1.Risk factors of metabolic bone disease associated fracture in very low birth weight infants
Shuting CHANG ; Chenchao FU ; Zhenyu LIAO ; Weiqing HUANG ; Xinhui LIU
Chinese Journal of Neonatology 2022;37(4):305-309
Objective:To study the risk factors of metabolic bone disease (MBD) associated fracture in very low birth weight premature infants.Methods:From January 2012 to December 2019, premature infants (gestational age <32 weeks, birth weight <1 500 g) were admitted to our hospital and followed-up regularly for 1.5 years (once every month within first 6 months, then once every 3 months). The infants were assigned into two groups according to X-ray diagnosis: the fracture group and the non-fracture group. The clinical data of the two groups were compared and the risk factors of fracture were analyzed.Results:A total of 62 preterm infants with MBD were included in this study, including 11 in the fracture group and 51 in the non-fracture group. The risk factors of MBD associated fracture included intrauterine growth restriction (IUGR), birth weight <1 000 g, gestational age, respiratory support duration and total parenteral nutrition (TPN) duration ( P<0.05). Logistic regression analysis showed that IUGR ( P<0.05, OR=2.159, 95% CI 1.536~2.759) and TPN duration ( P<0.05, OR=1.143, 95% CI 1.042~1.270) were independent risk factors for fracture. Serum alkaline phosphatase (ALP) in the fracture group was significantly higher than the non-fracture group and 25(OH)VitD was significantly lower than the non-fracture group ( P<0.05). Conclusions:IUGR and TPN duration are risk factors for MBD associated fracture in preterm infants. As biochemical markers of bone metabolism, ALP and 25(OH)VitD levels have clinical value predicting MBD associated fracture.
2.Preparation and MRI of CB86-DTPA-Gd targeting TSPO in rheumatoid arthritis model
Zhenyu HOU ; Tingting WANG ; Xinhui SU ; Zhide GUO ; Qiang WANG ; Huanhua WU ; Chao MA ; Fu SU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(1):41-46
Objective:To synthesize Gd labeled probe targeting transporter protein(TSPO) 2-(8-amino-2-(4-chlorophenyl)imidazo[1, 2-a]pyridine-3-yl)- N, N-dipropylacetamide (CB86)-diethylene triamine pentaacetic acid (DTPA), and investigate its MRI effect in rheumatoid arthritis (RA) model. Methods:CB86-DTPA was prepared by coupling a bifunctional chelating agent, and then chelated with Gd to obtain MRI targeted contrast agent CB86-DTPA-Gd. The cytotoxicity, MR relaxation rate and in vitro stability of CB86-DTPA-Gd were determined. RA model was established with Freund′s adjuvant and the biodistribution study and MRI was performed. The RA lesion and its surrounding normal tissue were used as regions of interest (ROI) to calculate the signal to noise ratio (SNR). Independent-sample t test was used to analyze the data. Results:CB86-DTPA-Gd had excellent biosafety and a good MR relaxation rate ( r1=11.05 mmol·L -1·s -1). The survival rate of RAW264.7 cells and 4T1 cells was still more than 90% at the maximum concentration (20 μmol/L) of Gd 3+. CB86-DTPA-Gd also exhibited good stability in human serum and phosphate buffer saline solution (PBS; pH=7.4). The in vivo biodistribution showed that CB86-DTPA-Gd had better inflammatory targeting efficiency, and the uptake of Gd in the inflamed site of the ankle joint was still (2.33±0.29) percent dose rate per gram of tissue (%ID/g) at 120 min after injection. MicroMRI showed that the inflammation of the right ankle joint displayed significant enhancement after the injection of CB86-DTPA-Gd and Gd-DTPA. The SNR of CB86-DTPA-Gd group was up to 23.21±1.44, and the maximum intensification time was 90 min after injection, and can be significantly inhibited by CB86-DTPA at all time points ( t values: 6.083-12.451, all P<0.05), while the Gd-DTPA group had a strengthening time of 30 min after injection with the SNR of 16.12±1.24. Conclusion:CB86-DTPA-Gd shows good macrophage targeting and good uptake in arthritic reaction sites, and is expected to be a novel MRI molecular probe for peripheral inflammation imaging.
3.Analysis of neoplasm invasion type in ovary of the orthotopic epithelial ovarian carcinoma model in nude mice and human epithelial ovarian cancer
Genhai ZHU ; Kang WANG ; Xinhui FU ; Fujin LIU ; Chunying CHEN ; Haiyan HUANG ; Lan HONG ; Shengtan WANG ; Lang ZHENG
Journal of Chinese Physician 2020;22(5):699-703,708
Objective:The aim of this study was to study the characteristics of neoplasm invasion type in ovary of two orthotopic models established with human epithelial ovarian cancer solid tumor tissue slices and human ovarian carcinoma cell line OVCAR-3 in nude mice and human epithelial ovarian cancer.Methods:Tumor tissues and cell line OVCAR-3 of human epithelial ovarian cancer were grown in subcutaneous tissue and the subcutaneous tumor source was fetched and inoculated in ovarian capsule of nude mice to establish the orthotopic implantation model. The neoplasm invasion type in the two kinds of models were observed. The neoplasm invasion types were also analyzed by pathological examination in 54 cases of International Federation of Gynecology and Obstetrics (FIGO) stageⅠ-Ⅱepithelial ovarian cancer.Results:Three neoplasm invasion types were found as follows: type of pseudocapsule, type of pseudocapsule invasion, type of pseudocapsule penetration. Pseudocapsule rate in the solid tumor slices group (18.2%) were lower than those in the cell line group (42.3%) ( P<0.05), while the pseudocapsule penetration rate in the solid tumor slices (50.0%) were higher than those in the cell line group (23.1%) ( P<0.05). No difference was found of pseudocapsule invasion rate between two groups ( P>0.05). Neoplasm invasion type in ovary changed with tumor planting time. High proportion of pseudocapsule type was found at the beginning of tumor planting, and the pseudocapsule penetration rate raised with tumor planting time increased. High proportion of pseudocapsule type was also found in patients with FIGO stageⅠepithelial ovarian cancer, and pseudocapsule penetration rate increased in those with FIGO stageⅡ. No difference in neoplasm invasion type was found between two kinds of pathological types ( P>0.05). Conclusions:There are differences between the two kinds of orthotopic models established with human epithelial ovarian cancer solid tumor tissue slices and human ovarian carcinoma cell line OVCAR-3. Compared to the solid tumor slices model, the cell line model is more stable for the follow-up study. The proportion of three neoplasm invasion types in ovary were more balanced in 8 weeks after tumor planting, and 8 weeks after tumor planting is the best start time for the follow-up experiment.
4.Preparation and imaging of 18 F-VUIIS1008 targeting TSPO in rheumatoid arthritis model
Liangliang WANG ; Zhenyu HOU ; Xinhui SU ; Huanhua WU ; Qiang WANG ; Wentao DONG ; Li-Chun CHEN ; Zhide GUO ; Chao MA ; Fu SU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2019;39(7):408-413
Objective To synthesize a novel 18 F labeled probe targeting translocator protein ( TSPO) ligand 2-( 5, 7-diethyl-2-( 4-( 2-fluoroethoxy ) phenyl ) pyrazolo [ 1, 5-a ] pyrimidin-3-yl )-N, N-diethylacet-amide (VUIIS1008), and evaluate its biodistribution and imaging in rheumatoid arthritis (RA) model. Methods The tosylate substrate was labeled with 18 F using a tosyloxy for fluorine nucleophilic aliphatic substitution to obtain 18 F-VUIIS1008. The labeling efficiency, radiochemical purity, and stability in vitro were determined. In vitro cellular uptake and competitive binding assay were performed on RAW264.7 mac-rophage cells. Biodistribution and microPET/CT imaging were investigated on RA mice established by Com-plete Freund's Adjuvant. Two-sample t test was used to analyze the data. Results 18 F-VUIIS1008 was syn-thesized with the labeling yield up to (41.00±5.00)%, the radiochemical purity>98.00%, and the specific radioactivity >1. 52 × 108 MBq/mmol. 18 F-VUIIS1008 was highly stable with the radiochemical purity >98. 00% at 4 h after incubation in mouse serum. In vitro, it also exhibited high specific TSPO binding in RAW264.7 macrophage cells. The uptake ratio was (14.00±0.30)% at 1 h after incubation, and decreased significantly ((4.00±0.70)%;t=12.894, P<0.05) after adding excessive unlabeled VUIIS1008. The half maximal inhibitory concentration (IC50) of 18F-VUIIS1008 binding to TSPO was 0.05 nmol/L in RAW264.7 macrophage cells. In vivo distribution results showed that the uptake of 18 F-VUIIS1008 in the left arthritic ankles reached the peak value of (1.33±0.02) percentage activity of injection dose per gram of tissue (%ID/g) at 1 h after injection. The radioactivity ratio of left ankle arthritic tissue to blood ( A/B) and to normal muscle ( A/M) was 4.40±0.22 and 1.65±0.07 respectively. MicroPET/CT imaging demonstrated that 18F-VUIIS1008 could specifically target and retained in the inflammation site. Conclusion 18 F-VUIIS1008 can be easily synthe-sized with high radiochemical purity and can clearly visualized in RA imaging with low background, suggesting its potential as a novel promising molecular probe targeting TSPO for RA PET imaging.
