OBJECTIVE To evaluate the cost-effectiveness of culmerciclib combined with fulvestrant as second-line treatment for patients with hormone receptor-positive（HR+）/human epidermal growth factor receptor 2-negative （HER2–） locally advanced or metastatic breast cancer， within the context of the Chinese healthcare system. METHODS A partitioned survival model was established based on the CULMATE-1 study， with a simulation time horizon set at 15 years and a cycle length of 28 days. The incremental cost-effectiveness ratio （ICER） of culmerciclib combined with fulvestrant versus fulvestrant monotherapy as second-line treatment for HR+/HER2– breast cancer was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Meanwhile， scenario analysis of culmerciclib price reduction was conducted； the required price reduction and price to reach the willingness-to-pay （WTP） threshold in this study were calculated. RESULTS The results of the base-case analysis indicated that， compared with the fulvestrant monotherapy regimen， culmerciclib combined with fulvestrant yielded an additional 0.823 quality-adjusted life year （QALY）， with a corresponding ICER of 371 696.26 yuan/QALY， which exceeded the WTP threshold （199 330 yuan/QALY）. The results of the univariate sensitivity analysis indicated that the cost of culmerciclib， the discount rate， the utility values for progression disease and progression free survival status were significant factors influencing the ICER； both the univariate sensitivity analysis and the probabilistic sensitivity analysis validated the robustness of the model results. Scenario analysis indicated that when the price of culmerciclib was reduced by 30%， 55% and 85% respectively， the corresponding ICER values fell below 3， 2， and 1 times China’s per capita GDP in 2025， with the probability of cost-effectiveness being 3.00%， 94.90%， 100%. When the cost of culmerciclib （60 mg） was reduced by 52.6% to 50.96 yuan， the ICER value met the WTP threshold established in this study. CONCLUSIONS When the WTP threshold is set at twice China’s per capita GDP in 2025， second-line treatment with culmerciclib combined with fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer does not exhibit cost-effectiveness advantage over fulvestrant monotherapy. Therefore， a reasonable price reduction is required to alleviate the financial burden on patients.

Achondroplasia (ACH) is a common inherited skeletal dysplasia (inherited dwarfism) that compromises quality of life across the lifespan. In 2021, vosoritide became the first approved precision therapy for ACH and is now available in more than 40 countries. Compared with prior symptomatic measures, vosoritide has demonstrated favorable efficacy and a reassuring safety profile. Nevertheless, existing international ACH guidelines largely emphasize complication management and symptomatic care, and there is no unified consensus on pharmacologic therapy. To address this gap, an international expert group developed the International Consensus Guidelines for the Implementation and Monitoring of Vosoritide Therapy in Patients with Achondroplasia providing systematic recommendations that span the continuum of care - from initial patient contact and pre-treatment assessment to medication counseling, injection training, and long-term outcome monitoring. These recommendations complement and refine current management and nursing protocols for individuals with ACH and offer practical guidance for clinicians across diverse regions. This article highlights key elements of the guideline to provide evidence-based support and clinical direction for healthcare professionals in China treating children with ACH using vosoritide.
