Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

Mediating role of anxiety and impulsivity in the association between child maltreatment and lifetime non-suicidal self-injury with and without suicidal self-injury.

BACKGROUND: Child maltreatment can increase the risk of lifetime non-suicidal self-injury (NSSI) and suicidal self-injury (SSI), but there is limited knowledge regarding the differences of potentially psychological mechanisms between NSSI with and without SSI. METHODS: Participants, 3918 community-based Chinese young men aged 18-34 years in Chengdu, were included in this study. We investigated the association between depression, anxiety, psychosis, child maltreatment, adulthood traumatic events, impulsivity, alcohol dependence, drug abuse, and lifetime of NSSI among participants with and without SSI. Parallel mediation analysis was utilized to explore the mediators for the relation between child maltreatment and NSSI. RESULTS: The prevalence of lifetime NSSI was 6.1 % (95 % CI: 5.4 %-6.9 %) among young men. Anxiety and impulsivity partially mediated the effect of child maltreatment on NSSI either with (indirect effect: 51.2 %) or without SSI (indirect effect: 34.3 %). Depression was independently and significantly associated with only NSSI but not with NSSI+SSI. Alcohol dependence and psychosis were independently and significantly associated with NSSI+SSI and mediated the effect of child maltreatment on NSSI+SSI. LIMITATIONS: The cross-sectional survey data limits the robustness of the proof to the causal relationships. CONCLUSIONS: Anxiety and impulsivity are associated with NSSI either with or without SSI and partially mediate the effect of child maltreatment on NSSI. Depression is associated with only NSSI, while alcohol dependence and psychosis are only associated with NSSI+SSI. It could be crucial to improve treatment and recovery of alcohol dependence and psychosis for preventing young men engaged in NSSI from attempting SSI.

Multivariate classification based on large-scale brain networks during early abstinence predicted lapse among male detoxified alcohol-dependent patients.

Identifying biomarkers to predict lapse of alcohol-dependence (AD) is essential for treatment and prevention strategies, but remains remarkably challenging. With an aim to identify neuroimaging features for predicting AD lapse, 66 male AD patients during early-abstinence (baseline) after hospitalized detoxification underwent resting-state functional magnetic resonance imaging and were then followed-up for 6 months. The relevance-vector-machine (RVM) analysis on baseline large-scale brain networks yielded an elegant model for differentiating relapsing patients (n = 38) from abstainers, with the area under the curve of 0.912 and the accuracy by leave-one-out cross-validation of 0.833. This model captured key information about neuro-connectome biomarkers for predicting AD lapse.

Differences among fathers, mothers, and teachers in symptom assessment of ADHD patients.

Background: The Swanson Nolan, and Pelham scale version IV (SNAP-IV) is the most critical tool for ADHD screening and diagnosis, which has two scoring methods. ADHD requires symptom assessment in multiple scenarios, and parent and teacher reports are indispensable for diagnosing ADHD. But the differences of assessment results from fathers, mothers and teachers, and the consistency of results from different scoring methods are unknown. Therefore, we carried out this study to understand the differences in the scores of fathers, mothers and teachers using SNAP-IV for children with ADHD and to explore the differences in scoring results under different scoring methods. Methods: The SNAP-IV scale and Demographics Questionnaire and Familiarity Index were used to survey fathers, mothers and head teachers. Measurement data are expressed as the mean ± standard deviation (x ± s). The enumeration data were described by frequency and percentage. ANOVA was used to compare group differences in mothers', fathers', and teachers' mean SNAP-IV scores. The Bonferroni method was used for post hoc multiple comparison tests. Cochran's Q test was used to compare the differences in the abnormal rate of SNAP-IV score results of mothers, fathers and teachers. Dunn's test was used for post hoc multiple comparison tests. Results: There were differences in scores among the three groups, and the differences showed inconsistent trends across the different subscales. Differences between groups were calculated again with familiarity as a control variable. The results showed the familiarity of parents and teachers with the patients did not affect the differences in their scores. The evaluation results were different under two assessment methods. Conclusion: Results concluded that fathers did not appear to be an appropriate candidate for evaluation. When using the SNAP-V for assessment, it should be comprehensively considered from both the scorer and symptom dimensions.

