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

Objective:To establish a predictive model for the risk of cognitive impairment in patients with hypertension.Methods:Data were obtained from the China Health and Retirement Longitudinal Study(CHARLS),and 17 indicators were analyzed,including demographic features,behavioral factors,and health status.The study cohort was randomly divided into a training set(n=2 918)and an internal validation set(n=1 249)at a ratio of 7∶3,and 1 457 patients with hypertension who were treated in Chongqing Traditional Chinese Medicine Hospital from January to December 2024 were included as an external validation set.The least absolute shrinkage and selection operator regression analysis was used to identify predictive variables,and 10-fold cross-validation was used to determine the optimal model.A logistic regression model was used to investigate the risk factors for cognitive impairment in patients with hypertension,and then a nomogram prediction model was established.The calibration curve was used to assess the accuracy of the model,and the area under the ROC curve(AUC)and the decision curve analysis were used to assess the predictive performance of the model.Results:A total of 4167 hypertensive patients aged≥45 years were included from the CHARLS database,among whom 668 had cognitive impairment.The multivariate logistic regression analysis showed that age(odds ratio[OR]=1.408,95%CI=1.040-1.056),sex(OR=0.570,95%CI=0.492-0.660),body mass index(OR=0.931,95%CI=0.914-0.948),educational level(OR=0.235,95%CI=0.200-0.277),place of residence(OR=1.674,95%CI=1.447-1.936),physi-cal activity(OR=0.459,95%CI=0.373-0.562),depression(OR=1.386,95%CI=1.198-1.604),and total cholesterol level(OR=0.997,95%CI=0.995-0.999)were predictive variables.The ROC curve analysis showed that the nomogram model had good performance,with an AUC of 0.814(95%CI=0.802-0.826)in the training set,0.817(95%CI=0.788-0.846)in the internal validation set,and 0.725(95%CI=0.699-0.752)in the external validation set.Conclusion:The nomogram model developed in this study can effectively predict the risk of cognitive impairment in Chinese patients with hyperten-sion and has a good application value.

Microneedles can penetrate the skin barrier to deliver drugs without touching the nociceptive nerves， to effectively increase the efficiency of transdermal drug delivery and improve patient compliance. Exosomes have multiple physiological functions and good biocompatibility， and are natural nanoscale drug carriers. This paper reviews the pathways and advantages of exosomes combined with microneedles for the treatment of diseases， and describes the current research status of exosome microneedle drug delivery system in various diseases. Exosome microneedles can be divided into two categories： （1） exosomes as therapeutic agents， their unique physiological origin can effectively avoid the toxicity and immunogenicity of conventional drugs and other problems； combined with microneedles directly in the specific medication site can greatly improve the metabolic consumption of oral drug delivery and patient compliance of injection drug delivery. （2） Exosomes as drug carriers， their natural vesicle structure and endogenous characteristics can protect the metabolism of foreign drugs in the body and enhance the targeting； combined with microneedles can effectively solve the problem of transdermal delivery of drugs with high efficacy but poor stability. Exosome microneedle drug delivery system is still in the laboratory stage， but it has shown great development prospects in repairing spinal cord injury， promoting diabetic ulcer wound healing， germinating， intervening myocardial infraction， relieving chronic pain and other diseases.

Objective:To understand the radiation protecton awareness of clinical staff for patients, and to provide strategies and suggestions for promoting the justification of medical exposure.Methods:From June to September 2023, 1 430 physicians or technicians from 10 tertiary hospitals, 9 secondary hospitals and 8 primary hospitals in Shanghai were selected by multi-stage stratified random sampling method to conduct a questionnaire survey about radiation-related cognition through a combination of offline and online survey. The contents of the questionnaire included the characteristics of the respondents, the training of radiation protection, the self-awareness of patients on radiation protection, the actual cognition of the basic knowledge of ionizing radiation, the cognition of the dose caused by different types of the radiological examinations, and the ways to access knowledge of ionizing radiation. SPSS software was used for statistical analysis.Results:A total of 1 229 valid questionnaires were received, of which 82.10% respondents belonged to the clinical department and 17.90% belonged to the radiology department. 58.37% of the respondents in clinical department have received radiation-related training, and 98.64% in radiology department have done so. The overall mastery of radiation protection-related knowledge in radiology department was better than in clinical department, and the difference was statistically significant ( χ2=39.58, P<0.05). Most of the respondents tended to underestimate the radiation dose to patients from CT scans, and the proportion of the respondents who underestimated the CT doses to different sites was all greater than 45%. Logistic regression analysis showed that the contributing factors affecting radiation protection cognition are a combination of technical titles, radiation protection training to a varing degree, the level of medical institutions and their majors (95% CI of the OR values did not include 1, χ2=5.66-28.26, P<0.05). Conclusions:Most clinical staff have realized the importance of controlling the radiation dose in radiological examinations, but there is less understanding of the dose magnitude caused by different radiological examinations. Education and training are the best way to improve the awareness of ionizing radiation. Radiation protection training should be integrated into general medical education or standardized training for physicians.

