Breast cancer poses a severe global health threat, necessitating effective therapeutic strategies. Traditional Chinese medicine (TCM) has demonstrated promise in breast cancer treatment. Xiang Bei San (XBS), an empirical formula used in TCM for breast cancer treatment. Despite its frequent clinical application, the anti-breast cancer mechanisms of XBS remain elusive. The present work initially analyzed XBS chemical composition with high-resolution ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). For evaluating the in vivo anti-breast cancer effects of XBS, an orthotopic 4T1 cell mouse model of breast cancer was established. Administration of XBS significantly inhibited tumor growth, with tumor inhibition rates of 45.59%, 49.48%, and 60.89% observed for low, medium, and high-dose groups, separately. Notably, XBS treatment exerted no significant impact on mouse body weight and exhibited no apparent toxic or side impacts. Furthermore, morphological, H&E, and immunohistochemical staining confirmed XBS's suppression of lung metastasis. Mechanisms were explored through transcriptome sequencing, flow cytometry, immunofluorescence, and immunoblotting. Our findings suggested that XBS inhibited polarization of M2 macrophages while facilitating that of M1 macrophages. Additionally, it also upregulated TNF-α and IL-1β while inhibiting Arg-1 expression. Moreover, XBS facilitated T-cell infiltration and reduced the expression of CD31 and VEGF, thereby inhibiting tumor angiogenesis, and upregulated α-SMA expression to stabilize vascular structure. Collectively, XBS exerts inhibitory effects on breast cancer growth and metastasis through regulating macrophage polarization and tumor vascularization within the tumor microenvironment. Therefore, XBS represents a potential candidate drug for treating breast cancer.
Obesity is a worldwide problem and a major public health issue in China. To evaluate the efficacy and safety of mazdutide (a once-weekly glucagon and glucagon-like peptide-1 receptor dual agonist) in Chinese adults with obesity (defined as a body mass index of ≥30). A double-blind, placebo-controlled, phase 3, randomized clinical trial including Chinese adults with or without type 2 diabetes that was conducted at 27 hospitals from December 2023 to November 2025. Participants were randomized in a 2:1 ratio to receive a once weekly, 9-mg dose of mazdutide administered subcutaneously (n = 308) or placebo (n = 154) as an adjunct to a reduced calorie diet and increased physical activity for 60 weeks. The coprimary outcomes were the percentage change in body weight from baseline and a weight reduction of at least 5% at week 60. The efficacy and safety analyses were performed in participants who received at least 1 dose of the study treatment. A total of 461 participants (295 [64.0%] female; 16.1% with type 2 diabetes; mean age, 33.9 [SD, 8.4] years; body weight, 94.0 [SD, 13.8] kg; BMI, 34.3 [SD, 3.2]) received the study treatment (307 in the mazdutide group and 154 in the placebo group) and were included in the analyses. At week 60, the mean percentage change in body weight from baseline was -16.65% (95% CI, -18.19% to -15.12%) in the mazdutide group compared with -1.50% (95% CI, -3.43% to 0.43%) in the placebo group (between-group difference, -15.15% [95% CI, -17.22% to -13.09%]; P < .001). At week 60, 84.3% of participants in the mazdutide group had a body weight reduction of 5% or greater compared with 33.1% in the placebo group (between-group difference, 51.6% [95% CI, 43.0% to 60.1%]; P < .001). Adverse events leading to study treatment discontinuation were reported in 2.9% of participants in the mazdutide group compared with 0% in the placebo group. The most common adverse events were vomiting (53.1% in the mazdutide group vs 1.3% in the placebo group), nausea (46.9% vs 3.2%, respectively), and diarrhea (39.4% vs 6.5%); most of the adverse events were mild to moderate in severity. Mazdutide provided clinically meaningful weight reduction in Chinese adults with moderate to severe obesity compared with placebo, but participants receiving the drug experienced gastrointestinal adverse reactions compared with those receiving placebo. ClinicalTrials.gov Identifier: NCT06164873.
