Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM＋EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P＜0.01); UCM＋EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P＜0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P＜0.05); ventricular remodeling was alleviated (P＜0.05), though there was no significant improvement in systolic function in UCM＋EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P＜0.01); the myocardial pathology improved with reduced collagen deposition in UCM＋EMPA group (P＜0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P＜0.01), while myocardial hypertrophy was alleviated in UCM＋EMPA group (P＜0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P＜0.05), but downregulated in UCM＋EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM＋EMPA group (P＜0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.

BackgroundPrevious studies have identified a close relationship among psychological neglect and abuse， negative affect， different stages of adolescence， and suicidal ideation. However， the mechanisms underlying the impact of psychological abuse and neglect on suicidal ideation among left-behind adolescents remain unclear， and this field of research is still in its relative infancy. ObjectiveTo explore the relationship between psychological neglect/abuse and suicidal ideation among left-behind adolescents， as well as the mediating role of negative affect and the moderating effect of different stages of adolescence， so as to provide insights for preventing and intervening suicidal ideation in this population. MethodsFrom November 2021 to May 2022， a cluster random sampling technique was utilized to select 2 309 left-behind adolescents in western China. Assessments were conducted using the Child Psychological Abuse and Neglect Scale （CPANS）， the Positive and Negative Suicide Ideation （PANSI） and the Positive and Negative Affect Schedule for Children （PANAS-C）. Spearman correlation coefficients were calculated across all samples， and Process 4.1 was employed to test the mediating role of negative affect and the moderating role of different stages of adolescence in the pathway linking psychological abuse/neglect to suicidal ideation. ResultsA total of 2 119 left-behind adolescents （mean age： 14.94±1.20 years） completed the study， with males comprising 51.34% （1 088/2 119） and females 48.66% （1 031/2 119）.Among left-behind adolescents， scores on CPANS psychological neglect subscale showed positive correlations with both psychological abuse subscale scores and PANAS-C negative affect subscale scores （r=0.446， 0.496， P<0.01）. Additionally， CPANS psychological neglect and psychological abuse subscale scores were also positively correlated with PANSI scores （r=0.487， 0.508， P<0.01）. Furthermore， PANAS-C negative affect subscale scores demonstrated a positive correlation with PANSI scores （r=0.499， P<0.01）. Negative affect partially mediated the relationship between psychological abuse/psychological neglect and suicidal ideation， with effect sizes of 0.166 （95% CI： 0.141~0.191） and 0.131 （95% CI： 0.112~0.152）. Different stages of adolescence moderated the latter part （negative emotion → suicidal ideation） of the indirect mediation path from psychological neglect to suicidal ideation through negative affect （β=-0.066， P<0.01）. ConclusionBoth psychological neglect and psychological abuse may influence suicidal ideation among left-behind adolescents via negative affect. Moreover， different stages of adolescence may moderate the indirect path from psychological neglect to suicide ideation through negative affect.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Objective To investigate the antioxidant activity of bamboo stem extracts and the therapeutic effect of bamboo stem water extract on oxidative inflammation induced by tert butyl hydroperoxide (t-BHP) in human colon adenocarcinoma cells (Caco-2). Methods In this study, ABTS, DPPH, and FRAP assays were used to determine the extracellular antioxidant activity of petroleum ether extract, ethyl acetate extract, n-butanol extract, 95% ethanol extract, and distilled water extract from bamboo stems. The human intestinal Caco-2 cell line was used as the model cell, and t-BHP was selected as the oxidative stress modeling agent. The CCK-8 assay was used to detect cell viability and the optimal oxidative damage concentration of t-BHP. The content of MDA, 8-OHdG, TNF-α and IL-1β were detected to assess antioxidant stress effect. Results The five extracts of bamboo all had certain antioxidant activity, among which the water extract of bamboo stem had the best comprehensive antioxidant activity with high cell viability in Caco-2 cells. The optimal modeling concentration of t-BHP was 200 μMol/L. The water extract of bamboo stem significantly reduced the content of oxidative stress related biomarkers and inflammatory factors in Caco-2 cells induced by t-BHP. Conclusion The stem extracts of bamboo in Xianning City have strong in vitro antioxidant activity. Among them, the water extract of bamboo stem has a protective effect on t-BHP induced oxidative damage in Caco-2 cells, suggesting that the water extract possesses a potential to be developed as new antioxidant products for clinical prevention and treatment of oxidative damage related diseases.

Objective:To analyze predictive risk indicators associated with the development of Kümmell's disease (KD) in patients with osteoporotic vertebral compression fractures (OVCFs).Methods:A 1∶1 frequency-matched case-control study design was employed, selecting patients who visited the Department of Spine Surgery at Liuzhou Workers' Hospital from January 2021 to June 2023. Patients were divided into case and control groups based on whether they progressed to Kümmell's disease (KD). Detailed demographic information, comorbidities, and laboratory data were collected, and baseline characteristics of the two groups were compared. Initial predictive variables significantly associated with the target variable were preliminarily screened through univariate analysis. A correlation heatmap was then constructed to assess collinearity among these variables, followed by further selection of potential predictors using the Lasso regression model. Finally, a multivariable logistic regression model was used for the prediction and analysis of KD-related risk indicators.Results:Univariate analysis identified significant predictors of Kümmell's disease, including patient age, bone mineral density, kyphotic Cobb angle, and multiple vertebral fractures. These were included in the subsequent Lasso regression analysis, which identified key predictors with non-zero coefficients: age, bone density, Cobb angle, multiple vertebral fractures, platelet count (PLT), aspartate aminotransferase/alanine aminotransferase (AST/ALT), albumin (Alb), albumin/globulin ratio (Alb/Glb), alkaline phosphatase (ALP), urea (UREA), serum uric acid (SUA), fibrinogen (Fn), blood glucose (BG), and C-reactive protein (CRP). The correlation heatmap revealed the correlation and collinearity risks between these variables, with ALT and AST/ALT showing a high correlation ( r=0.750) and PLT and Alb showing a low correlation ( r=-0.110). Multivariable logistic regression indicated that the presence of multiple vertebral fractures [ OR=2.078, 95% CI (1.072, 4.025), P=0.030], increased Cobb angle [ OR=1.033, 95% CI (1.008, 1.058), P=0.009], elevated levels of ALP [ OR=1.013, 95% CI(1.004, 1.023), P=0.006], and SUA [ OR=1.004, 95% CI (1.000, 1.007), P=0.043] were associated with an increased risk of KD in patients with OVCFs. Conversely, decreased levels of Fn [ OR=0.996, 95% CI (0.992, 0.999), P=0.008] were linked to an increased risk of KD. Conclusion:Multiple vertebral fractures, increased Cobb angle, elevated levels of ALP and SUA, along with decreased levels of Fn, can be used as early-warning indicators to predict whether patients with OVCFs will develop KD. Monitoring these indicators is crucial for the early detection and intervention in these patients.

Objective To systematically review the epidemiological studies on primary biliary cholangitis (PBC), and to investigate the prevalence rate of PBC in the Chinese general population and its influencing factors. Methods PubMed, Embase, The Cochrane Library, CNKI, and Wanfang Data were searched for articles on the epidemiology of PBC in China published up to 31th March 2022. Two researchers independently performed screening and data extraction, and then related analyses were performed. Results A total of 9 articles were included. The positive rate of AMA was 1 049.05/100 000 (ranging fr om 159.65/100 000 to 2287.40/100 000), and the prevalence rate of PBC was 123.68/100 000 (ranging from 42.70/100 000 to 276.59/100 000). The positive rate of AMA was 636.51/100 000 (ranging from 52.55/100 000 to 1 164.33/100 000) in men and 1 265.47/100 000 (ranging from 225.23/100 000 to 1 704.93/100 000) in women, with a male/female ratio of 1∶1.99 for the prevalence rate of AMA. The prevalence rate of PBC was 40.81/100 000 (ranging from 23.54/100 000 to 75.10/100 000) in men and 148.71/100 000 (ranging from 77.36/100 000 to 214.91/100 000) in women, with a male/female ratio of 1∶3.64 for the prevalence rate of PBC. Conclusion Different studies show great differences in the positive rate of AMA and the prevalence rate of PBC in the Chinese general population, which is mainly affected by sex, age, and region. The positive rate of AMA and the prevalence rate of PBC increase with age, and the patients aged ≥50 years have a significantly higher positive rate of AMA than those aged < 50 years. The positive rate of AMA is significantly higher than the prevalence rate of PBC. There are significantly more women than men in the AMA-positive population and the PBC patients, and the influence of sex on AMA is lower than that on PBC.

