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: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome

OBJECTIVES: Stigma is common among community-dwelling patients with schizophrenia and has a profound negative impact on both psychiatric symptoms and quality of life. This study aims to explore the association between stigma and quality of life in this population and to examine the multiple mediating roles of anxiety and depression symptoms. METHODS: The multi-stage stratified cluster random sampling method was used to select the community-dwelling patients with schizophrenics in Chengdu, Sichuan Province, China. The questionnaire included general demographic characteristics, stigma question, the Generalized Anxiety Disorder-7 (GAD-7) scale, the Patient Health Questionnaire-9 (PHQ-9), and the 12-item Short Form Health Survey (SF-12). The SF-12 was used to measure quality of life, including physical health and mental health dimensions. A multiple mediation model was used to analyse the mediating effects of anxiety and depression symptoms together between stigma and quality of life. RESULTS: A total of 1 087 community patients with schizophrenia were included with a mean age of 50.68±12.73 years; 525 (48.30%) were male. Stigma was reported by 543 patients (49.95%). Anxiety symptoms were present in 292 patients (26.86%), and depression symptoms in 407 patients (37.44%). The physical health quality of life score was 72.01 ± 20.99, and the mental health quality of life score was 71.68 ± 19.38. Multiple mediation analysis showed that stigma directly affected quality of life, and also indirectly affected quality of life through anxiety and depression symptoms. Anxiety and depression jointly mediated 42.26% of the total effect of stigma on physical health quality of life and 47.51% on mental health quality of life. CONCLUSIONS Reducing stigma and preventing anxiety and depression symptoms in community-dwelling patients with schizophrenia can effectively improve their quality of life and support reintegration into society.
Humans ; Quality of Life ; Male ; Depression/psychology* ; Middle Aged ; Social Stigma ; Schizophrenia ; Female ; Anxiety/psychology* ; China ; Surveys and Questionnaires ; Adult ; Schizophrenic Psychology ; Independent Living ; Aged

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.