Objective : To pathological changes and inducible nitric oxide synthase(iNOS), phosphorylated insulin receptor substrate 1 serine 307(p-IRS1ser 307), phosphorylated protein kinase B serine 473(p-AKTser 473), glycogen synthase kinase-3β(GSK-3β), and gluconeogenic synthase(GS) proteins were observed in the liver of rats under the condition of chronic intermittent hypoxia-replicated oxygen in control. And to explore the role of iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance. Methods : Forty SD rats were randomly divided into a control group(NC group) and an experimental group(CIH group), with 20 rats in each group. The NC group was placed in a normoxic environment for 12 weeks, while the CIH group was first subjected to intermittent hypoxia for 8 weeks, and then resumed normoxic rearing until the 12th week. Fasting blood glucose(FBG) and fasting insulin(FINS) were measured at baseline, week 8 and week 12, and liver tissues were taken for pathology and measurement of iNOS, p-IRS1ser 307, p-AKTser 473, GSK3β and GS levels, to compare the differences between groups. Results: t baseline, there was no significant difference in liver pathology between the two groups, and the observed indexes were not statistically significant(P>0.05); at 8 weeks, compared with the NC group, liver pathology in the CIH group showed significant disorganization of hepatic blood sinusoids and hepatocyte cords, obvious hepatocyte edema, smaller nuclei, increased lymphocyte infiltration, and a small number of fat vacuoles, significantly higher levels of FBG, FINS, insulin resistance index(HOMA-IR), iNOS mRNA, p-IRS1ser 307 protein, GSK-3β protein levels, and decreased p-AKTser 473 protein and GS protein levels, all of which were statistically significant(allP<0.05). IRS1ser 307 protein, GSK-3β protein levels were increased, p-AKTser 473 protein and GS protein levels were decreased, and the differences were statistically significant(allP<0.05); at 12 weeks, no lymphocyte infiltration was seen in the CIH group compared with that of the NC group and fat vacuoles significantly increased, and there was no improvement in the other pathological damage that had already occurred, and the levels of p-AKTser 473 protein significantly increased. AKTser 473 protein level significantly increased, p-IRS1ser 307 protein and GS protein levels were significantly reduced, all of which were statistically significant(allP<0.05), and the rest of the observational indexes were not statistically significant. Pearson′s correlation analysis showed that HOMA-IR of CIH group was significantly positively correlated with the levels of iNOS mRNA, p-IRS1ser 307 protein, and GSK-3β protein at 8 weeks(r=0.874, 0.817,0.872;allP<0.05), and significantly negatively correlated with the levels of p-AKTser 473 protein and GS protein(r=-0.886,-0.879;allP<0.05). Conclusion Chronic intermittent hypoxia can lead to hepatic pathological damage that cannot be reversed even by reoxygenation interventions and may mediate the development of insulin resistance by upregulating the IRS1/AKT/GSK-3β signaling pathway through the upregulation of iNOS mRNA expression.