Humans ; Achondroplasia/drug therapy* ; Consensus ; Practice Guidelines as Topic ; Child

Objective To explore the predictive value of peripheral blood cells in the efficacy of neoadjuvant immunotherapy combined with chemotherapy for esophageal squamous cell carcinoma. Methods A retrospective study was conducted on patients with esophageal squamous cell carcinoma (clinical stages Ⅱ-Ⅳa) who underwent neoadjuvant immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College from April 2020 to November 2023. According to whether the pathology was completely relieved after treatment, patients were divided into a pathological complete remission group and a pathological incomplete remission group. The College of American Pathologists criteria were used to evaluate the tumor pathological regression grade (TRG) after neoadjuvant therapy (TRG=0, 1 defined as a good efficacy group, TRG=2, 3 defined as a poor efficacy group). Results A total of 92 patients with esophageal squamous cell carcinoma were collected, including 72 males and 20 females. The average age was (65.86±7.66) years. The complete remission of pathology was closely related to the number of lymphocytes in the blood before treatment (P=0.019). The area under the curve (AUC) for predicting complete remission of esophageal squamous cell carcinoma after neoadjuvant immunotherapy combined with chemotherapy was 0.678, the maximum Youden index was 0.328, and the optimal cutoff value was 1.845. The incidence of postoperative pulmonary infection in the pathological incomplete remission group was higher than that in the pathological complete remission group (25.0% vs. 5.6%, P=0.030). Using the optimal cutoff value, there were statistically significant differences in pathological N stage and pathological TNM stage between patients with lymphocyte counts <1.845×109/L and ≥1.845×109/L (P<0.05). Treatment response (by TRG) was significantly associated with the pretreatment red blood cell count (P=0.009). The AUC for predicting a good TRG response was 0.669, with a maximum Youden index of 0.385 and an optimal cutoff value of 4.235. Between the good and poor response groups, there were statistically significant differences in postoperative pathological T stage (P<0.001), N stage (P=0.041), and TNM stage (P＜0.001). When stratified by the optimal cutoff value, there were statistically significant differences in age (P＜0.001) and the prevalence of hypertension (P=0.022) between patients with red blood cell counts <4.235×1012/L and ≥4.235×1012/L. Conclusion A pretreatment absolute lymphocyte count ≥1.845×109/L and a red blood cell count <4.235×1012/L are good predictors for pathological complete response and a good pathological response, respectively, following neoadjuvant immunotherapy combined with chemotherapy in patients with esophageal squamous cell carcinoma.

Objective:To investigate the current situation of nursing information ability of head nurses in different grades of hospitals in Jiaozuo City, and analyze its influencing variables based on the random forest model, so as to provide evidence-based basis for the construction of nursing information ability improvement strategies and training programs for head nurses.Methods:From August to September 2024, the head nurses of 20 hospitals of different grades were selected by cluster sampling method in Jiaozuo City as the research subjects. General Data Questionnaire and Nursing Information Ability Scale of Head Nurses were used to conduct a cross-sectional survey. Random forest model was used to evaluate the importance of variables, lasso regression analysis was applied to complete the variable screening, and the influencing factors of nursing information ability of head nurses were explored through stepwise multiple linear regression analysis.Results:A total of 305 questionnaires were ultimately collected, of which 297 were valid, the effective rate was 97.38%. Out of 297 head nurses, 6 were male and 291 were female; 49 individuals aged 20-29 years old, 127 individuals aged 30-39 years old, 92 individuals aged 40-49 years old, and 29 individuals aged ≥ 50 years old. The total score of nursing information ability was (139.06 ± 24.62). Random forest model and lasso regression analysis showed that the top 6 variables in terms of importance were the number of years serving as head nurses, participation in information function development, number of academic conferences in the past three years, hospital grade, participating in information training, and chairing or participating in scientific research in the past three years. Stepwise multiple linear regression analysis showed that the number of years serving as head nurses, participating in information training, participating in information function development and number of academic conferences in the past three years had significant effects on nursing information ability of head nurses (t values were -4.66 to 3.81, all P<0.05). Conclusions:The nursing information ability of head nurses in Jiaozuo city is in the middle level, and the nursing information ability of head nurses in different grades of hospitals is different. It is suggested to construct a stepped information ability continuing education framework and a research-information ability coupling development mechanism, and incorporate nursing information ability into the necessary conditions for the appointment of nursing management posts, so as to realize the balanced development of nursing information management ability and the continuous iteration of nursing manager information ability.