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Background: Metabolic reprogramming caused by SHMT1/2, as key enzymes in one-carbon metabolism, has been considered to play a critical role in occurrence and progression of hepatocellular carcinoma (HCC). However, the associations between single nucleotide polymorphisms (SNPs) in SHMT1/2 genes and susceptibility of HCC remains unknown. The purpose of this study was to investigate the relation between four candidate SNPs in SHMT1/2 and risk of HCC in Chinese population. Materials and methods: A case-control study including 514 HCC patients and 234 controls was performed to determine associations between SNPs of SHMT1/2 and HCC risk,isolated via mass spectrometry. Results: Our data revealed that SHMT2 rs2229717 was significantly associated with HCC risk when compared to healthy controls under multiple genetic models (Allele T: odds ratio (OR) = 0.73, P=0.023; Dominant Model: OR = 0.72, P=0.044). When our cohort was stratified by sex, male subjects with the T allele and TT genotype for rs2229717 exhibited a decreased risk for HCC risk (OR=0.67, 95%CI=0.50-0.91; OR=0.43, 95%CI=0.18-0.99). In addition, after age stratification was executed, the results showed that both the T allele and the GT genotype for rs2229717 were less common in HCC patients under 50 years old. Conclusion: These data indicate that rs2229717is a predisposing factor for HCC and may affect the occurrence of HCC in various age or sex subgroups, suggesting that SHMT2 rs2229717may be as a useful predictive or diagnostic tool for HCC in some populations.

The optimal oxygen concentration is unclear for normothermic machine perfusion (NMP) of livers from donation after circulatory death donors (DCD). Our purposes were to investigate the effect of air-ventilated NMP on liver retrieval from DCD rats, and to analyze the underlying mechanism. Normothermic liver perfusion was performed using the NMP system with either air ventilation or oxygen ventilation for 2h in the rat liver following warm ischemia and cold ischemia preservation. Proteomics and metabolomics were used to reveal the significant molecular networks. The bioinformation analysis was validated by administering peroxisome proliferator activator receptor-γ (PPARγ) antagonist and agonist via ex vivo perfusion circuit in the air-ventilated NMP. Results showed that air-ventilated NMP conferred a better functional retrieval and a less inflammatory response in the rat DCD liver; integrated proteomics and metabolomics analysis indicated that intrahepatic docosapentaenoic acid (DPA) downregulation and upregulation of cytochrome P450 2E1 (CYP2E1) expression and activity were associated with DCD liver retrieval with air-ventilated NMP; PPARγ antagonist worsened liver function under air-oxygenated NMP whereas PPARγ agonist played the opposite role. In conclusion, air-ventilated NMP confers a better liver retrieval from DCD rats through the DAP-PPARγ-CYP2E1 axis; CYP2E1 activity provides a biomarker of liver retrieval from DCD.

The optimal oxygen concentration is unclear for normothermic machine perfusion (NMP) of livers from donation after circulatory death (DCD). Our purposes were to investigate the effect of air-ventilated NMP on the DCD liver, analyze the underlying mechanism and select the targets to predict liver functional recovery with NMP. NMP was performed using the NMP system with either air ventilation or oxygen ventilation for 2 h in the rat liver following warm ischemia and cold-storage preservation. Proteomics and metabolomics were used to reveal the significant molecular networks. The bioinformation analysis was validated by administering peroxisome proliferator activator receptor-γ (PPARγ) antagonist and agonist via perfusion circuit in the air-ventilated NMP. Results showed that air-ventilated NMP conferred a better functional recovery and a less inflammatory response in the rat DCD liver; integrated proteomics and metabolomics analysis indicated that intrahepatic docosapentaenoic acid downregulation and upregulation of cytochrome P450 2E1 (CYP2E1) expression and activity were associated with DCD liver functional recovery with air-ventilated NMP; PPARγ antagonist worsened liver function under air-oxygenated NMP whereas PPARγ agonist played the opposite role. In conclusion, air-ventilated NMP confers a better liver function from DCD rats through the DAP-PPARγ-CYP2E1 axis; CYP2E1 activity provides a biomarker of liver functional recovery from DCD.

Small-for-size syndrome following liver surgery is characterized by compromised liver regeneration. Liver macrophages play key roles in initiating liver regeneration, and modulation of the immune microenvironment through macrophages may accelerate liver regeneration. In our current study, we aimed to explore the involvement of innate immunity after extended hepatectomy in rats and humans, and to test the effect of immunity modulation on small-for-size liver regeneration in rats.Serum programmed cell death protein ligand 1 (PD-L1) was measured after major hepatectomy and minor hepatectomy in humans and rats. Liver regeneration in rats was assessed using liver-to-body weight ratio and kinetic growth rate, antigen Ki67 and proliferating cell nuclear antigen (PCNA), and macrophage polarization was assessed by inducible nitric oxide synthase (iNOS), cluster of differentiation protein 163 (CD163) expression by immunohistochemistry (IHC) and iNOS/CD163 ratio. Rat hepatocyte BRL or human hepatocyte LO2 were co-cultured with rat bone marrow-derived macrophages or human macrophages THP-1. BMS-1 or Nivolumab were used to block programmed cell death protein 1 (PD-1)/PD-L1 in vitro and in vivo.PD-L1 expressions were significantly higher following major hepatectomy compared to minor resection in both humans and rats; compromised liver regeneration after extended hepatectomy in rats was associated with PD-L1 upregulation and M2 macrophage polarization. M1 macrophages increased proliferation of hepatocytes through interleukin-6 (IL-6), and M2 macrophages decreased hepatocyte proliferation; blocking PD-1/PD-L1 reversed the effect of M2 macrophages on the survival of hepatocytes in vitro and promoted liver growth in rats through M1 macrophage polarization.Compromised hepatic regeneration following extended hepatectomy is characterized by M2 macrophage polarization and upregulated PD-L1 expression. Blocking PD-1/PD-L1 may enhance small-for-size liver regeneration by inducing M1 macrophage polarization.

