[Chronic myeloid leukemia with e6a2 fusion gene: a case report and literature review].

Chronic myeloid leukemia (CML) with e6a2 transcript type is very rare in clinic,which is usually related to disease aggressiveness. Its clinical characteristics and relationship with tyrosine kinase inhibitor efficacy are still unclear. In this paper, the clinical characteristics and related laboratory tests of a patient with e6a2 fusion gene positive CML characterized by multiple osteolytic bone destruction throughout the body and eosinophil infiltration in gastrointestinal tract, lymph nodes and other organs were retrospectively analyzed, and the relevant literature was reviewed. The patient was Ph chromosome positive with chromosome +8, and the common BCR::ABL1 transcript of CML was negative, but e6a2 transcript was positive detected by RT-PCR. The patient was treated with dasatinib 100 mg/d. Three months later, the patients achieved CHR, CCyR and MR4.0. However, the e6a2 transcript is very rare in clinical practice, and more cases of e6a2 transcript need to be studied to clarify its clinical characteristics and improve the treatment effect of these rare cases.

Association of radiotherapy for prostate cancer and second primary colorectal cancer: a US population-based analysis.

BACKGROUND: Radiotherapy (RT) is a common treatment for prostate cancer, yet the risk of second primary colorectal cancer (SPCRC) in patients with prostate cancer undergoing RT has not been adequately studied. METHODS: This study employed a population-based cohort design using the US Surveillance, Epidemiology, and End Results (SEER) database to identify individuals diagnosed between January 1975 and December 2015. The cumulative incidence of SPCRC was estimated using Fine-Gray competing risk regression. Poisson regression analysis was used to estimate the risk associated with RT. Survival outcomes of patients with SPCRC were evaluated using the Kaplan-Meier method. RESULTS: A total of 287,607 patients diagnosed with prostate cancer were identified. The cumulative incidences were higher in patients who did not receive RT (2.00%) compared to those who underwent RT (2.47%) after 25 years. After adjustment for multiple variables, RT was associated with an increased risk of developing combined SPCRC (adjusted HR 1.590). Additionally, the overall survival was significantly lower in patients who developed colorectal cancer after receiving RT as compared to those who did not receive RT. CONCLUSION: These findings underscore the need for diligent long-term monitoring and effective management strategies to detect SPCRC in patients treated with RT for prostate cancer.

Zoledronic acid epigenetically alleviates high-glucose-suppressed osteogenic differentiation of MC3T3-E1 cells.

OBJECTIVE: Due to the impact of excessive glucose on osteogenic differentiation, diabetic osteopathy frequently results in skeletal fragility, osteoporosis, and bone pain. Zoledronic acid, a bisphosphonate (BP) that effectively inhibits osteoclastic bone resorption is given yearly to improve bone mineral density (BMD) in patients with osteoporosis. However, the detailed molecular mechanisms remained unclear. This study investigates the possible pathways by which zoledronic acid regulates osteogenesis when blood glucose levels are high. MATERIALS AND METHODS: MC3T3-E1 cells were treated with one mM zoledronic acid or not in a standard or high glucose culture medium. A quantitative polymerase chain reaction (qPCR) assay was utilized to assess the expression of the target candidate genes, including RUNX2, MALAT1, miR-133, miR-20a, and miR-204. RESULTS: In a high-glucose condition, zoledronic acid treatment significantly lowered MALAT1 (p < 0.0001) and miR-20a (p < 0.0001) expression. Conversely, in a high-glucose condition, RUNX2, miR-133, and miR-204 expressions were found to be significantly increased in the zoledronic acid treatment group as compared to no treatment (all p < 0.0001). CONCLUSIONS: In conclusion, under a high-glucose environment, zoledronic acid can modulate the expression of the RUNX2 transcription factor through epigenetic regulation.

[Phenotype and genotype analyses of two pedigrees with inherited fibrinogen deficiency].

