[Research on applying genetic and environmental risk score in risk-adapted colorectal cancer screening].

Objective: To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS). Methods: A polygenic risk score (PRS) was constructed based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy. Results: The high PRS group had a 26% increased risk of colorectal neoplasms compared with the low PRS group (OR=1.26, 95%CI: 1.03-1.54, P=0.026). Participants with the highest PRS and ERS were 3.03 times more likely to develop advanced colorectal neoplasms than those with the lowest score (95%CI: 1.87-4.90, P<0.001). As the risk-adapted screening simulation reached the third round, the detection rate of the PRS combined with ERS strategy was not statistically different from the all-acceptance colonoscopy strategy (8.79% vs. 10.46%, P=0.075) and had a higher positive predictive value (14.11% vs. 10.46%, P<0.001) and lower number of colonoscopies per advanced neoplasms detected (7.1 vs. 9.6, P<0.001). Conclusion: The risk-adapted screening strategy combining PRS and ERS helps achieve population risk stratification and better effectiveness than the traditional colonoscopy-based screening strategy.

Low expression of lncRNA MGC27345 is associated with poor prognosis in gastric cancer patients.

OBJECTIVE: A series of evidence showed that long non-coding RNAs (lncRNAs) play an essential regulatory role in the occurrence and development of human cancer, and is a potential biological target in the fight against cancer. PATIENTS AND METHODS: In this research, we investigated the role of lncRNA MGC27345 in gastric cancer (GC), the expression of MGC27345 in GC was detected by quantitative Real-Time PCR in GC tissue from 235 patients. The correlations between MGC27345 expression and clinicopathological variables and survival were evaluated by the Chi-square test. Kaplan-Meier method (log-rank test), univariate and multivariate Cox regression assays were carried out for the identification of the survival and independent risk factors for GC. RESULTS: MGC27345 expression levels were significantly decreased in GC tissues than in adjacent normal specimens. Lower expression of MGC27345 was found in advanced tumor stages. GC patients with low-expression of MGC27345 had a poorer overall survival compare to those with high-expression of MGC27345. Furthermore, MGC27345 was an independent protective prognosis factor in GC development. CONCLUSIONS: Our data indicated that MGC27345 may have a diagnostic and prognostic value for patients with advanced gastric cancer and assist to improve clinical outcomes for GC patients.

The long non-coding RNA DDX11-AS1 facilitates cell progression and oxaliplatin resistance via regulating miR-326/IRS1 axis in gastric cancer.

OBJECTIVE: The long non-coding RNA DDX11 antisense RNA 1 (DDX11-AS1) was found to be highly expressed in gastric cancer (GC). This study was to explore the role and molecular mechanism in oxaliplatin (OXA) resistance. PATIENTS AND METHODS: The levels of DDX11-AS1, microRNA-326 (miR-326) and insulin receptor substrate 1 (IRS1) were measured by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell proliferation, migration, invasion and apoptosis were examined by methylthiazolyldiphenyl-tetrazolium bromide (MTT), transwell and flow cytometry assays, respectively. Levels of all protein were detected using Western blot. The correlation between miR-326 and DDX11-AS1/IRS1 was confirmed by Dual-Luciferase reporter and RNA immunoprecipitation (RIP) assays. The xenograft model was constructed to explore the effect of DDX11-AS1 in vivo. RESULTS: DDX11-AS1 was overexpressed in OXA-resistant GC tissues and cells, and DDX11-AS1 knockdown inhibited cell proliferation, migration, invasion and OXA resistance, and promoted apoptosis in OXA-resistant GC cells. Mechanically, DDX11-AS1 directly targeted miR-326 and miR-326 could bind to IRS1 in OXA-resistant GC cells. Functionally, silencing DDX11-AS1 repressed the progression and OXA resistance in OXA-resistant GC cells by down-modulating IRS1 expression via sponging miR-326 in vitro and in vivo. CONCLUSIONS: DDX11-AS1 accelerated the progression and OXA chemoresistance of GC cells in vitro and in vivo by sponging miR-326, thus increasing the expression of IRS1, suggesting DDX11-AS1 might be a promising prognostic biomarker and therapeutic target in GC.

Overexpression of long noncoding RNA HOXC13-AS and its prognostic significance in hepatocellular carcinoma.

