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.

Malignant gastrointestinal tumors （GT） mainly include laryngeal cancer， esophageal cancer， gastric cancer， pancreatic cancer， hepatocellular carcinoma， bile duct cancer， and colorectal cancer. At present， the morbidity and mortality of GT are high. Tumor immune escape is one of the key reasons for cancer development and treatment failure， and it is also the main direction of current tumor immunotherapy research. Traditional Chinese medicine （TCM） plays a role in treating GT and alleviating systemic symptoms， especially showing potential advantages in regulating the immune escape mechanism. This article elaborates on the immune escape mechanism of GT and systematically reviews that TCM active components or compound prescriptions act on key immune checkpoints such as programmed cell death protein-1 （PD-1） and programmed cell death ligand-1 （PD-L1） to reduce the proportion of marrow-derived suppressor cells （MDSCs）， promote the polarization of M1 macrophages， activate effector immune cells， enhance CD8⁺ T cell recruitment and interferon （IFN）-γ secretion， enhance the killing activity of natural killers （NKs）， and reduce foxhead box protein P3（FoxP3⁺）-positive regulatory T （Treg） cell infiltration. TCM active components or compound prescriptions can remodel the tumor microenvironment （TME）， such as improving immunosuppressive factors， promoting vascular normalization， and regulating intestinal microbiota. Through the regulation of TME， enhancement of antigen presentation， inhibition of immune checkpoint molecules， regulation of cellular network factors and metabolites， etc.， TCM active components or compound prescriptions enhance the immune function， thereby inhibiting the immune escape of GT. This paper summarizes and reflects on the research results of TCM in regulating immune escape to treat GT in recent years， aiming to help transform TCM from empirical medication to precision treatment based on immune regulation， reduce drug resistance and enhance treatment effect.

AIM To study the chemical constituents from the bark of Toona sinensis(A.Juss.)Roem and their anti-inflammatory activity.METHODS Silica gel,RP-18 reverse phase silica gel and HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activity were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as(9Z)-18-hydroxyo-ctadec-9-en-4,6-diyn-3-one(1),toonapolyyne C(2),(9S,10E,16R)-octadec-10-ene-12,14-diyne-1,9,16-triol(3),(9S,10E,16R)-9,16-dihydroxyoctadec-10-ene-12,14-diy-n-1-yl acetate(4),toonapolyyne A(5),toonasindiyne B(6),scopoletin(7),sco-parone(8),3-O-acetyl(-)-epicatechin(9),p-ethoxyacetanilide(10),kulonic acid(11),β-sitosterol-3-O-β-D-glucopyranoside(12),vanillic acid(13),cleomiscosin A(14),(-)-isolariciresinol(15),resveratrol(16).The IC50 values of compounds 3-4,6,11-13 for NO were 6.90,10.49,20.03,9.49,18.34,24.36 μmol/L,respectively.CONCLUSION Compound 1 is a new polyacetylene,8-16 are isolated from T.sinensis for the first time.Compounds 3-4,6,11-13 have good anti-inflammatory activity.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Legionella pneumophila is an important pathogen responsible for legionellosis.Understanding the genetic diversity,evo-lutionary traits,and potential pathogenicity of L.pneumophila in Fujian Province is crucial for the implementation of effective public health interventions.This study was aimed at investigating these aspects through the analysis of environmental isolates collected from 2019 to 2024.A total of 69 environmental isolates of L.pneumophila were collected,and serotypes were determined with agglutination methods.The predominant serotypes were LP1 and LP5,identified in 23 isolates(33.33%)and 15 isolates(18.84%),respectively.Whole-genome sequencing was conducted to assess the genomic characteristics of these isolates.The genomic sizes ranged from 3.26 Mb to 3.81 Mb,and the GC content ranged from 38.0%to 38.3%.Sequence type(ST)1 880 emerged as the dominant strain among the isolates.All isolates carried several virulence-associated genes,including mip,iraA,htpB,LPG_RS03055,and lspM,thus indicat-ing strong potential for pathogenicity.The prevalence of the multidrug resistance genes lpeA and lpeB was 23.2%,thereby suggesting a concerning level of antibiotic resistance.Various mobile genetic elements,such as genomic islands,insertion sequences,phages,and CRISPR/Cas systems,were also detected.In conclusion,our findings emphasize the importance of continued research and surveil-lance of L.pneumophila,particularly the ST1880 clone,to gain a deeper understanding of its transmission mechanisms and to imple-ment control measures effectively.These insights should aid in enhancing public health responses to legionellosis in Fujian Province.

