Cost-Effectiveness of First-Line Atezolizumab versus Chemotherapy in Non-Small-Cell Lung Cancer Patients Ineligible for Platinum-Containing Regimens.

Purpose: The IPSOS study provided evidence supporting the efficacy and tolerability of first-line atezolizumab compared to single-agent chemotherapy for non-small-cell lung cancer (NSCLC) patients ineligible for treatment with a platinum-containing regimen. This study aimed to assess the cost-effectiveness of atezolizumab specifically in this population, considering the perspective of the Chinese healthcare system. Patients and Methods: In this analysis, a three-state Markov model was utilized. The survival data were derived from the IPSOS clinical trial. Direct medical costs and utility values were collected from national authoritative database and published literature. The primary outcomes were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). To ensure the robustness of our model, both one-way and probabilistic sensitivity analyses were conducted. Results: Atezolizumab monotherapy led to an increase in costs of $4139.23 compared to single-agent chemotherapy. Additionally, it resulted in a gain of 0.14 QALYs, leading to an ICER of $29,365.79 per QALY, which was below the willingness-to-pay threshold of $36,066 per QALY used in the model. One-way sensitivity analyses revealed cost of atezolizumab and utility of progressive disease (PD) as major influencing factors for ICER. Furthermore, probabilistic sensitivity analyses confirmed our base-case results. Conclusion: From the perspective of the Chinese healthcare system, atezolizumab emerges as a cost-effective choice for the first-line treatment of NSCLC patients ineligible for platinum-based chemotherapy.

The dynamic relationship among green logistics, technological innovation and green economy: Evidence from China.

Under the background of "double carbon", exploring the growth path of green logistics and enhancing the driving force of technological innovation is the urgent need of our country to comply with the green transformation of its economy and realize high-quality economic growth. Taking the panel data of 30 Chinese provinces from 2010 to 2020 as the sample, the green logistics index evaluation system is constructed based on the driver-press-state-impact-response (DPSIR) theoretical framework, and the green economic efficiency of each province in the sample period is measured by using the non-expected output Super- Slacks-based measure (SBM) model, and by constructing the panel vector autoregressive (PVAR) model including technological innovation is used to systematically elaborate the dynamic influence paths among the three. The study found that: China's green economy, technological innovation, and green logistics all have their own mechanisms for growth, which will gradually diminish over time. In the near and long term, green logistics will promote technological innovations and the evolution of a green economy, but there is a lag in the long-term benefits of green logistics on technological progress. In the short term, technological innovation does not lend support to the growth of a green economy, but over time, the impact of technological innovation on the growth of that economy will shift from negative to positive. This shows that improving technological innovation capability is an important path for green logistics to promote green economic efficiency. The findings of the study provide a basis for decision making to achieve the emission reduction target and improve the efficiency of the green economy.

Maturity degree assessment of hospital ward system using integrated fuzzy AHP-TOPSIS model.

BACKGROUND: The hospital ward system is the core service unit of a hospital and an important aspect of hospital management. The maturity of the hospital ward system represents the level of development and improvement in ward management and services. In order to improve the quality of hospital services, it is significant to assess the maturity of the ward system. Although various assessment methods have been proposed in existing studies, there are some issues such as a single-dimensional factor system, subjectivity in qualitative factor values, and insufficient objectivity in the evaluation methods. METHODS: Therefore, based on the data collection of the factors used in the existing literature, this study made correlation analysis, determined the similarity of factors, and established a maturity assessment factor system satisfying distinctiveness and comprehensiveness. Furthermore, an evaluation method for the weights of each factor was proposed based on the fuzzy analytic hierarchy process, while taking account of the ambiguity of expert information. In addition, through the technique for order of preference by similarity to ideal solution method, an objective evaluation method for the maturity of the hospital ward system was established. Finally, a case study involving 6 hospitals in a specific location was conducted. RESULTS: There are a total of 16 factors used to assess the maturity of the hospital ward system, among which the most important is Doctor service. The maturity degree of the 6 researched hospitals are 0.4517, 0.0035, 0.4254, 0.8681, 0.6636, 0.1586, and the maturity degree of the 6 researched hospitals are II, I, II, IV, III, I. CONCLUSION: The factor system constructed in this study effectively reflected the importance of human-related factors in the development process of ward system. The evaluation results were consistent with the actual situation, demonstrating the effectiveness of the proposed method.

Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer in China.

Purpose: The five-year update data from the KEYNOTE-407 study have unveiled noteworthy improvements in survival outcomes achieved with pembrolizumab plus chemotherapy (Pembro+Chemo) compared to placebo plus chemotherapy (Placebo+Chemo) for patients with previously untreated metastatic squamous non-small cell lung cancer (NSCLC). Building upon this finding, our study sought to evaluate the cost-effectiveness of Pembro+Chemo, utilizing the latest available data, from the perspective of the Chinese health care system. Patients and Methods: A Markov model was employed to compare the quality-adjusted life-year (QALY), life-year (LY), total cost, and incremental cost-effectiveness ratio (ICER) between Pembro+Chemo and Placebo+Chemo. The clinical and safety data were derived from the five-year update date of the KEYNOTE-407 study. Sensitivity analyses were conducted to assess the uncertainty of the model, and additional subgroup analyses were performed to explore specific subpopulations. Results: For patients with previously untreated metastatic squamous NSCLC, the utilization of Pembro+Chemo resulted in a improvement of 0.61 quality-adjusted life years (QALYs) along with a cost reduction of $17,491.52 when compared to Placebo+Chemo. Notably, across various subgroups with different tumor proportion scores (TPS), Pembro+Chemo demonstrated enhanced QALYs and lower total costs. Conclusion: From the perspective of the Chinese health care system, first-line Pembro+Chemo emerges as a dominant treatment option over Placebo+Chemo for the treatment of metastatic squamous NSCLC.

Dengue Incidence Trends and Its Burden in Major Endemic Regions from 1990 to 2019.

BACKGROUND: Dengue has become one of the major vector-borne diseases, which has been an important public health concern. We aimed to estimate the disease burden of dengue in major endemic regions from 1990 to 2019, and explore the impact pattern of the socioeconomic factors on the burden of dengue based on the global burden of diseases, injuries, and risk factors study 2019 (GBD 2019). METHODS: Using the analytical strategies and data from the GBD 2019, we described the incidence and disability-adjusted life years (DALYs) of dengue in major endemic regions from 1990 to 2019. Furthermore, we estimated the correlation between dengue burden and socioeconomic factors, and then established an autoregressive integrated moving average (ARIMA) model to predict the epidemic trends of dengue in endemic regions. All estimates were proposed as numbers and age-standardized rates (ASR) per 100,000 population, with uncertainty intervals (UIs). The ASRs of dengue incidence were compared geographically and five regions were stratified by a sociodemographic index (SDI). RESULTS: A significant rise was observed on a global scale between 1990 and 2019, with the overall age-standardized rate (ASR) increasing from 557.15 (95% UI 243.32-1212.53) per 100,000 in 1990 to 740.4 (95% UI 478.2-1323.1) per 100,000 in 2019. In 2019, the Oceania region had the highest age-standardized incidence rates per 100,000 population (3173.48 (95% UI 762.33-6161.18)), followed by the South Asia region (1740.79 (95% UI 660.93-4287.12)), and then the Southeast Asia region (1153.57 (95% UI 1049.49-1281.59)). In Oceania, South Asia, and Southeast Asia, increase trends were found in the burden of dengue fever measured by ASRs of DALY which were consistent with ASRs of dengue incidence at the national level. Most of the countries with the heaviest burden of dengue fever occurred in areas with low and medium SDI regions. However, the burden in high-middle and high-SDI countries is relatively low, especially the Solomon Islands and Tonga in Oceania, the Maldives in South Asia and Indonesia in Southeast Asia. The age distribution results of the incidence rate and disease burden of dengue fever of major endemic regions showed that the higher risk and disease burden are mainly concentrated in people under 14 or over 70 years old. The prediction by ARIMA showed that the risk of dengue fever in South and Southeast Asia is on the rise, and further prevention and control is warranted. CONCLUSIONS: In view of the rapid population growth and urbanization in many dengue-endemic countries, our research results are of great significance for presenting the future trend in dengue fever. It is recommended to policy makers that specific attention needs to be paid to the negative impact of urbanization on dengue incidence and allocate more resources to the low-SDI areas and people under 14 or over 70 years old to reduce the burden of dengue fever.

