Tailored extracellular matrix-mimetic coating facilitates reendothelialization and tissue healing of cardiac occluders.

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.

Exploring antithrombotic mechanisms and effective constituents of Lagopsis supina using an integrated strategy based on network pharmacology, molecular docking, metabolomics, and experimental verification in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Thrombosis is a common cause of morbidity and mortality worldwide. Lagopsis supina (Stephan ex Willd.) Ikonn.-Gal. ex Knorring is an ancient Chinese herbal medicine used for treating thrombotic diseases. Nevertheless, the antithrombotic mechanisms and effective constituents of this plant have not been clarified. AIM OF THE STUDY: This work aimed to elucidate the pharmacodynamics and mechanism of L. supina against thrombosis. MATERIALS AND METHODS: Systematic network pharmacology was used to explore candidate effective constituents and hub targets of L. supina against thrombosis. Subsequently, the binding affinities of major constituents with core targets were verified by molecular docking analysis. Afterward, the therapeutic effect and mechanism were evaluated in an arteriovenous bypass thrombosis rat model. In addition, the serum metabolomics analysis was conducted using ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrometry. RESULTS: A total of 124 intersected targets of L. supina against thrombosis were predicted. Among them, 24 hub targets were obtained and their mainly associated with inflammation, angiogenesis, and thrombosis approaches. Furthermore, 9 candidate effective constituents, including (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol, aurantiamide, (22E,24R)-5α,8α-epidioxyergosta-6,9 (11),22-trien-3ß-ol, lagopsinA, lagopsin C, 15-epi-lagopsin C, lagopsin D, 15-epi-lagopsin D, and lagopsin G in L. supina and 6 potential core targets (TLR-4, TNF-α, HIF-1α, VEGF-A, VEGFR-2, and CLEC1B) were acquired. Then, these 9 constituents demonstrated strong binding affinities with the 6 targets, with their lowest binding energies were all less than -5.0 kcal/mol. The antithrombotic effect and potential mechanisms of L. supina were verified, showing a positively associated with the inhibition of inflammation (TNF-α, IL-1ß, IL-6, IL-8, and IL-10) and coagulation cascade (TT, APTT, PT, FIB, AT-III), promotion of angiogenesis (VEGF), suppression of platelet activation (TXB2, 6-keto-PGF1α, and TXB2/6-keto-PGF1α), and prevention of fibrinolysis (t-PA, u-PA, PAI-1, PAI-1/t-PA, PAI-1/u-PA, and PLG). Finally, 14 endogenous differential metabolites from serum samples of rats were intervened by L. supina based on untargeted metabolomics analysis, which were closely related to amino acid metabolism, inflammatory and angiogenic pathways. CONCLUSION: Our integrated strategy based on network pharmacology, molecular docking, metabolomics, and in vivo experiments revealed for the first time that L. supina exerts a significant antithrombotic effect through the inhibition of inflammation and coagulation cascade, promotion of angiogenesis, and suppression of platelet activation. This paper provides novel insight into the potential of L. supina as a candidate agent to treat thrombosis.

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke: a special outlook on mitochondrial delivery.

Ischemic stroke is a secondary cause of mortality worldwide, imposing considerable medical and economic burdens on society. Extracellular vesicles, serving as natural nano-carriers for drug delivery, exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke. However, the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency. By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles, their delivery efficacy may be greatly improved. Furthermore, previous studies have indicated that microvesicles, a subset of large-sized extracellular vesicles, can transport mitochondria to neighboring cells, thereby aiding in the restoration of mitochondrial function post-ischemic stroke. Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components, such as proteins or deoxyribonucleic acid, or their sub-components, for extracellular vesicle-based ischemic stroke therapy. In this review, we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies. Given the complex facets of treating ischemic stroke, we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process. Moreover, given the burgeoning interest in mitochondrial delivery, we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

Synthesis of S-Alkyl Dithiocarbamates via Multicomponent Reaction of Cyclic Sulfonium Salts with CS2 and Amines.