Chrysophanol(Chr)and physcion(Phy)are primary active ingredients of a well-known traditional Chinese medicine namely rhubarb(Chinese name:Dahuang),and their glucuronides have been revealed as the dominant forms presenting in rats after oral administration.Either Chr or Phy has two glycosylation sites,resulting in a pair of positional isomers for glucuronides of either compound(CG1&CG2 and PG1&PG2).To confirmatively identify these glucuronides,energy-resolved mass spectrometry(ER-MS)was used to pursue the fragmentation trajectories of the targeted fragment ions,and the resultant breakdown graphs that were described by the optimal collision energy(OCE)were expected to exhibit the differences of glycosidic bond cleavage between the isomers.Quantum chemical calculation was thereafter conducted to produce the bond dissociation energy(BDE)of the glycosidic bonds.The isomers were unambiguously identified through applying the positive correlation rule between OCE and BDE.Fortunately,the glucuronides of Chr and Phy in vivo were observed through liver microsomes incubationin vitro.ER-MS was utilized to collect the Gaussian-shaped breakdown graphs in response to the neutral loss of 176 Da,and the absolute values of OCE were compared between positional isomers.The results revealed that CG1(-32.31 eV)>CG2(-31.61 eV),and nonetheless,PG1(-30.00 eV)Chr-8-GluA(-48.787 kJ/mol),and nonetheless,Phy-1-GluA(-48.672 kJ/mol)

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.

AIM To study the chemical constituents from the bark of Toona sinensis(A.Juss.)Roem and their anti-inflammatory activity.METHODS Silica gel,RP-18 reverse phase silica gel and HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activity were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as(9Z)-18-hydroxyo-ctadec-9-en-4,6-diyn-3-one(1),toonapolyyne C(2),(9S,10E,16R)-octadec-10-ene-12,14-diyne-1,9,16-triol(3),(9S,10E,16R)-9,16-dihydroxyoctadec-10-ene-12,14-diy-n-1-yl acetate(4),toonapolyyne A(5),toonasindiyne B(6),scopoletin(7),sco-parone(8),3-O-acetyl(-)-epicatechin(9),p-ethoxyacetanilide(10),kulonic acid(11),β-sitosterol-3-O-β-D-glucopyranoside(12),vanillic acid(13),cleomiscosin A(14),(-)-isolariciresinol(15),resveratrol(16).The IC50 values of compounds 3-4,6,11-13 for NO were 6.90,10.49,20.03,9.49,18.34,24.36 μmol/L,respectively.CONCLUSION Compound 1 is a new polyacetylene,8-16 are isolated from T.sinensis for the first time.Compounds 3-4,6,11-13 have good anti-inflammatory activity.

Objective:To investigate the longitudinal stability of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Activity of Daily Living Scale (ADL).Methods:The longitudinal cognitive assessment results of 68 dementia patients admitted to the Dementia and Leukoencephalopathy Outpatient Clinic, Department of Neurology, Peking Union Medical College Hospital, from January 2021 to January 2024, were retrospectively analyzed, including the total and sub-items scores of the MMSE, MoCA, and ADL. Two different rules were applied to analyze the abnormality rates: rule 1, where the current test result being better than the previous one was considered an abnormality; rule 2, where the current test result being better than the previous average score was considered an abnormality (If a patient had only 2 cognitive assessments, rule 2 was considered the same as rule 1). Two rules were used to analyze the abnormality rates of the scales. The statistical analyses were repeated after excluding patients with possible anxiety and depression status.Results:In assessing the total score stability, MMSE showed the lowest abnormality rates [27.2% (31/114) under rule 1 and 29.8% (34/114) under rule 2], while MoCA had the highest abnormality rates [41.3% (26/63) and 46.0% (29/63), respectively]. The ADL abnormality rates were 27.7% (23/83) and 33.7% (28/83), respectively. Among MoCA sub-items, category cue, multiple choice cue, second memory trial, orientation, and clock showed higher abnormality rates [31.7%(20/63), 30.2%(19/63), 23.8%(15/63), 22.2%(14/63), 22.2%(14/63), respectively]. After excluding population with possible anxiety and depression status, the relative abnormality rates of MMSE and ADL sub-items did not significantly change, while the abnormality rate of orientation in MoCA sub-items decreased relatively.Conclusion:The MMSE and ADL exhibit good stability in long-term monitoring of dementia patients, serving as essential tools for assessing and following up cognitive changes.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry