Objective To investigate the effect of high volume hemofiltration (HVHF) on expression of miRNA-146 in peripheral blood mononuclear cells in posttraumatic sepsis patients and its therapeutic mechanism.Methods Twenty-five cases of posttraumatic sepsis were included as HVHF group.Another 25 age-and gender-matched traumatic sepsis patients with similar APACHE-Ⅱ who received no HVHF treatment for some reasons were used as controls.Therapeutic measurements were the same of the two groups except for HVHF.At 0-,6-,12-,24-and 48-hour time points,the peripheral blood mononuclear cells were isolated from patients of both groups to detect level of miRNA-146.Peripheral blood mononuclear cells isolated at 24 hours were incubated with lipopolysaccharide (LPS) in vitro.At hours 4,8,12,24 and 48 after incubation,level of miRNA-146 in mononuclear cells was determined and levels of TNF-α,IL-6,and IL-10 in the substrate was detected by ELISA.Results (1) Level of miRNA-146 in HVHF group was decreased significantly over time as compared with that in sepsis group;(2) Before incubation and at 4-and 8-hour after incubation,miRNA-146 level was lowered significantly in HVHF group as compared with that in sepsis group.After LPS stimulation,mononuclear cell also presented a stronger inflammatory response in HVHF group than in sepsis group.Conclusions HVHF provides a definite effect on immune function recovery and a significant improvement in prognosis.Moreover,HVHF may attenuate the impact of miRNA-146 on mononuclear cell inflammatory factor release and enhance the cell ability to respond to external stimuli again via down-regulating miRNA-146,as may be one of the therapeutic mechanisms of HVHF for posttraumatic sepsis.

BACKGROUND: In the treatment of senile distal tibia fractures, locking compression plate (LCP) combined with minimally invasive percutaneous plate osteosynthesis (MIPO) exerts a satisfactory repair effect, and contributes to the function recovery of lower limbs.OBJECTIVE: To retrospectively analyze the efficacy of LCP combined with MIPO versus intramedullary interlocking nailing for senile distal tibia fractures.METHODS: Fifty-six elderly patients with distal tibia fracture were allotted to minimally invasive and intramedullary nailing groups (n=28 per group), and received the treatment of LCP combined with MIPO and intramedullary interlocking nailing fixation, respectively. The operation time, intraoperative blood loss, postoperative AOFAS ankle-hind foot scale scores, postoperative ambulation time, healing time, postoperative complications and the excellent and good rate in Johner-Wruhs' criteria were compared between two groups.RESULTS AND CONCLUSION: (1) The operation time, AOFAS ankle-hind foot scale scores, ambulation time, and healing time in the minimally invasive group were significantly superior to those in the intramedullary nailing group (P < 0.05). (2) The minimally invasive group showed a significantly higher excellent and good rate (96%) than the intramedullary nailing group (79%) (P < 0.05). (3) Compared with the intramedullary nailing group, the incidence of complications was significantly reduced in the minimally invasive group (P < 0.05). (4) Our findings suggest that the combination of LCP and MIPO not only preserves the most of blood supply, and soft tissues surrounding the fracture end as suggested by the BO principle, but also is conducive for fracture healing, and holds good efficacy.

Objective To understand willingness of current medical undergraduates to work at community health-care service(CHS)institutions after their graduation to provides information for professional training for them.Methods Totally,2714 medical undergraduate students were recruited from three medical schools in east,middle and west China by multi-level sampling methods for questionnaire survey on their basic information and willingness to be employed at CHS institutions.results of the survey were described by relative numeric and tested by chi-square test for smtistical inference.Results About 60.6%of medical undergraduate students were willing to work at CHS organizations permanently or temporarily.Their willingness to work there differed with their native living areas and grades they were studying significantly(P＜0.01).Reason for those they would work at CHS organizations after graduation included work less stress and easier,and that for those reluctant to work there included low-income and lack of social respect for general practitioners.Conclusions Nowadays,few medical undergraduate students would like to work at CHS organizations after their graduation,which was influenced mainly by traditional ideas and concepts of employment,personal career devdopment,economic income,and so on.It is suggested that ideas of community work be strengthened for medical undergraduate students and their employment concepts be changed in the future.

