Objective:To compare the therapeutic effects of different inhaled medications on patients with frequent cough in chronic obstructive pulmonary disease (COPD), including changes in symptoms and acute exacerbation.Methods:This study was based on the RealDTC study, and the study subjects were stable COPD patients from the Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University from December 2016 to March 2023. The demographic characteristics, smoking status, history of biofuel exposure, history of acute exacerbation in the past year, lung function, COPD Assessment Test (CAT) score, modified British Medical Research Council Respiratory Difficulty Questionnaire (mMRC) score, and inhalation medication regimen of the patients were collected. Patients with frequent cough are defined as having a cough score of ≥2 in the first item of the CAT score. According to the type of inhaled medication, patients with frequent cough are divided into l long-acting muscarine anticholinergic (LAMA), long-acting β2 agonists (LABA)+ LAMA, inhaled corticosteroids (ICS)+ LABA, and ICS+ LABA+ LAMA groups. At the 6th month follow-up, CAT scores were collected and symptom control was evaluated, including minimum clinical improvement (MCID) (defined as a decrease of ≥2 points from baseline in CAT scores at the 6th month) and improvement in cough symptoms (defined as a decrease of ≥1 point from baseline in cough scores). During a one-year follow-up, the number of acute exacerbations was evaluated. The relationship between different inhaled medications and prognosis in patients with frequent cough in COPD was evaluated using multivariate logistic regression analysis.Results:A total of 653 patients with frequent cough in COPD were included, with a CAT score of (16.4±6.1) and a cough score of 3(2, 3). After 6 months of follow-up, 403 patients (61.7%) achieved MCID, and 394 patients (60.3%) had improved cough symptoms; During a one-year follow-up, 227 patients (34.8%) experienced acute exacerbation. After receiving inhalation medication treatment, the CAT scores and cough scores of four groups of patients with frequent cough, namely LAMA, LABA+ LAMA, ICS+ LABA, and ICS+ LABA+ LAMA, decreased compared to before treatment (all P<0.05). There was a statistically significant difference in the proportion of △CAT score, MCID, and acute exacerbation among the four groups of LAMA, LABA+ LAMA, ICS+ LABA, and ICS+ LABA+ LAMA (all P<0.05), while there was no statistically significant difference in the proportion of △cough score and cough score reduction ≥1 point (all P>0.05). The results of multivariate logistic regression analysis showed that compared with patients treated with LAMA or ICS+ LABA drugs, patients with frequent cough in COPD treated with LABA+ LAMA or ICS+ LABA+ LAMA drugs were more likely to achieve MCID and less likely to experience acute exacerbation (all P<0.05). Conclusions:Compared with LAMA or ICS+ LABA, patients with frequent cough in COPD who receive LABA+ LAMA or ICS+ LABA+ LAMA drug treatment are more likely to improve symptoms and have a lower risk of acute exacerbation.

Objective:To analyze the response of patients with chronic obstructive pulmonary disease (COPD) with multiple and few symptoms to different inhalation drugs, including acute exacerbation and symptom changes.Methods:This study was a multi center, retrospective Cohort study. The subjects of this study were patients with chronic obstructive pulmonary disease in stable stage in 12 hospitals in Hunan and Guangxi from December 2016 to February 2022. Demographics data, lung function, Chronic Obstructive Pulmonary Disease Assessment test questionnaire (CAT) score, modified British Medical Research Council dyspnea questionnaire (mMRC) score and inhalation drug scheme of patients were collected. According to the CAT and mMRC scores, patients were divided into a multi symptom group (CAT≥10 points or mMRC≥2 points) or a few symptom group (CAT<10 points and mMRC<1 point); Subsequently, they were divided into four subgroups based on the inhalation drug regimen: long-acting anticholinergic drugs (LAMA) group, long-acting β2-receptor agonists (LABA)+ inhaled corticosteroids (ICS) group, LABA+ LAMA group, and LABA+ LAMA+ ICS group. All patients were followed up for 1 year, with minimum clinical improvement (MCID) defined as a decrease of ≥2 points in the patient′s CAT score at 6 months, and clinical symptom deterioration (CSD) defined as an increase of ≥2 points in the patient′s CAT score at 6 months.Results:A total of 929 patients with chronic obstructive pulmonary disease were included, including 719(77.4%) with multiple symptoms and 210(22.6%) with few symptoms. There was no statistically significant difference in MCID, CSD, acute exacerbation, hospitalization frequency, and mortality rate among subgroups of asymptomatic COPD patients treated with different inhalation drug regimens (all P>0.05). Among patients with multiple symptoms of chronic obstructive pulmonary disease, compared to those who use LAMA or LABA+ ICS, those who used LABA+ LAMA or LABA+ LAMA+ ICS were more likely to obtain MCID and had a more significant improvement in CAT scores, and the risk of acute exacerbation is lower (all P<0.05). Conclusions:Lesser symptomatic COPD patients should receive single drug LAMA as the initial inhalation treatment drug, while multi symptomatic COPD patients should receive LABA+ LAMA as the initial inhalation treatment drug.

Autism spectrum disorder (ASD) is one of the common neurodevelopmental disorders in children. Its etiology and pathogenesis are poorly understood. Previous studies have suggested potential changes in the complement and coagulation pathways in individuals with ASD. In this study, using multiple reactions monitoring proteomic technology, 16 of the 33 proteins involved in this pathway were identified as differentially-expressed proteins in plasma between children with ASD and controls. Among them, CFHR3, C4BPB, C4BPA, CFH, C9, SERPIND1, C8A, F9, and F11 were found to be altered in the plasma of children with ASD for the first time. SERPIND1 expression was positively correlated with the CARS score. Using the machine learning method, we obtained a panel composed of 12 differentially-expressed proteins with diagnostic potential for ASD. We also reviewed the proteins changed in this pathway in the brain and blood of patients with ASD. The complement and coagulation pathways may be activated in the peripheral blood of children with ASD and play a key role in the pathogenesis of ASD.
Child ; Humans ; Autism Spectrum Disorder/metabolism* ; Proteomics ; Brain/metabolism*

Higher alcohols are one of the main by-products of Saccharomyces cerevisiae in brewing. High concentration of higher alcohols in alcoholic beverages easily causes headache, thirst and other symptoms after drinking. It is also the main reason for chronic drunkenness and difficulty in sobering up after intoxication. The main objective of this review is to present an overview of the flavor characteristics and metabolic pathways of higher alcohols as well as the application of mutagenesis breeding techniques in the regulation of higher alcohol metabolism in S. cerevisiae. In particular, we review the application of metabolic engineering technology in genetic modification of amino transferase, α-keto acid metabolism, acetate metabolism and carbon-nitrogen metabolism. Moreover, key challenges and future perspectives of realizing optimization of higher alcohols metabolism are discussed. This review is intended to provide a comprehensive understanding of metabolic regulation system of higher alcohols in S. cerevisiae and to provide insights into the rational development of the excellent industrial S. cerevisiae strains producing higher alcohols.
Alcoholic Beverages ; Alcohols/analysis* ; Fermentation ; Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism*

OBJECTIVE：To study the effects of berberine on mic e macrophage polarization based on TLR 4-MyD88-NF-κB signaling pathway. METHODS ：Using mice RAW 264.7 macrophage as the object ，atorvastatin calcium as positive control ， inflammatory cell model was induced by lipopolysaccharide （LPS）；ELISA method was used to detect the contents of TNF-α，IL-6 and NF-κB in cell culture medium after treated with low，medium and high doses of berberine （5，10，20 μmol/L）for 24 h. The real-time fluorescence quantitative PCR was conducted to determine the mRNA expression of TLR 4 and MyD 88 in cells. Western blotting assay was used to detect the protein expression of TLR 4，MyD88，iNOS and CD 206 in cells. RESULTS ：Compared with blank control group ，the contents of TNF-α，IL-6 and NF-κB in cell culture medium，mRNA expression of TLR 4 and MyD 88， protein expression of TLR 4，MyD88 and iNOS in cells were increased significantly in LPS induction group （P＜0.05）. Compared with LPS induction group ，the contents of TNF-α and IL-6，mRNA and protein expression of TLR 4 and MyD 88 in atorvastatin calcium group ，berberine medium-dose and high-dose groupsas well as the content of NF-κ B and protein expression of iNOS in administration groups were decreased significantly ， while the content of NF-κB in berberine high-dose group was significantly lower than atorvastatin calcium group （P＜0.05）. The protein expressions of CD206 in atorvastatin calcium group and berberine high-dose group were increased significantly ，while the protein expression of CD 206 in berberine high-dose group was significantly higher than atorvastatin calcium group （P＜0.05）. CONCLUSIONS ：Different doses of berberine can intervene in mice macrophage polarization to different extents ，the mechanism of which may be associated with the regulation of TLR4/MyD88/NF-κB signaling pathway.

Objective To investigate the role of glucose transporter ( GLUT ) 2 and 4 in hyperuricemia-induced insulin resistance. Methods Male uric acid oxidase gene knock-out spontaneous hyperuricemia mice ( KO) and wild-type mice ( WT) were fed with high-fat diet to establish an insulin resistance model. Then, some of KO mice were treated with allopurinol for lowering uric acid. Uric acid, fasting plasma glucose (FPG), and fasting insulin ( FINS) were detected. Intraperitoneal glucose tolerance test ( IPGTT ) and insulin tolerance test ( ITT ) were performed. Finally, the expression levels of Slc2a4 and Slc2a2 mRNA in tissues were determined by real-time PCR, while those of GLUT2 and GLUT4 proteins in tissues were analyzed by Western blot. Results There was no significant difference in FPG among various groups. The level of FINS in KO group was significantly higher than that in WT group [(0.636± 0.07) vs (0.456 ± 0.03) ng/ml, P<0.01], with decreased insulin sensitivity and impaired glucose tolerance. The uric acid level in the KO group remained at a high level [ ( 549. 68 ± 48. 7 ) vs ( 216. 61 ± 27. 5 )μmol/L] . After uric acid level in KO mice was reduced by allopurinol, insulin sensitivity and glucose metabolism were improved. Compared with WT group, the expression levels of Slc2a4 and GLUT4 in the gastrocnemius muscle were decreased while the expression levels of Slc2a2 and GLTU2 in liver were increased in KO group, which were reversed by allopurinol-mediated uric acid reduction. Conclusion Uric acid may induce insulin resistance via decreasing Slc2a4/GLUT4 expressions in skeletal muscle, and increasing Slc2a2/GLTU2 expressions in liver.

AIM:To establish and characterize the patient-derived esophageal squamous-cell carcinoma xeno-graft (PDECX) in mice.METHODS:The samples of human esophageal cancer were grafted into severe combined immu-nodeficient ( SCID) mice.The xenografts were transferred to SCID mice when the first passage of xenografts grew up .The growth of tumors in the first, second and third passages was observed .HE staining was performed.The expression of CK5/6, p63 and p40 in the patient samples , and the first and third passages of the xenografts were detected by immunohisto-chemical analysis.The expression of mTOR, p-mTOR, p70S6K, p-p70S6K, Akt1, p-Akt (Ser473), Erk1/2 and p-Erk1/2 were determined by Western blot .RESULTS:The PDECX was successfully established .The positive expression of CK5/6, p63 and p40 in the xenografts was consistent with that in the patients ’ samples.The levels of phosphorylated and total proteins of proliferation-related signaling pathways were different in the xenografts from different patients .CONCLU-SION:The PDECX model adequately reflects the tumal heterogeneity that is observed in the patients .

Viral hepatitis is a major liver disease caused by virus infection .Viral hepatitis is popular in China , mainly caused by hepatitis B and hepatitis C viruses .Experimental animal model is a necessary platform for the research on mechanism of viral infection and pathogenicity , for treatment and vaccine development .Up to date, a great progress in the development of viral hepatitis animal models has been achieved in spite of the most of findings are limited to hepatitis B and C.Here, we summarize the recent findings of viral hepatitis animal models , focusing on the tree shrew animal model and its modeling strategy .

OBJECTIVETo screen the hepatocyte proteins that interact with hepatitis B virus X protein (HBx).

METHODSThe recombinant plasmid pSos-HBx was constructed by inserting Sos-HBx fragment into the bait vector, and after sequence verification the plasmid was transformed into competent yeast cells. The expression and self-activation of Sos-HBx protein was detected in the yeast cells. The hepatocyte proteins interacting with the bait protein was screened with CytoTrap yeast two-hybrid technique.

RESULTSThe reconstructed plasmid harboring HBx gene expressed Sos-HBx protein in the yeast cells without self-activation of the protein. CytoTrap yeast two-hybrid system identified 6 hepatocyte proteins that interacted with HBx, including fibronectin 1, translationally controlled tumor protein, IQ motif and WD repeats 1, follistatin, orosomucoid 1, and disulfide isomerase family A member 3.

CONCLUSIONSix HBx-binding hepatocyte proteins have been identified using the CytoTrap yeast two-hybrid system, which provides clues for further investigation of the role of HBx protein in hepatitis and liver cancer.

Genetic Vectors ; Hepatocytes ; metabolism ; Humans ; Plasmids ; Protein Interaction Domains and Motifs ; Proteins ; metabolism ; Trans-Activators ; metabolism ; Two-Hybrid System Techniques

BACKGROUNDDrug-resistance of tumor is the main reason of the failure of che-motherapy. Much attention has been paid to the expression of multidrug resistance-associated protein (MRP) and its mechanism of drug-resistance in non-small cell lung cancer (NSCLC). Results of this research will contribute to reversing drug-resistance and improving curative effect. The aim of this study is to investigate the relationships between the expression of MRP and clinicopathological parameters and prognosis in patients with NSCLC.

METHODSExpression of MRP was detected in 62 cases of paraffin-embedded NSCLC samples by streptavidin-biotin-peroxidase complex immunohistochemistry method, as well as in 30 fresh cases of NSCLC samples and corresponding normal lung tissues by immunohistochemistry and Western blot.

RESULTSMRP expression of NSCLC tissues was significantly higher than that of normal lung tissues. The survival time of patients with negative MRP expression was (69.81±17.41) months, and that of patients with positive MPR expression was (25.38±4.46) months (P=0.0156). This statistically significant relationship between the survival time and prognosis was also showed in squamous cell carcinoma patients (P=0.015), but not in adenocarcinoma. Multivariate COX model analysis suggested that the survival time was significantly related to lymphatic metastasis (P=0.038) and expression of MRP (P=0.035).

CONCLUSIONSMRP expression in NSCLC is significantly higher than that in the normal lung tissues. The mean survival time of patients with negative MRP expression is remarkably longer than that of patients with positive MRP expression. MRP expression may be an independent prognostic factor.