Objective: To analyze the phenotype and genotype of two pedigrees with inherited fibrinogen (Fg) deficiency caused by two heterozygous mutations. We also preliminarily probed the molecular pathogenesis. Methods: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and plasma fibrinogen activity (Fg∶C) of all family members (nine people across three generations and three people across two generations) were measured by the clotting method. Fibrinogen antigen (Fg:Ag) was measured by immunoturbidimetry. Direct DNA sequencing was performed to analyze all exons, flanking sequences, and mutated sites of FGA, FGB, and FGG for all members. Thrombin-catalyzed fibrinogen polymerization was performed. ClustalX 2.1 software was used to analyze the conservatism of the mutated sites. MutationTaster, PolyPhen-2, PROVEAN, SIFT, and LRT online bioinformatics software were applied to predict pathogenicity. Swiss PDB Viewer 4.0.1 was used to analyze the changes in protein spatial structure and molecular forces before and after mutation. Results: The Fg∶C of two probands decreased (1.28 g/L and 0.98 g/L, respectively). The Fg∶Ag of proband 1 was in the normal range of 2.20 g/L, while it was decreased to 1.01 g/L in proband 2. Through genetic analysis, we identified a heterozygous missense mutation (c.293C>A; p.BßAla98Asp) in exon 2 of proband 1 and a heterozygous nonsense mutation (c.1418C>G; p.BßSer473*) in exon 8 of proband 2. The conservatism analysis revealed that Ala98 and Ser473 presented different conservative states among homologous species. Online bioinformatics software predicted that p.BßAla98Asp and p.BßSer473* were pathogenic. Protein models demonstrated that the p.BßAla98Asp mutation influenced hydrogen bonds between amino acids, and the p.BßSer473* mutation resulted in protein truncation. Conclusion: The dysfibrinogenemia of proband 1 and the hypofibrinogenemia of proband 2 appeared to be related to the p.BßAla98Asp heterozygous missense mutation and the p.BßSer473* heterozygous nonsense mutation, respectively. This is the first ever report of these mutations.

[Application effects of bundle nursing of citric acid extracorporeal anticoagulation on continuous renal replacement therapy of severe burn patients].

