Modified whitehead hemorrhoidectomy versus partial hemorrhoidectomy for fourth-degree circular mixed hemorrhoids: A retrospective analysis.

Background: Grade IV circular hemorrhoids are difficult to treat. We aim to describe the modified whitehead hemorrhoidectomy procedure and to assess the effectiveness and safety of this procedure for grade IV circular hemorrhoid patients. Methods: Patients with grade Ⅳ circular hemorrhoids who underwent modified Whitehead hemorrhoidectomy and partial hemorrhoidectomy for fourth-degree circular mixed hemorrhoids were retrospectively reviewed. Clinical data were extracted from the database at our institution, and long-term postoperative complications were assessed through repeated outpatient examinations and telephonic communication. Results: A total of 205 patients were included in this study. The mean operative time was 59.2 ± 13.8 min. The average hospital stay was 4.6 ± 1.0 days. For postoperative complications, 66 (32.2%) patients had urinary retention, 10 (4.9%) patients had a sense of incomplete rectal emptying, 5 (2.4%) patients had anal incontinence, and 6 (2.9%) patients had wound infection. For long-term postoperative complications, 3 (1.5%) patients experienced mild to moderate anal stricture, 2 (1%) patients experienced mucosal ectropion, they all had smooth recoveries, and none of them needed secondary surgery. None of these patients had a hemorrhoid recurrence. A total of 205 patients who received modified Whitehead hemorrhoidectomy and 161 who received partial hemorrhoidectomy were included. There were no residual hemorrhoids in patients who received modified Whitehead hemorrhoidectomy, and none had hemorrhoid recurrence. Fifty-eight patients who received partial hemorrhoidectomy had hemorrhoidal residues, and 19 patients experienced hemorrhoid recurrence. After modified Whitehead hemorrhoidectomy, 3 patients developed anal stenosis, and 2 had mucosal ectropion. Four patients developed anal stricture after partial hemorrhoidectomy, and none had mucosal ectropion. They all had smooth recoveries, and none of them needed a secondary surgery. For the mean duration of surgery, postoperative bleeding, postoperative pain, wound infection, sense of incomplete rectal emptying, anal incontinence, and urinary retention, no statistically significant differences were found between the two groups. Conclusions: Compared with partial hemorrhoidectomy, modified whitehead hemorrhoidectomy is an effective and safe surgical procedure and does not significantly increase the risk of anal stenosis and mucosal ectropion for grade IV circular hemorrhoid patients. Prospective randomized controlled trials are needed to verify our results.

Redo inferior pubectomy for failed anastomotic urethroplasty in pelvic fracture urethral injury.

Objectives: To assess the effect of redo inferior pubectomy on the management of complicated pelvic fracture urethral injury (PFUI) in patients with a history of failed anastomotic urethroplasty. Materials and methods: We retrospectively reviewed all patients receiving redo anastomotic urethroplasty with redo inferior pubectomy for failed PFUI between January 2010 and December 2021. Patients with incomplete data and those who were lost to follow-up were excluded. Successful urethroplasty was defined as the restoration of a uniform urethral caliber without stenosis or leakage and further intervention. Functional results, including erectile function and urinary continence, were evaluated. Descriptive statistical analyses were then performed. Results: Thirty-one patients were included in this study. Among them, concomitant urethrorectal fistula occurred in 2 patients, and concomitant enlarged bladder neck occurred in 1. The stenosis site was the bulbomembranous urethra in 2 patients and the prostatomembranous urethra in 29. The mean length of urethral stenosis in all patients was 3.1 cm (range, 2.0-5.0 cm). After a mean follow-up of 34.6 months, the final success rate was 96.8%. The incidence of erectile dysfunction reached 77.4% (24/31). Normal continence was achieved in 27 (87.1%) patients. One patient developed urinary incontinence of grade II requiring urinary pads because of an enlarged bladder neck. According to the Clavien-Dindo classification, postoperative complications of grade I occurred in 7 patients and grade II in 4. Conclusions: Repeat anastomotic urethroplasty with repeat inferior pubectomy provides reliable success rates for failed PFUI. In complicated cases, it should be known and mastered.

