Endovenous Microwave Ablation Versus Laser Ablation for Small Saphenous Vein Varicosis.

INTRODUCTION: Laser and radiofrequency ablation are two thermal ablation methods currently widely used to treat lower limb venous insufficiency. However, very few studies have been conducted on the use of microwaves, a form of thermal ablation, for the treatment of small saphenous vein (SSV) insufficiency. This study aimed to examine the efficacy and safety of endovenous microwave ablation (EMA) for the treatment of SSV insufficiency. METHODS: The clinical data of 126 patients (126 lower limbs) with SSV insufficiency (SSV trunk reflux time ≥ 500 ms on lower limb color Doppler ultrasound) treated at the Surgery Department of The Sixth People's Hospital of Zhuji from January 2020 to June 2022 were analyzed retrospectively; 64 patients underwent EMA and 62 underwent endovenous laser ablation (EVLA). The perioperative marker data [duration of surgery, duration of hospitalization, length of thermal ablation, duration of thermal ablation, number of incisions, and numerical pain rating scale (NPRS)], complication data [skin ecchymosis, skin burns, surgical site infection, paresthesia, deep vein thrombosis (DVT), and heat-induced thrombosis (EHIT)], venous clinical severity score (VCSS), chronic venous disease quality of life questionnaire (CIVIQ-20) before and 1, 3, 12 months after surgery, and SSV trunk occlusion rate at 12 months after surgery were compared between the two groups. RESULTS: No significant differences in the surgery or hospitalization durations were observed between the two groups. There were no significant differences in the length of the SSV that required thermal ablation between the two groups; however, the thermal ablation time was shorter in the EMA group than that in the EVLA group (6.14 ± 1.47 min vs 7.05 ± 1.16 min, P < 0.001). There were no statistical differences in the number of incisions, volume of tumescent solution used, or quantity of sclerosing foam used. The NPRS scores of the EMA group at 24 h and 72 h after surgery were significantly greater than those of the EVLA group (4.03 ± 0.98 vs 3.52 ± 1.28, P = 0.013; 3.78 ± 1.06 vs 3.15 ± 1.03, P = 0.001). Moreover, the two groups showed no significant difference in the NPRS score at 1 month (1.14 ± 0.84 vs 1.07 ± 0.75, P = 0.623). The EMA and EVLA group patients experienced similar postoperative complications. The VCSS and CIVIQ-20 score significantly improved at 1, 3, and 12 months after surgery. The VCSS and CIVIQ-20 scores were compared between the two groups at 12 months after surgery, and there were no significant differences (1.44 ± 0.63 vs 1.56 ± 0.56, P = 0.261; 24.24 ± 4.96 vs 25.19 ± 5.36, P = 0.304). There was no significant difference in the incidence of SSV trunk occlusion at 12 months after surgery between the two groups (95.31% vs 96.77%, OR 1.475; 95% CI 0.238-9.146, P = 1.000). CONCLUSION: EMA and EVLA are equally effective treatment methods for SSV insufficiency. EMA is associated with higher NPRS scores in the early postoperative period.

Development and validation of glycosyltransferase related-gene for the diagnosis and prognosis of head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous cancer characterized by difficulties in early diagnosis and outcome prediction. Aberrant glycosylated structures produced by the aberrant expression of glycosyltransferases are prevalent in HNSCC. In this study, we aim to construct glycosyltransferase-related gene signatures with diagnostic and prognostic value to better stratify patients with HNSCC and improve their diagnosis and prognosis. METHODS: Bioinformatic tools were used to process data of patients with HNSCC from The Cancer Genome Atlas (TCGA) database. The prognostic model was formatted using univariate and multivariate Cox regression methods, while the diagnostic signature was constructed using support vector machine (SVM) and LASSO analysis. The results were verified using the Gene Expression Omnibus (GEO) cohort. The tumor microenvironment and benefits of immune checkpoint inhibitor (ICI) therapy in subgroups defined by glycosyltransferase-related genes were analyzed. Molecular biology experiments, including western blotting, cell counting kit (CCK)-8, colony formation, wound healing, and Transwell assays, were conducted to confirm the oncogenic function of beta-1,4-galactosyltransferase 3 (B4GALT3) in HNSCC. RESULTS: We established a five-gene prognostic signature and a 15-gene diagnostic model. Based on the median risk score, patients with low risk had longer overall survival than those in the high-risk group, which was consistent with the results of the GEO cohort. The concrete results suggested that high-risk samples were related to a high tumor protein (TP)53 mutation rate, high infiltration of resting memory cluster of differentiation (CD)4 T cells, resting natural killer (NK) cells, and M0 macrophages, and benefited from ICI therapy. In contrast, the low-risk subgroup was associated with a low TP53 mutation rate; and high infiltration of naive B cells, plasma cells, CD8 T cells, and resting mast cells; and benefited less from ICI therapy. In addition, the diagnostic model had an area under curve (AUC) value of 0.997 and 0.978 in the training dataset and validation cohort, respectively, indicating the high diagnostic potential of the model. Ultimately, the depletion of B4GALT3 significantly hindered the proliferation, migration, and invasion of HNSCC cells. CONCLUSIONS: We established two new biomarkers that could provide clinicians with diagnostic, prognostic, and treatment guidance for patients with HNSCC.

