Betulinaldehyde exhibits effective anti-tumor effects in A549 cells by regulating intracellular autophagy.

It is of great significance to find new effective drugs for an adjuvant therapy targeting lung cancer to improve the survival rate and prognosis of patients with the disease. Previous studies have confirmed that certain Chinese herbal extracts have clear anti-tumor effects, and in our preliminary study, betulinaldehyde was screened for its potential anti-tumor effects. The current study thus aimed to confirm the anti-tumor effect of betulinaldehyde, using in vitro experiments to explore its underlying molecular mechanism. It was found that betulinaldehyde treatment significantly inhibited the viability, proliferation, and migration of A549 cells in a dose-dependent manner. In addition, betulinaldehyde inhibited the activation of Akt, MAPK, and STAT3 signaling pathways in A549 cells in a time-dependent manner. More importantly, betulinaldehyde also decreased the expression level of SQSTM1 protein, increased the expression level of LC3 II, and increased the autophagy flux in A549 cells. The pretreatment of A549 cells with the autophagy inhibitor, 3-methyladenine, could partially negate the anti-tumor effects of betulinaldehyde. These findings suggest that betulinaldehyde could significantly inhibit the oncological activity of A549 cells by regulating the intracellular autophagy level, making it a potentially effective option for the adjuvant therapy used to treat lung cancer in the future.

A mixed-methods study of emotional support for families of organ donors in Hunan Province, China.

Background: Family consent is a prerequisite for the organ donation of the deceased in China. However, a large number of donors are individuals who died due to accidental injuries or unanticipated diseases, which means that most of the families of such donors have just experienced the sudden death of their loved one and have to make a donation decision in a short time. This decision may cause psychological stress and some psychological damage to the minds of relatives of the donors. In addition, cultural sensitivity also has largely caused the relatives of donors inner conflicts and contradictions. And sometimes organ donation may still be stigmatized. However, have they received any emotional support and what is their emotional support needs are some questions that need to be answered. Therefore, this study aims to investigate the emotional support, influencing factors, and needs of the family members of organ donors in Hunan Province, China. Materials and methods: This is mixed-methods research that combines quantitative and qualitative research methods. A cross-sectional survey was conducted among 102 donor families using a questionnaire to investigate their emotional support status. To further understand their emotional support needs, 12 donor families participated in the semi-structured interview. Results: The results confirmed that: (1) A total of 67.7% of the 102 respondents received emotional support or psychological comfort. Thus, only a small number of respondents (31.4%) felt respected by the public. (2) Emotional support came mainly from immediate family members (73.91%), and official organizations such as the Red Cross (43.48%). (3) Marital status, health status, occupation, and coping style can affect the emotional support of the donor families (p < 0.05). (4) Interview showed that the families of donors need emotional support and psychological aid from psychological professionals mostly. And they also wish to receive the understanding and respect of the public. Conclusion: Most families of organ donors received emotional support from family, Red Cross, and friends, but only a minority of families of donors reported receiving respect from the public after the donation. And families of donor showed a strong need for emotional support and professional psychological aid from institutions.

The Effect of Online Health Information Seeking on Physician-Patient Relationships: Systematic Review.

BACKGROUND: The internet has now become part of human life and is constantly changing people's way of life. With the increasing popularity of online health information (OHI), it has been found that OHI can affect the physician-patient relationship by influencing patient behaviors. OBJECTIVE: This study aims to systematically investigate the impact of OHI-seeking behavior on the physician-patient relationship. METHODS: Literature retrieval was conducted on 4 databases (Web of Science, PubMed, China National Knowledge Infrastructure, SinoMed), and the time limit for literature publication was before August 1, 2021. RESULTS: We selected 53 target papers (42 [79%] English papers and 11 [21%] Chinese papers) that met the inclusion criteria. Of these, 31 (58%) papers believe that patients' OHI behavior can enable them to participate in their own medical care, improve patient compliance, and improve the physician-patient relationship. In addition, 14 (26%) papers maintain a neutral attitude, some believing that OHI behavior has no significant effect on doctors and patients and others believing that due to changes in the factors affecting OHI behavior, they will have a negative or a positive impact. Furthermore, 8 (15%) papers believe that OHI search behavior has a negative impact on doctors and patients, while 6 (11%) papers show that OHI reduces Chinese patients' trust in doctors. CONCLUSIONS: Our main findings showed that (1) OHI-seeking behavior has an impact on patients' psychology, behavior, and evaluation of doctors; (2) whether patients choose to discuss OHI with doctors has different effects on the physician-patient relationship; and (3) the negative impact of OHI on China's internet users is worthy of attention. Due to the low quality of OHI, poor health information literacy, short physician-patient communication time, and various types of negative news, patients' trust in doctors has declined, thus affecting the physician-patient relationship. Improvement of people's health information literacy and the quality of OHI are important factors that promote the positive impact of OHI on the physician-patient relationship.