Adherence to diabetes risk reduction diet and the risk of head and neck cancer: a prospective study of 101,755 American adults.

Background: Adherence to the diabetes risk reduction diet (DRRD) may potentially reduce the risk of developing head and neck cancer (HNC) as the diet includes fruits and limits red and processed meats, known risk factors for HNC. However, there is currently no epidemiological research to investigate this potential association. Methods: The present study utilized data on demographics, lifestyles, medications, and diets of participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to explore the potential association between adherence to DRRD and the risk of HNC. We used a DRRD score to evaluate adherence to the dietary pattern and employed Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HNC risk. Several subgroup analyses were carried out to identify potential effect modifiers, and multiple sensitivity analyses were performed to evaluate the stability of the correlation. The nine components of the DRRD was assessed separately for its association with the risk of HNC. Results: During a mean follow up of 8.84 years, 279 cases of HNC were observed. DDRD score was found to be inversely associated with the risk of HNC (HR Q4 vs. Q1: 0.582; 95% CI: 0.396, 0.856; p = 0.005 for trend) in a linear dose-response manner (p = 0.211 for non-linearity). Subgroup analysis indicated this inverse correlation was more pronounced among participants who had never smoked (HRQ4 vs. Q1: 0.193; 95% CI: 0.073, 0.511; p < 0.001 for trend) compared to current or former smokers (p = 0.044 for interaction). The primary association of DDRD and HNC risk remained robust after several sensitivity analyses. Regarding the individual components of DRRD, an inverse association was also observed between the risk of HNC and increased intake of cereal fiber and whole fruit (all p < 0.05 for trend). Conclusion: Our findings provide evidence that following the DRRD pattern may reduce the risk of NHC, especially for non-smokers.

ANXA10 is a prognostic biomarker and suppressor of hepatocellular carcinoma: a bioinformatics analysis and experimental validation.

Liver hepatocellular carcinoma (LIHC) is one of the main cancers worldwide and has high morbidity and mortality rates. Although previous studies have shown that ANXA10 is expressed at low levels in LIHC tumor tissues, the biological function of ANXA10 in LIHC is still unclear. Therefore, we utilized TCGA, TIMER, GEPIA2, TISIDB, LinkedOmics, ssGSEA algorithms and CIBERSORT methodology to preliminarily evaluate the potential mechanism of ANXA10 in LIHC. In vitro experiments were used to further verify some functions of ANXA10. Consequently, we found that ANXA10 mRNA/protein expression was downregulated in LIHC tissue compared to normal tissue. ANXA10 was significantly linked with clinicopathological features, immunocytes, multiple cancer-related pathways, m6A modification and a ceRNA network. A three-gene prognostic signature rooted in ANXA10-related immunomodulators was determined and found to be an independent prognostic predictor. A nomogram was constructed to predict survival with good accuracy. Additionally, in vitro trials revealed that ANXA10 upregulation inhibited LIHC cell proliferation and migration. This study reveals that ANXA10 may serve as a prognostic marker and promising therapeutic target in LIHC clinical practice through various biologic functions.

Case report: A case report and literature review of extrapancreatic solid pseudopapillary neoplasm.