Novel IARS1 variants cause syndromic developmental disorder with epilepsy in a Chinese patient and the literature review.

BACKGROUND: Isoleucinyl-tRNA synthetase (IARS) is encoded by the IARS1 gene and catalyzes the binding of isoleucine to specific tRNA. OBJECTIVE: This study aims to investigate the pathogenicity of novel IARS1 variants and the genotype-phenotype association, in order to expand the spectrum of pathogenic variants and phenotypes of IARS1-related disease and provide new evidence for the phenotypic spectrum of IARS1 variants. METHODS: Clinical data of the proband were collected, and trio whole-exome sequencing (WES) was performed on the proband and the parents. Candidate variants were validated using Sanger sequencing. Bioinformatics software was utilized to analyze the functional consequences of identified variants and predict their potential deleteriousness. RESULTS: A 17-month-old female patient presented with microcephaly, left external ear malformation, decreased muscle strength and tone in all limbs, epileptic seizures, global developmental delay, and developmental regression. Trio WES identified compound heterozygous variants in the IARS1 gene, c.120-1G>A and c.2164C>A, which were novel pathogenic and likely pathogenic variants, respectively. The phenotype of developmental regression has not been reported before. Only one patient with IARS1 compound heterozygous variants has been reported in the world to have an epileptic phenotype, and this is the second patient with an epileptic phenotype. Bioinformatics analysis revealed that the splicing variant disrupted the canonical splice donor site, while the missense variant altered the local electrostatics of the IARS1 protein surface, potentially leading to functional abnormalities. CONCLUSION: This study identified novel IARS1 variants and the phenotype of developmental regression, expanding the spectrum of pathogenic variants and phenotypes of IARS1-related diseases and providing new evidence for the rare phenotype of epileptic seizures caused by IARS1 variants.

HMGB2 Deficiency Mitigates Abdominal Aortic Aneurysm by Suppressing Ang-II-Caused Ferroptosis and Inflammation via NF-κß Pathway.

Background: Ferroptosis is a new form of cell death, which is closely related to the occurrence of many diseases. Our work focused on the mechanism by which HMGB2 regulate ferroptosis and inflammation in abdominal aortic aneurysm (AAA). Methods: Reverse transcription-quantitative polymerase chain reaction and western blot were utilized to assess HMGB2 levels. CCK-8 and flow cytometry assays were utilized to measure cell viability and apoptosis. We detected reactive oxygen species generation, Fe2+ level, and ferroptosis-related protein levels in Ang-II-treated VSMCs, which were typical characteristics of ferroptosis. Finally, the mice model of AAA was established to verify the function of HMGB2 in vivo. Results: Increased HMGB2 level was observed in Ang-II-treated VSMCs and Ang-II-induced mice model. HMGB2 depletion accelerated viability and impeded apoptosis in Ang-II-irritatived VSMCs. Moreover, HMGB2 deficiency neutralized the increase of ROS in VSMCs caused by Ang-II. HMGB2 silencing considerably weakened Ang-II-caused VSMC ferroptosis, as revealed by the decrease of Fe2+ level and ACSL4 and COX2 levels and the increase in GPX4 and FTH1 levels. Furthermore, the mitigation effects of shHMGB2 on Ang-II-induced VSMC damage could be counteracted by erastin, a ferroptosis agonist. Mechanically, HMGB2 depletion inactivated the NF-κß signaling in Ang-II-treated VSMCs. Conclusions: Our work demonstrated that inhibition of HMGB2-regulated ferroptosis and inflammation to protect against AAA via NF-κß signaling, suggesting that HMGB2 may be a potent therapeutic agent for AAA.

Electronic structures and optical spectra of KDP crystals with Sp doping defects: a first-principles study.

