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Hyperoxia-induced acute lung injury (HALI) is a complication of oxygen therapy. Ferroptosis is a vital factor in HALI. This paper was anticipated to investigate the underlying mechanism of Wedelolactone (WED) on ferroptosis in HALI. The current study used hyperoxia to injure two models, one HALI mouse model and one MLE-12 cell injury model. We found that WED treatment attenuated HALI by decreasing the lung injury score and lung wet/dry weight ratio and alleviating pathomorphological changes. Then, the inflammatory reaction and apoptosis in HALI mice and hyperoxia-mediated MLE-12 cells were inhibited by WED treatment. Moreover, WED alleviated ferroptosis with less iron accumulation and reversed expression alterations of ferroptosis markers, including MDA, GSH, GPX4, SLC7A11, FTH1, and TFR1 in hyperoxia-induced MLE-12 cells in vitro and in vivo. Nrf2-KO mice and Nrf2 inhibitor (ML385) decreased WED's ability to protect against apoptosis, inflammatory response, and ferroptosis in hyperoxia-induced MLE-12 cells. Collectively, our data highlighted the alleviatory role of WED in HALI by activating the Nrf2/HO-1 pathway.
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BACKGROUND: Heat stroke (HS) generated liver injury is a lethal emergency that occurs when the body is exposed to temperatures up to 40 °C for a few hours. PURPOSE: This study aimed to evaluate the therapeutic prospects of Catalpol (CA) from the blood-cooling herb Rehamanniae Radix on liver injury by HS. STUDY DESIGN AND METHODS: A murine HS model (41 ± 0.5 °C, 60 ± 5 % relative humidity) and two cell lines (lipopolysaccharide + 42 °C) were used to assess the protective effects of CA on physiological, pathological, and biochemical features in silico, in vivo, and in vitro. RESULTS: CA treatment significantly improved survival rates in vivo and cell viability in vitro over those of the untreated group. Additionally, CA treatment reduced core body temperature, enhanced survival time, and mitigated liver tissue damage. Furthermore, CA treatment also reduced the activities of AST and ALT enzymes in the serum samples of HS mice. Molecular docking analysis of the 28 overlapping targets between HS and CA revealed that CA has strong binding affinities for the top 15 targets. These targets are primarily involved in nine major signaling pathways, with the JAK-STAT pathway being highly associated with the other eight pathways. Our findings also indicate that CA treatment significantly downregulated the expression of proinflammatory cytokines both in vivo and in vitro while upregulating the expression of anti-inflammatory cytokines. Moreover, CA treatment reduced the levels of JAK2, phospho-STAT5, and phospho-STAT3 both in vivo and in vitro, which is consistent with its inhibition of the apoptotic markers p53, Bcl2, and Bax. CONCLUSIONS: Heat stroke-induced liver injury was inhibited by CA through the downregulation of JAK/STAT signaling.
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Regulación hacia Abajo , Golpe de Calor , Hepatopatías , Hígado , Compuestos de Amonio Cuaternario , Transducción de Señal , Compuestos de Amonio Cuaternario/farmacología , Golpe de Calor/complicaciones , Hígado/efectos de los fármacos , Hígado/lesiones , Animales , Ratones , Regulación hacia Abajo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Quinasas Janus/metabolismo , Modelos Animales , Línea Celular , Hepatopatías/tratamiento farmacológico , Hepatopatías/etiología , Análisis de Supervivencia , Factores de Transcripción STAT/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps cicadae (C.cicadae), named "Chan Hua", an anamorph of Isaria cicadae Miquel, is an entomogenous complex formed by fungi parasitizing on the larvae of cicadas and belongs to the Claviciptaceae family and the genus Codyceps, which traditionally holds a significant place in Chinese ethnopharmacology, specifically for eye clarity and as a remedy for age-related ocular conditions. The underlying mechanisms contributing to its eyesight enhancement and potential effectiveness against Age-related macular degeneration (AMD) remain unexplored. AIM OF THE STUDY: This study aims to elucidate the protective role of C.cicadae and its active ingredient, Myriocin (Myr), against AMD. MATERIALS AND METHODS: A chemical inducer was employed to make retinal pigment epithelium (RPE) damage in vitro and in vivo. The key ingredients of C.cicadae and their related mechanisms for anti-AMD were studied through bioinformatic analysis and molecular biological approaches. RESULTS: Myr was identified through high-performance liquid chromatography (HPLC) as an active ingredient in C.cicadae, and demonstrated a protective effect on RPE cells, reducing the structural damage and cell death induced by sodium iodate (SI). Further, Myr reduced eyelid secretions in AMD mice and restored their retinal structure and function. The differentially expressed genes (DEGs) in Myr treatment are primarily associated with TNF and Necroptosis signaling pathways. Molecular docking indicated a strong affinity between TNF and Myr. Myr inhibited the TNF signaling pathway thereby reducing the expression of inflammatory factors in ARPE-19 cells. Additionally, Myr had consistent action with the necroptosis inhibitor Necrostatin-1 (Nec-1), inhibited the RIPK1/RIPK3/MLKL pathway thereby protecting ARPE-19 cells. CONCLUSION: The findings present Myr, as a potent protector against SI-induced AMD, predominantly through modulation of the TNF-RIPK1/RIPK3/MLKL signaling pathway, offering the insights of therapeutic C.cicadae as viable candidates for AMD treatment.
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Cordyceps , Yodatos , Degeneración Macular , Epitelio Pigmentado de la Retina , Factor de Necrosis Tumoral alfa , Animales , Degeneración Macular/tratamiento farmacológico , Cordyceps/química , Ratones , Factor de Necrosis Tumoral alfa/metabolismo , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Transducción de Señal/efectos de los fármacos , Humanos , Línea Celular , Ratones Endogámicos C57BL , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Masculino , Necroptosis/efectos de los fármacos , Ácidos Grasos MonoinsaturadosRESUMEN
Among the three most prevalent cancers affecting the female reproductive system, ovarian cancer (OV) ranks as the second most frequently diagnosed. It is important to investigate the genomic complexity of OV to develop diagnostic and therapeutic strategies. Through the utilization of bioinformatics analysis, it was determined that RacGTPase Activating Protein 1 (RACGAP1) holds significant significance in the field of OV chemotherapeutics, an aspect that has not been thoroughly explored in prior investigations. In our study, a notable increase in RACGAP1 expression was detected in ovarian cancer, demonstrating a robust association with clinicopathological features and patient prognosis. In vivo and in vitro testing revealed that RACGAP1 acts synergistically with chemotherapeutics to enhance their effects on ovarian cancer. Furthermore, an interaction between RACGAP1 and the subunit G2 of the condensin II complex, known as non-SMC condensin II complex subunit G2 (NCAPG2), has been identified. Our findings may provide new insight for improving therapeutic strategies for OV.
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Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. Systematic Review Registration: INPASY202350066.
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BACKGROUND: The aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. METHODS: Aqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. RESULTS: Compared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (P = 0.038), IL-13 (P = 0.027), IL-17/IL-17 A (P = 0.012), and IL-4 (P = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P = 0.013) and IL-17/IL-17 A (P = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes. CONCLUSION: Following sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.
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Humor Acuoso , Citocinas , Miopía , Humanos , Humor Acuoso/metabolismo , Masculino , Femenino , Miopía/cirugía , Miopía/metabolismo , Adulto , Citocinas/metabolismo , Implantación de Lentes Intraoculares , Inflamación , Persona de Mediana Edad , Presión Intraocular , Adulto JovenRESUMEN
BACKGROUND: Psychological distress is common among patients with acute coronary syndrome (ACS) and has considerable adverse impacts on disease progression and health outcomes. Mindfulness-based intervention is a promising complementary approach to address patients' psychological needs and promote holistic well-being. OBJECTIVE: This study aims to examine the effects of a social media-based mindfulness psycho-behavioral intervention (MCARE) on psychological distress, psychological stress, health-related quality of life (HRQoL), and cardiovascular risk factors among patients with ACS. METHODS: This study was a 2-arm, parallel-group randomized controlled trial. We recruited 178 patients (mean age 58.7, SD 8.9 years; 122/178, 68.5% male) with ACS at 2 tertiary hospitals in Jinan, China. Participants were randomly assigned to the MCARE group (n=89) or control group (n=89). The 6-week intervention consisted of 1 face-to-face session (phase I) and 5 weekly WeChat (Tencent Holdings Ltd)-delivered sessions (phase II) on mindfulness training and health education and lifestyle modification. The primary outcomes were depression and anxiety. Secondary outcomes included psychological stress, HRQoL, and cardiovascular risk factors (ie, smoking status, physical activity, dietary behavior, BMI, blood pressure, blood lipids, and blood glucose). Outcomes were measured at baseline (T0), immediately after the intervention (T1), and 12 weeks after the commencement of the intervention (T2). RESULTS: The MCARE group showed significantly greater reductions in depression (T1: ß=-2.016, 95% CI -2.584 to -1.449, Cohen d=-1.28, P<.001; T2: ß=-2.089, 95% CI -2.777 to -1.402, Cohen d=-1.12, P<.001) and anxiety (T1: ß=-1.024, 95% CI -1.551 to -0.497, Cohen d=-0.83, P<.001; T2: ß=-0.932, 95% CI -1.519 to -0.346, Cohen d=-0.70, P=.002). Significantly greater improvements were also observed in psychological stress (ß=-1.186, 95% CI -1.678 to -0.694, Cohen d=-1.41, P<.001), physical HRQoL (ß=0.088, 95% CI 0.008-0.167, Cohen d=0.72, P=.03), emotional HRQoL (ß=0.294, 95% CI 0.169-0.419, Cohen d=0.81, P<.001), and general HRQoL (ß=0.147, 95% CI 0.070-0.224, Cohen d=1.07) at T1, as well as dietary behavior (ß=0.069, 95% CI 0.003-0.136, Cohen d=0.75, P=.04), physical activity level (ß=177.542, 95% CI -39.073 to 316.011, Cohen d=0.51, P=.01), and systolic blood pressure (ß=-3.326, 95% CI -5.928 to -0.725, Cohen d=-1.32, P=.01) at T2. The overall completion rate of the intervention (completing ≥5 sessions) was 76% (68/89). Positive responses to the questions of the acceptability questionnaire ranged from 93% (76/82) to 100% (82/82). CONCLUSIONS: The MCARE program generated favorable effects on psychological distress, psychological stress, HRQoL, and several aspects of cardiovascular risk factors in patients with ACS. This study provides clues for guiding clinical practice in the recognition and management of psychological distress and integrating the intervention into routine rehabilitation practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033526; https://www.chictr.org.cn/showprojEN.html?proj=54693.
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Síndrome Coronario Agudo , Atención Plena , Medios de Comunicación Sociales , Humanos , Masculino , Persona de Mediana Edad , Femenino , Síndrome Coronario Agudo/terapia , Calidad de Vida , Terapia ConductistaRESUMEN
BACKGROUND: Adolescent non-suicidal self-injury (NSSI) is a major public health issue. Family factors are significantly associated with NSSI in adolescents, while studies on forecasting NSSI at the family level are still limited. In addition to regression methods, machine learning (ML) techniques have been recommended to improve the accuracy of family-level risk prediction for NSSI. METHODS: Using a dataset of 7967 students and their primary caregivers from a cross-sectional study, logistic regression model and random forest model were used to test the forecasting accuracy of NSSI predictions at the family level. Cross-validation was used to assess model prediction performance, including the area under the receiver operator curve (AUC), precision, Brier score, accuracy, sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: The top three important family-related predictors within the random forest algorithm included family function (importance:42.66), family conflict (importance:42.18), and parental depression (importance:27.21). The most significant family-related risk predictors and protective predictors identified by the logistic regression model were family history of mental illness (OR:2.25) and help-seeking behaviors of mental distress from parents (OR:0.65), respectively. The AUCs of the two models, logistic regression and random forest, were 0.852 and 0.835, respectively. LIMITATIONS: The key limitation is that this cross-sectional survey only enabled the authors to examine predictors that were considered to be proximal rather than distal. CONCLUSIONS: These findings highlight the significance of family-related factors in forecasting NSSI in adolescents. Combining both conventional statistical methods and ML methods to improve risk assessment of NSSI at the family level deserves attention.
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Trastornos Mentales , Conducta Autodestructiva , Humanos , Adolescente , Estudios Transversales , Conducta Autodestructiva/diagnóstico , Conducta Autodestructiva/epidemiología , Análisis de Regresión , Factores de Riesgo , Aprendizaje AutomáticoRESUMEN
AIM: To explore whether and to what extent, nurse-patient assessment differences mediate the association between nurse-to-patient ratios and readiness for hospital discharge, and examine whether nurse-patient characteristics moderate the indirect and/or direct effect of mediation model. DESIGN: A cross-sectional study was carried out from March 2021 to December 2022. METHODS: A total of 523 pairs of gastrointestinal cancer patients with PICC and their nurses were recruited. All the participants were invited to complete the general information questionnaire and the Readiness for Hospital Discharge Scale. Outcome measure was patient-reported readiness for hospital discharge. This study was reported according to the STROBE checklist. RESULTS: The patients reported a low level of readiness for hospital discharge. Nurse-patient assessment differences were positively associated with nurse-to-patient ratios but negatively associated with readiness for hospital discharge. Furthermore, nurse-patient assessment differences fully mediated the effect of nurse-to-patient ratios on readiness for hospital discharge, and age and gender of patients only moderated the indirect path of mediation model.
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Lista de Verificación , Alta del Paciente , Humanos , Estudios Transversales , Relaciones Enfermero-Paciente , HospitalesRESUMEN
OBJECTIVE: Many people with mental disorders are cared for by informed caregivers, but they usually have limited care-related training and lack caregiving capacity and support networks. In order to provide professional training and social support for informed caregivers, we designed the Caregivers-to-Caregivers Training Programme (C2C) and performed a pilot study to assess its effect. METHODS: Caregivers of persons with mental disorders who participated in the C2C were asked to participate in a quasi-experimental study to assess their knowledge and skills development, self-care ability, trainer engagement, and training content. A total of 800 participants completed self-designed evaluation questionnaires and two open-ended questions to gather suggestions and feedback. Assessments were carried out at pretest (baseline), post-test, and at 2-month follow-up. Results were analyzed using one-way repeated measures analysis of variance (ANOVA) and pairwise comparison method. RESULTS: At post-test, 667 assessments were considered valid and 515 were deemed valid at 2-month follow-up. One-way repeated-measures ANOVA showed that the main effect of the scores on knowledge and skills development and self-care ability from baseline to 2-month follow-up was significant (p < .001). Results of pairwise comparison method showed that the scores on each item of knowledge and skills development and self-care ability at post-test and at 2-month follow up were higher than those at baseline (p < .001). The scores on items of trainer engagement and training content were all above average (4/5). The open-ended questions resulted in 678 comments indicating that participants gained significant support from other caregivers and healthcare professionals in the alliance and wanted more and continuously updated material. CONCLUSION: This study demonstrated that C2C effectively improved the development of caregivers' knowledge, skills, and their self-care ability. Available social support for caregivers was better than average, including professional support and peer support.