OBJECTIVE: The long noncoding RNA HOXC13 antisense RNA (HOXC13-AS) was overexpressed in several tumor specimens, and its overexpression was correlated with cells metastasis of tumors. However, its effects in other tumors remained largely unclear. In this work, we aimed to identify whether HOXC13-AS was abnormally expressed in hepatocellular carcinoma (HCC) and further explore its prognostic value. PATIENTS AND METHODS: QRT-PCR was applied for the examination of HOXC13-AS levels in 197 paired HCC specimens and matched non-tumor specimens. Chi-square tests were carried out for the verification of the relations between the levels of HOXC13-AS and the clinicopathologic features of HCC patients. The Kaplan-Meier methods were applied for the exploration of the prognostic value of HOXC13-AS. Multivariate analysis was performed using the Cox proportional hazard assays. RESULTS: Up-regulation of HOXC13-AS was observed in HCC tissues compared to matched normal tissues (p < 0.01). Higher levels of HOXC13-AS were associated with TNM stage (p = 0.024) and lymph node metastasis (p = 0.043). Survival assays showed that HCC patients with high-HOXC13-AS expressions had significantly shorter overall survival (p < 0.0106) and disease-free survival (p < 0.0066) compared to their counterparts with low-HOXC13-AS expressions. Multivariate analyses suggested HOXC13-AS as an independent prognostic factor for HCC patients. CONCLUSIONS: We showed that HOXC13-AS might serve as a promising biomarker for prognosis prediction of HCC.

MiR-296-5p inhibits cell invasion and migration of esophageal squamous cell carcinoma by downregulating STAT3 signaling.

OBJECTIVE: Many studies have emphasized the function of microRNA-296 (miR-296) that inhibits tumor formation. To some extent, the role of miR-296 in esophageal squamous cell carcinoma (ESCC) remains misleading. Therefore, the current research was designed to investigate the regulatory mechanisms of miR-296 and signal transducer and activator of transcription 3 (STAT3) in ESCC. PATIENTS AND METHODS: The mRNA expression of miR-296-5p and STAT3 in ESCC tissues or cell lines was measured via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The protein level of STAT3 was measured by Western blotting assay. The Luciferase reporter assay was used to verify the binding sites between miR-296-5p and STAT3. The transwell assay was employed to identify cell migration and invasion. RESULTS: Down-regulation of miR-296-5p was detected in ESCC tissues and cell lines (p<0.01). Additionally, miR-296-5p was found to target STAT3 directly. Functionally, up-regulation of miR-296-5p or down-regulation of STAT3 significantly inhibited cell migration and invasion in ESCC. CONCLUSIONS: MiR-296-5p inhibited cell invasion and migration in ESCC by downregulating STAT3. The overexpression of miR-296-5p by targeting STAT3 suppressed tumorigenesis of ESCC cells.

[Giant angioleiomyoma of the neck: a rare tumor case and literature review].

Summary The patient was admitted of the chief complain "progressive snoring for two years, gradual enlargement of the neck neoplasm for six months". Specific examination indicated that bilateral cervical-mandibular margin to cervical root diffuse apophysis, most notably in the right thyroid plane.Posterior pharyngeal wall underwent an apophysis while no related vein engorgement was noticed. Ultrasound examination indicated that multiple hypoechoic nodules with calcification from posterior thyroid to submandibular. MRI examination indicated bilateral posterior pharyngeal plexus malformation. The patient was first treated with angiography and embolization in the department of interventional and followed by "cervical mass resection" in the department of otorhinolaryngology head and neck surgery. The tumor size was 11 cm×8 cm×3 cm. Histology of the tumor was angioleiomyoma with immunohistochemical results Desmin（+），SMA（+），CD31（-），CD34（+），Ki67（+，1%），Vimentin（+），D-240（-），p53（-）.

Long noncoding RNA LINC01510 is highly expressed in colorectal cancer and predicts favorable prognosis.

OBJECTIVE: Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in governing fundamental biological processes, as well as in tumorigenesis. LncRNA LINC01510 (LINC01510) was recently shown to be involved in colorectal cancer (CRC); however, its role in CRC remains unknown. The objective of this study was to evaluate LINC01510 expression and its relevance to the prognosis of CRC. PATIENTS AND METHODS: LINC01510 expression was detected in CRC tissues and cell lines by using quantitative real-time PCR (qRT-PCR). The correction between LINC01510 expression and clinical characteristics was evaluated with x2-test. Survival curves and log-rank test were used to analyze patients' survival. A Cox proportional hazard model was constructed to evaluate the association of LINC01510 expression with overall survival and disease-free survival, respectively. RESULTS: Here, we found that the levels of LINC01510 in CRC tissues were significantly higher than those in matched tumor-adjacent tissues. Moreover, high LINC01510 expression was observed to be closely correlated with histology/differentiation (p = 0.001), depth of invasion (p = 0.004) and TNM stage (p = 0.003). From the Kaplan-Meier survival curves, it was observed that patients with high expression of LINC01510 had shorter overall survival (p = 0.004) and disease-free survival (p = 0.000) as compared with the LINC01510-low group. In the multivariate analysis, high LINC01510 expression was an independent prognostic factor for both overall survival (p = 0.001) and disease-free survival (p = 0.001). CONCLUSIONS: We demonstrated that low LINC01510 expression was associated with the progression of CRC and could serve as a potential independent prognostic biomarker for patients with CRC.

[Effects and the associated factors of the 2016 China Motivational Healthy Walking Program among occupational population].

Objective: To examine the effects and associated factors of the China Motivational Healthy Walking Program among occupational population. Methods: The 2016 China Motivational Healthy Walking Program recruited 29 224 participants from 139 demonstration areas for comprehensive prevention and control of chronic and non-communicable disease at national level and 70 at provincial level. Intervention on walking was carried out by adopting group and individual motivating measures. Walking steps were recorded by electronic pedometer. We used percent of days achieving 10 000 steps (P10 000), percent of days fulfilling continuous walking (PCW), and proportion of valid walking (PVW) steps to reflect walking quantity, pattern and quality of participants. Motivation intensity was measured by summing up scores of each motivating activity. Questionnaire-based online survey collected information about demographic characteristics, lifestyle risk factors and chronic diseases. This study finally included 12 368 individuals in the analysis. Multilevel logistic regression model was used to assess the effect of group and individual motivating measures on walking activity and corresponding associated factors. Results: Age of the study sample was (41.2±8.99) years, and 58.17% (7 194) of them were female. After 100-day intervention, the P10 000, PCW and PVW of all participants were 93.89%±14.42%,92.01%±15.97% and 81.00%±7.45%, respectively. The mean P10 000 and PCW increased with rising group-motivated scores, self-motivated scores and individual-activity scores (P<0.001 for all). The mean PVW decreased with both higher group-motivated scores and self-motivated scores (both P<0.05), and varied little among groups with different level individual-activity scores (P=0.525). According to the results from the multilevel model, those who had greater group-motivated scores and self-motivated scores tended to have more likelihood of high-level of P10 000 and PCW. Age, sex, smoking status, education attainment and alcohol drinking were associated with P10 000 and PCW (P<0.05 for all). Conclusion: The Motivational Healthy Walking Program had positive effect on promoting healthy walking among occupational population. Group-motivated and self-motivated activities were associated with healthy walking.

Diagnostic value of various noninvasive indexes in the diagnosis of chronic hepatic fibrosis.

OBJECTIVE: Hepatic fibrosis is a repair response to chronic liver injury. This study evaluated the diagnostic value of various noninvasive indicators for hepatic fibrosis in patients with chronic liver disease. PATIENTS AND METHODS: 95 patients with liver biopsy were enrolled in this study. Routine clinical and laboratory examinations were collected, including age, sex, blood routine, biochemistry, serum fibrosis, and FibroTouch. APRI and FIB4 scores were calculated. The patients were grouped according to liver pathological staging to analyze the correlation between the fibrosis with serum fibrosis, APRI, FIB4 score, and FibroTouch. The receiver operator characteristics of S2, S3, and S4 were analyzed to calculate the area under the curve (AUC). RESULTS: No statistical difference was found on age, ALT, AST, GGT, BMI, TG, CHOL, and Glu (p > 0.05). Liver stiffness measurement (LSM), APRI, FIB4, PCIII, CIV, LN, and HA exhibited statistical significance (p < 0.05). Further correlation analysis showed that PCIII, IV-C, LN, APRI, LSM, and FIB4 were positively correlated with the stage of hepatic fibrosis (p < 0.05). ROC curve analysis demonstrated that LSM and FIB4 revealed good predictions of various stages of fibrosis in chronic liver disease with AUC greater than 0.7. The AUC of LSM in the diagnosis of liver cirrhosis (S4) reached 0.908. Its accuracy was influenced by liver inflammation. CONCLUSIONS: The LSM value in FibroTouch showed high coincidence rate with hepatic fibrosis staging. It is a valuable noninvasive method for assessing the progression of hepatic fibrosis in chronic liver disease.

Predictive values of FAP and HGF for tumor angiogenesis and metastasis in colorectal cancer.

This study aims to explore the correlation of hepatocyte growth factor (HGF) and fibroblast activation protein (FAP) expressions with the angiogenesis and metastasis in colorectal cancer (CRC). The immunohistochemical SABC method was used to detect HGF and FAP expressions in 127 CRC tissues, 51 colorectal polyp tissues and 28 normal tissues. HGF and FAP expressions in liver metastasis were detected using western blot to analyze the correlation of their expressions with lymph node metastasis and liver metastasis. Micro-vessel density (MVD) and clinic-pathologic information of CRC patients were recorded and analyzed. In CRC group, HGF and FAP expressions were greatly higher than those in normal group and colorectal polyps group (P < 0.05). Moreover, the positive rates of HGF and FAP expressions in lymph node metastasis were evidently higher than those in non-lymph node metastasis (P < 0.05). In liver metastasis group, HGF and FAP expressions were obviously higher than non-liver metastasis group (P < 0.05). CRC group had much more MVD in comparison with normal group and colorectal polyps group (P < 0.05).When compared with negative group, MVD was significantly higher than that in CRC tissue with positive HGF and FAP (P < 0.05). Spearman rank correlation analysis showed that HGF and FAP were in positive correlation with MVD (r = 0.542, P < 0.001; r = 0.753, P < 0.001). These results indicate that FAP and HGF play an important role in CRC angiogenesis, and their expression levels are valuable to predict CRC liver metastasis and lymph node metastasis.

[The effect of liraglutide in combination with human umbilical cord mesenchymal stem cells treatment on glucose metabolism and ß cell function in type 2 diabetes mellitus].

OBJECTIVE: To observe the effect of liraglutide (LIRA) in combination of umbilical cord mesenchymal stem cells (hUC-MSCs) in treating type 2 diabetes mellitus. METHODS: Eligibility criteria for subjects includes: type 2 diabetes mellitus with more than 10 years duration; having been treated with secretagogues, metformin and insulin in combination with LIRA for at least 6 months; poor glycemic control [glycosylated hemoglobin A1c(HbA1c) 7%-10%]. Totally, twelve patients were enrolled and randomly divided into two groups: the group A (LIRA group, n=6) and the group B (LIRA+ hUC-MSCs group, n=6). The hUC-MSCs were transplanted through infusing of 1×10(6) cells /kg via pancreatic artery directed by interventional radiology on the first day, and followed by infusing 1×10(6) cells /kg through peripheral vein on the eighth, the fifteenth and the twenty-second day sequentially. The control subjects were infused with saline. Both groups were treated with LIRA for 24 weeks at the same period. Fasting plasma glucose(FPG), 2h postprandial plasma glucose(2hPG) and HbA1c were measured. A 75 g oral glucose tolerance test(OGTT)was performed. The early phase of C peptide(CP) secretion function(ΔCP30/ΔG30), the total amount of C peptide secretion function(AUCCP180)and Homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. RESULTS: (1) The baseline FPG, 2hPG, HbA1c, ΔCP30/ΔG30, AUCCP180 and HOMA-IR were comparable between the two groups(P>0.05). (2) Compared with subjects in group A, FPG, 2hPG and HbA1c levels were significantly decreased in subjects in group B [(8.33±0.99) mmol/L vs (6.64±0.79)mmol/L, (13.85±0.86) mmol/L vs (8.65±1.12) mmol/L, (7.82±0.31)% vs (6.82±0.53)%, P<0.05]. (3) Compared with group A, ΔCP30/ΔG30 and AUCCP180 were significantly increased, and HOMA-IR was significantly decreased in group B(0.22±0.13 vs 0.70±0.38, 12.52±5.30 vs 21.16±3.17, 9.46±4.88 vs 4.30±2.68, P<0.05). CONCLUSION: LIRA treatment in combination with hUC-MSCs improves glucose metabolism and the ß cell function in type 2 diabetic patients. (ClinicalTrials.gov NCT01954147).

