The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

To investigate the clinical efficacy of neoadjuvant imatinib in the treatment of rectal gastrointestinal stromal tumor (GIST).

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Objective　A predictive model should be established during the early stages of dengue progression to evaluate the likelihood of severe dengue and dengue with warning signs, thereby preventing delayed clinical management and reducing dengue-related mortality. Methods　Clinical and laboratory examination data of 831 patients admitted to Ruili People's Hospital of Yunnan Province during 2019-2023 were retrospectively collected. The dataset was divided into a training set and a validation set in a 7∶3 ratio. Statistical description and univariate analysis were performed on the training set, with LASSO regression employed to screen variables, followed by logistic regression to develop a risk prediction model for severe dengue. Model performance was validated using ROC curves on both the training set and validation set. Results　A total of 831 dengue patients were included in the study, with a mean age of (44.20±15.02) years. Among them, 52.59% were male and 5.42% were Myanmar nationality. In total, 122 cases (14.68%) exhibited severe dengue or dengue with warning signs, predominantly female (58.20%). LASSO regression was used in the training set to screen 11 variables related to the risk of severe dengue and dengue with warning signs: Age, dizziness, vomiting, prothrombin time, partial activated thromboplastin time, hematocrit, platelet, monocyte percentage, absolute value of monocytes, hemoglobin, C-reactive protein (λmin= 0.011 59); Logistic regression identified statistically significant variables for the risk model of severe dengue and dengue with warning signs as follows: age [OR=1.034 (95%CI: 1.016-1.053)], red blood cells deposited [OR=1.258 (95%CI: 1.143-1.519)], platelet [OR=0.991 (95%CI: 0.985-0.997)], hemoglobin (OR=0.919 (95%CI: 0.873-0.950)], C-reactive protein [OR=1.019 (95%CI:1.004-1.034)]. The model achieved an AUC of 0.894 (95%CI: 0.796-0.867) in the training set and 0.862 (95%CI: 0.709-0.827) in the validation set. At a cut-off threshold of 0.197, sensitivity and specificity were 0.850 and 0.743, respectively. Conclusion　This study established a LASSO-logistic regression model, which can predict the risk of severe dengue and dengue with warning signs. The model enhances the capability of hospitals to prevent and manage severe dengue and provides valuable guidance for clinical decision-making.

Objective:To investigate the relation between temporal expression changes of proline-rich transmembrane protein 2 ( PRRT2) gene and clinical progression of PRRT2-related paroxysmal disorders (PRPDs). Methods:A retrospective analysis was performed; 19 patients with PRPDs admitted to Department of Neurology, Second Affiliated Hospital of Guangzhou Medical University from July 2021 to July 2024 were enrolled; their clinical data, including onset age and disease progression, were collected. Using Bgee database, the PRRT2 gene expressions in different age groups were analyzed to explore their relations with clinical progression. Results:Among the 19 patients, 8 were diagnosed as having infantile convulsion with choreoathetosis (ICCA), 1 patient as having infantile convulsion, and 10 as having paroxysmal kinesigenic dyskinesia (PKD). Among patients with ICCA, the disease course was divided into two stages: in infantile period, it manifested as infantile convulsions at the onset, with an onset age of (5.75±1.03) months, ranged 4-7 months; in early childhood, no seizures were noted, enjoying a silent period and lasting for a period ranged 7-15 years; subsequently, the disease relapsed during adolescent, presenting as dyskinesia, with an onset age of (11.75±3.11) years, ranged 8-16 years. Among patients with PKD, onset age was (10.40±3.17) years, ranged 5-17 years. PRRT2 expression peaked before 1 year old, declined to the lowest level at 10 years old, and then gradually increased, reaching a second peak at 17 years old; PRRT2 expression demonstrated bimodal peaks during early childhood and adolescence. Conclusion:PRPDs progression shows a certain consistency with the temporal change of PRRT2 gene expression.

Atypical hemolytic uremic syndrome(aHUS),a rare disease caused by complement abnor-malities,is characterized by microangiopathic hemolytic anemia,thrombocytopenia,and acute kidney injury.In this paper,we report a patient with severe renal insufficiency with rapidly progressive decline in binocular visual acuity,who developed eosinophilia during the course of the disease,and was diagnosed with aHUS after excluding other diseases.After glucocorticoid treatment,eosinophils decreased to normal,and after treatment with plasmapheresis combined with eculizumab,renal function tended to be stable,platelets returned to normal,but visual acuity did not improve significantly.This article reviews the diagnosis and treatment process of this patient and incorporates the review of literature,in the hope of providing reference for clinicians.

Objective:To investigate the relation between temporal expression changes of proline-rich transmembrane protein 2 ( PRRT2) gene and clinical progression of PRRT2-related paroxysmal disorders (PRPDs). Methods:A retrospective analysis was performed; 19 patients with PRPDs admitted to Department of Neurology, Second Affiliated Hospital of Guangzhou Medical University from July 2021 to July 2024 were enrolled; their clinical data, including onset age and disease progression, were collected. Using Bgee database, the PRRT2 gene expressions in different age groups were analyzed to explore their relations with clinical progression. Results:Among the 19 patients, 8 were diagnosed as having infantile convulsion with choreoathetosis (ICCA), 1 patient as having infantile convulsion, and 10 as having paroxysmal kinesigenic dyskinesia (PKD). Among patients with ICCA, the disease course was divided into two stages: in infantile period, it manifested as infantile convulsions at the onset, with an onset age of (5.75±1.03) months, ranged 4-7 months; in early childhood, no seizures were noted, enjoying a silent period and lasting for a period ranged 7-15 years; subsequently, the disease relapsed during adolescent, presenting as dyskinesia, with an onset age of (11.75±3.11) years, ranged 8-16 years. Among patients with PKD, onset age was (10.40±3.17) years, ranged 5-17 years. PRRT2 expression peaked before 1 year old, declined to the lowest level at 10 years old, and then gradually increased, reaching a second peak at 17 years old; PRRT2 expression demonstrated bimodal peaks during early childhood and adolescence. Conclusion:PRPDs progression shows a certain consistency with the temporal change of PRRT2 gene expression.

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.
Humans ; Carcinoma, Renal Cell/therapy* ; Immunotherapy ; Glycolysis ; Metabolic Reprogramming ; Kidney Neoplasms/therapy* ; Tumor Microenvironment

Atypical hemolytic uremic syndrome (aHUS), a rare disease caused by complement abnormalities, is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. In this paper, we report a patient with severe renal insufficiency with rapidly progressive decline in binocular visual acuity, who developed eosinophilia during the course of the disease, and was diagnosed with aHUS after excluding other diseases. After glucocorticoid treatment, eosinophils decreased to normal, and after treatment with plasmapheresis combined with eculizumab, renal function tended to be stable, platelets returned to normal, but visual acuity did not improve significantly. This article reviews the diagnosis and treatment process of this patient and incorporates the review of literature, in the hope of providing reference for clinicians.