1.The effect and mechanism of alcohol on liver injury in hepatitis B virus transgenic mice
Juanjuan HUANG ; Bing LI ; Libo CAO ; Linqi OUYANG ; Shikun LIU
Chinese Pharmacological Bulletin 2010;26(3):372-376
Aim To investigate the synergistic effects and possible molecular mechanism of hepatitis B virus (HBV) and alcohol on liver injury in HBV transgenic mice(HBV-Tg mice).Methods 20 HBV-Tg mice and 20 wild-type mice were randomly divided into 4 groups:alcohol-fed Tg mice and alcohol-fed Wt mice, and they were given intragastric administration with alcohol. Control Tg mice and control Wt mice received intragastric administration with saline.All groups were rasied for 10 weeks.The levels of ALT and AST in serum, the degree of inflammation, the degree of fibrosis, the mRNA expression of TGF-β_1, Smad3, Smad7, CTGF and the protein expression of TGF-β_1, CTGF, α-SMA in liver tissue were detected.Results The serumlevel of ALT and AST, the mRNA expression of TGF-β_1, Smad3, Smad7, CTGF and the protein expression of TGF-β_1, CTGF, α-SMA in liver all increased markedly in alcohol-fed Tg mice. Alcohol consumption induced hepatocyte steatosis and hepatic inflammation in alcohol-fed Tg mice, but the change of liver fibrosis was not remarkable.Conclusion HBV and alcohol have synergistic effects on early liver injury, possibly by enhancing the expression of TGF-β_1, Smad3, CTGF, α-SMA and inducing unbalanced expression of Smads.
2.Effect of lamivudine and silymarin on liver fibrosis-relevant factors in HBV transgenic mice with alcohol drinking
Juanjuan HUANG ; Shikun LIU ; Zuojun LI ; Libo CAO ; Linqi OUYANG
Journal of Central South University(Medical Sciences) 2017;42(3):257-263
Objective:To observe the role of lamividine and silymarin preventing and curing liver fibrosisrelevant factors induced by alcohol drinking in hepatitis B virus (HBV) transgenic mice (Tg mice).Methods:Forty HBV-Tg BALB/C mice with 1.3 copy were randomly divided into 4 groups:a control group,a model group,a lamivudine group and a silymarin group.Tg mice in control group were treated with normal saline via intragastric administration;Tg-mice in the model group were treated with 50% alcohol (5 mL/kg) once a day via intragastric administration;while Tg-mice in lamivudine group and silymarin group were treated with alcohol (5 mL/kg) plus laminvudine (100 mg/kg) and silymarin (200 mg/kg) once a day via intragastric administration respectively.All groups were raised for 10 weeks.The levels of HBV-DNA copy number,ALT,AST in serum,the degree of inflammation,the degree of fibrosis,the mRNA expression levels of TGF-β 1,Smad3,Smad7 and connective tissue growth factor (CTGF),and the protein expression levels of TGF-β1,CTGF and α-SMA in liver tissue were detected.All the images were scanned with electronic computer and the data were analyzed with SPSS13.0 software.Results:Compared with the control group,liver injury were significantly aggravated,while HBVDNA copies,mRNA levels ofTGF-β1,Smad3,Smad7 and CTGF as well as the protein levels of TGF-β1,CTGF and α-SMA were significantly increased (P<0.05).Compared with the model group,liver injury were significantly attenuated in silymarine group and lamivudine group,while mRNA levels of TGF-β 1,Smad3 and CTGF as well as the protein levels of TGF-β1,CTGF and α-SMA were significantly decreased;mRNA level of Smad7 was further increased (P<0.05);the levels of ALT and AST in serum were decreased in the silymarine group (P<0.05).Conclusion:Lamivudine and silymarin relieve the histological damage in the liver of alcohol-fed Tg mice.The mechanisms for the beneficial effects of lamivudine or silymarin might be related to inhibiting the expression of TGF-β 1,Smad3 and CTGF,modulating the expression of Smads and suppressing the activation of HSC.
