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.

ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

Objective:To perform routine plasma test, SARS-CoV-2 nucleic acid test, and respiratory pathogenic microorganism nucleic acid test on plasma samples collected from 1 040 healthy plasma donors in winter.Methods:Plasma samples were collected from 1 040 healthy plasma donors at Yunmeng Plasma Collection Station in the winter of 2020. Routine plasma test, HBV/HCV/HIV nucleic acid test, SARS-CoV-2 nucleic acid test, and 22 respiratory pathogenic microorganism nucleic acid test were performed to analyze the quality of blood plasmas.Results:All plasma samples were qualified in the routine tests, meeting the requirements of the Chinese Pharmacopoeia, and tested negative for SARS-CoV-2 nucleic acid. Respiratory pathogenic microorganism nucleic acids were detected in 29 samples with a positive rate of 2.79% (29/1 040). There were 21 cases of simple virus infections, including 17 cases of coronavirus subtype infection, three cases of parainfluenza virus type 2 infection, and one case of human bocavirus infection. Eight cases were mixed infections of viruses and bacteria, four of which were viral infection combined with Bordetella pertussis. The 29 positive samples were collected from people of different age groups, including two from 31-40 years old (1.96%, 2/102 ), three from 41-50 years old (1.59%, 3/189), five from 51-55 years old (1.94%, 5/257), and 19 from 56-60 years old (4.59%, 19/414). Samples from the people aged 56-60 years accounted for the most (39.81%, 414/1 040), as well as the infection rate in this age group. Conclusions:In autumn and winter, respiratory pathogenic microorganism nucleic acid test should be performed when collecting plasma samples from donors aged 56-60 years in addition to meeting the requirements of the Chinese Pharmacopoeia. It is also suggested to conduct respiratory pathogenic microorganism nucleic acid test on pooled plasma and blood products.

