1.Association of whole blood copper,zinc,calcium,magnesium,and iron with non-alcoholic fatty liver disease in overweight and obese children
Zhihang HUANG ; Miyang LUO ; Wen DAI ; Zhenzhen YAO ; Sisi OUYANG ; Ning'an XU ; Haixiang ZHOU ; Xiongwei LI ; Yan ZHONG ; Jiayou LUO
Journal of Central South University(Medical Sciences) 2024;49(3):426-434
Objective:Non-alcoholic fatty liver disease(NAFLD)is a common metabolic disorder in overweight and obese children,and its etiology and pathogenesis remain unclear,lacking effective preventive and therapeutic measures.This study aims to explore the association between whole blood copper,zinc,calcium,magnesium and iron levels and NAFLD in overweight and obese children aged 6 to 17 years,providing a scientific basis for the prevention and intervention of early NAFLD in overweight and obese children. Methods:A cross-sectional study design was used to collect relevant data from overweight and obese children who visited the Hunan Children's Hospital from January 2019 to December 2021 through questionnaire surveys.Fasting blood samples were collected from the subjects,and various indicators such as blood glucose,blood lipid,and mineral elements were detected.All children were divided into an overweight group(n=400)and a NAFLD group(n=202).The NAFLD group was divided into 2 subgroups according to the ALT level:A non-alcoholic fatty liver(NAFL)group and a non-alcoholic steatohepatitis(NASH)group.Logistic regression analysis was used to analyze the association between minerals(copper,zinc,calcium,magnesium,and iron)and NAFLD,NAFL and NASH. Results:A total of 602 subjects were included,of whom 73.6%were male,with a median age of 10(9,11)years,and a body mass index(BMI)of 24.9(22.7,27.4)kg/m2.The intergroup comparison results showed that compared with the overweight group,the NAFLD group had higher levels of age,BMI,diastolic blood pressure(DBP),systolic blood pressure(SBP),triglyceride(TG),low density lipoprotein(LDL),alanine transaminase(ALT)and aspartate aminotransferase(AST),and lower level of high density lipoprotein(HDL).The NAFL group had higher levels of age,BMI,DBP,SBP,ALT,and AST,and lower levels of HDL compared with the overweight group.The levels of age,BMI,DBP,SBP,TG,LDL,ALT,and AST of NASH were higher than those in the overweight group,while the level of HDL was lower than that in overweight group(all P<0.017).After adjusting for a variety of confounders,the OR of NAFLD for the highest quantile of iron was 1.79(95%CI 1.07 to 3.00)compared to the lowest quantile,and no significant association was observed between copper,zinc,calcium,and magnesium,and NAFLD.The subgroup analysis of NAFLD showed that the OR for the highest quantile of iron in children with NAFL was 2.21(95%CI 1.26 to 3.88),while no significant association was observed between iron level and NASH.In addition,no significant associations were observed between copper,zinc,calcium,and magnesium levels and NAFL or NASH. Conclusion:High iron level increases the risk of NAFLD(more likely NAFL)in overweight and obese children,while copper,zinc,calcium,magnesium,and other elements are not associated with the risk of NAFLD in overweight and obese children.