Objective:To explore the effects of childhood trauma on resting blood pressure, heart rate, and heart rate variability in patients with depression.Methods:A cross-sectional study was designed to prospectively collect clinical data on a total of 163 patients with depression, including 47 males and 116 females, aged 18-50 years,with mean[ M( Q1, Q3)] [29.0, (21.0, 37.0)]years, who were either the outpatients or the inpatients in the Mental Health Center of the First Hospital of Hebei Medical University from September 2022 to June 2024. The Childhood Trauma Questionnaire-Short form (CTQ-SF) was used to assess the experience of abuse and neglect during childhood. According to the CTQ-SF score, the subjects were divided into a trauma group ( n=80) and a non-trauma group ( n=83). The 17-item Hamilton Depression Scale (HAMD 17) and Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms in the participants, respectively. A digital blood pressure monitor and an autonomic nervous system response detector were employed to measure resting blood pressure, heart rate, and heart rate variability (HRV). Spearman correlation analysis was used to examine the relationships between childhood trauma and resting blood pressure, heart rate, and HRV. Multiple linear regression analysis was performed to analyze factors influencing these parameters. The Bootstrap method was employed to test the potential mediating role of parasympathetic nervous system activity in the relationships between childhood trauma and resting blood pressure, and heart rate. Results:No significant difference was observed in resting heart rate between the trauma and non-trauma groups ( P>0.05). However, the trauma group exhibited higher resting systolic and diastolic blood pressure [(123.3±9.1) mmHg (1 mmHg=0.133 kPa) vs(116.9±10.8) mmHg, (80.0±8.6) mmHg vs (77.0±8.0) mmHg; Z=4.08, 2.24, all P<0.05]. HRV indices, including the standard deviation of normal to normal interval (SDNN), root mean square of successive differences (RMSSD), total power (TP), low frequency (LF), and high frequency (HF), were significantly lower in the trauma group [25.3 (19.4, 30.4) me vs 36.3 (27.4, 49.0) ms, 18.3 (12.9, 27.2) me vs 26.2 (19.0, 38.5) ms, 6.0(5.4, 6.5)ms 2vs 7.0(6.3, 7.4)ms 2,4.4(3.7,5.3)ms 2vs 5.8(4.9,6.3)ms 2, 4.2(3.4, 5.2)ms 2vs 5.2(4.6, 6.1)ms 2, respectively; all P<0.001]. Spearman correlation analysis showed that childhood trauma experiences in patients with depression were positively correlated with resting systolic blood pressure and diastolic blood pressure ( r=0.309, 0.236; P<0.01), childhood trauma was negatively correlated with HRV (SDNN, RMSSD, TP, LF, HF) ( r=-0.264, -0.274, -0.271, -0.235, -0.279; all P<0.01). Multiple linear regression analysis showed that childhood trauma was positively correlated with resting-state systolic blood pressure and resting-state diastolic blood pressure ( β=0.305, 0.291; all P<0.001). Childhood trauma was negatively correlated with RMSSD, TP, LF, and HF( β=-0.244, -0.249, -0.233, -0.263; all P<0.01). Mediation effect analysis showed that parasympathetic activity partially mediated the relationship between childhood trauma and resting systolic blood pressure (effect size 0.04, standard error 0.02, 95% CI=0.01-0.09), accounting for 14.29% (0.04/0.28) of the total effect. Conclusion:Childhood trauma experiences are associated with elevated resting blood pressure and reduced HRV in patients with depression. Decreased parasympathetic activity partially mediates the relationship between childhood trauma and elevated resting systolic blood pressure in these patients.

