Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer.

BACKGROUND: The incidence and mortality of colorectal cancer (CRC) are among the highest in the world, and its occurrence and development are closely related to tumor neovascularization. When the balance between pigment epithelium-derived factors (PEDF) that inhibit angiogenesis and vascular endothelial growth factors (VEGF) that stimulate angiogenesis is broken, angiogenesis is out of control, resulting in tumor development. Therefore, it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment. AIM: To investigate the expression and significance of PEDF, VEGF, and CD31-stained microvessel density values (CD31-MVD) in normal colorectal mucosa, adenoma, and CRC. METHODS: In this case-control study, we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022. Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy (normal control group), 50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy (adenoma group), and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery (CRC group). An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens, analyze their differences, study the relationship between the two and clinicopathological factors in CRC group, record CD31-MVD in the three groups, and analyze the correlation of PEDF, VEGF, and CD31-MVD in the colorectal adenoma group and the CRC group. The F test or adjusted F test is used to analyze measurement data statistically. Kruskal-Wallis rank sum test was used between groups for ranked data. The chi-square test, adjusted chi-square test, or Fisher's exact test were used to compare the rates between groups. All differences between groups were compared using the Bonferroni method for multiple comparisons. Spearman correlation analysis was used to test the correlation of the data. The test level (α) was 0.05, and a two-sided P< 0.05 was considered statistically significant. RESULTS: The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group, adenoma group, and CRC group (100% vs 78% vs 50%, χ2 = 34.430, P < 0.001; ++~++ vs +~++ vs -~+, H = 94.059, P < 0.001), while VEGF increased gradually (0% vs 68% vs 96%, χ2 = 98.35, P < 0.001; - vs -~+ vs ++~+++, H = 107.734, P < 0.001). In the CRC group, the positive expression rate of PEDF decreased with the increase of differentiation degree, invasion depth, lymph node metastasis, distant metastasis, and TNM stage (χ2 = 20.513, 4.160, 5.128, 6.349, 5.128, P < 0.05); the high expression rate of VEGF was the opposite (χ2 = 10.317, 13.134, 17.643, 21.844, 17.643, P < 0.05). In the colorectal adenoma group, the expression intensity of PEDF correlated negatively with CD31-MVD (r = -0.601, P < 0.001), whereas VEGF was not significantly different (r = 0.258, P = 0.07). In the CRC group, the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF (r = -0.297, P < 0.05; r = -0.548, P < 0.05), while VEGF expression intensity was positively related to CD31-MVD (r = 0.421, P = 0.002). CONCLUSION: It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

Mucosa color and size may indicate malignant transformation of chicken skin mucosa-positive colorectal neoplastic polyps.

BACKGROUND: Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions, including colorectal adenoma. Screening colonoscopy frequently reveals chicken skin mucosa (CSM; white or yellow-white speckled mucosa) surrounding colorectal polyps, caused by macrophages engulfing and accumulating the lipids decomposed by colon cells or adjacent tumors. CSM-positive colorectal polyps are associated with various diseases; however, their prognosis varies greatly. Cold snare polypectomy is commonly used to resect lesions up to 10 to 15 mm in diameter without signs of submucosal invasion but is controversial for CSM-positive colorectal polyps. Improved imaging is required to diagnose and treat CSM-positive colorectal polyps. AIM: To highlight the clinical significance of CSM surrounding colorectal polyps and clarify the associated treatment for endoscopists. METHODS: This retrospective cohort study included 177 patients with CSM-positive colorectal polyps diagnosed using endoscopy. All patient-related information was extracted from the Goldisc soft-clinic DICOM system or electronic medical record system. Based on the pathological results, patients were classified as non-neoplastic polyps (five juvenile polyps), neoplastic polyps, non-invasive high-grade neoplasia (NHGN), or submucosal invasive carcinoma (SM stage cancer). We analyzed and compared the clinical features, suspected risk factors for malignant transformation of neoplastic polyps, and early infiltration of submucosal carcinoma. RESULTS: The diameters of NHGN and SM polyps were much smaller than those of neoplastic polyps. Most NHGN polyps had a deeper red mucosal color. On logistic regression analyses, diameter and deeper red mucosal color were independent risk factors for malignant transformation of neoplastic polyps. Type 1 CSM was more common in high-grade intraepithelial neoplasia and SM; type 2 CSM was more common in neoplastic polyps. Logistic regression analyses revealed no significant differences in the malignant transformation of neoplastic polyps or early submucosal invasion of CSM-positive colorectal cancer. Changes in the CSM mucosa surrounding neoplastic polyps and submucosal invasion of colorectal cancer disappeared within 12 months. No tumor recurrence was found during either partial or complete endoscopic resection of the CSM. CONCLUSION: CSM-positive colorectal polyps > 1 cm in diameter or with deeper red mucosa may be related to NHGN. Resection of CSM surrounding colorectal adenomas did not affect tumor recurrence.

