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Abstract Background The association between educational attainment (EA) and arterial thrombotic disease has been reported, but the causal relationship between EA and venous thromboembolism (VTE) is not clear. We aimed to assess the causal effect of EA on VTE using the two-sample mendelian randomization (MR) method. Methods Data mining was conducted on the genome wide association studies (GWAS), with exposure factor EA and outcome factor VTE. Two-sample Mendelian Randomization (TSMR) analysis was conducted, with the results obtained from the random effects inverse variance weighted method (IVW). Use the MR-Egger method for pleiotropy analysis and leave one method for sensitivity analysis to verify the reliability of the data. Results Genetically predicted decreased EA was associated with a decreased risk of VTE in both the FinnGen consortium and UK Biobank (FinnGen-VTE: OR = 0.848; 95% CI 0.776—0.927; P = 2.84 × 10–4; UKB-VTE OR = 0.996; 95% CI 0.994—0.999; P = 0.008) under a multiplicative random-effects IVW model. Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. Conclusions The MR technique instructed a potential inverse causative relationship between EA and occurrence of VTE. Therefore, patients with low EA should be more vigilant about the occurrence of VTE.

BackgroundThe occurrence of venous thromboembolism (VTE) after abdominal and pelvic cancer surgery increases the risk of mortality and disability. However, there is insufficient evidence supporting the choice of anticoagulation strategies.MethodsWe searched PubMed, The Cochrane Library, Embase, and Web of Science for randomized controlled trials from inception to January 2024. Studies concerning thrombosis prevention after abdominal and pelvic surgery were included. Network meta-analysis(NMA) and direct meta-analysis (DMA) methods were employed to evaluate the efficacy and safety of various prophylactic strategies.ResultsTwenty clinical trials involving a total of 4923 patients were included. The DMA results showed that low molecular weight heparin (LMWH) was more effective in preventing VTE compared to no treatment (OR = 1.96; 95% CI: 1.21 to 3.19), and LMWH plus physiotherapy was more effective than LMWH (OR = 10.95; 95% CI: 1.33 to 90.40). The NMA results indicated that DOACs (OR = 0.34; 95% CI: 0.11 to 0.76) and LMWH (OR = 0.51; 95% CI: 0.32 to 0.77) were significantly effective in preventing venous thrombosis compared with no treatment. The cumulative ranking probability curve (SUCRA) showed that direct oral anticoagulants (DOACs) were the best intervention. In terms of major bleeding, unfractionated heparin (UFH) had a higher risk than LMWH, physiotherapy, and no treatment, with statistically significant differences. The SUCRA analysis indicated that physiotherapy was the best intervention for major bleeding.ConclusionExisting evidence suggests that DOACs can provide better thromboprophylaxis efficacy for patients after abdominal and pelvic cancer surgery, achieving an optimal balance between efficacy and safety. LMWH has become an intervention with efficacy second only to DOACs, with similar safety.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024513090.

Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant tumor of vascular origin. It may be confusing as its manifestations of multifocal lesions on imaging and epithelial histomorphology in pathology. EHE is easy to be mistaken for a metastatic tumor by radiologists and clinicians. Correct diagnosis and therapy are important owing to the variable clinical course and special treatment. EHEs harbor major CAMTA1 rearrangement and

