[Patient factors influencing preoperative expectations of patients undergoing total knee arthroplasty].

OBJECTIVE: To investigate the expectations of patients for total knee arthroplasty (TKA), and to analyze its influencing factors. METHODS: Experimental design: Single center, retrospective, multiple regression analysis. The data including the age, height, and weight of 108 patients undergoing unilateral TKA due to end-stage osteoarthritis were obtained. The patients' preoperative Hospital for Special Surgery (HSS) knee arthroplasty expectation score, the Western Ontario and McMaster Universities (WOMAC) score, Knee Society score (KSS), the MOS 36-item short-from health survey (SF-36) score, and visual analogue scale (VAS) were evaluated, and the 30-second chair-stand test (30-CST), 40-meter fast-paced walk test (40-FPWT), 12-level stair-climb test (12-SCT), 3-meter timed up-and-go test (TUG), 6-minute walk test (6-MWT), and recorded daily steps for 7 consecutive days were performed. The SPSS 22.0 software was used for statistical analysis. The observed values of various data were described. Pearson correlation analysis was used to evaluate the correlation between various parameters, and the multi-factor linear regression analysis was used to investigate the influencing factors of the patients preoperative expectation scores. RESULTS: The average expectation score of this group of patients was 58.98±5.44. In the Pearson correlation analysis, the patient's preoperative expectation had a weak correlation to the result of the patient's 12-SCT, TUG, 6-MWT, KSS function score, and SF-36 mental component score (correlation coefficient 0.1-0.3). The patient's preoperative expectation had a moderate correlation to the patient's daily average steps, 30-CST, 40-FPWT, KSS, WOMAC and its pain, stiffness, function scores, SF-36 physical functioning, role-physical, bodily pain, vitality, and physical component score (correlation coefficient 0.3-0.6). In the multivariate linear regression analysis, only the results of 30-CST and the role-physical, bodily pain and vitality in the SF-36 scale were related to the patient's expectation score (P < 0.05). CONCLUSION: The estimated expectation score of patients before TKA is not high. Patients with more severe preoperative pain, worse physical function, and lower overall health are more eager to improve after surgery. Thus surgeons must communicate fully with patients with unrealistic expectations before surgery in order to obtain more satisfactory results postoperatively.

[Surgical treatment of gastric neuroendocrine neoplasms].

Neuroendocrine neoplasms (NEN) are rare neoplasms originating from all major systems, in which gastric neuroendocrine neoplasms (G-NEN) is rarely malignant neoplasm originated in stomach. In 2019, the 5th WHO classification of digestive system tumors updated the classification of G-NEN and solved several naming problems. Since the classification of G-NEN has become more specific and more scientific, the surgical treatment of G-NEN is becoming more individual and more precise. Generally, endoscopic resection is often recommended for the treatment of type I gastric neuroendocrine tumors (NET). Type II gastric NET is mostly secondary to gastrinoma originating from the duodenum or pancreas, and thus surgical treatment of primary gastrinoma deserves enough attention. The decision of operation for type III gastric NET needs comprehensive consideration of tumor size, invasive depth and lymph node metastasis. For gastric neuroendocrine carcinomas without distant metastasis, aggressive surgery should be performed, and the resection range of primary site and lymph nodes can refer to the standard of gastric adenocarcinoma. For locally advanced gastric NEC, it has not been reported whether neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy could reduce tumor stage and improve radical resection rate. In addition, for functional gastric NEN with distant metastasis, radical resection or palliative surgery can be performed to control hormone secretion and may improve the survival. In general, it is an important principle to thoroughly consider biological behavior, extent of primary and metastatic sites, resectability and function of tumor before surgery of gastric neuroendocrine neoplasm, and thus multi-disciplinary treatment (MDT) is recommended.

[Establishment and validation of a nomogram to predict overall survival of patients with gastric neuroendocrine neoplasms].