Case report: Orthostatic leg tremor as the initial manifestation in a patient with metabotropic glutamate receptor-5 encephalitis without cortical dysfunction: complexities in identification and treatment.

Objective: Metabotropic glutamate receptor 5 (mGluR5) encephalitis is such a rare type of autoimmune encephalitis that its diagnosis remains a challenge. Case report: A 19-year-old female patient initially presented with anxiety and orthostatic leg tremors without cortical dysfunction. We found that this patient was positive for mGluR5 antibodies in both serum (1:1,000) and cerebrospinal fluid (1:32). After comprehensive intervention, the patient showed complete recovery at the 18-month follow-up. Discussion: This report expands our knowledge of the possible presentations of mGluR5 encephalitis for early diagnosis, which makes it possible to prevent serious consequences and improve the prognosis.

Corrigendum: Differential effects of anxiety on internet gaming disorder: A large-scale cross-sectional survey.

[This corrects the article DOI: 10.3389/fpsyt.2021.802513.].

Data-driven study on resting-state functional magnetic resonance imaging during early abstinence of alcohol dependence in male patients and its predictive value for relapse.

BACKGROUND: Alcohol dependence is a mental disorder with a high relapse rate. However, specific neuroimaging biomarkers have not been determined for alcohol dependence and its relapse. We conducted data-driven research to investigate resting-state functional magnetic resonance imaging (rs-fMRI) during early abstinence from alcohol dependence and its potential ability to predict relapse. METHODS: Participants included 68 alcohol-dependent patients and 68 healthy controls (HCs). The regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) were compared between the alcohol dependence group and the HCs and between the relapse group and the nonrelapse group. The brain regions that presented significantly different ReHo and/or fALFF between the alcohol-dependent patients and HCs and/or between the relapsed and nonrelapsed patients were selected as the seeds to calculate the functional connectivities (FCs). RESULTS: During a 6-month follow-up period, 52.24% of alcohol-dependent patients relapsed. A regression model for differentiating alcohol-dependent patients and HCs showed that reductions in ReHo in the left postcentral region, fALFF in the right fusiform region, and FC in the right fusiform region to the right middle cingulum were independently associated with alcohol dependence, with an area under the receiver operating characteristic curve (AUC) of 0.841. The baseline FC of the left precentral to the left cerebellum of the relapse group was significantly lower than that of the nonrelapse group. The AUC of this FC to predict relapse was 0.774. CONCLUSIONS: Our findings contribute to advancing research on the neurobiological etiology and predictive biomarkers for relapse associated with alcohol dependence.

A bidirectional association between internet addiction and depression: A large-sample longitudinal study among Chinese university students.

BACKGROUND: Internet addiction (IA) is associated with adverse consequences, especially for younger people. Evidence indicates that IA is associated with depression, but no studies have yet investigated potential common vulnerability between them. METHODS: IA (measured by the Young's 20-item Internet Addiction Test Scale) and depressive symptoms (measured by the Patient Health Questionnaire-9 Scale) among 12 043 undergraduates were surveyed at baseline and at a respective 12 month follow-up for each participant. Application of a cross-lagged panel model approach (CLPM) revealed an association between IA and depression after adjusting for demographic variables. RESULTS: Rates of baseline IA and depression were 5.47% (95% CI: 5.07%, 5.88%) and 3.85% (95% CI: 3.51%, 4.20%), respectively; increasing to 9.47% (95% CI: 8.94%, 9.99%) and 5.58% (95% CI: 5.17%,5.99%), respectively, at follow-up. Rates of new-incidences of IA and depression over 12 months were 7.43% (95% CI: 6.95%, 7.91%) and 4.47% (95% CI: 4.09%, 4.84%), respectively. Models in the present analysis revealed that baseline depression had a significant net-predictive effect on follow-up IA, and baseline IA had a significant net-predictive effect on follow-up depression. LIMITATIONS: The follow-up survey response rate was moderate (54.69%) in this analysis of university students. Moreover, the IAT-20 scale did not allow differentiate between specific forms of Internet activity. CONCLUSIONS: Common vulnerability and bidirectional cross-causal effects may both contribute to the association between IA and depression, with common vulnerability likely playing a more significant role than cross-causal effects.

The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway.

OBJECTIVE: This study aimed to clarify the mechanism by which the long non-coding RNA cancer susceptibility candidate 9 (CASC9) alleviates sepsis-related acute kidney injury (S-AKI). METHODS: A lipopolysaccharide (LPS)-induced AKI model was established to simulate S-AKI. HK-2 human renal tubular epithelial cells were treated with LPS to establish an in vitro model, and mice were intraperitoneally injected with LPS to generate an in vivo model. Subsequently, the mRNA expression of inflammatory and antioxidant factors was validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Reactive oxygen species (ROS) production was assessed using an assay kit. Apoptosis was detected by western blotting and fluorescence-activated cell sorting. RESULTS: CASC9 was significantly downregulated in the LPS-induced AKI model. CASC9 attenuated cell inflammation and apoptosis and enhanced the antioxidant capacity of cells. Regarding the mechanism, miR-424-5p was identified as the downstream target of CASC9, and the interaction between CASC9 and miR-424-5p promoted thioredoxin-interacting protein (TXNIP) expression. CONCLUSIONS: CASC9 alleviates LPS-induced AKI in vivo and in vitro, and CASC9 directly targets miR-424-5p and further promotes the expression of TXNIP. We have provided a possible reference strategy for the treatment of S-AKI.

Posttraumatic stress disorder symptoms among child survivors of the 2008 Wenchuan earthquake: a comparison between Chinese ethnic Han and Hui groups.

BACKGROUND: Relatively few studies have compared posttraumatic stress disorder (PTSD) symptoms following a disaster among children of different ethnicities. We sought to investigate the differences in PTSD symptoms between the ethnic Hui and Han child survivors of the 2008 Wenchuan earthquake in China. METHODS: This study collected data from 1,951 Han and 247 Hui child survivors of the 2008 Wenchuan earthquake in China. The children ranged from 7 to 15 years of age. Earthquake-related exposures were measured using a modified version of the PsySTART Rapid Triage System. PTSD symptoms were evaluated using the University of California, Los Angeles PTSD-Reaction Index (UCLA PTSD-RI). Personality characteristics were assessed using the Junior Eysenck Personality Questionnaire (JEPQ). Multiple linear regression was used to investigate the association between the ethnicity and the severity of PTSD symptoms. Multiple logistic regression was used to investigate the association between the ethnicity and the percentage of screening positive for PTSD symptoms. RESULTS: The average UCLA PTSD-RI total score of the ethnic Hui group (27.01 ± 9.24) was significantly higher than that of the ethnic Han group (25.12 ± 9.17) (t = -3.05, p = 0.002), as were the avoidance/numbness (Hui: 10.02 ± 4.82; Han: 9.04 ± 4.60, t = -3.12, p = 0.002) and arousal scores (Hui: 9.36 ± 3.64; Han: 8.79 ± 3.42, t = -2.44, p = 0.015). The percentage of screening positive for D criteria (arousal symptoms) also differed significantly between the ethnic Han (41.9%, 95% CI [39.7-44.1%]) and Hui (48.6%, 95% CI [42.3-54.9%]) groups (χ2 = 3.97, p = 0.046). Ethnicity was associated with the avoidance/numbness symptom score following adjustments for sex, age, personality traits and earthquake exposure experiences by multiple linear regression (B: 0.61, 95% CI [0.04-1.17], p = 0.035). The initial significant associations between the ethnicity and the arousal symptoms score and the PTSD total score disappeared while adjusting for the subjective earthquake exposure experiences (Model 5: arousal symptoms, B = 0.41, 95% CI [-0.01 to 0.83], p = 0.056; PTSD, B = 1.00, 95% CI [-0.07 to 2.07], p = 0.066). The initial significant association between the ethnicity and the percentage of screening positive for D criteria disappeared while adjusting for the objective earthquake exposure experiences (Model 4: OR = 1.32, 95% CI [1.00-1.75], p = 0.052). CONCLUSION: This study is the first to report the relationship between the ethnicity and PTSD symptoms among child survivors following a disaster. The findings of this study suggest that the trauma-focused cognitive behavior therapy could also be an effective treatment for Chinese ethnic Hui and Han children who are suffering from PTSD. Future research could be designed to examine whether cultural differences in perceptions and interpretations may account for the variations in subjective experiences. More attention should be paid to the ethnic minority children with PTSD in the future.

The efficacy and safety of gemcitabine-based induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: A meta-analysis.

OBJECTIVES: To assess the efficacy and toxicity of gemcitabine-based induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: Both observational studies (OBS) and randomized controlled trials (RCT) were included in the meta-analysis. Systematic online searches were conducted in Web of Sciences, PubMed, Embase, meeting proceedings and ClinicalTrials.gov from the inception to May 25, 2020. The primary endpoint of interest was overall survival. RESULTS: five OBSs and 2 RCTs including 1680 patients were incorporated in the analysis. The evidence from the RCTs showed that adding gemcitabine-based induction chemotherapy to CCRT significantly improved progression free survival (hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.40-0.88; P = .010; chi square P = .25; I2 = 24%) and overall survival (HR: 0.47; 95% CI: 0.28-0.80; P = 0.005; chi square P = .49, I2 = 0%) and was related to a higher risk of hematological toxicities. Furthermore, based on the data of OBSs, overall survival (HR: 0.52; 95% CI: 0.31-0.88; P = .02; chi square P = .37, I2 = 6%) was significantly improved in patients treated with gemcitabine-based induction chemotherapy compared to those treated with taxane-based induction chemotherapy. However, the progression free survival (HR: 0.67; 95% CI: 0.45-1.01; P = .06; chi square P = .74; I2 = 0%) showed no significant difference. CONCLUSIONS: For LA-NPC patients, adding gemcitabine-based induction chemotherapy to CCRT significantly improved overall survival and progression free survival with a higher risk of hematological toxicities when compared to CCRT alone. Also, gemcitabine-based regimen could be used as an alternative induction chemotherapy regimen to taxane-based regimen in the treatment of LA-NPC.

Functional Connectivity of Nucleus Accumbens and Medial Prefrontal Cortex With Other Brain Regions During Early-Abstinence Is Associated With Alcohol Dependence and Relapse: A Resting-Functional Magnetic Resonance Imaging Study.

Background: Alcohol dependence (AD) is a chronic recurrent brain disease that causes a heavy disease burden worldwide, partly due to high relapse rates after detoxification. Verified biomarkers are not available for AD and its relapse, although the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) may play important roles in the mechanism of addiction. This study investigated AD- and relapse-associated functional connectivity (FC) of the NAc and mPFC with other brain regions during early abstinence. Methods: Sixty-eight hospitalized early-abstinence AD male patients and 68 age- and education-matched healthy controls (HCs) underwent resting-functional magnetic resonance imaging (r-fMRI). Using the NAc and mPFC as seeds, we calculated changes in FC between the seeds and other brain regions. Over a follow-up period of 6 months, patients were measured with the Alcohol Use Disorder Identification Test (AUDIT) scale to identify relapse outcomes (AUDIT ≥ 8). Results: Thirty-five (52.24%) of the AD patients relapsed during the follow-up period. AD displayed lower FC of the left fusiform, bilateral temporal superior and right postcentral regions with the NAc and lower FC of the right temporal inferior, bilateral temporal superior, and left cingulate anterior regions with the mPFC compared to controls. Among these FC changes, lower FC between the NAc and left fusiform, lower FC between the mPFC and left cingulate anterior cortex, and smoking status were independently associated with AD. Subjects in relapse exhibited lower FC of the right cingulate anterior cortex with NAc and of the left calcarine sulcus with mPFC compared to non-relapsed subjects; both of these reductions in FC independently predicted relapse. Additionally, FC between the mPFC and right frontal superior gyrus, as well as years of education, independently predicted relapse severity. Conclusion: This study found that values of FC between selected seeds (i.e., the NAc and the mPFC) and some other reward- and/or impulse-control-related brain regions were associated with AD and relapse; these FC values could be potential biomarkers of AD or for prediction of relapse. These findings may help to guide further research on the neurobiology of AD and other addictive disorders.

