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Xinhua Liao, Prakash Chaudhary, Guanglin Qiu, Xiangming Che, Lin Fan General Surgery Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China Purpose: The National Comprehensive Cancer Network guidelines indicate that radiotherapy in gastric cancer shows limited effectiveness at reducing the growth of gastric cancer. Therefore, enhancing the sensitivity and effect of radiotherapy with propranolol, a β-adrenoceptor antagonist, could reduce tumor growth. The role of propranolol as a radiosensitizer has not been adequately studied; therefore, the purpose of the present study is to evaluate the effect of propranolol as a radiosensitizer against gastric cancer in vivo. Methods: Sixty-four male nude mice bearing tumor xenografts were randomly divided into four groups. Cell culture was performed using the human gastric adenocarcinoma cell line SGC-7901. Mice with tumor xenografts were treated with propranolol, isoproterenol, and radiation. The data for tumor weight and volume were obtained for statistical analyses. Furthermore, the expression levels of COX-2, NF-κB, VEGF, and EGFR were examined using immunohistochemical techniques and Western blotting.Results: The growth in the volume and weight of the tumor was lower in mouse models treated with propranolol and radiation therapy compared to the other groups. Decreased expression of NF-κB was also observed in treatment groups where both propranolol and radiation were used, leading to the reduction of COX-2, EGFR, and VEGF expression compared to that in the other groups.Conclusion: The present study indicated that propranolol potentiates the antitumor effects of radiotherapy in gastric cancer by inhibiting NF-κB expression and its downstream genes: VEGF, EGFR, and COX-2. Keywords: propranolol, radiosensitizer, gastric cancer, radiation therapy

Rong Xie,* Yichao Zhang,* Chao Shen, Xiaoyun Cao, Shixin Gu,* Xiaoming Che*Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: “Glioblastoma multiforme” (GBM) is the frequent form of malignant glioma. Immature colon carcinoma transcript-1 (ICT1) is essential for cell vitality and mitochondrial function and has been recognized in several human cancers. In the study reported here, we attempted to evaluate the functional role of ICT1 in GBM cells. Lentivirus-mediated RNA interference (RNAi) was applied to silence ICT1 expression in human GBM cell lines U251 and U87. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony-formation assays. Cell-cycle progression was determined by flow cytometry with propidium iodide staining. The results revealed that lentivirus-mediated short hairpin RNA (shRNA) can specifically suppress the expression of ICT1 in U251 and U87 cells. Functional investigations proved for the first time, as far as we are aware, that ICT1 knockdown significantly inhibited the proliferation of both cell lines. Moreover, the cell cycle of U251 cells was arrested at Gap 2 (G2)/mitotic (M) phase after ICT1 knockdown, with a concomitant accumulation of cells in the Sub-Gap 1 (G1) phase. This study highlights the crucial role of ICT1 in promoting GBM cell proliferation, and provides a foundation for further study into the clinical potential of lentivirus-mediated silencing of ICT1 for GBM therapy. Keywords: glioblastoma multiforme, immature colon carcinoma transcript-1, lentivirus, proliferation, RNA interference

Objective: We designed this study to introduce the surgical strategy cerebrospinal fluid (CSF) decompression in treatment of Chiari malformation type I and compared CSF decompression with other surgical strategies to provide a solid basis for patient counseling., Methods: The study enrolled 528 consecutive patients with CMI who underwent surgical interventions from 2012 to 2022. The surgical strategy for these patients was bony and dural decompression, anatomical reduction of herniated tonsils, or CSF decompression. Short-term results were determined after 3 months; long-term outcomes were evaluated at last follow-up (at least 18 months)., Results: CSF decompression was independently associated with better long- or short-term primary outcomes than anatomical reduction of herniated tonsils or bony and dural decompression (P < 0.001). Compared with short-term, the long-term outcomes were better in patients who underwent CSF decompression (P = 0.035), but were worse in patients with bony and dural decompression (P = 0.03). Specific surgical techniques cannot affect the long- and short-term outcomes of patients with Chiari malformation type I. CSF decompression provided better long-term syringomyelia improvement than short-term (181/218, 83% vs. 169/218, 77.5%; P < 0.001)., Conclusions: CSF decompression, but not a specific surgical technique or operative method, was associated with favorable neurological outcomes in ADULT patients with Chiari malformation type I. The surgical technique and operative method should be selected according to the characteristics of each patient and the intraoperative condition to normalize CSF circulation at the craniovertebral junction area. The intraoperative target, smooth CSF flow out from the fourth ventricle and in to the bilateral Luschka foramina, could be observed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dysregulation of long non‑coding RNAs (lncRNAs) is involved in the development of colorectal cancer (CRC). In the present study, the identification of muscle blind like splicing regulator 1 antisense RNA 1 (MBNL1‑AS1) lncRNA was reported. Firstly, Cell Counting Kit‑8, EdU and colony formation assays were uesed to explore the role of MBNL1‑AS1 in regulating the proliferation of CRC cells. According to TCGA database, it was found that MBNL1‑AS1 was correlated with microRNA (miR)‑29c‑3p and blood vessel epicardial substance (BVES) expression in CRC cells. Then, the regulation among MBNL1‑AS1, miR‑29C‑3P and BVES was detected by dual luciferase reporter assay and the function of MBNL1‑AS1/miR‑29C‑3P/BVES axis was explored by rescue assay. The results demonstrated that MBNL1‑AS1 expression was decreased in CRC and was associated with the size of tumors derived from patients with CRC. Functionally, the upregulation of MBNL1‑AS1 suppressed CRC cell proliferation in vitro and inhibited tumor growth in vivo , while knockdown of MBNL1‑AS1 expression caused the opposite effects. MBNL1‑AS1 expression correlated with BVES expression in CRC tissues and MBNL1‑AS1 enhanced the stability of BVES mRNA by functioning as a competing endogenous RNA to sponge miR‑29c‑3p; the latter directly targeted MBNL1‑AS1 and BVES mRNA 3'UTR. Collectively, the results indicated that MBNL1‑AS1 suppressed CRC cell proliferation by regulating miR‑29c‑3p/BVES signaling, suggesting that the MBNL1‑AS1/miR‑29c‑3p/BVES axis may be a potential therapeutic target for CRC.

Background: Basilar invagination (BI) is a common disease in the craniocervical junction (CVJ) area. Posterior fossa decompression with/without fixation is a controversial surgical strategy for BI type B. This study aimed to evaluate the efficacy of simple posterior fossa decompression in treating BI type B., Methods: This study retrospectively enrolled BI type B patients who underwent simple posterior fossa decompression at Huashan Hospital, Fudan University between 2014.12 and 2021.12. Patient data and images were recorded pre- and postoperatively (at the last follow-up) to evaluate the surgical outcomes and craniocervical stability., Results: A total of 18 BI type B patients (13 females), with a mean age of 44.2±7.9 years (range 37-62 years), were enrolled. The mean follow-up period was 47.7±20.6 months (range 10-81 months). All patients received simple posterior fossa decompression without any fixation. At the last follow-up, compared with preoperation, the JOA scores were significantly higher (14.2±1.5 vs. 9.9±2.0, p = 0.001); the CCA was improved (128.7±9.6° vs. 121.5±8.1° p = 0.001), and the DOCL was reduced (7.9±1.5 mm vs. 9.9±2.5 mm, p = 0.001). However, the follow-up and preoperative ADI, BAI, PR, and D/L ratio were similar. No patients had an unstable condition between the C1-2 facet joints that was observed in the follow-up CT and dynamic X-ray., Conclusions: In BI type B patients, simple posterior fossa decompression could improve neurological function and will not induce CVJ instability in BI type B patients. Simple posterior fossa decompression could be a satisfactory surgical strategy for BI type B patients, but preoperative CVJ stability assessment is crucial., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: The purpose of this study was to analyze the techniques used to resection cervical extra-intraspinal neuromas (also known as cervical dumbbell neuromas) through the enlarged intervertebral foramen., Methods: A total of 34 consecutive patients (19 male, 15 female) with cervical dumbbell neuromas reviewed retrospectively between April 2008 and May 2020. Sixteen tumors were found in the intervertebral foramen of C 1 -C 3 , four in C 3 -C 4 , and 14 in C 4 -T 1 . The approach in all cases was to expose the tumors by intermuscular dissection and to remove them through the enlarged intervertebral foramen without excision of any bony structures. However, to expose tumors at different locations, the incisions shall be made accordingly. In this case series, the incisions were made along the posterior border of the sternocleidomastoid muscle for the C 1 -C 3 tumors and along the anterior border of the muscle for the C 3 -C 4 tumors. Transverse incisions were required for the C 4 -T 1 tumors., Results: Following the mentioned incising approach, all 34 tumors were completely exposed. 31 were completely removed in one stage, and 3 tumors underwent subtotal resection because of brachial plexus nerve adhesion. The vertebral artery and spinal cord were undamaged for all cases. The patients who had total tumor resection showed no sign of recurrence on enhanced magnetic resonance imaging during follow-ups. The status of patients who underwent subtotal resection was stable after radiation therapy. None of the patients developed spinal instability., Conclusions: Cervical dumbbell neuromas can be exposed and removed through the enlarged intervertebral foramen without causing spinal instability or injury to the spinal cord or vertebral artery. This operative approach can retain the integrity of the structures of spine and should be considered the ideal approach for cervical dumbbell neuromas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Chang, Che and Zhang.)