Understanding COVID-19 Vaccine Hesitancy in Ethnic Minorities Groups in the UK.

COVID-19 vaccines have been developed and administered at record pace in order to curtail the impact of the COVID-19 pandemic. Vaccine hesitancy has impacted uptake unequally across different groups. This study explores the drivers for vaccine hesitancy in ethnic minority groups in the UK, the impact of social media on vaccine hesitancy and how vaccine hesitancy may be overcome. Twelve semi-structured interviews were conducted, coded and thematically analyzed with participants from ethnic minority groups in the UK who identified as vaccine hesitant. Social media played a significant role in vaccine hesitancy. For those who considered themselves healthy, seeing misinformation of extreme side effects relating to COVID-19 vaccinations on social media resulted in the opinion that the risk of vaccination is greater than risk from COVID-19 infection. For women, misinformation on social media regarding fertility was a reason for delaying or not getting vaccinated. Participants who had sources of information they trusted in outside of social media were more likely to choose to get vaccinated. This study identified the broad spectrum of views on vaccine hesitancy in ethnic minority groups in the UK. Enabling factors such as a desire to travel, and positive public health messaging can increase vaccine uptake, whereas a lack of trusted sources of information may cause vaccine hesitancy. Further research is required to combat misinformation and conspiracy theories. Effective methods include actively responding and disproving the misinformation. For an inclusive vaccination programme that reduces health inequality, policy makers should build trust amongst marginalized communities and address their concerns through tailored public health messaging.

Characterization of multi-biomarkers for bone health assessment based on photoacoustic physicochemical analysis method.

Photoacoustic (PA) techniques are potential alternatives to histopathology. The physicochemical spectrogram (PCS) generated by the PA measurement at multiple wavelengths can presents the morphology and chemical composition target at multi-biomarkers simultaneously. In this work, via multi-wavelength PA measurements performed on rabbit bone models, we investigated the feasibility of using PCSs for bone health assessment. A comprehensive analysis of the PCSs, termed PA physicochemical analysis (PAPCA), was conducted. The "slope" and "relative content" were used as the PAPCA-quantified parameters to characterize the changes in the physical and chemical properties of bone tissue, respectively. The findings are consistent well with the gold-standard imaging results. It demonstrated that the PAPCA can be used to characterize both the microstructure and content of multi-biomarkers which highly related with bone health. Considering the PA technique is noninvasive and radiation-free, it has great potential in the implementation and monitoring of bone diseases progression.

Comparative life cycle assessment of biochar-based lignocellulosic biohydrogen production: Sustainability analysis and strategy optimization.

Lignocellulose has been considered a potential feedstock for biohydrogen production. Recently, a novel closed-loop concept of biochar approach was developed for enhanced lignocellulosic biohydrogen production. This study therefore targets to analyze the environmental impacts of the three existing lignocellulosic biohydrogen production processes, and evaluate the environmental performance of applying biochar in each process at this early stage of technological development. The results suggest that biochar dosing shows better environmental performance for all impact categories, especially in the consolidate bioprocessing case. Electricity consumption was found to be the dominant cause of environmental impact over the life cycle, while by-products generation was also found to have an effect on the life-cycle impacts. Future research focuses on the biohydrogen production scale, the electricity generation scheme transition towards renewable and cleaner energetic systems, and recovery the by-products to the maximum extent, that will make lignocellulosic biohydrogen production more environmentally sustainable.