2.Evaluation of effects of Mycobacterium marinum on macrophages through a metabolomics analysis
Lu YANG ; Zhenzhen WANG ; Ying SHI ; Huiting ZHONG ; Yuanyuan YU ; Han MA ; Yanqing CHEN
Chinese Journal of Dermatology 2024;57(11):1037-1044
Objective:To analyze changes in energy metabolism and oxylipin metabolism in macrophages after stimulation by Mycobacterium marinum ( M. marinum) using targeted metabolomics, and to provide insights into the mechanisms underlying the immune defense by macrophages against M. marinum infections. Methods:Mouse bone marrow-derived macrophages were obtained from the bilateral femurs of mice, and cultured cells were divided into two groups: the active M. marinum group and the inactivated M. marinum group. Bacterial suspensions were prepared using M. marinum clinical isolates; the active M. marinum group was treated with live M. marinum suspensions for 12 hours, while the inactivated M. marinum group with inactivated M. marinum suspensions for 12 hours. Cell morphology was observed through microscopy, and cell length was measured. Cell lysates collected from both groups were subjected to liquid chromatography-tandem mass spectrometry analysis to detect energy and oxylipin metabolites. A t-test was utilized to compare the lengths of macrophages between the two groups, while principal component analysis and orthogonal partial least squares-discriminant analysis were conducted to identify differential metabolites. Results:Under the microscope, macrophages in the active M. marinum group formed more granuloma-like cell aggregates compared with those in the inactivated M. marinum group; the macrophages were significantly thinner and longer in the inactivated M. marinum group (439.52 ± 91.67 μm) than in the active M. marinum group (289.96 ± 70.11 μm, P < 0.001). Principal component analysis and orthogonal partial least squares-discriminant analysis of energy metabolism and oxylipin metabolism in macrophages demonstrated good separation between the two groups. As for the energy metabolism, a total of 12 differential metabolites were identified, with the amino acid metabolism showing the most significant changes. Specifically, there was a significant increase in the content of L-citrulline, while the content of L-leucine and serine decreased. As for the oxylipin metabolism, 20 differential metabolites were identified, with the arachidonic acid metabolism showing the most significant changes. Conclusions:Macrophages stimulated by live M. marinum exhibited altered amino acid metabolism and arachidonic acid metabolism compared with those stimulated by inactivated M. marinum, characterized by an increase in L-citrulline content, a decrease in L-leucine and serine levels, and alterations in arachidonic acid content.
3.A study on the change of resting state functional connection of default mode network in clinically remitted patients with major depression disorder
Yang HAN ; Hui MA ; Zhenzhen WANG ; Jiaqi ZHONG ; Hui WANG ; Ning ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(5):394-399
Objective:To explore the functional connection (FC) changes of default mode network (DMN) with the patients who have clinically remitted from major depressed disorder (MDD) and the brain imaging basis of the rehabilitation mechanism of major depression.Methods:Seventeen right-handed outpatients in the medical and psychological ward of Nanjing Brain Hospital who met the inclusion criteria were recruited by psychiatrists.MDD subjects after enrollment were scanned by resting-state functional magnetic resonance (fMRI) in baseline period(rMDD) and a 6-month follow-up period (sMDD). Tweenty-two healthy controls (control group, HCs group) matched with the MDD group in gender, age, and educational level were recruited and given the same resting fMRI scan.The independent component analysis (ICA) was used to extract DMN brain regions of rMDD, sMDD and HCs in resting state separately and to compare the changes of DMN functional connectivity in full remitted MDD patients.Results:The DMN data showed that the functional connectivity of right orbital middle frontal gyrus(MNI: x, y, z=3, 54, -9), right posterior cingulate(MNI: x, y, z=6, -51, 30), and precuneus(MNI: x, y, z=9, -54, 27) in the rMDD was significantly higher than the HCs group, and no functional connectivity in the rMDD was found to be lower than that in HCs group.Furthermore, no significant difference been found between the sMDD and HCs group.Compared with the rMDD, the functional connectivity of orbital middle frontal gyrus(MNI: x, y, z=3, 54, -9) and left medial prefrontal cortex (mPFC) (MNI: x, y, z=-3, 66, 12)in the sMDD was significantly lower than that in the rMDD, and the functional connectivity of left angular gyrus in the sMDD(MNI: x, y, z=-57, -57, 33) was significantly higher than that in the rMDD.Conclusion:The DMN network has not fully returned to its normal level though the posttreatment Hamilton Depression Scale-17 score was lower than 7 points, and the injury of FC is still recovering in the following 6 months, suggesting that the recovery of the DMN network function was delayed in the full remission of clinical symptoms, and is related to the recure of MDD.
4.A follow-up study on the changes in salience network function connectivity in clinically cured patients with depression
Zhenzhen WANG ; Jiaqi ZHONG ; Hui MA ; Changjun TENG ; Yang HAN ; Hui WANG ; Ning ZHANG
Chinese Journal of Psychiatry 2020;53(5):400-405
Objective:To explore the change of salience network functional connectivity over time in patients with clinically cured depression.Methods:Twenty-two healthy controls (control group) and 17 clinically cured depressed patients (clinically cured group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan at baseline and 6 months later. Routine preprocessing of rs-fMRI data was performed. Salience network was extracted by independent component analysis (ICA) followed by a t-test to compare the differences of salience network functional connectivity between the control group and clinically cured patient group at both baseline and 6 months follow-up. Results were corrected by AlphaSim correction method. Results:At baseline, compared to the control group, clinically cured patient group showed a significantly increased functional connectivity in the dorsolateral prefrontal cortex ( t=2.84, P<0.01, AlphaSim correction) and a significantly increased functional connectivity in the medial prefrontal cortex ( t=4.08, P<0.01, AlphaSim correction) as well as a decreased functional connectivity in the left precuneus ( t=-3.06) and dorsolateral prefrontal cortex ( t=-2.98, P<0.01, AlphaSim correction) at 6 months follow-up. Conclusion:Patient′s functional connectivity of salience network may not stable during the first 6 months after being clinically cured. The abnormal functional connectivity in the dorsolateral prefrontal cortex when they are initially and clinically cured may gradually improve.
