[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.

[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.

[Clinical and genetic characteristics of young patients with myeloproliferative neoplasms].

Objectives: To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN). Methods: In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients. Results: 1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion: Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

Computer-assisted detection versus conventional colonoscopy for proximal colonic lesions: a multicenter, randomized, tandem-colonoscopy study.

BACKGROUND AND AIMS: Computer-assisted detection (CADe) is a promising technologic advance that enhances adenoma detection during colonoscopy. However, the role of CADe in reducing missed colonic lesions is uncertain. The aim of this study was to determine the miss rates of proximal colonic lesions by CADe and conventional colonoscopy. METHODS: This was a prospective, multicenter, randomized, tandem-colonoscopy study conducted in 3 Asian centers. Patients were randomized to receive CADe or conventional white-light colonoscopy during the first withdrawal of the proximal colon (cecum to splenic flexure), immediately followed by tandem examination of the proximal colon with white light in both groups. The primary outcome was adenoma/polyp miss rate, which was defined as any adenoma/polyp detected during the second examination. RESULTS: Of 223 patients (48.6% men; median age, 63 years) enrolled, 7 patients did not have tandem examination, leaving 108 patients in each group. There was no difference in the miss rate for proximal adenomas (CADe vs conventional: 20.0% vs 14.0%, P = .07) and polyps (26.7% vs 19.6%, P = .06). The CADe group, however, had significantly higher proximal polyp (58.0% vs 46.7%, P = .03) and adenoma (44.7% vs 34.6%, P = .04) detection rates than the conventional group. The mean number of proximal polyps and adenomas detected per patient during the first examination was also significantly higher in the CADe group (polyp: 1.20 vs .86, P = .03; adenoma, .91 vs .61, P = .03). Subgroup analysis showed that CADe enhanced proximal adenoma detection in patients with fair bowel preparation, shorter withdrawal time, and endoscopists with lower adenoma detection rate. CONCLUSIONS: This multicenter trial from Asia confirmed that CADe can further enhance proximal adenoma and polyp detection but may not be able to reduce the number of missed proximal colonic lesions. (Clinical trial registration number: NCT04294355.).

[Progress in the epidemiological studies on coal mine dust exposure with workers' health damage].

Coal is one of the major fuels, which brings huge energy and economic benefits to global industry and daily life. large amounts of coal dust produced in the process of coal mining and transportation, which seriously threatens the health of related workers. Productive coal dust exposure not only directly leads to respiratory diseases, but also may cause health damage to various systems throughout the body. Numerous studies have shown that coal dust exposure is closely associated with decreased lung function, coal worker's pneumoconiosis, chronic obstructive pulmonary disease, lung cancer, and cardiovascular diseases, and the severity of diseases is affected by coal rank, coal dust concentration, cumulative dust exposure, coal dust composition, and individual lifestyle, etc. The article comprehensively summarized the progress of the epidemiological studies on the health hazards of coal miners from coal dust exposure, in order to provide clues for further researches on health damage and protect the health of the occupational population.

[Clinical characteristics of 500 hospitalized patients with liver cirrhosis: a retrospective analysis from a tertiary hospital in Beijing].

