Nanjing, China
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Fu H.,Tianjin Medical University | Wang L.,Peking University | Zhu Y.,Peking University | Geng J.,The 81st Hospital of PLA | And 4 more authors.
Infection, Genetics and Evolution | Year: 2011

Hepatitis E is a worldwide public health problem, particular in areas where hygiene conditions are poor. Hepatitis E virus (HEV) has at least four genotypes: genotypes 1 and 2 exclusively infect human; while genotypes 3 and 4, are considered to be a zoonotic agent, infecting both humans and animals. This study was aimed at determining why genotype 3 and 4 HEV strains isolated from swine are able to cross species borders, whereas genotype1 and 2 strains isolated from humans are not. The full length genome of the swine HEV isolate CHN-XJ-SW13 was amplified as overlapping fragments using reverse-transcription-nested polymerase chain reaction (RT-nPCR) and rapid amplification of cDNA ends (RACE). The sequence of CHN-XJ-SW13 was compared with those of 90 HEV strains covering genotype 1-4 retrieved from GenBank. Possible regions of the viral genome, specifying the host range of HEV or associated with the severity of hepatitis E disease, were then screened for with the aid of the ALIGNX sequences alignment software package. The CHN-XJ-SW13 swine HEV isolate was determined to be a novel subtype of genotype 4, whose sequence provided several valuable clues for tracing the sources of human HEV infection. 25 specific nucleotide positions were identified to possibly being involved specifying the host range of HEV or determining the severity of hepatitis E disease. © 2011 Elsevier B.V.


PubMed | University of Electronic Science and Technology of China, Second Military Medical University, Shanghai University and The 81st Hospital of PLA
Type: Journal Article | Journal: Behavioural brain research | Year: 2017

Abundant researches indicate that neuroinflammation has important roles in the pathophysiology of depression. Our previous study found that the NLRP3 inflammasome mediated stress-induced depression-like behavior in mice via regulating neuroinflammation. However, it still remains unclear that how the NLRP3 inflammasome influences related inflammatory signaling pathway to contribute to neuroinflammation in depression.We used wild-type mice and NLRP3 gene knockout mice to explore the role of NLRP3 inflammasome and related inflammatory signaling pathways in chronic unpredictable mild stress (CUMS) induced depression mouse model.Both wild-type and NLRP3 knockout stress group mice gained less weight than control group mice after 4 weeks CUMS exposure. The wild-type mice subjected to 4 weeks CUMS displayed depression-like behaviors, including decreased sucrose preference and increased immobility time in the tail suspension test. The NLRP3 knockout stress group mice didnt demonstrate depression-like behaviors. The levels of interleukin-1 protein in serum and hippocampi of CUMS exposed wild-type mice were significantly higher, while the NLRP3 knockout stress group mice didnt show an elevation of interleukin-1 levels. Similarly to early researches, we found that CUMS led to promoted NLRP3 expression in hippocampi. In addition, the hippocampi in CUMS exposed wild-type mice had higher p-JNK and p-p38 protein expression, which indicated activation of the mitogen-activated protein kinases (MAPK) pathway. The knockout of NLRP3 gene inhibited CUMS-induced activation of the MAPK pathway. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) protein complex was activated in the hippocampi of wild-type mice after CUMS exposure, while knockout of NLRP3 gene hindered its activation.These data further proved that the NLRP3 inflammasome mediated CUMS-induced depression-like behavior. The NLRP3 inflammasome regulated CUMS-induced MAPK pathway and NF-B protein complex activation in depression mouse model. Further researches targeting the NLRP3 inflammasome-signaling pathway might be under a promising future in the prevention and treatment of depression.


PubMed | Guangdong Pharmaceutical University, Zhengzhou Orthopedics Hospital and The 81st Hospital of PLA
Type: Journal Article | Journal: Inflammation | Year: 2016

Rheumatoid arthritis (RA) is a common autoimmune disease associated with progressive disability, systemic complications, and early death. Multiple lines of evidence have placed adaptive immune responses in the center of RA pathogenesis. However, the functional roles of T helper cells are insufficiently described. Here, we examined the Th2 cell subsets and their functions in RA patients. A downregulation of IL-4(+) cells in CD4(+) T cells were observed in RA patients, indicating a downregulation of Th2 cells, and these results were confirmed by using and CXCR3 and CCR6 surface markers. We then found that CXCR3(-)CCR6(-) Th2 cells can be separated into IL-4(+) (single positive), IL-10(+) (single positive), and IL-4(+)IL-10(+) (double positive) subsets. Further results showed that CXCR5 only expressed on IL-10+ Th2 cells. The CXCR5(+) and CXCR5(-) Th2 cells each exhibited distinctive features in helping B cell antibody secretion. CXCR5(+) Th2 cells were more potent at stimulating total Ig and IgM secretion, while CXCR5(-) Th2 cells were more potent at stimulating IgE. IL-10 was required for helping B cell total Ig, IgM, and IgE production, while IL-4 was required for total Ig and IgE. The frequencies of IL-10(+) and IL-4(+)IL-10(+) Th2 cells were positively correlated with rheumatoid factor titer in vivo. Together, our study demonstrated distinctive subsets within Th2 cells, each with different impacts on antibody production and RA disease.


Si Y.,Peking Union Medical College | Liu X.,Peking Union Medical College | Cheng M.,Peking Union Medical College | Wang M.,The 81st Hospital of PLA | And 4 more authors.
PLoS ONE | Year: 2011

Liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) are commonly induced by chronic hepatitis C virus (HCV) infection. We aimed to identify and characterize the involvement of previously screened cytokine GDF15 in HCV pathogenesis. We examined the GDF15 expression after HCV infection both in vitro and in vivo. Cultured JFH-1 HCV was used to determine the GDF15 function on virus propagation. GDF15 overexpression and RNA interference were employed to profile the GDF15-regulated genes, signaling pathways and cell biology phenotypes. The mRNA expression and protein secretion of GDF15 was dramatically increased in HCV-infected hepatoma cells, which maybe a host response to viral proteins or infection-induced cell stress. Patients infected with HCV had an average 15-fold higher blood GDF15 level than that of healthy volunteers. Three HCC individuals in the HCV cohort showed extremely high GDF15 concentrations. Transfection or exogenously supplied GDF15 enhanced HCV propagation, whereas knockdown of endogenous GDF15 resulted in inhibition of virus replication. Overexpressed GDF15 led to Akt activation and the phosphorylation of Akt downstream targeted GSK-3β and Raf. Several HCC-related molecules, such as E-cadherin, β-catenin, Cyclin A2/B1/D1, were up-regulated by GDF15 stimulation in vitro. Overexpression of GDF15 in hepatoma cells resulted in increased DNA synthesis, promoted cell proliferation, and importantly enhanced invasiveness of the cells. In conclusion, these results suggest that an elevated serum GDF15 level is a potential diagnostic marker for viral hepatitis, and GDF15 may contribute to HCV pathogenesis by altering the signaling and growth of host cells. © 2011 Si et al.


Zong G.Q.,The 81st Hospital of PLA | Fei Y.,The 81st Hospital of PLA | Chen J.,The 81st Hospital of PLA | Liu R.-M.,The 81st Hospital of PLA | Xu Y.-F.,The 81st Hospital of PLA
Medical Ultrasonography | Year: 2014

Aim: Selective double portazygous disconnection with preserving vagus (SDPDPV) is currently used for the therapy of portal hypertension. Doppler ultrasonography (DU) has been proposed for non-invasive evaluation of splanchnic hemodynamics, but the effect of SDPDPV on portal vein (PV) hemodynamics has not been analyzed with DU. This was the aim of the study. Material and methods: Two hundred and thirty six patients with cirrhotic portal hypertension who underwent either SDPDPV or pericardial devascularization with splenectomy (PDS) for variceal bleeding were enrolled. The hemodynamics parameter, operation-relevant information, change of lavatory examination data, postoperative complications, and clinical outcomes were analyzed. Results: The free portal pressure (FPP) in the SDPDPV group was significantly lower than the PDS group after operation (p<0.05). Velocities and blood flow of PV after SDPDPV decreased; however, when the hepatic artery (HA) and superior mesenteric vein (SMV) increased, the differences were significant (p<0.05). The correlation between the decreased FPP and changed blood flow of portal vein(PVF), hepatic artery (HAF) or superior mesenteric vein (SMVF) was significant (p<0.05) after SDPDPV. The difference between pre and postoperative values of portal congestion index (CI) in SDPDPV was significant (p<0.05). Occurrences or development of postoperative rebleeding showed a great difference between the two groups (p< 0.05). PVF and SMVF were significant independent indicators of postoperative rebleeding (p< 0.05). Conclusions: Compared with the PDS, the SDPDPV apparently decreased the blood velocity and blood flow of PV, and increased that of HA and SMV which has a beneficial effect on hepatic function and encourages the controlof the recurrent bleeding from varices. PVF and SMVF may be value indicators in predicting postoperative rebleeding.


Yan B.,Shanghai University of Traditional Chinese Medicine | Yan B.,Chinese PLA General Hospital | Gu W.,Shanghai University of Traditional Chinese Medicine | Yang Z.,The 81st Hospital of PLA | And 4 more authors.
Tumor Biology | Year: 2014

In recent years, the role of long noncoding RNAs (lncRNAs) in cancer is increasingly focused. ncRuPAR is a newly detected lncRNA; in previous study, we found out that ncRuPAR could inhibit tumor progression by downregulating protease-activated receptor-1 (PAR-1), but its role in colorectal cancer (CRC) is never elucidated. Here, we conducted a self-control study which includes 105 CRC samples. By quantitative real time PCR (qRT-PCR) and immunohistochemical staining, we detected the expression of ncRuPAR and PAR-1 as well as their correlation; we further associated these data with the clinicopathologic parameters. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of ncRuPAR and PAR-1, respectively. Our results indicated that the expression of ncRuPAR was significantly downregulated in CRC compared with paired adjacent nontumor tissues, but the level of PAR-1 mRNA in cancerous tissues was significantly higher than in adjacent normal areas. The expression of ncRuPAR was significantly correlated with lymph node metastasis, distant metastasis, Duck’s stage, differentiation, and TNM stage and was potentially negatively associated with the mRNA levels and EI scores of PAR-1. The area under the ROC curve of ncRuPAR was 0.81 (95 % confidence interval (CI): 0.75–0.87); at a cutoff value of 8.34, the ncRuPAR measurement had a sensitivity of 97.14 %, a specificity of 65.87 %, and an accuracy of 82.86 % to predict CRC. © 2014, International Society of Oncology and BioMarkers (ISOBM).


Liu L.,Shanghai University of Traditional Chinese Medicine | Yan B.,Shanghai University of Traditional Chinese Medicine | Yang Z.,The 81st Hospital of PLA | Zhang X.,Shanghai University of Traditional Chinese Medicine | And 2 more authors.
Tumor Biology | Year: 2014

ncRuPAR is a newly discovered long noncoding RNA molecule that can upregulate protease-activated receptor-1 (PAR-1) during embryonic growth; however, its role in cancer has not been elucidated. Here, we conducted a study to investigate the role of ncRuPAR in gastric cancer. Significant downregulation of ncRuPAR was detected in gastric cancer tissues compared with paired adjacent nontumor tissues; however, both PAR-1 and vascular endothelial growth factor (VEGF) messenger RNA (mRNA) levels were significantly higher in cancerous tissues compared with adjacent normal tissues. Additionally, the expression level of ncRuPAR was found to be significantly correlated with tumor invasion depth, lymph node metastasis, distant metastasis, tumor size, and tumor-nodes-metastasis (TNM) stage and inversely associated with the mRNA levels and extent (E) × intensity (I) scores of PAR-1 and VEGF. The protein level of PAR-1 was significantly correlated with tumor size only, while the VEGF protein level was significantly correlated with invasion depth and tumor size. The area under the receiver operating characteristic (ROC) curve of ncRuPAR was 0.84 (95 % CI 0.79–0.88) at a cutoff value of 4.97; ncRuPAR had a sensitivity of 88.41 %, a specificity of 73.91 %, and an accuracy of 81.16 % for the prediction of gastric cancer. These results suggest that ncRuPAR inhibits gastric cancer development, and its underlying mechanism involves the inhibition of PAR-1. In addition, ncRuPAR could be regarded as a marker for gastric cancer in the future. © 2014, International Society of Oncology and BioMarkers (ISOBM).


