Objective: To investigate the current status of benefit finding among young and middle-aged patients with type 2 diabetes mellitus (T2DM) and analyze its influencing factors, so as to provide a reference for improving the level of benefit finding in this population. Methods: From November 2022 to May 2023, young and middle-aged patients with T2DM aged 18-59 years hospitalized in the endocrinology departments of 2 tertiary hospitals in Hengyang City, Hunan Province were selected as survey subjects by a convenience sampling method. Basic demographic information was collected using a general questionnaire survey. Benefit finding, resourcefulness, and stigma were evaluated using the Benefit Finding Scale, the Chinese Version of the Resourcefulness Scale, and the Type 2 Diabetes Stigma Assessment Scale, respectively. A multiple linear regression model was used to analyze the influencing factors of benefit finding among young and middle-aged patients with T2DM. Results: A total of 305 young and middle-aged patients with T2DM were investigated, including 222 males (72.79%) and 83 females (27.21%). There were 231 cases aged 45-59 years, accounting for 75.74%. The scores for benefit finding, resourcefulness, and stigma were (42.86±6.06), (75.12±11.30), and (41.20±10.10), respectively. Multiple linear regression analysis showed that young and middle-aged patients with T2DM who were male (β′=0.088), aged 18-<45 years (β′=0.083), absence of diabetes complications (β′=0.124), and had higher resourcefulness scores (β′=0.679) had higher levels of benefit finding, while patients with higher stigma scores (β′=-0.097) had lower levels of benefit finding. Conclusion The level of benefit finding among young and middle-aged patients with T2DM was moderate, and was related to gender, age, diabetes complications, resourcefulness, and stigma.

Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon (RAP). Despite its therapeutic effects, the surgical risk and unclear mechanism hamper the clinical application. Numerous evidences support macrophages as the key immune cells during bone remodeling. Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1^CreERT2; R26^GFP lineage tracing system. Fluorescence staining, flow cytometry analysis, and western blot determined the significantly enhanced expression of binding immunoglobulin protein (BiP) and emphasized the activation of sensor activating transcription factor 6 (ATF6) in macrophages. Then, we verified that macrophage specific ATF6 deletion (ATF6^f/f; CX3CR1^CreERT2 mice) decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy. In contrast, macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement. In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6. At the mechanism level, RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfα promotor and augmenting its transcription. Additionally, molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element (ERSE). Taken together, ATF6 may aggravate orthodontic bone remodeling by promoting Tnfα transcription in macrophages, suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.
Animals ; Mice ; Macrophages/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Tooth Movement Techniques/methods* ; Activating Transcription Factor 6/metabolism* ; Bone Remodeling ; Flow Cytometry ; Blotting, Western

ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

Objective To investigate the effects of Zhongfengting granule on plasma metabolites in acute cerebral ischemia MCAO model rats by non-targeted metabolomics techniques,and to elucidate the neuroprotective mechanism of Zhongfengting granule.Methods 24 male SD rats were randomly divided into blank group,model group and Chinese medicine group,with 8 rats in each group.Model group and Chinese medicine group were treated with middle cerebral artery thrombus method to establish the MCAO rat model,and the medicine was administered on the same day after the successful modeling.The Chinese medicine group was given(22.68 g·kg-1)Zhongfengting granule solution by gavage,and the blank group and model group were given equal volume normal saline for 7 days.After administration,blood was collected intravenously.Plasma samples from blank group,model group and Chinese medicine group were analyzed by ultra-high performance liquid chromatogre-quadrupole tandem time-of-flight mass spectrometer,and differential metabolites were screened by multivariate statistical analysis.The metabolic pathways of the differentiated metabolites were analyzed based on KEGG database.Results Multivariate statistical analysis showed that the content of 22 potential biomarkers in the rat model of acute cerebral ischemia had significant changes,and the above-mentioned 22 potential biomarkers were significantly reversed by Zhongfengting granule(P<0.05).The enrichment results of metabolic pathways showed that Zhongfengting granule mainly affected phenylalanine metabolism,tyrosine metabolism,ascorbic acid metabolism and arachidonic acid metabolism.Conclusion Metabolites and metabolic pathways in MCAO model rats with acute cerebral ischemia are changed,and the different metabolites and metabolic pathways can be reversed by Zhongfengting granule,which mainly involve phenylalanine metabolism and regulate energy metabolism.