The risk of chronic hepatitis B (CHB) infection is often affected by polyunsaturated fatty acids (PUFAs) metabolism which is strongly influenced by single nucleotide polymorphisms (SNPs) within the PUFA metabolic pathway. Given this, we designed this study to determine the relationship between specific polymorphisms within fatty acid desaturase 2 (FADS2), a key enzyme in PUFA metabolism, and CHB infection. We completed this evaluation using a case-control study comprising 230 CHB patients and 234 unrelated healthy controls in which the genetic relationships between three previously identified SNPs, isolated via mass spectrometry, and CHB infection. Our data revealed that none of these three SNPs (rs174568, rs174601, and rs2727270) were significantly associated with susceptibility to CHB infection when compared to healthy controls. However, when we stratified our cohort by sex, male subjects with the TC genotype for FADS2 exhibited a decreased risk for CHB infection (OR = 0.62, 95%CI = 0.39-0.96; OR = 0.64, 95%CI = 0.41-1.00; OR = 0.57, 95%CI = 0.36-0.90). Furthermore, age stratification revealed that both the T allele and the TC genotypes for each of the three target SNPs were less common in Chinese CHB cases in people younger than 50 years old. Correlation analysis also revealed that there was no statistically significant relationship between these three SNPs and HBV-DNA replication or hepatitis B surface antigen (HBsAg) levels. Thus, our data suggests that rs174568, rs174601, and rs2727270 may affect the CHB outcomes in various age or sex subgroups, suggesting that they may be useful predictive or diagnostic biomarkers of CHB infection in some populations.

We recently reported that a CB2R agonist, GW405833 (GW), reduced both the ACh-induced Ca2+ oscillations and the L-arginine-induced Ca2+ signal enhancement in mouse pancreatic acinar cells, suggesting that GW-induced inhibition may prevent the pathogenesis of acute pancreatitis. In this study, we aim to evaluate the effects of other cannabinoid ligands on Ca2+ signaling in acinar cells. Patch-clamp whole-cell recordings were applied to measure ACh-induced intracellular Ca2+ oscillations in pancreatic acinar cells acutely dissociated from wild-type (WT), CB1R knockout (KO), and CB2R KO mice, and the pharmacological effects of various cannabinoid ligands on the Ca2+ oscillations were examined. We found that all the 8 CB2R agonists tested inhibited ACh-induced Ca2+ oscillations. Among them, GW, JWH133, and GP1a caused potent inhibition with IC50 values of 5.0, 6.7, and 1.2 μmol/L, respectively. In CB2R KO mice or in the presence of a CB2R antagonist (AM630), the inhibitory effects of these 3 CB2R agonists were abolished, suggesting that they acted through the CB2Rs. The CB1R agonist ACEA also induced inhibition of Ca2+ oscillations that existed in CB1R KO mice and in the presence of a CB1R antagonist (AM251), suggesting a non-CB1R effect. In WT, CB1R KO, and CB2R KO mice, a nonselective CBR agonist, WIN55,212-2, inhibited Ca2+ oscillations, which was not mediated by CB1Rs or CB2Rs. The endogenous cannabinoid substance, 2-arachidonoylglycerol (2-AG), did not show an inhibitory effect on Ca2+ oscillations. In conclusion, CB2R agonists play critical roles in modulating Ca2+ signals in mouse pancreatic acinar cells, while other cannabinoid ligands modulate Ca2+ oscillations in a heterogeneous manner through a CB receptor or non-CB-receptor mechanism.

Yi Ru,1–4 Xiao-Jie Chen,5 Wen-Zhi Guo,1–4 She-Gan Gao,5 Yi-Jun Qi,5 Pan Chen,5 Xiao-Shan Feng,5 Shui-Jun Zhang1–4 1Henan Key Laboratory of Digestive Organ Transplantation, 2Open Laboratory of Key Disciplines of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation, 3Key Laboratory of Hepatobiliary and Pancreatic Diseases and Organ Transplant Medicine, 4Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 5Henan Key Laboratory of Cancer Epigenetics; Cancer Institute, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, People’s Republic of China Background: Liver cancer is a type of malignant tumor with high morbidity and mortality in People’s Republic of China. Its occurrence and development involve the variation and expression changes of multiple genes, and the pathogenesis and related regulatory networks are complex. Purpose: In the present research, we investigate the involvement of NEAT1_2 and SFPQ in cisplatin resistance in liver cancer. The effects of LncRNA NEAT1 and SFPQ expression on the chemotherapeutic resistance of liver cancer cells were analyzed. Methods: The expression level of NEAT1_2 and SFPQ mRNA in tissue specimens or cell lines were examined by RT-qPCR and western blotting. CCK-8 assay was performed to evaluate cell viability. Cell proliferation was performed using the EdU cell proliferation assay. Results: Our data showed that increase NEAT1_2 and SFPQ expressions in liver cancer specimens were associated with the development of cisplatin resistance; high SFPQ expression level impaired patients’ survival from liver cancer. Gain-and loss-of function assay using NEAT1_2 knock-in and knock-out cells constructed using CRISPER/Cas9 system revealed that NEAT1_2 is essential for liver cancer cell survival and mediates cisplatin resistance in liver cancer cells at least partially through SFPQ. Artificial change in NEAT1_2 expression level didn’t significantly influence SFPQ transcription or translation level. Conclusion: Our data revealed NEAT1_2—SFPQ axis as a novel cisplatin resistance mechanism in liver cancer cells in vitro. Keywords: NEAT1, NEAT1_1, NEAT1_2, SFPQ, liver cancer, cisplatin resistance