Objective: To establish a novel nomogram to predict overall survival of patients with gastric neuroendocrine neoplasms (g-NEN). Methods: A case control study was conducted. Clinicopathological and follow-up data of patients with g-NEN who were treated in two academic medical centers in Southern China between July 2008 and June 2018 were retrospectively collected, including 174 patients from Sun Yat-sen University Cancer Center and 102 patients from the First Affiliated Hospital of Sun Yat-sen University. Univariate survival analysis using Kaplan-Meier method and multivariate analysis using Cox regression were performed to identify prognostic factors. A nomogram was subsequently established based on prognostic factors. Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the performance of the model according to differentiation, calibration and clinical utility. Results: A total of 276 patients were enrolled in the study, of whom 189 patients were male and 87 were female. The age at diagnosis was below 60 years old in 150 patients and 60 years or older in 126 patients. There were patients diagnosed with gastric neuroendocrine carcinoma (g-NEC) and 101 patients with gastric neuroendocrine tumor (g-NET). The number of patients with primary tumor locating at upper, middle and lower parts of stomach was 131, 98 and 47, respectively. As for TNM stage, 72 patients were categorized as stage I, 26 patients stage II, 93 patients stage III, and 85 patients stage IV. Univariate analysis indicated that age, pathological type, primary site, Ki-67 index, T stage, N stage, and M stage were associated with overall survival of g-NEN patients (all P<0.05). Multivariate regression analysis testified that high Ki-67 index, advanced T stage and advanced M stage were independent prognostic factors (all P<0.05). The C-index of the nomogram was 0.806 (95%CI: 0.769-0.863). The calibration curve of the nomogram showed that the predicted survival rate was consistent with the actual survival rate in g-NEN patients. The ROC curves and DCA showed that the nomogram had better differentiation and clinical utility than the American Joint Committee on Cancer (AJCC) 8th TNM staging system (the area under the ROC curve was 0.862 vs. 0.792). Conclusion: The first nomogram to predict overall survival of patients with g-NEN is established and verified in this study, which provides individual prediction of 3-year overall survival rate and is applicable to both g-NET and g-NEC patients.

[Unrelated cord blood stem cell transplantation for high-risk/refractory childhood acute myeloid leukemia: a clinical analysis of 160 cases].

Objective: To retrospectively analyze the clinical outcomes of single unrelated cord blood transplantation (UCBT) in children with high risk and refractory acute myeloid leukemia (AML) . Methods: Between June 2008 and December 2018, a total of 160 consecutive pediatric patients with AML received single UCBT (excluding acute promyelocytic leukemia) . Myeloablative conditioning (MAC) regimen were applied. All patients received a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft -versus- host disease (GVHD) . Results: The cumulative incidence of neutrophil cells engraftment at day +42 and platelet recovery at day +120 was 95.0% (95% CI 90.0%-97.5%) at a median of 16 days after transplantation (range, 11-38 days) and 85.5% (95%CI 83.3%-93.4%) with a median time to recovery of 35 days (range, 13-158) , respectively. Incidence of grades Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD and chronic GVHD were 37.3% (95%CI 29.3%-45.2%) , 27.3% (95%CI 20.0%-35.0%) and 22.4% (95%CI 15.5%-28.7%) , respectively. The transplant-related mortality (TRM) at 360 day was 13.1% (95%CI 8.4%-18.9%) . The 5-year cumulative incidence of relapse was 13.8% (95%CI 8.5%-20.3%) . The 5-year disease-free survival (DFS) and overall survival (OS) were 71.7% (95%CI 62.7%-77.8%) and 72.2% (95%CI 64.1%-78.7%) , respectively. The 5-year GVHD and relapse free survival (GRFS) was 56.1% (95%CI 46.1%-64.9%) . The 5-year cumulative recurrence rates of CR1, CR2, and NR groups were 5.3%, 19.9%, and 30.9% (P=0.001) , and the 5-year OS rates were 79.9% (95%CI 70.3%-86.7%) , 71.1% (95%CI 50.4%-84.4%) and 52.9% (95%CI 33.0%-69.3%) (χ(2)=7.552, P=0.020) , respectively. Conclusions: For pediatric patients with high risk and refractory AML, UCBT is a safe and effective treatment option, and it is favorable to improve the survival rate in CR1 stage.

