OBJECTIVE To evaluate the cost-effectiveness of cefiderocol versus best available therapy （BAT） or standard-of- care （SOC） for the treatment of confirmed or suspected carbapenem-resistant Gram-negative bacterial （CRGNB） serious infections from the perspective of the Chinese healthcare system， and to explore its reasonable pricing. METHODS A decision tree model was constructed based on data from two phase Ⅲ clinical trials （CREDIBLE-CR and GAME CHANGER） to simulate the cost- effectiveness of cefiderocol in two scenarios： salvage therapy for confirmed CRGNB infection （scenario 1） and empirical therapy for suspected CRGNB infection （scenario 2）. The primary outcome measure was the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） was set at 1 to 3 times China’s per capita GDP in 2024. To verify the robustness of the results， one- way and probabilistic sensitivity analyses were conducted， and based on these， a reasonable price range for cefiderocol in the Chinese market was explored. RESULTS The results for scenario 1 showed that the clinical cure rate in the cefiderocol group was higher than that in the BAT group （47.50% vs. 34.21%）， but its ICER was 415 065.03 yuan per cured case， exceeding three times China’s GDP per capita. Scenario 2 revealed that the ICER for cefiderocol relative to SOC was as high as 1 362 446.16 yuan per cured case， far exceeding the WTP. Sensitivity analysis indicated that the treatment duration and price of cefiderocol were key factors affecting its cost-effectiveness. In the two scenarios described above， the unit price of cefiderocol must fall below 683.47 and 242.00 yuan/g， respectively， to be considered cost-effective. CONCLUSIONS Based on the current market price， cefiderocol lacks sufficient cost-effectiveness for treating confirmed or suspected CRGNB serious infections within China’s healthcare system. To improve its accessibility， price negotiations or a tiered medical insurance payment strategy are required.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of serplulimab as a first-line treatment of small- cell lung cancer （SCLC）， and provide an evidence-based basis for drug selection in hospitals. METHODS Rapid health technology assessment was adopted； PubMed， Cochrane Library， Embase， CNKI， Wanfang， VIP and official websites of domestic and international health technology assessment agencies were systematically searched from the inception to Oct. 2024. Two reviewers independently screened the literature， assessed the quality of included studies and carried out the qualitative analysis according to the inclusion and exclusion criteria. RESULTS A total of 13 systematic reviews/meta-analyses and 9 economic studies were included， and the literature quality was generally good. In terms of effectiveness， compared with chemotherapy alone， serplulimab combined with chemotherapy significantly improved progression-free survival， overall survival， and objective response rate in patients with SCLC. In terms of safety， serplulimab combined with chemotherapy showed no significant difference in the incidence of ≥3 grade adverse events compared with chemotherapy alone in the treatment of SCLC， indicating a good safety profile； compared with combination therapies involving other immunosuppressive agents， the incidence rate of adverse events was also lower. In terms of cost-effectiveness， compared with chemotherapy alone， serplulimab combined with chemotherapy is not cost- effective， which may be related to the high price of serplulimab. CONCLUSIONS Serplulimab is effective and safe in the treatment of SCLC， but has no obvious advantage in terms of cost-effectiveness.

Objective: To explore the isotemporal substitution effects among different intensities of physical activity within a 10 minute recess period on the mental health of junior high school students, aiming to provide evidence based references for targeted practical interventions. Methods: From May to November 2024, a total of 845 junior high school students from Tianjin,Taiyuan and L Liang in Shaanxi Province,Puyang in Henan Province,Xi an in Shaanxi Province,Quzhou in Zhejiang Province,and Chaoyang in Liaoning Province were selected by using a combination of stratified random sampling and convenience sampling. ActiGraph wGT3X-BT accelerometers was used to measure physical activity during a 10 minute recess period. Mental health status was assessed with the Depression Anxiety Stress Scale (DASS-21). An isotemporal substitution model was constructed in 1 minute increments to predict the effects of substituting different physical activity behaviors on students mental health. Results: During recess, sedentary behavior (SB) was predominant among junior high school students, with an average duration of [7.08(5.85,7.98)] minutes, while moderate to vigorous physical activity (MVPA) accounted for the shortest duration at [0.42(0.21,0.85)] minutes. There were statistically significant differences in MVPA,LPA and SB time between students of different genders and grades( Z/H =-9.08,-8.34,-9.51;84.87,126.82,135.27,all P <0.01). Isotemporal substitution analysis, adjusted for gender and age, showed that replacing 1 minute of SB with 1 minute of MVPA significantly improved anxiety levels ( β =-0.29, 95% CI =-0.53 to -0.04) and overall mental health ( β =-0.72, 95% CI =-1.39 to -0.04), with both results reaching statistical significance (both P <0.05). No significant effects were observed for other substitution patterns (both P >0.05). Conclusions Substituting SB with MVPA during a 10 minute recess period exerts a positive impact on the mental health of junior high school students. It is recommended to optimize the daily recess activity structure in schools to enhance students mental well being.