Background: Studies have confirmed that Caudal Type Homeobox 2 (CDX2) plays a tumor suppressor role in colorectal cancer (CRC) and as a prognostic and predictive marker for colorectal cancer. The epithelial to mesenchymal transition (EMT) is a transdifferentiation process, providing migratory and invasive properties to cancer cells during tumor progression. However, the role of CDX2 during the activation of EMT in CRC maintains controversial., Aim: To investigate whether CDX2 is associated with EMT in CRC., Methods: Forty-six CRC patients were included in the study. Expressions of CDX2, E-cadherin, and N-cadherin in all CRC patients were detected by IHC. ROC assays were applied to detect cut-off points for IHC scores to distinguish high and low expressions of CDX2 in 46 CRC samples. The prognostic value of CDX2 was statistically analyzed. MTT, Western blot, invasion, and migration assays in vitro were employed to explore the function of CDX2., Results: We observed that high expressions of CDX2 and E-cadherin as well as low expressions of N-cadherin were significantly correlated with favorable prognosis. The levels of CDX2 protein exhibited a positive associated with E-cadherin while negative correlation with N-cadherin. Then, the low expression of CDX2 and high expression of CA199 in combination are positively related with poor prognosis. Overexpression of CDX2 reduced expression of MMP-2 and diminished cell proliferation, invasion, and migration, while knockdown CDX2 enhanced MMP-2 expression and increased cell proliferation, invasion, and migration in HCT-116 cells. CDX2 was correlated with expression of EMT markers. Overexpression of CDX2 suppressed the EMT markers indicating that CDX2 suppresses CRC cell viability, invasion, and metastasis through inhibiting EMT. Finally, we found that the expression of CDX2 was negatively associated with Th1 cells, macrophages, Th2 cells, cytotoxic cells, T cells, and T helper cells., Conclusions: These results indicated CDX2 as prognostic biomarkers involved in immunotherapy response for CRC. CDX2 loss promotes metastasis in CRC through a CDX2-dependent mechanism., Competing Interests: The authors have declared that no competing interest exists., (Copyright © 2022 Yun-shuai Wang et al.)

Objective: To investigate the effect of visceral fat area (VFA) on the surgical efficacy and early postoperative complications of radical gastrectomy for gastric cancer. Methods: A retrospective cohort study method was used. Clinicopathological data and preoperative imaging data of 195 patients who underwent D2 radical gastric cancer surgery at the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to December 2017 were analyzed retrospectively. Inclusion criteria: (1) complete clinicopathological and imaging data; (2) malignant gastric tumor diagnosed by preoperative pathology, and gastric cancer confirmed by postoperative pathology; (3) no preoperative complications such as bleeding, obstruction or perforation, and no distant metastasis. Those who had a history of abdominal surgery, concurrent malignant tumors, poor basic conditions, emergency surgery, palliative resection, and preoperative neoadjuvant therapy were excluded. The VFA was calculated by software and VFA ≥ 100 cm 2 was defined as visceral obesity according to the Japan Obesity Association criteria . The patients were divided into high VFA (VFA-H, VFA≥100 cm 2 , n =96) group and low VFA (VFA-L, VFA<100 cm 2 , n =99) group . The clinicopathological characteristics, surgical outcomes and early postoperative complications were compared between the two groups. Univariate and multivariate Logistic regression models were used to analyze the risk factors of early complications. Receiver operating characteristic (ROC) curve was used to analyze predictive values of VFA for early complications. Pearson's χ 2 test was used to analyze the correlation between BMI and VFA. Results: There were no significant differences in terms of gender, age, American Society of Anesthesiologists physical status classification, preoperative comorbidities, preoperative anemia, tumor TNM staging, N staging, T staging and tumor differentiation, surgical method, extent of resection, and tumor location between the VFA-L group and the VFA-H group (all P >0.05). However, patients in the VFA-H group had higher BMI, larger tumor, lower rate of hypoalbuminemia and greater subcutaneous fat area (SFA) (all P <0.05). The VFA-H group presented significantly longer operation time and significantly less number of harvested lymph nodes as compared to the VFA-L group (both P <0.05). However, there were no significant differences in intraoperative blood loss, conversion to laparotomy and postoperative hospital stay (all P >0.05). Complications of Clavien-Dindo grade II and above within 30 days after operation were mainly anastomosis-related complications (leakage, bleeding, infection and stricture), intestinal obstruction and incision infection. The VFA-H group had a higher morbidity of early complications compared to the VFA-L group [24.0% (23/96) vs 10.1% (10/99), χ 2 =6.657, P =0.010], and the rates of anastomotic complications and incision infection were also higher in the VFA group [10.4% (10/96) vs. 3.0% (3/99), χ 2 =4.274, P =0.039; 7.3% (7/96) vs. 1.0% (1/99), P =0.033]. Multivariate logistic analysis showed that high BMI (OR=3.688, 95%CI: 1.685-8.072, P =0.001) and high VFA (OR=2.526, 95%CI: 1.148-5.559, P =0.021) were independent risk factors for early complications. The area under the ROC curve (AUC) of VFA for predicting early complications was 0.645, which was higher than that of body weight (0.591), BMI (0.624) and SFA (0.626). Correlation analysis indicated that there was a significantly positive correlation between BMI and VFA ( r =0.640, P <0.001). Conclusion: VFA ≥ 100 cm 2 is an independent risk factor for early complications after radical gastrectomy for gastric cancer.It can better predict the occurrence of above early postoperative complications.

Objective: To compare clinical efficacy between laparoscopic radical proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic radical total gastrectomy with Roux-en-Y reconstruction (LTG-RY) in patients with early upper gastric cancer, and to provide a reference for the selection of surgical methods in early upper gastric cancer. Methods: A retrospective cohort study method was carried out. Clinical data of 80 patients with early upper gastric cancer who underwent LPG-DTR or LTG-RY by the same surgical team at the Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into the DTR group (32 cases) and R-Y group (48 cases) according to surgical procedures and digestive tract reconstruction methods. Surgical and pathological characteristics, postoperative complications (short-term complications within 30 days after surgery and long-term complications after postoperative 30 days), survival time and nutritinal status were compared between the two groups. For nutritional status, reduction rate was used to represent the changes in total protein, albumin, total cholesterol, body mass, hemoglobin and vitamin B12 levels at postoperative 1-year and 2-year. Non-normally distributed continuous data were presented as median (interquartile range), and the Mann-Whitney U test was used for comparison between groups. The χ(2) test or Fisher's exact test was used for comparison of data between groups. The Mann-Whitney U test was used to compare the ranked data between groups. The survival rate was calculated by Kaplan-Meier method categorical, and compared by using the log-rank test. Results: There were no statistically significant differences in baseline data betweeen the two groups, except that patients in the R-Y group were oldere and had larger tumor. Patients of both groups successfully completed the operation without conversion to laparotomy, combined organ resection, or perioperative death. There were no significant differences in the distance from proximal resection margin to superior margin of tumor, postoperative hospital stay, time to flatus and food-taking, hospitalization cost, short- and long-term complications between the two groups (all P >0.05). Compared with the R-Y group, the DTR group had shorter distal margins [(3.2±0.5) cm vs. (11.7±2.0) cm, t =-23.033, P <0.001], longer surgery time [232.5 (63.7) minutes vs. 185.0 (63.0) minutes, Z =-3.238, P =0.001], longer anastomosis time [62.5 (17.5) minutes vs. 40.0 (10.0) minutes, Z =-6.321, P <0.001], less intraoperative blood loss [(138.1±51.6) ml vs. (184.3±62.1) ml, t =-3.477, P =0.001], with significant differences (all P <0.05). The median follow-up of the whole group was 18 months, and the 2-year cancer-specific survival rate was 97.5%, with 100% in the DTR group and 95.8% in the R-Y group ( P =0.373). Compared with R-Y group at postoperative 1 year, the reduction rate of weight, hemoglobin and vitamin B12 were lower in DTR group with significant differences (all P <0.05); at postoperative 2-year, the reduction rate of vitamin B12 was still lower with significant differences ( P <0.001), but the reduction rates of total protein, albumin, total cholesterol, body weight and hemoglobin were similar between the two groups (all P >0.05). Conclusions: LPG-DTR is safe and feasible in the treatment of early upper gastric cancer. The short-term postoperative nutritional status and long-term vitamin B12 levels of patients undergoing LPG-DTR are superior to those undergoing LTG-RY.