0.05).Conclusion The long-term curative effects of one end-to-side and double end-to-side neurorrhaphy are the same.The proximal end of the transected nerve can be reconnected with the distal end by double end-to-side neurorrhaphy,but the connected fibers have only partial effects on the recovery of the nerve.

Background Pancreatic cancer is a common malignant tumor of the digestive system.It is the fourth major cause of tumor-related death and its morbidity is increasing,and hence it is imperative to develop effective forms of therapy for pancreatic cancer.Peptide tyrosine-tyrosine (PYY) is an important gastrointestinal peptide hormone.According to previous literatures,PYY has been shown to inhibit tumor proliferation in cellular and animal models,but there has been limited research on the detailed mechanism of PYY in pancreatic cancer.This study was to observe the effects of PYY on pancreatic cancer cell and investigate the possible mechanism.Methods The expression of Y1,Y2,and Y5 receptors on pancreatic cancer cell lines were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR).The cytotoxicity of PYY toward the MiaPaCa-2 cell was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the cell morphology and structure changes were observed under inverted microscope and transmission electron microscope respectively.Apoptosis and cell cycle were evaluated by flow cytometry.The activity of caspase-3 was determined by activity assay kits and Western blotting.The expression of survivin,vascular endothelial growth factor (VEGF),and cyclooxygenase-2 (COX-2) were determined by RT-qPCR and Western blotting.Results Expression of Y2 receptor is the most abundant PYY receptor on pancreatic cancer cell.PYY inhibited MiaPaCa-2 cell proliferation,blocked it in G0/G1 phase,increased the proportion of apoptosis cells and caspase-3 activity,and reduced the expression of survivin,VEGF,and COX-2.Conclusions PYY weakened the ability of the pancreatic MiaPaCa-2 cell viability through cell cycle blocking and apoptosis inducing.The inhibition effect of PYY may be mediated by the Y2 receptor.The increased caspase-3 activity and reduced expression of survivin,VEGF,and COX-2 may serve as a novel mechanism in PYY inhibition effect on MiaPaCa-2 cell.

