Objective:To investigate the effects of Xiongcan Yishen Formula(XYF)on ferroptosis in mouse TM3 Leydig cells after oxidative stress injury(OSI)induced by H2O2.Methods:An oxidative stress injury model was established in mouse TM3 Leydig cells using H2O2 induction.The modeled TM3 cells were randomly divided into OSI group,XYF group,the ferroptosis inhibitor Ferrostatin-1(F-1)group,and F-1+XYF group,which were respectively intervened with blank serum,20%drug-containing serum,2μmol/L F-1,and2μmol/L F-1+20%drug-containing serum.A control group(normal TM3 cells+blank serum)was also set up.The morphology of cells in each group was observed,and the levels of testosterone,superoxide dismutase(SOD),reactive oxygen spe-cies(ROS),malondialdehyde(MDA),ferritin heavy chain 1(FTH1),solute carrier family 7 member 11(SLC7A11),glutathione(GSH),glutathione peroxidase 4(GPX4),fatty acid CoA ligase 4(FACL4),total iron ions,and ferrous ions were detected.Re-sults:Compared with the model group,the control group showed significantly decreased expression of ROS,MDA,FACL4,total iron,and ferrous ions(P<0.05),and significantly increased levels of testosterone,SOD,GSH,FTH1,SLC7A11,and GPX4(P<0.05).The male silkworm kidney-tonifying formula group significantly promoted testosterone secretion by TM3 cells and upregulated the expression of FTH1,SLC7A11,GPX4,GSH,and SOD in TM3 cells(P<0.05),while significantly downregulating ROS,MDA,FACL4,total iron ions,and ferrous ions(P<0.05).Conclusion:Following H2O2 exposure,oxidative stress can induce ferroptosis in mouse TM3 Leydig cells.XYF can antagonize OSI and ferroptosis in TM3 cells by activating the SLC7A11/GSH/GPX4 axis,which may underlie the mechanism of XYF in the treatment of male late-onset hypogonadism.

Objective: To analyze the association between exposure patterns of adverse childhood experiences (ACEs) and anxiety symptom trajectories in medical college students. Methods: A survey was conducted on first-year students from Anhui Medical College and Anqing Medical College, using the Childhood Abuse Questionnaire, Family Disability Questionnaire, Childhood Adverse Social Experience Item, and Anxiety Self Rating Scale. The baseline survey was conducted from November to December 2019, and two follow-up visits were conducted once every six months until November to December 2020. The latent class analysis (LCA) was used to analyze the exposure patterns of ACEs. The latent class growth analysis (LCGA) was used to analyze the development trajectory of anxiety symptoms. The multiple logistic regression model was used to analyze the correlation between different exposure patterns of ACEs and the trajectory of anxiety symptom trajectories. Results: A total of 3 662 college students aged (19.2±1.0) were surveyed. The LCA showed that the exposure patterns of ACEs could be divided into the "high ACEs" group (13.4%), "high neglect/emotional abuse" group (25.7%), "high family dysfunction" group (6.9%), "high neglect" group (27.1%), and "low ACEs" group (26.3%). The LCGA divided anxiety trajectories into four groups: "high anxiety decline" (7.1%),"anxiety increase "(4.1%), "moderate anxiety"(52.9%), and "low anxiety"(35.9%). Using the low ACEs group as a reference group, compared with the low anxiety trajectory, the high ACEs group, high neglect/emotional abuse group, high family dysfunction group, high neglect group, and medium to high-level anxiety trajectory were all associated with an increased risk (P<0.05). Conclusion: There is heterogeneity in ACEs exposure patterns among medical college students, and ACEs exposure patterns are important influencing factors for anxiety symptom trajectories.
Humans ; Adverse Childhood Experiences ; Anxiety/epidemiology* ; Child Abuse/psychology* ; Students/psychology* ; Surveys and Questionnaires ; Adolescent ; Young Adult

BACKGROUND: Normal tension glaucoma (NTG) is a less pressure-dependent type of glaucoma with characteristic optic neuropathy. Recently, the biomechanical mechanism has been thought to account for glaucomatous optic neuropathy to some degree. We intended to compare dynamic corneal response parameters (DCRs) among patients with primary open-angle glaucoma with normal tension or hypertension and controls. The correlations between DCRs and known risk factors for glaucoma were also analyzed. METHODS: In this cross-sectional study, 49 NTG subjects, 45 hypertension glaucoma (HTG) subjects, and 50 control subjects were enrolled. We compared the differences in DCRs using corneal visualization Scheimpflug technology among the NTG, HTG, and control groups. We also analyzed the correlations between DCRs and known risk factors for glaucoma (eg, central corneal thickness [CCT], intraocular pressure [IOP], etc). RESULTS: The maximum inverse concave radius (NTG: 0.18 [0.17, 0.20] mm-1; control: 0.17 [0.16, 0.18] mm-1; P = 0.033), deformation amplitude ratio of 2 mm (DAR 2 mm, NTG: 4.87 [4.33, 5.39]; control: 4.37 [4.07, 4.88]; P < 0.001), and DAR 1 mm (NTG: 1.62 [1.58, 1.65]; control: 1.58 [1.54, 1.61]; P < 0.001) were significantly higher in NTG than in the controls. The integrated radius (IR, NTG: 8.40 ± 1.07 mm-1; HTG: 7.64 ± 1.31 mm-1; P = 0.026) and DAR 2 mm (NTG: 4.87 [4.33, 5.39]; HTG: 4.44 [4.12, 5.02]; P < 0.007) were significantly higher, whereas the stiffness parameter at the first applanation (SP-A1, NTG: 91.23 [77.45, 107.45]; HTG: 102.36 [85.77, 125.12]; P = 0.007) was lower in NTG than in HTG. There were no significant differences in the DCRs between HTG and control groups (P > 0.05). In the univariate and multivariate analyses, some of the DCRs, such as IR, were negatively correlated with CCT and IOP, whereas SP-A1 was positively correlated with CCT and IOP. CONCLUSIONS The cornea was more deformable in NTG than in HTG or controls. There were no significant differences in corneal deformability between HTG and controls. The cornea was more deformable with the thinner cornea and lower IOP.
Biomechanical Phenomena ; Cornea ; Cross-Sectional Studies ; Glaucoma, Open-Angle ; Humans ; Hypertension ; Intraocular Pressure ; Low Tension Glaucoma

BACKGROUNDGlobally, the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.

METHODSAll the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed.

RESULTSA total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal.

CONCLUSIONSNeonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.

Cause of Death ; China ; Female ; Hospital Mortality ; Humans ; Infant ; Infant Mortality ; Infant, Newborn ; Infant, Newborn, Diseases ; mortality ; Intensive Care Units, Neonatal ; statistics & numerical data ; Male ; Perinatal Death ; Retrospective Studies

Objective To detect the neuronal network activity of specific brain areas in heroin addicts under craving state induced by heroin related cues with independent component analysis (ICA) of functional MRI (fMRI) data. Methods Fifteen heroin addicts,admitted to our hospital from February 2010 to December 2010, and 15 healthy controls were recruited in the case-control study; they were performed whole brain scan with 3.0Tesla MR scanner when being presented with heroin related cues.ICA was performed on these data and their neuronal network activities were compared. Results As compared with those in the controls,the bilateral prefrontal cortex,the left anterior cingulated cortex,the bilateral posterior cingulated cortex, the left inferior temporal gyrus and the left parietal lobe enjoyed obviously decreased activity, while bilateral nucleus accumbens, the right hippocampus, part of the temporal lobe and the occipital lobe enjoyed significantly increased activity (P＜0.05). Conclusion ICA is an advanced approach to identify fMRI data induced by related cues; the specific neuroanatomy mediated to cue-elicited heroin craving mostly locates in the learn-memory system and reward system,which involves the frontal cortex,the parietal lobe,the anterior eingulate,the posterior cingulate,the hippocampus and the nucleus accumbens.

Objective To explore the changes of functional connectivity of anterior cingulate cortex (ACC) in online game addicts during the resting state,and to analyze the function of ACC in the pathogenesis of online game addiction from a perspective of resting-state functional connectivity.Methods Seventeen online game addicts treated in our hospital from March 2011 to October 2011 were recruited as addiction group and 17 healthy controls at the same period were recruited as HC group.The baseline characteristics of all 34 subjects were investigated and compared between the addiction group and the HC group.All fMRI data were preprocessed after a resting-state fMRI scan,and then,the left and right anterior cingulate cortexes were selected as regions of interest (ROIs) to calculate the linear correlation between the ACC and the entire brain to compare the differences between the online game addicts and normal controls.Results Obvious differences between the addiction group and HC group were noted in hours and days of online game using and degree of thirst to play online games (P＜0.05);within the functional connectivity of ACC during the resting state,in contrast to the controls,the online game addicts showed increased connectivity with posterior cingulate,medium cingulate,midbrain,nucleus accumbens and supplementary motor area,but reduced connectivity with prefrontal cortex,temporal lobe and occipital lobe (P＜0.05).Conclusion Altered functional connectivity of the ACC reflects the dysfunction in ACC of online game addicts,which may be linked to the forming and maintaining of the online game addiction.

BACKGROUNDHypoxemic respiratory failure (HRF) is one of the most common causes for neonatal infants requiring aggressive respiratory support. Inhaled nitric oxide (iNO) has been established routinely as an adjunct to conventional respiratory support in developed countries. The aim of this study was to investigate effects of iNO in neonates with HRF in resource limited condition with no or limited use of surfactant, high frequency oscillatory ventilation (HFOV) and extracorporeal membrane oxygenation.

METHODSA non-randomized, open, controlled study of efficacy of iNO was conducted over 18 months. Eligible term and near-term neonates from 28 hospitals with HRF (oxygenation index > 15) were enrolled prospectively into two groups as either iNO or control. Oxygenation improvement and mortality as primary endpoint were determined in relation with dosing and timing of iNO, severity of underlying diseases, complications and burden. Intention-to-treat principle was adopted for outcome assessment. Response to iNO at 10 or 20 parts per million (ppm) was determined by oxygenation in reference to the control (between-group) and the baseline (within-group).

