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Objective: To evaluate the effectiveness of inserting a retrievable inferior vena cava filter (IVCF) to prevent pulmonary embolism (PE) in patients with bone fractures and acute deep venous thrombosis (DVT) before major orthopedic surgery., Methods: Clinical data of patients with fractures and acute DVT who underwent IVCF insertion were analyzed. The patients were divided into above-knee DVT (AKDVT), popliteal vein thrombosis (PVT), and below-knee DVT (BKDVT) groups., Results: An IVCF was successfully implanted in 964 patients, among whom 929 were followed up (335, 470, and 124 in AKDVT, PVT, and BKDVT groups, respectively). There was no significant difference in the incidence of filter thrombosis among the groups (11.04%, 11.70%, and 8.06%, respectively). No symptomatic PE occurred during follow-up. The mean filter indwelling time was 18.4 ± 4.3 days, and the total filter removal rate was 76.87%. There was no significant difference in the rate of filter implantation, retrieval, complications, or mortality among the groups., Conclusions: Retrievable filters can effectively prevent PE before orthopedic surgery in patients with fractures and acute DVT of the lower limbs. AKDVT more readily forms a ≥1-cm thrombus in the IVCF than does BKDVT, and PVT more readily forms a <1-cm thrombus than does AKDVT.

Neuroendocrine carcinoma (NEC) of the gallbladder (GB-NEC) is a rare but extremely malignant subtype of gallbladder cancer (GBC). The genetic and molecular signatures of GB-NEC are poorly understood; thus, molecular targeting is currently unavailable. In the present study, we applied whole-exome sequencing (WES) technology to detect gene mutations and predicted somatic single-nucleotide variants (SNVs) in 15 cases of GB-NEC and 22 cases of general GBC. In 15 GB-NECs, the C > T mutation was predominant among the 6 types of SNVs. TP53 showed the highest mutation frequency (73%, 11/15). Compared with neuroendocrine carcinomas of other organs, significantly mutated genes (SMGs) in GB-NECs were more similar to those in pulmonary large-cell neuroendocrine carcinomas (LCNECs), with driver roles for TP53 and RB1. In the COSMIC database of cancer-related genes, 211 genes were mutated. Strikingly, RB1 (4/15, 27%) and NAB2 (3/15, 20%) mutations were found specifically in GB-NECs; in contrast, mutations in 29 genes, including ERBB2 and ERBB3, were identified exclusively in GBC. Mutations in RB1 and NAB2 were significantly related to downregulation of the RB1 and NAB2 proteins, respectively, according to immunohistochemical (IHC) data (p values = 0.0453 and 0.0303). Clinically actionable genes indicated 23 mutated genes, including ALK, BRCA1, and BRCA2. In addition, potential somatic SNVs predicted by ISOWN and SomVarIUS constituted 6 primary COSMIC mutation signatures (1, 3, 30, 6, 7, and 13) in GB-NEC. Genes carrying somatic SNVs were enriched mainly in oncogenic signaling pathways involving the Notch, WNT, Hippo, and RTK-RAS pathways. In summary, we have systematically identified the mutation landscape of GB-NEC, and these findings may provide mechanistic insights into the specific pathogenesis of this deadly disease.

Background: As the largest group of mammalian species, which are also widely distributed all over the world, rodents are the natural reservoirs for many diverse zoonotic viruses. A comprehensive understanding of the core virome of diverse rodents should therefore assist in efforts to reduce the risk of future emergence or re-emergence of rodent-borne zoonotic pathogens., Results: This study aimed to describe the viral range that could be detected in the lungs of rodents from Mainland Southeast Asia. Lung samples were collected from 3284 rodents and insectivores of the orders Rodentia, Scandentia, and Eulipotyphla in eighteen provinces of Thailand, Lao PDR, and Cambodia throughout 2006-2018. Meta-transcriptomic analysis was used to outline the unique spectral characteristics of the mammalian viruses within these lungs and the ecological and genetic imprints of the novel viruses. Many mammalian- or arthropod-related viruses from distinct evolutionary lineages were reported for the first time in these species, and viruses related to known pathogens were characterized for their genomic and evolutionary characteristics, host species, and locations., Conclusions: These results expand our understanding of the core viromes of rodents and insectivores from Mainland Southeast Asia and suggest that a high diversity of viruses remains to be found in rodent species of this area. These findings, combined with our previous virome data from China, increase our knowledge of the viral community in wildlife and arthropod vectors in emerging disease hotspots of East and Southeast Asia. Video abstract.