Objective To investigate the effects of Zhongfengting granule on plasma metabolites in acute cerebral ischemia MCAO model rats by non-targeted metabolomics techniques,and to elucidate the neuroprotective mechanism of Zhongfengting granule.Methods 24 male SD rats were randomly divided into blank group,model group and Chinese medicine group,with 8 rats in each group.Model group and Chinese medicine group were treated with middle cerebral artery thrombus method to establish the MCAO rat model,and the medicine was administered on the same day after the successful modeling.The Chinese medicine group was given(22.68 g·kg-1)Zhongfengting granule solution by gavage,and the blank group and model group were given equal volume normal saline for 7 days.After administration,blood was collected intravenously.Plasma samples from blank group,model group and Chinese medicine group were analyzed by ultra-high performance liquid chromatogre-quadrupole tandem time-of-flight mass spectrometer,and differential metabolites were screened by multivariate statistical analysis.The metabolic pathways of the differentiated metabolites were analyzed based on KEGG database.Results Multivariate statistical analysis showed that the content of 22 potential biomarkers in the rat model of acute cerebral ischemia had significant changes,and the above-mentioned 22 potential biomarkers were significantly reversed by Zhongfengting granule(P<0.05).The enrichment results of metabolic pathways showed that Zhongfengting granule mainly affected phenylalanine metabolism,tyrosine metabolism,ascorbic acid metabolism and arachidonic acid metabolism.Conclusion Metabolites and metabolic pathways in MCAO model rats with acute cerebral ischemia are changed,and the different metabolites and metabolic pathways can be reversed by Zhongfengting granule,which mainly involve phenylalanine metabolism and regulate energy metabolism.

Objective:To explore the teaching effect of 3D simulated wound model combined with problem -based learning (PBL) teaching in the standardized residency training of plastic surgery department. Methods:Totally 90 residents trained in the plastic surgery department of Changhai Hospital of Naval Medical University from June 2016 to September 2019 as the research objects were divided into control group and experimental group in average. The control group received traditional teaching and the experimental group accepted the 3D simulated wound model combined with PBL teaching. Then the out -department examination results and questionnaires evaluation were compared between the two groups. SPSS 19.0 was used to conduct t test on the experimental data. Results:The theoretical and practical scores of residents in the experimental group [(49.23±7.25) points and (36.38±5.29)] points were significantly better than those in the control group [(44.43±5.57) points and (28.94±6.97)] points ( P<0.05). In the questionnaire, the scores of active learning initiative, practical operation ability and clinical strain capacity of residents in the experimental group were all higher than those in the control group ( P<0.05), and there was no statistically significant difference in teamwork ability between the two groups ( P>0.05). Conclusion:The 3D simulated wound model combined with PBL teaching can be used in the teaching of standardized residency training of plastic surgery. Compared with traditional teaching, this teaching method has significant advantages and is worthy of promotion.

Objective:To systematically summarize and assess risk prediction models for occurrence of cervical cancer and to provide evidence for selecting the most reliable model for practice, and guide cervical cancer screening.Methods:Two groups of keywords related to cervical cancer and risk prediction model were searched on Chinese databases (CNKI, and Wanfang) and English databases (PubMed, Embase, and Cochrane Library). Original articles that developed or validated risk prediction models and published before November 21, 2019, were selected. Information form was created based on the CHARMS checklist. The PROBAST was used to assess the risk of bias.Results:12 eligible articles were identified, describing 15 prediction models, of which five were established in China. The predicted outcomes included multiple stages from cervical precancerous lesions to cancer occurrence, i.e., abnormal Pap smear (1), occurrence or recurrence of CIN (9), and occurrence of cervical cancer (5), etc. The most frequently used predictors were HPV infection (12), age (7), smoking (5), and education (5). There were two models using machine learning to develop models. In terms of model performance, the discrimination ranged from 0.53 to 0.87, while only two models assessed the calibration correctly. Only two models were externally validated in Taiwan of China, using people in different periods. All of the models were at high risk of bias, especially in the analysis domain. The problems were concentrated in the improper handling of missing data (13), preliminary evaluation of model performance (13), improper use of internal validation (12), and insufficient sample size (11). In addition, the problems of inconsistency measurements of predictors and outcomes (8) and the flawed report of the use of blindness for outcome measures (8) were also severe. Compared with the other models, the Rothberg (2018) model had relatively high quality. Conclusions:There are a certain number of cervical cancer risk prediction models, but the quality is poor. It is urgent to improve the measurement of predictors and outcomes, the statistical analysis details such as handling missing data and evaluation of model performance and externally validate existing models to better guide screening.

