The impact of WeChat online education and care on the mental distress of caregivers and satisfaction of elderly postoperative colorectal cancer patients.

OBJECTIVE: WeChat-based nursing interventions alleviate mental distress. This study intended to investigate the effect of WeChat online education and care (WOEC) on the mental health of caregivers and the satisfaction of elderly postoperative colorectal cancer (CRC) patients. METHODS: In total, 92 elderly postoperative CRC patients and 92 caregivers were randomly separated into the WOEC group (46 patients and 46 caregivers) and the control care group (46 patients and 46 caregivers). Caregivers received corresponding intervention for 8 weeks. Beck depression inventory (BDI) and beck anxiety inventory (BAI) of caregivers, and self-report satisfaction (SRS) of patients were assessed. RESULTS: In caregivers, BDI scores at 8 weeks after enrollment (W8) (P=0.024) and BAI score at W8 (P=0.009), depression severity at W8 (P=0.036), as well as anxiety severity at 4 weeks after enrollment (W4) (P=0.028) and W8 (P=0.047) were declined in the WOEC group versus the control care group. Regarding patients, SRS scores at W4 (P=0.044) and W8 (P=0.025), the satisfaction degree at W4 (P=0.033) and W8 (P=0.034), as well as the satisfied and very satisfied rates at W4 (P=0.031) and W8 (P=0.029) were elevated in the WOEC group versus the control care group. By subgroup analyses, WOEC exhibited favorable effects on reducing mental stress in caregivers of patients with eastern cooperative oncology group performance status at enrollment <3, and in caregivers with an education level of high school & university and above. CONCLUSION: WOEC effectively relieves mental stress in caregivers of elderly postoperative CRC patients, and also elevates satisfaction in these patients.

Development and validation of a risk prediction model for aspiration in patients with acute ischemic stroke.

BACKGROUND: Aspiration is a frequently observed complication in individuals diagnosed with acute ischemic stroke, leading to potentially severe consequences. However, the availability of predictive tools for assessing aspiration probabilities remains limited. Hence, our study aimed to develop and validate a nomogram for accurately predicting aspiration probability in patients with acute ischemic stroke. METHODS: We analyzed 30 potential risk factors associated with aspiration in 359 adult patients diagnosed with acute ischemic stroke. Advanced statistical techniques, such as Least absolute shrinkage and selection operator (LASSO) and Multivariate Logistic regression, were employed to identify independent predictors. Subsequently, we developed a nomogram prediction model based on these predictors, which underwent internal validation through 1000 bootstrap resampling. Two additional cohorts (Cohort A n = 64; Cohort B, n = 105) were included for external validation. The discriminatory power and calibration performance of the nomogram were assessed using rigorous methods, including the Hosmer-Lemeshow test, area under the receiver operating characteristic curve (AUC), calibration curve analyses, and decision curve analyses (DCA). RESULTS: The nomogram was established based on four variables: sputum suction, brain stem infarction, temporal lobe infarction, and Barthel Index score. The predictive model exhibited satisfactory discriminative ability, with an area under the receiver operating characteristic curve of 0.853 (95 % confidence interval, 0.795-0.910), which remained consistent at 0.852 (95 % confidence interval, 0.794-0.912) during the internal validation. The Hosmer-Lemeshow test (P = 0.394) and calibration curve demonstrated favorable consistency between the predicted and observed outcomes in the development cohort. The AUC was 0.872 (95 % confidence interval, 0.783-0.962) in validation cohort A and 0.877 (95 % confidence interval, 0.764-0.989) in validation cohort B, demonstrating sustained accuracy. DCA showed a good net clinical benefit of the nomogram. CONCLUSIONS: A nomogram for predicting the probability of aspiration in patients with acute ischemia has been successfully developed and validated.

Prevalence of post-stroke delirium in acute settings: A systematic review and meta-analysis.