Background: Hepatocellular carcinoma (HCC) (about 85–90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. Summary: This guideline presents official recommendations of the National Health and Family Planning Commission of the People’s Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. Key Messages: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Background and aims The restenosis following percutaneous transluminal balloon angioplasty (PTBA) is high for Budd-Chiari syndrome (BCS) patients with hepatic venous obstruction (HVO). We aim to evaluate the safety and long-term outcome of PTBA with a large balloon catheter in a large series of patients with HVO. Methods Between January 2005 and December 2013, 93 consecutive BCS patients with HVO were referred for PTBA and subsequently underwent color Doppler ultrasonography or angiography follow-up. Data were retrospectively collected, and follow-up observations were performed at 1-, 2-, 2- to 5-, and 5- to 8-years postoperatively. Results Percutaneous transluminal balloon angioplasty was technically successful in all patients. Ninety-one patients (97.85%) were treated with PTBA and two with PTBA and stent. Major procedure-related complications occurred in six of the 93 patients (6.45%). The cumulative 1-, 2-, 2- to 5-, and 5- to 8-year primary patency rates were 97.5%, 92.9%, 90%, and 86.5%, respectively. Cumulative 1-, 2-, 2- to 5-, and 5- to 8-year secondary patency rates were 100%, 100%, 98.6%, and 97.3%, respectively. Mean and median primary patency rates were 51.50 ± 3.01 months and 55.0 ± 3.63 months, respectively. Cumulative 1-, 2-, 2- to 5-, and 5- to 8-year survival rates were 98.75%, 98.6%, 100%, and 100%, respectively. Mean and median survival times were 53.10 ± 3.04 months and 55.0 ± 3.64 months, respectively. Conclusion Percutaneous transluminal balloon angioplasty with a large balloon is a safe and effective treatment that could provide excellent rates of long-term patency and survival for the majority of Chinese patients with BCS and HVO.

// Ji-Feng Xu 1, * , Xiao-Hong Pan 2, * , Shui-Jun Zhang 1 , Chen Zhao 1 , Bin-Song Qiu 1 , Hai-Feng Gu 1 , Jian-Fei Hong 1 , Li Cao 1 , Yu Chen 1 , Bing Xia 1 , Qin Bi 1 , Ya-Ping Wang 2 1 Department of Orthopedics and Joint Surgery, Zhejiang Provincial People’s Hospital, Hangzhou 310014, PR China 2 Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China * These authors have contributed equally to this work Correspondence to: Ji-Feng Xu, e-mail: xu_jifeng@hotmail.com Ya-Ping Wang, e-mail: wangypzju@163.com Keywords: osteosarcoma, CD47, antibody, immunotherapy Received: April 21, 2015 Accepted: May 26, 2015 Published: June 08, 2015 ABSTRACT Osteosarcoma is the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease still have a poor prognosis, illustrating the need for alternative therapies. In this study, we explored the use of antibodies that block CD47 with a tumor growth suppressive effect on osteosarcoma. We first found that up-regulation of CD47 mRNA levels in the tumorous tissues from eight patients with osteosarcoma when compared with that in adjacent non-tumorous tissues. Further western-blot (WB) and immunohistochemistry (IHC) demonstrated that CD47 protein level was highly expressed in osteosarcoma compared to normal osteoblastic cells and adjacent non-tumorous tissues. Osteosarcoma cancer stem cell markers staining shown that the majority of CD44 + cells expressed CD47 albeit with different percentages (ranging from 80% to 99%). Furthermore, high CD47 mRNA expression levels were associated with a decreased probability of progression-free and overall survival. In addition, blockade of CD47 by specific Abs suppresses the invasive ability of osteosarcoma tumor cells and further inhibits spontaneous pulmonary metastasis of KRIB osteosarcoma cells in vivo . Finally, CD47 blockade increases macrophage phagocytosis of osteosarcoma tumor cells.In conclusion, our findings demonstrate that CD47 is a critical regulator in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by anti-CD47 may be a novel immunotherapeutic approach in the management of this tumor.

Hereditary multiple osteochondromas (HMO) is an autosomal dominant bone disorder characterised by the presence of multiple benign cartilage-capped tumours. Exostosin-1 (EXT1) and EXT2 are the major morbigenous genes associated with HMO, mutations in which are responsible for 90% of all HMO cases. In patients with HMO, osteochondromas arise adjacent to the metaphysis and typically remain in the metaphyseal region of the long bones. Therefore, it is rare for osteochondromas to be identified intra-articularly, although they may manifest as loose bodies. The present study describes a rare case of HMO manifesting as limited flexing range in the right knee joint of a 27-year-old male patient. Computed tomography and magnetic resonance imaging (MRI) revealed three intra-articular osteochondromas located in the intercondylar fossa of the patient's right knee. The intra-articular osteochondromas and protuberant extra-articular osteochondromas around the right knee were resected, resulting in improved right knee function and no postoperative recurrence. Pathological analysis revealed that the intra-articular osteochondromas had a thinner cartilage cap layer than the extra-articular osteochondromas. In addition, genetic analysis of the patient and the patient's mother was conducted. From this, it was determined that a nonsense mutation, c.115G>T (p.E39X) in exon 1 of the EXT1 gene, was the cause of HMO in this case. Thus, it is proposed that osteochondromas with a pedicle within the knee, may tear and become loose intra-articular bodies, resulting in limited joint function and thereby contributing to the progression of HMO.

We recently reported that a CB(2)R agonist, GW405833 (GW), reduced both the ACh-induced Ca(2+) oscillations and the L-arginine-induced Ca(2+) signal enhancement in mouse pancreatic acinar cells, suggesting that GW-induced inhibition may prevent the pathogenesis of acute pancreatitis. In this study, we aim to evaluate the effects of other cannabinoid ligands on Ca(2+) signaling in acinar cells. Patch-clamp whole-cell recordings were applied to measure ACh-induced intracellular Ca(2+) oscillations in pancreatic acinar cells acutely dissociated from wild-type (WT), CB(1)R knockout (KO), and CB(2)R KO mice, and the pharmacological effects of various cannabinoid ligands on the Ca(2+) oscillations were examined. We found that all the 8 CB(2)R agonists tested inhibited ACh-induced Ca(2+) oscillations. Among them, GW, JWH133, and GP1a caused potent inhibition with IC(50) values of 5.0, 6.7, and 1.2 μmol/L, respectively. In CB(2)R KO mice or in the presence of a CB(2)R antagonist (AM630), the inhibitory effects of these 3 CB(2)R agonists were abolished, suggesting that they acted through the CB(2)Rs. The CB(1)R agonist ACEA also induced inhibition of Ca(2+) oscillations that existed in CB(1)R KO mice and in the presence of a CB(1)R antagonist (AM251), suggesting a non-CB(1)R effect. In WT, CB(1)R KO, and CB(2)R KO mice, a nonselective CBR agonist, WIN55,212-2, inhibited Ca(2+) oscillations, which was not mediated by CB(1)Rs or CB(2)Rs. The endogenous cannabinoid substance, 2-arachidonoylglycerol (2-AG), did not show an inhibitory effect on Ca(2+) oscillations. In conclusion, CB(2)R agonists play critical roles in modulating Ca(2+) signals in mouse pancreatic acinar cells, while other cannabinoid ligands modulate Ca(2+) oscillations in a heterogeneous manner through a CB receptor or non-CB-receptor mechanism.

Idiopathic scoliosis is the most common pediatric spinal deformity affecting 1% to 3% of the population, and adolescent idiopathic scoliosis (AIS) accounts for approximately 80% of these cases; however, the etiology and pathogenesis of AIS are still uncertain. The current study aims to identify the relationship between G protein-coupled receptor 126 (GPR126) gene and AIS predisposition, to identify the relationship between the genotypes of the GPR126 SNPs and the clinical phenotypes of AIS. We conducted a case-control study and genotyped twenty SNPs of GPR126 gene including ten exonic SNPs and ten intronic polymorphisms in 352 Chinese sporadic AIS patients and 149 healthy controls. We provided evidence for strong association of three intronic SNPs of the GPR126 gene with AIS susceptibility: rs6570507 A > G (p =0 .0035, OR = 1.729), rs7774095 A > C (p = 0.0078, OR = 1.687), and rs7755109 A > G (p = 0.0078, OR = 1.687). However, we did not identify any significant association between ten exonic SNPs of GPR126 and AIS. Linkage disequilibrium analysis indicated that rs7774095 A > C and rs7755109 A > G could be parsed into one block. The association between the intronic haplotype and AIS was further confirmed in an independent population with 110 AIS individuals and 130 healthy controls (p = 0.046, OR = 1.680). Furthermore, molecular mechanisms underlying intronic SNP regulation of GPR126 gene were studied. Although intronic SNPs associated with AIS didn't influence GPR126 mRNA alternative splicing, there was a strong association of rs7755109 A > G with decreased GPR126 mRNA level and protein levels. Our findings indicate that genetic variants of GPR126 gene are associated with AIS susceptibility in Chinese populations. The genetic association of GPR126 gene and AIS might provide valuable insights into the pathogenesis of adolescent idiopathic scoliosis.

AIM To investigate the relationship between autophagy and perineural invasion (PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubule-associated protein 1A/1B-light chain 3 (LC3) and PNI marker ubiquitin carboxy-terminal hydrolase (UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis. RESULTS In 109 cases of pancreatic cancer, 68.8% (75/109) had evidence of PNI and 61.5% (67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels (P < 0.05). LC3 expression was related to lymph node metastasis (P < 0.05) and was positively correlated with neural invasion (P < 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients (P < 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer (P < 0.05). CONCLUSION PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.

To compare the outcomes of diffuse pigmented villonodular synovitis (PVNS) of the knee treated with routine anteroposterior open surgery or modified multi-directional arthroscopy.Medical records of patients with diffuse PVNS who underwent surgery between 2002 and 2010 were reviewed. Patients were followed up at 3, 6, 12, 24, and 36 months. Operative time, blood loss, length of hospital stay, recurrence rate, and International Knee Documentation Committee (IKDC) scores and Lysholm knee scores at 1- and 3-year postoperatively were compared between the open surgery and arthroscopy groups.A total of 41 patients with diffuse PVNS were included (20 in open surgery group and 21 in multi-directional arthroscopy group). There was no significant difference in the baseline characteristics between the two groups. Operation time, postoperative bleeding, and length of hospital stay were all significantly lower in the arthroscopy group than in the open surgery group (all, P0.05). There were four recurrences in the open surgery group and one in arthroscopy group. All five recurrences received a second surgery without any subsequent recurrences. At both 1- and 3-year postoperatively, IKDC and Lysholm scores were significantly greater in the arthroscopy group than the open surgery group (all P0.001).The multi-directional arthroscopic technique was associated with significantly shorter operation time and hospital stay, less blood loss, and better postoperative IKDC and Lysholm scores than open surgery.Retrospective study with controls, Level III.

Hereditary multiple exostoses (HME) is an autosomal dominant bone disorder characterized by the presence of multiple benign cartilage-capped tumors. EXT1 located on chromosome 8q23-q24 and EXT2 located on 11p11-p12 are the main disease-causing genes which are responsible for ~90% of HME cases. Mutations of EXT1 or EXT2 result in insufficient heparan sulfate biosynthesis, which facilitates chondrocyte proliferation, boosts abnormal bone growth of neighboring regions, causes multiple exostoses, and ultimately leads to possible malignant transformation. A family who displayed typical features of HME was enrolled in the present study. Mutation screening by Sanger sequencing identified a novel heterozygous nonsense mutation c.1902C>A (p.Tyr634X) in the EXT1 gene exclusively in all 3 patients, which is located in the glycosyltransferase domain and results in the truncation of 112 amino acids at the C-terminus of the EXT1 protein. Thus, the present study identified a novel disease-causing EXT1 mutation in a pedigree with HME, which provides additional evidence for developing quick and accurate genetic tools for HME diagnosis.