[Immunotherapy strategy for 35 cases of severe anti-N-methyl-D-aspartate receptor encephalitis].

OBJECTIVE: To provide evidence for establishing standardized treatment strategy of severe anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in China, by demonstrating the clinical characteristics and comparing the treatment strategy with that adopted in foreign countries. METHODS: A total of 35 hospitalized cases who met the diagnostic criteria for severe anti-NMDAR encephalitis were retrospectively analyzed. Demographic data, clinical history, past medical history, laboratory tests, imaging studies, treatment and the follow-up information were recorded using unified forms. RESULTS: Mental and behavioral abnormalities, seizures and consciousness disturbance occurred in all cases; involuntary movements, speech disorders, memory loss, central hypoventilation and autonomic dysfunction happened in 45%-65% of cases. Sixteen patients (45.71%) required mechanical ventilation. Modified Rankin score (mRS ) arranged 4-5 (mean mRS 4.86). The percentage of patients with elevated intracranial pressure, white blood cell and protein in cerebrospinal fluid were 42.86%, 60.00%, and 14.29%, respectively. Abnormal findings in brain magnetic resonance imaging scan happened in 31.43% cases, located in frontal lobe, temporal lobe, insular lobe, hippocampus, cingulate gyrus, corpus callosum, brain stem, and cerebellum. All cases received intravenous immunoglobulin, for one to maximum seven cycles, with an average of three cycles. 91.43% of cases received glucocorticoid therapy, including 54.29% of cases received high-dose methylprednisolone. Two patients (5.71%) received plasma exchange. Five patients(14.29%) received second-line therapy including rituximab for 4 patients and intravenous cyclophosphamide (CTX) for one. Fifteen patients(42.86%) received long-term immunosuppression therapy. All cases acquired improvement after immunotherapy and were transferred out from ICU, the median ICU time was 46 days and median hospitalized duration was 72 days. The mRS were 5 for 2 cases, 1-4 for the rest patients, and no patient died during hospitalization. During a median follow-up period of 17.6 months, 30 of 35 patients (85.71%) achieved complete recovery or a good outcome (mRS 0-2). Eleven patients (31.43%) relapsed. One patient(2.90%) died 2 years after discharge. CONCLUSION: Intravenous immunoglobulin combined with high-dose methylprednisolone therapy is effective for severe anti-NMDAR encephalitis. Retrial of the first-line immunotherapy is an option for initially unresponsive cases.

Rab1 in cell signaling, cancer and other diseases.

The endoplasmic reticulum (ER) and Golgi membrane system have major roles in cell signaling and regulation of the biosynthesis/transport of proteins and lipids in response to environmental cues such as amino acid and cholesterol levels. Rab1 is the founding member of the Rab small GTPase family, which is known to mediate dynamic membrane trafficking between ER and Golgi. Growing evidence indicate that Rab1 proteins have important functions beyond their classical vesicular transport functions, including nutrient sensing and signaling, cell migration and presentation of cell-surface receptors. Moreover, deregulation of RAB1 expression has been linked to a myriad of human diseases such as cancer, cardiomyopathy and Parkinson's disease. Further investigating these new physiological and pathological functions of Rab1 should provide new opportunities for better understanding of the disease processes and may lead to more effective therapeutic interventions.

[Monitoring and research on pathogen spectrum in patients with acute diarrhea from sentinel hospital of Zhejiang Province during 2009 to 2014].