Background: Solid pseudopapillary neoplasm (SPN) is a rare tumor with low malignant potential, which typically occurs in the pancreas. Extrapancreatic SPN is also extremely rare worldwide. Case presentation: We report a case of a 70-year-old woman hospitalized with abdominal pain and bloating. The patient did not have any underlying diseases, such as diabetes, coronary heart disease, or hypertension. More than 30 years ago, the patient underwent surgery for "ectopic pregnancy". The patient had no family history of hereditary disease, nor did any immediate family members have a history of cancer. Laboratory tests showed that her hemoglobin and albumin levels were low and she had a high level of cancer antigen 125 (CA125). Enhanced computed tomography (CT) showed a large tumor in the abdomen and pelvis. The patient subsequently underwent surgery, and it was found that the tumor was attached to the terminal ileum. Pathological findings suggested that the tumor was an extrapancreatic SPN, with an ectopic pancreas found in the tumor tissue. The patient did not receive chemotherapy or radiotherapy after surgery. After 13 months of follow-up, the patient was admitted again with abdominal pain. CT showed tumor recurrence with extensive systemic metastases. The patient and her family refused reoperation and biopsy, and the patient was discharged after the abdominal pain and anemia resolved. Conclusion: We report a rare case of extrapancreatic SPN of ileal origin, which could be the first report worldwide. It had aggressive biological features, with recurrence and metastasis 13 months after surgery. For extrapancreatic SPN, the risk of recurrence should be assessed, and for tumors suspected of malignant behavior, a longer follow-up after discharge may be needed. Although SPN generally has a good prognosis after surgery, there is no consensus on whether postoperative chemotherapy and other treatments are needed for patients with high recurrence risk.

Pelvic Fracture Urethral Distraction Defects in Preschool Boys: How to Recognize and Manage?

OBJECTIVE: To share the cases of pelvic fracture urethral distraction defect (PFUDD) in preschool boys and evaluate the transperineal anastomotic urethroplasty strategy for the treatment of these cases. MATERIALS AND METHODS: Between January 2010 and May 2021, 8 preschool boys (<6 years) with PFUDD underwent the transperineal anastomotic urethroplasty in our center were retrospectively reviewed. Etiology was traumatic pelvic fracture in all boys. The type of trauma included: fall injury in 1 and vehicle crush injury in 7. Urethroplasty was performed at least 3 months after initial trauma or the last failed intervention. One of them suffered from PFUDD associated with urethrorectal fistula received urethroplasty combined with fistula repair. A successful urethroplasty was defined as restoring the patency and continuity of urethra and no further interventions were needed. RESULTS: Follow-up was obtained in all the 8 preschool boys for 3-135 (median: 65) months. The average age was 4.1 years old (range 1-5). After operation, the final success rate was 100%. Neither stenosis recurrence nor urinary fistulas were reported during follow-up. Of the 8 boys, 1 developed urinary incontinence, only occurring after high-intensity exercise such as running. Potency state could not be evaluated for all boys due to the young age. One boy reported having normal morning erection after a follow-up of 135 months. CONCLUSION: PFUDD in preschool boys is a challenge for both the urologist and parent. Our study preliminarily confirmed that the progressive anastomotic urethroplasty strategy can ensure a high success rate.

Bioinformatic Analysis of Immune Significance of RYR2 Mutation in Breast Cancer.

BACKGROUND: Currently, immunotherapy is widely used for breast cancer (BC) patients, and tumor mutation burden (TMB) is regarded as a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in BC are not fully understood. METHODS: Comprehensive bioinformatic analyses were performed using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Survival curves were analyzed via Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used for prognosis analysis. Gene set enrichment analysis (GSEA) was performed to explore regulatory mechanisms and functions. The CIBERSORT algorithm was used to calculate the tumor-infiltrating immune cell fractions. RESULTS: We analyzed somatic mutation data of BC from TCGA and ICGC datasets and found that 19 frequently mutated genes were reported in both cohorts, namely, SPTA1, TTN, MUC17, MAP3K1, CDH1, FAT3, SYNE1, FLG, HMCN1, RYR2 (ryanodine receptor 2), GATA3, MUC4, PIK3CA, KMT2C, TP53, PTEN, ZFHX4, MUC16, and USH2A. Among them, we observed that RYR2 mutation was significantly associated with higher TMB and better clinical prognosis. Moreover, GSEA revealed that RYR2 mutation-enriched signaling pathways were related to immune-associated pathways. Furthermore, based on the CIBERSORT algorithm, we found that RYR2 mutation enhanced the antitumor immune response by enriching CD8+ T cells, activated memory CD4+ T cells, and M1 macrophages. CONCLUSION: RYR2 is frequently mutated in BC, and its mutation is related to increased TMB and promotes antitumor immunity; thus, RYR2 may serve as a valuable biomarker to predict the immune response.

circ_0038718 promotes colon cancer cell malignant progression via the miR-195-5p/Axin2 signaling axis and also effect Wnt/ß-catenin signal pathway.

