1.Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles
Liu DAYUE ; Yang ANNING ; Li YULIN ; Li ZHENXIAN ; You PEIDONG ; Zhang HONGWEN ; Quan SHANGKUN ; Sun YUE ; Zeng YALING ; Ma SHENGCHAO ; Xiong JIANTUAN ; Hao YINJU ; Li GUIZHONG ; Liu BIN ; Zhang HUIPING ; Jiang YIDENG
Journal of Pharmaceutical Analysis 2024;14(9):1301-1319
Rosuvastatin(RVS)is an excellent drug with anti-inflammatory and lipid-lowering properties in the aca-demic and medical fields.However,this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia(HHcy),including high oral dosage,poor targeting,and long-term toxic side effects.In this study,we applied nanotechnology to construct a biomimetic nano-delivery system,macrophage membrane(M?m)-coated RVS-loaded Prussian blue(PB)nanoparticles(MPR NPs),for improving the bioavailability and targeting capacity of RVS,specifically to the plaque lesions associated with HHcy-induced atherosclerosis.In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4(TLR4)/hypoxia-inducible factor-1α(HIF-1α)/nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathways,reducing pyroptosis and inflammatory response in macrophages.Additionally,MPR NPs reversed the abnormal distribution of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)/ATP binding cassette transporter G1(ABCA1)/ATP binding cassette transporter G1(ABCG1)caused by HIF-1α,promoting cholesterol efflux and reducing lipid deposition.In vivo studies using apolipoprotein E knockout(ApoE-/-)mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable bio-security,and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes.These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.
2.Changes in Whole-Brain Functional Connectivity Density in Primary Insomnia Based on Resting State Functional MRI
Xuehui REN ; Yulin LIU ; Jinli WANG ; Ruixue GAO ; Hongzhi YANG ; Bin ZHANG ; Xiaojun REN ; Ruwu YANG ; Zhengwei CHANG
Chinese Journal of Medical Imaging 2023;31(12):1244-1249
Purpose To investigate the difference of resting-state functional connectivity density(FCD)between chronic primary insomnia patients and healthy controls via resting state functional magnetic resonance imaging(rs-fMRI).Materials and Methods All rs-fMRI data of 35 patients with chronic primary insomnia from Xidian Group Hospital and Xi'an Encephalopathy Hospital of Traditional Chinese Medicine,and 35 healthy controls were prospectively collected from August 2020 to December 2021.The voxel-wise FCD approach was applied to explore the differences of whole-brain functional networks between chronic primary insomnia patients and healthy controls.The relationships between FCD value and Pittsburgh sleep quality index,self-rating scale of sleep,insomnia severity index,self-rating anxiety scale and self-rating depression scale in primary insomnia patients were investigated,respectively.Results Compared with healthy controls,the decreased FCD values were showed in the right insula,bilateral anterior cingulate gyrus,left orbitofrontal middle gyrus,left dorsolateral superior frontal gyrus,right medial superior frontal gyrus and bilateral thalamus(t<-5.271,Padjust<0.05),while the increased FCD values showed in the right superior temporal gyrus,bilateral middle temporal gyrus,bilateral precuneus and left posterior cingulate gyrus(t>4.379,Padjust<0.05)in the chronic primary insomnia patients group.The FCD values of bilateral thalamus(r=-0.620,P<0.001;r=-0.562,P<0.005)and right insula(r=-0.651,P<0.001)were negatively correlated with insomnia severity index in the chronic primary insomnia patients group,respectively.Conclusion The extensive functional connectivity abnormalities are observed in primary insomnia patients via FCD analysis.These findings explain the neural mechanisms of underlying emotional regulation and cognitive impairment in chronic insomnia from the perspective of functional integration and functional separation.