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Cuidadores , Trastornos Mentales , Humanos , Cuidadores/educación , Proyectos Piloto , Trastornos Mentales/terapia , Personal de Salud , Apoyo SocialRESUMEN
AIM: To evaluate the clinical significance of checking episcleral venous fluid wave (EVFW) during gonioscopy-assisted transluminal trabeculotomy (GATT) in patients with open angle glaucoma (OAG). METHODS: This retrospective case series study comprised 30 patients (45 eyes) with OAG underwent GATT. The location and extent of EVFW were examined and graded after intraoperative compression flushing of the anterior chamber angle during the operation. Patients were followed up for 1y. A complete success for surgery is defined as a postoperative intraocular pressure (IOP) <18 mm Hg without any anti-glaucoma medication. IOP<18 mm Hg with less than two anti-glaucoma medications is defined as qualified success, while the control of IOP requiring three anti-glaucoma medications is considered as unsuccess. RESULTS: The mean IOP was 35.38±7.16 mm Hg before surgery and 15.52±4.22 mm Hg 1y after surgery (P<0.01). The average number of anti-glaucoma medication was 2.8±1.2 (2-4) preoperation and 0.6±1.3 (0-3) 1y postoperation (P<0.01). The success rate of the operation was 93.33%. Complete success rate was 66.67%, qualified success rate was 26.67%, and 6.66% of unsuccessful cases required reoperation. EVFW of all cases was grade 2-4, and the percentages of grade 2, 3 and 4 were 33.33%, 40.0% and 26.67%, respectively. The distribution and percentage of EVFW were inferior (36%), nasal (28%), superior (20%), and temporal (16%). The EVFW grade of complete success patients was 3.4±0.6 (3-4), and that of qualified success patients was 2.6±1.0 (2-4). The larger the range of EVFW, the lower the IOP, and the better the IOP reduction effect. CONCLUSION: During GATT surgery, pressurized irrigation of anterior chamber to check EVFW can reduce the outflow resistance of aqueous humor and increase the effect of postoperative IOP. The range of EVFW is negatively correlated with postoperative IOP. Therefore, EVFW may be a valuable prognostic indicator for the success of GATT surgery.
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Inhibition of type II alveolar epithelial (AE-II) cell apoptosis is a critical way to cure hyperoxia-induced acute lung injury (HALI). It has been reported that miR-21-5p could reduce H2O2-induced apoptosis in AE-II cells. However, the upstream molecular mechanism remains unclear. Herein, we established a cellular model of HALI by exposing AE-II cells to H2O2 treatment. It was shown that miR-21-5p alleviated H2O2-induced apoptosis in AE-II cells. ROS inhibition decreased apoptosis of H2O2-evoked AE-II cells via increasing miR-21-5p expression. In addition, ROS induced MAPK and STAT3 phosphorylation in H2O2-treated AE-II cells. MAPK inactivation reduces H2O2-triggered AE-II cell apoptosis. MAPK activation inhibits miR-21-5p expression by promoting STAT3 phosphorylation in H2O2-challenged AE-II cells. Furthermore, STAT3 activation eliminated MAPK deactivation-mediated inhibition on the apoptosis of AE-II cells under H2O2 condition. In conclusion, ROS-mediated MAPK activation promoted H2O2-triggered AE-II cell apoptosis by inhibiting miR-21-5p expression via STAT3 phosphorylation, providing novel targets for HALI treatment.
