Objective To investigate the critical role of macrophage M1 polarization in mediating the effect of periodontitis on the progression of chronic obstructive pulmonary disease(COPD).Methods Alveolar lavage fluid samples were collected from COPD patients with comorbid periodontitis,and gene expression analysis was performed to validate the changes in the expression of M1 polarization-related genes.A mouse model of COPD,with experimentally induced periodontitis,were established.Hematoxylin and eosin(HE)staining of pathological sections was performed to observe the effect of periodontitis on COPD progression.Flow cytometry,immunofluorescence staining,and reverse transcription quantitative polymerase chain reaction(RT-qPCR)were performed to analyze the effect of periodontitis on macrophage M1 polarization and the expression of relevant genes in the alveolar lavage fluid and lung tissues.Results In clinical samples of alveolar lavage fluid from COPD patients with periodontitis,the expression of macrophage M1 polarization-related genes,including CD86,inducible nitric oxide synthase(iNOS),interleukin(IL)-1β,tumor necrosis factor(TNF)-α,IL-23,and IL-6,was upregulated compared with that of COPD patients without periodontitis.Analysis of a mouse disease model revealed that periodontitis affected the growth of COPD mice,with the final body mass of mice in the periodontitis and COPD comorbid group([21.3±0.52]g,day 34)lower than that of the COPD group([23.93±0.45]g,day 34).Pathological sections of the lung tissue showed that periodontitis exacerbated COPD progression,with more pronounced alveolar expansion and alveolar wall destruction observed in the periodontitis and COPD comorbid group.Flow cytometry revealed a higher proportion of M1-polarized macrophages in alveolar lavage fluid from COPD and periodontitis comorbid mice([31.36±2.51]%)compared with the COPD mice([23.19±1.07]%).Immunofluorescence assays indicated that periodontitis also promoted macrophage M1 polarization in the lung tissue of COPD mice.Gene expression analysis demonstrated that M1 polarization-related gene expression was significantly upregulated in both the alveolar lavage fluid and lung tissue of mice in the COPD and periodontitis co-morbid group compared to the COPD group.Conclusion Periodontitis exacerbates COPD progression by promoting macrophage M1 polarization in the lungs.Enhancing oral hygiene management and targeting the inhibition of macrophage M1 polarization may represent new therapeutic strategies for the clinical prevention and control of COPD.

Objective:To analyze the current allocation situation and equity of Class B large medical equipment in China,and provide references for reasonably optimizing the allocation of medical equipment.Methods:Based on the allocation data of Class B large medical equipment in China at the end of the 13th Five Year Plan period,the agglomeration degree method was used to evaluate the equity of equipment allocation in various regions from the dimensions of geography,population,and economic development.Results:The current allocation of Class B large medical equipment per million population was 3.19,and the eastern region(3.64)was higher than the central region(3.42),the central region(2.24)was higher than the western region.The agglomeration degree of medical equipment based on geographical area showed that most of the equipment in the eastern region was in a rich state,and the allocation equity was relatively good in the central region,but generally poor in the western region.The agglomeration degree of medical equipment based on population distribution was higher in the eastern region than in the central region and even higher in the western region.The equipment in the eastern region could basically meet the demand of the local population,while the allocation in the central and western regions was slightly insufficient.The distribution of medical equipment agglomeration degree based on economic development varied significantly among different regions,and the allocation equity of central region was generally better than that of eastern and western regions.Conclusion:The total allocation of Class B large medical equipment in China is not high,and the government needs to continue planning and improving it.The distribution of medical equipment allocation based on geography,population and economic development is unbalanced among the eastern,central and western regions.Improving the equity of medical equipment allocation also needs to consider regional differences and characteristics according to local conditions.

