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.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective To evaluate the efficacy,safety,and economic efficiency of toripalimab therapy for advanced esophageal cancer by rapid health technology assessment(rHTA),so as to provide clinical reference for drug use.Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data,VIP databases and official websites of health technology assessment institutions were electronically searched to collect high-quality clinical evidence and economic evaluation literature of toripalimab therapy for advanced esophageal cancer from inception to September 30,2025.Two reviewers independently identified studies,extracted data,assessed the quality of included studies,then the results were summarised and analysed using qualitative descriptive methods.Results A total of 18 articles were included,including 9 systematic reviews/Meta-analysis and 9 economic studies.In terms of efficacy,compared with the simple chemotherapy regimen,the combination chemotherapy regimen of toripalimab could significantly prolong the overall survival(OS)and progression free survival(PFS)of patients with advanced esophageal cancer,while improving the objective response rate(ORR)of patients.In terms of safety,there was no significant difference in the incidence of serious adverse events and overall adverse events between combination chemotherapy with toripalimab and chemotherapy alone.Moreover,compared with other immunotherapy combination therapies,the incidence of adverse events in combination chemotherapy with toripalimab was lower.In terms of economy,the combination of toripalimab and chemotherapy not only improves the clinical symptoms of advanced esophageal cancer patients,but also offers economic advantages.Conclusion Toripalimab is effective,safe and economical in the treatment of advanced esophageal cancer.

Objective To investigate whether Yiqicongming Decoction(YCD)can alleviate dry eye syndrome in rats.Methods Thirty-six male SD rats at 6 weeks of age were divided into blank group,model group,positive group,YCD high-dose group,YCD medium-dose group,and YCD low-dose group,with six rats in each group.The rats underwent iris,tear secretion volume,and corneal epithelial damage scoring assessments.Conjunctival tissue was stained with PAS,and the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)were detected using the en-zyme-linked immunosorbent assay(ELISA).The level of reactive oxygen species(ROS)was measured by flow cytometry.Western blot was used to detect the protein expression of nuclear factor erythroid 2-related factor 2(Nrf2)and hymeoxyge-nase-1(HO-1)in corneal tissues.Results Compared with the blank group,the number of goblet cells in the conjuncti-va,corneal epithelial injury score,MDA content and ROS level in the model group were significantly increased at all time points(all P＜0.05).The tear secretion volume of rats decreased on days 3,7,and 14,and the number of conjunctival goblet cells and SOD activity also decreased(all P＜0.05).Compared with the model group,the conjunctival score,corne-al epithelial injury score,MDA content,and ROS level in the positive control group and high-,medium-,and low-dose YCD groups were significantly reduced(all P＜0.05),while SOD activity and protein expression levels of Nrf2 and HO-1 in rats on day 14 were significantly increased(all P＜0.05).Compared with the high-dose YCD group,the conjunctival score,corneal epithelial injury score,and ROS level in the low-and medium-dose YCD groups were significantly increased(all P＜0.05),while SOD activity and protein expression levels of Nrf2 and HO-1 on day 14 were significantly decreased(all P＜0.05).On day 14,the tear secretion volume and the number of goblet cells in the conjunctiva of rats administered a low dose of Yiqi Congming Decoction both decreased(all P＜0.05).Compared with the medium-dose YCD group,the conjunc-tival score,corneal epithelial injury score and ROS level in the low-dose YCD group were significantly increased(all P＜0.05),while the tear secretion volume and protein expression levels of Nrf2 and HO-1 on day 14 were significantly de-creased(all P＜0.05).Conclusion YCD can increase tear secretion,alleviate iris and corneal epithelial damage,acti-vate Nrf2/HO-1 pathway,regulate oxidative stress,and alleviate dry eye syndrome.

Aim To investigate the interventional effects of polysaccharides from Dicliptera chinensis(L.)Juss.(DCP)on acute liver failure(ALF)in-duced by lipopolysaccharide(LPS)combined with D-galactosamine(D-GalN)in mice,and on LPS-induced inflammatory responses in RAW264.7 cells,based on the TLR-4/MyD88/NF-κB signaling pathway.Meth-ods Mice were randomly divided into the control,model,silymarin,DCP low,medium,and high dose groups,and toxicity test groups.After 10 consecutive days of treatment,ALF models were established by in-jecting mice with LPS+D-GalN.Additionally,an in-flammatory response model was established by stimula-ting RAW264.7 cells with LPS.Results Biochemical assays showed that compared with the model group,the medium-and high-dose DCP groups exhibited de-creased serum ALT,AST,ALP,TBIL,and γ-GT activi-ties(P＜0.05),reduced levels of ROS,MPO and MDA in liver(P＜0.05),increased activities of SOD,GSH-Px,CAT,and elevated T-AOC levels(P＜0.05).ELISA revealed lower levels of ICAM-1,VCAM-1,IL-6,IL-1β,and TNF-α in liver(P＜0.05).HE staining indicated reduced inflammatory cell infiltration and improved hepatocyte necrosis in liv-er after DCP administration.The use of DCP alone showed no significant organ toxicity.qRT-PCR and Western blot results indicated that DCP inhibited the expression of key factors in TLR-4/MyD88/NF-κB sig-naling pathway(P＜0.05).Cell validation experi-ments also confirmed that this pathway was inhibited by DCP.Conclusion DCP alleviates ALF primarily by inhibiting oxidative stress and blocking the activation of the TLR-4/MyD88/NF-κB signaling pathway.

Objective To evaluate the efficacy,safety,and economic efficiency of toripalimab therapy for advanced esophageal cancer by rapid health technology assessment(rHTA),so as to provide clinical reference for drug use.Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data,VIP databases and official websites of health technology assessment institutions were electronically searched to collect high-quality clinical evidence and economic evaluation literature of toripalimab therapy for advanced esophageal cancer from inception to September 30,2025.Two reviewers independently identified studies,extracted data,assessed the quality of included studies,then the results were summarised and analysed using qualitative descriptive methods.Results A total of 18 articles were included,including 9 systematic reviews/Meta-analysis and 9 economic studies.In terms of efficacy,compared with the simple chemotherapy regimen,the combination chemotherapy regimen of toripalimab could significantly prolong the overall survival(OS)and progression free survival(PFS)of patients with advanced esophageal cancer,while improving the objective response rate(ORR)of patients.In terms of safety,there was no significant difference in the incidence of serious adverse events and overall adverse events between combination chemotherapy with toripalimab and chemotherapy alone.Moreover,compared with other immunotherapy combination therapies,the incidence of adverse events in combination chemotherapy with toripalimab was lower.In terms of economy,the combination of toripalimab and chemotherapy not only improves the clinical symptoms of advanced esophageal cancer patients,but also offers economic advantages.Conclusion Toripalimab is effective,safe and economical in the treatment of advanced esophageal cancer.