Objective:To explore the effects of childhood trauma on resting blood pressure, heart rate, and heart rate variability in patients with depression.Methods:A cross-sectional study was designed to prospectively collect clinical data on a total of 163 patients with depression, including 47 males and 116 females, aged 18-50 years,with mean[ M( Q1, Q3)] [29.0, (21.0, 37.0)]years, who were either the outpatients or the inpatients in the Mental Health Center of the First Hospital of Hebei Medical University from September 2022 to June 2024. The Childhood Trauma Questionnaire-Short form (CTQ-SF) was used to assess the experience of abuse and neglect during childhood. According to the CTQ-SF score, the subjects were divided into a trauma group ( n=80) and a non-trauma group ( n=83). The 17-item Hamilton Depression Scale (HAMD 17) and Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms in the participants, respectively. A digital blood pressure monitor and an autonomic nervous system response detector were employed to measure resting blood pressure, heart rate, and heart rate variability (HRV). Spearman correlation analysis was used to examine the relationships between childhood trauma and resting blood pressure, heart rate, and HRV. Multiple linear regression analysis was performed to analyze factors influencing these parameters. The Bootstrap method was employed to test the potential mediating role of parasympathetic nervous system activity in the relationships between childhood trauma and resting blood pressure, and heart rate. Results:No significant difference was observed in resting heart rate between the trauma and non-trauma groups ( P>0.05). However, the trauma group exhibited higher resting systolic and diastolic blood pressure [(123.3±9.1) mmHg (1 mmHg=0.133 kPa) vs(116.9±10.8) mmHg, (80.0±8.6) mmHg vs (77.0±8.0) mmHg; Z=4.08, 2.24, all P<0.05]. HRV indices, including the standard deviation of normal to normal interval (SDNN), root mean square of successive differences (RMSSD), total power (TP), low frequency (LF), and high frequency (HF), were significantly lower in the trauma group [25.3 (19.4, 30.4) me vs 36.3 (27.4, 49.0) ms, 18.3 (12.9, 27.2) me vs 26.2 (19.0, 38.5) ms, 6.0(5.4, 6.5)ms 2vs 7.0(6.3, 7.4)ms 2,4.4(3.7,5.3)ms 2vs 5.8(4.9,6.3)ms 2, 4.2(3.4, 5.2)ms 2vs 5.2(4.6, 6.1)ms 2, respectively; all P<0.001]. Spearman correlation analysis showed that childhood trauma experiences in patients with depression were positively correlated with resting systolic blood pressure and diastolic blood pressure ( r=0.309, 0.236; P<0.01), childhood trauma was negatively correlated with HRV (SDNN, RMSSD, TP, LF, HF) ( r=-0.264, -0.274, -0.271, -0.235, -0.279; all P<0.01). Multiple linear regression analysis showed that childhood trauma was positively correlated with resting-state systolic blood pressure and resting-state diastolic blood pressure ( β=0.305, 0.291; all P<0.001). Childhood trauma was negatively correlated with RMSSD, TP, LF, and HF( β=-0.244, -0.249, -0.233, -0.263; all P<0.01). Mediation effect analysis showed that parasympathetic activity partially mediated the relationship between childhood trauma and resting systolic blood pressure (effect size 0.04, standard error 0.02, 95% CI=0.01-0.09), accounting for 14.29% (0.04/0.28) of the total effect. Conclusion:Childhood trauma experiences are associated with elevated resting blood pressure and reduced HRV in patients with depression. Decreased parasympathetic activity partially mediates the relationship between childhood trauma and elevated resting systolic blood pressure in these patients.

Objective The aim of this study was to use the fast causal inference(FCI)algorithm to construct a causal graph model,analyze the direct and indirect factors that affect the quality of treatment for non-small cell lung cancer(NSCLC),and provide a basis for improving the quality of patient treatment.Methods Case information of NSCLC patients from 10 tertiary hospitals was collected;the influencing factors were determined as the research variable,and the incidence of adverse events was the evaluation indi-cator of patient treatment quality,i.e.the outcome variable;the FCI algorithm to mine case data were used to construct a causal dia-gram model of research variables and outcomes,and analyze causal relationships between research variables and outcome variables,as well as between different research variables.Results A total of 2,846 patients with an average age of 56.00±7.70 years were includ-ed in this study,and the incidence of adverse events was 9.63%.The causal diagram model consisted 24 nodes and 71 edges,inclu-ding 54 directed edges and 7 bidirectional edges.The direct factors affecting the occurrence of adverse events included hospital type,histological grade,lymph node dissection,and length of hospitalization;indirect factors included occupation,medical insurance type,current medical history,pathological stage,comprehensive treatment,surgical nature,and type of lung resection;The analysis of the in-teraction between factors showed that the current medical history,histological classification,comprehensive treatment,surgical nature,and type of lung resection determined whether the patient received lymph node dissection;The nature of surgery,method of lung resec-tion,and comprehensive treatment affected the length of hospitalization;Medical history affected the histological classification of lung cancer;The type of occupation and medical insurance affected the type of hospital where patients sought medical treatment.Conclusion In the analysis of factors affecting the quality of NSCLC treatment,the causal diagram model can obtain direct and indi-rect factors that affect the occurrence of adverse events,identify target variables that can be intervened,and provide a basis for impro-ving the quality of NSCLC treatment;Hospitals can reduce the incidence of adverse events by increasing the acceptance rate of lymph node dissection and comprehensive treatment.