RESULTSCompared to 93 controls, initial dose of iNO at 10 ppm in 107 treated infants significantly improved oxygenation from first hour (P = 0.046), with more partial- and non-responders improved oxygenation with subsequent 20 ppm NO (P = 0.018). This effect persisted on days 1 and 3, and resulted in relatively lower mortalities (11.2% vs. 15%) whereas fewer were treated with surfactant (10% vs. 27%), HFOV (< 5%) or postnatal corticosteroids (< 10%) in both groups. The overall outcomes at 28 days of postnatal life in the iNO-treated was not related to perinatal asphyxia, underlying diseases, severity of hypoxemia, or complications, but to the early use of iNO. The cost of hospital stay was not significantly different in both groups.

CONCLUSIONSWith relatively limited use of surfactant and/or HFOV in neonatal HRF, significantly more responders were found in the iNO-treated patients as reflected by improved oxygenation in the first three days over the baseline level. It warrants a randomized, controlled trial for assessment of appropriate timing and long-term outcome of iNO.

Administration, Inhalation ; Female ; Humans ; Hypoxia ; drug therapy ; physiopathology ; Infant, Newborn ; Male ; Nitric Oxide ; administration & dosage ; therapeutic use ; Pregnancy ; Respiratory Insufficiency ; drug therapy ; physiopathology

Objective To explore the changes of functional connectivity of the prefrontal cortex in chronic heroin addicts under resting-state functional MRI (fMRI). Methods Resting fMRI examination was performed on 13 chronic heroin addicts and 14 healthy volunteers. After pre-processing the resting-state fMRI data, the prefrontal cortex was selected as the seed region, with which a whole-brain voxel temporal correlation in Iow frequency fMRI fluctuations was analyzed and the changes of functional connectivity of the prefrontal lobe in both chronic heroin addicts and healthy volunteers were calculated with SPM5 software. Results Compared with that in the control group, the functional connectivity between the left prefrontal cortex and the left hippocampus, right anterior cingulate, left middle frontal gyrus, right middle frontal gyrus, right precuneus in the heroin addiction group was significantly decreased. The functional connectivity between the right prefrontal cortex and the left orbital frontal cortex, left middle frontal gyrus in thc heroin addiction group was also significantly decreased as compared with that in the control group. Conclusion Functional connectivity of prefrontal cortex in chronic heroin addicts decreases, indicating that the prefrontal cortex may be involved in the maintenance of heroin addiction and relapse after withdrawal.

Objective To explore the functional location of brain regions related to internet game addiction using clue-reaction model and functional magnetic resonance imaging (fMRI). Methods Twenty participants with internet game addiction and 20 control subjects without addiction were tested. They were presented with different internet game videos and the paired common life videos while undergoing fMRI. Questionnaire survey was employed to investigate their emotion changes after watching the game video; the activation data produced by the stimulations were collected through the measurement of blood-oxygen-level dependent signals in the brain. Subtraction algorithm was adopted to analyze the corresponding regions of interest. The activated brain areas stimulated by the internet game videos were determined. Results Compared with the common life video watching, the interact game video watching showed significantly different results of psychological assessments, including emotional states, degree of thirst, degree of liking and wishing to re-watch in the addiction group (P<0.05); while the interact game video watching only had a strong degree of re-watching as compared with the common life video watching in the control group. As compared with the common life videos, internet game videos could induce significantly high activation in the parietal lobe and visual cortex of the temporal lobe of the left brain region in the control group (P<0.05);while significantly activation of all the brain regions, except the nucleus accumbens and the caudate nucleus of the left brain region, was found in the internet game video watching as compared with those in the common life video watching in the addiction group (P<0.05). Conclusion The regions of brain activation of the internet game addiction can be determined by fMRI and these areas may be involved in the generation and maintenance of the internet game addiction.

Objective To investigate the brain areas having functional connectivity with nucleus accumbens in heroin addicts with resting-state functional magnetic resonance imaging (fMRI), and explore the reward system of heroin addiction. Methods Fifteen participants with heroin addiction,voluntarily admitted to our drug rehabilitation center from June 2009 to March 2010, and 15 healthy controls at the same period were chosen in our study. Resting-state fMRI was performed on these patients; and then, the resting-state brain functional connectivity was also concluded by analyzing the left and right nucleus accumbens selected as regions of interests (ROIs). The corresponding brain areas having functional connections with ROIs were defined in the resting-state and the changes of functional connectivity were observed in heroin addicts. Results In the addiction group, the areas having functional connectivity with double nucleus accumbens included bilateral thalamus, the basal ganglia, the hippocampus, the midbrain and contralateral nucleus accumbens; and anterior cingulate cortex was also significantly correlated with left nucleus accumbens. However, in the control group, only the hippocampus and contralateral nucleus accumbens had these connection and their activity was much weaker than that in the addiction group. Conclusion In the resting-state, reward system of heroin addiction is constituted by the brain areas having functional connectivity with nucleus accumbens. And fMRI can be used to study the functional connections between the brain areas related to the heroin addiction from neuroimaging perspectives.