OBJECTIVE: Colon cancer (CC) is one of the most common cancers whose progression is regulated by a number of factors, including circular RNAs (circRNAs). Nonetheless, circ_0038718 is a novel circRNA, and its regulatory mechanism in CC remains unclear. METHODS: Real-time quantitative PCR (qRT-PCR) was performed to detect the expression of circ_0038718, miR-195-5p and Axin2. Western blot was conducted to determine the protein expression of Axin2 and the key proteins on Wnt/ß-catenin signaling pathway. Oligo (dT) 18 primers and RNase R were employed to identify the circular features of circ_0038718, and the location of circ_0038718 in cells was detected via nucleocytoplasmic separation. Dual-luciferase reporter assay and RNA binding protein immunoprecipitation experiment were carried out to investigate the molecular mechanism of circ_0038718/miR-195-5p/Axin2. Additionally, MTT assay was conducted to assess cell proliferation; Transwell assay was performed to evaluate cell migration and invasion, respectively. The effect of circ_0038718 on CC tumor growth was tested through tumor formation in nude mice. RESULTS: circ_0038718 was highly expressed in CC and could sponge miR-195-5p in cytoplasm. Silencing circ_0038718 suppressed the proliferative, migratory and invasive abilities of CC cells, while the promoting effect of high circ_0038718 expression on CC cells was reversed upon miR-195-5p over-expression. Axin2 was a downstream target of miR-195-5p and could regulate the Wnt/ß-catenin signaling pathway. Axin2 expression was modulated by circ_0038718/miR-195-5p. Knockdown of Axin2 could also attenuate the promoting effect of high circ_0038718 expression on CC cell malignant progression, thus inhibiting tumor growth. CONCLUSION: circ_0038718 is able to facilitate CC cell malignant progression via the miR-195-5p/Axin2 axis, which will provide a new idea for finding a novel targeted treatment of CC.

Transperineal anastomotic urethroplasty for the treatment of pelvic fracture urethral distraction defects: a progressive surgical strategy.

PURPOSE: The aim was to reduce the difficulty of transperineal anastomotic urethroplasty for pelvic fracture urethral distraction defect (PFUDD) and make it easy to master through an effective strategy. PATIENTS AND METHODS: Between January 2010 and December 2019, 1637 patients with PFUDDs were treated by transperineal anastomotic urethroplasty. The surgical strategy we used was the progressive transperineal anastomotic urethroplasty. First, after full mobilization of the distal bulbomembranous urethra, the stenotic urethra was transected directly at the proximal margin of the stenotic urethra to expose the proximal disrupted urethral end. Second, if the urethral stenosis location of some complicated cases was too deep to fully mobilize, the position of urethral transection was selected at the distal margin of the stenotic urethra. Then, the distal and proximal disrupted urethras were then trimmed and anastomosed without tension. A successful urethroplasty was defined as reestablishment of a uniform urethral caliber and no further interventions were needed. RESULTS: Follow-up was obtained in 1475 patients. The success rate was 92.4% (1363/1475). Among the 112 failed patients, 10 patients received endoscopic urethrotomy, 99 underwent a secondary or third anastomotic urethroplasty and 3 successfully treated with perineal skin flap urethroplasty. After final successful urethroplasty, 125 patients (8.5%) had different degrees of urinary incontinence and 15 (1.6%) developed de novo erectile dysfunction (1.6%). CONCLUSION: The progressive transperineal anastomotic urethroplasty strategy was effective for treating PFUDD cases, improving surgical efficacy and reducing complications. It may contribute to standardizing the transperineal anastomotic urethroplasty and making it easy to master.