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Lesión Pulmonar Aguda , Apoptosis , Hiperoxia , MicroARNs , Humanos , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/patología , Células Epiteliales Alveolares/metabolismo , Peróxido de Hidrógeno/metabolismo , Hiperoxia/complicaciones , MicroARNs/genética , MicroARNs/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
Background: The alkaline phosphatase-to-albumin ratio (APAR) has been demonstrated to be a promising non-invasive biomarker for predicting prognosis in certain diseases. However, the relationship between APAR and prognosis in non-dialysis chronic kidney disease (CKD) patients remains unclear. This study aims to identify the association between APAR and prognosis among CKD stages 1-4 in China. Methods: Patients with CKD stages 1-4 were consecutively recruited from 39 clinical centers in China from 2011 to 2016. New occurrences of end-stage kidney disease (ESKD), major adverse cardiovascular and cerebrovascular events, and all-cause deaths were the outcome events of this study. Subdistribution hazard competing risk and Cox proportional hazards regression models were adopted. Results: A total of 2,180 participants with baseline APAR values were included in the analysis. In the primary adjusted analyses, higher APAR level [per 1-standard deviation (SD) increase in natural logarithm transformed (ln-transformed) APAR] was associated with 33.5% higher risk for all-cause deaths [adjusted hazard ratio (HR) 1.335, 95% confidence interval (CI) 1.068-1.670]. In addition, there was evidence for effect modification of the association between APAR and ESKD by baseline estimated glomerular filtration rate (eGFR) (P interaction < 0.001). A higher APAR level (per 1-SD increase in ln-transformed APAR) was associated with a greater risk of ESKD among participants with eGFR ≥ 60 ml/min/1.73 m2 (adjusted SHR 1.880, 95% CI 1.260-2.810) but not in eGFR < 60 ml/min/1.73 m2. Conclusion: Higher APAR levels in patients with CKD stages 1-4 seemed to be associated with an increased risk of all-cause death. Thus, APAR appears to be used in risk assessment for all-cause death among patients with CKD stages 1-4.
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BACKGROUND: We implemented the QuantiFERON-TB Gold In-Tube (QFT-GIT) based on peripheral blood mononuclear cells (QFT-PBMCs) and QFT Gold Plus (QFT-Plus) in patients with indeterminate results, and use Mit-Nil value to identify false negatives and impaired cellular immunity. METHODS: One hundred seventy-one out of 2480 patients who had a QFT-GIT test were prospectively recruited and classified as high Nil (n = 35), low Mit (n = 75) and control (n = 61) cohorts. Head-to-head comparisons, i.e., QFT-PBMCs vs. QFT-GIT in high Nil cohort, QFT-Plus vs. QFT-GIT in low Mit cohort, and QFT-PBMCs vs. QFT-GIT in controls, were performed. Lymphocyte subsets counts were conducted in low Mit and control cohorts. RESULTS: A significant reduction of positive rate only occurred in Mit-Nil < 6 IU/ml (p < 0.001). QFT-PBMCs yielded 100 % valid results and had a significant Nil decline in high Nil cohort (0.98 ± 1.06 vs. 9.55 ± 0.64 IU/ml, p < 0.0001), while correlated well with QFT-GIT for qualitative (Cohen's k = 0.93) and quantitative (TB-Ag [R2 = 0.91] and Mit [R2 = 0.94]) analyses. QFT-Plus produced 61.3 % valid results and had a significant Mit increase in low Mit cohort (0.82 ± 0.95 vs. 0.17 ± 0.11 IU/ml, p < 0.0001). Mit-Nil value significantly correlated with lymphocyte subsets counts (R:0.49-0.56, p < 0.0001), separately corresponding to thresholds of 4.26, 5.33, 5.55 and 5.81 IU/ml for predicting decreased total lymphocyte, T lymphocyte, CD4+ and CD8+ cells. CONCLUSIONS: QFT that replacing whole blood with PBMCs should be recommended to handle high Nil samples, and QFT-Plus can declined the frequency of low Mit results. In addition, Mit-Nil < 6 and 5.81 IU/ml are potential thresholds to identify the risk of false negatives and impaired cellular immunity, respectively.