Background Lead and manganese are heavy metal pollutants widely existing in the environment, which can accumulate in the human body through the food chain, exert neurotoxicity, and cause neurodegenerative disorders. Especially in early childhood, the developing blood-brain barrier and nervous system are highly susceptible to environmental chemical pollutants. Most of the previous studies focused on the toxic effects of single heavy metal such as lead or manganese, while the studies on combined toxic effect are still scarce, and involved mechanisms are still unclear. c-Jun N-terminal kinase (JNK) is involved in neuronal development and regeneration, and some studies have found that JNK is involved in lead or manganese induced neurotoxicity. Its role in the toxicity of combined lead and manganese is unknown. Objective To understand the neurodevelopmental toxicity mechanism and to observe changes of JNK expression in zebrafish induced by combined lead and manganese exposure at environmentlly low concentrations. Methods Zebrafish embryos within 2 h post fertilization (hpf) were divided into four groups: control group, lead exposure group (0.1 mg·L⁻¹ lead acetate), manganese exposure group (0.3 mg·L⁻¹ manganous chloride), and lead-manganese combined exposure group (0.1 mg·L⁻¹ lead acetate +0.3 mg·L⁻¹ manganous chloride) and exposed to lead or/and manganese at designed levels for 7 d. Spontaneous movements and motor locomotion were observed, and mortality rate were calculated. The changes of JNK mRNA expression in zebrafish were evaluated. Results The experimental results showed that no significant effect of lead or/and manganese on spontaneous movements and mortality rate was found in zebrafish compared with the control group (P＞0.05). The results of locomotion analysis showed that compared with the control group, the activity counts and activity distance of zebrafish in the manganese exposure group were slightly increased (P＜0.01); the activity counts and activity distance of zebrafish in the lead exposure group were reduced by 50% and those in the lead-manganese exposure group were reduced by 80% (P＜0.01). Compared with the lead exposure group, the activity counts and activity distance of zebrafish in the lead-manganese combined exposure group decreased significantly by 60% (P＜0.05). The real-time quantitative PCR results showed that the JNK mRNA expression level was significantly increased in the lead-manganese combined exposure group compared with the control group(P＜0.01). Conclusion Lead exposure combined with manganese exposure at environmentlly low concentration can induce neurodevelopmental toxicity to zebrafish. JNK may be involved in neurodevelopmental toxicity induced by the combined exposure to lead and manganese.

Objective:To investigate the effects of single intermittent theta-burst stimulation on functional connectivity in patients with mild cognitive impairment(MCI).Methods:From July to November 2020, forty MCI patients were selected and randomly divided into iTBS true stimulation group and iTBS sham-stimulation group, with 20 patients in each group.iTBS targeted the left dorsolateral prefrontal cortex (DLPFC). Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), activity of daily living scale(ADL), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) were evaluated at baseline.The resting state electroencephalography (rsEEG) was collected for 5 minutes before and after iTBS in the two groups.The phase lag index(PLI) of EEG functional connectivity was calculated, and the functional connectivity matrix diagram was drawn.SPSS 26.0 software was used for statistical analysis.Data were statistically analyzed by χ2 test, Wilcoxon rank sum test and independent sample t-test. Results:There were no significant differences in scores of MoCA, ADL, HAMD and HAMA between the two groups(all P>0.05). In the iTBS true stimulation group, compared with that before iTBS treatment(0.140(0.133, 0.144)), the PLI of β band increased significantly after iTBS treatment(0.146(0.136, 0.167))( P<0.05). The region of increased PLI was mainly concentrated in the central region(C3/C4-T7/T8). Compared with that before iTBS treatment(0.251(0.232, 0.299)), the PLI of α band increased after iTBS treatment(0.286(0.241, 0.359)), but the difference was not statistically significant( P>0.05). Conclusion:Single iTBS treatment can significantly increase the EEG functional connectivity in patients with MCI, indicating that iTBS targeting the left DLPFC can effectively regulate the EEG functional connectivity in patients with MCI, which may reveal the mechanism of iTBS in improving cognitive function in patients with MCI.

