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Abstract Background The intricate balance between the advantages and risks of low-dose computed tomography (LDCT) impedes the utilization of lung cancer screening (LCS). Guiding shared decision-making (SDM) for well-informed choices regarding LCS is pivotal. There has been a notable increase in research related to SDM. However, these studies possess limitations. For example, they may ignore the identification of decision support and needs from the perspective of health care providers and high-risk groups. Additionally, these studies have not adequately addressed the complete SDM process, including pre-decisional needs, the decision-making process, and post-decision experiences. Furthermore, the East-West divide of SDM has been largely ignored. This study aimed to explore the decisional needs and support for shared decision-making for LCS among health care providers and high-risk groups in China. Methods Informed by the Ottawa Decision-Support Framework, we conducted qualitative, face-to-face in-depth interviews to explore shared decision-making among 30 lung cancer high-risk individuals and 9 health care providers. Content analysis was used for data analysis. Results We identified 4 decisional needs that impair shared decision-making: (1) LCS knowledge deficit; (2) inadequate supportive resources; (3) shared decision-making conceptual bias; and (4) delicate doctor-patient bonds. We identified 3 decision supports: (1) providing information throughout the LCS process; (2) providing shared decision-making decision coaching; and (3) providing decision tools. Conclusions This study offers valuable insights into the decisional needs and support required to undergo LCS among high-risk individuals and perspectives from health care providers. Future studies should aim to design interventions that enhance the quality of shared decision-making by offering LCS information, decision tools for LCS, and decision coaching for shared decision-making (e.g., through community nurses). Simultaneously, it is crucial to assess individuals’ needs for effective deliberation to prevent conflicts and regrets after arriving at a decision.

Abstract Background The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model. Methods The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by flow cytometry, and the levels of cytokines in cell supernatants or in sera of mice were measured (ELISA). The therapeutic effect of EgCF on sepsis was evaluated by observing the survival rates of mice for 72 h after CLP, and the pathological injury to the liver, kidney, and lung was measured under a microscope. The expression of TLR-2/MyD88 in tissues was measured by western blot to determine whether TLR-2/MyD88 is involved in the sepsis-induced inflammatory signaling pathway. Results In vitro culture with BMDMs showed that EgCF promoted macrophage polarization to M2 type and inhibited lipopolysaccharide (LPS)-induced M1 macrophages. EgCF treatment provided significant therapeutic effects on CLP-induced sepsis in mice, with increased survival rates and alleviation of tissue injury. The EgCF conferred therapeutic efficacy was associated with upregulated anti-inflammatory cytokines (IL-10 and TGF-β) and reduced pro-inflammatory cytokines (TNF-α and INF-γ). Treatment with EgCF induced Arg-1-expressed M2, and inhibited iNOS-expressed M1 macrophages. The expression of TLR-2 and MyD88 in EgCF-treated mice was reduced. Conclusions The results demonstrated that EgCF confers a therapeutic effect on sepsis by inhibiting the production of pro-inflammatory cytokines and inducing regulatory cytokines. The anti-inflammatory effect of EgCF is carried out possibly through inducing macrophage polarization from pro-inflammatory M1 to regulatory M2 phenotype to reduce excessive inflammation of sepsis and subsequent multi-organ damage. The role of EgCF in regulating macrophage polarization may be achieved by inhibiting the TLR2/MyD88 signaling pathway. Graphical Abstract

