1.Preparation and Evaluation of a Hepatocyte Targeting pH-Sensitive Liposome
Siyuan WEN ; Xiaohong WANG ; Li LIN ; Wei GUAN ; Shengqi WANG
Progress in Biochemistry and Biophysics 2001;28(1):113-117
In order to obtain liposomes with properties of heptocyte-specificity and pH-sensitivity,four galactosylated derivatives were synthesized. A series of liposomes were prepared by mixing the galactosylated derivatives with DC-chol/DOPE respectively. The liposome 18-gal was proven to have favorable gene transfer efficiency to human hepatoma HepG2 cells, which was significantly inhibited in the presence of galactose solution, indicating that the liposomal transfection activity was mediated by asialoglycoprotein receptors. The liposome showed prominent pH-sensitivity and low cytotoxicity. Its optimum gene transfer conditions were also determined. The results showed that the liposome may be developed as a potential hepatocyte targeting pH sensitive delivery system for nucleic acid drugs.
2.Value of 18F-FDG PET/CT in evaluation of curative effect and progression-free survival on lymphoma
Siyuan LI ; Wengui XU ; Guansheng TONG ; Li ZHANG ; Zhe WEN
Journal of International Oncology 2017;44(5):361-365
Objective To evaluate the value of 18F-fluorodeoxyglucose (FDG) PET/CT in evaluation of curative effect and progression-free survival (PFS) for lymphoma patients.Methods The data of 85 lymphoma patients were retrospectively analyzed.Before and after 4-8 cycles standardized chemotherapy,the patients were evaluated with 18F-FDG PET/CT.The two-year PFS rate was compared.The value of 18F-FDG PET/CT in evaluation of curative effect and PFS for lymphoma patients received chemoradiotherapy was analyzed.Results The non Hodgkin lymphoma (NHL) was the common type,and the common pathogenic sites were head and neck lymph nodes,mediastinum and retroperitoneum.The majority of patients were accompanied with spleen enlargement and local lesions with high metabolism.The complete remission (CR) rate of Hodgkin lymphoma (HL)patients in PET/CT negative group was significantly higher than that in positive group (86.4% vs.42.9%,P =0.038).The two-year PFS rates in PET/CT positive group and negative group were 42.9% and 81.8%,and the difference was statistically significant (x2 =7.70,P =0.006).Thirty-five NHL patients achieved CR,13 achieved partial remission (PR),and 8 achieved stable disease (SD) or disease progression (PD).The two-year PFS rates in the CR group,PR group,SD or PD group were 89.7%,65.3% and 19.4% respectively,and the difference was statistically significant (x2 =12.41,P =0.002).PET/CT imaging had a strong PFS predictive effect on T cell lymphoma (TCL) patients (x2 =13.85,P =0.001) and diffuse large B cell lymphoma (DLBCL)patients (x2=13.51,P =0.001),and had no predictive effect on follicular lymphoma (FL) patients (x2 =4.63,P =0.099).Conclusion 18 F-FDG PET/CT can evaluate the curative effect of lymphoma effectively and early predict prognosis,and has great guiding significance in choosing therapeutic schedule.