[Exploration and thoughts on perioperative treatment of advanced gastric cancer].

Perioperative treatment is critical to improve the outcomes of patients with advanced gastric cancer. There are three therapeutic modes of perioperative treatment for resectable gastric cancer: neoadjuvant chemotherapy+ D1/D2 surgery+ adjuvant chemotherapy, D0/D1 surgery+ adjuvant radiochemotherapy, and D2 surgery+ adjuvant chemotherapy. Over the decades, a large number of clinical studies had been conducted to optimize the perioperative treatment mode of gastric cancer, including the postoperative radiotherapy and chemotherapy, and perioperative chemotherapy, and to explore the feasibility of preoperative radiochemotherapy, targeted therapy, and immunotherapy in advanced gastric cancer. After nearly 20 years of development and exploration, although the perioperative treatment mode for advanced gastric cancer has become standardized, there are still some core issues that need to be solved urgently, including the selection of population for perioperative treatment, the limitation of efficaly evaluation criteria, insufficient emphasis on laparoscopic exploration before neoadjuvant treatment, and lack of exploration in esophagogastric junction cancer. We should fully integrate the current clinical research data into clinical practice, adopt a multidisciplinary diagnosis and treatment mode, and follow the principles of standardized diagnosis and treatment based on a multi-dimensional analysis of patient characteristics, and formulate the most reasonable treatment strategy to ultimately benefit patients.

[Bioinformatics analysis of key genes and prognosis-related genes during the onset of hepatocellular carcinoma].

Objective: To screen and analyze the differentially-expressed genes (DEGs) in primary hepatocellular carcinoma tissues and adjacent tissues using bioinformatics methods to explore the molecular mechanism of the occurrence and prognosis of primary hepatocellular carcinoma. Methods: GSE76427 data set was collected through GEO database, and DEGs were identified using GEO2R online analysis. Go and KEGG databases were used for enrichment and functional annotation of DEGs. Protein interaction network was built based on the STRING database and Cytoscape software to analyze the key genes of hepatocellular carcinoma, and the survival curve of these key genes were analyzed using the GEPIA database. Results: A total of 74 hepatocellular carcinoma DEGs were screened, of which 3 and 71 were up-and-down-regulated genes. The results of GO enrichment analysis showed that the down-regulated DEGs were mainly involved in cell response to cadmium and zinc ions, negative growth regulation, heterologous metabolic processes and hormone-mediated signaling pathways. KEGG pathway enrichment analysis results showed that the down-regulated DEGs pathway were mainly involved in retinol metabolism, chemical carcinogenesis, drug metabolism-cytochrome P450, cytochrome P450 metabolizing xenobiotics, tryptophan metabolism and caffeine metabolism. Protein interaction network had screened out 10 down-regulated core genes: MT1G, MT1F, MT1X, MT1E, MT1H, insulin-like growth factor 1, FOS, CXCL12, EGR1, and BGN. Among them, the insulin-like growth factor 1 was related to the prognosis of primary hepatocellular carcinoma. Conclusion: Bioinformatics analysis results of HCC chip data showed that 10 key genes may play a key role in the occurrence and development of HCC and the insulin like growth factor 1 is associated with the prognosis of primary hepatocellular carcinoma.

[Past and present of risk stratification of gastrointestinal stromal tumors and its clinical value].

