Rare diseases pose significant diagnostic and therapeutic challenges,carrying a high disease burden,their management critically reflects a nation's public health resilience.Currently,China faces key challenges such as scarce treatments,fragmented services,and low drug accessibility in rare disease care,which urgently require systemic solutions.Digital-intelligent technology as a key breakthrough are expected to resolve the challenges in this field.Although its application in the field of rare diseases is gradually expanding,there is a lack of systematic compilation of studies to elucidate how to precisely enhance the precision,synergy and sustainability of diagnosis and treatment.The key challenges in rare disease care concentrate in four areas:inefficiency in prenatal screening,uneven distribution of medical resources,low efficiency in social organization collaboration,and ineffective information dissemination.The"4C"strategy,based on digital-intelligent technology,can address these issues:①coordination,boost prenatal screening awareness and capacity via digital-intelligent platforms to strengthen prevention;②cooperation,deepen collaboration within specialist networks,empowering institutions to enhance diagnostic capacity;③co-creation,empower support organizations to optimize resources,efficiency;④cognition,minimize information dissipation through efficient platforms,improving patient and family quality of life.This establishes an integrated digital-intelligent rare disease model encompassing"screening-diagnosis-treatment-care".

Objective:To preliminarily explore therapeutic effects and possible molecular mechanisms of sinomenine on atopic dermatitis (AD) -like mouse models.Methods:Thirty female BALB/c mice (6 - 8 weeks old) were randomly divided into 5 groups: blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group. Except for the blank control group, all groups were subjected to repeated topical stimulation with 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin to establish an AD-like mouse model. After modeling, no special treatment was given to the blank control group, the positive control group was topically treated with 100 μg of 0.1% mometasone furoate cream twice daily on the lesions, the topical sinomenine group was topically treated with 100 μl of 10 mg/ml sinomenine solution twice daily on the lesions, and the oral sinomenine group was gavaged with sinomenine solution at a dose of 100 mg·kg -1·d -1 (100 μl per dose, twice daily) . Treatments lasted for 14 days. Twelve hours after the final treatment, the severity of skin lesions in each group was assessed. Blood samples were collected via enucleation, and serum levels of interleukin (IL) -1β, IL-6, and immunoglobulin E (IgE) were measured using enzyme-linked immunosorbent assay (ELISA) . Histopathological changes in dorsal skin lesions were observed, and immunohistochemical study was performed to detect the expression levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF) -κB p65 in skin tissues, expressed as the percentage of the immunopositive area. One-way analysis of variance was used for multiple group comparisons, while Tukey′s test or the Games-Howell test was applied for post-hoc comparisons between groups. Results:Compared with the blank control group, the model group exhibited epidermal hyperkeratosis with parakeratosis, thickening of the spinous layer, spongiosis, significant inflammatory cell infiltration, and prominent angiogenesis. In contrast, the positive control group, topical sinomenine group, and oral sinomenine group showed reduced spinous layer thicknesses, decreased inflammatory cell infiltration, and less pronounced angiogenesis compared to the model group. In the blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group, the severity scores of skin lesions were 0, 8.83 ± 0.75, 4.33 ± 1.08, 2.58 ± 0.49, 2.83 ± 0.93 respectively, the serum levels of IL-1β were 52.58 ± 1.72, 168.40 ± 7.23, 57.07 ± 6.39, 85.74 ± 4.15, 100.30 ± 11.55 pg/ml respectively, IL-6 levels were 86.88 ± 4.60, 215.00 ± 5.02, 79.34 ± 4.91, 127.20 ± 1.06, 149.00 ± 6.21 pg/ml respectively, IgE levels were 2 159.00 ± 176.00, 3 493.00 ± 89.61, 2 294.00 ± 158.10, 2 550.00 ± 214.70, 2 814.00 ± 119.70 μg/ml respectively, the expression levels of p38 MAPK in skin tissues were 3.03% ± 3.38%, 12.95% ± 6.89%, 2.14% ± 1.28%, 5.28% ± 3.71%, 3.85% ± 2.26% respectively, and NF-κB p65 expression levels were 0.61% ± 0.49%, 18.92% ± 6.96%, 3.77% ± 1.90%, 5.66% ± 2.28%, 6.25% ± 3.14% respectively; the differences in all the above parameters were statistically significant among groups (all P < 0.05) . Compared with the blank control group, the model group had significantly increased skin lesion severity scores, serum IL-1β, IL-6, and IgE levels, as well as elevated expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.01) . Compared with the model group, the positive control group, topical sinomenine group, and oral sinomenine group showed significantly reduced skin lesion severity scores, decreased serum IL-1β, IL-6, and IgE levels, and lower expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.05) . Compared with the positive control group, the topical and oral sinomenine groups exhibited further reductions in skin lesion severity scores (both P < 0.05) . Additionally, the topical sinomenine group showed significantly lower serum levels of IL-1β and IL-6 compared with the oral sinomenine group (both P < 0.05) . Conclusion:Sinomenine solution could obviously alleviate the severity of skin lesions in AD-like mouse models, likely by down-regulating the expression of IL-1β, IL-6 and IgE, inhibiting the MAPK/NF-κB signaling pathway, and thus reducing the degree of inflammation.

Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas with distinct clinical and pathological features. In recent years, advancements in molecular biology techniques have led to a deeper understanding of the molecular mechanisms underlying PACC. Progress in imaging, endoscopic, and molecular diagnostic technologies has improved the early detection rate of PACC. The primary treatment modalities for PACC include surgical resection, chemotherapy, targeted therapy and immunotherapy; however, the therapeutic efficacy still requires further improvement. This article reviews the current research status of PACC, covering its epidemiology, pathological characteristics, molecular alterations, diagnostic methods, and treatment strategies, and discusses the controversies and future directions in PACC research.

Objective:To investigate the trajectory of frailty in elderly patients on maintenance hemodialysis(MHD)following SARS-CoV-2 infection and its associated risk factors.Methods:This prospective cohort study focused on elderly patients who underwent baseline frailty assessment(T0)during hemodialysis treatment at Beijing Friendship Hospital for over 3 months between December 1st, 2022, and December 31th, 2022, and were diagnosed with SARS-CoV-2 infection.The Fried Frailty Phenotype was evaluated at 1 month(T1), 3 months(T2), and 6 months(T3)post-infection.Frailty trajectory after infection was analyzed using repeated measurement ANOVA.Patients were divided into stable/improvement or exacerbation groups based on their frailty status at T0 and T3, with logistic regression analysis employed to identify risk factors for different frailty trajectories.Results:A total of 130 elderly maintenance hemodialysis patients, with a median age of 66 years(range: 63-71 years)and 62 males(47.7%), were included in the study.Six months after the infection, a majority of surviving patients saw their frailty scores return to baseline levels.Specifically, 72 patients(55.4%)either maintained or improved to robust or pre-frail states, while 9 patients(6.9%)progressed to a pre-frail state, 18 patients(13.8%)progressed to a frail state, and 31 patients(23.8%)remained in a frail state.Results from multivariate logistic regression analysis indicated that low grip strength( OR: 6.30, 95% CI: 1.48-26.73)and all-cause hospitalization( OR: 5.01, 95% CI: 1.19-21.03)were identified as risk factors for non-frail patients transitioning to frailty( P<0.05). Conclusions:The majority of elderly maintenance hemodialysis patients who survived SARS-CoV-2 infection returned to their baseline level of frailty or showed improvement within 6 months.Non-frail patients with low grip strength or those who were hospitalized were more likely to deteriorate towards frailty.

