Bibliometric Analysis of Brain Stimulation Technologies in Sleep Disorders.

BACKGROUND Sleep disorders are a common disease faced by people today and can lead to fatigue, lack of concentration, impaired memory, and even death. In recent years, the development of brain stimulation techniques has provided a new perspective for the treatment of sleep disorders. However, there is a lack of bibliometric analyses related to sleep disorders and brain stimulation techniques. Therefore, this study analyzed the application status and trend of brain stimulation technology in sleep disorder research. MATERIAL AND METHODS Articles and reviews published between 1999 and 2023 were retrieved from the Web of Science. CiteSpace was used to visually analyze the publications, countries, institutions, journals, authors, references, and keywords. RESULTS A total of 459 publications were obtained. The number of studies was shown to be on a general upward trend. The country with the largest number of publications was the United States; UDICE-French Research Universities had the highest number of publications; Neurology had the highest citation frequency; 90% of the top 10 references cited were from Journal Citation Reports Q1; Brigo was the author with the highest number of publications; and the most frequent keywords were "transcranial magnetic stimulation", "deep brain stimulation", and "Parkinson disease". CONCLUSIONS Our study used CiteSpace software to analyze 459 studies published since 1999 on brain stimulation techniques for the treatment of sleep disorders, revealing research trends and the current state of the field. Our results will help researchers to understand the existing research quickly and provide direction for future research.

Distortion measurement of a lithography projection lens based on multichannel grating lateral shearing interferometry.

The optical distortion of the lithographic projection lens can reduce imaging quality and cause overlay errors in lithography, thus preventing the miniaturization of printed patterns. In this paper, we propose a technique to measure the optical distortion of a lithographic projection lens by sensing the wavefront aberrations of the lens. A multichannel dual-grating lateral shearing interferometer is used to measure the wavefront aberrations at several field points in the pupil plane simultaneously. Then, the distortion at these field points is derived according to the proportional relationship between the Z 2 and Z 3 Zernike terms (the tilt terms) and the image position shifts. Without the need for additional devices, our approach can simultaneously retrieve both the wavefront aberrations and the image distortion information. Consequently, it improves not only measurement speed and accuracy but also enables accounting for displacement stage positioning error. Experiments were conducted on a lithographic projection lens with a numerical aperture of 0.57 to verify the feasibility of the proposed method.

Revealing the optimal traditional processing methods and its protective effects against febrile seizures of Arisaema cum bile.

Arisaema cum bile (known as Dan Nanxing in Chinese, DNX) is a herbal medicine used for treating febrile seizure (FS), which commonly prepared by using Arisaematis Rhizoma and animal bile. This study was designed to explore the optimal processing time of DNX and its potential mechanism on the anti-FS effect. A total of 17 volatile organic compounds (VOCs) were the characteristic ones to distinguish different fermentation stages of DNX by using gas chromatography-ion mobility spectrometry (GC-IMS), such as 2-heptanone monomer, and heptanal monomer. DNX with fermentation for 3 months had an obvious pattern of VOCs with others, which could be regarded as the optimal fermentation time. The Enterococcus and Staphylococcus might be the core bacteria on the production of VOCs. Additionally, DNX (2.8 g/kg, p.o.) reversed hot water bath-induced FSs of rats, as indicated by increased seizure latency and decreased seizure duration time. It also prevented hippocampal neuronal loss, increased GABAAR, and decreased GRIA1 expression. At the genus level, relative abundance of Enterococcus and Akkermansia were enriched after DNX treatment. These findings suggested that fermentation for 3 months might be the optimal process time for DNX, and DNX possess an anti-FS effect through regulating neurotransmitter disorder and gut microbiota.

Carvacrol ameliorates skin allograft rejection through modulating macrophage polarization by activating the Wnt signalling pathway.

