1.Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4
Yang LIU ; Xin ZHANG ; Shuo CHEN ; Jiazhong WANG ; Shuo YU ; Yiming LI ; Meng XU ; Harouna ABOUBACAR ; Junhui LI ; Tao SHAN ; Jixin WANG ; Gang CAO
Clinical and Molecular Hepatology 2022;28(3):522-539
Background/Aims:
Binge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs).
Methods:
Serum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used.
Results:
A marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated.
Conclusions
Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.
2.Depressive symptoms detection among the urban elderly in Ya'an city and its influencing factors six years after Lushan earthquake
Jiazhong LI ; Shurong PENG ; Peihui HUANG ; Xiaoliang HU ; Zunkui TU ; Gaomei WU ; Ling YIN ; Ru GAO
Sichuan Mental Health 2021;34(6):550-554
ObjectiveTo investigate the prevalence and characteristics of depressive symptoms among urban elderly six years after Lushan earthquake in Ya'an, so as to provide references for the mental health interventions for elderly following catastrophic stressful life events. MethodsFrom March to April 2019, a multi-stage stratified cluster random sampling method was adopted to enroll 885 urban elderly people aged 60 and above in Ya'an. A self-compiled questionnaire was used to collect the general demographic information, health-related and disaster-related information, meantime, the elderly was assessed using Geriatric Depression Scale (GDS-30). Thereafter, univariate and multivariate Logistic regression were applied to explore the influencing factors of depressive symptoms in urban elderly. ResultsA total of 783 valid questionnaires were collected, with a questionnaires response rate of 88.47%. Depressive symptoms were detected in 161 cases (20.56%). The prevalence of depression showed statistical differences among the elderly of different gender, age, marital status, family relationship, monthly per capita household income, physical exercise status, health status, self-care ability, sleep status and disaster-affected degree (P<0.05 or 0.01). Logistic regression analysis showed that the urban elderly of the female gender (OR=1.552, P=0.040), monthly per capita household income of 2000~3000 yuan (OR=6.982, P<0.01), monthly per capita household income≤2000 yuan (OR=6.857, P<0.01), lack of physical exercise (OR=1.693, P<0.01), being less capable of self-care (OR=3.838, P<0.01), being incapable of self-care (OR=8.547, P<0.01), complicating multiple curable diseases (OR=4.892, P<0.01) and complicating refractory chronic diseases (OR=5.657, P=0.031) were at high risk of depressive symptoms. The risk of depressive symptoms among the divorced or widowed elderly was greater than that among married elderly (OR=0.063, P<0.01). ConclusionThe prevalence of depressive symptoms is relatively high among the urban elderly six years after Lushan earthquake in Ya'an, moreover, female gender, low monthly per capita household income, lack of physical exercise, being incapable of self-care and poor health status are risk factors affecting the depressive symptom, while being married is a protective factor.
3.Clinical value of 99Tcm-MIBI scintigraphy for bone lesions of indefinite diagnosis with 99Tcm-MDP bone imaging
Jiazhong REN ; Zongwei HUO ; Xiaohui WANG ; Yan LIU ; Peng ZHANG ; Ning YUE ; Yongcun FANG ; Guoliang LI ; Qingwei WU ; Minglu CHEN ; Guoren YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(3):182-186
Objective To investigate the clinical value of 99Tcm-methoxyisobutylisonitrile (MIBI) double-phase imaging in differential diagnosis of bone lesions in tumor patients,which was indefinite in 99Tcm-methylene diphosphonate (MDP) bone imaging,and evaluate the correlation between 99Tcm-MIBI imaging and chemotherapy efficacy.Methods Fifty-two tumor patients (23 males,29 females,mean age 58 years) with bone isolated lesions(≤3) found by 99Tcm-MDP bone scintigraphy was enrolled from June 2014 to November 2015.Since the results of 99Tcm-MDP imaging were indefinite,99Tcm-MIBI double-phase (10 min and 30 min after injection of 99Tcm-MIBI) SPECT/CT imaging was then performed within 1 week.The final diagnosis was made according to results of more than two imaging modalities (CT,MRI,PET/CT) and/or follow-up (≥6 months).The diagnostic efficacy of 99Tcm-MIBI SPECT/CT imaging was calculated.The clinical dataof chemotherapy were also collected.Patients with bone metastasis were grouped as the treatment response.Retention index (RI) of metastatic lesions was calculated and compared between different groups using two-sample t test.The relationship between RI and chemotherapy efficacy was investigated by Spearman correlation analysis.Results A total of 12 benign lesions and 84 malignant lesions were eventually diagnosed.The sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV) and Youden index of 99Tcm-MIBI imaging were 96.43%(81/84),83.33%(10/12),97.59%(81/83),76.92%(10/13),and 0.80,respectively.The RI was statistically different between complete remission (CR)+partial remission (PR) group and stable disease (SD) + progressive disease (PD) group:-0.142± 0.036 vs-0.384± 0.067 (t =2.367,P<0.05).The RI of 99Tcm-MIBI in bone metastases was positively correlated with the chemotherapy efficacy (rs =0.78,P<0.01).Conclusions 99Tcm-MIBI imaging is helpful in differential diagnosis of bone lesions with indefinite diagnosis by 99Tcm-MDP bone imaging in tumor patients.99Tcm-MIBI RI of bone metastasis may predict the therapeutic response of chemotherapy efficacy.
