Background: To evaluate the predictive value of serum adipsin and 25-hydroxyvitamin D [25(OH)D] combined detection in elderly diabetic peripheral neuropathy (DPN), aiming to provide new strategies for early intervention. Methods: Based on the electronic medical records of our hospital from January 2024 to June 2025, 161 elderly patients with T2DM (104 in the DPN group and 57 in the non-DPN group) were enrolled. ELISA detected serum adipsin, and 25(OH)D was measured via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The diagnostic efficacy of the combined detection was confirmed by univariate analysis, logistic regression model, and ROC curves. Disease course and age-stratified subgroup analyses were conducted. Results: DPN patients showed higher serum adipsin but lower 25(OH)D levels than non-DPN cases (P<0.05). Adipsin + 25(OH)D detection exhibited an AUC of 0.831 (sensitivity: 64.42%, specificity: 87.72%), higher than single-index predictions. Subgroup analysis indicated superior predictive efficiency of the combined detection in patients with a disease course of ≥6 years (AUC>0.85). According to correlation analysis, adipsin was positively correlated with FPG, HbA1c, and VPT, and negatively correlated with NCV and SCV, while the opposite was true for 25(OH)D. Conclusions: Serum adipsin combined with 25(OH)D has high predictive value for elderly DPN, and their synergistic effect may be mediated through interconnected pathways involving chronic inflammation, oxidative stress damage, and metabolic dysregulation - collectively termed the 'inflammation-oxidative stress-metabolic disorder' axis.

Immune checkpoint inhibitors (ICIs) significantly improve prognosis and survival outcomes in cancer patients by enhancing immune function, thereby providing new therapeutic hope for cancer patients. However, with the widespread clinical application of ICIs, an increasing number of immune-related adverse events (irAEs) have been reported. Immune checkpoint inhibitor-induced type 1diabetes mellitus (ICI-T1DM) is a rare but potentially life-threatening irAE, usually presenting as acute onset and easily progressing to diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS), which poses a serious threat to patients’ safety. This study reports a case of DKA in an 81-year-old female patient diagnosed with cervical squamous cell carcinoma without history of diabetes mellitus, which developed after multiple cycles of Cadonilimab. The patient’s blood glucose levels were effectively controlled via insulin therapy and fluid resuscitation, and a definitive diagnosis of ICI-T1DM was confirmed. Taking this case as a starting point, this article reviews the epidemiology, clinical characteristics, pathogenesis, and clinical management strategies of ICI-T1DM, aiming to enhance clinicians’ awareness of ICI-T1DM, especially the endocrine toxicity of dual-target ICIs such as cadonilimab, and provide practical reference for ensuring the safety of ICI therapy in cancer patients.

Loop-mediated isothermal amplification (LAMP) has garnered significant interest as a promising technique for nucleic acid testing, especially in point-of-care and on-site applications, due to its rapid assay speed and simple operating conditions. However, the wide adoption and acceptance of LAMP technology remain a challenge, primarily due to the insufficient sensitivity, poor stability, and strong subjectivity in the interpreting color transition stage. To address these, we developed a novel fluorescent probe, namely, FC-NAPH-PZ, for the LAMP assay. Its high Stokes shift and excellent pH reversibility generated a large and stable fluorescence "turn-on" signal, enabling the highly sensitive (single-copy) and ultrahigh selective detection in the LAMP assay. Meanwhile, its high stability minimized interference with efficient amplification in closed-tube LAMP. Using this probe, we achieved a highly sensitive and specific one-step detection on lambda DNA and Escherichia coli O157:H7 through either visual inspection or quantitative real-time fluorescence monitoring.

