BACKGROUNDCD44v6 plays an important role in invasion and metastasis of tumor, Livin has anti-apoptotic effects. The present study aimed to explore the expression and clinical significance of CD44v6 and Livin in gastric cancer tissue.

METHODSStreptavidin-peroxidase linked immunohistochemical method was used to determine the expression of CD44v6 and Livin in gastric cancer tissue and adjacent normal gastric tissues from 59 patients with histopathologically confirmed gastric cancer, and in gastric tissue specimens of 15 patients with gastric polyps, and 15 patients with chronic non-atrophic gastritis. The chi-square test was used for comparison of the relevant factors, Spearman's rank correlation test was applied for relationship among positive expression of the proteins.

RESULTSThe expresion of CD44v6 was positive in 64.4% of the gastric cancer patients; 5.1%, 0 and 13.3% in specimens of normal tissues adjacent to the cancer tissues, in gastric tissue specimens of patients with gastric polyps, and patients with chronic non-atrophic gastritis, respectively. The expression of Livin was positive in 52.5% of the gastric cancer tissues, 6.8%, 0 and 6.7% in the adjacent normal gastric tissue, specimens of patients with gastric polyps and chronic non-atrophic gastritis, respectively. The expression of CD44v6 was significantly correlated with the depth of invasion, the degree of differentiation, and lymphnode metastasis of gastric cancer (P < 0.05). The positive expression rate of Livin protein was also significantly correlated with degree of differentiation of gastric cancer cells and metastasis to lymphnodes (P < 0.05), but not correlated with the depth of invasion and pathological types (P > 0.05). The expression of CD44v6 and Livin in the gastric cancer tissue was positively correlated (r(s) = 0.286, P = 0.028).

CONCLUSIONSThe increased expression of CD44v6 and Livin in gastric cancer tissue may be closely related with development and progression of gastric cancer. CD44v6 and Livin may be new biological markers of gastric cancer.

Adaptor Proteins, Signal Transducing ; analysis ; physiology ; Aged ; Female ; Humans ; Hyaluronan Receptors ; analysis ; physiology ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; analysis ; physiology ; Male ; Middle Aged ; Neoplasm Proteins ; analysis ; physiology ; Stomach Neoplasms ; chemistry ; metabolism ; pathology

Aim To investigate the protective effect of sinomenine(SIN)against dibutyltin(DBT)induced injury in HL02 cells and explore the potential mechanism.Methods HL02 cells were cultured and divided into control,model and SIN-treated groups.Cell proliferation was detected by MTT method.Cell morphology was observed.Cell apoptosis was detected by Acridine orange/ethidium bromide(AO/EB)fluorescent staining and Annexin V-FITC/PI double staining.Meanwhile,intracellular reactive oxygen species(ROS)concentration was detected by DCFH-DA staining.Mitochondrial membrane potential(MMP)was tested by JC-1 dye.Moreover,the mRNA expression of apoptosis-related proteins was detected by qRT-PCR,and the protein expression of Bcl-2,Bax,caspase-9,cleaved-caspase-3 were measured via Western blot.Results The pretreatment with SIN increased the cell viability and decreased morphological changes induced by DBT in a dose-dependent manner.Meanwhile,cell apoptotic rates and intracellular ROS decreased,and the loss of MMP was partially restored.Compared to DBT-treated group,SIN treatment could increase the mRNA levels of Bcl-2,Bcl-xL and decrease the mRNA levels of Bax,Bad,cytochrome-c,Apaf-1,caspase-9 and caspase-3.Furthermore,SIN could significantly up-regulated the DBT-induced decrease in Bcl-2/Bax ratio,and down-regulated the DBT-induced over-expressions of caspase-9 and cleaved-caspase-3.Conclusions SIN could protect HL02 cells against DBT-induced cell injury,which is related to the inhibition of ROS-mediated mitochondrial apoptosis.

OBJECTIVETo sequence PrM and E gene of the Japanese encephalitis virus isolated from Gansu province in 2008 and analysis the genotype of new JEV isolates and the molecular characterization of E gene.

METHODSComputer software was used to analyze nucleic acid sequence and deduced amino acid sequence, and draw phylogenetic trees, including ClustalX2.09, MegAlign and Mega4.

RESULTSThe six JEV strains were clustered in genotype I. 87.5%-87.9% identity in nucleotide sequence and 96.8%-97.2% identity in amino acid sequence were found in E gene when compared with the vaccine strain SA14-14-2. Eleven common amino acid differences were observed in E protein between new isolates and the vaccine strain.

CONCLUSIONGenotype I JEVs were isolated from mosquitoes collected in Gansu province. The amino acid difference occurred in sites that were not the key ones affecting the antigenic of JEV.

Amino Acid Sequence ; Animals ; Cell Line ; China ; Cricetinae ; Encephalitis Virus, Japanese ; chemistry ; classification ; genetics ; isolation & purification ; Encephalitis, Japanese ; virology ; Humans ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; Viral Proteins ; chemistry ; genetics

OBJECTIVES: To establish a combined high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) method to detect the synthetic cannabinoid CUMYL-PEGACLONE in e-cigarette oil and hair. METHODS: HPLC-MS/MS and GC-MS were used to establish the detection method of CUMYL-PEGACLONE, and the hair of drug-involved persons and the seized e-cigarette oil were detected. RESULTS: The main mass spectrometry characteristic ions m/z of CUMYL-PEGACLONE measured by GC-MS were 91, 179, 197, 254 and 372. CUMYL-PEGACLONE had a good linear relationship in the mass concentration range of 2-50 ng/mL, and the linear correlation coefficient (r) was greater than 0.99. The limit of detection (LOD) of CUMYL-PEGACLONE in hair was 0.01 ng/mg, and the limit of quantitation (LOQ) was 0.02 ng/mg. The LOD of CUMYL-PEGACLONE in e-cigarette oil was 1 ng/mg, and the LOQ was 2 ng/mg. The average recoveries of CUMYL-PEGACLONE under the attempt at high, intermediate and low levels in blank human hair and e-cigarette oil matrix were 98.2%-132.4% and 93.5%-110.6%, and the intraday and intraday precision were 1.2%-12.9% and 0.7%-2.9%. CUMYL-PEGACLONE was detected in the hair of 15 drug-involved persons. Except for 1 person who was lower than LOQ, the concentration of CUMYL-PEGACLONE in the hair of other 14 persons was 0.035-0.563 ng/mg. The mass fraction of CUMYL-PEGACLONE in 2 e-cigarette oil were 0.17% and 0.21%, respectively. CONCLUSIONS The established HPLC-MS/MS and GC-MS methods are applied to the detection of HPLC-MS/MS in drug-related cases, which provides strong evidence support for the handling authority to quickly investigate these cases, and also provides a reference for the identification of such substances in future.
Humans ; Illicit Drugs/analysis* ; Tandem Mass Spectrometry ; Electronic Nicotine Delivery Systems ; Cannabinoids ; Hair/chemistry* ; Limit of Detection ; Substance Abuse Detection/methods*

This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.

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