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.

OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

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.

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

Objective To investigate the relationships of the expression of interferon-induced protein 27(IFI27)and dynamin 3(DNM3)with angiogenesis and platinum-resistant recurrence in epithelial ovarian cancer(EOC).Methods A prospective cohort study design was adopted,and 129 EOC patients scheduled for surgery combined with platinum-based chemotherapy were enrolled as the study subjects.Cancerous tissues and adjacent non-cancerous tissues were collected from the pa-tients.The expression levels of IFI27 mRNA and DNM3 mRNA in the tissue samples were detected using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).The expressions of angiogenesis markers,microvascular density(MVD)and vascular endothelial growth factor(VEGF),were detected by immunohistochemistry(IHC).After surgery,the patients received standard platinum-based chemotherapy regimen.They were regularly followed up for recurrence and divided into platinum-resistant group and platinum-sensitive group.The associations of the expressions of IFI27 and DNM3 with platinum-resistant recurrence were analyzed.Results All 129 patients completed surgery combined with chemotherapy.Forty-nine patients with chemotherapy-resistant recurrence were included in platinum-resistant group,and the remaining 80 patients were included in platinum-sensitive group.There was a significant difference in the degree of differentiation between the two groups(P=0.001).The expression level of IFI27 mRNA in cancerous tissues was higher than that in adjacent non-cancerous tissues,while the expression level of DNM3 mRNA was lower than that in adjacent non-cancerous tissues.The expression levels of MVD and VEGF were higher than those in adjacent non-cancerous tissues,with statistically significant differences(P＜0.001).In the plati-num-resistant group,the expression level of IFI27 mRNA was higher than that in the platinum-sensi-tive group,the expression level of DNM3 mRNA was lower than that in the platinum-sensitive group,and the expression levels of MVD and VEGF were higher than those in the platinum-sensitive group,with statistically significant differences(P＜0.05 or P＜0.001).Pearson correlation analy-sis showed that the expressions of VEGF and MVD in EOC patients were positively correlated with the expression of IFI27(r=0.643,0.765,P＜0.05),respectively,and negatively correlated with the expression of DNM3(r=-0.573,-0.632,P＜0.05),respectively.Low degree of differen-tiation and high expression of IFI27 were independent risk factors for platinum-resistant recurrence in EOC patients(P＜0.05),while high expression of DNM3 was an independent protective factor(P＜0.05).The receiver operating characteristic curve showed that the area under the curve(AUC)for the combined prediction of platinum-resistant recurrence in EOC patients by IFI27 and DNM3 was 0.863,which was greater than the AUCs for their individual indicators(0.815,0.704).Conclusion High expression of IFI27 and low expression of DNM3 are significantly asso-ciated with angiogenesis and platinum-resistant recurrence in EOC.Their combined detection has a high predictive efficacy for platinum-resistant recurrence in EOC patients within one year.

This research investigates the regulatory role of the transcription factor PU.1 in type 1 conventional dendritic cells(cDC1)and its therapeutic potential of modulating the nuclear factor kappaB(NF-κB)cells signaling pathway in non-small cell lung cancer(NSCLC).Utilizing single-cell transcriptome sequencing and comprehensive bioinformatics tools,including the CIBERSORT algorithm,we analyzed the immune cell landscape within NSCLC tissues.Our analysis revealed distinct NSCLC subtypes and delineated the developmental trajectories and functional distinctions of cDC1 cells.Key differentially expressed genes(DEGs)and pivotal functional modules within these cells were identified,highlighting PU.1 as a critical mediator underexpressed in NSCLC samples.Functionally,PU.1 demonstrated the induction of the NF-κB pathway,which led to inhibited tumor proliferation and enhanced activation of cDC1,thereby suggesting its role in tumor immune surveillance.In vivo models confirmed the suppressive effect of PU.1 on NSCLC progression,mediated through its influence on cDC1 functionality via the NF-κB pathway.These findings propose PU.1 as a promising target for NSCLC therapeutic strategies,emphasizing the importance of transcriptional regulators in the tumor microenvironment.

Objective:To analyze the factors influencing postoperative complications and survival in patients undergoing hepatectomy for primary liver cancer (PLC).Methods:Two hundred and eighty-eight patients with PLC who underwent hepatectomy at Tianjin Medical University Cancer Hospital from April 2018 to December 2020 were prospectively enrolled, including 235 males and 53 females, aged (58.5±9.5) years. Nutritional evaluations included the nutritional risk screening 2002 (NRS-2002), patient-generated subjective global assessment (PG-SGA), and physical metrics such as body mass index, handgrip strength, arm circumference, mid-arm muscle circumference (MAMC), and triceps skinfold thickness (TSF). Based on the occurrence of postoperative complications during hospitalization including abdominal infection, bleeding, bile leakage, intra-abdominal fluid accumulation, pulmonary infection, intestinal fistula, and wound dehiscence, patients were divided into two groups: the complication group ( n=205) and the non-complication group ( n=83). Multivariate logistic regression analysis was performed to identify the factors related to postoperative complications, while Cox proportional hazards regression was used to evaluate the impact of various variables on postoperative survival. Survival analysis was conducted using the Kaplan-Meier method, and differences in survival rates were compared using the log-rank test. Results:Compared with the non-complication group, patients in the complication group had a significantly longer postoperative hospital stay [13(8, 16) d vs. 7(5, 9) d], higher proportions of low MAMC [34.1% (24/83) vs. 20.0% (41/205)], lower grip strength [28.9% (24/83) vs. 17.6% (36/205)], higher incidence of intraoperative blood loss ≥200 ml [44.6% (37/83) vs. 22.0% (45/205)], and greater proportion of resection involving ≥3 liver segments [45.8% (38/83) vs. 26.3% (54/205)] (all P<0.05). Multivariate logistic regression analysis identified the low MAMC ( OR=2.01, 95% CI: 1.09-3.71, P=0.025), intraoperative blood loss ≥200 ml ( OR=2.75, 95% CI: 1.55-4.90, P=0.001), and resection involving ≥3 liver segments ( OR=2.02, 95% CI: 1.15-3.55, P=0.015) as independent risk factors for postoperative complications in patients undergoing hepatectomy for PLC. Multivariate Cox regression analysis revealed that low TSF ( HR=1.94, 95% CI: 1.01-3.72, P=0.047), low handgrip strength ( HR=2.23, 95% CI: 1.29-3.88, P=0.004), and resection involving ≥3 liver segments ( HR=1.96, 95% CI: 1.15-3.36, P=0.014) were risk factors associated with poor survival after surgery. Conclusions:Low MAMC, intraoperative blood loss ≥200 ml, and resection involving ≥3 liver segments are risk factors for postoperative complications in patients undergoing hepatectomy for PLC, while low TSF, reduced handgrip strength, and resection involving ≥3 liver segments are predictors of poor postoperative survival.

Objective:To design one kind of adjustably assistive walking wheelchair with multi postures,so as to improve the quality of life of people with motion disorders,disabilities or semi disabilities on lower limbs.Methods:The adjustably assistive walking wheelchair with multi postures composed of walking mechanism,mechanism of adjusting posture,and chair,which can achieve five postures,including sitting,low sitting,high sitting,standing and lying.One kinematic model of the wheelchair mechanism was established,and Admas software was used to conduct kinematic simulation.Aimed at key components,the statics simulation was analyzed.The test for adjustment of 5 kinds of postures,the test for the reachable range of hands and the test for the stability of adjusted postures were conducted on the physical prototype of the wheelchair.Results:The results of kinematic simulation showed that the method and formula derivation of motion analysis were correct.Static simulation showed that the seat cushion bracket of key load-bearing component did not affect the normal use of wheelchair under the effect of 100 kg load on seat posture.Experimental tests showed that all parameters of posture transformation were consistent with the design objectives and theoretical analysis.The reachable range of hands was between 500 mm and 2300 mm.The tested results of transformation between sitting and lying postures showed that the stability of the system of adjusting posture of wheelchair was favorable.Conclusion:The adjustably assistive walking wheelchair with multi postures can meet the requirement of user in getting things at low and high position through adjusts the height of sitting posture,which can suit the requirement of user at different home scenarios with larger difference at height,such as table,stove and cabinet.

Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.