Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

Objective:To research on the teaching effect of constructing and applying the test bank of Medical Immunology.Methods:A total of 475 students from Hainan Medical College in 2019 were set as the experimental group,the test bank was used in the teaching process,and 463 students from 2018 were set as the control group.The correlation between the test bank and final test scores of students of the two grades were analyzed and compared.Results:The final paper scores of grade 2019 students were not higher than those of grade 2018(P>0.05),the score distribution,average score,minimum score and pass rate of the 2019 grade were better than those of the 2018 grade(P<0.05).The experimental group had a significantly better learning effect on Medical Immunology than the control group(P<0.05).Conclusion:The construction and application of Medical Immunology test bank can improve students'learning effect.

This article summarizes Professor Wang Yuliang's clinical experience using the"soothing the liver,regulating qi,and resolving stasis method"in the treatment of diabetic retinopathy(DR).Based on the theoretical foundation of the close physiological connection and pathological influence between the liver and eyes,and incorporating the pathological characteristics of retinal disease,Professor Wang believes that liver qi stagnation is the initiating factor in DR,with qi stagnation and blood stasis,as well as obstruction of the collateral vessels,as the core pathological components of DR.Qi stagnation and blood stasis transform into fire over time,dama-ging yin,burning the collaterals,and transforming fluid into phlegm,leading to liver and kidney yin deficiency,the intertwining of phlegm and stasis,and the superposition of multiple pathological factors.Treatment should consistently adhere to the principle of"soothing the liver,regulating qi,and removing stasis".Based on the pathological changes of DR at different stages,treatment should incorporate liver and kidney tonification,cooling blood and stopping bleeding,and resolving phlegm and dampness.While soothing the liver and regulating qi,it can also dispel pathogenic factors such as stasis,phlegm,and heat,thereby restoring retinal function.This provides new insights into the clinical diagnosis and treatment of DR.

Objective To develop a new cardiac rehabilitation exercise program based on the LEARNS health education model for patients undergoing percutaneous coronary intervention(PCI),and to evaluate its effectiveness.Methods A total of 78 inpatients with acute coronary syndrome(ACS)who received PCI between February and May 2024 in a tertiary hospital were enrolled.Using a random number table,participants were assigned to either an intervention group or a control group(n=39 each).The control group received routine health education,while the intervention group received a cardiac rehabilitation exercise program developed based on the LEARNS model.The intervention started during hospitalization and lasted for two weeks.After the intervention,patients'willingness to participate in Phase II cardiac rehabilitation,exercise self-efficacy and exercise behavior,were evaluated.Results All 76 patients completed the study.After the intervention,the intervention group showed significantly higher scores in willingness to participate in rehabilitation(P<0.001)and exercise self-efficacy(P<0.001)compared with the control group.In terms of exercise behaviors,the intervention group also performed better than the control group,with statistically significant differences across related indicators(P<0.05).Conclusion The application of a new PCI postoperative rehabilitation program based on the LEARNS health education model can significantly enhance patients'willingness to participate in Phase II cardiac rehabilitation,improve their exercise self-efficacy and behavior,and effectively promote the implementation and sustainability of cardiac rehabilitation.

Objective:To investigate the possible mechanism of Zaogong Erteng decoction (ZGETD) in the treatment of endometritis.Methods:Femal mice were injected 2.5 mg/mL lipopolysaccharide into uterine horn to induce endometritis model. After modelling, low-dose ZGETD, high-dose ZGETD or amoxicillin was given once a day for 7 d. The appearance of the uterus and pathological changes of uterine tissue were observed 7 d later, and the uterine index was calculated. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in mouse uterine tissue was detected by enzyme-linked immunosorbent assay. The activity of myeloperoxidase (MPO) in mouse uterine tissue was measured by redox reaction. The active ingredients of ZGETD and the target and signal pathway of treatment of endometritis were analyzed by network pharmacology. Western blotting and qRT-PCR were used to detect the expressions of Toll-like receptor 4 (TLR4), P65, p-P65, interferon regulatory factor 3 (IRF3) and p-IRF3 proteins and chemokines CXCL5 and CXCL8 in the mouse uterus, respectively. Terminal dUTP nick end labeling detected endometrial cell apoptosis and endometrial thickness was measured. After treatment, the female rats were mated with the male rats, and the mating rate, the pregnancy rate and the number of implantation sits in the injected uterine horn on day 8 of gestation were counted. Results:Both ZGETD and amoxicillin have atherapeutic effect on endometritis, but compared with low-dose ZGETD and amoxicillin, high-dose ZGETD can significantly alleviate the edema and congestion of uterine tissue and reduce the uterine index (all P=0.001). After treatment, the uterine cavity epithelium of mice was smooth and complete, the uterine gland structure was normal, and no bleeding area and inflammatory cell aggregation were observed. Compared with amoxicillin, high-dose ZGETD significantly decreased the expression of inflammatory factors (TNF-α, IL-1β and IL-6) and MPO activity (all P<0.001). The expression of chemokines ( CXCL5 and CXCL8) was significantly reduced (all P<0.05). The signaling pathways TLR4, nuclear factor kappa-B (NF-κB) and TNF related to the treatment of endometritis by ZGETD were screened by network pharmacology, and their action targets (TLR4, NF-κB and IRF3) were verified. Quercetin, fisetin and luteolin were found to be the most active ingredients acting on these targets. High-dose ZGETD significantly inhibited the activation of TLR4/NF-κB and TLR4/IRF3 pathways ( P<0.05), decreased endometrial cell apoptosis ( P<0.05), and increased endometrial thickness ( P<0.001), mating rate ( P<0.001), pregnancy rate ( P<0.001) and implantation site number of uterine horn on the injection side of LPS after treatment ( P=0.001). Conclusion:High-dose ZGETD has a significant therapeutic effect on endometritis, which may be closely related to the down-regulation of TLR4 signaling pathway.

Objective Based on the phosphatidylinositol kinase(PI3K)/protein kinase B(AKT)pathway and M2 polarization of macrophages,the effects of polydatin on malignant phenotype of osteosarcoma cells were investigated.Methods The macrophages were divided into M0 group,M2 group,polydatin group,and polydatin+PI3K pathway agonist 740Y-P group.The expression of arginase-1(Arg-1)and CD206 mRNAs and proteins in macrophages were detected by RT-qPCR and Western blot.Western blot was used to detect p-PI3K/PI3K and p-AKT/AKT protein expression in macrophages.The osteosarcoma cells MG-63 were divided into control group,control group(RPMI-1640 medium culture),CM-M0 group(M0 group M0 macrophage supernatant is collected for osteosarcoma cells),CM-M2 group(M2 group M2 macrophage supernatant is collected for osteosarcoma cells),CM-polydatin group(M2 macrophage supernatant in the polydatin group was collected on osteosarcoma cells),and CM-polydatin+740Y-P group(M2 macrophage supernatant was collected on osteosarcoma cells in the CM-polydatin+740Y-P group).Edu staining assay was used to detect the proliferation of MG-63 cells.Scratches and Transwell assays were used to detect the migration and invasion of MG-63 cells.Results Compared with the M0 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the M2 group significantly(P<0.05).Compared with the M2 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT decreased in the polydatin group significantly(P<0.05).Compared with the polydatin group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the polydatin+740Y-P group significantly(P<0.05).Compared with the CM-M0 group,the proportion of Edu-positive cells in the CM-M2 group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Compared with the CM-M2 group,the proportion of Edu-positive cells in the CM-polydatin group decreased significantly(P<0.05),and MG-63 cell migration and invasion rates decreased significantly(P<0.05).Compared with the CM-polydatin group,the proportion of Edu-positive cells in the CM-polydatin+740Y-P group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Conclusion Polygonum cuspidatum can inhibit the proliferation,migration and invasion of osteosarcoma cells by inhibiting the M2 polarization of macrophages,and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

