Objective To establish an epirubicin (EPI)-resistant murine triple-negative breast cancer (TNBC) (4T1/EPI) cell line and evaluate its biological characteristics and drug resistance. Methods The EPI-resistant cell line 4T1/EPI was developed through intermittent induction with gradually increasing EPI concentrations in vitro. Morphological changes were observed under an inverted microscope. Drug resistance index (MTT assay), cell doubling time (CCK-8 assay), and migration ability (wound healing assay) were evaluated. Western blot was used to detect the expression of drug resistance-related proteins. Transcriptome sequencing and KEGG pathway enrichment analysis were performed to identify the pathways and targets involved in EPI resistance, followed by experimental validation. Results The 4T1 cells eventually grew normally in a medium containing 100 ng/mL EPI, confirming the establishment of the 4T1/EPI resistant cell line. After stable resistance was acquired, morphological alterations were observed. Compared with their parental 4T1 cells, 4T1/EPI cells showed significantly prolonged doubling time (P<0.01) and enhanced migration ability (P<0.05). Expression levels of drug resistance-related proteins MDR1, MRP1 (P<0.01), and ABCG2 (P<0.05) were elevated in 4T1/EPI cells. In vivo models also demonstrated significant EPI resistance in 4T1/EPI tumors in terms of tumor weight and volume. Transcriptome sequencing highlighted the involvement of the PI3K/Akt signaling pathway and ABC transporter pathway. Validation experiments showed the upregulation of Erbb3, Egfr, PI3K, and Akt (P<0.05) and significant downregulation of Fgfr1 (P<0.01) in 4T1/EPI cells. Conclusion The EPI-resistant TNBC cell line 4T1/EPI was successfully established, exhibiting significant resistance in vitro and in vivo. The mechanism may involve the EPI-induced upregulation of Egfr and Erbb3, activating the PI3K/Akt pathway and subsequently enhancing ABC transporter expression.

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.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

To systematically analyzed the reporting status of core elements in publicly available clinical practice guideline(hereafter referred to as "guideline") protocols published domestically and internationally over the past decade, identified existing problems, and provided evidence to inform the standardized writing and publication of future guideline protocols.

OBJECTIVE To analyze the characteristics and influencing factors of disposal behavior of expired medicines among Chinese residents across regional divisions， and to provide references for regional classification management and precise policy implementation regarding expired medicines. METHODS A stratified random sampling method was employed to conduct a questionnaire survey among residents across sample provinces and cities， utilizing a combination of online and offline approaches. Binary Logistic regression analysis was used to systematically explore the regional （eastern， central and western regions） and urban-rural disparities in the recycling of expired medicines among Chinese residents， identify the core driving factors influencing standardized disposal behaviors， and propose corresponding recommendations. RESULTS A total of 2 200 ques tionnaires were collected， with 2 159 deemed valid， yielding an effective response rate of 98.1%. The surveyed residents commonly stored medicines at home （67.7%）， yet the rate of regular medicine clearance was low （only 57.7%）. Nearly half of the residents （49.7%） had expired medicines in their households， with improper disposal of expired medicines remaining the predominant behavior. Insufficient convenience in recycling was identified as the primary reason for improper disposal of expired medicines （50.1%）. Statistically significant differences were observed between residents in the eastern， central and western regions， as well as between urban and rural residents， in terms of household medicine storage rates and the prevalence of expired medicine possession （ P ＜0.05）. However， no statistically significant difference was found in the standardized disposal rates across regional divisions （ P ＞0.05）. Furthermore， the residents demonstrated a higher level of awareness regarding the health hazards of expired medicines compared to their awareness of environmental hazards， with 46.0% and 32.1% indicating they were “relatively familiar” and “very familiar”， respectively. The participation rate in standardized recycling was only 37.6%. Among non-participating residents， the three primary barriers were “recycling points being too far away” （46.6%）， “unawareness of recycling channels” （46.1%） and “lack of incentives” （48.1%）. The surveyed residents showed relatively high trust in pharmaceutical regulatory authorities and on-site recycling personnel， with “high trust” accounting for 31.2% and 34.7%， respectively. Binary Logistic regression analysis results indicated that the awareness of environmental hazards and the accessibility of recycling points were the core driving factors for proper disposal. CONCLUSIONS Significant issues exist in the recycling of expired medicines among Chinese residents， characterized by “improper behavior， cognitive bias， and unbalanced system”. It is recommended to construct a tiered recycling network focusing on “quality improvement in the eastern region， expansion in the central region， and basic coverage in the western region”， implement targeted educational campaigns and differentiated incentive policies. Moreover， the specific needs of groups such as the elderly should be addressed to achieve spatial equalization and service optimization of the recycling system.

Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

ObjectiveTo perform metabolic associated fatty liver disease （MAFLD） screening among individuals attending community health institutions， to identify the patients at a low， moderate or high risk of advanced liver fibrosis based on fibrosis-4 index （FIB-4） and liver stiffness measurement （LSM） measured by liver transient elastography， and to implement stratified management. MethodsA cross-sectional study was conducted among 630 individuals attending Beijing Baizhifang Community Health Service Center from January to July 2024， and they were divided into MAFLD group and non-MAFLD group. According to body mass index （BMI）， the MAFLD group was further divided into lean MAFLD group （BMI<23 kg/m²） and non-lean MAFLD group （BMI≥23 kg/m²）. The above groups were compared in terms of demographic features， laboratory markers， hepatic steatosis， and LSM. Fibrosis risk stratification was performed for MAFLD patients based on FIB-4 and LSM， and a closed-loop management system involving referral to tertiary hospitals and follow-up at community health institutions was implemented. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThere were 445 individuals （70.6%） in the MAFLD group and 185 individuals （29.4%） in the non-MAFLD group. Compared with the non-MAFLD group， the MAFLD group had a significantly lower proportion of male individuals （χ²=4.299， P<0.05）， a significant reduction in the level of high-density lipoprotein cholesterol （Z=3.484， P<0.05）， and significant increases in body weight （Z=-7.366， P<0.05）， BMI （Z=-9.740， P<0.05）， waist circumference （Z=-6.397， P<0.05）， hip circumference （Z=-6.935， P<0.05）， alanine aminotransferase （ALT） （Z=-2.765， P<0.05）， fasting blood glucose （Z=-3.646， P<0.05）， triglyceride （TG） （Z=-6.569， P<0.05）， total cholesterol （Z=-2.033， P<0.05）， low-density lipoprotein cholesterol （Z=-2.935， P<0.05）， controlled attenuation parameter （CAP） （Z=-19.784， P<0.05）， and LSM （Z=-5.703， P<0.05）. Within the MAFLD group， there were 124 individuals （27.9%） in the lean MAFLD group and 321 individuals （72.1%） in the non-lean MAFLD group. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly lower body weight （Z=-12.414， P<0.05）， BMI （Z=-16.363， P<0.05）， waist circumference （Z=-7.733， P<0.05）， hip circumference （Z=-8.595， P<0.05）， ALT （Z=-2.835， P<0.05）， aspartate aminotransferase （Z=-1.972， P<0.05）， TG （Z=-2.407， P<0.05）， CAP （Z=-4.429， P<0.05）， degree of steatosis （χ²=16.588， P<0.05）， and LSM （Z=-3.908， P<0.05）. Based on the results of FIB-4 and LSM， 76 patients at a moderate or high risk of liver fibrosis should be referred to a higher-level hospital for further management. ConclusionThe detection rate of MAFLD reaches 70.6% among the individuals attending community health institutions， among whom 76 （17.1%） should be referred to a higher-level hospital. Establishing a liver fibrosis risk stratification and management system based on FIB-4 and LSM among MAFLD individuals in communities provides a practical pathway for chronic disease management and referral system construction in community health institutions.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

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.