3.Application of auricular composite tissue flap graft in reconstruction of nasal alar defect
Le LI ; Linqi LIU ; Xiaoge LI ; Liang CHEN ; Zhenxiang WANG
Journal of Regional Anatomy and Operative Surgery 2014;(5):489-491,492
Objective To evaluate the clinical efficacy of the application of auricular composite tissue flap in treatment of nasal alar de-fect. Methods 43 cases of nasal defects patients were admitted to our hospital from January 2008 to March 2013, 23 cases of them were treated with auricular composite tissue flap transplantation, and the other 20 cases were given nasolabial sulcus flap transfer operation. All patients were followed-up for 6 to 12 months, and the rate of secondary surgery, proliferation of scar, and flap survival of the two groups were compared. Results Treatment of auricular composite tissue flap transplantation has more advantages in terms of the rate of secondary surgery, proliferation of scar, and flap survival, and the difference is of statistical significance (P<0. 05). And there is no obvious differ-ence in satisfaction degree of cosmetic outcomes. Conclusion Auricular composite tissue flap surgery has the advantages of simple opera-tion, good appearance and good efficacy.
4.Expression and significance of nuclear factor-κB-related proteins in idiopathic orbital inflammatory pseudotumor
Linqi, YANG ; Pengxiang, ZHAO ; Yanan, WU ; Xujuan, ZHANG ; Lei, SHANG ; Mengyu, LIU ; Xiao, LIU ; Jianmin, MA ; Xuemei, MA
Chinese Journal of Experimental Ophthalmology 2017;35(9):786-791
Background Idiopathic orbital inflammatory pseudotumor (IOIP) is a commom orbital disease,with serious eye symptoms and replase tendency,and its pathogenesis is still unclear.Nuclear factor-κB (NF-κB)-related proteins participate in many important pathophysiological process,however,whether NF-κB plays a role in the IOIP process is worthy of attention.Objective This study was to explore the roles of NF-κB pathway in IOIP pathogenesis.Methods Twenty-four IOIP specimens were collected during surgery in Beijing Tongren Hospital from September 2010 to May 2016.The histopathological characteristics of IOIP were examined by hematoxylin and eosin staining.The expression and location of NF-κB/p65,p-p65,p50 and inhibitor of κB (IκB-ot) were detected by immunohistochemistry and verified by immunocytochemistry and Western blot assay.Results The histopathological features of IOIP were numerous small lymphocyte infiltraion and fibrous tissue proliferation,and a lot of epithelioid cells were seen in lacrimal gland-involved specimens.NF-κB/p65 was positively expressed in the cytoplasm of all 24 specimens and the nucleus in 15 specimens with the expressing rate of 62.5%.p50 was expressed in the cytoplasm in 22 specimens with the expressing rate of 91.7% and in the nucleus in 17 specimens with the expressing rate of 70.8%.The positive expression of p-p65 was found in 22 specimens with the expressing rate of 91.7%,and IκB-α was expressed in the cytoplasm of 11 specimens with the expressing rate of 45.8%.These results were confirmed by immunocytochemistry and Western blot assay.Conclusions NF-κB pathway is activiated during IOIP process,and NF-κB pathway may be involved in the pathogenesis of IOIP.
5.Comparison of the Immunogenicities of HIV-1 Mutants Based on Structural Modification of env
Jianhui NIE ; Chuntao ZHANG ; Huihui CHONG ; Xueling WU ; Chuyu LIU ; Yu WU ; Chenyan ZHAO ; Linqi ZHANG ; Youchun WANG
Virologica Sinica 2008;23(4):233-246
Eleven env mutants were designed and generated by site-directed mutagenesis of the regions around Nab epitopes and deletions of variable regions in env.The immunogenicities of the generated mutants were evaluated using single-cycle infection neutralization assays with two pseudoviruses and IFN-γELISPOT.Overall,five mutants(dWt,M2,M5-2,M5-1 and dM7)induced highed neutralization activities for both pseudoviruses than plasmid Wt,while only two of the mutants(dWt and M5-2)showed significant differences(P<0.05).Two mutants(M2 and dM2)induced more Env-specific T cells than plasmid Wt.Statistically however,significance was only reached for mutant M2.Thus,properly modified HIV-1 Env may have the potential to induce potent cellular and humoral immune responses.