Mucin 4 mutation is associated with tumor mutation burden and promotes antitumor immunity in colon cancer patients.

At present, immunotherapy is widely used for different mismatch repair (dMMR) or highly microsatellite instability (MSI-H) colorectal cancer patients, and tumor mutation burden (TMB) is a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in colon cancer remains unclear. In the present study, we analyzed somatic mutation data of colon cancer from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets, and found that 17 frequently mutated genes were occurred in both cohorts, including APC, TP53, TNN, KRAS, MUC16, MUC4 (mucin 4), SYNE1, FLG, FAT4, OBSCN, FAT3, RYR2, PIK3CA, FBXW7, DNAH11, MUC5B and ZFHX4. Interestingly, only MUC4 mutation was associated with higher TMB and patient clinical prognosis among the 17 mutated genes. Moreover, according to gene set enrichment analysis (GSEA) and the CIBERSORT algorithm, we revealed that MUC4 mutation activated signaling pathways involved in the immune system and enhanced the antitumor immune response. In conclusion, MUC4 may have important clinical implications for immune therapy of colon cancer.

Glutamine protects intestine against ischemia-reperfusion injury by alleviating endoplasmic reticulum stress induced apoptosis in rats.

PURPOSE: Glutamine, as an essential part of enteral nutrition and parenteral nutrition agent, has been widely recognized to be a kind of important intestinal mucosa protectant in clinical practice and experimental research. However, the mechanisms of its protective effects are still not fully understand. Consequently, this study aimed to explore the potential mechanism of glutamine on ischemia-reperfusion (I/R) injury induced endoplasmic reticulum (ER) stress in intestine. METHODS: An experimental model of intestinal I/R in rats was established by 1 hour occlusion of the superior mesenteric artery followed by 3 hours of reperfusion. Morphologic changes of intestinal mucosa, apoptosis of epithelial cells, and expression of intestinal Grp78, Gadd153, Caspase-12, ATF4, PERK phosphorylation (P-PERK) and elF2αphosphorylation(P-elF2α) were determined. RESULTS: After I/R, the apoptotic index of intestinal mucosa epithelial cells observably increased with notable necrosis of intestinal mucosa, and the expressions of Grp78, Gadd153, Caspase-12, ATF4, P-PERK and P-elF2αall were increased. However, treatment with glutamine could significantly relieve intestinal I/R injury and apoptosis index. Moreover, glutamine could clearly up-regulate the expression of Grp78, restrain P-PERK and P-elF2α, and reduce ATF4, Gadd153 and Caspase-12 expressions. CONCLUSION: Glutamine may be involved in alleviating ER stress induced intestinal mucosa cells apoptosis.

18ß-glycyrrhetinic acid inhibits migration and invasion of human gastric cancer cells via the ROS/PKC-α/ERK pathway.

18ß-glycyrrhetinic acid (18ß-GA) is a bioactive component of licorice root which exerts pharmacological activities including anti-inflammatory, antiviral, anti-oxidative and anti-cancer effects. The current study further investigated the molecular mechanisms associated with the inhibitory effects of 18ß-GA on tumor metastasis in human gastric cancer cells. The results indicated that 18ß-GA significantly reduced invasion and migration activities and suppressed MMP-2 and 9 activities on SGC-7901cells in a dose-dependent manner. Further study showed 18ß-GA upregulated E-cadherin expression but downregulated vimentin expression. The results also showed that 18ß-GA inhibited ROS formation, PKC-α expression and the phosphorylation of ERK in a dose-dependent manner. In conclusion, this study revealed that 18ß-GA inhibits migration and invasion via the ROS/PKC-α/ERK signaling pathway in gastric cancer cells. This suggests that 18ß-GA has the potential to be used as an effective chemopreventive agent for the prevention of gastric cancer metastasis.

[Genetic characterization analysis on epidemic rubella virus strains isolated in Liaoning from 2007 to 2012].

To analyze the genetic characterization of epidemic rubella virus strains isolated in Liaoning from 2007-2012, a total of 145 rubella virus strains were isolated using Vero/Slam cell line from the patients' throat swabs during rubella outbreaks and sporadics cases in Liaoning Province from 2007 to 2012. Fragments of 945 nucleotides containing 1E gene from 145 rubella virus isolates were amplified by RT-PCR, the PCR products were sequenced and analyzed. Based on the 739 nucleotides of 1E gene, the phylogenetic trees were constructed with 32 WHO rubella reference strains of 13 genotypes downloaded from GenBank and 145 rubella virus strains. The results showed that the 145 rubella virus strains in 2007 -2012 belonged to genotype 1E, nucleotide acids and amino acids similarities were 97.2%-100.0% and 97.6%-100.0%, respectively. Compared to the 1E reference strains(Rvi/ Dezhou.CHN/02, RVi/MYS/01), the nucleotide acids and amino acids similarities were 96.6%-99.2% and 98.2%-100.0%, respectively except for one amino acid change (Val246-Ala246) of RVi/Shenyang. Liaoning. CHN/13.11/13, and Asp262-Asn262 of RVi/Shenyang. Liaoning. CHN/13.11/4 and RVi/Liaoyang. Liaoning. CHN/26. 11/2. there had no change found in the important antigenic epitope sites, the hemagglutination inhibition and neutralization epitopes of the other rubella viruses. All the 145 strains isolated had the same amino acid change (Leu338--Phe338) in E1 protein. These findings suggested that genotype 1E of rubella virus was the predominant genotype in Liaoning province. the rubella prevailed in recent six years was mainly caused by rubella viruses genotype 1E with multi-transmission routes.

High-intensity focused ultrasound combined with herpes simplex virus thymidine kinase gene-loaded ultrasound-targeted microbubbles improved the survival of rabbits with VX2 liver tumor.

BACKGROUND: To explore the anti-tumor effect of high-intensity focused ultrasound (HIFU) combined with herpes simplex virus thymidine kinase (HSV-TK) gene-loaded ultrasound-targeted microbubbles on VX2 rabbit liver tumors. METHODS: Seventy-five New Zealand white rabbits were randomly divided into five groups after the models of VX2 rabbit liver tumors were established: (a) HIFU group; (b) HIFU and HSV-TK group (HIFU + HSV-TK); (c) HIFU, HSV-TK and ultrasound group (HIFU + HSV-TK + US); (d) HIFU, HSV-TK gene-loaded microbubbles and ultrasound group (HIFU + HSV-TK-MBs + US); and (e) HSV-TK gene-loaded microbubbles and ultrasound group (HSV-TK-MBs + US). After 2 weeks of VX2 liver tumor implantation, rabbits in groups (a), (b), (c) and (d) received HIFU to establish rabbit models of residual tumor by ablating 80% of the tumor volume. After HIFU ablation, rabbits in different groups received MBs wrapped around HSV-TK or HSV-TK solution via marginal ear veins and/or local ultrasonic irradiation to the tumor. Six rabbits in each group were sacrificed 48 h after the corresponding treatment, and tumors were extracted for in vitro experiments. Thymidine kinase mRNA was detected by the real-time polymerase chain reaction. The green fluorescent protein expression in liver tumor was detected by western blotting and immunohistochemistry. Tumor cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. The growth curves of VX2 liver tumors and survival curves of rabbits were compared. RESULTS: Forty-eight hours after treatment, TK mRNA and protein were the highest in the HIFU + HSV-TK + US + MBs group and the HSV-TK + US + MBs group (p < 0.05). At 48 h after treatment, the apoptotic index of tumor cells in HIFU + HSV-TK-MBs + US group was the highest (p < 0.05). Compared to other groups, HIFU combined with MBs wrapped HSV-TK suicide gene significantly inhibited tumor growth in vivo (p < 0.05) and prolonged the survival time of animals (p < 0.05). CONCLUSIONS: HIFU combined with HSV-TK gene-loaded ultrasound-targeted MBs significantly inhibited the growth of VX2 rabbit liver tumors in vivo and prolonged the survival time of the animals, providing a novel gene delivery method and a novel strategy for liver tumor treatment.

