The purpose of this study was to compare the impact of modified heart preservation techniques with conventional heart preservation techniques on heart transplant recipients. The goal was to determine if these modified preservation techniques could extend the preservation of the donor heart without increasing the risk of recipient mortality. A retrospective analysis was carried out on 763 cases of orthotopic heart transplantation performed at Wuhan Union Hospital and Nanjing First Hospital, from September 2008 to October 2022. Among these, 656 cases underwent modified heart preservation and were assigned to the study group, while 107 cases underwent conventional heart preservation and were designated as the control group. Detailed information from both groups was collected and compared, including demographic and donor characteristics, survival status, disease type, and recipient/donor characteristics. The study revealed that the modified heart preservation method did not increase the risk of mortality compared to the conventional method. However, it was found that patient factors such as diagnostic classification, recipient age, and donor age significantly influenced mortality risk and were strongly associated with patient survival. The preservation time of the donor heart was significantly longer in the study group compared to the control group, without affecting the survival of the transplant recipients. The findings of our study suggest that modified heart preservation techniques hold promise as a potential method for prolonging heart preservation time. Despite extending the preservation period, these modified techniques did not increase the mortality risk in heart transplant recipients. This could potentially allow for more flexibility in the long-distance transport and preservation of hearts, thereby broadening the scope of viable donors for heart transplantation.

This study investigates the role of DNA methyltransferase 1 (DNMT1) in T cell senescence and heart transplant rejection using mouse models and clinical data. In the mouse heart transplantation model, DNMT1 was found to be highly expressed in graft-infiltrating T cells. Using Dnmt1flox/floxCd4cre/+ mice, researchers demonstrated that T cell-specific knockout of DNMT1 led to long-term graft survival by impairing effector differentiation and promoting senescence in CD4+ T cells rather than in CD8+ T cells. Whole-genome methylation sequencing and RNA sequencing revealed that DNMT1 knockout decreased methylation of the cyclin-dependent kinase inhibitor 1A (CDKN1A) promoter, upregulating CDKN1A expression. Depletion of CDKN1Ahigh cells reversed DNMT1-inhibitor-induced T cell senescence. Clinically, increased T cell senescence was observed in post-transplant patients and is known to increase with age. Additionally, data from the UNOS database showed lower rejection rates in older recipients (age >65). These findings suggest that DNMT1 ablation accelerates CD4+ T cell senescence by altering CDKN1A methylation, thereby reducing T cell function and mitigating rejection. DNMT1 may thus serve as a potential therapeutic target for heart transplant rejection.

Compared with inactivated vaccines, live attenuated vaccines can theoretically induce potent cellular and humoral responses through both exogenous and endogenous antigen-presentation pathways. However, the percentage of live virus particles in the final vaccine products can vary between manufacturers, potentially due to variations in production processes such as lysis and purification. Whether the live-to-dead viral particles ratio influences the resulting immune response pattern remains unclear. To address this question, we formulated varicella vaccines (VarV) mimicking high-viability and low-viability compositions and systematically analyzed the immune response they induced in mice. Surprisingly, the percentage of viable viral particles in VarV products appears to modulate immune polarization. Higher viability tended to be associated with stronger Th1-oriented cellular responses and more robust humoral immunity, contributing to an overall immune profile resembling that induced by endogenous antigen presentation. This finding supports incorporating virus viability into VarV quality control, in addition to conventional viral titers, to optimize vaccine-induced cellular immunity and long-term protection against VZV reactivation.

This cross-sectional study aimed to examine public attitudes toward postmortem organ donation and allocation fairness preferences in China. To this end, an online survey was administered through the Wenjuanxing platform among adults aged ≥ 18 years (N = 895). Only 15.1% of respondents had decided to donate, whereas 74.1% remained undecided; nevertheless, 73.7% would accept a donated organ if needed. Reciprocity (76.0%), first-come-first-served (70.5%), and medical urgency (65.7%) were most frequently endorsed as fair allocation principles. In the full-sample logistic regression (N = 895), positive attitudes (odds ratio [OR] = 5.65, p < 0.001), higher knowledge (OR = 1.56, p < 0.001), and knowing someone who had donated or was considering donating (OR = 1.96, p = 0.013) predicted willingness to donate. Further, a conditional analysis among decision-makers (N = 232) revealed that married status (OR = 0.18, p = 0.007), religious beliefs (OR = 0.22, p = 0.020), and higher education (OR = 1.50, p = 0.024) significantly differentiated donors from non-donors. Collectively, these findings indicate that organ donation willingness in China remains low despite broadly positive attitudes. Knowledge deficits, procedural uncertainty, and family-centered decision-making norms impede commitment, thereby underscoring the need for enhancing public education and institutional transparency.