3.Clinical features and expression of PLA2R in renal tissue with idiopathic membranous nephropathy in children
Yanfei DONG ; Liwen SUN ; Bin ZHANG ; Xinyu KUANG ; Xiaoling NIU ; Yulin KANG ; Sheng HAO ; Ping WANG ; Zhi LI ; Guanghua ZHU ; Wenyan HUANG ; Ying WU
Chinese Journal of Pediatrics 2018;56(3):206-210
Objective To explore the clinical features and expression of PLA2R in renal tissue of children with idiopathic membranous nephropathy.Methods Retrospective study was performed in patients with membranous nephropathy diagnosed through renal biopsy and the follow-up time was at least half a year in Shanghai Children's Hospital from January 2010 to February 2017.We compared their clinicopathological and pathological findings of IMN.Indirect immunofluorescence assay was used to detect glomerular PLA2R expression.We analyzed the differences of clinical features between the PLA2R negative and positive groups.T test,rank-sum test and Fisher exact test were used.Results Eleven cases had hematuria and proteinuria,9 cases presented with nephrotic syndrome,and 2 cases showed isolated proteinuria.Of the 22 cases of children with IMN,16 patients had complete remission (complete remission rate was 72.8%),and 22 patients had partial remission.The renal functiou of all cases was normal and in all cases the estimated glomerular filtration rate was > 90 ml/(min· 1.73m2).Of 22 cases with IMN,7 cases were PLA2R-positive in renal tissue and 15 cases were PLA2R-negative.The age of positive group(10 years old) was older than the negative group (6 years old)(Z=-2.483,P<0.05) and the time of positive group (6 months) for urine protein to return to negative was longer than the negative group (2.5 months) through treatment.These differences were significantly different (Z=-2.072,P<0.05).Conclusions Hematuria and proteinuria can be found in most children with idiopathic primary membranous nephropathy.Prednisone combined with immunosuppressant was effective.The positive rate of PLA2R in renal tissue of children with IMN was about 32%.The age of PLA2.R positive group was older than the negative group.And the time of urine protein turning to negative in positive group was longer than that in the negative group.
4.Distribution and homology of foodborne-associated extended-spectrumβ-lactamases-producing Escherichia coli
Chinese Journal of Infection Control 2016;15(12):907-912
Objective To study the distribution and homology of foodborne-associated extended-spectrumβ-lacta-mases (ESBLs)-producing Escherichiacoli (E. coli).Methods ESBLs-producing E. coli were isolated from differ-ent food specimens in Shaoguan from 2014 to 2015,strains were typed with pulsed-field gel electrophoresis (PFGE) and BioNumerics software.Results 1 1 strains of diarrhea-causing E. coli and 29 strains of ESBLs-producing E. co-li were isolated from 347 different sources of food specimens. PFGE analysis showed that 29 strains could be divided into 21 cluster groups,group A was predominant pattern,which included 7 strains(J2,J3,J4,J7,J9,B4,S3), group B included 2 strains (J6,J8),the other strains were sporadic clones. Similarity coefficient (SC)of 3 strains (J2,J7,J9)from health practitioners was 100% ,SC of strains from drinking water and patients with diarrhea (B4) was 97. 1% ,SC of S3 strain and 4 strains (J2,J3,J7,J9 )from health practitioners were all>90. 0% . Conclusion Foodborne-associated ESBLs-producing E. coli are widely distributed in food,water,animal,and pop-ulations,and can be transmitted through food chain,surveillance should enhanced to avoid further spread.
5.Physicochemical properties of a polysaccharide RAP-B-1 from Rubus amabilis and its immunomodulating effects
Yulin DIAO ; Hao MA ; Jinwei REN ; Guiqiang ZHANG ; Shuai LI ; Junjie SHAN ; Bin LIU
Journal of International Pharmaceutical Research 2014;(4):461-467
Objective To investigate the physicochemica l properties and immunobiological activity of a polysaccharide (RAP-B-1) from stems of Rubus amabilis. Methods The crude polysaccharide (RAP) was obtained successively by boiling, ethanol precipitating and dialyzing. RAP was isolated with DEAE-cellulose and Sephadex G-100 to obtain a polysaccharide RAP-B-1. The physicochemical properties of RAP-B-1 were studied by hydrolysis, periodate oxidation, Smith degradation and methylation, CE, IR, NMR and GC-MS. The immunobiological activities were estimated by the proliferative activity of spleen lymphocytes and phagocytic activity of peritoneal macrophages in mice. Results The molecular weight of RAP-B-1 was 4.80×104 with specific optical rotation value [α] 20D+68.3 (c=1,H2O), and was composed of eight monosaccharides. The molar ratios were as Xyl: Ara: Glc: Rha:Gal: Man: GlcA: GalA = 1.0:6.9:0.8:1.1:6.9:0.3:0.5:3.3. RAP-B-1 was an arabinogalactan. The linkages of arabinose were →1) Ara (2,3→,→1) Ara(5→and→1) Ara, and the linkages of galactose were→1) Gal(4→,→1) Gal(6→and→1) Gal. RAP-B-1 could improve the proliferative activity of spleen T cells(P<0.05) and booste phagocytic activity of peritoneal macrophages at 50μg/ml concentration(P<0.01). Conclusion RAP-B-1 is an arabinogalactan and has immunobiological activity.