Capecitabine plus oxaliplatin compared with 5-fluorouracil plus oxaliplatin in metastatic colorectal cancer: Meta-analysis of randomized controlled trials.

The aim of this study was to evaluate the curative effects and safety of capecitabine plus oxaliplatin compared with 5-fluorouracil (5-FU) plus oxaliplatin in patients with metastatic colorectal cancer (MCRC). We searched the Cochrane Central register of Controlled Trials (CENTRAL), PubMed, Ovid, ScienceDirect, EBSCO, EMBASE and conference proceedings for eligible trials. A meta-analysis was performed using Review Manager 5.0. A total of 3,603 cancer patients from 7 trials were analyzed, and the baseline patient characteristics were comparable in all studies. Curative effect outcomes including complete response (CR) (OR=0.78; 95% CI 0.47-1.31; p=0.35), partial response (PR) (OR=0.81; 95% CI 0.65-1.00; p=0.05) and the overall response rate (ORR) (OR=0.85; 95% CI 0.71-1.02; p=0.08) showed similar curative effects between the capecitabine plus oxaliplatin group and the 5-FU plus oxaliplatin group. Moreover, the median overall survival (OS) and progression-free survival (PFS) had no statistically significant differences. Regarding safety, hand-foot syndrome was more frequently observed in the capecitabine plus oxaliplatin group (OR=2.71; 95% CI 2.04-3.61; p<0.00001), while stomatitis and neutropenia were reversed. Other toxic effects had no statistically significant differences between the two groups. Our results showed that capecitabine plus oxaliplatin had similar curative effects to 5-FU plus oxaliplatin, however, it was safer in patients with MCRC.

Expression of vascular endothelial growth factor-C in gastric carcinoma and the effect of its antisense gene transfection on the proliferation of human gastric cancer cell line SGC-7901.

PURPOSE: The aim of this study was to investigate the relationship between the expression of vascular endothelial growth factor-C (VEGF-C) in gastric carcinoma and tumor lymphangiogenesis and to determine the effect of antisense-VEGF-C gene transfection on proliferation. METHODS: Adjacent cancer tissues were collected from 72 gastric carcinoma cases and compared with 10 nongastric carcinoma tissues to detect the expression of VEGF-C and its messenger RNA (mRNA) and calculate the density of neonatal lymphatic microvessels. The in vitro-cultured gastric cancer cell line SGC-7901 was transfected with recombinant plasmid pCI-neo-anti VEGF-C. The expression in the transfected cells and the proliferation were determined. RESULTS: The positive rate of VEGF-C mRNA in the lymph node metastasis tissues was 85.7% compared with negative controls (20%, P < .05). The density of lymphatic vessels in the metastasis group was 6.65 ± 1.57 compared with the negative group (3.75 ± 1.47, P < .05). Protein and mRNA of VEGF-C were reduced in transfected cells. Proliferation was inhibited as well. CONCLUSIONS: VEGF-C can increase the invasiveness of gastric cancer and promote lymphangiogenesis in adjacent tissues. Transfection with antisense VEGF-C can reduce the expression of VEGF-C and inhibit the proliferation. VEGF-C can inhibit the tumor growth and reduce its metastasis and recurrence.

Effects of tumor necrosis factor, endothelin and nitric oxide on hyperdynamic circulation of rats with acute and chronic portal hypertension.