BACKGROUND: Although post-stroke delirium is a frequent complication in acute settings and has significant long-lasting implications for patients, the prevalence of post-stroke delirium diagnosed according to gold-standard criteria remains uncertain. This highlights the importance of updating the current evidence. OBJECTIVE: This review aims to provide a precise estimation of the prevalence of delirium in acute post-stroke settings and to explore potential differences in the reported prevalence according to the characteristics of the study and stroke survivors. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Post-stroke survivors with delirium in acute settings. DATA SOURCES: Five English and two Chinese language databases from inception to June 2023, and the reference lists of published reviews. METHODS: Studies reporting the prevalence of post-stroke delirium according to the Diagnostic and Statistical Manual of Mental Disorders criteria with the description of assessment method in the absence of interventions for delirium were eligible. Two reviewers independently screened searched records and extracted data from eligible studies. A meta-analysis was conducted using a random-effects model to evaluate the prevalence of post-stroke delirium, and predefined subgroup analyses, sensitivity analyses, and mixed-effects meta-regression were conducted to explore the contribution of heterogeneity. RESULTS: Twenty-nine eligible studies involving 8839 survivors were included. In acute settings, the overall weighted prevalence of post-stroke delirium was 25 % (95 % CI, 20-30; I2, 95 %). Subgroup analyses revealed age-dependent variations in delirium prevalence, with rates of 20 %, 25 %, and 34 % for ages 60-64, 65-74, and 75-79, respectively. Delirium prevalence varied by assessment duration (7 days: 31 %, >7 days: 24 %, <7 days: 20 %). Initial screening significantly reduced reported prevalence to 15 %, compared with 30 % when no initial screening was conducted. Delirium prevalence was lower when nurses were involved in assessments (13 % vs. 29 %). No significant effects were detected for economic status, publication year, female percentage, onset-to-admission time, stroke type, and assessment frequency. Meta-regression analysis revealed that higher delirium prevalence was associated with increased survivors' age (ß = 0.051; 95 % CI, -0.0002 to 0.103; P = 0.05; R2 = 13.36 %). CONCLUSION: A high prevalence of post-stroke delirium was observed in acute settings. Nurses are required to integrate and coordinate the prevention, early detection, and management of delirium following stroke into their nursing practice, particularly for older stroke survivors. The findings necessitate the need for incorporating specialized training within nursing education to identify and manage the delirium effectively and accurately. This reinforces the pivotal role of nurses in the early detection and prevention of delirium within the acute stroke care continuum. REGISTRATION: The protocol was registered on PROSPERO (CRD42022352097). TWEETABLE ABSTRACT: Evidence suggests 25 % prevalence of post-stroke delirium in acute settings, with higher rates in older patients, emphasizing the need for prevention, early detection, and management in nursing practice.

Acceptance and Commitment Therapy Among Informal Caregivers of People With Chronic Health Conditions: A Systematic Review and Meta-Analysis.

Importance: Although there is substantial evidence to suggest the health benefits of acceptance and commitment therapy (ACT) among informal caregivers of people with chronic health conditions, the great variation in intervention designs among published studies limits its application. Objectives: To identify intervention characteristics of ACT that are associated with improved psychological health and to assess the acceptability of ACT among informal caregivers. Data Sources: Seven English- and 3 Chinese-language databases without limits on publication dates, the reference lists of previous reviews, and gray literature were searched up to February 2023. Study Selection: Randomized clinical trials comparing the effect of ACT vs control groups on improving psychological health among informal caregivers. Data Extraction and Synthesis: Two reviewers independently screened searched records and extracted data from eligible studies. Random-effects meta-analysis and mixed-effects metaregression were performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed. Main Outcomes and Measures: Psychological health outcomes (eg, depressive symptoms) measured by valid measurements and the acceptability of ACT based on identified parameters. Results: A total of 29 studies with 2010 participants, published between 2015 and 2023, were identified. ACT showed moderate to large effect sizes for improving psychological health at postintervention assessments (Hedges g range, -0.55 [95% CI, -0.98 to -0.12] to -1.14 [95% CI, -1.83 to -0.45]) and at 1-to-3-month and 4-to-6-month follow-ups (Hedges g range, -0.47 [95% CI, -0.69 to -0.25] to -1.29 [95% CI, -2.33 to -0.24]). Multivariable metaregression analysis regarding intervention characteristics found that ACT delivered in a mixed individual- and group-based format, face-to-face, or through more intervention sessions was associated with greater improvements for experiential avoidance (face-to-face: ß = -1.170 [95% CI, -2.020 to -0.319]; number of sessions: ß = -0.242 [95% CI, -0.353 to -0.130]), depressive symptoms (mixed delivery format: ß = -2.583 [95% CI, -4.845 to -0.321]; face-to-face: ß = -1.555 [95% CI, -3.002 to -0.108]), or anxiety symptoms (face-to-face: ß = -1.241 [95% CI, -2.337 to -0.146]). In general, ACT had low attrition rates (11%), and participants' adherence (51%-80%) and satisfactory ratings (72%-95%) lend support to its acceptability. Conclusions and Relevance: This systematic review and meta-analysis found that ACT was consistently associated with improvements in psychological health, supporting its application to improve informal care for chronic disease management. This review provides specific details on the design parameters of ACT for achieving greater efficacy.