Objective To investigate the effects of chronic intermittent hypoxia(CIH)and reoxygenation on insulin resistance(IR)and expressions of miR-27a-3p/PPARγ/IRS1/PI3K/AKT in rat skeletal muscle.Methods GEO database was used for screening the differentially expressed miRNAs in CIH,and their target genes were subjected to GO and KEGG enrichment analysis followed by construction of the miRNA-mRNA-pathway regulatory network using Cytoscape.In the animal experiment,48 male SD rats were randomly divided into normoxia group and CIH group(8 weeks of CIH followed by 4 weeks of normoxic recovery).Blood and skeletal muscle samples were collected at baseline,8 weeks,and 12 weeks to evaluate the changes in fasting blood glucose(FBG)and fasting insulin(FINS)levels and muscular pathology.RT-qPCR and Western blotting were used to detect the changes in the expressions of miR-27a-3p,PPARγ,GLUT4,IRS1,p-IRS1,PI3K,p-AKT and AKT in the muscular tissues.Results No muscular miRNA datasets for CIH were available in GEO database,from which only a kidney-related dataset(GSE202480)was obtained,based on which a total of 165 differentially expressed miRNAs were identified.GO/KEGG analysis suggested that these miRNAs were involved in muscular regulation and insulin signaling.The miRNA-mRNA-pathway network highlighted miR-27a-3p as a crucial regulator in the PPAR and PI3K/AKT pathway.In the animal experiment,the rats subjected to CIH for 8 weeks showed significantly increased FBG,FINS,HOMA-IR,and PPARγ levels,loose muscle fiber arrangement,decreased cross-sectional area of the muscle fibers,and lowered expressions of miR-27a-3p,p-IRS1/IRS1,PI3K,and p-AKT/AKT in the skeletal muscles.Conclusion CIH increases IR,causes skeletal muscle pathology,downregulates miR-27a-3p expression,upregulates PPARγ expression,and inhibits IRS1/PI3K/AKT insulin signaling in the skeletal muscles of rats,and these changes can be reversed by reoxygenation.MiR-27a-3p may participate in CIH-induced IR by modulating the PPAR γ/IRS1/PI3K/AKT signaling pathway.

Objective To investigate the effects of chronic intermittent hypoxia(CIH)and reoxygenation on insulin resistance(IR)and expressions of miR-27a-3p/PPARγ/IRS1/PI3K/AKT in rat skeletal muscle.Methods GEO database was used for screening the differentially expressed miRNAs in CIH,and their target genes were subjected to GO and KEGG enrichment analysis followed by construction of the miRNA-mRNA-pathway regulatory network using Cytoscape.In the animal experiment,48 male SD rats were randomly divided into normoxia group and CIH group(8 weeks of CIH followed by 4 weeks of normoxic recovery).Blood and skeletal muscle samples were collected at baseline,8 weeks,and 12 weeks to evaluate the changes in fasting blood glucose(FBG)and fasting insulin(FINS)levels and muscular pathology.RT-qPCR and Western blotting were used to detect the changes in the expressions of miR-27a-3p,PPARγ,GLUT4,IRS1,p-IRS1,PI3K,p-AKT and AKT in the muscular tissues.Results No muscular miRNA datasets for CIH were available in GEO database,from which only a kidney-related dataset(GSE202480)was obtained,based on which a total of 165 differentially expressed miRNAs were identified.GO/KEGG analysis suggested that these miRNAs were involved in muscular regulation and insulin signaling.The miRNA-mRNA-pathway network highlighted miR-27a-3p as a crucial regulator in the PPAR and PI3K/AKT pathway.In the animal experiment,the rats subjected to CIH for 8 weeks showed significantly increased FBG,FINS,HOMA-IR,and PPARγ levels,loose muscle fiber arrangement,decreased cross-sectional area of the muscle fibers,and lowered expressions of miR-27a-3p,p-IRS1/IRS1,PI3K,and p-AKT/AKT in the skeletal muscles.Conclusion CIH increases IR,causes skeletal muscle pathology,downregulates miR-27a-3p expression,upregulates PPARγ expression,and inhibits IRS1/PI3K/AKT insulin signaling in the skeletal muscles of rats,and these changes can be reversed by reoxygenation.MiR-27a-3p may participate in CIH-induced IR by modulating the PPAR γ/IRS1/PI3K/AKT signaling pathway.

Long non-coding RNAs (lncRNAs) reportedly function as important modulators of gene regulation and malignant processes in the development of human cancers. The lncRNA JPX is a novel molecular switch for X chromosome inactivation and differentially expressed JPX has exhibited certain clinical correlations in several cancers. Notably, JPX participates in cancer growth, metastasis, and chemoresistance, by acting as a competing endogenous RNA for microRNA, interacting with proteins, and regulating some specific signaling pathways. Moreover, JPX may serve as a potential biomarker and therapeutic target for the diagnosis, prognosis, and treatment of cancer. The present article summarizes our current understanding of the structure, expression, and function of JPX in malignant cancer processes and discusses its molecular mechanisms and potential applications in cancer biology and medicine.
Humans ; RNA, Long Noncoding/genetics* ; Neoplasms/genetics* ; MicroRNAs/genetics* ; Gene Expression Regulation ; X Chromosome Inactivation

Objective: To compare the efficacy of femoral triangle versus adductor canal approach to saphenous nerve block for postoperative analgesia in the patients undergoing knee arthroplasty. Methods: Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes, aged 53-68 yr, scheduled for elective total knee arthroplasty under general anesthesia, were assigned into 2 groups (n=30 each) using a random number table method: femoral triangle approach to saphenous nerve block group (group F) and adductor canal approach to saphenous nerve block group (group A). Femoral triangle and adductor canal approach to saphenous nerve block was performed by injecting 0.5% ropivacaine 20 ml in group F and group A, respectively.Patient-controlled saphenous nerve block analgesia was used in two groups, and the analgesic pump solution contained 1% ropivacaine 400 mg diluted to 160 ml in 0.9% sodium chloride injection.The analgesic pump was set up with a 5 ml bolus dose, a 30-min lockout interval and background infusion at a rate of 5 ml/h, and analgesia lasted until 72 h after operation.When visual analog scale score > 4 and pain was not relived after 30-min pressing by patients, pethidine hydrochloride 100 mg was intramuscularly injected as rescue analgesic.The muscle strength of quadriceps femoris was assessed by manual muscle test at 4, 8, 24, 48 and 72 h after operation.The patient′s satisfaction score was assessed and recorded at 72 h after operation.Rescue analgesia and development of adverse reactions (local anesthetic intoxication, itching, dizziness, urinary retention, nausea and vomiting) were recorded within 72 h after operation. Results: Compared with group F, the muscle strength of quadriceps femoris was significantly increased at 4, 8 and 24 h after operation, the rate of postoperative rescue analgesia was decreased (P<0.05), and no significant change was found in patient′s satisfaction score or incidence of adverse reactions in group A (P>0.05). Conclusion Adductor canal approach to saphenous nerve block provides better efficacy for postoperative analgesia than femoral triangle approach to saphenous nerve block in the patients undergoing knee arthroplasty.

