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.

Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

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.

Objective: To investigate the damaging effects of red blood cell supernatant (RBC-S) stored for different durations (7 d, 14 d, and 28 d) on vascular endothelial cells, and to explore the underlying mechanisms using bioinformatics analysis, so as to provide references for optimizing red blood cell transfusion strategies. Methods: Human umbilical vein endothelial cells (HUVECs) were co-cultured with RBC-S stored for 7, 14 and 28 days, designated as the 7 d group, 14 d group and 28 d group respectively, which were collectively defined as the experimental groups. Cell damage was evaluated by cell proliferation assay (Cell Counting Kit8, CCK8), lactate dehydrogenase (LDH) release assay, 4′, 6diamidino2phenylindole (DAPI) staining, and flow cytometry for apoptosis and reactive oxygen species (ROS) levels. The damage degree of RBC-S on vascular endothelial cells was assessed by statistical analysis of damage data among different groups. Since the damage effect reached a plateau at all time points, the 28 d storage group was selected as the representative for further mechanistic studies. Transcriptomic analysis was performed to explore the role of frizzled class receptor 1 (FZD1) and Wnt signaling pathway in red blood cell storagerelated endothelial dysfunction. Results: Compared with the control group, the storage groups treated with 7 d, 14 d, and 28 d RBC-S showed significantly decreased cell proliferation rates [control group 100%, 7 d group (69.51±2.30)%, 14 d group (74.54±2.89)%, 28 d group (73.59±2.36)%, P<0.05], significantly reduced numbers of DAPI-stained cell nuclei [control group (213±12.5) per field, 7 d group (140.33±17.04) per field, 14 d group (152.00±23.72) per field, 28 d group (144.33±19.09) per field, P<0.05] and significantly increased LDH release [control group (1), 7 d group (8.33±1.41), 14 d group (9.23±0.83), 28 d group (9.16±0.60), P<0.05]. There was no significant difference in the degree of damage caused by RBC-S among different storage groups (P>0.05). With the prolongation of storage time, free hemoglobin (FHb) gradually increased [control group (not detected), 7 d (16.57±6.38) mg/L, 14 d (76.80±22.83) mg/L, 28 d (286.97±29.02) mg/L, P<0.05]. The apoptotic rate (20.53±2.94)% and ROS relative intensity (5.13±0.91) in the 28 d storage group were significantly higher than those in the control group (P<0.05). Transcriptomic analysis showed that FZD1 played a key role in vascular endothelial dysfunction induced by red blood cell storage and was closely related to the Wnt signaling regulatory network. Conclusion: RBC-S stored for 7 d, 14 d, or 28 d can all significantly damage vascular endothelial cells, and the damaging effect reaches a plateau at 7 d of storage. Mechanistic investigation of the 28 d group indicated that the downregulation of the FZD1/Wnt signaling pathway may play a critical role in vascular endothelial dysfunction induced by red blood cell storage, providing a theoretical basis for further optimizing red blood cell storage and transfusion strategies.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Objective To investigate the association between dietary patterns and adolescent development in girls in Pudong New Area，Shanghai. Methods Using a stratified cluster sampling method, a total of 998 girls were selected from the cohort of growth, development, and health of children and adolescents in Pudong New Area of Shanghai. Physical development examinations and dietary surveys were conducted on these girls. Principal component analysis was used to determine girls' dietary patterns, and their relationship with adolescent development was analyzed using logistic regression. Results Among the 998 participants, 770 (77.15%) were pubertal girls. The factor analysis identified three dietary patterns, fungi and algae~nuts~legumes pattern, meat-vegetables and fruits-cereals pattern, and milk-eggs pattern. Logistic regression analysis revealed that after adjusting for age, waist circumference, residential district, mother's education level, and father's education level, the Q2 level (OR=0.54, 95% CI: 0.30-0.99), Q3 level (OR=0.50, 95% CI: 0.27-0.91), and Q4 level (OR=0.49, 95% CI: 0.26-0.90) of the fungi and algae-nuts-legumes pattern were negatively correlated with adolescent development. The Q2 level (OR=0.48, 95% CI: 0.27-0.87) and Q3 level (OR=0.49, 95% CI: 0.27-0.88) of the milk-eggs pattern were also negatively correlated with adolescent development. Conclusion The fungi and algae~nuts~legumes pattern and milk-eggs patterns are inversely related to pubertal development.

Objective:To investigate the anti-fatigue effect of Dendrobium and Panax Quinquefolius Granules(DPQG)on the overtrained mice,and to clarify its possible mechanism.Methods:A total of 48 mice were randomly divided into control group(equal volume of distilled water),low dose of DPQG group(400 mg·kg-1 DPQG),medium dose of DPQG group(800 mg·kg-1 DPQG),and high dose of DPQG group(1 600 mg·kg-1 DPQG).The DPQG were administered by gavage for 35 d,and the rotarod test and swimming endurance test were performed 30 min after last administration.Serum,liver tissue,and muscle tissue were collected from the mice in various groups.ELISA method was used to detect the serum lacticacid(LAC)levels and lactate dehydrogenase(LDH)activities,and the malondialdehyde(MDA)levels,superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)activities,and the liver glycogen and muscle glycogen levels in muscle tissue of the mice in various groups;HE staining was used to observe the pathomorphology of muscle tissue of the mice.Transcriptomics and metabolomics technologies were used to identify the key genes and metabolites in muscle tissue of the mice in control group and high dose of DPQG group and to analyze the correlations between differentially expressed genes(DEGs)and differentially expressed metabolites.Results:Compared with control group,the rod turning exhaustion time of the mice in different doses of DPQG groups were significantly increased(P＜0.05),and the swimming exhaution time of the mice in high dose of DPQG group was increased(P＜0.05).Compared with control group,the LDH,SOD,and GSH-Px activities of the mice in medium and high doses of DPQG groups were increased(P＜0.01).Compared with control group,the levels of MDA and liver glycogen of the mice in medium and high doses of DPQG groups were decreased(P＜0.05 or P＜0.01).The transcriptomics sequencing results showed that DPQG mainly acted on DEGs such as Trib3 and Olfr495;the Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis results showed that the DEGs were mainly enriched in olfactory-related processes and signaling pathways;the metabolomics KEGG analysis results showed that the differential metabolites were mainly enriched in the regulation pathway of inflammatory mediators on tryptophan(TRP);the combined analysis of transcriptomics and metabolomics results showed that the piezo1 gene had high correlations with the differential metabolites β1-solamarine(r=-1,P＜0.05)and tilidine(r=1,P＜0.05).Conclusion:DPQG can exert an anti-fatigue effect on the overtrained mice by modulating LAC metabolism and glycogen homeostasis,as well as maintaining the oxidative/antioxidant balance in the body;its anti-fatigue mechanism is related to the Olfr495 and piezo1 genes and the regulation pathway of inflammatory mediators on TRP channels.

Objective:To establish a dose-response curve of dicentric chromosomes and centromeric rings (dic+ r) in γ-ray irradiation-induced chromosomal aberrations in human peripheral blood lymphocytes through automated analysis.Methods:Peripheral blood samples from three healthy donors were irradiated in vitro at doses of 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, and 5 Gy and a dose rate of 0.80 Gy/min using a 137Cs γ-ray source. Post-irradiation, lymphocytes were cultured based on standard protocols, harvested using an automatic cell harvester, and prepared on slides using an automatic slide preparation system. dic+ r were analyzed fully automatically using the DCScore software, and a dose-response curve of dic+ r was established through fitting and then validated using the CABAS software. Results:The dose-response curve followed a linear-quadratic model, i. e., y = 0.093 65+ 0.030 21 D+ 0.025 31 D2 ( R2 = 0.999 2), where y was the quantity of dic+ r and D was the absorbed dose of γ-ray irradiation (Gy). Doses to samples for blind validation were estimated using this curve, yielding deviations of less than 24% from the actual irradiation doses. Conclusions:The fully automated analysis of dic+ r in 137Cs γ-ray irradiation-induced chromosomal aberrations, followed by the construction of the dose-response curve, holds significant potential for rapid, high-throughput biodosimetry in large-scale nuclear emergencies.

Objective To investigate the efficacy of Ustekinumab combined with fecal microbiota transplantation in the treatment of inflammatory bowel disease(IBD)and its impact on intestinal mucosal barrier and immune function.Methods A total of 106 IBD patients treated from January 2023 to March 2024 were selected and divided into the Usteinumab group and the Usteinumab combined with fecal microbiota transplantation group(combination group)by random number table method,with 53 patients in each group.The Ustekinumab group was treated with Ustekinumab,while the combination group was treated with Ustekinumab combined with fecal microbiota transplantation.The clinical efficacy,intestinal mucosal barrier indicators,immune function indicators,scores of the Inflammatory Bowel Disease Quality of Life Questionnaire(IBDQ)and the total incidence of adverse reactions were compared between the two groups.Results The total effective rate of the combination group was 94.34%(50/53),which was higher than that of the Ustekinumab group[73.58%(39/53)](P<0.05).After treatment,the levels of endotoxin,D-lactic acid and diamine oxidase in the combination group were all lower than those in the Ustekinumab group,while the levels of CD3+,CD4+,CD4+/CD8+and the scores of IBDQ were all higher than those in the Ustekinumab group(P<0.05).There was no significant difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion The clinical efficacy of Ustekinumab combined with fecal microbiota transplantation is remarkable in the treatment of IBD.It can effectively alleviate intestinal mucosal injury,promote the recovery of intestinal mucosal barrier function,improve the intestinal microbial environment,enhance the immune function of patients,effectively control the progression of the disease,and has high safety.

In recent years,with the advancement of microbial detection technologies,an increasing number of studies have revealed significant differences in the gut microbiota composition of kidney transplant recipients before and after surgery.These changes in the gut microbiota may influence graft function and the occurrence of post-transplant complications through a variety of factors.This article will review the research progress in the relationship between gut microbiota and kidney transplantation.It focuses on the changes in gut microbiota after kidney transplantation.The role of gut microbiota in immune regulation,drug metabolism,graft function protection,and post-transplant complications is also studied.At the same time,these effects may be of great significance in improving the short-term and long-term prognosis of kidney transplant recipients,thus providing a novel idea for further improving kidney transplant prognosis.