5.A follow-up study on the changes in salience network function connectivity in clinically cured patients with depression
Zhenzhen WANG ; Jiaqi ZHONG ; Hui MA ; Changjun TENG ; Yang HAN ; Hui WANG ; Ning ZHANG
Chinese Journal of Psychiatry 2020;53(5):400-405
Objective:To explore the change of salience network functional connectivity over time in patients with clinically cured depression.Methods:Twenty-two healthy controls (control group) and 17 clinically cured depressed patients (clinically cured group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan at baseline and 6 months later. Routine preprocessing of rs-fMRI data was performed. Salience network was extracted by independent component analysis (ICA) followed by a t-test to compare the differences of salience network functional connectivity between the control group and clinically cured patient group at both baseline and 6 months follow-up. Results were corrected by AlphaSim correction method. Results:At baseline, compared to the control group, clinically cured patient group showed a significantly increased functional connectivity in the dorsolateral prefrontal cortex ( t=2.84, P<0.01, AlphaSim correction) and a significantly increased functional connectivity in the medial prefrontal cortex ( t=4.08, P<0.01, AlphaSim correction) as well as a decreased functional connectivity in the left precuneus ( t=-3.06) and dorsolateral prefrontal cortex ( t=-2.98, P<0.01, AlphaSim correction) at 6 months follow-up. Conclusion:Patient′s functional connectivity of salience network may not stable during the first 6 months after being clinically cured. The abnormal functional connectivity in the dorsolateral prefrontal cortex when they are initially and clinically cured may gradually improve.
6.Analysis of extreme obesity in two pedigrees due to leptin receptor mutation
Jingya YE ; Zhenzhen FU ; Wei GUAN ; Yizhe MA ; Yingyun GONG ; Shuai MA ; Xuan YE ; Chenxi ZHAO ; Xiaomei GENG ; Zhong LI ; Hui LIANG ; Hongwen ZHOU
Chinese Journal of Endocrinology and Metabolism 2019;35(1):32-36
This study reported two women with extreme obesity who underwent metabolic surgery due to their mutations in leptin receptor (LEPR).Genomic DNA was extracted from the anticoagulant blood samples of the two patients and their parents.A panel of genes related to metabolic diseases or whole exon sequencing was screened and the results were confirmed by Sanger sequencing.This is the first time that these three mutations in LEPR were reported.Two patients complained insatiety and early-onset obesity since childhood at clinics.Patient 1 was a 39-year-old woman with height 150 cm,weight 130 kg,and BMI 57.8 kg/m2.Serum leptin level was 156.4 μg/L.A homozygous mutation of c.2317G>T was found in exon 15 of LEPR gene in patient 1,which was descended from her father and mother respectively.Patient 2 was a 37-year-old woman with height 158 cm,weight 167 kg,and BMI 67 kg/m2.Serum leptin level was 193.4 μg/L.Genetic analysis showed compound heterozygous mutations of c.1482delT and c.1892C > A.Her father showed heterozygous c.1482delT mutation,and her mother carried heterozygous c.1892C > A mutation.Two patients all underwent metabolic surgery with body weight reduction of about 22 kg and 40 kg respectively after first six months.However,the follow-up studies showed that the body weight of patient 1 rebounded to pre-surgery level in two years and patient 2 did not further lose weight in the following six months.
7. The functional connection of central executive network in patients with depression after clinical cure
Jiaqi ZHONG ; Zhenzhen WANG ; Yang HAN ; Changjun TENG ; Hui WANG ; Ning ZHANG ; Hui MA
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(12):1085-1090
Objective:
To study the changes in the functional connections of the central executive network in patients with depression after clinical cure.
