OBJECTIVE: To investigate the therapeutic potential of octaarginine (R8)-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres (EOFAZ@^R8LM) for cardiovascular therapy. METHODS: EOFAZ@^R8LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM, followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury. The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels, as well as inflammatory factors interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels. RESULTS: EOFAZ@^R8LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells, thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels. Moreover, it attenuated the expression levels of IL-6 and IL-1β, exerting protective effects on the vascular endothelium. CONCLUSION Our findings highlight the significant therapeutic potential of EOFAZ@^R8LM in cardiovascular therapy, providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

Objective: To address the relation among pelvic inflammatory disease (PID), genetic vulnerability and ovarian cancer (OC) risk, we assessed the association between PID and OC risk, alongside the interplay with germline homologous recombination repair (gHR) mutation, utilizing the UK Biobank. Methods: We conducted a prospective cohort study in the UK Biobank by tracking OC incidences between individuals with and without a PID history. Identification of gHR mutations (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1) carriers were accomplished through paired whole-exome sequencing data. We used Cox’s regression models to evaluate the hazard ratios (HRs) for OC risks under PID. Results: In the large prospective cohort study, the adjusted HR for OC in patients with PID was 1.45 (95% confidence interval [CI]=0.90, 2.32) compared with those with non-PID.Intriguingly, age-stratified analysis unveiled a positive association between PID history and OC risk in those aged under 55 years (HR=1.92; 95% CI=1.02, 3.63). Moreover, individuals aged younger than 55 years harboring both a history of PID and gHR mutations exhibited the highest risk of OC (HR=7.40; 95% CI=1.03, 53.10). Conclusion An association between PID and OC risk emerged, notably in the subgroup aged younger than 55 years old. Individuals with both a PID history and gHR mutations exhibited the highest risk of OC. These findings imply PID as a potential precursor for OC, underscoring the importance of early intervention, particularly in the younger population with gHR mutations.

Objective:To construct an evaluation the index system of entrustable professional activities for resident training doctors in psychiatric department,and to provide reference for formulating training strategies and assessment standards.Entrustable professional activities refers to the ability of trainees to perform and complete spe-cific clinical tasks independently after they have been trusted.Methods:Through documental analysis and semi-structured interviews,the item database of entrustable professional activities for psychiatric resident training physi-cians was established.Delphi consultation was conducted among 63 experts in the field of psychiatry from 7 national resident training bases and 3 medical colleges in China.Indicators were comprehensively screened and sorted out,and indicators at all levels and their weights were determined by the analytic hierarchy process.Results:A hierarchi-cal evaluation index system of entrustable professional activities for psychiatric resident training doctors was con-structed,including 4 first-level indicators,17 second-level indicators and 68 third-level indicators.The weights of the first-level,second-level and third-level indicators were determined.Conclusion:The evaluation index system of en-trustable professional activities is comprehensive and systematic,which is suitable for clinical work and convenient for practical application.It could provide quantitative standards for the assessment of psychiatric residents and pro-mote the improvement of training quality.

Objective:To investigate the Kub stage classification of clinical renal tuberculosis and provide a reference for disease evaluation and management.Methods:A retrospective analysis was conducted on clinical data from 180 patients diagnosed with renal tuberculosis who were admitted to the First Affiliated Hospital of Dali University between January 2011 and December 2022. The 180 cases included 82 males and 98 females. The average age was (44.56±9.62) years. The tuberculosis lesions of 101 cases were on left kidney, while that of 79 cases were on right kidney. Localized/multiple lesions were observed in 118 cases, whereas extensive destruction was found in 62 cases. Moreover, the ureters were involved in 165 cases, and bladder invasion occurred in 139 cases. For patients undergoing renal preservation treatment, a comprehensive approach was employed, including ureteral stricture stenting and regular replacement of double-J stent, percutaneous nephrostomy, excision of tuberculosis lesions or partial nephrectomy, ureter reconstruction, and sigmoidocystoplasty. In cases requiring nephrectomy, either laparoscopic or open surgical approaches are utilized. Based on the results of patient imaging and endoscopy, staging and classification were performed based on the extent of tuberculosis lesions involving the kidneys (K), ureters (u), and bladder (b). The state for each above organ was divided into four stages: K stage (K 1-4), u stage (u 0-u 3), and b stage (b 0-b 3), which were then combined with the actual disease condition for further categorization. The classifications included local intrarenal type(K 1-2u 0b 0), local renal-ureteral involvement type(K 1-2u 1-2b 0-2), multiple renal-ureteral invasion type(K 3u 1-3b 0-2) and extensive destruction type(K 4u 1-3b 1-3). Further analysis was conducted on kidney preservation and subsequent disease progression among patients with different subtypes. Results:Among the 180 patients, 15 cases of local intrarenal type underwent kidney-preserving treatment. Out of these cases, 6 patients (4 patients in stage K 1u 0b 0 and 2 patients in stage K 2bu 0b 0) achieved clinical cure after receiving a pure durative anti-tuberculosis for two years. Additionally, 4 patients in stage K 2au 0b 0 attained clinical cure following anti-tuberculosis drugs combined with partial nephrectomy after two years of follow-up. Furthermore, 5 patients in stage K 2bu 0b 0 underwent ureteroscopy and D-J stent placement for regular stent replacement. The stents were subsequently removed after two years, and the patients remained clinically stable. Among the 47 cases with localized renal-ureteral involvement type, all initially underwent kidney-preserving treatment. Of these, 5 patients in stage K 1u 1b 0-2 achieved clinical remission, while disease progression necessitated nephrectomy for 3 patients in stage K 2au 1-2b 0-2 and 7 patients in stage K 2bu 1-2b 0-2. The remaining patients maintained stable conditions. Among the 56 cases of multiple renal-ureteral invasion type, stable conditions were observed in 9 out of 24 patients with stage K 3u 1-2b 0-2, while disease progression necessitated nephrectomy in 15 cases. Nephrectomy was performed for all 32 patients with stage K 3u 3b 0-2. In instances of extensive destruction type, nephrectomy was conducted for all 62 cases. The progression rates of the local renal-ureteral involvement type and the multiple renal-ureteral invasion type were 21.28% (10/47) and 48.39% (15/31), and the difference was statistically significant ( P<0.05). The kidney preservation rates of the local renal-ureteral involvement type and multiple renal-ureteral invasion type were 78.72% (37/47) and 16.07% (9/56), and the difference was statistically significant ( P<0.001). Conclusions:The Kub stage classification can provide reference to management and monitoring for renal tuberculosis. The patients in the local intrarenal type and local renal-ureteral involvement type are often treated with anti-tuberculosis plus ureteral stent implantation or partial nephrectomy or ureteral reconstruction. The patients in the multiple renal-ureteral invasion type and extensive destruction type are mostly managed by nephrectomy.

BACKGROUND: China bears the biggest atrial fibrillation (AF) burden in the world. However, little is known about the incidence and predictors of AF. This study aimed to investigate the current incidence of AF and its electrocardiographic (ECG) predictors in general community individuals aged over 60 years in China. METHODS: This was a prospective cohort study, recruiting subjects who were aged over 60 years and underwent annual health checkups from April to July 2015 in four community health centers in Songjiang District, Shanghai, China. The subjects were then followed up from 2015 to 2019 annually. Data on sociodemographic characteristics, medical history, and the resting 12-lead ECG were collected. Kaplan-Meier curve was used for showing the trends in AF incidence and calculating the predictors of AF. Associations of ECG abnormalities and AF incidence were examined using Cox proportional hazard models. RESULTS: This study recruited 18,738 subjects, and 351 (1.87%) developed AF. The overall incidence rate of AF was 5.2/1000 person-years during an observation period of 67,704 person-years. Multivariable Cox regression analysis indicated age (hazard ratio [HR], 1.07; 95% confidence interval [CI]: 1.06-1.09; P < 0.001), male (HR, 1.30; 95% CI: 1.05-1.62; P = 0.018), a history of hypertension (HR, 1.55; 95% CI: 1.23-1.95; P < 0.001), a history of cardiac diseases (HR, 3.23; 95% CI: 2.34-4.45; P < 0.001), atrial premature complex (APC) (HR, 2.82; 95% CI: 2.17-3.68; P < 0.001), atrial flutter (HR, 18.68; 95% CI: 7.37-47.31; P < 0.001), junctional premature complex (JPC) (HR, 3.57; 95% CI: 1.59-8.02; P = 0.002), junctional rhythm (HR, 18.24; 95% CI: 5.83-57.07; P < 0.001), ventricular premature complex (VPC) (HR, 1.76; 95% CI: 1.13-2.75, P = 0.012), short PR interval (HR, 5.49; 95% CI: 1.36-22.19; P = 0.017), right atrial enlargement (HR, 6.22; 95% CI: 1.54-25.14; P = 0.010), and pacing rhythm (HR, 3.99; 95% CI: 1.57-10.14; P = 0.004) were independently associated with the incidence of AF. CONCLUSIONS The present incidence of AF was 5.2/1000 person-years in the studied population aged over 60 years in China. Among various ECG abnormalities, only APC, atrial flutter, JPC, junctional rhythm, short PR interval, VPC, right atrial enlargement, and pacing rhythm were independently associated with AF incidence.
Humans ; Male ; Middle Aged ; Aged ; Atrial Fibrillation/epidemiology* ; Prospective Studies ; Incidence ; Atrial Flutter/complications* ; Risk Factors ; China/epidemiology* ; Electrocardiography