BACKGROUND:Although the hepatitis A vaccine has been introduced into in China's National Immunization Program for many years, an immunity gap persists among young adults, posing a continued risk of hepatitis A outbreaks. This study aimed to evaluate the cost-effectiveness of hepatitis A vaccination in adults (≥20 years). METHODS:We developed a decision tree Markov model to evaluate various hepatitis A vaccination strategies from a societal perspective, incorporating parameters derived from previously published data. The strategies included serological screening followed by vaccination of susceptible individuals, as well as vaccination without prior screening. Both live attenuated and inactivated vaccines were considered. The incremental cost-effectiveness ratio (ICER) of each strategy was calculated relative to the status quo (no vaccination). The robustness of the findings was assessed through one-way deterministic sensitivity analysis and probabilistic sensitivity analysis. RESULTS:In a cohort of 100,000 individuals aged 20-78 years, the four vaccination strategies prevented 4024-4180 hepatitis A cases. Compared to no vaccination, all strategies were cost-saving at a willingness-to-pay threshold of one time China's per capita GDP, with incremental savings of $1584-$2733 per QALY gained. However, when applying standard incremental analysis to compare active strategies, screening followed by single-dose live attenuated hepatitis A vaccine (HepA-L) was the most cost-effective option compared to the previous non-dominated option. The two non-screening strategies were dominated by screening-based strategies. Results remained robust across sensitivity analyses. CONCLUSION:Compared to the status quo (no vaccination), hepatitis A vaccination in Chinese adults is cost-saving, while pre-vaccination serological screening yields additional cost savings. Screening followed by administration of a single-dose of live attenuated hepatitis A vaccine (HepA-L) for the population aged 20-78 years was the most cost-saving strategy. Our findings offer evidence-based support for the future adjustment and optimization of immunization strategies for policymakers.

In China, inpatient/outpatient visits for rotavirus (RV)-associated diarrhea are common among children aged < 5 years. An interim analysis evaluated RV genotype circulation in China in an ongoing observational effectiveness study of a pentavalent (RV5) vaccine. Data were collected (October 2020-March 2021) from children eligible for vaccination with three doses of RV5 and receiving treatment for acute gastroenteritis. RV gastroenteritis was reported in 494 (62.1

In the present study, by building on the previous development of a DC-SIGN-targeting virus-like structure (VLS) vaccine platform and a comprehensive characterization of SARS-CoV-2 structural biology, particularly insights into the role of the nucleocapsid (N) protein in eliciting cytotoxic T lymphocyte (CTL) responses during infection, we designed a SARS-CoV-2 virion-mimetic structural vaccine that encapsulates an mRNA encoding the spike S1 antigen complexed with N protein complexes, with S1 proteins loaded on its surface. This characterized virion-mimetic structural vaccine not only induces the production of high-efficiency antibodies against both the spike and N proteins but also elicits robust S1-specific and N-specific CTL responses in animal models. Furthermore, the generated antibodies exhibit cross-reactive neutralizing activity against multiple SARS-CoV-2 variants and provide protective immunity against challenge with mutant viruses in immunized hosts. This SARS-CoV-2 virion-mimetic structure effectively recapitulates natural infection pathways, comprehensively activating the innate immune system and thereby creating an optimal microenvironment for eliciting potent and broad-spectrum adaptive immune responses.