BackgroundThe current guideline recommended the use of intravenous thrombolysis (IVT) before Endovascular thrombectomy (EVT), but the effectiveness and safety of tenecteplase compare to alteplase in patients before EVT remain uncertain.MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane Library to identify eligible articles from inception until September 16, 2023. The primary outcome was functional independence (mRS 0–2) at 90 days. Secondary outcomes included excellent outcome (mRS 0–1) at 90 days, all-cause mortality at follow-up, successful reperfusion (TICI 2b–3) after the end of EVT, symptomatic intracranial hemorrhage (sICH) or any intracranial hemorrhage (aICH). The PROSPERO registration number is CRD42023470419.ResultsEight randomized controlled trials (RCTs) were included involving 2,836 acute ischemic stroke (AIS) patients. Compared to EVT alone, tenecteplase (0.25 mg/kg and 0.4 mg/kg) + EVT and 0.9 mg/kg alteplase + EVT were significant difference associated with higher successful reperfusion (TICI 2b–3) after the end of EVT (RR = 2.31; 95% CI 1.15–4.63; RR = 2.31; 95% CI 1.00–5.33; RR = 1.05; 95% CI 1.01–1.09). And compared to 0.25 mg/kg tenecteplase + EVT, alteplase (0.6 mg/kg and 0.9 mg/kg) + EVT were significant difference associated with lower successful reperfusion (TICI 2b–3) after the end of EVT (RR = 0.45; 95% CI 0.22–0.90; RR = 0.45; 95% CI 0.23–0.91). The risk of aICH (RR = 1.50; 95% CI 1.07–2.09) was significantly higher for 0.6 mg/kg alteplase + EVT than EVT alone. There was no significant difference in functional independence (mRS 0–2), excellent outcome (mRS 0–1), all-cause mortality or sICH among the different IVT strategies (0.25 mg/kg or 0.4 mg/kg tenecteplase and 0.6 mg/kg or 0.9 mg/kg alteplase) before EVT.ConclusionThe use of alteplase before EVT may potentially improve the successful reperfusion after EVT compared to tenecteplase. Due to the insufficient sample size, more high-quality RCTs are needed to confirm effectiveness and safety of tenecteplase compare to alteplase in patients before EVT.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42023470419.

This study attempted to solve the waste of soybean dregs resources problem and the limited scale production of moldy Meitauza to achieve the high-value utilization of soybean dregs. The traditional fermented Meitauza of Hubei Xianning were used as the material for microbial isolation and identification. A total of 5 bacteria and 3 fungi were obtained, named J1~J8, respectively. The morphological observation, physiological and biochemical analysis, 16S rRNA and ITS sequencing analysis revealed that J1~J5 were Rahnella aquatilis strain B13, Pediococcus pentosaceus strain S1, Pantoea agglomerans strain NSD, Leuconostoc mesenteroides strain 2020GS202 and Bacillus subtilis strain A10, respectively, while J6~J8 were respectively Fusarium proliferatum strain CanR-8, Aspergillus niger strain DZ-4-3-1, and Mucor racemosus f. racemosus strain M-22. In addition, the enzyme-producing ability determination of 8 strains showed that Bacillus subtilis (J5) had strong ability to produce protease and cellulase, reaching 153.247 and 66.552 U/mL, respectively, compared to others strains. The study also found that Bacillus subtilis, Mucor racemosa, and Aspergillus niger might be the main fermentative strains for nutrition and flavor of the traditional Meitauza.

With the semi-finished and finished products of pickled and dried mustard in Ningbo as experimental materials, the dominant bacteria strains were isolated by ten-fold dilution method. The results showed that seven and three bacteria were obtained from the semi-finished and finished products, respectively, which were named as strain MGCB1~MGCB7 and strain MGC1~MGC3. The ten strains were identified by morphological observation, physiological and biochemical tests, and 16S rRNA sequence analysis. They were likely belong to Bacillus subtilis (MGCB1), Bacillus aerius (MGCB2), Bacillus altitudinis (MGCB3), Bacillus pumilus (MGCB4), Staphylococcus succinus (MGCB5), Staphylococcus succinus (MGCB6) and Bacillus amyloliquefaciens (MGCB7), Bacillus sp. (MGC1), Virgibacillus halodenitrificans (MGC2), and Cytobacillus gottheilii (MGC3), respectively. The protease activities of MGCB1 and MGCB7 were 16.39±0.79 and 13.45±0.46 U/mL, and the cellulase activities of MGCB1 and MGCB7 were 3.27±0.13 and 1.60±0.02 U/mL, respectively, after cultured at 37 ℃ for 96 h. These findings provide a useful reference for developing appropriate starter cultures to improve the quality of traditional pickled and dried mustard.