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective To evaluate the value of molecular markers of thrombine-antithrombin complex(TAT),soluble thrombomodulin(sTM),tissue-plasminogen activator-inhibitor complex(t-PAIC)in the early diagnosis of disseminated intravascular coagulation(DIC)in sepsis patients.Methods Thirty patients diagnosed with DIC secondary to hemoinfect-induced sepsis were selected as the DIC group in the intensive care unit(ICU)of the First Hospital of Lanzhou University from July to September 2023.Thirty patients with sepsis caused by bloodstream infection without DIC were randomly selected as the sepsis group.General data and procalcitonin(PCT),platelet count(PLT),white blood cell count(WBC),the levels of traditional clotting indexes activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen(Fib),D-dimer and new clotting indexes(TM,TAT,t-PAIC)were collected.The indicators with statistical significance in univariate analysis were included in multivariate Logistic regression analysis to screen the independent risk factors for DIC in sepsis patients.Receiver operator characteristic curve(ROC curve)was drawn to analyze the diagnostic value of TM,TAT,t-PAIC and their combination in the occurrence of DIC in sepsis patients.Results A total of 60 patients with sepsis were included.There was no significant difference in gender,age,PCT,PLT and WBC between the DIC group and the sepsis group.In terms of traditional coagulation indexes,the PT level in sepsis DIC group was significantly lower than that in sepsis group,and the Fib level was significantly higher than that in sepsis group(both P<0.05).There were no statistically significant differences in APTT and D-dimer levels between the two groups.In terms of new coagulation indexes,TAT,sTM and t-PAIC levels in sepsis DIC group were significantly higher than those in sepsis group(all P<0.05).Multivariate Logistic regression analysis showed that TAT,sTM were independent risk factors for DIC in sepsis patients(both P<0.05).ROC curve analysis showed that TAT,sTM,t-PAIC combined detection had certain value in diagnosis of DIC in sepsis patients,area under the curve(AUC)was 0.735;when the cut-off value was 0.73,the sensitivity was 100.0%and specificity was 43.3%.Conclusion TAT,sTM and t-PAIC could help to predict DIC in sepsis.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

Objective:To investigate the differences in electroencephalographic (EEG) microstate characteristics between children with autism spectrum disorder (ASD) and typically developing (TD) children, and to explore the correlation between irritability and EEG microstate features in ASD children.Methods:A total of 104 children with ASD [ASD group, 83 boys, 21 girls; aged 4-13 years, mean age (9.47±1.74)years] from the Autism Cohort of Nanjing Medical University and 60 TD children [TD group; 50 boys, 10 girls; aged 5-13 years, mean age(9.86±1.78) years ]from the IEEE Dataport database were enrolled. Irritability severity was assessed using the Affective Reactivity Index-Parent (ARI-P). Resting-state EEG data with eyes closed were recorded using a 24-channel dry-electrode EEG cap. Group-level EEG microstate topographic maps and microstate parameters, including mean duration, frequency, and time coverage, were extracted and compared between groups using nonparametric tests. In the ASD group, Spearman correlation analysis was used to examine the associations between microstate features and ARI-P in ASD children. Multiple linear regression was used to identify predictors of irritability.Results:Four group-level microstates (A, B, C, D) were identified in both groups. Compared to TD children, ASD children exhibited significantly longer mean duration for all microstates, in microstates A[ M(Q1, Q3)]: 0.060 (0.054,0.070) vs 0.091 (0.0530, 0.155) s, microstate B: 0.059 (0.050, 0.066) vs 0.087 (0.057,0.149) s, microstate C: 0.059 (0.050, 0.066) vs 0.095 (0.056, 0.183) s and microstate D: 0.055 (0.049,0.075) vs 0.095 (0.053,0.162) s ( Z=-3.51, -4.89, -4.71, -4.21; all P<0.001); However, microstate occurrence frequencies were significantly lower in the ASD group: A: 5.423 (3.640,21.024) vs 1.834 (1.327,3.395) Hz, microstate B: 4.949 (3.439,20.038) vs 2.146 (1.314,3.834) Hz, microstate C: 5.888 (3.998,22.078) vs 2.234 (1.441,3.768) Hz and microstate D: 5.371 (3.170,15.208) vs 2.074 (1.147,3.582) Hz ( Z=-7.72, -6.41, -7.85, -6.60; all P<0.001). In the ASD group, ARI-P scores were positively correlated with the mean duration of microstates B, C, and D ( r=0.28, 0.26, 0.33; all P<0.05) and negatively correlated with the occurrence frequency of microstates A, C, and D ( r=-0.26, -0.27, -0.21; all P<0.05). Multiple linear regression analysis revealed that the mean duration of microstate B was a significant predictor of irritability severity ( β=0.436, 95% CI: 1.260-4.202, P<0.001). Conclusion:Resting-state EEG microstate characteristics in Children with ASD differ from those in TD children and are associated with the severity of irritability. Prolonged duration of microstate B may serve as a risk factor for increased irritability in children with ASD.

