Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Objective:To explore the common causes and solutions for artifacts in clinical visual electrophysiological examination.Methods:A cross-sectional study was performed.The clinical visual electrophysiological examination results of 25 001 cases were collected from 2012 to 2020 at the Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University). Artifacts were identified and analyzed according to the standard waveform provided by the International Society for Clinical Electrophysiology of Vision.The characteristics and causes of the artifact were analyzed.The solutions to reduce and eliminate the artifact were proposed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University) (No.KY2020053).Results:There were 60 typical artifacts identified among the 25 001 cases.Common causes of the artifacts were classified as three categories, the factors related to subjects, environment, or instruments.Among the 60 cases, 42(70.0%) were caused by tension in head and facial muscles of patients, 9(15.0%) due to blinking of patients, 4(6.7%) resulted from 50 Hz power frequency artifact, 2(3.3%) arisen from abnormal amplifier, and 3(5.0%) for other reasons.The strategies to avoid artifact were as follows.First, examiners could inform patients of the examination process in advance to help patients to relax and avoid the influencing factors, such as muscle tension in head and face, blinking, inattention and so on; second, high-quality 50 Hz hardware wave trap was recommended to reduce 50 Hz artifact, with good ground connection and removing of the high-power electrical appliances near the visual electrophysiological instrument; third, clean the skin sufficiently to reduce the reference electrode impedance to less than 1 kΩ.Conclusions:There is a variety of artifact waveforms and causes.The technicians should make correct judgments and handle the artifact in time to provide more accurate examination results.The doctors should know about artifact, which is helpful for better interpretation of visual electrophysiological examination reports.

Objective:To investigate the effects of the interaction between ubiquitin-specific peptidase 22 (USP22) and hepatitis B virus X protein (HBx) on the protein level and the biological function of HBx.Methods:The interactions between HBx and USP22 were analyzed by GST pull-down, co-immunoprecipitation assay and confocal laser scanning assay. USP22 recombinant plasmids or specific siRNA were transiently co-transfected with HBx plasmids. Western blot were used to detect the protein level of HBx. The half-life and degradation pathway of HBx in the transfected cells treated with cycloheximide (CHX) or proteasome inhibitor MG132 were detected. In vivo ubiquitination assay was used to detect the ubiquitination of HBx with USP22 overexpression. Moreover, dual-luciferase reporter assay and colony formation assay were used to analyze the effects of USP22 on the biological function of HBx. Results:USP22 could interact with HBx in vivo and in vitro. USP22 significantly increased the stability of HBx and inhibited the proteasome-mediated degradation of HBx protein by reducing the ubiquitination of HBx, thereby enhancing the biological function of HBx. Conclusions:USP22 inhibited HBx protein degradation through ubiquitin-dependent proteasome pathway, thus enhancing the stability and biological function of HBx.

Objective:To evaluate the in vivo osteogenic activity of titanium implants with strontium loaded TiO 2 nanotubes (NTSr). Methods:The strontium loaded titanium nanotubes were formed on pure titanium implants through anodization and hydrothermal treatment, and the unmodified titanium (Control) and sheer TiO 2 nanotubes (NT) were set to be control groups and treatment group. Inductively coupled plasma mass spectrometry (ICP-MS) was used to evaluate the Sr release at 28 days. Field emission scanning electron microscopes (FE-SEM) was used to view the micro-topography, atomic force microscope was used to exam the surface roughness, and nano-indenter was used to evaluate the hardness of three groups ( n=3). Three groups of implant samples were inserted into the distal femoral metaphysis of New Zealand rabbits ( n=4 at each time point). After 4 weeks and 12 weeks, samples were harvested. Micro-CT scanning, immunofluorescent and histological examinations were carried out. Results:The strontium ions could be released slowly for at least 28 days [the Sr concentration at 28 Day was (2.6±1.5) ng/ml]. NTSr coating exhibited a nanoscale tube array (the diameter was about 70 nm), and the surface roughness of implant was increased with the nanobube coating [Control (34.8±5.3) nm, NT (66.2±4.3) nm, NTSr (85.7±10.6) nm, F=37.59, P<0.001]. The surface roughness (Ra) of NT and NTSr groups was higher than the control group ( P<0.05). Comparing to Control implants, NTSr implants exhibited a better osteogenic ability [the bone volume/total volume (BV/TV) value was Control (24.7±1.1)% vs. NTSr (37.7±1.9)% at 4 weeks ( P<0.05), and Control (40.7±0.9)% vs. NTSr (51.9±2.1)% at 12 weeks ( P<0.05)]. The fluorescent examination revealed that NTSr coating can also accelerated the generation of new bone tissue (bone tissue area% labelled by alizarin red at day 7 was Control (19.2±2.9)% vs. NT (35.4±3.7)% vs. NTSr (40.9±0.9)% ( F=42.74, P<0.01). The results in the NT and NTSr group were statistically higher than that in the control group ( P<0.05). Conclusions:The strontium loaded TiO 2 nanotubes can enhance new bone formation around titanium implants.