Biomarkers of Waterpipe Tobacco Smoke Exposure: A Systematic Review and Meta-Analysis.

INTRODUCTION: The prevalence of waterpipe tobacco smoking is increasing globally. Biomarkers of waterpipe tobacco smoke (WTS) exposure are less studied. METHODS: To identify the types of biomarkers of WTS exposure and estimate changes in biomarker concentrations pre to post WTS exposure. PubMed, Embase, Web of Science, CINAHL Plus, PsycINFO, and Cochrane Library were searched for studies up to April 24, 2023. The types of biomarkers were identified. Random-effects models were used to estimate changes of biomarker concentrations pre to post WTS exposure. RESULTS: Seventy-three studies involving 3,755 participants who exposed to WTS (49% male, mean age: 24.8 years) and 11 types of biomarkers of WTS exposure were identified. The biomarkers included tobacco alkaloids, expired carbon monoxide (eCO), carboxyhemoglobin (COHb), tobacco-specific nitrosamines, volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), heavy metals, unmetabolized VOCs, unmetabolized PAHs, furan metabolites, and heterocyclic aromatic amines. Compared with pre WTS exposure, eCO (breath; mean difference[MD] 27.00 ppm; 95% confidence interval[CI]: 20.91 to 33.08), COHb (blood; MD4.30%; 95%CI: 2.57 to 6.03), COHb (breath; MD7.14%; 95%CI: 4.96 to 9.31), nicotine (blood; MD8.23 ng/mL; 95%CI: 6.27 to 10.19), and cotinine (urine; MD110.40 ng/mL; 95%CI: 46.26 to 174.54) significantly increased post WTS exposure. CONCLUSIONS: Biomarkers of WTS exposure were systematically identified. The similarity between the biomarkers of WTS exposure and those of cigarette smoke and higher concentrations of some biomarkers post WTS exposure underscore the need for further research on applying biomarkers in surveillance, interventions, and regulations to mitigate the harms of waterpipe tobacco smoking. IMPLICATIONS: This study provides the first comprehensive overview of biomarkers investigated and available for assessing WTS exposure and their concentration changes in the human body. Researchers can use biomarkers such as eCO, COHb, nicotine, and cotinine to measure the health risks associated with WTS exposure and objectively evaluate the effectiveness of public health interventions aimed at reducing waterpipe tobacco smoking. Public health policymaking can also be informed through increased biomarker concentrations following WTS exposure, to implement regulations and public health education campaigns on limiting or preventing waterpipe tobacco smoking.

Virtual reality simulation-enhanced blood transfusion education for undergraduate nursing students: A randomised controlled trial.

BACKGROUND: Nurse-administered blood transfusion (BT) is a common form of medical treatment, but nursing students are often excluded from participating in and observing BTs during clinical placements. To address clinical placement limitations, nursing educators have increasingly adopted technology-guided simulation pedagogies, including virtual reality (VR) simulation, for nursing students' clinical skills education. OBJECTIVES: To develop VR simulation for BT practice and investigate its effectiveness with nursing students. DESIGN: A single-blinded, two-arm randomised controlled trial. SETTINGS: One university in Hong Kong. PARTICIPANTS: A total of 151 nursing students enrolled in a nursing undergraduate course at a university in Hong Kong were recruited via convenience sampling in March 2022. METHODS: Evidence-based VR simulation videos consisting of 1) animated blood formation physiology and side effects of BT and 2) 360° BT nursing practice were developed. The nursing students were randomly allocated into intervention and control groups. The intervention group (n = 75) received the usual BT education (i.e. Zoom lecture) with the developed VR video education, whereas the control group (n = 76) received the usual BT education (Zoom). The BT knowledge (RBTKQ-O), student satisfaction and self-confidence (SSSC) and self-efficacy (GSES) of BT practice were measured before and after BT education. Intention-to-treat analyses were performed. RESULTS: The primary and secondary outcomes (RBTKQ-O, SSCS and GSES, respectively) improved over time in both groups. Analysis of covariance revealed that students who received VR simulation reported higher post-intervention measurement scores in BT knowledge and SSCS than those who did not receive VR simulation. CONCLUSIONS: VR simulation-enhanced BT education effectively enhances the knowledge and SSCS of BT practice amongst nursing students. Nurse educators may adopt VR simulation to enhance the effectiveness of existing BT education for nursing students.

