1.The study of effects of repetitive transcranial magnetic stimulation in the treatment of schizophrenia and its social function
Wei FU ; Daqi LI ; Qingjun LI ; Junshan CHEN ; Hualong SU
Chongqing Medicine 2014;(4):399-400
ObjectiveAssess the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of schizophrenia and its social function .Methods 156 patients with schizophrenia were randomly assigned to a real rTMS treatment group (n=78) or a sham rTMS treatment group(n=78) ,each patient in the real rTMS group received 20 rTMS sessions over 4 weeks .Efficacy was evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at 4 weeks .Social function was evaluated u-sing the Personal and Social Performance Scale(PSP) at baseline and at 4 weeks .Results The study group is better than the control group in PANSS total and negative symptoms and PSP total after treatment (P<0 .05) .There is not serious adverse reactions in the treatment .Conclusion rTMS can reduce the negative symptoms and improve social function in schizophrenia with high safety .
2.Relationship of bone mineral density and bone metabolism indicators with osteoporosis in elderly patients with post-stroke hemiplegia
Wanying FU ; Yongwen ZHAI ; Guowei TAN ; Hualong YANG ; Hong GU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2023;25(12):1306-1309
Objective To explore the relationship of changes in bone mineral density and bone me-tabolism indicators with osteoporosis in elderly patients with hemiplegia after cerebral infarction.Methods A total of 197 elderly patients suffering post-stroke hemiplegia admitted to our hospital were enrolled between February 2018 and February 2021.Their bone mineral density and bone metabolism indicators were analyzed based on gender,disease course and hemiplegia severity.According to disease severity,they were divided into mild group(112 cases),moderate group(62 cases)and severe group(32 cases).Results Among the 197 elderly patients,83(42.13%)had osteoporosis.The males had significantly higher bone mineral density of proximal femur and levels of bone alkaline phosphatase(BALP)and osteocalcin,and lower levels of serum type Ⅰ collagen(CICP)and C-terminal telopeptides of type Ⅰ collagen(CTXI)than the females(P<0.01,P<0.05).Compared with the patients with hemiplegia course for 3-6 months,bone mineral density values of greater trochanter and total hip,and levels of BALP and osteocalcin were obviously de-creased,while levels of CICP and CTXI were notably increased in those with the course of 7-12 months and 13-24 months(P<0.05).Compared with the mild group,bone mineral density val-ues of greater trochanter and total hip,and levels of BALP and osteocalcin were significantly de-creased,while levels of CICP and CTXI were significantly increased in moderate group and severe group(P<0.05).Compared with the moderate group,bone mineral density values of greater tro-chanter,intertrochanteric site and total hip were significantly decreased in the severe group(P<0.05).The bone mineral density of above parts was negatively correlated with CICP levels(r=-0.458,r=-0.403,r=-0.355,r=-0.482,P<0.01)and CTXI levels(r=-0.305,r=-0.291,r=-0.273,r=-0.384,P<0.05,P<0.01),while positively correlated with BGP level(r=0.476,r=0.428,r=0.386,r=0.518,P<0.01).Conclusion The incidence of osteoporosis is quite higher in the elderly patients with post-stroke hemiplegia.There exist bone mineral density decline and abnormal bone metabolism,and their changes are related to gender,course and severi-ty of hemiplegia.
3.Simultaneous detection of tumor markers in human serum using time-resolved fluorescence microspheres immunochromatographic assay
Mingming GUO ; Hualong XIAO ; Jianbo ZHOU ; Lixin FU ; Bin ZHOU ; Jue ZHANG ; Biao HUANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(4):266-270
Objective To develop a time-resolved fluorescent microspheres immunochromatographic assay (TRFMIA) for detection of alphafetoprotein (AFP) and carcinoembryonic antigen (CEA) in human serum and to evaluate its performance.Methods The Eu-time-resolved fluorescent polystyrene particles conjugated with monoclonal antibody AC18# for AFP and AE03# for CEA were used as fluorescent labels.The monoclonal antibody AC17# for AFP,AE05# for CEA and goat anti-rabbit antibody were immobilized on the nitrocellulose membrane as the test lines and control line.Several performances indicators were measured,including linear range,detection limit,and specificity.AFP and CEA were measured by the new method and the results were compared with those obtained by time-resolved fluoroimmunoassay (TRFIA) and electro-chemiluminescence immunoassay (ECLIA) using linear correlation analysis.Results The measurement ranges of AFP were 0.07-1 000.00 kU/L with the intra-and inter-assay CV of 5.93% and 11.07%,and those of CEA were 0.12-500.O0 μg/L with the intra-and inter-assay CV of 7.53% and 12.13% respectively.The average recovery rate of AFP and CEA was 92.77% and 94.73%,respectively.Measurements obtained by TRFMIA had strong correlation coefficients ranging from 0.93 to 0.97 when compared with those obtained by TRFIA and ECLIA.Conclusion TRFMIA,which can simultaneously detect AFP and CEA,has been successfully established.