Chicken skin mucosa surrounding small colorectal cancer could be an endoscopic predictive marker of submucosal invasion.

BACKGROUND: Chicken skin mucosa (CSM) surrounding colon polyps is a common endoscopic finding with pale yellow-speckled mucosa during a colonoscopy screening. Although reports about CSM surrounding small colorectal cancer are scarce, and its clinical significance in intramucosal and submucosal cancers is unclear, previous studies have suggested it could be an endoscopic predictive marker for colonic neoplastic and advanced polyps. Currently, because of the inaccurate preoperative evaluation by endoscopists, many small colorectal cancers, particularly lesions with a diameter < 2 cm, are improperly treated. Therefore, more effective methods are required to better assess the depth of the lesion before treatment. AIM: To explore potential markers of small colorectal cancer early invasion under white light endoscopy, providing patients with better treatment alternatives. METHODS: This retrospective cross-sectional study included 198 consecutive patients [233 early colorectal cancers (ECCs)] who underwent endoscopy or surgical procedures at the Digestive Endoscopy Center of Chengdu Second People's Hospital between January 2021 and August 2022. The participants had pathologically confirmed colorectal cancer with a lesion diameter < 2 cm and received endoscopic or surgical treatment, including endoscopic mucosal resection and submucosal dissection. Clinical pathology and endoscopy parameters, including tumor size, invasion depth, anatomical position, and morphology, were reviewed. Fisher's exact test, the χ2 test, and Student's t-test were used to analyze the patient's basic characteristics. Logistic regression analysis was used to examine the relationship between morphological characteristics, size, CSM prevalence, and ECC invasion depth under white light endoscopy. Statistical significance was set at P < 0.05. RESULTS: The submucosal carcinoma (SM stage) was larger than the mucosal carcinoma (M stage) with a significant difference (17.2 ± 4.1 vs 13.4 ± 4.6 mm, P < 0.01). M- and SM-stage cancers were common in the left colon; however, no significant differences were found between them (151/196, 77% and 32/37, 86.5%, respectively, P = 0.199). The endoscopic features of colorectal cancer revealed that CSM, depressed areas with clear boundaries, and erosion or ulcer bleeding were more common in the SM-stage cancer group than in the M-stage cancer group (59.5% vs 26.2%, 46% vs 8.7%, and 27.3% vs 4.1%, respectively, P < 0.05). CSM prevalence in this study was 31.3% (73/233). The positive rates of CSM in flat, protruded, and sessile lesions were 18% (11/61), 30.6% (30/98), and 43.2% (32/74), respectively, with significant differences (P = 0.007). CONCLUSION: CSM-related small colorectal cancer was primarily located in the left colon and could be a predictive marker of submucosal invasion in the left colon.

Tumor attachment to Major intrahepatic vascular for Colorectal liver metastases.