Hyperfibrinogenemia and cancer-associated systemic inflammatory response are strongly associated with cancer progression and prognosis. We aimed to develop a novel prognostic score (F-SII score) on the basis of preoperative fibrinogen (F) and systemic immunoinflammatory index (SII), and evaluate its predictive value in patients with resectable gastric cancer (GC). Patients diagnosed with GC between January 2012 and December 2016 were reviewed. The F-SII score was 2 for patients with a high fibrinogen level (≥ 3.37 g/L) and a high SII (≥ 372.8), whereas that for patients with one or neither was 1 or 0, respectively. A high F-SII score was significantly associated with older patient age, a high ASA score, large tumor size, large proportion of perineural invasion, and late TNM stage. Multivariate analysis indicated that the F-SII score, histological grade, and TNM stage were independent factors for overall survival (OS). The Harrell's concordance index (C-index) of a nomogram based on the F-SII score and several clinicopathological manifestations was 0.72, which showed a better predictive ability for OS than the TNM stage alone (0.68). In conclusion, preoperative F-SII may serve as a useful predictive factor for OS and refine outcome prediction for patients with resectable GC combined with traditional clinicopathological analysis.

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly ( P < 0.05); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly ( P < 0.05) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly ( P < 0.05); YAP and MMP9 mRNA expression increased significantly ( P < 0.05) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect., Competing Interests: The authors declare that they have no conflict of interests., (Copyright © 2020 Jia-Huang Liu et al.)

The underlying molecular mechanisms that the hypoxic microenvironment could aggravate neuronal injury are still not clear. In this study, we hypothesized that the exosomes, exosomal miRNAs, and the mTOR signaling pathway might be involved in hypoxic peritumoral neuronal injury in glioma. Multimodal radiological images, HE, and HIF-1 α staining of high-grade glioma (HGG) samples revealed that the peritumoral hypoxic area overlapped with the cytotoxic edema region and directly contacted with normal neurons. In either direct or indirect coculture system, hypoxia could promote normal mouse hippocampal neuronal cell (HT22) injury, and the growth of HT22 cells was suppressed by C6 glioma cells under hypoxic condition. For administrating hypoxia-induced glioma-derived exosomes (HIGDE) that could aggravate oxygen-glucose deprivation (OGD)/reperfusion neuronal injury, we identified that exosomes may be the communication medium between glioma cells and peritumoral neurons, and we furtherly found that exosomal miR-199a-3p mediated the OGD/reperfusion neuronal injury process by suppressing the mTOR signaling pathway. Moreover, the upregulation of miRNA-199a-3p in exosomes from glioma cells was induced by hypoxia-related HIF-1 α activation. To sum up, hypoxia-induced glioma-derived exosomal miRNA-199a-3p can be upregulated by the activation of HIF-1 α and is able to increase the ischemic injury of peritumoral neurons by inhibiting the mTOR pathway., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 Jian-Lan Zhao et al.)

Objective: To compare and analyze the effect of minimally invasive surgery and traditional open surgery in patients with spinal canal tumors, including intraspinal and extraspinal communication tumors. Methods: From 2017 to 2019, 31 patients (minimally invasive channel group) were included in the neurosurgery department of Huashan Hospital Affiliated to Fudan University, and 38 patients (open operation group) were selected as the control group. From the aspects of intraoperative condition, operative effect, postoperative muscle injury, postoperative complications, postoperative spinal stability, the minimally invasive access group and the open operation group were compared and analyzed. Results: The bleeding volume (70.2 ml±4.9 ml), operation time (164.7 min±16.0 min) and hospitalization days (9.5±2.5) in the minimally invasive access group were significantly lower than those in the open operation group ( P< 0.001). The creatine kinase CK (363.9 U/L±51.6 U/L) in the minimally invasive group was significantly lower than that in the open group (514.2 U/L±68.3 U/L) ( P< 0.001). According to Panjabi standard, the effect of spinal cord stability in minimally invasive group was significantly lower than that in open operation group ( P< 0.001), and the symptom improvement rate in minimally invasive group was significantly higher than that in open hand group ( P< 0.05). Conclusions: Compared with the open surgery, the amount of bleeding, the length of incision, the time of operation and the days of hospitalization were significantly shorter, the degree of muscle damage was also significantly reduced, the incidence of complications was lower, the impact of spinal stability was smaller, and the overall advantage was obvious.

Poly( R-3-hydroxybutyrate- co- R-3-hydroxyhexanoate) (PHBHHx), a family member of microbial polyhydroxyalkanoates (PHA), is a biodegradable and biocompatible material with some hydrophobicity and reasonable strength for packaging and tissue engineering applications. In this study, superhydrophobic PHBHHx is fabricated via a simple nonsolvent-assisted process. The material can absorb all tested hydrophobic solvents and oil up to 6-fold of the material weights from water, permitting applications for cleaning environmental oil or solvent pollutions with convenience of disposal after the usage due to its biodegradability. With an excellent combination of biodegradability and biocompatibility, superhydrophobic PHBHHx films are evaluated for antibioadhesion properities to exploit possible implant usages. Up to 100% reductions for platelet adhesions on the superhydrophobic PHBHHx surfaces are observed compared with that on the control material surfaces. Superhydrophobic biodegradable and biocompatible PHBHHx films demonstrate promising low value and high volume or high value and low volume applications.

Escherichia coli was metabolically engineered to effectively produce a series of biopolymers consisted of four types of monomers including glycolate, lactate, 3-hydroxybutyrate and 4-hydroxybutyrate from glucose as the carbon source. The biosynthetic route of novel quadripolymers was achieved by the overexpression of a range of homologous and heterologous enzymes including isocitrate lyase, isocitrate dehydrogenase kinase/phosphatase, glyoxylate/hydroxypyruvate reductase, propionyl-CoA transferase, β-ketothiolase, acetoacetyl-CoA reductase, succinate semialdehyde dehydrogenase, 4-hydroxybutyrate dehydrogenase, CoA transferase and PHA synthase. In shake flask cultures using Luria-Bertani medium supplemented with glucose, the recombinant E. coli reached 7.10g/l cell dry weight with 52.60wt% biopolymer content. In bioreactor study, the final cell dry weight was 19.61g/l, containing 14.29g/l biopolymer. The structure of the produced polymer was chemically characterized by proton NMR analysis. Assessment of thermal and mechanical properties demonstrated that the quadripolymer possessed decreased crystallinity and improved toughness, in comparison to poly-3-hydroxybutyrate homopolymer. This is the first study reporting efficient microbial production of the quadripolymer poly(glycolate-co-lactate-co-3-hydroxybutyrate-co-4-hydroxybutyrate) from glucose., (Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

A previous study from our group using an in vivo model demonstrated that diet induced-obesity increases the risk of gastric cancer and may prompt its growth. However, the molecular mechanisms underlying this association remain unclear and require further investigation. The aim of the present study was to investigate the potential molecular mechanisms through which obesity affects gastric cancer growth. In a subcutaneous mouse model, tumors were significantly larger in obese mice compared with non-obese and lean mice. In addition, markedly increased levels of Sirt1 and YAP protein were observed in the nucleus of cells from subcutaneous tumors from obese mice compared with those from lean mice. Murine forestomach carcinoma (MFC) cells treated with 5% sera from obese mice exhibited significantly increased expression of Sirt1 and YAP compared with MFC cells treated with sera from lean mice. In addition, a positive correlation was observed between Sirt1 expression and YAP expression, and between Sirt1 expression and serum visfatin levels in mice. These results suggested that diet-induced obesity could promote murine gastric cancer growth by modulating the Sirt1/YAP signaling pathway.