Animals ; Mice ; Motor Neurons/physiology* ; Spinal Cord

Objective:To develop an artificial intelligence system for detecting dental plaque on permanent teeth and find the influenced factors.Methods:Photos of the labial or buccal surfaces of the permanent teeth were taken by using an intraoral camera (1 280×960 pixels; TPC Ligang, Shenzhen, China) before and after applying the plaque-disclosing agent (Cimedical, Japan) in 25 volunteers [12 males, 13 femals, aged (23±3) years] recruided in accordance with the inclusion criteria from the students of Peking University School of Stomatology from October 2018 to June 2019. A total of 549 groups of photos were captured and then divided into a training dataset containing 440 groups of photos and a test dataset including 109 groups of photos. The scopes of teeth and dental plaque on photos were labeled using LabelMe (Windows 3.2.1, MIT, U S A). A DeepLab based deep learning system was designed for the intelligent detection of dental plaque on permanent teeth. The mean intersection over union (MIoU) was employed to indicate the detection accuracy. Matlab (Windows R2017a, MathWorks, U S A) was used to extract the plaque edge line of 109 groups of photos and to calculate the number of pixels for the measurement of the complexity of the plaque edge line. The percentage of dental plaque area was calculated. Multivariate linear regression was used to explore whether tooth site, plaque percentage, number of plaque edge line pixels and lens light spot location would influence the detection accuracy, of which P<0.05 was considered statistically significant. Results:The MIoU of the permanent tooth model was 0.700±0.191 when 440 photos were used for training and 109 photos were used for testing. In the regression model of significance test ( P<0.05), the percentage of plaque and the number of pixels on the edge of plaque had significant influence on the accuracy of dental plaque detection. The standardized coefficient of the number of pixels of the plaque edge line is -0.289, and the standardized coefficient of the percentage of plaque is -0.551. Conclusions:In the present study, an artificial intelligence system was built to detect dental plaque area on tooth photos collected by family intraoral camera. The system showed the ability to detect the dental plaque of permanent teeth. The more complex the marginal line of dental plaque and higher the percentage of dental plaque are, the lower the accuracy of plaque recognition is.

To improve the oral bioavailability of insulin, an insulin-loaded enteric polymer-lipid hybrid nanoparticles(INS-NPs L100)was prepared using methoxy PEG-poly(D, L-lactide)(PEG-PLA), phospholipid s75 and Eudragit L100; in vitro and in vivo behaviors of INS-NPs L100 were evaluated. Insulin-loaded polymer-lipid hybrid nanoparticles(INS-NPs)were prepared by W/O/W double emulsion solvent evaporation method. INS-NPs formulation was optimized by single factor experiment using encapsulation efficiency, particle size, and in vitro release behavior of the corresponding INS-NPs L100 as evaluation indexes. The morphology, in vitro drug release profile and hypoglycemic effect of the INS-NPs L100 using the optimal INS-NPs and Eudragit® L100(used as enteric polymer)were assessed. The results showed that the encapsulation efficiency of the optimal INS-NPs was(62. 18±4. 51)%. The average particle size, PDI and Zeta potential was(225. 2±94. 3)nm, 0. 191±0. 068, and -(14. 84±1. 26)mV, respectively. The cumulative drug release from the INS-NPs L100 was only 8. 01% at 2 h in pH 1. 0 HCl solution, exhibiting a slow drug release behavior; while the drug release from INS-NPs L100 was 67. 31% at 6 h in phosphate buffer of pH 6. 8. Mereorer, after oral administration of INS-NPs L100 with a dose of 38 IU/kg, the blood glucose concentration of healthy rats was reduced to 76% of the initial values at 3. 5 h, exhibiting a sustained hypoglycemic effect. In summary, the INS-NPs L100 prepared in this study could effectively decrease the release rate of insulin in gastric juice, improve the stability of protein in the gastrointestinal tract, and provide a new approach for the oral administration of peptides and protein drugs.

Objective To investigate the role of high mobility group box l protein (HMGB1) in the pathogenesis of ankylosing spondylitis (AS). Methods Enzyme-linked immuno sorbent assay (ELISA) was used to test the levels of plasma HMGB1 levels in 58 patients with active AS [bath ankylosing spondylitis disease activity index (BASDAI)>6, or 6>BASDAI>4 and erythrocyte sedimentation rate (ESR)>22 mm/1 h, 6>BASDAI>4 and hypersensitive C reactive protein (hsCRP)>9 mg/L], 73 cases of stable AS (BASDAI<4) and 70 healthy control. Twelve patients who were treated with TNF-alpha antagonist for 6 month were followed-up. Their plasma levels of HMGB1 were detected before and after treatment. Quantitative data were described by, while qualitative data were described by case number. Variance analysis or rank sum test was adopted for the difference between measurement data groups, LSD method was adopted for further pair-wise comparison. The correlation between variables was analyzed by using Spearman correlation analysis. Results The levels of plasma HMGB1, ESR, hsCRP, White blood cell WBC, GR, Mo and GLOB were significantly higher in the AS patients than those in the healthy control group (P<0.001), and the level of plasma HMGB1 in the AS patients was significantly positively correlated with BASDAI, Bath ankylosing spondylitis functional index (BASFI), ESR, hsCRP, WBC, GR, Mo, and GLOB (r=0.288, 0.174, 0.308, 0.243, 0.261, 0.301, 0.279, 0.289; P=0.004, 0.047, 0.000, 0.005, 0.003, 0.000, 0.001 ,0.001). The level of plasma HMGB1, BASDAI, BASFI, ESR, hsCRP, WBC, GR, GLOB were significantly higher in the active AS group than in the stable group (Z=-3.598,-9.456,-5.907, -2.562, -3.178, 4.134, -2.574, -4.582; P=0.000, 0.000, 0.000, 0.012, 0.002, 0.000, 0.011, 0.000). The level of plasma HMGB1 was not found statistically poor in the patients with different expressions of HLA-B27, or hip involvement and history of vuvitis (P>0.05). The plasma HMGB1 level, BASDAI, BAIFI, ESR, hsCRP and GLOB in the 12 followed-up patients were significantly decreased (P=0.034, 0.002, 0.002, 0.005, 0.004, 0.004) after being treated with biological agents for 6 months. Conclusion HMGB1 might play a vital role in the pathogenesis of ankylosing spondylitis,and the HMGB1 might be used as a clinical indicator to evaluate the activity of AS and to assess the clinical efficacy.