Acupressure can reduce preoperative anxiety in adults with elective surgery: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Preoperative anxiety is prevalent amongst adults with elective surgery and is associated with multiple detrimental perioperative physiological effects. Increasing studies support the effectiveness of acupressure in managing preoperative anxiety. However, the magnitude of acupressure's positive association with preoperative anxiety is still unclear due to a lack of rigorous evidence synthesis. OBJECTIVE: To estimate the efficacy of acupressure on preoperative anxiety and physiological parameters amongst adults scheduled for elective surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Search terms were combined for acupressure and preoperative anxiety in PubMed, Cochrane Library, EMBASE, CINAHL, China National Knowledge Infrastructure, and WanFang Data Knowledge Service Platform to search for eligible randomised controlled trials from the inception of each database through September 2022. METHODS: Pairs of researchers independently screened and extracted data from included studies. The risk of bias was assessed using the Cochrane risk of bias tool Version 2.0. Meanwhile, random-effects meta-analysis of overall effects and prespecified subgroup (i.e., surgery types, intervention providers, and acupressure stimulation tools) was conducted using Review Manager Software 5.4.1. Meta-regression was performed to explore study-level variables that may contribute to heterogeneity using STATA 16. RESULTS: Of 24 eligible randomised controlled trials, there were a total of 2537 participants from 5 countries contributed to this synthesis. When comparing acupressure with usual care or placebo, acupressure showed a large effect size for preoperative anxiety (SMD = -1.30; 95%CI = -1.54 to -1.06; p < 0.001; I2 = 86%). The significant mean reduction of heart rate, and systolic and diastolic blood pressure was -4.58 BPM (95%CI = -6.70 to -2.46; I2 = 89%), -6.05 mmHg (95%CI = -8.73 to -3.37; p < 0.001; I2 = 88%), and -3.18 mmHg (95%CI = -5.09 to -1.27; p = 0.001; I2 = 78%), respectively. Exploratory subgroup analyses showed significant differences in surgery types and acupressure stimulation tools, whilst the intervention providers (i.e., healthcare professionals and self-administered) showed no statistically significant difference for acupressure therapy. None of the predefined participants and study-level characteristics moderated preoperative anxiety through meta-regression. CONCLUSION: Acupressure appears efficacious as a therapy for improving preoperative anxiety and physiological parameters amongst adults with elective surgery. Self-administered acupressure, which is effective with a large effect, may be considered as an evidence-based approach to managing preoperative anxiety. Hence, this review aids in the development of acupressure in different types of elective surgeries and the improvement of the rigour of acupressure therapy.

Spurious Platelet Counts Due to Cell Fragmentation in a Patient with Influenza B Virus.

BACKGROUND: In clinical practice, thrombocytopenia is very dangerous for patients, because it has the risk of bleeding and may cause serious adverse consequences. Therefore, timely and accurate identification of spurious platelet counts is very important to improve patient safety. METHODS: This study reported a case of spurious platelet counts in a patient with influenza B virus. RESULTS: Leukocyte fragmentation is responsible for the inaccurate platelet detection results by resistance method in this influenza B patient. CONCLUSIONS: In practical work, if abnormalities are found, blood smear staining and microscopic examination should be carried out in time, and clinical data should be combined to avoid the occurrence of adverse events and ensure patient safety.

[Analysis and evaluation on Paeoniae Radix Alba from different cultivars by UPLC-Q-TOF-MS and HPLC].

In this study, an established ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method was combined with multivariate statistical analysis to investigate the commonality and difference of main chemical components in the medicinal parts of Paeonia lactiflora from different cultivars; in addition, a high performance liquid chromatography(HPLC) method was established to simultaneously determine the content of eight active components in Paeoniae Radix Alba. Non-targeted analysis was carried out by UPLC-Q-TOF-MS on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm) column with a gradient elution of 0.1% aqueous formic acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 0.2 mL·min~(-1). The column temperature was 30 ℃, and an electrospray ionization source was used to acquire mass spectrometry data in positive and negative ion modes. According to the accurate molecular weight and fragment ion information provided by multi-stage mass spectrometry and by comparison with reference substances and literature reports, thirty-six identical components were identified in Paeoniae Radix Alba from different cultivars with positive and negative ion modes. In the negative ion mode, two groups of samples were well separated; specifically, seventeen components with significant differences in content were screened and identified, and one component unique in "Bobaishao" was obtained. Quantitative analysis was conducted by high-performance liquid chromatography(HPLC) on an Agilent HC-C_(18)(4.6 mm×250 mm, 5 µm) column with a gradient elution of 0.1% aqueous phosphoric acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃ and the detection wavelength was at 230 nm. An HPLC method was developed for the simultaneous determination of eight active components(gallic acid, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, galloylpaeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, benzoyl-paeoniflorin) in Paeoniae Radix Albaa from different cultivars. Satisfactory linearity was achieved within the investigated linear ranges and with fine coefficients(r>0.999 0), and the methodological investigation showed that the method had good precision, repeatability and stability. The mean recoveries were 90.61% to 101.7% with RSD of 0.12% to 3.6%(n=6). UPLC-Q-OF-MS provided a rapid and efficient qualitative analytical method for the identification of the chemical components in Paeoniae Radix Alba, and the developed HPLC method was simple, rapid and accurate, which could provide a scientific basis for the evaluation of the germplasm resources and herbal quality of Paeoniae Radix Alba from different cultivars.