PubMed | Nanjing Medical University and The 81st Hospital of PLA
Type: | Journal: Critical reviews in oncology/hematology | Year: 2016

With the advances in radiotracers, positron emission tomography/computed tomography (PET/CT) is recognized as a useful adjunct to anatomic imaging with CT, MRI and endoscopic ultrasonography (EUS). The objective of this review was to comprehensively analyze the roles of PET/CT for the radiotherapy of esophageal cancer.In this review, we focused on issues concerning the application of PET/CT in TNM staging, target volume delineation and response to therapy, both for the primary tumor and regional lymph nodes. Furthermore, the following questions were addressed: how does PET/CT guide appropriate treatment protocols, how does it allow accurate tumor delineation and how does it guide prognosis and future treatment decisions.For the staging of esophageal cancer, PET/CT played a crucial role in exploring distant malignant lymph nodes and metastasis with high sensitivity, specificity and accuracy. PET/CT using different radiotracer provided a serial of thresholding methods based on standardized uptake value (SUV) to assist in auto-contouring the gross tumor volume (GTV). The change in SUV may offer a potential paradigm of personalized treatment to definitive chemoradiotherapy (CRT). In total, PET/CT has sought to further optimize radiotherapy treatment planning for patients with esophageal cancer.


PubMed | The 81St Hospital Of Pla
Type: Journal Article | Journal: Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis | Year: 2016

To evaluate the value of d-dimer, P-selectin, and platelet count in patients with cirrhotic portal hypertension (PHT) for prediction of portal vein thrombosis (PVT) after devascularization.A total of 137 patients with cirrhotic PHT who undergone devascularization from January 2012 to April 2014 were retrospectively reviewed, all of them were divided into 2 groups (PVT group and non-PVT group) by Doppler ultrasonography (DU) examination. The level of d-dimer, P-selectin, and platelet count was tested during the perioperative period.In all, 38 (27.7%) patients were found to have PVT by DU examination postoperatively. In contrast to the non-PVT group, the level of d-dimer, P-selectin, and platelet count in the PVT group was much higher significantly at 1, 3, and 7 days after devascularization. (P < .05). However, in the 15 days after surgery, the difference in P-selectin between the 2 groups was not significant (P = .260). It was shown that the highest sensitivity of the 3 markers for PVT was d-dimer, the highest specificity belonged to P-selectin. The area under receiver-operating characteristic (ROC) curve of P-selectin was the biggest of the 3 markers. When the 3 markers were combined to be used to diagnose PVT, the sensitivity was increased to 0.907, with a slight drop of specificity to 0.693, the area under the ROC curve was 0.927.The level of d-dimer, P-selectin, and platelet count might be good candidate predictive markers for PVT in patients with cirrhotic PHT after devascularization. The combined test of the 3 markers can increase the value of prediction.


PubMed | Nanjing Medical University and The 81st Hospital of PLA
Type: Journal Article | Journal: Journal of biochemistry | Year: 2016

Oesophageal carcinoma is one of the most lethal cancer types in the world, especially in some part of China. Oesophageal squamous cell carcinoma (OSCC) is a major subtype, which has been shown to be associated with unhealthy diet habit, smoking, environmental carcinogens etc. The OSCC often progress slowly, however, it is often diagnosed at an advanced stage. Thus it is imperative to elucidate the molecular mechanisms involved in the initiation and progression of OSCC. Long noncoding RNAs (lncRNA) has emerged as a novel functional player transcribed from the genome. Here, we describe a novel lncRNA POU6F2-AS2 specifically expressed in OSCC. POU6F2-AS2 is involved in the DNA damage response and regulates cells survival after ionizing radiation. POU6F2-AS2 interacts with Ybx1 protein and regulates its chromatin localization. Our current study represents the first description of an OSCC associated lncRNA that modulates DNA repair.

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