Objective To investigate whether Yiqicongming Decoction(YCD)can alleviate dry eye syndrome in rats.Methods Thirty-six male SD rats at 6 weeks of age were divided into blank group,model group,positive group,YCD high-dose group,YCD medium-dose group,and YCD low-dose group,with six rats in each group.The rats underwent iris,tear secretion volume,and corneal epithelial damage scoring assessments.Conjunctival tissue was stained with PAS,and the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)were detected using the en-zyme-linked immunosorbent assay(ELISA).The level of reactive oxygen species(ROS)was measured by flow cytometry.Western blot was used to detect the protein expression of nuclear factor erythroid 2-related factor 2(Nrf2)and hymeoxyge-nase-1(HO-1)in corneal tissues.Results Compared with the blank group,the number of goblet cells in the conjuncti-va,corneal epithelial injury score,MDA content and ROS level in the model group were significantly increased at all time points(all P＜0.05).The tear secretion volume of rats decreased on days 3,7,and 14,and the number of conjunctival goblet cells and SOD activity also decreased(all P＜0.05).Compared with the model group,the conjunctival score,corne-al epithelial injury score,MDA content,and ROS level in the positive control group and high-,medium-,and low-dose YCD groups were significantly reduced(all P＜0.05),while SOD activity and protein expression levels of Nrf2 and HO-1 in rats on day 14 were significantly increased(all P＜0.05).Compared with the high-dose YCD group,the conjunctival score,corneal epithelial injury score,and ROS level in the low-and medium-dose YCD groups were significantly increased(all P＜0.05),while SOD activity and protein expression levels of Nrf2 and HO-1 on day 14 were significantly decreased(all P＜0.05).On day 14,the tear secretion volume and the number of goblet cells in the conjunctiva of rats administered a low dose of Yiqi Congming Decoction both decreased(all P＜0.05).Compared with the medium-dose YCD group,the conjunc-tival score,corneal epithelial injury score and ROS level in the low-dose YCD group were significantly increased(all P＜0.05),while the tear secretion volume and protein expression levels of Nrf2 and HO-1 on day 14 were significantly de-creased(all P＜0.05).Conclusion YCD can increase tear secretion,alleviate iris and corneal epithelial damage,acti-vate Nrf2/HO-1 pathway,regulate oxidative stress,and alleviate dry eye syndrome.

Objective This study aimed to explore the clinical and etiological characteristics of bloodstream infections in diabetic patients with different levels of glycosylated hemoglobin(HbA1c)for improving empirical diagnosis and treatment in clinical practice.Methods A retrospective study was conducted for diabetic patients with bloodstream infections who were admitted to Sichuan Mental Health Center from 2017 to 2023.Patients were assigned to one of the three groups based on HbA1c levels:low level(HbA1c＜7.0％),medium level(7.0％≤HbA1c＜9.0％),high level(HbA1c≥9.0％).The clinical data,pathogen distribution,and antimicrobial resistance were analyzed and compared between groups.Results A total of 426 diabetic patients with bloodstream infection were included.The proportion of community-acquired bloodstream infection,acidosis,and liver abscess in the high level HbA1c group were significantly higher than those in the medium and low level HbA1c groups.Overall,452 strains of nonduplicate pathogenic bacteria were isolated,the most common of which were Escherichia coli(47.1％),Klebsiella pneumoniae(23.0％),and Staphylococcus aureus(5.8％).The pathogens of bloodstream infections varied with different HbA1c levels.The proportion of K.pneumoniae in the high-level HbA1c group(30.7％)was significantly higher than that in the low-level HbA1c group(15.1％)and medium level HbA1c group(16.0％).More than 50％of E.coli isolates were resistant to piperacillin,cefazolin,and ampicillin,while lower than 10％of the isolates were resistant to cefoxitin and minocycline,and lower than 1％of the isolates were resistant to piperacillin-tazobactam,meropenem,imipenem,and amikacin.The E.coli strains isolated from hospital-acquired infections showed slightly higher resistance rates to penicillin,cephalosporins,aminoglycosides,and fluoroquinolones than the strains isolated from community-acquired infections.K.pneumoniae strains showed low resistance rates(＜30％)to the commonly used antibiotics.However,the strains isolated from hospital-acquired infections were significantly more resistant to cephalosporins,carbapenems,and aminoglycosides than the strains isolated from community-acquired infections.Conclusions E.coli,K.pneumoniae and S.aureus were the common pathogens of bloodstream infections in diabetic patients.Poor HbA1c control was associated with K.pneumoniae bloodstream infection,especially those originated from liver abscess.The antibiotic-resistant E.coli and K.pneumoniae strains were prevalent in hospital-acquired bloodstream infections in diabetic patients.Antimicrobial resistance surveillance should be strengthened for this patient population.