Effectiveness of auricular acupoint therapy targeting menstrual pain for primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Primary dysmenorrhea (PD) is a global public health concern affecting women's health and quality of life, leading to productivity loss and increased medical expenses. As a non-pharmacological intervention, auricular acupoint therapy (AAT) has been increasingly applied to treat PD, but the overall effectiveness remains unclear. AIMS: The aim of this review was to synthesize the effects of AAT targeting menstrual pain among females with PD. METHODS: Eight databases (PubMed, EMBASE, AMED, CINAHL Plus, Cochrane Library, Web of Science, China National Knowledge Infrastructure and Wanfang Data) and three registries (ClinicalTrials.gov, ISRCTN Registry and the Chinese Clinical Trial Registry) were searched to identify existing randomized controlled trials (RCTs) from inception to 21 August 2022. Two reviewers independently screened, extracted the data, and appraised the methodological quality and the evidence strength using the Cochrane risk-of-bias tool for randomized trials (RoB 2) and the GRADE approach. RESULTS: A total of 793 participants from 11 RCTs were included. Despite substantial heterogeneity, AAT was more effective in reducing menstrual pain and related symptoms than placebo and nonsteroidal anti-inflammatory medications (NSAIDs). No significant subgroup differences were found between study locations as well as invasiveness, duration, type, acupoints number, ear selection and provider of AAT. Only minor adverse effects of AAT were reported. LINKING EVIDENCE TO ACTION: AAT can help women with PD, particularly those who are refrained from pharmaceuticals. Primary healthcare professionals, including nurses, can be well-equipped to provide evidence-based and effective AAT for people with PD. AAT can be used in a broader global clinical community. To provide an optimal effect and have wider usability, a unified practice standard is required, which would necessitate further adaptation of clinical care of people with PD. AAT effectively decreased menstrual pain and other accompanying symptoms of PD. More research is needed to identify effective AAT features and explore optimal therapy regimes for PD.

Analysis and evaluation on Paeoniae Radix Alba from different cultivars by UPLC-Q-TOF-MS and HPLC / 中国中药杂志

In this study, an established ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method was combined with multivariate statistical analysis to investigate the commonality and difference of main chemical components in the medicinal parts of Paeonia lactiflora from different cultivars; in addition, a high performance liquid chromatography(HPLC) method was established to simultaneously determine the content of eight active components in Paeoniae Radix Alba. Non-targeted analysis was carried out by UPLC-Q-TOF-MS on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) column with a gradient elution of 0.1% aqueous formic acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 0.2 mL·min~(-1). The column temperature was 30 ℃, and an electrospray ionization source was used to acquire mass spectrometry data in positive and negative ion modes. According to the accurate molecular weight and fragment ion information provided by multi-stage mass spectrometry and by comparison with reference substances and literature reports, thirty-six identical components were identified in Paeoniae Radix Alba from different cultivars with positive and negative ion modes. In the negative ion mode, two groups of samples were well separated; specifically, seventeen components with significant differences in content were screened and identified, and one component unique in "Bobaishao" was obtained. Quantitative analysis was conducted by high-performance liquid chromatography(HPLC) on an Agilent HC-C_(18)(4.6 mm×250 mm, 5 μm) column with a gradient elution of 0.1% aqueous phosphoric acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃ and the detection wavelength was at 230 nm. An HPLC method was developed for the simultaneous determination of eight active components(gallic acid, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, galloylpaeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, benzoyl-paeoniflorin) in Paeoniae Radix Albaa from different cultivars. Satisfactory linearity was achieved within the investigated linear ranges and with fine coefficients(r>0.999 0), and the methodological investigation showed that the method had good precision, repeatability and stability. The mean recoveries were 90.61% to 101.7% with RSD of 0.12% to 3.6%(n=6). UPLC-Q-OF-MS provided a rapid and efficient qualitative analytical method for the identification of the chemical components in Paeoniae Radix Alba, and the developed HPLC method was simple, rapid and accurate, which could provide a scientific basis for the evaluation of the germplasm resources and herbal quality of Paeoniae Radix Alba from different cultivars.