OBJECTIVE:This study aimed to investigate the impact of the National Volume-Based Procurement (NVBP) policy on antimicrobial use intensity, prescribing structure, and medical costs among inpatients in a tertiary hospital in China. METHODS:This study retrospectively extracted 1200 inpatient prescriptions from a tertiary hospital between April 2019 and March 2024. Using interrupted time series (ITS) analysis, the study assessed the immediate-level changes and long-term trend effects of the NVBP policy on medication indicators such as defined daily doses (DDDs) and costs. RESULTS:Following NVBP implementation, antimicrobial prescribing structure changed significantly, with β-lactam utilization decreasing by 13.85%. The combination rate of β-lactams + fluoroquinolones fell significantly by 75.93%, while overall combination therapy remained unchanged. Use of special-grade antimicrobials showed a numerical increase (+31.98%), although not statistically significant. Cost indicators decreased significantly following policy implementation. ITS analysis further revealed a significant immediate decrease in the proportion of DDDs for NVBP antimicrobial agents (β2 = -15.464 units, p = 0.009), followed by a sustained upward trend (β3 = 1.400/month, p < 0.001). Similarly, DDDs of NVBP antimicrobial agents showed a significant upward trend (β3 = 0.135 units/month, p = 0.017) after the policy. CONCLUSION:This study demonstrates that while the NVBP policy significantly reduced patient drug expenditures and promoted the use of NVBP varieties and nonrestricted antimicrobial agents, it also increased the proportion of special-grade antimicrobials agents, suggesting the need for caution against potential antimicrobial resistance and strengthened supervision of prescription.

Abstract Diabetic kidney disease (DKD) progression is accelerated by tubulointerstitial inflammation (TI), yet no therapies specifically target this pathogenic process. Xanthotoxol (XT), a natural furanocoumarin with demonstrated anti-inflammatory properties in neuroinflammatory contexts, remains unexplored for its potential in DKD-associated TI. This study explored the pharmacological effects and underlying mechanisms of XT on DKD-associated TI through experiments combined with bioinformatics technology. We found that TI was significantly exacerbated in models of DKD. In vitro experiments showed that XT dose-dependently inhibited the upregulation of inflammatory factors, including Interleukin-6 (IL-6), Interleukin-1-beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in human renal proximal tubule (HK-2) cells induced by high glucose (HG). Network pharmacology and molecular docking analyses identified heat shock protein 90 kDa alpha beta 1 (HSP90αβ1) as a pivotal target of XT in this context. Subsequent mechanistic experiments confirmed the existence of a direct physical interaction between HSP90αβ1 and NOD-like receptor family pyrin domain-containing 3 (NLRP3). A high dose of XT was able to effectively inhibit the upregulation of HSP90αβ1 and NLRP3 expression and their interaction induced by HG. Furthermore, the use of the HSP90αβ1 activator tamoxifen eliminated the inhibitory effect of XT on the production of NLRP3 and downstream pro-inflammatory cytokines. In summary, our study is the first to demonstrate that XT may alleviate the DKD-associated TI by targeting the HSP90αβ1/NLRP3 signaling axis. These results indicate that XT is a promising therapeutic candidate for the treatment of DKD.

Methamphetamine (MA) abuse still constantly increases in the world, which is seriously harmful for people's health. Cucurbituril-mediated sensors for detection of illicit drugs have received growing attention. However, urine samples contain inorganic salts with high concentration, which could disturb the interaction between cucurbituril host and fluorescence dye or target guest. Magnetic solid phase extraction (MSPE) technology exhibits excellent potential to remove impurity and ameliorate sensitivity for detection in complex biofluids. This work demonstrated a strategy for MA detection, in which MSPE was coupled with cucurbituril-mediated chemosensor to reduce interference of salts and overcome dilution issues in biological samples. The magnetic nanoparticles Fe3O4@polydopamine (PDA) were used as adsorbent and chemosensor 2*proflavine@cucurbit[8] uril (2 PF@Q[8]) was applied for the fluorescence detection of MA. In the end, a linear range of 1.3-20 ng/mL and limit of detection of 0.4 ng/mL were achieved. Besides, the proposed method showed a pronounced selectivity in the presence of other illicit drugs. In general, we introduced an example focusing on coupling of MSPE with cucurbituril-mediated chemosensor, where small organic molecule MA was adsorbed and retained while inorganic salts were separated. This study underscores the potential of coupling MSPE with cucurbiturilmediated chemosensor in biological samples.

