2.Synthesis of 6-18F-Py-AMD3465 and the microPET/CT imaging of this agent in mice bearing A549 tumor
Nan LIU ; Qiang YOU ; Yue FENG ; Qiang WAN ; Yue CHEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;36(2):122-126
Objective To synthesize 628F-Py-AMD3465,to investigate its biodistribution in mice and to perform the microPET/CT imaging on mice bearing human lung cancer cell (A549).Methods AMD3465 quaternary ammonium salt precursor was directly labeled with 18F,then 628F-Py-AMD3465 was synthesized through nucleophilic reaction,hydrolysis,neutralization and the product was purified using HPLC.The labeling yield and radiochemical purity were analyzed by HPLC.Fifteen Kunming mice were injected with 5.55 MBq of 628F-Py-AMD3465 and sacrificed at 5,20,40,60 and 120 min postinjection.The selected tissues were harvested and weighed,and the radioactivity in the tissues was measured by an automated γ-spectrometer.The %ID/g was calculated.MicroPET/CT studies were performed on A549-bearing mice after injecting 6-18F-Py-AMD3465 through vena caudal.Paired t test was used.Results 6-18F-Py-AMD3465 was successfully synthesized with the labeling yield of (9.0±2.0)%,the total synthesis time was about 60 min,and the radiochemical purity was more than 98%.Biodistribution studies showed that the radiouptake was higher in the kidneys and bladder of normal mice,which demonstrated that 6-18 F-Py-AMD3465 was mainly excreted through the kidneys.Biodistribution in A549-bearing mice was similar to that in normal mice.The tumor/muscle ratio at 40 min was 5.0,but the radiouptake of the tumor was still lower than that of the normal lung:(8.05±0.35) %ID/g vs (9.33±0.66) %ID/g;t=5.26,P<0.05.MicroPET/CT imaging showed that the high-uptake location of 6-18F-Py-AMD3465 in tumor-bearing mice was similar to the normal mice,and the tumor uptake reached the maximum level at 45 min post-injection (SUV 0.67).Conclusions 6-18F-Py-AMD3465 can be synthesized by a simple method.A lower uptake could be shown in the tumor compared to that in the lung and the tracer has limited diagnostic value for lung cancer.
3.Advances of Notch signaling regulating fetal liver stem/progenitor cells: implications for the therapy of end-stage liver diseases
Qike HUANG ; Nan YOU ; Lili DANG ; Guangxin LIU ; Kaishan TAO
Chinese Journal of Hepatobiliary Surgery 2014;20(1):66-69
Cell therapy has a very promising potential for end-stage liver diseases (ESLD).Fetal liver stem/progenitor cells (FLSPCs) have advantages of safety,high survival and proliferation rates,and a small volume,all which make them ideal for liver disease stem cell therapy.During the early phase of our study,we applied a three-step separation method to enrich FLSPCs and obtained a separation efficiency similar to that of the flow-cell sorting method.Additionally,using a fulminant hepatic failure model in rats,we have demonstrated that FLSPCs can contribute to morphological and functional recovery of the liver.This manuscript will discuss how FLSPCs can be induced to accurately differentiate into hepatocytes and cholangiocytes and how FLSPCs maintain self-renewal.The Notch signaling plays a critical role in regulating the differentiation and self-renewal of many types of stem cells.Our previous findings have shown that the Notch signaling plays an important role in FLSPCs differentiation into hepatocytes.Therefore,the Notch signaling might be involved in the differentiation and self-renewal of FLSPCs.We conducted a study on the regulatory effects and relative molecular mechanisms of the Notch signaling on FLSPCs and found the corresponding interfering target,which might become an index for the clinical application of FLSPCs.
4.Effect of diabetes mellitus and blood sugar status on treatment outcome of tuberculosis patients
Nan-nan YOU ; Wei LU ; Li-mei ZHU ; Qiao LIU
Chinese Journal of Disease Control & Prevention 2020;24(1):90-96
Diabetes mellitus patients are at high risk of tuberculosis, and tuberculosis is one of the important reasons for inducing and aggravating acute complications of diabetes. At present, China is facing a serious dual epidemic of tuberculosis and diabetes, which has caused great harm to the health of our people, but also brought great burden to our social economy. In this paper, PubMed, Web of Science, CNKI and Wanfang data knowledge service platform were used to search the relevant literature. Research progress on the epidemiology of tuberculosis patients complicated with diabetes, the effect of diabetes and blood glucose on the treatment outcome of tuberculosis patients, and the mechanism of diabetes affecting the treatment outcome of tuberculosis patients were analyzed and summarized, and some references were provided for the treatment and management of tuberculosis patients in China in the future.