Objective A Social Care Needs Assessment Tool for Terminal Patients at Home is constructed and tested for its reliability and validity.Methods In view of the Social Ecosystem Theoiy,based on the semi-structured interviews,participatory observation and literature analysis of the social care needs of terminal patients at home,a questionnaire item pool was formed.Through 3 rounds of Delphi expert consultations,the initial version of the tool was formed.From April to December 2023,a convenient sampling method was used to select 504 terminal patients from 22 hospitals in 5 provinces as the research subjects.The reliability and validity of the tool were tested.Result The constructed tool in this study contained 3 dimensions:micro,meso,macro,with a total of 34 items.Cronbach's α of the tool was 0.966 and split-half reliability was 0.877;I-CVI at the item level was 0.875～1.000 and S-CVI/Ave was 0.989;the exploratory factor analysis results showed that the factors load of each dimension were greater than 0.4;the results of confirmatory factor analysis showed that the tool had good fitting degree.Conclusion The reliability and validity of the nursing-based social care needs assessment tool for terminal patients at home constructed in this study are good,and it can provide a valid tool for healthcare professionals to assess the home-based social care needs of terminal patients.

Objective To develop a scientific and reliable sensitive index system of nursing quality in enteral nutrition for neurocritical patients to ensure the effective implementation of enteral nutrition.Methods Literature on enteral nutrition for neurocritical patients were systematically retrieved from databases,such as BMJ Best Practice,UpToDate,Joanna Briggs Institute(JBI)Evidence-Based Healthcare Database,American Society for Parenteral and Enteral Nutrition(ASPEN),European Society for Clinical Nutrition and Metabolism(ESPEN),National Guideline Clearinghouse(NGC),Guidelines International Network(GIN),Medlive,the Cochrane Library,PubMed,Cumulative Index to Nursing and Allied Health Literature(CINAHL),SinoMed,and China National Knowledge Infrastructure(CNKI)and Wanfang Data.The initial questionnaire was formulated by using the quality evaluation model of"structure-process-outcome".The index system was established by using the Delphi method,and the index weight was determined by the analytic hierarchy process.Results A total of 11 papers were included,of which 5 were graded in A and 6 in B.The effective recovery rates of the two rounds of correspondence questionnaires were 100%(19/19),the expert authority coefficients was 0.864,and the Kendall harmony coefficients were 0.328 and 0.392(P<0.01),respectively.Consequently,a sensitive index system of nursing quality in enteral nutrition for neurocritical patients was established,which encompassed 3 primary indexes,10 secondary indexes and 28 tertiary indexes.Conclusion The index system developed in this study is scientific,reliable and clinically applicable.It conforms to the characteristics of clinical management and nursing,thereby it provides a reference for assessment of the nursing quality in enteral nutrition for neurocritical patients.