Cellular Calcium Signals in Cancer Chemoprevention and Chemotherapy by Phytochemicals.

Identifying novel agents for cancer treatment is critical because of obstacles with anticancer drug resistance and lack of drug effectiveness. Intracellular calcium ion (Ca2+), a common second messenger, regulates various cellular pathophysiological processes including cell proliferation, differentiation and apoptosis. Recent studies have shown that the remodeling of Ca2+ signals is associated with cancer occurrence, progression and metastasis. Ca2+ channels, transporter and pumps regulate calcium movement, and alteration of Ca2+ signal component expression/activity is associated with numerous cancer cell activities. Therefore, targeting Ca2+ signals is an attractive research focus in cancer treatment. Phytochemicals, secondary metabolites in plants, exhibit multifaceted effective anticancer activities in various cancers. Although the mechanisms of the anticancer effects of phytochemicals remain unclarified, studies have indicated that many phytochemicals inhibit cancer progression through modulating calcium signals. In this review, we summarize the phytochemicals with demonstrated anticancer effects through their influence on calcium signaling, which may provide new ideas and directions in cancer research.

Diffuse Large B-Cell Lymphoma Promotes Endothelial-to-Mesenchymal Transition via WNT10A/Beta-Catenin/Snail Signaling.

Diffuse large B-cell lymphoma (DLBCL) is one type of highly heterogeneous lymphoid malignancy with 30%~40% of patients experiencing treatment failure. Novel risk stratification and therapeutic approaches for DLBCL are urgently needed. Endothelial-to-mesenchymal transition (EndMT), which contributes to tumor angiogenesis, metastasis, drug resistance, and cancer-associated fibroblast generation, has been detected in the microenvironment of many types of cancers. However, the existence of EndMT in the hematological malignancies microenvironment remains unknown. Here, we identified the existence of EndMT in DLBCL-associated endothelial cells and the clinical relevance of EndMT markers in DLBCL, which was associated with advanced clinical stage and poor prognosis. In vitro experiments confirmed that DLBCL cells stimulated angiogenesis and EndMT of human umbilical vein endothelial cells (HUVECs). We further unveiled the molecular mechanisms underlying this process. We demonstrated that WNT10A, a WNT family member overexpressed in DLBCL tissues and correlated with clinical features in DLBCL, promoted EndMT through glycogen synthase kinase 3ß (GSK3ß)/ß-catenin/snail signaling. WNT10A inhibited the binding of GSK3ß to ß-catenin/snail, resulting in ß-catenin and snail nuclear accumulation and target gene transcription. Silencing ß-catenin and snail respectively attenuated WNT10A-induced angiogenesis and EndMT. The interplay between ß-catenin-dependent and snail-dependent signaling was also confirmed in this study. Collectively, these findings identified that WNT10A/GSK3ß/ß-catenin/snail pathway performed vital roles in DLBCL-induced EndMT and indicated that EndMT markers and WNT10A may serve as novel predictors of clinical outcome.

3,3'-Diindolylmethane induces ferroptosis by BAP1-IP3R axis in BGC-823 gastric cancer cells.

To investigate the effect and potential mechanism of 3,3'-diindolylmethane (DIM) on ferroptosis against gastric cancer, cells proliferation, lipid reactive oxygen species (ROS) and GSH level were measured in the BGC-823 gastric cancer cells after DIM treatment. Western blotting was used to detect the expression of SLC7A11, GPX4, IP3R and BAP1. Results showed that DIM could induce ferroptosis in the BGC-823 gastric cancer cells via upregulating lipid-ROS level and decreasing GSH generation. Besides, DIM also significantly reduced the protein level of SLC7A11 and GPX4, which was an important regulator of ferroptosis. In addition, DIM promoted the protein level of BAP1 and IP3R in a concentration-dependent manner in the BGC-823 gastric cancer cells. The knockdown of BAP1 could reduce IP3R level and DIM-induced ferroptosis of gastric cancer cells. Taken together, these results indicated that DIM could induce ferroptosis to exert anti-cancer effects via BAP1-IP3R axis, suggesting its effective therapeutic potential in gastric cancer.