Apart from primary tumor development and metastasis, cancer-associated thrombosis is the second cause of cancer death in solid tumor malignancy. However, the mechanistic insight into the development of gallbladder cancer (GBC) and cancer-associated thrombosis remains unclear. This study aimed to investigate the mechanistic role of Sciellin (SCEL) in GBC cell proliferation and the development of venous thromboembolism. The expression level of SCEL was determined by immunohistochemical staining. Roles of SCEL in gallbladder cancer cell were determined by molecular and cell biology methods. SCEL was markedly upregulated in GBC and associated with advanced TNM stages and a poor prognosis. Furthermore, SCEL interacted with EGFR and stabilized EGFR expression that activates downstream PI3K and Akt pathway, leading to cell proliferation. In addition, SCEL induces tumor cell IL-8 production that stimulates the formation of neutrophil extracellular traps (NETs), accelerating thromboembolism. In xenografts, SCEL-expressing GBCs developed larger tumors and thrombosis compared with control cells. The present results indicate that SCEL promotes GBC cell proliferation and induces NET-associated thrombosis, thus serving as a potential therapeutic target.

MOB kinase activator 1A (MOB1A) plays an important role in many diseases and cancers. Here, we observed that MOB1A was substantially overexpressed in gallbladder carcinoma (GBC) tissues compared with nontumor tissues. The high expression of MOB1A was closely associated with poor survival in patients with GBC at advanced TNM stages. Furthermore, our study indicated that MOB1A promoted autophagy by activating the IL6/STAT3 signaling pathway and regulating the chemosensitivity to gemcitabine under glucose deprivation conditions both in vitro and in vivo. In conclusion, these findings suggested that MOB1A is critical for the development of GBC via the MOB1A-IL6/STAT3-autophagy axis., Competing Interests: None., (AJCR Copyright © 2020.)

Objective: A prospective randomized control study investigated the feasibility and efficacy of adjuvant radiotherapy on patients with central hepatocellular carcinoma (HCC) after narrow-margin hepatectomy (<1 cm). This study presents an updated 10-year real-world evidence to further characterize the role of adjuvant radiotherapy., Methods: Patients with central HCC after narrow-margin hepatectomy (<1 cm) were prospectively assigned to adjuvant radiotherapy group and control group. Patients' outcome, adverse events, long-term recurrence and survival rates were investigated., Results: The 1-, 5-, and 10-year recurrence-free survival (RFS) rates were 81.0%, 43.9%, and 38.7%, respectively in adjuvant radiotherapy group and 71.7%, 35.8%, and 24.2%, respectively in control group (log-rank test, P=0.09). The 1-, 5-, and 10-year overall survival (OS) rates were 96.6%, 54.7%, and 42.8%, respectively in adjuvant radiotherapy group and 90.2%, 55.1%, and 30.0%, respectively in control group (log-rank test, P=0.20). The 1-, 5-, and 10-year RFS rates for patients with small HCC (≤5 cm) were 91.1%, 51.6%, and 48.4%, respectively in adjuvant radiotherapy group and 80.0%, 36.6%, and 26.6%, respectively in control group (log-rank test, P=0.03). Landmark analysis demonstrated that patients with small HCC in adjuvant radiotherapy group had a significantly improved OS in second five years after treatment in comparison to patients in control group (log-rank test, P=0.05)., Conclusions: Our updated results showed a sustained clinical benefit on reducing recurrence, improving long-term survival for small central HCC by adjuvant radiotherapy after narrow-margin hepatectomy. Long-term survival data also indicated that hepatectomy is an optimal treatment for selected patients with central HCC., (Copyright © 2020 Chinese Journal of Cancer Research. All rights reserved.)

