Objective:To develop a comprehensive training curriculum to enhance the effective implementation of the national initiative promoting dementia care and prevention.Methods:The Delphi method was utilized in an expert consultation that included 44 participants.The initial draft of the training curriculum was developed based on the current state of dementia care and prevention.This draft was subsequently evaluated for its importance, feasibility, and ease of dissemination.Experts offered targeted modifications and additional recommendations.Results:The recovery rate of the expert consultation questionnaire was 95.5%, with a recovery validity rate of 90.9%.The expert authority coefficient was 0.91, and the Kendall's coordination coefficient( W)for expert scoring was 0.316, with a significance level of P<0.001.Four course modules were ultimately identified: the foundation of memory clinic work, the complete management practice skills, group counseling techniques for caregivers, and practical skills for caregivers.The importance of these modules was rated with a mean of 4.92 to 4.95, and the coefficient of variation ranged from 0.044 to 0.063.Each module had a mean value of 4.92 to 4.95, with a coefficient of variation of 0.044 to 0.063; the mean value for practicality was between 4.78 and 4.92, with a coefficient of variation of 0.055 to 0.098; and the mean value for ease of generalization ranged from 4.28 to 4.65, with a coefficient of variation from 0.140 to 0.203.The four modules comprised a total of 55 specific course content items, with the mean value for each item ranging from 4.76 to 5.00 and a coefficient of variation from 0.000 to 0.121.The mean value of usefulness assigned to each entry ranged from 4.55 to 4.98, with a coefficient of variation from 0.031 to 0.150.Additionally, the mean value for ease of propagation assigned to each entry ranged from 4.00 to 4.83, with a coefficient of variation from 0.091 to 0.245. Conclusions:The developed training curriculum, which comprises four course modules and 55 items, demonstrated consistently high levels of importance, practicality, and ease of dissemination.These findings indicate that the curriculum is well-aligned with national initiatives aimed at enhancing dementia care and prevention.

Objective: To investigate the therapeutic effect of bone marrow mesenchymal stem cells ( BMSCs) mod- ified by bone morphogenetic protein ( BMP) -2 gene combined with nano-hydroxyapatite ( nHA) / polyamide 66 ( PA66) on femoral nonunion in rats． Methods : Rat BMSCs were isolated and divided into the stent + BMSCs group，stent + BMSCs + rhBMP-2 group，and stent + BMSCs + Ad-BMP-2 group; human recombinant BMP-2 ( rh- BMP-2) or adenovirus-infected BMP-2 ( Ad-BMP-2) vector was transfected into BMSCs and loaded onto nHA / PA66 stent materials．Flow cytometry was used to detect that BMSCs expressed specific surface markers．Cell pro- liferation was detected by MTT assay，related bioactive factors［platelet-derived growth factor ( PDGF) ，transfor- ming growth factor-β ( TGF-β) ，vascular endothelial growth factor ( VEGF) ，fibroblast growth factor ( FGF) ，os- teocalcin ( OCN) ，osteonectin ( ON) ］were detected by ELISA，alkaline phosphatase ( ALP) activity was detec- ted，and cell growth and adhesion were observed by scanning electron microscopy ( SEM) ．In the atrophic nonun- ion model of SD rats，the stent + BMSCs + rhBMP-2 or stent + BMSCs + Ad-BMP-2 complex was implanted into the defect area，which was divided into the rhBMP-2 group and the Ad-BMP-2 group，and the therapeutic effect was e- valuated by X-ray and MicroCT． Results: The surface of the nHA / PA66 stent was smooth and porous，and BMSCs adhered well．Flow cytometry showed high expression of CD29 and CD90 and low expression of CD45 and CD34 in BMSCs．MTT showed that the cells proliferated rapidly after 72 h．Compared with the stent + BMSCs group and the stent + BMSCs + rhBMP-2 group，the ALP activity，the expressions of PDGF，TGF-β , VEGF，FGF，OCN，and ON in the stent + BMSCs + Ad-BMP-2 group were significantly up-regulated ( P＜0. 05) ．12 weeks after surgery， the stent complex in the Ad-BMP-2 group of rats was completely wrapped by newly formed cortical bone，and the surface was smooth and intact．X-ray showed that the complex in the Ad-BMP-2 group was completely wrapped by newly formed cortical bone，and the recovery degree was better than that in the rhBMP-2 group．Micro-CT results showed that compared with the rhBMP-2 group，the bone volume fraction，trabecular thickness，trabecular num- ber，bone mineral density，and bone mineral content in the Ad-BMP-2 group all increased 12 weeks after surgery ( P＜0. 05) ，and the trabecular separation level decreased ( P＜0. 05) ． Conclusion Ad-BMP-2-transfected BM- SCs combined with nHA / PA66 stent material can express bioactivity more effectively，provide a continuous and good microenvironment for the proliferation and differentiation of BMSCs，which is beneficial to promoting local os- teogenic activity and bone defect repair．

Mitophagy is a selective degradation process of damaged mitochondria in response to mitochondrial toxicity,which plays a crucial role in regulating mitochondrial quality and quantity.Abnormal mitophagy can cause or exacerbate mitochondrial dysfunction,which is closely associated with the pathogenesis of numerous diseases.Given that cochlear hair cells are highly sensitive to energy metabolism,proper regulation of mitophagy is essential for maintaining auditory function.Mitochondrial damage resulting from mitophagy dysfunction involves diverse pathophysiological mechanisms underlying sensorineural hearing loss.This review summarizes the latest progress on mitophagy and its role in the pathogenesis of sensorineural hearing loss,aiming to enhance our understanding of the involvement of mitophagy in auditory function and provide a theoretical basis for future research on targeted therapy for mitochondria.