3.The effects of hypertension on the risk of recurrence among TOAST subtype of ischemic stroke
Jiamei LIU ; Siyuan QIN ; Lulu XIAO ; Lili XU ; Wen BAI ; Gelin XU
Journal of Medical Postgraduates 2014;(10):1052-1055
Objective The relationship between hypertension ( HTN) and ischemic stroke recurrence is unclear , but there may be different effects of HTN on the risk of recurrence .This study aims to explore whether HTN contributes differently to the recur-rence among subtypes of ischemic stroke ( IS) . Methods We eventually enrolled 1114 patients with ischemic stroke from Jul 2008 to Dec 2012 registered in Nanjing Stroke Registry Program (NSRP) in this study.All the patients were classified according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria: 315 (28.3%) patiwnts were classified as Large-artery atheroselerosis (LAA), 212 (19.0%) as cardioembolism (CE), 266 (23.9%) as small-artery occlusion (SAO), and 321 (28.8%) as other de-termined and undetermined etiologies ( Other) .The association between HTN and stroke recurrence in patients with different IS sub-types was analyzed using multivariate Cox regression analysis . Results The average follow-up duration was (19.4 ±10.3) months. Of 1114 patients with IS, 158 (14.2%) patients experienced a recurrent stroke .Patients with HTN had a significantly higher stroke recurrence rate than those without (16.5%vs 10.5%, P<0.05).Multivariate Cox regression analysis indicated that HTN increased the risk of ischemic stroke recurrence (HR=1.722, 95%CI:1.181-2.512, P=0.005).After stratification by TOAST subtypes, analysis revealed an association between HTN and stroke recurrence in LAA( HR=3 .767, 95%CI:1.866-7.585, P=0.001) and SAO (HR=3.530, 95%CI:1.156-12.740, P=0.028), but not in the other subtypes (CE: HR=0.773, 95%CI:0.370-1.615, P=0.493;Other:HR=1.498, 95%CI:0.590-3.807, P=0.395). Conclusion HTN is an independent risk factor for recurrent ischemic stroke and is related to the recurrent ischemic stroke in patients with large-artery and small-vessel disease .
4.Multiply Labeled Primers Amplifying Fluorescent Signal on Oligonucleotide Microarray
Siyuan WEN ; Hengjie CAO ; Junbo LIU ; Yu DING ; Suhong CHEN ; Shengqi WANG
Progress in Biochemistry and Biophysics 2005;32(8):747-752
Oligonucleotide microarray technology is a powerful data-mining platform and has been widely applied in biosciences. To improve the performance of assays on the oligonucleotide microarray, the factors that influence the hybridization effects such as surface chemistry, probe size, spacer length, hybridization conditions etc were intensely studied and optimized. However, it is a key problem with DNA microarrays how to generate higher fluorescent signals to improve the detection sensitivity. Two types of multiply labeled primers, termed multiply labeled linear primer and multiply labeled branched primer, were used to enhance the fluorescent signal obtained from two-dimensional DNA microarrays.The signal was intensified by increasing the number of fluorophores labeled on the target DNA segment. It was indicated that the detection limit (minimum template amoumt for detection) of the multiply labeled primers is about 1% of that of the singly labeled primer. Multiple labeling is an effective signal amplification method to increase the detection sensitivity of the probes in a miniaturized array format.
5.Synthesis of N-(2-18F-fluoropropionyl)-L-glutamine and its biodistribution study in mice
Caihua TANG ; Ganghua TANG ; Siyuan GAO ; Shaoyu LIU ; Fuhua WEN ; Dahong NIE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;36(2):112-115
Objective To synthesize 18F labeled N-(2-18 F-fluoropropionyl)-L-glutamine (18 F-FPGLN) for tumor PET imaging,and to perform its biodistribution study on normal mice and PC-3 tumorbearing nude mice.Methods 4-nitrophenyl-2-18F-fluoropropionate (18F-NFP) was synthesized on the MF2V-IT-I synthesizer and was purified by semi-preparative HPLC.Anhydrous 18F-NFP was added to a solution of L-glutanine t-butyl ester to synthesize 18F-FPGLN t-butyl ester,which was hydrolyzed by HCl (3 mol/L) and neutralized with NaOH (2 mol/L) solution.18F-FPGLN product was collected for further study.Biodistribution study was performed on normal Kunming mice and PC-3 prostate cancer tumor-bearing nude mice,respectively.Results 18F-FPGLN was synthesized with 10%-15% (decay uncorrected) overall radiochemical yield after 130 min of radiosynthesis.The radiochemical purity was higher than 96%.Rapid and high uptake of radiotracer was observed within the kidneys,and was quickly excreted through the urinary bladder.The uptake in kidney reached (35.0±1.2) %ID/g at 5 min post-injection,and descended to (1.5±0.3) %ID/g at 120 min.The liver,lung,heart and small intestine showed relatively moderate uptake of radioactivity.The uptake in the pancreas,muscle,spleen,stomach and brain was low,and the lowest uptake of (1.5±0.3) %ID/g was found in the brain at 30 min post injection.High accumulation of 18F-FPGLN in PC-3 xenograft was observed,and the tumor/muscle ratio reached 2.07 at 60 min post injection.Conclusion A novel N-position 18F-labeled glutamine analogs 18F-FPGLN,with favorable pharmacokinetic characteristics,is synthesized successfully,which makes it possible to perform tumor PET imaging using 18F-FPGLN subsequently.