H7N9 influenza virus was first isolated in 2013 and has caused five epidemic waves among humans to date. Treatment opinions are currently limited. Previously, we characterized a human neutralizing antibody, HNIgGA6, by isolating rearranged heavy- and light-chain genes from convalescent patients. The mAb disrupts viral attachment to the cellular receptor by directly interposing into the receptor binding site (RBS) and broadly neutralizing divergent H7N9 strains. To increase the protective efficacy of HNIgGA6, we employed a structure-based design to enhance its binding affinity and neutralization potency. When the serine at position 28 on light-chain complementarity-determining region 1 (LCDR1) was substituted by a histidine, compared to HNIgGA6, the mutated antibody showed an approximately three-fold increase in HA-binding affinity and 10-fold enhancement in neutralization potency in vitro . Importantly, the S28H variant also exhibited broad H7N9-neutralizing activity. When administered to BALB/c mice, mAb S28H showed enhanced potency in inhibiting the pulmonary virus titre and reducing lung lesions and resulted in better protection of the animals than did the original antibody., (Copyright © 2020 Chen, Liu, Liu, Wang and Jin.)

Tuberculosis (TB) is a continuing major threat to global health and a leading cause of death, particularly in developing countries. In this study, we aimed to identify a specific and sensitive diagnostic biomarker and develop a vaccine to prevent this disease. We investigated membrane proteins to reveal biomarkers in serum and peripheral blood mononuclear cells (PBMCs) obtained from TB patients. We employed Western blotting to evaluate serological immunoglobulin G levels, and Enzyme Linked Immunospot (ELISpot) to assess the antigen-specific cellular interferon-γ secretion from PBMCs after membrane protein stimulation. A total of 219 membrane proteins were identified, 52 exhibited at a higher levels than the 38-kDa prositive control. Of these 18 exhibited reacted ratios above 1, especially Rv1111c (427-981), with a ratios at 3.38. Accuracy and sensitivity were markedly higher for the top two antigen candidates, Rv0232 and Rv1115, after two rounds of ELISpot tests than ESAT-6 in the commercial kit (42.15 and 43.62%, respectively). These two proteins were administered to mice to detect whether they acted as effective antigens in vivo. These data provide a comprehensive view of the membranes involved in humoural and cellular immune responses that may be used as biomarkers for TB and candidates for a vaccine.

Whole-genome sequencing was used to analyze the profiles of isoniazid (INH) resistance-related mutations among 188 multidrug-resistant strains of Mycobacterium tuberculosis (MDR-TB) and mono-INH-resistant isolates collected in a recent Chinese national survey. Mutations were detected in 18 structural genes and two promoter regions in 96.8% of 188 resistant isolates. There were high mutation frequencies in katG, the inhA promoter, and ahpC-oxyR regulator regions in INH-resistant isolates with frequencies of 86.2%, 19.6%, and 18.6%, respectively. Moreover, a high diversity of mutations was identified as 102 mutants contained various types of single or combined gene mutations in the INH-resistant group of isolates. The cumulative frequencies of katG 315 or inhA-P/inhA mutations was 68.1% (128/188) for the INH-resistant isolates. Of these isolates, 46 isolates (24.5% of 188) exhibited a high level of resistance. A high level of resistance was also observed in 21 isolates (11.2% of 188) with single ahpC-oxyR mutations or a combination of ahpC-oxyR and katG non-315 mutations. The remaining 17 mutations occurred sporadically and emerged in isolates with combined katG mutations. Such development of INH resistance is likely due to an accumulation of mutations under the pressure of drug selection. Thus, these findings provided insights on the levels of INH resistance and its correlation with the combinatorial mutation effect resulting from less frequent genes (inhA and/or ahpC). Such knowledge of other genes (apart from katG) in high-level resistance will aid in developing better strategies for the diagnosis and management of TB.

H7N9 influenza virus has been circulating among humans for five epidemic waves since it was first isolated in 2013 in China. The recent increase in H7N9 infections during the fifth outbreak in China has caused concerns of a possible pandemic. In this study, we describe a previously characterized human monoclonal antibody, HNIgGA6, obtained by isolating rearranged heavy-chain and light-chain genes from patients who had recovered from H7N9 infections. HNIgGA6 recognized multiple HAs and neutralized the infectivity of 11 out of the 12 H7N9 strains tested, as well as three emerging HPAI H7N9 isolates. The only resistant strain was A/Shanghai/1/2013 (H7N9-SH1), which carries the avian receptor alleles 186V and 226Q in the sialic acid-binding pocket. The mAb broadly neutralized divergent H7N9 strains from 2013 to 2017 and represents a potential alternative treatment for H7N9 interventions.

The global epidemic of drug-resistant tuberculosis is a catastrophic example of how antimicrobial resistance is undermining the public health gains made possible by combination drug therapy. Recent evidence points to unappreciated bacterial factors that accelerate the emergence of drug resistance. In a genome-wide association study of Mycobacterium tuberculosis isolates from China, we find mutations in the gene encoding the transcription factor prpR enriched in drug-resistant strains. prpR mutations confer conditional drug tolerance to three of the most effective classes of antibiotics by altering propionyl-CoA metabolism. prpR-mediated drug tolerance is carbon-source dependent, and while readily detectable during infection of human macrophages, is not captured by standard susceptibility testing. These data define a previously unrecognized and clinically prevalent class of M. tuberculosis variants that undermine antibiotic efficacy and drive drug resistance.

Background: Colorectal cancer (CRC) is a commonly diagnosed digestive malignancy worldwide. Ras-related protein 1A (RAP1A) is a member of the Ras superfamily of small GTPases and has been recently identified as a novel oncoprotein in several human malignancies. However, its specific role in CRC remains unclear., Method: In this study, we firstly analyzed its expression and clinical significance in a retrospective cohort of 144 CRC patients. Then, cellular assays in vitro and in vivo were performed to clarify its biological role in CRC cells. Finally, microarray analysis was utilized to investigate the molecular mechanisms regulated by RAP1A in CRC progression., Results: Firstly, RAP1A expression was abnormally higher in CRC tissues as compared with adjacent normal tissues, and significantly correlated tumor invasion. High RAP1A expression was an independent unfavourable prognostic factor for CRC patients. Combining RAP1A expression and preoperative CEA level contributed to a more accurate prognostic stratification in CRC patients. Secondly, knockdown of RAP1A dramatically inhibited the growth of CRC cells, while it was opposite for RAP1A overexpression. Finally, the microarray analysis revealed RAP1A promoted CRC growth partly through phosphatase and tensin homolog (PTEN)/forkhead box O3(FOXO3)/cyclin D1(CCND1) signaling pathway. FOXO3 overexpression could partly mimic the inhibitory effect of RAP1A knockdown in CRC growth. Moreover, FOXO3 overexpression inhibited CCND1 expression, but had no impact on RAP1A and PTEN expression., Conclusion: RAP1A promotes CRC development partly through PTEN/FOXO3 /CCND1 signaling pathway. It has a great potential to be an effective clinical biomarker and therapeutic target for CRC patients.

Solute carrier family 34 member 2 (SLC34A2) is a well-known sodium-dependent phosphate transporter that has recently been linked to cancer development. However, its specific oncogenic role remains controversial in numerous human malignancies, and is currently unknown in colorectal cancer (CRC). Therefore, in this study we firstly used Oncomine database to determine its expression in cancer tissues and found it is overexpressed in thyroid, ovarian and renal cancer, while it is opposite in lung, breast and pancreas cancer. Using qRT-PCR and western blot, we then demonstrated its overexpression in CRC tissues as compared with adjacent normal tissues (n = 20). In a retrospective cohort enrolling 190 CRC patients, we proved its expression was significantly correlated with N stage. Furthermore, high SLC34A2 expression is associated with higher postoperative metastasis rate and serves as an independent adverse factor affecting patient prognosis. In subgroup analysis, SLC34A2 expression could stratify the patient prognosis in stage II and III CRC, but failed in stage IV CRC. In cellular assays in vitro, knockdown of SLC34A2 dramatically inhibited the proliferation and colony formation, induced the apoptosis and arrests the cell cycle progression of HCT-116 CRC cells. In cellular assays in vivo, knockdown of SLC34A2 significantly inhibited the growth of xenografts, decreasing Ki-67 and proliferating cell nuclear antigen (PCNA) expression and increasing apoptosis rate. Taken together, our study indicates SLC34A2 plays a crucial promoting role in CRC development and therefore has great potential to be further developed as a reliable biomarker for CRC diagnosis and treatment., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Transcatheter arterial embolization (TAE) is a method for the treatment of liver hemangioma, but fewer studies reported the long-term result.Retrospective study was conducted to liver hemangioma patients who received TAE. The inclusion criteria included the following: the period of follow-up was more than 5 years; and patients were followed up for less than 5 years, but received surgical treatment due to the enlargement of tumor or severe complications of TAE. The collected data included sex, age, size of the tumor, times of TAE, complications, period of follow-up, long-term result, and whether or not surgery was finally performed.Fifty-five patients were included, and the average age was 43.1 ± 8.6 years. The average size of liver hemangioma was 9.0 ± 4.3 cm. Four patients (7.3%) had severe complications after TAE, including 2 cases of biloma which were cured by surgery. The tumor size was smaller or the same in 19 patients after 5 years follow-up, and the long-term effective rate was 35.8%. The size of tumor became larger in the other 34 patients (64.2%), and 29 patients (54.7%) received surgery finally. The long-term effective rate for patients with ≥10 cm tumor and <10 cm tumor were 12.5% and 45.9%, respectively, and the difference was significant (P = .019).The long-term result of TAE for liver hemangioma was not satisfying, and the treatment had the risk of severe complication. For patients with asymptomatic liver hemangioma, TAE should not be conducted.

Background: The location of liver haemangioma may affect surgical decisions, but no study has ever examined this issue., Methods: A retrospective study was performed on 338 liver haemangioma patients who visited at clinic. The collected data included demographics, location, symptoms and whether surgical treatment was performed. For patients with surgical treatment, the collected data included radiologic characteristics, surgical procedures, surgical variables, postoperative stay, morbidity, and mortality. According to the location, patients were divided into left or right group and comparison was made between them., Results: Compared to the right group, patients in the left group were more likely to have symptoms (P = 0.018), especially patients with 5- to 10-cm haemangiomas (P < 0.001). Patients in the left group had higher rates of exophytic lesions and gastric outlet compression (63.8% vs 7.1%, 56.5% vs 5.1%, P < 0.001 each), while patients in the right group had a higher rate of vessel compression (36.4% vs 21.7%, P = 0.043). Higher ratio of patients in left group received liver resection (75.4% vs 26.3%, P < 0.001). The surgical time, amounts of collected blood and autologous transfusion were all greater in the right group (P = 0.008, P = 0.001 and P = 0.003, respectively). The postoperative stay was longer in the right group (P = 0.007)., Conclusion: The location of liver haemangioma should be considered when making surgical decisions, and it may be one of the main considerations for surgical procedures., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) is a common digestive malignancy and emerging studies have closely linked its initiation and development with gut microbiota changes. Fusobacterium nucleatum ( Fn ) has been recently identified as a pathogenic bacteria for CRC; however, its prognostic significance for patients is poorly investigated and is less for patients within late stage. Therefore, in this study, we made efforts to analyze its level and prognostic significance in a retrospective cohort of 280 stage III/IV CRC patients. We found that the Fn level was abnormally high in tumor tissues and correlated with tumor invasion, lymph node metastasis status, and distant metastasis. We also identified it as an independent adverse prognostic factor for cancer-specific survival (CSS) and disease-free survival (DFS). The following subgroup analysis indicated that Fn level could stratify CSS and DFS in stage IIIB/C and IV patients but failed in stage IIIA patients. In addition, stage III/IV patients with low Fn level were found to benefit more from adjuvant chemotherapy than those with high Fn level, in terms of DFS. Finally, we analyzed the expression and clinical significance of epithelial-to-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) and cancer stem cell (CSC) markers (Nanog, Oct-4, and Sox-2) in CRC tissues. The results indicated that N-cadherin, Nanog, Oct-4, and Sox-2 were adverse prognostic factors in these patients, while the opposite was true for E-cadherin. More importantly, expression of E-cadherin, N-cadherin, and Nanog was significantly correlated with Fn level in tumor tissues, suggesting the potential involvement of Fn in EMT-CSC cross talk during CRC progression. Taken together, these findings indicate that Fn is a novel predictive biomarker for clinical management in stage III/IV patients, and targeting Fn may be an effective adjuvant approach for preventing CRC metastasis and chemotherapy resistance., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: To explore the primary site and pathological feature of neuroendocrine neoplasm (NEN), especially the NEN of digestive system., Methods: Clinicopathological data of NEN patients at China-Japan Friendship Hospital from January 2012 to December 2016 were retrospectively analyzed. Tumor primary sites were summarized. Association between tumor site and pathological grading in gastroenteropancreatic neuroendocrine neoplasm(GEP-NEN) was examined., Results: There were a total of 903 cases of NEN. Sites of primary tumor included the digestive system in 699 cases(77.4%), the thorax(including lung, thymus and mediastinum) in 87 cases(9.6%), other sites in 60 cases (6.6%), unknown in 57 cases(6.3%). Among 699 GEP-NEN cases, the primary sites included the stomachin in 207 cases (29.6%), pancreas in 201 (28.8%), rectumin in 185 (26.5%), duodenum in 43(6.2%), jejunum and ileum in 18(2.6%), appendix in 15 (2.1%), gallbladder in 11(1.6%), esophagus in 10(1.4%), and the colon in 9 cases (1.3%). Pathologically, the tumor grading was neuroendocrine tumor (NET) G1 in 336 cases(48.1%), NET G2 in 203 cases (29.0%), neuroendocrine carcinoma (NEC) G3 in 139 cases (19.9%). All the esophagus NEN(10/10), most gallbladder NEN(9/11) and colon NEN(6/9) were poorly-differentiated NEC (G3), while all appendix NEN(15/15), most stomach NEN(147/207, 71.0%), pancreas NEN (156/201, 77.6%), rectum NEN (169/185, 91.4%), duodenum NEN (31/43, 72.1%), jejunum and ileum NEN(16/18, 88.9%) were well-differentiated NET G1 or G2., Conclusions: The most common primary site of NEN is the digestive system. The stomach, pancreas and rectum are most common primary sitesof GEP-NEN. Difference in pathological grading is quite greatin different primary sites of GEP-NEN. Most NENs fromesophagus, colon and gallbladder are poorly-differentiated NEC.