OBJECTIVE To quantify pulmonary vascular endothelial subpopulations during bleomycin-induced pulmonary fibrosis in mice.METHODS Sixty male C57BL/6 mice were randomly divided into five groups(n=12 per group)corresponding to distinct observation timepoints:0,1,2,3,and 4 weeks.A model was established via intratracheal instillation of bleomycin(3 mg·kg-1).Lung tissues were harvested at 0,1,2,3 and 4 weeks post-bleomycin induction.Pathological staining was performed to assess lung histoarchitecture and collagen fiber deposition.Single-cell suspensions were analyzed by flow cytometry to quantify temporal changes in pulmonary vascular endothelial subpopulations,including pulmonary macrovascular endothelial cells,general capillaries,and aerocyte capillaries.Immunofluo-rescence staining was performed to validate the expressions of endothelial markers(CD31,APLN,APLNR,CD93).Single-cell transcriptomic data from the Tabula Muris database was analyzed to evalu-ate gene expression profiles of vascular endothelial subpopulations.RESULTS Pathological staining revealed progressive destruction of lung histoarchitecture and collagen deposition during bleomycin-induced pulmonary fibrosis.Flow cytometry demonstrated three-phase dynamics in vascular endothelial cells(CD45-CD31+CD90.2-):a significant decrease during the acute inflammatory phase,stabilization in the fibrotic phase,and partial recovery during the resolution phase.The proportion of von Willebrand factor-positive(VWF+)vascular endothelial cells significantly decreased during the resolution phase,whereas VWF-vascular endothelial cells increased.Single-cell transcriptomics identified Cd93 asa specific gene for general capillary endothelial cells,with a negative correlation with"aerocyte"genes enriched in gas-exchange alveolar capillary endothelial cells.Immunofluorescence confirmed CD93 localization to general capillary endothelial cells.A flow sorting strategy based on CD45-CD31+CD90.2-VWF-CD93-effectively enriched alveolar capillary endothelial cells.This subpopulation trended upward in pulmonary vascular endothelial composition during bleomycin induction.CONCLUSION During bleo-mycin-induced pulmonary fibrosis in mice,pulmonary vascular endothelial subpopulations exhibit dynamic compositional heterogeneity across fibrotic injury and repair phases.

Objective To investigate the association between polymorphisms at rs1044122 of the metalloprotease12(ADAM12)gene and rs1553005 of the calcitionin related peptide alpha(CALCA)gene and disease susceptibility in patients with knee osteoarthritisc(KOA).Methods A total of 188 KOA patients admitted to the First Hospital of Qinhuangdao from January 2022 to January 2024 were selected as the study objects.Another 100 healthy subjects in the same hospital during the same period were selected as the control group.The polymorphisms of ADAM12 rs1044122 and CALCA rs1553005 were analyzed by PCR+gel imaging system.The frequency distribution of alleles and genotypes was compared between control group and KOA group.Logistic regression model was used to analyze the relationship between ADAM12 rs1044122 and CALCA rs1553005 and susceptibility to KOA under three genetic models(co-dominant,dominant and recessive).Results The genotypes of ADAM12 rs1044122 and CALCA rs1553005 in control group and KOA group were consistent with Hardy-Weinberg equilibrium law(all P>0.05),indicating population representation.Compared with the control group,the allele C frequency(41.49%vs 32.00%)of ADAM12 rs1044122 and the allele C(42.55%vs 30.00%)and genotype CC(18.08%vs 9.00%)frequencies of CALCA rs1553005 in KOA group were significantly increased,with statistical significance(χ2=4.980,8.715,8.631,all P<0.05).Logistic regression model showed that in the co-dominant model(AA vs CC)of ADAM12 rs1044122,the risk of KOA occurrence in CC genotype was significantly higher than that in AA genotype(OR=1.656,P<0.05).In the dominant model(AC+CC vs AA),the risk of developing KOA was higher in patients with C allele than in patients with A allele(OR=1.458,P<0.05).Under the codominant model(GG vs CC)of CALCA rs1553005,the risk of KOA in CC genotype was significantly higher than that in GG genotype(OR=1.643,P<0.05).Under the dominant model(GC+CC vs GG)and recessive model(GC+GG vs CC),the risk of developing KOA with C allele was significantly higher than that with G allele(OR=1.491,0.795,all P<0.05).Conclusion ADAM12 gene rs1044122 allele C and CALCA gene rs1553005 allele C and genotype CC increased the risk of KOA.