In order to further clarify the effect of sulfur doping on the laser damage threshold of potassium dihydrogen phosphate (KDP), the properties of sulfur substituting for phosphorus doping defects (SP) in KDP crystals with paraelectric (PE) and ferroelectric (PE) phases are studied in this article. More accurate defect transition levels were obtained by band edge correction, and the band edge corrected values were 1.28 eV and 1.88 eV for the PE and FE phases, respectively. The defect formation energies with four different defect charges (0, +1, +2, and-1) were obtained using the finite size correction scheme. The stable defect charge states were (+2 charge state) (+1 charge state) and (-1 charge state) in turn when the Fermi level moved from the valence band maximum (VBM) to the conduction band minimum (CBM). Moreover, by considering the electron-phonon coupling, the optical absorption and emission spectra were obtained. The absorption peak for the state of the PE phase at 4.63 eV was close to the experimental value. We predicted that the absorption peak at 4.50 eV belongs to the state with the FE phase. The emission peaks at 0.10 eV and 1.36 eV were related to the PE and FE phases, accordingly. The absorption may affect the application of S-KDP crystals and reduce the laser damage threshold.

Correlation of TGF-ß signaling pathway gene polymorphisms with unexplained recurrent spontaneous abortion.

BACKGROUND: The association of key genes in the transforming growth factor-ß (TGF-ß) signaling pathway and their gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) is unclear. OBJECTIVE: To investigate the association of gene polymorphisms related to the TGF-ß signaling pathway in URSA women. METHODS: The study population consisted of 80 women with URSA and 90 normal control women, of which 10 women with URSA and 10 normal control women underwent high-throughput sequencing to select loci, and the remaining 70 women with URSA and 80 normal control women underwent flight mass spectrometry experiments to verify gene loci polymorphism. A total of 7 polymorphic loci in interleukin-6 (IL-6), TGF-ß1, TNF-α, SMAD1, and TNFRSF4 genes were screened by high-throughput sequencing combined with a review of databases. An SNP flight mass spectrometer (Mass ARRAY detection system) was applied to detect the polymorphisms and their frequencies in 70 women with URSA and 80 normal control women at the 7 gene loci. RESULTS: Among the 7 loci of IL-6, TGF-ß1, TNF-α, SMAD1, and TNFRSF4 genes, 2 loci were found to have significantly different allele and genotype frequency distributions between the 70 URSA and 80 normal controls, one was the IL-6 gene -174G/C locus (rs1800795), the risk of disease was 2.636 and 3.231 times higher in individuals carrying the C allele and CC genotype than in those carrying the G allele and GG genotype, respectively; the other was the TGF-ß1 gene -509T/C locus (rs1800469), and the risk of disease was 1.959 and 3.609 times higher in individuals carrying the T allele and TT genotype than in those carrying the C allele and CC genotype, respectively. The remaining 5 genetic loci have no statistically significant. CONCLUSION: IL-6 gene -174G/C locus (rs1800795) genotype CC and allele C may be the causative factor of URSA, TGF-ß1 gene -509T/C locus (rs1800469) genotype TT and allele T may be the causative factor of URSA, and polymorphisms of the 2 loci may be associated with URSA.

Prenatal diagnosis in a fetuses with a clenched hands, overlapping fingers, and clubfoot due to MED12 deficiency in three affected siblings: A case report.

A fetal clenched hand with overlapping fingers is more common in aneuploidy syndrome and was not well-documented in MED12 deficiency. This study reports the clinical and genetic findings of three affected siblings from a Chinese family. The chromosome karyotype analysis diagram shows that karyotypes of the three children were normal. Trio whole-exome sequencing and Sanger sequencing verification found that there was a MED12 R296Q variant in normal mothers and their two offspring. A pattern of clenched hand with overlapping fingers (clinodactyly) and clubfoot was found in all the three affected siblings by three-dimensional ultrasound. The discovery of this case shows that even if the chromosome karyotype is normal, comprehensive prenatal genetic diagnosis is required when the ultrasound results show a clenched hand with clinodactyly and clubfoot symptoms.

In vivo prediction of abdominal fat and breast muscle in broiler chicken using live body measurements based on machine learning.

