Objective:To investigate the effect of p38MAPK signaling pathway mediating progesterone regulation on IL-8 protein secretion by decidual stromal cells(DSCs)on early spontaneous miscarriage.Methods:IHC and Western blot were applied to detect protein expressions of p38MAPK and p-p38MAPK in decidual tissues of miscarriage group and control group.Human DSCs in early pregnancy were isolated in vitro and cultured to be treated with different concentrations of progesterone(0.01 μmol/L,0.1 μmol/L,1 μmol/L and 10 μmol/L),with ELISA measuring IL-8 protein secretion from DSCs and Western blot measuring protein expressions of p38MAPK and p-p38MAPK in DSCs.After treatment with p38MAPK inhibitor SB203580,IL-8 protein secretion was detected by ELISA in progesterone+inhibitor group,progesterone group and control group.Results:Protein expression of p-p38MAPK in decidual tissues of miscarriage group was significantly higher than that of control group(P=0.002 3).Protein secretion of IL-8 in DSCs of 0.01 μmol/L progesterone group was lower than that of control group(P=0.027 6),protein expression of p-p38MAPK in DSCs of 0.1 μmol/L proges-terone group was lower than that of control group(P=0.025 3),IL-8 protein expression was significantly lower than that in control group(P=0.007 0),and protein expressions of both IL-8 and p-p38MAPK from DSCs in 1 μmol/L and 10 μmol/L progesterone groups were significantly lower than those in control group(P=0.003 2,P=0.001 9;P=0.002 2,P=0.001 3).IL-8 protein secretion in proges-terone+p38MAPK inhibitor group was further reduced compared to progesterone group(P=0.046 6).Conclusion:Abnormal activation of p38MAPK signaling pathway is involved in early spontaneous miscarriage,and progesterone may down-regulate IL-8 expression in DSCs by inhibiting p38MAPK phosphorylation to correct early spontaneous miscarriage caused by Th1/Th2 cytokine imbalance.

Objective:To investigate the effect of p38MAPK signaling pathway mediating progesterone regulation on IL-8 protein secretion by decidual stromal cells(DSCs)on early spontaneous miscarriage.Methods:IHC and Western blot were applied to detect protein expressions of p38MAPK and p-p38MAPK in decidual tissues of miscarriage group and control group.Human DSCs in early pregnancy were isolated in vitro and cultured to be treated with different concentrations of progesterone(0.01 μmol/L,0.1 μmol/L,1 μmol/L and 10 μmol/L),with ELISA measuring IL-8 protein secretion from DSCs and Western blot measuring protein expressions of p38MAPK and p-p38MAPK in DSCs.After treatment with p38MAPK inhibitor SB203580,IL-8 protein secretion was detected by ELISA in progesterone+inhibitor group,progesterone group and control group.Results:Protein expression of p-p38MAPK in decidual tissues of miscarriage group was significantly higher than that of control group(P=0.002 3).Protein secretion of IL-8 in DSCs of 0.01 μmol/L progesterone group was lower than that of control group(P=0.027 6),protein expression of p-p38MAPK in DSCs of 0.1 μmol/L proges-terone group was lower than that of control group(P=0.025 3),IL-8 protein expression was significantly lower than that in control group(P=0.007 0),and protein expressions of both IL-8 and p-p38MAPK from DSCs in 1 μmol/L and 10 μmol/L progesterone groups were significantly lower than those in control group(P=0.003 2,P=0.001 9;P=0.002 2,P=0.001 3).IL-8 protein secretion in proges-terone+p38MAPK inhibitor group was further reduced compared to progesterone group(P=0.046 6).Conclusion:Abnormal activation of p38MAPK signaling pathway is involved in early spontaneous miscarriage,and progesterone may down-regulate IL-8 expression in DSCs by inhibiting p38MAPK phosphorylation to correct early spontaneous miscarriage caused by Th1/Th2 cytokine imbalance.

BACKGROUND: Despite some studies identifying a potential association between obesity and chronic obstructive pulmonary disease (COPD) risk, previous research had overlooked the dynamic nature of body weight over time, leading to inconsistent findings. The purpose of this study is to elucidate the relationship between adult weight change and COPD risk by adjusting for potential confounding factors. METHODS: We conducted a retrospective analysis using data from ten NHANES cycles (1999-2018), including adults aged 40-74 years. Weight change patterns were assessed using BMI at three time points and classified into five categories per period. Absolute weight change was also grouped into five levels. Multivariate logistic regression models, incorporating sampling weights, were used to examine associations between weight change and COPD, adjusting for demographic and lifestyle covariates. RESULTS: Compared with participants who maintained normal weight, stable obesity participants had increased risk of COPD from age 25 years to 10 years before the survey (OR = 1.45, 95% CI = 1.15 to 1.83), in the 10 years period before the survey (OR = 1.75, 95% CI = 1.47 to 2.08), and from age 25 years to survey (OR = 1.84, 95% CI = 1.46 to 2.31). Three periods indicate that weight gain in adulthood was associated with risk of COPD. In addition, substantial weight gain of more than 20 kg was associated with a higher risk of COPD. In stratified analyses, we also observed a more significant association between weight change and the risk of COPD in never smokers compared to former smokers. CONCLUSIONS Our study suggested that stable obesity and weight gain in adulthood were associated with an increased risk of COPD compared to those who maintain a normal weight, and that the association between weight gain and the incidence of COPD appears closer in patients who have never smoked.
Humans ; Pulmonary Disease, Chronic Obstructive/etiology* ; Middle Aged ; Male ; Female ; Adult ; Aged ; Retrospective Studies ; Weight Gain ; Obesity/complications* ; Risk Factors ; United States/epidemiology* ; Nutrition Surveys ; Body Mass Index