Modelled Economic Analysis for Dacomitinib-A Cost Effectiveness Analysis in Treating Patients With EGFR-Mutation-Positive Non-Small Cell Lung Cancer in China.

OBJECTIVES: To establish the cost-effectiveness of dacomitinib compared to gefitinib from the Chinese healthcare system perspective. PATIENTS: Advanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. METHODS: Partitioned survival analysis was undertaken to examine the cost-effectiveness of dacomitinib utilising individual patient data (IPD) from the pivotal randomised controlled trial (RCT) (ARCHER 1050). The three health states modelled were progression-free, post-progression, and death. Parametric survival distributions were fitted to IPD against the Kaplan-Meier survival curves corresponding to progression-free survival (PFS) and overall survival (OS) outcomes by randomised groups. Costs included drug acquisition and administration, outpatient management (outpatient consultation and examinations), and best supportive care costs. Utility weights were sourced from the pivotal trial and other published literature. The incremental cost-effectiveness ratio (ICER) was calculated with costs and quality-adjusted life years (QALYs) discounted at an annual rate of 5%. Both deterministic and probabilistic sensitivity analyses were undertaken. RESULTS: In the base case, dacomitinib (CNY 265,512 and 1.95 QALY) was associated with higher costs and QALY gains compared to gefitinib (CNY 247,048 and 1.61 QALYs), resulting in an ICER of CNY 58,947/QALY. Using the empirical WTP/QALY threshold, dacomitinib is a cost-effective treatment strategy for patients with EGFR-mutation-positive advanced NSCLC. The probabilistic sensitivity analysis suggested that dacomitinib had a 97% probability of being cost-effective. CONCLUSIONS: Dacomitinib is a cost-effective treatment strategy in treating patients with EGFR-mutation-positive NSCLC from the Chinese healthcare system perspective. The uncertainty around the cost-effectiveness of dacomitinib could be reduced if long-term survival data become available. CLINICAL TRIAL REGISTRATION: NCT01024413.

Threshold Effect of Foreign Direct Investment and Carbon Emissions Performance From the Perspective of Marketization Level: Implications for the Green Economy.

Exploring the path and mechanism of marketization level in the effect of foreign direct investment (FDI) on carbon emission performance will help to maximize the stimulation effect of foreign investment on green and low-carbon development. This study used the panel data of 11 provinces and cities in the Yangtze River Economic Belt from 2008 to 2016. A panel threshold model is constructed to explore the non-linear relationship between FDI and carbon emissions performance from the perspective of marketization level. The main conclusions are as follows: First, from the perspective of marketization level, a significant double threshold effect exists between foreign participation and carbon emission intensity, with threshold values of 4.4701 and 9.2516 respectively. Second, as the marketization level increases, the technology spillover effect of FDI increases, and the stimulation effect of foreign participation on carbon intensity decreases significantly, but it does not inhibit carbon intensity, indicating that the overall benefits brought by FDI technology spillovers are still insufficient to offset pollution caused by foreign investment. Third, the eastern region of the Yangtze River Economic Belt has crossed the second threshold. In the central and western regions, the marketization process is relatively slow except for Chongqing, and the regions are still firmly stuck between the first and second thresholds. In response to the conclusions of the empirical research, relevant policy suggestions are put forward from three dimensions, namely, the strategy of introducing foreign investment, construction of the marketization system, and environmental regulation, to achieve low-carbon and green development in the Yangtze River Economic Belt.

Detection of collagen by multi-wavelength photoacoustic analysis as a biomarker for bone health assessment.

Collagen is an important biomarker of osteoporosis progression. Noninvasive, multispectral, photoacoustic (PA) techniques use pulsed laser light to induce PA signals to facilitate the visualization of chemical components that are strongly related to tissue health. In this study, the feasibility of multi-wavelength PA (MWPA) measurement of the collagen in bone, using the wavelength range of 1300-1800 nm, was investigated. First, the feasibility of this approach for detecting the collagen content of bone was demonstrated by means of numerical simulation. Then, ex vivo experiments were conducted on both animal and human bone specimens with different bone densities using the MWPA method. The relative collagen content was extracted and compared with the results of micro-computed tomography (micro-CT) and histology. The results showed that the "relative collagen content" parameter obtained using the MWPA approach correlated well with the bone volume ratio obtained from micro-CT images and histological analysis results. This study highlights the potential of the proposed PA technique for determining the collagen content of bones as a biomarker for bone health assessment.