Objective: To explore the application effects of bundle nursing of citric acid extracorporeal anticoagulation on continuous renal replacement therapy (CRRT) of severe burn patients. Methods: A non-randomized controlled study was conducted. Forty-six patients who met the inclusion criteria and received regular nursing of citric acid extracorporeal anticoagulation during CRRT in the First Affiliated Hospital of Army Medical University (the Third Military Medical University) from January to December 2017 were included in regular nursing group (30 males and 16 females, aged 42.0 (38.7,47.0) years, with 201 times of CRRT performed), and 48 patients who met the inclusion criteria and received bundle nursing of citric acid extracorporeal anticoagulation during CRRT in the same hospital from January to December 2018 were included in bundle nursing group (32 males and 16 females, aged 41.0 (36.0,46.0) years, with 164 times of CRRT performed). The clinical data of all the patients in the two groups were recorded, including the length of intensive care unit (ICU) stay, total cost of treatment in ICU, cost of CRRT, unplanned ending of treatment, ending of treatment due to operation (with the rates of unplanned ending of treatment and ending of treatment due to operation calculated), times of disposable hemodialysis filter and supporting pipeline filter (hereinafter referred to as filter) with use time>24 h, times of CRRT, and lifetime of filter. For the patients in both groups who continuously received CRRT for 3 days or more from the first treatment, the prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), total calcium, ionic calcium (with the difference of total calcium or ionic calcium between before and after treatment calculated), creatinine, urea, ß2 microglobulin, cystatin C, platelet count, mean arterial pressure, pH value, oxygenation index, bicarbonate radical, and lactic acid levels before the first treatment (hereinafter referred to as before treatment) and 3 days after the first treatment (hereinafter referred to as after 3 days of treatment). The treatment-related complications of all patients in the two groups were recorded during hospitalization. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. Results: Compared with those in regular nursing group, the length of ICU stay was significantly shortened (Z=-4.71, P<0.01), the total cost of treatment in ICU was significantly reduced (t=-1.39, P<0.01), the cost of CRRT had no significant change (P>0.05), the rates of unplanned ending of treatment and ending of treatment due to operation were both significantly decreased (with χ2 values of 12.20 and 17.83, respectively, P<0.01), the times of filter service time>24 h was increased significantly (Z=-5.93, P<0.01), the times of CRRT were significantly reduced (Z=-4.75, P<0.01), and the filter service life was significantly prolonged (Z=-9.24, P<0.01) among patients in bundle nursing group. Thirty-one patients in bundle nursing group and 28 patients in regular nursing group continuously received CRRT for 3 days or more from the first treatment. Before treatment, PT, APTT, and INR of patients in bundle nursing group were 24.10 (16.08, 39.20) s, 38.81 (32.32, 45.50) s, and 1.17 (1.12, 1.19), respectively, similar to 31.75 (22.99, 40.96) s, 41.82 (35.05, 48.06) s, and 1.15 (1.11, 1.19) of patients in regular nursing group (P>0.05); the levels of total calcium and ionic calcium of patients in the two groups were similar (P>0.05). After 3 days of treatment, PT, APTT, and INR of patients in bundle nursing group and regular nursing group were 29.06 (20.11, 39.46) s, 35.25 (30.06, 40.28) s, 1.13 (1.09, 1.17) and 36.51 (26.64, 42.92) s, 39.89 (34.81, 46.62) s, 1.14 (1.10, 1.18), respectively, similar to those before treatment (P>0.05); the level of ionic calcium of patients in regular nursing group was significantly higher than that before treatment (Z=-2.08, P<0.05); the levels of total calcium and ionic calcium of patients in bundle nursing group were both significantly higher than those before treatment (with Z values of -3.55 and -3.69, respectively, P<0.01); compared with those in regular nursing group, APTT of patients was significantly shorter (Z=-2.29, P<0.05), while the total calcium level of patients was significantly higher in bundle nursing group (Z=-2.26, P<0.05). The difference of total calcium between before and after treatment of patients in bundle nursing group was significantly higher than that in regular nursing group (Z=-3.15, P<0.01). The differences of ionic calcium between before and after treatment of patients in the two groups were similar (P>0.05). Before treatment, the level of ß2 microglobulin of patients in bundle nursing group was significantly higher than that in regular nursing group (Z=-2.84, P<0.01), the platelet count of patients in bundle nursing group was significantly lower than that in regular nursing group (Z=-2.44, P<0.05), while the levels of creatinine, urea, cystatin C, mean arterial pressure, pH value, oxygenation index, bicarbonate radical, and lactic acid of patients in the two groups were similar (P>0.05). After 3 days of treatment, the levels of creatinine, urea, ß2 microglobulin, cystatin C, pH value, bicarbonate radical, and lactic acid of patients were all significantly lower than those before treatment (with Z values of -2.10, -2.90, -3.11, -2.02, -2.34, -2.63, and -2.84, respectively, P<0.05 or P<0.01), while the levels of platelet count, oxygenation index, and mean arterial pressure of patients were all significantly higher than those before treatment in bundle nursing group (with Z values of -6.65 and -2.40, respectively, t=-9.97, P<0.05 or P<0.01); the levels of creatinine, urea, ß2 microglobulin, cystatin C, platelet count, pH value, bicarbonate radical, and lactic acid of patients were all significantly lower than those before treatment (with Z values of -5.32, -2.31, -2.41, -2.21, -3.68, -2.93, -2.20, and -2.31, respectively, P<0.05 or P<0.01), while the oxygenation index and mean arterial pressure of patients were both significantly higher than those before treatment in regular nursing group (Z=-5.59, t=-7.74, P<0.01). After 3 days of treatment, compared with those in regular nursing group, the levels of creatinine, cystatin C, platelet count, oxygenation index, bicarbonate radical, and mean arterial pressure of patients were all significantly higher (with Z values of -2.93, -1.99, -6.39, -2.09, and -2.52, respectively, t=-3.28, P<0.05 or P<0.01), while the levels of urea, ß2 microglobulin, pH value, and lactic acid of patients were all significantly lower (with Z values of -3.87, -2.58, -4.24, and -2.75, respectively, P<0.05 or P<0.01) in bundle nursing group. During hospitalization, there were no treatment-related bleeding events or hypernatremia related to citric acid treatment of patients in the two groups. The ratio of total calcium to ionic calcium in one patient in bundle nursing group was >2.5, but there was no manifestation of citric acid accumulation poisoning; 1 patient had hypoionic calcemia, and 1 patient had severe metabolic alkalosis. Five patients had hypoionic calcemia and 2 patients had severe metabolic alkalosis in regular nursing group. Conclusions: The implementation of bundle nursing of citric acid extracorporeal anticoagulation during CRRT for severe burn patients shortens the length of ICU stay, reduces the total cost of treatment in ICU and the occurrence of treatment-related complications, relieves the economic burden of patients, and improves the continuity and quality of treatment.

[Diagnosis and treatment status of perioperative anemia in patients with gastrointestinal neoplasms: a multi-center study in Hubei Province].

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ2 test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.

[Effectiveness of TRB3 on human hepatocellular carcinoma cells proliferation, apoptosis and migration].

Objective: To explore the regulatory role and mechanism of tribbles pseudokinase 3 (TRB3) on hepatocarcinoma (HCC) cells proliferation, apoptosis and migration. Methods: Immunohistochemistry and Western blot were used to detect TRB3 expression in cancerous and adjacent cancerous liver tissues of HCC patients. TRB3 expression was detected in vitro in HepG2 and Huh7 hepatocarcinoma cell lines. Simultaneously, CCK8 and EdU were used to detect cell proliferation after TRB3 targeted inhibition with small interfering RNA. CCK8 and EdU were used to detect cell proliferation. Flow cytometry assay was used to detect apoptosis. Transwell assay was used to evaluate migration ability. Simultaneously, Western blot was used to detect changes in apoptosis, migration-related proteins and AKT phosphorylation activity. The mean comparison between the two groups was performed by t-test, and the comparison between multiple groups was performed by one-way analysis of variance. Results: Western blot showed that the expression of TRB3 was significantly up-regulated in HCC tissues. Compared with normal liver tissues adjacent to cancer, the relative expression levels were 0.78 ± 0.12 and 0.29 ± 0.09, respectively, P < 0.01, and the difference was statistically significant. After interfering siRNA inhibited TRB3, CCK8 and EdU tests showed that the proliferation activity of HepG2 and Huh7 cells were significantly weakened (P < 0.05). Flow cytometry results showed that the apoptotic proportions of HepG2 and Huh7 cells was significantly increased (P < 0.01). Western blot also showed that the expression of apoptosis regulatory proteins BAX and BIM were significantly increased (P < 0.01). Transwell assay results showed that the migration ability of HepG2 and Huh7 cells was decreased (P < 0.05), and the expression of migration regulatory proteins MMP4 and MMP9 was also significantly down-regulated. Western blot results showed that the AKT phosphorylation level was significantly increased. Conclusion: TRB3 regulates hepatocarcinoma cells proliferation, apoptosis and migration by inhibiting the AKT phosphorylation activity. Therefore, TRB3 may be a potential target site for the liver cancer treatment.

Insurance status and risk of suicide mortality among patients with cancer: a retrospective study based on the SEER database.