Differential Effects of Anxiety on Internet Gaming Disorder: A Large-Scale Cross-Sectional Survey.

BACKGROUND: Internet gaming disorder (IGD) has become a serious public health problem in East Asia, and studies have reported IGD to be significantly associated with anxiety, but no causal relationship between the two has yet been demonstrated. Children are at high risk of developing IGD, however, previous studies have principally focused on the condition in adults and adolescents and reported non-clinical samples. A large-scale survey is needed to research and evaluate IGD and anxiety in children and adolescents to understand the current situation of IGD in children and explore the impact of IGD on anxiety. METHODS: A cross-sectional study using an online questionnaire was conducted between March 1 and July 31, 2021. A total of 10,479 school children and adolescents in the western provinces of China were selected by convenience sampling. A questionnaire was used to collect data anonymously. The questionnaire covered IGD and the Revised Children's Manifest Anxiety Scale (RCMAS). Welch's ANOVA Test and Games-Howell test were used to test for differences in anxiety levels between IGD groups. Poisson regression analysis was used to further investigate the key predictors of IGD. RESULTS: 3.2% of participants (n = 334) (95% CI: 2.9-3.2%) were classified as at high risk of presenting with IGD, 71.1% (n = 7,454) (95% CI: 70.3-72.0%) were classified as low-risk players, and 25.7% (n = 2,691) (95% CI: 24.9-26.5%) were classified as non-gaming. The average RCMAS score was (7.18 ± 7.534). The high-risk group had a higher total score RCMAS, as well as scoring higher in its three dimensions. Regression analysis using gender, age, and total RCMAS score as independent variables, and risk of IGD as a dependent variable showed that the odds ratio (OR) for gender was 2.864 (95% CI: 2.267-3.618), and the OR for total RCMAS score was 1.101 (95% CI: 1.087-1.114). The OR for age was not statistically significant. CONCLUSION: Anxiety was a predictor of IGD, with statistically significant group differences in total anxiety, as well as the dimensions of physiological anxiety, social correlation, and sensitivity. The timely assessment of anxiety in children and adolescents, training social skills, and facilitating effective integration into society could be effective ways of reducing the incidence and impact of IGD.

A real-world study on clinical predictors of relapse after hospitalized detoxification in a Chinese cohort with alcohol dependence.

BACKGROUND: The relapse rate of alcohol dependence (AD) after detoxification is high, but few studies have investigated the clinical predictors of relapse after hospitalized detoxification in real-world clinical practice, especially among Chinese patients. METHODS: This longitudinal cohort study followed up 122 AD patients who were discharged from January 1, 2016 to January 30, 2018 from their most recent hospitalization for detoxification. These patients were interviewed by telephone from May 20, 2017, to June 30, 2018, at least 6 months after discharge. During the interview, the relapse were assessed by using a revised Chinese version of the Alcohol Use Disorder Identification Test. Candidate predictors, such as therapeutic modalities during hospitalization and at discharge, medical history data related to alcohol use, and demographic information, were obtained from the medical records in the hospital information system. RESULTS: During the 6-24 months (with a median of 9 months) follow-up period, the relapse rate was 53.3%. Individuals with a college education level and those who had not been treated with the brief comprehensive cognitive-motivational-behavioural intervention (CCMBI) were more likely than their counterparts to relapse after hospitalized detoxification, and their adjusted HRs (95% CIs) were 1.85 (1.09, 3.16) and 2.00 (1.16, 3.46), respectively. The CCMBI use predicted a reduction in the relapse rate by approximately one-fifth. CONCLUSION: Undergoing the CCMBI during detoxification hospitalization and having less than a college-level education could predict a reduced risk of AD relapse. These findings provide useful information both for further clinical research and for real-world practice.