Background Programmed death-1 (PD-1) inhibitors combined with chemotherapy have become a standard first-line treatment for advanced oesophageal squamous cell carcinoma (ESCC). Given the high costs associated with immunotherapy, evaluating the cost-effectiveness of different PD-1 inhibitors in the Chinese healthcare setting is essential for guiding treatment decisions and policy development.Methods A cost-effectiveness analysis was conducted comparing six PD-1 inhibitors—sintilimab, toripalimab, tislelizumab, camrelizumab, serplulimab, and pembrolizumab—combined with chemotherapy for first-line treatment of advanced ESCC. A partitioned survival model was used to calculate incremental cost-effectiveness ratios (ICERs) from healthcare system perspective, with a willingness-to-pay (WTP) threshold set at $36,598.19 per quality-adjusted life year (QALY). Sensitivity analyses were performed to evaluate the robustness of the results.Results The ICERs for toripalimab, camrelizumab, pembrolizumab, serplulimab, sintilimab, and tislelizumab were $32,356.79/QALY, $48,410.64/QALY, $312,743.54/QALY, $121,200.84/QALY, $29,663.42/QALY, and $35,304.33/QALY, respectively. Sintilimab, toripalimab, and tislelizumab were below the WTP threshold. Among all regimens, the top three in life years (LYs) gained were toripalimab, serplulimab, and tislelizumab. Sensitivity analysis showed that utility values and drug prices were key factors influencing ICERs. Probabilistic analysis indicated that toripalimab, sintilimab, and tislelizumab had the highest probabilities of being cost-effective, at 83.1%, 81.4%, and 70.0%, respectively.Conclusion Sintilimab, toripalimab, and tislelizumab are the most cost-effective PD-1 inhibitors when combined with chemotherapy for the first-line treatment of advanced ESCC in China, with ICERs below the WTP threshold. While all six PD-1 inhibitors demonstrated clinical benefits, pembrolizumab and serplulimab were less favourable from a cost-effectiveness standpoint. Sensitivity analysis confirmed that drug prices and utility values are significant determinants of cost-effectiveness.

Purpose:Metabolic dysfunction-associated steatosic liver disease (MASLD) poses a global health challenge with limited therapeutic options. Hesperetin, a flavonoid extracted from citrus, exhibits multiple pharmacological properties, but its mechanisms in MASLD-associated lipid metabolism remain unclear. This study aimed to explore the mechanism of hesperetin for treating MASLD. Methods:Network pharmacology identified the therapeutic targets for MASLD. Key targets were selected based on network topology analysis. Subsequently, Kyoto Encyclopedia of genes and genomes (KEGG) pathways and gene ontology enrichment were conducted. Molecular docking was performed to evaluate the binding affinity between hesperetin and the identified key targets. In vitro validation included lipid accumulation assays and verification of core target modulation via western blotting. Results:Hesperetin significantly attenuated lipid accumulation in free fatty acid -induced HepG2 cells. Forty core targets of hesperetin for MASLD mitigation were identified. Notably, MYC, IL-6, IL1B, and PTGS2 had high network association values. KEGG analysis revealed predominant involvement in cancer-related pathways, non-alcoholic fatty liver disease, and JAK/STAT signaling. Biological processes included inflammatory response regulation and cytokine activity. Molecular docking confirmed strong hesperetin-IL-6 binding. Experimental data suggested that hesperetin may ameliorate lipid accumulation by modulating the IL-6-mediated STAT3-SOCS3 signaling pathway. Conclusion:Hesperetin may ameliorate MASLD by targeting the IL-6-STAT3-SOCS3 axis, underscoring its therapeutic potential.

Metal chalcogenide quantum dots (MCQDs) have received tremendous attention in biomedical field for their fascinating optical properties and the admirable biomolecular modifiability. However, challenged by low stability and notorious biocompatibility, MCQDs make them limited for direct biomedical use. Herein, a novel designed and synthesized poly(allylamine) and cysteine co-capped silver indium sulfide quantum dots (PAA-CysAIS QDs) with excellent photostability is reported for the specific rapid detection of Cd2+ and Zn2+ ions. The obtained water-soluble PAA-Cys-AIS QDs emitted a stable orange fluorescence at 625 nm with an average size of 3.639 +/- 1.006 nm. The unusual anti-photobleaching property of PAA-Cys-AIS QDs is demonstrated to be owing to the introducing of poly(allylamine) and cysteine, which uniquely increased the crystallinity and hydrodynamic size of the structure system. Unexpectedly, unlike most reported approaches for Cd2+ and Zn2+ detection based on the quenching fluorescence mechanism, the PAA-Cys-AIS QDs showed remarkable and rapid fluorescence enhancement after being exposed to Cd2+ and Zn2+ ions aqueous solutions. Notably, the detection limits of the new probe for Cd2+ and Zn2+ are 175 and 50 nM respectively. Complexation and metal ions doping mechanisms are proposed to be responsible for the enhancement of photoluminescence intensity based on the metal ions capture capacity coming from PAA-Cys-AIS QDs' intrinsic defects and abundant surface amino functional groups. Moreover, the intracellular photostability and biocompatibility of PAA-Cys-AIS QDs are strong enough to prompt us to investigate the metal ions imaging applications in SH-SY5Y cells to further demonstrate the potential for real-live biomedical applications.