A convenient and practical method for the synthesis of various S-alkyl dithiocarbamates through three-component reaction of sulfonium salts, CS2 and amines has been developed. The reaction proceeds efficiently without any catalyst and additive under mild and open-air conditions, making it potential applications in pharmaceutical chemistry and sulfur chemistry.

Biological characteristics of a new long-chain fatty acid transport protein 1 from Trichinella spiralis and its participation in lipid metabolism, larval moulting, and development.

Long-chain fatty acid transport protein 1 (FATP1) is a member of the fatty acid transporter family. It facilitates transmembrane transport of fatty acids and participates in lipid metabolism. Lipids are essential components of the cell and organelle membranes of Trichinella spiralis. The nematode has lost the capacity to synthesise the necessary lipids de novo and has instead evolved to obtain fatty acids and their derivatives from its host. This study aims to ascertain the primary biological characteristics and roles of T. spiralis FATP1 (TsFATP1) in lipid metabolism, larval moulting, and the development of this nematode. The results show that TsFATP1 is highly expressed at enteral T. spiralis stages, mainly localised at the cuticle, the stichosome and the intrauterine embryos of the parasite. The silencing of the TsFATP1 gene by TsFATP1-specific dsRNA significantly decreases the expression levels of TsFATP1 in the worm. It reduces the contents of ATP, triglycerides, total cholesterol, and phospholipids both in vitro and in vivo. RNAi inhibits lipid metabolism, moulting, and the growth of this nematode. The results demonstrate that TsFATP1 plays an essential role in lipid metabolism, moulting, and the development of T. spiralis. It could also be a target candidate for the anti-Trichinella vaccine and drugs.

Single cell RNA sequencing provides novel cellular transcriptional profiles and underlying pathogenesis of presbycusis.

Age-related hearing loss (ARHL) or presbycusis is associated with irreversible progressive damage in the inner ear, where the sound is transduced into electrical signal; but the detailed mechanism remains unclear. Here, we sought to determine the potential molecular mechanism involved in the pathogeneses of ARHL with bioinformatics methods. A single-cell transcriptome sequencing study was performed on the cochlear samples from young and aged mice. Detection of identified cell type marker allowed us to screen 18 transcriptional clusters, including myeloid cells, epithelial cells, B cells, endothelial cells, fibroblasts, T cells, inner pillar cells, neurons, inner phalangeal cells, and red blood cells. Cell-cell communications were analyzed between young and aged cochlear tissue samples by using the latest integration algorithms Cellchat. A total of 56 differentially expressed genes were screened between the two groups. Functional enrichment analysis showed these genes were mainly involved in immune, oxidative stress, apoptosis, and metabolic processes. The expression levels of crucial genes in cochlear tissues were further verified by immunohistochemistry. Overall, this study provides new theoretical support for the development of clinical therapeutic drugs.

Sex differences in the metabolic activation of and platelet response to vicagrel in mice: Androgen as a key player.

As a biological variable, sex influences the metabolism of and/or response to certain drugs. Vicagrel is being developed as an investigational new drug in China; however, it is unknown whether sex could affect its metabolic activation and platelet responsiveness. This study aimed to determine whether such differences could exist, and to elucidate the mechanisms involved. Orchiectomized (ORX) or ovariectomized (OVX) mouse models were used to investigate the effects of androgen or estrogen on the metabolic activation of and platelet response to vicagrel. Plasma vicagrel active metabolite H4 concentrations, platelet inhibition of vicagrel, and protein levels of intestinal hydrolases Aadac and Ces2 were measured, respectively. Further, p38-MAPK signaling pathway was enriched, whose role was determined using SB202190. Results showed that female mice exhibited significantly elevated systemic exposure of H4 and enhanced platelet responses to vicagrel than males, and protein expression levels of Aadac and Ces2 differed by sex. OVX mice exhibited less changes than sham mice. ORX mice exhibited increases in protein levels of intestinal hydrolases, systemic exposure of H4, and platelet inhibition of vicagrel, but dihydrotestosterone (DHT) reversed these changes in ORX mice and suppressed these changes in OVX mice. Phosphorylated p38 levels were reduced in female or ORX mice but increased in ORX mice by DHT. SB202190 reversed DHT-induced changes observed in ORX mice. We concluded that sex differences exist in metabolic activation of and platelet response to vicagrel in mice through elevation of p38 phosphorylation by androgen, suggesting sex-based vicagrel dosage adjustments for patient care.

One-step cascade amplification system based on entropy-driven catalysis and DNAzyme triggered DNA walker for label-free detection of acetamiprid.

Herein, an electrochemical aptasensor for highly sensitive detection of acetamiprid (ACE) was constructed based on a one-step cascade amplification strategy. This innovative strategy integrated DNA walker containing DNAzyme sequence into entropy-driven catalysis (EDC) system. The trigger strand was released by aptamer-specific binding to ACE, initiating the EDC amplification circuit and delivering DNA walker strands. The dangling DNA walker continuously bound and cleaved hairpin substrate to form G-quadruplex fragments with the assistance of Mg2+. The G-quadruplex fragments folded and captured hemin to form multitudinous G-quadruplex/hemin complexes in the presence of K+, generating significantly enhanced current, enabling enzyme-free, label-free and highly sensitive detection of ACE, with a linear detection range of 100 fM to 50 nM and a detection limit of 68.36 fM (S/N = 3). The constructed aptasensor achieved the reliable detection of ACE in vegetable soil and cucumber samples, demonstrating its potential application prospects in environmental protection and food supervision.

An integrated 3-M workflow for accelerated annotation of natural products: Flavonoids in Daemonorops draco as a case study.

Efficient annotation and dereplication of metabolites, particularly those from resource-endangered plants lacking reference standards, is crucial for natural products development. Advanced techniques like high resolution mass spectrometry (LC-HRMS) have significantly enhanced metabolite characterization. However, challenges such as redundant spectral data, limited reference databases, and inferior dereplication capacity hinder its broad applicability. In this study, we propose an integrated annotation strategy utilizing various computational tools, including mass defect filters (MDF), molecular fingerprints, and molecular networks (3-M strategy). We demonstrate this approach using Daemonorops draco (D. draco), a renowned yet resource-endangered natural product rich in functional flavonoids. By applying pre-defined flavonoids MDF windows, the MS1 peaks reduced by 85 % (from 10,043 to 1,585) in positive mode. Subsequent de novo molecular formula annotation and molecular fingerprint-based structure elucidation were automatically performed using the SIRIUS machine learning platform. Additionally, two complementary cluster tools were incorporated, including feature-based molecular network (FBMN) and t-distributed stochastic neighbor embedding (t-SNE) molecular network, to efficiently dereplicate metabolites and discover novel flavonoids in D. draco. Totally, 108 flavonoids (containing flavones, flavanes, flavanones, chalcones, chalcanes, dihydrochalcones, anthocyanins, homoisoflavanes, homoisoflavanones, and isoflavones), 18 flavone derivatives, and 54 flavone oligomers were identified. Among them, 25 compounds were firstly reported in D. draco. This 3-M workflow shed light on the composition of D. draco and validate the effectiveness of our approach, which facilitated the rapid annotation and screening of subclass metabolites in complex natural products.

High-throughput screening of the natural STK11 agonist dauricine: a biphenylisoquinoline alkaloid exerting anti-NSCLC effects and reversing gefitinib resistance.

BACKGROUND: Serine / threonine kinase 11 (STK11) deletion and downregulation caused cancer progression, and were widely associated with drug resistance. Accurate screening of natural small molecules about anti-cancer and anti-drug resistance is the key to the development and utilization of natural product application, which could promote traditional Chinese medicine in the treatment of cancer. Dauricine, which is derived from the rhizome of Menispermum dauricum DC., has certain potential but unexplored mechanism for the treatment of cancer. PURPOSE: The aim of this study was to screen and validate the role and mechanism of natural STK11 agonists with anti-drug resistance from plants in the treatment of NSCLC. METHODS: A lentiviral STK11 overexpression cell model was employed for the screening of natural STK11 agonists. The efficacy of dauricine in the treatment of NSCLC was validated on PC-9 and HCC827 cells. In vivo validation of dauricine activity was performed using nude mouse models equipped with PC9 xenografts. To investigate the anti-resistant effects of dauricine, gefitinib-resistant PC9 cell models were constructed. RESULTS: As a natural agonist of STK11, it causes the activation of the STK11/AMPK pathway and inhibits the growth of PC-9 cells. Dauricine synergises the inhibitory effect with gefitinib on PC9. The up-regulation of STK11 protein expression by dauricine was demonstrated in vitro and in vivo, while restoring the sensitivity of PC9 / GR to gefitinib by down-regulating the protein expression of Nrf2 and Pgp. CONCLUSION: Dauricine, a natural agonist of STK11, effectively inhibited NSCLC, and its combination treatment with gefitinib reversed drug-resistant NSCLC.

The challenges of investigating RNA function.

High-throughput sequencing methods have led to the discovery of many non-coding RNAs, RNA modifications, and protein-RNA interactions. While the list keeps growing, the challenge of determining their functions remains. For our focus issue on RNA biology, we spoke with several researchers about their perspective on investigating the functions of RNA.

Dynamic conformation: Marching toward circular RNA function and application.

Circular RNA is a group of covalently closed, single-stranded transcripts with unique biogenesis, stability, and conformation that play distinct roles in modulating cellular functions and also possess a great potential for developing circular RNA-based therapies. Importantly, due to its circular conformation, circular RNA generates distinct intramolecular base pairing that is different from the linear transcript. In this perspective, we review how circular RNA conformation can affect its turnover and modes of action, as well as what factors can modulate circular RNA conformation. We also discuss how understanding circular RNA conformation can facilitate learning about their functions as well as the remaining technological issues to further address their conformation. These efforts will ultimately inform the design of circular RNA-based platforms for biomedical applications.

A single-cell RNA-seq dataset describing macrophages in NSCLC tumor and peritumor tissues.

Examining tumor-associated macrophages in the immune microenvironment of non-small cell lung cancer (NSCLC) is essential for gaining an understanding of the genesis and development of NSCLC as well as for identifying key clinical therapeutic targets. Although previous studies have reported the diverse phenotypes and functions of macrophages in tumor tissues, thereby highlighting their significant role in the tumor microenvironment, the characteristic differences and correlations between tumor and peritumor tissue-derived macrophages that are necessary for an understanding of NSCLC progression remain unclear. Based on single-cell RNA sequencing, we generated a comprehensive dataset of transcriptomes from NSCLC tumor and peritumor tissues, thereby facilitating comprehensive analysis and providing significant insights. In summary, our dataset will serve as a valuable transcriptomic resource for further studies investigating NSCLC development.