Objective: To understand the clinical characteristics of hospitalized patients with liver cirrhosis, so as to provide theoretical basis for disease diagnosis and treatment, formulation of intervention measures, and improve the level of disease diagnosis and treatment. Methods: Hospitalized patients who were initially diagnosed with liver cirrhosis at Peking University First Hospital from August 2017 to December 2018 were selected retrospectively as the research objects. Liver cirrhosis demographic data, etiology, severity classification, incidence of complications, diagnosis and prognosis were recorded. Statistical analysis was performed using SPSS software. Results: Among all liver cirrhosis cases, there were 291 males and 209 females, with a male-to-female ratio of 1.4:1 and an age of 59.5±12.9 years as at August 2017 to December 2018. HBV infection, alcoholic liver disease, and autoimmune liver diseases were the most common etiology of liver cirrhosis. HBV infection alone, HBV infection combined with other factors, alcoholic liver disease alone, alcoholic liver disease combined with other factors, autoimmune liver disease alone, and autoimmune liver disease combined with other factors were presented in 163 (32.6%), 57 (11.4%), 47 (9.4%), 63 (12.6%), 85 (17.0%), and 22 (4.4.0%) cases, respectively. Ascites (221 cases, 44.2%), followed by esophagogastric varices (214 cases, 42.8%), and other including hypersplenism (137 cases), liver cancer (126 cases), upper digestive system tract hemorrhage (66 cases), hepatic encephalopathy (40 cases), infection (37 cases), portal vein thrombosis (23 cases), hepatorenal syndrome (20 cases) were the most common complications. The most common site of infection was the abdominal cavity (20 cases), accounting for 54.1%; followed by respiratory tract infection (8 cases), accounting for 21.6% in patients with liver cirrhosis with concurrent infection. Among them, there were 32 cases of bacterial infection alone, one case of bacterial infection combined with fungal infection, one case of bacterial infection combined with viral infection, and three cases of unknown pathogens. There were 69 cases in Child Pugh grade C, and the average hospitalization times were 12.6 days in terms of prognosis. There were total seven cases of death, of which five cases were due to upper gastrointestinal hemorrhage and two due to hepatic encephalopathy. Conclusion: HBV infection, ascites, and upper gastrointestinal bleeding were the most common etiologies, complications, and causes of death in patients with liver cirrhosis at our hospital.

MicroRNA-543 inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of triple-negative breast cancer cells via down-regulation of ACTL6A gene.

PURPOSE: To investigate the effect of microRNA-543 (miR-543) on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of triple-negative breast cancer (TNBC) cells, and the associated mechanism. METHODS: Human breast cancer cells (MDA-MB-231, HCC1937, and MCF-7, ZR-75-1) and normal human breast epithelial cell line (MCF10A) were transfected with miR-543 mimics or inhibitor using lipofectamine 2000. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the mRNA and protein expression levels of miR-543, actin-like protein 6A (ACTL6A), vimentin, Snail, and E-cadherin in breast cancer cells/tissue. Cell counting kit-8 (CCK-8), wound-healing, and Transwell assays were used to measure the effect of miR-543 on TNBC cell proliferation, invasion, and migration. Overall survival was determined using data from Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis and luciferase reporter gene assay were used to determine the regulatory effect of miR-543 on ACTL6A. RESULTS: The level of expression of miR-543 was significantly lower in breast cancer cells/tissue than in normal human breast epithelial cell/tissue (p < 0.05). MicroRNA-543 expression level was significantly reduced in TNBC cells/tissue, relative to the other breast cancer cells/normal breast tissue (p < 0.05). MicroRNA-543 significantly suppressed tumor growth and the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of TNBC cells, in mouse xenograft model (p < 0.05). CONCLUSIONS: miR-543 influences the biological behavior of TNBC cells by directly targeting ACTL6A gene. miR-543 could serve as a novel diagnostic and therapeutic target for TNBC.

[Controversy and progress on whether to retain left colonic artery in radical resection of rectal cancer].

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guideline 2019 recommended that lymph node dissection for advanced rectal cancer should include the lymphatic adipose tissue at the root of the inferior mesenteric vessels, but the ligation site of the inferior mesenteric artery (IMA) was not determined, and the NCCN guideline did not indicate clearly whether to retain the left colonic artery (LCA). Controversy over whether to retain LCA is no more than whether it can reduce the incidence of anastomotic complications or postoperative functional damage without affecting the patients' oncological outcome. Focusing on the above problems, this paper reviews the latest research progress. In conclusion, it is believed that the advantages of retaining LCA are supported by most studies, which can improve the blood supply of the proximal anastomosis, and technically can achieve the same range of lymph node dissection as IMA high ligation. However, whether it affects the survival of patients, reduces the incidence of anastomotic leakage, and improves the quality of life of patients, more high-quality evidence-based medical evidence is still needed.

[Treatment status of tyrosine kinase inhibitors in Chinese patients with chronic myeloid leukemia in 2020].