Abstract Background The emergence of SARS-CoV-2 becomes life-threatening for the older and immunocompromised individuals, whereas limited treatment is available on these populations. Mesenchymal stromal cells (MSCs) have been reported to be useful in SARS-CoV-2 treatment and reduce SARS-CoV-2-related sequelae. Results In this study, we developed an autonomous cellular machine to secret neutralizing antibody in vivo constantly based on the clinical-grade MSCs, to combat SARS-CoV-2 infections. First, various modified recombinant plasmids were constructed and transfected into clinical-grade MSCs by electroporation, for assembly and expression of neutralizing anti-SARS-CoV-2 antibodies. Second, the stable antibody secreting MSCs clones were screened through pseudovirus neutralization assay. Finally, we investigated the pharmacokinetics and biodistribution of neutralizing antibody secreted by engineered MSCs in vivo. The stable clinical-grade MSCs clones, expressing XGv347-10 and LY-CoV1404-5 neutralizing antibodies, exhibited their feasibility and protective efficacy against SARS-CoV-2 infection. Transplanted engineered clinical-grade MSCs effectively delivered the SARS-CoV-2 antibodies to the lung, and the immune hyperresponsiveness caused by COVID-19 was coordinated by MSC clones through inhibiting the differentiation of CD4 + T cells into Th1 and Th17 subpopulations. Conclusions Our data suggested that engineered clinical-grade MSCs secreting effective neutralizing antibodies as cellular production machines had the potential to combat SARS-CoV-2 infection, which provided a new avenue for effectively treating the older and immunocompromised COVID-19 patients.

Abstract Background It is critical to find optimal forms to identify perinatal depression (PND) and its vulnerable factors and make them more applicable to depression screening. This study aims to evaluate the reliability and validity of the Chinese version of the Leiden Index of Depression Sensitivity (LEIDS-RR-CV) among perinatal women in China and determine the cut-off values for screening for high-risk depression. Methods Women in their third trimester of pregnancy and six weeks postpartum completed the LEIDS-RR-CV and a diagnostic reference standard online. We assessed the LEIDS-RR-CV using classical test theory (CTT) and item response theory (IRT). We also assessed the test performance for cut-off scores using receiver operator characteristic analysis to further screen for high-risk depression at each time point. Results In total, 396 (third trimester) and 321 (six weeks postpartum) women participated. Cronbach’s alpha, two-week test–retest reliability, and marginal reliability for the scale were all greater than 0.8. It showed a five-factor model; the cut-off values were 58 (third trimester) and 60 (six weeks postpartum). The areas under the curve were acceptable (≥ 0.7), and the LEIDS-RR-CV was positively correlated with the total Edinburgh Postnatal Depression Scale (EPDS) score (r = 0.52 and 0.56, p = 0.00), indicating its predictive validity. An IRT analysis further confirmed its discriminative validity. Conclusions The LEIDS-RR-CV was found to be reliable, valid, and can be used to quantify cognitive reactivity among perinatal Chinese women and for screening for high-risk depression during this period.

Abstract Background After spinal cord injury (SCI), dysregulated or nonresolving inflammatory processes can severely disturb neuronal homeostasis and drive neurodegeneration. Although mesenchymal stromal cell (MSC)-based therapies have showed certain therapeutic efficacy, no MSC therapy has reached its full clinical goal. In this study, we examine interleukin-10 (IL10) genetically modified clinical-grade MSCs (IL10-MSCs) and evaluate their clinical safety, effectiveness, and therapeutic mechanism in a completely transected SCI mouse model. Methods We established stable IL10-overexpressing human umbilical-cord-derived MSCs through electric transduction and screened out clinical-grade IL10-MSCs according to the criteria of cell-based therapeutic products, which were applied to mice with completely transected SCI by repeated tail intravenous injections. Then we comprehensively investigated the motor function, histological structure, and nerve regeneration in SCI mice, and further explored the potential therapeutic mechanism after IL10-MSC treatment. Results IL10-MSC treatment markedly reinforced locomotor improvement, accompanied with decreased lesion volume, regeneration of axons, and preservation of neurons, compared with naïve unmodified MSCs. Further, IL10-MSC transplantation increased the ratio of microglia to infiltrated alternatively activated macrophages (M2), and reduced the ratio of classically activated macrophages (M1) at the injured spinal cord, meanwhile increasing the percentage of Treg and Th2 cells, and reducing the percentage of Th1 cells in the peripheral circulatory system. In addition, IL10-MSC administration could prevent apoptosis and promote neuron differentiation of neural stem cells (NSCs) under inflammatory conditions in vitro. Conclusions IL10-MSCs exhibited a reliable safety profile and demonstrated promising therapeutic efficacy in SCI compared with naïve MSCs, providing solid support for future clinical application of genetically engineered MSCs.

Abstract Background Coronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood lipid metabolism is an important risk factor. Transforming growth factor-ß (TGF-ß) and its receptor (TGF-ßR) can inhibit the release of inflammatory factors through the SMAD pathway-mediated immune response, thereby suppressing the progression of CAD. Endoglin (TGF-ßRIII), a TGF-ßR family homologous receptor protein, is directly involved in the immunoregulatory process, but the exact mechanism is unclear. This study aimed to clarify the pathophysiological effects of endoglin on the development of atherosclerosis and to explore the mechanism of the signalling pathway. Methods We downloaded the GEO dataset to perform a functional analysis of SMAD family activity and TGF-ß receptor protein expression in the monocyte expression profiles of patients with familial hyperlipidaemia (FH). The effect of endoglin on endothelial cell proliferation, migration, and apoptosis was examined by disrupting the endoglin gene in human umbilical vein endothelial cells (HUVECs) and validated by western blotting. The related genes and pathways regulated by endoglin were obtained by analysing the sequencing data. Results Research has shown that interference with endoglin can promote the proliferation and migration and significantly inhibit the apoptosis of vascular endothelial cells. Interference with endoglin particularly encourages the expression of VEGFB in vascular endothelial cells. Conclusion The endoglin gene in vascular endothelial cells regulates the PI3K-Akt, Wnt, TNF, and cellular metabolism pathways by activating the SMAD pathway. RAB26, MR1, CCL2, SLC29A4, IBTK, VEGFB, and GOLGA8B play critical roles. Endoglin interacts closely with 11 proteins such as CCL2 and SEPRINE1, which participate in the vital pathway of plaque formation. Interference with endoglin can alter the course of coronary atherosclerosis.

Abstract Background The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are the most commonly used scales to detect mild cognitive impairment (MCI) in population-based epidemiologic studies. However, their comparison on which is best suited to assess cognition is scarce in samples from multiple regions of China. Methods We conducted a cross-sectional analysis of 4923 adults aged ≥55 years from the Community-based Cohort Study on Nervous System Diseases. Objective cognition was assessed by Chinese versions of MMSE and MoCA, and total score and subscores of cognitive domains were calculated for each. Education-specific cutoffs of total score were used to diagnose MCI. Demographic and health-related characteristics were collected by questionnaires. Correlation and agreement for MCI between MMSE and MoCA were analyzed; group differences in cognition were evaluated; and multiple logistic regression model was used to clarify risk factors for MCI. Results The overall MCI prevalence was 28.6% for MMSE and 36.2% for MoCA. MMSE had good correlation with MoCA (Spearman correlation coefficient = 0.8374, p

Abstract Background HIV stigma is a common barrier to HIV prevention, testing, and treatment adherence, especially for low- and middle-income countries such as Myanmar. However, there was no validated Myanmar version of a stigma scale. Therefore, we adapted the English version of the 40-item Berger’s HIV stigma scale and the 7-item Indian HIV stigma scale into a 47-item Myanmar HIV stigma scale and then evaluated the scale’s psychometric properties. Method From January 2020 to May 2020, using random sampling methods, 216 eligible Myanmar people living with HIV/AIDS (PLWHA) were contacted from a closed Facebook group that included more than 10,000 PLWHA. A sample of 156 Myanmar PLWHA completed the online self-reported survey. Results A six-factor structure for the scale was determined through exploratory factor analysis, explaining 68.23% of the total variance. After deleting 12 items, the 35-item HIV stigma scale achieved Cronbach ‘s α of 0.72 to 0.95. Construct validity of the scale was demonstrated by significant association with self-reported depression and social support levels (r = 0.60, and − 0.77, p