A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) can effectively degrade articular cartilage matrix proteoglycan and damage the intervertebral disc of spinal tuberculosis patients, resulting in deterioration of the physical properties of articular cartilage. Transforming growth factor β activated kinase 1 (TAK1) is similar to vascular cell adhesion molecule 1 (VCAM-1) and closely related to a variety of pathophysiological processes. This study intended to explore the expression of ADAMTS-4, VCAM-1, and TAK1 in cartilage tissue obtained from spinal tuberculosis patients and their inter-relationships, aiming to provide new treatment approaches for spinal tuberculosis. Patients with spinal tuberculosis (N = 60) from the department of orthopedics and patients with traumatic spinal fracture (N = 60, controls) were recruited for the study. ADAMTS-4, VCAM-1, and TAK1 expression was detected by immunohistochemistry. SPSS 19.0 software was used for data processing and analysis. The score values of ADAMTS-4, TAK1, and VCAM-1 were 1.45 ± 0.10, 1.33 ± 0.09, and 1.54 ± 0.11, respectively, which were significantly higher than those in normal controls (P < 0.05). ADAMTS-4 showed positive correlation with VCAM-1 and TAK1. ADAMTS-4, TAK1, and VCAM-1 expressions increased in spinal tuberculosis patients. They could provide clinical reference for spinal tuberculosis diagnosis and new treatment strategies can be devised by focusing on their positive correlation.

Objective: The purpose of this study was to compare the ligation of intersphincteric fistula tract (LIFT) with an additional plug (LIFT-plug) in the treatment of transsphincteric anal fistula., Summary Background Data: Both LIFT and LIFT-plug are recently reported effective alternatives of transsphincteric anal fistula., Methods: This multicenter prospective randomized study (NCT01478139) was conducted at 5 university hospitals throughout China. A total of 235 patients were randomly assigned to undergo LIFT (118 patients) or LIFT-plug (117 patients) between March 2011 and April 2013. The primary outcome measured was primary healing rate at 6 months postoperatively and healing time. Secondary outcomes included recurrence rate, postoperative pain, and incontinence rate., Results: The LIFT procedure showed shorter operative time than the LIFT-plug procedure (26.7 min vs 28.5 min, P = 0.03). Median healing time was 22 days in LIFT-plug group vs 30 days in LIFT group (P < 0.001). The difference in visual analog scale scores across all time points was not statistically significant between the groups (P = 0.13). The primary healing rate was higher in LIFT-plug group than in LIFT group [94.0% (95% confidence interval 89.7%-98.3%) vs 83.9% (95% confidence interval 77.2%-90.6%), P < 0.001]. There were no reported incontinence and recurrence within the follow-up period of 6 months., Conclusions: In patients with transsphincteric anal fistulas, both LIFT-plug and LIFT are simple, safe, and effective procedures. LIFT-plug has the advantage of a higher healing rate, less healing time, and a lower early postoperative pain score.

The aim of the present study was to investigate the effect of penehyclidine (PHC) on endotoxin-induced acute lung injury (ALI), as well as to examine the mechanism underlying this effect. A total of 60 rats were randomly divided into five groups, including the control (saline), LPS and three LPS + PHC groups. ALI was induced in the rats by injection of 8 mg lipopolysaccharide (LPS)/kg body weight. The rats were then treated with or without PHC at 0.3, 1 or 3 mg/kg body weight 1 min following LPS injection. After 6 h, serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were determined by ELISA. In addition, the mRNA expression levels of toll-like receptor (TLR)2 and TLR4 were examined by reverse transcription-quantitative polymerase chain reaction in the lung tissue samples, and nuclear factor (NF)-κB p65 protein expression levels were examined by western blot analysis. The results demonstrated that lung injury was ameliorated by treatment with PHC (1 and 3 mg/kg body weight) as compared with treatment with LPS alone. Injection of LPS significantly increased the mRNA expression levels of TLR2 and TLR4, as well as the protein expression levels of NF-κB p65 in the lung tissue samples. Serum levels of TNF-α and IL-6 were also upregulated by LPS injection. Treatment of the rats with PHC following LPS injection suppressed the LPS-induced increase in TLR2/4 mRNA and NF-κB p65 protein expression levels. PHC also inhibited the increase in TNF-α and IL-6 serum levels. In addition, PHC reduced LPS-induced ALI and decreased the serum levels of TNF-α and IL-6, possibly by downregulating TLR2/4 mRNA expression and inhibiting NF-κB activity, and consequently alleviating the inflammatory response.

Aim: To explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms., Methods: SGC7901, MKN45, MKN28, N87, and AGS human gastric cancer cell lines were used to screen for radioresistant gastric cancer cell lines. A 3-(4,5-dimeth-ylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay was used to determine the effects of β-elemene and IPA-3 on cell viability in MKN45 and SGC7901 gastric cancer cell lines. A clonogenic survival assay and annexin V-FITC/PI apoptosis detection assay were used to evaluate cellular radiosensitivity and radiation-induced cell death, respectively. A proteomic method, isobaric tags for relative and absolute quantitation (iTRAQ), was employed to screen the proteins regulated by β-elemene pretreatment prior to ionizing radiation (IR) in SGC7901 gastric cancer cell line. IPA-3 was used as a specific small molecule inhibitor of p21-activated protein kinase 1 (Pak1) to target Pak1 signaling. Protein levels of PAK1IP1 (p21-activated protein kinase-interacting protein 1), total Pak1 (t-Pak1), phospho-Pak1 (T423), phospho-ERK1/2 (Thr202/Tyr204), and cleaved caspase-3 (17 kDa) were assessed by western blotting., Results: MKN45 and SGC7901 gastric cancer cell lines were relatively more resistant to IR. β-elemene pretreatment decreased clonogenic survival following IR in MKN45 and SGC7901 gastric cancer cell lines. Additionally, β-elemene pretreatment prior to IR increased radiation-induced cell death compared with IR alone in MKN45 (10.4% ± 0.9% vs 34.8% ± 2.8%, P < 0.05) and SGC7901 (11.6% ± 0.9% vs 46.7% ± 5.2%, P < 0.05) human gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Through iTRAQ analysis and western blot validation, we found that β-elemene upregulated PAK1IP1 and downregulated phospho-Pak1 (T423) and phospho-ERK1/2 in SGC7901 gastric cancer cells. IR increased the level of phospho-Pak1 (T423). Pretreatment with β-elemene decreased radiation-induced Pak1 and ERK1/2 phosphorylation. Inhibition of Pak1 using IPA-3 decreased clonogenic survival following IR. In addition, IPA-3 increased radiation-induced cell death in MKN45 (13.4% ± 0.3% vs 26.6% ± 1.0%, P < 0.05) and SGC7901 (16.0% ± 0.6% vs 37.3% ± 1.7%, P < 0.05) gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Western blotting showed that IPA-3 decreased radiation-induced Pak1 and ERK1/2 phosphorylation., Conclusion: This is the first demonstration that β-elemene enhances radiosensitivity of gastric cancer cells, and that the mechanism involves inhibition of Pak1 signaling.

The aim of the present study was to determine whether gastric cancer chemoresistance was increased under high glucose conditions by means of a clinical case study and experimental cytology. The expression of nicotinamide phosphoribosyltransferase (Nampt), silent information regulator 1 (sirt1), p53, p-glycoprotein (P-gp) and topoisomerase (topo)-IIα was evaluated in gastric cancer tissues and gastric cancer with diabetes tissues by immunohistochemistry. Subsequently, the survival time of the patients was assessed. For further investigation, the human gastric cancer cell line SGC7901 was subjected to different glucose concentrations and the aforementioned proteins were detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Finally, cell sensitivity to chemotherapy treatment was examined in order to elucidate the role of high glucose in MDR. Positive expression of Nampt, Sirt1, p53, P-gp and Topo-IIα was observed to be higher in gastric cancer with diabetes patients compared with gastric cancer patients (P=0.01, 0.003, 0.0025, 0.016 and 0.336, respectively) with reduced survival time. Similar results were observed in SGC7901 cells. Additionally, cell proliferation rates of SGC7901 cells increased at glucose concentrations of 4,500 and 9,000 mg/l. Notably, the inhibition rates of 5-fluorouracil on cells decreased over 48 h when treated with 4,500 and 9,000 mg/l glucose compared with 1,000 mg/l. In conclusion, patients suffering from gastric cancer and diabetes exhibited greater negative effects, such as a poorer response to chemotherapy and had a lower survival time. High glucose conditions promoted gastric cancer cell proliferation and reduced susceptibility to chemotherapy drugs. These data provided a potential diagnostic and therapeutic strategy for gastric cancer chemoresistance.

