The development of the rare disease discipline is a crucial pathway for enhancing the diagnosis and treatment of rare diseases, cultivating specialized professionals, and fostering technological innovation. Currently, China' rare disease discipline is accelerating its development driven by both policy and demand. However, it still faces multi-dimensional challenges, including an incomplete clinical management mechanism, a shortage of interdisciplinary talents, a weak scientific research system, and limited outreach capacity. To address these challenges, this paper proposes and constructs an integrated development system with clinical diagnosis and treatment as the foundation, talent cultivation as the engine, scientific research as the support, and disciplinary outreach capacity as the extension. Specific strategies include: enhancing clinical management through artificial intelligence-assisted diagnosis systems and multidisciplinary collaboration platforms; strengthening the talent pool through textbooks, curricula, and hierarchical training mechanisms; bolstering research collaboration and translational outcomes by leveraging international data-sharing platforms, national rare disease medical centers, the State Key Laboratory of Complex Severe and Rare Diseases, and the National Key Scientific Infrastructure for Translational Medicine; and expanding grassroots outreach and public awareness through the National Rare Disease Diagnosis and Treatment Collaboration Network, the National Rare Disease Quality Control Center, and integrated media communication channels. In the future, the rare disease discipline should further deepen the integration of medicine and engineering, expand international cooperation, focus on the translational closed loop, improve the regional collaboration network, so as to build a more resilient and dynamic disciplinary ecosystem, and ultimately achieve a comprehensive improvement in the diagnosis and treatment of rare diseases.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

bjective To analyze the growth trends of height and weight among primary and secondary school students, and explore the developmental characteristics and gender differences at different age groups, and to provide a scientific basis for adolescent health policy formulation. Methods Based on 675 175 health examination records of 227 978 students aged 6-17 years in Shiyan City from 2015 to 2024, a logistic growth model was employed to fit the curves of height and weight changes with age. Results From 2015 to 2024, height and weight showed steady increases across all age groups, exhibiting typical sigmoidal growth patterns. The growth rates varied across age groups: the younger age group (6-9 years) showed a moderate growth (annual height increase of 0.5-1.0 cm, weight increase of 0.03-0.06 kg/year), while the older age group (10-17 years) demonstrated a significant growth (annual height increase of 1.5-2.0 cm, weight increase of 0.22-0.38 kg/year). The growth rate curves displayed a unimodal distribution. The growth inflection points of male students occurred later than that of female students (height inflection point: 9.87 years for males vs. 8.98 years for females; weight inflection point: 10.70 years for males vs. 9.99 years for females). Female students experienced a more concentrated but shorter period of growth and development. The peak height growth rate was 7.40 cm/year at age 9 for females and 7.09 cm/year at age 10 for males, while the peak weight growth rate was 5.04 kg/year at age 10 for females and 5.27 kg/year at age 11 for males. Conclusion The physical development of primary and secondary school students in Shiyan City follows a logistic growth pattern, with significant gender differences and characteristics of adolescent growth spurts. Female students exhibit an earlier and more concentrated growth process.

ObjectiveTo analyze the epidemiological and clinical characteristics of the 21 confirmed monkeypox cases in a district of Chengdu City, and to provide scientific guidance for the prevention and control of subsequent monkeypox epidemics. MethodsData of confirmed monkeypox cases residing in this district were collected from the Disease Control and Prevention Information System of China. A retrospective descriptive epidemiological analysis was used to analyze the demographic, distributional and behavioral characteristics of the cases. ResultsThe first confirmed case of monkeypox was reported on July 5, 2023. Up to April 30, 2025, a total of 21 confirmed cases of monkeypox have been reported. All cases were male, with a mean age of (30.9±6.2) years. The highest proportion of cases(47.62%) was in the 30‒40 years age group. The majority were men who have sex with men (MSM) population (90.48%, 19/21). The results showed that 19.05% of cases were co-infected with HIV, and 19.05% had a history of syphilis infection. Within 21 days prior to symptom onset, 19 cases (90.48%) self-reported engaging in male-to-male sexual contact, among whom 10 cases (52.63%) reported having taken protective measures, while 9 cases (47.37%) did not take safety precautions. Thirteen cases (61.90%) had no travel history to areas with reported monkeypox cases during the 21 days before symptom onset. The predominant manifestation was exanthem (100%, 21/21), followed by fever (57.14%, 12/21) and lymphadenectasis (47.62%, 10/21). Among febrile cases, 50.00% (6/12) had low-grade fever (37.3‒38.0 ℃). All cases were identified through active medical consultation. The median interval from symptom onset to the first medical visit was 3 (2, 6) days, with a maximum interval of 14 days. The median interval from symptom onset to laboratory confirmation was 7 (5, 9) days. Six cases (28.57%) had two or more visits to the hospital, with bacterial infection being the primary initial diagnosis. ConclusionMonkeypox prevention and control efforts in a district of Chengdu City should prioritize MSM population and young and middle-aged adults aged 30 to <40 years. It is recommended to establish an integrated monkeypox epidemic prevention and control network by leveraging existing HIV/AIDS prevention and control network. Concurrently, accelerating the deployment of the national intelligent infectious disease monitoring and early warning front-end software will strengthen early detection capabilities and be beneficial for the overall effectiveness of epidemic prevention and control efforts.

Objective: To explore the regulatory role of paternal involvement in parenting in the association between parental adverse childhood experiences (ACEs) and autism like behavioral problems in children aged 3-6, so as to provide a basis for intervention strategies targeting the intergenerational health effects of ACEs. Methods: A longitudinal study design was used to select 1 780 children aged 3-6 from 12 kindergartens in Wuhu City, Anhui Province in June 2021 as the subjects of the baseline survey by convenient sampling, and the follow up surveys were conducted once every six months, for a total of two follow ups. Pearson correlation analysis was used to examine the association of parental ACEs and paternal involvement in parenting with autism like behavioral problems in children. A binary Logistic regression model was used to explore the association between parental ACEs and autism like behavioral problems in children. Based on stratification, the potential role of paternal involvement in the association between parental ACEs and autism like behavioral problems in children aged 3-6 was explored. Results: Autism like behavioral problem score in children aged 3-6 was positively correlated with the total score ACEs of parents as well as scores of emotional abuse, physical abuse, sexual abuse, emotional neglect, physical neglect, community violence, peer bullying, and family dysfunction( r =0.18,0.16,0.18,0.14,0.06,0.05,0.12,0.18,0.09,all P <0.05). Autism like behavioral problem score in children was negatively correlated with score of paternal involvement in parenting( r =-0.16, P <0.01). After adjusting for covariates such as gender, age, and birth weight of children, binary Logistic regression analysis showed that children whose parents had experiences of childhood emotional abuse, physical abuse, sexual abuse, community violence, peer bullying, or family dysfunction had higher risks of developing autism like behavioral problems than those in the non exposed group ( OR =3.29, 3.28, 6.71, 2.34, 4.08, 2.02, all P <0.01). In the group with low paternal involvement in parenting, all dimensions of parental ACEs(emotional abuse, physical abuse, sexual abuse, community violence, peer bullying, and family dysfunction) were significantly associated with an increased risk of autism like behavioral problems in children ( OR =1.84-8.34, all P <0.05). In contrast, in the group with high paternal involvement in parenting, no statistically significant associations were found between any dimension of parental ACEs and children s autism like behavioral problems ( OR =0.57-1.82, all P >0.05). Conclusion A high level of paternal involvement in parenting can reduce the adverse effects of parental ACEs on the occurrence of autism like behaviors in preschool children.

Background Lung tissue fibrosis caused by exposure to free silica (SiO₂) dust is the core pathological feature of silicosis. Lipocalin-2 (LCN2), as a secreted glycoprotein, plays an important role in various inflammatory diseases, but its specific role in silicosis-induced inflammatory injury remains unclear. Objective To identify differentially expressed genes (DEGs) and enriched pathways in the lung tissues of rats with silicosis, and to explore the regulatory mechanism of LCN2 in silicosis inflammation. Methods Twenty specific pathogen-free male SD rats were randomly divided into a control group and a silicosis model group (n=10 per group). The silicosis model was established via a single intratracheal instillation of silicon dioxide (SiO₂) suspension (50 mg), while the control group received an equal volume of normal saline. In vitro, NR8383 cells were divided into a control group and a SiO₂ treatment group. Hematoxylin-eosin (HE) staining and Van Gieson (VG) staining were used to evaluate alveolar structure damage, inflammatory infiltration, and collagen deposition in the lung tissues. Transcriptomic sequencing was applied to screen for DEGs and enriched signaling pathways. Western blot was used to detect the protein expression of interleukin-6 (IL-6), E-cadherin (ECA), cluster of differentiation 36 (CD36), liver X receptor (LXR), ATP-binding cassette transporter A1 (ABCA1), and LCN2 in both rat lung tissues and NR8383 cells. Immunohistochemistry was used to further assess LCN2 expression and localization. Additionally, NR8383 cells were treated with the LCN2 inhibitor ZINC00640089 and assigned to four groups: control, ZINC00640089-only, SiO₂, and SiO₂+ZINC00640089. Western blot was used to evaluate the expression of LCN2, IL-6, and interleukin-1β (IL-1β). Results HE and VG staining revealed disorganized lung tissue structure, damaged alveolar walls, nodule formation, and increased collagen deposition in the silicosis model group compared to the controls. Transcriptomic analysis identified 2723 DEGs in the lung tissues of silicosis rats (312 down-regulated and 2411 up-regulated) with LCN2 expression being significantly up-regulated. These DEGs were primarily enriched in pathways related to the innate immune response, extracellular matrix (ECM)-receptor interaction, and inflammatory response. Immunohistochemical staining confirmed elevated LCN2 levels in the lung tissues of the model rats. Western blot demonstrated that the protein levels of IL-6, CD36, and LCN2 were significantly increased (P<0.05), whereas ABCA1 and ECA were significantly decreased in the silicosis group (P<0.05). Similarly, in SiO₂-treated NR8383 cells, IL-6, CD36, and LCN2 expressions significantly increased (P<0.05), while ABCA1 and LXR significantly decreased (P<0.05). Compared with the SiO₂ group, treatment with ZINC00640089 significantly reduced the expression levels of LCN2, IL-6, and IL-1β (P<0.05). Conclusion LCN2 is significantly upregulated in both the lung tissues of silicosis rats and SiO₂-treated NR8383 cells. Inhibiting LCN2 expression effectively reduces the SiO₂-induced inflammatory response, indicating that LCN2 serves as a potential therapeutic target for silicosis.

Objective To investigate the prevalence of pinworm infections among kindergarten children and the effectiveness of health interventions among teachers and parents in Gaoyou City, so as to provide insights into optimization of enterobiasis control strategies. Methods From September to November each year from 2023 to 2025, Gaoyou City’s 57 kindergartens were divided into five zones based on the five cardinal directions: east, west, south, north, and center. At least one kindergarten was randomly selected as a survey site in each zone, with a minimum of 200 children surveyed per site. The transparent adhesive tape anal swab method was used to detect pinworm infection in the surveyed children, while the transparent adhesive tape sticking method was employed to assess pinworm egg contamination in the children’s home and classroom environments. Concurrently, health education interventions were conducted for kindergarten teachers and parents. Additionally, self-administered questionnaires were administered to teachers and parents to evaluate children’s hygiene behaviors and the awareness rates of pinworm prevention knowledge among teachers and parents before and after the health education interventions. Results From 2023 to 2025, a total of 1 939 children from nine kindergartens in Gaoyou City were tested for pinworm infection, with two cases detected, resulting in an overall infection rate of 0.10% (2/1 939). No pinworm eggs were found in the samples from the children’s families or classroom environments. In public kindergartens, the proportions of children practicing the four hygiene habits, namely “handwashing after defecation” [96.10% (1 305/1 358) vs. 74.65% (212/284); χ² = 153.646, P < 0.05], “regular nail trimming” [92.93% (1 262/1 358) vs. 77.82% (221/284); χ² = 61.349, P < 0.05], “not biting toys or pencils” [88.14% (1 197/1 358) vs. 76.76% (218/284); χ² = 25.549, P < 0.05], and “showering twice or more per week” [89.03% (1 209/1 358) vs. 74.65% (212/284); χ² = 41.699, P < 0.05], were all higher than those in private kindergartens. Before health education intervention, the awareness rates of pinworm prevention knowledge among teachers in public and private kindergartens were 86.89% (53/61) and 75.00% (21/28), respectively, with no statistically significant difference (χ² = 1.935, P > 0.05). The awareness rates among parents of children in public and private kindergartens were 64.73% (879/1 358) and 57.39% (163/284), respectively, showing a statistically significant difference (χ² = 5.447, P < 0.05). After the intervention, the awareness rates among teachers in public and private kindergartens increased to 96.72% (59/61) and 82.14% (23/28), respectively, while those among parents rose to 88.95% (1 208/1 358) and 77.81% (221/284), both with statistically significant differences (χ² = 5.628 and 25.808, both P < 0.05). Among the questionnaire items, teachers [32.58% (29/89)] and parents [26.00% (427/1 642)] had the lowest overall awareness rate regarding the “main reasons for the difficulty in preventing and controlling pinworm disease”. After the intervention, these rates increased to 77.53% (69/89) and 70.77% (1 162/1 642), respectively. Conclusions The prevalence of pinworm infection in kindergarten children in Gaoyou City is at a low level. Health intervention can effectively improve the knowledge level of teachers and parents on the prevention and treatment of pinworm disease, but further efforts are needed to strengthen the health education and management of pinworm disease in private kindergartens.

[摘 要] 目的：探究乌头酸酶2（ACO2）发生核转位的条件和作用机制并探讨ACO2核转位对肝癌细胞PLC/PRF/5增殖、迁移和侵袭的影响。方法：借助Human Protein Atlas（HPA）数据库分析ACO2在人肝癌组织中的表达与亚细胞定位；利用NLStradamus网站预测ACO2的潜在核定位信号（NLS），并通过基因截短技术构建NLS缺失的ACO2基因（ACO2 ∆NLS）；将野生型（ACO2WT）及突变型（ACO2ΔNLS）质粒转染至人肝癌PLC/PRF/5细胞，分别在常氧及低氧（1% O₂）条件下培养；采用免疫荧光染色技术，分析低氧条件影响ACO2入核的机制；通过EdU染色、划痕实验及Transwell实验评估PLC/PRF/5细胞的增殖、迁移与侵袭能力；借助WB检测胞核和胞质中ACO2的表达水平以及迁移、侵袭相关蛋白MMP2与MMP9表达水平的变化。结果：HPA数据库分析显示，ACO2在肝癌细胞的细胞核和细胞质中均呈高表达；免疫荧光染色和WB结果显示，低氧能够以NLS依赖的方式显著诱导ACO2发生核转位（均P < 0.01）；功能学实验显示，低氧诱导的ACO2核转位能进一步显著促进PLC/PRF/5细胞的增殖、迁移（均P < 0.05）和侵袭（均P < 0.05）能力。WB实验表明，ACO2核转位可上调迁移、侵袭相关蛋白MMP2与MMP9的表达水平（均P < 0.05）。结论：低氧能以NLS依赖的方式诱导ACO2发生核转位，从而增强PLC/PRF/5细胞的增殖、迁移和侵袭能力。

Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.