As SARS-CoV-2 variants continue to spread, breakthrough infections (BTI) provide real-world insights into the durability and heterogeneity of COVID-19 vaccine-induced immunity. This study aimed to characterize the immune response dynamics and reconstruction characteristics after BTI in participants with different vaccination regimens in Zhejiang Province, China.

A total of 370 participants were enrolled from a stratified random sample of permanent residents. Participants were either unvaccinated or had received one of the following vaccine regimens: one dose of adenoviral vector vaccine, two or three doses of inactivated vaccine, or, three doses of recombinant protein subunit vaccine. Paired serum samples were collected after vaccination and after BTI. RBD-IgG levels, pseudovirus neutralizing activity, and eight cytokines were systematically quantified. Correlation analyses and post-infection lower-quartile subgroup (T2-LQ) analyses were performed to assess immune heterogeneity.

All vaccine groups exhibited robust seroconversion, with post-vaccination RBD-IgG positivity exceeding 90% for both inactivated and recombinant vaccines. Following BTI, antibody levels and neutralizing activity increased significantly across all vaccine groups, consistent with the boosting effect of hybrid immunity. Cytokine profiling analyses revealed minimal differences between vaccine groups post-infection, with immune dynamics primarily driven by longitudinal changes. Notably, IL-13 levels declined consistently across all groups, accompanied by modest changes in the overall cytokine profile. Correlation analyses did not identify a stable concordance between antibodies and cytokines. However, variant-specific RBD-IgG measurements were highly correlated at both time points. Additionally, a post-infection lower-quartile subgroup (T2-LQ) was identified. Among BTI participants, baseline WT-specific RBD-IgG levels were comparable between T2-LQ and non-LQ individuals, suggesting that the low-responder phenotype is not simply attributable to pre-infection antibody levels.

This paired-sample, population-based study suggests that BTI may further enhance humoral responses and be accompanied by changes in inflammatory/immunoregulatory markers on top of prior vaccine-induced immunity, while reducing some overall immune differences across vaccine platforms. The identification of the T2-LQ subgroup highlights persistent heterogeneity in post-infection immune responses and suggests the potential value of continued immune monitoring in the post-pandemic era.

The three components of the definition of CFTR-related disorders (CFTR-RD) recently proposed by European Cystic Fibrosis Society (ECFS) are the presence of specific clinical features, the exclusion of a diagnosis of cystic fibrosis (CF), and evidence of a partially functional CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) protein, whose activity deficit does not reach the diagnostic thresholds for CF. Among the phenotypes suggestive of CFTR-RD, recurrent acute pancreatitis (RAP) is frequently observed. We report the case of a 12-year-old girl presenting with multiple episodes of RAP, an intermediate sweat chloride test result, and two CFTR gene variants in probable compound heterozygosity (p.Phe508del/p.Arg1438Trp). This case highlights the diagnostic complexity of CFTR-RD and the importance of a multidimensional approach. Early recognition of these disorders is essential in the era of CFTR modulator therapies. Improved clinician awareness is necessary to optimize the diagnosis and management of these still underrecognized conditions.

Pneumocystis jirovecii, formerly known as Pneumocystis carinii, is an opportunistic fungus responsible for Pneumocystis pneumonia (PPJ). This is a serious and potentially fatal infection in immunocompromised individuals. This is mainly observed in patients with human immunodeficiency virus (HIV), but also in patients undergoing immunosuppressive treatment immunosuppressive therapy, patients with hematological malignancies, solid tumours and organ transplants. The incidence of pneumonia has risen steadily in recent years, due to the increased use of by the increasing use of immunosuppressive medication. Its diagnosis is based on detection of the pathogen in pulmonary secretions. PPJ is associated with high morbidity and mortality (35-50 %), particularly in the absence of early diagnosis and adequate treatment (90 %). Moreover, the prognosis is poorer in these non-HIV patients. The treatment of choice is trimethoprim-sulfametoxazole (TMP-SMX). The epidemiology, clinical presentation and treatment differ from those of HIV patients and will not be will not be discussed in this article devoted to non-HIV patients.

To observe the effect of acupuncture based on the theory of "exterior-interior relationship between lung and large intestine" on acute exacerbation of bronchial asthma on the basis of the conventional western medicine therapy.

Forty-eight patients with acute exacerbation of bronchial asthma were randomly divided into an observation group (24 cases, 2 cases were eliminated) and a control group (24 cases, 1 case was eliminated). The control group was treated with conventional western medicine therapy. Based on the treatment of the control group ,the patients in the observation group were treated with acupuncture based on the theory of "exterior-interior relationship between lung and large intestine", bilateral Feishu (BL13), Dachangshu (BL25) and Dingchuan (EX-B1) were selected, 20 min each session，once every other day, 3 times a week for 14 days. Before and after treatment, the peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC), asthma control questionnaire 5 (ACQ5) score and TCM symptom score were observed in the two groups.

