Objective To investigate the effect of resveratrol on murine macrophage cell line (RAW264 .7 cells) polarizing phenotype induced by lipopolysaccharide .Methods RAW264 .7 mouse macrophages seeded in a 6 well plate ,then randomly divided into phosphate buffer saline(PBS) control group ,LPS (100 ng/mL) group ,and LPS (100 ng/mL)+ resveratrol (30 μmol/L) group .In the LPS+ resveratrol group ,LPS was added after incubation with resveratrol for 12 h .Cells were harvested and superna‐tant were collected after incubation with LPS for 12 h .Both the mRNA expression levels of M1 associated markers iNOS and TNF‐αand M2 associated markers IL‐10 ,PPARγ and Arg‐1 were measured by real time quantitative PCR .Expression of iNOS ,Arg‐1 protein were detected by Western blot ,inflammatory factor IL‐12 p40 ,IL‐10 and TNF‐αprotein in the supernatant of were assayed by ELISA .Results PCR detection showed that the mRNA expression levels of M1 associated markers iNOS and TNF‐αin the LPS group were significantly higher than that of LPS+ resveratrol group(P<0 .05) ,but the mRNA expression levels of M2 associated markers IL‐10 ,PPARγand Arg‐1 were significantly lower than that of LPS+ resveratrol group(P<0 .05) .Compared with LPS+resveratrol group ,western blot assay showed that iNOS protein level in LPS group was significantly higher than it (P<0 .05) ,but Arg‐1 protein level was significantly lower than it(P<0 .05) .The levels of IL‐12 p40 and TNF‐αin LPS group were significantly higher than that in LPS+ resveratrol group(P<0 .05) ,but the levels of IL‐10 was significantly lower than it(P<0 .05) .Conclusion Resveratrol may promote LPS stimulated RAW264 .7 macrophage polarization to M2 phenotype .

AIM: To study the effect of safflower injection on expression of COX-2 mRNA in chronic hypoxic hypercapnic rat pulmonary arterioles.METHODS: Sprague-Dawley rats were randomly divided into normal control group,hypoxic hypercapnic group(B),hypoxic hypercapnia+ safflower injection group(C).The concentration of TXB2 and 6-Keto-PGF1? in plasma and in lung were detected by the technique of radioimmunoassay.COX-2 mRNA was observed in arterioles from rats by the technique of in situ hybridization.RESULTS: ① Mean pulmonary arterial pressure(mPAP),weight ratio of right ventricle(RV) to left ventricle plus septum(LV+S) were much higher in B group than those in control group.No significant difference of mean carotid arterial pressure(mCAP) was observed in three groups.② The concentration of TXB2 and the ratio of TXB2/6-keto-PGF1? were significantly higher in B group than those in control group.③ Light microscopy showed that vessel wall area/total area,the density of medial smooth muscle cells and the thickness of medial smooth cell layer were significantly higher in B group than those in control group.Electron microscopy showed proliferation of medial smooth muscle cells and collagenous fibers in pulmonary arterioles in B group.Safflower injection reversed the changes mentioned above.④ Expression of COX-2 mRNA in pulmonary arterioles was much higher in C group than those in B group.Differences of COX-1 mRNA in pulmonary arterioles were not significant between these two groups.CONCLUSION: Safflower injection increases the expression of COX-2 mRNA in chronic hypoxic hypercapnic rat pulmonary arterioles,indicating an important mechanism that safflower injection inhibits the formation of hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling.

Objective To compare the mandibular advancement appliance(MAA) with mandibular advancement and left-leaning appliance (MALA) in the treatment of mild or moderate obstructive sleep ap-nea-hypopnea syndrome (OSAHS). Methods Twenty-two cases of mild or moderate OSAHS were treated with MAA, and 19 cases with MALA. After 1-3 months, they were examined again with Epworth score and polysonmography (PSG). Results After 1-3 months of the MAA or MALA treatment, the Epworth score was improved evidently. The apnea -hypopnea index, max apnea time, mean apnea time, oxygen desaturatian index, and the longest time of oxygen desaturation were all lowered after the treatment, and the lowest SaO2 and the mean SaO2 were higher after the treatment. The differences were all distinctive (P<0.05 or<0.01). When patients treated with MAA were compared with those treated with MALA,only the max apnea time [(35.5±6.9),(31.3±6.0) s, respectively] and the longest time of oxygen desaturation [ (41.0±18.9), (29.9±9.3) s, respectively] had significant difference. Conclusion MALA may be helpful for shortening max apnea time and the longest time of oxygen desaturation, thus MAA is an effective alternative to patients of OSAHS. Further research should be done.