Autophagy is mediated by multiple molecules and pathways. In cardiovascular diseases， autophagy can play a role through key signaling pathways such as phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， adenosine monophosphate-activated protein kinase （AMPK）/mTOR， mitogen-activated protein kinases （MAPK）， p53， Wnt/β-catenin， etc. Traditional Chinese medicine （TCM） monomers for promoting blood circulation and removing blood stasis such as hydroxysafflor yellow A， ginsenoside Rb1， salidroside， ligustrin， curcumin， etc.， and TCM prescription and preparations such as Huangqi baoxin decoction， Taohong siwu decoction， Tongxinluo capsule， Shuangshen ningxin capsule， Suxiao jiuxin pills， etc. can regulate autophagy through the above-mentioned key signaling pathways， thereby alleviating the progression of cardiovascular diseases.

[摘 要] 目的：探讨富含丝氨酸/精氨酸剪接因子7（SRSF7）对肝细胞癌（HCC）细胞HepG2增殖、迁移和侵袭的影响及其可能机制。方法：通过癌症基因组图谱（TCGA）和Kaplan-Meier Plotter在线分析SRSF7在HCC和癌旁组织中的差异表达及其与患者预后的关系。常规培养HepG2细胞，用转染试剂将SRSF7 RNA敲减序列（siSRSF7#1和siSRSF7#2）、对照序列（NC）、SRSF7过表达载体（hSRSF7-oe）和对照载体（hSRSF7-nc）转染至HepG2细胞中，实验分为NC组、siSRSF7#1组、siSRSF7#2组、NC + hSRSF7-nc组、siSRSF7 + hSRSF7-nc组和siSRSF7 + hSRSF7-oe组。通过qPCR和WB法检测各组HepG2细胞中SRSF7 mRNA和蛋白的表达，MTS实验、平板克隆形成实验、划痕愈合实验、Transwell小室实验分别检测各组HepG2细胞的增殖、迁移和侵袭的能力。WB法检测各组HepG2细胞中JAK1/STAT3信号通路的相关蛋白的表达。结果：数据库数据分析显示SRSF7 mRNA在HCC组织中呈高表达（P < 0.001），SRSF7 mRNA高表达与HCC患者不良预后有关联（P < 0.05）。敲减SRSF7后，HepG2细胞的增殖、迁移和侵袭能力均显著下降（均P < 0.01）。敲减SRSF7组细胞中JAK1和STAT3磷酸化水平显著降低（均P < 0.05），同时过表达SRSF7后，JAK1和STAT3磷酸化水平又明显升高（均P < 0.05）。结论：SRSF7在HCC组织中呈高表达，其可能通过调控JAK1/STAT3信号通路促进HepG2细胞的增殖、迁移和侵袭。

Objective:To explore the real work experience and needs of nursing assistants of elderly patients with disability and mental disorders, and provide reference for relevant institutions to develop a reasonable support system and promote their physical and mental health.Methods:From October to November 2022, purposive sampling was used to select nursing assistants of elderly patients with disability and mental disorders from the Affiliated Brain Hospital of Guangzhou Medical University as the research subject. The phenomenological method was used to conduct in-depth interviews, recordings, and transcripts of 12 nursing assistants. The Colaizzi analysis program was used to analyze, organize, refine, and summarize.Results:A total of five themes were extracted, including multiple emotional experiences, lack of rest and relaxation, insufficient professional identity and external support, lack of care knowledge and skills, heavy workload and poor treatment.Conclusions:Accompanying management institutions and hospitals need to strengthen their attention to nursing assistants, reduce their physical and mental burden, attach importance to skill training, increase welfare benefits, enhance professional identity, and improve the quality of care.

Objective:To establish a HPLC method for determinating 9 components simultaneously in Swertia chirayita. Methods:By useing water Sunfire C18 column (4.6 mm× 250 mm,5 μm); Gradient elution was carried out with methanol-0.05% phosphoric acid solution as mobile phase. Setting the column temperature at 30 ℃, the flow rate at 1.0 ml/min, and the detection wavelength at 254 nm.Results:9 components showed good linear relationship within the injection quality range. The recovery rates of wertiamarin, Gentiopicroside, Angelica glycosides,Mangiferin, Isolysine, Gentianoside, Diol glycoside, 8-hydroxy-1,3,5 trimethoxyketone, and Daisy leaf gentinone were 95.38%, 92.41%, 95.14%, 91.87%, 92.24%, 92.51%, 95.08%, 91.72%, 95.74% ( n=6). Conclusion:The method is simple, efficient, sensitive, accurate, economical and practical, with repeatability and stability. It could provide reference for the quality control and comprehensive utilization of Swertia chirayita.

