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 explore the echocardiographic features of critically ill patients with infection, and to evaluate the predictive value of echocardiographic parameters for 28-day mortality and myocardial injury. Methods Using a single-center prospective cohort design, 120 critically ill patients with infection admitted to the Intensive Care Unit, Jinshan Hospital of Fudan University from January 2024 to January 2025 were enrolled consecutively. According to the severity of infection, patients were divided into the sepsis group (n＝75) and the non-sepsis group (n＝45). Cox proportional hazards models and modified Poisson regression were used to analyze risk factors of 28-day all-cause mortality and myocardial injury. Kaplan-Meier survival curve and log-rank test were used to assess prognosis differences among patients with different ultrasound parameters. ROC curve and area under the curve (AUC) were applied to evaluate the predictive performance of ultrasound parameters, and restricted cubic spline (RCS) model was used to explore nonlinear relationships. Results The E/e′ ratio was significantly higher in the sepsis group than in the non-sepsis group (P＜0.001), while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the sepsis group (P＜0.05). The Cox proportional hazards model found no association between ultrasound parameters and 28-day all-cause mortality. Modified Poisson regression showed that, after adjusting for confounding factors, elevated E/e′ was an independent risk factor of myocardial injury (RR＝1.12, 95% CI 1.07–1.17, P＜0.001). Survival analysis demonstrated that patients with E/e′ ＞10.9 had lower 28-day survival rates (P＝0.02), and the AUC for E/e′ predicting myocardial injury was 0.835. RCS analysis suggested a nonlinear relationship between E/e′ and myocardial injury risk (P＜0.001). Conclusions E/e′, LVEF, and LVFS have no significant predictive value for 28-day mortality risk in critically ill patients with infections. Elevated E/e′ is an independent risk factor of myocardial injury in such patients, with a nonlinear relationship.

Objective To analyze personal external exposure dose monitoring results of pet hospital radiation workers in Beijing from 2022 to 2024, and to provide scientific evidence for developing effective monitoring protocols, standardizing radiological practices in pet hospitals, and protecting the health of both workers and the public. Methods Personal dose equivalents, H_p(10), were measured using GR-200A thermoluminescent dosimeters. Monitoring included radiation workers at 286 pet hospitals across all 16 districts of Beijing from 2022 to 2024. Each monitoring cycle lasted no more than 90 days. Annual effective doses were calculated by summing the results of four consecutive quarterly cycles. Data were processed and analyzed using Access and TLPS 6.41 software. All evaluations complied with national laws, regulations, and technical standards. Results A total of 1,579 person-time measurements were recorded. Only 51.87% of workers completed the full four-cycle annual monitoring schedule. Over the study period, the mean annual effective dose was 0.29 mSv, and the median dose was 0.14 mSv. The collective effective dose was 238.34 man-mSv. Notably, 94.26% of workers had annual effective doses below 1.0 mSv, and only 0.12% had doses at or above 5 mSv. Dose levels showed a statistically significant downward trend (P<0.05). Both independent and chain-branded clinics had a median annual effective dose of 0.14 mSv. In independent clinics, the proportion of workers with doses below 1.0 mSv increased from 80.77% in 2022 to 98.82% in 2024. In chain-branded clinics, this proportion rose from 96.88% to 98.11% over the same period. Conclusion Radiation exposure among pet hospital workers in Beijing remains at low levels, well below regulatory limits, and shows an overall declining trend. The disparity in personal doses between independent and chain-branded pet hospitals has diminished over time. Nevertheless, the industry still faces challenges such as high staff turnover and low monitoring completion rates. Expanding monitoring coverage and harmonizing protection standards would provide a scientific basis for precise, nationwide regulation.

Objective To establish and compare rat models of psoriasis with blood-heat syndrome and blood-stasis syndrome.Methods The blood-heat syndrome model was induced by compound heat potion decoction and imiquimod.The blood-stasis syndrome model was induced by fatigue,hunger,cold dampness,panic and imiquimod.The groups were evaluated for TCM syndromes,psoriasis lesions,pathological tissue,spleen index,hemorheology and key gene expression levels.Results The blood-heat syndrome model group showed significant differences from the control group in syndrome manifestations,PASI score,Baker score,spleen index and plasma viscosity(P<0.05).The blood-stasis model group showed significant differences from the control group in syndrome manifestations,body weight,PASI score,Baker score,spleen index,whole blood viscosity(60s-1),whole blood viscosity(10s-1)and plasma viscosity(P<0.05).The key gene expression levels were different among all syndrome groups.Conclusion The animal models had the typical features of psoriasis and matched the signs of blood-heat syndrome and blood-stasis syndrome of TCM.The models can provide a basis for explaining the scientific meaning of TCM syndrome differentiation in treating psoriasis.

Objective:To investigate the clinical characteristics and genetic etiology of fetal Dandy-Walker spectrum (DWS) anomalies.Methods:This retrospective cohort study analyzed 28 fetuses with ultrasonographically confirmed DWS (ten classic Dandy-Walker malformations and 18 Dandy-Walker variants) at the First Affiliated Hospital, Zhengzhou University from January 2019 to June 2024. All cases underwent systematic ultrasonographic evaluation. Genetic analyses included chromosomal karyotyping alone ( n=4) or combined with copy number variation sequencing (CNV-seq) ( n=10). Descriptive statistics and Chi-square tests (or Fisher's exact test) with Bonferroni correction were applied. Results:(1) Among 28 fetuses, seven (25.0%) had isolated DWS and 21 (75.0%) non-isolated DWS. Central nervous system anomalies were most common (53.6%, 15/28). (2) Karyotyping identified abnormalities in four cases (4/14), including two triploidies, one case of mosaicism for a derivative chromosome der(1;10), and one 17p deletion. CNV-seq detected anomalies in six cases (25.0%, 6/24), four of which were missed by karyotyping: 3q23 deletion (encompassing ZIC1/ ZIC4), 13q11 duplication, and other critical variants. (3) Combined testing yielded a higher detection rate (28.6%, 8/28) than karyotyping alone (4/14, χ2=4.62, P=0.032) or CNV-seq alone (25.0%, 6/24, χ2=4.83, P=0.028) ( P=0.048 and 0.044 after Bonferroni correction). Conclusions:DWS demonstrates significant genetic heterogeneity, primarily involving chromosomal numerical anomalies (e.g., triploidy) and copy number variations (e.g., 3q23 deletion). Combined karyotyping and CNV-seq improves detection rates of genetic abnormalities.

Diabetic kidney disease(DKD)is one of the most prevalent complications of diabetes mellitus,with progressive proteinuriaas the main clinical manifestation.Podocytes,a key structural component of the renal filtration barrier,age faster in diabetic state.Theirand morphologies gradually change,mainly in the form of multinucleation,widening of the peduncle,podocyte detachment and increased secretion of senescence-related secretory phenotypes.Various essential signaling pathways in senescent podocytes are altered in the high glucose environment,which results in mitochondrial dysfunction,increased oxidative stress and increased secretion of inflammatory factors.The removal of senescent podocyte,targeting and modulating senescence-related signaling pathways and blocking the secretionofsenescence associated secretory phenotypes may slow down the progression of DKD due to podocyte senescence.This article reviews the research progress on the mechanism of podocyte aging in DKD.

AIM:To examine the impact of the transcription factor 7 analogue 2(TCF7L2)gene polymorphism on the hypoglycaemic effect of ex-enatide in patients with type 2 diabetes mellitus(T2DM).METHODS:A total of 100 newly diagnosed Han Chinese patients with T2DM who had not re-ceived any drug treatment were selected from the Affiliated Hospital of Xuzhou Medical University and treated with exenatide monotherapy for 6 months.The TCF7L2 rs290487 was genotyped by SnaPshot method,and blood glucose levels,lipids profiles and pancreatic function evaluation indica-tors were measured at baseline,3 months and 6 months after exenatide treatment.Multiple linear regression analysis was employed to assess the cor-relation between each indicator and the reduction in glycated hemoglobin(HbA1c)levels after 6 months of exenatide treatment.The expression of TCF7L2 protein in the plasma of T2DM patients was detected by enzyme-linked immunosorbent assay(ELISA)kit.Furthermore,western blotting was con-ducted to ascertain TCF7L2 expression in pancreat-ic tissues obtained from db/db mice and INS-1 cells cultured under high glucose conditions.Lentivirus transfection was used to overexpress or knock down TCF7L2 in insulinoma cell line(INS-1)cells,followed by measurement of KSIS activity and insu-lin content after a 24-hour intervention with exena-tide.RESULTS:The distribution pattern of TCF7L2 rs290487 was found to be in accordance with Har-dy-Weinberg equilibrium(P＞0.05).Following 6 months of exenatide treatment,there was a nota-ble reduction in blood glucose levels and an im-provement in lipid profiles when compared to base-line values.Additionally,there was a significant in-crease in the homeostasis model assessment of be-ta-cell function(HOMA-B)values.Patients with the TT genotype exhibited significantly lower postpran-dial plasma glucose(PPG)levels and HbA1c values compared to those with the CC or CT genotypes(P＜0.05).After adjusting for age,gender,body mass in-dex(BMI),and waist to hip ratio(WHR)in the mul-tiple linear regression model,a significant associa-tion was observed between the rs290487 TT geno-type,baseline HbA1c levels,and family history of diabetes with the reduction in HbA1c after six months of exenatide treatment(P＜0.05).Further-more,individuals with the rs290487 TT genotype demonstrated a notable elevation in TCF7L2 expres-sion in plasma among T2DM patients in comparison to those with the CC genotype(P＜0.05).In particu-lar,pancreatic tissue from db/db mice exhibited markedly elevated TCF7L2 expression compared to db/m mice.However,this up-regulation was re-versed by exenatide treatment.Similarly,INS-1 cells cultured under high glucose conditions dem-onstrated an increase in TCF7L2 expression,which was ameliorated upon exenatide administration.The knockdown of TCF7L2 using shRNA enhanced the KSIS function of pancreatic β cells and aug-mented the insulinotropic effect of exenatide.Con-versely,the upregulation of TCF7L2 impaired the KSIS function of pancreatic β cells and attenuated the insulinotropic effect of exenatide.CONCLU-SION:The TCF7L2 rs290487 gene polymorphism is closely associated with the hypoglycaemic efficacy of exenatide therapy.The risk allele C may diminish the effectiveness of exenatide by impacting the lev-els of PPG and HbA1c in T2DM patients.The muta-tion at TCF7L2 rs290487 site(C→T)influenced the expression of TCF7L2 protein.By exerting its regula-tory effect,exenatide may be capable of regulating the impact of TCF7L2 on the function of pancreaticβ cells.

Objective:To identify the trajectories of dietary choline intake in middle-aged and older population, and to analyze its longitudinal association with cognitive function.Methods:Subjects aged 55 to 79 years with at least two rounds of completed population economics, lifestyle, disease history, cognitive function, dietary assessments and physical measurements in 1997-2018 and those with at least three rounds of dietary measures in 1991-2015 were selected from the China Health and Nutrition Survey. Dietary survey was conducted using three consecutive 24-hour dietary recalls combined with a weighing inventory at the household level. Cognitive assessment was performed using part of the Telephone Interview for Cognitive Status Scale. Group-based univariate trajectory modeling was used to identify trajectory of choline intake, and three-level linear mixed-effects models or three-level logistic mixed-effects models was employed to analyze the relationship between trajectory groups and cognitive function. Subgroup analyses were conducted by gender and age at baseline.Results:Four trajectories of dietary choline intake were identified in the whole population, named as low-intake-stable group (61.0%), medium-intake-stable group (23.9%), medium-intake-slowly-declined group (11.2%), and high-intake-stable group (3.9%). Three trajectories were identified for each subgroup. Low-intake-stable group accounted for more than 60% in total population as well as each subgroup, especially in women and 55-59 years group. After adjusting for covariates, global cognitive scores were 0.54 (95% CI: 0.26-0.82), 0.77 (95% CI: 0.36-1.18), and 0.85 (95% CI: 0.21-1.48) points higher in medium-intake-stable, medium-intake- slowly-declined and high-intake-stable groups in the whole population, respectively, compared with the low-intake-stable group. The likelihoods of cognitive decline were 18.4% ( OR=0.816,95% CI: 0.709-0.939), 17.6% ( OR=0.824, 95% CI: 0.680-0.998), 24.4% ( OR=0.756, 95% CI: 0.589-0.970) and 22.4% ( OR=0.776,95% CI: 0.623-0.968) lower in medium-intake-stable group of dietary choline in the whole population, medium-intake-stable group in males, medium-intake-slightly-increased group in females and medium-intake-slowly-increased group in 55-59 years at baseline than in low-intake-stable group, respectively. Conclusions:Dietary choline intake is generally lower in the Chinese population aged 55-79 years. Long-term lower choline intake has a negative impact on cognitive function in middle-aged and older adults and may increase the risk of cognitive decline. The increment in the consumption of choline-enriched foods should be recommended.

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 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.