Background:Health anxiety can escalate rapidly during infectious disease outbreaks, yet existing assessment tools lack specificity for such contexts. This study aimed to develop and validate the Peking Health Anxiety Scale for Infectious Diseases (PHAID), a brief, context-sensitive measure tailored to infectious disease-related health anxiety. Methods:The PHAID was adapted from the Short Health Anxiety Inventory, with items revised to focus on COVID-19. Psychometric validation was conducted in a sample of 1,660 adults recruited primarily from the United States via Amazon's MTurk during the COVID-19 pandemic. Factor structure was determined using exploratory and confirmatory factor analyses. Reliability, convergent and discriminant validity, and test-retest stability were assessed. A clinical cutoff and the relationship with preventive behaviors were examined. A 5-item short form (PHAID-S) was developed using Item Response Theory. Results:The PHAID demonstrated a stable two-factor structure (Catastrophic Thinking and Infection Worries), excellent internal consistency (α = 0.931 and ω = .947), good test-retest reliability (r = 0.83), and strong convergent and discriminant validity. PHAID scores showed a cubic relationship with handwashing frequency, distinguishing adaptive vigilance from excessive behaviors. The PHAID-S retained good reliability (α = 0.85) and screening accuracy. The cutoff scores were 24 for PHAID and 11 for PHAID-S. Conclusions:The PHAID and its short form provide reliable and valid tools for identifying infectious disease-related health anxiety. They show promise for supporting research and public health screening during outbreaks, though further validation in more diverse populations and clinical settings is warranted.

Objective: The impact of underweight or low-BMI donors on heart transplantation (HTx) outcomes remains poorly understood. This study aims to investigate the effect of underweight donors on post-transplant outcomes. Methods: We retrospectively analyzed 574 patients divided into 2 groups based on donor BMI: underweight donors (BMI < 20 kg/m2, n = 101, 17.6%) and normal-weight donors (BMI 20-25 kg/m2, n = 473, 82.4%). Baseline variables and postoperative outcomes were compared using the Student's t-test for continuous variables and the chi-squared test for categorical variables. Propensity score matching (PSM) was performed to balance baseline differences and control for confounders. Survival analysis was performed using the Kaplan-Meier method. Results: The matched cohort included 71 patients per group, with balanced baseline characteristics. Compared to the normal-weight group, recipients of underweight donors had significantly higher rates of respiratory complications (64.8% vs. 47.9%, p = 0.042), neurological complications (15.9% vs. 4.2%, p = 0.021), renal complications (17.4% vs. 5.6%, p = 0.029), and longer postoperative hospital stay (37.2 vs. 28.4 days, p < 0.001). No significant difference was observed in hospital mortality (2.8 vs. 4.2%, p = 0.649). The overall follow-up time was 72.2 ± 1.9 months (range 68.5 to 75.8). The 1-, 3-, and 5-year survival rates for the underweight and normal-weight donor BMI groups were 83.1% vs. 85.9% (p = 0.624), 75.6% vs. 80.2% (p = 0.527), and 72.0% vs. 77.3% (p = 0.468), respectively. Conclusions: Patients receiving hearts from underweight donors demonstrate comparable long-term survival to those from normal-weight donors but have a higher risk of postoperative complications. These findings suggest that underweight donors could be cautiously utilized to expand the donor pool, offering lifesaving opportunities to recipients who might otherwise experience adverse outcomes due to donor scarcity, albeit with an increased risk of postoperative complications.

Heart transplantation offers the only life-saving option for patients with terminal heart failure; yet, the sequential "innate-adaptive" avalanche initiated by ischemia-reperfusion injury (IRI) remains the Achilles' heel of long-term graft acceptance. Current regimens overwhelmingly focus on either the adaptive or the IRI-triggered innate arm, failing to interrupt the positive-feedback loop that amplifies allo-rejection. To address this unmet need, we herein present a single ROS-responsive nanoplatform that weds dual immunosuppression with on-demand oxygenation Fe3O4@CaO2@Tac@HA. The core-shell Fe3O4@CaO2 carrier simultaneously loads hyaluronic acid (HA), which is a potent dampener of innate inflammatory signaling, and tacrolimus (Tac), which is a calcineurin inhibitor that arrests adaptive T-cell activation. Upon exposure to the ROS-rich milieu of the reperfused graft, CaO2 undergoes conversion to O2, promptly relieving tissue hypoxia while reducing oxidative stress. In vitro, the nanocomposite exhibits rapid ROS scavenging, sustained oxygen release and inhibit T cell activation; in vivo, it markedly prolongs cardiac-allograft survival by synchronously suppressing innate immune cells infiltration and CD8+ T-cell cytotoxicity. Collectively, Fe3O4@CaO2@Tac@HA offers a translatable "one-two punch" strategy that unites innate and adaptive immunomodulation, setting the stage for precision nanotherapy in cardiac transplantation.