Methods:
Seventeen depression patients who met the clinical cure standard (patient group) and twenty-two healthy controls (control group) were selected.The baseline rs-fMRI data were collected from the healthy control group and the patient group respectively, and the rs-fMRI data in the patient group were collected again after 6 months.Compared the changes of central executive network function connection between the two groups.
Results:
At baseline, there was a high functional connection in the left inferior parietal lobule(MNI: x, y, z=-39, -69, 33)and right insula(MNI: x, y, z=15, -45, 30) in the patient group compared with the control group.Compared with the baseline, there were high functional connections in part of the left inferior parietal lobe (MNI: x, y, z=-60, -48, 21) and the right dorsolateral prefrontal lobe (MNI: x, y, z=24, 18, 60), and low functional connections in part of the left inferior parietal lobe (MNI: x, y, z=-51, -69, 18) in patient group 6 months after clinical cure.Compared with the control group, there was a high functional connection in the right dorsolateral prefrontal lobe (MNI: x, y, z=45, 51, -6) and the right inferior parietal lobe (MNI: x, y, z=42, -48, 27) in patient group 6 months after clinical cure.
Conclusion
The functional connection of central executive network of depression patients has not been restored, and the related abnormality is not stable in six months after reaching the clinical cure standard.
8.Pulse index continuous cardiac output combined with intracranial pressure monitoring in patients with severe craniocerebral injury
Jianguo YANG ; Xingming ZHONG ; Yiqi WANG ; Zhaohui ZHAO ; Yong CAI ; Zhenhai FEI ; Lei ZHANG ; Hua GU ; Tao YANG ; Zhenzhen XU ; Kankai TANG ; Zhidong CHEN
Chinese Journal of Neuromedicine 2019;18(12):1201-1208
Objective To explore the value of pulse index continuous cardiac output (PICCO) combined with intracranial pressure monitoring in patients with severe craniocerebral injury.Methods One hundred and thirty-eight patients with severe craniocerebral injury accepted controlling decompression surgical treatment in our hospital from February 2015 to February 2019 were prospectively chosen.According to patients' families will,postoperative application of PICCO combined with intracranial pressure monitoring for fluid management was performed in 72 patients (treatment group) and application of central venous pressure combined with intracranial pressure monitoring for fluid management was performed in 66 patients (control group).All patients were adjusted according to the monitoring results.The intracranial pressure and cerebral perfusion pressure one week after surgery,incidences of new traumatic cerebral infarction,neurogenic pulmonary edema,pulmonary infection,scalp exudation,and intracranial infection,average hospitalization days,total hospitalization costs,intensity of antimicrobial use,and Glasgow coma scale scores two weeks after operation were compared and analyzed between the two groups.Glasgow outcome scale was used to evaluate the prognoses of the patients 6 months after injury.Results There were 7 patients (3 from the control group and 4 from the treatment group) dropped out of the study due to various reasons and 131 patients (63 from the control group and 68 from the treatment group) included in the final statistical analysis;there was no significant difference in drop-out rate of the two groups (P>0.05).The intracranial pressure in the treatment group ([14.28±2.98] mmHg) was significantly lower than that in the control group ([18.99±2.78] mmHg) and cerebral perfision pressure ([66.72±2.25] mmHg) was significantly higher than that in the control group ([52.96±3.12] mmHg) one week after operation (P<0.05).During hospitalization,the incidences of new traumatic cerebral infarction,neurogenic pulmonary edema,pulmonary infection,scalp exudation and intracranial infection in the treatment group (8.8%,13.2%,11.8%,7.4%,and 2.9%) were significantly lower than those in the control group (22.2%,27.0%,25.4%,19.0%,and 12.7%,P<0.05).The average hospitalization days,total hospitalization expenses and intensity of antimicrobial use in the treatment group were significantly shorter/lower than those in the control group (P<0.05).Glasgow coma scale scores (11.88±1.78) and good recovery rate (76.5%) in the treatment group were significantly higher than those in the control group (8.06±1.12,54.0%) two weeks after operation (P<0.05).Good recovery rate (76.5%) in the treatment group was significantly higher than that in the control group (54.0%,P<0.05).The mortality rate (5.9%) was significantly lower than that in the control group (17.5%,P<0.05).Conclusion PICCO combined with intracranial pressure monitoring can effectively improve intracranial pressure,optimize cerebral perfusion,reduce complications such as traumatic cerebral infarction,neurogenic pulmonary edema,pulmonary infection and intracranial infection in patients with severe craniocerebral injury,thereby improving prognosis and reducing mortality;besides that,it can reduce patients' exposure to anti-brain infection,and the breadth and intensity of bacterial drugs can reduce the length of hospitalization and total cost of hospitalization,thereby reducing the burden of family and society.