The comparative superiority among the triglyceride-glucose (TyG) index and its obesity-related composite indicators in identifying hypertension and carotid atherosclerosis (CAS) remains unknown. This study aims to evaluate and compare the discriminative ability of these indices in a large-scale population to identify the optimal marker for cardiovascular risk assessment. This cross-sectional study included 154,873 participants who underwent routine physical examinations and carotid ultrasonography. Binary logistic regression, restricted cubic spline (RCS), receiver operating characteristic (ROC) analyses, and mediation analyses were used to evaluate the associations of TyG, TyG-waist circumference (TyG-WC), TyG-waist-to-height ratio (TyG-WHtR), and TyG-body mass index (TyG-BMI) with hypertension and CAS. The mean age of participants was 45.7 ± 12.5 years, with 42.1% being female and 91.0% being married. A total of 16,235(10.5%) participants had hypertension, and 81,337 (52.5%) had CAS. Comparing the highest to the lowest quartile, TyG-WHtR demonstrated the strongest association with hypertension (OR = 8.644, 95% CI: 7.927-9.426) and CAS (OR = 2.173, 95% CI: 2.086-2.263). RCS analyses revealed monotonic increases for hypertension and complex nonlinear patterns for CAS. Stratified analyses revealed distinct phenotypic signatures. For hypertension, risk magnitudes were markedly amplified in younger adults (≤ 60 years) (P for interaction < 0.001 for all indices). For CAS, a significant interaction between sex and the indices was observed (P for interaction < 0.05 for TyG, TyG-WHtR, and TyG-BMI): TyG-WHtR exhibited the strongest association in women (OR = 1.504), whereas in men, the isolated TyG index was inversely associated with CAS, and only TyG-BMI showed a significant positive association (OR = 1.091). Mediation analyses revealed that obesity indicators (WHtR, BMI) demonstrated substantial direct associations with on outcomes, with TyG providing negligible or partial mediation, which may account for the stronger associations observed with composite indices. TyG-obesity composite indices are strongly associated with hypertension and CAS, particularly in younger adults. TyG-WHtR is optimal for women and the general population, while TyG-BMI is superior for men. These easily accessible and cost-effective metrics can serve as practical tools for early cardiovascular risk screening in primary care. Implementing such age-targeted and sex-specific risk stratification could facilitate more precise and timely preventive interventions.
Colchicine, an ancient anti-inflammatory alkaloid, has been successfully repurposed as a cardiovascular therapeutic agent. This review synthesizes the evolving clinical evidence and mechanistic underpinnings of colchicine's action across a spectrum of cardiovascular diseases. Robust data from randomized trials support its efficacy in reducing recurrences of acute and recurrent pericarditis. In atherosclerotic coronary artery disease, long-term, low-dose colchicine has been shown to significantly reduce major adverse cardiovascular events in patients with chronic coronary syndromes, prompting its inclusion in international guidelines. However, not all trials have yielded consistent results; for instance, in the setting of recurrent myocardial infarction, some studies have failed to demonstrate significant benefit, highlighting issues of reproducibility and patient heterogeneity that have emerged across cardiovascular outcome trials. Evidence for its utility in other settings, such as preventing postoperative atrial fibrillation or ischemia-reperfusion injury, remains inconsistent, and a clear dose-response relationship has yet to be established. The therapeutic benefits are primarily attributed to the pleiotropic anti-inflammatory mechanisms, including microtubule disruption, inhibition of the NLRP3 inflammasome, and modulation of neutrophil and macrophage functions. Despite a narrow therapeutic index, low-dose regimens are generally well-tolerated, with gastrointestinal disturbances being the most common adverse effect. Its pharmacokinetics, notably metabolism via CYP3A4 and transport by P-glycoprotein, necessitate caution regarding drug interactions and use in renal/hepatic impairment. Future research should focus on precise patient stratification, combination therapies, and exploring its potential in emerging cardiovascular indications, solidifying its role in anti-inflammatory therapy.
Löfgren's syndrome is an acute variant of sarcoidosis, characterized by the classic triad of erythema nodosum, bilateral hilar lymphadenopathy, and arthralgia or arthritis. Its low incidence in the Chinese population contributes to limited clinical awareness and diagnostic challenges. We report the case of a Chinese man with long-standing ankylosing spondylitis who had been experiencing recurrent joint swelling, pain, and fever over the past year. At the most recent presentation, he had developed tender, erythematous subcutaneous nodules on the limbs, clinically consistent with erythema nodosum, and was diagnosed with ankylosing spondylitis and Löfgren's syndrome. A comprehensive review of his treatment course revealed a favorable response to glucocorticoid therapy. Notably, he had received adalimumab for ankylosing spondylitis over the past year, and the temporal relationship suggested that adalimumab precipitated Löfgren's syndrome relapse. We further reviewed the literature comparing Löfgren's syndrome between Western and Asian populations. Our findings indicate that Asian Löfgren's syndrome patients are more likely to receive a delayed diagnosis and often require lengthier glucocorticoid therapy. These differences may stem from genetic predispositions influencing disease expression and immune response. Therefore, we recommend that glucocorticoid regimens for Löfgren's syndrome in Chinese patients be carefully titrated and monitored. In a similar manner, when Löfgren's syndrome coexists with other rheumatic immune diseases, tumor necrosis factor-α inhibitors such as adalimumab should be used with heightened vigilance to minimize disease relapse.
Urinary stone disease (USD, or urolithiasis) is common and poses a substantial healthcare and economic burden on the working-age population. This study aimed to provide epidemiological insights into the prevalence, incidence, trends, and risk factors of USD among the Chinese population. We conducted a prospective cohort study involving 966,481 participants from the CHinese Electronic health Records Research during 2009-2022 in Yinzhou, China (CHERRY). Temporal trends were estimated using annual percentage changes (APC) via Joinpoint regression analyses. Stratified Cox proportional hazards regression and propensity score analyses were employed to evaluate potential risk factors, population attribution factor (PAF) and number needed to prevent (NNTP). From 2014/2015 to 2021, there was an annualized increase in USD incidence by 5.3-6.8% (P < 0.05). Identified risk factors for USD included tobacco smoking, alcohol drinking, high body mass index, diabetes, hyperlipidemia, hypertension, and cardiovasculardisease while regular exercising served as a protective factor of USD. The PAF ranged from 1.3% for non-drinking behavior to 22.5% for regular exercising (weekly). Correspondingly, the NNTP ranged from 182 for non-smoking behavior to 21 for weekly exercising. USD is a common disease affecting approximately 1 in 10 Chinese, with the incidence rate increasing by 5-6% annually over the past 6-7 years. Lifestyle factors and metabolic syndromes are potential risk factors for the development of USD.
Coptidis Rhizoma (CR) is a typical cold-attribute herb with potential anti-anxiety properties. Bile is of cold nature and can also interfere with the central nervous system. Bile-processed CR (BCR) exhibits synergistically enhanced anti-anxiety performance. However, the underlying mechanism and material basis for this synergism are not clear. To decipher the enhanced anti-anxiety mechanism and material basis of BCR from the perspective of cross-organ regulation. A rat model of anxiety with sthenic heat syndrome was established to systematically evaluate the enhanced anti-anxiety efficacy of BCR in terms of anxiety behaviour, liver metabolism, and histopathology. Subsequently, the gut microbiome sequencing and untargeted metabolomics of the brain, liver, and serum were performed to explore the mechanism of BCR and CR in regulating the gut-liver-brain axis. In vivo and in vitro molecular biology experiments were performed to further clarify the mechanisms underlying the differential efficacy of BCR and CR. Finally, supramolecular self-assembly simulation and tissue distribution in target organs were carried out to predict the material basis for the enhanced efficacy of BCR. BCR performed better than CR in improving the anxiety behaviour and liver metabolism and in alleviating cerebral injury in the rat model of anxiety. The results of gut microbiome and metabolomic analyses indicated that BCR was superior to CR in reshaping the gut microbiota composition and correcting the metabolic disorders in the brain, liver, and serum. Mechanistically, multiomic analysis revealed that BCR and CR (especially BCR) could block the TLR4/NF-κB pathway in the colon, attenuate hepatic inflammation, improve the integrity of the intestinal mucosa and blood-brain barrier, and inhibit the NLRP3/Caspase-1/IL-1β pathway in the brain, thereby blocking the transmission of inflammation along the gut-liver-brain axis and exerting anti-anxiety effects. BCR and CR (particularly BCR) could suppress the overactivation of ammonia-induced MAPK/NF-κB/iNOS pathway and overexpression of glutamine synthetase in the brain, consequently maintaining the normal morphology and glutamate uptake function (GLAST and GLT-1 activities) of astrocytes, alleviating neuronal apoptosis caused by glutamate excitotoxicity (GluN2B), and ultimately blocking the transmission of neurotoxicity along the gut-liver-brain axis to relieve anxiety. The alkaloid-bile acid supramolecules assembled during the decoction of BCR enabled more alkaloids and bile acids to be distributed in the brain and liver, providing material support for the enhanced effect of BCR. BCR was superior to CR in blocking the transmission of inflammation and neurotoxic substances along the gut-liver-brain axis and, hence, exerted stronger efficacy in alleviating neuroinflammation and improving neuronal survival in the rat model of anxiety. The alkaloid-bile acid supramolecules may provide the material foundation. This study fully considers the characteristic of traditional Chinese medicine being able to exert therapeutic effects through multiple pathways, providing novel avenues for research on the processing mechanism.
Limited investigation exists regarding the relationships among the triglyceride-glucose index-frailty index (TyGFI) and incident asthma. This study investigates the association between TyGFI and risk of incident asthma in older Chinese people by combining TyG and FI, using prospective cohort data from the China Health and Retirement Longitudinal Study (CHARLS). We used data from CHARLS Wave 1 (2011) as the baseline and Wave 3 (2015) as the follow-up. Cox hazard regression models were used to analyze the association between TyGFI and incident asthma risk. Restricted cubic spline (RCS) regression was used to test for nonlinearity, and stratified analyses were used to evaluate effect modification. The highest TyGFI quartile showed the greatest risk (HR = 4.30, 95% CI: 2.66-6.95). A significant nonlinear association was observed, with asthma risk rising dramatically when TyGFI exceeded 1.343. Stratified analyses indicated interaction by age. Higher TyGFI is significantly associated with risk of incident asthma in middle-aged and older Chinese adults, suggesting that integrating metabolic-frailty assessment may enhance the ability to identify individuals at high risk for incident asthma at an earlier stage.
Dual-task cost (DTC) is the performance decline observed during simultaneous motor and cognitive tasks. It is associated with cognitive and physiological vulnerability. However, it remains unclear how specific frailty dimensions and cognitive domains contribute to DTC during arithmetic and verbal fluency tasks. We aim to investigate the independent associations between physical, social and oral frailty dimensions versus cognition function with DTC in community-dwelling older adults. We studied 281 participants from the GeriLABS-2 study. Physical frailty was assessed using Fried's Frailty Phenotype, social frailty using the 8-item Social Frailty Scale (SF8) and oral frailty using the Oral Frailty Index-8 (OFI-8). Cognitive function was assessed with Chinese Mini Mental State Examination (CMMSE) and Chinese Frontal Assessment Battery (CFAB). DTC on gait was assessed with arithmetic (counting backwards from 100) and verbal fluency (animal naming) cognitive tasks. Association of DTC with frailty dimensions and cognition were evaluated via hierarchical linear regression, adjusted for demographics. Higher CFAB score was significantly associated with lower DTC in both arithmetic (B=-2.067, p < 0.001) and verbal fluency (B=-1.489, p = 0.020) tasks, suggesting individuals with better executive function showed lower DTC. Social frailty (Factor 2 - social activity and financial resources) and oral frailty (Factor 3 - dietary and social habits) were significantly associated with DTC for arithmetic task (B = 2.664, p = 0.030; B = 3.718, p = 0.007). No significant association was observed for physical frailty. The final composite model showed that CFAB has a significant associated with DTC arithmetic (B=-2.012, p < 0.001) and DTC verbal fluency (B=-1.537, p = 0.016) tasks. Cognitive frailty, particularly executive dysfunction, is a key factor contributing to difficulties with dual tasking. Social and oral frailty factors may influence DTC during arithmetic tasks, however their effects were attenuated after adjusting for cognition. Interventions addressing cognitive frailty may be a promising target for mitigating DTC in older adults.
This study describes a TaqMan qPCR assay targeting the VP2 gene for the sensitive detection and quantification of amdoparvovirus DNA in various small mammals. The assay demonstrated high specificity, a low detection limit (3.60 × 101 copies/µL), and excellent repeatability (CV < 1.57%), proving 100-fold more sensitive than conventional PCR. Applying this method to 148 fecal and tissue samples from small mammals across four zoos in Guangdong, China, revealed an overall amdoparvovirus DNA detection rate of 25.0% (95%CI: 18.6% to 32.6%), significantly higher than the 18.92% detected by conventional PCR. High viral loads were notably found in spleen, lung, and mesenteric lymph nodes of individual animals, indicating systemic distribution of viral DNA in these cases. This research provides the first molecular evidence of amdoparvovirus circulation within the sampled zoo populations in Chinese, suggesting potential exposure among captive small mammals in these facilities. However, due to the opportunistic sampling design and heterogeneous sample types, further systematic surveillance is needed to assess the true prevalence and associated risks.
Chronic Obstructive Pulmonary Disease (COPD) is increasingly recognized as a systemic inflammatory condition closely linked to metabolic dysfunction. While traditional obesity metrics often fail to capture visceral adiposity and insulin resistance simultaneously, the Triglyceride-glucose body shape index (TyG-ABSI) has emerged as a composite marker of cardiometabolic risk. This study aimed to evaluate the association between TyG-ABSI and COPD risk and to assess its predictive utility using machine learning algorithms. Data were analyzed from two large-scale distinct cohorts: the China Health and Retirement Longitudinal Study (CHARLS, N = 2,771) and the National Health and Nutrition Examination Survey (NHANES, N = 1,925 pre-diabetic participants). The relationship between TyG-ABSI and COPD was assessed using multivariable logistic regression, subgroup analyses, and Restricted Cubic Splines (RCS). Furthermore, five machine learning models (XGBoost, LightGBM, CatBoost, Random Forest, and KNN) were developed to predict COPD risk. Model interpretability was achieved using SHapley Additive exPlanations (SHAP). In both cohorts, elevated TyG-ABSI levels were significantly associated with an increased risk of COPD. Fully adjusted regression models revealed a linear dose-response relationship, with the highest quartile of TyG-ABSI showing a 59% increased risk in CHARLS (OR: 1.591) and a four-fold risk increase in NHANES (OR: 4.017) compared to the lowest quartile. Tree-based machine learning models, particularly XGBoost and LightGBM, demonstrated superior discriminative performance with AUCs exceeding 0.96 in the CHARLS dataset. SHAP analysis consistently identified TyG-ABSI as a high-priority feature contributing to disease prediction, irrespective of demographic variations. The TyG-ABSI index serves as a robust, independent risk factor for COPD across Chinese and American populations. Its integration into screening protocols, augmented by explainable machine learning, offers a valuable tool for early identification of high-risk individuals, highlighting the critical intersection of metabolic health and respiratory function.
Staphylococcus hyicus is recognized as one of causative agents of porcine exudative epidermitis in piglets. However, research on clinical pathogenic S. hyicus remains limited. In this study, multidrug-resistant S. hyicus was isolated from a large-scale pig farm with cases of fatal exudative epidermitis in piglets. By characterizing the phenotypes and genotypes of S. hyicus isolates, we provide insights for clinical management of exudative epidermitis. Two 21-day-old piglets with clinical signs underwent necropsy and histopathological examination. 48 samples from lactating sows and suckling piglets were collected for pathogen identification. Antimicrobial and disinfectant susceptibility of the isolates was determined using broth microdilution, as well as whole-genome sequencing (WGS) was used to identify antimicrobial resistance genes. Moreover, comparative genomic analysis with public genomes in the Genbank database was performed. The virulence of mecA-carrying S. hyicus was evaluated using the Galleria mellonella infection model. Exudative epidermitis was first observed in 3-day-old piglets. Through necropsy, pathogen isolation, and other diagnostic approaches, S. hyicus was preliminarily identified as the primary causative agent of this episode, and 23 S. hyicus were isolated from samples. Antimicrobial susceptibility testing indicated most of isolated S. hyicus were susceptible to doxycycline, vancomycin and linezolid, while resistant to florfenicol, erythromycin, spectinomycin, amoxicillin, ceftiofur, enrofloxacin that are commonly used for pigs. Twelve resistance genes were identified by WGS, including aadD, ant(6)-Ia, aph(2'')-Ia, blaZ, erm(B), erm(C), fexA, lnu(B), lsa(E), mecA, tet(L), and tet(M). Compared with 39 GenBank genomes, mecA-carrying S. hyicus in our study carried more resistance genes and exhC islands closely related to previous Chinese strains. Based on our findings, we implemented a targeted treatment protocol that brought the outbreak under control and reduced piglet mortality to below 5%. This study successfully isolated pathogenic mecA-carrying S. hyicus responsible for high mortality in piglets, characterized its drug resistance phenotypes and genotypes, offering valuable insights for the prevention and control of this pathogen in piglets.