Objective To observe the effects of adiponectin (APN) on anxiety-and depression-like behaviors occurred in APP/PS1/tau triple transgenic Alzheimer's disease (3xTg-AD) model mice and investigate the possible mechanism.Methods The 9-month-old 3xTg-AD mice and wild type (WT) mice were randomly divided into four groups (n=8 for each group):WT+Saline,WT+APN,3xTg-AD+Saline and 3xTg-AD+APN groups.The mouse was chronically intracerebroventricular injection of APN or saline under free moving condition.Elevated plus maze task was used to evaluate the anxiety-like behaviors.Sucrose preference test and tail suspension test were used to evaluate the depression-like behaviors.Western blot was used to detect the protein expression levels of p-AMPK,AMPK,p-GSK-3β (Ser9),GSK-3β and SIRT1 in the hippocampus of each mouse.Results In the elevated plus maze test,the time percentage spent in open arms of 3xTg-AD+Saline mice was ((4.2±2.7) ％),which significantly lower than that in WT+Saline group ((10.1±4.1)％) (q=4.349,P＜0.01) and in 3xTg-AD+APN group ((9.7±3.3)％) (q=4.065,P＜0.01).In the sucrose preference test,the sucrose preference percentage in 3xTg-AD+Saline group((48.8±5.3) ％) was lower than that in WT+Saline group ((60.9±6.7) ％) (q=4.522,P＜0.01) and in 3xTg-AD+APN group ((59.3±6.2)％) (q=3.911,P＜0.05).As for tail suspension test,the immobility time percentage in 3xTg-AD+Saline group((40.7±9.9)％) was higher than that in WT+Saline group ((27.1±4.8)％) (q=5.257,P＜0.001) and in 3xTg-AD+APN group ((31.4±6.0)％) (q=3.624,P＜0.05).The result of Western blot showed that there was no significant difference in expression level of AMPK and GSK-3β among four groups.However,compared with that in WT+Saline group,the expression levels of p-AMPK (q=3.586,P＜0.05),p-GSK-3β (Ser9) (q=3.125,P＜0.05),and SIRT1 (q=3.044,P＜0.05) in 3xTg-AD+Saline group were significantly decreased.In addition,compared with that in 3xTg-AD+Saline group,the expression levels of p-AMPK (q=3.374,P＜0.05) and p-GSK-3β (Ser9) (q=3.063,P＜0.05) in 3xTg-AD+APN group were obviously up-regulated without affecting the SIRT1.Conclusion Adiponectin can effectively alleviate the anxiety-and depression-like behaviors of 9-month-old 3xTg-AD mice by up-regulating the protein expression of p-AMPK and p-GSK-3β (Ser9) in the hippocampus.

OBJECTIVETo evaluate the correlation of liver hardness testing

RESULTSobtained by FibroTouch and FibroScan and the liver pathological stage.

METHODSSeventy-five patients with chronic hepatitis B who presented to our clinic between January 2011 and April 2013 were examined with FibroTouch and FibroScan to evaluate the degree of liver fibrosis. Forty-six of those patients also underwent liver biopsy examination.

THE RESULTSfrom technology-based testing and histopathological evaluation of the biopsy were compared by statistical analysis to determine the consistency of FibroTouch and FibroScan in regard to histological stage.

RESULTSAnalysis by paired t-test showed that the

RESULTSfrom FibroTouch and FibroScan were not significantly different (t = -0.17, P =0.8616), and the correlation coefficient from Pearson's correlation analysis was 0.9949 (P less than 0.05), suggesting that the two technologies'

RESULTSare correlated. Based on the histopathology

RESULTSfor liver fibrosis stage, the FibroTouch diagnosis of liver fibrosis more than or equal to S 1 had a receiver operating characteristic (ROC) area under the curve (AUC) of 0.889, diagnosis of liver fibrosis more than or equal to S2 had a ROC AUC of 0.941, diagnosis of liver fibrosis more than or equal to S3 had a ROC AUC of 0.908, and diagnosis of liver fibrosis more than or equal to S4 had a ROC AUC of 0.911.

CONCLUSIONCompared to FibroScan, FibroTouch has a better ability for detecting liver fibrosis and a better consistency with liver pathological stage determined by histopathological analysis.

Adult ; Aged ; Area Under Curve ; Biopsy ; Case-Control Studies ; Elasticity Imaging Techniques ; instrumentation ; Female ; Hepatitis B, Chronic ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Prospective Studies ; Young Adult