Objective: To investigate the current status of treatment choice and responses in patients with chronic myeloid leukemia (CML) in China. Methods: From the end of April to mid-May in 2020, a cross-sectional survey, by filling out a survey questionnaire, was conducted to explore the first-line choice of tyrosine kinase inhibitors (TKI) , current medications, drug switch and major molecular responses (MMR) as well as the variables associated with them in patients in China. Results: Data of 2933 respondents with CML from 31 provinces, municipalities, and autonomous regions across the country were included in this study. 1683 respondents (57.4%) were males. Median age was 38 (16-87) years old. 2481 respondents (84.6%) received imatinib as first-line TKI; 1803 (61.5%) , the original new drug (branded drug) . When completing the questionnaire, 1765 respondents (60.2%) were receiving imatinib; 1791 (61.1%) , branded drug. 1185 respondents (40.4%) had experienced TKI switch. With a median follow-up of 45 (3-227) months, 1417 of 1944 (72.9%) respondents with newly diagnosed CML in the chronic phase achieved MMR. Multivariate analysis showed that the respondents with urban household registration (OR=0.6, 95%CI 0.5-0.8, P<0.001) , ≥ bachelor degree (OR=0.5, 95%CI 0.4-0.7, P<0.001) , and in the advanced phase at diagnosis (OR=0.5, 95%CI 0.3-0.8, P=0.001) less preferred Chinese generic TKI, while the respondents from the central region in China more preferred Chinese generic TKI more than those from the eastern region (OR=1.7, 95%CI 1.4-2.0, P<0.001) . Moreover, the respondents in the advanced phase at diagnosis more preferred second-generation TKI (OR=5.4, 95%CI 3.6-8.2, P<0.001) ; those ≥60 years old, less preferred second-generation TKI (OR=0.4, 95%CI 0.2-0.7, P=0.002) . Being in the advanced phase at diagnosis (OR=2.2, 95%CI 1.6-3.2, P<0.001) , first-line choice of imatinib (OR=2.0, 95%CI 1.6-2.6, P<0.001) or Chinese generic drugs (OR=1.3, 95%CI 1.1-1.6, P=0.002) , longer interval from diagnose of CML to starting TKI treatment (OR=1.2, 95%CI 1.1-1.2, P<0.001) and longer duration of TKI therapy (OR=1.1, 95%CI 1.0-1.1, P<0.001) were significantly associated with TKI switch; urban household registration (OR=0.7, 95%CI 0.6-0.8, P<0.001) , ≥MMR (OR=0.6, 95%CI 0.5-0.8, P<0.001) and unknown response (OR=0.7, 95%CI 0.6-0.9, P=0.003) , no TKI switch. Female sex (OR=1.4, 95%CI 1.1-1.7, P=0.003) , urban household registration (OR=1.6, 95%CI 1.3-2.0, P<0.001) , front-line imatinib therapy (OR=1.4, 95%CI 1.1-1.9, P=0.016) and longer duration of TKI treatment (OR=1.2, 95%CI 1.2-1.3, P<0.001) were significantly associated with achieving a MMR or better response; age ≥ 60 years old (OR=0.7, 95%CI 0.4-1.0, P=0.047) and TKI switch (OR=0.6, 95%CI 0.5-0.7, P<0.001) , achieving no MMR. Conclusions: By 2020, the majority of Chinese CML patients received imatinib as the fist-line TKI therapy and continue to take it. More than half of TKIs were branded drugs. Socio-demographic characteristics and clinical variables affect their TKI choice, drug switch, and treatment response.

Surgical outcomes after radioactive 125I seed versus hookwire localization of non-palpable breast cancer: a multicentre randomized clinical trial.

