Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer(P<0.001),and its expression promoted malignant progression of the tumor(all P<0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients(P=0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer(P<0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P<0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P<0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group(P<0.001,P<0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group(P<0.001,P=0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.
Humans ; Stomach Neoplasms/genetics* ; Cyclin D1/metabolism* ; Tumor Suppressor Protein p53 ; Phosphoproteins/metabolism* ; Ki-67 Antigen ; Cell Line, Tumor ; Prognosis ; Cell Proliferation ; Phosphoprotein Phosphatases/metabolism* ; Threonine ; Serine

OBJECTIVE: To investigate the expression of aldehyde dehydrogenase 3B1 (ALDH3B1) in gastric cancer and explore its correlation with the pathological parameters and long-term prognosis of the patients. METHODS: We analyzed the clinical data of 101 patients who underwent radical gastrectomy for gastric cancer in our hospital between January, 2013 and November, 2016, and examined the expression of ALDH3B1 in paraffin-embedded samples of gastric cancer tissues and adjacent tissues from these cases by immunohistochemical staining. We evaluated the correlation between ALDH3B1 expressions and histopathological parameters and assessed the predictive value of ALDH3B1 expression for long-term survival of the patients. We also examined the effect of lentivirus-mediated interference and overexpression of ALDH3B1 on the malignant behaviors of MGC-803 gastric cancer cells. RESULTS: The expressions of ALDH3B1 and Ki67 were significantly higher in gastric cancer tissues than in adjacent tissues (P < 0.05). In gastric cancer patients, ALDH3B1 expression was positively correlated with peripheral blood CEA and CA19-9 levels (P < 0.01). The proportion of patients with CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T stage of 3- 4, and N stage of 2-3 was significantly greater in high ALDH3B1 expression group than in low expression group. Kaplan-Meier survival analysis showed that the 5-year survival rate was significantly lower in gastric cancer patients with high ALDH3B1 expressions (P < 0.01). Univariate and Cox multiple regression analyses identified a high expression of ALDH3B1 (P < 0.05, HR= 0.231, 95% CI: 0.064-0.826), CEA≥5 μg/L (P < 0.01, HR=4.478, 95% CI: 1.530-13.110), CA19-9≥37 kU/L (P < 0.01, HR=3.877, 95% CI: 1.625-9.247), T stage of 3-4 (P < 0.01, HR=4.953, 95% CI: 1.768-13.880), and N stage of 2-3 (P < 0.05, HR=2.152, 95% CI: 1.152-4.022) as independent risk factors affecting 5-year survival after radical gastrectomy. The relative ALDH3B1 expression level, at the cut-off point of 4.66, showed a sensitivity of 76.47% and a specificity of 76% for predicting 5-year postoperative death (P < 0.01). In the cell experiment, overexpression of ALDH3B1 obviously promoted the proliferation, migration and invasion of MGC-803 cells. CONCLUSION As an independent risk factor affecting 5-year survival after radical gastrectomy, ALDH3B1 is highly expressed in gastric cancer and correlated with pathological parameters of the tumor, and a high ALDH3B1 expression may promote proliferation, invasion and metastasis of gastric cancer cells.
Aldehyde Oxidoreductases ; CA-19-9 Antigen ; Carcinoembryonic Antigen ; Gastrectomy ; Humans ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/pathology*

OBJECTIVE: To analyze the expression of centromere protein U (CENPU) in colorectal cancer and its predictive value for long-term prognosis of the patients. METHODS: We retrospectively analyzed the data of 102 patients with colorectal cancer undergoing radical resection in our hospital between January, 2005 and December, 2011. The expression level of CENPU in colorectal cancer tissue was detected immunohistochemically, and its association with clinicopathological characteristics of the patients were analyzed. The patients were divided into low expression group (n=51) and high expression group (n=51) based on the median CENPU expression level for analysis the value of CENPU for predicting long-term prognosis of the patients after radical resection of the tumors. In the in vitro study, we constructed colorectal cancer cell lines with CENPU interference and CENPU overexpression by lentiviral transfection and assessed the changes in the proliferation, migration and invasion of the cells using CCK-8 assay and Transwell assay. RESULTS: The protein expression level of CENPU was significantly higher in colorectal cancer tissues than in the adjacent tissues (P < 0.05) and was positively correlated with the expressions levels of Ki67 (r=0.569, P < 0.05) and VEGF-C (r=0.629, P < 0.05). CENPU expression level in colorectal cancer tissue was closely related with tumor progression and clinicopathological stage of the tumor (P < 0.05). Kaplan-Meier survival analysis showed that the patients with high CENPU expression had significantly decreased postoperative overall survival (χ²=11.155, P < 0.05); Cox multivariate regression analysis suggested that CENPU expression level was an independent risk factor affecting the overall survival of the patients after radical resection (HR=1.848, P < 0.05). The results of cell experiments demonstrated that high CENPU expression significantly promoted the proliferation, migration and invasion of the tumor cells. CONCLUSION CENPU is highly expressed in colorectal cancer tissues in closely correlation with tumor progression and may serve as a potential biomarker for evaluating the long-term prognosis of colorectal cancer patients.
Centromere/pathology* ; Colorectal Neoplasms/pathology* ; Humans ; Kaplan-Meier Estimate ; Prognosis ; Retrospective Studies

Computerized system has been played an increasingly important role in preclinical safety evaluation of drugs and has been used directly or indirectly for data acquisition,processing,reporting as well as raw data storage.However,the computerized system has not been widely used in facilities for preclinical safety evaluation of drugs or only some functions of modules of computerized system have been used.Based on the current application status of the computerized system in the facilities for preclinical safety evaluation of drugs in China,this paper briefly introduced the following aspects about validation of computerized system,such as GLP regulatory requirements of validation of the computerized system,validation process of the computerized system,maintenance of validation state of the computerized system,safety precautions of performance of the computerized system,as well as electronic records and electronic signatures with the purpose to provide some references for carrying out and speeding up the validation of computerized system and to further improve the efficiency of the computerized system in facilities for preclinical safety evaluation of drugs in China and to be in line with international practice.

Objective To establish the three-dimensional (3D) and biomechanical model of lower limb for kinematics and dynamics analysis, and construct the control platform of lower limb for providing theoretical basis for the design of active transfemoral prosthesis and lower limb exoskeleton orthosis. Methods Motion information of the hip joint, knee joint and ankle joint was collected by VICON 3D motion capture system. The 3D model of lower limb was designed by Solidworks for kinematics analysis. Based on SimMechanics in Matlab toolbox, the biomechanical model of lower limb was built to analyze dynamics of lower limb. Based on hardware-in-the-loop simulation platform of Quanser, the control model was constructed to receive control signal from SimMechanics and realize the control of lower limb motion platform. Results The velocity, acceleration and moment of force in each joint were obtained through kinematics and dynamics simulation. The established model of lower limb was validated by simulation, and the simulation signal was used to control the lower limbs motion platform to and realize the function of level walking. Conclusions The platform can be used for the research on kinematics, dynamics and control of lower limb, which has paved way for further investigation on the control of active transfemoral prosthesis and lower limb exoskeleton orthosis.

Objective To introduce our experience of resection of petrous apex cholesteatoma through endoscopic,transnasal,trans-sphenoidal approach in 3 cases,and present a surgical technique of intracystic resection of lesion which yielded a relatively stable long-term outcome.Methods Resection of parasellar and petrous apex cholesteatoma via endoscopic transsphenoidal approach was performed in three patients between 2001 and 2006.Surgical technique was as follows: the ethmoid and sphenoid sinuses were opened under endoscope,the petrous apex was accessed by drilling skull base bone at the lateral wall of sphenoid sinus and anterior to the internal carotid artery,the cyst wall of cholesteatoma was incised and expanded,then intracystic removal of cholesteatoma was achieved by the suction,curette and rinsing.Results The petrous apex cholesteatoma in all 3 patients were removed clearly by endoscopic,transnasal,trans-sphenoidal surgery in one time.Before surgery,two patients with headache and orbital apex syndrome had a remarkable improvement just on the day after operation and completely recovered in 1-4 weeks.No postoperative complications happened in all three patients.All patients had no recurrence in symptoms and no imaging evidences of recurrence at a follow-up of 3-7 years. Conclusion The petrous apex cholesteatoma around the parasellar region could be treated by intracystic removal via endoscopic,transnasal,transsphenoidal approach,without the need to strip and remove the cyst wall,and the long-term efficacy was reliable.

Objectives To explore the time regularity of nasal mucous transitionary course of different sinuses after functional endoscopic sinus surgery.Methods Seventy-seven chronic rhinosinusitis patients following functional endoscopic sinus surgery were prospectively collected. The endoscopic appearances of different sinuses were respectively evaluated with Lund-Kennedy scoring system in 2 weeks,1,2,3,6,9 months,and 12 months postoperatively. Then the endoscopic scores and epithelization proportions of different sinuses in different stages were analyzed and compared.Results Of 77 patients,154 maxillary sinuses,154 ethmoidal sinuses,138 frontal sinuses,and 129 sphenoidal sinuses were scored endoscopically and analyzed statistically.In the 2 weeks after operation,the mucosa scores of sphenoidal sinus (3.5 ± 1.5 ),ethmoidal sinus(3.6 ± 1.4),maxillary sinus(3.7 ± 1.5 ),and frontal sinus (3.8 ±1.5 ) showed no significant differences by nonparameter tests ( x2 =1.674,P =0.643 ).In the 2,3,6,and 9 months postoperatively,the assessment of four kinds of sinuses showed separate transitionary tendency and the descending deflection points of scores and ascending peaks of epithelization proportions gradually emerged.In the 12 months postoperatively,by the above statistical methods,the mucosal scores (Z =-3.417,P =0.001 ) and epithelization proportions ( x2 =4.313,P =0.038 ) of sphenoidal sinus were superior to that of ethmoidal sinus,the mucosal scores ( Z =-2.218,P =0.027 ) and epithelization proportions (x2 =4.292,P =0.038 ) of ethmoidal sinus were superior to that of maxillary sinus,and the mucosal scores (Z =-2.244,P =0.025) and epithelization proportions (x2 =4.100,P =0.043) of maxillary sinus were superior to that of frontal sinus.Conclusions The transitionary course of different sinus mucosa after functional endoscopic sinus surgery shows significant time difference.The time sequencing to complete epithelization of sinuses is successively sphenoidal sinus,ethmoidal sinus,maxillary sinus,and frontal sinus.

Objective To explore the cause,urgent management,further treatment,outcome and prevention of internal carotid artery (ICA) injury during transnasal endoscopic surgery.Methods Five ICA injury happened during transnasal endoscopic surgery of sphenoidal sinus and (or) sellar region,involving 1 case of traumatic optic neuropathy,1 case of sphenoidal cyst,1 case of fungal sphenoid sinusitis,1 case of sellar adenoid cystic carcinoma and 1 case of pituitary tumor.These five cases were from three different hospitals in 1990 -2009,and the clinical data were collected and retrospectively reviewed.Results Injury of ICA was related with improper anatomic localization and operative procedures.The locations of injury were in cavenous segement in 3 cases,lacerum segment in 1 case,and clinic segment in 1 case,respectively.The types of injury included 3 cases of bleeding of laceration,1 case of carotid cavernous fistula and 1 case of pseudoaneurysme.Salvage sphenoid sinus packing with vaseline strip and subsequent intravascular stent graft implantation (2 cases) and endovascular embolization (2 cases) effectively controlled bleeding.Four cases were successfully treated without craniocerebral or ocular complications,only 1 case died of massive blood loss.Among 4 survival cases,1 patient abandoned further therapy,the other 3 patients were curcd of primary disease by reoperation or subsequent treatment.Conclusion Preoperatively,reading carefully the imaging data,intraoperatively,identifying anatomical positions accurately,performing proper operation,and stopping bleeding decidedly, postoperatively, seeking interdisciplinary cooperation to repair vascular damages,all these procedures can effectively reduce the surgical risk of ICA injury.

Objective This study was focused on the clinical effects of topical steroid for chronic rhinosinusitis (CRS) in Chinese adults.Methods The CRS patients were randomly selected in the department of otorhinolaryngology,first affiliated hospital of Sun Yat-sen university between november 2010 and December 2011.Thirty-four CRS patients with polyps (CRSwNP) or CRS without polyps (CRSsNP),no prior surgeries were included.These patients were prescribed to use budesonide nasal spay for three months.Evaluation included visual analog score (VAS),sino-nasal outcome test-20(SNOT-20),CT scan (Lund-Mackay score).SPSS 16.0 software was used to analyze the data.Results Four patients were lost to follow up,while the other 30 patients finished the 3-months' follow up.Except for smelling disturbance which was not statistically changed (t =0.902,P＞0.05),VAS for nasal blockage(baseline:4.84 ±3.15,after treatment:2.26 ± 2.27),rhinorrhea (baseline:6.03 ± 2.93,after treatment:1.96 ± 2.23),headache(baseline:1.68 ± 2.66,after treatment:0.42±0.95),facial pressure (baseline:2.04 ± 2.97,after treatment:0.58 ± 1.42) and general symptom(baseline:6.00 ±2.75,after treatment:2.71 ± 1.90)were statistically decreased(t value was 4.386,6.740,2.445,2.980,6.989,respectively,all P＜0.05).VAS of nasal blockage,rhinorrhea and general symptom were statistically decreased after one-month's treatment(all P ＜0.05),but no statistical improvements were observed between first,second and the third month(all P＞0.05).SNOT-20 was significantly decreased after treatment (t=3.687,P ＜ 0.01).22.2％patients were cured on CT scan.Conclusions Topical steroid improves objective symptoms and quality of life in CRS patients.Some of the patients can be cured in CT scores.The symptoms improvements begin from the first month,but do not change during the latter two months.

Objective To explore the feasibility of endoscopic modified agger nasi approach for the surgical treatment of frontal sinus diseases. Methods The data of patients undergoing modified agger nasi approach for frontal diseases were prospecitvely collected since January 2009, including demographic data,findings at surgery, presence of postoperative symptoms, endoscopic appearance of the frontal recess and sinus, and complications. Results Nineteen patients were enrolled from January 2009 to August 2010.Seventeen patients had chronic rhinosinusitis, in which 13 patients (76. 5% ) completely healed, 3 patients ( 17. 6% ) improved and 1 patient (5. 9% ) failed Two patients had frontal sinus and anterior ethmoid sinus inverted papilloma, with no recurrence. The patients were followed up from 6 to 24 months, medium 16 months. No severe complication occurred. No frontal recess adhesion was found. Four sides of frontal recess showed stenosis caused by tissue hypertrophy. Conclusion The modified agger nasi approach provides excellent access to frontal recess and frontal sinus, with good effect for preventing re-stenosis after surgery.