Gastrointestinal stromal tumor (GIST) is the most common soft tissue sarcoma in the gastrointestinal tract. Biological behavior of GIST is varied. It is very important to accurately assess the risk of recurrence and metastasis after resection of primary tumor in order to guide adjuvant therapy and predict prognosis. With increasing understanding of the biological behavior of GIST, the risk stratification criterion has undergone continuous reform and improvement since its introduction. In the early stage, clinical parameters such as tumor size and mitotic rate were formulated as risk stages, and then tumor site, tumor rupture and other factors were included to form a more accurate AFIP standard and modified NIH risk stratification. Recently, more researches have used new statistical methods such as nomogram and contour maps, which more accurately predict risk of recurrence and better guide adjuvant treatment. Thus, individualized treatment of GIST becomes possible.

[Integrated analysis of DNA methylation and gene expression profiles of hepatocellular carcinoma to construct miR-1180-3p relevant ceRNA regulatory network].

Objective: This study analyzes the expression level of miR-1180-3p and constructs the regulatory network of relevant ceRNA by integrating the DNA methylation and gene expression profile of hepatocellular carcinoma from the Cancer Genome Atlas (TCGA). Methods: Firstly, the expression level of miR-1180-3p in hepatocellular carcinoma and adjacent tissues was analyzed by TCGA database, and the differential expression of lncrna and mRNA was screened. Secondly, the LncBase database and the TargetScan database were used to predict the relationship between miR-1180-3p and lncRNA and mRNA, and the DNA methylation-mediated lncRNA was screened by the DNA methylation profile of lncRNA. Finally, Cytoscape software was used to construct miR-1180-3p relevant ceRNA network, and WebGestalt website was used to perform GO and KEGG analysis of related mRNA in ceRNA. Results: Compared with patients with low expression of miR-1180-3p (mean overall survival duration, 5.69 ± 0.35 years), patients with high expression of miR-1180-3p had shorter overall survival time (mean overall survival duration, 3.99 ± 0.47 years), indicating that the high expression of miR-1180-3p was hepatocellular carcinoma risk factor affecting the prognosis (HR = 1.28, 95% CI = 1.1 ~ 1.5, P < 0.01). A miR-1180-3p related ceRNA regulatory network was constructed in this study, which contained 2 lncRNAs (F11-AS1 and LINC01511) and 37 mRNAs. Conclusion: This study has successfully constructed miR-1180-3p relevant ceRNA regulatory network, and DNA methylation-mediated F11-AS1 and F11-AS1/miR-1180-3p/C11of54 ceRNA regulatory axis has played an important role in the occurrence and development of hepatocellular carcinoma.

Imatinib-induced ophthalmological side-effects in GIST patients are associated with the variations of EGFR, SLC22A1, SLC22A5 and ABCB1.

Imatinib-induced ophthalmological side-effects, including conjunctiva hemorrhage and periorbital oedema, although very common and still remain relatively little understood. The present study investigated the effects of genetic polymorphisms of drug targets and membrane transporters on these side effects. We found that the minor allele of EGFR rs10258429 and SLC22A1 rs683369 were significant risk determinants of conjunctival hemorrhage with OR of 7.061 (95%CI=1.791-27.837, P=0.005 for EGFR rs10258429 CT+TT vs CC), and 4.809 (95%CI=1.267-18.431, P=0.021 for SLC22A1 rs683369 GG+CG vs CC). The minor allele of SLC22A5 rs274558 and ABCB1 rs2235040 were protective factors to periorbital oedema with OR of 0.313 (95%CI=0.149-0.656, P=0.002 for SLC22A5 rs274558 AA+AG vs GG), and 0.253 (95%CI=0.079-0.805, P=0.020 for ABCB1 rs2235040 CT vs CC). These results indicated that variants in EGFR, SLC22A1, SLC22A5 and ABCB1 influenced the incidence of Imatinib-induced ophthalmological toxicities, and polymorphism analyses in associated genes might be beneficial to optimize Imatinib treatment.

[The significance of preservation of the supraclavicular nerve in endoscopic thyroidectomy via gasless anterior chest approach].