Objective:To explore the mechanism of TLR4/ERK1/2 signaling pathway in progesterone regulating expression of IL-8 in decidual stromal cells(DSCs).Methods:Human DSCs on early pregnancy were isolated and cultured in vitro.The cells were treated with 0.01 μmol/L,0.1 μmol/L and 1 μmol/L progesterone,respectively.Expressions of IL-8,TLR4,ERK1/2 and p-ERK1/2 were detected by Western blot.TLR4 inhibitor TAK-242 and ERK1/2 inhibitor U0126 were further treated,and expression of IL-8 in progesteron+inhibitor group,progesterone group and control group was detected by Western blot.Results:With the increase of pro-gesterone concentration,expression of IL-8 in DSCs decreased gradually.Expressions of DSCs IL-8,TLR4 and p-ERK1/2 in 0.01 μmol/L progesterone group were lower than those in control group(P=0.035 8,P=0.019 4 and P=0.047 1).Expressions of IL-8,TLR4 and p-ERK1/2 in DSCs in 0.1 μmol/L progesterone group were significantly lower than those in control group(P=0.003 5,P=0.004 0 and P=0.009 9).Expressions of IL-8,TLR4 and p-ERK1/2 in DSCs in 1 μmol/L progesterone group were significantly lower than those in control group(P=0.003 3,P=0.001 6 and P=0.005 0).Expression of IL-8 in progesterone+TAK-242 group was signifi-cantly lower than that in progesterone group(P=0.009 1),and expression of IL-8 in progesterone+U0126 group was significantly lower than that in progesterone group(P=0.004).Conclusion:TLR4/ERK1/2 signaling pathway is involved in the physiological process of progesterone regulating expression of IL-8 in DSCs,and progesterone reduces IL-8 expression by inhibiting expression of TLR4 and phosphorylation activation of ERK1/2.

Objective:To explore the mechanism of TLR4/ERK1/2 signaling pathway in progesterone regulating expression of IL-8 in decidual stromal cells(DSCs).Methods:Human DSCs on early pregnancy were isolated and cultured in vitro.The cells were treated with 0.01 μmol/L,0.1 μmol/L and 1 μmol/L progesterone,respectively.Expressions of IL-8,TLR4,ERK1/2 and p-ERK1/2 were detected by Western blot.TLR4 inhibitor TAK-242 and ERK1/2 inhibitor U0126 were further treated,and expression of IL-8 in progesteron+inhibitor group,progesterone group and control group was detected by Western blot.Results:With the increase of pro-gesterone concentration,expression of IL-8 in DSCs decreased gradually.Expressions of DSCs IL-8,TLR4 and p-ERK1/2 in 0.01 μmol/L progesterone group were lower than those in control group(P=0.035 8,P=0.019 4 and P=0.047 1).Expressions of IL-8,TLR4 and p-ERK1/2 in DSCs in 0.1 μmol/L progesterone group were significantly lower than those in control group(P=0.003 5,P=0.004 0 and P=0.009 9).Expressions of IL-8,TLR4 and p-ERK1/2 in DSCs in 1 μmol/L progesterone group were significantly lower than those in control group(P=0.003 3,P=0.001 6 and P=0.005 0).Expression of IL-8 in progesterone+TAK-242 group was signifi-cantly lower than that in progesterone group(P=0.009 1),and expression of IL-8 in progesterone+U0126 group was significantly lower than that in progesterone group(P=0.004).Conclusion:TLR4/ERK1/2 signaling pathway is involved in the physiological process of progesterone regulating expression of IL-8 in DSCs,and progesterone reduces IL-8 expression by inhibiting expression of TLR4 and phosphorylation activation of ERK1/2.