Post-transplantation immune rejection remains an important factor for transplant patients. However, conventional immunosuppressants are associated with substantial adverse effects. Natural immunosuppressants present a promising alternative to conventional counterparts, boasting exceptional biological activity, minimal toxicity and reduced side effects. We identified carvacrol as a prospective immunosuppressive agent following T cell proliferation experiment and validated carvacrol's immunosuppressive efficacy in the murine allogeneic skin graft model. T cell proliferation assay was used to screen natural small molecule compounds and the immunosuppressive effect of compounds was evaluated in MHC-mismatched murine allogeneic skin graft model. H&E and immunohistochemical staining were applied to evaluate the pathological grade. Furthermore, flow cytometry was uitlized to analyse the immunophenotype changes of immune cells. Western blotting and q-PCR were used to detect the expression of key molecules in macrophages. In vitro, carvacrol demonstrates significant inhibition of the proliferation of CD4+ T and CD8+ T cells. It notably reduces inflammatory factor expression within the allografts, suppresses T cell differentiation toward Th1 phenotype and expansion. Furthermore, carvacrol prominently hinders M1-type macrophages polarization by activating Wnt signaling. Notably, the anti-rejection efficacy of carvacrol was significantly weakened upon the removal of macrophages in mice using chlorophosphate liposomes. Carvacrol could significantly inhibit T cell proliferation, alleviate graft rejection and has outstanding toxicological safety. The molecular mechanism of the anti-rejection effect of carvacrol is closely related to its mediating activation of macrophage Wnt pathway, inhibiting M1 polarization and inducing T cell differentiation.

Graph Attention Informer for Long-Term Traffic Flow Prediction under the Impact of Sports Events.

Traffic flow prediction is one of the challenges in the development of an Intelligent Transportation System (ITS). Accurate traffic flow prediction helps to alleviate urban traffic congestion and improve urban traffic efficiency, which is crucial for promoting the synergistic development of smart transportation and smart cities. With the development of deep learning, many deep neural networks have been proposed to address this problem. However, due to the complexity of traffic maps and external factors, such as sports events, these models cannot perform well in long-term prediction. In order to enhance the accuracy and robustness of the model on long-term time series prediction, a Graph Attention Informer (GAT-Informer) structure is proposed by combining the graph attention layer and informer layer to capture the intrinsic features and external factors in spatial-temporal correlation. The external factors are represented as sports events impact factors. The GAT-Informer model was tested on real-world data collected in London, and the experimental results showed that our model has better performance in long-term traffic flow prediction compared to other baseline models.

Kaempferol inhibited invasion and metastasis of gastric cancer cells by targeting AKT/GSK3ß pathway based on network pharmacology and molecular docking.

This study aims to explore the mechanisms of the inhibitory effect of kaempferol on the invasion and metastasis of gastric cancer (GC) cells through network pharmacology prediction and experimental verification. It identifies core targets via PPI network analysis and finds that kaempferol binds to these targets well. In vitro experiments showed that kaempferol could inhibit the proliferation, colony formation, migration and invasion of GC cells. Western blotting indicated kaempferol may reduce AKT and GSK3ß phosphorylation, leading to lower expression of invasion-related genes SRC, MMP9, CXCR4, KDR, and MMP2. Overall, kaempferol may prevent migration and invasion of GC cells via the AKT/GSK3ß signaling pathway.

PANI/GO and Sm co-modified Ti/PbO2 dimensionally stable anode for highly efficient amoxicillin degradation: Performance assessment, impact parameters and degradation mechanism.

The abuse and uncontrolled discharge of antibiotics present a severe threat to environment and human health, necessitating the development of efficient and sustainable treatment technology. In this work, we employ a facile one-step electrodeposition method to prepare polyaniline/graphite oxide (PANI/GO) and samarium (Sm) co-modified Ti/PbO2 (Ti/PbO2-PANI/GO-Sm) electrode for the degradation of amoxicillin (AMX). Compared with traditional Ti/PbO2 electrode, Ti/PbO2-PANI/GO-Sm electrode exhibits more excellent oxygen evolution potential (2.63 V) and longer service life (56 h). In degradation experiment, under optimized conditions (50 mg L-1 AMX, 20 mA cm-2, pH 3, 0.050 M Na2SO4, 25 °C), Ti/PbO2-PANI/GO-Sm electrode achieves remarkable removal efficiencies of 88.76% for AMX and 79.92% for chemical oxygen demand at 90 min. In addition, trapping experiment confirms that ·OH plays a major role in the degradation process. Based on theoretical calculation and liquid chromatography-mass spectrometer results, the heterocyclic portion of AMX molecule is more susceptible to ·OH attacks. Thus, this novel electrode offers a sustainable and efficient solution to address environmental challenges posed by antibiotic-contaminated wastewater.

Distributed cyber attack detection and physical fault diagnosis for a class of interconnected large-scale systems.

In this paper we focus on the distributed cyber attack detection and physical fault diagnosis problem for a class of interconnected large-scale systems (ILSSs). In the proposed scheme, apart from node measurement, edge measurement is also used to construct distributed Kalman filter to estimate the state of each subsystem. The gain matrices of Kalman filter are determined by minimizing the covariance of estimation error in the attack-free and fault-free case, which reduces the false alarm rate of cyber attack detection and physical fault diagnosis. Based on this filter, a bank of adjacent residual generators is constructed to characterize the influence of cyber attack on the edge measurement, and the Chi-square test is used to detect whether the received edge measurements are attacked. At the same time, a local residual generator is constructed for each subsystem to characterize the influence of physical faults on it, and the residual signal is evaluated by variance and directional residual, so as to make distributed fault detection and isolation of each subsystem. It is worth noting that at each step, each subsystem first performs attack detection on the received edge measurements, and then estimates its own state using the attack-free edge measurements and node measurement, which further improves the accuracy of fault detection and isolation. In addition, a sufficient condition that ensuring the mean square exponential boundedness of the estimation error is given. Finally, the proposed scheme is verified by an illustrative example.

Exploring the Potential Mechanisms of Action of Gentiana Veitchiorum Hemsl. Extract in the Treatment of Cholestasis using UPLC-MS/MS, Systematic Network Pharmacology, and Molecular Docking.

INTRODUCTION: Gentiana veitchiorum Hemsl. (GV) has a long history in Tibetan medicine for treating hepatobiliary disease cholestasis. However, the mechanisms mediating its efficacy in treating cholestasis have yet to be determined. AIM: To elucidate the mechanisms of action of GV in the treatment of cholestasis, an integrated approach combining ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis with network pharmacology was established. MATERIALS AND METHODS: A comprehensive analysis of the chemical composition of GV was achieved by UPLC-MS/MS. Subsequently, a network pharmacology method that integrated target prediction, a protein-protein interaction (PPI) network, gene set enrichment analysis, and a component- target-pathway network was established, and finally, molecular docking and experiments in vitro were conducted to verify the predicted results. RESULTS: Twenty compounds that were extracted from GV were identified by UPLC-MS/MS analysis. Core proteins such as AKT1, TNF, and IL6 were obtained through screening in the Network pharmacology PPI network. The Kyoto Encyclopedia of the Genome (KEGG) pathway predicted that GV could treat cholestasis by acting on signaling pathways such as TNF/IL-17 / PI3K-Akt. Network pharmacology suggested that GV might exert a therapeutic effect on cholestasis by regulating the expression levels of inflammatory mediators, and the results were further confirmed by the subsequent construction of an LPS-induced RAW 264.7 cell model. CONCLUSIONS: In this study, UPLC-MS/MS analysis, network pharmacology, and experiment validation were used to explore potential mechanisms of action of GV in the treatment of cholestasis.

Temporal and Spatial Trends in HIV Positivity Rate for VCT Clinics - China, 2015-2022.

Introduction: Human immunodeficiency virus (HIV) voluntary counseling and testing (VCT) clinics play a critical role in identifying and diagnosing HIV cases. This study aimed to describe the trend of HIV positivity rate (HPR) among Chinese VCT clinics between 2015 and 2022. Methods: This study utilized data from the China Information System for Disease Control and Prevention to analyze the trend in the HPR for VCT clinics from 2015 to 2022. The HPR was calculated by dividing the number of newly-reported HIV cases by the number of HIV tests, multiplied by 100%. To identify temporal and spatial trends in the HPR, we employed joinpoint regression analysis and the Getis-Ord hotspot analysis. Results: From 2015 to 2022, VCT clinics in China performed a total of 22,075,386 HIV tests, leading to the identification of 260,353 HIV cases, resulting in a HPR of 1.18%. The HPR consistently declined over the study period, with an average annual percent change (AAPC) of -7.5% (95% confidence interval: -12.6%, -2.2%, P<0.05). The number of HPR hotspots also decreased from 41 in 2015 to 23 in 2022. These HPR hotspots were primarily located in Yunnan, Sichuan, Guangdong, and Guangxi provincial-level administrative divisions (PLADs). Among the 31 PLADs, 16 showed a significant decrease in HPR during the study period (AAPC<0, PAAPC<0.05). Conclusions: VCT clinics in China have played a significant role in identifying HIV cases. The declining HPR observed in these clinics may indicates the progress has been made in some degree in mitigating HIV among high-risk populations. Therefore, it is crucial to further improving the utilization of VCT clinics for HIV testing.

