[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[Epidemiological investigation of iron deficiency among preschool children in 10 provinces, autonomous regions, or municipalities in China].

Objective: To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China. Methods: A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test. Results: A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) µg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region (χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference (χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) (χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant (χ2=0.51, P=0.476). Conclusions: There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Long-term evaluation and physical and mental effects of residual tinnitus following treatment of sudden hearing loss].

Objective: To clarify the long-term characteristics of tinnitus following treatment of sudden deafness and its long-term physical and mental effects on patients. Methods: A retrospective analysis was performed on 88 patients (46 males and 42 females; Age from 11 to 89 years) with sudden deafness treated in Department of Otoscope Surgery of Peoples's Libration Army General Hospital in Beijing from April 2020 to January 2021, and the occurrence of tinnitus and treatment effect of all patients were analyzed. Follow-up was conducted for patients with residual tinnitus after treatment for more than 1 year by the investigation and filling in the survey information collection form, Tinnitus Evaluation Questionnaire (TEQ) and Tinnitus Handicap Inventory (THI). Descriptive statistics and SPSS 22.0 software were used for statistical data analysis. Results: In this study, 93.2% (82/88) of patients with sudden deafness were accompanied by tinnitus at the onset, and the proportion of long-term tinnitus after treatment was 90.2% (74/82). After 1 year of treatment for sudden deafness, the improvement of tinnitus was significant in low-frequency sudden deafness compared with those of high-frequency, flat and total deafness sudden deafness (χ2 value was 6.801, 4.568 and 4.038, all P<0.05). In patients with residual tinnitus, 9 (12.2%) patients felt minimal loudness or even no loudness, 34 (46.0%) patients felt slight loudness, 28 (37.8%) patients felt tinnitus was relatively loud, and 3 (4.1%) patients felt tinnitus was loud or noisy. Nine (12.2%) patients's sleep was often affected, 41 (55.4%) patients's sleep was sometimes affected, 9 (12.2%) patients's sleep was rarely affected, 15 (20.3%) patients's sleep was almost not affected. Twenty-eight (37.8%) patients basically completely adapted to tinnitus and 46 (62.2%) patients did not completely adapted to residual tinnitus. Eight (10.8%) patients had no impact on life, 39 (52.7%) patients had slight impact, 22 (29.7%) patients had moderate impact, and the other 5 (6.8%) patients had greater impact. According to tinnitus evaluation questionnaire(TEQ), there were 12 cases (16.2%) of grade Ⅰ, 26 cases (35.1%) of grade Ⅱ, 28 cases (37.8%) of grade Ⅲ, 7 cases (9.5%) of grade Ⅳ and 1 case (1.4%) of grade Ⅴ. According to tinnitus handicap inventory(THI), tinnitus disability was classified into grade Ⅰ, 22 cases (29.7%), grade Ⅱ, 14 cases (18.9%), Grade Ⅲ, 27 cases (36.5%) and grade Ⅳ, 11 cases (14.9%). Conclusion: The rate of residual tinnitus following treatment of sudden deafness is high. Some of the patients can completely adapt residual tinnitus after one year, but some of them will be affected when sleep, work and study. Residual tinnitus can lead to tinnitus disability in different degrees.

HOXA13 upregulation in gastric cancer is associated with enhanced cancer cell invasion and epithelial-to-mesenchymal transition.

The article "HOXA13 upregulation in gastric cancer is associated with enhanced cancer cell invasion and epithelial-to-mesenchymal transition, by Y.-X. He, X.-H. Song, Z.-Y. Zhao, H. Zhao, published in Eur Rev Med Pharmacol Sci 2017; 21 (2): 258-265-PMID: 28165563" has been retracted by the authors due to controversial issues with author contributions. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/12092.

[Evaluation and embolization strategy by ASITN/SIR grade for injured internal carotid artery of nasopharyngeal carcinoma].