Objective:To investigate the relationship between the angiotensinogen (AGT) rs5051 single nucleotide polymorphism (SNP) and the onset risk of coronary heart disease (CHD) in patients with non-alcoholic fatty liver disease (NAFLD) in the Han Chinese population.Methods:A total of 454 subjects were enrolled in this study. Among them, 140 cases were with NAFLD, 112 cases with NAFLD combined with CHD, and 202 healthy controls. Blood samples of all subjects were examined for biochemical indexes. Genotype at AGT rs5051 locus was detected by polymerase chain reaction. SPSS 21.0 statistical software was used for data statistical analysis.Results:The differences in distribution of AGT rs5051 genotypes and alleles between the NAFLD and the control group were not statistically significant ( P > 0.05). The differences in the distribution of AGT rs5051 genotypes and alleles between the NAFLD combined with CHD and the NAFLD group were statistically significant ( χ2 = 10.32, P = 0.001; χ2 = 11.72, P < 0.001). Binary logistic regression analysis results showed that TC + CC genotype had increased the occurrence risk of CHD in NAFLD patients ( OR = 2.203, 95% CI: 1.322 ~ 3.670, P = 0.02) than AGT rs5051 TT genotype carriers. After adjusting for gender, age, and body mass index, the TC + CC genotype still significantly increased the occurrence risk of CHD in NAFLD patients ( OR = 2.378, 95% CI: 1.384 ~ 4.087, P = 0.02). In addition, AGT rs5051 C allele mutations had significantly increased the occurrence risk of CHD in patients with NAFLD ( OR = 2.018 before adjustment, 95% CI: 1.345 ~ 3.027, P = 0.001; OR = 2.161, 95% CI: 1.406 ~ 3.322 after adjustment. P < 0.001). Conclusion:This study is the first to report the correlation between AGT rs5051 polymorphism and the occurrence risk of CHD in patients with NAFLD in Han Chinese population. AGT rs5051 polymorphism can significantly increase the risk of CHD in patients with NAFLD.

Objective:To explore the correlation between oxidative stress markers malondialdehyde(MDA), superoxide dismutase(SOD), magnetic resonance burden and vascular cognitive impairment in patients with ischemic cerebrovascular disease (CSVD).Methods:Totally 300 patients with ischemic cerebral small vessel diseases who were admitted to the Department of Neurology, North China University of Science and Technology Affiliated Hospital were selected as the research subjects, and 60 healthy outpatients in the same period were selected as the control group.According to the results of mini mental state examination(MMSE), patients with ischemic cerebral small vessel diseases were divided into cognitive normal group (106 cases) and cognitive impairment group (194 cases). The cognitive impairment group was further divided into mild cognitive impairment group (101 cases), moderate cognitive impairment group (58 cases ) and severe cognitive impairment group (35 cases) according to Montreal cognitive assessment (MoCA). MDA and SOD were determined by double antibody sandwich method and the results were compared and analyzed.Results:(1) Compared with the control group(MDA: (8.40±1.81)μmol/L, SOD: (112.73±83.48)U/ml), the level of MDA increased while the level of SOD decreased significantly in normal group(MDA: (8.46±2.05)μmol/L, SOD: (108.90±88.72)U/ml) and cognitive impairment group(MDA: (12.19±7.02)μmol/L, SOD: (62.64±20.34)U/ml). Compared with the cognitive normal group, the level of SOD decreased significantly and MDA increased significantly in cognitive impairment group, the differences were statistically significant (all P<0.05). Compared with the normal cognitive group (1.18±1.10), the cognitive impairment group (1.93±1.05) had a higher MRI burden score ( P<0.05). (2)Multivariate analysis showed that the decrease of plasma SOD level( β=-0.024, OR=0.977, 95% CI=0.961-0.992)and the increase of plasma MDA level( β=0.110, OR=1.117, 95% CI=1.005-1.241)and the MRI overall burden( β=0.453, OR=1.573, 95% CI=1.011-2.446)were independent protective factors of vascular cognitive impairment in patients with ischemic CSVD.(3) Compared with mild cognitive impairment group(MDA: (9.79±5.79)μmol/L, SOD: (81.64±58.09)U/ml, MRI overall burdern (1.69±0.99)), the level of SOD decreased significantly and the level of MDA and the MRI overall burden increased significantly in moderate cognitive impairment group and severe cognitive impairment group(MDA: (7.95±2.44)μmol/L, SOD: (76.13±46.00)U/ml, MRI overall burden: (1.78±0.86)), (MDA: (11.16±6.68)μmol/L, SOD: (63.49±20.04)U/ml, MRI overall burden: (2.89±1.02). Compared with the moderate cognitive impairment group, the level of SOD decreased significantly and the level of MDA and the MRI overall burden increased significantly in the severe cognitive impairment group (all P<0.05). Conclusion:Increased plasma MDA level, MRI burden score and decreased SOD level in patients with CSVD are all risk factors for the occurrence of cognitive impairment.It is suggested that oxidative stress injury and cerebral small vessel lesions may be involved in the occurrence and development of cognitive impairment of CSVD from multiple aspects.

