Cancer is one of the main causes of death for human beings. Clinical oncologists increasingly rely upon imaging for diagnosis, stage, response assessment, and follow-up in cancer patient. However, 18F-FDG is not a tumor specific agent, inflammation and infection also have intensive uptake of 18F-FDG, resulting in false positive diagnosis, and some tumors have low uptake of 18F-FDG or even do not uptake 18F-FDG, leading to false negative diagnosis. So it is urgent to develop non-18F-FDG novel tumor targeting agent. Recently, a large number of researches in vitro have demonstrated that berberine has anti-tumor activity against a variety of tumor cells by inducing tumor cell apoptosis through inhibition of mitochondrial respiratory chain etc. So far, there is no credible evidence of berberine targeting in tumor in vivo. We proposed a hypothesis that berberine has the characteristics of tumor targeting biodistribution in vivo, and verified the proposal by 18F-berberine PET/CT imaging in VX2 muscle tumor-bearing rabbit model. In this review, we intend to give an overview of the progress of berberine anticancer, the structural bases of berberine anticancer and the uderlying molecular mechanisms of berberine anticancer indentified so far. We also introduce the first visualization of 18F labeled berberine derivatives targeting tumor in VX2 muscle tumor-bearing rabbit model by PET/CT. These breakthrough findings suggest that 18F-berberine derivatives as a potential PET/CT tumor targeted molecular imaging agent may have important implications for cancer targeting therapy, molecular imaging and modernization of Traditional Chinese Medicine.
Berberine ; chemistry ; Fluorodeoxyglucose F18 ; chemistry ; Humans ; Molecular Imaging ; Neoplasms ; diagnosis ; Positron-Emission Tomography ; Tissue Distribution ; Tomography, X-Ray Computed

Abstract] Objective To establish an assay for the detection of porcine parvovirus ( PPV) and to verify its application for monitoring cells used for production.Methods A pair of primers and one probe were designed according to the conserved sequence encoding non-structural protein 1 (NS1).Based on the designed primers, a real-time fluorescent quantitative PCR assay for the detection of PPV was developed. Several parameters including the linearity, precision, minimum detection limit and anti-interference of the established assay were evaluated.A stock of PPV strains was prepared by infecting swine testicle ( ST) cells with PPV strains.An assay for the detection of PPV infection was developed by using ST cells as sensitive cells.A combined ST cell infection-PCR test was developed by combining the ST cell infection assay with the real-time fluorescent quantitative PCR assay.The sensitivity of ST cell infection-PCR test was analyzed.The cell samples used for production of biological products were detected by using the established assay.Results The real-time fluorescent quantitative PCR assay was specific for the detection of PPV without cross-reaction to other species of parvovirus virus, SV40 virus and other porcine viruses.The linear range of the assay was 1×109-1×104 copies/μl with a R2 value more than 0.98.The sensitivity of the real-time quantitative PCR assay was 1×104 copies/μl.Both of the intra-and inter-coefficient of variation (CV) were less than 5%in Ct values.The intra-and inter-CV in copies of detection were 5%-15% and 30%-40% respectively.The minimum detection limit of the real-time fluorescent quantitative PCR assay was 1CCID50/ml.The PPV strains were detected in cell samples with no interference.The sensitivity of ST cells infection-PCR test was 0.01CCID50/ml.All of the 22 cell samples were negative for PPV by using the real-time fluorescent quanti-tative PCR assay.Conclusion The real-time fluorescent quantitative PCR and the ST cell infection-PCR test for the detection of PPV in cells were established successfully.The application of the two assays was conducive to further enhance the safety of using cells for production and therapy.