Abstract Objectives To investigate the safety for clinic use and therapeutic effects of basic fibroblast growth factor (bFGF)-overexpressing human umbilical cord-derived mesenchymal stem cells (HUCMSCs) in mice with completely transected spinal cord injury (SCI). Methods Stable bFGF-overexpressing HUCMSCs clones were established by electrotransfection and then subjected to systematic safety evaluations. Then, bFGF-overexpressing and control HUCMSCs were used to treat mice with completely transected SCI by tail intravenous injection. Therapeutic outcomes were then investigated, including functional recovery of locomotion, histological structures, nerve regeneration, and recovery mechanisms. Results Stable bFGF-overexpressing HUCMSCs met the standards and safety of MSCs for clinic use. In the mouse SCI model, stable bFGF-overexpressing HUCMSCs markedly improved therapeutic outcomes such as reducing glial scar formation, improving nerve regeneration and proliferation of endogenous neural stem cells (NSCs), and increasing locomotion functional recovery of posterior limbs compared with the control HUCMSCs group. Furthermore, bFGF-overexpressing HUCMSCs promoted the proliferation and neuronal differentiation of NSCs in vitro through the PI3K-Akt-GSK-3β pathway. Conclusion bFGF-overexpressing HUCMSCs meet the requirements of clinical MSCs and improve evident therapeutic outcomes of mouse SCI treatment, which firmly supports the safety and efficacy of gene-modified MSCs for clinical application.

Abstract Background Health-Related Quality of Life (HRQoL) of hypertensive patients is not only affected by the disease itself but also by some subjective factors. Low health literacy is prevalent among ethnic minorities. Considering the Kazakh-Chinese people have the highest prevalence of hypertension in Xinjiang, and the High Blood Pressure-Health Literacy (HBP-HL) has not been included in the study of HRQoL. The synergistic effects and the potential mechanism HBP-HL, self-management behavior, therapeutic adherence, self-efficacy, social support on HRQoL remain unclear. This study aimed to introduce the HBP-HL, and develop a structural equation model (SEM) to identify the factors influencing of the HRQoL among Kazakh hypertensive patients. Methods The data was obtained by questionnaire survey and physical examination in 2015. Patients with hypertension were recruited through random cluster sampling in Kazakh settlements in Xinjiang. Firstly, the blood pressure was measured. Then the one-for-one household interviews were conducted by Kazakh investigators. The questionnaires regarding HBP-HL, HRQoL, self-management behavior, therapeutic adherence, self-efficacy, and social support were used to collect data. Finally, SEM was constructed, and p ≤ 0.05 was taken as significant. Results The data was analysed by SPSS18.0 and AMOS18.0 software. 516 Kazakh hypertension patients were recruited, and 94.4% of them had a relatively low HBP-HL score. The mean standardized scores of HRQoL, self-management, therapeutic adherence were poor; they were 63.5, 66.2, and 64.4, respectively. But 96.1% and 98.3% of the participants had high levels of self-efficacy and social support. The SEM of the HRQoL had a good overall fit (χ2/df = 2.078, AGFI = 0.944, GFI = 0.968, CFI = 0.947, IFI = 0.949, RMSEA = 0.046). The model indicated that the HBP-HL has the highest correlation with HRQoL, following with self-management behavior, social support, and self-efficacy. Conclusions Low HBP-HL is a major influenced factor of HRQoL among Kazakh hypertensive patients. Future programs should consider HBP-HL as the breakthrough point when designing targeting intervention strategies.

