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.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

BackgroundAdverse childhood experiences （ACEs） are strong predictors of psychopathology across the lifespan， exerting extensive adverse effects on physical and mental health during early development. While ACEs increase the risk of childhood psychopathology， sleep quality and impair cognitive function， the early neurobiological mechanisms mediating ACE-induced cognitive impairment remain unclear. ObjectiveTo explore the association between ACEs exposure and the risk of psychopathology， sleep disorders， and cognitive function， and to examine the mediating role of the putamen volume in the relationship between ACEs and cognitive function from a neurodevelopment perspective. MethodsData were obtained from the Adolescent Brain Cognitive Development （ABCD） study， comprising 10 572 children aged 9 to 10. Participants were categorized into five groups based on the cumulative score of ACEs reported by their parents and the children themselves： no-exposure group （0 types of ACEs）， the one-exposure group， the two-exposure group， the three-exposure group， and the high-risk exposure group （≥ 4 types of ACEs）. Logistic regression analysis was employed to evaluate the association between ACEs and psychopathological symptoms ［T score of the Child Behavior Checklist （CBCL） ≥ 65］. Multiple linear regression analysis was ultilized to analyze the correlations between ACEs and the scores of the Sleep Disturbance Scale for Children （SDSC）， the NIH Toolbox Cognition Battery （NIHTB-CB）， as well as the multiple structures in the cerebral cortex and subcortex. The Bootstrap method was applied to test the mediating effect of the putamen volume between ACEs and neurocognitive function. ResultsAfter adjusting for confounders， ACEs cumulative score was correlated with children's psychopathological symptoms in a dose-response manner. Compared with the no-exposed group， the high-risk exposure group had a 2.08-fold （OR=2.080， 95% CI： 1.401–3.088） increased risk of internalizing problems and a 3.13-fold （OR=3.132， 95% CI： 1.703–5.760） increased risk of externalizing problems， and the risk of conduct problems was 4.68 times that of the no-exposed group （OR=4.681， 95% CI： 2.528–8.669）. ACEs cumulative score positively predicted the total score of SDSC （β=0.080， 95% CI： 0.059–0.102）， with relatively stronger predictive effects on sleep-wake transition disorder （β=0.086， 95% CI： 0.063–0.109） and sleep onset and maintenance disorder （β=0.066， 95% CI： 0.043–0.089）. In terms of neurocognition and brain structure， ACEs cumulative score negatively predicted the overall cognitive composite score （β=-0.025， 95% CI： -0.050–-0.001）， the crystallized cognitive composite score （β=-0.035， 95% CI： -0.060–-0.010）， the volume of the left putamen nucleus （β=-0.025， 95% CI： -0.046– 0.003）， and the volume of the right putamen nucleus （β=-0.023， 95% CI： -0.044– 0.003）. The total putamen volume played a partial mediating role between ACEs and the overall cognitive composite score， the effect value was -0.002 （95% CI： -0.004–-0.001）， accounting for 7.49% of the total effect. ConclusionACEs exposure may increase the risk of psychopathological and sleep disturbances in children and may impair neurocognitive function. Reduced putamen volume may serve a potential neurobiological pathway underlying the impact of ACEs on childhood cognition. ［Funded by National Natural Science Foundation of China-Young Scientists Program （number， 82401763）； Sichuan University West China Hospital Full-time Postdoctoral Research and Development Fund Project （number， 2023HXBH084）］

Objective To investigate the correlation between gut microbiota characteristics and immunotherapy efficacy in patients with advanced microsatellite stable (MSS) advanced gastrointestinal tumors. Methods Thirty patients with advanced MSS gastrointestinal tumors, including fourteen cases of gastric cancer and sixteen cases of colorectal cancer, who were admitted from November 1, 2022, to July 31, 2025 were enrolled. All patients underwent gut microbiota testing and received corresponding interventions on the basis of the results, followed by treatment with antiangiogenic agents combined with immunotherapy. Some patients additionally received probiotics or fecal microbiota transplantation. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analyses were used to assess potential prognostic factors. Results Among the thirty patients, no complete response was observed. Two cases of partial response (PR), twelve cases of stable disease, and sixteen cases of progressive disease were recorded. The ORR was 6.7%, and the DCR was 46.7%. The median PFS was 6.4 months, and the median OS was 8.3 months. Both PR patients were classified as having a medium risk of gut microbiota dysbiosis and exhibited a Bacteroides-dominated enterotype. Multivariate analysis indicated that tumor type, liver metastasis, and bone metastasis were potential prognostic factors for PFS and OS. Conclusion Patients with a medium risk of gut dysbiosis may exhibit a relatively favorable response to immunotherapy, suggesting that gut microbiota status could serve as a potential biomarker for predicting treatment efficacy in advanced MSS gastrointestinal tumors.