OBJECTIVE To evaluate the cost-utiliby of capivasertib combined with fulvestrant for the second-line treatment of hormone receptor-positive/human epidermal growth factor receptor-2-negative （HR+/HER2－） advanced breast cancer from the perspective of the Chinese healthcare system. METHODS A partitioned survival model was constructed using clinical data from the CAPItello-291 trial. Costs and quality-adjusted life years （QALYs） were used as the output indicators of the model， and the incremental cost-effectiveness ratio （ICER） was used as the evaluation indicator of the model. Using three times the per capita gross domestic product （GDP） of China in 2024 as the willingness-to-pay threshold （WTP）， this study analyzed the cost-utility of capivasertib combined with fulvestrant versus fulvestrant monotherapy in the treatment of HR+/HER2－ advanced breast cancer， and conducted sensitivity analysis and scenario analysis under conditions where the price of capivasertib was reduced by 50%， 60%， 70% and 95%， respectively. RESULTS The results of the basic analysis showed that compared with the fulvestrant monotherapy regimen， the ICER of capivasertib combined with fulvestrant was 843 038.46 yuan/QALY， which was higher than the WTP（287 247 yuan/QALY）. The one-way sensitivity analysis revealed that the top three factors with the most substantial influence on ICER were the utility value in the progression disease state， the price of capivasertib， and the utility value inthe progression free survival state. Probabilistic sensitivity analysis demonstrated the robustness of the basic analysis results. Scenario analysis revealed that even if the price of capivasertib were reduced by 95%， capivasertib combined with fulvestrant did not exhibit cost-effectiveness at the current WTP. CONCLUSION At a WTP of three times China’s GDP per capita in 2024， compared to fulvestrant monotherapy， capivasertib combined with fulvestrant as the second-line treatment for HR+/ HER2－ advanced breast cancer is not cost-effective.

This article introduces a recent paper published in JAMA titled " Tirzepatide for weight reduction in Chinese adults with obesity: The SURMOUNT-CN randomised clinical trial". The paper details the design, results, and implications of a randomized controlled clinical study of the efficacy and safety of tirzepatide in overweight/obese adults in China(SURMOUNT-CN). This study represents the first Chinese evidence supporting tirzepatide for the treatment of obesity, offering a potent therapeutic option for the prevention and treatment of obesity and weight-related comorbidity.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Objective:To explore the factors affecting the prognosis of severe pediatric acute respiratory distress syndrome (ARDS) after receiving extracorporeal membrane oxygenation (ECMO) support.Methods:It was a multicenter prospective observational study. A total of 95 children with severe ARDS who were treated with ECMO salvage therapy from January 2018 to December 2022 in 9 pediatric ECMO centers in China were enrolled in the study. The general data, disease severity, organ function, comprehensive treatment and prognosis were recorded, and they were divided into survival group and death group according to the outcome at discharge. T test, chi-square test, multivariate Logistic regression and mixed linear model were used to analyze the relationship among baseline before ECMO treatment, some important indicators (pediatric critical scores, platelet count, albumin, fibrinogen, etc) during ECMO treatment and prognosis. Results:Among the 95 children with severe ARDS who received ECMO, 55 (58%) were males and 40 (42%) were females, aged 36.9 (0.5, 72.0) months. Twelve children (13%) were immunodeficient. Sixty-eight (72%) children were treated with venous artery (VA) mode and 27 (28%) with venous vein (VV) mode. The discharge survival rates of overall, VA, and VV mode children were 51% (48/95), 47% (32/68), and 59% (16/27), respectively. The number of immunodeficient children in the death group was higher, and there were lower pediatric critical scores, platelet count, albumin, fibrinogen and arterial oxygen partial pressure/fraction of inspired oxygen (PaO 2/FiO 2), higher ventilator driving pressure (ΔP), oxygenaion index (OI), and longer ARDS duration before ECMO (all P<0.05). There were no statistically significant differences in other indicators, including age, gender, weight, and ECMO mode among different prognostic groups (all P>0.05). High ΔP, high OI, low P/F, and low albumin were high-risk factors affecting prognosis(all P<0.05). After further grouping, it was found that ΔP≥25 cmH 2O (1 cmH 2O=0.098 kPa), P/F≤67 mmHg (1 mmHg=0.133 kPa) and OI≥35 were the thresholds for predicting poor prognosis ( P<0.05). From 24 h after ECMO, there were significant differences in ΔP, P/F and OI between the dead group and the survival group (all P<0.05), and the differences gradually increased with the ECMO process. The platelet level was significant from 7 days after ECMO ( P<0.05) and gradually expanded. Blood lactate levels showed a significant difference between the 2 groups on before and after ECMO ( P<0.05) and gradually increased from 24 h after ECMO. Conclusions:The risk factors affecting the prognosis of severe ARDS in ECMO include high ΔP, high OI, low P/F and low albumin purification therapy before ECMO. The gradual decrease of ΔP, OI and increase of P/F from 24 h of ECMO predicted a good prognosis, while the gradual increase of lactate after ECMO application showed a poor prognosis.

