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 evaluate the cost–utility of lecanemab and donanemab in the treatment of early Alzheimer’s disease （AD） in China. Methods A Markov model was developed from a societal perspective to compare standard of care （SOC）, lecanemab plus SOC, and donanemab plus SOC in terms of costs, quality-adjusted life years （QALY）, and incremental cost–utility ratios （ICUR）. Deterministic and probabilistic sensitivity analyses were conducted to assess parameter uncertainty. Results Both intervention strategies increased QALY compared with SOC but were associated with substantially higher costs, and neither was cost-effective under the current willingness-to-pay threshold. Conclusion Lecanemab and donanemab may be more appropriately considered within a multi-tiered healthcare reimbursement framework in China rather than relying solely on basic medical insurance.

ObjectiveTo understand the epidemiological distribution and gene evolutionary variation of influenza A (H3N2) viruses in Fengxian District, Shanghai, in the surveillance year of 2023, and to provide a reference basis for influenza prevention and control. MethodsThe prevalence of influenza virus in Fengxian District in the 2023 influenza surveillance year (April 2023‒March 2024) was analyzed. The hemagglutinin (HA) gene, neuraminidase (NA) gene, and amino acid sequences of 75 strains of H3N2 influenza viruses were compared with the vaccine reference strain for similarity matching and phylogenetic evolutionary analysis, in addition to an analysis of gene characterization and variation. ResultsIn Fengxian District, there was a mixed epidemic of H3N2 and H1N1 in the spring of 2023, with H3N2 being the predominant subtype in the second half of the year, and Victoria B becoming the predominant subtype in the spring of 2024. A total of 75 influenza strains of H3N2 with HA and NA genes were distributed in the 3C.2a1b.2a.2a.2a.3a.1 and B.4 branches, with overall similarity to the reference strain of the 2024 vaccine higher than that of the reference strain of the 2022 and 2023 vaccine. Compared with the 2023 vaccine reference strain, three antigenic sites and one receptor binding site were changed in HA, with three glycosylation sites reduced and two glycosylation sites added; where as in NA seven antigenic sites and the 222nd resistance site changed with two glycosylation sites reduced. ConclusionThe risk of antigenic variation and drug resistance of H3N2 in this region is high, and it is necessary to strengthen the publicity and education on the 2024 influenza vaccine and long-term monitoring of influenza virus prevalence and variation levels.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Objective To investigate the relationship between abnormal expression of angiotensin-converting enzyme(ACE)and lipoprotein(a)[Lp(a)]with hypertension-diabetes comorbidity.Methods A case-control analysis was conducted on 342 patients with metabolic diseases admitted in our hospital between January 2021 and May 2024,and they were divided into in a diabetes-hypertension comorbidity group(114 cases),a diabetes group(114 cases)and a hypertension group(114 cases).Another 114 matched healthy individuals who taking physical examination in our hospital during the same period were subjected and served as the control group.Clinical data were collected and serum levels of ACE and Lp(a)were measured in all the groups.Multivariate logistic regression analysis was applied to analyze the independent risk factors for hypertension-diabetes comorbidity,and ROC curve analysis was performed to evaluate and predict the efficacy.Results The serum levels of ACE and Lp(a)were significantly higher in the comorbidity group than the control,hypertension and diabetes groups(P＜0.01),and in the hypertension and diabe-tes groups than the control group(P＜0.01).After adjusting for waist-to-hip ratio,alanine amin-otransferase and triglyceride,multivariate logistic regression analysis revealed that serum ACE and Lp(a)still were risk factors for the occurrence of hypertension-diabetes comorbidity(P＜0.01).ROC curve analysis demonstrated that when the cut-off value was 39.01 pg/L,ACE had an AUC value of 0.884(95％CI:0.789-0.980),a sensitivity of 76.67％and a specificity of 75.28％in predicting the comorbidity,and when the cut-off value for Lp(a)was 254.33 mg/L,the AUC value was 0.899(95％CI:0.799-0.919),the sensitivity was 85.83％,and the specificity was 82.22％.Their combination improved the AUC value to 0.993(95％CI:0.979-1.000),with a sensitivity of 95.00％and a specificity of 95.28％in the prediction.Conclusion Serum ACE and Lp(a)are independent risk factors for hypertension-diabetes comorbidity,and can be combined together and regarded as biomarkers for early identification of the comorbidity.

