Objective To evaluate the feasibility of 3-(4-~(18)F-fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno [3,4-c]pyridin-5-one ( is F-FDTP) as a potential dopamine D4 receptor PET imaging agent.Methods ~(18)F-FDTP solution in ethanol-physiological saline was incubated with calf serum to test its in vitro stability through the determination of radiochemical purity.Normal rats were injected intravenously with ~(18)F-FDTP and then sacrificed at 2,5,10,15,30,60 and 120 min after anesthesia.Blood,organs and brain tissue samples were collected.All samples were weighed and measured for radioactivity.The uptake of samples was expressed as percentage activity of injection dose per gram of tissue ( % ID/g).Results The stability of ~(18)F-FDTP was satisfactory and its radiochemical purity was above 95% after incubation 120 min at 37℃ in calf serum.The biodistribution showed that ~(18)F-FDTP could penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal certex,hippocampus,cerebellum,where the D_4 receptor was reportedly located.The radioactivities in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum,pons were (0.42±0.03),(0.46±0.05),(0.54±0.04),(0.39±0.04),(0.45±0.06),(0.35±0.04) %ID/g,respectively,2 min post injection.And there was difference between the normal biodistribution results and the blocking experimental results:(0.36 ±0.05),( 0.33±0.05 ),(0.55±0.05 ),(0.30±0.07 ),(0.34±0.07 ) and (0.32±0.04) % ID/g in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum and pons,respectively.Conclusions ~(18)F-FDTP can penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal cortex,hippocampus,cerebellum,where the D_4 receptor was known to concentrate.These preliminary results suggest that ~(18)F-FDTP is a potential dopamine D_4 receptor imaging agent and further studies are needed.

Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP).This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP.A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study.The percentages of CD4+,CD8+,natural killer (NK),and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14,and 28 after admission were determined by flow cytometry.Eighteen patients presented with the symptoms of infection.Among them,55.6％ patients (10/18) developed MDR infection.The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii.The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections.In patients without infection,the HLA-DR percentage was maintained at a high level throughout the 28 days.Compared to the patients without any infection,the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28.In patients with MDR infection,the HLA-DR percentage remained below normal levels at all-time points.It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.

Objective To explore potential predictive biomarkers for preeclampsia by analyzing the expression and characteristics of vascular-related inflammatory proteins in the serum of preeclamptic pregnant women.Methods A case-control study was conducted from Sep 2017 to Sep 2018 in the Obstetrics and Gynecology Hospital,Fudan University.Preeclamptic pregnant women and normotensive pregnant controls during the same period were recruited.The concentration of 12 vascular inflammation-related proteins in the patients'serum was determined by multiplex flow cytometry.The vascular-related inflammatory molecules were subjected to differential analysis by non-parametric t-test to obtain preeclampsia-related vascular inflammatory proteins.Finally,high-risk preeclampsia pregnancy serum samples from the biobank were retrieved.Serum concentrations of preeclampsia-related vascular inflammatory proteins were determined,and receiver operating characteristic(ROC)curve analysis was conducted for preliminary predictive assessment of preeclampsia.Results This study conducted a quantitative analysis of serum vascular inflammatory proteins in 39 cases of preeclampsia and 43 cases of control pregnant women,detecting 10 vascular inflammatory proteins expressed in maternal serum.Among these,myoglobin and vascular cell adhesion molecule-1(VCAM-1)exhibited significant elevation in the serum of preeclamptic pregnant women,while matrix metalloproteinase-9(MMP-9)showed a marked decrease.ROC curve analysis revealed that in 96 high-risk early pregnancy women,the area under the curve(AUC)for VCAM-1 reached 0.802,whereas myoglobin and MMP-9 did not significantly predict the occurrence of preeclampsia.Conclusion Preeclampsia patients exhibit abnormal expression of serum inflammatory proteins,among which VCAM-1 may be a potential biological marker for early pregnancy preeclampsia risk prediction.

