Guaranteed minimum withdrawal benefits with high-water mark fee structure.

The Guaranteed Minimum Withdrawal Benefit (GMWB), an adjunct incorporated within variable annuities, commits to reimbursing the entire initial investment regardless of the performance of the underlying funds. While extensive research exists in financial and actuarial literature regarding the modeling and valuation techniques of GMWBs, much of it is founded on a static fee structure. Our study introduces an innovative fee structure based on the high-water mark (HWM) principle and a regime-switch jump-diffusion model for the pricing of GMWBs, employing numerical solutions through the Monte Carlo method for solving the stochastic differential equation (SDE). Furthermore, a companion piece of research addresses the risk management of GMWBs within the same analytical framework as the pricing component, an aspect that has received limited attention in the existing literature. In assessing the necessary capital reserves for unforeseen losses, our methodology involves the computation of two risk metrics associated with the tail distribution of net liability from the insurer's perspective, Value-at-Risk (VaR) and Conditional-Tail-Expectation (CTE). Comprehensive numerical results and sensitivity analyses are also provided.

The prevalence and possible risk factors of gaming disorder among adolescents in China.

BACKGROUND: Nowadays, moderate gaming behaviors can be a pleasant and relaxing experiences among adolescents. However, excessive gaming behavior may lead to gaming disorder (GD) that disruption of normal daily life. Understanding the possible risk factors of this emerging problem would help to suggest effective at preventing and intervening. This study aimed to investigate the prevalence of GD and analyze its possible risk factors that adolescents with GD. METHODS: Data were collected between October 2020 and January 2021. In total, a sample of 7901 students (4080 (52%) boys, 3742 (48%) girls; aged 12-18 years) completed questionnaires regarding the Gaming-Related Behaviors Survey, Gaming Disorder Symptom Questionnaire-21 (GDSQ-21); Behavioral Inhibition System and Behavioral Activation System Scale (BIS/BAS Scale); Emotion Regulation Questionnaire (ERQ); Short-form Egna Minnenav Barndoms Uppfostran for Chinese (s-EMBU-C); and Adolescent Self-Rating Life Events Checklist (ASLEC). RESULTS: The prevalence of GD was 2.27% in this adolescent sample. The GD gamers were a little bit older (i.e., a higher proportion of senior grades), more boys, with more gaming hours per week in the last 12 months, with more reward responsiveness, maternal rejecting and occurrence of negative life events (e.g., interpersonal relationships, being punished and bereavement factors). CONCLUSION: These possible risk factors may influence the onset of GD. Future research in clinical, public health, education and other fields should focus on these aspects for provide target prevention and early intervention strategies.

Compound prebiotics as prophylactic and adjunctive treatments ameliorate DSS-induced colitis through gut microbiota modulation effects.

The prophylactic and adjunctive impacts of compound prebiotics (CP), comprising galacto-oligosaccharides, fructo-oligosaccharides, and isomalto-oligosaccharides, on colitis remain unclear. This study aimed to elucidate the effects of CP on dextran sodium sulfate (DSS)-induced colitis via modulation of the gut microbiota. Mice received prophylactic CP (PCP) for three weeks and DSS in the second week. In the third week, therapeutic CP, mesalazine, and a combination of CP and mesalazine (CPM) were administered to mice with DSS-induced colitis. The administration of PCP and CPM was found to ameliorate colitis, as evidenced by increases in body weight and colon length, elevation of the anti-inflammatory cytokine IL-10, and reductions in the disease activity index, histological scores, and levels of pro-inflammatory cytokines in mice with DSS-induced colitis on days 14 or 21. Furthermore, an increase in the relative abundance of probiotics (Ligilactobacillus, Bifidobacterium, and Limosilactobacillus), alpha diversity indices, short-chain fatty acids (SCFA) contents, and microbial network complexity was observed following PCP or CPM treatment. Correlation analysis revealed positive associations between these probiotics and both SCFA and IL-10, and negative associations with pro-inflammatory cytokines. This study highlighted the potential of CP as novel prophylactic and adjunctive treatments for alleviating DSS-induced intestinal inflammation and maintaining gut microbiota homeostasis.

Oral delivery of probiotics using single-cell encapsulation.

Adequate intake of live probiotics is beneficial to human health and wellbeing because they can help treat or prevent a variety of health conditions. However, the viability of probiotics is reduced by the harsh environments they experience during passage through the human gastrointestinal tract (GIT). Consequently, the oral delivery of viable probiotics is a significant challenge. Probiotic encapsulation provides a potential solution to this problem. However, the production methods used to create conventional encapsulation technologies often damage probiotics. Moreover, the delivery systems produced often do not have the required physicochemical attributes or robustness for food applications. Single-cell encapsulation is based on forming a protective coating around a single probiotic cell. These coatings may be biofilms or biopolymer layers designed to protect the probiotic from the harsh gastrointestinal environment, enhance their colonization, and introduce additional beneficial functions. This article reviews the factors affecting the oral delivery of probiotics, analyses the shortcomings of existing encapsulation technologies, and highlights the potential advantages of single-cell encapsulation. It also reviews the various approaches available for single-cell encapsulation of probiotics, including their implementation and the characteristics of the delivery systems they produce. In addition, the mechanisms by which single-cell encapsulation can improve the oral bioavailability and health benefits of probiotics are described. Moreover, the benefits, limitations, and safety issues of probiotic single-cell encapsulation technology for applications in food and beverages are analyzed. Finally, future directions and potential challenges to the widespread adoption of single-cell encapsulation of probiotics are highlighted.

Identification of a novel LFNG variant in a Chinese fetus with spondylocostal dysostosis and a systematic review.

Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.

[Genetic background of lily germplasm resources based on SSR markers].

To study the genetic background of lily (Lilium spp.) germplasm resources, and accurately evaluate and select excellent germplasm for genetic improvement of lily, we analyzed the genetic background of 62 lily germplasm accessions from 11 provinces of China by using simple sequence repeat (SSR) molecular markers. The results showed that 15 out of 83 pairs of lily SSR primers were polymorphic. A total of 157 allelic loci were amplified, with the number of alleles per locus ranging from 5 to 19 and the average number of effective alleles per locus being 4.162 8. The average observed heterozygosity and expected heterozygosity were 0.228 2 and 0.694 1, respectively. The average polymorphic information content was 0.678 8. The average Nei's diversity index and Shannon's information index were 0.694 1 and 1.594 9, respectively, indicating that the tested lily germplasm had high genetic diversity. The 62 germplasm accessions were classified into 5 groups by the unweighted pair group method with arithmetic mean (UPGMA) and into 3 groups by the principal component analysis. The two analyses revealed a geographic correlation among different groups. The majority of lily germplasm accessions from the same source tended to cluster together. The population structure analysis classified the lily accessions into 4 populations and 1 mixed population. The above results provide a theoretical basis and genetic resources for the precise identification and breeding of lily germplasm resources.

An RRM domain protein SOE suppresses transgene silencing in rice.

Gene expression is regulated at multiple levels, including RNA processing and DNA methylation/demethylation. How these regulations are controlled remains unclear. Here, through analysis of a suppressor for the OsEIN2 over-expressor, we identified an RNA recognition motif protein SUPPRESSOR OF EIN2 (SOE). SOE is localized in nuclear speckles and interacts with several components of the spliceosome. We find SOE associates with hundreds of targets and directly binds to a DNA glycosylase gene DNG701 pre-mRNA for efficient splicing and stabilization, allowing for subsequent DNG701-mediated DNA demethylation of the transgene promoter for proper gene expression. The V81M substitution in the suppressor mutant protein mSOE impaired its protein stability and binding activity to DNG701 pre-mRNA, leading to transgene silencing. SOE mutation enhances grain size and yield. Haplotype analysis in c. 3000 rice accessions reveals that the haplotype 1 (Hap 1) promoter is associated with high 1000-grain weight, and most of the japonica accessions, but not indica ones, have the Hap 1 elite allele. Our study discovers a novel mechanism for the regulation of gene expression and provides an elite allele for the promotion of yield potentials in rice.

USP40 promotes hepatocellular carcinoma progression through a YAP/USP40 positive feedback loop.

Yes-associated protein (YAP) is an essential driver of hepatocellular carcinoma (HCC) progression and the ubiquitin-proteasome system controls its abundance. However, the role of ubiquitin-specific protease 40 (USP40) in YAP stability remains unclear. Here, USP40 was first identified as a novel regulator of YAP abundance and its target genes in HCC cells. USP40 interacted with YAP to remove the lysine 48 (K48)-linked polyubiquitination of YAP at K252 and K315 sites, thereby maintaining YAP stability. USP40 facilitated the proliferation, colony formation, migration and spheroid formation of HCC cells in vitro and promoted HCC growth in vivo in a YAP-dependent manner. In turn, YAP transcriptionally activated USP40 expression in HCC cells. RNA sequencing analysis showed that about 37% of USP40-regulated genes overlapped with YAP-regulated genes. Interestingly, stiffness-induced USP40 upregulation was abolished by YAP knockdown, and USP40 knockdown attenuated stiffness-induced YAP accumulation in HCC cells. Clinical data demonstrated that USP40 was positively associated with YAP expression in HCC tissues and its high expression indicated a poor prognosis. In conclusion, the USP40/YAP positive feedback loop contributes to HCC progression, suggesting that USP40 may be a promising drug target for anti-HCC.

Tailless Information-Energy Metasurface.

Programmable metasurface technology can achieve flexible manipulations of electromagnetic waves in real time by adjusting the surface structure and material properties and has shown extraordinary potential in many fields such as wireless communications and the Internet of Things. However, most of the programmable metasurfaces have a common feature: a tail (electrical wires and DC powers), which is difficult to supply in some particular application scenarios such as canyons and mountains. To eliminate the limitation of DC power supply, the programmable metasurface and wireless power transfer technology are combined to propose a tailless information-energy metasurface (IEMS). The tailless IEMS platform can dynamically control electromagnetic waves without relying on an external DC power supply; instead, the required DC power is provided internally by the IEMS platform itself. In the tailless IEMS experiments, the concept is demonstrated through the dynamic regulation of wireless channels and the wireless transmission of DC power. This work provides a self-powered method for programmable metasurfaces, expands the application scenarios, facilitates the miniaturization of systems, and makes it easy to integrate with other systems.

Multimodal non-invasive evaluation in MRI-negative epilepsy patients.

Presurgical evaluation is still challenging for MRI-negative epilepsy patients. As non-invasive modalities are the easiest acceptable and economic methods in determining the epileptogenic zone, we analyzed the localization value of common non-invasive methods in MRI-negative epilepsy patients. In this study, we included epilepsy patients undergoing presurgical evaluation with presurgical negative MRI. MRI post-processing was performed using a Morphometric Analysis Program (MAP) on T1-weighted volumetric MRI. The relationship between MAP, magnetoencephalography (MEG), scalp electroencephalogram (EEG), and seizure outcomes was analyzed to figure out the localization value of different non-invasive methods. Eighty-six patients were included in this study. Complete resection of the MAP-positive regions or the MEG-positive regions was positively associated with seizure freedom (p = 0.028 and 0.007, respectively). When an area is co-localized by MAP and MEG, the resection of the area was significantly associated with seizure freedom (p = 0.006). However, neither the EEG lateralization nor the EEG localization showed statistical association with the surgical outcome (p = 0.683 and 0.505, respectively). In conclusion, scalp EEG had a limited role in presurgical localization and predicting seizure outcome, combining MAP and MEG results can significantly improve the localization of epileptogenic lesions and have a positive association with seizure-free outcome. PLAIN LANGUAGE SUMMARY: Due to the lack of obvious structure abnormalities on neuroimaging examinations, the identification of epilepsy lesions in MRI-negative epilepsy patients can be difficult. In this study, we intended to use non-invasive examinations to explore the potential epileptic lesions in MRI-negative epilepsy patients and to determine the results accuracy by comparing the neuroimaging results with the epilepsy surgery outcomes. A total of 86 epilepsy patients without obvious structure lesions on MRI were included, and we found that the combinations of different non-invasive examinations and neuroimaging post-processing methods are significantly associated with the seizure freedom results of epilepsy surgery.

Quantitative ultrasound parameters from scattering and propagation may reduce the biopsy rate for breast tumor.

Breast cancer has become the most common cancer worldwide, and early screening improves the patient's survival rate significantly. Although pathology with needle-based biopsy is the gold standard for breast cancer diagnosis, it is invasive, painful, and expensive. Meanwhile it makes patients suffer from misplacement of the needle, resulting in misdiagnosis and further assessment. Ultrasound imaging is non-invasive and real-time, however, benign and malignant tumors are hard to differentiate in grayscale B-mode images. We hypothesis that breast tumors exhibit characteristic properties, which generates distinctive spectral patterns not only in scattering, but also during propagation. In this paper, we propose a breast tumor classification method that evaluates the spectral pattern of the tissues both inside the tumor and beneath it. First, quantitative ultrasonic parameters of these spectral patterns were calculated as the representation of the corresponding tissues. Second, parameters were classified by the K-Nearest Neighbor machine learning model. This method was verified with an open access dataset as a reference, and applied to our own dataset to evaluate the potential for tumors assessment. With both datasets, the proposed method demonstrates accurate classification of the tumors, which potentially makes it unnecessary for certain patients to take the biopsy, reducing the rate of the painful and expensive procedure.

Digital Adoption levels and income generation in rural households in China.

With the increasing digital transformation of rural industries, the digital economy is considered a new driving force for consolidating the achievements of eradicating poverty and comprehensively promoting rural revitalization. This study constructs a multidimensional index to measure the digital application level of rural households based on microsurvey data and empirically investigates the economic returns and mechanism of its effects. The results show that digital application significantly improves the economic situation of households. For every 1 unit increase in the level of digital application, per capita net income of households will increase by 0.427 units, and the relative poverty incidence will decrease by 0.421 units. Mechanism analysis shows that the level of digital application in rural households can significantly improve the technical abilities of household members, promote non-agricultural employment, and increase the share of agricultural and sideline business operations, thus improving the economic situation of households. Further research shows that the economic returns obtained from digitization in rural households exhibit significant regional differences. This study provides research support on how to better examine the role of the digital economy for rural households to generate wealth and increase income.

miR-30c-2-3p suppresses the proliferation of human renal cell carcinoma cells by targeting TOP2A.

Background: The ambiguity of renal cell carcinoma (RCC) symptoms hinders early diagnosis, thereby contributing to high mortality rates. By attaching to the 3'-untranslated region (UTR) of the target gene, microRNAs (miRNAs) exert significant control over the expression of genes. Objectives: To investigate the influence of miR-30c-2-3p and DNA topoisomerase II alpha (TOP2A) on RCC growth and the mechanisms underlying the regulation of its expression. Methods: The expression of miRNA-30c-2-3p and TOP2A in RCC cells was examined using quantitative real-time polymerase chain reaction (qRT-PCR). MiR-30c-2-3p mimics, its inhibitors, and controls, as well as TOP2A short hairpin RNA (shRNA) and controls, were used to transfect the human RCC cell lines 786-O, Caki-1, and ACHN. Additionally, the roles of miRNA-30c-2-3p and TOP2A in the growth of RCC were evaluated using the cell counting kit (CCK)-8 test, colony formation assay, apoptosis analysis, and Western blotting. Meanwhile, binding of miRNA-30c-2-3p and TOP2A was verified using dual-luciferase reporter assays and Western blotting. Results: miR-30c-2-p is underexpressed in RCC cells. Overexpression of miR-30c-2-p promotes apoptosis and inhibits proliferation of ACHN, Caki-1, and 786-O cells. miR-30c-2-3p targets TOP2A, which is elevated in RCC tissues and cells, whereas TOP2A silencing inhibits the proliferation ability of RCC cells. The miRNA-30c-2-3p inhibitor compromises TOP2A shRNA-induced apoptosis of RCC. RCC cells cotransfected with miRNA-30c-2-3p inhibitors and TOP2A shRNAs have a higher proliferation rate than those transfected with only TOP2A shRNAs. Conclusions: Collectively, our results verify that miRNA-30c-2-3p has a tumor suppressor property. miRNA-30c-2-3p inhibits the proliferation of RCC through regulation of TOP2A. The data provide a viable therapeutic target for RCC.

Advances in Extraction, Purification, and Analysis Techniques of the Main Components of Kudzu Root: A Comprehensive Review.

Kudzu root (Pueraria lobate (Willd.) Ohwi, KR) is an edible plant with rich nutritional and medicinal values. Over the past few decades, an ample variety of biological effects of Pueraria isoflavone have been evaluated. Evidence has shown that Pueraria isoflavone can play an active role in antioxidant, anti-inflammatory, anti-cancer, neuroprotection, and cardiovascular protection. Over 50 isoflavones in kudzu root have been identified, including puerarin, daidzein, daidzin, 3'-hydroxy puerarin, and genistein, each with unambiguous structures. However, the application of these isoflavones in the development of functional food and health food still depends on the extraction, purification and identification technology of Pueraria isoflavone. In recent years, many green and novel extraction, purification, and identification techniques have been developed for the preparation of Pueraria isoflavone. This review provides an updated overview of these techniques, specifically for isoflavones in KR since 2018, and also discusses and compares the advantages and disadvantages of these techniques in depth. The intention is to provide a research basis for the green and efficient extraction, purification, and identification of Pueraria isoflavone and offers investigators a valuable reference for future studies on the KR.

Research on the mechanism of promoting coordinated development of ecological well-being in rural counties through industrial transformation.

The balanced development of ecological quality and residents' well-being is an important factor in achieving sustainable economic development in rural counties. In order to promote the improvement of the coupling coordination degree between ecology and well-being in rural counties, this study explores the impact mechanism of industrial structural transformation and upgrading on the coupling of ecology and well-being in the Sichuan-Chongqing. A dual-fixed-space Durbin model is constructed to analyze the influence mechanism and spatial interaction effects of industrial transformation and upgrading on the coordination of ecology and well-being. The research indicates: (1) From 2010 to 2020, the overall coordination degree of ecology and well-being in the Sichuan-Chongqing rural counties has steadily increased, with higher coordination in the eastern region and lower coordination in the western region. The growth rate of coordination degree is faster in the east and slower in the west, with significant and increasing differences between the east and west. 2) The coupling coordination degree of ecology and well-being in the Sichuan-Chongqing rural counties has a strong positive spatial spillover effect. (3) The more reasonable the industrial structure, the higher the level of coordinated development in the local and surrounding rural counties. The higher the index of industrial advancement, the better the level of coordinated development locally, but the lower the level of coordinated development in the surrounding areas.

A translational regulator MHZ9 modulates ethylene signaling in rice.

Ethylene plays essential roles in rice growth, development and stress adaptation. Translational control of ethylene signaling remains unclear in rice. Here, through analysis of an ethylene-response mutant mhz9, we identified a glycine-tyrosine-phenylalanine (GYF) domain protein MHZ9, which positively regulates ethylene signaling at translational level in rice. MHZ9 is localized in RNA processing bodies. The C-terminal domain of MHZ9 interacts with OsEIN2, a central regulator of rice ethylene signaling, and the N-terminal domain directly binds to the OsEBF1/2 mRNAs for translational inhibition, allowing accumulation of transcription factor OsEIL1 to activate the downstream signaling. RNA-IP seq and CLIP-seq analyses reveal that MHZ9 associates with hundreds of RNAs. Ribo-seq analysis indicates that MHZ9 is required for the regulation of ~ 90% of genes translationally affected by ethylene. Our study identifies a translational regulator MHZ9, which mediates translational regulation of genes in response to ethylene, facilitating stress adaptation and trait improvement in rice.

Busulfan-induced hepatic sinusoidal endothelial cell injury: Modulatory role of pirfenidone for therapeutic purposes.

Transplantation conditioning using Busulfan has been known to cause hepatotoxicity, which has great individual differences. Some have mild symptoms like the increase of hepatic drug-metabolizing enzyme, while others may have very serious ones, like hepatic sinusoidal obstruction syndrome. However, simply controlling the exposure of Busulfan may not effectively prevent or reduce the occurrence of hepatic sinusoidal obstruction syndrome. The occurrence of hepatic sinusoid obstruction syndrome is closely related to hepatic sinusoidal endothelial cells (HSECs). The objective of this study is to investigate the potential protective effect of Pirfenidone against Busulfan-induced damage to hepatic sinusoidal endothelial cells and to preliminarily explore the mechanisms underlying this protective effect. Our results indicate that Pirfenidone has a great protective effect on the injury induced by Busulfan. In addition, Busulfan increased the relative mRNA expression of transforming growth factor-ß1 (TGF-ß1), collagen and tissue inhibitor of metalloproteinase-1 in HSECs. After pretreatment with Pirfenidone, the expression level of TGF-ß1 was down-regulated. Mechanically, Pirfenidone primarily improves liver fibrosis by inhibiting collagen formation and hepatic stellate cell activation, thereby providing a protective effect on HSECs damaged by Busulfan. Therefore, Pirfenidone may reduce the hepatotoxicity caused by transplantation conditioning regimens based on Busulfan.

Microbiome changes involves in mercaptopurine mediated anti-inflammatory response in acute lymphoblastic leukemia mice.

BACKGROUND: Inflammasome has been reported to play an important role in the pathogenesis and progression of hematologic malignancies. As one of the backbone drugs for treating acute lymphoblastic leukemia (ALL), the anti-inflammatory effect of mercaptopurine (6-MP) and the impact of gut microbiome changes caused by 6-MP on anti-inflammasome remain unclear. OBJECTIVE: We aimed to explore the association between 6-MP therapeutic effects and microbiome-involved inflammatory responses in ALL mice models. STUDY DESIGN: ALL murine model was built by i.v. injecting murine L1210 cells into DBA/2 mice (model group). Two weeks after cell injections, 6-MP was orally administrated for 14 days (6-MP group). Fecal samples of mice were collected at different time points. Cecum short-chain fatty acids (SCFAs) concentrations were determined by LC-MS/MS method. Serum cytokines were measured using a cytometric bead array. Gut microbiota composition in mice was explored using 16S rRNA gene sequencing. RESULTS: The anti-tumor effect of 6-MP was proved in ALL mice models. The levels of pro-inflammatory factors IL-6 and TNFα significantly decreased after the administration of 6-MP. Cecum contents' acetate, propionate, and butyrate levels were negatively correlated with IL-6 (correlation coefficient: acetate, -0.24; propionate, -0.26; butyrate, -0.17) and TNFα (correlation coefficient: acetate, -0.45; propionate, -0.42; butyrate, -0.31) changes. Relative abundance changes of f_Lachnospiraceae.g_ASF356 and f_Peptococcaceae.g_uncultured were in accordance with the changes of butyrate levels and opposite to the changes of pro-inflammatory levels. CONCLUSION: The anti-inflammatory response of 6-MP influenced by intestinal microbiota and its metabolites SCFAs, especially butyrate, played an essential role in improving ALL progression.

First-line immunotherapy combinations for recurrent or metastatic nasopharyngeal carcinoma: An updated network meta-analysis and cost-effectiveness analysis.

OBJECTIVES: Recently updated results of randomized clinical trials (RCTs) have confirmed that toripalimab, camrelizumab, and tislelizumab plus chemotherapy (TOGP, CAGP, and TIGP) significantly prolonged survival compared to placebo plus chemotherapy (PLGP) in the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). However, the high cost of immunotherapies imposes a huge financial burden on patients and health care systems. MATERIALS AND METHODS: RCTs estimating immunotherapies for R/M-NPC were searched. A Bayesian network meta-analysis (NMA) was carried out; the main outcomes were hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS). The cost and efficacy of four first-line therapies were evaluated using the Markov model. The main outcome in the cost-effectiveness analysis (CEA) was incremental cost-utility ratios (ICURs). The model robustness was assessed by one-way, three-way, and probabilistic sensitivity analyses. RESULTS: Three RCTs (JUPITER-02, CAPTAIN-1st, and RATIONALE-309) involving 815 patients were included in the NMA. Compared with PLGP, chemo-immunotherapies have significantly longer PFS and OS. Compared to the PLGP group, TOGP, CAGP, and TIGP groups resulted in additional costs of $48 339, $22 900, and $23 162, with additional 1.89, 0.73, and 0.960 QALYs, respectively, leading to the ICURs of $25 576/QALY, $31 370/QALY, and $31 729/QALY. Pairwise comparisons showed TOGP was the most cost-effective option among chemo-immunotherapy groups. CONCLUSION: From the Chinese payers' perspective, first-line immunotherapy combination therapies provided significant survival and cost-effectiveness superiority over chemotherapy alone for patients with R/M-NPC at the WTP of $38 029/QALY. Among the three chemo-immunotherapy groups, TOGP was the most cost-effective option.