BACKGROUND: Colorectal liver metastases attached major intrahepatic vessels has been considered to be a risk factor for survival outcome after liver resection. The present study aimed to clarify the outcomes of R1 surgery (margin < 1 mm) in CRLM patients, distinguishing parenchymal margin R1 and attached to major intrahepatic vessels R1. METHODS: In present study, 283 CRLM patients who were evaluated to be attached to major intrahepatic vessels initially and underwent liver resection following preoperative chemotherapy. They were assigned to two following groups: R0 (n = 167), R1 parenchymal (n = 58) and R1 vascular (n = 58). The survival outcomes and local recurrence rates were analyzed in each group. RESULTS: Overall, 3- and 5-year overall survival rates after liver resection were 53.0% and 38.2% (median overall survival 37 months). Five-year overall survival was higher in patients with R0 than parenchymal R1 (44.9%% vs. 26.3%, p = 0.009), whereas there was no significant difference from patients with vascular R1 (34.3%, p = 0.752). In the multivariable analysis, preoperative chemotherapy > 4 cycles, clinical risk score 3-5, RAS mutation, parenchymal R1 and CA199 > 100 IU/ml were identified as independent predictive factors of overall survival (p < 0.05). There was no significant difference for local recurrence among three groups. CONCLUSION: Parenchymal R1 resection was independent risk factor for CRLM. Vascular R1 surgery achieved survival outcomes equivalent to R0 resection. Non-anatomic liver resection for CRLM attached to intrahepatic vessels might be pursued to increase patient resectability by preoperative chemotherapy.

Clinical guideline on magnetically controlled capsule gastroscopy (2021 edition).

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians.

Irinotecan- vs oxaliplatin-based regimens for neoadjuvant chemotherapy in colorectal liver metastasis patients: A retrospective study.

BACKGROUND: Neoadjuvant chemotherapy (NC) improves the survival outcomes of selected patients with colorectal liver metastasis (CRLM). The benefits of irinotecan-based regimens in these patients are still under debate. AIM: To compare the benefits of irinotecan- and oxaliplatin-based regimens in patients with resectable CRLM. METHODS: From September 2003 to August 2020, 554 patients received NC and underwent hepatectomy for CRLM. Based on a 1:1 propensity score matching (PSM) model, 175 patients who received irinotecan were matched to 175 patients who received oxaliplatin to obtain two balanced groups regarding demographic, therapeutic, and prognostic characteristics. RESULTS: Chemotherapy was based on oxaliplatin in 353 (63.7%) patients and irinotecan in 201 (36.3%). After PSM, the 5-year progression-free survival (PFS) and overall survival (OS) rates with irinotecan were 18.0% and 49.7%, respectively, while the 5-year PFS and OS rates with oxaliplatin were 26.0% and 46.8%, respectively. Intraoperative blood loss, operating time, and postoperative complications differed significantly between the two groups. In the multivariable analysis, carbohydrate antigen 19-9, RAS mutation, response to NC, tumor size > 5 cm, and tumor number > 1 were independently associated with PFS. CONCLUSION: In NC in patients with CRLM, irinotecan is similar to oxaliplatin in survival outcomes, but irinotecan is superior regarding operating time, intraoperative blood loss, and postoperative complications.

Neoadjuvant chemotherapy improves overall survival in resectable colorectal liver metastases patients with high clinical risk scores-- A retrospective, propensity score matching analysis.