Abstract Background The geriatric depression scale (GDS) is used widely as a screening instrument for depression worldwide. The present study aims to examine the reliability and validity of the GDS with 30 items (GDS-30) in Chinese cognitively normal elderly, and to preliminarily investigate the appropriateness of the GDS-30 among screened mild cognitive impairment (MCI) elderly and among the large-scale community-dwelling Chinese elderly. Methods A total of 12,610 Chinese elderly completed GDS-30 in the project of Community-based Cohort Study on Nervous System Diseases. Of these, 5503 individuals with the ability to perform basic daily living activities were randomly sampled to further complete the Montreal Cognitive Assessment to screen for MCI. The cutoff value of screened depression was 11, and the cutoff values of MCI were education-dependent. Internal consistency was used to evaluate the reliability. Exploratory factor analysis (EFA) was used to determine the factor structure. Confirmatory factor analysis (CFA) was conducted to assess the construct validity in the elderly screened normal cognition, screened MCI, and the whole population, respectively. Results The Kuder-Richardson coefficient (KR20) was 0.834, 0.821 and 0.840 for the cognitively normal elderly, screened MCI and the whole population, respectively. EFA showed that GDS-30 can be either a four-factor model (named positive mood, dysphoria, worry, and social withdrawal-cognitive impairment) or a two-factor model (named depression and positive mood). The latter was easier to interpret. CFA showed that the two-factor model fitted well in the elderly with normal cognition, with screened MCI, and the whole sample. The factors loaded from 0.900 to 0.588, 0.882 to 0.529, and 0.888 to 0.556 in these three populations respectively. Conclusions The GDS-30 has good reliability and validity and can be appropriately applied to screen depression in the large-scale community-dwelling Chinese elderly regardless of the presence of mild cognitive impairment.

Abstract Background The Perceived Stress Scale (PSS) is a globally used and self-report scale measuring perceived stress. Three versions of PSS (PSS-14, PSS-10 and PSS-4) are available which comprise 14, 10 and 4 items respectively. However, the Chinese version of the PSS has not yet been validated in a large community-based general population. The aims of this study were to evaluate the psychometric properties of the Chinese PSS in a large community-based general population and to compare the appropriateness of the three versions of PSS. Methods A total of 9507 adults with at least a junior high school education and completed PSS-14 from the China Health and Nutrition Survey were involved in this study. The internal consistency reliability of PSS was assessed using Cronbach’s alpha coefficient and confirmatory factor analysis was employed to test the construct validity. Modification index was used for model extension and the critical ratio was used for model restriction. Results The internal consistency coefficients were satisfactory for PSS-14 and PSS-10, but not for PSS-4. The corresponding Cronbach’s alpha were 0.830, 0.754 and 0.473 respectively. A 2-factor structure was confirmed for the PSS-14 and PSS-10, and all items’ standardized factor loadings exceeded 0.4 for either negative or positive factors. Given that item 12 loaded on both negative and positive factors for PSS-14 and the goodness of fit for PSS-14 was not acceptable, PSS-13 (PSS-14 excluding item 12) was studied. The construct validities of PSS-13 and PSS-10 were satisfactory, but the goodness of fit for PSS-10 were better than that for PSS-13. Conclusions PSS-13 (PSS-14 excluding item 12) and PSS-10 have satisfactory psychometric properties. PSS-10 are more applicable to measure the perceived stress than PSS-13 in a large community-based general population in China.

Abstract Background The China Dietary Guidelines Index (CDGI) is a diet quality evaluation index that can present the overall diet quality and is comparable between individuals. The aim of this study was to revise CDGI for Chinese adults according to the Chinese Dietary Guidelines 2016 (CDG-2016), evaluate adherence to recommended diets between 1991 and 2015, and analyze the trend, variation, and determinants of diet quality. Methods Food, cooking oil, and condiment intakes were estimated based on twenty-four-hour dietary recalls over three consecutive days and the household weighing method. Based on the food and nutrients recommendations for people with different energy requirements in CDG-2016, CDGI was revised as China Dietary Guidelines Index (2019)-Adults (CDGI(2019)-A) by equal weight continuity scoring. Three-level random intercept-slope growth models were applied to analyze the trend, variation, and determinants at both the community and individual levels. Results CDGI(2019)-A, the sum of fourteen component scores with a range of 0–110 points, increased significantly from 38.2 in 1991 to 47.3 in 2015. Components with a score of less than half were milk (91.6%), fruits (72.0%), nuts (82.5%), other cereals and beans (82.6%), and seafood (77.7%). Between-individual accounted for 25.6% of the total score variation, of which 87.4% derived from the community level. CDGI(2019)-A score displayed a positive association with being female, having higher education, having higher income, living in an urban area, and knowing the CDG-2016 recommendations. The impact of income and awareness of CDG-2016 varied significantly across communities. Conclusions Although quality of diet has been improving in China, overall quality remains poor, primarily because of inadequate intake of milk and dairy products, nuts, fruits, other cereals and miscellaneous beans, and seafood. Intervention at the community level may improve diet quality more efficiently than at the individual level, and the most effective intervention should be selected in different communities according to local conditions.