Objective:To study whether curcumin inhibits the proliferation and promotes the apoptosis of nephroblastoma through activating the miR-192-5p/PI3K/Akt signaling pathway.Methods:CCK-8 assay was used to investigate the effects of curcumin on the proliferation of nephroblastoma SK-NEP-1 cells and the appropriate concentration. The apoptosis rate of SK-NEP-1 cells was detected by V-FITC/PI. Luciferase reporter assay was used to verify the binding activity between miR-192-5p and PI3K. RT-PCR was performed to detect the expression of miR-192-5p at mRNA level. Western blot was used to detect the expression of PI3K and Akt at protein level.Results:Curcumin could significantly inhibit the proliferation of SK-NEP-1 cells and induce cell apoptosis in a dose-dependent manner. RT-PCR results showed that curcumin could significantly increase the expression of miR-192-5p. In addition, miR-192-5p significantly inhibited cell proliferation, induced cell apoptosis, and enhanced the effects of curcumin on the proliferation and apoptosis of SK-NEP-1 cells. Luciferase reporter assay suggested that miR-192-5p could bind to PI3K. Western blot results showed that curcumin down-regulated the expression of PI3K and Akt at protein level by mediating the expression of miR-192-5p.Conclusions:Curcumin could inhibit the proliferation and induce the apoptosis of nephroblastoma cells through mediating the expression of miR-192-5p and further inhibiting the downstream PI3K/Akt signaling pathway.

Objective:To investigate the application and effect of frontal flap combined with tarsalconjunctiva flap in the repair of widely full-thickness defects of the lower eyelid.Methods:From January 2016 to March 2018, 9 patients with extensive full-thickness lower eyelid defect were admitted to the Plastic Surgery Department of Changhai Hospital Affiliated to the Naval Military Medical University. All the lengths of lower eyelid defects were greater than a half of the full length. Then we designed forehead flaps combined with tarsalconjunctival flaps to cover the wounds. The second stage operation was done after 4-6 weeks to cut the pedicle and dress the eyelid.Results:All the frontal flaps of 9 patients survived. One patient had lower eyelid retraction and the lid position returned to normal half a year later. One underwent thinning surgery because of lower eyelid flap hypertrophy and one were because of pedicle hypertrophy. The appearance and function of other patients were greatly improved after surgery, and they were satisfied with the operation effect. No repair operation was performed in the future.Conclusions:The frontal flap with good quality of blood supply has a high survival rate and can be used to repair the wide defect of the lower eyelid with tarsalconjunctival flaps.

Objective:To investigate the application and effect of frontal flap combined with tarsalconjunctiva flap in the repair of widely full-thickness defects of the lower eyelid.Methods:From January 2016 to March 2018, 9 patients with extensive full-thickness lower eyelid defect were admitted to the Plastic Surgery Department of Changhai Hospital Affiliated to the Naval Military Medical University. All the lengths of lower eyelid defects were greater than a half of the full length. Then we designed forehead flaps combined with tarsalconjunctival flaps to cover the wounds. The second stage operation was done after 4-6 weeks to cut the pedicle and dress the eyelid.Results:All the frontal flaps of 9 patients survived. One patient had lower eyelid retraction and the lid position returned to normal half a year later. One underwent thinning surgery because of lower eyelid flap hypertrophy and one were because of pedicle hypertrophy. The appearance and function of other patients were greatly improved after surgery, and they were satisfied with the operation effect. No repair operation was performed in the future.Conclusions:The frontal flap with good quality of blood supply has a high survival rate and can be used to repair the wide defect of the lower eyelid with tarsalconjunctival flaps.