Objective To analyze the effects of individualized lifestyle intervention on compliance and metabolic status of patients with type 2 diabetes mellitus (T2DM).Methods Two hundred T2DM patients were selected and randomly divided into experimental and control groups of 100 patients respectively.The experimental group was given individualized lifestyle intervention for 6 months in addition to conventional oral medications.The intervention was to prescribe diet control and exercise therapy according to the patients' individual conditions.The control group was given conventional treatment and verbal lifestyle intervention for 6 months.Comparison was made in patients compliance and various metabolic markers between the two groups.Results The percentage of conduction of diet control and exercise therapy in experimental group was significantly higher than control group ( Diet control:80 vs.52,x2=7.08,P=0.029;Exercise therapy:78 vs.44,x2=11.207,P=0.004).After intervention,the fasting plasma glucose (FPG),2-hour postprandial blood glucose (2hPG),glycated hemoglobin ( HbA1c),body mass index ( BMI),triglyceride ( TG),total cholesterol (TC),low-density lipoprotein ( LDL-C ),and insulin resistance index ( HOMA-IR ) in experimental group decreased significantly,and high-density lipoprotein ( HDL-C ) increased significantly [FPG:( 8.45 ± 1.46 ) mmol/L vs.(6.66 ± 0.67) mmol/L,P=0.000;2hPG:( 12.76 ± 2.25 ) mmol/L vs.(8.22 ± 1.79) mmol/L,P=0.000;HbA1c:(7.68 ± 1.06 ) ％ vs.( 6.48 ± 0.69 ) ％,P=0.000;BMI:( 25.90 ± 1.72 ) kg/m2 vs.( 22.81 ±1.41 ) kg/m2,P=0.016;TG:(2.57 ±0.68) mmol/Lvs.( 1.88 ±0.35) mmol/L,P=0.006;TC:(5.72 ±0.13) mmol/L vs.(5.14 ± 1.38) mmol/L,P=0.043;LDL-C:(3.28 ±0.10)mmol/L vs.(2.81 ±0.57)mmol/L,P=0.009;HOMA-IR:7.58 ± 0.19 vs.4.58 ± 1.98,P=0.000;HDL-C:( 1.29 ± 0.04) mmol/L vs.( 1.62 ± 0.27 ) mmol/L,P=0.003].The levels of FPG,2hPG,HbA1c,BMI,TG,HOMA-IR also decreased in control group after intervention compared with before intervention [FPG:( 8.67 ± 2.71 ) mmol/L vs.( 7.26 ± 1.21 ) mmol/L,P=0.001;2hPG:( 12.82 ± 2.15 ) mmol/L vs.( 10.85 ± 1.98 ) mmol/L,P=0.000,HbA1c:( 7.75 ± 1.08 ) ％ vs.( 7.01 ± 0.87 ) ％,P=0.002;BMI:( 25.82 ± 1.74 ) kg/m2 vs.( 24.23 ± 1.36 ) kg/m2,P=0.024;TG:(2.47 ±0.75) mmol/L vs.(2.13 ± 0.43 ) mmol/L,P=0.018;HoMA-IR:7.88 ± 0.20 vs.6.15 ± 2.01,P=0.042].No significant difference was found on the values of TC,HDL-C and LDL-C before and after intervention in control group (P ＞ 0.05).The effect of intervention of experimental group was more obvious when compared with control group ( FPG:P=0.036;2hPG:P=0.000;HbA1c:P=0.045;BMI:P=0.037;TG:P=0.022;HoMA-IR:P=0.000).Conclusion Individualized lifestyle intervention can improve the compliance of T2DM patients,and was in favor of control metabolic status of T2DM patients to delay the occurrence and development of complications.

Actins ; metabolism ; Adult ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Calcium-Binding Proteins ; metabolism ; Cell Differentiation ; Desmin ; metabolism ; Diagnosis, Differential ; Female ; Fibroadenoma ; metabolism ; pathology ; surgery ; Hamartoma ; pathology ; Humans ; Hyperplasia ; Leiomyoma ; pathology ; Microfilament Proteins ; metabolism ; Muscle, Smooth ; pathology ; Phyllodes Tumor ; pathology

Objective To study the profiling and authentication of human cell lines in cell bank of our department using short tandem repeat (STR) loci and to analyze the situation of cell contamination and misjudgment. Methods Sixty-one human cells including cells collected and preserved by our cell bank and cells from the other departments were detected by the 16 STR loci-method. To analyze the cross contamina-tion between human cell lines, the results were aligned with profiles published by international cell banks. Isoenzyme detection was employed to authenticate the cell species when the STR signal can not be detected. Results Among the 61 cells, specific profiles were produced by 41 ceils and there was no cross contamina-tion. Thirty-six cells had the completely same STR profiles in 9 STR loci with the same cells preserved by ATCC or JCRB, while 5 cells have different profiling just in the vWA loci. The cells referred above can be recognized as correct cells; Eleven cells (18.0%) were the false cells. Among them, cancer cells of tongue named Tca8113 and cancer cell of liver named HHCC(changed to FHCC98 now) had the same profile with HeLa and HeLa S3 respectively; Two ceils both named HUT-102 have the completely different profiles with ATCC; The signal of 4 cells was not be detected, and all of them were determined as hamster cell lines by u-sing isoenzyme detection. Also 2 cells were identified to be mixed cells. Conclusion The phenomenon of cell misjudgment and cross contamination between cells is serious. Authentication of cell lines correctly, es-pecially for the re-authenticatian of domestic self-established cells, is very important for the guarantee of the reliability and reproducibility for scientific researches.

