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.

This study aimed to design and synthesize a series of novel photocaged compounds based on the precise binding mode of cyclin-dependent kinase 2 (CDK2) inhibitor AT7519 with its target, to achieve precise optical control over molecular activity. Using AT7519 as the structural foundation, different types of photoremovable protecting groups were introduced at its key interaction sites (the NH of the pyrazole ring and the NH of the piperidine ring), resulting in the synthesis of eight dual-photocaged compounds. Their structures were confirmed by NMR and mass spectrometry, and their photochemical properties—including photolysis wavelength, photolysis time, and photolysis efficiency—were systematically evaluated. The optically controlled inhibitory effects of the compounds on HCT116 cell proliferation were assessed using MTT assay. The photoresponsive characteristics of the photocaged compounds were significantly influenced by the type of photoremovable protecting group and its introduction site. Among them, compounds 1a, 1b, and 2d exhibited excellent photolysis efficiency, each achieving a rate exceeding 90%. Particularly, compounds 1b and 2d demonstrated excellent optically controlled activity: under dark conditions, their half maximal inhibitory concentration (IC50) values were both greater than 150 µmol/L, indicating negligible cell proliferation inhibitory activity; however, upon irradiation, their cell proliferation inhibitory activity significantly increased, with IC50 values comparable to those of the positive control AT7519. The obtained compounds 1b and 2d possess excellent optically controlled properties, and can be further investigated as potential candidates for optically controlled CDK2 inhibitors.

ObjectiveTo explore the anti-eczema efficacy and mechanism of Mongolian medicine Cymbaria dahurica n-butanol extract. MethodsThe compounds of C. dahurica n-butanol extract were obtained by ultra-performance liquid chromatography-quadrupole-electrostatic field orbital trap high resolution mass spectrometry （UPLC-Q-Exactive MS） analysis and literature mining. GEO chip analysis and network pharmacology were employed to predict potential targets and pathways for the anti-eczema effect. Seventy-five mice were randomized into a normal group （10 mice） and a modeling group （65 mice）. The model was induced by 1% dinitrochlorobenzene （DNCB） for 3 days. The modeled mice were grouped as follows： Positive drug （hydrocortisone butyrate cream， 250 mg·kg^-1·d^-1） and low-， medium-， and high-dose （95.94， 191.88， and 383.76 mg·kg^-1·d^-1， respectively） C. dahurica n-butanol extract， with 13 mice in each group. From day 5 of the experiment， 0.5% DNCB was applied， once every other day， until day 22. At the same time， drugs were applied daily from day 5. The appearance damage of back skin of mice in each group was analyzed. The pathological changes of the back skin of mice in each group were observed by hematoxylin-eosin （HE） staining and toluidine blue （TB） staining. The levels of inflammatory factors ［histamine （HIS）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TFN-α）］， thymic stromal lymphopoietin （TSLP）， and immunoglobulin E （IgE） in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. Metabolomics analysis was performed for the mouse skin. The HaCaT cell model of eczema was induced with TNF-α/interferon-γ （IFN-γ）. The secretion levels of IL-6， IL-8， thymus and activation-regulated chemokine （TARC/CCL17）， macrophage-derived chemokine （MDC）， and TSLP in the cell supernatant from each group were measured by ELISA， while the protein levels of phosphorylated （p）-Janus kinase 2 （JAK2）， JAK2， p-signal transducer and activator of transcription 3 （STAT3）， and STAT3 were assessed by Western blot. ResultsThrough UPLC-Q-Exactive MS and literature review， a total of 125 compounds of C. dahurica n-butanol extract were obtained. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis showed that the anti-eczema mechanism of C. dahurica n-butanol extract may be related to the Janus kinase/signal transducer and activator of transcription （JAK/STAT） pathway. The results of animal experiments showed that compared with the normal group， the modeling group exhibited redness， swelling， exudation， erosion， and scab formation on the back skin surface， and thickened dermis and epidermis with inflammatory cell infiltration. Compared with the modeling group， the positive drug and C. dahurica n-butanol alleviated the skin lesions （including redness， swelling， exudation， roughness， and keratosis and scab formation on the back）， reduced the thickness of dermis and epidermis， mitigated inflammatory cell infiltration， and restored the skin tissue structure. Compared with the normal group， the modeling group showed elevated levels of HIS， IL-4， IL-6， IL-8， TNF-α， TSLP， and IgE （P<0.05， P<0.01）， which were reversed in the positive drug group and C. dahurica n-butanol extract groups （P<0.05， P<0.01）. The results of metabolomics analysis showed that 12 differential metabolites might be the key substances for mitigating metabolic disorders of the skin and were closely related to the JAK/STAT signaling pathway. The cell experiement showed that compared with the normal group， the model group exhibited upregulated expression levels of IL-6， IL-8， MDC， TARC， TSLP， p-JAK2， p-STAT3， p-JAK2/JAK2， and p-STAT3/STAT3 in HaCaT cells （P<0.05， P<0.01）. Compared with the model group， C. dahurica n-butanol extract and dexamethasone downregulated the expression levles of these molecules （P<0.05， P<0.01）. ConclusionC. dahurica n-butanol extract may play an anti-eczema role by inhibiting the JAK2/STAT3 signaling pathway， reducing the inflammatory response， and correcting the metabolic disorder.