OBJECTIVE: Given that the presence of insurance may affect the risk of suicide mortality in cancer patients, we aimed to examine the association in a population-based study using the Surveillance, Epidemiologic, and End Results (SEER) database. STUDY DESIGN: A retrospective analysis of data from the SEER database. METHODS: We conducted a retrospective study using the SEER database. Hazard ratios (HRs), adjusted HRs (aHRs), and 95% confidence intervals (95% CIs) of suicide death were calculated using Cox proportional hazard models to evaluate the risk of suicide mortality among the cohorts. RESULTS: Multivariable analysis revealed that cancer patients without insurance had an increased risk of suicide death compared with patients with private insurance (aHR, 1.37; 95% CI, 1.01-1.72), whereas no significant result was observed in patients with any Medicaid (aHR, 1.10; 95% CI, 0.93-1.30; P = 0.27). In addition, the stratified analysis indicated that the risk of suicide death in patients in the uninsured and Medicaid groups presented with localized stage of disease (aHR, 1.32; 95% CI, 1.02, 1.69), White (aHR, 1.34; 95% CI, 1.05, 1.71), and American Indian/Alaska Native and Asian/Pacific Islander (aHR, 1.89; 95% CI, 1.08, 3.30) were greater than insured patients. CONCLUSION: Overall, our results indicated that insurance status was a statistically significant predictor of suicide death in patients with cancer. Healthcare providers should identify those patients at high risk of suicide and provide appropriate mental health and psychosocial oncology services in time.

LncRNA DCST1-AS1 accelerates the proliferation, metastasis and autophagy of hepatocellular carcinoma cell by AKT/mTOR signaling pathways.

OBJECTIVE: The previous research revealed that long noncoding RNAs (lncRNAs) play a vital role in the development of hepatocellular carcinoma (HCC). To further discuss the underlying mechanisms of lncRNA DCST1-AS1 in the pathogenesis of HCC. PATIENTS AND METHODS: We screened the abnormally expressed genes in HCC tissues through microarray analysis and found that lncRNA DCST1-AS1 was one of the genes significantly up-regulated. Real Time-Polymerase Chain Reaction (RT-qPCR) was used to test the gene expression of lncRNA DCST1-AS1 in HCC tissues and HepG2 cells. Respectively, CCK-8 assay, flow cytometry detection, transwell assay, wound healing assay, transmission electron microscopy, and immunofluorescence staining were used to assess the proliferation, apoptosis, migration, and autophagy of HepG2 cells. Meanwhile, the expression of signaling pathway proteins was detected by Western blot. RESULTS: LncRNA DCST1-AS1 was confirmed hyper-expression both in HCC tissues and HCC cells. High expression of lncRNA DCST1-AS1 was significantly correlated with inferior prognosis. Moreover, lncRNA DCST1-AS1 depletion suppressed proliferation and accelerated apoptosis, activated cycle arrest, restrained cell migration, and stimulated autophagy in HCC cells. In addition, it is found that the depletion of lncRNA DCST1-AS1 on HepG2 cells exhibits anti-tumor characteristics and was mediated by the AKT/mTOR signal transduction pathway. Furthermore, pre-treated HepG2 cells with SC79, an AKT signal activator, partially restored the effect of lncRNA DCST1-AS1 silencing on HepG2 cell proliferation, apoptosis, migration, and autophagy. CONCLUSIONS: Our results suggested that lncRNA DCST1-AS1, as a carcinogenic factor in HCC, promoted cell proliferation, and invasion, inhibited apoptosis and autophagy by modulating the AKT/mTOR signaling cascade. Therefore, our findings showed that lncRNA DCST1-AS1 may improve potential treatment strategies for HCC.

Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China.

BACKGROUND: Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown. PATIENTS AND METHODS: A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City. RESULTS: Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49). CONCLUSION: IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis. CLINICAL TRIAL NUMBER: NCT00941538.

[ß-catenin nuclear translocation represses thyroid cancer stem cells differentiating into cells with sodium-iodine symporter functional expression].