Objective: To investigate the association between parenting styles and attention deficit hyperactivity disorder (ADHD) in preschool children，so as to provide a basis for family based interventions for ADHD in the population. Methods: Between August and December 2023, a random cluster sampling method was used to recruit 6 454 preschool children from 60 kindergartens in two counties/districts in Wuhu City, Anhui Province. The Swanson, Nolan, and Pelham Rating Scale, version IV was used to assess ADHD symptoms, and the Caregiver Parenting Style Questionnaire was applied to collect data on parenting styles. Multivariate Logistic regression was used to analyze the associations between parenting styles and ADHD subtypes. Results: Among the preschool children, 235 were screened positive for ADHD, with a positivity rate of 3.64%. Parenting style scores were as follows:indulgent parenting for 8.00 (7.00, 10.00), authoritative parenting for 38.00 (33.00, 41.00), permissive parenting for 14.00 (11.00, 17.00), authoritarian parenting for 17.00 (14.00, 20.00), and inconsistent parenting 10.00 (7.00, 12.00). Multivariate Logistic regression analysis showed that, after adjustment for confounding factors such as childrens sex, age, and family characteristics, preschool children with authoritarian parenting style were associated with higher odds of hyperactive ( OR = 1.13 ) and combined ADHD subtypes ( OR =1.11), while those with inconsistent parenting style were associated with higher odds of the inattentive subtype ( OR =1.09) (all P <0.01). Indulgent, democratic and permissive parenting styles showed no statistically significant associations with any ADHD subtype ( OR =1.02-1.07, 0.98-1.00, 1.01-1.03, all P >0.05). Conclusions Parenting styles are closely associated with the occurrence and subtypes of ADHD in preschool children. Authoritarian and inconsistent parenting styles are potential risk factors for ADHD in preschool children, and modifying adverse parenting styles may serve as an important strategy for family based interventions for ADHD in preschool children.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective To explore the value of transvaginal ultrasound parameters combined with clinical features for predicting success pregnancy or not of polycystic ovary syndrome(PCOS)patients with infertility after in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI).Methods Totally 348 PCOS patients with infertility were retrospectively analyzed.Patients with presence of a gestational sac on ultrasound and did not experience miscarriage within 4 months after IVF/ICSI were classified as success pregnancy(pregnancy group,n=178),while the rest 170 patients were enrolled in non-pregnancy group.Univariable and multivariable logistic regression analyses were employed to assess clinical data,IVF/ICSI and transvaginal ultrasound parameters to identify the independent predictors of non-pregnancy in PCOS patients with infertility after IVF/ICSI,and a regression equation was constructed.The predictive efficacy,calibration and clinical value of this model were evaluated.Results Patients'age,duration of infertility,ovulation induction protocol(long protocol),duration of gonadotropin treatment,numbers of antral follicles and dominant follicles,total ovarian area,ovarian medullary area and endometrial thickness showed on transvaginal ultrasound before IVF/ICSI,as well as IVF with 2 pronuclei(IVF 2PN)and ICSI with 2 pronuclei(ICSI 2PN)or not were all independent predictors of success pregnancy or not in PCOS patients with infertility after IVF/ICSI(all P＜0.05).The area under the curve of the regression model was 0.771,and its predicted probabilities correlated with actual probabilities.Decision curve analysis indicated that the regression model had good clinical benefit.Conclusion Transvaginal ultrasound parameters combined with clinical features could effectively predict success pregnancy or not in PCOS patients with infertility after IVF/ICSI.