Objective To investigate the relationship between Toxoplasma gondii (T.gondii) infection and metabolic syndrome (MS).Methods A total of 20 577 patients who received serum test of anti-T.gondii IgG antibody in the National Health and Nutrition Examination Survey ( NHANES) of the United States from 2009 to 2014 were collected to analyze the clinical features of anti-T.gondii IgG antibody positive patients , and to compare metabolic related indicators in the antibody IgG positive and negative groups .The independent sample t-test, chi-square test, and logistic regression analysis were used to explore the risk factors of MS . Results A total of 2 746 participants were positive for the T.gondii antibody (13.34%), with a higher prevalence of male (14.44%vs 12.27%, χ2 ＝15.99, P＜0.01).Meanwhile, the prevalence of T.gondii increased with age and body mass index (BMI) (χ2 ＝979.98 and 50.85,respectively, both P＜0.01).Among the 2 191 patients with MS, 449 (20.49%) patients were positive for T.gondii.While 2 297 (12.49%) patients were anti-T.gondii positive in 18 386 non-MS patients.The difference was statistically significant (χ2 ＝78.504, P＜0.01).Age (t＝-37.37), BMI (t＝-4.28), glycosylated hemoglobin (t＝-11.81), fasting blood glucose (t＝-9.38), triacylglycerol (t＝-6.32), cholesterol (t＝-7.16), serum uric acid (t＝-5.25) and serum creatinine (t＝-7.69) in the seropositive group were all higher than those in the seronegative group (all P＜0.01).After adjusting for age and gender , the prevalence of T.gondii was an independent risk factor for MS (odds ratio [OR]＝1.147,P＝0.023).Conclusions BMI, blood lipids, blood uric acid and blood glucose are significantly increased in patients with T.gondii infection.T.gondii infection is an independent risk factor for MS.

Objective To explore the efficacy of moderate dose bromocriptine by one-off oral administration in treatment of patients with non-acute prolactin (PRL) type pituitary adenoma.Methods Forty-three patients with definite diagnosis of non-acute prolactin type pituitary adenoma,admitted to our hospital from January 2016 to December 2017,were chosen in our study.All patients were administrated with 5 mg bromocriptine at 18 pm;the serum PRL levels were examined at 2,3 and 12 h after bromocriptine administration.The curative effects of these patients were judged by decline rate of PRL,and the curative effects of patients with different genders,different initial PRL levels and different ages were compared.Results In these 43 patients,bromocriptine showed excellent effect in 20 patients,obvious effect in 18 and invalid effect in 5.There were statistically significant differences in the efficacy of bromocriptine between different genders (P＜0.05).There were statistically significant differences in efficacy of patients with different genders after taking bromocriptine (P＜0.05).The female patients had obviously higher rate of obvious effect than the male patients.Patients with different initial PRL values had statistically significant differences in efficacy after taking bromocriptine (P＜0.05).Patients with PRL initial value of 40-200 ng/mL had significantly higher rate of obvious effect than patients with PRL initial value of ＞200 ng/mL.There was no significant difference in efficacy between patients ＜ 45 years old and patients＞45 years old (P＞0.05).Conclusion The treatment ofhyperprolactin caused by prolactin type pituitary adenoma with moderate dose bromocriptine by one-off oral administration is effective;female patients have obviously better effect than male patients;and for patients with initial prolactin＞200 ng/mL,the effect is better.

OBJECTIVE: To investigate the effect of G protein-coupled receptor 17 (GPR17) on hypoxia injury in retinal ganglion cells . METHODS: CoCl (400 μmol/L) was used to induce hypoxic injury in RGC-5 cells. The expression of GPR17 and the effect of GPR17 ligands were investigated, and the role of GPR17 in hypoxia injury was further studied by transfection of RGC-5 cells with GPR17 small interfering RNA (siRNA). The cell viability was determined by MTT and the cell apoptosis rate was detected by flow cytometry analysis. The expression of GPR17 mRNA was determined with RT-PCR. RESULTS: mRNA expressions of GPR17 in RGC-5 cells with and without CoCl treatment were 0.36±0.05 and 0.26±0.08(<0.01). Compared with hypoxia without any treatment, pretreatment with GPR17 agonists (LTD, UDP, UDP-G) significantly reduced cell viability (the survival rates of cells decreased by 29.6%, 31.8% and 33.9%, all <0.01), while the effect of GPR17 antagonist (cangrelor) was the opposite (the survival rates of cells increased by 33.2%, <0.01). Transfection with GPR17 SiRNA inhibited hypoxia-induced up-expression of GPR17 mRNA (<0.01)and reduced cell apoptosis[rates of cell apoptosis were(39.73±2.06)%,(42.50±3.64)% and (24.98±2.16)% for blank control, NC siRNA and GPR17 siRNA groups, <0.01]. CONCLUSIONS GPR17 may mediate hypoxia injury in RGC-5 cells, while the knockdown of GPR17 can reduce the hypoxia injury.
Apoptosis ; Cell Hypoxia ; genetics ; Cell Line ; Cell Survival ; Cobalt ; Gene Expression Regulation ; drug effects ; Gene Knockdown Techniques ; Humans ; Hypoxia ; chemically induced ; genetics ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Retinal Ganglion Cells ; drug effects

Objective To investigate the antibiotic resistance in clinical isolates in the Second Hospital of Hebei Medical University from 2015 to 2016.Methods A total of 16 292 strains of non-duplicate bacterial strains were collected.The isolates were subjected to identification and antimicrobial susceptibility testing on VITEK 2-Compact system.The data were processed and analyzed using WHONET 5.6 software.Results Specifically,7 961 and 8 331 strains of pathogens were collected in 2015,2016,respectively.Gram-negative bacteria accounted for 62.0％ in 2015 and 66.9％ in 2016,respectively.The top five pathogens isolated in these two years were still Klebsiella pneumoniae,Escherichia coli,Acinetobacter baumannii,Pseudomonas aeruginosa,and Staphylococcus aureus.The proportion of K.pneumoniae increased to the first place in 2016 which accounted for 16.1％.Coagulase negative Staphylococcus in blood samples decreased from 42.6％ in 2015 to 30.0％ in 2016.Vancomycin resistant strains were not found in Staphylococcus.In 2015 and 2016,the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was 56.2％ and 51.3％,respectively.The prevalence of methicillinresistant coagulase negative Staphylococcus (MRCNS)was 79.3％ and 63.1％,respectively.Enterococcus faecalis and Enterococcus faecium accounted for 25.2％ and 73.2％ respectively in the 911 strains of Enterococcus.In 2015 and 2016,3.1％ and 2.9％ of the E.faecium strains were resistant to vancomycin,respectively.In 2016,the prevalence of carbapenemresistant strains increased in K.pneumoniae,E.coli and E.cloacae.K.pneumoniae showed increasing resistance rate to all the antimicrobial agents tested except for gentamicin and amikacin.The percentage of the K.pneumoniae strains resistant to imipenem and meropenem increased from 19.3％,18.5％ in 2015 to 24.2％,23.1％,respectively.A.baumannii isolates were still highly resistant to the commonly used antibiotics in these two years,but relatively susceptible to polymyxin B,tigecycline,cefoperazone-sulbactam and minocycline (＜30％ resistant).P.aeruginosa isolates showed lower resistance rate to amikacin (11.7％),cefoperazonesulbactam (15.5％),piperacillin-tazobactam (18.7％),ceftazidime (20.1％),cefepime (21.9％).P.aeruginosa presented a trend of declining resistance to all the antimicrobial agents tested from 2015 to 2016,except aztreonam,to which the resistant P.aeruginosa strains increased from 27.0％ in 2015 to 34.7％ in 2016.Conclusions The antimicrobial susceptibility profile of clinical bacterial isolates has been changing constantly.We need to adopt effective infection prevention and control measures in hospital and further standardize and control the use of antibacterial agents.