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 explore the medicinal qualities and background of CHEN Xiuyuan in treating gynecological disorders.[Methods]By reading CHEN Xiuyuan's book Gynaecological Essentials and analyzing its theoretical aspects,treatment concepts and medicinal aspects in relation to regulating women's menstruation,preparing for pregnancy,the perinatal and postnatal periods,etc.[Results]Gynaecological Essentials points out,in terms of diagnostic and therapeutic features,the gynecological disorders are always leukorrheal diseases;it emphasizes the importance of pulse diagnosis,advocates that regulating menstruation should be preceded by stabilizing the spleen and stomach,highlights that four essentials should support preparing for pregnancy,emphasizes spleen and kidney preservation for the fetus and that postpartum illnesses should not be limited in course of disease.In the drug characteristics,Ligusticum chuanxiong Hort(Chuan xiong)and Angelica sinensis(Danggui)are the first choice to replenish Qi and blood,Atractylodes macrocephalae(Baizhu)is an essential part of a prescription for calming the fetus,and the use of blood,flesh and sentimental products is preferred,while the use of medicines during pregnancy is advised to be within a reasonable range.[Conclusion]CHEN Xiuyuan learned the ancients but didn't stick stubbornly in treating gynecological diseases,emphasized the importance of pulse diagnosis,paid attention to the spleen and stomach,used medication to replenish Qi and blood,and the principle-method-recipe-medicines was very distinctive,which was of great significance to the differentiation and treatment of gynecological diseases in later generations.

Objective:Constructing a risk prediction model to assess the impact of various factors on the need for auxiliary bone grafting with implant placement following alveolar ridge preservation (ARP) in posterior teeth.Methods:According to the sample size calculation formula, the sample size was calculated using the pmsampsize package of R 4.1.3 software, based on inclusion and exclusion criteria, a total of 110 posterior teeth in 98 patients who underwent ARP at the Department of Periodontology, School and Hospital of Stomatology, China Medical University, from January 2018 to May 2024 were conducted. Teeth were randomly divided into modeling group and validation group with 7∶3 ratio according to the random number table. The modeling group was divided into direct implantation group and auxiliary bone grafting group on the basis of whether auxiliary bone grafting was performed 6 months after ARP. Univariate and multivariate analyses were conducted to identify factors influencing auxiliary bone grafting with implant placement following ARP. Nomogram was constructed using R software. Receiver operator characteristic (ROC) curve and calibration curve were drawn to evaluate model differentiation and consistency. The decision curve analysis (DCA) was used to assess the clinical application value of the model.Results:Age ( OR=1.06, P=0.001), maximum attachment loss (AL) ( OR=1.75, P<0.001), reason of tooth extraction ( OR=12.73, P<0.001), smoking [<10 cigarettes/d ( OR=7.59, P<0.001);≥10 cigarettes/d ( OR=28.12, P<0.001)] and stage of periodontitis [stage Ⅱ ( OR=2.57, P=0.430); stage Ⅲ ( OR=21.00, P=0.007); stage Ⅳ ( OR=76.50, P<0.001)] influenced the necessity for auxiliary bone grafting with implant placement after ARP. After multivariate analysis of the above influencing factors, it was found that smoking [<10 cigarettes/d ( OR=7.02, P=0.009);≥10 cigarettes/d ( OR=10.27, P=0.026)] was an independent risk factor for the need of auxiliary bone grafting with implant placement after ARP. The area under the ROC curve for internal verification was 0.90 (95 %CI: 0.84-0.97), and the H-L goodness of fit test results were χ 2=4.79, P=0.780, indicating a good agreement. The area under the externally verified ROC curve was 0.97 (95 %CI: 0.92-1.00), suggesting that the fitting effect was slightly lower than that of the modeling group, and the predicted value of the model was slightly lower than the true value, which might underestimate the risk of additional surgery in patients. Results:of H-L goodness of fit test were χ 2=5.03, P=0.754. The DCA curve showed that when the probability of high-risk threshold was between 0.06 and 0.93, the clinical application value of the prediction model was higher. Conclusions:Age, smoking, reason of tooth extraction, stage of periodontitis, and maximum AL of the affected teeth were related to the necessity for auxiliary bone grafting with implant placement 6 months after ARP. Smoking was an independent risk factor for auxiliary bone grafting surgery. The constructed nomogram model had good discrimination and consistency.

Objective:To evaluate the efficacy and safety of telitacicept in the treatment of systemic lupus erythematosus (SLE) .Methods:The clinical data of 25 SLE patients who received standard therapy combined with telitacicept at the Department of Dermatology, Xiangya Second Hospital, Central South University, from 2021 to 2024 were retrospectively collected. Baseline demographic and clinical characteristics were analyzed. Changes in skin lesions, joint pain symptoms, complete blood count, and biochemical parameters at 4, 12, and 24 weeks of treatment were compared with baseline (week 0). The Wilcoxon signed-rank test was used to compare complement C3 and C4 levels before and after treatment, and univariate logistic regression analysis was performed to explore factors influencing the efficacy of telitacicept.Results:Among the 25 SLE patients, 3 were male (12.0%) and 22 were female (88.0%). Based on the SLE Disease Activity Index (SLEDAI) -2000 scores, 8 patients were mild, 13 were moderate, and 4 were severe. Of the 11 SLE patients with rashes before treatment, 6 achieved complete remission at 12 weeks. Among the 7 patients with joint pain before treatment, 4 experienced symptom resolution at 24 weeks. The proportion of patients with leukopenia at baseline and at 4, 12, and 24 weeks was 10/25 (40.0%), 0/24 (0), 1/22 (4.5%), and 2/19 (10.5%), respectively. The proportion of patients with thrombocytopenia was 6/25 (24.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively, and the proportion of patients with anemia was 7/25 (28.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively. At baseline, 11 out of 25 patients (44.0%) had proteinuria. At 12 weeks, the urinary protein quantification level (0.4 [0, 0.6] g/L) was significantly lower than at baseline (0.9 [0.8, 1.2] g/L). The SLE responder index-4 (SRI4) response rates at 4, 12, and 24 weeks were 14/18, 15/17, and 12/14, respectively. Complement C3 and C4 levels were significantly higher at 4, 12, and 24 weeks compared to baseline (all P < 0.001). Univariate logistic regression analysis showed that age, disease duration, glucocorticoid dosage, baseline complement C4 levels, antinuclear antibody titer, and SLEDAI-2K score did not significantly affect the efficacy of telitacicept (SRI4 response rate at 12 weeks) (all P > 0.05). No serious adverse reactions related to telitacicept were observed in patients. Conclusions:Telitacicept improved skin lesions, complement C3 and C4 levels, and anti-double-stranded DNA antibody levels in SLE patients. No association was found between the efficacy of telitacicept and baseline SLEDAI-2K scores, antinuclear antibody titers, or complement C4 levels, suggesting that telitacicept is an effective and safe treatment for SLE patients.

Objective To investigate the interaction relationship among symptoms in middle-aged patients during the recovery period of stroke and explore its correlation with rehabilitation confidence,providing a reference for the implementation of precise rehabilitation nursing.Methods A cross-sectional study was conducted,and 365 middle-aged patients in the recovery period of stroke who were hospitalized in 4 tertiary general hospitals in Wuhan from April 20 to August 31,2024 were conveniently selected as the subjects of the investigation.Data were collected using the General Information Questionnaire,Stroke Symptom Experience Scale,and Confidence after Stroke Measure Questionnaire.Symptom network analysis was conducted using R software,and a network structure model of symptoms-rehabilitation confidence was constructed;meanwhile,the stability of the network structure was evaluated.Results Finally,350 middle-aged stroke patients in the recovery period were included.The most common symptom was"limb weakness"(81.1％).Symptom network analysis showed that"limited limb movement"was the core symptom(rs=1.118).The symptoms strongly associated with recovery confidence were"limited physical movement","annoyance at not being able to do what you want to do"and"slow reaction times".Stability tests suggest that the model results are all good.Conclusion Symptoms of middle-aged patients in the recovery period after stroke are interrelated,and the mechanisms by which different symptoms affect rehabilitation confidence are also different.It is recommended that healthcare professionals prioritize interventions based on core symptoms and inter-symptom relationships in order to accurately enhance patient outcomes and improve recovery outcomes.

Objective:To explore the influences of FibroScan detection on the pregnancy outcomes of pregnant rats transfected with hepatitis B virus and the growth of their offspring rats.Methods:Sixty SPF-grade SD rats with a male-to-female ratio of 5∶1 were selected，randomly divided the female rats into the groups of mid-pregnancy with hepatitis B，late-pregnancy with hepatitis B，normal mid-pregnancy，normal late-pregnancy，and control group，and the rats in the mid-pregnancy and late-pregnancy groups were subjected to FibroScan testing on the 10th and 15th days of gestation respectively. The number of offspring rats in each group was randomly reduced to 10 on the 3rd day after delivery，and the offspring rats were divided into the groups of mid-pregnancy with hepatitis B，late-pregnancy with hepatitis B，normal mid-pregnancy，normal late-pregnancy，and control group. The pregnancy outcome levels of pregnant rats were observed by adopting a stratified analysis strategy，including differences in weight changes，number of deliveries，fetal rat outcomes，lactation conditions，litter size，and litter weight. The growth levels of offspring rats，including differences in weight，body length，tail length，and the time of fur growth，tooth eruption，eye opening，and ear standing on the 21st day were observed，and the survival rate of the offspring rats was compared.Results:With regard to the pregnancy outcome levels of the pregnant rats，there were no statistically significant differences in weight changes during pregnancy among the five groups of pregnant rats［ F（4，45）=2.627，Adjusted P=0.222］. There were also no statistically significant differences in the number of deliveries，fetal rat outcomes，and lactation conditions（Adjusted P=1.000）. The number of deliveries［ F（4，21.095）=2.280，Adjusted P=0.222］and litter weight［ F（4，20.128）=2.159，Adjusted P=0.222］showed no statistically significant differences. After correction using the BH method，none of the indicators showed significant differences（ P>0.05）. In terms of the growth levels of the offspring rats，among the five groups of offspring rats，there were no statistically significant differences in body weight on the 21st day［H（4）=11.623，Adjusted P=0.135］，body length on the 21st day［H（4）=10.962，Adjusted P=0.135］，and tail length on the 21st day［H（4）=9.126，Adjusted P=0.058］. Besides，the differences in the time of fur growth，tooth eruption，eye opening，and ear standing［H（4）=0.000，Adjust P=1.000］showed no statistical significance. The survival rate on the 7th day，14th day，and 21st day was 100%，with no significant differences（Adjusted P=1.000）. After correction using the BH method，none of the indicators showed significant differences（ P>0.05）. Conclusion:FibroScan detection had no significant influences on the pregnancy outcomes of pregnant rats with hepatitis B or on the growth of their offspring rats in multiple stages，dimensions，and indicators，indicating that FibroScan detection is safe for pregnant rats. This research provides an animal experimental basis for the safe use of FibroScan in pregnant women with chronic HBV infection.