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.

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

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.

Objective:To investigate the application value of Da Vinci robotic transanal minimally invasive surgery (R-TAMIS) for local resection of rectal neoplasms.Methods:The retros-pective and descriptive study was conducted. The clinicopathological data of 7 rectal neoplasms patients undergoing R-TAMIS in Daping Hospital of Army Medical University from June 2017 to March 2021 were collected. There were 3 males and 4 females, aged (60±7)years. Observation indicators: (1) intraoperative situations; (2) postoperative recovery; (3) postoperative histopatholo-gical examinations; (4) follow-up. Follow-up was conducted using telephone interview or outpatient examination to detect readmission of patients within postoperative 30 days, tumor recurrence and metastasis and survival of patients. Follow-up was performed at postoperative 1, 3, 6 months and once every 6 months thereafter up to April 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative situations. All the 7 patients underwent R-TAMIS successfully without conversion to laparotomy or laparoscopic surgery. Of the 7 patients, 2 cases underwent full-thickness rectal resection and 5 cases underwent submucosal dissection of tumor. The rectal wounds were not sutured in 2 cases because of large lesions, and the rectal wounds were sutured with synthetic sutures in 5 cases after resection of lesions. Transanal drainage tube was placed in 2 cases and not in 5 cases. The volume of intra-operative blood loss of the 7 patients was 15(range, 2?50)mL. The total operation time of the 7 patients was (91.4±18.4)minutes, including (19.1±2.3)minutes for transanal platform placement and Da Vinci robotic surgical system installation, and (72.3±16.6)minutes for operation. There was no intraoperative complication such as urethral injury. (2) Postoperative recovery. All the 7 patients started water drinking and out-of-bed activities at postoperative day 1 and liquid food intake at postoperative day 2. The time to postoperative first flatus of the 7 patients was 1(range, 1?3)days. The two cases with transanal drainage underwent removing of transanal drainage at postoperative day 2. There was no postoperative complication and the duration of postoperative hospital stay of the 7 patients was 3(range, 3?9)days. (3) Postoperative histopathological examinations. Of the 7 patients, 3 cases had villous adenoma, 2 cases had villous adenoma combined with high grade intraepithelial neoplasia, local canceration and tumor invasion into submucosa (stage SM1), 1 case had villous adenoma combined with high grade intraepithelial neoplasia, local canceration and tumor localized in the inner mucosa (stage Tis) and 1 case had moderately differentiated adeno-carcinoma with tumor invasion into superficial muscle layer (stage T2). All the 7 patients had negative surgical margins with none of tumor cell remained in the base. (4) Follow-up. All the 7 patients were followed up for 18(range, 1?42)months. One of the 7 patients showed rectal adenocarcinoma with tumor invasion into superficial muscle layer by the postoperative histopathological examina-tion and was recommended for remedial radical surgery. The patient refused further surgery and underwent 3 courses of oral capecitabine chemotherapy. The other 6 patients did not receive postoperative chemotherapy. None of 7 patients underwent readmission within postoperative 30 days, and no patient had tumor local recurrence, distant metastasis or death during the follow-up.Conclusion:R-TAMIS for local resection of rectal neoplasms is safe and feasible for patients with rectal adenoma and early rectal cancer, with reliable short-term efficacy and short-term oncological efficacy.

ObjectiveTo investigate the value of peripheral blood long non-coding RNA-LET (lncRNA-LET) in the diagnosis of chronic hepatitis B (CHB) cirrhosis, and to provide a basis for early clinical diagnosis and treatment of liver cirrhosis. MethodsA total of 175 CHB patients who attended The Affiliated Hospital of Chengde Medical University from March 2017 to May 2019 were enrolled, among whom 52 patients with hepatitis B cirrhosis were enrolled as cirrhosis group and 123 patients without the pathological changes of liver cirrhosis were enrolled as non-cirrhosis group. A total of 40 healthy individuals who underwent physical examination in our hospital during the same period of time were enrolled as normal control group. Liver function parameters and the level of lncRNA-LET in peripheral blood were measured for all subjects. The t-test was used for comparison of continuous data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H test was used for comparison of ranked data. A Pearson correlation analysis was performed to investigate correlation. The receiver operating characteristic (ROC) curve was used to investigate the value of peripheral blood lncRNA-LET in predicting liver cirrhosis. Results Compared with the normal control group, the cirrhosis group and the non-cirrhosis group had significantly higher serum levels of the liver function parameters total bilirubin (TBil), total bile acid (TBA), albumin (Alb), and alanine aminotransferase (ALT) (all P＜0.05) and a significantly lower serum level of cholinesterase (ChE) (P＜0.05); compared with the non-cirrhosis group, the cirrhosis group had significantly higher serum levels of TBil, TBA, Alb, and ALT (all P＜0.05) and a significantly lower serum level of ChE (P＜0.05). Compared with the normal control group, the cirrhosis group and the non-cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood (P＜0.05), and the cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood than the non-cirrhosis group (P＜0.05). The relative expression of lncRNA-LET decreased significantly with the increase in liver fibrosis stage (P＜0.05). In the patients with CHB, the relative expression of lncRNA-LET in peripheral blood was negatively correlated with liver fibrosis stage, TBil, TBA, Alb, and ALT (r=-0.352,-0.372,-0.364, and -0.410, all P＜0.001) and was positively correlated with ChE (r=0.340, P＜0.001). The ROC curve was used to analyze the value of peripheral blood lncRNA-LET in predicting liver cirrhosis, and the area under the ROC curve was 0934, with an optimal cut-off value of 0.833, a sensitivity of 84.57%, and a specificity of 80.57%. ConclusionThe expression level of lncRNA-LET in peripheral blood decreases with the progression of liver fibrosis and has a good value in the diagnosis of CHB cirrhosis, and therefore, it can be used as a potential biological indicator for the diagnosis of liver cirrhosis.

Objective To designe, synthesize a series of chlorin p₆ ether photosensitizers and preliminarily investigate their photodynamic antitumor activity based on previous research results that alkoxyl ether derivatives of 3-vinyl on chlorin f exhibited stronger photosensitive antitumor activity than parent compound. Methods Purpurin-18 (4) was obtained by oxidative degradation with air and alkali on pheophorbide a (5) which was prepared through acid hydrolysis of chlorophyll a from crude chlorophyll extracts in Chinese traditional herb named Silkworm excrement. Then, chlorin p₆ trimethylester (2) were formed via basic hydrolysis of internal anhydride ring for lead compound 3 and following immediately methylation with CH₂N₂. The intermediate 2 reacted with 33% HBr, following nucleophilic substitution with various alkoxyl alcohol to get six title compounds (1). All title compounds were subjected to photodynamic antitumor activity screening for melanoma B16-F10 cell in vitro. Results All title compounds showed much higher phototoxicity against melanoma B16-F10 cells than talaporfin and verteporfin. Their structures were confirmed by ¹H-NMR, ¹³C-NMR, ESI-MS and ESI-HRMS spectra. Conclusion Chlorin p₆ ether compounds were promising candidate photosensitizers for PDT applications due to theirs high dark toxicity/phototoxicity ratio and excellent phototoxicity, which were worthy of further research and development.