Inhibition of miR-214-3p Protects Endothelial Cells from ox-LDL-Induced Damage by Targeting GPX4.

It is generally believed that excessive production of reactive oxygen species (ROS) during cardiovascular diseases impairs endothelial function. In this study, we aimed to investigate whether miR-214-3p is involved in the endothelial dysfunction induced by oxidized low-density lipoprotein (ox-LDL). In cultured vascular endothelial cells (VECs), the effects of miR-214-3p on endothelial injury induced by 100 mg/L ox-LDL were evaluated by knockdown of miR-214-3p. Western blotting was used to determine the expression of glutathione peroxidase 4 (GPX4) and endothelial nitric oxide synthase (eNOS) in VECs under different conditions. A luciferase reporter assay was used to identify GPX4 as the target of miR-214-3p. Our data showed that 100 mg/L ox-LDL significantly decreased the expression of GPX4 and eNOS, which was associated with increases in ROS levels and impairments of VEC viability and migration. Knockdown of miR-214-3p could partially reduce the increase in ROS, restore the decreased expression of GPX4 and eNOS, and thus rescue the impaired endothelial function caused by ox-LDL. Our data demonstrated that ox-LDL could induce upregulation of miR-214-3p and result in suppression of GPX4 in VECs. Downregulation of miR-214-3p could protect VECs from ROS-induced endothelial dysfunction by reversing its inhibitory effect on GPX4 expression.

Interactive Effects of Glucocorticoids and Cytochrome P450 Polymorphisms on the Plasma Trough Concentrations of Voriconazole.

Aims: To explore the interactive influence of glucocorticoids and cytochrome P450 (CYP450) polymorphisms on voriconazole (VRC) plasma trough concentrations (Cmin) and provide a reliable basis for reasonable application of VRC. Methods: A total of 918 VRC Cmin from 231 patients was collected and quantified using high-performance liquid chromatography in this study. The genotypes of CYP2C19, CYP3A4, and CYP3A5 were detected by DNA sequencing assay. The effects of different genotypes and the coadministration of glucocorticoids on VRC Cmin were investigated. Furthermore, the interactive effects of glucocorticoids with CYP450s on VRC Cmin were also analyzed. Results: The median Cmin of oral administration was lower than that of intravenous administration (1.51 vs. 4.0 mg l-1). Coadministration of glucocorticoids (including dexamethasone, prednisone, prednisolone, and methylprednisolone) reduced the VRC Cmin/dose, respectively, among which dexamethasone make the median of the VRC Cmin/dose ratio lower. As a result, when VRC was coadministrated with glucocorticoids, the proportion of VRC Cmin/dose in the subtherapeutic window was increased. Different CYP450 genotypes have different effects on the Cmin/dose of VRC. Mutations of CYP2C19*2 and *3 increased Cmin/dose of VRC, while CYP2C19*17 and CYP3A4 rs4646437 polymorphisms decreased Cmin/dose of VRC. The mutation of CYP3A5 has no significant effect. Furthermore, CYP2C19*17 mutants could strengthen the effects of glucocorticoids and decrease VRC Cmin/dose to a larger extent. Conclusion: Our study revealed that glucocorticoids reduced the Cmin/dose levels of VRC and different SNPs of CYP450 have different effects on the Cmin/dose ratio of VRC. Glucocorticoids and CYP2C19*17 mutants had a synergistic effect on reducing VRC Cmin/dose. The present results suggested that when VRC is combined with glucocorticoids, we should pay more attention to the clinical efficacy of VRC, especially when CYP2C19*17 mutants exist.