Association Between a Type 2 Inflammatory Disease Burden Score and Outcomes Among Patients with Asthma.

BACKGROUND: Although prevalence of co-existing type 2 inflammatory diseases (cT2) in asthma patients has been reported, limited data exist regarding their impact on asthma outcomes. OBJECTIVE: To assess the impact of cT2 burden on asthma outcomes and to evaluate patterns of clustering of cT2 in a real-world setting. METHODS: From medical records of 4.5 million enrollees in 650 primary care practices in the UK (January 2010-December 2017), patients with ≥1 diagnosis code for asthma at any time pre-index date (date of most recent asthma-related medical encounter) and ≥2 asthma-related prescriptions during the year before index date were categorized into the Global Initiative of Asthma (GINA) guideline severity steps. A cT2 burden score (range 0-9) was assigned based on the total number of co-existing conditions (allergic conjunctivitis, allergic rhinitis, anaphylaxis, eczema/atopic dermatitis, chronic rhinosinusitis, eosinophilic esophagitis, food allergy, nasal polyps, or urticaria) for which patients received a medical diagnosis. Multivariate regression models evaluated associations between cT2 burden score and asthma exacerbations and asthma control. Factor analysis was performed to assess which cT2 comorbidities were correlated and exhibited patterns of clustering. RESULTS: Overall, 245,893 patients with asthma were included (mean [SD] age 44.8 [22.1] years; 43.8% male). Between 55% (GINA step 1) and 60% (GINA step 5) of asthma patients had a medical diagnosis for ≥1 other type2dx. Patients with increased cT2 burden were significantly more likely to experience asthma exacerbations and less likely to achieve asthma control. CONCLUSION: Asthma patients with a higher cumulative cT2 burden score were more likely to experience worse asthma outcomes than those without any cT2 (burden score of 0).

3,3'-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry.

3,3'-Diindolylmethane (DIM), a natural phytochemicals isolated from cruciferous vegetables, has been reported to inhibit human gastric cancer cells proliferation and induce cells apoptosis as well as autophagy, but its mechanisms are still unclear. Store-operated calcium entry (SOCE) is a main Ca2+ influx pathway in various of cancers, which is activated by the depletion of endoplasmic reticulum (ER) Ca2+ store. Stromal interaction molecular 1 (STIM1) is the necessary component of SOCE. In this study, we focus on to examine the regulatory mechanism of SOCE on DIM-induced death in gastric cancer. After treating the human BGC-823 and SGC-7901 gastric cancer cells with DIM, cellular proliferation was determined by MTT, apoptosis and autophagy were detected by flow cytometry or Hoechst 33342 staining. The expression levels of related proteins were evaluated by Western blotting. Free cytosolilc Ca2+ level was assessed by fluorescence monitoring under a laser scanning confocal microscope. The data have shown that DIM could significantly inhibit proliferation and induce apoptosis as well as autophagy in two gastric cancer cell lines. After DIM treatment, the STIM1-mediated SOCE was activated by upregulating STIM1 and decreasing ER Ca2+ level. Knockdown STIM1 with siRNA or pharmacological inhibition of SOCE attenuated DIM induced apoptosis and autophagy by inhibiting p-AMPK mediated ER stress pathway. Our data highlighted that the potential of SOCE as a promising target for treating cancers. Developing effective and selective activators targeting STIM1-mediated SOCE pathway will facilitate better therapeutic sensitivity of phytochemicals acting on SOCE in gastric cancer. Moreover, more research should be performed to validate the efficacy of combination chemotherapy of anti-cancer drugs targeting SOCE for clinical application.

3,3'-diindolylmethane exerts antiproliferation and apoptosis induction by TRAF2-p38 axis in gastric cancer.

3,3'-diindolylmethane (DIM), an active phytochemical derivative extracted from cruciferous vegetables, possesses anticancer effects. However, the underlying anticancer mechanism of DIM in gastric cancer remains unknown. Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), one of the signal transduction proteins, plays critical role in proliferation and apoptosis of human gastric cancer cells, but there are still lack of practical pharmacological modulators for potential clinical application. Here, we further explored the role of TRAF2 in inhibiting cell proliferation and inducing apoptosis by DIM in human gastric cancer BGC-823 and SGC-7901 cells. After treating BGC-823 and SGC-7901 cells with DIM for 24 h, cell proliferation, apoptosis and TRAF2-related protein were measured. Our findings showed that DIM inhibited the expressions of TRAF2, activated p-p38 and its downstream protein p-p53, which were paralleled with DIM-triggered cells proliferation, inhibition and apoptosis induction. These effects of DIM were reversed by TRAF2 overexpression or p38 mitogen-activated protein kinase (MAPK)-specific inhibitor (SB203580). Taken together, our data suggest that regulating TRAF2/p38 MAPK signaling pathway is essential for inhibiting gastric cancer proliferation and inducing apoptosis by DIM. These findings broaden the understanding of the pharmacological mechanism of DIM's action as a new modulator of TRAF2, and provide a new therapeutic target for human gastric cancer.