Subjective and Objective Assessment of Monoenergetic and Polyenergetic Images Acquired by Dual-Energy CT in Breast Cancer.

OBJECTIVE: To objectively and subjectively assess and compare the characteristics of monoenergetic images [MEI (+)] and polyenergetic images (PEI) acquired by dual-energy CT (DECT) of patients with breast cancer. MATERIALS AND METHODS: This retrospective study evaluated the images and data of 42 patients with breast cancer who had undergone dual-phase contrast-enhanced DECT from June to September 2019. One standard PEI, five MEI (+) in 10-kiloelectron volt (keV) intervals (range, 40-80 keV), iodine density (ID) maps, iodine overlay images, and Z effective (Zeff) maps were reconstructed. The contrast-to-noise ratio (CNR) and the signal-to-noise ratio (SNR) were calculated. Multiple quantitative parameters of the malignant breast lesions were compared between the arterial and the venous phase images. Two readers independently assessed lesion conspicuity and performed a morphology analysis. RESULTS: Low keV MEI (+) at 40-50 keV showed increased CNR and SNRbreast lesion compared with PEI, especially in the venous phase ([CNR: 40 keV, 20.10; 50 keV, 14.45; vs. PEI, 7.27; p < 0.001], [SNRbreast lesion: 40 keV, 21.01; 50 keV, 16.28; vs. PEI, 10.77; p < 0.001]). Multiple quantitative DECT parameters of malignant breast lesions were higher in the venous phase images than in the arterial phase images (p < 0.001). MEI (+) at 40 keV, ID, and Zeff reconstructions yielded the highest Likert scores for lesion conspicuity. The conspicuity of the mass margin and the visual enhancement were significantly better in 40-keV MEI (+) than in the PEI (p = 0.022, p = 0.033, respectively). CONCLUSION: Compared with PEI, MEI (+) reconstructions at low keV in the venous phase acquired by DECT improved the objective and subjective assessment of lesion conspicuity in patients with malignant breast lesions. MEI (+) reconstruction acquired by DECT may be helpful for the preoperative evaluation of breast cancer.

Quantitative Assessment of the Physical Virus Titer and Purity by Ultrasensitive Flow Virometry.

Rapid quantification of viruses is vital for basic research on viral diseases as well as biomedical application of virus-based products. Here, we report the development of a high-throughput single-particle method to enumerate intact viral particles by ultrasensitive flow virometry, which detects single viruses as small as 27 nm in diameter. The nucleic acid dye SYTO 82 was used to stain the viral (or vector) genome, and a laboratory-built nano-flow cytometer (nFCM) was employed to simultaneously detect the side-scatter and fluorescence signals of individual viral particles. Using the bacteriophage T7 as a model system, intact virions were completely discriminated from empty capsids and naked viral genomes. Successful measurement of the physical virus titer and purity was demonstrated for recombinant adenoviruses, which could be used for gene delivery, therapeutic products derived from phage cocktails, and infected cell supernatants for veterinary vaccine production.

A Novel External Quality Assessment of Chromosomal Karyotype Analysis Based on Chimera Image Assembly.