Background: Giant liver hemangioma >20 cm may cause severe complications; therefore, operative treatment can be highly difficult and risky. No studies have been performed to determine the characteristics of this subgroup., Methods: A retrospective study was performed on 141 patients who underwent operative treatment for liver hemangioma. The patients were divided into an extremely giant hemangioma group (>20 cm, 36 cases) and a giant hemangioma group (>10 cm but <20 cm, 105 cases). A comparison was then made between the groups. For patients in the extremely giant hemangioma group, further comparison was also made between liver resection and enucleation., Results: Compared with the giant hemangioma group, patients in the extremely giant hemangioma group had greater rates of leukopenia (P < .001), anemia (P < .001), thrombocytopenia (P < .001), pancytopenia (P < .001), prolonged prothrombin time (P < .001), and Kasabach-Merritt syndrome (P = .001). Patients in the extremely giant hemangioma group also had greater rates of compression of the hepatic vein (P < .001), inferior vena cava (P < .001), and porta hepatis (P < .001). The extremely giant hemangioma group had more blood loss (P < .001) and autologous transfusion (P < .001), greater rates of blood transfusion (P < .001), and greater postoperative stays (P < .001). Morbidity was greater in the extremely giant hemangioma group; however, this difference was not statistically significant (P = .076). For patients in the extremely giant hemangioma group, no differences were detected regarding autologous transfusion, blood transfusion, or morbidity between enucleation and liver resection., Conclusion: Extremely giant hemangiomas may cause abnormalities in the hematologic and coagulation systems. Operative treatment may be difficult and risky but can be completed safely., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Dual specificity phosphatase 5 (DUSP5) is a negative regulator of Mitogen-activated protein kinase (MAPK) signaling pathway and has recently been identified as a tumor suppressor in several human malignancies. However, its clinical significance in colorectal cancer (CRC) remains unclear. In this study, we aimed to investigate the potential utility of DUSP5 as a novel biomarker for progression indication and chemotherapy benefit in CRC patients. Through quantitative real time-polymerase chain reaction and western blot, we determined that DUSP5 expression is dramatically lower in CRC tissues than that in matched normal tissues. The statistical analysis based on immunohistochemistry revealed that DUSP5 expression is significantly correlated with tumor differentiation, TNM stage, lymph node metastasis and distant metastasis. For the whole study cohort, patients with high DUSP5 expression had a better CRC-specific and disease-free survival than those with low DUSP5 expression and DUSP5 expression is an independent prognostic factor for patient survival. In subgroup analysis, DUSP5 has no prognostic significance in low-risk stage II patients, but could predict treatment response in high-risk stage II and stage III/IV patients who received standard FOLFOX chemotherapy scheme. Finally, the correlation analysis suggested that DUSP5 expression is associated with Epithelial-to-Mesenchymal Transition (EMT) phenotype in CRC tissues, suggesting that downregulated DUSP5 may contribute to poor prognosis partly by involving EMT. Taken together, our study proposes that DUSP5 is a promising biomarker for predicting CRC progression and advanced patients with high DUSP5 expression appear to benefit from standard FOLFOX chemotherapy scheme.