Cytotoxic abietane and kaurane diterpenoids from Celastrus orbiculatus.

Celastrus orbiculatus is a medicinal plant belonging to the Celastraceae family. In this survey on the secondary metabolites of plants for obtaining antitumor substances, the chemical constituents of the stems of C. orbiculatus were investigated. Nortriptonoterpene (1), a new C19-norabietane diterpenoid, together with six other known abietane-type diterpenoids (2-7) and five known kaurane-type diterpenoids (8-12) were isolated and identified from the EtOAc extract of C. orbiculatus. Their structures were elucidated on the basis of extensive spectroscopic methods, including UV, IR, HR-ESI-MS, ECD, and NMR experiments, and by comparison with literature data. Compound 1 is a new C19-norabietane diterpenoid with 19 carbons. All compounds except for 10 and 11 were isolated from C. orbiculatus for the first time. The NMR data of 9 were reported for the first time. Compounds 1, 7 and 11 showed cytotoxicities against SGC-7901 with IC50 values of 63.2, 80.9 and 56.7 µM, respectively.

Patient-specific three-dimensional printed heart models benefit preoperative planning for complex congenital heart disease.

BACKGROUND: Preoperative planning for children with congenital heart diseases remains crucial and challenging. This study aimed to investigate the roles of three-dimensional printed patient-specific heart models in the presurgical planning for complex congenital heart disease. METHODS: From May 2017 to January 2018, 15 children diagnosed with complex congenital heart disease were included in this study. Heart models were printed based on computed tomography (CT) imaging reconstruction by a 3D printer with photosensitive resin using the stereolithography apparatus technology. Surgery options were first evaluated by a sophisticated cardiac surgery group using CT images only, and then surgical plans were also set up based on heart models. RESULTS: Fifteen 3D printed heart models were successfully generated. According to the decisions based on CT, 13 cases were consistent with real options, while the other 2 were not. According to 3D printed heart models, all the 15 cases were consistent with real options. Unfortunately, one child diagnosed with complete transposition of great arteries combined with interruption of aortic arch (type A) died 5 days after operation due to postoperative low cardiac output syndrome. The cardiologists, especially the younger ones, considered that these 3D printed heart models with tangible, physical and comprehensive illustrations were beneficial for preoperative planning of complex congenital heart diseases. CONCLUSION: 3D printed heart models are beneficial and promising in preoperative planning for complex congenital heart diseases, and are able to help conform or even improve the surgery options.

Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication.

BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury (AKI) in rats with paraquat intoxication. METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group (n=8), paraquat group (n=8) and Xuebijing-treated group (n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing (8 mL/kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-inflammatory cytokines mRNA levels in kidney were assayed using real-time RT-PCR. RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group (P<0.05, respectively). Moreover, interleukin (IL)-1ß, IL-6 and TNF-α mRNA levels were significantly higher in the paraquat group (P<0.01, respectively). However, intravenous Xuebijing significantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1ß, IL-6 and TNF-α mRNA levels, compared with the paraquat group (P<0.05, respectively). CONCLUSION: Intravenous Xuebijing attenuates AKI following paraquat poisoning by suppressing inflammatory response.

Function of JARID2 in bovines during early embryonic development.