Objective:To explore the application and clinical significance of pathological diagnostic criteria for medically refractory epilepsy in children.Methods:Cross-sectional study.A retrospective analysis was conducted on 490 children(pathology involved) with medically refractory epilepsy treated continuously in the Pediatric Epilepsy Center of Peking University First Hospital from January 2019 to May 2022.The distribution of different pathological types was observed, and the differences in clinical characteristics among different pathological types were analyzed through Kruskal-Wallis or χ2 tests.The impact of clinical and pathological features on patient prognosis was evaluated through regression analysis. Results:Focal cortical dysplasia (FCD) was the predominant lesion (49.59%, 243/490).The electroencephalograms ( χ2=6.720, P=0.035) and clinical seizure characteristics ( χ2=26.370, P<0.001) in FCDⅡ were more focal than those in FCD Ⅰ and Ⅲ.Moreover, the proportions of focal resection in surgery ( χ2=24.286, P<0.001) and central involvement ( χ2=22.849, P<0.001) in FCDⅡ were higher than those in FCD Ⅰ and Ⅲ.Univariate and multivariate regression analyses revealed that FCD Ⅱ had a better prognosis than other dysplastic patients among the 375 cases of dysplasia ( P=0.049).Next-generation sequencing was performed on 35 cases of cortical malformations with such morphological characteristics as increased numbers of neurons in the white matter and Olig2-positive glial cell hyperplasia, and SLC35A2 mutations were detected in 2 cases (5.71%). Conclusions:Pathology of refractory epilepsy is specialized and continuously evolving.Standardized specimen processing and the accumulation of morphological, immunohistochemical, and molecular genetic data provide the foundation for clarifying the neuropathological nature of epilepsy, improving integrated classification, and advancing prognosis prediction and targeted therapy.

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.

Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.

