Noncovalent composites of meso-substituted A2B2-porphyrins and carbon nanotubes for enhanced electrocatalytic oxygen reduction.

Exploring highly active oxygen reduction electrocatalysts with low precious metals content is imperative but remains a considerable challenge. Herein, a series of heterobimetallic multi-walled carbon nanotubes (MWCNTs) electrocatalysts based on metal complexes are presented. These electrocatalysts feature diverse transition metals (M=Mn, Fe, Co, Ni) 5,15-bromophenyl-10, 20-methoxyphenyl porphyrin (MBMP) and tetrakis(triphenylphosphine)palladium (0) (Pd[P(Ph3)4]) anchored non-covalently on its surface. The resulting NiBMP-based MWCNTs with Pd[P(Ph3)4] (PdNiN4/MWCNTs) display outstanding electrocatalytic oxygen reduction activity (onset potential, 0.941 V; half wave potential, 0.830 V) and robust long-term durability in alkaline electrolyte. While in neutral condition, the MnBMP-based MWCNTs with Pd[P(Ph3)4] (PdMnN4/MWCNTs) are the most active heterobimetallic ORR catalyst and produce ultra-low concentration hydrogen peroxide (H2O2yield, 1.2%-1.3%). Synergistically tuning the ORR electrocatalytic activity and electron transfer pathway is achieved by the formation of NiBMP/MnBMP-Pd[P(Ph3)4] active sites. This work indicates such metalloporphyrin-Pd[P(Ph3)4] active sites on MWCNTs have significantly positive influence on electrocatalytic ORR systems and provides facile and mild strategy for designing highly efficient ORR electrocatalysts with ultra-low loading precious metal.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

ß2-AR regulates the expression of AKR1B1 in human pancreatic cancer cells and promotes their proliferation via the ERK1/2 pathway.

Psychological stress has been recognized as a well-documented risk factor associated with ß2-adrenergic receptor (ß2-AR) in the development of pancreatic cancer. Aldo-keto reductase 1 member B1 (AKR1B1) is a potential interacting partner of ß2-AR, but the effect of their interaction on pancreatic cancer cells is not known at present. We found a positive correlation between AKR1B1 and ß2-AR expression in pancreatic cancer tissue samples, and co-localization of these proteins in the human pancreatic cancer BXPC-3 cell line. Compared to the controls, the CFPAC-1 and PANC-1 pancreatic cancer cells overexpressing ß2-AR and AKR1B1 respectively showed significantly higher proliferation rates, which is attributed to higher proportion of cells in the S phase and decreased percentage of early apoptotic cells. Furthermore, overexpression of ß2-AR led to a significant increase in the expression of AKR1B1 and phosphorylated extracellular signal-regulated kinase (p-ERK1/2). Overexpression of AKR1B1 significantly decreased ß2-AR levels and increased that of p-ERK1/2. Taken together, ß2-AR directly interacted with and up-regulated AKR1B1 in pancreatic cancer cells, and promoted their proliferation and inhibited apoptosis via the ERK1/2 pathway. Our findings also highlight the ß2-AR-AKR1B1 axis as a potential therapeutic target for pancreatic cancer.

A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer.

PD-L1 is a member of the B7 family co-inhibitory molecules and plays a critical role in tumor immune escape. In this study, we found a polymorphism rs10815225 in the PD-L1 promoter region was significantly associated with the occurrence of gastric cancer. The GG homozygous frequency was higher in the cancer patients than that in the precancerous lesions, which was higher than that in the health controls. This polymorphism locates in the binding-site of Sp1 transcription factor (SP1). The expression level of PD-L1 mRNA in the GG homozygous cancer patients was apparently higher than that in the GC heterozygotes. Luciferase reporter results showed that SP1 bonded to rs10815225 G-allelic PD-L1 promoter instead of C-allelic. Upregulation and knockdown of SP1 resulted in elevation and attenuation of PD-L1 in SGC-7901 cells, respectively. The chromatin immunoprecipitation results further confirmed the binding of SP1 to the promoter of PD-L1. Additionally, rs10815225 was found to be in disequilibrium with a functional polymorphism rs4143815 in the PD-L1 3'-UTR, and the haplotypes of these two polymorphisms were also markedly related to gastric cancer risk. These results revealed a novel mechanism underlying genetic polymorphisms influencing PD-L1 expression modify gastric cancer susceptibility.