Background: The use of neoadjuvant chemotherapy (NAC) in resectable colorectal liver metastases (CRLM) patients is controversial. High-risk patients are more likely to benefit from NAC despite its hepatotoxic effects. Since patients with a high tumor burden receive NAC more frequently, previous retrospective studies have imbalanced baseline characteristics. The results of randomized controlled trials are still pending. This study aimed to assess the efficacy of NAC in resectable CRLM patients with high clinical risk scores (CRS) proposed by Fong et al. after balancing baseline characteristics by propensity score matching (PSM). Methods: Resectable CRLM patients with high CRS (3-5) undergoing hepatectomy between January 2003 and May 2021 were retrospectively studied. Patients were divided into the NAC and the upfront surgery group. Survival outcomes and surgical outcomes were compared after PSM. Results: The current study included 322 patients with a median follow-up of 40 months. After one-to-two PSM, patients were matched into the upfront surgery group (n = 56) and the NAC group (n = 112). Baseline characteristics were balanced after matching. There was no difference in long-term progression-free survival (PFS), while overall survival (OS) from the initial diagnosis was improved in the NAC group (P = 0.048). Postoperative hospital stays were shorter in the NAC group (P = 0.020). Surgical outcomes were similar, including major hepatectomy rate, intraoperative ablation rate, blood loss, operative time, perioperative blood transfusion, positive surgical margin, and postoperative intensive care unit stay. In multivariable analysis, RAS mutation, maximum tumor diameter≥3cm, and no NAC were independent risk factors for OS. The 1-year PFS in the NAC group was improved, although it failed to reach a statistical difference (P = 0.064). Conclusions: NAC could improve OS in resectable CRLM patients with high CRS (3-5) and have a shorter postoperative hospital stay.

Prognostic factors in colorectal liver metastases patients with various tumor numbers treated by liver resection: a single-center, retrospective study.

BACKGROUND: Multiple liver metastases is considered a risk factor for overall survival of colorectal liver metastases patients (CRLM) after curative resection. However, whether the prognostic factors were constant in patients with various liver metastases (LM) numbers has not been adequately investigated. This retrospective study aimed to evaluate the changing of prognostic factors on overall survival (OS) in CRLM patients with various LM after curative resection. METHODS: Patients who underwent liver resection for CRLM between January 2000 and November 2020 were retrospectively studied. They were divided into three subgroups according to LM numbers by X-tile analysis. Multivariable analysis identified prognostic factors in each subgroup. Nomograms were built using different prognostic factors in three subgroups, respectively. Performance of the nomograms was assessed according to the concordance index (C-index) and calibration plots. The abilities of different scoring systems predicting OS were compared by calculating the area under the time-dependent receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 1095 patients were included. Multivariable analysis showed tumor number increasing was an independent risk factor. Patients were subsequently divided into 3 subgroups according to the number of LM by X-tile analysis, namely solitary (n = 375), 2-4 (n = 424), and ≥ 5 (n = 296). The 3-year and 5-year OS rates were 64.1% and 54.0% in solitary LM group, 58.1% and 41.7% in 2-4 LM group, and 50.9% and 32.0% in ≥ 5 LM group, respectively (p < 0.001). In multivariable analysis, RAS mutation was the only constant independent risk factor in all subgroups. The nomograms were built to predict survival based on independent factors in three subgroups. The C-index for OS prediction was 0.707 (95% CI 0.686-0.728) in the solitary LM group, 0.695 (95% CI 0.675-0.715) in the 2-4 LM group, and 0.687 (95% CI 0.664-0.710) in the ≥ 5 LM group. The time-dependent AUC values of nomograms developed using different risk factors after stratifying patients by tumor number were higher than the traditional scoring systems without patient stratification. CONCLUSIONS: The prognostic factors varied among CRLM patients with different LM numbers. RAS mutation was the only constant risk factor. Building prediction models based on different prognostic factors improve patient stratification.

Establishment of Early Multi-Indicator Prediction Models of Moderately Severe Acute Pancreatitis and Severe Acute Pancreatitis.

