Insulin-like growth factor binding proteins (IGFBPs) are crucial to cell growth, development, proliferation, and apoptosis in humans. Among IGFBPs, IGFBP2 is recognized as a regulator of insulin-like growth factor (IGF). Besides binding with IGF, IGFBP2 also interacts with extracellular matrix through its specific structure. IGFBP2 promotes the malignant phenotype of tumor by activating several important intracellular signal pathways. IGFBP2 is specifically overexpressed in several malignant tumors, and this overexpression is correlated with patient prognosis. IGFBP2 is regarded as a potential biomarker and a therapeutic target. This review briefly summarizes the latest progress of research on the role of IGFBP2 in tumor malignant biological behavior and its clinical application.

Objective To investigate the potential of AFP-targeted ultrasmall superparamagnetic particles of iron oxide (USPIO) molecular probe in specific detection of hepatocellular carcinoma (HCC) with MRI.Methods The targeted probe was synthesized by conjugating AFP antibody with modified USPIO.Two groups treated with AFP-USPIO and USPIO were set up in the study.The HepG2 cells were incubated with AFP-USPIO or USPIO (100 μg/ml) respectively with the dosage of 50 μ1,100 μl or 150 μl for 4 hours,followed by MR imaging in vitro.The signal-noise ratio (SNR) of the cells on T2-weighted image (T2WI) was measured.The rat models with orthotopic HCC were divided into two groups with 5 rats for each group at random.Pre-and post-contrast enhanced (after 1 hour) MR imaging were performed with caudal vein injection at a dosage of 20μg/ml.The contrast noise ratio (CNR) on T2WI and the difference of CNR between pre-and post-enhancement or between both groups were calculated.The relationship of SNR or CNR with the iron particles in cells or tumors was confirmed by Prussian blue iron staining.Results Cytology experiment showed the SNR in both groups was decreased with the increase of the dosage of AFP-USPIO or USPIO,indicating statistically significantdifference in SNR among three different doseage groups (P＜0.05).Prussian blue iron staining showed that the iron particles in cells were increased with the increase of AFP-USPIO dosage,and was negatively correlated with SNR (P=0.00,r=-0.926).However,the iron particles were less in cells in USPIO group.The CNRs of liver tumors in Wistar rat of pre-and post-AFP-USPIO injection were 2.05±0.88 and 0.96±0.31 respectively,indicating a significant difference (P=0.028,t=3.380).However,the CNRs in USPIO group,2.25±1.50 and 2.57±1.49,showed no statistical difference (P=0.275,t=1.263).The CNR after enhancement also had a statistical difference between both groups(P=0.042,t=3.487).Pathological results confirmed more iron particles in tumor tissues in AFP-USPIO group,whereas less in USPIO group.Conclusion AFP-USPIO molecular probes can initiatively target to the HepG2 cells and the liver cancer of rat models expressing AFP,which may help to achieve the specificity of MR imaging in the diagnosis of HCC.

Objective: To explore the value of edema ring around the ablation zone on FS-T2WI for early phase effect evaluation of radiofrequency ablation (RFA) for treatment of malignant hepatic tumors. Methods: Totally 18 patients with liver cancer and 4 with liver metastasis who underwent RFA therapy were enrolled. Plain MR images were obtained to observe the morphological features of the edema ring around the ablation zone on FS-T2WI on the third day after RFA. Plain and multiphase enhanced MRI were obtained after RFA to observe the effect, as well as tumor markers. The value of continuity of edema ring on FS-T2WI for evaluating the effect of RFA was assessed. Results: High-signal edema ring was seen around the ablation zone on FS-T2WI in all 22 cases. The edema rings were continuous in 19 cases, among them the thickness of the edema rings were uniform in 11 cases, while were uneven but with regular shape and clear boundary in the other 8 cases. No abnormal enhancement was detected on the following enhanced MRI after RFA, and the tumor markers were stable in above 19 cases, both suggesting completed ablation. The edema rings were discontinuous in 3 cases of liver cancer, with protruding slightly high signal nodule which enhanced on MRI 1 month after RFA, and the serum alpha-fetoprotein were elevated, suggesting that the ablation area did not completely cover the tumor area, and the ablations were not complete. Conclusion: The edema ring around the ablation zone on plain FS-T2WI early phase after RFA has certain value in assessing the effect of RF for malignant liver tumors, especially for short-term effect of RFA.