Preliminary study of acoustic analysis for evaluating speech-aid oral prostheses: Characteristic dips in octave spectrum for comparison of nasality.

BACKGROUND/PURPOSE: Acoustic analysis is often used in speech evaluation but seldom for the evaluation of oral prostheses designed for reconstruction of surgical defect. This study aimed to introduce the application of acoustic analysis for patients with velopharyngeal insufficiency (VPI) due to oral surgery and rehabilitated with oral speech-aid prostheses. METHODS: The pre- and postprosthetic rehabilitation acoustic features of sustained vowel sounds from two patients with VPI were analyzed and compared with the acoustic analysis software Praat. RESULTS: There were significant differences in the octave spectrum of sustained vowel speech sound between the pre- and postprosthetic rehabilitation. Acoustic measurements of sustained vowels for patients before and after prosthetic treatment showed no significant differences for all parameters of fundamental frequency, jitter, shimmer, noise-to-harmonics ratio, formant frequency, F1 bandwidth, and band energy difference. The decrease in objective nasality perceptions correlated very well with the decrease in dips of the spectra for the male patient with a higher speech bulb height. CONCLUSION: Acoustic analysis may be a potential technique for evaluating the functions of oral speech-aid prostheses, which eliminates dysfunctions due to the surgical defect and contributes to a high percentage of intelligible speech. Octave spectrum analysis may also be a valuable tool for detecting changes in nasality characteristics of the voice during prosthetic treatment of VPI.

Evaluation and clinical significance of the stomach age model for evaluating aging of the stomach-a multicenter study in China.

BACKGROUND: A higher prevalence of chronic atrophic gastritis (CAG) occurs in younger adults in Asia. We used Stomach Age to examine the different mechanisms of CAG between younger adults and elderly individuals, and established a simple model of cancer risk that can be applied to CAG surveillance. METHODS: Stomach Age was determined by FISH examination of telomere length in stomach biopsies. Δψm was also determined by flow cytometry. Sixty volunteers were used to confirm the linear relationship between telomere length and age while 120 subjects were used to build a mathematical model by a multivariate analysis. Overall, 146 subjects were used to evaluate the validity of the model, and 1,007 subjects were used to evaluate the relationship between prognosis and Δage (calculated from the mathematical model). ROC curves were used to evaluate the relationship between prognosis and Δage and to determine the cut-off point for Δage. RESULTS: We established that a tight linear relationship between the telomere length and the age. The telomere length was obvious different between patients with and without CAG even in the same age. Δψm decreased in individuals whose Stomach Age was greater than real age, especially in younger adults. A mathematical model of Stomach Age (real age + Δage) was successfully constructed which was easy to apply in clinical work. A higher Δage was correlated with a worse outcome. The criterion of Δage >3.11 should be considered as the cut-off to select the subgroup of patients who require endoscopic surveillance. CONCLUSION: Variation in Stomach Age between individuals of the same biological age was confirmed. Attention should be paid to those with a greater Stomach Age, especially in younger adults. The Δage in the Simple Model can be used as a criterion to select CAG patients for gastric cancer surveillance.

Effect of PI3K gene silencing on growth, migration and related proteins expression of CD40 signal-mediated gastric cancer cells.

In this study, we investigate effect of PI3K gene silencing on growth, migration and related proteins expression of CD40 signal-mediated gastric cancer cells. We observed that combination of sCD40L with PI3K siRNA could significantly inhibit AGS cells growth, block cells in G1 phase, and promote tumour cells apoptosis after 24 h treatment. Transwell test showed that numbers of cells per visual field in group PI3K siRNA or group sCD40L (after 24 h PI3K siRNA or sCD40L alone treatment) were fewer than that (32.54 ± 4.22) in control group. Numbers of cells per visual field in (after 24 h combination treatment of PI3K siRNA with sCD40L) were significantly fewer than that in group PI3K siRNA or group sCD40L. Compared with group sCD40L, expression level of Fas protein in group sCD40L + PI3K siRNA was significantly increased. The findings suggest that PI3K siRNA may strengthen CD40-induced specific antitumour effect via blocking PI3K/Akt signal pathway, resisting tumour immunoediting regulated by CD40 signal. Combination of sCD40L and PI3K siRNA is an important mechanism of gastric cancer therapy.