In order to study genetic variation diversity of porcine circovirus type 2 (PCV2) strains in Shanxi,the genomic sequences of nine PCV2 strains including SXQX,SXCZ,SXTY2,SXJC,SXJX,SXLL,SXPY,SXPG and SXXY recently isolated from some areas of Shanxi from 2013 to 2016,was cloned,sequenced and received by GenBank.The amplified PCV2 genomic sequences,ORF2 sequences and Cap protein amino acid of these nine strains were analysed and compared with those of published 28 PCV2 strains by DNAStar,drawing phylogenetic tree.The results showed that the genomic sequences of SXJX,SXJC and SXXY PCV2 strains were 1 768 bp,and the others were 1 767 bp,which accounted for 33％ and 67％,respectively.The homologies of nucleotide sequences of the nine strains were 94.7％-99.8％,the homologies of nucleotide sequences of the nine strains with the 28 isolates from different regions of the world PCV strain were 93.9％-99.9％,and the homologies of nucleotide sequences of the nine strains with the domestic vaccine strains were 95.1％-99.8％.The phylogenetic analysed that SXJX,SXJC and SXXY belonged to genotype PCV-2D,SXLL,SXPY and SXCZ belonged to genotype PCV-1C,and SXTY14,SXPG and SXQX belonged to genotype PCV-1A/1B.Thus it proved that the epidemic strain of PCV2 was mainly PCV-2b in Shanxi.The homologies of ORF2 nucleotide sequences and Cap amino acid of the nine strains were 90.0％-100.0％ and 87.1 ％-100.0％ respectively,the homologies of ORF2 nucleotide sequences and Cap amino acid of the nine strains with the 28 isolates from different regions of the world PCV strain were 87.6％-100.0％ and 84.1％-100.0％ respectively,and the homologies of ORF2 nucleotide sequences and Cap amino acid of the nine strains with the domestic vaccine strains were 91.0％-100.0％ and 89.3％-100.0％ respectively.The Cap amino acids of SXQX,SXJX,SXTY14,SXPG,SXJC and SXXY PCV2 were 233,ORF2 of SXQX,SXTY14 and SXPG located at 1 033-1 734 bp,ORF2 of SXXY,SXJX and SXJC located at 1 033-1 734 bp,and the Cap amino acids of SXCZ,SXLL and SXPY PCV2 were 234,ORF2 of them located at 1 030-1 734 bp,in addition,the positions of 1 030-1 734 bp were more three bases TCA than other ORF2 genome sequence of 1 767 bp,resulting in increasing a K (Lys) of amino acid sequencein at the 234 position.Also Cap protein of 9 PCV2 strains showed more amino acid variation in addition to the only high-ly conserved glycosylation sites (NYS) (pp.143-145 amino acid).It provided theoretical basis for the PCV2 immune prevention of research in Shanxi,and the data of basic theory of molecular pathogenesis of PCV2.

Objective To detect the protection induced by HPV-58 L2 11-200 AA in animal, and analyze the relationship between antibody or neutralizing antibody titers and the protection generated by the immunizmg agent. Methods The peptide of HPV-58 L2 11-200 AA was expressed in E. coli and the mice were immunized with the peptide after purification and adsorption with aluminum adjuvant. The protection provided by different immunizing doses was detected in the mouse model against the challenge of the pseud-ovirions of human papiilomavirus types 58. The total antibodies and neutralizing antibody titers of serum were tested with ELISA and neutralization assay against HPV-58 pseudovirus, respectively. The total antibodies or neutralizing antibody titers that can protect the mouse from infection were analyzed. Results The mice can be protected from the challenge with HPV pseudovirus when the immunizing dose was 8 μg. The neutralizing antibody can not be detected in the immune serum by neutralization assay against pseudovirus. The total anti-body level has a corresponding relationship with the protection showed in mouse model. The results of total antibodies detected by ELISA showed that when the titer of total antibodies was ≥25 000, luminescent signal can not be detected and the mice can be protected from pseudovirus infection. Conclusion HPV-58 L2 11-200 AA peptide can protect mice from pseudovirus infection. L2 peptide has a promising perspective to be a candidate vaccine and the level of total antibodies in the immune serum can be used as a surrogate for the evaluation of protection against HPV infection.