4.Effect of ligustrazine on cardiac inflammation in rats with type 2 diabetes mellitus
Xinyuan ZHAO ; Kui XU ; Cairong LI ; Juan LI ; Fengping LIN ; Caiyan LI ; Jiazhong SUN ; Xiao CHEN
Chinese Journal of Pathophysiology 2017;33(4):744-748
AIM: To study the effect of ligustrazine on the cardiacmyocyte lesion in rats with type 2 diabetes mellitus.METHODS: Male Wistar rats were injected with STZ via tail vein under high-glucose and high-fat feeding for 4 weeks to establish the animal model of type 2 diabetes mellitus.Ligustrazine at different doses was used to treat the diabetic rats.The body weight, blood glucose and the morphology of heart tissues were observed.The myocardial levels of IL-1β, IL-6 and TNF-α were detected by ELISA, and the protein expression of IKKβ and NF-κB in the myocardium was determined by Westeren blotting.RESULTS: Ligustrazine at high dose alleviated the body weight reduction and blood glucose elevation cause by diabetes, and reduced pro-inflammatory factors IL-1β, TNF-α and IL-6.Moreover, the protein expression of IKKβ and NF-κB was significant decreased by ligustrazine.CONCLUSION: Ligustrazine inhibits the myocardial inflammation caused by diabetes through anti-inflammatory pathway.
5.Effects of calcitriol on femoral biomechanics index of diabetic rats
Guangsen LI ; Jing DAI ; Ji LI ; Li CAI ; Mengting KE ; Jiazhong SUN
Chinese Journal of Endocrinology and Metabolism 2016;(2):139-142
[Summary] 45 male SD rats with 4 week old were assigned to 3 groups after normal feedstuff for 2 weeks:control group(n=15), diabetic group(n=15), and calcitriol group(n=15).Diabetic rat model were induced using intraperitoneal injection with streptozotocin( STZ) after 12 h fasting.Calcitriol group and diabetic group were treated with calcitriol for 24 weeks.Femoral biomechanics indexes were measured at end of the study.Total 30 SD rats ( 10 rats of each groups) were analyzed.Compared to normal controls, the rats in diabetic group had lower body weight [(437.02±18.66vs267.93±15.64)g,P<0.05],decreasedserumcalciumconcentration[(2.89±0.31vs2.60 ±0.38) mmol/L, P<0.05], and increased serum phosphorus concentration[(2.21 ±0.35 vs 2.80 ±0.66) mmol/L, P<0.05].At the end of the study, the ultimate force[(98.07 ±2.94 vs 70.87 ±5.75) N, P<0.05], ultimate displacement[(0.66 ±0.02 vs 0.51 ±0.02) mm, P<0.05], Young′s modulus[(139 188.51 ±10 617.69 vs 81 969.06 ±6 393.21) N/mm2, P<0.05], and modulus for toughness[(22 492.59 ±2 429.15 vs 8 292.87 ± 1 291.43) N/mm2 , P<0.05 ] of diabetic group were significantly lower than normal control group.However, calcitrol could reverse these changes at some extent.SD rats with diabetes had significant disorder of bone metabolism and decreased bone strength.Calcitriol could improve the decreased bone strength in diabetic rats.