Prostate cancer (PCa) is characterized by a unique metabolic dependency on the hyperactivated tricarboxylic acid (TCA) cycle, creating a distinct vulnerability to cuproptosis-a copper-dependent form of regulated cell death. However, metabolic plasticity allows tumor cells to evade single-pathway inhibition through compensatory glycolysis, limiting the efficacy of copper-based therapies. Therefore, there is an urgent need to develop integrated nanoplatforms capable of orchestrating a dual-pathway metabolic blockade to overcome this therapeutic resistance. Herein, we engineered a self-assembling copper-epigallocatechin gallate (EGCG) nanoreactor (Cu-EQ NP) designed to execute a synchronized dual-metabolic assault. The Cu-EQ NPs leverage the tumor microenvironment to release copper ions that trigger TCA-dependent cuproptosis, while the EGCG component simultaneously inhibits key glycolytic enzymes to prevent metabolic escape. Mechanistically, this lethality is self-amplified by EGCG-quinone-mediated depletion of glutathione (GSH) and the downregulation of the ATPase copper-transporting beta (ATP7B) efflux pump, leading to irreversible intracellular copper accumulation. Furthermore, we demonstrate that this metabolic collapse is highly immunogenic. In a syngeneic RM-1 mouse model, Cu-EQ NP-induced immunogenic cell death (ICD) released damage-associated molecular patterns (DAMPs) that successfully transformed the immunologically "cold" tumor microenvironment. This remodeling was characterized by enhanced dendritic cell maturation, M2-to-M1 macrophage repolarization, and robust infiltration of cytotoxic CD8 + T cells, resulting in potent tumor regression. The Cu-EQ nanoreactor represents a precision nanomedicine strategy that converts the specific metabolic vulnerabilities of PCa into a fatal weakness. By integrating dual-metabolic disruption with robust immune activation, this platform offers a promising therapeutic paradigm for overcoming resistance in advanced prostate cancer.
The bulb of Fritillaria unibracteata is a valuable traditional Chinese medicinal material whose bioactive compound accumulation is closely linked to carbon metabolism. As a perennial herb, its bulbs undergo multi-year developmental cycles, with starch and sucrose serving as key storage and mobilizable carbohydrates, respectively. However, the age-dependent dynamics of starch-sucrose interconversion during bulb development and its expression patterns remain poorly understood, limiting our comprehension of the carbon allocation dynamics that support biomass accumulation and medicinal metabolite production. Starch content increased progressively from the first to fourth year, peaked in the fourth year, and then significantly declined in the fifth year. By contrast, sucrose levels exhibited an opposite trend, decreasing in the fourth year and rising sharply in the fifth year, indicating a marked shift in carbohydrate allocation during the late developmental stage. Transcriptome analysis identified 21,964 differentially expressed genes, among which the starch and sucrose metabolic pathway was significantly enriched. Notably, key genes involved in starch biosynthesis, including ADP-glucose pyrophosphorylase and soluble starch synthase/granule-bound starch synthase, showed their highest expression levels in the fourth year, coinciding with maximum starch accumulation. Conversely, the expression of genes associated with sucrose biosynthesis, particularly sucrose phosphate synthase, was significantly upregulated from the fourth to fifth year, corresponding to the observed sucrose increase. Enzyme activity assays mirrored these transcriptional patterns. Weighted gene co-expression network analysis further identified modules associated with starch-sucrose metabolic traits, providing evidence for coordinated transcriptional networks in carbon allocation. Collectively, these findings reveal a pronounced metabolic transition from starch accumulation to sucrose synthesis during bulb development. The transition from the fourth to fifth year represents a critical developmental stage, during which the carbon allocation pattern shifts from starch-dominated storage to enhanced sucrose accumulation and mobilization. This study provides evidence for an age-dependent starch-sucrose metabolic pattern during bulb development in F. unibracteata, offering a theoretical basis for understanding carbon allocation dynamics in Fritillaria bulbs.