BACKGROUND: Previous studies have suggested improved efficiency and patient outcomes with 125I seed compared with hookwire localization (HWL) in breast-conserving surgery, but high-level evidence of superior surgical outcomes is lacking. The aim of this multicentre pragmatic RCT was to compare re-excision and positive margin rates after localization using 125I seed or hookwire in women with non-palpable breast cancer. METHODS: Between September 2013 and March 2018, women with non-palpable breast cancer eligible for breast-conserving surgery were assigned randomly to preoperative localization using 125I seeds or hookwires. Randomization was stratified by lesion type (pure ductal carcinoma in situ (DCIS) or other) and study site. Primary endpoints were rates of re-excision and margin positivity. Secondary endpoints were resection volumes and weights. RESULTS: A total of 690 women were randomized at eight sites; 659 women remained after withdrawal (125I seed, 327; HWL, 332). Mean age was 60.3 years in the 125I seed group and 60.7 years in the HWL group, with no difference between the groups in preoperative lesion size (mean 13.2 mm). Lesions were pure DCIS in 25.9 per cent. The most common radiological lesion types were masses (46.9 per cent) and calcifications (28.2 per cent). The localization modality was ultrasonography in 65.5 per cent and mammography in 33.7 per cent. The re-excision rate after 125I seed localization was significantly lower than for HWL (13.9 versus 18.9 per cent respectively; P = 0.019). There were no significant differences in positive margin rates, or in specimen weights and volumes. CONCLUSION: Re-excision rates after breast-conserving surgery were significantly lower after 125I seed localization compared with HWL. Registration number: ACTRN12613000655741 (http://www.ANZCTR.org.au/).

[Health-related quality of life and its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms].

Objectives: To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) . Methods: In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) . Results: The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 (P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 (P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 (P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (|r| = 0.193-0.457, all P<0.001) , PV (|r| = 0.192-0.529, all P<0.01) , and MF (|r| = 0.180-0.488, all P<0.001) , respectively. Conclusions: HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.

[The role of DFO in Al (mal) (3)-induced ferroptosis in PC12 cells].

Objective: To investigate the mechanism of Al (mal) (3)-induced ferroptosis in rat adrenal pheochromocytoma cells (PC12), to explore the effect of deferoxamine (DFO) . Methods: Taken PC12 cells growing at logarithmic phase and divided into 6 groups: control group, 200 µmol/L Al (mal) (3) group, 0.5% DMSO group, 200 µmol/L DFO group, Al (mal) (3)+DMSO group, Al (mal) (3)+DFO group. DMSO and DFO were added to the DMSO group and the Al (mal) (3)+DMSO group, the DFO group and the Al (mal) (3)+DFO group for 2 h, respectively, Al (mal) (3) was then added to the Al (mal) (3) group, Al (mal) (3)+DMSO group, and the Al (mal) (3)+DFO group to a final concentration of 200 µmol/L. The cell viability was detected by CCK8, the morphology and ROS levels of PC12 cells was observed by inverted microscope, the cell proliferation toxicity and intracellular iron ion content were detected by colorimetry, the GSH content and GSH-PX activity were detected by biochemical method. Results: Al (mal) (3) exposure significantly inhibited the growth of PC12 cells and destroyed the cell morphological structure, resulting in increased LDH activity and intracellular iron ion content in PC12 cells, decreased GSH content and GSH-PX activity, increased ROS levels; the combined treatment of Al (mal) (3)+DFO can significantly improve the cell viability of PC12 cells, improved cell morphology, decreased cell LDH activity and intracellular iron ion content (P>0.05), increased GSH content and GSH-PX activity, decreased ROS levels. Conclusion: Al (mal) (3) can induce ferroptosis in PC12 cells, DFO may inhibit ferroptosis by reducing intracellular iron levels and reducing oxidative damage.

[Regulation of hypoxia inducible factor-1α on permeability of vascular endothelial cells and the mechanism].

