With the rapid development of medical big data and artificial intelligence,Clinical Prediction Models(CPMs)have become pivotal tools for disease prevention,diagnosis,and treatment.Current research predominantly focuses on the economic analysis of pharmacological or public health interventions,yet a comprehensive methodological framework for the economic evaluation of CPMs has been notably absent.The Guidelines for Economic Evaluation of Clinical Prediction Models(hereafter the Guidelines),jointly initiated by the Chinese Research Hospital Association and Peking University,Tsinghua University,and Capital Medical University,adheres to the WHO Handbook for Guideline Development and the Reporting Items for Practice Guidelines in Healthcare(RIGHT)standards.A multidisciplinary collaboration,including a steering committee,expert panel,secretariat,and external review group,was established to develop the guideline following evidence-based principles and procedures.Consensus recommendations were formulated through the Delphi method.It describes the background,objectives,target group,and the development methodology and process,ensuring the entire compilation process of the Guidelines is transparent and standardized.Through comprehensive evidence retrieval,systematic evidence appraisal,and a scientific approach to forming recommendations,the scientific rigor and validity of the Guidelines were further enhanced.

Objective To observe the value of CT angiography(CTA)for classifying type of peripheral arteriovenous fistula(AVF)in children.Methods Totally 22 children with peripheral AVF were retrospectively enrolled,the type of AVF was classified with preoperative CTA,and therapeutic planning was developed.Taken digital subtraction angiography(DSA)findings during interventional therapy as gold standards,the efficacy of CTA for classifying type of AVF was analyzed.Results Among 22 cases,DSA detected 3 cases of type Ⅰ,13 cases of type Ⅱa and 6 cases of typeⅡb peripheral AVF,while 3 cases of type Ⅰ,14 cases of type Ⅱa and 5 cases of type Ⅱb peripheral AVF were classified based on CTA.CTA misdiagnosed 1 case of type Ⅱa as type Ⅱb,and 2 cases of type Ⅱb as type Ⅱa peripheral AVF,its accuracy of CTA for classifying type Ⅰ,Ⅱa and Ⅱb peripheral AVF was 100%(3/3),92.31%(12/13)and 66.67%(4/6),respectively.Among 22 cases,13 cases underwent interventional closure,2 cases underwent interventional therapy combined with surgery,while 3 cases did not receive relevant treatment due to drainage vein occlusion.One month after treatments,the symptoms of 19 cases who underwent treatment improved significantly,and no signs of AVF was found with re-examination of ultrasound nor CTA.Conclusion CTA was helpful to classifying type of peripheral AV in children,which could provide references for interventional therapy.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

With the rapid development of medical big data and artificial intelligence,Clinical Prediction Models(CPMs)have become pivotal tools for disease prevention,diagnosis,and treatment.Current research predominantly focuses on the economic analysis of pharmacological or public health interventions,yet a comprehensive methodological framework for the economic evaluation of CPMs has been notably absent.The Guidelines for Economic Evaluation of Clinical Prediction Models(hereafter the Guidelines),jointly initiated by the Chinese Research Hospital Association and Peking University,Tsinghua University,and Capital Medical University,adheres to the WHO Handbook for Guideline Development and the Reporting Items for Practice Guidelines in Healthcare(RIGHT)standards.A multidisciplinary collaboration,including a steering committee,expert panel,secretariat,and external review group,was established to develop the guideline following evidence-based principles and procedures.Consensus recommendations were formulated through the Delphi method.It describes the background,objectives,target group,and the development methodology and process,ensuring the entire compilation process of the Guidelines is transparent and standardized.Through comprehensive evidence retrieval,systematic evidence appraisal,and a scientific approach to forming recommendations,the scientific rigor and validity of the Guidelines were further enhanced.