Histone lysine modifications are important epigenetic modifications in early embryonic development. JARID2, which is a member of the jumonji demethylase protein family, is a regulator of early embryonic development and can regulate mouse development and embryonic stem cell (ESC) differentiation by modifying histone lysines. JARID2 can affect early embryonic development by regulating the methylation level of H3K27me3, which is closely related to normal early embryonic development. To investigate the expression pattern of JARID2 and the effect of JARID2-induced H3K27 methylation in bovine oocytes and early embryonic stages, JARID2 mRNA expression and localization were detected in bovine oocytes and early embryos via qRT-PCR and immunofluorescence in the present study. The results showed that JARID2 is highly expressed in the germinal vesicle (GV), MII, 2-cell, 4-cell, 8-cell, 16-cell and blastocyst stages, but the relative expression level of JARID2 in bovine GV oocytes is significantly lower than that at other oocyte/embryonic stages (p < 0.05), and JARID2 is expressed primarily in the nucleus. We next detected the mRNA expression levels of embryonic development-related genes (OCT4, SOX2 and c-myc) after JARID2 knockdown through JARID2-2830-siRNA microinjection to investigate the molecularpathwayunderlying the regulation of H3K27me3 by JARID2 during early embryonic development. The results showed that the relative expression levels of these genes in 2-cell embryos weresignificantly higher than those in the blastocyst stage, and expression levels were significantly increased after JARID2 knockdown. In summary, the present study identified the expression pattern of JARID2 in bovine oocytes and at each early embryonic stage, and the results suggest that JARID2 plays a key role in early embryonic development by regulating the expression of OCT4, SOX2 and c-myc via modification of H3K27me3 expression. This work provides new data for improvements in the efficiency of in vitro embryo culture as well as a theoretical basis for further studying the regulatory mechanisms involved in early embryonic development.

Polarization of macrophages in the blood after decompression in mice.

The veins are a major site of bubble formation after decompression and the lung is a target organ of bubbles. Bubble-induced inflammation has been implicated in the pathogenesis of decompression sickness (DCS). Macrophages play a central role in the inflammation, and macrophage polarization is closely related to the pathogenesis of some lung diseases. This study aimed to investigate the blood macrophage polarization in mice after decompression. BALB/c mice were exposed to hyperbaric air for 60 minutes, and rapid decompression was performed to induce DCS. Slow decompression and hyperoxia (150 kPa, 60 minutes) served as control groups, and hyperbaric oxygen (HBO; 250 kPa, 60 minutes) was employed for DCS treatment. Macrophage phenotype was determined by flow cytometry, and cytokines related to macrophage polarization were measured by enzyme-linked immunosorbent assay. Our results showed rapid decompression significantly induced the shift to M1 phenotype, which was not observed in slow decompression group, HBO and hyperoxia groups. These changes were consistent with the change in blood tumor necrosis factor α level. Moreover, any treatment could significantly increase the M2 macrophages, but blood interleukin-10 remained unchanged after different treatments. In addition, the blood and lung levels of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 increased significantly after rapid decompression, but reduced markedly after HBO treatment. Taken together, rapid decompression is able to induce the shift to M1 phenotype in blood macrophages, which may then migrate into the lung involving decompression-induced lung injury.

Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication / 世界急诊医学杂志（英文）

@#BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury (AKI) in rats with paraquat intoxication. METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups:sham group (n=8), paraquat group (n=8) and Xuebijing-treated group (n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing (8 mL/kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-inflammatory cytokines mRNA levels in kidney were assayed using real-time RT-PCR. RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group (P<0.05, respectively). Moreover, interleukin (IL)-1β, IL-6 and TNF-α mRNA levels were significantly higher in the paraquat group (P<0.01, respectively). However, intravenous Xuebijing significantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1β, IL-6 and TNF-α mRNA levels, compared with the paraquat group (P<0.05, respectively). CONCLUSION: Intravenous Xuebijing attenuates AKI fol owing paraquat poisoning by suppressing inflammatory response.