Abstract Background In cell-based therapy, the transmission of communicable diseases imposes a substantial threat to recipients. In this study, we investigated whether cell-based screening could detect hepatitis B virus (HBV) in human umbilical cord-derived mesenchymal stem cells (HUMSCs) isolated from HBV-infected donors to understand the susceptibility of HUMSCs to HBV infection. Methods HBV assay was performed in HUMSCs derived from healthy and HBV-infected donors with enzyme-linked immunosorbent assay (ELISA), fluorescence quantitative PCR (FQ-PCR) assay, and droplet digital PCR (ddPCR) assay. Further, HBV DNA was assayed in HUMSCs derived from healthy donors after incubation with human sera containing a high titer of HBV using FQ-PCR. Results HBV antigen/antibody and DNA failed to be detected using ELISA, FQ-PCR, and ddPCR. After incubation with HBV infection sera, HBV DNA could be detected, but below the valid titer of the assay kit. The HBV DNA levels in HBV-incubated HUMSCs gradually decreased with medium change every 2 days and then significantly decreased, not even detected after passage. Conclusions The current cell-based screening methods could not detect HBV in HUMSCs derived from HBV-infected donors, indicating the importance of more stringent donor eligibility to reduce the risk of transmission of communicable diseases in cell-based therapy. To solve the problem of an occult HBV window period in donor eligibility determination, we recommend that the donors undergo another HBV serological test 3 months after the first serological communicable disease screening.

Abstract Background Vitamin A plays an important role in human functions, which mainly come from foods. This study aims to examine dietary vitamin A intake and major food sources of Chinese adults. Methods We analyzed the cross-sectional data from 12,246 adult aged 18 to 64 years old in 2015 China Nutritional Transition Cohort Study. Three consecutive 24-h dietary recalls combined with household weighing method were used to assess dietary vitamin A intake. Results The average dietary vitamin A intakes were 480.9 μg retinol equivalents (RE) or 307.2 μg retinol activity equivalents (RAE). The carotenes and retinol intake of subjects were 2084.7 μg/day and 133.5 μg/day, respectively. Approximately 87% of adults consumed less vitamin A than the Chinese Estimated Average Requirement (EAR), and only 6% of adults consumed more than Chinese Recommended Nutrient Intake (RNI). Chinese adults derived vitamin A mainly from plant source foods, which is supplied as carotenes (67.4% RE or 56.4% RAE). Dark- and light- vegetables and fruits were major contributors of carotenes (accounted for 84.2%). The most import food sources of retinol were egg, meats and meat products, poultry, fish and milk, representing 94.7% of retinol intake. The major four contributors of total vitamin A (as both RE and RAE) were dark vegetables, egg, light vegetables, and meats and meat products. In conclusion, dietary vitamin A remains a problem for Chinese adults. Conclusions Public health actions are needed to increase vitamin A intake in China.