Inhibition of endogenous hydrogen sulfide biosynthesis enhances the anti-cancer effect of 3,3'-diindolylmethane in human gastric cancer cells.

AIMS: 3,3'-Diindolylmethane (DIM) has limited anti-cancer effects in gastric cancer. Hydrogen sulfide (H2S) plays an important role in the tumor development and therapy, cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE), two key endogenous H2S biosynthesis enzymes, can affect endogenous H2S levels and alter cancer treatment. Our main objective was to investigate whether the aminooxyacetic acid (AOAA) and DL-Propargylglycine (PAG), two specific inhibitors of CBS and CSE, could assist DIM to exert a stronger anti-cancer effects in gastric cancer BGC-823 and SGC-7901 cells. MATERIALS AND METHODS: Cell proliferation was assayed by MTT and cell colony-forming assay. Apoptosis and migration were detected by Hoechst staining and scratch test respectively. Western blot was used to evaluate the expression of proteins related to proliferation, apoptosis and migration. KEY FINDINGS: Combination of AOAA or PAG with DIM synergistically inhibited proliferation and migration, increased apoptosis in gastric cancer cells. The p38-p53 axis was also further activated by the combination of AOAA or PAG with DIM. Exogenous H2S from sodium hydrosulfide, attenuated the efficacy of DIM in cancer cells by reducing the activation level of p38-p53 axis. Taken together, AOAA or PAG inhibited the expression of endogenous H2S biosynthesis enzymes and effectively enhanced susceptibility of gastric cancer to DIM through activating p38-p53 axis. SIGNIFICANCE: The current study highlight more precise requirements for the clinical application of sulfur-containing anti-cancer drugs, and open a new way to enhance the sensitivity of DIM in chemotherapy of gastric cancer.

Patient-Centric Structural Determinants of Adherence Rates Among Asthma Populations: Exploring the Potential of Patient Activation and Encouragement Tool TRUSTR to Improve Adherence.

BACKGROUND: Lack of adherence with prescribed medications among the asthma populations exacerbates health outcomes and increases social and economic costs. OBJECTIVES: The proposed study aims to model patient-centric structural determinants of adherence rates among asthma patients and explore the potential of mobile health apps such as the TRUSTR platform to improve adherence using its power of monetary and non-monetary chatbotting and non-non-monetary nudges. Following specific hypotheses are tested: (1) Patient attributes, such as their age and monetary medical condition, have significant effect on their adherence with the prescribed treatment plans. (2) Behavioral nudging with rewards and engagement via mobile health apps will increase adherence rates. METHODS: The patient population (N = 37 359) consists of commercially insured patients with asthma who have been identified from administrative claims in the HealthCore Integrated Research Database (HIRD) between April 1, 2018 and March 31, 2019. Two Structural Equation Models (SEMs) are estimated to quantify direct, indirect, and total effect sizes of age and medical condition on proportion of days covered (PDC) and medical possession ratio (MPR), mediated by patient medical and pharmacy visits. Fourteen additional SEMs were estimated to lateralize TRUSTR findings and conduct sensitivity analysis. RESULTS: HIRD data reveal mean adherence rate of 59% (standard deviation (SD) 29%) for PDC and 58% for MPR (SD 36%). Key structural findings from SEMs derived from the HIRD dataset indicate that each additional year in the age of the patient has a positive total effect on the adherence rate. Patients with poor medical condition are likely to have lower adherence rate, but this direct effect is countered by mediating variables. Further, each additional reward and higher engagement with a mobile app is likely to have a positive total effect on increasing the adherence rate. CONCLUSIONS: HIRD data reveal mean adherence rate of 59% (SD 29%), providing the evidence for the opportunity to increase adherence rate by around 40%. Statistical modeling results reveal structural determinants, such as the opportunity to nudge, are higher among younger patients, as they have higher probability of being non-adherent. Methodologically, lateralization approach demonstrates the potential to capture real-world evidence beyond clinical data and merge it with clinical data.