Objective To analyze the related factors of long-term prognosis of patients with localized renal cell carcinoma after laparoscopic partial nephrectomy.Method Clinical data of 110 patients with localized renal cell carcinoma who underwent laparoscopic partial nephrectomy from January 2020 to January 2021 were retrospectively analyzed.According to whether the patients died within 3 years after operation,they were divided into death group(n=19)and survival group(n=91).The related factors of long-term prognosis of the two groups were compared.Results Compared with the survival group,the proportion of hyperlipidemia,diabetes,hypertension,sarcomatoid differentiation,clear cell type,T1b～T3a stage and American Society of Anesthesiologists(ASA)grade Ⅲ～Ⅵ in the death group increased(P＜0.05),the maximum diameter of tumor increased(P＜0.05),score of Mayo adhesive probability(MAP)and perirenal fat density increased(P＜0.05),the operation time and indwelling drainage tube time prolonged(P＜0.05),and the levels of blood urea nitrogen(BUN),creatinine(Cr),hypersensitive C-reactive protein(Hs-CRP),total cholesterol(TC)and microalbuminuria(MAU)increased(P＜0.05).Sarcomatoid differentiation(OR=1.737,95％CI:1.074～2.807),T stage of T1b～T3a(OR=1.627,95％CI:1.182～2.240)and level of Cr≥91.27 μmol/L(OR=1.923,95％CI:1.064～3.476)were risk factors for long-term prognosis of patients with localized renal cell carcinoma after laparoscopic partial nephrectomy(P＜0.05).Conclusion The mortality rate of patients with localized renal cell carcinoma within 3 years after laparoscopic partial nephrectomy is high.Sarcomatoid differentiation,T stage of T1b～T3a and level of Cr ≥ 91.27 μmol/L are related to the long-term prognosis of patients with localized renal cell carcinoma after laparoscopic partial nephrectomy.Clinical interventions could be taken for high-risk patients.