4.Discovery and development of brain-penetrant 18F-labeled radioligands for neuroimaging of the sigma-2 receptors.
Ying ZHANG ; Tao WANG ; Xiaojun ZHANG ; Winnie DEUTHER-CONRAD ; Hualong FU ; Mengchao CUI ; Jinming ZHANG ; Peter BRUST ; Yiyun HUANG ; Hongmei JIA
Acta Pharmaceutica Sinica B 2022;12(3):1406-1415
We have discovered and synthesized a series of indole-based derivatives as novel sigma-2 (σ 2) receptor ligands. Two ligands with high σ 2 receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities, and evaluated in rodents. In biodistribution studies in male ICR mice, radioligand [18F]9, or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[18F]fluoroethoxy)-1H-indole, was found to display high brain uptake and high brain-to-blood ratio. Pretreatment of animals with the selective σ 2 receptor ligand CM398 led to significant reductions in both brain uptake (29%-54%) and brain-to-blood ratio (60%-88%) of the radioligand in a dose-dependent manner, indicating high and saturable specific binding of [18F]9 to σ 2 receptors in the brain. Further, ex vivo autoradiography in male ICR mice demonstrated regionally heterogeneous specific binding of [18F]9 in the brain that is consistent with the distribution pattern of σ 2 receptors. Dynamic positron emission tomography imaging confirmed regionally distinct distribution and high levels of specific binding for [18F]9 in the rat brain, along with appropriate tissue kinetics. Taken together, results from our current study indicated the novel radioligand [18F]9 as the first highly specific and promising imaging agent for σ 2 receptors in the brain.
5.Detection and analysis of antibodies against SARS-CoV-2 in blood donors at different periods in Guangzhou
Zhengang SHAN ; Hualong YANG ; Ledong YANG ; Jieting HUANG ; Min WANG ; Ru XU ; Qiao LIAO ; Huishan ZHONG ; Bochao LIU ; Yongshui FU ; Xia RONG
Chinese Journal of Blood Transfusion 2023;36(12):1094-1097
【Objective】 To detect the anti-SARS-CoV-2 antibody levels in blood donors in Guangzhou, so as to provide laboratory data support for the collection and clinical use of convalescent plasma. 【Methods】 Anti-SARS-CoV-2 antibodies were measured by ELISA in qualified donors. Among them, 326 donors who gave blood in February 2023 were tested for IgG antibodies, 444 donors were tested for neutralizing antibodies. In July 2023, 398 donors were tested for IgG and IgM. 【Results】 399 of 724 blood samples diluted with normal saline (1∶160) were IgG reactive, with a reactive rate of 55.11%. Chi-square test showed that there was a significant difference in the reactive rate of IgG among samples collected at different times (25.46% in February vs 79.40% in July, χ2=210.74, P<0.01, 95%CI: 7.97, 15.98), but there was no significant difference in the reactive rate between different genders and different age groups. IgM was detected in 5 of 398 blood samples, with a reactive rate of 1.26%. The IgG test results of these five blood donors were all reactive, whereas the nucleic acid test results were negative. Neutralizing antibody was detected in 440 of 444 blood samples, with a reactive rate of 99.10%, and 71.59% of the reactive donors had a neutralizing antibody level of 10 μg/mL or more. 【Conclusion】 Blood donors in Guangzhou have a high level of SARS-CoV-2 antibody, which is sufficient to provide convalescent plasma for clinical treatment.
6.18FMAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models.
Tuo SHAO ; Zhen CHEN ; Jian RONG ; Vasily BELOV ; Jiahui CHEN ; Andre JEYARAJAN ; Xiaoyun DENG ; Hualong FU ; Qingzhen YU ; Steve H RWEMA ; Wenyu LIN ; Mikhail PAPISOV ; Lee JOSEPHSON ; Raymond T CHUNG ; Steven H LIANG
Acta Pharmaceutica Sinica B 2022;12(1):308-315
Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an 18F-labeled MAGL inhibitor ([18F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [18F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl4) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [18F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [18F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [18F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [18F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.
7.Maternal liver damage induced by cadmium exposure in pregnant mice through hypoxia inducible factor-1α-mediated upregulation in DRP1
Limin DAI ; Hualong ZHU ; Yongwei XIONG ; Weibo LIU ; Guoxiang ZHOU ; Shuang ZHANG ; Zhengjia LING ; Lulu TAN ; Jin ZHANG ; Yufeng ZHANG ; Yiting FU ; Daixin LI ; Hua WANG
Journal of Environmental and Occupational Medicine 2023;40(1):68-75
Background Mitochondrial dynamin-related protein 1 (DRP1) regulates mitochondrial division and plays an important role in maintaining hepatocyte function. However, the role of DRP1 in cadmium exposure-induced maternal liver damage in pregnant mice remains unclear. Objective To investigate the role and mechanism of DRP1 in maternal liver damage induced by cadmium exposure during pregnancy. Methods This study consisted of animal experiments and cell experiments. (1) Animal experiments. Mice at 14 days of gestation were randomly divided into three groups: a control group, a low-dose cadmium group (LCd group: 2.5 mg·kg−1), and a high-dose cadmium group (HCd group: 5 mg·kg−1). The pregnant mice were intraperitoneally injected with cadmium chloride (CdCl2) for 6 and 24 h in the next morning. The weights of pregnant mice, uterus, maternal liver, and fetal mice were recorded after sacrifice. Serum and liver of pregnant mice were collected, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver tissues were stained with HE to observe changes in liver function and liver tissue structure. The expressions of oxidative phosphorylation-related proteins, hypoxia inducible factor-1α (HIF-1α) and DRP1 proteins in liver of pregnant mice were detected by Western blotting. (2) Cell experiments. AML12 cells were treated with CdCl2 (10 μmol·L−1) for 0, 2, 6, 12, and 24 h. The expressions of oxidative phosphorylation-related proteins, DRP1, and hypoxia inducible factor-1α (HIF-1α) proteins were detected. AML12 cells were pretreated with DRP1 inhibitor Mdivi-1 for 1 h and then CdCl2 (10 μmol·L−1) for 12 h to detect the expression of oxidative phosphorylation-related proteins and DRP1 protein. AML12 cells were treated with Hif-1α siRNA for 48 h and CdCl2 (10 μmol·L−1) for 6 h to detect the expression of HIF-1α and DRP1 proteins. Results The results of animal experiments showed that cadmium exposure in pregnant mice had no effects on maternal liver weight and liver coefficient. However, the histomorphological changes and necrosis in hepatocytes were observed. Compared with the control group, the serum ALT and AST levels of pregnant mice in the LCd group were significantly increased after 6 h (P<0.05), and the levels in the HCd group were significantly increased after 6 and 24 h (P<0.05). Cadmium exposure during pregnancy significantly up-regulated HIF-1α and DRP1 expressions and down-regulated the expressions of oxidative phosphorylation-related proteins in maternal livers. In vitro cell experiments showed that the expressions of oxidative phosphorylation-related proteins was significantly decreased and HIF-1α and DRP1 protein expressions were significantly increased in the AML12 cells treated with CdCl2 for 6 h. Mdivi-1 pretreatment significantly antagonized the inhibitory effect of cadmium on the expressions of oxidative phosphorylation-related proteins in AML12 cells, while Hif-1α siRNA pretreatment significantly antagonized the up-regulative effect of cadmium on DRP1 expression in AML12 cells. Conclusion Cadmium exposure in pregnant mice may up-regulate DRP1 expression by activating HIF-1α signaling, then inhibit oxidative phosphorylation level of hepatic cells, and ultimately lead to maternal liver damage.