Objective: To report five cases of isolated IgG4-related sclerosing cholangitis (IAC) and to summarize their clinical characteristics and the differential diagnosis., Method: The clinical data of five patients with isolated IAC were retrospectively analyzed, including laboratory tests, imaging examination and liver pathology. Their treatment and prognosis were also discussed., Results: All five patients had no history of pancreatitis. All five patients presented with jaundice and three of them had fluctuant jaundice. The serum IgG4 levels was increased in all five patients. The images study showed bile duct stenosis in all 5 patients (2 in hilar bile duct, 2 in intrahepatic bile duct and 1 in hilar associated distal bile duct). The enlargement of pancreas was found in 2 patients. Liver pathology revealed fibrosis around small bile duct and IgG4-positive plasma cells infiltration in all 5 patients. Two patients underwent surgical procedure without relief. All five patients were relieved after the treatment of steroid. All patients were followed up from 6 months to 2 years and no recurrence was detected., Conclusions: Isolated IAC is a rare disease and it could be misdiagnosed as cholangiocarcinoma. The surgical procedure has the limited effect for the treatment of IAC and it should be avoided. IAC should be considered for patients with fluctuant jaundice of long history and enlargement of pancreas on imaging. Serum IgG4 test and liver biopsy are helpful for the diagnosis of IAC.

Objective: To study the clinical features of nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC)., Methods: The clinical manifestations, imaging features, pathological subtypes and treatment outcome of two cases with NAFLD-associated HCC were analyzed., Results: In these two cases, both were young, obese male patients, with contrast enhanced CT scan of hemangioma-like features. They had undergone surgical resection and both were reported as well-differentiated HCC pathologically. They were followed-up respectively up to 46 and 36 months post-operatively with no evidence of recurrence or metastasis., Conclusions: NAFLD-associated HCC has different radiological presentations from typical HCC. Incidental finding of any liver occupying lesions in NAFLD patients should raise immediate clinical attention.

Post-translational modifications regulate many aspects of protein behavior and provide options for expanding protein functionality in organisms. Protein phosphorylation is one of the major PTMs observed in bacteria, which are involved in regulating a myriad of physiological processes. Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been recognized as an important weapon in the fight against tuberculosis (TB) worldwide for over 80 years. In this study, we conducted phosphoproteomic analysis in BCG bacteria using gel-based and gel-free complementary approaches and high-resolution Fourier transform mass spectrometry. In total, 501 phosphopeptides derived from 398 phosphoproteins were identified, representing the first phosphoproteomic analysis of BCG reported to date. Thirty-three novel protein products supported by 36 unique phosphorylated peptides were detected. Additionally, the translational start sites of 28 proteins were confirmed, and 31 proteins were validated through the extension of translational start sites based on N-terminus-derived peptides. The expression of three randomly selected phosphoproteins was validated through Western blotting. A number of proteins involved in metabolic pathways, including glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation and two-component system, are discussed. We believe some of the proteins identified in this study may represent potential targets for the development of novel antibiotics for treating TB., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To investigate the role of CCL20/CCR6/Th17 axis in vascular invasion and metastasis of primary hepatocellular carcinoma (HCC)., Methods: Expression levels of CCL20 mRNA in the normal human liver cell line L-02, and human hepatocellular carcinoma cell lines Hep3B, Huh7 and HepG2 were quantified by using SYBR green real time PCR. CCL20 secretions from these cell lines were quantified by using ELISA. The chemotactic effect of HCC cell line Hep3B on human peripheral blood mononuclear cells was determined by using transwell chemotaxis assay. Pre-therapy serum levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17, IL-23, IFN-γ, TNF-α and CCL20 in 93 patients with HCC were measured by using 9-plex array and ELISA. All the patients were chronic hepatitis B virus associated HCC, and 51 cases were those with vascular invasion and metastasis (metastasis group) and 42 cases were not (non-metastasis group). CCL20 and CCR6 mRNA expressions in the HCC and tumor-adjacent tissues were determined by using SYBR Green real time PCR in 41 patients, among them, 20 cases were from the group of patients with metastasis and 21 cases were from the group of patients without metastasis. The CCL20 expression was further determined by immunohistochemistry., Results: The HCC cell lines expressed and secreted higher amount of CCL20, which effectively recruited CCR6(+) T cells. Pre-therapy serum levels of CCL20 in 93 HCC patients were (38.2 ± 28.4)pg/ml, significantly increased than those with benign hepatic hemangiomas [(7.8 ± 17.8)pg/ml, P < 0.01]. In addition, the serum levels of CCL20 were positively correlated with the tumor diameters in HCC patients (r = 0.32, P = 0.0018). CCL20 was dominantly expressed in the cytoplasm in HCC cells, and it was also expressed by some infiltrating immune cells. The mRNA expression levels of CCL20 of the tumor tissues were significantly higher than that in the tumor-adjacent tissues (P < 0.05). Multivariate logistic regression analysis showed that serum levels of IL-17 and CCL20 were independent risk factors of metastasis in HCC patients (P < 0.05 for both). CCL20 mRNA showed no statistically significant differences between patients with metastasis and without metastasis in both tumor tissues and tumor-adjacent tissues (P > 0.05 for both). But the patients with metastasis showed significantly higher expressions of CCR6 both in their tumor [5.75 (1.79, 19.13)]and tumor-adjacent tissues [7.99 (4.49, 19.54)] than those with non-metastasis [1.69 (0.76, 2.87) and 3.58 (1.84, 4.32), P < 0.05 for both]., Conclusion: CCL20/CCR6/Th17 axis may promote vascular invasion and metastasis hepatocellular carcinoma.