OBJECTIVE To conduct qualitative analysis of chemical constituents in the crude extract of Modified Ermiao Formu-la,along with its blood-absorbed components and metabolites in rats post-administration employing ultra-performance liquid chroma-tography coupled with quadrupole-exactive orbitrap tandem mass spectrometry(UPLC-Q-Exactive Orbitrap-MS/MS).METHODS Separation was performed on a Waters HSS T3 column(100 mm×2.1 mm,1.8 μm)using gradient elution with 0.1%formic acid in water(mobile phase A)and 0.1%formic acid in acetonitrile(mobile phase B),under controlled conditions:column temperature maintained at 40℃,flow rate set to 0.3 mL·min-1,and injection volume fixed at 2 μL.Mass spectrometric data acquisition utilized an electrospray ionization(ESI)source with scanning in both positive and negative ion modes.RESULTS By analyzing precise mo-lecular weights,retention times,and MS/MS fragmentation patterns,and cross-referencing these against established databases and published literature,173 chemical constituents were definitively identified in the Modified Ermiao Formula crude extract.These prima-rily comprised flavonoids,organic acids,and alkaloids.Additionally,32 prototype components and 13 metabolites were characterized in the serum of dosed rats.Organic acids constituted the predominant class of serum prototype components,undergoing in vivo metabo-lism principally through demethylation and carboxyl glucuronidation.CONCLUSION This study provides the initial delineation of blood-absorbed prototype components derived from Modified Ermiao Formula,with concomitant identification of their metabolites,thereby establishing a foundational framework for elucidating the pharmacologically active constituents of this formula.

Objective To compare and find an optimal model for predicting the risk of DKD occurrence in patients with type 2 diabetes mellitus(T2DM).Methods A total of 2005 patients with T2DM were enrolled in this study from The Second Hospital of Shijiazhuang City during December 2017 to December 2022.All the subjects were divided into a training set(n=1403)and a validation set(n=602)according to the ratio of 3∶1 by simple random sampling.With the occurrence of DKD as the outcome variablein the training set,important feature variables were screened by LASSO regression.Six different machine learning models were established according to the feature variables,thenthe optimal model was determined by comparison,and anonlinerisk predictor for DKD occurrence was constructed in patients with T2DM.Results Taking the occurrence of DKD as the outcome variable in the training set,the results of LASSO regression analysis showed that the optimal value of the model was 10-fold cross validation lambda.1se=0.01662473,and 15 characteristic variables with nonzero coefficient were screened out to be related to the occurrence of DKD.The data included sex,age,family history of DM,DM duration,LDL-C,HbA1c,WBC,PDW,Scr,urine α1-microglobulin,urine β2-microglobulin,urine microalbumin,hypertension,hypokalemia,and DR.In the training set and validation set,the prediction performance of XGBoost model was better than that of other models(AUC=0.872,0.893,95%CI 0.853～0.891,0.865～0.921),the sensitivity was 0.779,0.863,and the specificity was 0.721,0.758,respectively.The F1 scores were 0.774 and 0.787.DCA analysis showed that the XGBoost model had a greater net benefit and threshold probability.According to the XGBoost model,the online predictor of DKD risk in T2DM patients was laid out,and two patients were selected for application,the results showed that the predictive value of the model was 0.185 in non-DKD patients,and the predictive value was 0.510 in DKD patients.Conclusions The XGBoost model is the best model for predicting the occurrence of DKD in T2DM patients,and an online predictor was successfully built.

Prostaglandin D2(PGD2)is a biologically active substance with important roles in a variety of physiological and pathological processes.PGD2 exerts its biological functions mainly through prostaglandin D2 synthase(PGDS),which is closely related to inflammation and immune regulation.Recent studies have found that PGD2 and its synthase,PGDS,are able to directly inhibit tumor cell proliferation,induce apoptosis,suppress migration and invasion,and further regulate the tumor immune microenvironment to affect the immunotherapy of tumors,demonstrating good tumor therapeutic potential.In this paper,we review the biological properties of PGD2 and its synthase,focusing on its role in the immunotherapy of tumor models.We explore the immunotherapeutic efficacy of PGD2 and its synthase,and their roles in promoting immune cell infiltration in the tumor microenvironment,and discuss their potential as new targets for tumor therapy.

OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Five new flavan-4-ol glycosides jixueqiosides A-E (1-5) and two new flavan glycosides jixueqiosides F and G (6 and 7), along with twelve known flavan-4-ol glycosides (8-19), were isolated from the roots of Pronephrium penangianum. Comprehensive spectral analyses, X-ray single-crystal diffraction, and theoretical electronic circular dichroism (ECD) calculations established structures and absolute configurations. A single crystal structure of flavan-4-ol glycoside (14) was reported for the first time, while the characteristic ECD and NMR data for all isolated flavan-4-ol glycosides (1-5 , 8-19) were analyzed, establishing a set of empirical rules. Activity screening of these isolates showed that 8 and 9 could inhibit the proliferation of MDA-MB-231 and MCF-7 cells with IC₅₀ values of 7.93 ? 2.85 ?mol?L^-1 and 5.87 ? 1.58 ?mol?L^-1 (MDA-MB-231), and 2.21 ? 1.38 ?mol?L^-1 and 3.52 ? 1.55 ?mol?L^-1 (MCF-7), respectively. Western blotting and flow cytometry analyses demonstrated that 8 and 9 dose-dependently induced apoptosis in MDA-MB-231 cells by up-regulating BAX, activating caspase-3 and down-regulating BCL-2. Additionally, compound 8 affected autophagy-related proteins, increasing the ratio of LC3-II/LC3-I and Beclin-1 levels to inhibit MDA-MB-231 cell proliferation. Moreover, anti-inflammatory studies indicated that 2, 3, 7, 13, 14, and 18 moderately inhibited tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and nitric oxide (NO) release.
Humans ; Plant Roots/chemistry* ; Glycosides/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Flavonoids/isolation & purification* ; Cell Proliferation/drug effects* ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Molecular Structure ; Apoptosis/drug effects* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6/immunology* ; Animals ; Mice

Objective To explore the mediating role of mindful attention and awareness in depressive symptoms and insomnia severity among patients with comorbid depression and insomnia.Methods A cross-sectional study was conducted,enrolling 267 patients with comorbid depression and insomnia who were treated in the outpatient Department of Medical Psychology of Second Affiliated Hospital of Army Medical University,from March to May 2024.Basic demographic and clinical data were collected using a general information questionnaire.Depressive symptom severity was measured via the Patient Health Questionnaire-9(PHQ-9),insomnia severity via the Insomnia Severity Index(ISI),perceived stress via the Perceived Stress Scale-10(PSS-10),and mindful attention and awareness via the Mindful Attention Awareness Scale(MAAS).Pearson correlation analysis was used to examine the correlations between depressive severity,insomnia severity,perceived stress,and mindful attention and awareness.Mediation analysis was performed using Process 4.1.Results The PHQ-9 score was(13.80±5.98)and the ISI score was(17.10±5.56)in the 267 patients.Pearson correlation analysis showed that depressive severity and insomnia severity were positively correlated with perceived stress(r=0.531,0.351,P<0.001)and negatively correlated with mindful attention and awareness(r=-0.373,-0.350,P<0.001).Mediation analysis using Process 4.1 indicated that the combined mediating effect of mindful attention and awareness and insomnia between perceived stress level and depressive level was 0.157,with a 95%confidence interval(CI)of 0.102～0.217,and the total mediating effect was significant(P<0.001).Conclusion Perceived stress directly positively affects depression and indirectly exacerbates depression through insomnia as a mediator,and mindful attention and awareness can weaken the promoting effect of perceived stress on insomnia.

OBJECTIVE To conduct qualitative analysis of chemical constituents in the crude extract of Modified Ermiao Formu-la,along with its blood-absorbed components and metabolites in rats post-administration employing ultra-performance liquid chroma-tography coupled with quadrupole-exactive orbitrap tandem mass spectrometry(UPLC-Q-Exactive Orbitrap-MS/MS).METHODS Separation was performed on a Waters HSS T3 column(100 mm×2.1 mm,1.8 μm)using gradient elution with 0.1%formic acid in water(mobile phase A)and 0.1%formic acid in acetonitrile(mobile phase B),under controlled conditions:column temperature maintained at 40℃,flow rate set to 0.3 mL·min-1,and injection volume fixed at 2 μL.Mass spectrometric data acquisition utilized an electrospray ionization(ESI)source with scanning in both positive and negative ion modes.RESULTS By analyzing precise mo-lecular weights,retention times,and MS/MS fragmentation patterns,and cross-referencing these against established databases and published literature,173 chemical constituents were definitively identified in the Modified Ermiao Formula crude extract.These prima-rily comprised flavonoids,organic acids,and alkaloids.Additionally,32 prototype components and 13 metabolites were characterized in the serum of dosed rats.Organic acids constituted the predominant class of serum prototype components,undergoing in vivo metabo-lism principally through demethylation and carboxyl glucuronidation.CONCLUSION This study provides the initial delineation of blood-absorbed prototype components derived from Modified Ermiao Formula,with concomitant identification of their metabolites,thereby establishing a foundational framework for elucidating the pharmacologically active constituents of this formula.