Background: It is critical to accurately identify patients with severe acute pancreatitis (SAP) and moderately SAP (MSAP) in a timely manner. The study was done to establish two early multi-indicator prediction models of MSAP and SAP. Methods: Clinical data of 469 patients with acute pancreatitis (AP) between 2015 and 2020, at the First Affiliated Hospital of Fujian Medical University, and between 2012 and 2020, at the Affiliated Union Hospital of Fujian Medical University, were retrospectively analyzed. The unweighted predictive score (unwScore) and weighted predictive score (wScore) for MSAP and SAP were derived using logistic regression analysis and were compared with four existing systems using receiver operating characteristic curves. Results: Seven prognostic indicators were selected for incorporation into models, including white blood cell count, lactate dehydrogenase, C-reactive protein, triglyceride, D-dimer, serum potassium, and serum calcium. The cut-offs of the unwScore and wScore for predicting severity were set as 3 points and 0.513 points, respectively. The unwScore (AUC = 0.854) and wScore (AUC = 0.837) were superior to the acute physiology and chronic health evaluation II score (AUC = 0.526), the bedside index for severity in AP score (AUC = 0.766), and the Ranson score (AUC = 0.693) in predicting MSAP and SAP, which were equivalent to the modified computed tomography severity index score (AUC = 0.823). Conclusions: The unwScore and wScore have good predictive value for MSAP and SAP, which could provide a valuable clinical reference for management and treatment.

12-Lipoxygenase promotes epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway in gastric cancer cells.

BACKGROUND: 12-Lipoxygenase (12-LOX) plays a major role in the progression and metastasis of various types of cancer. In gastric cancer (GC), the expression level of 12-LOX is significantly up-regulated; however, its function, and underlying mechanism of action remain unclear. METHODS: The mRNA and protein expression levels of 12-LOX were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses, respectively, in GC cell lines. 12-LOX expression was stably up-regulated using lentiviral vector in BGC823 and MGC803 cells, and cell-counting kit-8 (CCK8), colony formation, and invasion assays were performed to verify the function of 12-LOX in proliferation and metastasis. In addition, the expression levels of epithelial-mesenchymal transition (EMT) differentiation markers and downstream targets of the Wnt/ß-catenin signaling pathway were examined by Western blotting. A nude mouse model of tumor growth and metastasis was established to investigate the role of 12-LOX in vivo. RESULTS: Our findings demonstrate that 12-LOX mRNA and protein were highly expressed in GC cell lines. 12-LOX overexpression promoted GC cell proliferation, migration, and invasion both in vitro and in vivo. In addition, up-regulation of 12-LOX promoted the EMT in GC cells, as reflected by a decrease in E-cadherin expression and an increase in N-cadherin and Snail expression. 12-LOX overexpression in GC cells also increased the expression of multiple downstream targets of the Wnt/ß-catenin signaling pathway. CONCLUSION: These findings revealed that 12-LOX functions as an oncogene in promoting GC cell proliferation and metastasis in vitro and in vivo. In addition, 12-LOX might regulate the EMT via the Wnt/ß-catenin signaling pathway, indicating a potential role for 12-LOX as a target in GC treatment.

A New Quantum Blind Signature Scheme with BB84-State.

The blind signature is widely used in cryptography applications because it can prevent the signer from gaining the original message. Owing to the unconditional security, the quantum blind signature is more advantageous than the classical one. In this paper, we propose a new provable secure quantum blind signature scheme with the nonorthogonal single-photon BB84-state and provide a new method to encode classical messages into quantum signature states. The message owner injects a randomizing factor into the original message and then strips the blind factor from the quantum blind signature signed by the blind signer. The verifier can validate the quantum signature and announce it publicly. At last, the analytical results show that the proposed scheme satisfies all of the security requirements of the blind signature: blindness, unforgeability, non-repudiation, unlinkability, and traceability. Due to there being no use of quantum entanglement states, the total feasibility and practicability of the scheme are obviously better than the previous ones.

Lack of association between SREBF-1c gene polymorphisms and risk of non-alcoholic fatty liver disease in a Chinese Han population.