The influence of genotype makeup on the effectiveness of growth hormone therapy in children with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare multisystemic hereditary illness. Recombinant human growth hormone (rhGH) therapy is widely recognized as the primary treatment for PWS. This study aimed to examine how different PWS genotypes influence the outcome of rhGH treatment in children with PWS. METHODS: A review was conducted on 146 Chinese children with PWS, genetically classified and monitored from 2017 to 2022. Unaltered and modified generalized estimating equations (GEE) were employed to examine the long-term patterns in primary outcomes (growth metrics) and secondary outcomes (glucose metabolism metrics and insulin-like growth factor-1 (IGF-1)) during rhGH therapy. The study also evaluated the prevalence of hypothyroidism, hip dysplasia, and scoliosis before and after rhGH treatment. RESULTS: Children with PWS experienced an increase in height/length standard deviation scores (SDS) following rhGH administration. The impact of rhGH therapy on growth measurements was similar in both the deletion and maternal uniparental diploidy (mUPD) cohorts. Nevertheless, the deletion group was more prone to insulin resistance (IR) compared to the mUPD group. No significant variations in growth metrics were noted between the two groups (P > 0.05). At year 2.25, the mUPD group showed a reduction in fasting insulin (FINS) levels of 2.14 uIU/ml (95% CI, -4.26, -0.02; P = 0.048) and a decrease in homeostasis model assessment of insulin resistance (HOMA-IR) of 0.85 (95% CI, -1.52, -0.17; P = 0.014) compared to the deletion group. Furthermore, there was a decrease in the IGF standard deviation scores (SDS) by 2.84 (95% CI, -4.84, -0.84; P = 0.005) in the mUPD group during the second year. The frequency of hip dysplasia was higher in the mUPD group compared to the deletion group (P < 0.05). CONCLUSIONS: rhGH treatment effectively increased height/length SDS in children with PWS, with similar effects observed in both deletion and mUPD genotypes. Children with mUPD genetype receiving rhGH treatment may experience enhanced therapeutic effects in managing PWS.

Intestinal flora and bile acid interactions impact the progression of diabetic kidney disease.

In recent years, with the rapid development of omics technologies, researchers have shown that interactions between the intestinal flora and bile acids are closely related to the progression of diabetic kidney disease (DKD). By regulating bile acid metabolism and receptor expression, the intestinal flora affects host metabolism, impacts the immune system, and exacerbates kidney injury in DKD patients. To explore interactions among the gut flora, bile acids and DKD, as well as the related mechanisms, in depth, in this paper, we review the existing literature on correlations among the gut flora, bile acids and DKD. This review also summarizes the efficacy of bile acids and their receptors as well as traditional Chinese medicines in the treatment of DKD and highlights the unique advantages of bile acid receptors in DKD treatment. This paper is expected to reveal a new and important potential strategy for the clinical treatment of DKD.

Enhanced knowledge graph recommendation algorithm based on multi-level contrastive learning.

Integrating the Knowledge Graphs (KGs) into recommendation systems enhances personalization and accuracy. However, the long-tail distribution of knowledge graphs often leads to data sparsity, which limits the effectiveness in practical applications. To address this challenge, this study proposes a knowledge-aware recommendation algorithm framework that incorporates multi-level contrastive learning. This framework enhances the Collaborative Knowledge Graph (CKG) through a random edge dropout method, which constructs feature representations at three levels: user-user interactions, item-item interactions and user-item interactions. A dynamic attention mechanism is employed in the Graph Attention Networks (GAT) for modeling the KG. Combined with the nonlinear transformation and Momentum Contrast (Moco) strategy for contrastive learning, it can effectively extract high-quality feature information. Additionally, multi-level contrastive learning, as an auxiliary self-supervised task, is jointly trained with the primary supervised task, which further enhances recommendation performance. Experimental results on the MovieLens and Amazon-books datasets demonstrate that this framework effectively improves the performance of knowledge graph-based recommendations, addresses the issue of data sparsity, and outperforms other baseline models across multiple evaluation metrics.

Enhancement of cold-adapted heterotrophic nitrification and denitrification in Pseudomonas sp. NY1 by cupric ions: Performance and mechanism.

Cupric ions can restrain biological nitrogen removal processes, which comprise nitrite reductase and nitric oxide reductase. Here, Pseudomonas sp. NY1 can efficiently perform heterotrophic nitrification and aerobic denitrification with cupric ions at 15 °C. At optimal culturing conditions, low cupric ion levels accelerated nitrogen degradation, and ammonium and nitrite removal efficiencies increased by 2.33%-4.85% and 6.76%-12.30%, respectively. Moreover, the maximum elimination rates for ammonium and nitrite increased from 9.48 to 10.26 mg/L/h and 6.20 to 6.80 mg/L/h upon adding 0.05 mg/L cupric ions. Additionally, low cupric ion concentrations promoted electron transport system activity (ETSA), especially for nitrite reduction. However, high concentrations of cupric ions decreased the ETSA during nitrogen conversion processes. The crucial enzymes ammonia monooxygenase, nitrate reductase, and nitrite reductase possessed similarly trends as ETSA upon exposure to cupric ion. These findings deepen the understanding for the effect of cupric ions on nitrogen consumption and bioremediation in nitrogen-polluted waters.