OBJECTIVETo investigate the drug resistance of imipenem-resistant (IR) Gram-negative bacilli (GNB) in coal workers' pneumoconiosis (CWP)-chronic obstructive pulmonary disease (COPD) patients with lower respiratory tract infection (LRTI) and to provide a basis for clinical treatment.

METHODSSixty-six strains of IR-GNB were isolated from the sputum of CWP-COPD patients with LRTI, and the bacterial spectrum was investigated. The drug resistance of bacterial strains was studied by KB disk diffusion method.

RESULTSAmong the 66 strains of IR-GNB, 29 (43.9%) were Pseudomonas aeruginosa, 17 (25.8%) were Acinetobacter baumannii, and 11 (16.7%) were Stenotrophomonas maltophilia. The drug sensitivity test showed that all bacteria had high drug resistance; Pseudomonas aeruginosa had a susceptibility rate higher than 50% to ciprofloxacin, polymyxin B, fosfomycin, and amikacin, Acinetobacter baumannii had a susceptibility rate higher than 55% to fosfomycin, polymyxin B, and cefoperazone/sulbactam, Stenotrophomonas maltophilia had a susceptibility rate higher than 50% to cotrimoxazole, ciprofloxacin, piperacillin/tazobactam, levofloxacin, polymyxin B, and cefoperazone/sulbactam, and Pseudomonas cepacia had a susceptibility rate higher than 50% to piperacillin/tazobactam, ciprofloxacin, cefoperazone/sulbactam, and polymyxin B.

CONCLUSIONThe main species of IR-GNB are such non-fermentative bacteria as Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia in CWP-COPD patients with LRTI. These bacteria have high drug resistance and are sensitive to only a limited range of antibiotics.

Aged ; Aged, 80 and over ; Anthracosis ; complications ; microbiology ; Drug Resistance, Multiple, Bacterial ; Gram-Negative Bacteria ; drug effects ; Humans ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; complications ; microbiology

OBJECTIVETo study the therapeutic effect of agonistic CD40 monoclonal antibody combined with tumor specific cytotoxic T lymphocyte (CTL) on B lymphoma.

METHODSHuman B lymphoma cell line, Daudi cells, were cultured with CD40 mAb (5C11) for 24 and 48 hours, respectively. Annexin V/PI-binding assay was employed to analyze apoptosis, and FCM to analyze Fas (CD95) expression. Human peripheral monocyte-derived DC were loaded with apoptotic Daudi cells and stimulated by SC11 for further maturation. Tumor specific CTL were generated in vitro by co-culture of mature DC with autologous T lymphocytes. DNA fragmentations of Daudi cells treated with 5C11, CTL or 5C11 combined with CTL were determined by JAM assay. To establish the B lymphoma model, Daudi cells were subcutaneously injected into humanized SCID mice (hu-SCID). 1 or 3 weeks after tumor transfer. tumor-bearing mice were respectively treated with SC11, CTL, 5C11 combined with CTL by intraperitoneal injection. Tumor volume in differently treated mice was measured every week after therapy, and the survival of tumor-bearing mice was recorded.

RESULTS5C11 significantly up-regulated FAS expression in Daudi cells, but had no significant effect on apoptosis rate of Daudi cells. Tumor-specific CTL could effectively kill Daudi cells. Fragmentation of Daudi cells co-cultured with CTL was remarkably enhanced by combination with SC11. Tumor growth in hu-SCID mice was apparently delayed by treatment with SC11, CTL, or SC11 combined with CTL. Moreover, minimal tumor burden mice got 30.0% or 70.0% complete remission (CR), respectively, when received CTL treatment or combination treatment of SC11 with CTL, and the lifespan of tumor bearing mice was also prolonged significantly.

CONCLUSIONSC11 may enhance the sensitivity of Daudi cells to apoptosis by up-regulation of Fas expression and promote cytotoxicity of CTL in vitro and therapeutic effect in vivo.