6.Effect of Codonopsis and Glycyrrhiza glycoconjugates on migration and membrane potential of IEC-6 cells
Ruliu LI ; Yuzhu TAO ; Peng WEN ; Xiaohua TU ; Jiazhong CAI ; Weiwen CHEN
Chinese Journal of Pharmacology and Toxicology 2015;(6):917-923
OBJECTIVE To observe the effect of Codonopsis and Glycyrrhiza glycoconjugates on migration and membrane potential of small intestinal epithelial cells(IEC-6),and to explore the promoting effects of Yiqi jianpi herb Codonopsis and Glycyrrhiza on gastrointestinal mucosal injury repair and the underlying mechanisms. METHODS Under normal conditions or loaded with the inhibitor of potassium channel 4-aminopyridine(4-AP),IEC-6 cells were treated with Codonopsis and Glycyrrhiza glycoconjugates (25-200 mg · L-1) for 24 h,respectively. IEC-6 cell migration was observed by the phase contrast microscope and cell membrane potential was detected by flow cytometry. RESULTS Codonopsis and Glycyrrhiza glycoconjugates (50 and 100 mg · L-1) increased the number of migrated IEC-6 cell compared with normal control group(P<0.01,P<0.05). Compared with normal control group,4-AP reduced the number of migrated IEC-6 cell(P<0.01). Codonopsis and Glycyrrhiza glycoconjugates (50-200 mg · L-1)reversed cell migration inhibited by 4-AP significantly when compared with 4-AP model group(P<0.01). The results of flow cyometry analysis showed that the cell membrane poten?tial was increased after treatment with Codonopsis and Glycyrrhiza glycoconjugates(50 mg · L-1)compared with normal control group and resulted in an increase in cell membrane hyperpolarization(P<0.01). Compared with normal control group,4-AP decreased the cell membrane potential(P<0.01)and resulted in cell membrane depolarization. Also,compared with 4-AP model group,cell membrane depolarization induced by 4-AP was reversed by treatment with Codonopsis and Glycyrrhiza glycoconjugates(100 and 200 mg·L-1). CONCLUSION Codonopsis and Glycyrrhiza glycoconjugates may promote gastrointestinal mucosal injury repair and the mechanisms may involve the activation of signaling pathways by affecting polyamine-dependent intestinal epithelial cell migration voltage-gated K+channels.
7.Impacts of low-grade inflammation on the correlation of serum testosterone and carotid intima-media thickness in type 2 diabetes mellitus men
Xin LI ; Li JIANG ; Miao YANG ; Suxin SUN ; Yuwen WU ; Jiazhong SUN
Journal of Chinese Physician 2015;17(1):61-64
Objective To investigate the impacts of low-grade inflammation on the correlation of serum testosterone (T) and carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM) men.Methods Based on the concentration of C-reactive protein (CRP) and T,a total of 247 patients was divided into low-grade inflammation with low T group (LI-LT,CRP ≥ 2.0 mg/L,T < 12.0 nmol/L,n =65),low-grade inflammation with normal T group (LI-NT,n =67),non-low-grade inflammation with low T group (NLI-LT,n =56),and non-low-grade inflammation with normal T group (NLI-NT,n =59).General information,medical history,and anthropometry data were collected.Glycosylated hemoglobin AI c (HbA1c),blood fat,and CIMT were detected.Results Compared to NLI-NT group,CIMT in NLI-LT group was increased without statistical significance [(0.87 ±0.09) vs (0.90 ±0.10)mm,t =1.693,P =0.090].CIMT in LI-LT group was increased significantly compared to that of LI-NT group [(0.99 ± 0.10) vs (1.07 ±0.12)mm,t =5.208,P =0.000].Correlation analysis indicated that serum T correlated negatively with CIMT (n =247,r =-0.368,P <0.01) in whole.The correlation coefficient of T and CIMT was-0.582 (P =0.000),and-0.098 (P =0.087) in patients with (n =132) and without (n =115) low-grade inflammation,respectively.To make CIMT dependent coefficient and serum T independent coefficient in multiple regression analysis,the partial regression coefficient was-0.062 (95% CI:-0.094 ~-0.029,P =0.008),and-0.045 (95% CI:-0.087 ~-0.002,P =0.036),respectively,before and after the adjustment of age,smoking,family history,T2DM course,body mass,blood pressure,HbAlc,and blood fat.After the additional adjustment of CRP,the partial regression coefficient was-0.019 (95% CI:-0.120 ~ 0.042,P =0.287).Conclusions The negative relationship between serum T and CIMT in T2DM men might be modulated by low-grade inflammation.