The purpose of this study was to predict the carcass characteristics of broilers using support vector regression (SVR) and artificial neural network (ANN) model methods. Data were obtained from 176 yellow feather broilers aged 100-day-old (90 males and 86 females). The input variables were live body measurements, including external measurements and B-ultrasound measurements. The predictors of the model were the weight of abdominal fat and breast muscle in male and female broilers, respectively. After descriptive statistics and correlation analysis, the datasets were randomly divided into train set and test set according to the ratio of 7:3 to establish the model. The results of this study demonstrated that it is feasible to use machine learning methods to predict carcass characteristics of broilers based on live body measurements. Compared with the ANN method, the SVR method achieved better prediction results, for predicting breast muscle (male: R2 = 0.950; female: R2 = 0.955) and abdominal fat (male: R2 = 0.802; female: R2 = 0.944) in the test set. Consequently, the SVR method can be considered to predict breast muscle and abdominal fat of broiler chickens, except for abdominal fat in male broilers. However, further revaluation of the SVR method is suggested.

The enigmatic helicase DHX9 as a candidate prognostic biomarker for resected pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, and current therapies have limited efficacy on PDAC. The DEAH-box helicase 9 (DHX9) is widely reported to influence cell biological behavior via regulating DNA replication, genomic stability, transcription, translation, and microRNA biogenesis. However, the prognostic role of DHX9 in PDAC remains unclear. Thus, the objective of this study is to investigate the prognostic value of DHX9 expression in PDAC patients. Methods: Tumor specimens from PDAC patients with surgical resection were obtained, and DHX9 was stained and analyzed in this study. Univariate and multivariate Cox regression analyses were utilized to identify independent risk factors of overall survival (OS) and recurrence-free survival (RFS). The prognostic nomograms for predicting OS and RFS were established to obtain superior predictive power. Results: Among the enrolled 110 patients, 61 patients were identified as having high expression of DHX9. The correlation analysis revealed that higher DHX9 expression in PDAC was prone to have advanced N stage (p = 0.010) and TNM stage (p = 0.017). For survival, the median OS (21.0 vs. 42.0 months, p < 0.001) and RFS (12.0 vs. 24.0 months, p < 0.001) of patients in the high DHX9 group were significantly shorter than those in the low DHX9 group. Within the univariate and multivariate analyses, American Joint Committee on Cancer (AJCC) N stage (p = 0.036) and DHX9 expression (p = 0.041) were confirmed as independent prognostic factors of OS, while nerve invasion (p = 0.031) and DHX9 expression (p = 0.005) were independent prognostic factors of RFS. Finally, the novel prognostic nomograms for OS and RFS were established and showed superior predictive accuracy. Conclusion: This study identified the independent prognostic value of DHX9 for RFS and OS in resected PDAC patients, and higher DHX9 expression was prone to have an earlier recurrence and shorter OS. Therefore, DHX9 may be a promising and valuable biomarker and a potential target for treating PDAC. More accurate and promising predictive models would be achieved when DHX9 is incorporated into nomograms.

A Multicenter Randomized Trial Assessing ZENFlow Carrier-Free Drug-Coated Balloon for the Treatment of Femoropopliteal Artery Lesions.

Backgrounds and Objectives: Drug-coated balloons (DCBs) have shown promising benefits in improving the outcomes for patients with peripheral artery disease. Several randomized clinical trials have reported that paclitaxel-coated balloon significantly reduce the rates of restenosis and the need for reintervention in comparison with regular balloon angioplasty. Due to the differences in excipients, paclitaxel dose, and coating techniques, variable clinical outcomes have been observed with different DCBs. In this study, we aimed to evaluate the safety and efficacy of a novel ZENFlow carrier-free DCB in the treatment of femoropopliteal artery occlusive disease. Methods: In this randomized controlled trial conducted at 15 sites, 192 patients with Rutherford class 3-5 were randomly assigned into two groups: drug-coated balloon group and percutaneous transluminal angioplasty group. The primary endpoint was a late lumen loss at 6 months based on blinded angiographic core laboratory evaluations, and the secondary endpoints included primary patency rate, binary restenosis, clinically driven target lesion revascularization, ankle-brachial index, Rutherford class change, and major adverse events. Results: In this multicenter trial, 93 patients received DCB angioplasty, whereas 99 patients underwent regular balloon angioplasty. The late lumen loss at 6-month follow-up was 0.50 ± 0.82 and 1.69 ± 0.87 mm in the drug-coated balloon and percutaneous transluminal angioplasty groups, respectively (p < 0.001). During the 12-month follow-up period, the drug-coated balloon group showed a significantly higher primary patency rate (54 vs. 31.3%, p = 0.009) and markedly lower rates of target vessel restenosis (22.1 vs. 64.3%, p < 0.001) and clinically driven target lesion revascularization rate (5.4 vs. 19.2%, p = 0.006) than the percutaneous transluminal angioplasty group. Compared with the percutaneous transluminal angioplasty group, the drug-coated balloon group had significant improvements in the ankle-brachial index and Rutherford class. The all-cause mortality rate was comparable, and no device-related deaths occurred in either groups. Conclusions: Balloon angioplasty using a ZENFlow carrier-free drug-coated balloon is a safe and effective treatment method for femoropopliteal artery lesions. This novel drug-coated balloon catheter achieved satisfactory early and 1-year outcomes in this trial. Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT03844724.

Overexpressed lncRNA ROR Promotes the Biological Characteristics of ox-LDL-Induced HUVECs via the let-7b-5p/HOXA1 Axis in Atherosclerosis.

The long non-coding RNA regulator of reprogramming (lncRNA ROR) is involved in atherosclerosis (AS), but the specific mechanism remains unclear. The expressions of lncRNA ROR, let-7b-5p, Homeobox A1 (HOXA1), and apoptosis-associated proteins in the serum of AS patients and human umbilical vein endothelial cells (HUVECs) were determined by quantitative real-time PCR (qRT-PCR) and Western blot. The relationships of lncRNA ROR, let-7b-5p, and HOXA1 were analyzed by Pearson's correlation test. The viability and the migration of HUVECs were measured by Cell Counting Kit-8, wound healing, and Transwell assays. The predicted target gene and the potential binding sites were confirmed by dual-luciferase reporter assay. lncRNA ROR was highly expressed in AS, which promoted the cell viability and migration of HUVECs, while lncRNA ROR silencing produced the opposite results. The expression of let-7b-5p, which bound to lncRNA ROR, was downregulated in AS, indicating that the two genes were negatively correlated. Besides this, let-7b-5p reversed the effects of upregulated lncRNA ROR expression on let-7b-5p expression, cell viability, and migration as well as the expressions of apoptosis-related proteins of ox-LDL-treated HUVECs. HOXA1 was targeted by let-7b-5p and upregulated in AS, with its expression being negatively correlated with let-7b-5p but positively correlated with lncRNA ROR. In ox-LDL-treated HUVECs, overexpressed HOXA1 reversed the effects of let-7b-5p, and HOXA1 silencing reversed the effects of lncRNA ROR. In AS, lncRNA ROR promoted the biological characteristics of oxidation of low-density lipoprotein-induced HUVECs via the let-7b-5p/HOXA1 axis.

Matrine protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via upregulation of miR-9.

Context: Matrine is a well-known anti-inflammatory quinolizidine alkaloid derived from leguminous plant Sophora flavescens Ait. (Leguminosae).Objective: This study was designed to uncover the potential application of matrine in treating spinal cord injury (SCI).Materials and methods: Neuron-like PC12 cells in experimental groups were pre-treated with/without matrine (200 µM) for 24 h and then stimulated by lipopolysaccharide (LPS, 5 µg/mL) for 12 h. PC12 cells in control group were cultured in complete medium. CCK-8 assay, flow cytometry, qRT-PCR, western blot and ELISA were performed to evaluate cell damage. Moreover, after cells were transfected with miR-9 inhibitor for 48 h, above indicators were tested again. qRT-PCR and western blot were also conducted to uncover the downstream effectors and signalling pathways for matrine.Results: LPS (5 µg/mL) decreased cell viability about 50%. Matrine (200 µM) decreased cell viability about 0%, 13.8% and 30% at 24 h, 48 h and 72 h, respectively. The loss of viability, stimulation of apoptosis, and release of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) evoked by LPS were attenuated by the pre-treatment of matrine partly. Meanwhile, LPS reduced miR-9 expression about 60%, but matrine completely reversed LPS-decreased miR-9 level. By silencing miR-9 expression, the protective properties of matrine towards PC12 cells were impeded. Besides, matrine inhibited the activation of JNK and NF-κB pathways even under the condition of LPS. And the impact of matrine on the signalling were attenuated by miR-9 silencing.Discussion and Conclusion: This paper provided in vitro evidence that matrine was able to protect PC12 cells against LPS-evoked damage. The neuroprotective properties of matrine may be due to its regulation of miR-9 expression as well as JNK and NF-κB pathways.

Vorapaxar stabilizes permeability of the endothelial barrier under cholesterol stimulation via the AKT/JNK and NF­κB signaling pathways.