Objective: To evaluate the significance for the preservation of the supraclavicular nerve in endoscopic thyroidectomy via gasless anterior chest approach. Methods: We retrospectively evaluated 168 patients who underwent unilateral endoscopic thyroidectomy via gasless anterior chest approach, with preservation of the medial branch of the supraclavicular nerve in 110 patients and not in other 58 patients. Semmes-Weinstein monofilament (SWM) test and a visual analogue scale (VAS) were used to assess the recovery of sensation in anterior chest within 1-12 months postoperatively. Difference in the scores of SWM or VAS between groups was tested with Mann-Whitney U test, and the rates of SWM and VAS scores returning to normal levels in individual periods after surgery was compared with Chi-square test. Results: The preserved group showed more favorable results than the non-preserved group in both SMW and VAS scores. Compared to control group, SWM score in preserved group possessed a higher rate recovery to normal level at any period after operation, which was close to complete normality in 7-9 months postoperatively, and SWM score in non-preserved group was still partially normal in 10-12 months from surgery. Preferable results for VAS were also found in the preserved group, except no significant difference in VAS between groups in1-3 months or 10-12 months after operation. Conclusion: Preservation of the medial branch of the supraclavicular nerve in endoscopic thyroidectomy via gasless anterior chest approach can improve sensation recovery in anterior chest, thus improving postoperative quality of life of patients.

Validation of a nomogram for selecting patients for chemotherapy after D2 gastrectomy for cancer.

BACKGROUND: According to some guidelines for the management of gastric cancer, adjuvant chemotherapy is recommended for patients with pT3-4 or node-positive disease. The aim of this study was to define low- and high-risk groups in terms of survival, and to predict the benefit of adjuvant fluoropyrimidine plus oxaliplatin (F-OX) chemotherapy. METHODS: Patients with pT3-4 or node-positive gastric cancer after gastrectomy with D2 lymphadenectomy between 2000 and 2013 were included. The performance of a previously published nomogram was assessed by discrimination and calibration. Patients were stratified into risk groups on the basis of the nomogram-predicted overall survival probability. The efficacy of F-OX within each risk subgroup was assessed using the log rank test and Cox regression analysis weighted by inverse propensity score. RESULTS: Some 1464 patients were included. The nomogram showed better discrimination than the seventh AJCC staging classification (concordance index 0·72 versus 0·68 respectively; P = 0·008) and accurate calibration. F-OX was not associated with improved survival in patients in the low-risk group, whereas it reduced the risk of death by over 20 per cent in the intermediate- and high-risk groups (P = 0·036 and P < 0·001 respectively) (P for interaction = 0·014). CONCLUSION: A nomogram can aid in individualized decision-making regarding the administration of F-OX after gastrectomy for cancer.

Accuracy of three-dimensional facial soft tissue simulation in post-traumatic zygoma reconstruction.

The aim of this study was to evaluate the accuracy of novel software-CMF-preCADS-for the prediction of soft tissue changes following repositioning surgery for zygomatic fractures. Twenty patients who had sustained an isolated zygomatic fracture accompanied by facial deformity and who were treated with repositioning surgery participated in this study. Cone beam computed tomography (CBCT) scans and three-dimensional (3D) stereophotographs were acquired preoperatively and postoperatively. The 3D skeletal model from the preoperative CBCT data was matched with the postoperative one, and the fractured zygomatic fragments were segmented and aligned to the postoperative position for prediction. Then, the predicted model was matched with the postoperative 3D stereophotograph for quantification of the simulation error. The mean absolute error in the zygomatic soft tissue region between the predicted model and the real one was 1.42±1.56mm for all cases. The accuracy of the prediction (mean absolute error ≤2mm) was 87%. In the subjective assessment it was found that the majority of evaluators considered the predicted model and the postoperative model to be 'very similar'. CMF-preCADS software can provide a realistic, accurate prediction of the facial soft tissue appearance after repositioning surgery for zygomatic fractures. The reliability of this software for other types of repositioning surgery for maxillofacial fractures should be validated in the future.

[Effects of pretreatment with dimethyloxalylglycine on the survival of multi-territory perforator flap in rat and related mechanism].

OBJECTIVE: To observe the effects of pretreatment with dimethyloxalylglycine (DMOG) on the survival of multi-territory perforator flap and the vessels of choke zone (CZ) 2 in rat, and to explore related mechanism. METHODS: Sixty adult SD rats were divided into group DMOG and normal saline group (NS) according to the random number table, with 30 rats in each group. Perforator flap with three angiosomes was made on the right dorsal side of rat, including deep iliac circumflex artery perforator, intercostal artery perforator, thoracodorsal artery perforator, as well as CZ 1 and CZ 2. Rats in group DMOG were intraperitoneally injected with 2 mL NS containing DMOG (40 mg/kg) 2 days before operation, 2 hours before operation, and 2 days after operation. Rats in group NS were intraperitoneally injected with equivalent volume of NS at the same time point. On post operation day (POD) 7, gross observation was conducted, and the survival rate of flap was calculated. On POD 7, the vascularity in CZ 2 and potential zone of flap was observed using angiography. On POD 7, new vessel in CZ 2 of flap was observed with HE staining, and the microvessel density (MVD) was calculated. On POD 7, the expression of vascular endothelial growth factor (VEGF) in CZ 2 of flap was detected by immunohistochemistry and Western blotting (respectively denoted as integral absorbance values and ratio of gray value), and blood flow volume of vessel in CZ 2 of flap was examined by laser Doppler perfusion imager. The sample number of each index was 6 in each group. Data were processed with t test. RESULTS: (1) On POD 7, rats in two groups all survived, and the flaps were not infected. In group DMOG, the necrotic area of flaps of rats with dark yellow crust and soft texture was observed approximately at the distal end of skin entry point of thoracodorsal artery perforator. In group NS, the necrotic area of flaps of rats with brownish black crust and hard texture was observed approximately at the distal end of CZ 2. The survival rate of flap of rats in group DMOG was (88±3) %, which was significantly higher than that in group NS [(82±3) %, t=3.38, P<0.01]. (2) On POD 7, there were clear vascular structure and many new vessels in CZ 2 of flaps of rats in group DMOG, with intact vascular structure in potential zone. On POD 7, there were unclear vascular structure and few new vessels in CZ 2 of flaps of rats in group NS, with disorder vascular structure in potential zone. (3) On POD 7, MVD in CZ 2 of flaps in rats of group DMOG was (29.2±2.2)/mm(2,) which was significantly higher than that of group NS [(20.3±3.6)/mm(2,) t=5.10, P<0.01]. (4) On POD 7, the expressions of VEGF in CZ 2 of flaps in rats of group DMOG detected by immunohistochemistry and Western blotting were 5 060±432 and 0.48±0.04 respectively, which were significantly higher than those of group NS (2 811±382 and 0.26±0.06, with t values respectively 9.54 and 5.67, P values below 0.01). (5) On POD 7, blood flow volume of vessel in CZ 2 of flaps in rats of group DMOG was (58±4) perfusion units (PU), which was significantly more than that of group NS [(46±4) PU, t=5.20, P<0.01]. CONCLUSIONS: DMOG can increase the survival rate of multi-territory perforator flap through promoting angiogenesis in CZ 2 of flap on the back of rat and improving blood supply of flap.

The TrkB+ cancer stem cells contribute to post-chemotherapy recurrence of triple-negative breast cancers in an orthotopic mouse model.