Abstract Background The prevalence of childhood overweight and obesity in developed countries appears to be plateauing. The purpose of this study was to provide the most recent data on the prevalence and trends in overweight and obesity among Chinese children and adolescents from 2011 to 2015. Methods We used data collected in the China Health and Nutrition Survey (CHNS) and China Nutritional Transition Cohort Study (CNTCS). We used two waves of the survey in 12 provinces conducted in 2011 (aged 7–18 years; n = 1458) and 2015 (aged 7–18 years; n = 1084) to perform a trend analysis. We used data collected in 15 provinces (aged 7–18 years; n = 1617) to estimate the prevalence of overweight and obesity among Chinese children and adolescents in 2015. Results In 2015, based on the Working Group for Obesity in China (WGOC) criteria, the prevalence of overweight and obesity were 14.0% (95% CI, 11.6–16.3) and 10.5% (95% CI, 8.4–12.6) in boys, and 9.7% (95% CI, 7.7–11.8) and 7.1% (95% CI, 5.2–8.9) in girls, respectively. The increase in BMI z-scores from 2011 to 2015 was statistically significant among adolescents (p = 0.0083), but not among children. No significant changes were observed in prevalence of overweight and obesity between 2011 and 2015, excepting adolescents aged 12–18 years (p = 0.0086). Conclusions Since 2011, overweight has remained stable, and obesity has stabilized in children, though not in adolescents. Although levels of childhood overweight and obesity in China are not high compared to other developed countries, they remain concerning enough that effective policies and interventions need to be sustained and intensified for lowering rates of childhood overweight and obesity.

Abstract Background Our research aimed to investigate whether lymphadenectomy was required in patients with intermediate-risk endometrioid endometrial cancer (EEC). Methods Between 1989 and 2015, 1009 patients with intermediate-risk EEC: grade 1 or 2 tumor,

Abstract Background Baicalin, an important flavonoid in Scutellaria baicalensis Georgi extracts, exerts a variety of pharmacological effects. In this study, we explored the effects of baicalin on chronic hypoxia-induced pulmonary arterial hypertension (PAH) and investigated the mechanism underlying these effects. Moreover, we examined whether the inflammatory response was mediated by the A2A receptor (A2AR) and stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-induced phosphatidyl inositol-3-kinase (PI3K) signaling in vivo. Methods We established a hypoxia-induced pulmonary hypertension (HPH) mouse model by subjecting wild-type (WT) and A2AR knockout (A2AR−/−) animals to chronic hypoxia, and we examined the effects of a 4-week treatment with baicalin or the A2AR agonist CGS21680 in these animals. Invasive hemodynamic parameters, the right ventricular hypertrophy index, pulmonary congestion, the pulmonary arterial remodeling index, blood gas parameters, A2AR expression, and the expression of SDF-1/CXCR4/PI3K/protein kinase B (PKB; AKT) signaling components were measured. Results Compared with WT mice, A2AR−/− mice exhibited increased right ventricular systolic pressure (RVSP), right ventricle-to-left ventricle plus septum [RV/(LV + S)] ratio, RV weight-to-body weight (RV/BW) ratio, and lung wet weight-to-body weight (Lung/BW) ratio in the absence of an altered mean carotid arterial pressure (mCAP). These changes were accompanied by increases in pulmonary artery wall area and thickness and reductions in arterial oxygen pressure (PaO2) and hydrogen ion concentration (pH). In the HPH model, A2AR−/− mice displayed increased CXCR4, SDF-1, phospho-PI3K, and phospho-AKT expression compared with WT mice. Treating WT and A2AR−/− HPH mice with baicalin or CGS21680 attenuated the hypoxia-induced increases in RVSP, RV/(LV + S) and Lung/BW, as well as pulmonary arterial remodeling. Additionally, baicalin or CGS21680 alone could reverse the hypoxia-induced increases in CXCR4, SDF-1, phospho-PI3K, and phospho-AKT expression. Moreover, baicalin improved the hypoxemia induced by 4 weeks of hypoxia. Finally, we found that A2AR levels in WT lung tissue were enhanced by hypoxia and that baicalin up-regulated A2AR expression in WT hypoxic mice. Conclusions Baicalin exerts protective effects against clinical HPH, which are partly mediated through enhanced A2AR activity and down-regulated SDF-1/CXCR4-induced PI3K/AKT signaling. Therefore, the A2AR may be a promising target for baicalin in treating HPH.

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