Smoking causes death of millions of people every year. However, available therapies for nicotine addiction are partially effective and exhibit frequent side effects. Thus vaccines targeted at drug nicotine not brain offer a promising strategy to treat nicotine addiction. They cannot pass blood-brain barrier, avoiding serious side effects relevant with central nervous system. The specific nicotine antibody produced by vaccines would convert to complex after combined with nicotine in serum, decreasing or even blocking the distribution of nicotine in brain. This review summarizes the pre-clinical and clinical advances of nicotine vaccines and then addresses future directions of nicotine vaccine and the practical aspects of deployments.

ObjectiveThis study aimed to evaluate mecapegfilgrastim utilization for the prophylaxis of chemotherapy-induced neutropenia in cancer patients and to assess changes caused by the National Health Insurance Coverage (NHIC) policy.MethodsIndividual patient data, including demographics, medical insurance status, cancer type, and tumor stage, were extracted from electronic medical records in an oncology specialty tertiary hospital in Jiangsu Province, China. An interrupted time series (ITS) analysis with a segmented regression model was applied to evaluate the NHIC policy’s effects, and multivariate binary logistic regression analysis was used to identify key factors influencing mecapegfilgrastim utilization.ResultsThe proportion of cancer patients receiving mecapegfilgrastim increased from 8.17% before the NHIC policy implementation to 36.05% after its implementation (P < 0.001). Utilization rose abruptly following the policy intervention (β = 0.143, P < 0.001) and continued to increase significantly afterward (β = 0.011, P = 0.004). However, inequities were observed in mecapegfilgrastim usage among patient subgroups, with utilization closely associated with patients’ location, cancer type, and tumor stage after the policy implementation.ConclusionThe NHIC policy significantly increased mecapegfilgrastim utilization, enabling more cancer patients to access this medication and effectively benefiting them. To address persistent inequities, the government should consider introducing additional measures, such as increasing the insurance reimbursement cap and separating the cost of expensive innovative anticancer medicines from hospital medical insurance budgets.

Molybdenum (Mo) was initially discovered in 1778, which was recognized as an essential element. Over the past few decades, Mo-based materials emerged as popular member in the field of industrial manufacture such as electrodes and catalysts due to their appealing strength and corrosion resistance. In recent years, with the vigorous development of nanotechnology, Mo-based nanomaterials have gradually drawn extensive attention in biomedical field due to their physicochemical versatility including excellent biocompatibility, high catalytic activity, redox chemistry and strong photothermal conversion efficiency (PCE), which greatly promoted diversified applications of Mo-based nanomaterials in biomedical area. Up to date, scientific workers have exhibited thousands of bio-applications of Mo-based nanomaterials, but a systematical overview in this filed is still rare. In this review, the specific applications outline of Mo-contained nanomaterials in biomedical field are summarized via six aspects including reactive oxygen species (ROS) scavenging, photodynamic therapy (PDT) and photothermal therapy (PTT), antibacterial performance, drug delivery, bioimaging, and biosensors. And the unique properties of Mo-based nanomaterial momentous to its biomedical applications are accordingly expounded. Finally, the relevant existing challenges and future objectives of Mo-contained nanomaterials applied in biomedicine are thoroughly discussed.