Cerebral glioma is the most common brain tumor as well as one of the top ten malignant tumors in human beings. In spite of the great progress on chemotherapy and radiotherapy as well as the surgery strategies during the past decades, the mortality and morbidity are still high. One of the major challenges is to explore the pathogenesis and invasion of glioma at various "omics" levels (such as proteomics or genomics) and the clinical implications of biomarkers for diagnosis, prognosis or treatment of glioma patients. Establishment of a standardized tissue bank with high quality biospecimens annotated with clinical information is pivotal to the solution of these questions as well as the drug development process and translational research on glioma. Therefore, based on previous experience of tissue banks, standardized protocols for sample collection and storage were developed. We also developed two systems for glioma patient and sample management, a local database for medical records and a local image database for medical images. For future set-up of a regional biobank network in Shanghai, we also founded a centralized database for medical records. Hence we established a standardized glioma tissue bank with sufficient clinical data and medical images in Huashan Hospital. By September, 2013, tissues samples from 1,326 cases were collected. Histological diagnosis revealed that 73 % were astrocytic tumors, 17 % were oligodendroglial tumors, 2 % were oligoastrocytic tumors, 4 % were ependymal tumors and 4 % were other central nervous system neoplasms.

Gastric cancer is a common malignancy with a poor prognosis. β-elemene is a broad-spectrum anticancer drug extracted from the traditional Chinese medicinal herb Curcuma wenyujin. In the present study, we investigated the anticancer effects of β-elemene in gastric cancer cells and the potential proteins involved. Human SGC7901 and MKN45 gastric cancer cells were treated with different concentrations of β-elemene. Cell viability, clonogenic survival and apoptotic cell death were assessed. β-elemene inhibited viability and decreased clonogenic survival of gastric cancer cells in a dose-dependent manner. Apoptosis induction contributed to the anticancer effects. We then employed a proteomic method, isobaric tags for relative and absolute quantitation (iTRAQ), to detect the proteins altered by β-elemene. In total, 147 upregulated proteins and 86 downregulated proteins were identified in response to β-elemene treatment in SGC7901 gastric cancer cells. Among them, expression of p21-activated protein kinase‑interacting protein 1 (PAK1IP1), Bcl-2-associated transcription factor 1 (BTF) and topoisomerase 2-α (TOPIIα) were validated by western blot analyses and the trends were consistent with iTRAQ results. Top pathways involved in β-elemene treatment in SGC7901 gastric cancer cells included ribosome signaling, peroxisome proliferator-activated receptors (PPARs) signaling pathway, regulation of actin cytoskeleton, phagosome, biosynthesis and metabolism of some amino acids. Collectively, our results suggest a promising therapeutic role of β-elemene in gastric cancer. The differentially expressed proteins provide further insight into the potential mechanisms involved in gastric cancer treatment using β-elemene.

Background: The ability of preoperative MRI-sequences to predict the consistency of intracranial meningiomas has not yet been clearly defined. We aim to demonstrate that diffusion tensor imaging (DTI) improves the prediction of intracranial meningiomas consistency., Methods: We prospectively studied 110 meningioma patients operated on in a single center from March 1st to the 25th of May 2012. Demographic data, location and size of the tumor, peritumoral edema, T1WI, T2WI, proton density weighted (PDWI), fluid-attenuated inversion recover (FLAIR) sequences, and arterial spin labeling (ASL) perfusion were studied and compared with the gray matter signal to predict meningioma consistency. Diffusion tensor imaging (DTI) with fractional anisotropy (FA) and mean diffusivity (MD) maps were included in the preoperative MRI. Meningioma consistency was evaluated by the operating surgeon who was unaware of the neuroradiological findings., Results: In univariate analysis, meningioma size (diameter > 2 cm) and supratentorial or sphenoidal wing location were more frequently associated with hard-consistency meningiomas (p < 0.05). In addition, isointense signal on MD maps (p = 0.009), hyperintense signal on FA maps, and FA value > 0.3 (p = 0.00001) were associated with hard-consistency tumors. Age and sex, T1WI, T2WI, PDWI, FLAIR, or ASL perfusion sequences and peritumoral edema were not significantly associated with meningioma consistency. In logistic regression analysis, the most accurate model (AUC: 0.9459) for predicting a hard-consistency meningioma shows that an isointense signal in MD-maps, a hyperintense signal in FA-maps, and an FA value of more than 0.3 have a significant predictive value., Conclusions: FA value and MD and FA maps are useful for prediction of meningioma consistency and, therefore, may be considered in the preoperative routine MRI examination of all patients with intracranial meningiomas.

Hyperglycemia is common in critical patients and high blood glucose levels have a negative effect on their prognosis. The aim of this study was to investigate the effect of hyperglycemia and glycosylated hemoglobin (GHb) in critical patients. A total of 648 critical patients were enrolled in the study and received a random blood glucose test when they entered the emergency department. If blood glucose was more than 11.1 mM, a GHb test was followed within 24 h. All patients were followed up for 28 days. According to diabetes mellitus (DM) history, GHb value, and outcome of follow-up, patients were divided into different groups, and mortality rates were calculated, respectively. Hyperglycemia was found in 67.44% (437/648) of patients, and 51.49% (225/437) and 48.51% (212/437) had normal and elevated GHb levels, respectively. At the end of the follow-up period, 14 of the normal GHb patients and 32 of the elevated GHb patients died (6.22 and 15.09%, respectively). In the normal GHb group, 53 had a DM history, 23 were newly diagnosed with DM, and 149 had hospital-related hyperglycemia (HRH); the mortality rates were 11.32% (6/53), 8.70% (2/23), and 4.03% (6/149), respectively. In the elevated GHb group, 114 had a DM history, 83 were newly diagnosed with DM, and 15 had HRH; the mortality rates were 13.16% (15/114), 19.27% (16/83), and 6.67% (1/15), respectively. Hyperglycemia and GHb might play important roles in the prognosis and assessment for critical patients, and the prognosis would vary according to the different causes of hyperglycemia.

Obesity increases the risk of gastric cancer and may promote its growth, as was recently demonstrated by our novel in vivo mouse model. However, the underlying mechanisms of this correlation remain unclear. The purpose of this study was to investigate the precise effects of obesity on gastric cancer growth and to elucidate the potential molecular mechanisms. Diet-induced obese mice were insulin-resistant, glucose-intolerant and had high serum visfatin concentration. In the subcutaneous mouse model, tumors were more aggressive in diet-induced obese mice compared with lean mice. Tumor weights showed a significant positive correlation with mouse body weights, as well as serum insulin and visfatin concentrations. Immunohistochemical staining showed that the expression levels of iNampt, Sirt1 and c-MYC proteins were upregulated in the subcutaneous tumors from obese mice compared to those from lean animals. Furthermore, obesity not only prompted significantly murine forestomach carcinoma cell migration, proliferation, but also affected cellular apoptosis and cell cycle by endocrine mechanisms. These were associated with increased expression of the pro-survival nampt/sirt1/c-myc positive feedback loop confirmed by RT-PCR and western blotting. These results suggested that diet-induced obesity could promote murine gastric cancer growth by upregulating the expression of the nampt, sirt1 and c-myc genes.

Papillary meningioma is a rare subtype of malignant meningiomas, which is classified by the World Health Organization as Grade III. Because of lack of large sample size case studies, many of the specific characteristics of papillary meningioma are unclear. This study investigated by retrospective analysis the clinical, radiological and histopathological findings of 17 papillary meningioma patients who underwent surgical resection or biopsy, to assess the characteristics of papillary meningioma. Eight female and nine male patients were included, with a mean age of 40 (range: 6 to 55) years. Tumors were mostly located in the cerebral convexity and showed irregular margins, absence of a peritumoral rim, heterogeneous enhancement and severe peritumoral brain edema on preoperative images. Brain invasion was often confirmed during the operations, with abundant to exceedingly abundant blood supply. Intratumoral necrosis and mitosis was frequently observed on routinely stained sections. The average MIB-1 labeling index was 6.9%. Seven cases experienced tumor recurrence or progression, while seven patients died 6 to 29 months after operation. Radiation therapy was given in 52.9% of all cases. Univariate analysis showed that only the existence of intratumoral necrosis and incomplete resection correlated with tumor recurrence. The 3-year progression free survival was 66.7% after gross total resection and 63.6% for other cases. The 3-year mortality rate was 50% after gross total resection and 63.6% for other cases. Papillary meningioma has specific clinical and histopathological characteristics. Tumor recurrence (or progression) and mortality are common. Gross total tumor resection resulted in less recurrence and mortality.

Background: Meningioma is one of the most common primary tumors of the central nervous system, but there are not many detailed studies on the sex, age, subtypes and locations of large series. This study was a retrospective analysis of the characteristics of meningioma cases consecutively operated on at a single institution in China from 2001 to 2010., Methods: This study investigated the demographic background of 7084 meningioma cases, and the subtypes and locations of the tumors. Sex and age distributions were analyzed, and the pathological subtypes were classified according to the World Health Organization (WHO) classification. The location of the meningiomas was also categorized., Results: The female:male ratio of the 7084 cases was 2.34:1. The mean age was 51.4 years (range, 11 months-86 years). The mean age of cases of WHO grade I meningioma was significantly older than that of grade II or III meningiomas (P < 0.001, Fisher's Least Significant Digit test). There was a significantly higher female:male ratio in WHO grade I meningiomas than in grade II or grade III meningiomas (2.57, 1.03 and 0.76, respectively; P < 0.001, χ(2) test). Meningothelial (n = 2061) and fibrous meningiomas (n = 3556) were the most common subtypes, comprising 79.3% of all meningiomas. All meningioma cases were classified into 23 locations in this study, with the cerebral convexity the most common site (38.33%, n = 2722). Cases with uncommon locations such as extra-cranial and sylvian fissure meningiomas were also present in this series., Conclusions: Female predominance was found for benign meningiomas, while malignant subtypes showed male predominance. The mean age of patients with WHO grade I meningiomas was older than that of patients with higher-grade tumors. Meningothelial and fibrous meningiomas were the most common subtypes. The cerebral convexity was the most common meningioma location.

Obesity increases the risk of gastric cancer and may affect its development and progression, however, the mechanisms underlying this association are completely unknown. The purpose of the current study was to investigate the effect of obesity on gastric cancer growth by adopting a novel in vivo model. Diet-induced obese and lean mice were inoculated with murine forestomach carcinoma cells, and studied for 2 weeks. Tumor histology, cellular proliferation and apoptosis were evaluated. Serum glucose, insulin, visfatin levels and peripheral CD3(+), CD4(+/-), CD8(+/-) lymphocytes were assayed. All mice were alive and developed no metastasis, a greater number of obese mice developed palpable tumors than lean mice. The tumors from obese mice had a larger volume, greater intratumoral adipocyte mass, and exhibited a higher proliferation and reduced apoptosis rate compared to those of lean animals. Both serum insulin and visfatin concentrations correlated positively with tumor proliferation and negatively with tumor apoptosis. Obese mice had a significantly lower level of CD3(+), CD3(+)CD4(+) T lymphocytes, and a lower level of CD4(+)/CD8(+) in peripheral blood compared to these lymphocyte levels in the lean mice. In conclusion, the altered adipocytokine milieu and insulin resistance observed in obesity may lead directly to alterations in the tumor microenvironment and cell immunity for avoiding cancer, thereby, promoting gastric cancer survival and growth.

Aim: To investigate whether the side population (SP) cells possess cancer stem cell-like characteristics in vitro and the role of SP cells in tumorigenic process in gastric cancer., Methods: We analyzed the presence of SP cells in different human gastric carcinoma cell lines, and then isolated and identified the SP cells from the KATO III human gastric cancer cell line by flow cytometry. The clonogenic ability and self-renewal were evaluated by clone and sphere formation assays. The related genes were determined by reverse transcription polymerase chain reaction. To compare tumorigenic ability, SP and non-side population (NSP) cells from the KATO III human gastric cancer cell line were subcutaneously injected into nude mice., Results: SP cells from the total population accounted for 0.57% in KATO III, 1.04% in Hs-746T, and 0.02% in AGS (CRL-1739). SP cells could grow clonally and have self-renewal capability in conditioned media. The expression of ABCG2, MDRI, Bmi-1 and Oct-4 was different between SP and NSP cells. However, there was no apparent difference between SP and NSP cells when they were injected into nude mice., Conclusion: SP cells have some cancer stem cell-like characteristics in vitro and can be used for studying the tumorigenic process in gastric cancer.

Objectives: To study the expression of nicotinamide phosphoribosyl transferase (Nampt) and vascular endothelial growth factor-A (VEGF-A) in gastric carcinoma and investigate their correlations to clinicopathologic features and prognostic significance., Methods: The proteins of Nampt and VEGF-A in 68 specimens of gastric carcinoma and 59 specimens normal gastric tissue were detected by immunohistochemistry during January 2000 to December 2004, and the 68 patients were followed up., Results: Nampt protein was detected in the cytoplasm of both tissues, and Nampt in gastric carcinoma (13 ± 5) were significantly higher than that in normal gastric tissue (6 ± 3) (t = 7.46, P < 0.01). The expression of Nampt was correlated to invasive depth (F = 4.693, P = 0.034), lymph node metastasis (F = 4.027, P = 0.049), clinical TNM stage (F = 9.979, P = 0.002), but not to gender, age, tumor location, tumor size, differentiation (P > 0.05). The expression of Nampt is correlated with survival of patients that underwent surgical resection for gastric cancer. The survival rate of patients in negative of Nampt was very higher than that of the positive patients, and its co-expression with VEGF-A showed a trend towards poorer survival. The positive correlation was found between the expression of Nampt and VEGF-A in gastric carcinoma (r = 0.293, P = 0.015)., Conclusions: The expression of Nampt is positively correlated to that of VEGF-A in gastric carcinoma. The correlation between the expression of Nampt and VEGF-A in gastric carcinoma plays an important role cooperatively in carcinogenesis, development and metastasis of gastric carcinoma.

Objective: To evaluate the application of virtual reality technology in neurosurgical anatomy we compared the virtual three-dimensional (3D) microanatomy of the temporal bridging veins as part of the resection of tumors across the petrosal crest in 25 patients against the actual microanatomy of the temporal bridging veins on 20 cadaveric head sets., Patients and Methods: The experiment was carried out by two groups of data: a virtual group made of 25 clinical cases and a physical body group made of 20 cadaveric head sets. In the physical body group, the temporal bridging veins on the cadaveric heads were examined under the microscope from the number of their tributaries to termination and measure the distance between emptying point on sinus of labbé vein and sigmoid transverse sinus. In the virtual group, the dissection of the temporal bridging veins was simulated on Dextroscope. We compared the anatomical features of temporal bridging veins in two groups. Virtual reality technology was used in the planning of 25 cases for which the anatomy of temporal bridging veins needed to be studied carefully by the neurosurgical team., Results: Four basic configurations of veins were found: venous lakes running in the tentorium before emptying the sinuses 17.5% (7 hemispheres), candelabra of veins uniting to form one large drainage 40% (16 hemispheres), single independent draining veins 20% (8 hemispheres) and multiple independent draining veins 22.5% (9 hemispheres) in physical body group, venous lake16% (8 hemispheres), candelabra of veins uniting to form one large drainage 42% (21 hemispheres), single independent draining veins 18% (9 hemispheres) and multiple independent draining veins 24% (12 hemispheres) in virtual group. 213 tributaries (85 drainage to labbé veins) and 87 terminations of temporal bridging veins were found in cadaveric heads, whereas 167 tributaries (80 to labbé veins) and 81 terminations of temporal bridging veins were found in the virtual group. The distribution of anatomical terminations of temporal bridging veins were divided into three groups: transverse area 52.87% (46) tentorium area 24.13% (21) and petrosal area 23.10% (20) in physical body group, whereas 54.35% (50) 23.91% (22) and 21.74% (20) in virtual group, respectively. The proportion of fore-placed type veins of labbé is 7.69% in physical body group and 8.33% in virtual group (P>0.05). The distance from the emptying point of the labbé veins to the sigmoid transverse point in the virtual group was 18.75 ± 1.95 mm, in the physical body group was 20.12 ± 2.51 mm (P>0.05). The anatomical features of labbé veins found during the operation of the 25 patients with tumors extended from middle fossa to posterior fossa and were identical to what was seen in presurgical planning., Conclusions: Virtual reality technology can accurately simulate the anatomical feature of the temporal bridging veins which facilitates the planning of individual operations in neurosurgery., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Background: Tumours in the petroclival region have been a challenge to neurosurgeons. We present a cohort of 24 patients with petroclival meningioma (PCM) and trigeminal schwannoma (TS) in the petroclival region with extension to the middle fossa which were removed with the temporal base intradural transpetrosal (TBIT) approach., Methods: To avoid damage to the important surrounding structures in the petrosal bone, a morphometric analysis in the TBIT approach was performed in 15 cadaveric heads, and the 'safe area of intradural petrosectomy' was identified in the TBIT approach. Subsequently, 14 patients with PCM and 10 patients with TS in the petroclival region were operated on with the TBIT approach., Results: There were no operative deaths in this cohort related to the surgery. Common complications included light hemiparesis in two patients (8.0%), new cranial nerve paresis in nine (37.5%), post-operative pneumonia in one (4.0%) and transient cerebrospinal fluid leak in one (4.0%). Total tumour resection was achieved in 20 patients (83.3%) and subtotal resection in 4 (16.7%). There was no tumour recurrence in all patients at follow-up with a mean duration of 37 months., Conclusions: Surgical strategy for PCM and TS in the petroclival region should be tailored to individual patients. The TBIT approach may improve the exposure of tumours in the petroclival region. A clear description of the 'safe area of intradural petrosectomy' appears to decrease the risk associated with petrosectomy procedure in the TBIT approach.

Nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in the NAD⁺ salvage pathway, is over-expressed and important in the carcinogenesis in several types of cancers. The expression of Nampt and its role in gastric cancer remain largely unknown. In this study, using real-time PCR and Western blotting we found that Nampt was overexpressed at the mRNA and protein levels, respectively, in established gastric cancer cells and human gastric cancer tissues. The specific Nampt inhibitor FK866 repressed gastric cancer cell proliferation, as assessed by MTT assay. Using transwell and soft agar clonogenic assays, we also found that FK866 suppressed gastric cancer cell migration and anchorage-independent growth, respectively. These inhibitory effects of FK866 were accompanied by significantly decreased expression of VEGF, MMP2, MMP9 and NF-κB. As determined by MTT assay and flow cytometry, FK866 also increased the chemo-sensitivity of gastric cancer cells to fluorouracil by greater inhibition of cell proliferation and the induction of apoptosis. Our findings indicate that Nampt may be a new therapeutic target for gastric cancer.

Aim: To ascertain whether side population (SP) cells in HXO-Rb44 retinoblastoma cell line have cancer stem cell-like property in vitro and in vivo., Methods: We analyzed and sorted SP from HXO-Rb44 retinoblastoma cell line by Hoechst 33342 staining on flow cytometry. SP and NSP cells were determined their ability of proliferation and self-renewal by SP reanalysis, soft agar assay and tumor sphere assay in vitro. Clone formation was detected by seeding HXO-Rb44 and HXO-Rb44 -RFP cells into soft agar. The expression of ABCG2, MDRI, Bmi-1 and Oct-4 was determined by RT-PCR between SP and non-SP (NSP) cells. Moreover, they were injected into nude mice to determine their tumorigency in vivo., Results: SP from HXO-Rb44 retinoblastoma cell line could grow clonally in soft agar assays and form tumor spheres from single cells in conditioned media. The expressions of ABCG2, MDRI, Bmi-1 and Oct-4 were significantly higher in SP than NSP cells. As few as SP cells resulted in tumor formation in 6 of 12 injected sites, however, the injection of NSP cells failed to form new tumor., Conclusion: SP cells isolated by Hoechst 33342 from the HXO-Rb44 retinoblastoma cell line had property of high tumorigency in vivo and in vitro. Therefore, SP might be a target while developing retinoblastoma therapies.

Nampt/PBEF/visfatin is the rate-limiting enzyme that catalyzes the first step in NAD biosynthesis from nicotinamide and regulates growth, apoptosis and angiogenesis of mammalian cells. This enzyme was originally cloned as a putative cytokine shown to enhance the B cell precursor maturation in the presence of IL-7 and stem cell factor. A number of cancers have increased expression of Nampt/PBEF/visfatin, which regulates a variety of different signaling pathways such as PI3K/Akt, ERK1/2 and STAT3. FK866/APO866 and CHS828/GMX1777 are two known inhibitors of Nampt/PBEF/visfatin and have been evaluated as anticancer agents in the clinic. This review will focus on its role in carcinogenesis and cancer progression and its inhibitors as therapeutic target for cancer treatment.

Background: Patient-specific approach design, comprehensive evaluation on perioperative data, and follow-up of postoperative life quality (KPS) were carried out to evaluate the application of VR technology of Dextroscope in procedures of patients with skull base tumors., Methods: Eighty-four patients with skull base tumors involved in this research were randomized into 2 groups (test group and control group), each with 42 patients. Before operation, image data such as MR, MRA, or CTA of head were collected and imported into the Dextroscope workstation. The detailed preoperative plans were made in the test group, but no Dextroscope plans in control group. The resection rate of tumors, preoperative evaluation including the duration of operation, total blood loss, the postoperative LOS, the number of cases with cerebrovascular injury complications in operation, and postoperative KPS of patients on discharge and the sixth month follow-up in the 2 groups were recorded and compared., Results: The total resection rate of tumors was 83.33% in test group and 71.42% in the control group (P > .05). The total resection rate of meningioma was 86.67% in test group and 76.47% in control group. The total resection rates of trigeminal Schwannoma in the 2 groups were all 100% (P > .05). The duration of operation and the postoperative LOS of each patient were 5.25 +/- 0.64 hours and 8.50 +/- 1.10 days in the test group and 7.36 +/- 0.87 hours and 12.50 +/- 1.52 days in the control group, respectively (P < .05). Total blood loss of each patient was 456.75 +/- 55.76 mL in the test group and 523.85 +/- 66.78 mL in the control group (P > 05). There were 3 cases with complications of cerebral vessels injury in the test group and 7 cases in the control group (P < .05). During follow-up, KPS of patients in the test group on discharge (85.75 +/- 9.68) was significantly superior to that in the control group (81.66 +/- 9.24; P < .05). The KPS of patients on the sixth-month follow-up in the test group was 92.35 +/- 9.95, which was significantly superior to that in the control group (85.6 +/- 9.34; P < .05). Karnofsky performance scores of patients in the test group improved significantly from discharge to the sixth month after procedure (P < .05), whereas there were adverse results in the test group (P < .05). The 2 cases with CSF leakage were cured completely., Conclusion: The preoperative plans with VR technology in patients with skull base tumor or CSF leakage operations can help certain the diagnosis, individually locate the position of skull base lesions, and design patient-specific approach, which also facilitate to shorten operation duration and the postoperative LOS, reduce total blood loss and injury of vessels in operation, and improve the postoperative KPS., (Copyright 2009. Published by Elsevier Inc.)

Trigeminal neurinomas are the second most common intracranial neurinomas next to the vestibular neurinomas. Eighty-four patients with trigeminal neurinomas were treated between 2003 and 2007. There were 40 women and 44 men (mean age 43 years). The most frequent symptoms were headache or numbness of the ipsilateral hemiface. There were 24 type A, nine type B, 45 type C, and six type D tumors. Dextroscope virtual reality technology was used for preoperative planning in recent eight cases. Gross total resection was achieved in 63 patients. We found that the major impediments to complete removal were adherent to the brainstem and skull base vascular structure, the frontotemporal approach with zygomatic or orbitozygomatic osteotomy or subtemporal approach could offer excellent exposure of the middle fossa and access to the posterior fossa, and Dextroscope virtual reality technology was a very useful tool to identify surgical and anatomic nuances and enhance preoperative planning in trigeminal neurinomas resection.

Aim: To determine the effect of human DNA binding protein (dbpA) on the biology of gastric cancer cells., Methods: DbpA expression was analyzed by Western blot analysis and immunofluorescence staining in gastric cancer tissues and cell lines. A dbpA-specific small interference (si) RNA was designed and synthesized. Suppressive effect of siRNA on dbpA expression was assessed by real-time RT-PCR. Transwell migration and colony formation assays were used to assess the inhibitory effects of dbpA siRNA on cell invasion and tumorigenesis in vitro. Drug-sensitivity was evaluated using a conventional 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay., Results: The expression of dbpA was upregulated in gastric cancer tissues and cell lines as compared to adjacent normal tissues or gastric epithelial cells. siRNA treatment successfully silenced dbpA expression. Silencing of dbpA increased expression of E-cadherin, decreased expression of adenomatous polyposis coli (APC), beta-catenin and cyclin D1, but had no effect on expression of NF-kappaB. Silencing of dbpA also suppressed cell invasion and colony formation of SGC7901 cells, and enhanced their chemosensitivity to 5-fluorouracil., Conclusion: DbpA plays an important role in the pathogenesis and development of gastric cancer, and the process involves E-cadherin, APC, beta-catenin and cyclin D1. Silencing of dbpA might be a novel therapeutic strategy for increasing chemosensitivity to 5-fluorouracil in gastric cancer.

The petrous apex is a complex area surrounded by the cavernous sinus, Dorello's canal and Meckel's cave. The petrosphenoidal ligament (PSL) and the petrolingual ligament (PLL) are important structures located in the region. These two ligaments were examined under a surgical microscope in 10 specimens of five adult cadaveric heads fixed in formalin. They were found to span from the petrous apex to the posterior clinoid process, and the lingula of the sphenoid bone, respectively. The dural sleeve of the abducens nerve, the dorsal meningeal artery or its medial branch, and the venous blood space were located below the PSL in all specimens, and the petrous or sphenoidal insertion of the PSL varied in five specimens. The PLL invariably surrounded part of the dorsal and lateral walls of the lacerum segment of the internal carotid artery (ICA), just under the anteroinferior portion of the anteromedial wall of Meckel's cave in all specimens. The PSL and PLL are valuable anatomical landmarks for identifying the ICA and the nerves in this region. A thorough understanding of the relationship of the two ligaments with neurovascular structures is a prerequisite for surgery in and around the petrous apex., ((c) 2009 Wiley-Liss, Inc.)