5.Debating some issues on the formulation and application of standardized manipulations of acupuncture and moxibustion-part 6: acupoint injection.
You-Nan CHEN ; Chang-Qing GUO ; Qing-Guo LIU
Chinese Acupuncture & Moxibustion 2009;29(7):581-584
Some issues on the formulation of Standardized manipulations of acupuncture and moxibustion-part 6: acupoint injection are debated in this paper, including the definition of acupoint injection, characteristics of the standard and application of technical index etc. In the paper, the authors suggest that the issues on the selecting acupoints and drugs should be paid attention during the standard in use. Finally, the authors propose that the technical description of the acupoint injection in the reported literatures needs to be improved in order to better serve for clinical and scientific research.
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6.Roles of UGT 1A1 gene mutation in the development of neonatal hyperbilirubinemia in Guangxi.
Zong-yan GAO ; Dan-ni ZHONG ; Yi LIU ; You-nan LIU ; Lu-ming WEI
Chinese Journal of Pediatrics 2010;48(9):646-649
OBJECTIVENeonatal unconjugated hyperbilirubinemia is one of the most common conditions encountered by the practicing pediatricians. Although it is usually self-limited and benign, the condition is of importance because of the rare instances in which severe hyperbilirubinemia can lead to bilirubin encephalopathy or kernicterus. The uridine diphosphate-glucuronosyl transferase 1A1 (UGT 1A1) gene controls bilirubin conjugation by determining the structure of the enzyme glucuronosyltransferase, which is synthesized in the hepatocyte. In the recent years much has been learned about the relationship between UGT 1A1 gene mutation and neonatal hyperbilirubinemia. This study aimed to investigate the roles of UGT 1A1 gene mutation in the development of neonatal hyperbilirubinemia in Guangxi.
METHODSA total of 73 cases with hyperbilirubinemia and 31 healthy neonates were enrolled. UGT 1A1 G71R genotypes were identified by the (amplification refractory mutation system, ARMS) and direct sequencing method in all the neonates. To analyze the incidence of bilirubin encephalopathy, the peak (total serum bilirubin, TSB) concentration after 72 hours of age, and the possibility of TSB > 20 mg/dl of each group.
RESULTS(1) The frequencies of allele G71R were 0.1915 in this study, 0.2329 in hyperbilirubinemia group vs. 0.097 in healthy groups. The allele gene frequency of G71R in neonatal hyperbilirubinemia was higher than that in the normal group (P < 0.05). (2) Homozygous neonates had higher possibility to develop bilirubin encephalopathy and higher TSB concentration 72 hours after birth (28.57%, 23.12 ± 4.58) than the normal group (0%, 17.68 ± 2.69). The difference between the former two was significant (P < 0.001). (3) The TSB of the 5 neonates was > 20 mg/dl in G71R homozygous type, the odds ratio and 95%CI were 7.955 (1.349, 46.899).
CONCLUSION(1) G71R mutation gene was associated with neonatal jaundice in Guangxi region. (2) The possibility of TSB > 20 mg/dl in G71R homozygous was higher than those of the wild-type. (3) The incidence of bilirubin encephalopathy and TSB concentration after 72 hours of age for neonates who were homozygous to G71R gene were higher than the wild-type.
Case-Control Studies ; China ; epidemiology ; Genotype ; Glucuronosyltransferase ; genetics ; Humans ; Hyperbilirubinemia, Neonatal ; epidemiology ; genetics ; Infant, Newborn ; Mutation
7.Relationship between glucose-6-phosphate dehydrogenase gene mutations and neonatal jaundice in Naning, Guangxi.
Dan-Ni ZHONG ; Zong-Yan GAO ; You-Nan LIU ; Yi LIU ; Lu-Ming WEI
Chinese Journal of Contemporary Pediatrics 2009;11(12):970-972
OBJECTIVETo study the correlation between glucose-6-phosphate dehydrogenase (G-6-PD) activities and three common mutations of G-6-PD gene G1388A, G1376T and A95G and investigate the effects of G-6-PD gene mutations on neonatal jaundice in Nanning, Guangxi.