Getah virus (GETV) is a mosquito-borne zoonotic arbovirus, and clinical infections in animals have been reported with increasing frequency in recent years, posing a potential threat to animal health and public health. In this study, a Getah virus strain, designated GETV-HN2024, was isolated from a spleen sample collected from an aborted fetus in a swine herd in Anhui Province. Phylogenetic trees based on the complete genome and the E2 gene revealed that HN2024 belongs to GETV genotype GIII and is relatively distant from the original Malaysian prototype strain (MM2021), while exhibiting higher genetic homology with porcine-derived GETV strains. Amino acid sequence analysis of the E2 coding region further demonstrated that HN2024 shared 96.9% to 99.8% amino acid identity with reference strains deposited in GenBank. Using the field isolate, rabbit polyclonal antibodies targeting the GETV E1 protein were generated. Simultaneously, the full-length viral genome was cloned into the pBluescript SK(+) vector downstream of the T7 promoter, leading to the successful rescue of the recombinant virus rHN2024. The results showed that the rescued virus exhibited biological characteristics similar to those of the parental strain and maintained good genetic stability. In conclusion, we isolated a contemporary GETV strain, constructed a full-length infectious cDNA clone, and successfully rescued the recombinant GETV. This infectious clone provides a practical reverse genetics platform that will facilitate detailed studies on the virulence determinants, pathogenic mechanisms of GETV, as well as the development of novel vaccines and control strategies in veterinary preventive medicine.
The most prevalent malignant tumor of the urinary system, bladder cancer, exhibits a rising global incidence rate. However, recent diagnostic and therapeutic techniques, such as ostomy surgery, can effectively prolong patient survival. The majority of patients require support from family carers, presenting considerable challenges to these caregivers. Although existing research has primarily focused on patients' physiological adaptation, quality of life, and the burden on family carers, the moral dilemmas faced by these caregivers have not been explored yet. This study aimed to explore the psychological and moral dilemmas of family caregivers in a specific care situation. Using a descriptive research design, we conducted one-on-one qualitative interviews with 23 patients who had undergone urostomy. The interview time for each patient lasted over 60 min. All the interviewees emphasized that urostomy had significantly influenced their sexual experience. Moreover, we used thematic analysis to analyze the data. All the interviewees emphasized that a urostomy had significantly influenced their sexual experience. Our analysis yielded three primary themes: (1) the tearing of care responsibility and self-life, (2) reconstruction of family roles and relationships, and (3) the contradiction between the best care and practical limitations, and eight subthemes: guilt of giving up, social alienation, sacrifice of physical and mental health, the challenge of intimacy, balance of multiple responsibilities, great economic pressure, limited knowledge and skills, and emotional collapse. This study reveals that family carers of Chinese urostomy patients perceive caregiving as a moral obligation rather than a mere action, viewing self-sacrifice as evidence of virtue within a Confucian ethical framework. Hence, providers must develop culturally sensitive assessment tools, redesign supportive interventions respecting diverse moral perspectives, and establish ethical support systems to bridge understanding between differing moral contexts. This might foster a healthcare system that genuinely honors the carers' moral dignity.
Steamed Panax notoginseng has long been used in traditional medicine to enrich the blood, and its principal constituents are saponins. This traditional blood-enriching property suggests its potential value in treating chemotherapy-induced anemia. To elucidate the underlying mechanism and identify the key active components through which steamed Panax notoginseng saponins (SPNS) ameliorate cyclophosphamide-induced anemia. A model of anemia was established by intraperitoneal injection of cyclophosphamide combined with acetylphenylhydrazine. Cell proliferation was evaluated by examining peripheral blood and HE-stained bone marrow sections. Our multiomics analysis revealed hematopoiesis-related pathways, and surface plasmon resonance (SPR) confirmed saponin binding to target proteins. The proliferative effect of individual saponins on erythrocytes was validated in zebrafish with fluorescently-labeled red blood cells. Cellular damage was assessed by flow cytometry and electron microscopy. The expression of hemoglobin-related genes and signaling pathway proteins was detected by real-time PCR and Western blotting, respectively. The cAMP and PI3K/AKT signaling pathways were significantly enriched in the SPNS group. The ginsenosides Rk3 and Rh4 were bound strongly to G protein-coupled receptors (GPCRs) and guanylate cyclase (GC), while F1 was bound to integrin α5 (ITGA5). All three ginsenosides enhanced erythrocyte proliferation in zebrafish. SPNS also repaired cyclophosphamide (CTX)-induced damage in K-562 cells, promoted the expression of hemoglobin-related genes, and increased the phosphorylation of key proliferative pathway proteins. SPNS mitigates cyclophosphamide-induced anemia by activating the cAMP/PI3K/AKT/cGMP pathway, an effect that is likely mediated by its active components Rk3, Rh4, and F1, thereby promoting erythropoiesis, inhibiting apoptosis, and restoring hematopoietic function. This study provides valuable insights into clinical applications of the active ingredients of SPNS.
