Objective:To investigate the effects of ursolic acid (UA) on the proliferation and differentiation of osteoclasts (OC), and to explore its role in orthodontic force-induced root resorption and its relationship with OC.Methods:The mononuclear / macrophage cells RAW264.7 were induced to the OC.Tacrolimus acid phosphatase (TRAP) staining and bone resorption lacunae observation were used to identify the induction.CCK-8 method was used to select the appropriate concentration of UA for RAW264.7 cell-free biotoxicity and to observe its effect on the proliferation and differentiation of RAW264.7.In experimental groups, UA with gradient concentrations (1.0,2.5,5.0,10.0,20.0and 40.0 μmol·L-1)were added.UA was not added in control group.Results:The TRAP staining and bone resorption lacunae observation showed that after the RAW264.7 cells were induced for 5 d, the TRAP staining positive cells were found;the resorption lacunae were rounded,and oval, etc,the bottom wall was coarser,and the boundary was clear,which indicated that the RAW264.7 cells were successfully differentiated into the osteoclasts.The CCK-8 detection results showed that high concentration of UA (> 10.0 μmol·L-1) significantly inhibited the proliferation of OC;the appropriate concentration of UA (5.0 μmol·L-1) was in the biological safety concentration range and could inhibit the OC proliferation;low concentration of UA (<2.5 μmol·L-1) had no effect.Conclusion:RANKL can induce the differentiation and maturation of RAW264.7 cells.UA is correlated with the proliferation and differentiation of OC;UA has inhibitory effect on OC at the appropriate concentration (5.0 μmol·L-1) in a time-dependent manner.

Objective:To explore the difference of coagulation function and its correlation with prognosis in patients with acute respiratory distress syndrome (ARDS) caused by extrapulmonary sepsis and pulmonary infection.Methods:ARDS patients caused by extrapulmonary sepsis and pulmonary infection admitted to the ICU were retrospectively analyzed at the First Affiliated Hospital of China Medical University from July 2017 to June 2019. The clinical characteristics were collected including sequential organ failure assessment (SOFA), coagulation parameters [prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib), D-Dimer (D-D), fibrinogen degradation product (FDP), antithrombin Ⅲ(AT-Ⅲ), platelet (PLT)], duration of mechanical ventilation, length of stay (LOS) in ICU and 28-day mortality. According to the risk factors, the patients were divided into extrapulmonary sepsis group and pulmonary infection group. The correlation analysis between coagulation parameters and the prognosis of ARDS patients were analyzed by multivariate logistic regression analysis.Results:A total of 268 ARDS patients were screened and 28 cases were excluded. Finally, 240 ARDS patients were enrolled, including 145 caused by extrapulmonary sepsis and 95 by pulmonary infection. PT, INR and APTT in the extrapulmonary sepsis group were significantly higher than those in pulmonary infection group ( P<0.05). AT-Ⅲ level was lower than that in pulmonary infection group ( P<0.05). Ninty-three patients survived at 28 days in the non-pulmonary sepsis group, the mortality rate was 35.9% (52/145). PT, INR, APTT in patients who died at 28 days were significantly higher than those of the patients who survived ( P<0.05), while AT-Ⅲ level was lower than those of the patients who survived ( P<0.05). 49 patients survived at 28 days in the pulmonary infection group, the mortality rate was 48.4% (46/95). There was no significant difference in the coagulation parameters between two groups. Multivariate logistic regression analysis showed that SOFA score without PLT( OR=1.210,95% CI 1.067-1.372, P=0.003) and INR ( OR=2.408,95% CI 1.007-5.760, P=0.048) were independent risk factors for 28-day mortality in extrapulmonary sepsis group. Coagulation parameters are not independent risk factors for 28-day mortality in ARDS patients related to pulmonary infection. Conclusion:There are significant differences in coagulation function between ARDS patients caused by extrapulmonary sepsis or pulmonary infection. INR is an independent risk factor for 28-day mortality in extrapulmonary sepsis group.

Objective:To investigate the implementation of the currently recognized and effective treatment strategies for acute respiratory distress syndrome (ARDS) in Liaoning Province in order to improve the clinical implementation of ARDS treatment strategies.Methods:From January 1st to January 31st, 2019, doctors from the department of critical care medicine of the First Affiliated Hospital of China Medical University applied the self-designed Questionnaire about critical care physicians' clinical behaviors on ARDS patients to investigate the critical care physicians in all levels of hospitals in Liaoning Province. The questionnaire was sent and retrieved in the form of Email and WeChat applet. The investigation included physicians' basic information and treatment behavior. The treatment strategies included 25 multiple-choice questions, such as ventilator mode, sedation, analgesia and other related questions about ARDS patients with different severities. Results:Totally 160 questionnaires were retrieved in this study, 14 questionnaires with a completion rate of less than 75% were excluded, and there were totally 146 questionnaires finally accepted. The surveyed 146 critical care physicians came from 28 hospitals in Liaoning Province, and the majority were 25-44 years old (80.2%) and attending physicians (34.2%). Years of medical service and intensive care units (ICU) service were mainly less than 5 years (31.5% and 43.9%, respectively). 88.4% of the hospitals were Grade Ⅲ Level A hospitals, 89.0% were teaching hospitals, and 48.6% had more than 2 000 beds. The number of ICU beds was mainly 10-19 (39.0%), and only 4.1% had over 60 beds. 77.2% of the hospitals did not have respiratory therapists, however there were 19.1% of the hospitals owning 1-4 respiratory therapists. Most physicians had positive implementation of currently recognized effective treatment strategies in ARDS, yet some of them still depended on the severity of the patients. More than 80% of the physicians monitored the peak pressure, plateau pressure and respiratory compliance of all ARDS patients (no significant differences between severity of illness). The control range of above monitoring indicators would be changed with patients' condition. Half of the physicians controlled the peak pressure of mild ARDS patients at 20-29 cmH 2O (1 cmH 2O = 0.098 kPa) and plateau pressure at 15-34 cmH 2O. However, for severe patients, more physicians chose peak pressure and plateau pressure of 30-39 cmH 2O (67.8%) and 25-34 cmH 2O (70.3%) respectively. For the moderate to severe ARDS patients, majority of the physicians had positive implementation in improving oxygenation, choosing positive end expiratory pressure (PEEP) and applying low tidal volume (LVT) strategy, while conservative method was put toward on mild patients. For severe patients, 97.3% of the physicians preferred immediate invasive mechanical ventilation, 92.4% ensured tidal volume below 8 mL/kg, 61.7% chose PEEP of 15-20 cmH 2O, 97.8% applied deep sedation, 82.5% chose neuromuscular blocking agents, 82.3% preferred to prone positioning ventilation, and 84.3% of the physicians chose to use hormone therapy. For mild ARDS patients, 77.2% of the physicians chose LVT strategy and mostly control PEEP at 5-9 cmH 2O. There were three main reasons that affect the physicians' implementation. The first reason was physicians' subjective attitude, the second was lacking in execution conditions, and the third was physicians' considering of the complications. Conclusions:Most critical care physicians in Liaoning Province had positive implementation toward the currently recognized effective ARDS treatment strategies, but a few performed poorly. According to the reasons that affected the physicians' treatment behaviors, it is necessary to strengthen physicians' awareness of treatment, apply strict training, standardize the clinical implementation of effective treatment strategies, and then improve the prognosis of ARDS patients.

Objective:To investigate the expression of mBmi-1 in papillary thyroid cancer (PTC) and to analyze its relationship with clinical features of PTC and its mechanism.Methons:A total of 60 tissue samples were collected from Jun. 2018 to Dec. 2018 in Department of Oncology Surgery of Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the expression level of B cell-specific MLV integration site-1 (mBmi-1) in PTC tissues and its relationship with pathological features was analyzed. Bmi-l microRNAs (miRNAs) were predicted by bioinformatics sites targetscan and microRNA.org and confirmed by luciferase reporter gene experiments. CCK-8 (Cell Counting Kit-8) kit and Transwell chamber were used to measure changes in PTC proliferative capacity and invasive ability.Results:In this study, we found that mBmi-1 expression was positively correlated with PTC lesion size and invasion ability. Bioinformatics prediction results suggested that Bmi-1 was a target gene of microRNA-203 (MicroRNA-203, miR-203) , and the 3’-UTR target sequence of miR-203 against Bmi-1 was GUAAAGU. After transfection of the miR-203 mimetic, the expression of Bmi-1 mRNA in the PTC cell line TPC-1 was significantly down-regulated. The dual luciferase reporter gene assay demonstrated that miR-203 can act on the 3’UTR region of the Bmi-1 gene to predict the target. In addition, the transfection of miR-203 mimetic effectively inhibited the proliferation and invasion of PTC cells, and the ability of proliferation and invasion of PTC cell TPC-1 was restored after overexpression of Bmi-1 in PTC cell TPC-1 transfected with miR-203 mimic.Conclusions:Bmi-1 is positively correlated with the proliferation and invasion ability of PTC. miR-203 can inhibit the proliferation and invasion of PTC cells by directly targeting Bmi-1 gene.

Objective:To compare the efficacy and adverse events of salvage radiotherapy and other treatments for recurrent esophageal cancer after chemoradiotherapy in this Meta-analysis.Methods:Databases including PubMed, Embase, Cochrane Library, CNKI and Wanfang data were searched from the inception to April 2020 to collect the clinical trials which comparatively analyzed the efficacy and safety between radiotherapy and other treatments for recurrent esophageal cancer after chemoradiotherapy. Meta-analysis was performed using RevMan 5.1 software. RR and 95% CI were used to describe the differences among different groups. Results:According to the inclusion and exclusion criteria, a total of 11 clinical trials involving 842 patients were included. Meta-analysis showed that the overall survival in the salvage radiotherapy group was significantly lower than that in the salvage esophagectomy group ( RR=0.40, 95% CI: 0.27-0.61, P<0.001), whereas significantly higher than that in the chemotherapy group ( RR=2.91, 95% CI: 1.43-5.95, P=0.003). There was no significant difference in the treatment-related mortality between the salvage radiotherapy and salvage esophagectomy groups ( RR=0.53, 95% CI: 0.14-1.98, P=0.350), but the incidence was significantly higher in the salvage esophagectomy group (1.7%-11.4% vs. 1.9%-2.8%). Conclusion:Salvage radiotherapy is an effective treatment for recurrent esophageal cancer after chemoradiotherapy, which can be regarded as one choice for clinical patients.

ARNTL Transcription Factors ; deficiency ; metabolism ; Animals ; Cyclic AMP ; metabolism ; Gluconeogenesis ; Glucose ; biosynthesis ; HEK293 Cells ; Histone Deacetylases ; metabolism ; Humans ; Liver ; metabolism ; Mice ; Mice, Knockout

Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.
Humans ; Pregnancy ; Female ; Lupus Erythematosus, Systemic/pathology* ; Signal Transduction ; N-Acetylneuraminic Acid/metabolism* ; Immunoglobulin G ; Dendritic Cells/pathology*

Adult ; Atherosclerosis ; Cardiovascular Diseases ; China ; Habits ; Humans ; Lipids