Atherosclerosis (AS) is an inflammatory disease that occurs in the arterial wall and is characterized by progressive lipid accumulation within the intima of large arteries, leading to the dysfunction of endothelial cells and further destruction of the endothelial barrier and vascular tone. Arterial intima injury accelerates the adhesion and activation of platelets at the injury site. The activation of platelets results in the secretion of growth factors, leading to the migration and proliferation of vascular smooth muscle cells (VSMCs), promoting the formation of plaque, resulting in the formation of thrombus. The present study found that vorapaxar could alleviate the inflammatory response induced by a high concentration of cholesterol stimulation and increase the release of nitric oxide (NO) via the protein kinase B (AKT) signaling pathway and regulation of the intracellular concentration of Ca2+ ([Ca2+]i). We also found that vorapaxar could reduce the damage of DNA caused by cholesterol stimulation and regulate the cell cycle via the AKT/JNK signaling pathway and its downstream molecules glycogen synthase kinase 3ß (GSK­3ß) and connexin 43, maintaining the integrity of the endothelial barrier and proliferation of endothelial cells, serving a protective role in endothelial cells.

[Endovascular treatment of abdominal aortic aneurysm and aortic bifurcation stenosis by unibody bifurcation stent graft].

OBJECTIVE: To sum up experience in unibody bifurcation stent graft in the treatment of abdominal aortic aneurysm with aortic bifurcation stenosis. METHODS: Clinical data of 19 cases of abdominal aortic aneurysm and aortic bifurcation stenosis received endovascular treatment using unibody bifurcation stent graft in Zhejiang Provincial People's Hospital during March 2009 and March 2018 were collected. The clinical characteristics, surgery procedure and follow-up results were reviewed. RESULTS: Stent graft was successful in all patients, and the average operation time was (70.0±2.3) min. Leakage was found in 3 patients, in which 2 patients with type Ⅰ leakage and 1 patient with type Ⅱ leakage. All leakage disappeared 15 days after surgery. The 19 cases were followed-up for 9-48 months with the median follow-up time of 27 months, and no displacement, leakage and lower limb ischemia was observed. CONCLUSIONS: Unibody bifurcation stent graft is of satisfactory long-term effect for patients with abdominal aortic aneurysm and aortic bifurcation stenosis, and can avoid displacement of stent graft after operation.

Prognostic value of clinicopathological characteristics in patients with pancreatic cancer.

BACKGROUND: The purpose of this study was to analyze the effects of all clinical characteristics on the overall survival time, in order to provide a basis for determining the prognostic factor of patients with pancreatic cancer. METHODS: A total of 103 pancreatic cancer patients were admitted to the Department of Radiotherapy and Chemotherapy of the Ruijin Hospital, Shanghai Jiaotong University School of Medicine, between January 2002 and December 2012. There were 68 men and 35 women; the median age was 62 years. Diagnoses of pancreatic cancer in all patients were confirmed by histopathology, cytology, or clinical diagnosis. The Kaplan-Meier method was performed to calculate the overall survival rate. The log-rank method was used to examine the univariate analysis. The Cox regression model was performed for multivariate analysis. RESULTS: The median survival time was 293 days, the 1-, 2-, and 3-year survival rates were 27.18%, 5.83%, and 1.94%, respectively. Cox regression analysis revealed that age (P=0.015), Karnofsky performance status (PS) (P=0.002), surgical types (P<0.001), and platelet counts (P<0.001) were independent prognostic factors affecting the overall survival of patients with pancreatic cancer. CONCLUSIONS: Pancreatic cancer had a poor prognosis, the general physical condition, age, the availability of radical surgery, and platelet counts were factors influencing the overall survival of patients with pancreatic cancer.

Ferulic Acid Exerts Anti-Angiogenic and Anti-Tumor Activity by Targeting Fibroblast Growth Factor Receptor 1-Mediated Angiogenesis.

Most anti-angiogenic therapies currently being evaluated target the vascular endothelial growth factor (VEGF) pathway; however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here, we identified ferulic acid as a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor and a novel agent with potential anti-angiogenic and anti-cancer activities. Ferulic acid demonstrated inhibition of endothelial cell proliferation, migration and tube formation in response to basic fibroblast growth factor 1 (FGF1). In ex vivo and in vivo angiogenesis assays, ferulic acid suppressed FGF1-induced microvessel sprouting of rat aortic rings and angiogenesis. To understand the underlying molecular basis, we examined the effects of ferulic acid on different molecular components and found that ferulic acid suppressed FGF1-triggered activation of FGFR1 and phosphatidyl inositol 3-kinase (PI3K)-protein kinase B (Akt) signaling. Moreover, ferulic acid directly inhibited proliferation and blocked the PI3K-Akt pathway in melanoma cell. In vivo, using a melanoma xenograft model, ferulic acid showed growth-inhibitory activity associated with inhibition of angiogenesis. Taken together, our results indicate that ferulic acid targets the FGFR1-mediated PI3K-Akt signaling pathway, leading to the suppression of melanoma growth and angiogenesis.

miR-34a regulates cisplatin-induce gastric cancer cell death by modulating PI3K/AKT/survivin pathway.