Objective:To investigate the expression of Toll-like receptor 4(TLR4)and extracellular signal-regulated protein kinase 1/2(ERK1/2)in decidua tissue of patients with unexplained spontaneous abortion and their correlation.Methods:The expres-sions of TLR4,ERK1/2 and p-ERK1/2 in decidua tissues of 32 patients with unexplained spontaneous abortion(abortion group)and 32 normal pregnancy(control group)were detected by immunohistochemistry and Western blot,respectively.The correlation between TLR4 and p-ERK1/2 in abortion group were analyzed by Pearson hierarchical correlation analysis.Results:In immunohistochemical experiments,the cytoplasm of decidua cells in the two groups is the expression locus of TLR4,ERK1/2 and p-ERK1/2,the expression of the three proteins were different,and the expressions of TLR4 and p-ERK1/2 in abortion group were significantly higher than that in control group(P<0.01).There was no significant difference in ERK1/2 expression between abortion group and control group(P>0.05);In decidua tissue samples of abortion group,the protein level of TLR4 was higher than that of control group(P<0.05);the pro-tein level of p-ERK1/2 was significantly higher than that of control group(P<0.01),and the protein level of ERK1/2 in decidua tissue of abortion group was not statistically different from that of control group(P>0.05).TLR4 was positively correlated with p-ERK1/2 expression in abortion group(r=0.890,P<0.01).Conclusion:Abnormal activation of TLR4/ERK1/2 signaling pathway may be one of the mechanisms of unexplained spontaneous abortion.

Propriospinal myoclonus(PSM)is a rare painless movement disorder characterized by recurrent axial myoclonus during the wake and sleep transition periods.The recurrent muscle twitches during the hypnotic period severely affect the patient's sleep.In this paper,we reported a case of typical PSM.The patient was treated for involuntary limb shaking before sleep for more than 1 year,and no significant positive signs were found after physical examination in hospital.After perfecting video polysomnography and polymyography,he was diagnosed as having idiopathic PSM,and he responded well to 1/3 of clonazepam tablets,suggesting the necessity of video polysomnography and polymyography in the diagnosis of PSM.

The orbitofrontal cortex (ORB), a region crucial for stimulus-reward association, decision-making, and flexible behaviors, extensively connects with other brain areas. However, brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized. Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons. We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions, albeit with quantitative variations, particularly in somatomotor areas and medial groups of the dorsal thalamus. By counting parvalbumin (PV) or somatostatin (SST) interneurons innervated by neurons in specific ORB subregions, we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons. These results provide insights into understanding and investigating the function of specific ORB neurons.
Animals ; Neurons/physiology* ; Mice ; Prefrontal Cortex/cytology* ; Parvalbumins/metabolism* ; Brain Mapping/methods* ; Neural Pathways/physiology* ; Somatostatin/metabolism* ; Male ; Interneurons/physiology* ; Mice, Inbred C57BL ; Thalamus/physiology* ; Mice, Transgenic

Objective To compare the general conditions， clinical characteristics， and polysomnographic features of patients before， around， and after menopause.Methods Participants were divided into premenopausal， perimenopausal， and postmenopausal groups by the age of 45 years and 55 years. General conditions， clinical characteristics， and polysomnographic indicators were compared across these groups.Results A total of 316 patients before， around， and after menopause were included in this study. There were no significant between-group differences in the body mass index， smoking and alcohol consumption rates， sleep latency， sleep duration， sleep efficiency， and the durations and proportions of deep and light sleep. The perimenopausal and postmenopausal groups showed significantly increased nocturnal awakenings and significantly decreased nocturnal oxygen saturation compared with the premenopausal group. The apnea-hypopnea index （AHI） differed significantly between the three groups， showing an increasing trend.Conclusion Changes in reproductive status do not alter objective sleep duration and efficiency， and subjective perception contributes more to sleep disturbances around menopause. Changes in nocturnal sleep continuity， the AHI， and nocturnal minimum oxygen saturation suggest complex neuro-molecular mechanisms underlying the effects of hormonal variations on sleep in women.
Perimenopause

OBJECTIVE: To investigate the consistency and diagnostic performance of magnetic resonance imaging (MRI) for detecting microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and the validity of deep learning attention mechanisms and clinical features for MVI grade prediction. METHODS: This retrospective study was conducted among 158 patients with HCC treated in Shunde Hospital Affiliated to Southern Medical University between January, 2017 and February, 2020. The imaging data and clinical data of the patients were collected to establish single sequence deep learning models and fusion models based on the EfficientNetB0 and attention modules. The imaging data included conventional MRI sequences (T₁WI, T₂WI, and DWI), enhanced MRI sequences (AP, PP, EP, and HBP) and synthesized MRI sequences (T1mapping-pre and T1mapping-20 min), and the high-risk areas of MVI were visualized using deep learning visualization techniques. RESULTS: The fusion model based on T1mapping-20min sequence and clinical features outperformed other fusion models with an accuracy of 0.8376, a sensitivity of 0.8378, a specificity of 0.8702, and an AUC of 0.8501 for detecting MVI. The deep fusion models were also capable of displaying the high-risk areas of MVI. CONCLUSION The fusion models based on multiple MRI sequences can effectively detect MVI in patients with HCC, demonstrating the validity of deep learning algorithm that combines attention mechanism and clinical features for MVI grade prediction.
Humans ; Carcinoma, Hepatocellular ; Retrospective Studies ; Liver Neoplasms ; Magnetic Resonance Imaging ; Algorithms