Objective: To confirm whether ß-catenin nuclear translocation in thyroid cancer stem cells can differentiate into thyroid cancer cells without functional membrane expression of sodium-iodine transporter (NIS) and be resistant to iodide 131 treatment. Methods: Thyroid cancer stem cells were firstly isolated as a side population (SP) from human thyroid cancer cell line FTC133. The SP cells from FTC133 were transfected with ß-catenin, and then differentiated. The cells were further collected for Western blot, Transwell and MTT assay to investigate the epithelial-mesenchymal transition (EMT) characteristics, tumor growth, invasion, and iodine uptake potency in vitro. Functional NIS expression and iodide uptake in differentiated cells were detected with immunofluorescent staining and iodide uptake assay, respectively. Subcutaneous severe combined immunodeficient (SCID) mice tumor model was induced with differentiated cancer cells to explore the in vivo effect of radioiodine treatment. Further immunohistochemical staining was performed to reveal the changes of functional proteins involved in tumor radioiodine treatment. Results: Side population was isolated from FTC133 accounting for about 0.03%, with high expression of stem cell markers and decreased expression of differentiated cell markers. Western blot showed prominent EMT phenotype in the differentiated cells from ß-catenin transfected stem cell model, with absence of epithelial expression of E-cadherin and cytokeratin 18, as well as abnormal expression of vimentin,fibronectin and urokinase-type plasminogen activator. Moreover,compared with cells differentiated from untransfected or empty plasmid transfected stem cells, in vitro proliferation markedly increased 85.4% and 81.0%, respectively (both P<0.01); while in vitro invasion augmented 78.8% and 84.4%, respectively (both P<0.01). Immunofluorescent staining identified that, after transfected with ß-catenin, differentiated cells underwent ß-catenin nuclear translocation and NIS localization transferred from membrane to plasma, compared with cells from untransfected or empty plasmid transfected stem cells. Cell iodide uptake in vitro decreased about 52.8% and 45.2%, respectively (both P<0.01). Furthermore, in vivo experiment further demonstrated that, cells differentiated from ß-catenin transfected stem cells were found with much higher tumor proliferation,tumor growth rate and larger tumor mass after radioiodine 131 treatment (both P<0.05). Conclusion: Induction of ß-catenin nuclear translocation in stem cells may generate differentiated thyroid cancer cells that are not sensitive to radioiodine treatment.

RUNX3 protects against acute lung injury by inhibiting the JAK2/STAT3 pathway in rats with severe acute pancreatitis.

OBJECTIVE: Acute lung injury (ALI) is the most common complication of severe acute pancreatitis (SAP) in the early stage, which causes systemic inflammatory response and organ damage. Human runt-associated transcription factor 3 gene (RUNX3) has been reported to participate in various inflammatory diseases. However, the exact role of RUNX3 in SAP and its-related ALI remains unclear. MATERIALS AND METHODS: To establish the model of SAP, rats were retrogradely injected with 5% sodium taurocholate (1 mg/kg body weight) into the biliary-pancreatic duct. Cytokine level in serum was measured by ELISA, and the polymorphonuclear neutrophil (PMN) was isolated from rat's blood 12 h-post SAP induction. RESULTS: We found RUNX3 expression was significantly decreased with the progression of SAP. Both pancreas damages and cytokine production abilities were reduced in RUXN3-overexpressed SAP rats compared with control rats. Moreover, SAP-associated ALI was also improved upon RUNX3 overexpression in SAP rats. RUNX3 upregulation enhanced PMN apoptosis and inhibited Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) phosphorylation. CONCLUSIONS: Our study indicates that RUNX3 protects against SAP and SAP-associated ALI through controlling PMN apoptosis and regulating JAK2/STAT3 signaling pathway. RUNX3 could be regarded as a potent therapeutic target in SAP for future studies.

[Clinical analysis and surgical treatment evaluation of 23 cases with primary parapharyngeal space tumors].

Objective: To analyze the clinical characters and surgical treatment of primary parapharyngeal space (PPS) tumors. Methods: A total of 23 cases of primary PPS tumors which were treated from November 2011 to December 2017 were included for the retrospective analysis in this study. Results: Twenty-three cases of patients with primary PPS tumors were analyzed in this study. Surgical approach was as follows: transcervial approach applied in 7 cases, transparotid approach in 4 cases, transoral approach in 2 cases, transmandibular approach in 4 cases, and the combined approaches on 6 cases. Besides, among 7 cases with upper PPS tumor, we applied the surgical navigation system in the surgery of 3 cases. The mean surgery duration of these cases, 3.5 h, was shorter than unused ones, while the mean maximum size (MMS) of tumors, 5.7 cm, was also larger. So far, 23 cases had no recurrence and metastasis. The most frequent histopathological type of all the cases was pleomorphic adenoma (8 cases), followed by Schwannoma (5 cases). With an 8-to-72-months follow up, 23 cases had no recurrence, metastasis or death. Conclusions: Surgical resection is preferred in the treatment of PPS tumors. In the upper PPS tumor cases, the surgical navigation system could reduce the operative duration significantly and is more suitable for larger tumors.