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder among older adults, significantly impairs behavioral and cognitive functions, posing a severe threat to patients' health and quality of life. The Tricetin (TRN), a natural flavonoid found in wheat, pomegranate, and eucalyptus honey, has demonstrated anti-inflammatory, antitumor, and neuroprotective properties. However, its role in the context of AD has not been previously explored. This study investigated the antineuroinflammatory and autophagic protective effects of TRN in lipopolysaccharide (LPS)-induced BV2 cells and D-galactose/sodium nitrite/aluminum chloride (D-gal/NaNO2/AlCl3)-induced AD mice. The RNA sequencing examined the underlying mechanisms by which TRN ameliorates AD-related pathologies. Our research findings revealed that TRN significantly improved memory and mobility in AD mice, reduced Aβ deposition, and inhibited Tau protein phosphorylation. Furthermore, TRN regulated enzyme activities and reduced pathological markers associated with AD. Moreover, it modulated inflammatory mediators, inhibited the nuclear translocation of NF-κB in LPS-induced BV2 cells, and exerted anti-inflammatory and autophagic protective effects via the PI3K/Akt/mTOR signaling pathway. In conclusion, TRN demonstrated robust neuroprotective effects in vitro and in vivo AD models by regulating the PI3K/Akt/mTOR signaling pathway. These findings highlight its potential as a promising therapeutic agent for treating AD.

Background:Cancer is a leading cause of death globally, with China accounting for a significant portion of new cases and deaths. The Government of China has introduced the National Drug Price Negotiation (NDPN) policy to mitigate the high costs of anticancer drugs, especially multi-indication drugs, aimed at improving patient access to effective treatments. Methods:In this retrospective study, we examined 24 multi-indication anticancer drugs for solid tumours included in the National Reimbursement Drug List (NRDL) between 2016 and 2023. We collected characteristics of indication, clinical trial evidence, and clinical benefits of these drugs, calculated monthly drug costs, and assessed the associations the two by regression and correlation analyses. Results:We observed a significant reduction in the median monthly drug cost from USD 3863.08 before NDPN to USD 732.91 after their inclusion in the NRDL. However, the correlation analyses showed no significant relationships between drug costs and characteristics of indications, clinical trial evidence, and clinical benefits, while American Society of Clinical Oncology Value Framework scores demonstrated a negative correlation with costs, indicating that pricing may not accurately reflect clinical benefits. Conclusions:While we found that the NDPN policy has significantly reduced drug costs, we did not observe a significant correlation between costs and specific characteristics. This highlights a need for a more transparent pricing mechanism linked to clinical efficacy to improve the accessibility and affordability of cancer therapies that effectively balance the interests of pharmaceutical companies, patients, and health insurance funds.

Objective:Resveratrol(Res)is a promising anticancer drug against hepatocellular carcinoma(HCC),but whether its anti-HCC effects implicate mitophagy remains unclear.Therefore,we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. Methods:HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-,middle-and high-dose of Res on HCC progression and mitophagy in vitro and in vivo,respectively.A series of approaches including cell counting kit-8,flow cytometry,wound healing and transwell assays were used to evaluate tumor cell functions.Transmission electron microscopy,immunofluorescence and Western blotting were used to assess mitophagy.Mitochondrial oxygen consumption rate,reactive oxygen species and membrane potential were used to reflect mitochondrial function.After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1(MALAT1),miR-143-3p,and ribonucleoside reductase M2(RRM2),the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro.Additionally,dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. Results:Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro,while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mito-chondrial dysfunction in vivo.Interestingly,MALAT1 was highly expressed in HCC cells and its knock-down upregulated miR-143-3p expression in HCC cells,which subsequently inhibited RRM2 expression.Furthermore,in nude mice grafted with HCC tumors and treated with Res,the expression of MALAT1,miR-143-3p and RRM2 were altered significantly.In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2.Therefore,a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC;these experiments revealed that MALAT1 knockdown,miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. Conclusion:Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis.

