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.

To investigate the clinical efficacy of neoadjuvant imatinib in the treatment of rectal gastrointestinal stromal tumor (GIST).

Interferon stimulating factor STING, a transmembrane protein residing in the endoplasmic reticulum, is extensively involved in the sensing and transduction of intracellular signals and serves as a crucial component of the innate immune system. STING is capable of directly or indirectly responding to abnormal DNA originating from diverse sources within the cytoplasm, thereby fulfilling its classical antiviral and antitumor functions. Structurally, STING is composed of 4 transmembrane helices, a cytoplasmic ligand binding domain (LBD), and a C terminal tail structure (CTT). The transmembrane domain (TM), which is formed by the transmembrane helical structures, anchors STING to the endoplasmic reticulum, while the LBD is in charge of binding to cyclic dinucleotides (CDNs). The classical second messenger, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), represents a key upstream molecule for STING activation. Once cGAMP binds to LBD, STING experiences conformational alterations, which subsequently lead to the recruitment of Tank-binding kinase 1 (TBK1) via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.

Objective To investigate the effect of early closed reduction and percutaneous Kirschner wire pinning for Gartland type Ⅱ and Ⅲ pediatric supracondylar humerus fractures.Methods Clinical data of 123 children with Gartland type Ⅱ and Ⅲsupracondylar humerus fractures admitted to our hospital from January 2021 to December 2022 were retrospectively analyzed.According to the time from injury to operation,they were divided into early group(≤ 24 h)and delayed group(＞24 h).The perioperative conditions,postoperative complications,fracture healing,and elbow joint functional recovery were compared between the two groups.Results Compared to the delayed group,the early group had less operation time[(22.9±11.3)min vs.(40.3±17.5)min,t=-6.116,P=0.000],less number of intraoperative fluoroscopy[(10.6±4.5)times vs.(17.4±5.5)times,t=-7.471,P=0.000],shorter hospital stay[(3.3±1.0)d vs.(4.2±1.3)d,t=-3.866,P=0.000],and less hospitalization cost[(10 555.0±971.2)yuan vs.(10 972.4±938.9)yuan,t=-2.345,P=0.021].The rate of anatomical reduction in the early group was higher than that in the delayed group[79.0％(60/76)vs.59.6％(28/47),x2=5.354,P=0.021].No serious complications such as vascular and nerve injury,compartment syndrome,ischemic myosclerosis,myositis ossificans,or cubitus varus and valgus occurred in both group after surgery.The incidences of tension blisters[6.6％(5/76)vs.23.4％(11/47),x2=7.265,P=0.007],plaster loosening[22.4％(17/76)vs.40.4％(19/47),x2=4.574,P=0.032],and pin tract infection[2.6％(2/76)vs.14.9％(7/47),x2=4.757,P=0.029]in the early group were lower than those in the delayed group.The fracture union time,and the time to start active and full weight-bearing activities in the early group were earlier than those in the delayed group(P＜0.05).The Flynn elbow joint scores at 3 and 6 months after surgery in the early group were better than those in the delayed group(Z=-3.469,P=0.001;Z=-2.961,P=0.003).Conclusion Early closed reduction and percutaneous Kirschner wire pinning is effective in the treatment of pediatric supracondylar humerus fractures,which can shorten the operation time and hospital stay,reduce the hospitalization cost,lower the incidence of complications,and restore elbow joint function in early stage.

OBJECTIVE To understand the drug resistance among the acquired immune deficiency syndrome(AIDS)population who failed in the antiviral therapy from 2022 to 2023 and analyze the molecular network.METHODS The plasma specimens were collected from the population with viral load no less than 1000 cps/ml who received antiviral therapy for more than 6 months in Aksu area from 2022 to 2023,which were delivered to Aksu Regional Center for Disease Control and Prevention for test.MEGA5 and the Stanford University drug resistance database were employed to determine the subtypes and drug resistance after the sequences of human immunodefi-ciency virus type Ⅰ polymerase gene region(HIV-1pol)were obtained,and the molecular network was established by HIV-trace.RESULTS Totally 648 sequences of HIV-1pol region were obtained,CRF07_BC(97.69％)was the major subtype,and the drug resistance rate was 58.33％;the drug resistance rates to non-nucleoside reverse transcriptase inhibitor(NNRTI),nucleoside reverse transcriptase inhibitor(NRTI)and protease inhibitor(PI)were 51.70％,19.75％and8.64％,respectively.The univariate analysis showed that year(x2=6.341),age(x2=18.455)and route of infection(x2=14.061)had remarkable effects on the drug resistance among the population with failed ART(P＜0.05).Multivariate regression analysis indicated that the drug resistance rate was higher in 2022 than in 2023(95％CI:1.132 to 2.191),and the drug resistance rate was higher among the population aged less than 60 years old than among the population more than 6 years old(95％CI:3.647 to 70.268,95％CI:1.435 to 8.235,95％CI:1.061 to 6.164,re-spectively).With 1.5％of the genetic distance set as the threshold,the molecular network was established,the network access rate was 49.07％,77.14％of the clusters had drug-resistant mutation sites,and the male population was at higher risk of network access than the female population.CONCLUSIONS The drug resistance rate is relatively high among the AIDS population with failed ART,and the drug-resistant strains appear in clusters in the molecular network.It is neces-sary to further strengthen the monitoring of drug resistance and improve the quality of the follow-up so as to reduce the occurrence of drug resistance and transmission of virulent strains.

Objectives:To investigate the clinical characteristics and prognosis of patients with pulmonary arterial hypertension(PAH)concomitant with obstructive sleep apnea(OSA).Methods:We analyzed the data of 208 patients diagnosed with PAH in the Pulmonary Vascular Diseases Ward of our hospital from September 2019 to August 2024,who underwent sleep breathing monitoring and echocardiography during hospitalization.Three clusters were identified:Cluster 1(n=121)had no OSA and mildly elevated N-terminal pro-B-type natriuretic peptide(NT-proBNP),Cluster 2(n=71)exhibited mild OSA and mildly elevated NT-proBNP,and Cluster 3(n=16)presented with moderate to severe OSA along with significantly elevated NT-proBNP.Results:The mean age of this patient cohort was(39±12)years,mean body mass index was(21.74±3.67)kg/m2,and 27.9%patients were male.Sixty-five patients(31.3%)had OSA.The echocardiographic indicators reflecting the structural function of the heart chambers and hemodynamic parameters in patients with PAH showed a significant correlation with nocturnal hypoxia.Compared to Cluster 1,patients in Cluster 2 and Cluster 3 had wider pulmonary arteries and inferior vena cava diameters,larger right ventricular diameters,higher pulmonary artery pressure,higher pulmonary vascular resistance,and lower cardiac index(all P<0.05).Cluster 3 patients had a significantly higher risk of death(log-rank P=0.022).Conclusions:Thirty-one percent of PAH patients in this study had concomitant OSA.PAH patients with significantly elevated NT-proBNP and comorbid moderate-to-severe OSA had a significantly higher risk of death compared to those with only mild or without OSA without significantly elevated NT-proBNP.Management strategies that address both PAH and OSA might be effective in improving the outcomes of these patients.