OBJECTIVE: This study aimed to establish a new external quality assessment (EQA) of chromosomal karyotype analysis. METHODS: Chimeric assembly A1 was established by collecting chimeric chromosome images prepared artificially from chromosomally abnormal amniocytes remaining after prenatal diagnosis. Chimeric assembly B1 and nonchimeric assembly C1 were constructed through the collection of chimeric and nonchimeric chromosome images from prenatal diagnosis, respectively. Then, chromosome images were selected randomly from assemblies A1, B1, or C1 to send to 20 technicians via email to verify the validity of a new EQA of chromosomal karyotype analysis. RESULTS: According to the EQA of 20 technicians, 47,XX,+mar from assembly A was easily misdiagnosed as 47,XX,+19 or 47,XXY, and 45,XX,t(13;22) (q10;q10) was misdiagnosed as 45,XX,13S+,-22. The total misdiagnosis rate was 3.8%. For assembly B, 46,X,+mar and 46,X,idic(Y) were easily misdiagnosed as 46,XY and 46,X,+mar, respectively. In addition, some testers missed 47,XXX in 47,XXX[2]/46,XX[48], as well as 47,XX,+18 in 46,XX [47]/47,XX,+18[3], and 45,X and 47,XXX in 46,XX[47]/45,X[2]/47,XXX[1]. The total misdiagnosis rate was 4.2%. All karyo-types from assembly C were correctly diagnosed, although incorrect descriptions used for 4% of cases. CONCLUSION: The quality of chromosome karyotype analysis can be comprehensively evaluated by a new EQA based on assembly A1 or B1.

Characteristics of Persons Who Died with COVID-19 - United States, February 12-May 18, 2020.

During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City).

Knowledge, attitude and willingness of different ethnicities to participate in cadaver donation programs.

Knowledge, attitude and willingness of ethnic minorities in China towards cadaver donation programs were assessed. Questionnaire and interviews were conducted to investigate Yi, Bai, Hani, Dai and Han ethnicities. Educational level and per capita income of ethnic minorities were lesser than those of Han ethnicity (p<0.01). Agriculture was the primary occupation and proportions of technical personnel and public officials was lesser among ethnic minorities (p<0.01). Surveyed ethnic minorities universally practice religious traditions, Bai and Dai ethnicities practice Buddhist beliefs also (p<0.01). Knowledge of Yi, Bai, Hani and Dai ethnic respondents was lesser than those of Han ethnicity (p<0.01). Over 83.8% of Yi, Bai, Hani and Dai ethnicity residents were unwilling to register for body donation programs with receiving a driver's license (p<0.01). Less than 46.9% of ethnic minorities supported use of honorary certificates (p<0.01). Ethnic minorities were supportive of financial compensation for body donations and denied that financial compensation led to the commercialization of cadaver donation (p<0.01, p<0.01). Willingness of ethnic minorities to participate in cadaver donation programs was primarily related to religious beliefs (p<0.01), economic status (p<0.01). Knowledge, attitude and willingness of ethnic minorities to participate in cadaver donation programs were markedly different from those of Han ethnicity, and the religious belief and economic status played a decisive role. To increase participation, programs based on respecting religious belief should be developed to support improvements in economy, education, medical care and social security system.

Cost-Effectiveness Analysis of Helicobacter pylori Eradication Therapy for Prevention of Gastric Cancer: A Markov Model.

BACKGROUND: Helicobacter pylori (H. pylori) eradication can reduce the prevalence of gastric cancer. However, whether H. pylori eradication therapy should be performed in infected patients, especially in asymptomatic cases, is still controversial. AIMS: The aims of this study were to determine whether H. pylori screening and eradication could prevent gastric cancer in a cost-effective way, and further whether eradication therapy should be administered to asymptomatic individuals. METHODS: Cost-effectiveness analysis was performed using a Markov model. We established two groups, each with 10,000 hypothetical Chinese individuals at the age of 40 years. Clinical outcomes and cost of H. pylori eradication were compared between the eradication and control groups. RESULTS: There was a lower morbidity with gastric cancer in the eradication group than in the control group, which was most significant after running the model for 15 years. The eradication group experienced an average of 34.64 quality-adjusted life years (QALYs) per person, and the average cost was US $1706.52 per person. The control group exhibited an average of 32.63 QALYs per person, and the average cost was US $2045.10 per person. The cost-effectiveness analysis showed that eradication saved $1539 per LY per person and $168.45 per QALY per person. CONCLUSIONS: H. pylori screening and eradication therapy effectively reduces the morbidity of gastric cancer and cancer-related costs in asymptomatic infected individuals. Therefore, we believe that H. pylori eradication can prevent gastric cancer in a cost-effective way.