Objective: To explore pathogen spectrum constitution of acute diarrhea in outpatient and emergency of Zhejiang Province, and provide basis for treatment, prevention and control of the disease. Methods: During January 2009 to December 2014, we selected seven sentinel hospitals in different regions of Zhejiang, monitored and researched on pathogen spectrum in patients with acute diarrhea from outpatient and emergency. We recorded patients' personal basic information, the main symptoms and signs, and collected stool samples (5 g). Eight kinds of bacteria (Vibrio cholerae, Shigella spp., Salmonella spp., Diarrheagenic E. coli, Vibrio parahaemolyticus, Aeromonas hydrophila, Yersinia enterocolitica and Plesiomonas shigelloides) and five kinds of viruses (Rotavirus, Norovirus, Sappovirus, Astrovirus and Adenovirus) were detected. Chi-square test and Fisher's exact probability method were used to compare different characteristics of patients with single bacterial infection, single virus infection and multiple infection (bacteria-bacteria, bacteria-viruses, virus-virus). Results: During 2009 to 2014, 9 364 fecal samples from acute diarrhea patients were collected and tested, among which 3 500 cases were tested positive, with total positive rate of 37.38%. Positive rates of bacteria and viruses were 13.14% (1 230 cases) and 20.75% (1 943 cases), respectively. Mixed infection positive rate of multiple pathogens was 3.49% (327 cases). Positive rate of Vibrio parahaemolyticus (5.96% , 558 cases) was the highest among bacterial pathogens, followed by pathogenic Escherichia coli (3.86%, 361 cases). Viruses were mainly Norovirus (10.73%, 1 005 cases) and rotavirus (8.35%, 782 cases). A big difference existed in diarrheogenic pathogen spectrum between patients less than 15 years old and patients equal or older than 15 years old. Pathogens for patients less than 15 years old were mainly virus, with the positive rate of 32.69% (1 014 cases). However, the positive rate of bacteria was 16.86% (1 056 cases) in patients equal or older than 15 years old. Single bacterial infection was highest in age group of 25-34 years old (18.62%, 302 cases) , single virus infection was highest in age group of 1-4 years old (41.12%, 435 cases) , and mixed infections of multiple pathogens were mainly existed in age group of 1-4 years old (7.37%, 78 cases) . Pathogen positive rate were increasing year by year. Pathogen positive rate of patients with acute diarrhea has obvious seasonality, with single bacterial infection being highest during July to September and single virus infection being highest during December to March. Pathogen spectrum of outpatient and emergency patients with acute diarrhea in Zhejiang Province changed a little from 2009 to 2014, mainly rotavirus (22.34% (782/3 500)), norovirus (28.71% (1 005/3 500)), vibrio parahaemolyticus (15.92% (558/3 500)) and Escherichia coli (10.31% (361/3 500)). However, pathogen spectrums in different years owned different features. Conclusion: Common pathogens in outpatient and emergency patients with acute diarrhea in Zhejiang Province were tested with significant seasonal epidemic law. The composition of pathogenic spectrum was variant in different age group. Constitutes of major pathogen spectrum in different years differed a little.

[Clinical characteristics and prognosis in 12 patients with adult T cell leukemia/lymphoma confirmed by HTLV-1 provirus gene detection].

Objective: To analyze the clinical characteristics and prognosis of adult T cell leukemia/lymphoma (ATLL). Methods: Peripheral blood samples from patients who were suspected as ATLL from March, 2013 to July, 2015, were collected for HTLV-1 provirus genes detection in genomic DNA extraction by PCR. Cases showing positive results were confirmed as ATLL. Clinical and laboratory characteristics, therapeutic outcomes and survival evaluation were collected. Results: 12 out of 23 suspected patients were confirmedly diagnosed as ATLL through HTLV-1 provirus genes detection by PCR. Eight patients were male and four patients were female. Median age was 51 (range 28-66) years old. All of those patients came from coastal cities of Fujian province where a HTLV-1 epidemic area locates. In the subtype classification of these 12 ATLL, 11 patients were classified as acute type and one case as lymphoma type ATLL. As one of the clinical characteristics of ATLL, ' flower cells ', with typical or atypical morphology had been observed in a high rate (81.8%). Clinical symptom such as hepatomegaly, splenomegaly and lymphadenectasis were detected in most of patients, and hypercalcemia and elevated LDH were also noted commonly. The ATLL cells immunophenotype were typical, and the major subtype was CD4+ CD8- type. Confection of hepatitis B virus was detected in a high rate (54.5%). Ten patients received chemotherapy, and 2 cases in complete remission after chemotherapy received allogeneic hematopoietic stem cell transplantation. At the end of the follow-up, 7 cases died, 4 cases survived, 1 case was lost, and the median survival was 2.8 (0.9-10.8) months. We found a case had HTLV-1 provirus negative after transplantation. Conclusion: In the coastal area of Fujian Province, ATLL is not rare. Characteristics of those ATLL are typical. But prognosis is still unsatisfactory.