Objective To observe the value of CT angiography(CTA)for classifying type of peripheral arteriovenous fistula(AVF)in children.Methods Totally 22 children with peripheral AVF were retrospectively enrolled,the type of AVF was classified with preoperative CTA,and therapeutic planning was developed.Taken digital subtraction angiography(DSA)findings during interventional therapy as gold standards,the efficacy of CTA for classifying type of AVF was analyzed.Results Among 22 cases,DSA detected 3 cases of type Ⅰ,13 cases of type Ⅱa and 6 cases of typeⅡb peripheral AVF,while 3 cases of type Ⅰ,14 cases of type Ⅱa and 5 cases of type Ⅱb peripheral AVF were classified based on CTA.CTA misdiagnosed 1 case of type Ⅱa as type Ⅱb,and 2 cases of type Ⅱb as type Ⅱa peripheral AVF,its accuracy of CTA for classifying type Ⅰ,Ⅱa and Ⅱb peripheral AVF was 100%(3/3),92.31%(12/13)and 66.67%(4/6),respectively.Among 22 cases,13 cases underwent interventional closure,2 cases underwent interventional therapy combined with surgery,while 3 cases did not receive relevant treatment due to drainage vein occlusion.One month after treatments,the symptoms of 19 cases who underwent treatment improved significantly,and no signs of AVF was found with re-examination of ultrasound nor CTA.Conclusion CTA was helpful to classifying type of peripheral AV in children,which could provide references for interventional therapy.

Objective:To assess the prognostic impact of frailty on elderly inpatients with heart failure.Methods:This prospective cohort study enrolled 121 in elderly patients with heart failure from Beijing Hospital, the General Hospital of the People's Liberation Army, and Beijing Tsinghua Changgung Hospital between September 2018 and April 2019.Patients were assessed for frailty using the Fried frailty phenotype and categorized into frail and non-frail groups.Follow-ups were conducted at 3-, 6-, and 12-months post-enrollment through clinic visits or phone calls to record adverse events.Composite endpoints include all-cause mortality and rehospitalization duo to deterioration of heart failure.Results:The study included 121 patients with an average age of 78.0±7.4 years, of whom 71(58.7%)were male and 57(47.1%)were classified as frail.Compared to the non-frail group, the frail group had lower estimated glomerular filtration rates[49.5±20.7 ml/(min·1.73m 2) vs.(64.0±27.1)ml/(min·1.73m 2)], lower scores in Basic Activities of Daily Living[5.0(4.0, 6.0) vs.6.0(5.0, 6.0)], Instrumental Activities of Daily Living[2.0(1.3, 7.8) vs.7.0(5.0, 8.0)], and Mini-Mental State Examination[26.0(16.0, 28.0) vs.27.0(22.3, 29.0)], all P<0.05.They also experienced longer hospital stays[10.5(6.0, 18.8)days vs.8.0(6.0, 11.8)days, P=0.008].During the follow-up period, the incidence of composite endpoint events was significantly higher in the frail group(43.9% vs.25.0%, P=0.029).Kaplan-Meier survival analysis demonstrated that the one-year incidence of composite endpoint events was significantly higher in the frail group( P=0.013).Multivariable Cox regression analysisindicated that frailty was an independent risk factor for composite endpoint events( HR=2.201, 95% CI: 1.089-4.447, P=0.028). Conclusions:Frailty is an independent risk factor for poor outcomes in elderly hospitalized patients with heart failure and should be considered a crucial factor in clinical assessment and treatment strategies.