Bazedoxifene Plays a Protective Role against Inflammatory Injury of Endothelial Cells by Targeting CD40.

The inflammatory response and oxidative stress play key roles in the formation and development of atherosclerosis. Bazedoxifene is a new IL6/GP130 inhibitor recommended by the FDA for clinical use as a selective estrogen receptor modulator. However, its role in cardiovascular diseases has been poorly studied. In our study, we explored the mechanism of bazedoxifene's protective effect against inflammatory injury of vascular endothelial cells (VECs) stimulated by TNF-α. Various methods were used to verify the effect of bazedoxifene on VECs, including a cell viability assay, a wound healing assay, immunofluorescence staining, and western blotting. Our results showed that TNF-α could induce inflammatory damage to VECs, which manifested as upregulated expression of CD40, increased production of ROS, enhanced adhesion of THP-1 cells to VECs, and impaired viability and migration of VECs, while bazedoxifene could significantly reduce the endothelial damage caused by TNF-α. In addition, we found that an siRNA targeting CD40 dramatically alleviated the VEC damage induced by TNF-α. Therefore, we explored the potential relationship between bazedoxifene and CD40. Our data suggest that bazedoxifene has a protective effect against VEC damage induced by TNF-α and that its underlying mechanism may be related to the regulation of CD40.

Bazedoxifene inhibits PDGF-BB induced VSMC phenotypic switch via regulating the autophagy level.

There is increasing evidence that Bazedoxifene, as an FDA-approved selective estrogen inhibitor, approved by FDA, not only inhibits estrogen receptors, but also has other pharmacological effects. The purpose of this study was to investigate the effects of Bazedoxifene on the functional changes of vascular smooth muscle cells (VSMCs) after PDGF-BB stimulation. VSMCs were divided into control group, PDGF-BB treatment group, and PDGF-BB treatment group with different concentrations of Bazedoxifene. CCK-8 and EdU staining were used to determine the VSMCs viability and proliferation. Western blot was used to detect the expressions of vimentin, SMA, ERK, p-ERK, STAT3, p-STAT3, AKT, p-AKT, and LC3 I/II. Wound healing method was used to detect the migration of VSMCs. PDGF-BB treatment significantly enhanced the viability and proliferation of VSMCs as indicated by CCK-8 and EdU assays (P < 0.01), while Bazedoxifene pretreatment could reduce the increased viability and proliferation of VSMCs caused by PDGF-BB (P < 0.05). Wound healing test also showed Bazedoxifene significantly attenuated the migration in the PDGF-BB stimulated VSMCs (P < 0.01). PDGF-BB also induced the phenotypic switch and decreased the autophagy level in VSMCs, manifested as a reduction in vimentin, SMA, and LC3 II (P < 0.01). These effects of PDGF-BB were partially reversed by Bazedoxifene (P < 0.05). Bazedoxifene may inhibit the proliferation and migration of VSMCs through up-regulate the autophagy level after PDGF-BB stimulation.

Factors in Organ Donation Coordinators: A Cross-Sectional Study in China.

BACKGROUND Organ donation coordinators play an important role in the organ transplantation process. Job burnout can seriously affect their turnover rates and the organ donation rate. The present study investigated the level of job burnout and its related factors among organ donation coordinators in China. MATERIAL AND METHODS From March to May 2017, we administered questionnaire surveys to 320 organ donation coordinators from 32 cities. The questionnaire included the following: the Chinese version of MBI-GS was used to evaluate the burnout levels of organ donation coordinators, the Chinese version of GSES was used to assess related personal factors, and the Job Demands Scale and the SSRS were used to evaluate related environmental factors. RESULTS We received a total of 283 questionnaires with a response rate of 88.4%. Out of 283 organ donation coordinators, 169 coordinators (59.7%) showed burnout symptoms. Among them, 161 (56.9%) had mild burnout and 8 (2.8%) had severe burnout. Analysis by multiple linear regression reveals that gender, marital status, educational level, work unit, type of coordinator, job demands, self-efficacy, social support, and job satisfaction are the main factors affecting job burnout in organ donation coordinators. CONCLUSIONS The prevalence of job burnout among Chinese organ donation coordinators is relatively high, with mild burnout as the main symptom and reduced personal accomplishment as the main clinical feature. We hope this study will provide a reference for the recruitment and reduction of coordinator burnout.