Objective:To investigate whether vestibular-evoked myogenic potentials (VEMP) can be used to assess brainstem and its supplementary diagnostic value in patients with early-stage Parkinson′s disease (PD).Methods:A total of 123 patients with early-stage PD (PD group) diagnosed in the Department of Neurology of the Second Affiliated Hospital of Soochow University from January 2019 to January 2022 were consecutively enrolled, and 122 healthy controls (healthy control group) were included. Cervical VEMP (cVEMP) and ocular VEMP (oVEMP) examinations were performed on all subjects. VEMP parameters between the 2 groups were compared, and receiver operating characteristic curve was used to evaluate the auxiliary diagnostic efficacy of VEMP for early-stage PD. Correlations between VEMP parameters and motor and non-motor symptoms such as autonomic dysfunction were analyzed in the PD group using Spearman correlation analysis.Results:Bilateral latencies of cVEMP [left P1 latency (Lp13): 19.0 (16.4, 20.9) ms vs 13.1(12.0, 14.2) ms, Z=-11.18, left N1 latency (Ln23): 27.4 (24.6, 29.9) ms vs 21.2 (19.8, 23.0) ms, Z=-10.14; right P1 latency (Rp13): 18.8 (16.2, 20.9) ms vs 13.0 (11.7, 14.1) ms, Z=-10.84, right N1 latency (Rn23): 27.7 (24.3, 29.7) ms vs 21.1 (19.6, 22.9) ms, Z=-10.50] and bilateral latencies of oVEMP [left N1 latency (Ln10): 12.7 (10.7, 14.4) ms vs 10.4 (9.7, 11.4) ms, Z=-8.02, left P1 latency (Lp15): 16.5 (15.1, 18.3) ms vs 14.5 (13.4, 15.3) ms, Z=-7.96; right N1 latency (Rn10): 12.8 (11.4, 14.0) ms vs 10.5 (9.7, 11.5) ms, Z=-8.85, right P1 latency (Rp15): 16.7 (15.3, 18.3) ms vs 14.4 (13.3, 15.1) ms, Z=-9.39] of the PD group significantly prolonged compared to the healthy control group (all P<0.001). Compared to the healthy control group, the area under the curve (AUC) values of Lp13, Ln23, Rp13 and Rn23 of cVEMP in the PD group were all greater than 0.7, and the AUC values of Lp13 and Rp13 in the PD group were greater than 0.9 (all P<0.001); the AUC values of Ln10, Lp15, Rn10, and Rp15 of oVEMP in the PD group were all greater than 0.7 (all P<0.001). The Rn10-p15 corrected amplitude in PD patients was positively correlated with levodopa equivalent dose ( r=0.21, P=0.020). The Rn10 in PD patients was positively correlated with the Non-Motor Symptoms Questionnaire scores ( r=0.21, P=0.023). The Lp13-n23 corrected amplitude was negatively correlated with the Scale for Outcomes in Parkinson′s Disease-Autonomic scores ( r=-0.20, P=0.023). There was no significant correlation between VEMP parameters and Unified Parkinson′s Disease Rating Scale part Ⅲ score ( P>0.05). Conclusion:VEMP, especially cVEMP, as a non-invasive neuroelectrophysiological index, is an objective marker for brainstem damage and could be used for screening early-stage PD patients.

Exosome is a kind of vesicle secreted by a variety of cells with lipid bilayer membrane structure， which has good biocompatibility， high targeting and high stability， and is a natural nanoscale drug carrier with great development potential in drug delivery system. In this paper， exosomes and their properties， exosome drug delivery pathways and methods， the design strategy of engineered exosome drug delivery systems for targeted disease therapy， and the application of exosome drug delivery systems in the treatment of a variety of diseases were reviewed. Exosome drug delivery pathways could be divided into two categories： exogenous and endogenous. Common exosome drug delivery methods included electroporation， co-incubation， and ultrasound. Engineered exosome drug delivery system can further improve drug loading and enhance drug targeting. The main way of engineering is to modify exosome surface through genetic engineering technology， physical modification， chemical modification， etc. Exosome drug delivery system provides a new idea for targeted therapy of arthritis， tumor， brain and other diseases.