Cancer stem cells (CSCs) are believed to have a crucial role in triple-negative breast cancer (TNBC) recurrence. However, the exact mechanisms that are functionally critical in CSCs-mediated recurrence remain unclear. Here, we showed that CSCs derived from recurrent TNBCs are endowed with increased self-renewal capacity as compared with those from the matched primary lesions. Using patient-derived specimens, we demonstrated the existence of paracrine brain-derived neurotrophic factor (BDNF) signaling between differentiated recurrent TNBC cells and CSCs characterized by the expression of TrkB, the receptor of BDNF. We showed that paclitaxel induced BDNF expression and apoptosis simultaneously in a cell cycle-dependent manner. BDNF promotes the self-renewal potential of the TrkB+CSCs through induction of KLF4. The TrkB+CSCs represent a particular subset indispensable for TNBC relapse. In line with this, TrkB is proved to be a superior predictor for TNBC recurrence. Using a genetically engineered mouse model of TNBC, we observed that ablation of the TrkB+CSCs potentially prevents relapse of malignant tumors. Further preclinical investigation of this promising approach may lead to development of a novel therapeutic strategy to improve the devastating prognosis of TNBC patients.

PI-3K/AKT signal pathway modulates vascular smooth muscle cells migration under cyclic mechanical strain.

BACKGROUND: The migration of vascular smooth muscle cells (VSMCs), exposed to altered mechanical strain, contributes to vascular remodeling which is the key event underlying the pathogenesis of vascular diseases such as atherosclerosis and restenosis. Signal transduction pathways in VSMCs activated by mechanical strain that influence cell migration remain unclear. Herein, we provide evidence that higher mechanical strain enhances VSMCs migration, which is mediated, at least in part, through Akt/protein kinase B (PKB) included pathway. MATERIAL AND METHODS: VSMCs were exposed to mechanical strain at 15 % elongation and 5 % elongation, 60 cycles/min using FX-4000T system from at least three independent experiments. VSMCs were incubated with 100nmol/L wortmannin, 10 uM Akti, 10 uM PD98059 and 10 uM SB202190 prior to strain for inhibitor studies, respectively. VSMCs migration,the activation of Akt/PKB, the inhibition of STI-571 and immunofluorescence for actin fibers were detected, respectively. Activation of the Akt pathway and inhibition of STI-571 were assessed with the Western blot technique. RESULTS: (1) Our study demonstrated that VSMCs migration under 15 % strain was facilitated compared with 5 % strain (15 % strain vs. 5 % strain, P < 0.01); and the activation of P-Akt was enhanced compared to the control (15 % strain and 5 % strain vs. static control, P < 0.01, respectively); whereas wortmannin could markedly inhibit serine/threonine kinase Akt/PKB phosphorylation, reduced VSMCs migration following higher mechanical strain stimulation (15 % strain + wortmannin vs. 15 % strain, P < 0.01). Immunofluorescence revealed actin rearrangement, which could also be inhibited by wortmannin in VSMCs induced by cyclic strain. (2) Akti significantly inhibited VSMCs migration (15 % strain + Akti and 5 % strain + Akti vs. static control, P < 0.05,respectively), neither PD98059 nor SB202190 inhibited VSMCs migration (5 % strain + PD98059 or +SB202190 vs. static control, P < 0.01; 15 % strain + PD98059 or +SB202190 vs. static control P < 0.01,respectively). (3) Higher mechanical strain inhibits STI-571 activity in VSMCs (5 % strain vs. static control, P < 0.05; 15 % strain vs. static control, P < 0.01). CONCLUSIONS: Our data shows that higher mechanical strain activated-Akt/PKB is required for VSMC migration and probably functions through its effects on actin rearrangement.

Tumor-ratio-metastasis staging system as an alternative to the 7th edition UICC TNM system in gastric cancer after D2 resection--results of a single-institution study of 1343 Chinese patients.

BACKGROUND: In this study, we assessed the prognostic value of the lymph node ratio (LNR), established a hypothetical tumor-ratio-metastasis (TRM) staging system and compared it with the 7th edition International Union Against Cancer pathological N (pN) and tumor-node-metastasis (TNM) system. PATIENTS AND METHODS: A total of 1343 gastric cancer patients undergoing D2 resection were staged using the TRM staging system and the 7th edition TNM system. Optimal cut points of LNR were calculated using X-tile software and validated by bootstrapping. Homogeneity, discriminatory ability, and monotonicity of gradients of the TRM and TNM systems were compared using linear trend χ(2), likelihood ratio χ(2) statistics, and Akaike information criterion (AIC) calculations. RESULTS: Optimal cut points classified patients into LNR0 (0%), LNR1 (1%-30%), LNR2 (31%-60%), and LNR3 (61%-100%) groups. In univariate, multivariate and stratified analyses, the LNR staging showed superiority to the 7th edition pN staging. The TRM staging system had higher linear trend and likelihood ratio χ(2) scores and smaller AIC values compared with those for the TNM system, which represented the optimum prognostic stratification. CONCLUSIONS: The novel TRM staging system predicts survival of gastric cancer more accurately than the 7th edition TNM system. It may be considered as an alternative to TNM system.

Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer.

PURPOSE: Colorectal cancer is one of the most common cancers worldwide. We tested the hypothesis that differences in the expression of certain molecular markers of colon cancer may account for different clinical outcomes. METHODS: Tissue microarray technology was used to assay the expression of 17 biological markers [beta-catenin, CD44v7, c-myc, cyclin D1, estrogen receptor beta, mitogen-activated protein kinase/extracellular signal-regulated kinase, maspin, matrix metalloproteinase-7 (MMP7), p53, Pin1, peroxisome proliferators-activated receptor-gamma, survivin, T cell transcription factor 4 (TCF4), transforming growth factor beta receptor II (TGFbetaR II), TGFbeta, TROP2, and Wnt] by immunohistochemistry in 620 colon cancer patients. The Cox proportional hazards regression model was applied to analyze the lifetime data, including time to death, time to recurrence, and time to liver metastasis. RESULTS: All the markers were present at significantly higher expression levels in tumor specimens than in normal colonic specimens. Kaplan-Meier analysis showed that high expression of TROP2, MMP7, and survivin were related to decreased survival; TCF4 and TROP2 were related to disease recurrence; and CD44v7, cyclin D1, MMP7, p53, survivin, and TCF4 were related to liver metastasis. However, the results of the multivariate analysis only showed that expression of MMP7, survivin, and TROP2 were significant predictors of lower patient survival, while TROP2 and MMP7 were significantly related to disease recurrence and liver metastasis, respectively. CONCLUSIONS: We conclude that elevated survivin, MMP7, and TROP2 expression levels are related to decreased survival. In addition, elevated MMP7 and TROP2 expression levels are predictors of disease recurrence and liver metastasis, respectively.

[The pathological changes of nasopharyngeal carcinoma cases treated by stereotactic radiosurgery].

OBJECTIVE: To study the pathological changes of nasopharyngeal carcinoma cases after the treatment of stereotactic radiosurgery. METHOD: 15 cases with recurrent or residual squamous cell carcinoma of nasopharynx diagnosed as T1-4 N0M0 were selected, which had undergone previous radiotherapy. The patients were treated by Gamma Knife while the isodose curve was 50% and the margin dose was 20 Gy. The nasopharynx biopsy was performed before the treatment and 1, 3, 6, 12 months after the treatment. The biopsy specimen was taken to make a pathological examination. RESULT: 1. Before the Gamma Knife treatment, carcinoma cell could be seen in the tissue; 2. 1-3 months after the treatment, cell necrosis and acute inflammation cell infiltration could be seen in the target; 3. 6-12 months after the treatment, infiltration of chronic inflammation cell, proliferation of fibrous tissue and capillary could be found in the target. CONCLUSION: This research implies that the short-term pathological changes after the treatment of stereotactic radiosurgery can be defined as two phases: The first phase occurs from 1 to 3 months after the treatment called necrosis period. The second phase occurs from 6 to 12 months after the Gamma Knife treatment named as absorption period.