Medical technology proficiency is a key indicator of a municipal-level hospital′s core competitiveness. To continuously enhance its medical capabilities, a tertiary prefecture-level hospital in Zhejiang province launched the " 100 high-tech projects" in 2010, designating it as a priority technical development program. The hospital established a hospital-level knowledge management team in 2020 to build a knowledge management system for high-tech projects. This system fostered a virtuous cycle of synergistic advancement in medical technology innovation, knowledge management, and talent development by extracting both explicit and tacit knowledge from the hospital′s high-tech projects, absorbing tacit knowledge from benchmark hospitals′ relevant technologies, and establishing a knowledge-sharing platform. From January 2021 to October 2024, the hospital secured approval for 9 national and provincial-level clinical key specialties, established 7 municipal key technological innovation teams, and enrolled 46 provincial/municipal-level talents. A the same time, talent attrition remained low. The implementation of the knowledge management system to empower high-tech development had achieved phased results. This practice could provide references for other hospitals to enhance their medical technology capabilities.

Objective To explore the latent profiles of kinesiophobia among patients with peritoneal dialysis and analyze the influencing factors of different categories.Methods A convenience sampling method was used to select peritoneal dialysis patients treated in the outpatient and ward of nephrology department in 7 tertiary A hospitals in Jiangsu Province from December 2023 to March 2024.General data questionnaire,Tampa Kinesiophobia-11 Scale,Exercise Self-efficacy Scale,Exercise Social Support Scale and Self-Rating Anxiety Scale were used for investigation.Results A total of 291 cases were included,and 3 potential categories of kinesiophobia were finally identified,namely low kinesiophobia-active exercise group(20.96％),high kinesiophobia-exercise avoidance group(24.06％),and moderate kinesiophobia-general exercise group(54.98％).Exercise self-efficacy,exercise social support,anxiety,monthly per capita household income,marital status and daily number of dialysis dose were influencing factors of kinesiophobia in peritoneal dialysis patients(P＜0.05).Conclusion There are significant category characteristics of kinesiophobia in patients with peritoneal dialysis.Medical staff should judge the category and influencing factors of kinesiophobia in time,and take targeted interventions to reduce the level of kinesiophobia in patients.

Nitrogen oxides(NOx=NO+NO2)are important precursors of ozone(O3),and NOx and its oxides together constitute reactive nitrogen oxides(NOy)in the atmosphere.A comprehensive understanding of the total NOy level in the atmosphere is of great significance for a deeper understanding of the atmospheric nitrogen cycle and oxidation,as well as for formulating strategies for air pollution prevention and control.In this work,a thermal decomposition-broadband cavity enhanced absorption spectroscopy(TD-BBCEAS)technique for online measurement of total NOy in the atmosphere was developed.With this method,the NOy was efficiently converted into NO2,and the total NOy concentration in the atmosphere was indirectly obtained by measuring NO2.Focusing on the key factors affecting the measurement of total NOy,the influence of NO titration efficiency and other NOy component TD efficiency on measurement accuracy was emphasized.By changing the oxygen(O2)flow rate through the mercury lamp to alter the O3 concentration for titrating NO,the conversion efficiency of NO was evaluated.At O2 flow rate of 6 mL/min,the conversion efficiency of NO was greater than 99%.TD efficiency testing and analysis on NO2,peroxyacetyl nitrate(PAN),nitric acid(HNO3),and nitrous acid(HONO),which account for a large proportion of atmospheric NOy components,was carried out using 680℃as the optimal TD temperature for efficient conversion of NOy.With NO and HONO sample gases as typical verification gases,the conversion efficiency of NOy and the accuracy of NOy measurement by TD-BBCEAS system were verified by switching the on and off modes of mercury lamp and TD device.At integration time of 60 s,the detection limit of the system for NOy was 2.83×1010 molecules/cm3(60 s,2σ).A comparative measurement of actual atmospheric NOy was conducted between the TD-BBCEAS system and the NOy analyzer.The observation results showed a correlation coefficient(R2)of 0.98 and a slope of 0.93,further verifying the feasibility and accuracy of applying the TD-BBCEAS system to measurement of total NOy.