Sensory symptoms have been increasingly recognized as core characteristics of tic disorders (TD). This study aimed to systematically investigate the core features of sensory processing abnormalities in Chinese children with tic disorders, analyze their association with tic severity, and explore potential subtypes based on sensory profiles. This cross-sectional study recruited 151 children diagnosed with TD (encompassing Tourette syndrome, chronic motor tic disorders, and provisional tic disorders) along with 100 age-matched healthy controls (HC). Sensory processing characteristics were assessed using the Short Sensory Profile, and tic severity was evaluated with the Yale Global Tic Severity Scale. Principal component analysis (PCA) and latent profile analysis (LPA) were employed to explore sensory subtypes. Correlation analyses and regression models were used to examine sensory-symptom relationships. Children with TD showed significantly lower total SSP scores than HCs (P < 0.001), with deficits primarily in "under-responsive/sensation seeking", "auditory filtering" and "low energy/weakness". PCA extracted two core dimensions: "sensory dysfunction" and "sensory hypersensitivity". A significant positive graded relationship was found between the degree of sensory abnormality and tic severity (P for trend = 0.025). The "under-responsive/ sensation seeking" dimension was an independent predictor of tic severity (β = -0.164, P = 0.044). LPA identified two subtypes: a "relatively typical sensory processing" subtype (88.7%) and a "sensory over-responsivity" subtype (11.3%). However, no significant difference in tic severity was found between these subtypes. Sensory processing abnormalities, particularly generalized sensory modulation dysfunction, are prevalent across TD subtypes and are closely associated with tic severity. Sensory under-responsivity represents a core risk dimension, while the unique "sensory over-responsivity" subtype may be relatively independent of tic severity. This study provides important evidence for sensory-based subtyping of TD and for developing individualized interventions targeting sensory symptoms.
DNA methylation is a crucial epigenetic regulatory mechanism in eukaryotes, and its dysregulation is closely associated with numerous diseases. Recent advances in long-read sequencing (LRS) have transformed the ability to comprehensively characterize the methylation modifications in DNA, including the technically difficult genomic regions. However, the translation of this technological potential into reliable biological insights relies heavily on accurate computational analysis of raw signal data. Currently, a growing number of bioinformatic tools have emerged, demonstrating superior performance in LRS-based methylation detection. Our review first briefly describes the detection principles and technological improvement of LRS, and then provides a comprehensive overview of the existing LRS-based methylation detection tools and related benchmarking studies. We further explore the applications in biomedical research, the current challenges, and the future perspective of LRS-based methylation detection. By highlighting the research progress and key issues in the field, this review aims to provide researchers with an essential framework to advance the further development and application of LRS-based methylation detection.
Despite its remarkable efficacy in hematologic malignancies, chimeric antigen receptor T-cell (CAR-T) therapy is often limited by atypical clinical outcomes, necessitating predictive biomarkers. Here, prompted by a patient with low-tumor-burden non-Hodgkin lymphoma who develops severe and persistent cytokine release syndrome (CRS), we identify the germline TNFR2M196R single-nucleotide polymorphism, rs1061622, as a candidate genetic determinant of atypical responses. The TNFR2M196R variant is found to enhance the antitumor efficacy of CAR-T cells by reducing their apoptosis. Paradoxically, however, patients carrying the TNFR2M196R variant exhibit higher rates of early tumor progression. Further investigation reveals that while the TNFR2M196R mutation increases tumor susceptibility to CAR-T-mediated killing, it also accelerates tumor proliferation kinetics. Together, these results establish the TNFR2M196R SNP as a dual-function genetic determinant that modulates both CAR-T cell efficacy and intrinsic tumor behavior, highlighting the critical impact of germline genetics on cancer immunotherapy.