6.A novel rat model of cardiopulmonary bypass for deep hypothermic circulatory arrest without blood priming.
Weihua ZHANG ; Yanbo ZHANG ; Donghai LIU ; Yaobin ZHU ; Chenhui QIAO ; Jiaxiang WANG ; Yulin XU ; Yang LIU ; Bin LI ; Yao YANG
Chinese Medical Journal 2014;127(7):1317-1320
BACKGROUNDLarge animal cardiopulmonary bypass (CPB) models are expensive, and prevent assessment of neurocognitive function, and difficulties with long-term recovery. The purpose of this study was to establish a novel rat model of cardiopulmonary bypass for deep hypothermic circulatory arrest without blood priming.
METHODSTwenty adult male Sprague-Dawley rats weighing 450-560 g were randomized to CPB with deep hypothermic circulatory arrest (DHCA) and control groups, with 10 rats each. The experimental protocols, including blood and crystalloid fluid administration, anesthesia, orotracheal intubation, ventilation, cannulation, and heparinization were identical in both groups. After inducing cardiac arrest, the circuit was turned off and rats were left in a DHCA state for 15 minutes. Rats were rewarmed to 34°C to 35°C over a period of 36 to 42 minutes using CPB-assisted rewarming, a heating blanket, and a heating lamp along with administration of 0.1 mEq of sodium bicarbonate and 0.14 mEq of calcium chloride. The remaining priming volume was reinfused and animals were weaned from CPB.
RESULTSAll CPB with DHCA processes were successfully achieved. Blood gas analysis and hemodynamic parameters were in the normal range. The vital signs of all rats were stable.
CONCLUSIONSOur CPB circuit has several novel features, including a small priming volume, active cooling/rewarming processes, vacuum-assisted venous drainage, peripheral cannulation without thoracotomy or sternotomy, and an accurate means of monitoring peripheral tissue oxygenation.
Animals ; Cardiopulmonary Bypass ; methods ; Circulatory Arrest, Deep Hypothermia Induced ; methods ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar
7.An experimental research of magnetic resonance tumor targeting imaging with Gd labeled human telomerase reverse transcriptase antisense oligonucleotide (Gd-DOTA-hTERT ASON)
Gaohong ZHU ; Bingxiu REN ; Jiangliang WEI ; Yulin SU ; Rui HE ; Wei ZHANG ; Jing CAI ; Bin SONG
China Oncology 2013;(10):821-828
Background and purpose:Researches had indicated that about over 85%of malignant tumors highly express telomerase activity. So telomerase has become one of the important methods in the research field of tumor diagnosis and treatment. Nowadays, several reports about malignant tumor which over expresses hTERT targeting imaging with radionuclide labeled hTERT ASON had been published. In these reports, high quality of pictures can hardly be acquired because of poor anatomical and spacial resolution in nuclear imaging itself. Accordingly, in this study, we developed a method of detecting human telomerase in vivo with magnetic resonance imaging (MRI) and evaluate its feasibility. Methods:Firstly, Uniformly phosphorothioate-modified human telomerase reverse transcriptase antisense oligonucleotide (hTERT ASON) was labeled with Gd3+ through the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-N, N’, N’’, N’’’-tetraacetic acid (DOTA) and iv vitro experiments were performed to characterize the antisense probes (for biodistribution and cellular uptake, 99mTc-DOTA-ASON was used in stead of Gd-DOTA-ASON). Then Gd-DOTA-ASON was injected intraperitoneally in pulmonary adenocarcinoma A375 nude mice tumor-bearing BALB/c for in vivo imaging using 7.0 T Micro MRI periodically, tumors and their surrounding tissues were defined as region of interest (ROI) to calculate the signal to noise ratio (SNR) of tumor to muscle using Gd-DTPA as control. Finally, immunohistochemical analysis of telomerase activity of each xenograft was operated 2 days after imaging. Results:The binding efficiency of Gd-DOTA-ASON reached was as high as 65%(63.2±2.4, n=6). And it can maintain 61%in fresh human serum and normal saline at 37℃over 24 h;A375 cells showed an uptake of 8.5%when incubated with 99mTc-DOTA-ASON;In comparing with DOTA-ASON and Gd-DTPA, cells transected with Gd-DOTA-ASON had higher SI when performed MRI with T1WI. The hTERT-expressing xenografts were obviously enhanced by Gd-DOTA-ASON at 0.5-6 h after injection and the SNR can reach 2.37, whereas obvious enhancement only could be found within 2 h after injection of Gd-DTPA. Both labeled and non-labeled antisense probes can suppress the activity of telomerase of A375 cells either in vitro or in vitro. Conclusion:Our research offers proof that Gd-DOTA-ASON can be used as tumor specific targeting MR probe for diagnosing malignant tumors with high expression of telomerase.
8. HPLC-DAD fingerprint of Shengxinfa Capsules
Chinese Traditional and Herbal Drugs 2013;44(14):1935-1938
Objective: To establish the fingerprint of Shengxinfa Capsules (consisted of Psoraleae Fructus, Polygonui Multiflori Radix, Ligustri Lucidi Fructus, Angelicae Sinensis Radix, Gastrodiae Rhizoma, Polygonati Rhizoma, etc.) for the quality evaluation. Methods: The fingerprint was established by HPLC with Photodiode Array Detector (PADA). The acetonitrile-0.1% phosphoric acid (gradient elution) was employed as the mobile phase, column temperature was at 35°C, flow rate was 1.0 mL/min, and detection wavelength was at 246 nm. Results: There were 13 common peaks appeared in the PADA fingerprint, which were defined by software published by the Chinese Pharmacopeia Committee. The similarity of 11 batches was more than 0.99. Conclusion: The method is simple, accurate, and sensitive. It is suitable to be used for the quality evaluation of Shengxinfa Capsules.
9.Endoscopic mucosal resection for lesions at gastroesophageal junction
Xiaoping ZOU ; Bin ZHANG ; Wen LI ; Yonghua SHEN ; Yulin WU ; Ying Lü
Chinese Journal of Digestive Endoscopy 2010;27(3):127-130
Objective To evaluate the long-term efficacy and safety of endoscopic mucosal resection (EMR) for lesions at gastroesophageal junction (GEJ). Methods A total of 51 lesions located at GEJ from 51 patients, with an average size of 10. 9±4. 0 mm (3-28 mm), were treated with EMR between November 2005 and March 2009, among which 39 were diagnosed as low grade dysplasia and 12 as high grade dysplasia pathologically after EMR. The histopathologic results were compared between biopsies and EMR samples. All patients were followed up endoscopically. Results Complete resection was achieved in 44 ( 86. 3% ). The histopathologic diagnosis of 25 cases (49. 9% ) was inconsistent between biopsy and EMR samples, with 24 exhibited higher grade dysplasia after EMR. Main complication during EMR was bleeding in 17 patients ( 33. 3% ), all of which were successfully managed. No perforation or postoperative stenesis occurred. Endoscopic follow-up was carried out in 8 patients for more than 3 years, in 17 for 2-3 years, in 12 for 1-2 years and in 14 for less than 1 year. No death occurred during follow-up. Conclusion EMR can be adquately adopted as an effective treatment for pre-cuncerous lesions at GEJ, which is important in blocking malignant progression of dysplastic lesions.
10.Treatment of complex fractures around the knee.
Kai-jing LI ; Yong-bin LI ; Zhong HE
China Journal of Orthopaedics and Traumatology 2009;22(3):187-188
Adult
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Aged
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Female
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Fracture Fixation, Internal
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Fractures, Bone
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surgery
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Humans
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Knee Injuries
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surgery
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Male
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Middle Aged
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Postoperative Care

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