Objective: To conduct economic evaluation of treatments under dental general anesthesia (DGA) and protective stabilization (PS), in order to compare the cost and the final therapeutic effect of these two treatments. Methods: Retrospectively studied twenty-six 2 to 4 years old patients treated under DGA and twenty-seven treated under PS in the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology. The general information, treatment information and total treatment cost information of patients were collected. The cost and cost-survival time ratio of the two groups were compared in units of people and tooth respectively. When compared in unit of people, patients were divided into two groups depending on the number of teeth treated, when compared in unit of tooth, teeth were divided into two groups depending on the treatment received, i.e. restoration or root canal treatment. In addition, we recalculated and compared two groups under the assumption that the treatment charges of DGA was consistent with common outpatient charges. Results: The tooth average cost and cost-survival time ratio of each patient in DGA group which were [(1 133.87±87.37) yuan] and [3.51 (1.30, 5.72) yuan/d] respectively were significantly higher than those in PS group which were [(303.81±155.34) yuan] and [1.54 (0.95, 2.13) yuan/d] respectively (P<0.01). The number of teeth and the way of treatments wouldn't change the result. The recalculated result of the cost-survival time ratio of each patient in DGA group [1.63 (0.72, 2.55) yuan/d] and PS group [1.54 (0.95, 2.13) yuan/d] showed no significant difference (P=0.455). Conclusions Patients treated in Peking University School and Hospital of Stomatology showed a significant higher cost and cost-survival time radio in DGA group than that in PS group. If the treatment charges of DGA group was consistent with common outpatient charges, PS group will no longer have economic advantage.

:In order to improve the compliance of patients with Alzheimer′s disease and maintain the continuity of treatment by reducing administration frequency of memantine hydrochloride, a series of memantine long-acting nanosuspension-based injectable formulations were prepared using a hydrophobic salt formation method. Four hydrophobic salt forms of memantine were prepared, including memantine oleate(Mem-Ole), memantine stearate(Mem-Ste), memantine palmitate(Mem-Pal)and memantine pamoate(Mem-Pam). The salt forms of memantine were characterized using fourier transform infrared(FTIR)spectroscopy, proton nuclear magnetic resonance(1H NMR)spectroscopy and powder X-ray diffraction(PXRD)analysis. The equilibrium solubilities of different salt forms of memantine and the in vitro drug release of long-acting injectable formulations were investigated. In comparison with memantine alone, the equilibrium solubilities of Mem-Ole, Mem-Ste, Mem-Pal and Mem-Pam in simulated body fluid were decreased by 95. 1%、96. 2%、96. 7% and 99. 6%, respectively. Meanwhile, the equilibrium solubilities of Mem-Pam in simulated body fluid with pH ranging from 5 to 8 were all lower than 0. 07 mg/mL. The order of the in vitro drug release rate of the four long-acting injectable formulations with nanosuspensions of memantine was Mem-Ste> Mem-Pal≈Mem-Ole> Mem-Pam> Memantine. The Mem-Pam nanosuspensions could sustain drug release for seven days and exhibited a zero-order drug release profile(y=0. 549 9x+7. 594 2, r=0. 988 3). In conclusion, injectable Mem-Pam nanosuspensions showed desired drug release behavior and might potentially be applied in vivo for a week with a steady plasma drug concentration-time profile.