symptoms, but had a lower prevalence of small airway dysfunction. CONCLUSIONS: Defining airflow obstruction according to LLN, instead of using an FR, identified younger individuals with more frequent clinical symptoms of airflow obstruction and small airway dysfunction.

Rapid increasing burden of diabetes and cardiovascular disease caused by high body mass index in 1.25 million Chinese adults, 2005-2018.

BACKGROUND: Temporal trends and geographical variations in disease burden for diabetes mellitus (DM) and cardiovascular disease (CVD) attributable to high body mass index (BMI) in China have not been fully elucidated. METHODS: We estimated deaths and years of life lost (YLLs) for DM and CVD attributable to high BMI by age, sex, year, and region from 2005 to 2018 based on pooled data of 1.25 million adults. FINDINGS: Approximately 497,430 (95% uncertainty interval [UI], 470,520-525,720) deaths for DM and CVD were attributable to high BMI in China in 2018, with 453,750 deaths from CVD and 43,700 deaths from DM. Between 2005 and 2018, there was a 17.35% increase in age-standardized mortality rate for DM and CVD attributable to high BMI. The high BMI-related DM and CVD YLL rates increased from 127.46 (95% UI 108.70-148.62) per 100,000 people aged 20-24 years to 5,735.54 (95% UI 4,844.16-6,713.53) per 100,000 people aged ≥80 years, respectively. The highest age-standardized mortality rate for high BMI-related DM and CVD in northeast, northwest, and circum-Bohai Sea regions of China. CONCLUSION: The disease burden for DM and CVD attributable to high BMI increased substantially between 2005 and 2018. Urgent measures are required at both national and regional levels for resource mobilization to slow the growing burden. FUNDING: The work was supported by the National Key Research and Development Program of China, China National Science & Technology Pillar Program, and National Health Commission of the People's Republic of China.

Association between circulating fatty acid metabolites and asthma risk: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Fatty acids are involved in a wide range of immunological responses in humans. Supplementation of polyunsaturated fatty acids has been reported to help alleviate symptoms and airway inflammation in asthma patients, whereas the effects of fatty acids on the actual risk of asthma remain controversial. This study comprehensively investigated the causal effects of serum fatty acids on asthma risk using two-sample bidirectional Mendelian Randomization (MR) analysis. METHODS: Genetic variants strongly associated with 123 circulating fatty acid metabolites were extracted as instrumental variables, and a large GWAS data of asthma was used to test effects of the metabolites on this outcome. The inverse-variance weighted method was used for primary MR analysis. The weighted median, MR-Egger regression, MR-PRESSO, and leave-one-out analyses were utilized to evaluate heterogeneity and pleiotropy. Potential confounders were adjusted by performing multivariable MR analyses. Reverse MR analysis was also conducted to estimate the causal effect of asthma on candidate fatty acid metabolites. Further, we performed colocalization analysis to examine the pleiotropy of variants within the fatty acid desaturase 1 (FADS1) locus between the significant metabolite traits and the risk of asthma. Cis-eQTL-MR and colocalization analysis were also performed to determine the association between RNA expression of FADS1 and asthma. RESULTS: Genetically instrumented higher average number of methylene groups was causally associated with a lower risk of asthma in primary MR analysis, while inversely, the higher ratio of bis-allylic groups to double bonds and the higher ratio of bis-allylic groups to total fatty acids, were associated with higher probabilities of asthma. Consistent results were obtained in multivariable MR when adjusted for potential confounders. However, these effects were completely eliminated after SNPs correlated with the FADS1 gene were excluded. The reverse MR also found no causal association. The colocalization analysis suggested that the three candidate metabolite traits and asthma likely share causal variants within the FADS1 locus. In addition, the cis-eQTL-MR and colocalization analyses demonstrated a causal association and shared causal variants between FADS1 expression and asthma. CONCLUSIONS: Our study supports a negative association between several PUFA traits and the risk of asthma. However, this association is largely attributed to the influence of FADS1 polymorphisms. The results of this MR study should be carefully interpreted given the pleiotropy of SNPs associated with FADS1.

The impact of multi-drug resistant Pseudomonas aeruginosa infections on acute pancreatitis patients.

INTRODUCTION: Acute pancreatitis (AP) accounts for a high proportion of digestive diseases worldwide and has a high risk of infection. Pseudomonas aeruginosa, a common pathogen of hospital infections, has been observed to increase the resistance rate to several antibiotics, causing difficulties in treatments. Our study aims to investigate the impact of the multi-drug resistant Pseudomonas aeruginosa (MDR-PA) infections on AP patients. METHODS: At two Chinese tertiary referral centers for AP patients infected with MDR-PA, a retrospective case-control study with a 1:2 case-control ratio was performed. Comparisons were preformed between with/without MDR-PA infections and different drug-resistance of MDR-PA infections patients, respectively. Independent risk factors of overall mortality were assessed via univariate and multivariate binary logistic regression analyses, and the distribution and antibiotic resistant rates of strains were described. RESULTS: Mortality in AP patients with MDR-PA infections was significantly higher than in those without MDR-PA infections (7 (30.4%) vs. 4 (8.7%), P = 0.048). The rate of prophylactic use of carbapenem for 3 days (0 vs. 50%, P = 0.019) and the incidence rate of multiple organ failure (MOF) (0 vs. 57.1%, P = 0.018) were remarkably higher in the carbapenem-resistant Pseudomonas aeruginosa group compared with the carbapenem-sensitive Pseudomonas aeruginosa group. In the multivariate analysis, the severe categories of AP (OR = 13.624, 95% CIs = 1.567-118.491, P = 0.018) and MDR-PA infections (OR = 4.788, 95% CIs = 1.107-20.709, P = 0.036) were independent risk factors for mortality. The resistance rates of MDR-PA strains were low for amikacin (7.4%), tobramycin (3.7%), and gentamicin (18.5%). The resistance rates of MDR-PA strains to imipenem and meropenem were up to, 51.9% and 55.6%, respectively. CONCLUSION: In AP patients, severe categories of AP and MDR-PA infections were both independent risk factors for mortality. Inappropriate use of carbapenem antibiotics and MOF were related to carbapenem-resistant Pseudomonas aeruginosa infections. Amikacin, tobramycin, and gentamicin are recommended for the treatment of AP patients with MDR-PA infections.

Lactiplantibacillus plantarum attenuates Coxsackievirus B3-induced pancreatitis through the BAX/BCL2/CASP3 signaling pathway.

Lactiplantibacillus plantarum is a lactic acid bacterium widely used in food production. Coxsackievirus B3 (CVB3) is an important human pathogen associated with acute pancreatitis development, and no antiviral therapeutics or vaccines are approved to treat or prevent its infection. However, whether L. plantarum could inhibit CVB3 infection remains unclear. Here, L. plantarum FLPL05 showed antiviral activity against CVB3 infection in vivo and in vitro. Pretreatment with L. plantarum FLPL05 reduced serum amylase levels, CVB3 viral load in the pancreas, serum pro-inflammatory cytokine levels, and macrophage infiltration in CVB3-infected mice. In mice, L. plantarum FLPL05 inhibited CVB3-induced pancreas apoptosis via the B cell leukemia/lymphoma 2 (BCL2)/BCL2-associated X protein (BAX)/caspase-3 (CASP3) signaling pathway. Furthermore, L. plantarum FLPL05 reduced CVB3 replication, protected cells from the cytopathic effect of CVB3 infection, and inhibited cell apoptosis. Moreover, L. plantarum FLPL05's exopolysaccharide (EPS) had activity against CVB3 in vitro, reducing the CVB3 titer and improving cell activity. Therefore, L. plantarum FLPL05 pretreatment improved CVB3-induced pancreatitis by partially reversing pancreatitis, which might be associated with EPS. Consequently, L. plantarum FLPL05 could be a potential probiotic with antiviral activity against CVB3.

Modulation of electromagnetic wave absorption via porosity in Pechini-derived carbon guided by a random network model.

It is well established that porosity in carbon materials can benefit electromagnetic wave absorption by providing stronger interfacial polarization, better impedance matching, multiple reflections, and lower density, but an in-depth assessment is still lacking on this issue. The random network model describes the dielectric behavior of a conduction-loss absorber-matrix mixture with two parameters related to the volume fraction and conductivity, respectively. In this work, the porosity in carbon materials was tuned by a simple, green, and low-cost Pechini method, and the mechanism of how porosity affects EM wave absorption was investigated quantitatively based on the model. It was discovered that porosity was crucial for the formation of a random network, and a higher specific pore volume led to a larger volume fraction parameter and a lower conductivity parameter. Guided by the high throughput parameter sweeping based on the model, the Pechini-derived porous carbon could achieve an effective absorption bandwidth of 6.2 GHz at 2.2 mm. This study further verifies the random network model, unveiling the implication and influencing factors of the parameters, and opens a new path to optimize the electromagnetic wave absorption performance of conduction-loss materials.

Polymorphisms in the FCER2 gene have associations with asthma and chronic obstructive pulmonary disease.

Background: Asthma and chronic obstructive pulmonary disease (COPD) are heterogenetic diseases and exhibit many similarities. Dutch hypothesis proposed that these two diseases may have common genetic origins. This study aims to investigate whether asthma and COPD share a common genetic background in Chinese patients. Methods: In this case-control study, single nucleotide polymorphisms (SNPs) were genotyped using SNaPshot. Haplotype disease analysis and haplotype phenotype analysis were applied to assess the relationship between three polymorphisms of the FCER2 gene and the risk of COPD/asthma. Additionally, associations between polymorphisms of the FCER2 gene and phenotypes were analyzed. Results: We detected ten SNPs of seven genes (FCER1A, FCGR2A, FCGR2B, CHI3L1, ADRB2, STAT6, and FCER2) expressed by airway epithelial cells. We detected genotypes and allele distributions in 251 COPD patients, 597 asthma patients, and 632 healthy controls. A significant difference was found in the FCER2 gene (rs28364072) between COPD patients and controls (P=0.009). Significant differences were observed in the genotype and allele distributions of rs1801274 (FCGR2A), rs12368672 (STAT6), and rs2228137 (FCER2) between asthma patients and controls (P=0.004, 0.007 and 0.010, respectively). Notably, polymorphisms of FCER2 gene were associated with the risk of both COPD (P=0.009 for rs28364072) and asthma (P=0.01 for rs2228137). Haplotype analysis revealed that haplotype T-G-T (alleles of rs28364072, rs2228137, and rs3760687, respectively) was significantly associated with a higher risk of asthma [odds ratios (OR) =2.25, 95% confidence interval (CI): 1.26-4.01, P=0.006]. Further analysis showed that the C-A-C haplotype and C-G-T haplotype were associated with increased blood eosinophils in either COPD or asthma patients (P=0.034, and P<0.001, respectively). Moreover, haplotypes C-A-C, C-G-C, and T-G-C showed significant associations with serum IgE levels in asthma patients (P=0.002, 0.041, and 0.004, respectively). Conclusions: Our data suggest that the FCER2 gene might associate with predisposition to asthma and COPD, while FCER2 haplotypes were associated with pulmonary function measurements and blood eosinophils counts in both diseases. Our findings support the common genetic basis for asthma and COPD, suggesting a potential therapeutic target for the two diseases.