After treatment, the PEF, FEV1 and FEV1/FVC in the two groups were increased compared with those before treatment (P<0.01, P<0.05)，the ACQ5 scores and TCM symptom scores were decreased compared with those before treatment (P<0.01); the changes of PEF, ACQ5 score and TCM symptom score in the observation group were larger than those in the control group (P<0.05, P<0.01).

On the basis of the conventional western medicine therapy, acupuncture based on the theory of "exterior-interior relationship between lung and large intestine" could improve pulmonary function and alleviate clinical symptoms in patients with acute exacerbation of bronchial asthma.

Some patients with corticobasal degeneration (CBD) present with neuropsychiatric symptoms, including frontal lobe symptoms. However, stupor is rarely reported. Here, we report a case of acute restlessness at onset, which was clinically diagnosed as frontotemporal dementia (FTD) but was found to be CBD at autopsy. A 71-year-old woman with COVID-19 presented to our hospital. At the age of 62, she had suddenly become restless and confused without any preceding motor or psychiatric symptoms. She was treated with psychotropic drugs but subsequently entered stupor and was admitted to a psychiatric hospital. Magnetic resonance imaging showed mild atrophy of the frontal lobe. Single-photon emission computed tomography showed decreased blood flow in the frontal lobe, and the patient was clinically diagnosed with FTD. At the age of 71, she was transferred to our hospital from a psychiatric hospital for COVID-19 treatment. Upon transfer to our hospital, the patient presented with akinetic mutism. The patient died of respiratory failure 10 days after the onset of COVID-19. Immunostaining with AT8 and RD4 antibodies revealed astrocytic plaques, pretangles, coiled bodies, and threads, predominantly in the frontal lobes and basal ganglia. Other pathologies include accumulation of pTDP43 in the basal ganglia, thalamus, and frontal lobes. Argyrophilic grains were observed in the amygdala and the hippocampus, which corresponded to Saito stage 2. Other neurodegenerative proteins, such as amyloid β or α-synuclein, were not observed. The patient was pathologically diagnosed with CBD. We present a rare autopsy case involving a patient with CBD who presented with acute psychiatric symptoms and stupor. The psychiatric symptoms were characterized by agitation and fear-related behavior, which differ from the disinhibition and antisocial behavior typically associated with frontal lobe symptoms. Further autopsies are needed to examine the extent of tau pathology spread and accumulation to better understand the psychiatric symptoms of CBD.

The validity of mediation analysis critically depends on the assumption of no unmeasured confounding, which is typically evaluated through sensitivity analysis. However, existing sensitivity analysis methods for mediation analysis with survival outcomes often rely on the rare outcome assumption and neglect the relationship between exposure and unmeasured confounding. To address this challenge, we developed a sensitivity analysis approach to assess the robustness of mediation results. Specifically, it can assess sensitivity to both mediator-outcome confounding and confounding involving the exposure in observational studies. Our method innovatively generates a simulated unmeasured confounder from its conditional distribution, constructed through sensitivity parameters such as regression coefficients linking the outcome, mediator, and exposure to the unmeasured confounder. Then the sensitivity of mediation analysis can be evaluated by comparing the results before and after adjusting for the simulated unmeasured confounder. A three-dimensional visualization tool was developed to visualize the sensitivity of mediation analysis results. We validated our methodology on simulated datasets and further applied it to a real dataset from the China Health and Nutrition Survey (CHNS) to investigate the relationship between obesity and stroke mediated by hypertension. An R package "medsenssurv" has also been developed to facilitate implementation of our proposed method ( https://github.com/Guo-yi-y/medsenssurv).

Despite significant advances in the management of myocardial infarction (MI), therapeutic options targeting upstream pathogenic mechanisms remain scarce. This study introduces a novel multiomics-to-drug discovery framework to identify and validate causal therapeutic targets for MI. We conducted a systematic two-sample Mendelian randomization (MR) analysis integrating expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) data from the IEU OpenGWAS database, with replication in the UK Biobank cohort. Causal inference was rigorously validated using HEIDI heterogeneity tests, Bayesian colocalization, bidirectional MR, and multivariate MR (MVMR) to account for potential confounders. Downstream applications were explored via protein-protein interaction (PPI) network analysis, phenome-wide association studies (PheWAS), and molecular docking simulations. Initial screening identified four candidate genes (BMP1, APOB, FABP2, and ALDH2) associated with MI risk in both discovery and replication cohorts. However, only BMP1 demonstrated consistent causal effects at both transcriptional and proteomic levels, passing all sensitivity analyses with no evidence of horizontal pleiotropy in PheWAS. Colocalization and bidirectional MR further confirmed BMP1 as a robust, independent causal driver of MI. Molecular docking revealed that UK-383367, a selective BMP1 inhibitor, exhibits high binding affinity to the BMP1 active site. While BMP1 is traditionally associated with extracellular matrix remodeling, this study provides the first genetic evidence establishing it as an independent causal risk factor for MI, distinct from conventional traits such as hypertension. By bridging causal genetic inference with structure-based drug prediction, we propose BMP1 inhibition, specifically via agents like UK-383367, as a promising therapeutic strategy to mitigate MI-related pathological remodeling.