Objective: To investigate the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in patients with gastric carcinoma in different stages., Methods: The expressions of HB-EGF protein and mRNA in normal gastric tissues, metaplasic intestinal mucosa, early-stage gastric cancer and advanced-stage gastric cancer tissues were detected by immunohistochemistry and in situ hybridization., Results: HB-EGF expression was only detected in the parietal cells of the gastric fundic glands and in gastrin cells of the pyloric glands in normal gastric tissues. Weak HB-EGF expression was detected in the epithelial cells of the gastric mucosa in intestinal metaplasic mucosa, and the expression increased in all layers of the gastric mucosa in early-stage gastric cancer. Intense HB-EGF expression was observed in advanced gastric cancer., Conclusion: Increased HB-EGF expression may be implicated in the pathogenesis and development of gastric carcinoma.

Side population (SP) cells can be used to identify putative cancer stem cells (CSC), but this technique is hampered by the requirement for an ultraviolet (UV) laser source. DyeCycle Violet reagent (DCV) is a DNA-binding dye that can be used in the common violet laser diode (VLD)-equipped flow cytometer. In this paper, we analyzed SP cells from several bladder cancer cell lines using either Hoechst 33342 or DCV staining. The Hoechst 33342-stained SP cells were identified with a UV-equipped flow cytometer, while the DCV-stained SP cells were identified with a VLD-equipped flow cytometer. DCV staining was also used to sort SP and non-SP (NSP) cells from SW780 cells. Further analysis revealed that SP cells could give rise to both SP and NSP cells. The colony-forming ability of SP cells was significant greater than that of NSP cells. When injected into nude mice, as few as 1 x 10(3) SP cells could initiate tumors in eight of twelve injection sites. In contrast, the injection of NSP cells into nude mice failed to initiate tumors. RT-PCR data showed that the expression of ABCG2, MDRI, Bmi-1 and Oct-4 differed between SP and NSP cells, suggesting that SP cells possess some stem cell characteristics. We conclude that SP cells identified by DCV staining are capable of asymmetric division, self-renewal and tumor initiation. Our study also indicates that DCV is a useful reagent for the identification of SP cells.

Objective: The clinical diagnosis and surgical management of intramedullary spinal cord cavernous angioma were discussed., Method: Total 19 patients with intramedullary cavernous angioma were analyzed retrospectively on the clinical manifestation, radiographic feature, diagnosis and differentiation, surgical technique and caution. Of all the 19 patients, averaging 38.7 years old, 14 were male and 5 were female. Nine patients were followed., Result: All the 19 patients pathologically diagnosed with spinal cord cavernous angioma got good surgical results, besides one patient showed loss of proprioception. Nine patients were followed up and all demonstrated improvement on neurological function., Conclusion: The clinical symptom of most of the patients with spinal cord cavernous angioma presented mildly at onset, but deteriorated gradually because of repeated prehemorrhage. Since the lesion showed some characteristic in MRI, MRI examination was regarded as an important diagnostic tool. Dissection should be done between the tumor and the gliosis during the surgical procedure, special attention should be paid to avoiding tumor residual. It was not necessary to aggressively evacuate the hematoma derived from tumor hemorrhage, which extended along the central canal up and down, except obvious occupied syndrome exited.

Objective: To evaluate the protective effect of ischemic preconditioning against cold ischemia and reperfusion injury of rat intestinal graft following orthotopic transplantation., Methods: Eighty SD rats were randomly assigned into two groups with and without ischemic preconditioning, and each group was divided into 4 subgroups (n=10) according to the intestinal graft cold ischemia time of 3, 6, 12, and 18 h, respectively. Ischemic preconditioning model was established, and the small intestinal graft was preserved at 4 degrees celsius; in Ringer lactate solution for the corresponding time, followed by orthotopic transplantation of the graft. The graft samples were collected for histological examination 1 h after reperfusion, and nuclear factor-kappaB (NF-kappaB) expression in the epithelial cells was detected., Results: Ischemia preconditioning obviously relieved the histological ischemia/reperfusion injury, as shown by regular alignment of the small intestinal villi, alleviated muscular layer edema and decreased expression of NF-kappaB in the epithelia of the graft in groups with cold preservation., Conclusion: Ischemic preconditioning can protect the intestinal graft from cold ischemia/reperfusion injury, and NF-kappaB is an important cytokine in ischemia preconditioning.

Objective: To study the diagnosis and treatment of spinal cord hemangioblastoma., Method: The clinical data of 42 patients with spinal cord hemangioblastoma who were operated on between 1997 and 2005 were analyzed., Result: Spinal cord hemangioblastoma mostly showed space occupying lesions with clear boundary and Dd-DTPA homogenous enhancement by MRI. All the 42 patients underwent complete excision. 27 patients showed improvement of their symptoms, the 6 patients failed to show any change, and neurological deficits were aggravated in the 5 patients., Conclusion: MRI and DSA are helpful in qualitative and localized diagnoses of the spinal cord hemangioblastoma. Surgical outcomes are favorable.

Objective: To investigate the curative effect and mechanism of beta-elemene interventional treatment on VX2 carcinoma transplanted on kidney in rabbits., Methods: The rabbits were all transplanted with VX2 carcinoma on kidney. Fifty-five rabbits were randomly divided into 11 groups. Rabbits in these groups were administered interventional treatment of normal saline, iodinated oil, mitomycin, 5-fluorouracil, beta-elemene, cisplatin, carboplatin, adriamycin, thiotepa, cyclophopsphamide, and vincristine, respectively. After corresponding intervention, the tumor volume in each group was measured by ultrasonography and spiral computed tomography, and the tumor growth rate (TGR) was calculated. Nenal and hepatic functions of the rabbits in each group were compared 1 day, 7 and 14 days after the interventional treatment. Morphologic change of the tumor was observed by a light microscopy and a transmission electron microscopy 14 days after interventional treatment. The expressions of Bax and Bcl-2 were measured by immunohistochemical straining., Results: There was statistical significance in the effects of different medicines intervened on VX2 kidney transplanted carcinoma. The VX2 carcinoma of rabbits had high-sensitivity to iodized oil embolism, mitomycin, cisplatin and carboplatin, which showed serious damage to the kidney function, medium-sensitivity to beta-elemene, adriamycin and 5-fluorouracil, in which beta-elemene showed slight damage to the kidney function, and resistance to thiotepa, cyclohosphamide and vincristine. Most tumor cells displayed apoptosis in the beta-elemene interventional treatment group under light microscopy and transmission electron microscopy, and only few tumor cells displayed necrosis. The Bax expression was up-regulated (P<0.05) and the Bcl-2 expression had no significant difference (P>0.05) in the beta-elemene interventional treatment group., Conclusion: Intervention treatment of beta-elemene has significant effect on VX2 kidney transplanted carcinoma and little side effect on the kidney function. Its mechanism is related to enhancing the apoptosis of tumor cells, and Bax gene participates in this action.

Objective: To investigate the radiosensitization of beta-elemene on VX2 carcinoma transplanted on kidney in rabbits in vivo., Methods: The rabbits were all transplanted with VX2 carcinoma on kidney. The appropriate dose of beta-elemene infusion via renal artery for further study on radiosensitization was determined. Then fifty-five rabbits were divided into three groups: untreated group, radiation group and radiation plus beta-elemene-treated group. After corresponding intervention for each group, the tumor volume was measured by ultrasonography and spiral computed tomography. The sensitization enhancement ratio (SER) of beta-elemene was calculated. The pathological change of tumor tissue in kidney was observed by light microscopy and electron transmission microscopy. The apoptotic index was also examined by TdT-mediated dUTP-biotin nick end labeling method., Results: The most significant radiosensitivity was observed in the radiation plus beta-elemene-treated group with 6 Mev X-ray radiation dose of 3 Gy.Fx(-1).d(-1) x 5 d and beta-elemene dose of 10 mg.kg(-1).d(-1). The average time delayed for tumor growth was obviously longer in the radiation plus beta-elemene-treated group than those in the untreated group and radiation group. The SER of beta-elemene was 1.89. The apoptotic index of tumor cells in the radiation plus beta-elemene-treated group was also significantly higher than those in the untreated group and radiation group., Conclusion: The beta-elemene can enhance the effects of irradiation on VX2 carcinoma transplanted to kidney in rabbits in vivo by inducing apoptosis of tumor cells.