Objective:To explore the expression level of Porphyromonas gingivalis, downstream of tyrosine kinase 3 (DOK3) and tumor-associated macrophage (TAM) in the tumor immunomicroenvironment of oral squamous cell carcinoma (OSCC) and the correlation with clinicopathological characteristics and prognosis of patients.Methods:A retrospective case-control study was conducted. The clinical data of 200 OSCC patients with Porphyromonas gingivalis-positive confirmed by 16S rDNA sequencing technology in the First Affiliated Hospital, Xinjiang Medical University between June 2008 and June 2020 were collected. The tumor tissues and the corresponding adjacent normal mucosal tissues of 6 OSCC patients (including 3 cases with Porphyromonas gingivalis -positive and 3 cases with Porphyromonas gingivalis-negative) were selected for high-throughput sequencing to screen differentially co-expressed genes. Immunohistochemistry method was used to detect the expressions of Porphyromonas gingivalis, DOK3, and CD206 (a TAM marker). The median H score of OSCC tissues was used as the threshold to categorize the expression level of Porphyromonas gingivalis, DOK3 and CD206 into low-expression (H score < threshold) and high-expression (H score ≥ threshold) groups. The overall survival (OS) analysis was conducted by using the Kaplan-Meier method, and the log-rank test was employed.Results:The high-throughput sequencing results revealed that DOK3 is a differentially co-expressed gene among normal oral mucosa, Porphyromonas gingivalis-positive, and Porphyromonas gingivalis-negative OSCC. In 200 patients with Porphyromonas gingivalis-positive OSCC, 139 exhibited high expression of Porphyromonas gingivalis (H score ≥ 7 points), while 61 showed low expression (H score < 7 points). There were statistically significant differences in the expression levels of Porphyromonas gingivalis in patients with different survival status, pathological T stage, pathological N stage, clinical stage, tumor diameter, degree of tumor differentiation and recurrence (all P < 0.05). Among the 139 OSCC patients with high expression of Porphyromonas gingivalis, 92 cases showed high expression of DOK3 (H score ≥ 6 points) and 47 showed low expression (H score < 6 points); 78 cases exhibited high expression of CD206 (H score ≥ 6 points), while 61 showed low expression (H score < 6 points). There were statistically significant differences in the DOK3 expression level in the high expression of Porphyromonas gingivalis OSCC patients with different age, survival status, pathological T stage, pathological N stage, and recurrence (all P < 0.05). There were statistically significant differences in the CD206 expression level in the high expression of Porphyromonas gingivalis OSCC patients with different pathological T stage, clinical stage, and degree of tumor differentiation (all P < 0.05). The expression of Porphyromonas gingivalis was positively correlated with the expressions of DOK3 and CD206 (both P < 0.01). At the last follow-up on April 6th, 2024, the median follow-up time was 45 months (3 to 106 month range). The median OS time of the 200 patients was 2 429 d, and the 3-year OS rate was 63.9%. The OS of OSCC patients with high expressions of Porphyromonas gingivalis, DOK3, and CD206 was worse than that in those with low expressions (all P < 0.05). Conclusions:The high expression levels of Porphyromonas gingivalis, DOK3, and TAM are associated with a poor prognosis of OSCC patients, suggesting their potential as key biomarkers for prognostic evaluation.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To summarize the clinical characteristics of focal cerebral arteriopathy (FCA) in children, and to analyze its influencing factor of prognosis.Methods:A retrospective cohort study was conducted. Clinical data from 40 children with FCA who were hospitalized at the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from September 2015 to August 2024 were collected. A centralized follow-up was conducted in October 2024 via outpatient clinics or the internet. The pediatric stroke outcome measure (PSOM) was used to evaluate their outcomes. Based on the PSOM, the children were further divided into a group with normal neurological function and another group with abnormal neurological function. Differences between groups were analyzed using the Mann-Whitney U test and Fisher exact test. Univariate Logistic regression analysis was performed to identify the influencing factors for neurological outcomes in children with FCA. Results:A total of 40 children were included, with 20 males and 20 females, and the onset age of 9.2 (6.8, 12.5) years. Among them, 12 cases (30%) had a history of varicella within 1 year before onset. There were 23 cases (58%) presenting with transient ischemic attack (TIA) or recurrent fluctuating symptoms of onset, while 3 cases (8%) developed progressive stroke within the first month of onset. The M1 segment of the middle cerebral artery was the most commonly affected vascular site, with a total of 16 cases (40%). Arterial occlusion occurred in 8 cases (20%). Lumbar puncture was completed in 36 children, and white blood cell counts in cerebrospinal fluid was increased in 6 cases. All 23 patients who completed magnetic resonance vessel wall imaging (VWI) showed circular enhancement of the arterial wall. A total of 28 patients (70%) received antiplatelet or anticoagulation therapy, and 16 patients (40%) received hormone therapy. At admission, the pediatric National Institute of Health Stroke Scale (PedNIHSS) score was 6.0 (2.0, 8.8) points, which decreased to 0.5 (0, 3.0) points at discharge. The follow-up duration was 1.6 (0.8, 4.9) years, with 1 case lost to follow-up. There was 1 case presenting with recurrence course manifesting as TIA. Among the 39 cases who completed the follow-up, 23 cases (59%) were assessed as neurologically normal by PSOM, while 16 cases (41%) were assessed as neurologically abnormal. Among the 29 cases who completed the imaging review, magnetic resonance angiography (MRA) review in 23 cases indicated stability or improvement in the original arterial stenosis, with 6 cases experiencing transient worsening of arterial stenosis early in the disease course (within 2 months), which later improved. Arterial stenosis progression occurred in 6 cases at the final review of 29 cases who completed the imaging review, with 1 case developing progressive cerebral arteriopathy. The proportion of patients with headache, altered consciousness, and aphasia in the abnormal neurological function group, as well as the PedNISS scores at admission and discharge, were all higher than those in the normal neurological function group (all P<0.05). Univariate Logistic regression analysis revealed that only a PedNISS score>6 points at onset was an influencing factor for abnormal neurological function ( OR=20.58, 95% CI 3.93-107.70, P<0.001). Conclusions:Childhood FCA often presents with fluctuating onset, and the proximal segment of the middle cerebral artery is frequently affected. Progression of arterial stenosis is common within 2 months of the disease course, but clinical progression and new ischemic lesions are uncommon. Most patients have a favorable long-term prognosis. PedNIHSS score>6 points at admission is related to abnormal neurological function outcomes.

There are no reports on the application of perirenal fat covering technique in lingual mucosal graft ureteroplasty（LMGU），and its safety and effectiveness need to be observed. This study retrospectively analyzed clinical data of 7 patients who underwent lingual mucosa ureteroplasty with intraoperative perirenal fat covering technique. The median stricture length was 5.5（range 4.0 to 6.0）cm，operative duration was 170（range 120 to 230）min，estimated blood loss was 92（range 15 to 110）ml. No conversions to open surgery occurred. During a median follow-up of 46（range 8 to 86）months，all procedures achieved clinical success. The application of perirenal fat covering technique in LMGU is safe and effective.

The traditional Chinese medicine(TCM) industry is a crucial part of China's pharmaceutical sector and plays a strategic role in ensuring public health and promoting economic and social development. In response to the practical demand for high-quality development of the TCM industry, this paper focused on the bottlenecks encountered during the digital and intelligent transformation of TCM production systems. Specifically, it explored technical strategies and methodologies for constructing the best TCM production mode. An innovative artificial intelligence(AI)-centered technical architecture for TCM production was proposed, focusing on key aspects of production management including process modeling, state evaluation, and decision optimization. Furthermore, a series of critical technologies were developed to realize the best TCM production mode. Finally, a novel AI-driven TCM production mode characterized by a closed-loop system of "measurement-modeling-decision-execution" was presented through engineering case studies. This study is expected to provide a technological pathway for developing new quality productive forces within the TCM industry.
Artificial Intelligence ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional/methods* ; Humans

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged