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 investigate ameliorative effects and mechanisms of two probiotics （Bacillus subtilis， Lactobacillus acidophilus） combined with Aurantii Fructus Immaturus （AFI） on functional dyspepsia （FD） in rats. METHODS Rats were randomly divided into blank group， model group， positive control group （domperidone group， 2.7 mg/kg）， AFI group （9 g/kg）， L. acidophilus group （5×107 cfu/kg）， B. subtilis group （5×107 cfu/kg）， L. acidophilus+ AFI group （L. acidophilus 5×107 cfu/kg+ AFI 9 g/kg）， and B. subtilis+AFI group （B. subtilis 5×107 cfu/kg+AFI 9 g/kg）， with 8 rats in each group. Except for the blank group， FD model was established by tail-clamping stimulation+hunger and satiety disorder+swimming exhaustion in other groups. After modeling， each group was given the corresponding drug/probiotic suspensions/physiological saline intragastrically， once a day， for 14 consecutive days. After the last medication， gastric emptying rate and the rate of propulsion of the small intestine in rats were measured； the levels of brain-gut peptide-related indicators [gastrin （GAS）， substance P （SP）， vasoactive intestinal peptide （VIP）， somatostatin （SS） and cholecystokinin （CCK）] in the serum of rats were measured. The pathological morphology of the gastric antrum tissue and duodenal tissue was observed. Cecal contents from the rats were collected for gut microbiota sequencing analysis. The protein expression levels of tyrosine kinase receptor c-Kit and stem cell factor （SCF） in the gastric antrum tissue， as well as Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor κB （NF-κB） in the duodenal tissue of the rats were detected. RESULTS Compared with the blank group， model group showed significantly lower gastric emptying rate， small intestinal propulsion rate， serum levels of GAS and SP， relative abundance of Firmicutes， Ace， Chao and Sobs indexes of the gut microbiota， and protein levels of SCF and c-Kit in gastric antrum （P＜0.05）， while serum levels of VIP， SS and CCK， relative abundance of Bacteroidetes， as well as protein expressions of TLR4， MyD88， and NF-κB， were significantly higher （P＜0.05）. The histological structure JZYC23S53） of the gastric antrum tissue appeared basically normal； however， abnormalities were observed in the duodenal structure， with a significant infiltration of inflammatory cells visible. Compared with the model group， all treatment groups significantly modulated most of the above indexes （P＜0.05）. The histological structure of the gastric antrum tissue was normal. Except for the B. subtilis group and the B. subtilis+AFI group， the pathological states of the duodenum in the remaining rats gradually recovered. Compared with each single drug group， most of above indexes in rats from each combination group showed further improvement （P＜0.05）. CONCLUSIONS The combination of AFI with two probiotics can improve gastrointestinal motility in FD rats， and the effect is superior to that of using the drugs alone. The specific underlying mechanisms may be related to the activation of the SCF/c-Kit signaling pathway and the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Objective: To investigate the distribution of pupil diameter and its association with myopia in school age children, providing ideas into the mechanisms of the role of pupil diameter in the onset and development of myopia. Methods: Adopting a combination of stratified cluster random sampling and convenience sampling method, 3 839 children from six schools in Shandong Province were included in September 2021. Pupil diameters distribution was analyzed by age, sex, and myopic status. Pearson correlation analysis was used to assess the relationship between pupil diameter and cycloplegic spherical equivalent (SE), as well as axial length (AL) and other variables. Propensity score matching (PSM) was applied to match myopic and non myopic children at a 1∶1 ratio based on age and sex. A generalized linear model (GLM) was constructed with pupil diameter as the dependent variable to identify independent factors influencing pupil size and its association with myopia. Results: The mean pupil diameter of school age children was (5.77±0.80)mm. Pupil diameter exhibited a significant increasing trend with age ( F =49.34， P trend ＜ 0.01). Myopic children had a significantly larger mean pupil diameter [(6.10±0.73)mm] compared to non myopic children [(5.62±0.79)mm] with a statistically significant difference( t=18.10, P <0.01). Multivariable GLM analysis, adjusted for age, amplitude of accommodation, and uncorrected visual acuity, revealed a negative correlation between pupil diameter and cycloplegic SE (before PSM: β =-0.089, after PSM: β =-0.063, both P ＜0.01). Conclusions Myopic school age children exhibite larger pupil diameters than their non myopic counterparts. Pupil diameter may serve as a potential indicator for monitoring myopia development in school age children.

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.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

A subset of patients with non-alcoholic fatty liver disease(NAFLD)can progress to nonalcoholic steatohepatitis(NASH).When NASH reaches a fibrosis degree of F≥2 and a NAS score of≥4,this stage of NASH is referred to as fibrotic NASH,which is a key focus in clinical drug trials.Currently,liver biopsy is the gold standard for assessing the histological changes of the liver,but its clinical application is limited by its invasiveness,and therefore,it is of particular importance to develop noninvasive detection methods for fibrotic NASH.This article summarizes the recent research achievements in novel noninvasive diagnostic methods for fibrotic NASH and elaborates on these new diagnostic methods for predicting fibrotic NASH in terms of current status,challenges faced,and prospects for future development.

Objective To establish the rapid identification method of Hedysari Radix wild and cultivated products by integrating the identification characteristics of TCM traits obtained by intelligent senses such as electronic nose and colorimeter based on the multivariate statistical analysis method;To provide new ideas and methods for the formulation of commodity specification standards and the application research of market quality control for Hedysari Radix.Methods Totally 29 batches of samples of Hedysari Radix were detected based on colorimeter and electronic nose technology to obtain their sensory information,and the effective components of Hedysari Radix were determined by high performance liquid chromatography(HPLC)and other methods for joint analysis.After establishing the optimal experimental conditions of Hedysari Radix electronic nose,multivariate statistical analysis methods,such as principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA)and clustering analysis,were used to establish the identification model of Hedysari Radix wild and cultivated commodities.Results The optimum test conditions of Hedysari Radix electronic nose(particle size of 65 mesh):the sample weight was 2.0 g,the optimum temperature of the sample was 50℃,and the time was 25 min.A single intelligent sensory result could not quickly and accurately identify the two,but the fusion information could quickly identify the wild and cultivated commodities of Hedysari Radix,and the chemical composition had a certain correlation with the color and taste.Conclusion Electronic nose and colorimeter can quickly and accurately distinguish wild and cultivated Hedysari Radix after multivariate statistical analysis,which is simple and feasible.The combined analysis of its related properties and active components can be used for the quality evaluation of Hedysari Radix.

Objective:To investigate the clinical phenotype and genotype characteristics of lipoyltransferase 1 deficiency (LIPT1D).Methods:A retrospective analysis of the clinical data was conducted for one case of LIPT1D, admitted to the Department of Neonatology at Shanghai Children's Hospital on May 7, 2023. Key terms "lipoyltransferase 1 deficiency", " LIPT1", and "lipoic acid" were used to search national databases including CNKI, Wanfang Data, VIP, and Yiigle; and international databases PubMed, Embase, and Web of Science until September 15, 2023, to summarize the clinical presentations, biochemical phenotypes, and genotypic characteristics of LIPT1D. Descriptive statistical analysis was employed. Results:(1) The case concerned: At 1.5 h after birth, the infant exhibited cyanosis and poor responsiveness, presenting with uncorrectable metabolic acidosis (blood pH value 6.9, base excess -27 mmol/L, bicarbonate 5.7 mmol/L), and hyperlactatemia (the highest was 24 mmol/L). The condition progressed rapidly, and the infant died 9 h after birth. Whole exome sequencing performed 6 h postnatally identified compound heterozygous variants in the LIPT1 gene (NM_001204830.1) in the infant. Variants c.986C>A (p.Ser329*) from the mother and c.405_406del (p.Arg135Serfs*18) from the father were detected, both suspected to be pathogenic. (2) Literature review: A review of the literature identified seven cases of LIPT1D caused by LIPT1 gene mutations, totaling eight cases including the current one. The main presentations of LIPT1D in these infants were hyperlactatemia, metabolic acidosis, neurodevelopmental delay, and epilepsy, with four cases presenting in the neonatal period and resulting in death. Conclusions:The primary clinical manifestations of LIPT1D are severe hyperlactatemia, metabolic acidosis, and neurological involvement, potentially leading to early neonatal death. Whole-exome sequencing is instrumental in diagnosing this condition.

With the rapid development of perinatal medical technology, the survival rate of preterm infants has increased significantly, but the incidence of bronchopulmonary dysplasia(BPD)is still at a high level.BPD is a common chronic respiratory disease in preterm infants, and the incidence of other complications and death rates of preterm infants with BPD are significantly higher.Currently, the "classic BPD" characterized by lung injury has been converted to "new BPD, " but the pathophysiological mechanism of BPD has not yet been elucidated.In recent years, some experimental studies in vitro and in vivo have demonstrated that alveolar type II epithelial cells can induce epithelial mesenchymal transition(EMT)through multiple signaling pathways, including TGF-β as a hub and Wnt, SPHK1/S1P, etc., which can promote the development of pulmonary fibrosis, and thus provide a new idea for the prevention and treatment of BPD.This article reviews the mechanisms of multiple signaling pathways in EMT in BPD, in order to give a reference for the clinical treatment of BPD.

In the context of the prevention and control for coronavirus disease (COVID), public health emergency governance has been incorporated into an important part of the national governance system, and the "combination of peacetime and wartime" has become an important principle of public health emergency governance. Based on the experience of public health emergency management in large cities and the theory of collaborative governance, this study analyzed the problems and obstacles of general hospitals in coping with emerging respiratory infectious diseases. It is proposed to select general hospitals above tertiary level in the region to build peacetime and wartime combined emergency hospital, establish standardized conversion procedures and strengthen the construction of key elements of integrated emergency hospitals, so as to provide new ideas for the construction of emergency medical system "combination of peacetime and wartime" mechanism and improve the "combination of civilian and combat" public health emergency governance system.