Since 1921, Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been recognized as an important vaccine to prevent tuberculosis worldwide. Nonetheless, a global analysis of BCG proteome has not been clearly investigated. In this study, we performed an in-depth proteomic analysis of BCG under an in vitro cultivation condition using SDS-PAGE and high resolution Fourier transform mass spectrometry. In total, 3434 proteins (35,259 unique peptides) including 512 transmembrane proteins were identified, covering ~87% of the predicted BCG proteome. Seven pseudogene protein products were also obtained and validated by RT-PCR at gene transcript level. Additionally, translational start sites of 832 proteins were confirmed and 186 were extended using N-terminus-derived peptides. The physicochemical characteristics of all identified proteins were determined. Some predominant proteins, including PE and PPE family proteins, lipoproteins, heat shock proteins, transport proteins and low molecular weight protein antigens, are discussed, which represent potential prominent antigens in the humoral and cellular immune response. This study represents the most comprehensive BCG proteome to date, which will likely facilitate the design of vaccination and immunodiagnostic strategies against TB., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background and Objectives: Intrahepatic biliary cystadenoma and biliary cystadenocarcinoma are extremely rare neoplasms of the liver. They share similar radiological characteristics, and the clinicopathological features are poorly defined. We aim to provide an algorithm for preoperative differentiation of the two diseases., Methods: Patients who underwent liver resection between May 2001 and May 2011 at Peking Union Medical College Hospital with biliary cystadenoma (20 cases) and biliary cystadenocarcinoma (10 cases) were reviewed., Results: Significant differences were shown in age (P=0.030), gender (P=0.002) and symptom duration (P=0.012). Most biliary cystadenomas occurred in women ≤60 years old (85%), whilst most biliary cystadenocarcinomas occurred in older males (50%). Shorter symptom duration indicated a higher risk of biliary cystadenocarcinoma. Arterial blood flow and wall/nodule enhancement tended to be more common in biliary cystadenocarcinoma, but the difference was not significant (P=0.348). A score system was developed. The case-by-case validation and leave-one-out cross-validation showed an accuracy of 95.5% and 90.9%, respectively. The discriminative accuracy for cases from another hospital during the same period was 90.9%., Conclusions: Older age, male gender, and shorter symptom duration are associated with higher possibility of biliary cystadenocarcinoma. Location and blood supply by radiology might be instrumental but still need further verification., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

A system for automatic null ellipsometric measurement, which uses a new kind of achromatic rhomb-type lambda/4 retarder, is designed and constructed. By use of terbium glass as the modulator's material, a magneto-optical modulator and its driving circuit are constructed. The polarized light is modulated by dc and ac. Combined with an ultra-low noise frequency-selective amplifier and a lock-in amplifier, the null time of the mechanical and photoelectric automatic null system can be less than 15 s. After the error of the mechanical parts is excluded, the repeatability standard deviation S4 of nulling angles can be less than 0.00025 deg.