6. Inhibitory effect of flufenidone on TGF-β1/Smads pathway in hepatocytes of rats with diethylnitrosamine (DEN)-induced liver injury
Feng WEI ; Yang HE ; Zhiqiang FAN ; Linqi OUYANG ; Shikun LIU ; Linqi OUYANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(7):739-746
AIM: To explore the protective effect of fluorofenidone (AKF-PD) on diethylnitrosamine-induced liver injury in rats and its inhibition of the TGF-β1/Smads pathway in hepatocytes. METHODS: Fifty-five male Sprague Dawley (SD) rats were randomly divided into three groups: model group (DEN group, n=20) were gavaged with DEN (10 mg/kg), 5 times for 14 weeks; control group (n=20) were gavaged with saline with the same volume of the model group; treatment group (DEN+AKF-PD Group, n=15), after 4 weeks of modeling, they were gavaged with AKF-PD (500 mg/kg) daily, and stopped at 14 weeks. At the end of experiment, the rats were killed by anesthesia and spinal dislocation. Masson staining was used to observe collagen deposition; primary hepatocytes were extracted and identified, and the levels of α-smooth muscle actin (α-SMA), TGF-β1, Smad3, and Smad7 mRNA, and the expression of Smad3 and Smad7 proteins in hepatocytes were detected. RESULTS: Compared with the control group, Masson staining showed that collagen deposition increased in the DEN group; AKF-PD treatment could significantly improve liver pathological damage and reduce collagen deposition. In addition, compared with the DEN group, the α-SMA, TGF-β1, and Smad3 mRNA levels of the AKF-PD group were significantly reduced, and the Smad7 mRNA level was increased. Moreover, AKF-PD treatment could dependably reduce the expression of Smad3 and increase Smad7. CONCLUSION: AKF-PD can significantly improve liver injury and fibrosis in rats caused by DEN. This effect may be related to the down-regulation of α-SMA, TGF-β1, and Smad3 mRNA levels in hepatocytes and the increase of Smad7 mRNA levels.
7.Mechanical Properties Analysis and Improved Design of Scaffolds for Bone Tissue Engineering Based on Finite Element Method
Xiaoquan SHI ; Linqi BAI ; Yazhou SUN ; Haitao LIU
Journal of Medical Biomechanics 2019;34(3):E262-E268
Objective To analyze the mechanical properties of bone tissue engineering scaffolds with different pore structure and porosity, and improve the mechanical properties of scaffolds by changing pore structure. Methods Square pore, spherical pore and cylindrical pore with different porosities from 55% to 75% were established by SolidWorks software, and the surface-volume ratio of different structures was calculated. The stress distribution and equivalent compression modulus of different scaffolds were obtained by ANSYS Workbench software. According to the stress distribution results, the scaffold with rectangular pore structure and cuboid element structure was improved instead of square pores. Results With the increase of porosity, the surface-volume ratio of the three structures increased. For the same porosity, the surface-volume ratio of square pores and spherical pores was larger, while that of cylindrical pores was the smallest. The modulus and porosity of the three structures were approximately linear. The modulus of the square pore and the cylindrical pore were similar. The stress analysis on the square pore and two improved structures with 60% porosity showed that for the two improve structures, the wall stress on 4 edges parallel to the direction of applied stresses could be reduced by 15%. Conclusions The surface-volume ratio and mechanical property of square pores were more advantageous than spherical pores and cylindrical pores with the same porosity, and the two improved structures could improve the mechanical properties of square pores. The two improved pores enriched the structure of tissue engineering scaffolds. The research findings provide the mechanical references for their clinical application.
8.The performance of the microbial barrier of needleless positive pressure closed connectors.
Yuyin XU ; Juanli ZHANG ; Zhipeng GAO ; Haitao LIU ; Linqi TIAN
Chinese Journal of Medical Instrumentation 2013;37(5):365-366
OBJECTIVEAnalyzing the performance of microbial barrier of needleless positive pressure closed connectors.
METHODSThree kinds of brand needleless positive pressure closed connectors were chosen to do the access of microorganisms test.
RESULTSPositive results were detected in the three experimental groups.
CONCLUSIONSSo far, lots of the connectors are not qualified strictly on the market, some improvement is required in the structure design and process.
Equipment Contamination ; prevention & control ; Infusions, Parenteral ; instrumentation ; methods
9.Clinical value of helium-free magnetocardiography in diagnosis of coronary heart disease
Feng XU ; Chenchen TU ; Shuwen YANG ; Ming DING ; Bin CAI ; Huan ZHANG ; Linqi LIU ; Xueyao YANG ; Shu ZHOU ; Zhao MA ; Xiantao SONG ; Hongjia ZHANG
Chinese Journal of General Practitioners 2023;22(11):1159-1166
Objective:To assess the clinical value of helium-free magnetocardiography(MCG) in the diagnosis of coronary artery disease(CAD).Methods:A total of 213 patients with suspected CAD undergoing MCG in Beijing Anzhen Hospital were enrolled in the study. All patients underwent coronary CT angiography/invasive coronary angiography(CCTA/ICA) within 48 hours after MCG scanning. The parameters of MCG, including magnetic field multipolarization, magnetic field unipolarization, T-wave flattened, change in magnetic field distribution at TT segment, abnormal T-peak amplitude ration of maximum to minimum, significant movement of poles, magnetic field angle deviation and abnormal distribution of positive pole were used for the evaluation of the stenosis of coronary arteries.Results:Among 213 patients, MCG scanning was completed in 193 cases(90.6%), while 20 cases were excluded for various reasons. The CCTA/ICA results were taken as gold standard, the total coincidence rate of MCG with the degree of stenosis was 88.60%(95% CI: 83.25%-92.72%), the sensitivity and specificity of MCG in the diagnosis of CAD was 89.63%(95% CI: 83.21%-94.21%) and 88.23%(95% CI:78.12%-94.78%), respectively; the positive and negative predictive value were 93.80%(95% CI:88.72%-96.68%) and 81.08%(95% CI:72.15%-87.64%), respectively. Conclusion:MCG is highly accurate in the diagnosis of CAD, it may be widely used clinically as an non-invasive method free of radiation or contrast agent.
10.Therapeutic effect of Xiayuxue decoction on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet and its mechanism
Linqi HOU ; Zhiyi WANG ; Xin ZHAO ; Jie ZHANG ; Wenting MA ; Xuling LIU ; Wei ZHANG ; Le TAO ; Cheng LIU ; Liu WU
Journal of Clinical Hepatology 2024;40(4):712-719
ObjectiveTo investigate the mechanism of action of Xiayuxue decoction in inhibiting nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet in mice by regulating nucleotide binding oligomerization domain like receptor containing pyrin domain protein 6 (NLRP6). MethodsA total of 15 male C57BL/6 mice were randomly divided into low-fat diet (LFD) group, high-fat diet (HFD) group, and Xiayuxue decoction-HFD group (XYXD group), with 5 mice in each group. Liver function parameters (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and blood lipid metabolic indicators (triglycerides [TG] and total cholesterol [TC]) were measured; HE staining and oil red O staining were performed for liver tissue to observe histomorpholoty and lipid droplet deposition; quantitative real-time PCR was used to measure the expression levels of inflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], interleukin-18 [IL-18], and NLRP6) in liver tissue; Western blot was used to measure the protein expression levels of NLRP6, nuclear factor-kappa B (NF-κB), and NF-κB p65; immunohistochemistry was used to measure the expression of NLRP6 and CD68. Mouse Raw264.7 cells were treated with palmitic acid (PA), lipopolysaccharide, and serum containing Xiayuxue decoction to observe inflammation. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the LFD group, the HFD group had significant increases in the serum levels of ALT, AST, TC, and TG (all P<0.05). Liver histopathological examination showed that the HFD group had marked hepatic steatosis and a signficant increase in NAS score (P<0.05), and quantitative real-time PCR showed significant increases in the inflammatory factors such as IL1β and IL-18 and a significant reduction in the expression of NLRP6 (all P<0.05). Immunohistochemistry showed that the expression of NLRP6 showed a similar trend as that of the macrophage marker CD68. Western blot showed that after the downregulation of NLRP6 expression, there was a significant increase in phosphorylated NF-κB p65 (P<0.05). Compared with the HFD group, Xiayuxue decoction effectively improved liver inflammation, upregulated the expression of NLRP6, and downregulated phosphorylated NF-κB p65 in HFD mice (all P<0.05). After Raw264.7 cells were treated with PA, NLRP6 was downregulated to promote the progression of inflammation (P<0.05), and treatment with Xiayuxue decoction could upregulate NLRP6 and inhibit inflammation NF-κB (P<0.05). ConclusionXiayuxue decoction can effectively improve hepatic steatosis and liver inflammation in a mouse model of NAFLD, possibly by regulating NLRP6/NF-κB to alleviate macrophage activation.