Objective:To investigate the correlation of Mena protein expression with the invasion and metastasis of Mena SNPs with genetic susceptibility in gastric cancers (GC). Methods:A tissue microarray that simulates the invasion and metastasis process of GC was created, and immunohistochemistry was performed to detect the expression of Mena protein. The Mena gene 5 SNP loci geno-types of 188 healthy people and 389 GC patients were assayed using PCR-based LDR analysis. Results:The expression of Mena pro-tein in GC was significantly upregulated and greatly increased in the intestinal-type and mixed-type GC than that in the diffuse-type and was negatively related to the invasion and metastasis of GC. Patients with Mena overexpression had better prognosis. The frequen-cies of the A and G alleles, as well as the AA, AG, and GG genotypes, at the Mena SNP rs3795443 locus were significantly different be-tween patients with gastric carcinoma and the control groups (OR=2.1489,95%CI 1.4607~3.1613, P<0.01). The frequencies of these five Mena gene SNP loci were not significantly related with the survival of patients with gastric carcinoma. Conclusion:The upregula-tion of Mena expression is involved in maintaining the histological phenotype, invasion, metastasis, and prognosis of gastric adenocarci-noma. Individuals with GG and AG genotypes at the Mena rs3795443 locus have increased risk of gastric carcinoma, which suggests that screening for this genotype would be helpful in assessing the genetic susceptibility of gastric carcinoma.

Purpose Investigating the significance of ZO-1 different domains in the invasion and metastasis of gastric carcinoma (GC).Methods A tissue microarray that simulates the invasion and metastasis process of GC was created,and immunohistochemistry was performed to detect the expression of ZO-1 (α-pan),ZO-1 (α +) and ZO-1 (ZU5).Results The GC cell exhibited aberrant expression of ZO-1 (α-pan),ZO-1 (α +) and ZO-1 (ZU5) from membrane translocated to cytoplasm or no expression.The aberrant degree was increased with the invasion,however,was decreased in metastatic lymph node.The aberrant expression was associated with histological types.Conclusion The aberrant expression of ZO-1 (α-pan),ZO-1 (α +) and ZO-1 (ZU5),from membrane translocated to cytoplasm or no expression suggest that domains of PDZ3,GUK,SH3,ZU5 and alpha motif in ZO-1 might be involved in the invasion and metastasis of GC and maintaining of GC phenotype.The aberrant expression of these domains may be the one mechanism of ZO-1 involved in EMT or MET.

Objective To investigate the effect of IGF1R β subunit mutants sb-IGF1R and ma-IGF1R on the biological behavior of osteosarcoma 143B cells. Methods We designed and constructed sb-IGF1R and ma-IGF1R fragments. They were cloned into adenovirus AdEasy shuttle plasmid, to obtain Ad-sbIGF1R and Ad-maIGF1R. We observed the proliferation, migration and apoptosis of the osteosarcoma cells transfected with Ad-sbIGF1R, Ad-maIGF1R and Ad-IGF1R. The Ad-sbIGF1R, Ad-maIGF1R and Ad-GFP nude mouse models were constructed to evaluate the tumor growth in vitro. Results By plasmid PCR, IGF-1R β subunit mutant was overexpressed in osteosarcoma cells. Ad-sbIGF1R and Ad-maIGF1R significantly inhibited the proliferation and migration of osteosarcoma cells, and promoted cell apoptosis, and inhibited tumor growth in subcutaneous tumor-bearing nude mouse models. Conclusion IGF1R β subunit mutants inhibit the proliferation and migration of osteosarcoma cells and induce cell apoptosis.

Kv2.1 channel currents in pancreatic beta-cells are thought to contribute to action potential repolarization and thereby modulate insulin secretion. Because of its central role in this important physiological process, Kv2.1 channel is a promising target for the treatment of type 2 diabetes. Jingzhaotoxin-XI (JZTX-XI) is a novel peptide neurotoxin isolated from the venom of the spider Chilobrachys jingzhao. Two-microelectrode voltage clamp experiments had showed that the toxin inhibited Kv2.1 potassium currents expressed in Xenopus Laevis oocytes. In order to investigate the structure-function relationship of JZTX-XI, the natural toxin and a mutant of JZTX-XI in which Arg3 was replaced by Ala, were synthesized by solid-phase chemistry method with Fmoc-protected amino acids on the PS3 automated peptide synthesizer. Reverse-phase high performance liquid chromatography (RP-HPLC) and matrix assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were used to monitor the oxidative refolding process of synthetic linear peptides to find the optimal renaturation conditions of these toxins. The experiments also proved that the relative molecular masses of refolded peptides were in accordance with their theoretical molecular masses. RP-HPLC chromatogram of co-injected native and refolded JZTX-XI was a single peak. Under the whole-cell patch-clamp mode, JZTX-XI could completely inhibit hKv2.1 and hNav1.5 channels currents expressed in HEK293T cells with IC50 values of 95.8 nmol/L and 437.1 nmol/L respectively. The mutant R3A-JZTX-XI could also inhibit hKv2.1 and hNav1.5 channel currents expressed in HEK293T cells with IC50 values of 1.22 micromol/L and 1.96 micromol/L respectively. However, the prohibitive levels of R3A-JZTX-XI on hKv2.1 and hNav1.5 channels were reduced by about 12.7 times and 4.5 times respectively, indicating that Arg3 was a key amino acid residue relative to the hKv2.1 channel activity of JZTX-XI, but it is also an amino acid residue correlated with the binding activity of JZTX-XI to hNav1.5 channel. Our findings should be helpful to develop JZTX-XI into a molecular probe and drug candidate targeting to Kv2.1 potassium channel in the pancreas.
Animals ; HEK293 Cells ; Humans ; Insulin-Secreting Cells ; metabolism ; Mutant Proteins ; genetics ; pharmacology ; NAV1.5 Voltage-Gated Sodium Channel ; metabolism ; Neurotoxins ; chemical synthesis ; genetics ; pharmacology ; Protein Refolding ; Shab Potassium Channels ; antagonists & inhibitors ; metabolism ; Sodium Channel Blockers ; pharmacology ; Spider Venoms ; genetics ; pharmacology ; Transfection

Objective:To study the risk factors of intra-abdominal infection after hepatectomy in patients with primary liver neoplasms.Methods:The clinical data of patients with primary liver neoplasms who underwent hepatectomy at the Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2019 to December 2021 were retrospectively analyzed. Of 1 229 patients who were enrolled, 48 patients developed postoperative abdominal infection. There were 45 males and 3 females, with age of 58.0 (45.0, 66.0) years old in the infected group. Forth-eight patients without postoperative abdominal infection were selected based on the random number formula to be allocated to the uninfected group to include 44 males and 4 females with age of 58.5 (48.5, 64.8) years old. The general data, preoperative and postoperative laboratory test results, types of liver neoplasms and hepatectomy, pathogenic infective microorganisms and their drug sensitivity tests were collected. Univariate analysis was used to analyze the related factors of intra-abdominal infection after hepatectomy, and significant factors were included in logistic multivariate regression analysis.Results:Of 24 pathogenic strains which were detected in the 143 samples of abdominal infection, the positive rate of culture was 16.78%(24/143). Multivariate logistic regression analysis showed that prealbumin <180 mg/L ( OR=3.757, 95% CI: 1.117-12.634), intraoperative blood transfusion ( OR=6.363, 95% CI: 1.301-31.113) and the time of drainage tube placement ≥7 d ( OR=31.098, 95% CI: 6.906~140.029) were independent risk factors of intra-abdominal infection after hepatectomy. Conclusion:Prealbumin <180 mg/L, intraoperative blood transfusion and the time of drainage tube placement ≥7 d were independent risk factors of intra-abdominal infection after hepatectomy for primary liver neoplasms.

PURPOSE: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. MATERIALS AND METHODS: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. RESULTS: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. CONCLUSIONS: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.
Adenocarcinoma ; Chromogranin A ; Classification ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Neural Cell Adhesion Molecules ; Prognosis ; Stomach ; Stomach Neoplasms ; Synaptophysin

Diagnosis, Differential ; Humans ; Lung Neoplasms/genetics* ; Neoplasm Metastasis ; Neoplasms, Multiple Primary/diagnosis*