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Ensayos de Liberación de Interferón gamma , Leucocitos Mononucleares , Humanos , Linfocitos T CD8-positivos , Inmunidad Celular , Recuento de LinfocitosRESUMEN
BACKGROUND: People frequently experience physical and psychological challenges (e.g., depression and anxiety) and high risk of poor prognosis after an acute coronary event. Mindfulness-based intervention holds promise as an effective approach to promoting health and well-being. OBJECTIVES: To explore the feasibility, acceptability, and potential effects on psychological distress, cardiovascular risk factors and health-related quality of life of a mindfulness-oriented psycho-behavioral intervention for patients with acute coronary syndrome. METHODS: We conducted a pilot randomized controlled trial to test the feasibility, acceptability and potential effects of the intervention in 50 patients with acute coronary syndrome. The intervention included six weekly sessions, including one face-to-face session and five WeChat-delivered sessions that incorporated mindfulness training with health education and lifestyle modification. Eligible patients were recruited in two public hospitals in China and randomly allocated into the intervention group (n = 25) or control group (n = 25). RESULTS: Intervention feasibility was supported by a relatively high recruitment rate (66.7%) and retention rate (84%) and a smooth and brief data collection procedure (15 to 25 min) of the pilot study. Positive responses of the acceptability dichotomous scale ranged from 81% to 100%, suggesting the intervention was generally acceptable. The intervention had a significant group × time effect on dietary behavior (B = 0.31,95% CI: 0.08, 0.54, P = 0.008) with an effect size (Cohen's d) of -0.72. CONCLUSIONS: The mindfulness-oriented psycho-behavioral intervention appears to be feasible and acceptable and have a promising effect on dietary behavior in patients with acute coronary syndrome. A fully powered randomized controlled trial is warranted to further assess the efficacy of the intervention. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No., ChiCTR2000033526.
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Síndrome Coronario Agudo , Atención Plena , Humanos , Atención Plena/métodos , Proyectos Piloto , Calidad de Vida , Síndrome Coronario Agudo/terapia , Ansiedad/psicología , Estudios de FactibilidadRESUMEN
Heat stroke (HS) is the deadliest disease. Due to the complex pathogenesis of HS, lack of effective therapeutic drugs for clinical treatment. Shikonin (SK) is the main active compound of Radix Arnebiae, which was evaluated on the HS model (temperature: (41 ± 0.5) â, relative humidity: (60 ± 5) %) via pathological and biochemical approaches in vivo and in vitro. Upon the dose of 10 mg.kg-1, SK delays the rising rate of core temperature, prolongs the survival time of mice, and improves organ injury and coagulation function markedly. Serum HS biomarkers interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were decreased significantly by SK, which contribute to liver and lung protection in the models. Three pathways' responses to heat-stress were found to have a close connection with the IL-17 pathway via RNA sequencing and network analysis. WB and IHC results showed that the nuclear factor-κB (NF-κB) p65 in the SK group was down-regulated (P < 0.05). The expressions of nuclear factor erythroid 2 like 2 (NFE2L2/Nrf2) and heat shock protein 70 (HSP70) were up-regulated (P < 0.05). Additional administration of recombinant IL-17A protein on the HS model up-regulated the expression level of NF- κB p65 in the liver and lung tissue, additional intraperitoneal injection of IL-17A antibody in mice has a synergistic effect with SK in inhibiting tissue inflammatory response and protecting HS. In summary, SK was proved an effective compound for fulfilling the anti-inflammatory and antioxidative capacity of the HS model by reducing the production and inhibiting the expression of IL-17A.
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Golpe de Calor , Naftoquinonas , Animales , Ratones , Interleucina-17 , Golpe de Calor/tratamiento farmacológico , Naftoquinonas/farmacología , Naftoquinonas/uso terapéutico , Estrés OxidativoRESUMEN
Understanding the intention of community residents to seek help from mental health professionals (MHPs) is essential in targeting interventions that promote the prevention and treatment of depression. This study aimed to investigate the current status of Chinese community populations' depression help-seeking intentions from MHPs and explore factors influencing the intentions. Data were used from a survey conducted in a city in central China (n = 919 aged 38.68 ± 17.34, 72.1% female). Help-seeking intentions, help-seeking attitude, depression stigma, family function and depressive symptoms were measured. The total mean score on the intent to seek help from MHPs was 11.01 ± 7.78 and most of respondents were unwilling to seek professional help. Multiple linear regression showed that participants who were students, held a positive help-seeking attitude and had low personal stigma were more likely to have the intention to seek help from MHPs. It is necessary to utilize effective interventions to improve community residents' intention to seek professional help. These include promoting the importance of seeking professional assistance, optimizing the quality of mental health services and altering residents' prejudice to seeking professional help.