6.Evaluation of hospital diagnosis and treatment quality based on the quality-evaluation model of STEMI
Liu YANG ; Hui CHEN ; Siyuan WEN ; Xiaowei MA ; Yueli MENG ; Keqin RAO
Chinese Journal of Hospital Administration 2015;31(6):459-463
Objective To evaluate and compare the diagnosis and treatment quality of 15 tertiary hospitals in Beijing with the quality-evaluation model of STEMI.Methods The quality-evaluation model has been formatted with the document analysis method and expert consultation method,with the indicators weighted by analytic hierarchy process.By collecting the data of 15 hospitals,we can get the values of indicators,then synthetically evaluate and compare the diagnosis and treatment quality at these 15 hospitals with the method of WRSR.Results In the diagnosing and treating the cases of STEMI at the hospitals,gaps are found between the clinical guidelines and the tests,patient evaluation,reperfusion treatment and drug therapy,with some indicators falling even below 22%.Also,there are significant differences in the diagnosis and treatment quality among hospitals.All hospitals are consistent on the five dimensions-tests,patient evaluation,reperfusion treatment,drug therapy and prognosis.Conclusion The quality-evaluation model of STEMI can comprehensively reflect the diagnosis and treatment quality of cardiovascular medicine,and partly reflect hospital's overall management level,so as to provide operating methods in improving hospital diagnosis and treatment quality.
7.Biomechanical evaluation and optimal design of two parameters of dental implant with arbitrarily adjusted angles
Siyuan CHENG ; Hailin WEN ; Jingqiu SI ; Rui LIANG ; Jing NIE ; Hang WANG ; Jie LONG ; Wei TANG ; Yongtao WEI ; Weidong TIAN
Chinese Journal of Tissue Engineering Research 2014;(34):5473-5479
BACKGROUND:Oversize stress of a dental implant and its surrounding tissue is the main factor to affect the
long-term use of dental implants. So, the reasonable and precise design of implant shape is one of the important methods of prolonging the life span of dental implants.
OBJECTIVE:To make the optimal analysis and design of the diameters of connector screw and central screw of the adjustable-angle dental implant invented in the earlier stage.
METHODS: The finite element analysis model of the edentulous mandible with adjustable-angle dental implant was established by software Pro/E 5.0, Mimics 10.0 and ANSYS Workbench 14.5. The maximum equivalent
stress of dental implant-edentulous mandibular model was analyzed.
RESULTS AND CONCLUSION:The maximum equivalent stress of dental implant-edentulous mandibular model
8.Study on differentially expressed gene of the liver of treble fatty metabolism genes mutant mice using cDNA microarray.
Xiao-lei JIN ; Wen-xia SUN ; Yu-ping SHI ; Jia-hui LI ; Han-min CHEN ; Jie PAN
Chinese Journal of Medical Genetics 2005;22(1):27-30
OBJECTIVETo study the gene expression profile of liver of young apoE(-/-)/LDLR(-/-)/Lepr(db/db) treble genes mutant mice and disclose its relationship to hyperlipidemia and the following atherosclerotic lesion.
METHODSThe gene expression profile was investigated using cDNA microarray technique; the plasma total cholesterol(TC) and triglyceride(TG) levels were analyzed by COD-PAP and GPO-PAP method. And morphological observations of the aorta were made.
RESULTSAmong the 4000 target genes, 92 genes were up-regulated and 105 genes were down-regulated in the treble genes mutants, compared with wild type control. Among the differentially expressed lipid metabolism related genes, cholesterol synthesis gene coding for farnesyl diphosphate farnesyl transferase was down-regulated, while triglyceride metabolism gene e.g. pancreatic lipase related protein 1 gene (Pnliprp1) was up-regulated. Expression profile of carbohydrate, cell skeleton and immune related genes were also altered. On the other hand, in the plasma from the treble genes mutant mice at 5 weeks of age, hyperlipidemia was found to be combined with atheroslerotic lesion. All these biochemical and pathological changes were aggravated following aging.