In order to explore and utilize the microbial strain resources of traditional fermented soybean products, the bacterial diversity of five traditional fermented soybean products (natto, douche, soybean paste, meitauza, tempeh) from different regions were analyzed by using Illumina Miseq high-throughput sequencing technology. The results showed that the total bacteria count of 5 products were at 7.0~10.1 lg (CFU/g). There were 58 genera whose relative abundance was more than 1% in 5 products. Among them, the dominant bacteria with relative abundance more than 10% were Bacillus, Virgibacillus, Proteus, Ignatzschineria, Tetragenococcus, Pseudomonas, Acinetobacter, Ureibacillus, Pantoea and Pediococcus. Principal component analysis and cluster analysis showed that the microbial community structure of Natto 1, Natto 2 and Douchi 1 were similar, Meitauza 1 and Meitauza 2 were similar, and Meitauza 3 and Soybean paste 1 were similar, however, Tempeh 1 was significantly different from the other 4 products. This study would provide a theoretical basis for the exploitation and industrial utilization of microbial resources in traditional fermented soybean products.

Abstract This study investigated the factors influencing intravenous methylprednisolone pulse (IVMP) therapy for recovering visual acuity in Chinese patients with aquaporin-4 (AQP4) antibody-seropositive neuromyelitis optica-related optic neuritis (NMO-ON). This retrospective case series included 243 affected eyes of 182 patients (36 male, 146 female) diagnosed with NMO-ON in the Neuro-Ophthalmology Clinic of Beijing Tongren Hospital from September 2012 to September 2020. All patients with AQP4-antibody seropositivity had clinical manifestations of acute ON, excluding other diagnoses and received IVMP treatment at 500 mg/day or 1000 mg/day for 3 days. Primary outcome was the extent of improvement in logMAR visual acuity after IVMP treatment. The therapeutic influences of sex, age, baseline visual acuity, therapeutic intervals, and IVMP dose on acute NMO-ON were analysed. Chi-square tests, Mann–Whitney U-tests, Kruskal–Wallis tests, Spearman’s correlation coefficients, and multiple linear regression were used for statistical analysis. Age ranged between 7 and 80 years (median age, 44; interquartile range [IQR], 29–52) years. Among the 243 eyes, the median improvement in logMAR visual acuity was 0.3 (IQR, 0–0.9). Therapeutic efficacy of IVMP was significantly higher in female than in male patients (Z = 2.117, P = 0.034). The treatment effect gradually decreased with increase in age at onset (Rs = 0.157, P = 0.015), and visual improvement was significantly lower in patients aged > 50 years than in those ≤ 50 years (Z = 2.571, P = 0.010). When patients had low visual acuity at onset, improvements were more obvious (rho = − 0.317, P

Simultaneous localization and mapping (SLAM) is one of the crucial techniques applied in autonomous robot navigation. The majority of present popular SLAM algorithms are built within probabilistic optimization frameworks, achieving high accuracy performance at the expense of high power consumption and latency. In contrast to robots, animals are born with the capability to efficiently and robustly navigate in nature, and bionic SLAM algorithms have received increasing attention recently. Current bionic SLAM algorithms, including RatSLAM, with relatively low accuracy and robustness, tend to fail in certain challenging environments. In order to design a bionic SLAM system with a novel framework and relatively high practicality, and to facilitate the development of bionic SLAM research, in this paper we present LFVB-BioSLAM, a bionic SLAM system with a light-weight LiDAR-based front end and a bio-inspired vision-based back end. We adopt a range flow-based LiDAR odometry as the front end of the SLAM system, providing the odometry estimation for the back end, and we propose a biologically-inspired back end processing algorithm based on the monocular RGB camera, performing loop closure detection and path integration. Our method is verified through real-world experiments, and the results show that LFVB-BioSLAM outperforms RatSLAM, a vision-based bionic SLAM algorithm, and RF2O, a laser-based horizontal planar odometry algorithm, in terms of accuracy and robustness.