BACKGROUND: There is an intimate temporal and spatial relationship between growth of primitive cardiac cells, septum transversum mesenchyme and liver development. The signal from primitive cardiac cells and septum transversum mesenchyme induces the ventral foregut endoderm cells specialize toward hepatocytes. While the septum transversum mesenchyme provides a suitable environment for forming the liver bud and promoting the growth and differentiation. However, the molecular mechanism of this induction is not yet delineated.OBJECTIVE: Using alpha-fetal protein (AFP), c-Met and cytokeratin (CK) 19 as markers of hepatic stem cells, the growth of early human embryo of 3-5 weeks and morphologic characteristic of hepatic stem cells were observed to demonstrate the characteristic and factors that affected the proliferation and differentiation of hepatic stem cell, which provided experimental evidence for basic research and clinical application of hepatic stem cells.DESIGN: An opening experiment was designed.SETTING: Department of Anatomy, Weifang Medical College.MATERIALS: The experiment was carried out at the Scientific Research Center of Chengdu Medical College between September 2004 and January 2005. Twenty cases fresh human embryos aged less than 2 months were collected with signed agreements of the pregnant women suffering from pregnancy termination with mifepristone. The samples were fixed with 40 g/L polymerisatum in 20 minutes and embedded routinely in paraffin, and then 5 μm thick series sections were continuously made. After hematoxylin-eosin staining, the embryonicage was determined under the microscope according to the length of embryos, the number of somites and the development of organs, which was referring to the Jirasek's staging standard of human embryo.METHODS: The immunohistochemical staining was conducted with SABC method on one of every ten sections, which were incubated overnight at 4 ℃ with polyclonal antibodies against hepatocyte growth factor (HGF),c-Met, insulin-like growth factor (IGF-Ⅰ), IGF-Ⅰ receptor (IGF-IR), transforming growth factor (TGFβ1), TGFβR1, TGFβR2 or monoclonal antibodies against proliferating cell nuclear antigen (PCNA), AFP and CK19.The following day, the sections were incubated for 2 hours at room temperature with biotinylated anti-mouse or anti-rabbit IgG and SABC liquid respectively, and then diaminobenzidine (DAB) was used to color them. The negative control was conducted with the phosphate buffer, then the sections were observed and photographed under light microscope.MAIN OUTCOME MEASUERS: ①the morphologic characteristic of human hepatic stem cells and immunohistochemical staining of markers②the expression of HGF, IGF-Ⅰ, TGFβ1 and their receptors on human embryonic livers of 3-5 weeks, primitive cardiac cells and septum transversum mesenchyme.RESULTS: ①The morphologic characteristic of human hepatic stem cells and immunohistochemical staining of markers: The hepatic bud formed at the end of 3rd week and migrated into the septum transversum mesenchyme to form the hepatic cords at the 4th week. The cells structuring the hepatic cords displayed the typical characteristic of immature cells. At the 5th week, the number of cells within the hepatic cords, the size of cell body,the cytoplasmic acidophilia all increased, whereas the basophilia of nuclei decreased. However the cellular forms were still homogeneous and displayed the typical characteristic of immature cells. The cells of hepatic cords were negative for PCNA response during 3rd-4th week but began to express positive at the 5th week, mainly in the nucleus and minority cellular cytoplasm showed weak positive. Most hepatic cells during 3rd-5th weeks were positive for AFP, c-Met and negative for CK19. The immunologic reaction depositors of AFP positive cells were located in the nuclei, cytoplasm and membrane of the hepatocytes, and c-Met presented mainly in the nuclei and the positive signal was weak in the cytoplasm. ②Expressions of HGF, IGF-Ⅰ, TGFβ1 and their receptors in the embryonic human liver, primitive heart and septum transversum mesenchyme: At the 4th week,the c-Met expressed only in all hepatocytes, whereas the other growth factors and their receptors were undetectable. At the 5th week, all the growth factors, except HGF, were expressed in the hepatocytes. The immunologic reaction depositors of TGFβ1, TGFβ1R1 and TGFβ1R2 were located in the cytoplasm and cell membrane. The positive response of IGF-Ⅰ and IGF-IR were present at nuclei, cytoplasm and cell membrane. At the 3rd-5th week, myocardial cells surrounding liver bud or hepatic cord and the septum transversum mesenchyme were positive for HGF, TGFβ1 and IGF-Ⅰ,with the signals were aggregated mainly in cytoplasm and minority nucei.CONCLUSION: ①It was at the end of 3rd week that part of endoderm cells in foregut ventral were specialized to hepatic stem cells. ②The undifferentiated hepatic stem cells could be drawn to develop to the liver stem cells with bi-directional differentiation potentials by using specific markers for studying human embryonic liver stem cells. According to the corresponding relation of embryonic age between human and rats, the time studying the rat hepatic stem cells could be calculated. ③HGF, IGF-Ⅰ,TGFβ1 and their receptors promoted the early development of human embryonic liver.

Previous studies have suggested that various kinds of inflammatory factors can influence the formation and development of tumor cells.Researche has shown that gallbladder cancer is closely linked with local inflammation,which is a risk factor for the development of gallbladder cancer.It is widely known that cholecystitis is closely correlated with gallstones,and that bile obtained from patients with gallbladder cancer contains a large variety of bacteria,such as Salmonella typhi,Helicobacter,and Escherichia coli.It is proposed that the gallbladder may be the result of the joint action of inflammation with the bacterial flora.Similarly,the inflammatory “tumor infiltrating lymphocyte” (TIL)can be observed in the tumor and its surrounding tissues,and may also play a role in tumor growth and metastasis.However,detailed mechanisms about the relationship between inflammation and gallbladder cancer is still not clear.No specific anti-inflammatory drugs for gallbladder cancer have been developed. In the near future,anti inflammatory drugs may play a more important role in gallbladder cancer prevention and treatment.