Screening and test of CD40 related signal transduction pathway in AGS cells and construction of gene silencing vector.

This study is designed to screen the CD40 related signal transduction pathway in AGS cells and construction of gene silencing vector. Analysis results showed 414 differential genes expression, including upregulation of 209 genes and downregulation of 205 genes. Basing on the ratio of signal in experimental group to signal in control group, 45 genes (38 genes upregulation and seven genes downregulation) with significant (P<0.01) change in expression levels were screened according to the screening standard (signal log ratio≥1 or ≤-1). These genes involved into metabolism, cell cycle and apoptosis, signal transduction and stress response. Furthermore, PI3K mRNA expression level in PI3K siRNA transfected AGS cells was 0.2335±0.0116 72 h after transfection. This value was significantly (P<0.05) lower than that in blank and negative control groups. PI3K protein expression in PI3K siRNA transfected AGS cells was significantly (P<0.05) lower than that in blank and PI3K siRNA/N transfected groups. Therefore, PI3K siRNA gene silencing vector can significantly inhibit PI3K mRNA and protein expression in AGS cells.

Evaluation of early precut with needle-knife in difficult biliary cannulation during ERCP.

BACKGROUND: There is scarce information on whether performing the precut procedure early rather than after several cannulation attempts is associated with different success and complication rates. OBJECTIVE: The aim of this retrospective study was is to compare the early precut technique with the standard one in terms of the results and complications. METHODS: The contemporary success rate and postoperative complications in 792 endoscopic retrograde cholangiopancreatography cases were frequently observed during the period from June 2007 to May 2011, and 56 of these cases were carried out with precut biliary sphincterotomy after the standard sphincterotomy had failed. RESULTS: The success rate for standard sphincterotomy was 89.8%: 51 out of 56 cases were carried out with precut biliary sphincterotomy and succeeded. The total success rate was 96.3%. The difference was significant (χ2=25.62, p<0.01) compared to the success rate of first cannulation, while the difference in complication rates between precut and standard sphincterotomy was minor (9.9 vs. 12.5%, p>0.05). CONCLUSION: Early precut with a needle-knife in a difficult biliary cannulation was safe and effective if performed by experienced endoscopists.

Markers CD40, VEGF, AKT, PI3K, and S100 correlate with tumor stage in gastric cancer.

BACKGROUND: To better understand gastric cancer occurrence and prognosis, we explored the expression of molecules in the CD40 pathway and their correlation with gastric cancer prognosis. PATIENTS AND METHODS: We measured the expression of CD40, VEGF, AKT, PI3K, and S100 in gastric cancer tissues and adjacent normal tissues from 128 patients by immunohistochemistry. RESULTS: The expression of CD40, VEGF, AKT, and PI3K were significantly higher in tumor tissue than in normal tissue, while S100 expression in dendritic cells (DC) was lower. Expression of CD40, VEGF, AKT, and PI3K significantly increased with T stage, while S100 expression decreased with T stage. Lymph node metastasis was associated with low or negative S100 expression. PI3K expression increased with clinical stage, while negative S100 expression was associated with higher clinical stages. Multivariate analysis did not indicate significant associations between any of these markers and recurrence or mortality. CONCLUSION: The correlation between T stage of gastric cancer and the higher expression of CD40, VEGF, AKT, and PI3K, along with lower S100 expression in DC, may provide insights into future targets for more effective immunotherapy for cancer.

Increase of cyclooxygenase-2 inhibition with celecoxib combined with 5-FU enhances tumor cell apoptosis and antitumor efficacy in a subcutaneous implantation tumor model of human colon cancer.

BACKGROUND: The purpose of this study was to investigate the anti-tumor effect and explore the mechanisms of celecoxib (a selective cyclooxygenase-2 inhibitor) combined with 5-fluorouracil (5-FU) on the treatment of human colorectal cancer in a BALB/C nude mouse subcutaneous xenograft model. METHODS: Effects of celecoxib combined with 5-FU on the proliferation of xenograft carcinoma induced by HT-29 were investigated. The apoptotic cells were detected by electron microscope and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. Immunohistochemistry and Western blot were used to estimate the expression of cytochrome C, caspase-3 and caspase-9. RESULTS: Compared with the control group, treatment groups showed significant inhibition of tumor growth. More apoptotic cells existed after treatment with celecoxib combined with 5-FU. Cytochrome C, caspase-3 and caspase-9 were increased in treated groups, and more obviously in the drug combination group. Cyclooxygenase-2 (COX-2) were decreased after treatment with celecoxib only or combined with 5-FU. And the combined group showed a greater decrease. CONCLUSIONS: Celecoxib combined with 5-FU could inhibit the growth of tumors in vivo by inducing apoptosis and activation of the cytochrome C dependency apoptosis signal pathway. A decrease of COX-2 and an increase of cytochrome C, caspase-3 and caspase-9 may be involved in this process.

[The expression of peripheral Th1 and Th17 cells in inflammatory bowel disease and its potential clinical value].

OBJECTIVE: To explore the probable role of Th1 and Th17 cells in the pathogenesis of inflammatory bowel disease (IBD). METHODS: The peripheral blood mononuclear cells (PBMCs) from peripheral blood specimens were collected in the study, including 40 healthy controls, 42 ulcerative colitis (UC) and 39 Crohn's disease (CD). The proportion of Th1 and Th17 cells in the PBMCs was detected with flow cytometry after stimulated by PMA and ionomycin. The result and the clinical data were analyzed. RESULT: The Th1 cell expression was increased in CD (38.32 ± 16.18)% and UC group (34.23 ± 11.60)%, compared with the controls (24.58 ± 10.02)% (P < 0.01). During the convalescence, the Th1 expression in the CD and UC groups in vivo was significantly reduced without difference between the two groups (P > 0.05) . In the IBD group , significant difference in the frequency of Th17 cells could be found between the CD group (2.51 ± 1.59)% and the UC group (4.15 ± 2.75)%, while the Th17 cells were increased in both groups, compared with the controls (1.44 ± 0.73)% (P < 0.05) . Obvious difference in the frequency of Th17 cells could be found between patients at different activity stages and remission stages. The proportion of Th17 cells were higher in the UC patients than that in the CD patients (P < 0.01) . The Th17/Th1 ratio of CD patients, UC patients were 0.08 ± 0.06, 0.14 ± 0.11, which were both higher that in the controls (0.07 ± 0.06). Significant difference could be found between the UC group and the CD group (P < 0.01). CONCLUSIONS: The higher proportion of Th1 and Th17 cells are detected in the peripheral blood of IBD patients, which is correlated closely to the activity of the disease. Th1 and Th17 cells may play an important role in the pathogenesis of IBD.

The construction of high efficient visible-light-driven 3D porous g-C3N4/Fe3O4 photocatalyst: A new photo-induced bacterial inactivation material enhanced by cascade photo-Fenton reaction.

Photocatalytic disinfection is considered a promising method for eliminating the hazards of pathogenic bacteria. Graphitic carbon nitride (g-C3N4) is an ideal photocatalytic bacterial inactivation material for its advantage of tunable band structure, good stability and easy preparation. This work has constructed a novel defective 3D porous g-C3N4 by cyanamide carbonation using dendritic mesoporous silica template. The direct loading of Fe3O4 nanoparticles provided an excellent pg-C3N4-Fe3O4 photocatalyst suitable for water disinfection. Compared to pristine g-C3N4, the prepared 3D porous defective g-C3N4-Fe3O4 exhibited the enhanced visible light absorbance as indicated by the band gap decreasing of 0.66 eV, and about 3 and 10 fold increase of photo-induced current response and O2 adsorption respectively. The pg-C3N4-Fe3O4 showed excellent visible-light-driven photocatalytic bactericidal activity. It could kill 1 × 107 cfu mL-1Escherichia coli completely within 1 h under visible-light illumination (100 mW cm-2) with good reusability, its logarithmic bacterial inactivation efficiency was about 2.5 fold higher than pg-C3N4. The enhanced bactericidal performance is mainly ascribed to the Fe3O4 involved cascade photo-Fenton reaction.

Gastric cancer cell lines AGS before and after CD40 signal activating.