Objective To analyze the clinical characteristics of cancer related anemia(CRA)in older cancer patients undergoing multi-line anti-tumor treatment.Methods A cross-sectional study was conducted,including patients with CRA who were≥65 years old and had received or were currently undergoing multi-line treatment at 9 hospitals in Beijing from June 1,2018 to September 30,2023.Data on gender,age,past history,family history,tumor type,metastasis site,clinical symptoms,blood routine,specialized examination for anemia,anti-tumor and anemia correction treatment were collected.The basic characteristics of the included patients,clinical symptoms,the status of blood cell reduction,treatment conditions,and the distribution of traditional Chinese medicine(TCM)syndrome characteristics were analyzed.Results A total of 602 patients were included.The tumor types included lung cancer,colorectal cancer,gastric cancer,esophageal cancer,breast cancer,gynecological tumors,lymphoma.The overall median hemoglobin(HGB)level was 99.00(88.00,107.00)g/L.The HGB levels of patients with different tumor types showed significant differences(P<0.001).The HGB levels of patients with gynecological tumors were significantly lower than those of patients with colorectal cancer,lung cancer and esophageal cancer(P<0.05).The most common clinical symptoms were fatigue,loss of appetite,irregular bowel movements and pain.In terms of anti-tumor treatment,405 patients were receiving multi-line anti-tumor treatment(including combined chemotherapy,combined radiotherapy,combined targeted therapy,and combined immunotherapy),197 patients were receiving symptomatic supportive treatment after multi-line anti-tumor treatment.In terms of anemia correction treatment,183 patients received erythropoietin,folic acid,iron,vitamin B12,or blood transfusion,while 293 patients received TCM for correcting anemia(including Chinese patent medicines,Chinese herbal decoctions,combinations of Chinese patent medicines and Chinese herbal decoctions).Specialized tests for anemia,such as serum iron,total iron binding capacity,transferrin saturation,transferrin,erythropoietin et al,have a detection rate of only 3.65%～27.91%.In terms of the characteristics of TCM syndromes,the main TCM syndrome types of the patients were as follows:syndrome of spleen-stomach weakness,syndrome of qi and blood deficiency,syndrome of heart-spleen deficiency,syndrome of spleen-kidney yang deficiency,syndrome of liver and kidney yin deficiency.Some patients also have the accompanying symptoms of internal binding of static blood and poison,phlegm dampness retention.Further comparison revealed that the HGB level of older patients with CRA who had syndrome of spleen-stomach weakness was significantly lower than patients with other symptom types(P<0.001).The HGB level of patients with syndrome of qi and blood deficiency was significantly lower than patients with syndrome of spleen-kidney yang deficiency(P<0.01)and syndrome of liver and kidney yin deficiency(P<0.001).Patients with symptoms of internal binding of static blood and poison,or symptoms of phlegm dampness retention had significantly lower HGB levels compared to those without accompanying symptoms(P<0.01).Conclusion The rate of specialized blood test for anemia in older patients with CRA was relatively low.The most common TCM syndrome types were syndrome of spleen-stomach weakness and syndrome of qi and blood deficiency.The overall treatment rate was also low.The screening,specialized diagnosis and monitoring of older patients with CRA need to be given more attention,and treatment methods such as TCM,Western medicine,and integrated TCM-Western medicine should be selected based on the patient's condition.

Objective:To investigate the anticipatory grief and to explore its correlates among family caregiv-ers of patients with advanced gastrointestinal cancer.Methods:A total of 283 family caregivers of patients with ad-vanced digestive cancer in the gastroenterology ward of a hospital were assessed using the Perceptive Social Support Scale(PSSS),Simplified Coping Style Questionnaire(SCSQ),Mishel Illness Uncertainty Scale for Family Member(MULS-FM)and Anticipatory Grief Scale(AGS).Results:The median AGS score was 91.00(80.00,98.00).Multiple linear regression analysis revealed that the AGS scores were negatively correlated with PSSS scores(β=-0.21),positive coping scores(β=-0.43),education level(β=-4.99)and age(β=-4.23),but positively correlated with MULS-FM scores(β=0.24).Conclusion:Family caregivers exhibited moderate-to-high anticipato-ry grief,which significantly influenced by age,perceived social support,positive coping style,illness uncertainty and education level.