8.Multisession cyberknife radiosurgery for cavernous sinus hemangiomas: medium- and long-term outcomes.
Xin WANG ; Enmin WANG ; Email: WANGEM@FUDAN.EDU.CN. ; Xiaoxia LIU ; Li PAN ; Jiazhong DAI ; Yang WANG
Chinese Journal of Surgery 2015;53(10):767-771
OBJECTIVETo investigate the medium- and long-term outcomes of multisession cyberknife radiosurgery intreating cavernous sinus hemangiomas (CSH).
METHODSBetween January 2008 and February 2012, 45 patients with CSH, including 35 female and 10 male patients with a mean age of 53 years (range: 26-80 years), underwent multisession cyberknife radiosurgery. The mean diameter of the CSH was 47.0 mm (range: 23.0-75.0 mm). The tumor volume ranged from 2.9 to 140.1 cm³, with a mean of 40.1 cm³. Eleven giant CSH with tumor volume ≥ 40.0 cm³ were irradiated by cyberknife in 4 fractions, 28 large tumors with tumor volume 10.0-40.0 cm³ in 3 fractions, 4 tumors with tumor volume 5.0-10.0 cm³ in 2 fractions, 2 small tumors with tumor volume ≤ 5.0 cm³ in 1 fraction. After the treatment, all patients had regular clinical and radiological follow-up at 6-month intervals. A combination of the neurologic examination and MRI information was used to evaluate the overall response.
RESULTSAll patients were followed up for 22-70 months with a mean of 37.7 months. One patient died of stroke 3 years post cyberknife, but the follow-up MRI showed that the CSH shrank in volume. Eight patients with giant CSH had slight headache after finishing cyberknife radiosurgery, and relieved with mannitol and dexamethasone treatment. Neurological deficits in patients had improved or disappeared at 6 to 12 months post cyberknife. None of these patients showed any deterioration in symptoms or new cranial nerve deficits during the follow-up. Latest follow-up imaging demonstrated that tumors decrease > 80% in 15 patients, > 60% to 80% in 18 patients (including the death patient), 40%-60% in 12 patients post cyberknife. Two patients reported occurrence of seizures and maintaining seizure control after antiepileptic drugs administration.
CONCLUSIONSMultisession cyberknife radiosurgery is confirmed to provide medium and long-term local tumor control and symptom improvement. It is a safe and effective treatment modality for CSH, and may serve as a promising treatment option in the future.