CONCLUSIONThe data suggested that the multiple genes mutations, especially those involved in lipid metabolism, were contributing to the alteration of liver gene expression profile that might lead to hyperlipidemia and atherosclerotic lesion in the young apoE(-/-)/LDLR(-/-)/Lepr(db/db) mutants.
Animals ; Apolipoproteins E ; genetics ; Cholesterol ; blood ; Farnesyl-Diphosphate Farnesyltransferase ; genetics ; metabolism ; Female ; Gene Expression Profiling ; methods ; Hyperlipidemias ; blood ; genetics ; metabolism ; Lipase ; genetics ; metabolism ; Lipid Metabolism ; Male ; Mice ; Mice, Knockout ; Oligonucleotide Array Sequence Analysis ; methods ; Receptors, LDL ; genetics ; Receptors, Leptin ; genetics ; Triglycerides ; blood
9.Clinicopathologic characteristics of lupus nephritis with positive antineutrophil cytoplasmic antibody
Siyuan ZHAO ; Jingping WEN ; Xin WANG ; Qiong WEN ; Zhijian LI ; Wei CHEN ; Xionghui CHEN
Chinese Journal of Nephrology 2022;38(11):961-968
Objective:To explore the clinical and histopathologic features of lupus nephritis (LN) patients with positive antineutrophil cytoplasmic antibody (ANCA), so as to provide more theoretical basis to recognize and treat this disease.Methods:Clinical data of biopsy-proven LN patients with ANCA test in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2002 to September 11, 2020 were collected and analyzed retrospectively. The difference of clinical data, laboratory examination, and pathological examination of renal biopsy between ANCA-positive group and ANCA-negative group. The clinicopathological characteristics between different ANCA serotypes were compared.Results:A total of 1 304 patients with LN confirmed by renal biopsy and ANCA test results were enrolled. Eighty ANCA-positive patients from 1 304 LN patients were screened. There are 55(68.8%) ANCA-positive LN patients with positive anti-myeloperoxidase antibodies (MPO). There were 14(17.5%) ANCA-positive LN patients with positive anti-proteinase 3 antibodies (PR3), and 11(13.8%) ANCA-positive patients with double positive antibodies of MPO and PR3. ANCA-positive LN patients had significantly higher serum creatinine [135.5(68.0, 361.8) μmol/L vs 88.0(64.0, 165.0) μmol/L, P=0.004] and blood urea nitrogen [12.35(6.35, 21.18) mmol/L vs 8.60 (5.50, 15.70) mmol/L, P=0.026] as well as lower estimated glomerular filtration rate [45.70(13.83, 84.10) ml·min -1·(1.73 m 2) -1 vs 66.75(38.43, 96.22) ml·min -1·(1.73 m 2) -1, P=0.001] than ANCA-negative patients (stratified sampling of 160 patients). ANCA-positive LN patients had higher chronicity index than ANCA-negative LN patients [3(2, 7) vs 2(0, 5), P=0.006]. There were statistically significant difference in hemoglobin, serum creatinine and estimated glomerular filtration rate among ANCA-positive group, ANCA-negative group, and MPO-ANCA and PR3-ANCA double positive group. MPO-ANCA and PR3-ANCA double positive LN patients had the lowest hemoglobin and estimated glomerular filtration rate, and highest serum creatinine among the three groups (all P<0.05). Conclusions:ANCA-positive LN patients have worse renal function and higher renal histological chronicity index than ANCA-negative LN patients, especially for patients with double positive MPO-ANCA and PR3-ANCA. More stringent monitoring and therapy may be needed in this subgroup of LN patients.
10.The 504th case: Multiple lymph node enlargement, renal insufficiency, blindness, and white matter lesions of the brain
Chong WEI ; Zhe ZHUANG ; Yunlong LI ; Xiaoxiao SHI ; Yubing WEN ; Wei CAO ; Siyuan FAN ; Xiao ZHANG ; Yan ZHANG ; Wei ZHANG ; Daobin ZHOU
Chinese Journal of Internal Medicine 2024;63(3):316-320
A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians′ awareness of opportunistic virus reactivation during anti-tumor treatment.