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.

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.

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.

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.

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.

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 .

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

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

Objective To explore whether Yes-associated protein(YAP)affects occurrence and progression of liver fibrosis by regulating epithelial-mesenchymal transition(EMT).Methods In a 8-week-old C57BL/6 mouse model of CCl4-induced liver fibrosis,the effect of verteporfin(a YAP inhibitor)intervention was assessed with HE staining and by detecting liver biochemistry and expressions of YAP and EMT-related genes using immunohistochemistry and Western blotting.Transcriptome and proteomic sequencing and informatics analysis were used to investigate the main downstream pathways of YAP in liver fibrosis.Serum levels of YAP,N-cadherin,vimentin and Twist were examined in 60 healthy individuals,60 patients with chronic hepatitis B(CHB),and 60 patients with HBV-related liver cirrhosis.In another 24 C57BL/6 mice,the effects of Twist inhibitor alone or in combination with harmine(a YAP activator)on CCl4-induced liver fibrosis were evaluated by histopathological examination and Western blotting.Results The mouse models of liver fibrosis showed obvious structural damages of the liver lobes with formation of pseudolobules,and verteporfin treatment significantly improved these pathologies and lowered plasma ALT and AST levels of the mice.Transcriptome and proteomic sequencing and informatics analysis suggested that N-cadherin and Twist were differentially expressed in liver fibrosis in close correlation with YAP.Inhibition of YAP obviously downregulated hepatic N-cadherin and Twist protein expressions in the mice with liver fibrosis.In patients with CHB and liver cirrhosis,serum levels of YAP elevated obviously with the severity of liver fibrosis and were significantly correlated with N-cadherin,vimentin and Twist levels.In mice with liver fibrosis,inhibiting Twist effectively improved liver inflammation and fibrosis,while the combined treatment with YAP activator worsened hepatic collagen fiber deposition and increased hepatic YAP and α-SMA expressions.Conclusion EMT is an important pathogenic mechanism of liver fibrosis,and inhibiting YAP can alleviate liver fibrosis by reducing EMT.

Objective To explore the potential pathogenic genes of intestinal metaplasia.Methods Twenty-one patients with intestinal metaplasia admitted to the Department of Gastroenterology at the Second Affiliated Hospital of Anhui University of Chinese Medicine from January,2022 to June,2022,and 21 healthy subjects undergoing gastroscopic examination during the same period were enrolled in this study.All the participants underwent gastroscopy and pathological examination,and gastric tissue samples were collected for transcriptome sequencing to screen for differentially expressed genes(DEGs).The biological functions of the DEGs were analyzed using bioinformatics analysis,and qRT-PCR was used to validate the results.Results Transcriptomic sequencing identified a total of 1373 DEGs,including 827 upregulated and 546 downregulated ones.The top 6 upregulated genes(AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2),ranked based on their significance and average expression level,were selected for validation,and qRT-PCR showed significant upregulation of their mRNAs in the gastric tissues of patients with intestinal metaplasia(P<0.05).Conclusion AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2 participate in the occurrence and development of intestinal metaplasia,and may serve as potential biomarkers for diagnosing intestinal metaplasia.