We mainly disscused hearing impedimemt due to damage tothe tympanic membrane which is no more than 50 decibel of hearing loss with describing the signs of traumatic hearing loss, characteristics of its pathology and hearing tests on the basis of 40 eases with traumatic deafness coming to the forensic identification and the forensic identification of hearing Loss with objective data, What ABR audiometry is of great significance has been luther demonstrated in determining hearing Loss whith is supeuior to other hearing tests in distinguishing exaggeration and simulated desfness. We also analyzed rules for seriors hearing loss in Standard for Identifying serious Injury to Human Body(trial draft)from point of classification of hearing loss degree in clinics.

Objective To investigate the effect of 3-bromopyruvate (3-BrPA) on transplanted rectal tumors in experimental rabbit models. Methods A total of 60 New Zealand white rabbits with transplanted rectal tumor were randomly and equally divided into low-dose (0.5 mmol/L), medium-dose (1.0 mmol/L), high-dose (2.0 mmol/L) treatment groups and saline control group with 15 rabbits in each group. Arterial perfusion of 10 ml 3-BrPA with concentration of 0.5 mmol/L, 1.0 mmol/L and 2.0 mmol/L via caudal mesenteric artery was respectively employed for the rabbits of the corresponding treatment group; the control group was perfused with equal amounts of saline. Four days later, rectal tumors were removed by vivisection. The necrosis degree of tumor cells was determined by microscopic examination, and the necrosis rate was calculated. The effect of different 3-BrPA concentrations on the rectal tumor was evaluated. Results The rectal tumor transplantation and transcatheter 3-BrPA or saline perfusion was successfully completed in all 60 experimental rabbits. Microscopically, tumor cells showed different degrees of damage in experimental rabbits. In low-dose (0.5 mmol/L) treatment group, gradeⅠnecrosis was observed in 3 rabbits, gradeⅡin 11 rabbits, and gradeⅢin one rabbit;the effective rate was 6.7%. In medium-dose (1.0 mmol/L) treatment group, gradeⅡnecrosis was seen in 2 rabbits, grade Ⅲ in 10 rabbits, and grade Ⅳ in 3 rabbits; the effective rate was 86.6%. In high-dose (2.0 mmol/L) treatment group, gradeⅢnecrosis was detected in 2 rabbits and gradeⅣin 13 rabbits;the effective rate was 100.0%. In the saline control group, grade I necrosis was observed in 15 rabbits. Statistically significant differences in tumor necrosis rate and effective rate existed between medium-dose (1.0 mmol/L) treatment group and high-dose (2.0 mmol/L) treatment group (P<0.05). Statistically significant differences in tumor necrosis rate also existed between each other among the four groups with necrosis of gradeⅠto gradeⅣ(P<0.05). 3-BrPA had obvious therapeutic effect, while it showed no damage to the normal intestinal tissue. Conclusion For the treatment of transplanted rectal tumor in rabbit models, arterial infusion of 3-BrPA has certain therapeutic effect. In the high-dose group, the necrosis rate and effective rate are the highest, and the therapeutic results are the most significant.

Objective To explore the new operation method and clinical effect of treating degloving injuries of the whole thumb.Methods Nine cases of the whole thumb degloving injury caused by machine were treated with free wrap-around flap from the big toe and the flap from the opposite foot.The phalanges,joints and tendons of all injured thumbs were integral relatively,except that the interphalangeal joints in 3 cases were destroyed and the flexor and extensor pollicis longus were ruptured.The size of the dorsal tissue defects varied from 4.8 cm × 2.9 cm to 6.2 cm × 3.4 cm,and the volar tissue defects ranged from 4.7 cm × 3.2 cm to 6.1 cm × 4.0 cm.The area of the wraparound flap from the big toe harvested was from 5.0 cm × 3.2 cm to 6.7 cm × 3.9 cm.The flap from the opposite foot was tibial flap with dorsalis pedis flap from the opposite second toe,and the area of the flap was from 5.0 cm × 3.5 cm to 6.6 cm × 4.5 cm.Results All 9 combined flaps survived.The wound healed primarily.Skin grafts in the donor sites of the foot also survived.Postoperative follow-up ranged from 6 to 20 months,with an everage of 9 months.The pulp of the thumb was well-stacked.Sensory recovery ranged from S3 to S3 +.Thumb nail grew well.Thumbs performed good functions as grabbing,grasping and nipping.The range of motion of the MP joints of the reconstructed thumb was normal.The motion of interphalangeal joints were acceptable in 6 cases,but worse than the normal thumb.The interphalangeal joint in 3 cases destroyed was fused.There was no obvious influence on the function of the foot.Conclusion Applying combined wrap-around flap from the big toe with the tibial flap and dorsalis pedis flap from the opposite foot in treating degloving injuries of the whole thumb is a new operation method,which could achieve good appearance and function,but have a small influence on the donor site.It is worthy being used widely in clinical.

Objective To analyze the investigation and treatment of signet ring cell carcinoma of pancreas.Method The clinical data of patients with histopathologically confirmed signet ring cell carcinoma of pancreas were analyzed retrospectively.Results There were 4 patients with signet ring cell carcinoma.There was no patient who presented with a typical carcinoid syndrome.Most patients presented with upper abdominal pain,backache or jaundice caused by bile duct obstruction.In one patient CA19-9 and CEA were raised.All patients received palliative biliary bypass and needle biopsy of the tumour.The median survival was 2.8 months.Conclusions Pancreatic signet ring cell carcinoma is a rare disease with poor prognosis.Surgery is the only effective treatment but the resectability rate is low.Whether this tumour responds to chemotherapy requires further studies.

ObjectiveTo investigate the biological effects and its mechanisms of ascorbic acid on pancreatic cancer PANC1 cells. Methods PANC1 cells were treated by ascorbic acid of different concentrations (0 ～40 mmol/L) for 24,48,72 hours.The proliferation of PANC1 cells was analyzed by MTT method; cell cycle and apoptosis were assessed by flow cytometry (FCM); inverted microscopy and transmission electron microscopy were used to observe cell morphology. The membrane potential of mitochondria were mearured by with JC-1 staining and FCM.Meanwhile,the changes of cell morphology and mitochondrial membrane potential induced by ascorbic acid after pretreatment with hydrogen peroxidescavenging enzyme (catalase) and red blood cells were also detected. Results Ascorbic acid in pharmacologic concentrations selectively inhibited the proliferation of PANC1 cells in a dose and time dependent manner.PANC1 cells were arrested in G2/M phase after treatment with 5 mmol/L ascorbic acid [ (32.55 ± 7.14)％ vs (22.00 ±1.27)％,t =5.808,P＜0.05],but there was no changes on apoptosis rate [ (1.98 ± 1.80)％ vs (1.09 ±0.16)％ ].Inverted microscope and transmission electron microscopy showed that oncosislike cell death of PANC1 cells was induced after treatment with ≥5 mmol/L ascorbic acid.Mitochondrial membrane potential of PANC1 cells was significantly lower than that of the control group in a dose dependent manner.The descent of mitochondrial membrane potential was significantly inhibited by pretreatment with catalase and red blood cells,and the degree of cell oncosis was attenuated.ConclusionsAscorbic acid significantly inhibited the proliferation of pancreatic cancer PANC1 cells in vitro.Ascorbic acid induced PANC1 cell oncosis,but not apoptosis.The possible mechanisms of inducing oncosis may be related to the descent of mitochondrial membrane potential.