Objective:To investigate the prognoses of patients with medial medullary infarction (MMI) or lateral medullary infarction (LMI) and their influencing factors.Methods:A retrospective analysis was performed; 489 patients with acute medullary infarction admitted to Department of Neurology, Tianjin Huanhu Hospital from January 2017 to January 2024 were enrolled. Among them, 186 patients had MMI, which was divided into isolated MMI group ( n=126) and group of MMI with other infarcts ( n=60); 303 patients had LMI, which was divided into isolated LMI group ( n=176) and group of LMI with other infarcts ( n=127). Prognosis 90 days after onset was assessed by modified Rankin Scale (mRS, scores of 3-6 as poor prognosis). Clinical data, prognosis and mortality 90 days after onset, early neurological deterioration, respiratory failure, and complications were compared between isolated MMI group and group of MMI with other infarcts and between isolated LMI group and group of LMI with other infarcts. Univariate and multivariate Logistic regression analyses were used to identify the independent influencing factors for poor prognosis 90 days after onset in patients with MMI or LMI. Results:(1) Compared with isolated MMI group, group of MMI with other infarcts had significantly lower rates of alcohol history and sensory symptoms but higher rates of Horner's syndrome, dysphagia, dysarthria, and facial palsy ( P<0.05). Compared with isolated LMI group, group of LMI with other infarcts had significantly lower rates of sensory symptoms but higher rates of dizzy and dysarthria, and statistically different Trial of ORG 10172 in Acute Stroke Treatment types ( P<0.05). (2) The poor prognosis rate 90 days after onset in patients with MMI was significantly higher than that in patients with LMI (31.8% vs. 18.8%, P<0.05). Compared with isolated MMI group, group of MMI with other infarcts had significantly higher rates of respiratory failure, urinary retention, and pulmonary infection ( P<0.05). Compared with isolated LMI group, group of LMI with other infarcts had significantly higher rates of poor prognosis 90 days after onset, mortality 90 days after onset, early neurological deterioration, respiratory failure, stress ulcers, and pulmonary infection ( P<0.05). (3) Multivariate Logistic regression analysis revealed that dyskinesia ( OR=10.522, 95% CI: 1.246-88.853, P=0.031) and vertical multi-level involvement ( OR=4.585, 95% CI: 1.405-14.962, P=0.012) were independent influencing factors for poor prognosis in isolated MMI patients 90 days after onset; age ( OR=1.089, 95% CI: 1.017-1.166, P=0.015), vertical multi-level involvement ( OR=9.429, 95% CI: 1.625-54.502, P=0.012) were independent influencing factors for poor prognosis in MMI patients with other infarcts 90 days after onset; age ( OR=1.069, 95% CI: 1.006-1.136, P=0.031) and vertical multi-level involvement ( OR=7.125, 95% CI: 2.243-22.636, P<0.001) were independent influencing factors for poor prognosis in isolated LMI patients 90 days after onset; diabetes ( OR=2.807, 95% CI: 1.056-7.461, P=0.038), dysphagia ( OR=6.821, 95% CI: 1.978-23.518, P=0.002), and temporal-occipital infarcts ( OR=3.419, 95% CI: 1.133-10.302, P=0.029) were independent influencing factors for poor prognosis in LMI patients with other infarcts. Conclusion:Patients with LMI had better prognosis compared with patients with MMI; however, LMI patients with other infarcts had poorer prognosis compared with LMI patients; LMI patients with diabetes mellitus, dysphagia or temporal-occipital infarcts are prone to have poor prognosis.