Evolving trends, regional differences, determinants, and disease sources of provincial-level health inequalities in china 1990-2019: a temporal convergence and novel triple decomposition analysis.

BACKGROUND: Promoting health equity has been a worldwide goal, but serious challenges remain globally and within China. Multiple decomposition of the sources and determinants of health inequalities has significant implications for narrowing health inequalities and improve health equity. METHODS: Life expectancy (LE), healthy life expectancy (HALE), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life-year (DALY) rates in 31 provinces of mainland China were selected as health status indicators, obtained from the Global Burden of Disease (GBD) database. Temporal convergence analysis was used to test the evolving trends of health status. Dagum's Gini coefficient decomposition was used to decompose the overall Gini coefficient based on intraregional and interregional differences. Oaxaca-Blinder decomposition was used to calculate contributions of determinants to interregional differences. The factor-decomposed Gini coefficient was used to analyze the absolute and marginal contribution of each component to overall Gini coefficients. RESULTS: From 1990-2019, China witnessed notable improvements in health status measured by LE, HALE, ASMR and age-standardized DALY rates.Nevertheless, the three regions (East, Central and West) exhibited significant inter-regional differences in health status, with the differences between the East and West being the largest. The adjusted short-term conditional ß-convergence model indicated that the inter-provincial differences in LE, HALE, ASMR, and age-standardized DALY rates significantly converged at annual rates of 0.31%, 0.35%, 0.19%, and 0.28% over 30 years. The overall Gini coefficients of LE, HALE, and age-standardized DALY rates decreased, while the ASMR exhibited an opposite trend. Inter-regional and intra-regional differences accounted for >70% and <30% of overall Gini coefficients, respectively. Attribution analysis showed that socioeconomic determinants explained 85.77% to 91.93% of the eastern-western differences between 2010-2019, followed by health system determinants explaining 7.79% to 11.61%. The source-analysis of Gini coefficients of ASMR and age-standardized DALY rates revealed that noncommunicable diseases (NCDs) made the largest and increasing absolute contribution, while communicable, maternal, neonatal, and nutritional diseases (CMNNDs) had a diminishing and lower impact. However, NCDs exerted a negative marginal effect on the Gini coefficient, whereas CMNNDs exhibited a positive marginal effect, indicating that controlling CMNNDs may be more effective in reducing health inequities. CONCLUSIONS: Regional differences are a major source of health inequities in China. Prioritizing prevention and control of CMNNDs, rather than NCDs, may yield more pronounced impacts on reducing health inequalities from the perspective of marginal effect, although NCDs remain the largest absolute contributor to health inequalities.

The diagnosis and management of mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II) is a rare X-linked recessive inherited lysosomal storage disease. With pathogenic variants of the IDS gene, the activity of iduronate-2-sulfatase (IDS) is reduced or lost, causing the inability to degrade glycosaminoglycans (GAGs) in cells and influencing cell function, eventually resulting in multisystemic manifestations, such as a coarse face, dysostosis multiplex, recurrent respiratory tract infections, and hernias. Diagnosing MPS II requires a combination of clinical manifestations, imaging examinations, urinary GAGs screening, enzyme activity, and genetic testing. Currently, symptomatic treatment is the main therapeutic approach. Owing to economic and drug availability issues, only a minority of patients opt for enzyme replacement therapy or hematopoietic stem cell transplantation. The limited awareness of the disease, the lack of widespread detection technology, and uneven economic development contribute to the high rates of misdiagnosis and missed diagnosis in China.