BackgroundDual antiplatelet therapy (DAPT) with aspirin and potent P2Y₁₂ inhibitors such as ticagrelor effectively reduces ischemic events but increases bleeding risk. In patients requiring long-term DAPT, switching from ticagrelor to a thienopyridine is often considered to reduce bleeding risk or address other clinical concerns. However, such switching may cause a transient reduction in platelet inhibition, raising concerns about thrombotic complications. In particular, evidence is limited regarding the optimal loading dose strategy for East Asian patients undergoing this transition.MethodsIn this randomized, open-label trial, 43 patients with acute coronary syndrome (ACS) who had received ticagrelor-based DAPT for > 6 months after stent implantation were randomized to clopidogrel 600 mg loading/75 mg maintenance, clopidogrel 300 mg loading/75 mg maintenance, or prasugrel 30 mg loading/5 mg maintenance. Platelet reactivity and inflammatory markers (MMP-2, MMP-9, TNF-α) were assessed at baseline, 48 h, and 5 days after switching. The primary endpoint was the proportion of patients achieving optimal platelet reactivity (OPR).ResultsThe proportion of patients achieving OPR was similar among groups at baseline (p = 0.483), 48 h (p = 0.699), and 5 days (p = 0.729). No significant intergroup differences were observed in inflammatory marker levels at any time point. No major adverse cardiovascular events occurred during follow-up.ConclusionsIn stable ACS patients on long-term DAPT, switching from ticagrelor to either clopidogrel or prasugrel maintained consistent platelet inhibition and inflammatory profiles, indicating that these switching strategies produce comparable pharmacodynamic profiles in East Asian populations during the early post-switch period.Trial RegistrationThis investigator-initiated pharmacodynamic study was not prospectively registered.

IntroductionHypertension has emerged as a significant comorbidity among people living with Human Immunodeficiency Virus (HIV). However, the prevalence and determinants of hypertension in Ethiopia remain inconsistent across studies.MethodsA systematic search of PubMed, Science Direct, Cochrane Library, Hinari, and Google Scholar was conducted following PRISMA 2020 guidelines. Both published and grey literature conducted in Ethiopia were included. The Newcastle Ottawa scale was used to assess the quality of included studies.ResultsPooled prevalence of hypertension among people living with HIV in Ethiopia was 22% (95% CI: 17.0-28.0). Factors significantly associated with hypertension among people living with HIV included physical inactivity (AOR=2.73; 95% CI: 2.05-3.41), excessive alcohol drinking (AOR=3.01; 95% CI: 1.41-4.61), and ART duration ≥5 years (AOR=2.50; 95% CI: 1.46-3.54).ConclusionHypertension affects approximately one in five people living with HIV in Ethiopia. Physical inactivity, alcohol use and long-term ART were significantly associated with Hypertension.

The C-reactive protein-triglyceride-glucose index (CTI) reflects systemic inflammation and insulin resistance, but its relationship with coronary artery calcium (CAC) progression remains unclear. This study examined the association between CTI and CAC progression in a longitudinal cohort.

Participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study with CAC measurements at years 15, 20, and 25 were included. CTI was calculated from fasting blood samples at year 15 and categorized into quartiles. CAC was quantified using standardized computed tomography. CAC progression was defined as incident CAC > 0 for those with baseline CAC = 0, an annualized CAC increase ≥ 10 units for those with baseline CAC: 0-100, or an annualized percent increase ≥10% for those with baseline CAC ≥ 100. Cox proportional hazards models estimated hazard ratios (HRs), adjusting for cardiovascular risk factors.

Among 2655 participants (mean age 40.3 ± 3.6 years; 44.7% men), 704 (26.5%) experienced CAC progression over 8.9 ± 2.0 years. After adjustment, individuals in the highest CTI quartile had a 38% higher risk of CAC progression compared with the lowest quartile (HR = 1.380; 95% CI: 1.072-1.775). Subgroup analyses by age, sex, race, body mass index, and baseline CAC status were consistent, and results remained robust after excluding participants with baseline diabetes or lipid-lowering medication use.

Higher CTI was independently associated with increased CAC progression, supporting its potential utility as a biomarker for identifying individuals at elevated risk of subclinical atherosclerosis.

URL: https://www.

gov; Unique identifier: NCT00005130.