Abstract Background Early dissemination to distant organs accounts for the dismal prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Chronic, dysregulated, persistent and unresolved inflammation provides a preferred tumor microenvironment (TME) for tumorigenesis, development, and metastasis. A better understanding of the key regulators that maintain inflammatory TME and the development of predictive biomarkers to identify patients who are most likely to benefit from specific inflammatory-targeted therapies is crucial for advancing personalized cancer treatment. Methods This study identified cell-specific expression of CALB2 in human PDAC through single-cell RNA sequencing analysis and assessed its clinicopathological correlations in tissue microarray using multi-color immunofluorescence. Co-culture systems containing cancer-associated fibroblasts (CAFs) and patient-derived organoids (PDOs) in vitro and in vivo were employed to elucidate the effects of CALB2-activated CAFs on PDAC malignancy. Furthermore, CUT&RUN assays, luciferase reporter assays, RNA sequencing, and gain- or loss-of-function assays were used to unravel the molecular mechanisms of CALB2-mediated inflammatory reprogramming and metastasis. Additionally, immunocompetent KPC organoid allograft models were constructed to evaluate CALB2-induced immunosuppression and PDAC metastasis, as well as the efficacy of inflammation-targeted therapy. Results CALB2 was highly expressed both in CAFs and cancer cells and correlated with an unfavorable prognosis and immunosuppressive TME in PDAC patients. CALB2 collaborated with hypoxia to activate an inflammatory fibroblast phenotype, which promoted PDAC cell migration and PDO growth in vitro and in vivo. In turn, CALB2-activated CAFs upregulated CALB2 expression in cancer cells through IL6-STAT3 signaling-mediated direct transcription. In cancer cells, CALB2 further activated Ca2+-CXCL14 inflammatory axis to facilitate PDAC metastatic outgrowth and immunosuppression. Genetic or pharmaceutical inhibition of CXCL14 significantly suppressed CALB2-mediated metastatic colonization of PDAC cells in vivo and extended mouse survival. Conclusions These findings identify CALB2 as a key regulator of inflammatory reprogramming to promote PDAC metastatic progression. Combination therapy with αCXCL14 monoclonal antibody and gemcitabine emerges as a promising strategy to suppress distant metastasis and improve survival outcomes in PDAC with CALB2 overexpression.

Abstract Background Low molecular weight heparin (LMWH) has been the standard treatment for preventing venous thromboembolism after total joint arthroplasty. However, the evidence supporting specific LMWH dosing regimens is limited. Objectives This study assessed the efficacy and safety of three enoxaparin dosing regimens to prevent venous thromboembolism. Methods Participants undergoing hip or knee replacement were randomly assigned to receive 20 mg of enoxaparin 6 h postoperatively (Group A), 40 mg 6 h postoperatively (Group B), or 40 mg 12 h postoperatively (Group C). The primary outcomes included thromboembolic and major bleeding events within 3 months, while the secondary outcomes comprised ecchymosis, wound exudation, drainage volume, allogeneic red blood cell transfusion, and first postoperative day hemoglobin levels. Results A total of 536 patients were analyzed. The occurrence of thromboembolic events was comparably low across all groups. Group C exhibited the lowest postoperative ecchymosis rate at 19.3%, significantly less than Group A (32.8%, p = 0.004) and Group B (37.7%, p < 0.001). Ecchymosis rates were about double in Group A and 1.5 times higher in Group B compared to Group C. Significant differences were also observed in 24-hour and total postoperative drainage volumes, with Group B having higher volumes than the other groups. Clinical trial registration This trial was prospectively registered at the China Clinical Trials Registry (registration date: November 14, 2021; registration number: ChiCTR2100053191). Conclusion No significant differences in venous thromboembolism rates were seen between the tested enoxaparin dosing regimens after total joint arthroplasty. The 40 mg dose administered 12 h after surgery was associated with reduced postoperative ecchymosis and drainage volumes without an increased thrombosis risk, suggesting it is a safer and more effective option than earlier or lower dosages. Graphical Abstract