Assessment of biological functions for C3A cells interacting with adverse environments of liver failure plasma.

BACKGROUND: For its better differentiated hepatocyte phenotype, C3A cell line has been utilized in bioartificial liver system. However, up to now, there are only a few of studies working at the metabolic alternations of C3A cells under the culture conditions with liver failure plasma, which mainly focus on carbohydrate metabolism, total protein synthesis and ureagenesis. In this study, we investigated the effects of acute liver failure plasma on the growth and biological functions of C3A cells, especially on CYP450 enzymes. METHODS: C3A cells were treated with fresh DMEM medium containing 10% FBS, fresh DMEM medium containing 10% normal plasma and acute liver failure plasma, respectively. After incubation, the C3A cells were assessed for cell viabilities, lactate dehydrogenase leakage, gene transcription, protein levels, albumin secretion, ammonia metabolism and CYP450 enzyme activities. RESULTS: Cell viabilities decreased 15%, and lactate dehydrogenase leakage had 1.3-fold elevation in acute liver failure plasma group. Gene transcription exhibited up-regulation, down-regulation or stability for different hepatic genes. In contrast, protein expression levels for several CYP450 enzymes kept constant, while the CYP450 enzyme activities decreased or remained stable. Albumin secretion reduced about 48%, and ammonia accumulation increased approximately 41%. CONCLUSIONS: C3A cells cultured with acute liver failure plasma showed mild inhibition of cell viabilities, reduction of albumin secretion, and increase of ammonia accumulation. Furthermore, CYP450 enzymes demonstrated various alterations on gene transcription, protein expression and enzyme activities.

Chaihu-Shugan-San and absorbed meranzin hydrate induce anti-atherosclerosis and behavioral improvements in high-fat diet ApoE-/- mice via anti-inflammatory and BDNF-TrkB pathway.

The comorbidity of coronary heart disease (CHD) and depression in patients is extremely prevalent, with a rate from 20 to 50%, while depression-like behaviors exist in a larger percentage of patients. Therefore, the study of comorbidities is particularly urgent. Chaihu-Shugan-San (CSS), a classical traditional Chinese medicine formula, has been used to treat CHD with depression for hundreds of years. However, the mechanism of its action on comorbidities remains unclear. Here, we focused on the behavioral changes in ApoE-/- mice fed a high-fat diet (HFD) and elucidated the mechanism of CSS and its main absorbed component, meranzin hydrate (MH), as an anti-atherosclerosis and anti-depression agent. In the present study, mice were fed an HFD for 16 weeks and were intragastrically administered high and low doses of CSS and MH. Depressive-like behaviors were evaluated by the sucrose preference test, the open-field test, the light-dark test and the tail-suspension test, after which atherosclerotic plaques, plasma lipids, inflammatory cytokine levels and the expression of BDNF/TrkB were measured. We demonstrated that the atherosclerosis model group exhibited significant depressant behaviors. Moreover, CSS inhibited depressive-like behavioral changes, reduced atherosclerotic plaque areas, plasma total cholesterol, triglycerides, LDL-cholesterol levels and inflammatory cytokines including TNF-α, IL-1ß, and IL-6 in plasma and hippocampi, increased the protein and mRNA expression of BDNF and TrkB in the aorta and the hippocampus. Interestingly, MH, the main component in CSS that is absorbed in the plasma and hippocampus, exerted effects similar to those of CSS. In addition, MH increased the protein and mRNA expression of BDNF and TrkB in human umbilical vein endothelial cells (HUVECs) induced by LPS. Collectively, these results suggest that MH represents the CSS decoction, induces anti-atherosclerosis effects and improves depression-like behaviors in HFD-fed ApoE-/- mice. Moreover, the regulation of proinflammatory factors and BDNF-TrkB signaling are possibly involved in this process. Our findings indicate that MH is a potential phytochemical compound for the prevention of the comorbidity of atherosclerosis and depression.