Objective:To investigate the predictive value of the Japanese nutritional risk index(NRI)for one-year all-cause mortality risk among elderly maintenance hemodialysis (MHD)patients.Additionally, it seeks to compare the predictive abilities of NRI with those of the geriatric nutritional risk index (GNRI)and the mini nutritional assessment short-form(MNA-SF).Methods:This research was conducted as a prospective cohort study.Elderly patients(aged ≥60 years)who underwent hemodialysis treatment at Beijing Friendship Hospital of Capital Medical University for more than three months between July and October 2019 were selected for inclusion.The NRI score was utilized to evaluate the nutritional status of the participants, with the maximum point of the Jordan index designated as the cut-off value, thereby categorizing patients into high-risk and low-risk groups.The follow-up period concluded in August 2020, with all-cause mortality serving as the primary outcome measure.Kaplan-Meier methods were employed to construct survival curves, and the Cox proportional hazards model was applied to analyze the association between NRI and all-cause mortality.Furthermore, area under the curve(AUC) of receiver operating characteristic(ROC)curves were utilized to compare the predictive values of the three nutritional assessment methods(NRI, GNRI, and MNA-SF)regarding mortality risk.Results:A total of 150 patients were included in the study, with a median age of 69(64.75) years.The cohort comprised 73 males(48.7%)and 77 females(51.3%). Based on the NRI, patients were categorized into a low-risk group(NRI<5; n=81, 54.0%)and a high-risk group(NRI ≥ 5; n=69, 46.0%). Of the 150 patients, 147 completed the follow-up.During the follow-up period, 15 patients died, with 13 from the high-risk group and 2 from the low-risk group.The Kaplan-Meier survival curve indicated that the 1-year cumulative survival rate for patients in the high-risk group was significantly lower than the low-risk group (log-rank χ2=11.71, P<0.001). Furthermore, multivariate Cox regression analysis revealed a significant association between NRI and 1-year all-cause mortality in elderly patients undergoing MHD ( HR=3.779, 95% CI: 1.036-13.783, P=0.044). Additionally, NRI demonstrated a high predictive value for 1-year all-cause mortality risk in elderly MHD patients, with an AUC of 0.755(95% CI: 0.654-0.855), a sensitivity of 86.7%, and a specificity of 59.1%.Its predictive capability was slightly superior to that of the GNRI(AUC=0.691, 95% CI: 0.548-0.835)and the MNA-SF(AUC=0.634, 95% CI: 0.475-0.793), although no statistically significant differences were observed( Z=0.880, 1.177, P=0.379, 0.239). Conclusions:The NRI score demonstrates effective predictive capability for one-year all-cause mortality risk in elderly MHD patients and may serve as a more suitable nutritional assessment method for this population.

Mycobacterium tuberculosis ( Mtb) is the causative agent of tuberculosis in humans and animals. Mtb invades the host′s lungs via airborne transmission, infects macrophages and causes tuberculosis. In some cases, the infection can spread to other tissues and organs. Despite the availability of several drugs for the treatment of tuberculosis, the emergence of multi-drug-resistant tuberculosis has led to high morbidity and mortality rates worldwide. Therefore, there is an urgent need for researchers to develop new anti-tuberculosis drugs that can treat tuberculosis more efficiently. Recent studies have shown that the virulence factors of Mtb play a crucial role in its pathogenicity. These factors primarily include secreted proteins, transcription factors, proteases, stress response proteins, metabolism-associated proteins, and cell-surface components. By evading the host′s immune surveillance through mechanisms such as anti-oxidative stress, regulating nutrient synthesis and metabolism, and modulating host cells apoptosis, Mtb is able to achieve long-term survival and spread with in the host. Understanding the mechanisms of Mtb virulence factors can provide new directions for targeted tuberculosis therapy. Therefore, knowledge of these virulence factors is essential for the development of new vaccines and anti-tuberculosis drugs. In this review, we summarize the latest research progress in the virulence factors of Mtb to provide a reference for targeted treatment of tuberculosis.

With the advancement of the "New Medical Science" reform, the "Medicine+X" model has emerged as a key direction for the future development of medical education. Multidisciplinary integration places higher demands on both educators and students. Emerging technologies, such as intelligent tutoring systems, adaptive learning platforms, intelligent campus management systems, and ChatGPT, have made personalized learning possible. Such approaches offer notable advantages, including improving learning efficiency, enhancing motivation, eliminating the spatiotemporal constraints of clinical education, and alleviating teachers′ workloads. Nevertheless, the application of artificial intelligence in personalized medical education still faces multiple challenges, such as issues of data quality and reliability, the need for faculty development, shifts in educational paradigms, and ethical considerations. This study explored the current status of artificial intelligence in personalized medical education and offered recommendations to promote its development, including strengthening the integration of technology and education, enhancing the digital literacy of educators, establishing ethical guidelines, and fostering multi-stakeholder collaboration.

In traditional teaching, medical students have limited opportunities to interact with patients, which constrains the development of their clinical skills. Virtual standardized patients offer a potential solution to this limitation. This article analyzes the advantages of virtual standardized patients and their application in clinical teaching.