Tislelizumab has emerged as a promising therapy for unresectable hepatocellular carcinoma (uHCC), although its economic viability across different healthcare systems remains uncertain. This study compared the cost-effectiveness of tislelizumab versus sorafenib as a first-line treatment for uHCC from the perspectives of the healthcare systems of China, the United States and Europe. A partitioned survival model was developed using data from the RATIONALE-301 trial. Costs and utilities were sourced from local healthcare charges, publicly available databases, and published literature. Total costs, quality-adjusted life years, and incremental cost-effectiveness ratios (ICERs) were assessed. Price simulations were conducted to identify cost-effective pricing within established willingness-to-pay (WTP) thresholds. Sensitivity and scenario analyses were performed to test the robustness of the model. Tislelizumab (priced at 1587.45/100 mg) was cost-effective in the US at a WTP threshold of150,000, with an ICER of 108,812.52. In Europe, tislelizumab was cost-effective at a WTP threshold of100,000, with an ICER of 94,880.40. For186.18/100 mg in China, tislelizumab was cost-effective with an ICER of 14,206.80. Price simulation analyses showed that in the US, tislelizumab was favored when priced below1438.30/100 mg at a 100,000 WTP threshold and below2284.56/100 mg at a 150,000 WTP threshold. In Europe, it was favored below1661.82/100 mg and 2501.93/100 mg for the same thresholds. In China, tislelizumab was cost-effective at a WTP threshold of38,184 when priced below 582.11/100 mg. Tislelizumab presents a cost-effective first-line treatment option for uHCC, potentially supporting its broader adoption in health policy. Future research should focus on long-term efficacy and real-world data to further validate these findings.

Background: Despite the availability of guidelines and official policies, antibiotic prophylaxis in clean surgery remains suboptimal. Objective: The aim of this study was to evaluate the clinical effects and cost-effectiveness of pharmacist-led intervention in the perioperative anti-infection prophylaxis of patients undergoing orthopedic internal fixation. Methods: We performed a retrospective analysis based on the medical records of internal fixation surgery in a tertiary hospital from July 2019 to June 2020. Data were divided into two groups based on whether a full-time pharmacist participated in the treatment. The research parameters included use of antibiotics, rationality of medication, postoperative complications, and related cost. To deal with selection bias, propensity score matching method was employed at a ratio of 1:1. Meanwhile, a cost-effectiveness analysis was used to evaluate the impact of pharmacist intervention on antibiotic prevention in internal fixation surgery. Results: A total of 537 participants were included in this study. After matching, 236 patients were comparable in each group. During the pharmacist intervention period, less pharmacologic prophylaxis (96.6% vs 100.0%, p = 0.007) and shorter prophylaxis duration (1.60 vs 2.28 days, p < 0.001) were observed. The reasonable rate increased dramatically in usage and dosage (96.6% vs 83.9%, p < 0.001), timing of administration (94.5% vs 78.4%, p < 0.001) and medication duration (64.4% vs 37.7%, p < 0.001). In addition, pharmacist intervention yielded net economic benefits. A remarkable reduction was observed in average length of stay (10.43 vs 11.14 days, p = 0.012), drug cost ($610.57 vs $706.60, p = 0.001) and defined daily doses (2.31 vs 3.27, p < 0.001). The cost-effectiveness ratios, divided drug cost savings by cost of pharmacist time, were 28:1 for drug and 2:1 for antibiotics, respectively. Conclusion: Pharmacist-driven antibiotic stewardship for orthopedic internal fixation patients improved compliance with peri-procedure antibiotic prophylaxis, and reduced the cost and utilization of antibiotics. This helped to bring significant clinical and economic benefits.

OBJECTIVE:Camrelizumab combination therapy for advanced or metastatic esophageal squamous cell carcinoma (ESCC) has considerable survival benefits. This study investigated the cost-effectiveness of camrelizumab combination therapy versus chemotherapy alone as a first-line treatment for patients with ESCC from the perspective of the Chinese healthcare system.METHODS:A three-state partitioned survival model was developed to estimate total costs, life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net health benefits (INHBs) over a 20-year time horizon. Sensitivity and scenario analyses were also performed.RESULTS:Camrelizumab plus chemotherapy increased QALYs by 0.30 (0.43 LYs), with an incremental cost of $9,272. The ICERs for camrelizumab plus chemotherapy vs chemotherapy alone was $31,062/QALY ($21,599/LY), and the INHB was 0.05 QALY at the cost-effective threshold of $37,653/QALY (3 times China's GDP per capita). One-way sensitivity analyses showed that the ICER was the most sensitive to utility values in the PFS state. Probabilistic sensitivity analyses suggested that camrelizumab combination therapy had a probability of 74.04% cost-effectiveness at a threshold of $37,653/QALY. Scenario analyses confirmed that the findings were robust.CONCLUSIONS:Camrelizumab combination therapy is likely to have a cost-effectiveness advantage over chemotherapy alone for previously untreated advanced or metastatic ESCC in China.