Objective: To study the strategy of endovascular treatment for patients with the risks of internal carotid artery (ICA) rupture and bleeding during the treatment of nasopharyngeal carcinoma (NPC) based on American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grade of collateral circulation. Methods: A total of 56 patients (45 males and 11 females, aged from 28 to 76 years old) diagnosed with nasopharyngeal carcinoma and admitted to the Department of Neurosurgery, the Third Affiliated Hospital of Southern Medical University from July 2018 to January 2020 were retrospectively analyzed. There were 15 cases of ASITN/SIR grade 4, 24 cases of ASITN/SIR grade 3, 5 cases of ASITN/SIR grade 2, 5 cases of ASITN/SIR grade 1, and 7 cases of ASITN/SIR grade 0. The events of stroke and death were analyzed statistically. Results: ALL patients with ASITN/SIR grade 4 or 3 and some of patients with ASITN/SIR grades 2-0 passed balloon occlusion test and electrophysiological monitoring. ICA pseudoaneurysm was found in 35 patients, and one-stage ICA embolization was performed in 29 patients after evaluation. Among them, 8 cases of ASITN/SIR grade 4 and 10 cases of ASITN/SIR grade 3 with obvious posterior circulation compensation obtained successful one-stage ICA embolization without cerebral ischemia; cerebral ischemic events occurred in 5 (55.6%) of 9 patients with ASITN/SIR grade 3 and in 1(50.0%) of 2 patients with ASITN/SIR grade 2. The total incidence of ischemic events was 20.7% (6/29) and 1 case was disabled (1/29, 3.4%). Among patients with ASITN/SIR 3, there were statistically significant differences in stroke event rate between patients with obvious posterior circulation compensation and patients with slight or without posterior circulation compensation (0/10 vs. 5/9, χ(2)=4.95, P=0.026). Follow-up time was 10.1±7.8 months, and 46 patients were survival (46/56, 82.1%) and 10 patients died (10/56, 17.9%) with a mean survival time of 2.6±1.4 months. Conclusions: For NPC patients with ICA invasion, ASITN/SIR based on DSA can simplify the assessment process of cerebral blood flow compensation. ICA can be embolized directly in patients with ASITN/SIR 4 or 3 with obvious posterior communicating compensation.

Long non-coding RNA TUG1 regulates the progression and metastasis of osteosarcoma cells via miR-140-5p/PFN2 axis.

OBJECTIVE: Osteosarcoma (OS) is a frequently occurred tumor. Recently, increasing reports disclosed that long non-coding RNA taurine upregulated gene 1 (TUG1) was associated with OS development. Nevertheless, the precise regulatory pattern was not completely understood. Hence, we aimed to investigate the biological role of TUG1 in OS tumorigenesis. PATIENTS AND METHODS: The levels of TUG1, microRNA-140-5p (miR-140-5p), and Profilin 2 (PFN2) were measured via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the protein level of PNF2 was assessed using Western blot. In addition, MTT assay was employed to detect the ability of cell proliferation in MG63 and U2OS cells. Cell migration and invasion were estimated adopting transwell assay. Moreover, the Dual-Luciferase reporter assay was performed to verify the interrelation between miR-140-5p and TUG1 or PFN2. RESULTS: TUG1 and PFN2 levels were evidently upregulated in OS tissues and cell lines. The knockdown of either TUG1 or PFN2 could restrain cell proliferation, migration, and invasion in OS cells. In addition, miR-140-5p was a target of TUG1 to regulate PFN2. The functions of PFN2 knockdown in cell behaviors were rescued after co-transfection with either miR-140-5p inhibitor or overexpression vector of TUG1. Importantly, TUG1 silencing could impede tumor progression in vivo. CONCLUSIONS: TUG1 modulated cell proliferation, migration, and invasion via miR-140-5p/PFN2 axis in OS progression, which might trigger the development of therapeutic strategies for the treatment of OS.

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.

Connexin 43 enhances oxaliplatin cytotoxicity in colorectal cancer cell lines.

Oxaliplatin, a platinum-based chemotherapeutic agent, is an important first-line drug in the treatment of colorectal cancers, but drug resistance causes treatment failure. It has been reported that gap junctional communication can enhance the cytotoxicity of platinum drugs.  The gap junction formed of connexin proteins provides a direct pathway for electrical and metabolic cell-cell interaction. The voltage-dependent gating of gap junction allows small hydrophilic molecules and ions to permeate to adjacent cells. Connexin 43 is a diagnostic marker for cancer therapy and the predominant connexin isoform in many cell types. The purpose of this study was to investigate the role of connexin 43 in oxaliplatin activity by using colorectal cancer cell lines. LoVo and HCT116 cell lines were used for analysis. Connexin 43 expression was confirmed by western blot and immunocytochemistry. MTT, western blot, "Parachute" dye-coupling assays and reactive oxygen species measurement were used to detect cytotoxicity and the inhibition of connexin 43 expression induced by oxaliplatin. Results showed that connexin 43 enhanced oxaliplatin cytotoxicity through gap junctional communication function and high concentration of oxaliplatin inhibited connexin 43 expression to counteract its cytotoxicity. This study suggested that connexin 43 could be considered a molecular target of oxaliplatin activity in colorectal cancer.

HOXA13 upregulation in gastric cancer is associated with enhanced cancer cell invasion and epithelial-to-mesenchymal transition.

OBJECTIVE: In this study, we investigated the association between HOXA13 dysregulation and gastric cancer progression. We also explored the functional role of HOXA13 in invasion and epithelial-to-mesenchymal transition (EMT) of gastric cancer cells and the possible signaling pathway it might involve in. MATERIALS AND METHODS: The microarray (E-GEOD-19826) examined the transcription profiles of 12 adjacent normal/tumor-matched gastric tissues was downloaded from the ArrayExpress and reanalyzed. Immunohistochemistry (IHC) staining was performed to assess HOXA13 expression in 23 stage I and 69 stage II/III/IV gastric cancer tissues. The human gastric cancer cell line AGS and SGC-7901 cells were transfected with HOXA13 siRNA and then were subjected to detection of epithelial and mesenchymal markers and cell invasion. The involvement of HOXA13 in TGF-ß signaling was further studied. RESULTS: HOXA13 is one of the most upregulated genes in gastric cancer tissues compared to adjacent normal tissues. Also, HOXA13 is further upregulated in the higher stage tumors. HOXA13 staining was significantly stronger in stage II/III/IV tumors than in stage I tumors. HOXA13 siRNA significantly restored the epithelial property and reduced the mesenchymal property of the cancer cells. Transwell assay showed that HOXA13 siRNA impaired the invasion capability of the cancer cells. The gastric cancer cells with HOXA13 knockdown had decreased expression of p-SMAD2 and p-SMAD3. CONCLUSIONS: This study provides additional evidence about the association between HOXA13 upregulation and gastric cancer progression. Also, we showed that HOXA13 contributes to invasion and EMT of gastric cancer cells via the TGF-b signaling pathway.

Relationship between the gene polymorphism of osteoprotegerin and bone mineral density in hemodialysis patients.

OBJECTIVE: To investigate the relationship between the gene polymorphism of osteoprotegerin (OPG) and bone mineral density (BMD) in hemodialysis patients. PATIENTS AND METHODS: A total of 147 patients with end-stage renal disease (ESRD) who were admitted to the Weifang People's Hospital for maintenance hemodialysis between January 2014 and December 2015 were enrolled. Peripheral blood was collected from the subjects for assay of the polymorphism of A163G and G1181C loci of OPG. The measurements of the levels of RANK, RANKL, TNF-α, IL-6, PINP, CTX-I, CTX-II and TRACP5 in the isolated serum were taken. RESULTS: For the polymorphism of A163G locus on the OPG gene, the BMDs of left femoral neck and lumbar poster anterior L1-L4 of the AA genotype were significantly higher than those of the AG and GG genotypes. There was no significant difference in comparison of BMDs at the forearm (distal 1/3) between the AA genotype and AG and GG genotypes. No significant differences were found in the comparison of BMDs at all sites between AG and GG genotypes. The serum level of RANKL of the AA genotype was significantly higher than levels of AG and GG genotypes, but the levels of RANK, TNF-α, IL-6, PINP, CTX-I, CTX-II and TRACP5 were prominently lower than those levels of AG and GG genotypes. For the polymorphism of G1181C locus on the OPG gene, the BMDs of left femoral neck and lumbar poster anterior L1-L4 of the CC genotype were significantly higher than the BMDs of GG and GC genotypes, There was no significant difference in the comparison of BMDs at the forearm (distal 1/3) between the CC genotype and GG and GC genotypes. No significant differences were found in the comparison of BMDs at all sites between GG and GC genotypes. The serum level of RANKL of the CC genotype was significantly higher than the level of GG and GC genotypes. However, the levels of RANK, TNF-α, IL-6, PINP, CTX-I, CTX-II and TRACP5 were prominently lower than those levels of GG and GC genotypes. CONCLUSIONS: The polymorphisms of A163G and G1181C loci on the OPG gene were correlated with the BMD of hemodialysis patients. The genotype AA of A163G and genotype CC of G1181C were identified as the protective factors for BMD.

[Copy number variants analysis in whole-genome of patients with lipoma tethered cord syndrome].