The transcription factor sterol regulatory element-binding protein-1c (SREBP-1c) is a key regulator of lipogenesis and insulin sensitivity, and is associated with non-alcoholic fatty liver disease (NAFLD). Here, we assessed the impact of common single nucleotide polymorphisms (SNPs) in SREBF-1c on NAFLD susceptibility and associated metabolic phenotypes in a Han Chinese population. Four common SNPs (rs62064119, rs2297508, rs11868035 and rs13306741) in the SREBP-1c gene were selected and genotyped in 593 patients with NAFLD and 593 healthy controls. Unconditional logistic regression was performed to assess the risk of NAFLD by determining odds ratios and 95% confidence intervals (CIs). No significant differences in genotype and allele frequencies of these four SNPs were found between the NAFLD population and the controls (all P > 0.05). In addition, we did not find any association between the SREBF-1c SNPs and the clinical and biochemical parameters, such as body mass index, total cholesterol, high density lipoprotein-and low density lipoprotein-cholesterol or systolic and diastolic blood pressure, except that the rs2297508 C-allele or rs11868035 G-allele showed significant associations with lower triglyceride levels in control subjects (P < 0.01). Our findings suggested that the four polymorphisms in SREBF-1c gene are not associated with risk of NAFLD in the Chinese Han population.

The roles of HBV infection and host factors in ultrasound-diagnosed fatty liver: a case-control study.

BACKGROUND/AIMS: The present study is to evaluate the roles of HBV infection, host factors and their interactions in the development of ultrasound-diagnosed fatty liver in Fujian province of China, a highly HBV endemic area. METHODOLOGY: From June 2007 to May 2008, 527 ultrasound-diagnosed fatty liver patients and 1042 controls were ultrasonically diagnosed in this hospital-based case-control study. Their demographic, anthropometric, biochemical, behavioral factors and HBV markers were compared, and factors associated with fatty liver were determined by multivariate logistic regression analysis. RESULTS: Multivariate ORs and 95% confidence intervals (Cls) of fatty liver were 3.96 (2.10-7.48) for HBsAg positivity, 2.97 (1.78-4.94) for HBsAg negativity with antibodies positivity (either anti-HBe or anti-HBc or both), 1.66 (1.10-2.51) for low alcohol consumption, 7.09 (4.28- 11.75) for obesity, 3.19 (1.75-5.81) for reduced high density lipoprotein cholesterol (HDL-C), 2.17 (1.00-4.72) for elevated fasting plasma glucose (FPG), 2.71 (1.72-4.27) for hypertriglyceridemia, 9.19 (4.32-19.57) for hypertension, and 2.89 (1.86-4.48) for hyperuricemia. Furthermore, synergistic interactions on the additive model were observed between HBV infection and obesity, hypertriglyceridemia, reduced HDL-C, and hyperuricemia with regard to the risk of fatty liver. CONCLUSIONS: Ultrasound-diagnosed fatty liver in Fujian province of China is closely associated with HBV infection, low alcohol consumption, obesity, and other features of the metabolic syndrome. In addition, HBV infection was synergistic with obesity, hypertriglyceridemia, reduced HDL-C, and hyperuricemia as far as the risk of fatty liver concerned.

12-lipoxygenase induces apoptosis of human gastric cancer AGS cells via the ERK1/2 signal pathway.

12-Lipoxygenase (12-LOX) is over-expressed in a variety of human tumors, but its exact effect on the tumorogenesis of gastric cancer remains largely obscure. To investigate the effect of 12-LOX and its inhibitor baicalein on proliferation and apoptosis of human gastric cancer, AGS cells were separately treated with 12-hydroxyeicosatetraenoic acid (12-HETE, a metabolite of 12-LOX) and baicalein. MTT assay revealed that the absorbance of the 12-HETE-treated group was significantly (P < 0.01) higher than that of control group and that the absorbance of baicalein-treated group was significantly (P < 0.01) less than that of the control group, and that 48 h after treatment the apoptosis index of the baicalein-treated group was significantly (P < 0.01) higher than that of the untreated group and was significantly (P < 0.01) lower in the 12-HETE-treated group. Western blotting analysis was used to investigate the mechanism of these effects. The results revealed that the concentration of phosphorylated ERK in cells treated with 100 nmol L(-1) 12-HETE was significantly (P < 0.05) higher than in the untreated group and that the concentration of phosphorylated ERK1/2 in cells treated with 40 micromol L(-1) baicalein was significantly (P < 0.05) lower than in the untreated group. The expression level of bcl-2 was up-regulated and down-regulated after separate treatment with 12-HETE and baicalein, respectively, and both of these effects could be blocked by PD98059. Protein kinase C (PKC) activity was increased by treatment with 12-HETE and reduced by treatment with baicalein (P < 0.05). The PKC inhibitor BIM (bisindolymaleimide-I) blocked the phosphorylation of ERK1/2 and activation of PKC induced by 12-LOX. When pretreated with BIM, the concentration of phospho-ERK1/2 or bcl-2 in the BIM + 12-HETE-treated group was significantly (P < 0.05) lower than in that treated with 12-HETE only, and the concentration in the BIM + baicalein-treated group was significantly (P < 0.05) higher than in that treated with baicalein only. On the basis of these data we conclude that, via its metabolite 12-HETE, 12-LOX abolishes proliferation of AGS cells and protect cells from apoptosis by activating the ERK1/2 pathway and, eventually, enhances expression of bcl-2. Because PKC is also involved in the activation of ERK1/2 induced by 12-LOX, 12-LOX inhibitors would be potentially powerful anticancer agents for prevention and cure of human gastric cancer.

[Effects of medium-chain fatty acid on weight gain and lipids metabolism in obese rats].

OBJECTIVE: Some researchers considered medium chain fatty acids a group of potential agents in the prevention of obesity for their particular metabolism characters. METHODS: In this study, the authors investigated the effects of medium chain fatty acids on body weight gains, food intake, adipose depots and serum lipid profiles. Healthy male Sprague-Dawley rats were fed for 38 days with over-fat diets and oils containing MCFA at different level. RESULTS: Significant decreases of body weight [( 295.2 +/- 29.7) g vs. (324.6 +/- 9.1) g] (P < 0.05), the weight of adipose pads [(5.30 +/- 1.57) g vs. (7.20 +/- 1.74) g](P < 0.05), the level of leptin in serum[(1.61 +/- 0.39) ng/ml vs. (2.04 +/- 0.46) ng/ml] (P < 0.05), the sizes of fat cells but increase of HDL-C [(0.73 +/- 0.12) mmol/L vs. (0.60 +/- 0.06)mmol/L] (P < 0.05) were noted in the group fed MCFA at 0.975 g/kg bw per day as compared with those of the group fed soybean oil. CONCLUSION: The results suggested the role of MCFA in prevention of obesity and there is no adverse effect on lipid metabolism if the proportion of MCFA to total fat scouce is mild.

Overexpression of HBxAg in hepatocellular carcinoma and its relationship with Fas/FasL system.

AIM: To study the expression and serum level of HBxAg, Fas and FasL in tissues of HCC patients, and to assess the relationship between HBxAg and Fas/FasL system. METHODS: Tissues from 50 patients with HCC were tested for the expression of HBxAg, Fas and FasL by S-P immunohistochemistry. Serum levels of sFas/sFasL and HBsAg/HBeAg were measured by ELISA assay. HBV X gene was detected by PCR in serum and confirmed by automatic sequencing. Fifty cases of liver cirrhosis and 30 normal controls were involved in serum analysis. RESULTS: The expression of HBxAg, Fas and FasL in carcinoma tissues was 96 %, 84 % and 98 %, respectively. Staining of HBxAg, Fas and FasL was observed predominately in cytoplasms, no significant difference was found in intensity between HBxAg, Fas and FasL (P>0.05). HBxAg, Fas and FasL might express in the same area of carcinoma tissues and this co-expression could be found in most patients with HCC. The mean levels of sFas in serum from HCC, cirrhosis and normal controls were 762.29 +/- 391.56 microg.L(-1), 835.36 +/- 407.33 microg.L(-1) and 238.27 +/- 135.29 microg.L(-1). The mean levels of sFasL in serum from HCC, cirrhosis and normal controls were 156.36 +/- 9.61 microg.L(-1), 173.63 +/- 18.74 microg.L(-1) and 121.96 +/- 7.83 microg.L(-1). Statistical analysis showed that both sFas and sFasL in HCC and cirrhosis patients were significantly higher than those in normal controls (P<0.01). Serum HBV X gene was found in 32% of HCC patients and 46% of cirrhotic patients. There was no significant relationship between serum level of sFas/sFasL and serum X gene detection (P>0.05). Eight percent of HCC patients with negative HBsAg and HBeAg in serum might have X gene in serum and HBxAg expression in carcinoma tissues. CONCLUSION: Our data suggest that HBxAg and Fas/FasL system plays an important role in the development of human HCC. Expression of HBxAg can leads to expression of Fas/FasL system which and reverse apoptosis of hepatocellular carcinoma induced by FasL.

Expression of insulin-like growth factor 1 and insulin-like growth factor 1 receptor and its intervention by interleukin-10 in experimental hepatic fibrosis.

AIM: To study the expression of IGF-1 and IGF-1R and its intervention by interleukin-10 in the course of experimental hepatic fibrosis. METHODS: Hepatic fibrosis was induced in rats by carbon tetrachloride intoxication and liver specimens were taken from the rats administered CCl4 with or without IL-10 treatment and the animals of the control group. Immunoreactivities for insulin-like growth factor-1 (IGF-1) and IGF-1 receptor(IGF-1R) were demonstrated by immunohistochemistry, and their intensities were evaluated in different animal groups. RESULTS: The positive levels for IGF-1 and IGF-1R were increased with the development of hepatic fibrosis, with the positive signals localized in cytoplasm and/or at the plasmic membrane of hepatocytes. The positive signals of IGF-1 and IGF-1R were observed more frequently (P<0.01) in the CCl4-treated group (92.0 % and 90.0 %) compared to those in the control group. The positive signals decreased significantly (P<0.05) in IL-10-treated group. The responses in IGF-1 and IGF-1R expression correlated with the time of IL-10 treatment. CONCLUSION: The expression of IGF-1 and IGF-1R immunoreactivities in liver tissue seems to be up-regulated during development of hepatic fibrosis induced by CCl(4), and exogenic IL-10 inhibits the responses.

Nimesulide inhibits proliferation via induction of apoptosis and cell cycle arrest in human gastric adenocarcinoma cell line.

AIM: To evaluate the potential role of Nimesulide, a selective COX-2 inhibitor, in proliferation and apoptosis of gastric adenocarcinoma cells SGC7901. METHODS: Cell counts and MTT assay were used to quantify the influence of Nimesulide in the proliferation of SGC7901 cells. Transmission electron microscopy and flow cytometry were used to observe the induction of Nimesulide the apoptosis of SGC7901 cells and influence in the distribution of cell cycle. The expression of P27(kip1) protein was observed by immunocytochemical staining. RESULTS: SGC-7901 Cells treated with Nimesulide at various concentrations exhibited a profound dose- and time-dependent reduction in the proliferation rate over the 72 h test period. The highest survival rate of the cells was 78.7 %, but the lowest being 22.7 %. Nimesulide induced apoptosis of the cells in a dose-dependent and non-linear manner and increased the proportion of cells in the G(0)/G(1) phase and decreased the proportion in the S and G(2)/M phase of the cell cycle. Meanwhile, Nimesulide could up-regulate the expression of P27(kip1) protein. CONCLUSION: The induction of apoptosis and cell cycle arrest are both anti-proliferative responses that likely contribute to the antineoplastic action of nimesulide on SGC-7901 cells. The up-regulation of P27(kip1) gene may contribute to the accumulation of these cells in the G(0)/G(1) phase following treatment with Nimesulide. Selective COX-2 inhibitor may be a new channel of the chemoprevention and chemotherapy for gastric carcinoma.