[Screening of differentially expressed genes of allergic rhinitis with asthma].

Objective:To detect the differentially expressed genes of allergic rhinitis(AR) with asthma and screen the pathogenic genes. Method: Eight nasal mucosa tissue samples from patients with nasal septum deviation (healthy control group), eight nasal mucosa tissue samples from patients with allergic rhinitis（AR） and eight nasal mucosa tissue samples from patients with AR and asthma were collected. Allergy & Asthma PCR Array was used to analyze allergy related genes expression level. Result: Compared to the control group, there are 84 related genes were found and 15 genes were up-regulated, 69 genes were down-regulated. Furthermore, there are 17 genes（ADAM33, BCL6, IFNGR2, IL12A, IL12B, IL13RA1, IL17A, IL31, IL4R, IL5, KIT, LTB4R, MS4A2, RORC, STAT5A, STAT6, TBX21） differentially expressed. Compared AR with asthma group to the AR group, there was 1 gene differentially expressed(RORC). Conclusion: ADAM33, BCL6, IFNGR2, IL12A, IL12B, IL13RA1, IL17A, IL31, IL4R, IL5, KIT, LTB4R, MS4A2, RORC, STAT5A, STAT6, TBX21 are the possible pathogenic genes of AR with asthma. RORC may be the specific marker gene in asthma induced by allergic rhinitis.

[Application of pegylated recombinant human granulocyte colony-stimulating factor to prevent chemotherapy-induced neutropenia in patients with lymphoma: a prospective, multicenter, open-label clinical trial].

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion: During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

Xanthine dehydrogenase downregulation promotes TGFß signaling and cancer stem cell-related gene expression in hepatocellular carcinoma.

Xanthine dehydrogenase (XDH), a rate-limiting enzyme involved in purine metabolism, has an essential role in inflammatory cascades. Researchers have known for decades that XDH activity is decreased in some cancers, including hepatocellular carcinoma (HCC). However, the role of XDH in cancer pathogenesis has not been fully explored. In this study, we showed that low XDH mRNA levels were correlated with higher tumor stages and poorer prognoses in patients with HCC. Knocking down or inhibiting XDH promoted migration and invasion but not proliferation of HCC cells. The abovementioned phenotypic changes are dependent on increases in epithelial-mesenchymal transition marker gene expression and transforming growth factor-ß-Smad2/3 signaling activity in HCC. XDH overexpression suppressed HCC cell invasion in vitro and in vivo. In addition, the expression and activity of XDH were associated with the expression of CSC-related genes, such as CD44 or CD133, in HCC cells. These data suggest that downregulated XDH expression may be a useful clinical indicator and contribute to the development and progression of HCC.

Open peroral endoscopic myotomy (O-POEM) for the treatment of achalasia.

With the development of endoscopic interventions and inspired by the success of peroral endoscopic myotomy (POEM) for the treatment of achalasia, we investigated an old method of direct peroral endoscopic myotomy without a submucosal tunnel for the treatment of achalasia, which we call open peroral endoscopic myotomy (O-POEM). In this study, Clinical success was achieved in the patient after O-POEM. A reduction of LES pressure, Eckardt score, and a timed barium esophagogram were observed during follow-up. There were no severe complications and no recurrences during two months of follow-up. Therefore, open peroral endoscopic myotomy is a feasible and effective endoscopic treatment modality for achalasia. However, long-term outcomes of O-POEM requires further follow-up.