Objective: To explore the abnormality of chromosomes of patients with lipoma tethered cord syndrome and the probable association between Copy Number Variations (CNV) and lipoma tethered cord syndrome. Methods: By using the Agilent SurePrint G3 Human CGH 8×60K Microarray Kit, we performed genome-wide screening for CNV on 11 patients with lipoma tethered cord syndrome adopted by the Neurosurgery Department of Chinese PLA General Hospital and their healthy parents from March 2015 to May 2015. We analyze CNVs got by the kit against the gene databases. Unrelated confirmed polymorphisms contained in Database of Genomic Variants (DGV) were discarded. Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER) helps us with similarity inquiry, and UCSC Genome Browser helps in identification of non-polymorphic CNV. Biological process, cellular component and molecular function enrichment of these genes were conducted to confirm the association between the CNV and lipoma tethered cord syndrome. Results: 17 CNV were discovered by aCGH in 11 patients. Chr8: 39258894-39386158 and Chr15: 20481702-22509254 showed a high frequency of 5/11. Angelman syndrome and Prader-Wolli syndrome were found to be associated with the CNV of Chr15. Gene function enrichment analysis revealed that ADAM5P and ADAM3A contained in CNV obtained from patients with lipoma tethered cord syndrome was also associated with orofacial clefts. Conclusions: CNV in Chr8 and Chr15 of patients with lipoma tethered cord syndrome had a higher frequency than that of common human. It revealed that there is probable association between these two pieces of CNV and lipoma tethered cord syndrome. To explorer related genes or CNV, focusing on certain type of NTDs may increase the research efficiency and get more accurate results.

[Clinical efficacy of of endoscopic assisted open pathway combined with radiotherapy in the treatment of advanced maxillary sinus malignant tumor].

Objective:The aim of this study is to analyze the clinical effect of endoscopic assisted open pathway combined with radiotherapy in the treatment of patients with advanced maxillary sinus malignant tumor.Method:A retrospective analysis was performed on the survival of 29 patients with advanced maxillary sinus malignant tumor treated by endoscopic assisted open approach combined with radiotherapy.Result:A total of twenty nine patients with cancer lesions were successfully resected, of which 7 cases underwent preoperative radiotherapy plus surgery plus postoperative radiotherapy, 22 cases were treated by surgery plus radiotherapy after operation. The median follow up time was 60 months (23-129 months). The 3 year and 5 year survival rate of the patients was 72% and 61%, respectively (90% and 80% was in Ⅱ stage respectively. 63% and 51% was in Ⅲ+Ⅳ stage respectively).Conclusion:Endoscopic assisted open pathway combined with radiotherapy is an effective method for the treatment of maxillary sinus carcinoma, and it can still be well treated with preoperative radiotherapy in patients with stage Ⅳ without distant metastasis.

[Relationship and clinical significance between mutated BRAF with prophylactic central-neck nodal dissection in papillary thyroid carcinoma].

OBJECTIVE: To evaluate the molecular diagnosis marker of papillary thyroid carcinoma (PTC), the relationship between lymphatic metastasis of central neck compartment PTC, and the operation indication of prophylactic central neck dissection. METHODS: We conducted a retrospective study, including 275 PTC patients and detected their BRAF mutation rates during 2012 and 2014 and explored the risk factors of the central node lymphatic metastasis by Logistic regression model. RESULTS: Of the 275 PTC patients, 224 (81.5%) were female and 51 (18.5%) were male. BRAF mutational rates were 53.8% (148/275) and lymphatic metastasis 57.8% (159/275). Multivariate analysis showed calcification (OR(adjusted)=1.47, 95%CI: 1.10-1.98, P=0.01), tumor diameter (OR(adjusted)=1.48, 95%CI: 1.04-2.30, P=0.048) and age (OR(adjusted)=1.48, 95%CI: 1.04-2.30, P=0.048) were associated with lymphatic metastasis. In stratified analysis, BRAF mutation (OR(adjusted)=3.19, 95%CI: 1.18-9.43, P=0.023) in clear boarder group and BRAF mutation (OR(adjusted)=4.84, 95%CI: 1.68-13.84, P=0.003) in calcification group were more likely to have lymphatic metastases. CONCLUSION: Central neck metastasis takes up a high ratio in papillary thyroid cancer patients, BRAF mutation in papillary thyroid carcinoma is a characteristic molecular event. Furthermore, patients with calcification under ultrasound detection, lower age group and longer tumor diameter are more susceptible to suffer central neck metastasis. Especially for stratified analysis, non-calcified BRAF mutation or BRAF mutation with clear border under ultrasound detection are more susceptible to suffer central neck metastasis, and radical prophylactic central neck dissection should be carried on for these patients.