Objective To investigate the clinical efficacy of modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 28 patients diagnosed as borderline resectable pancreatic cancer who were admitted to the Tianjin Medical University Cancer Institute and Hospital between April 2013 and October 2015 were collected.Twenty-eight patients were treated with modified FOLFIRINOX (irinotecan 135 mg/m2,oxaliplatin 64 mg/m2,leucovorin 400 mg/m2,5-FU 2 400 mg/m2,repeat the regimen every 2 weeks) as neoadjuvant chemotherapy.After the completion of neoadjuvant chemotherapy,patients were evaluated operation feasibility and developed surgical planning in 3 weeks.Observation indicators:(1) Efficacy of neoadjuvant chemotherapy;(2) adverse events of neoadjuvant chemotherapy;(3) surgical and postoperative situations;(4)follow-up situations.Follow-up using outpatient examination,telephone interview and we-chat was performed to detect survival of patients up to January 2017.Measurement data with skewed distribution were described as median (range).The survival curve was drawn by Kaplan-Meier method and the survival analysis was done by Log-rank test.Results (1) Efficacy of neoadjuvant chemotherapy:28 patients received chemotherapy with a median cycle of 6 cycles (range,3-12 cycles).Chemotherapy reaction of 28 patients:14 had partial remission,10 had stable disease and 4 had progressive disease.(2) Adverse events of neoadjuvant chemotherapy:there were 22 adverse events of 28 patients during chemotherapy,including 15 with grade1-2 and 7 with grade 3-4.(3)Surgical and postoperative situations:of 28 patients,18 received radical resection for pancreatic cancer including 11 receiving pancreaticoduodenectomy,7 receiving distal pancreatectomy with splenectomy.Surgeries included 6 with portal vein and superior mesenteric vein resection and reconstruction,1 with coeliac trunk resection.Ten patients received R0 resection and 8 received R1 resection.Of 18 patients,8 with postoperative complications were improved by conservative treatment,including 2 with pancreatic fistula,1 with biliary fistula,3 with delayed gastric empty,1 with anastomotic hemorrhage,1 with lympha fistula.No patient received re-operation or died within 30 days postoperatively.Pathological TNM staging:2 patients were detected in stage Ⅰ-Ⅱ,14 in stage Ⅲ and 2 in stage Ⅳ.All the 18 patients received chemotherapy after operation.Ten patients without operation continued chemotherapy.(4) Following up:28 patients were followed up for 5-21 months with a median time of 13 months.Of the 15 died patients,5 received operation and 10 received no operation.The median progressionfree survival time and median overall survival time were 14 months and 19 months in the 18 operative patients,7 months and 11 months in the 10 non-operative patients,respectively,with statistically significant differences (x2=7.335,9.950,P＜0.05).Conclusions Modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer is safe and effective,and patients can tolerate mild adverse reactions.Operable patients undergo surgeries after chemotherapy have relatively good outcome.

Objective: To explore the expression of PTK7 in pancreatic ductal adenocarcinoma and its clinical significance. Methods: The clinical and follow-up data of 85 patients with pancreatic ductal adenocarcinoma who underwent radical surgery at Tianjin Medical University Cancer Institute and Hospital from May 2011 to January 2016 were analyzed. The expression of PTK7 in 85 pancreatic cancer tissues and the corresponding para-cancer tissues was detected by immunohistochemistry, and the relationship between PTK7 expression level and the clinical pathological features and prognosis was analyzed. Results: Positive expression of PTK7 was observed mainly in the cytoplasm, presenting as brownish yellow granules. It was noted that expression of PTK7 in pancreatic ductal adenocarcinoma tissues and para-carcinoma tissues was 70.6% (60/85) and 52.9% (45/85), respectively, and the positive rate in pancreatic ductal adenocarcinoma tissues was significantly higher than that in para-carcinoma tissues; the difference was statistically significant (P<0.05). The abnormal expression of PTK7 was correlated with the tumor stage, lymph node metastasis, and the vascular tumor embolus (P<0.05). The survival analysis suggested that the survival time or recurrence-free time of patients with PTK7 high expression in pancreatic duct adenocarcinoma was significantly shorter than in those with low expression (P<0.05, respectively). ShRNA interference of PTK7 was successfully established in the cell stabilizing system, verified by MTT and clone formation. Results indicated that cell survival was significantly lower in the shRNA experimental group compared to the control group (P<0.05), the number of colonies formed was significantly smaller in the shRNA experimental group compared to the control group (P<0.05), and the expression of proliferation-related proteins Ki-67 and PCNA was significantly lower in the shRNA experimental group compared to the control group (P<0.05, respectively). Conclusions: The up-regulation of PTK7 expression in pancreatic ductal ad-enocarcinoma tissues was associated with the tumor stage, lymph node metastasis, and the vascular tumor thrombus, suggesting poor prognosis. It was also found that in pancreatic cancer cell lines, PTK7 could promote the proliferation of pancreatic cancer cells by regulating the levels of proliferative factors Ki-67 and PCNA.