ATAD2 is overexpressed in gastric cancer and serves as an independent poor prognostic biomarker.

OBJECTIVE: ATPase family, AAA domain containing 2 (ATAD2) has been found overexpressed in various cancer types and correlated with malignant status and poor prognosis. However, little is known about the clinical significance of ATAD2 in gastric cancer patients. The aim of this study was to explore the clinical and prognostic significance of ATAD2 in gastric cancer. METHODS: The mRNA and protein levels expression of ATAD2 were detected in clinical tissue samples by qRT-PCR and immunohistochemistry, respectively. We examined the ATAD2 protein expression by immunohistochemistry. Furthermore, we analyzed the association between ATAD2 expression and clinicopathological features including prognosis in 166 gastric cancer samples. RESULTS: In our results, ATAD2 mRNA and protein were highly expressed in gastric cancer samples. ATAD2 overexpression was correlated with advanced clinical stage, tumor depth, lymph node metastasis, and distant metastasis. According to the survival analysis, ATAD2 protein overexpression was a poor independent prognostic factor for gastric cancer patients. CONCLUSIONS: In summary, ATAD2 could serve as a prognostic biomarker for gastric cancer patients.

Conjunctiva reconstruction by induced differentiation of human amniotic epithelial cells.

In this study, we aimed to investigate the feasibility of directed differentiation of human amniotic epithelial cells into conjunctival epithelium under specific conditions as well as of constructing tissue-engineered conjunctiva for ocular surface reconstruction. Human amniotic epithelial cells were cultured with induced denuded conjunctival matrix and conjunctival homogenate. Immunohistochemistry of cytokeratin-4, cytokeratin-13, and muc5ac as well as PAS staining were performed. The concentration of muc5ac at different times was measured using ELISA. The differentiated cells with quantum dots were transferred onto a denuded amniotic membrane to establish tissue-engineered conjunctiva and transplanted into a rabbit model with a conjunctival defect. After induction of human amniotic epithelial cells, differentiated cells showed conjunctival epithelium phenotype, while trace amounts of mu5ac in the culture medium measured by ELISA increased gradually within 1 to 7 days. Successfully tissue-engineered conjunctiva had similar structure as normal conjunctiva and was transplanted into a rabbit model with conjunctiva defect. After 2 weeks post-surgery, conjunctiva grafts survived and were integrated. Immunohistochemistry showed conjunctival epithelium phenotype, positive cells were found in PAS staining. Thus, human amniotic epithelial cells could differentiate into conjunctival epithelium-like cells and goblet cells with partially physiological function, and we successfully restored ocular surface integrity in the rabbit model using tissue-engineered conjunctiva.

CD52 expression is induced in the mouse uterus at the time of embryo implantation.

CD52 is a GPI anchor protein present in lymphocytes, the epithelial cells of the epididymis and sperm. It has been reported that male reproductive tract CD52 induces antibodies interfering with sperm function and causes infertility. CD52 is also expressed in ovulated cumulus cells in female reproductive tissues. In the present study, we examined the distribution and the mechanism of regulation of CD52 in the uterus. CD52 expression was evaluated in uterine tissue recovered at 0.5, 4.5, 8.5 and 12.5dpc (days post-coitum). Immunohistochemistry, RT-PCR, Western blotting and gel shift analysis were performed to determine localization and transcriptional regulation of CD52. Cd52 mRNA and CD52 protein were found to increase simultaneously from 0.5 to 4.5dpc. Gel shift analysis revealed that NKX2.2, a transcriptional factor, binds to the promoter region of the Cd52 gene. CD52 and NKX2.2 were co-localized in the endometrium of the uterus. Pathway analysis using Ingenuity pathway analysis predicted that Cd52 is associated with genes involved in the formation of uterosomes which are necessary for embryo attachment. These findings suggest that CD52 synthesis is regulated by NKX2.2 at a transcriptional level, and that Cd52 may be a member of the network of genes regulating uterine receptivity for embryo implantation.