Objectives:To investigate clinical characteristics, outcomes and antimicrobial resistance of community-acquired Pseudomonas aeruginosa (CAPA) infections in Chinese pediatric patients. Methods:This retrospective study was conducted at 6 tertiary hospitals in China during January 2016 to December 2018. The clinical and microbiological data of CAPA infected hospitalized children in Hainan and in other regions were collected and compared, and the antimicrobial resistance patterns, clinical characteristics and antibiotic therapy were analyzed. Between different groups were compared using the Chi-square test and Mann-Whitney U test. Results:Among 91 patients, 63 cases were males, 28 cases were females, and 74 cases were from Hainan province, 17 cases were from other regians. The age of consultation was 22.5 (5.4, 44.0) months. Twenty-four cases (26%) had underlying diseases. Fever (79 cases (87%)) and cough (64 cases (70%)) were common initial symptoms. Other concomitant symptoms included wheezing 8 cases (9%), diarrhea 3 cases (3%) and vomiting 4 cases (4%). Twenty-eight cases (31%) had organ infections, including pneumonia 22 cases (24%), skin infection 5 cases (5%), meningitis, intra-abdominal infection and upper urinary tract infection each 1 case (1%). The resistance rate of CAPA isolates to cefepime (4% (4/90)), amikacin (1% (1/90)), ciprofloxacin (2% (2/90)) and levofloxacin (1% (1/89)) was low, and to ceftazidime, piperacillin, piperacillin-azobactam, carbapenem was 12% (11/90), 3/16, 18% (10/56) and 6% (5/90), respectively. Antimicrobial combination therapy accounted for 52% (47/91) of empirical therapy and 59% (52/88) of definite therapy. Two cases (2%) were hopeless discharged, and 3 cases (3%) died during hospitalization. The worse prognosis of CAPA infection is significantly different among children in other regions and in Hainan (4/17 vs. 1% (1/74), χ2=9.74, P<0.05). Conclusions:The invasive CAPA-infection has regional difference in incidence and prognosis in China. Clinical symptoms and signs are non-specific. CAPA strains isolated from pediatric patients display low level of resistance to most of the common antipseudomonal antibiotics. The proportion of poor prognostic outcome is lower in Hainan than in other regions.

Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.

Objective To explore the relationship between SERPINE1 gene related to lactic acid metabo-lism and clinical prognosis of gastric cancer(GC).Methods A total of 89 patients with GC who underwent surgical resection in the hospital from January 2018 to December 2020 were enrolled in the study.In the pre-liminary experiment,the levels of 5 genes related to lactic acid metabolism(F5,MTTP,SERPINE1,CYP19A1,SLC52A3)in 24 serum samples from GC patients with stage Ⅰ(n=12)and stage Ⅳ(n=12)were analyzed.In the second step,the candidate genes with significant changes in serum of GC patients with stage Ⅳ and GC patients with stage Ⅰ in the preliminary experiment were verified in a larger independent co-hort,which included serum samples of 65 GC patients and 22 healthy controls.Results Among the genes re-lated to lactic acid metabolism(F5,MTTP,SERPINE1,CYP19A1,SLC52A3)analyzed in the preliminary ex-periment,SERPINE1 was significantly up-regulated in the serum of patients with stage Ⅳ compared with that in the serum of patients with stage Ⅰ(P＜0.001).The expression level of SERPINE1 in serum of GC pa-tients was significantly lower than that of healthy controls(P＜0.000 1).In addition,the expression level of SERPINE1 increased with the progress of TNM staging(P＜0.05).Based on the receiver operating charac-teristic curve,the maximum predictive value of SERPINE1 on overall survival(OS)rate was analyzed(area under the curve=0.725,cut off value=0.002 1),and GC patients were divided into high expression group(n=39)or low expression group(n=26).Compared with the SERPINE1 low expression group,the cases of venous infiltration,T3/T4 stage,lymph node metastasis and distant metastasis in the SERPINE1 high expres-sion group increased,and the differences were statistically significant(P＜0.05).The OS rate of GC patients with low expression of SERPINE1 was significantly higher than that of patients with high expression of SER-PINE1(P＜0.05).Multivariate analysis showed that the high expression of SERPINE1 in serum(HR=4.51,95％CI=1.23-23.69,P=0.021)was an independent prognostic marker for predicting the poor prog-nosis of GC patients.Conclusion SERPINE1 gene related to lactic acid metabolism in serum could be used as a reliable biomarker for the prognosis of GC.