5.Efficacy and safety of 13-cis retinoid acid and all trans retinoid acid in the redifferentiation therapy of poorly differentiated thyroid cancer
Qun FAN ; Anren KUANG ; Gengbiao YUAN ; Xinhui SU ; Fu SU ; Weixing WANG
Chinese Journal of Endocrinology and Metabolism 2017;33(4):285-290
Objective To evaluate the efficacy and safety of 13-cis retinoid acid (13-CRA) and all trans retinoid acid (ATAR) redifferentiation therapy in patients with poorly differentiated thyroid cancer. Methods A single-center, randomized, double-blind, parallel controlled clinical trial was preformed. All patients were randomized into three groups. 78 cases were enrolled in each group. The patients were treated by 13-CRA in A group, by ATRA in B group, and by placebo in control group. The induced effects of retinoid acid (RA) and 131I treatment efficacies were defined as primary outcome of efficacy. Results After RA induction therapy, the effective rates in A, B, and control groups were 59.72%, 52.86% and 7.69%, respectively, with statistically significant difference among 3 groups (P<0.05). Compared with control group, A and B groups revealed significant induced efficacies (P<0.017), but there was no significant difference between A group and B group. After 131I treatment, the effective rates in A, B, and control group were 70.83%, 64.29%, and 28.21% respectively, with statistically significant difference (P<0.05). Compared with control group, the effective rates of 131I treatment in A and B groups were significantly raised (P<0.017), but there was no significant difference between A group and B group. The damage of skins and mucous membranes such as desquamation, dry skin, dry lips, dry eyes, etc occurred mostly in A group. The symptoms of nervous system such as headache, dizziness, etc occurred mostly in B group. Conclusions The induced differentiation of 13-CRA or ATRA is an effective method for the treatment of poorly differentiated thyroid carcinoma.
6.Experimental study on abnormal expression of TPH2,DDC and MAO-A involved in depression-like behaviors of rats induced by CUS
Ting CUI ; Wei XIE ; Xiaoyan FU ; Haiyan LI ; Xinhui JIANG ; Hongmei QIU
Chinese Pharmacological Bulletin 2016;32(12):1677-1682,1683
Aim To investigate the role of tryptophan hydroxylase-2 (TPH2),dopa-decarboxylase (DDC)and monoamine oxidase-A(MAO-A)in depression-like be-haviors induced by chronic unpredictable stress (CUS).Methods 30 male SD rats were randomly di-vided into model group(MG)and control group(CG). Rat depression model was developed by CUS for 28 consecutive days in a solitary condition.The depres-sion-like behaviors of rats were evaluated by open-field test(OFT)and forced-swimming test(FST).The real time PCR and Western blot test were used to determine the mRNA and protein expression of TPH2,DDC and MAO-A in rat telencephalon and hippocampus.Re-sults The movement scores of rats were obviously de-creased in OFT(P<0.01 ).The immobility time was obviously increased in FST (P <0.01 ).The mRNA and protein expressions of TPH2 and DDC were de-creased significantly (P <0.01,P <0.05 )and the MAO-A mRNA and protein expressions were increased significantly(P <0.01,P <0.05 )in telencephalon and hippocampus of MG rats, when compared with those in CG rats.Conclusion The TPH2,DDC and MAO-A in rat telencephalon and hippocampus were closely related with the depression-like behaviors of rats induced by CUS.
7.Influence of Poly (ADP-ribose) Polymerase Inhibitor PJ34 on Blood Brain Barrier in Rats with Cerebral Ischemia-reperfusion Injury
Yan LI ; Penglian WU ; Lianghe DU ; Xinhui FU ; Dongyu WANG
Journal of China Medical University 2015;44(8):709-713
Objective To investigate the influence of poly(ADP-ribose)polymerase inhibitor PJ34 on blood brain barrier(BBB)in rats with cere-bral ischemia-reperfusion injury. Methods Rat model of cerebral ischemia-reperfusion injury was established by the middle cerebral artery occlu-sion. A total of 135 SD rats were randomly divided into 3 groups:sham-operated group(sham group),ischemia-reperfusion group(IR group)and PJ34 group(PJ34 group). 45 animals in each group were then equally divided into subgroups and the rats were sacrificed at 6 h,24 h,48 h after re-perfusion,respectively. BBB permeability was evaluated by detection of extravasated Evans blue(EB). The expression of tumor necrosis factorα(TNF-α)and matrix metalloproteinase 9(MMP-9)activity were measured by immunohistochemistry and western blot at different time points. Re?sults Compared with sham group,the contents of EB and the expressions of TNF-αand MMP-9 in IR group were increased significantly(P<0.05). Compared with IR group,the contents of EB and the expressions of TNF-αand MMP-9 in PJ34 group were markedly decreased at the same time point(P<0.05). Conclusion The present study provided in vivo evidence that PARP inhibitor PJ34 can protect against cerebral ischemia re-perfusion injury,and the mechanism might be related to maintaining the stability of blood-brain barrier by suppressing the expression of TNF-αand MMP-9 in ischemic cortex.