9.Relationship between dynamic CT angiography-based collateral flow evaluation and outcome of patients with stroke induced by acute basilar artery occlusion.
Zhenzhen LAI ; Sheng ZHANG ; Genlong ZHONG ; Xiaocheng ZHANG ; Qingmeng CHEN ; Min LOU
Journal of Zhejiang University. Medical sciences 2017;46(4):371-376
OBJECTIVETo evaluate the collateral flow in patients with ischemic stroke due to acute basilar artery occlusion by dynamic CT angiography and to predict the outcome after reperfusion therapy.
METHODSForty-five patients with stroke due to acute basilar artery occlusion undergoing reperfusion treatment in the Second Affiliated Hospital of Zhejiang University School of Medicine during January 2012 and August 2016 were retrospectively reviewed. Univariate and binary logistic regression model were used to identify the independent predictors of patient's outcome, and the receiver operating characteristic (ROC) curve was used to determine the optimal threshold of the posterior circulation collateral score (PC-CS) in predicting the prognosis of the patients.
RESULTSBinary logistic regression analysis indicated that the baseline National Institutes of Health Stroke Scale (NIHSS) score (=0.886, 95%:0.802-0.979,<0.05) and PC-CS (=1.962, 95%:1.026-3.752,<0.05) were independent predictors of patient's outcome, and PC-CS 4.5 was the optimal threshold (AUC:0.837, sensitivity of 68.2%, specificity of 87.0%).
CONCLUSIONSDynamic CT angiography based on CT perfusion imaging can be used to evaluate collaterals in posterior circulation, and to predict clinical outcome after reperfusion therapy in patients with acute basilar artery occlusion.
10.Clinical study on biochemical levels in patients with Parkinson's disease
Shunzhi ZHUANG ; Shuxiang PU ; Zhenzhen ZHONG ; Rongjuan XU ; Cong GAO ; Haiyan YAO ; Yihua HE
The Journal of Practical Medicine 2017;33(8):1298-1302
Objective To analyze the relationship between biochemical level and severity levels and clinical,duration of disease in patients with Parkinson Disease (PD).Methods 69 patients with PD and 69 healthy persons of similar sex and age were selected in the research.Serum uric acid and lipids levels were examined and compared.Results The serum uric acid,triglycerides,total cholesterol and low-density lipoprotein cholesterol (LDL-C) were (322.48 ± 66.18) μmol/L,(1.22 ± 0.86) mmol/L,(4.70 ± 0.92) mmol/L and (3.00 ± 0.85) mmol/L in control group,and (384.23 ± 88.28) μmol/L、(1.64 ± 0.94) mmol/L、(5.37 ± 1.31) mmol/L、(3.53 ± 1.03) mmol/L in control group.The differences are significant (t =-4.68,P =0.000;t =-2.74,P =0.007;t =-2.74,P =0.007;t =-3.49,P =0.001;t =-3.27,P =0.001).Serum UA concentration and high-density lipoprotein cholesterol (HDL-C),LDL-C were lower in patients with Parkinson's disease in duration of disease more than 3 years than those in duration of disease less than 3 years (t =3.373,P =0.001;t =2.440,P =0.017).The serum UA levels of any stages of PD patients were lower than the control group (P < 0.05) according to Hoehn-Yahr staging.All lipid levels in early and middle stage PD disease patients were lower than those in control group (P < 0.05).Serum UA,total cholesterol and HDL-C in female PD patients were (305.69 ± 54.25) μmol/L,(4.99 ± 0.95) mmol/L,(1.25 ± 0.27) mmol/L,and (339.76 ± 73.40) μmol/L,(4.41 ± 0.81) mmol/L,(1.06 ± 0.19) mmol/L in male patients.The difference is significant (t =2.198,P =0.031;t =-2.721,P =0.008;t =-3.266,P =0.002).Multivariate logistic regression models assessed lower uric acid concentrations is the risk of PD (OR =1.01,95% CI 1.004 ~ 1.015,P =0.001).Conclusion Biochemical level changed differently in Parkinson disease and uric acid reduction could be a risk factor for PD.

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