[UPLC-MS/MS determination of tanshinone â ¡A, salvianolic acid B and ginsenoside Rg1 in Fufang Danshen preparation in rat plasma and brain tissues].

A sensitive and specific ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for analysis of tanshinone ⅡA(TSⅡA), salvianolic acid B(SAB) and ginsenoside Rg1 (GRg1) in rat plasma and brain tissues. Male healthy Sprague-Dawley(SD) rats were orally given single dose of Fufang Danshen preparation (TS ⅡA 60 mg•kg⁻¹, SAB 300 mg•kg⁻¹, GRg1 150 mg•kg⁻¹, borneol 300 mg•kg⁻¹), and their blood samples and brain tissues were collected at different time points. The drug plasma and brain tissue concentrations of the three analytes were determined by UPLC-MS/MS method. Subsequently, the main pharmacokinetics parameters of plasma and brain tissues were calculated by using Phoenix WinNolin 6.1 software. The methodological test showed that all of analytes in both plasma and brain homogenate exhibited a good linearity within the concentration range(r>0.992 2). Their mean recoveries were between 58.86% and 112.1%. Intra-day and inter-day precisions of the investigated components exhibited RSD≤9.7%, and the accuracy(RE) ranged from -9.68% to 8.20% at all quality control levels. The results of accuracy and stability meet the requirements for biopharmaceutical analysis. For TSⅡA, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.58±0.081) h, (725.4±88.20) µg•L⁻¹, (2 101.3±124.85) µg•h•L⁻¹ and (3.66±0.05) h, respectively. For SAB, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.29±0.21) h, (307.9±46.75) µg•L⁻¹, (537.4±88.24) µg•h•L⁻¹ and (2.08±0.11) h, respectively. For GRg1, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.42±0.20) h, (460.38±154.60) µg•L⁻¹, (383.4±88.16) µg•h•L⁻¹ and (1.87±0.046) h, respectively. For TSⅡA, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the brain tissue were (0.75±0.22) h, (1.41±0.42) ng•g⁻¹, (4.34±2.48) ng•h•g⁻¹ and (4.00±1.90) h, respectively. For SAB, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.08±0.20) h, (21.09±4.850) ng•g⁻¹, (14.83±3.160) ng•h•g⁻¹ and (0.99±0.08) h, respectively. For GRg1, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (0.50±0.16) h, (130.96±54.220) ng•g⁻¹, (136.24±34.350) ng•h•g⁻¹ and (2.87±0.33) h, respectively. The developed method was successfully applied in pharmacokinetic studies on content of TS ⅡA, SAB and GRg1 in rat plasma and brain tissues.

Development and validation of an LC-MS/MS method for the determination of tolvaptan in human plasma and its application to a pharmacokinetic study.

Tolvaptan is a selective vasopressin V(2)-receptor antagonist mainly used for the treatment of hyponatremia. This study described the development and validation of an LC-MS/MS method for the determination of tolvaptan in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 2-demethyl tolvaptan (internal standard, IS). Chromatographic separation was performed on a Zorbax XDB C(18) column with an isocratic mobile phase consisting of water (containing 0.1% formic acid) and methanol (25:75, v/v). Determination of the analytes was achieved by tandem-mass spectrometry with positive electrospray ionization. The multiple reaction monitoring (MRM) transitions were performed at m/z 449.2→252.1 for tolvaptan and m/z 435.2→238.1 for IS. The assay was linear over the concentration range of 0.457-1000ng/mL, with a lower limit of quantification of 0.457ng/mL. The intra- and inter-day precisions at three concentration levels (0.914, 111 and 800ng/mL) were less than 15% and their accuracies were within the range of 97.7-107.8%. The mean recovery ranged from 99.2 to 104.6% and the matrix effect from 89.3 to 99.5%. Tolvaptan was stable under all tested conditions. This validated method was successfully applied to a pharmacokinetic study in healthy volunteers after oral administration of single-dose tolvaptan tablets.