// Ji-Feng Xu 2, 3 , Ya-Ping Wang 1 , Shui-Jun Zhang 2 , Yu Chen 2 , Hai-Feng Gu 2 , Xiao-Fan Dou 2 , Bing Xia 2 , Qing Bi 2 and Shun-Wu Fan 3 1 Department of Cardiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310009, P.R. China 2 Department of Orthopedics, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China 3 Department of Orthopedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China Correspondence to: Shun-Wu Fan, email: fansw@srrsh.com Keywords: osteosarcoma (OS), chemotherapy sensitivity, exosome, microRNA, poor chemotherapeutic response Received: January 12, 2017 Accepted: April 15, 2017 Published: June 06, 2017 ABSTRACT A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p

BACKGROUND Little is known about neuronal death mechanisms following spinal cord ischemia. The present study aimed to investigate the protective effect of pentoxifylline (PTX) against spinal cord ischemia/reperfusion (I/R) injury. METHODS Rabbits sustained spinal cord ischemia following 45 minutes cross-clamping of the infrarenal aorta. Experimental groups were as follows: the first group of animals (sham, n = 8) underwent laparotomy alone and served as the sham group; the second group (I/R, n = 20) received carrier (3 ml saline solution) and served as the control group; the third group (PTX-A, n = 20) received PTX intravenously 10 minutes prior to ischemia; and the fourth group (PTX-B, n = 20) received PTX intravenously at the onset of reperfusion. Rabbits were evaluated for hind-limb motor function with the Tarlov scoring system at 48 hours. Serum was assayed with enzyme-linked immunosorbent assay for tumor necrosis factor alpha (TNF-alpha) and spinal cords were harvested for myeloperoxidase (MPO) activity, histopathological analysis, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling staining, platelet/endothelial cell adhesion molecule-1 (PECAM-1) and caspase-3 immunohistochemistry, and the number of necrotic and apoptotic neuron were counted and data analyzed at 12, 24, 48 and 72 hours of reperfusion. Spinal cords were studied by electron microscopy. RESULTS Improved Tarlov scores were seen in PTX-treated rabbits as compared with ischemic control rabbits at 48 hours. A significant reduction was found in TNF-alpha in serum, activity of MPO and immunoreactivity of the PECAM-1 and caspase-3 in PTX-treated rabbits. There were fewer apoptotic neurons than necrotic neurons (P < 0.05). A significant decrease in both necrotic and apoptotic neurons was observed in the PTX-treated groups (PTX-A and PTX-B) compared with the I/R group (P < 0.05). Both necrotic and apoptotic neurons were found with the electron microscope. CONCLUSIONS PTX may induce protection against ischemia injury in the spinal cord, thereby preventing both necrosis and apoptosis. A major mode of cell death in spinal cord ischemia/reperfusion injury is necrosis while apoptosis is not dominant.

To investigate the clinical effect of arthroscopic treatment for stenosing tenosynovitis of radial styloid process.Ninety nine patients diagnosed as stenosing tenosynovitis of radial styloid process from August, 2009 to July, 2013 were divided into three groups, including arthroscopic treatment group(32 cases), traditional operation group (34 cases) and local blocking therapy group(33 cases). Ache, tenderness, swollen situations and movement degrees of wrist joints and thumbs were observed before treatment and one week and one month after treatment. Total effective rates were calculated.Pain score of the wrist and thumb in activity state was lower in arthroscopic treatment group and traditional operation group than that in local blocking therapy group one week and one month after treatment(Compared with traditional operation and local blocking therapy, arthroscopic treatment has certain effects for the treatment of stenosing tenosynovitis of radial styloid process, with less operation trauma and complications, and it is worthy of clinical promotion.

AIM: To review and evaluate the diagnostic dilemma of xanthogranulomatous cholecystitis (XGC) clinically. METHODS: From July 2008 to June 2014, a total of 142 cases of pathologically diagnosed XGC were reviewed at our hospital, among which 42 were misdiagnosed as gallbladder carcinoma (GBC) based on preoperative radiographs and/or intra-operative findings. The clinical characteristics, preoperative imaging, intra-operative findings, frozen section (FS) analysis and surgical procedure data of these patients were collected and analyzed. RESULTS: The most common clinical syndrome in these 42 patients was chronic cholecystitis, followed by acute cholecystitis. Seven (17%) cases presented with mild jaundice without choledocholithiasis. Thirty-five (83%) cases presented with heterogeneous enhancement within thickened gallbladder walls on imaging, and 29 (69%) cases presented with abnormal enhancement in hepatic parenchyma neighboring the gallbladder, which indicated hepatic infiltration. Intra-operatively, adhesions to adjacent organs were observed in 40 (95.2%) cases, including the duodenum, colon and stomach. Thirty cases underwent FS analysis and the remainder did not. The accuracy rate of FS was 93%, and that of surgeon’s macroscopic diagnosis was 50%. Six cases were misidentified as GBC by surgeon’s macroscopic examination and underwent aggressive surgical treatment. No statistical difference was encountered in the incidence of postoperative complications between total cholecystectomy and subtotal cholecystectomy groups (21% vs 20%, P > 0.05). CONCLUSION: Neither clinical manifestations and laboratory tests nor radiological methods provide a practical and effective standard in the differential diagnosis between XGC and GBC.

The aim of this study was to investigate the microRNA (miRNA) expression pattern in synovial fluid from patients with knee osteoarthritis (OA) after treatment with intra-articular injection of hyaluronan (HA).Twelve OA patients were enrolled in accordance with the Kellgren-Lawrence classification of knee OA. All patients received intra-articular injection of HA once a week for 5 weeks and were evaluated with the Western Ontario and McMaster Universities (WOMAC) index at baseline. TaqMan miRNA assay profiling was performed on synovial fluid RNAs extracted from OA patients pre-injection and after 5 weeks of treatment with HA. Validation was performed using independent samples, including ten healthy controls and ten matched OA patients.Forty-three miRNAs (21 overexpressed miRNAs and 22 underexpressed miRNAs) were differentially expressed in OA patients before and after treatment with HA (P 0.05, false discovery rate corrected). Further bioinformatics prediction by mirPath indicated that the differential miRNA signatures in synovial fluid extracted from the OA patients demonstrated primarily upregulation of the PI3K-Akt signaling pathway, mitogen-activated protein kinase signaling pathway, regulation of autophagy, mRNA surveillance pathway, and B cell receptor signaling pathway. In addition, TaqMan real-time reverse transcription polymerase chain reaction was performed for validation on miR-146a, miR-155, let-7a, miR-181a, miR-454, and let-7b, which were significantly changed in abundance, using an independent cohort of ten healthy controls and ten OA patients as compared with those with intra-articular injection of HA.Our results demonstrated that dysregulation in miRNAs in synovial fluid from OA patients and their affected biologic cellular processes might play important role in OA pathogenesis and HA-mediated therapeutics.