Glucose transporter 1(GLUT1)overexpression in tumor cells is a potential target for drug therapy,but few studies have reported screening GLUT1 inhibitors from natural or synthetic compounds.With cur-rent analysis techniques,it is difficult to accurately monitor the GLUT1 inhibitory effect of drug molecules in real-time.We developed a cell membrane-based glucose sensor(CMGS)that integrated a hydrogel electrode with tumor cell membranes to monitor GLUT1 transmembrane transport and screen for GLUT1 inhibitors in traditional Chinese medicines(TCMs).CMGS is compatible with cell membranes of various origins,including different types of tumors and cell lines with GLUT1 expression knocked down by small interfering RNA or small molecules.Based on CMGS continuous monitoring technique,we inves-tigated the glucose transport kinetics of cell membranes with varying levels of GLUT1 expression.We used CMGS to determine the GLUT1-inhibitory effects of drug monomers with similar structures from Scutellaria baicalensis and catechins families.Results were consistent with those of the cellular glucose uptake test and molecular-docking simulation.CMGS could accurately screen drug molecules in TCMs that inhibit GLUT1,providing a new strategy for studying transmembrane protein-receptor interactions.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

Objective:To establish a quality evaluation method for the simultaneous determination of Calycosin-7-O-β-D-Glucopyranoside and Lobetyolin in Danqi Xinmaikang boiled powders and pieces.Methods:Quantitative analysis of multi-components was performed to determine contents of Calycosin-7-O-β-D-Glucopyranoside and Lobetyolin with Calycosin-7-O-β-D-Glucopyranoside as the reference substance by single-maker (QAMS). The chromatogram conditions were established, with C18 column as solid phase, acetonitrile-water as flowing phase, 268 nm as detecting wavelength, 1.0 ml/min as flowing rate, 30 ℃ as column temperature, and 10 μl as injection volume.Results:The relative correction factor between Calycosin-7-O-β-D-Glucopyranoside and Lobetyolin was 1.14. There was no significant difference of measured values between the external standard method and QAMS ( P>0.05). With Calycosin-7-O-β-D-Glucopyranoside retention time of 1.00, the relative retention time of Lobetyolin was 1.51 and RSD was less than 5%. Conclusion:It is feasible and accurate to evaluate the quality of Danqi Xinmaikang boiled powders and pieces by QAMS.

Background: Classical swine fever virus (CSFV), the causative agent of classical swine fever (CFS), is a highly contagious disease that poses a serious threat to Chinese pig populations. Objectives: Many provinces of China, such as Shandong, Henan, Hebei, Heilongjiang, and Liaoning provinces, have reported epidemics of CSFV, while the references to the epidemic of CSFV in Yunnan province are rare. This study examined the epidemic characteristics of the CSFV in Yunnan province. Methods: In this study, 326 tissue samples were collected from different regions in Yunnan province from 2015 to 2021. A reverse transcription-polymerase chain reaction (RT-PCR), sequences analysis, and phylogenetic analysis were performed for the pathogenic detection and analysis of these 326 clinical specimens. Results: Approximately 3.37% (11/326) of specimens tested positive for the CSFV by RTPCR, which is lower than that of other regions of China. Sequence analysis of the partial E2 sequences of eleven CSFV strains showed that they shared 89.0–100.0% nucleotide (nt) and 95.0–100.0% amino acid (aa) homology, respectively. Phylogenetic analysis showed that these novel isolates belonged to the subgenotypes 2.1c and 2.1d, with subgenotype 2.1c being predominant. Conclusions The CSFV was sporadic in China’s Yunnan province from 2015 to 2021. Both 2.1c and 2.1d subgenotypes were found in this region, but 2.1c was dominant.