Objective: To investigate the regulation of hypoxia-inducible factor-1α (HIF-1α) on permeability of rat vascular endothelial cells and the mechanism. Methods: Twelve male Sprague-Dawley rats aged 35 to 38 days were collected and vascular endothelial cells were separated and cultured. The morphology of cells was observed after 4 days of culture, and the following experiments were performed on the 2nd or 3rd passage of cells. (1) Rat vascular endothelial cells were collected and divided into blank control group, negative control group, HIF-1α interference sequence 1 group, HIF-1α interference sequence 2 group, and HIF-1α interference sequence 3 group according to the random number table (the same grouping method below), with 3 wells in each group. Cells in negative control group, HIF-1α interference sequence 1 group, HIF-1α interference sequence 2 group, and HIF-1α interference sequence 3 group were transfected with GV248 empty plasmid, recombinant plasmid respectively containing HIF-1α interference sequence 1, interference sequence 2, and interference sequence 3 with liposome 2000. Cells in blank control group were only transfected with liposome 2000. After transfection of 24 h, expression levels of HIF-1α mRNA and protein of cells in each group were respectively detected by reverse transcription real-time fluorescent quantitative polymerase chain reaction and Western blotting (the same detecting methods below) . The sequence with the highest interference efficiency was selected. (2) Another batch of rat vascular endothelial cells were collected and divided into blank control group, negative control group, and HIF-1α low expression group, with 3 wells in each group. Cells in blank control group were only transfected with liposome 2000, and cells in negative control group and HIF-1α low expression group were respectively transfected with GV248 empty plasmid and low expression HIF-1α recombinant plasmid selected in experiment (1) with liposome 2000. After 14 days of culture, the mRNA and protein expressions of HIF-1α in each group were detected. (3) Another batch of rat vascular endothelial cells were collected and divided into blank control group, negative control group, and HIF-1α high expression group, with 3 wells in each group. Cells in blank control group were transfected with liposome 2000, and cells in negative control group and HIF-1α high expression group were respectively transfected with GV230 empty plasmid and HIF-1α high expression recombinant plasmid with liposome 2000. After 14 days of culture, the mRNA and protein expressions of HIF-1α of cells in each group were detected. (4) After transfection of 24 h, cells of three groups in experiment (1) and three groups in experiment (2) were collected, and mRNA and protein expressions of myosin light chain kinase (MLCK), phosphorylated myosin light chain (p-MLC), and zonula occludens 1 (ZO-1) of cells were detected. Data were processed with one-way analysis of variance and t test. Results: After 4 days of culture, the cells were spindle-shaped, and rat vascular endothelial cells were successfully cultured. (1) The interference efficiencies of HIF-1α of cells in HIF-1α interference sequence 1 group, HIF-1α interference sequence 2 group, and HIF-1α interference sequence 3 group were 47.66%, 45.79%, and 62.62%, respectively, and the interference sequence 3 group had the highest interference efficiency. After transfection of 24 h, the mRNA and protein expression levels of HIF-1α of cells in interference sequence 3 group were significantly lower than those in blank control group (t=18.404, 9.140, P<0.01) and negative control group (t=15.099, 7.096, P<0.01). (2) After cultured for 14 days, the mRNA and protein expression levels of HIF-1α of cells in HIF-1α low expression group were significantly lower than those in blank control group (t=21.140, 5.440, P<0.01) and negative control group (t= 14.310, 5.210, P<0.01). (3) After cultured for 14 days, the mRNA and protein expression levels of HIF-1α of cells in HIF-1α high expression group were significantly higher than those in blank control group (t=19.160, 7.710, P<0.01) and negative control group (t= 19.890, 7.500, P<0.01). (4) After transfection of 24 h, the mRNA expression levels of MLCK and p-MLC of cells in HIF-1α low expression group were significantly lower than those in blank control group (t=2.709, 4.011, P<0.05 or P<0.01) and negative control group (t=2.373, 3.744, P<0.05 or P<0.01). The mRNA expression level of ZO-1 of cells in HIF-1α low expression group was significantly higher than that in blank control group and negative control group (t=4.285, 5.050, P<0.01). The mRNA expression levels of MLCK and p-MLC of cells in HIF-1α high expression group were significantly higher than those in blank control group (t=9.118, 11.313, P<0.01) and negative control group (t=9.073, 11.280, P<0.01). The mRNA expression level of ZO-1 of cells in HIF-1α high expression group was significantly lower than that in blank control group and negative control group (t=2.889, 2.640, P<0.05). (5) After transfection of 24 h, the protein expression levels of MLCK and p-MLC of cells in HIF-1α low expression group were significantly lower than those in blank control group (t=2.652, 3.983, P<0.05 or P<0.01) and negative control group (t=2.792, 4.065, P<0.05 or P<0.01). The protein expression of ZO-1 of cells in HIF-1α low expression group was significantly higher than that in blank control group and negative control group (t=3.881, 3.570, P<0.01). The protein expression levels of MLCK and p-MLC of cells in HIF-1α high expression group were 1.18±0.24 and 0.68±0.22, which were significantly higher than 0.41±0.21 and 0.35±0.14 in blank control group (t=5.011, 3.982, P<0.05 or P<0.01) and 0.43±0.20 and 0.36±0.12 in negative control group (t= 4.880, 3.862, P<0.05 or P<0.01). The protein expression level of ZO-1 of cells in HIF-1α high expression group was 0.08±0.06, which was significantly lower than 0.20±0.09 in blank control group and 0.19±0.09 in negative control group (t=4.178, 3.830, P<0.05 or P<0.01). Conclusions: HIF-1α up-regulates expressions of MLCK and p-MLC and down-regulates expression of ZO-1, thereby increasing the permeability of rat vascular endothelial cells.