The aim of this study was to investigate the molecular mechanisms underlying the antitumour effects of CD40L through analysing the change of genes expression profile in AGS using Affymetrix Gene Chip. Human gastric carcinoma AGS cells were first incubated with 2 µg/ml sCD40L or equal volume of medium (control) in F12 medium. RNA was isolated from AGS and were reverse transcribed, labeled with digoxigenin-11-dUTP, and then hybridized with Clontech Atlas mouse cDNA expression arrays for comparison. Performing clustering analysis, we found that 7 detected genes were down-regulated and 38 were upregulated as the sCD40L acted on AGS. To further verify the results of gene chip screening, Gene Database was searched, finding that the most significantly up-regulated genes were Gadd45a, c-Jun and Bcl-2, and the most significantly down-regulated genes were Cyclin D1, CDC6, TNFR10B, c-IAP2 and ORC5L. Based upon these findings, the signalling pathways that possibly mediate CD40-induced apoptosis are proposed.

Combined effect of sCD40L and PI3K siRNA on transplanted tumours growth and microenvironment in nude mice with gastric cancer.

The objective of the paper is to investigate the combined effect of sCD40L and phosphatidylinositol 3-kinase (PI3K) siRNA on transplanted tumours growth and microenvironment in nude mice with gastric cancer. 48 h after modeling, the animals were randomly divided into saline + AGS group (A), sCD40L + AGS group (B), saline + PI3K siRNA group (C) and sCD40L + PI3K siRNA group (D), six mice in each group. The mouse in the groups was inoculated with exponential phase AGS cell or PI3K gene silencing cells (100 µl, 5 × 10(6)). After tumour size reaches 0.2-0.3 cm, Tumours in animals of groups were injected with sCD40L (100 µl, 10 mg/kg) or equal volume of saline, thrice each day, respectively. Microvessel density (MVD), apoptosis index, and expression levels of PI3K, Survivin and vascular endothelial growth factor (VEGF) proteins in transplanted tumor cells in gastric cancer nude mice were analyzed by utilizing Immunohistochemistry, western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling assays. Results showed that combination of sCD40L with PI3K siRNA could significantly decrease tumour size, MVD, expression levels of PI3K, Survivin and VEGF proteins, and increase apoptosis index. It can be concluded that combination of sCD40L with PI3K siRNA provides a promising future for gastric cancer therapy.

CD40 signal expression in gastric cancer tissue and its correlation with prognosis of gastric cancer patients.

CD40 signaling plays a critical role in the survival rate of gastric cancer patients. Tumour samples were collected from 73 patients with who were diagnosed as gastric cancer in general surgery department in the 1st affiliated hospital of Suzhou University between September 2002 and July 2003. All patients had not received radiotherapy and chemotherapy before operation. These patients include 46 male and 27 female. Here we show that CD40 is constitutively expressed in the human gastric carcinoma tissues, and CD40 protein and mRNA positive expression in gastric cancer tissues closely correlated with lymph node metastasis and tumour TNM stage. CD40 positive expression in gastric cancer patients with lymph node metastasis was markedly higher than that in gastric cancer patients without lymph node metastasis. CD40 positive expression in stage III-IV gastric cancer patients was markedly higher than that in stage I-II gastric cancer patients. Moreover, CD40 expression closely correlated with prognosis of gastric cancer patients. Therefore, CD40 was taken as grouping variable, and lymph node metastasis and clinical staging were taken as stratification variables, respectively, further analysis showed that prognosis in gastric cancer patients with lymph node metastasis and CD40 positive expression was markedly worse than that in gastric cancer patients without lymph node metastasis and CD40 negative expression (P = 0.0076). These results suggest that CD40 signaling plays a critical role in the survival of gastric cancer patients.

Influence of sCD40L on gastric cancer cell lines.

The CD40 signaling pathway plays a key role in tumor cell proliferation, differentiation, and apoptosis. Gastric cancer usually possesses a higher level of CD40 expression than normal tissue. We evaluated inhibition of soluble CD40 ligand (sCD40L) in apoptosis induction of gastric cancer cells. Gastric cancer cells (AGS and BGC-823) were incubated with sCD40L. Cell viability and cell cycle were determined by methyl-tetrazolium (MTT) assay and flow cytometry, respectively. The results showed that sCD40L hindered cell growth, arrested cells at G0/G1 phase and induced apoptosis. In conclusion, sCD40L suppress growth of gastric cancer cells through apoptosis induction and cell cycle quiescence. This work will provided a new approach to gene therapy of gastric cancer.

Tissue microarrays in Chinese human rectal cancer: study of expressions of the tumor-associated genes.

BACKGROUNDS/AIMS: The cellular basis for rectal cancer development is still unclear. The aim of this study was to evaluate the relationship between the expression of p53, cyclinD1, bcl-2, ß-catenin, c-myc, cyclooxygenase-2 (COX-2) and nm23-H1 and the clinicopathological characteristics of rectal cancer. METHODOLOGY: Expressions of p53, cyclinD1, bcl-2, ß-catenin, c-myc, COX-2 and nm23-H1 proteins were detected by immunohistochemical staining to two tissue microarrays containing tissues accumulated from 54 human rectal cancers and 40 para-cancer mucosa. RESULTS: Significant differences were demonstrated between the rectal cancers and their benign para-cancer counterparts according to the expressions of p53, cyclinD1, bcl-2, ß-catenin, c-myc, COX-2 and nm23-H1 (p<0.05). Additionally, positive correlations of ß-catenin with cyclinD1 and c-myc (r=0.412, p=0.002; r=0.447, p=0.000) and of p53 with bcl-2 (r=0.332, p=0.001) were found. Cancer tissues with overexpression of ß-catenin or bcl-2 were less likely to differentiate to advanced grade. Expression of cyclinD1 had a correlation with clinical stages (p=0.039). In addition, a negative correlation was found between nm23-H1 expression and the histological grades, distance metastasis and Duke's stages. CONCLUSIONS: Aberrant expression of p53, cyclinD1, bcl-2, ß-catenin, c-myc, COX-2 and nm23-H1 might attribute to the carcinogenesis of human rectal cancer. Furthermore, cyclinD1 and nm23-H1 might be involved in rectal cancer progression. This study recommends the application of tissue microarrays in rectal cancer research for its reliable quick throughput.

The Immunomodulatory Effects and Mechanisms of Tim-3 Action in the Early Stage of Mice with Severe Acute Pancreatitis.

BACKGROUND: Tim-3 has been considered as an ideal target for the immunotherapy of inflammation, but it is unclear whether Tim-3 also plays an important role in acute pancreatitis (AP), as well. OBJECTIVE: To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe acute pancreatitis in mice. METHODS: Male BALB/c mice were randomly divided into sham injection group, severe acute pancreatitis group, and anti-Tim-3 treated group. Histopathological scores of the pancreas were calculated, pancreatic myeloperoxidase (MPO) activity was assessed. The concentrations of serum IL-6, IL-10, and TNF-α were evaluated by ELISA method. Quantitative RT-PCR was performed to detect the transcripts of Tim-3, IL-6, IL-10, TNF-α, and TLR4 in peritoneal macrophages. The levels of peritoneal macrophages Tim-3, TLR4, MyD88, and NF-kB p65 were measured by western blot analysis. RESULTS: The pathological scores of the anti-Tim-3 treated group (11.5 ± 1.3) significantly increased compared with the sham (1.3 ± 0.5) and SAP groups (6.9 ± 1.0). Furthermore, the downregulation of Tim-3 significantly aggravated mouse pancreatic tissue damage. It was further shown that Tim-3 negatively regulated the production of pro-inflammatory cytokines, IL-6 and TNF-α, as well as anti-inflammatory cytokine IL-10. Of note, the negative regulation of inflammatory cytokines by Tim-3 was mediated by the activation of TLR4/MyD88 NF-kB signaling pathway. CONCLUSION: Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response.

Expression of CD40 and CD40L in gastric cancer tissue and its clinical significance.

To study expression of CD40 and CD40L in gastric cancer tissue we assessed gastric cancer patients admitted to the Department of Gastroenterology of The First Affiliated Hospital of Soochow University and control subjects. Gastric cancer and normal (from around tumours) tissue samples were obtained from patients. Venous blood samples (gastric cancer and ulcer groups) were drawn on the morning of the day before surgery for the measurement of peripheral sCD40L. The expression of CD40 in gastric carcinoma specimens was examined immuno-histochemically. The clinicopathological factors, including age, sex, tumor size, gross appearance, degree of cellular differentiation, histological classification, depth of tumor invasion, lymph node metastasis, peritoneal dissemination, and TNM stage were analyzed according to the different expression of CD40. The results indicated a high CD40 expression in gastric cancer tissues. This positive expression of CD40 revealed a significant (P < 0.05) correlation with lymphatic metastasis and tumor TNM stage in gastric cancer patients. It is concluded that higher CD40 expression existed in expanding type tumors and could play an important role in clinical diagnosis of gastric cancer patients.