Objective:To evaluate the role of peptidylarginine deiminase 4 (PAD4)-mediated development of neutrophil extracellular traps (NETs) in lung ischemia-reperfusion injury (LIRI) in mice.Methods:Ninety-six clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=24 each) using a table of random numbers: sham operation group (group S), sham operation + PAD4 specific inhibitor GSK484 group (group S+ G), lung ischemia-reperfusion group (group L), and lung ischemia-reperfusion + GSK484 group (group L+ G). After anesthesia and mechanical ventilation, mice were subjected to left hilum occlusion for 1 h followed by 2 h of reperfusion to establish the LIRI model in L and L+ G groups. Mice underwent thoracotomy for 3 h without left hilum occlusion in S and S+ G groups. In S+ G and L+ G groups, GSK484 4 mg/kg was intraperitoneally injected once a day for 3 days before developing the model. At the end of reperfusion, blood samples were collected from the abdominal aorta for blood gas analysis to record arterial partial pressure of oxygen (PaO 2). Mice were then sacrificed to collect bronchoalveolar lavage fluid (BALF) and to obtain lung tissues. The concentrations of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in BALF were measured using enzyme-linked immunosorbent assay. The wet/dry lung weight (W/D) ratio was calculated. The lung tissues were obtained for microscopic examination of pathological changes (with a light microscope) which were scored after hematoxylin-eosin staining and for determination of the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) (by colorimetric assay) and expression of PAD4, neutrophil elastase (NE), high-mobility group box 1 (HMGB1), and citrullinated histone 3 (Cit-H3) (by Western blot). Results:Compared with group S, lung injury scores and W/D ratios were significantly increased, PaO 2 was decreased, the concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were increased, the content of SOD was decreased, the content of MDA was increased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was up-regulated in L and L+ G groups ( P<0.05), and no significant changes were observed in the aforementioned parameters in group S+ G ( P>0.05). Compared with group L, lung injury scores and W/D ratios were significantly decreased, PaO 2 was increased, concentrations of IL-1β, IL-6, TNF-α, and MPO in BALF were decreased, the content of SOD was increased, the content of MDA was decreased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was down-regulated in group L+ G ( P<0.05). Conclusions:Up-regulated PAD4 expression can promote the development of NETs and aggravate oxidative stress and inflammatory responses in lung tissues, thereby participating in LIRI in mice.

Objective To develop a new cardiac rehabilitation exercise program based on the LEARNS health education model for patients undergoing percutaneous coronary intervention(PCI),and to evaluate its effectiveness.Methods A total of 78 inpatients with acute coronary syndrome(ACS)who received PCI between February and May 2024 in a tertiary hospital were enrolled.Using a random number table,participants were assigned to either an intervention group or a control group(n=39 each).The control group received routine health education,while the intervention group received a cardiac rehabilitation exercise program developed based on the LEARNS model.The intervention started during hospitalization and lasted for two weeks.After the intervention,patients'willingness to participate in Phase II cardiac rehabilitation,exercise self-efficacy and exercise behavior,were evaluated.Results All 76 patients completed the study.After the intervention,the intervention group showed significantly higher scores in willingness to participate in rehabilitation(P<0.001)and exercise self-efficacy(P<0.001)compared with the control group.In terms of exercise behaviors,the intervention group also performed better than the control group,with statistically significant differences across related indicators(P<0.05).Conclusion The application of a new PCI postoperative rehabilitation program based on the LEARNS health education model can significantly enhance patients'willingness to participate in Phase II cardiac rehabilitation,improve their exercise self-efficacy and behavior,and effectively promote the implementation and sustainability of cardiac rehabilitation.