The purposes of this study were to determine the expression profiles of microRNA-34a (miR-34a) in human gastric cancer cell line (SGC-7901) and cisplatin-resistant cell lines (SGC-7901/DDP), and to establish the correlation between miR-34a expression profile and the sensitivity of human gastric cancer cell to cisplatin-based pattern, thereby providing new methods and strategies for treating gastric cancer. Gastric cancer cell line (SGC-7901) and cisplatin-resistant cell line (SGC-7901/DDP) were cultivated in vitro, respectively. Quantitative real-time PCR (qRT-PCR) and Western blot were utilized to determine the expression profiles of miR-34a and survivin in both gastric cancer cell lines. With miR-34a mimic and miR-34a inhibitor transfected into SGC-7901 and SGC-7901/DDP for 48 h, post-transfection changes of miR-34a expression was determined; the effects of miR-34a ectopic expression on the viability of cisplatin-induce gastric cancer cell were assayed by the MTT method. The effects of miR-34a ectopic expression on apoptosis of cisplatin-induce gastric cancer cell were determined by Annexin V/propidium iodide (PI) double staining method and flow cytometry. The effects of miR-34a ectopic expression on the AKT and p-AKT expression of cisplatin-induce gastric cancer cells were determined by Western blot and flow cytometry with the PI3K pathway inhibitor Wortmannin. As shown by qRT-PCR and Western blot analyses, the expression of miR-34a in cisplatin-resistant cell lines decreased significantly in comparison to that of SGC-7901 cell line (p < 0.05), while significant up-regulation of survivin expression was also observed (p < 0.05). Compared with the control group, the expression of miR-34a increased significantly in SGC-7901 cells transfected with miR-34a mimic for 48 h (p < 0.01). After miR-34a inhibitor transfection, the expression of miR-34a decreased significantly (p < 0.05). The viability of cisplatin-induce gastric cancer cells increased significantly (p < 0.05) with significant decrease of apoptosis after miR-34a expression inhibition, as demonstrated by MTT and flow cytometry with miR-34a over-expression, the viability of cisplatin-induce gastric cancer cells decreased significantly (p < 0.05), with significant apoptosis increase (p < 0.05). As shown by Western blot and flow cytometry, in comparison to the control group, Wortmannin could inhibit miR-34a inhibitor and DDP induced up-regulation of p-AKT significantly (p < 0.05) and stimulated apoptosis. In conclusion, miR-34a expression was down-regulated in cisplatin-resistant cell lines. miR-34a over-expression could improve the sensitivity of gastric cancer cells against cisplatin-based chemotherapies, with PI3K/AKT/survivin signaling pathway possibly involved in the mechanism.

Expression and regulatory function of miRNA-34a in targeting survivin in gastric cancer cells.

We aimed to investigate the expression of microRNA-34a (miR-34a) in human gastric cancer cells and to evaluate the effects of miR-34a, acting via its gene survivin, on gastric cancer cell HGC-27 to provide potential new strategies for treating gastric cancer. In vitro cultures of the human gastric cancer cell lines MGC80-3, HGC-27, NCI-N87, and SGC-7901 and the normal human gastric epithelial cell line GES-1 were established. The expression of miR-34a in each gastric cancer cell line and GES-1 normal human gastric epithelial cell line was detected using quantitative real-time polymerase chain reaction (qRT-PCR). After the HGC-27 cells were transfected with a miR-34a mimic for 48 h, the changes in the expression levels of miR-34a were detected using qRT-PCR. The effect of miR-34a on HGC-27 cell viability was measured using a tetrazolium-based colorimetric [-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT)] assay. Flow cytometry was used to analyze the effects of miR-34a on HGC-27 cell proliferation. Annexin V/propidium iodide double staining and flow cytometry were used to analyze the effects of miR-34a on HGC-27 cell apoptosis. A Transwell invasion chamber was used to detect the effects of miR-34a on HGC-27 cell invasion. Finally, western blotting was used to analyze the effects of miR-34a on survivin protein expression. The qRT-PCR test determined that miR-34a expression in gastric cancer cells was significantly reduced compared to the normal gastric epithelial cell line GES-1 (p < 0.01). Compared to the control group, cellular miR-34a expression levels were significantly increased in HGC-27 human gastric carcinoma cells after transfection with a miR-34a mimic for 48 h (p < 0.01). The MTT assay demonstrated that after overexpressing miR-34a in HGC-27 cells, cellular viability was significantly reduced (p < 0.05). Flow cytometry analysis determined that upon miR-34a overexpression, the proliferation index decreased significantly (p < 0.05), and cellular apoptosis was significantly increased (p < 0.01). The Transwell invasion chamber assay illustrated that after increasing the expression of miR-34a, the number of cells passing through the Transwell chamber was significantly reduced (p < 0.01). Based on western blotting, compared with the control group, survivin protein expression levels were significantly decreased in the HGC-27 cells transfected with the miR-34a mimic for 48 h (p < 0.01). In conclusion, the expression level of miR-34a was downregulated in human gastric cancer cell lines. miR-34a can negatively regulate survivin protein expression and inhibit gastric cancer cell proliferation and invasion. Therapeutically enhancing miR-34a expression or silencing the survivin gene may benefit patients with gastric cancer.

Using detection of survivin-expressing circulating tumor cells in peripheral blood to predict tumor recurrence following curative resection of gastric cancer.

BACKGROUND AND OBJECTIVES: The present study was designed to investigate the clinicopathological role of survivin-expressing circulating tumor cells (CTCs) and to determine whether the presence of survivin-expressing CTCs is an independent predictor of tumor recurrence following curative resection of gastric cancer. METHODS: This study included 98 patients who underwent potentially curative resection. Reverse transcription polymerase chain reaction enzyme linked immunosorbent assay (RT-PCR ELISA) was used to measure survivin mRNA in peripheral blood. RESULTS: Of the 98 patients studied, 45 (45.9%) were positive for survivin mRNA. Survivin mRNA expression correlated with Lauren classification (P < 0.001), pathological tumor (pT) stage (P < 0.001), pathological tumor node metastasis (pTNM) stage (P = 0.009), and degree of differentiation (P = 0.001). The pTNM stage and the status of survivin mRNA were independent prognostic factors of disease-free survival (P = 0.007 and <0.001, respectively). CONCLUSIONS: The detection of CTCs expressing survivin mRNA could be a good clinical biomarker used to predict the prognosis of patients with curatively resected gastric cancer.

A phase II study of paclitaxel and nedaplatin as first-line chemotherapy in patients with advanced esophageal cancer.

OBJECTIVE: The aim of this study was to assess the efficacy and toxicity of the combination of paclitaxel and nedaplatin as a first-line chemotherapy for patients with advanced esophageal cancer. METHODS: Patients with advanced esophageal cancer received 175 mg/m(2) of paclitaxel over a 3 h infusion, followed by nedaplatin 80 mg/m(2) in a 1 h infusion on day 1 every 3 weeks until the documented disease progression, unacceptable toxicity or patient's refusal. RESULTS: Between March 2005 and December 2007, 48 patients entered in the study. Forty-six (95.8%) of the 48 patients were assessable for response. The overall response rate was 41.7% (95% CI, 27.8-55.7%) with 2 complete responses and 18 partial responses. The median follow-up period was 20.5 months (range, 12.5-27.2 months). The median overall time to progression and overall survival (OS) were 6.1 months (95% CI, 4.8-7.4 months) and 11.5 months (95% CI, 9.1-13.9 months), respectively. The estimate of OS at 12 and 24 months was 43.8% (95% CI, 29.7-77.8%) and 10.4% (95% CI, 1.8-19.1%), respectively. Most patients experienced anemia, during their course of therapy with 6 (13.0%) patients for grade 3/4 anemia, and grade 1 or 2 anemia was detected in 23 (50%) patients. Grade 3 leucopenia, neutropenia and thrombocytopenia were documented in 8 (17.4%), 9 (17.4%) and 2 (4.3%) patients, respectively. Grade 3 nausea and vomiting were detected in 3 (6.5%) and 2 (4.3%) patients, respectively. Two patients (4.3%) were hospitalized because of treatment-related complications. The treatment was well tolerated and no toxic death occurred. CONCLUSIONS: Combination of paclitaxel and nedaplatin is a tolerated treatment modality with promising activity in previously untreated advanced esophageal cancer.