Objective To investigate the differences in clinical characteristics,surgical outcomes,and prognosis between sporadic intracranial hemangioblastoma(IC-HB)and von Hippel-Lindau(VHL)syndrome-associated IC-HB.Methods A retrospective consecutive series of patients who underwent microsurgical resection at the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University,between April 2014 and January 2024,with postoperative pathological confirmation of IC-HB,was included.Clinical and imaging data were collected,including demographics(sex,age),preoperative clinical manifestations(asymptomatic,headache,dizziness,vertigo or imbalance,blurred vision or papilledema,nausea or vomiting,other symptoms),number of symptoms,lesion type(solid or solid-cystic),lesion size(volume,longest diameter,anteroposterior diameter,superoinferior diameter,transverse diameter),lesion location(cerebellar region:hemisphere,vermis;brainstem region:medulla oblongata,fourth ventricle;skull base region:cerebellopontine angle,jugular foramen,petroclival region),Karnofsky performance status(KPS)score(preoperative,postoperative;KPS score＞70 and 70),surgical information,and follow-up data.Based on past medical history,family history,and VHL gene test results,patients were classified into sporadic IC-HB and VHL syndrome-associated IC-HB groups.Differences in clinical characteristics,surgical outcomes,and follow-up status were compared between the groups.Improved outcomes were defined as increases in KPS scores over 0 at 6-month follow-ups in comparison with preoperative KPS,while non-improved outcomes were defined by unchanged or decreased(＞0 point)KPS scores.Survival outcomes,including postoperative recurrence(newly occurring abnormally enhancing nodules at the surgical site or periphery with continuous development during follow-ups.Recurrence could be verified through the combination of imaging enhancement features,clinical manifestations and post-operative pathological examinations),postoperative KPS improvement,and death of any cause during follow-up.The outcomes of postoperative KPS improvement versus non-improvement(unchanged or worsened)were analyzed through univariate analysis with the Firth penalized maximum likelihood Logistic regression model.Variables meeting the criteria(P＜0.05 in univariate analysis,clinical importance,statistical model feasibility)were included in a multivariate Logistic regression model to identify independent factors influencing functional outcomes.Survival outcomes were analyzed using Cox proportional hazards regression models.Kaplan-Meier survival analysis was used to assess recurrence-free survival rates between groups with the Log-rank test.Furthermore,univariate and multivariate Logistic regression analyses were performed separately for the sporadic IC-HB and VHL syndrome-associated IC-HB subgroups to explore independent factors for postoperative KPS improvement.Results A total of 82 IC-HB patients(41 male,41 female),aged 11-73 years(mean[42±15]years),were included.Among which,68 had sporadic IC-HB and 14 had VHL syndrome-associated IC-HB.39 patients had improved postoperative KPS and 43 patients showed no improvements in KPS scores.(1)For clinical characteristics,the age of onset was younger in the VHL syndrome-associated IC-HB group([35±14]years vs.[44±15]years,P=0.044).Lesions in VHL syndrome-associated IC-HB patients were more likely to involve the brainstem and adjacent critical structures(8/14 of which involved medulla oblongata),while sporadic IC-HB was more common in the cerebellar hemispheres(70.6％[48/68]).The distribution of lesion location across cerebellar,skull base,and brainstem regions differed significantly between groups(P=0.015),while other characteristics showed no significant differences(all P＞0.05).(2)For treatment and follow-ups,all patients underwent gross total microsurgical resection.Preoperative angiography via femoral artery was performed in 22 patients,with partial preoperative embolization in 4 patients.Postoperatively,KPS improved in 39 patients,remained unchanged in 33 patients,and worsened in 10 patients.The change in KPS scores pre-to post-operatively did not differ significantly between groups(P=0.707).The recurrence rate was higher in the VHL syndrome-associated IC-HB group(4/14 vs.5.9％[4/68],P=0.026),but there was no significant difference in mortality(P=0.999).(3)For analysis of factors influencing postoperative KPS improvement,univariate Logistic regression showed preoperative asymptomatic(OR,0.05,95％CI0.00-0.39,P=0.002),preoperative dizziness(OR,2.62,95％CI 1.09-6.47,P=0.031),vertigo/imbalance(OR,3.60,95％CI 1.04-15.45,P=0.043),nausea/vomiting(OR,4.49,95％CI 1.65-13.53,P=0.003),preoperative symptoms(OR,2.27,95％CI 1.46-3.86,P＜0.01)and preoperative KPS ≤70(OR,7.65,95％CI 1.60-74.47,P=0.009)were strongly associated with KPS improvement.Multivariate Logistic regression only identified the number of preoperative symptoms as an independent predictor of postoperative KPS improvement(OR,2.44,95％CI 1.04-6.32,P=0.049).(4)For survival outcome analysis,no significant differences in the risk of postoperative recurrence,KPS improvement,or death were observed between the VHL syndrome-associated and sporadic IC-HB patients(recurrence:HR,4.88,95％CI 0.97-24.69,P=0.055;KPS improvement:HR,0.60,95％CI 0.25-1.43,P=0.246;mortality:P=0.999).Kaplan-Meier curves showed no statistically significant difference in recurrence-free survival rate between groups(P=0.053).(5)In the subgroup analysis,in sporadic IC-HB patients,multivariate Logistic regression identified the number of preoperative symptoms as an independent predictor of postoperative KPS improvement(OR,1.97,95％CI 1.14-3.68,P=0.021).Due to the small sample size,reliable parameter estimation was not possible for the VHL syndrome-associated IC-HB subgroup due to the small sample size.Conclusions VHL syndrome-associated IC-HB patients have a higher risk of recurrence in comparison with sporadic IC-HB patients.The number of preoperative symptoms can guide survival ending assessment.

Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.