Objective To study the effect of pioglitazone on the differentiation and function of rat osteoclast-like cells (OLC), and to probe the relationship between activated PPARγ2 and osteoclasts. Methods On day 1 of OLC formation from nonadherent bone marrow ceils (BMC) obtained from rats induced by M-CSF and receptor activator of NF-кB ligand (RANKL), 1, 5 and 10μmol/L pioglitazone hydrochloride was added. RT- PCR was performed to determine the mRNA expressions of PPARγ2 and receptor activator of NF-кB (RANK) on day 3, 5 and 7 during incubation, the number of tartrate-resistant acid phosphatase (TRAP)-positive cells,the number of bone resorption pits and the ratio of its area on dentin slice were counted, the activity of TRAP and the mean fluorescence intensity of integrin β3 (CD61) of OLC were also measured. Results (1) The effect on the differentiation of OLC: The addition of pioglitazone at the start of the culture period induced a dose-dependent decrease in TRAP-positive OLC and the activity of TRAP (P < 0.01 or P < 0.05) ; the mRNA expression of PPARγ2 was up-regulated by 5 and 10 μmol/L pioglitazone in the early stage of incubation and attenuated with thematuration of OLC on the contrary, however, the expression of RANK was down-regulated by 5 and 10 μmol/L piolitazone in every stage of incubation (P < 0.05 or P < 0.01), combined with decrease in TRAP-positive OLC from day 3 by 10 μmol/L pioglitazone. (2) The effect on the function of OLC: the number of bone resorption pits and the ratio of its area on dentin slice were decreased in groups of 5 and 10 μmol/L pioglitazone (P < 0.01 orP < 0.05), no obvious change was noted in the group with 1 μmol/L pioglitazone compared with the control group; the mean fluorescence intensity of CD61 were down-regulated in groups of 5 and 10 μmol/L pioglitazone (P < 0.05 or P <0.01). Conclusion Activation of PPARγ2 pathway by pioglitazone could partially inhibit differentiation and function of OLC derived from rat BMC.

Objective To determine the value of using B-type natriuretic peptide (BNP) and D-dimer in preliminary recognition of cardioembolic stroke patients.Methods A mutilple-center study was conducted in Foshan Hospital of traditional Chinese Medicine (TCM) and its affiliated hospitals from July 2015 to July 2016.In the emergency departments (EDs),emergency physicians prospectively assessed consecutive adult patients with acute cardioembolic stroke and measured plasma BNP by POCT platform on admission,then followed up.Stroke neurologists evaluated patients' functional outcome at hospital discharge and also made discharge diagnosis and stroke etiologic subtypes according to the TOAST criteria.Results In this study,290 acute ischemic stroke patients met the study criteria [mean age (68.41 ± 12.06) years;53.8％ female].Of the enrolled patients,28.3％ were diagnosed with LAA at discharge,17.9％ with CE,42.8％ with SAO,11.0％ with SOE or SUE.And the mean BNP concentration was significantly higher in the CE group than that in other three subtypes (P ＜ 0.001).After adjustment for multiple clinical predictors like gender,age,coronary artery disease,atrial fibrillation and renal function,BNP and D-dimer were associated with CE [BNP OR:1.044 (95％ CI 1.025,1.064),P ＜ 0.001;D-dimer OR:1.511(95％ CI 1.020,2.238),P =0.039,respectively].Conclusion Through POCT technique in the EDs,cardioembolic stroke patients can be differentiated from other TOAST subtypes.BNP with/without D-dimer has good but different corresponding diagnostic performance in preliminary recognition of cardioembolic stroke patients.

Pseudouridine(Ψ)is the most prevalent post-transcriptional RNA modification and is widespread in small cellular RNAs and mRNAs.However,the functions,mechanisms,and precise distribution of Ψs(especially in mRNAs)still remain largely unclear.The landscape of Ψs across the transcriptome has not yet been fully delineated.Here,we present a highly effective model based on a convolutional neural network(CNN),called PseudoUridyLation Site Estimator(PULSE),to analyze large-scale profiling data of Ψ sites and characterize the contextual sequence features of pseudouridylation.PULSE,consisting of two alternatively-stacked convolution and pooling layers followed by a fully-connected neural network,can automatically learn the hidden patterns of pseu-douridylation from the local sequence information.Extensive validation tests demonstrated that PULSE can outperform other state-of-the-art prediction methods and achieve high prediction accu-racy,thus enabling us to further characterize the transcriptome-wide landscape ofΨ sites.We fur-ther showed that the prediction results derived from PULSE can provide novel insights into understanding the functional roles of pseudouridylation,such as the regulations of RNA secondary structure,codon usage,translation,and RNA stability,and the connection to single nucleotide vari-ants.The source code and final model for PULSE are available at https://github.com/mlcb-thu/PULSE.