BackgroundPembrolizumab and cemiplimab have been approved as treatment for advanced non-small-cell lung cancer (NSCLC) with high programmed death ligand-1 (PD-L1) expression. This study aimed to evaluate the cost-effectiveness of pembrolizumab compared with that of cemiplimab in the treatment of advanced NSCLC with high PD-L1 expression from a societal perspective in the United States.Materials and methodsCost-effectiveness analysis integration of the network meta-analysis framework was performed using data from the EMPOWER-Lung 1, KEYNOTE 024, and KEYNOTE 042 phase 3 randomized clinical trials. A network meta-analysis including 2289 patients was constructed, and the Markov and partitioned survival (PS) models were used to assess the cost-effectiveness of pembrolizumab compared with that of cemiplimab for the treatment of high PD-L1 expression (≥50% of tumor cells). The time horizon was 10 years. The main outcomes were overall costs, incremental cost-effectiveness ratios (ICERs), quality-adjusted life-years (QALYs), life-years, incremental net health benefits (INHB), and incremental net monetary benefits (INMB). The robustness of the model was verified using one-way and probabilistic sensitivity analyses, and subgroup analyses were conducted.ResultsTreatment of advanced NSCLC with high PD-L1 expression with pembrolizumab achieved 0.093 QALYs and was associated with an incremental cost of $10,657 compared with cemiplimab, yielding an ICER of $114,246/QALY. The ICER in the PS model was similar to that in the Markov model, with a difference of $3,093/QALY. At a willingness-to-pay (WTP) threshold of $100,000/QALY, INHB, and INMB of pembrolizumab were -0.013 QALYs and -$1,329, respectively, and the probability of cemiplimab was 51% when compared with pembrolizumab. When the WTP threshold increased to $150,000/QALY, the INHB and INMB of pembrolizumab were 0.022 QALYs and $3,335, respectively, and the probability of pembrolizumab was 51.85%. One-way sensitivity analysis indicated that the models were sensitive to pembrolizumab and cemiplimab costs. Subgroup analysis revealed that treatment with pembrolizumab was related to a higher INHB in several subgroups, including patients with brain metastases at baseline.ConclusionOur findings suggest that the WTP threshold should be considered when choosing between cemiplimab and pembrolizumab to treat advanced NSCLC with high PD-L1 expression. Reducing the cost of pembrolizumab may lead to valuable outcomes.

Background: The study aimed to report a boy with familial exudative vitreoretinopathy and amblyopia harboring a new mutation of the LRP5 and OPA1 gene abnormality.Case presentation: A 9-year-old boy presented with a 2-year history of deteriorating visual acuity in the right eye. His best-corrected visual acuity was −7.00/−1.75 × 100 = 0.3 in the right eye and −2.50/−1.50 × 170 = 0.8 in the left eye. Two autosomal dominant gene mutation sites were identified in the patient: LRP5 (c.2551C > T, p.His851Tyr) from his father and OPA1 (c.565G > A, p.Glu189Lys) from his mother. Interestingly, his fraternal twin brother harbored no abnormal gene mutations, and his eye tests were normal.Conclusion: This case expands the spectrum of LRP5 gene mutations among Chinese patients with familial exudative vitreoretinopathy, and it is the first time to report a patient harboring both LRP5 and OPA1 gene mutations having anisometropic amblyopia and strabismus as the primary manifestations. These four family members exhibited individual heterogeneity of phenotypes and genotypes associated with hereditary ophthalmopathy. A comprehensive analysis of clinical phenotypes and genotypes provides clinical clues for improving the level of clinical and genetic diagnoses and a deeper understanding of the disease.

Objective: Nivolumab improves overall survival (OS) and is associated with fewer adverse events than sorafenib for the treatment of advanced hepatocellular carcinoma (aHCC). However, the cost-effectiveness of nivolumab compared with sorafenib treatment for aHCC remains unclear. This study evaluated the cost-effectiveness of nivolumab and sorafenib in the treatment of aHCC.Materials and methods: A partitioned survival model that included three mutually exclusive health states was used to evaluate the cost-effectiveness of nivolumab and sorafenib for treating aHCC. The clinical characteristics and outcomes of the patients in the model were obtained from the CheckMate 459. We performed deterministic one-way sensitivity and probabilistic sensitivity analyses to evaluate the robustness of the model. Subgroup analyses were also performed. Costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were measured.Results: The base case analysis showed that compared with sorafenib, treatment with nivolumab was associated with an increment of 0.50 (2.45 vs. 1.95) life-years and an increment of 0.32 (1.59 vs. 1.27) QALYs, as well as a $69,762 increase in cost per patient. The ICER was $220,864/QALY. The INHB and INMB were −0.15 QALYs and −$22,362 at a willingness-to-pay (WTP) threshold of $150,000/QALY, respectively. The probabilistic sensitivity analysis demonstrated that the probability of nivolumab being cost-effective was only 10.38% at a WTP threshold of $150,000/QALY. The model was most sensitive to the costs of sorafenib and nivolumab according to the one-way sensitivity analysis. When the price of sorafenib exceeded $0.93/mg or nivolumab was less than $24.23/mg, nivolumab was more cost-effective. The subgroup analysis illustrated that the probability of cost-effectiveness was >50% in the Barcelona Clinic Liver Cancer Stage B subgroups for nivolumab at a WTP threshold of $150,000/QALY. This study also showed that the probability of cost-effectiveness was

Context Aidi injection is one of the most commonly use antitumor Chinese medicine injections for advanced non-small cell lung cancer (NSCLC). It is made from the extraction of Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. Objective To evaluate the efficacy and safety of Aidi injection in combination with gemcitabine-based chemotherapy (GBC) for advanced NSCLC. Materials and methods PubMed, Embase, Cochrane Library, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and VIP were searched for relevant randomised controlled trials (RCTs) comparing Aidi injection plus GBC treatment with GBC alone in NSCLC, from inception up to October 2020. The primary outcomes were objective response rate (ORR), and disease control rate (DCR). Secondary outcomes were quality of life (QOL) and adverse drug reactions (ADRs). The quality of evidence was rated using the GRADE approach. This study was registered with PROSPERO: CRD42021221225. Results In total, 54 RCTs involving 4318 NSCLC patients were included in this meta-analysis. Compared with GBC alone, Aidi injection plus GBC significantly improve ORR (risk ratios [RR] = 1.38, 95% confidence interval [CI] 1.29–1.48), DCR (RR = 1.15, 95% CI 1.12–1.19), QOL (RR = 1.71, 95% CI 1.54–1.89), and reduced the risk of gastrointestinal toxicity, thrombocytopenia, neutropenia, liver injury, renal injury, and anaemia. The evaluation results of the evidence ranged from moderate to low. Conclusions Current moderate evidence revealed that Aidi injection as an adjunctive treatment to GBC was associated with superior benefits in patients with advanced NSCLC and alleviate toxicities. High-quality RCTs are needed to further confirm the results.

Background: Considering the extensive exploration of Chinese herbal injections (CHIs) and the limitations of paclitaxel-based chemotherapy (TBC) for non-small cell lung cancer (NSCLC), systematically and critically evaluating the efficacy and safety of CHIs combination with TBC in the treatment of NSCLC is necessary. Purpose: To investigate the combined efficacy and safety of CHIs plus TBC on patients with advanced NSCLC. Methods: The databases PubMed, Embase, Medline, Cochrane Library, CINAHL, China Biology Medicine disc, Wanfang, VIP, and China National Knowledge Infrastructure were systematically searched from their inception to Oct. 15, 2020. We selected randomized controlled trials (RCTs) regarding CHIs plus TBC to treat NSCLC. The methodological quality of included studies was evaluated based on the Cochrane risk-of-bias tool. Data synthesis was performed by WinBUGS 14.0 software and meta packages implemented in R 3.6.2 software. Random-effects network meta-analysis was performed and dichotomous data were expressed as odds ratios (ORs) with their 95% confidence intervals. The surface under the cumulative ranking curve probability values was used to rank the efficacy and safety of CHIs. The objective response rate (ORR) and disease control rate (DCR) was defined as the primary outcomes, and the secondary endpoints were quality of life (QOL) and adverse drug reactions (ADRs). Results: Ninety-three RCTs recruiting 6626 advanced NSCLC patients were included and 7 types of CHIs were evaluated. Compared to TBC alone, CHIs plus TBC can significantly improve ORR, DCR, and QOL; and reduce the risk of neutropenia, thrombocytopenia, anemia, nausea and vomit, and liver injury. Multidimensional cluster analysis results demonstrated that Huachansu injection (HCS) plus TBC and Xiaoaiping injection (XAP) plus TBC were preferable improvements on ORR, DCR, and QOL, as well as a decrease in the risk of ADRs, compare with other types of CHIs. Conclusions: Current moderate evidence revealed that CHIs plus TBC showed significantly higher efficacy and lower risk of ADRs for advance NSCLC patients than TBC alone. Thereinto, HCS plus TBC and XAP plus TBC were related to higher rank probabilities considering the efficacy and safety. High-quality RCTs with longer follow-ups are urgently needed to confirm the results further.

Objective: This study aims to construct a systematic mRNA-miRNA-lncRNA network to identify novel lncRNAs and miRNAs biomarkers for laryngeal squamous cell carcinoma (LSCC). Methods: The mRNA, miRNA and lncRNA expression profiles of LSCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were screened between LSCC tissues and controls. Functional analysis of DEmRNAs, DEmRNAs targeted by DEmiRNAs and DEmRNAs targeted by DElncRNAs were respectively performed. The miRWalk, starbase and DIANA-LncBase were respectively used to predict DEmiRNAs-DEmRNAs, DElncRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. ceRNA network was built by DEmiRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. LncRNA subcellular localization was predicted using lncLocator. Using published The Cancer Genome Atlas (TCGA) and external datasets (GSE127165 and GSE133632), we also validated the expression of key DElncRNAs and DEmiRNAs in ceRNA network. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively. Results: There were 5 mRNA datasets, 3 miRNA datasets and 2 lncRNA datasets in this study. Totally, 2957 DEmRNAs, 61 DElncRNAs and 23 DEmiRNAs were identified. Functional analysis of DEmRNAs shows that they were significantly enriched in cancer-related pathways, such as DNA replication and extracellular matrix organization. There were 11 DEmiRNAs, 17 DElncRNAs and 967 DEmRNAs in the ceRNA network. Notably, up-regulated lncRNA DGCR5-down-regulated has-miR-338-3p/has-miR-139-5p pairs in this network were experimentally validated. Moreover, down-regulated AL121839.2, down-regulated LINC02147, up-regulated AC079328.2, up-regulated AC004943.2 and up-regulated HMGA2-AS1 were located in the cytoplasm. AL121839.2 and LINC02147 interacted with has-miR-1246. AC004943.2, AC079328.2 and HMGA2-AS1 targeted has-miR-3185, has-miR-3137 and has-miR-582-5p, respectively. Based on the TCGA and external datasets (GSE127165 and GSE133632), DGCR5 and AC004943.2 were significantly up-regulated while AL121839.2 and LINC02147, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p were significantly down-regulated, which were consistent with our integration analysis. DGCR5, AL121839.2, LINC02147, AC004943.2, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p could predict the occurrence of LSCC. Survival analysis suggested that only, AL121839.2 has potential prognostic value for LSCC. Conclusion: This study provided novel insights into the ceRNA network and uncovered novel lncRNAs and miRNAs with diagnostic value in LSCC.

It is well accepted that low-dose ionizing radiation (LDIR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Alterations in messenger RNA (mRNA) and long noncoding RNA (lncRNA) expression were to crucially underlie these LDIR responses. However, lncRNAs in LDIR-induced immune responses have been rarely reported, and its functions and molecular mechanisms have not yet been characterized. Here, we used microarray profiling to determine lncRNA in BALB/c mice exposed to single (0.5 Gy×1) and chronic (0.05 Gy×10) low-dose γ-rays radiation (Co 60 ). We observed that a total of 8274 lncRNAs and 7240 mRNAs were altered in single LDIR, while 2077 lncRNAs and 796 mRNAs in chronic LDIR. The biological functions of these upregulated mRNAs in both 2 groups using Gene Ontology functional and pathway enrichment analysis were significantly enriched in immune processes and immune signaling pathways. Subsequently, we screened out the lncRNAs involved in regulating these immune signaling pathways and examined their potential functions by lncRNAs-mRNAs coexpression networks. This is the first study to comprehensively identify lncRNAs in single and chronic LDIR responses and to demonstrate the involvement of different lncRNA expression patterns in LDIR-induced immune signaling pathways. Further systematic research on these lncRNAs will provide new insights into our understanding of LDIR-modulated immune hormesis responses.

Background: Pembrolizumab and cemiplimab have been approved as treatment for advanced non-small-cell lung cancer (NSCLC) with high programmed death ligand-1 (PD-L1) expression. This study aimed to evaluate the cost-effectiveness of pembrolizumab compared with that of cemiplimab in the treatment of advanced NSCLC with high PD-L1 expression from a societal perspective in the United States. Materials and methods: Cost-effectiveness analysis integration of the network meta-analysis framework was performed using data from the EMPOWER-Lung 1, KEYNOTE 024, and KEYNOTE 042 phase 3 randomized clinical trials. A network meta-analysis including 2289 patients was constructed, and the Markov and partitioned survival (PS) models were used to assess the costeffectiveness of pembrolizumab compared with that of cemiplimab for the treatment of high PD-L1 expression (=50% of tumor cells). The time horizon was 10 years. The main outcomes were overall costs, incremental costeffectiveness ratios (ICERs), quality-adjusted life-years (QALYs), life-years, incremental net health benefits (INHB), and incremental net monetary benefits (INMB). The robustness of the model was verified using one-way and probabilistic sensitivity analyses, and subgroup analyses were conducted. Results: Treatment of advanced NSCLC with high PD-L1 expression with pembrolizumab achieved 0.093 QALYs and was associated with an incremental cost of $10,657 compared with cemiplimab, yielding an ICER of $114,246/QALY. The ICER in the PS model was similar to that in the Markov model, with a difference of $3,093/QALY. At a willingness-to-pay (WTP) threshold of $100,000/QALY, INHB, and INMB of pembrolizumab were -0.013 QALYs and -$1,329, respectively, and the probability of cemiplimab was 51% when compared with pembrolizumab. When the WTP threshold increased to $150,000/QALY, the INHB and INMB of pembrolizumab were 0.022 QALYs and $3,335, respectively, and the probability of pembrolizumab was 51.85%. Oneway sensitivity analysis indicated that the models were sensitive to pembrolizumab and cemiplimab costs. Subgroup analysis revealed that treatment with pembrolizumab was related to a higher INHB in several subgroups, including patients with brain metastases at baseline. Conclusion: Our findings suggest that the WTP threshold should be considered when choosing between cemiplimab and pembrolizumab to treat advanced NSCLC with high PD-L1 expression. Reducing the cost of pembrolizumab may lead to valuable outcomes. [ABSTRACT FROM AUTHOR]