New records of Chrysochroinae Laporte de Castelnau, 1835 (Coleoptera, Buprestidae) from China.

Background: Chrysochroinae Laporte de Castelnau, 1835 is the very colourful subfamily of Buprestidae. There are 127 species and subspecies of the subfamily which have been recorded in China. New information: In this paper, we reported three genera, two subgenera and five species of the subfamily Chrysochroinae Laporte de Castelnau, 1835 (Coleoptera, Buprestidae) which are all newly recorded from China. These reported taxa belong to two tribes and four genera: Chrysochroa (Chroodema) corbetti (Kerremans, 1893), Chrysochroa (Pyranthe) fulgens ephippigera White, 1843, Demochroa (Demoxantha) gratiosa indica Csiki, 1900, Xanthocatabonvouloirii (Deyrolle, 1861) (all the above four being Chrysochroini) and Cardiaspismouhotii E. Saunders, 1866 (Dicercini). The five newly-recorded species are briefly described, illustrated and supplemented with relevant biological information.

Revision of the rare Buprestis subgenus Akiyamaia Kurosawa, 1988 (Coleoptera: Buprestidae: Buprestinae), with description of two new species.

In this paper, two new species of Buprestis subgenus Akiyamaia Kurosawa, 1988 are described: B. (A.) gengmini Qi & Song, new species from Yunnan Province, China and B. (A.) wenii Qi & Song, new species from Yen Bai Province, Vietnam. The descriptions and illustrations of two new species are provided, and the diagnostic characters are provided to distinguish the two new species from other related species. A key is given for identification of all Akiyamaia species.The holotype of B. (A.) costipennis (Fairmaire, 1891) and pictures of living individuals are illustrated for the first time.

The impact of HIV self-testing on risk behaviors among men who have sex with men: a mixed-methods study.

Background: Men who have sex with men (MSM) have a high prevalence of HIV and a low rate of HIV testing in China. HIV self-testing (HIVST) presents a viable strategy for expanding HIV testing among MSM. However, the impact of HIVST on risk behaviors among MSM remains controversial. Our study sought to ascertain this impact. Methods: From April 2021 to January 2022, a mixed-methods study was conducted in Qingdao City, employing both quantitative and qualitative methodologies. The quantitative component entailed a cohort study among MSM who had used HIVST. Generalized estimating equations fitting Poisson regressions were used to analyze the changes in risk behaviors of MSM in short time after HIVST (ST-HIVST) and longer time after HIVST (LT-HIVST) compared to before HIVST. Subsequently, we conducted in-depth interviews with 18 MSM who completed the follow-up to delve deeper into the impact of HIVST on MSM. Results: A total of 410 MSM were recruited in the cohort, of whom 83 were lost to follow-up. Compared to before HIVST, there were no significant changes in risk behaviors in ST-HIVST (p > 0.05), while the proportion of recreational drugs abuse (20.7% vs. 33.3%), commercial sex (14.6% vs. 22.9%), and unprotected anal sex (95.9% vs. 98.5%) increased significantly in LT-HIVST (p < 0.05). Specific changes varied across demographic characteristics. According to qualitative interviews, MSM might have decreased risk perception and increased risk behaviors after HIVST. Conclusion: The use of HIVST may promote MSM to engage in risk behaviors. In the future, customized HIVST promotion programs need to be developed to expand HIV testing among MSM and simultaneously control their risk behaviors.

Baicalin enhances the chemotherapy sensitivity of oxaliplatin-resistant gastric cancer cells by activating p53-mediated ferroptosis.

Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

Utilization of post-exposure prophylaxis potentially contributed to the changes of risk behaviors among men who have sex with men in China.

Background: The HIV infection status among men who have sex with men (MSM) in China is a cause for concern. Post-exposure prophylaxis (PEP) serves as a highly effective biomedical preventive measure against HIV infection. Substantial evidence has established an association between PEP utilization and risk behaviors among MSM, but whether the utilization of PEP has an impact on risk behaviors remains unknown. This study sought to elucidate the impact of PEP usage on risk behaviors among MSM and provide recommendations for developing targeted HIV prevention programs. Methods: A cohort study was conducted in Qingdao, China, from April 2021 to January 2022. Participants were enlisted by volunteers from community-based organizations through a snowball sampling method. Face-to-face interviews were conducted to collect sociodemographic and behavioral information of participants. The study encompassed a retrospective investigation, baseline survey, and follow-up survey, representing periods before, during, and after PEP usage, respectively. Generalized estimating equations, fitting a Poisson regression model, were applied to scrutinize changes in risk behaviors of MSM during and after PEP usage, in comparison to before PEP usage. Results: A total of 341 MSM were recruited in the cohort study, with 179 individuals completing the follow-up survey. In comparison to before PEP usage, there was a significant increase in the proportion of Rush Popper usage (17.6% vs. 23.8% vs. 29.6%) and commercial sexual partners (10.9% vs. 17.6% vs. 21.8%) among MSM during and after PEP usage. Before PEP usage, 88.7% of MSM reported having ≥3 temporary sexual partners in the last 6 months. This proportion exhibited no significant change during PEP usage (91.8%), but it significantly increased to 97.8% after PEP usage (P < 0.05). Notably, there was a significant decrease in group sex during and after PEP usage compared to before PEP usage (30.8% vs. 21.4% vs. 21.2%). Conclusion: The utilization of PEP may impact risk behaviors among MSM, potentially leading to increased Rush Popper usage, temporary sexual partners, and commercial sexual partners after PEP usage, accompanied by a decrease in group sex. Further research is imperative to elucidate the impact of PEP utilization on MSM and develop targeted HIV prevention programs.

How the perfectionistic climate of a sports team predicts the athletic performance of elite athletes: a case study of the CUBAL women's basketball team.

Objective: In competitive sports, understanding how the perfectionistic climate within teams influences the performance of elite female athletes can provide valuable insights for enhancing coaching practice and athletic achievement. Based on the cognitive appraisal theory of stress, this study constructs a dual-path model using stressors and coping strategies as mediators, referred to as the Perfectionistic Climate on Athletic Performance model (PCPM). The study explores the predictive role of the perfectionistic climate within sports teams on the athletic performance of elite female basketball players. Methods: The empirical study the relationships among the variables in the model using a sample of 125 core players from the top-level women's basketball teams in the 24th CUBAL24 tournament in 2022. A Structural Equation Modeling (SEM) analysis was conducted using AMOS 20.0, primarily employing the bias-corrected Bootstrap method to test the dual-path model. Results: The findings reveal double-edged paths towards a perfectionistic climate on athletic performance. In the positive pathway, a perfectionistic climate can positively predict athletic performance through challenge-related sources of stress and positive coping strategies. In the negative pathway, a perfectionistic climate can negatively predict athletic performance through threat-related sources of stress and negative coping strategies. Conclusion: Coaches need to pay attention to athletes' cognitive evaluations of the perfectionistic climate as a source of pressure. By setting challenging goals, coaches can guide athletes to view the perfectionistic climate of the sports team as a source of challenging pressure, thus unleashing their potential. Coaches should actively guide athletes in coping with the pressure brought about by the perfectionistic climate, enhancing their ability to handle stress. This will enable athletes to better adapt to the team's perfectionistic climate and further improve individual and team athletic performance.

Experimental study on the full cycle evolution of high-intensity atmospheric dc arc discharge from breakdown to extinguishment.

In this study, the spatiotemporal evolution of full cycle of high-intensity dc argon arc discharge at atmospheric pressure is investigated by using a transferred arc device, which is easy to be directly observed in the experiment. Combining the voltage and current waveforms with high-speed images, the full cycle evolution process of high-intensity atmospheric dc arc can be divided into five different stages: breakdown pulse stage, cathode heating stage, current climbing stage, stable arc discharge stage, and finally arc extinguishing stage. The characteristics of each different stage are analyzed in detail through the electrical properties, high-speed pictures, and spectroscopic measurements. The results show that the strong luminescence region develops from the vicinity of cathode and anode to the middle in the breakdown pulse stage, which is explained from the spatiotemporal evolution of distributions of excited argon atom and ions. The development velocity of emission intensity of argon ions is mainly determined by the dominant stepwise ionization process. Then the cathode heating stage appears with many bright and nonuniformly distributed light spots on the cathode surface, and the electron emission mechanism of cathode gradually changes to the thermionic emission as the surface temperature rises. With the increase of arc current, the discharge channel significantly expands, then becomes stable due to the increment of the Lorentz force. The characteristics of arc extinguishing stage are clarified in terms of the decay of charged particles density.

IRGM is a novel regulator of PD-L1 via promoting S6K1-mediated phosphorylation of YBX1 in hepatocellular carcinoma.

Immunity-related GTPase M (IRGM), an Interferon-inducible protein, functions as a pivotal immunoregulator in multiple autoimmune diseases and infection. However, the role of IRGM in hepatocellular carcinoma (HCC) development remains unveiled. Here, we found interferon-γ (IFN-γ) treatment in HCC drastically triggered the expression of IRGM, and the high level of IRGM indicated poor prognosis in HCC patients. Functionally, IRGM promoted the malignant progression of HCC. Single-cell sequencing revealed that IRGM inhibition promoted the infiltration of CD8+ cytotoxic T lymphocytes (CTLs) with significant downregulation of PD-L1 expression in HCC. Furthermore, Immunoprecipitation-Mass Spectrometry assay revealed that IRGM interacted with transcription factor YBX1, which facilitated PD-L1 transcription. Mechanistically, IRGM promoted the interaction of YBX1 and phosphokinase S6K1, increasing phosphorylation and nuclear localization of YBX1, transcription of PD-L1. Additionally, the combination of IRGM inhibition with α-PD1 demonstrated a stronger anti-tumor effect compared to the single application of α-PD1. In summary, IRGM is a novel regulator of PD-L1, which suppresses CD8+ CTLs infiltration and function in HCC, resulting in cancer progression. This study may raise a novel therapeutic strategy combined with immune checkpoint inhibitors (ICIs) against HCC.

Cost-effectiveness of tirofiban for acute ischemic stroke without large or medium-sized vessel occlusion: A Markov modelling analysis from the Chinese and United States perspectives.

BACKGROUND: The RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness. METHODS: A hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results. RESULTS: The study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios. CONCLUSION: Tirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US.

Synergistic antitumor activity of baicalein combined with almonertinib in almonertinib-resistant non-small cell lung cancer cells through the reactive oxygen species-mediated PI3K/Akt pathway.

Introduction: Almonertinib is an important third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) exhibiting high selectivity to EGFR-sensitizing and T790M-resistant mutations. Almonertinib resistance is a major obstacle in clinical use. Baicalein possesses antitumor properties, but its mechanism of antitumor action against almonertinib-resistant non-small cell lung cancer (NSCLC) remains unelucidated. Methods: CCK-8 assay was used to examine the survival rate of H1975/AR and HCC827/AR cells following treatment for 24 h with different concentrations of baicalein, almonertinib or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/Akt signaling pathway were observed in baicalein- and/or almonertinib-treated cells. A nude mouse model bearing subcutaneous HCC827/AR cell xenograft were treated with baicalein (20 mg/kg) or almonertinib (15 mg/kg), and the tumor volume and body mass changes was measured. Results: Both baicalein and almonertinib represses the viability of HCC827/AR and H1975/AR cells in a concentration-dependent manner. Compared with baicalein or almonertinib alone, the combined application of the two drugs dramatically attenuates cell proliferation; triggers apoptosis; causes cleavage of Caspase-3, PARP, and Caspase-9; downregulates the protein expressions of p-PI3K and p-Akt; and significantly inhibits tumor growth in nude mice. Furthermore, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS) and preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction, with partial recovery of the decline of p-PI3K and p-Akt. Discussion: The combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.