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Depresión , Conducta de Búsqueda de Ayuda , Humanos , Femenino , Masculino , Depresión/terapia , Depresión/psicología , Salud Mental , Intención , Vida Independiente , Aceptación de la Atención de Salud/psicología , Estigma Social , ChinaRESUMEN
BACKGROUND: Dopamine is a neurotransmitter and has been found to regulate lymphocytes by acting on dopamine receptors (DRs). CD4+ T cells express all the five subtypes of DRs, D1R to D5R. Although CD4+ T cells have been involved in pathogenesis of rheumatoid arthritis (RA), roles of DRs expressed on these cells in RA are poorly understood. This study determined whether D2R expressed on CD4+ T cells regulates inflammatory responses and signs in collagen type II (CII)-induced arthritis (CIA), a mouse model of RA. METHODS: DBA/1 mice and C57BL/6 mice with global D1r or D2r deficiency (D1r-/- or D2r-/-) or CD4+ T cell-specific D2r deletion (D2rfl/fl/CD4Cre) were used to prepare CIA model by intradermal injection of CII. D2R agonist sumanirole was intraperitoneally administered in CIA mice. CD4+ T cells obtained from CIA mice were exposed to sumanirole or/and D2R antagonist L-741,626 in vitro. Arthritic symptoms were assessed by clinical arthritis scores. Flow cytometric assay measured frequencies of CD4+ T cell subsets (Th1, Th2, Th17 and Treg cells). Expression of specific transcription factors for the CD4+ T cell subsets was tested by Western blot. Cytokine production was estimated by quantitative PCR and ELISA. RESULTS: CIA mice manifested a bias of CD4+ T cells towards Th1 and Th17 cells. D2r-/- CIA mice showed a stronger bias towards Th1 and Th17 phenotypes than CIA mice, while D1r-/- CIA mice did not show the changes. CD4+ T cell-specific D2r deletion exacerbated both the polarization towards Th1 and Th17 cells and the symptoms of arthritis. Sumanirole administration in CIA mice ameliorated the bias of CD4+ T cells towards Th1 and Th17 phenotypes as well as arthritic symptoms. Sumanirole treatment of in vitro CD4+ T cells obtained from CIA mice promoted the shift to Treg cells, and the effect of sumanirole was blocked by L-741,626. CONCLUSIONS: D2R expressed on CD4+ T cells is protective against imbalance between pro-inflammatory and anti-inflammatory T cells and arthritic symptoms in CIA.
Asunto(s)
Artritis Experimental , Artritis Reumatoide , Receptores de Dopamina D2 , Animales , Ratones , Artritis Experimental/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Receptores de Dopamina D2/metabolismo , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismoRESUMEN
Two air-stable sulfur-ligated dysprosium(III) complexes [HN(Et)3][Dy2NaL8] (1) and [DyNaL4(MeOH)x(H2O)2-x]n (2) based on 2-pyridinethiol 1-oxide (HL) were synthesized and structurally characterized. Discrete 1 and polymeric 2 share the same anionic unit of [DyL4]- with the O4S4 coordination environment, but differ in the precise geometry with triangular dodecahedron geometry in 1 and biaugmented trigonal prism geometry in 2. The subtle change leads to observable temperature-independent relaxation for 2 while a faster relaxation with invisible peak for 1 at zero dc field. Under an optimal dc field, both display the typical Raman process with a smaller pre-factor and higher exponent for 2. Ab initio calculations reveal that the predicted energy barriers are 287 cm-1 for 1 and 303 cm-1 for 2. These results demonstrate the construction and magnetic modulation of air-stable sulfur-ligated Dy-SMM architectures.