Adult ; Aged ; Aged, 80 and over ; Cavernous Sinus ; pathology ; surgery ; Cranial Nerves ; physiopathology ; Female ; Hemangioma ; surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Radiosurgery ; methods ; Treatment Outcome ; Tumor Burden
9.CTRP3 increased insulin sensitivity of insulin resistant 3 T3-L1 adipocytes via decreasing expression of inflammatory factors
Xin LI ; Li JIANG ; Miao YANG ; Yuwen WU ; Suxin SUN ; Jiazhong SUN
Chinese Journal of Pathophysiology 2014;(10):1833-1838
AIM:To investigate the effects of C1q/TNF related protein 3 (CTRP3) on the insulin sensitivity of insulin resistant 3T3-L1 adipocytes.METHODS: The insulin resistance model of 3T3-L1 adipocytes was induced by palmic acid cultivation.The adipocytes were treated with different concentrations of recombinant CTRP3 protein (10, 50, 250,1 250 μg/L) for 12 h, and for different times (2, 6, 12, 24 h) at the concentration of 250μg/L.The glucose con-sumption was detected by the glucose oxidase method.The glucose transport ratio was measured by 2-deoxidation-[3H]-glucose intake method.The contents of TNF-αand IL-6 in the supernatant were detected by ELISA.The mRNA expression of TNF-α, IL-6 and glucose transporter-4 (GLUT-4) was measured by real-time PCR.The protein expression of GLUT-4 was detected by Western blotting.RESULTS:Compared with normal control ( NC) group, the glucose consumption and glucose intake ratio of insulin resistance ( IR) group was decreased by 50.6%and 57.9%, respectively.Compared with IR group, with the increase in CTRP3 (10, 50, 250,1 250 μg/L) in intervention groups, the glucose consumptions were in-creased by 22.1%, 42.9%, 76.6% and 80.5%, respectively, and the glucose intake ratios were increased by 39.0%, 68.0%, 108.0%and 111.0%, respectively.With the increased duration (2, 6, 12 and 24 h) of CTRP3 treatment at the concentration of 250 μg/L, the glucose intake ratio was increased by 23.0%, 79.0%, 109.0%and 114.0%, respectively. The contents of TNF-αand IL-6 in the supernatant were decreased by 17.4%and 17.1%respectively as treated with CTRP3 at the concentration of 250 μg/L for 12 h, and the mRNA expression of TNF-αand IL-6 was decreased by 26.0% and 18.9%respectively, while the mRNA and protein expression of GLUT-4 was increased by 61.5%and 55.6%respectively. CONCLUSION:CTRP3 may increase the insulin sensitivity of insulin resistant 3T3-L1 adipocytes by down-regulating the expression of inflammatory factors, improving the insulin signal transduction and increasing the expression of GLUT-4.
10.Different impacts of the components of metabolic syndrome on cardiovascular risk in newly-diagnosed type 2 diabetes mellitus
Xin LI ; Suxin SUN ; Miao YANG ; Yuwen WU ; Jiazhong SUN
Journal of Chinese Physician 2013;15(10):1342-1345
Objective To investigate the different impacts of the components of metabolic syndrome (MS) on cardiovascular disease (CVD) risk factors and Framingham risk value (FRV) in newly-diagnosed type 2 diabetes mellitus (T2DM) patients without coronary heart disease (CHD).Methods A total of 212 newly-diagnosed T2DM patients was divided into three groups based on the components of MS,including body mass index (BMI),triglyceride (TG),high density lipoproteins cholesterol (HDL-C),and mean arterial pressure (MAP) tertile,respectively.The general CVD risk factors [smoking,BMI,TG,HDL-C,total cholesterol (TC),low density lipoproteins cholesterol (LDL-C),HbA1 C,homeostasis model assessment of insulin resistance (HOMA-IR),and FRV] were compared among the groups.Logistic regression analysis was used to observe the different impact of MS components on CVD risk.Results With the increasing of BMI,TG and MAP tertiles,all the CVD risk factors and the ratio of FRV middle-risk group or high-risk group had the tendency of augmentation.With the increasing of HDL-C tertiles,all the CVD risk factors and the ratio of FRV middle-risk group or high-risk group was in downtrend.Binary logistic regression analysis indicted that BMI,systolic pressure,diastolic pressure,HbA1 c and TG were risk factors of FRV non-low-risk group (middle-risk and high-risk groups),HDL-C was the protective factor.The odds ratios (ORs) of BMI,systolic pressure,diastolic pressure,HbA1 c,TG and HDL-C were 2.794 (95% CI:2.390-2.408),2.601 (95 % CI:1.974-3.701),1.476 (95 % CI:1.231-2.048),2.964 (95 % CI:1.925-3.282),1.464(95% CI:0.934-2.294),and 0.732(95% CI:0.023-0.962),respectively.Logistic stepwise regression analysis indicated that systolic pressure,BMI,HbA1 C,and HDL-C were entered into the regression equation,and the partial regression coefficient was 0.784,1.213,1.679,and-0.854,respectively (P < 0.05 or P < 0.01).Conclusions All the components of MS in newly-diagnosed T2DM were correlated with CVD risk factors.However,they should be weighed differently.

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