Animals ; Antibodies, Monoclonal ; immunology ; therapeutic use ; Apoptosis ; immunology ; CD40 Antigens ; immunology ; Cell Line, Tumor ; Coculture Techniques ; Female ; Flow Cytometry ; Humans ; Immunotherapy, Adoptive ; methods ; Lymphoma, B-Cell ; immunology ; pathology ; therapy ; Mice ; Mice, SCID ; Remission Induction ; Survival Analysis ; T-Lymphocytes, Cytotoxic ; cytology ; immunology ; Xenograft Model Antitumor Assays ; fas Receptor ; immunology

OBJECTIVETo study the impact of gonadotropin-releasing hormone analogs (GnRHa) on body mass index (BMI) in girls with idiopathic central precocious puberty (ICPP).

METHODSOne hundred and thirty-four girls with ICPP were enrolled. Fifty-seven out of the 134 girls were treated with GnRHa for 1.69±0.43 years. The height, weight, bone age and BMI were measured before treatment, at the end of the treatment and after reaching near adult height and compared with those in the untreated 77 girls.

RESULTSThe adult predicted height standard deviation score (SDS) at the end of treatment was significantly higher than that before treatment (P<0.01) and was similar to the target height SDS in the GnRHa treatment group (P>0.05). With GnRHa treatment, the near-adult height SDS was higher than the target height SDS (P<0.01). At the end of treatment, the BMI SDS slightly increased compared with pretreatment level (P>0.05). A significant reduction in the BMI was observed when reaching the near-adult height in the GnRHa treatment group compared to the level of pretreatment and the untreated group (P<0.01). However, the BMI in the GnRHa treatment group before treatment, at the end of the treatment and after reaching near adult height remained in the normal range (±1 SD).

CONCLUSIONSGnRHa may improve the final height in girls with ICPP. The alterations of BMI after GnRHa therapy fluctuate in a normal range.

Body Height ; drug effects ; Body Mass Index ; Child ; Female ; Follow-Up Studies ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; therapeutic use ; Humans ; Puberty, Precocious ; drug therapy ; physiopathology

OBJECTIVETo elucidate the relationship between surgical time and postoperative complications in senile patients with hip fractures, and try to find out other factors which are related to these complications.

METHODSSixty-two patients, 28 males aged from 65 to 72 years with a mean age of 76.3 years and 34 females aged from 65 to 95 years with a mean age of 78.1 years, who had undergone orthopedic surgery because of hip fractures, were enrolled in a retrospective cohort study. The surgical time and pattern, the type of fracture, preoperative comorbidities, American Society of Anesthesiologists (ASA) score and the volume of blood transfusion during operation were obtained from these patients who were followed up by telephone calls for postoperative complications. All the patients were followed up at least for 1 year and were divided into subgroups according to their clinical characteristics and the results were analyzed by the Statistical Analysis System software.

RESULTSThere was no significant difference in the morbidity of postoperative complications with the gender, age, surgical time and pattern, or ASA score. There was significant difference in the morbidity of postoperative complications related to preoperative comorbidities and the volume of blood transfusion. There was a significant causality between preoperative comorbidities and postoperative complications. The morbidity of postoperative complications was 1.651 times higher in patients with preoperative comorbidities than those without.

CONCLUSIONSThere is no relationship between the surgical time and postoperative complications in senile patients who received surgery for hip fracture within 1 year. No correlation is found between the postoperative complications and gender, age, type of fracture, surgical pattern, ASA score and the volume of blood transfusion. Preoperative comorbidities are an independent predictor for postoperative complications.

Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Hip Fractures ; surgery ; Humans ; Logistic Models ; Male ; Morbidity ; Postoperative Complications ; epidemiology ; Retrospective Studies ; Time Factors

Hepcidin can regulate cell irons' efflux transport. The expression of hepcidin can be influenced by the body signals (such as serum ferritin and erythropoietin levels) as well as inflammation, hypoxia and other disease states. These stimulus activate the signaling pathway of BMP-the SMAD, the JAK-STAT and HIF1 through the liver parenchymal cell surface type I transmembrane glycoprotein of HFE, transferrin receptor 1, 2, hepcidin regulatory proteins, thereby changing the hepcidin gene transcription, regulating the expression levels of hepcidin. However, the molecular mechanism that regulate hepcidin expression is unclear. From the signal factors that affect hepcidin expression and signaling pathways involved in its expression, the latest research progress on regulatory mechanism of hepcidin are summarized.
Animals ; Antimicrobial Cationic Peptides ; metabolism ; Hepcidins ; Humans ; Membrane Proteins ; metabolism ; Signal Transduction

OBJECTIVETo develop a tight tetracycline-controlled HCV-C double transgenic mouse model.

METHODSBy crossbreeding of ApoE-rtTA-tTS transgenic mice with TRE-HCV-C transgenic mice, the double transgenic mice were produced in the F1 generation. The presence of HCV-C and tTS gene in the F1 generation was confirmed by PCR, followed by further identification and quantification of the transgene using Southern blot hybridization. The expression of HCV-C in the liver of the mouse model was detected immunohistochemically.

RESULTS AND CONCLUSIONTwo transgenic mice were obtained, which contained ApoE-rtTA-tTS and TRE-HCV-C genes in the genome. Five founders contained HCV-C gene as confirmed by PCR and Southern blot hybridization. The tight tetracycline-controlled system may facilitate further study of HCV-C gene expression and gene therapy of hepatic cellular carcinoma.

Animals ; Apolipoproteins E ; genetics ; Blotting, Southern ; Breeding ; Crosses, Genetic ; Female ; Gene Expression Regulation, Viral ; drug effects ; Hepacivirus ; genetics ; immunology ; Hepatitis C Antigens ; genetics ; immunology ; Male ; Mice ; Mice, Transgenic ; Polymerase Chain Reaction ; Tetracycline ; pharmacology ; Trans-Activators ; genetics ; Viral Core Proteins ; genetics

This study was purposed to explore the expression of p57kip2 in the bone marrow of patients with de novo myelodysplastic syndrome (MDS) and its role in MDS pathogenesis, as well as the relationship between the expression of p57kip2 and SDF-1/CXCR4 signal. The expression of p57kip2 and CXCR4 in 67 de novo MDS patients was measured by real-time quantitative PCR. The percentage of CD34(+) cells in the bone marrow from MDS patients was measured by flow cytometry. 18 healthy volunteers were recruited for control. The effect of SDF-1 on p57kip2 expression in bone marrow mononuclear cell (BMMNC) from MDS or normal controls was investigated in vitro, and difference between them was compared. The results showed that low-risk MDS and high-risk MDS displayed a significant reduction of p57kip2 mRNA expression in BMMNC compared with that in control group (P < 0.001) and there was a negative correlation between p57kip2 expression and percentage of CD34(+) (r = -0.458, P < 0.001); the patients with abnormal karyotype showed lower expression of p57kip2 gene, compared to patients with normal karyotype (P = 0.045). Although the expression of CXCR4 had no difference between MDS patients and normal controls, a positive correlation between p57kip2 and CXCR4 in MDS patients was still found (r = 0.609, P < 0.001). Moreover, SDF-1 increased p57kip2 expression in normal BMMNC in dose-dependent manner, but BMMNC from MDS patients showed no response to SDF-1. SDF-1-induced p57 expression was blocked by AMD3100. It is concluded that the low expression of p57 gene in MDS may play a role in the pathogenesis of MDS. Furthermore, SDF-1-induced p57kip2 expression in BMMNC, and the decreasing response of BMMNC to SDF-1 may contribute to the low expression of p57kip2 in MDS patients.
Case-Control Studies ; Chemokine CXCL12 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p57 ; genetics ; metabolism ; Flow Cytometry ; Humans ; Myelodysplastic Syndromes ; genetics ; metabolism ; Receptors, CXCR4 ; metabolism