Objective:To explore the impact of anterior cruciate ligament(ACL) augmented repair versus autologous hamstring tendon single-bundle reconstruction on long-term joint function and radiological outcomes in patients with ACL tear.Methods:A prospective study was conducted, including medical records of 100 patients with anterior cruciate ligament (ACL) tears admitted to the 983rd Hospital of the Joint Logistic Support Force of the Chinese People′s Liberation Army from January 2020 to January 2023. There were 68 males and 32 females, who were aged from 35 to 63 years old, with a mean age of (44.73±6.31) years. The lesion was on the left side in 41 cases and on the right side in 59 cases. According to the Sherman classification, 43 cases were type Ⅰ and 57 cases were type Ⅱ. Patients were sequentially numbered according to admission order, and a random integer generator was used to assign random numbers (1 or 2). Patients assigned "1" were included in the Group 1, while those assigned "2" were allocated to the Group 2, with 50 cases in each group.The Group 1 received ACL augmented repair, while the Group 2 was treated with autologous hamstring tendon single-bundle reconstruction. After treatment, the two groups were compared in terms of knee joint function[International Knee Documentation Committee (IKDC) score], motor function(Tegner score), knee joint stability(pivot shift test) at 12 and 24 months after surgery; the incidence of active pain[visual analog scale (VAS) score] at 1-3 months, 4-6 months, 7-12 months, and 13~24 months after surgery; radiological outcomes; and the rate of secondary revision. Measurement data with normal distribution were expressed as mean ± standard deviation( ± s), and comparisons between the two groups were performed using t-test. Comparisons among multiple time points within the group were conducted using repeated measures analysis of variance. Count data were presented as cases and percentages [ n(%)], and comparisons between groups were made using the chi-square test. Ranked data were analyzed using the Wilcoxon signed-rank test. Results:As of the last follow-up, a total of 45 patients were included in Group 1 (the repair group), and 48 patients were included in Group 2 (the reconstruction group). At 12 and 24 months postoperatively, the IKDC scores in the repair group showed significant improvements compared to preoperative values ( t =11.29, P<0.05; t=14.86, P<0.05), as did the Tegner scores ( t=36.13, P<0.05; t=52.21, P<0.05). Additionally, pivot-shift test results demonstrated significant improvement ( χ2=79.33, P<0.05; χ2=90.00, P<0.05). Similarly, in the reconstruction group, both IKDC scores ( t=10.02, P<0.05; t=13.73, P<0.05) and Tegner scores ( t=44.87, P<0.05; t=60.65, P<0.05) significantly increased at 12 and 24 months postoperatively, with pivot-shift test results also showing marked improvement ( χ2=89.33, P<0.05; χ2=96.00, P<0.05). However, no statistically significant differences were observed between the repair and reconstruction groups in Tegner scores or pivot-shift test results at either time point. However, no statistically significant differences were observed between the two groups for any outcome at either time point (IKDC: t=0.93, P>0.05 at 12 months; t=0.75, P>0.05 at 24 months; Tegner: t=1.52, P>0.05; t=0.77, P>0.05; pivot-shift: χ2=1.16, P>0.05; χ2=1.34, P>0.05). The duration of postoperative activity-related pain was significantly shorter in the repair group (3.24±0.61 months) compared to the reconstruction group (4.48±0.59 months) ( t=9.95, P<0.05). During postoperative months 1-3 and 4-6, pain levels were also significantly lower in the repair group ( t=5.32, P<0.05; t=8.71, P<0.05). However, no statistically significant differences in pain levels were observed between groups at postoperative 7th to 12th months ( t=0.40, P>0.05) and 13th to 24th months ( t=0.37, P>0.05). At 24th months postoperatively, the majority of patients in both groups exhibited ligament thicknesses approaching normal levels, with fibro-osseous bridging between the ligament and bone tunnel walls. The revision rates were 2.2% (1/45) in the repair group and 2.1% (1/48) in the reconstruction group, with no statistically significant difference between groups ( χ2=0.00, P>0.05). Conclusions:The effects of ACL augmented repair for treating ACL tears on patients′ knee joint function, knee joint stability, motor function, and ligament healing are comparable to those of autologous hamstring tendon single-bundle reconstruction. However, ACL augmented repair can reduce the incidence of early active pain in patients.

A 15-year-old boy developed abdominal pain and melena two weeks after COVID-19 infection, which was followed by gross hematuria and proteinuria. Laboratory studies revealed significantly elevated inflammatory markers. Endoscopic examinations showed multiple jejunal and ileal ulcers. Renal biopsy suggested mesangial proliferative glomerulonephritis with crescent formation, necrosis of capillary loops, and mesangial IgA deposits. IgA vasculitis without purpura was considered as a possible diagnosis, and the treatment with prednisone led to remission of both gastrointestinal and renal diseases.

Objective: To evaluate the efficacy of the left spermatic vein transposition to the great saphenous vein in treating left varicocele (VC) secondary to nutcracker syndrome (NCS). Methods: Clinical data of 8 patients treated during Feb.2020 and Feb.2023 in our hospital were retrospectively analyzed.A meticulous preoperative evaluation of the vascular status of the spermatic vein and the great saphenous vein was performed using color Doppler ultrasound.A spermatic vein-great saphenous vein shunt surgery was performed in patients who were strictly selected.The clinical symptoms and hemodynamics of renal vein were compared before and after operation. Results: The median age of patients was 23.5(18-33) years.There was a notable reduction in post-exercise scrotal and lower back pain in all patients，and the score of scrotal pain decreased to 0 in 7 patients. The median quantification of urinary protein was 352.8(54.4-687.3) mg prior to surgical intervention，which significantly diminished to 125.5(25.9-255.1) mg 6 months after operation.Notably，3 cases of preoperative positive urine occult blood tests were undetectable in the subsequent postoperative assessments.The median peak blood flow velocity at the site of stenosis in the left renal vein measured at 74.4(48.7-117.6) cm/s preoperatively，subsequently reduced to 45.1(25.5-61.2) cm/s postoperatively.During the 6-month follow-up，no recurrence of varicocele，vascular anastomotic stenosis or thrombosis were observed. Conclusion: Our research indicates that spermatic vein to great saphenous vein bypass is safe and feasible in the treatment of left varicocele secondary to nutcracker syndrome for strictly selected patients，which can effectively alleviate renal vein congestion without significant complications.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People