The restenosis following percutaneous transluminal balloon angioplasty (PTBA) is high for Budd-Chiari syndrome (BCS) patients with hepatic venous obstruction (HVO). We aim to evaluate the safety and long-term outcome of PTBA with a large balloon catheter in a large series of patients with HVO.Between January 2005 and December 2013, 93 consecutive BCS patients with HVO were referred for PTBA and subsequently underwent color Doppler ultrasonography or angiography follow-up. Data were retrospectively collected, and follow-up observations were performed at 1-, 2-, 2- to 5-, and 5- to 8-years postoperatively.Percutaneous transluminal balloon angioplasty was technically successful in all patients. Ninety-one patients (97.85%) were treated with PTBA and two with PTBA and stent. Major procedure-related complications occurred in six of the 93 patients (6.45%). The cumulative 1-, 2-, 2- to 5-, and 5- to 8-year primary patency rates were 97.5%, 92.9%, 90%, and 86.5%, respectively. Cumulative 1-, 2-, 2- to 5-, and 5- to 8-year secondary patency rates were 100%, 100%, 98.6%, and 97.3%, respectively. Mean and median primary patency rates were 51.50 ± 3.01 months and 55.0 ± 3.63 months, respectively. Cumulative 1-, 2-, 2- to 5-, and 5- to 8-year survival rates were 98.75%, 98.6%, 100%, and 100%, respectively. Mean and median survival times were 53.10 ± 3.04 months and 55.0 ± 3.64 months, respectively.Percutaneous transluminal balloon angioplasty with a large balloon is a safe and effective treatment that could provide excellent rates of long-term patency and survival for the majority of Chinese patients with BCS and HVO.

To study on the efficacy, prognosis and security of high-intensity focused ultrasound (HIFU) combined with transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC).Totally 72 HCC patients treated by HIFU from December 2009 to January 2011 were divided into two groups according to treatment methods: 40 cases in HIFU group, 32 cases in TACE + HIFU treatment group (combined group). Then set up a control group include 40 cases treated by only TACE in the same period (TACE group). The improvement of clinical symptoms, AFP, reduce rate of tumor volume, survival rate of 1 year after operation and postoperative complications in front and behind the treatment were analyzed.There was no significant statistical difference on the improvement of clinical symptoms in all these three groups (P0.05) after treatment for HCC. There is no significant statistical difference also on reduce rate of tumor volume and decrease rate of AFP in both HIFU group (35.0%, 41.4%) and TACE group (37.5%, 41.9%) (χ² = 0.054, P = 0.816; χ² = 0.002, P = 0.965). Both reduce rate of tumor volume (62.5%) and decrease rate of AFP (72.0%) in combined group were better than HIFU group (χ² = 5.394, P = 0.020; χ² = 5.098, P = 0.024) and TACE group (37.5%, 41.9%) (χ² = 4.448, P = 0.035; χ² = 5.062, P = 0.024). Kaplan-Meier survival curve showed that there was no significant statistical difference on short-term survival rate in the 3 groups. But the long-term survival rate of combined group was better than TACE group and HIFU group.TACE combined with HIFU is a effective, safe and noninvasive treatment method to HCC.

This study aimed to assess the diagnostic value of three types of MRI sequences and to observe the clinical outcomes of arthroscopy surgery for ankle joint impingement syndrome. Ankle joint impingement syndrome was confirmed by FSE-T2WI, FSE-PDWI, and FS-3D-FISP MRI in 23 patients with arthroscopically proven ankle impingement. All 23 patients underwent arthroscopic surgery and the ankle joint function was evaluated before, 1 week after and 6 months after the operation. The patients were followed-up for 12-64 months (average 28 months). There was no significant difference in ankle function score between preoperatively and 1 week postoperatively, but 86.96 % patients got overall excellent or good scores 6 months after the surgery, significantly higher than before the surgery. The FS-3D-FISP MRI exhibited a good consistency with arthroscopic examination and had higher sensitivity and specificity for the diagnosis of ankle impingement than FSE-T2WI and FSE-PDWI. In summary, arthroscopy surgery for ankle impingement syndrome has several advantages such as good efficacy, minimal trauma, quick recovery, and much less complications. The preoperative FS-3D-FISP MRI allows accurate diagnosis and positioning of ankle impingement syndrome.

Post-operative liver regeneration may contribute to tumor recurrence. There is a theoretical need for an adjuvant therapy that can suppress tumor growth without adversely affecting post-operative liver regeneration.To evaluate the effect of RAF inhibitor Sorafenib on cell viability and proliferation of hepatoma cells and hepatocytes in vitro and in an in vivo rat model.Cell viability, DNA synthesis, and RAF/MAPK kinase activity in the primary hepatocyte and hepatoma cell lines were investigated after Sorafenib exposure. Sequence analysis of the B-RAF gene in hepatic cells was determined. Tumor markers were compared within the rats after 70% hepatectomy with or without daily oral gavages of Sorafenib. Liver regeneration was assessed by liver function tests and proliferation markers.Primary hepatocytes showed higher cell viability, proliferation rate, and stronger RAF/MAPK kinase activity compared with hepatoma cell lines. The in vivo tumor volumes, size, and metastases were significantly decreased (P 0.05) whereas no significant change in liver regeneration related to Sorafenib exposure was found (P 0.05). B-RAF V600E mutation was not detected neither in the hepatic cells nor untransformed hepatocytes.The RAF targeted inhibitor can reduce tumor growth without retarding liver regeneration in this experiment.

The aim of this research was to determine the efficacy of combination therapy using an alginate dressing and mouse epidermal growth factor (mEGF) on proliferation and differentiation of epidermal stem cells (ESCs) in patients with refractory wounds.Eighteen patients (12 males and 6 females, aged from 18 to 61 years (mean 36.4 years)) with various skin wounds, were treated by dressing changing for one month. The wounds were located in the foot (11), calf (3), thigh (2) and forearm (2). The patients were randomly divided into 3 groups: alginate dressing and mEGF (group A; n = 6), mEGF (group B; n = 6) and control (group C; n = 6). Wound closure indexes were measured at 7, 14, 21 and 28 days. Samples were harvested for pathologic examination, at 7 and 14 days following treatment. Cytokeratin 10 (CK10) and cytokeratin 15 (CK15) positive cells were evaluated using the super-sensitivity (SP) immunohistochemical staining technique.Wound healing was promoted in groups A and B. In group A, the wound closure index was increased significantly (P0.05), and in one case the maximum cure area reached 102 cm(2). Pathological examination identified a thicker epidermis, active angiogenesis and enhanced granulation in group A compared with groups B and C. Using the SP immunohistochemical staining technique, we showed that ESCs in group A were bigger in size and larger in number than in groups B and C. Overall, there was a significant difference in ESCs proliferation and differentiation between group A and group B (or C).Combination therapy using an alginate dressing and mEGF shows increased proliferation and differentiation of ESCs in patients with refractory wounds compared with those treated with mEGF alone.

To elucidate the molecular mechanism of norcantharidin (NCTD) in inducing apoptosis of liver cancer cells so as to provide basic rationales for its application in liver cancer treatment.Liver cancer cell lines of SMMC-7721 and BEL-7402 were treated with NCTD. The cell growth inhibition was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, cell death detected by trypan blue exclusion assay and apoptosis examined by Annexin V/PI staining and flow cytometry. The cleavage of caspase-9, -3 and PARP, and the expression of the anti-apoptotic Bcl-2 proteins were analyzed by Western blot.The MTT results showed that, after a treatment with NCTD for 24, 48 and 72 h, the IC50 of NCTD in SMMC-7721 cell line was 12, 6 and 1.6 µg/ml respectively; in BEL-7402, the IC50 10, 4 and 2 µg/ml respectively. Trypan blue exclusion assay showed that NCTD mediated substantial cell death in two cancer cell lines. Apoptosis assay showed that, after a 12 h treatment with 10 µg/ml NCTD, 27% of SMMC-7721 cells were induced to undergo apoptosis, an increment of 20% over the untreated control cells (7%); 30% of BEL-7402 cells became apoptotic, an increment of 22% over the untreated control cells (8%). Western blot analysis showed that NCTD treatment potently induced the activation of caspase-9, -3 and the cleavage of PARP, and markedly down-regulated the expression of Bcl-2, Bcl-X(L) and Mcl-1.NCTD strongly inhibits liver cancer cell growth and potently induces apoptotic cell death in two liver cancer cell lines. The strong anticancer activity of NCTD may be induced through targeting multiple Bcl-2 anti-apoptotic family members.

To compare several sequences of MRI and arthroscopy for detecting the ankle articular cartilage lesions and to evaluate the clinical outcome of special sequence of FS-3D-FISP.Forty patients (41 ankles) with iterative ankle pain who were scheduled for arthroscopy underwent MR scanning, including FS-3D-FISP, FSE T2WI and FSE PDWI sequences. The results of each sequence were then compared with the arthroscopic findings.Using arthroscopic results as the standard of reference, the FS-3D-FISP images had the higher sensitivity (92.86%) than the other two sequences. The FS-3D-FISP sequence was well consistent with the result of arthroscopy. Kappa value (0.7590) was higher than the other two sequences (P0.01).As a favorable scanning sequence, FS-3D-FISP imaging can show the early-stage pathological changes of articular cartilage and it has an excellent correlation with the arthroscopic findings. A 3-D reconstruction is helpful to determine the location and the degree of lesion and obtain a more accurate classification to guide clinical decisions.

To investigate the expression and clinical significance of EphA7 protein in primary hepatocellular carcinoma.Immunohistochemistry and Western blot were used to detect the expression of EphA7 protein in 40 cases of primary hepatocellular carcinoma, their corresponding adjacent liver tissues and 10 cases of normal liver tissues. The relations with its clinical pathological parameters were analyzed too.Expression of EphA7 protein was mainly located in the cytoplasm and the blood vessels of the septa, which was found in hepatocellular carcinoma tissues, their corresponding adjacent liver tissues and normal liver tissues. Western blot analysis showed that the expression level of EphA7 protein in hepatocellular carcinoma (0.58 +/- 0.26) was greater than that in corresponding adjacent liver tissues (0.40 +/- 0.22, P0.05) and normal liver tissues (0.32 +/- 0.16, P0.05). But it had no significant difference between corresponding adjacent liver tissues and normal liver tissues (P0.05). EphA7 protein expression was correlated with histological differentiation, tumor thrombi in portal vein, lymph node metastasis and high AFP level (P0.05).EphA7 protein expression is significantly correlated with the biological behavior of primary hepatocellular carcinoma. The high expression of EphA7 protein may play an important role in the malignancy transformation, invasion progression and metastasis of primary hepatocellular carcinoma.

Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs.One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8), controls 1, 2 and 3 (C1, C2, C3, n=16), and experimental 1, 2 and 3 (E(1), E(2), E(3), n=16). For groups C(1) and E(1), C(2) and E(2), and C(3) and E(3), the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degree centigrade Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation.At 1 hour after portal vein reperfusion, the levels of NO in groups E(1), E(2), E(3) and C(1), C(2), C(3) were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P0.05). At 1, 3, and 24 hours, the levels of NO in groups E(1), E(2), E(3) were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C(1), C(2), C(3) (P0.05). The levels of NO in groups C(2) and C(3) were lower than in group C1 (P0.05), and the level of NO in group C(3) was lower than in group C(2) (P0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E1, E2, E3 were lower than those in the corresponding control groups (C(1), C(2), C(3)) (P0.05). The levels of plasma ET, serum ALT, and AST were lower in group C(3) than in groups C(1) and C(2) (P0.05). Pathological changes in groups E(1), E(2), E(3) were milder than those in the corresponding experimental control groups (C(1), C(2), C(3)).The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.

Brain-dead donors are the main sources for organ transplantation, but many studies show that brain-death affects the organ's function after transplantation. This study was undertaken to investigate liver injury after brain-death in BA-Ma mini pigs and the protective effects of breviscapine on hepatic function and on PKC-alpha mRNA and its protein expression.Fifteen BA-Ma mini pigs were equally divided into 3 groups at random: brain-dead (group B), breviscapine pretreated (group P), and control (group C). The brain-dead model was established by increasing intracranial pressure in a modified, slow and intermittent way. At 3, 6, 12, 18 and 24 hours after the initial brain-death, the levels of serum AST, ALT, TNF-alpha, IL-1beta, and IL-6 were determined. The changes in hepatic tissues were assessed, and the expression of PKC-alpha and PKC-alpha mRNA was detected by immunohistochemistry and RT-PCR, respectively.The levels of AST and ALT in groups B and P began to increase 12 hours after brain-death, while the values in group P were lower than those in group B (P0.05). The levels of IL-1beta, IL-6, and TNF-alpha in groups B and P at 3, 6, 12 and 18 hours were lower than those in group B (P0.05). At 6, 12 and 24 hours, the expressions of PKC-alpha mRNA and PKC-alpha protein in group P were lower than those in group B (P0.05). The degree of injury to hepatic cells in group P was milder than that in group B.Breviscapine inhibits the degree of PKC-alpha mRNA transcription and its protein translation, decreases the release of inflammatory factors, and thus alleviates hepatic injury during brain-death.

To investigate the expression and clinical significance of Ephrin-A1 mRNA and protein expression level in hepatocellular carcinoma.Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry technique were used to detect the expression of the Ephrin-A1 mRNA and protein of 40 cases of hepatocellular carcinoma and their corresponding para-cancerous tissues and 10 cases of normal liver tissues. The relationships with its clinical pathology characters were analyzed.The mRNA of Ephrin-A1 was expressed in all of the 40 cases of hepatocellular carcinoma and their corresponding para-cancerous tissues and 10 cases of normal liver tissues. Semiquantitative analysis showed that the mRNA expression level of Ephrin-A1 in hepatocellular carcinoma (0.5413 +/- 0.1527) was greater than that in corresponding para-cancerous tissues (0.3895 +/- 0.0549, P0.05) and normal liver tissues (0.3770 +/- 0.1055, P0.05); but between corresponding para-cancerous tissues (0.3895 +/- 0.0549) and normal liver tissues (0.3770 +/- 0.1055), the mRNA expression level had no significant difference (P0.05). The positive rates of Ephrin-A1 protein were 20% (2/10) in normal tissues, 35% (14/40) in para-cancerous tissues and 62% (25/40) in hepatocellular carcinoma tissues, respectively; the protein expression level of Ephrin-A1 was gradually rising (chi(2) = 14.762, P0.05). The overexpression of Ephrin-A1 protein was correlated with histological differentiation, tumor thrombi in portal vein and lymph node metastasis (P0.05).The overexpression of Ephrin-A1 protein is correlated with histological differentiation, the lymph node metastasis and tumor thrombi in portal vein. It indicates that Ephrin-A1 may play an important role in the malignancy transformation, invasion progression and metastasis of hepatocellular carcinoma.

To evaluate the clinical results of treatment of midshaft tibial fracture with expandable intramedullary nails compared with interlocking intramedullary nails.From June 2003 to August 2005, 46 patients (27 males and 19 females, aged 20-74 years, mean=38.4 years) with midshaft tibial fracture were treated surgically in our department. The causes of fractures were traffic injury in 21 patients, fall injury in 6, tumbling injury in 11 and crushing injury in 8. According to AO/ASIF classification, Type A fracture was found in 16 patients, Type B in 11, Type C(1) in 5, and Type C(2) in 2. Open fractures were found in 12 patients, according to Gustilo classification, Type I in 9 patients and Type II in 3 patients. Based on the patients'consent, 24 patients were treated with expandable intramedullary nails (Group A) and 22 with interlocking intramedullary nails (Group B). The operation time, blood loss during operation, X-ray fluoroscopic times, hospitalization time, weight bearing time after operation, healing time of fracture and complications of all the patients were recorded. The clinical effects of all the cases were evaluated according to the criteria of Johner-Wruhs.All the patients were followed up for 12-34 months (mean equal to 16.2 months). The time of operation, the blood loss, X-ray fluoroscopic times, hospitalization time and healing time of fracture of Group A significantly decreased (P less than 0.05) compared with those of Group B, but the time for weight bearing after operation, the Johner-Wruhs degree of clinical effects and complications had no significant difference between Group A and Group B (P larger than 0.05).Expandable intramedullary nail can shorten operation time, decrease blood loss and reduce invasion, which is a safe and effective treatment method for tibial midshaft fracture.

To evaluate the safety and feasibility of binding fistulojejunostomy, a new operative procedure, in the treatment of external pancreatic fistula.Eight patients suffering from external pancreatic fistula, 4 males and 4 females, aged 49 (22 approximately 69), underwent binding fistulojejunostomy: 2 cm-length of fistula was isolated and a tube was inserted therein, the jejunum was transected and the distant cut end was everted for the length of 3 cm, the mucosa of the everted jejunum was destroyed with carbolic acid, the everted mucosa of jejunum and the fistula were brought together and sutured with silk, the everted jejunum was then turned back to wrap over the fistula, a silk tie was lopped around the entire circumference of the anastomosis, and lastly, the tube was led out of the abdominal wall.all 8 patients recovered smoothly without pancreatic leakage and other complications.Binding fistulojejunostomy is safe and effective for the treatment of external pancreatic fistula.