Comparative study of neural differentiation of bone marrow mesenchymal stem cells by different induction methods.

Neurogenic differentiation of bone marrow (BM) mesenchymal stem cells (MSCs) offers a new hope for patients with many neurological disorders. Several chemical inducers are employed to induce BMMSCs differentiation into nerve cells. In the present study, we compared different inducers [2-mercaptoethanol (BME), tretinoin (ATRA), dimethyl sulfoxide/butylated hydroxyanisole (DMSO/BHA), and indomethacin/3-isobutyl-1-methylxanthine (indomethacin/IBMX)] on the neurogenic differentiation of BMMSCs and aimed to identify a more efficient and safer method. The MSCs were first identified by their ability to adhere to plastic and by the expression of positive (CD44, CD90, and CD105) and negative (CD34) markers assessed by flow cytometry. The efficiency of the neurogenic differentiation was determined by assessing the mRNA and protein expression of nestin, microtubule-associated protein-2 (MAP2), neuron specific enolase (NSE), and glial fibrillary acidic protein (GFAP) by reverse transcription-polymerase chain reaction and western-blot, respectively. The effect of these inducers on cell viability was also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. This comprehensive study shows that indomethacin/IBMX is better than BME, DMSO/BHA, and ATRA both in terms of efficiency and safety, while BME suppressed the growth and proliferation of MSCs.

The relationship between the alternative exon 7 splice variant of the BF gene and MHC-related Marek's disease resistance in chickens.

The study was to analyse the relationship between the alternative exon 7 splice variant of the BF gene and MHC-related Marek's disease (MD) resistance in chickens. The experiment first determined whether or not the cocks of Xiayan chickens have alternative splicing-out of the exon 7 of the BF gene from peripheral blood leucocytes (PBLs). Then, selected two groups: Group K included the offspring of the selected cocks which have no alternative splicing-out of the exon 7 of the BF gene; Group Y included the offspring of the selected cocks which have alternative splicing-out of the exon 7 of the BF gene. All hens used in the cross-breeding were non-selected. The experimental chickens were challenged with a very virulent strain of Marek's disease virus (MDV) at 4 days old and were raised for 12 weeks. At this time, all the surviving chickens were killed and necropsy was also performed during the experiment whenever chickens died from the infection. Tumour incidence and mortality were calculated using SPSS, and the tissues were collected to detect MDV by PCR. The results showed that the mortalities of Group K and Y were 52.75% and 70.65%, respectively; and that the tumour incidences of non-alternative splicing-out of the exon 7 of the BF for Groups K and Y were 15.38% and 38.89%, respectively; the tumour incidences for the alternative splicing-out of the exon 7 were 46.15% and 56.76%, respectively. The results demonstrated the tumour incidence was highly related with the alternative exon 7 splice variant of the BF gene (P < 0.05).

Neurobehavioural analysis of developmental iron deficiency in Oreochromis aureus × Oreochromis niloticus.

The objective of this study was to examine the association between brain iron measurements of monoamine function and behavioural measurements of learning and memory. Male hybrid tilapias Oreochromis aureus × Oreochromis niloticus were fed either an iron-deficient (ID) diet or an iron-adequate (IA) diet for 8 weeks. The ID fishes showed significantly lower iron content in brain and decreasing learning and memory capacity. The fishes that showed increased learning and memory capacity had higher levels of iron and monoamine oxidase activity in brain. In addition, the results showed that learning and memory behaviours were related to monoamine (dopamine and noradrenaline) concentration in the brain. This suggests that iron can enhance learning and memory capacity in fishes and that the effect may have monoaminergic mediation in discrimination learning and memory tasks. The experimental data suggest that the properties and neural basis of learning and memory of teleosts are notably similar to those of land vertebrates.

Molecular characterization of the pseudorabies virus UL2 gene.