AIM: To evaluate the effect of tumor necrosis factor (TNF), endothelin (ET) and nitric oxide (NO) on hyperdynamic circulation (HC) of rats with acute and chronic portal hypertension (PHT). METHODS: Chronic portal hypertension was induced in Wistar rats by injection of carbon tetrachloride. After two weeks of cirrhosis formation, L-NMMA (25 mg/kg) was injected into one group of cirrhotic rats via femoral vein and the experiment was begun immediately. Another group of cirrhotic rats was injected with anti-rat TNFalpha (300 mg/kg) via abdominal cavity twice within 48 h and the experiment was performed 24 h after the second injection. The blood concentrations of TNFalpha, ET-1 and NO in portal vein and the nitric oxide synthase (NOS) activity in hepatic tissue were determined pre-and post-injection of anti-rat TNFalpha or L-NMMA. Stroke volume (SV), cardiac output (CO), portal pressure (PP), superior mesenteric artery blood flow (SMA flow) and iliac artery blood flow (IAflow) were measured simultaneously. Acute portal hypertension was established in Wistar rats by partial portal-vein ligation (PVL). The parameters mentioned above were determined at 0.5 h, 24 h, 48 h, 72 h and 120 h after PVL. After the formation of stable PHT, the PVL rats were injected with anti-rat TNFalpha or L-NMMA according to different groups, the parameters mentioned above were also determined. RESULTS: In cirrhotic rats, the blood levels of TNFalpha, NO in portal vein and the liver NOS activity were significantly increased (P<0.05) while the blood level of ET-1 was not statistically different (P>0.05) from the control animals (477.67+/-83.81 pg/mL vs 48.87+/-32.79 pg/mL, 278.41+/-20.11 micromol/L vs 113.28+/-14.51 micromol/L, 1.81+/-0.06 u/mg.prot vs 0.87+/-0.03 u/mg.prot and 14.33+/-4.42 pg/mL vs 8.72+/-0.79 pg/mL, respectively). After injection of anti-rat TNFalpha, the blood level of TNFalpha was lower than that in controls (15.17+/-18.79 pg/mL vs 48.87+/-32.79 pg/mL). The blood level of NO and the liver NOS activity were significantly decreased, but still higher than those of the controls. The blood level of ET-1 was not significantly changed. PP, SV, CO, SMAflow and IAflow were ameliorated. After injection of L-NMMA, the blood level of NO and the liver NOS activity were recovered to those of the controls. PP and CO were also recovered to those of the controls. SV, SMAflow and IAflow were ameliorated. In PVL rats, the blood levels of TNFalpha, NO in portal vein and the liver NOS activity were gradually increased and reached the highest levels at 48 h after PVL. The blood level of ET-1 among different staged animals was not significantly different from the control animals. PP among different staged animals (2.4+/-0.18 kPa at 0.5 h, 1.56+/-0.08 kPa at 24 h, 1.74+/-0.1 kPa at 48 h, 2.38+/-0.05 kPa at 72 h, 2.39+/-0.16 kPa at 120 h) was significantly higher than that in controls (0.9+/-0.16 kPa). After injection of anti-rat TNFalpha in 72 h PVL rats, the blood level of TNFalpha was lower than that in controls (14+/-14 pg/mL vs 48.87+/-32.79 pg/mL). The blood level of NO and the liver NOS activity were significantly decreased, but still higher than those of the controls. The blood level of ET-1 was not significantly changed. PP was decreased from 2.38+/-0.05 kPa to 1.68+/-0.12 kPa, but significantly higher than that in controls. SV, CO, SMAflow and IAflow were ameliorated. After injection of L-NMMA in 72 h PVL rats, the blood level of NO and the liver NOS activity were recovered to those of the controls. PP, SV, CO, SMAflow and IAflow were also recovered to those of the controls. CONCLUSION: NO plays a critical role in the development and maintenance of HC in acute PHT and is a key factor for maintenance of HC in chronic PHT. TNFalpha may not participate in the hemodynamic changes of HC directly, while play an indirect role by inducing the production of NO through activating NOS. No evidence that circulating ET-1 plays a role in both models of portal hypertension has been found.