Objective:To explore the efficacy and safety of daratumumab in late antibody-mediated rejection (late AMR) after kidney transplantation (KT).Methods:From December 2020 to December 2021, the relevant clinical data were reviewed for 8 patients with late AMR after receiving daratumumab at Affiliated Tongji Hospital. In intensive phase, the combination of plasma exchange (PP)/intravenous immunoglobulin (IVIG) and daratumumab were dosed once a week; in maintenance phase, once every 2 to 4 weeks. The levels of donor-specific antibody (DSA) and renal function were compared pre-treatment and Month 3/12 post-treatment. The treatment-related toxicities were observed. Independent sample T test was utilized for inter-group comparison.Results:The median treatment course during intensive period was 9(4-17) sessions. Maintenance treatment lasted for 5 to 19 months and 2 cases withdrew after 5 to 6 treatments for achieving antibody clearance. A total of 11 DSAs were detected in 8 recipients. At Month 3/12, mean fluorescent intensity (MFI) of DSA was 6 016±4 775 and 6 438±3 668. Both were significantly lower than 11 944±5 237 pre-treatment and the difference was statistically significant ( P=0.012, 0.004). Seven recipients achieved stable renal function during treatment and one recipient resumed hemodialysis at Month 18 due to acute rejection. Glomerular filtration rate of 7 recipients was (40.6±20.1), (53.6±20.9) and (49.0±17.2) ml·min -1· (1.73 m 2) -1 pre-treatment and Month 3/12 and no significant differences existed among different timepoints. During follow-ups, 2 cases developed mild nasal congestion during an early stage of daratumumab infusion while the remainders had no obvious discomfort during infusion and tolerance was decent. Conclusion:Early combination of daratumumab with PP/IVIG, followed by a course of daratumumab has demonstrated an excellent antibody reduction effect on late AMR. During treatment, renal function remains generally stable.

Objective:To study the overall training effect of segmented training model on key fiberoptic bronchoscopy techniques for anesthesiology residents and the influence of key technique training order on the training effect.Methods:Different fiberoptic bronchoscopy simulators were used for specialized training in different key techniques of fiberoptic operation. To examine the effect of key technique learning order on the teaching effect, 40 anesthesiology residents who participated in fiberscope simulation training at Ruijin Hospital, Shanghai Jiaotong University School of Medicine between November 2022 and March 2023 were selected for this study. They were randomly divided into two groups (Group S and Group M) using a numerical table method. The teaching was completed using two orders of key techniques. The operation time, operation quality score, and theoretical knowledge mastery score of the two groups were recorded to compare the effect of key technique learning order on the mastery of fiberoptic skills. SPSS 29.0 statistical software was used for data analysis. Measurement data that conformed to normal distribution were expressed as mean ± standard deviation, and the independent samples t-test or Fisher's exact test were used for comparison between groups. The chi-square test was used for comparison of enumeration data. Results:After segmented training in each key technique, both groups of trainees were able to shorten the operation time of the corresponding key technique [SM simulator operation time (132.25±14.69) s vs. (49.80±4.46) s in group S, P<0.01; M simulator operation time (82.30±11.60) s vs. (57.10±6.77) s in group S, P<0.01; SM simulator operation time (83.10±10.62) s vs. (52.10±5.20) s in group M, P<0.01; M simulator operation time (132.25±14.69) s vs. (55.40±5.91) s in group M, P<0.01)]. Moreover, both groups showed a reduced number of wall touches [SM simulator wall touches (3.35±0.93) times vs. (0.65±0.49) times in group S, P<0.01; M simulator wall touches (2.50±1.05) times vs. (0.70±0.80) times in group S, P<0.01; SM simulator wall touches (1.55±1.15) times vs. (0.40±0.50) times in group M, P<0.01; M simulator wall touches (5.90±1.29) times vs. (1.10±0.79) times in group M, P<0.01]. There were no significant differences between the two groups in the performance score of fiberoptic-guided tracheal intubation after training [(92.50±5.97) points vs. (91.75±5.45) points] and in the lung segment localization time [(23.15±4.39) s, (21.40±4.84) s, (22.85±4.42) s vs. (22.75±5.11) s, (21.00±5.40) s, (21.50±5.10) s]. Conclusions:Segmented training on key fiberoptic bronchoscopy techniques is an effective model of fiberscope training for anesthesiology residents, and the order of training key techniques does not affect the effectiveness of training.

Objective:To evaluate the efficacy and safety of the gemcitabine combined with oxaliplatin (GEMOX) regimen in the postoperative adjuvant treatment for the patients with cisplatin-intolerant uroepithelial cancer.Methods:The clinical data of 98 patients with uroepithelial carcinoma intolerant to cisplatin chemotherapy who underwent radical surgery from August 2017 to October 2022 at Drum Tower Hospital of Nanjing University School of Medicine were retrospectively analysed. The patients were divided into the adjuvant chemotherapy group and the observation group according to whether or not they underwent adjuvant chemotherapy after surgery. The adjuvant chemotherapy group received postoperative chemotherapy with the GEMOX regimen (gemcitabine 1 000 mg/m 2 intravenously on days 1 and 8, oxaliplatin 130 mg/m 2 intravenously on day 2, every 3 weeks as a cycle), and the observation group did not undergo postoperative adjuvant chemotherapy. In the adjuvant chemotherapy group, there were 33 males and 10 females, the patients’ age was (67.8±7.3) years old, 33 cases with estimated glomerular filtration rate (eGFR) ≤60 ml/(min·1.73m 2), and 10 cases with a Eastern Cooperative Oncology Group (ECOG) functional status score of >1. The postoperative pathology showed 39 cases were in stage T 3, 4 cases in stage T 4, and lymph node positivity (N+ ) was found in 10 cases. There were 55 cases in the observation group, with 42 males and 13 females and the age of (70.7±7.7) years old. Forty-two of them had an eGFR ≤60 ml/(min·1.73m 2), and 13 of them had a ECOG score of >1. The postoperative pathology showed 48 cases were in stage T 3, 7 cases in stage T 4, and 13 cases of N+. The changes in renal function, ECOG scores, and adverse reactions were observed in adjuvant chemotherapy group. Kaplan-Meier method was used to estimate the survival rate, and the log-rank test was used to compare the survival rate between groups. Multifactorial Cox regression was used to analyse the correlation between age, lymph nodes, whether or not to combine with adjuvant chemotherapy and the survival of patients. Results:All patients in this study were followed up for 3 to 75 months, with a median follow-up time of 22 (14, 34) months. The recurrence rates were 83.6%(46/55) and 65.1%(28/43) in the observation and adjuvant chemotherapy groups, respectively, and the disease mortality rates were 52.7%(29/55) and 27.9%(12/43), respectively. The results of the Kaplan-Meier survival analyses showed that the 1-, 2- and 3-year disease-free survival rates in the adjuvant chemotherapy group were 62.8%, 48.6% and 41.1%, respectively, and the 1-, 2- and 3-year overall survival rates were 86.0%, 79.0% and 76.4%, respectively. The 1-, 2- and 3-year disease-free survival rates of the observation group were 58.2%, 22.6% and 9.6%, respectively, and the 1-, 2- and 3-year overall survival rates were 78.2%, 49.4% and 42.8%, respectively. The adjuvant chemotherapy group had an advantage over the observation group regarding disease-free and overall survival rates (all P<0.05). The results of multifactorial Cox regression analysis suggested that the functional status score and the presence or absence of positive lymph nodes, diabetes mellitus, and co-adjuvant chemotherapy were independent risk factors affecting the survival of the patients ( P<0.05). Forty-three cases had 1 to 6 courses of adjuvant chemotherapy, with a median course of 4 (2, 4). In terms of safety, the most common adverse reaction in the gastrointestinal tract was loss of appetite (53.4%, 23/43), the most common grade 1 to 2 adverse reaction in myelosuppression was a decrease in haemoglobin (51.2%, 22/43), and the most common grade 3 to 4 adverse reaction was thrombocytopenia (9.3%, 4/43). The eGFR of 33 patients with renal insufficiency in the adjuvant chemotherapy group was higher after each administration cycle than before ( P<0.05), and renal function did not deteriorate with the increase in administration cycles. Ten patients with a ECOG score of 2 remained with a score of 2 after chemotherapy. Conclusions:In patients with cisplatin-intolerant uroepithelial cancer, gemcitabine in combination with an oxaliplatin regimen improves the overall survival of patients. At the same time, it is well tolerated without increasing nephrotoxicity, making it an optional postoperative adjuvant treatment for patients with cisplatin-intolerant uroepithelial cancer.