A comprehensive study of risk factors for post-operative pneumonia following resection of meningioma.

BACKGROUND: Post-operative pneumonia (Pop) following meningioma surgery is the dominant systemic complication which could cause serious threats to patients. It is unclear whether hematological biochemical markers are independently associated with the Pop. This study attempted to perform a more comprehensive study of taking both clinical factors and hematological biomarkers into account to promote the management of patients after meningioma surgery. METHODS: We collected clinical and hematological parameters of 1156 patients undergoing meningioma resection from January 2009 to January 2013. According to whether the symptoms of pneumonia had manifested,patients were divided into the Pop group and the Non-Pop group. We analyzed the distinctions of clinical factors between the two groups. We successively performed univariate and multivariate regression analysis to identify risk factors independently associated with the Pop. RESULTS: 4.4% patients infected with the Pop (51 of 1156). The median age at diagnosis of the Pop patients was significantly older than the Non-Pop group (p = 0.002). There were strike distinctions of post-operative hospital stays between two groups, with 21 days and 7 days each (p < 0.001). On multivariate analysis, tumor relapse (p < 0.001), skull base lesions (p = 0.001), intra-operative blood transfusion (p = 0.018) and cardiovascular diseases (p = 0.001) were linked with increased risk of the Pop following meningioma resection. For hematological biochemical markers, it was the factor of Red blood cell distribution width-standard deviation (RDW-SD) (OR 5.267, 95%CI 1.316, 21.078; p = 0.019) and Neutrophils lymphocytes ratio (NLR) (OR 2.081, 95%CI 1.063, 4.067; p = 0.033) that could appreciably predict the Pop. CONCLUSIONS: Apart from tumor recurrence, localizations, intra-operative blood transfusion and cardiovascular diseases are independent risk factors for the Pop. We initially found hematological RDW-SD and NLR are also important predictors.

[Evaluation of quality of life on children with cochlear implants].

Objective:To provide theoretical basis for developing comprehensive and individualized rehabilitation programs,we evaluate the quality of life on children with cochlear implants（CI）and explore the influencing factors.Method:One hundred and three children with CI using the Mandaren children with cochlear implants: parental perspectives questionnaire were rated from communication, basic functions,independence ability, well-being,social relations, education, effect and influence of cochlear implants,and the support for children.The comparison was made according to different groups between duration of cochlear implants and age at assessment.Result:With the increasing of age at evaluation and the duration of cochlear implants,the scores of children in each dimension were also increased gradually.Four important factors affecting the quality of life of children with cochlear implants were the age at implantation,the duration of cochlear implants,the level of education with parents and the place of residence.Conclusion:The children with hearing impairment should use the cochlear implants as early as possible.While paying attention to the effect of postoperative hearing and speech rehabilitation,we should pay more attention to the evaluation of the quality of life,so that the children with cochlear implants can return to the mainstream society better.

Influence of Spin-Orbit Coupling in Iron-Based Superconductors.

We report on the influence of spin-orbit coupling (SOC) in Fe-based superconductors via application of circularly polarized spin and angle-resolved photoemission spectroscopy. We combine this technique in representative members of both the Fe-pnictides (LiFeAs) and Fe-chalcogenides (FeSe) with tight-binding calculations to establish an ubiquitous modification of the electronic structure in these materials imbued by SOC. At low energy, the influence of SOC is found to be concentrated on the hole pockets, where the largest superconducting gaps are typically found. This effect varies substantively with the k_{z} dispersion, and in FeSe we find SOC to be comparable to the energy scale of orbital order. These results contest descriptions of superconductivity in these materials in terms of pure spin-singlet eigenstates, raising questions regarding the possible pairing mechanisms and role of SOC therein.