Objective The clinical data of postoperative perirenal hematoma after renal biopsy in recent 10 years were retrospectively analyzed,and its relationship with pathological type was explored.Methods From April 2003 to April 2013,2062 patients of renal biopsy were enrolled and divided into 3 groups:youth group (18-39 years,1634 cases),middle age group (40-59 years,323 cases) and aged group (≥60 years,105 cases).Relationship between renal hematoma and pathology was analyzed.Results There were 1370,255,69 cases of primary glomerular disease respectively in 3 groups,and 264,68,36 cases of secondary glomerular diseases.Three hundred and seventy-nine in all patients were complicated with perirenal hematoma,and the incidence rates were 15.8％ (325/2062),1.8％ (37/2062),0.8％ (17/2062) respectively.Incidence rate of hematoma in primary glomerular disease was higher than that in secondary diseases [19.0％ (322/1694) vs.15.5％ (57/368)].Three most common primary glomerular disease in which perirenal hematoma occured was IgA nephropathy 7.4％ (126/1694),focal/segmental lesions 4.2％(71/1694) and membranous nephropathy 2.4％ (41/1694); while the incidence rate of lupus nephritis hematoma was as high as 9.0％ (33/368).Conclusion Single-center data shows that the most common pathology types of perirenal hematoma are lupus nephritis,IgA nephropathy,focal/segmental lesions and membranous nephropathy.

Objective To conduct extensive quality control tests on Madin-Darby Canine Kidney ( MDCK) cells used for the production of influenza vaccine .Methods Tests for characteristics , extraneous agents, endogenous agents and tumorigenicity were performed on MDCK cells according to Chinese Pharma -copeia Book III .Cell lysate and DNA of MDCK cells were tested for oncogenicity in the light of new interna -tional requirements .Results The MDCK cells extracted from canis were adherent cells with an epithelial morphology, whose average number of chromosome was 80±1.No bacteria, fungi and mycoplasma contami-nation were detected . The detection for extraneous and endogenous virus showed that there was no nonspecific virus causing cytopathic effect , hemadsorption , hemagglutination or animal death .Tests for re-verse transcriptase , bovine viruses and canine viruses were all negative .Each nude mouse was injected with 107 viable cells to observe their tumorigenicity .Twelve weeks after cell injection , no node was found at the injection site and in large organs by gross anatomy .There was no significant difference between test group and negative control group .The test for tumorigenicity of viable cells was negative .Cell lysate and cellular DNA collected from equivalent amount of cells were respectively injected into nude mice , and no node forma-tion was found.There was no significant difference between the test cells and negative controls in pathology indicating that the tested MDCK cells were non-oncogenic .Conclusion It showed the possibility of using MDCK cells for the production of influenza vaccine .

Objective To establish an assay for the detection of Torque teno sus virus ( TTSuV) strains and to analyze its preliminary application to biologics.Methods Primers and probe were designed according to the conserved sequences.A fluorescent PCR assay for the detection of TTSuV strains was estab-lished.Several parameters including the specificity, linearity, accuracy, sensitivity and anti-interference of the established assay were verified.The fluorescent PCR assay was performed to detect the samples of por-cine blood, cell substrate and rotavirus vaccine.The porcine blood samples positive for TTSuV strains were further genotyped.Results The established fluorescent PCR assay was confirmed to have high specificity as no cross-reactions with parvovirus virus of various species, SV40 and porcine circovirus strains were detec-ted.The linear range of the assay was 1×109-1×103 copies/μl for TTSuV1 genotype and 1×109-1×102 cop-ies/μl for TTSuV2 genotype with a R2 value more than 0.993.The sensitivity of the fluorescent PCR assay was 1×103 copies/μl for TTSuV1 genotype and 1×102 copies/μl for TTSuV2 genotype.The intra-and inter-CVs were both less than 7%in Ct values and less than 25% and 45% respectively in copies.No interfer-ence was found in the detection of TTSuV nucleic acids from cell samples.8 out of 20 porcine blood samples were positive for TTSuV strains, among which one sample was positive for TTSuV1 genotype, four samples were positive for TTSuV2 genotype and the rest were positive for both TTSuV1 and TTSuV2 genotypes.Com-pared with the reference strain, strains genotyped as TTSuV1 and TTSuV2 were respectively shared 98%-99%and 98%homologies in sequences.All of the cell substrate and rotavirus vaccine samples detected by the fluorescent PCR assay were negative for TTSuV strains.Conclusion The fluorescent PCR assay for the detection of TTSuV was established successfully, the application of which would further improve the safety of biologics.