8.The research progress of treating senile constipation from blood stasis
Xinhui ZHAN ; Wei WANG ; Si FU
International Journal of Traditional Chinese Medicine 2015;(2):190-192
Senior citizens have many diseases related to blood stasis, which was often overlooked by clinicians, and thus affected the treatment of the disease. Through analyzing and summarizing of related literature in recent five years of senile constipation treated from blood stasis, we found that the blood stasis is closely linked to senile constipation. Blood stasis in the gut forms constipation, and constipation with the passing of time forms blood stasis in returen. Blood stasis and constipation often influence each other.
9.Influence of PJ34 on the Expression of MMP-9 and Claudin-5 in Rat with Focal Cerebral Ischemia Reperfusion Injury
Penglian WU ; Yan LI ; Xinhui FU ; Lianghe DU ; Dongyu WANG
Journal of China Medical University 2015;44(8):694-698,703
Objective To investigate the effects of PJ34,a poly ADP-ribose polymerase(PARP)inhibitor,on the expression of matrix metallopro-teinases-9( MMP-9 )and Claudin-5 in ischemic cortex of rats with focal cerebral ischemia-reperfusion(I/R)injury. Methods The focal cerebral ischemia-reperfusion model of middle cerebral artery occlusion(MCAO)was established by intraluminal suture . PJ34 was injected intraperitoneal-ly. Blood-brain barrier(BBB)permeability was quantitatively determined by Evans blue assay. Infarct volume changes were observed by 2,3,5-tri-phenyltetrazolium chloridedyeing(TTC)staining. The expression of the MMP-9 and Claudin-5 in rats of cerebral cortex were measured by immuno-histochemistry assay and western blot analysis . Results Compared with sham group,the expression of MMP-9,the contents of EB and infarct vol-ume increased progressively over time after I/R,and reached maximum levels at 48 h(P<0.05);The expression of Claudin-5,the contents of EB and infarct volume reduced significantly over time after I/R,and reached the minimum levels at 48 h in model group(P<0.05). Compared with model group,the expression of MMP-9,the contents of EB and infarct volume was reduced significantly and the expression of Claudin-5,the con-tents of EB and infarct volume was increased at the same time point in PJ34 group(P<0.05). Conclusion PJ34 maintained the blood-brain barri-er permeability by inhibiting the expression of MMP-9,and increasing the expression of Claudin-5,which had neuroprotection on cerebral ischemia-reperfusion injury.
10.Measurement of Particle Volatility Using Single Particle Aerosol Mass Spectrometry Tandem Thermodiluter
Shouhui DAI ; Xinhui BI ; Huan HUANG ; Guohua ZHANG ; Junjie HE ; Gengchen WU ; Guoying SHENG ; Jiamo FU ; Zhen ZHOU
Chinese Journal of Analytical Chemistry 2014;(8):1156-1161
Volatility can influence the lifetime of particles in the atmosphere, and provide useful information on the formation of secondary aerosol. The previous studies generally utilized thermodenuder ( TD ) to investigate the volatility behavior of particles. Using TD, semivolatile species are vaporized at different temperature, and the vaporized gas is adsorpted by activated charcoal. However, carbon might be emitted from activated charcoal under high temperature or activated charcoal ageing. In this study, a new method was developed for the measurement of particle volatility by coupling a thermodiluter system to an online single particle aerosol mass spectrometer ( SPAMS) . Aerosol particles were passed into two different channels, and then analyzed by SPAMS. Through Channel 1, aerosol particles were heated to different temperature by heating tube, then non-volatile particles and volatile gas entered into the diluter. After diluting and cooling by diluent air, the non-volatile particles were analyzed by SPAMS. Through Channel 2, aerosol particles were analyzed directly by SPAMS without the heating process. Particle volatility was obtained by comparing the information ( particle size, particle number and mass spectrum ) of particles through Channels 1 and 2. Laboratory tests showed that the diluter could avoid the re-condensation of volatiles to the particles. This developed method was applied in the real time measurement of individual particle volatility in the spring of Guangzhou. The results showed that these particles were primarily comprised of highly volatile and moderate volatile species.

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