Influence of inhibitors on the adhesion of SRB to the stainless steel in circulating cooling water.

Influence of the surface characteristics of three stainless steels (SS304, 316L and 317) and presence of scale inhibitors on adhesion kinetics of sulfate reducing bacteria (SRB) in circulating cooling water, were investigated by evaluating surface free energy, adhesion kinetic constants in a parallel plate flow chamber. Results show that the surface free energy values of SS317, SS316L and SS304 are -31.69, -24.18 and -13.92 mJ m-2, respectively. SS317 surface had higher surface hydrophobicity than SS316L and SS304. In the process of bacteria cells adhesion onto SS surfaces, electrostatic interaction for SS is slightly more than hydrophobic interaction. The number of adhering bacteria and the adhesion kinetic constants are different on the three types of stainless steel. The adhesion kinetic constants for SS317 and 316L are greater than that for SS304, which are 0.0354, 0.0282 and 0.0190 min-1, respectively. Scale inhibitors of hydrosy ethyl fork phosphonic acid (HEDP) and phosphono butane-1, 2, 4-tricarboxylic acid (PBTCA) have a certain influence on the initial adhesion of bacteria cell and adhesion kinetics constants are reduced in the presence of HEDP and PBTCA.

[Long non-coding RNA RAB11B-AS1 prevents osteosarcoma proliferation via its sense gene RAB11B].

Objective: To detect the expression of lncRNA RAB11B-AS1 in osteosarcoma and investigate its role in osteosarcoma cells proliferation and the responsible mechanisms. Methods: Osteosarcoma and corresponding adjacent normal tissues were collected from 24 patients subjected to operations from October 2015 to October 2017 in the Third Affiliated Hospital of Southern Medical University.RAB11B-AS1 expression was detected in osteosarcoma specimens by quantitative real-time polymerase chain reaction (qRT-PCR). Lentiviral vectors that stably over-expressing RAB11B-AS1 were constructed and transfected into U2OS osteosarcoma cell line.The effect of RAB11B-AS1 on osteosarcoma cell proliferation and apoptosis was investigated by cell counting kit (CCK-8) assay and flow cytometry.U2OS osteosarcoma xenograft model of nude mice was established to observe the effect of RAB11B-AS1 on xenograft growth in mice, and the role of RAB11B-AS1 in proliferation and apoptosis of osteosarcoma cells was investigated by immunohistochemistry and TUNEL staining of osteosarcoma slices.The relationship between RAB11B-AS1 and RAB11B was explored using luciferase reporter assay.The data were compared with t test between the two groups. Results: Expression of RAB11B-AS1 was significantly down-regulated in osteosarcoma (0.010±0.015) versus their paired non-neoplastic tissues (0.022±0.030) (t=2.117, P=0.045). Up-regulation of RAB11B-AS1 resulted in decreased proliferative rate of U2OS cells (F=15.659, P<0.001). The ratios of cells in G0-G1 phase, S phase, G2-M phase were 62.6%±6.3%, 21.4%±2.2%, 16.3%±1.6% respectively in RAB11B-AS1 up-regulated group versus 59.4%±5.9%, 25.9%±2.6%, 15.5%±1.1% respectively in control group, and cell ratio in G0-G1 and S phase were increased significantly by RAB11B-AS1 up-regulation (t=17.124, 17.321, both P<0.05). Apoptosis rate was significantly elevated in RAB11B-AS1 over-expressed cells (12.7%±1.3%) when compared with that in control (10.3%±1.0%)(t=17.321, P=0.003). Mice transplanted with osteosarcoma cells that overexpressed RAB11B-AS1 exhibited lower growth rate of tumor (F=8.798, P=0.009). Mechanistically, RAB11B-AS1 expression correlated negatively with RAB11B expression (r=-0.356, P=0.044). Conclusions: lncRNA RAB11B-AS1 expression is down-regulated significantly in osteosarcoma tissues.RAB11B-AS1 may suppress the progression of osteosarcoma via down-regulating RAB11B.