Objective:Using bioinformatics methods to find key genes related to asthma and discussing their molecular mecha-nisms.Methods:Weighted gene co-expression network analysis(WGCNA)was performed on GSE143303 microarray dataset to screen out the modules significantly related to asthma.Module genes were subjected to protein-protein interaction(PPI)network analysis and function and pathway enrichment analysis.Key genes were obtained by intersecting WGCNA analysis results with differentially expressed genes.miRDB and miRwalk databases were used to predict upstream miRNAs of key genes,and Cytoscape was used to construct key mRNA-miRNA regulatory network.GSE147878 dataset was used to verify expressions of key genes,and evaluate diag-nostic value of key genes according to ROC curve.Results:Genes in magenta module and purple module were significantly related to asthma,mainly involved in Wnt signaling pathway,cell adhesion and so on.A total of 13 key genes were obtained,including ATP6V1G1,TXNDC17,NDUFA4,RHOA,SEC61B,RPS3A,PSMC5,GSPT1,MBP,SMARCC2,GNL3L,RPL7L1,RAD21 and their potential miRNA-mRNA regulatory networks.Conclusion:Key genes such as ATP6V1G1,GSPT1,SEC61B play an important role in bronchial asthma and have clinical diagnostic value.

Objective:Using bioinformatics methods to find key genes related to asthma and discussing their molecular mecha-nisms.Methods:Weighted gene co-expression network analysis(WGCNA)was performed on GSE143303 microarray dataset to screen out the modules significantly related to asthma.Module genes were subjected to protein-protein interaction(PPI)network analysis and function and pathway enrichment analysis.Key genes were obtained by intersecting WGCNA analysis results with differentially expressed genes.miRDB and miRwalk databases were used to predict upstream miRNAs of key genes,and Cytoscape was used to construct key mRNA-miRNA regulatory network.GSE147878 dataset was used to verify expressions of key genes,and evaluate diag-nostic value of key genes according to ROC curve.Results:Genes in magenta module and purple module were significantly related to asthma,mainly involved in Wnt signaling pathway,cell adhesion and so on.A total of 13 key genes were obtained,including ATP6V1G1,TXNDC17,NDUFA4,RHOA,SEC61B,RPS3A,PSMC5,GSPT1,MBP,SMARCC2,GNL3L,RPL7L1,RAD21 and their potential miRNA-mRNA regulatory networks.Conclusion:Key genes such as ATP6V1G1,GSPT1,SEC61B play an important role in bronchial asthma and have clinical diagnostic value.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Metabolic associated fatty liver disease (MAFLD) is a liver disease with hepatocyte steatosis caused by metabolic disorders, which is closely related to obesity, diabetes, metabolic dysfunction, and other factors. Its pathological process changes from simple steatosis, liver inflammation to non-alcoholic steatohepatitis (NASH), and then leads to liver fibrosis, cirrhosis, and liver cancer. At present, no specific therapeutics are available for treatment of MAFLD targeting its etiology. Celastrol is the main active component of the traditional Chinese medicine Celastrus orbiculatus Thunb. In recent years, it has been found that celastrol shows important medicinal value in regulating lipid metabolism, reducing fat and weight, and protecting liver, and then ameliorates MAFLD. This article reviews the related research progress of celastrol in the prevention and treatment of MAFLD, so as to provide a reference for the comprehensive development and utilization of celastrol.
Humans ; Non-alcoholic Fatty Liver Disease/metabolism* ; Liver/pathology* ; Pentacyclic Triterpenes/metabolism* ; Obesity

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

The chromatic values of the broken-fried and single-fried Gardeniae Fructus Praeparatus(GFP) were measured by the color analyzer to analyze the color variation rule, and the contents of 10 main components were determined by ultra-high performance liquid chromatography(UPLC). The multivariate statistical analysis, Pearson correlation analysis, and discriminant analysis were conducted to investigate the color and components of GFP samples. The experimental results revealed that L~*, a~*, b~*, and E~*ab decreased continuously during processing, and the color of samples gradually deepened. The trend and range of chromatic values during broken-frying and single-frying processes were basically identical. Gardenoside, crocin-Ⅰ(C-Ⅰ), and crocin-Ⅱ(C-Ⅱ) showed an obviously downward trend, while the contents of geniposidic acid and 5-hydroxymethylfurfural(5-HMF) increased significantly. Shanzhiside, deacetyl-asperulosidic acid methyl ester, and geniposide(G2) showed a downward trend. Scandoside methyl ester rose first and fell later. Genipin-1-O-gentiobioside(G1) went through a decrease-increase-decrease trend. The change trends of component contents during broken-frying and single-frying processes were generally consistent, but the change range was different. Among all the components, scandoside methyl ester and G1 showed obvious change. Because of different stir-frying time, the change rate of each component content in the process of broken-frying was higher than that in single-frying process. Additionally, geniposidic acid, gardenoside, scandoside methyl ester, C-Ⅰ, C-Ⅱ, and 5-HMF exhibited a higher correlation with apparent color. On the basis of above findings, the discriminant function of two frying processes was established, which could be applied to the discrimination of broken-fried and single-fried samples. This study analyzed the dynamic quality change rule of GFP during broken-frying and single-frying processes based on color-component correlation analysis, and found the two methods showed consistent change trend, yet with slight difference in the quality of samples. This study can provide data support for the processing of GFP.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Fruit ; Gardenia

Fufang Danshen preparation (FDP) is consisted of Salviae Miltiorrhizar Radix et Rhizoma (Danshen), Notoginseng Radix et Rhizoma (Sanqi) and Borneolum Syntheticum (borneol). FDP is usually used to treat myocardial ischemia hypoxia, cerebral ischemia and alzheimer's disease, etc. In the treatment of cerebrovascular diseases, borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs, especially to the brain. The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA (TS IIA), salvianolic acid B (SAB) and ginsenoside Rg1 in FDP. Male healthy Sprague-Dawley (SD) rats were given Danshen extracts, Sanqi extracts (Panax notoginsengsaponins) or simultaneously administered Danshenextracts, Sanqi extracts and borneol. Plasma and brain samples were collected at different points in time. The concentration of TS IIA, SAB and Rg1 was determined by UPLC-MS/MS method. The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software. In comparison with Danshen and Sanqi alone, there were significant differences in pharmacokinetic parameters of TS IIA, SAB and Rg1, and the brain distribution of SAB and TS IIA when Danshen, Sanqi and borneol were administrated together. Borneol statistically significant shortened t

Objective: To investigate the distribution of polymorphisms of glucagon-like peptide-1 receptor gene (GLP-1R) rs10305420 and rs3765467 in Chinese Han type 2 diabetic patients, and the effects on body weight, blood glucose and serum lipid levels. Methods: Two SNPs of GLP-1R rs3765467 and rs10305420 were genotyped by Sanger dideoxy termination sequencing method. The racial difference and the association between the gene polymorphisms and the metabolic markers including BMI, serum lipids and blood glucose were analyzed. Results: The distribution of gene polymorphisms was consistent with the Hardy-Weinberg equilibrium. High-density lipoprotein (HDL-C) levels were significantly lower in the rs10305420 T allele carriers than in the CC genotype (1.00±0.18 vs 1.09±0.22, P=0.02). The triglyceride (TG) level of the rs3765467 A allele carrier was higher than that of the GG type (2.75±2.19 vs 2.07±1.36, P=0.03). The allele frequency of rs10305420 C/T was highly statistically significant compared with European population (P=0.000 3). The allele frequency of rs3765467 G/A was statistically different from that of European and African populations (P<0.01). Conclusions The two genetic polymorphisms were significantly associated with lipid levels in patients with type 2 diabetes, and there was a significant racial difference in the frequency distribution of the two variants.

The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on the activation of caspase-12, a key molecule in endoplasmic reticulum stress (ERS)-associated apoptotic pathway, and to elucidate the underlying molecular mechanisms of macrophage apoptosis. RAW264.7 macrophages were treated with AGE-alb (2, 4 and 6 g/L), control albumin (C-alb, 4 g/L), tunicamycin (TM, 4 mg/L), or pretreated with 4-phenylbutyric acid (PBA, 5 mmol/L) for 1 h and then treated with AGE-alb (4 g/L). After incubation for 24 h, the cell viability and apoptosis were determined by using MTT assay and TUNEL detection kit, respectively. Lactate dehydrogenase (LDH) activity in media was determined by using an assay kit. The protein levels of caspase-12 were examined by Western blot analysis. The results showed that like TM (an ERS inducer), incubation with AGE-alb led to significant decrease in viability and increase in LDH activity in media and apoptotic rate in a dose-dependent manner. In addition, AGE-alb induced activation of caspase-12 especially at the concentration of 4 and 6 g/L (P < 0.01), which was similar to TM. However, PBA (an ERS inhibitor) protected RAW264.7 macrophages from AGE-alb-induced decrease in viability and increases in LDH activity and apoptosis. Moreover, PBA also inhibited the caspase-12 activation induced by AGE-alb (P < 0.05). These results suggest that AGE-alb may induce apoptosis in RAW 264.7 macrophages, and the mechanism may be related to the activation of ERS-associated apoptotic pathway mediated by caspase-12.
Animals ; Apoptosis ; Caspase 12 ; Cell Line, Tumor ; Cell Survival ; Endoplasmic Reticulum Stress ; Macrophages ; Mice ; Phenylbutyrates ; Serum Albumin ; Tunicamycin

OBJECTIVEThis study was to investigate the therapeutic effectiveness and side effect of decitabine combined with modified CAG regimen for relapse or refractory patients with acute myeloid leukemia.

METHODSTen patients suffered from relapsed or refractory acute myeloid leukemia from January 2013 to July 2013 were analyzed retrospectively, and the clinical characteristics, therapeutic effectiveness, side effect were observed. Among 10 patients 7 patients were males and 3 patients were females, the ratio of male to female was 7:3, median age was 45 (17-61) years.

RESULTSAfter treatment by using decitabine combined with modified CAG regimen, 7 patients achived complete remission, 1 patient achived partial remission, 2 patient did not achieve remission, the overall remission rate was 80% (8/10), the median time of white blood cell count recovery was 18.5 (5-28) days, median time of platelet level recovery was 19 (12-29) days. The main side effects of treatment were myelosuppression. There was no new lung infection in all cases, one case died of exacerbation of primary lung infection after therapy.

CONCLUTIONThe treatment of decitabine combined with modified CAG regimen for relapsed and refractory AML shows high response rate, low side effects, so it worthy to further clinical study.

Aclarubicin ; Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; analogs & derivatives ; Cytarabine ; Female ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Recurrence ; Remission Induction ; Retrospective Studies ; Treatment Outcome ; Young Adult