The live-attenuated varicella-zoster virus (VZV) vaccine, mainly based on the Oka strain, is essential for the prevention and control of chickenpox (varicella). Although genomic profiles of internationally prevalent Oka vaccine strain (vOka)-derived preparations have been reported, the comprehensive single-nucleotide polymorphism (SNP) profiles of multiple commercially available Chinese vOka-derived vaccines are still lacking. We performed next-generation sequencing (NGS) on five Chinese-manufactured VZV vaccines, comparing genomic variations against the wild-type parental Oka (pOka) strain and internationally prevalent vaccine products. Notably, among 54 key SNPs distinguishing Chinese vaccines from the wild-type pOka strain, 4 novel China-specific SNPs were identified. What’s more, we identified 6 near-fixed (the vaccine allele frequency >90%) non-synonymous SNPs that consistently co-occurred across all production batches, potentially impacting protein function through amino acid substitutions. Genetic heterogeneity across manufacturers revealed manufacturer-specific signatures, whereas consistent batch production underscored manufacturing stability. By systematically mapping SNPs in Chinese VZV vaccines, this study bridges a critical knowledge gap and provides essential insights into manufacturer-specific genomic signatures.

Biomarker dynamics after neoadjuvant therapy (NAT) may affect molecular subtype classification and treatment decisions. Although previous studies have described receptor conversion after NAT, the clinical significance of integrated biomarker remodeling, including ER, PR, HER2, Ki-67, and AR, particularly in relation to multiple pathological response indicators in real-world clinical practice, remains incompletely understood. We retrospectively analyzed 644 patients with breast cancer who received neoadjuvant therapy followed by surgery. Changes in ER, PR, HER2, Ki-67, and AR were evaluated using McNemar’s test and the Wilcoxon signed-rank test. Multivariable logistic regression was used to assess associations between biomarker evolution and treatment response, including pCR, Miller–Payne grade, ypT stage, and ypN status, with emphasis on residual disease. Exploratory analyses also evaluated biomarker-change patterns according to pretreatment Nottingham grade. A sensitivity analysis was performed using the more stringent pCR definition of ypT0 ypN0. ER, PR, and HER2 conversion rates were 13.4

We examine how prenatal exposure to air pollution interacts with gender-biased parental investments to shape long-run cognitive performance. Using nationally representative survey data from China, we show that fetal PM2.5 exposure significantly reduces cognitive ability for women, particularly among those with brothers. Our evidence suggests that the family investment channel operates primarily through education rather than health, with gender-biased educational resource allocation compounding negative outcomes for females. Specifically, conditional on the same level of fetal PM2.5 exposure, females receive less homework assistance from their families and attain lower levels of education. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

A significant numerical increase of genotype GII.17 norovirus-associated sporadic infections was observed in multiple cities in China during the 2024-2025 season. We collected fecal samples from hospitalized children with acute gastroenteritis from 29 sentinel hospitals nationwide to screen for norovirus. A total of 18.7% (n = 412) of the samples tested positive, with a decrease in genotype GII.4 (27% of all positive cases) coinciding with an increase in GII.17 (62%). Comparative phylogenetic analysis of RNA-dependent RNA polymerase and capsid gene sequences revealed that these GII.17[P17] strains were most closely related to strains circulating in the United States and European countries during 2023-2024, with which they shared a recent common ancestor. The evolving epidemiology of norovirus, characterized by the circulation of multiple genotypes, highlights the need for ongoing surveillance and research to better understand its impact and guide the development of vaccines.

Adeno-associated virus (AAV)-mediated gene therapy represents a promising approach for treating genetic disorders. However, challenges remain in achieving stable transgene expression and mitigating liver injury during long-term therapy. Previous studies have implicated the activation of RIG-I-like receptors (RLRs), which detect double-stranded RNA (dsRNA), as a potential inhibitor of transgene expression. In this study, we investigated the role of the RLR pathway in AAV-transduced cells, with a focus on the generation of sense and antisense RNA, as well as the formation of dsRNA. Our findings revealed that dsRNA is produced following AAV transduction, leading to the activation of the RLR pathway and the induction of innate immune responses. Prolonged AAV transduction in mice resulted in significant liver injury, which was independent of adaptive immune activation. Instead, mitochondrial antiviral signaling protein (MAVS) activation emerged as a critical mediator of these effects. Notably, downregulation of MAVS enhanced transgene expression, suggesting that modulating MAVS could enhance the efficacy of AAV-based gene therapy. This study elucidates the mechanisms underlying dsRNA formation and RLR pathway activation, highlighting their impact on the efficacy of AAV gene therapy. These findings suggest that strategies aimed at minimizing dsRNA production and targeting the RLR-MAVS pathway could reduce immune activation and enhance therapeutic transgene expression, thereby optimizing AAV-based interventions for genetic disorders.

Primary human aortic valvular interstitial cells (pHAVICs) play crucial roles in maintaining the mechanical structure and microenvironmental homeostasis of aortic valves. Pathologic processes such as inflammation, senescence, apoptosis, and metabolic disorders of valvular interstitial cells often lead to calcified aortic valve disease (CAVD). However, the lack of clinically relevant cellular models has impeded our understanding of CAVD. Here, we immortalized primary HAVICs with SV40 LTA. The iHAVICs (immortalized human aortic valvular interstitial cells) were maintained in a nonsenescent state and still had the potential to be induced into a senescent phenotype. In calcification induction experiments, iHAVICs can be induced to transform into osteogenic phenotypes via different stimuli via different pathways, accompanied by variations in different markers. In conclusion, we established and characterized a novel human immortalized aortic valve interstitial cell line as a practical in vitro experimental tool for the study of aortic valve calcification disease.

Myocardial ischemia–reperfusion injury (IRI) is the major cause of primary graft dysfunction in heart transplantation, which is characterized by mitochondrial dysfunction. Hyperoside is a bioactive compound that has been reported to have pharmacological potential for cardiac and mitochondrial protection. Here, we investigated the protective effect of hyperoside during myocardial IRI and identified the underlying mechanisms. In this study, we established IRI in an in vivo murine heterotopic heart transplantation model and an in vitro hypoxia–reoxygenation cell model. Inflammatory responses, oxidative stress level, mitochondrial function, and cardiomyocyte apoptosis were evaluated. We found that hyperoside pretreatment alleviated through reducing MDA content, LDH activity, TUNEL positive cells, serum cTnI level, Bax protein expression and the level of inflammatory cytokines, and increasing SOD activity and Bcl-2 protein expression. Furthermore, hyperoside pretreatment improved Opa1-mediated mitochondrial fusion, upregulated mitochondrial ATP content and downregulated NADP+/NADPH and GSSG/GSH ratios. Opa1 inhibitor blunted the protective effects of hyperoside. Mechanistically, Co-immunoprecipitation experiments showed the binding property between Tom70 and Opa1, siRNA knockdown, AAV-mediated loss-of-function and gain-of-function approaches suggested that hyperoside-promoted Opa1-mediated mitochondrial fusion required the upregulation of Tom70. Collectively, we demonstrated for the first time that hyperoside administration alleviates myocardial IRI by promoting Opa1-mediated mitochondrial fusion in vivo and in vitro. The Tom70-Opa1 pathway was essential for cardioprotective effects of hyperoside treatment. The results in our study indicated that hyperoside or promotion of mitochondrial fusion might be a new potential option for the prevention and treatment of IRI in heart transplantation.

Purpose:Early relapsed breast cancer, characterized by recurrence within two years post-surgery, often results from drug resistance and rapid progression. The clinicopathological, prognostic and molecular features of these patients still await exploration. Methods:In this study, 43 patients with early relapsed breast cancer were included as well as 42 advanced breast cancer patients who experienced a recurrence after two years since surgery as the control group. Clinicopathological factors and prognosis were compared among the two groups, and tumor tissue from 27 available early relapsed patients was subjected to genetic sequencing. Results:Compared with the control group, early relapsed group exhibited more aggressive malignant biological characteristics, shorter median overall survival (27.8 vs 49.8 months, P=0.005) and lower objective response rate for the first line treatment (42.90% vs 86.8%, P<0.001). Genetic sequencing of 27 early relapsed breast cancer demonstrated with TP53 (52%), PIK3CA (22%), and MLL3 (19%) as the top three frequently mutated genes, suggesting potential therapeutic targets for personalized treatment strategies. Conclusion:Early relapsed breast cancer patients demonstrated poor prognosis and treatment response, indicating a reagent need of effective treatment combination for disease control. Genetic sequencing may identify potential therapeutic targets, providing new therapeutic opportunities for such patients. These findings underline the urgent need for personalized therapeutic strategies informed by genetic profiling to improve outcomes for early-relapsed breast cancer patients.