A 948-bp sequence of the UL2 gene was amplified from the pseudorabies virus (PRV) Becker strain genome using polymerase chain reaction, and the gene identity was confirmed through further cloning and sequencing. Bioinformatic analysis indicated that the PRV UL2 gene encodes a putative polypeptide with 315-amino acid residues. Its encoding protein, designated UL2, has a conserved uracil-DNA glycosylase (UDG)_F1 domain, which is closely related to the herpesvirus UDG family and is highly conserved among its counterparts encoded by UDG genes. Multiple nucleic acid and amino acid sequence alignments suggested that the product of PRV UL2 has a relatively higher homology with UL2-like proteins of Alphaherpesvirinae than that of other subfamilies of Herpesviridae. In addition, phylogenetic analysis showed that PRV UL2 had a close evolutionary relationship with members of Alphaherpesvirinae, especially members of the genus Varicellovirus of bovine herpesvirus 1 and bovine herpesvirus 5. Antigen prediction indicated the presence of several potential B-cell epitopes in PRV UL2. In addition, secondary structure and 3-dimensional structure prediction revealed that PRV UL2 consisted predominantly of an α-helix. Taken together, these results provide molecular biological insight for the further study of the function and mechanism of UL2 during PRV infection.

Molecular cloning and characterization of the pseudorabies virus US1 gene.

Using polymerase chain reaction, a 1050-bp sequence of the US1 gene was amplified from the pseudorabies virus (PRV) Becker strain genome; identification of the US1 gene was confirmed by further cloning and sequencing. Bioinformatics analysis indicated that the PRV US1 gene encodes a putative polypeptide with 349 amino acids. The encoded protein, designated PICP22, had a conserved Herpes_IE68 domain, which was found to be closely related with the herpes virus immediate early regulatory protein family and is highly conserved among the counterparts encoded by Herpes_IE68 genes. Multiple nucleic acid sequence and amino acid sequence alignments suggested that the product of PRV US1 has a relatively higher homology with ICP22-like proteins of genus Varicellovirus than with those of other genera of Alphaherpesvirinae. In addition, phylogenetic analysis showed that PRV US1 has a close evolutionary relationship with members of the genus Varicellovirus, especially Equid herpes virus 1 (EHV-1), EHV-4 and EHV-9. Antigen prediction indicated that several potential B-cell epitopes are located in PICP22. Also, subcellular localization analysis demonstrated that PICP22 is predominantly located in the cytoplasm, suggesting that it might function as a cytoplasmic-targeted protein.

Prevalence of the metabolic syndrome in Zhejiang Chinese obese children and adolescents and the effect of metformin combined with lifestyle intervention.

OBJECTIVE: We aimed to evaluate the prevalence of metabolic syndrome (MS) in a group of obese children and adolescents in Zhejiang in the south of China, and to compare risk factors such as insulin resistance, adiponectin level and impaired glucose tolerance (IGT) etc with that of simple obese group (SOB) and non-obese healthy group, and also to evaluate the effect of metformin and lifestyle intervention in MS group by up to a 3-month follow-up. METHODS: Three hundred and forty eight moderately or severely obese adolescents aged between 7 and 16 years were enrolled. Oral glucose tolerance test (OGTT), biochemical indicators, blood pressure and body mass index (BMI) were assessed in all of them. Three subgroups were selected (MS group, SOB and healthy control). Adiponectin levels, Whole body insulin sensitive index (WBISI), homeostasis model of insulin resistance (HOMA-IR), plasma lipid and blood pressure were compared in these three groups. Thirty out of thirty-six MS subjects with age over 10 years received metformin treatment combined with lifestyle modification. RESULTS: (1) The prevalence of MS was 10.34% among all obese subjects, which increased with the severity of obesity and reached 22.1% in severely obese children and adolescents. The occurrence of more than one complication reached 72.13%. The incidence of type 2 diabetes and IGT were 1.44 and 1.44% respectively. (2) BMI, waist-to-hip ratio (WHR) and HOMA-IR increased stepwise in the control group, SOB and MS group, whereas serum adiponectin and WBISI decreased stepwise (all P<0.01). Systolic pressure, triglyceride, total cholesterol, low-density lipoprotein cholesterol and postprandial 2-h blood glucose in the MS group increased significantly compared to those in control and SOBs (all P<0.01). A correlation analysis showed that serum levels of adiponectin and WBISI were associated with the components of MS (all P<0.05). (3) After metformin and lifestyle intervention, clinical symptoms were ameliorated, serum adiponectin levels were actually increased and HOMA-IR was dropped in 20/30 MS children who had finished a 3-months follow-up (all P<0.01). CONCLUSION: The prevalence of MS in severely obese children and adolescents in Zhejiang area has reached a high level. Insulin resistance and hypoadiponectinemia were found in these MS children. Metformin combined with lifestyle modification was confirmed to be efficient and safe in treating the obese adolescents with MS.