METHODSOne hundred and twenty-four neonates from Nanning, Guangxi, with hyperbilirubinemia were enrolled. The ARMS-PCR and PCR/REA methods were used to determine G-6-PD gene mutations. G-6-PD activities were measured using the NBT method. The incidence of acute bilirubin encephalopathy and the peak bilirubin concentration 72 hrs after birth were compared between the neonates with different genotypes and between the G-6-PD mutation and normal groups. The risk of blood serum bilirubin >340 mumol/L was evaluated by logistic regression analysis.
RESULTSOf the 124 cases, gene mutations were found in 37 cases, including G1388A (n=20), G1376T (n=14), A95G (n=4) and G1388A+A95G (n=1). Five cases (25%) showed normal G-6-PD activities in the G1388A gene mutation group and 4 (29%) had normal G-6-PD activities in the G1376T G1388A gene mutation group. All of 4 cases of A95G G1388A gene mutation showed a deficiency of G-6-PD activities. There were no significant differences in the incidence of acute bilirubin encephalopathy and the peak bilirubin concentration 72 hrs after birth between the G1388A and G1376T G1388A gene mutation groups. The incidence of acute bilirubin encephalopathy, the peak bilirubin concentration 72 hrs after birth and the risk of serum bilirubin >340 micromol/L in the G-6-PD mutation group were not different from the normal group.
CONCLUSIONSG1388A, G1376T and A95G are common G-6-PD gene mutations in Nanning, Guangxi. The false negative results may be received when the NBT method is used for diagnosis of G-6-PD deficiency. There are similar effects on the incidence of acute bilirubin encephalopathy and the peak bilirubin concentration 72 hrs after birth between different gene mutation groups. G-6-PD gene mutations alone may not contribute to the development of acute bilirubin encephalopathy and the changes of peak bilirubin concentration 72 hrs after birth and the risk of serum bilirubin >340 micromol/L.
Bilirubin ; blood ; Encephalitis ; etiology ; Female ; Genotype ; Glucosephosphate Dehydrogenase ; genetics ; metabolism ; Glucosephosphate Dehydrogenase Deficiency ; genetics ; Humans ; Infant, Newborn ; Jaundice, Neonatal ; blood ; genetics ; Male ; Mutation
8.Association of CXCR4 and SDF-1alpha with organ-specific metastasis of nasopharyngeal carcinoma.
Hua-nan LUO ; Xiang-ping LI ; Xiong LIU ; Guo-hua ZHANG ; You-li LIU
Chinese Journal of Oncology 2009;31(4):260-264
OBJECTIVETo explore the role of CXCR4/SDF-1alpha axis in organ-specific metastasis of nasopharyngeal carcinoma (NPC) by assessment of CXCR4 expression in NPC cells and SDF-1alpha expression in distant target organs of NPC.
METHODSThirty patients with NPC and fifteen normal subjects were recruited in this study. The expressions of CXCR4 in NPC and normal cases were identified by RT-PCR and immunohistochemistry (IHC), then the relationship between CXCR4 expression and clinicopathological factors was analyzed. IHC was also used to analyze the SDF-1alpha protein expression in normal cervical lymph nodes (including normal superior and inferior deep cervical lymph nodes), bone marrow, lung, liver, kidney and colon tissues of NPC patients (5 cases/each group).
RESULTSThe relative expression level of CXCR4 mRNA in NPC (0.71 +/- 0.22) was significantly higher than that of normal nasopharynx tissues (0.14 +/- 0.07, F = 27.94, P < 0.05). The relative expression level of CXCR4 protein in NPC (1.58 +/- 0.59) was significantly higher than that of normal nasopharynx tissues (0.51 +/- 0.22, F = 17.75, P < 0.05). The high expression levels of CXCR4 mRNA and protein in NPC were closely related to clinical stage, cervical lymph node metastasis and cancer cell differentiation (P < 0.05). SDF-1alpha protein was strongly expressed in normal superior deep cervical lymph nodes, bone marrow, lung and liver (2.35 +/- 0.67), but absent or very poor expression in inferior deep cervical lymph nodes, kidney and colon tissues (0.68 +/- 0.23), and the differences between them were statistically significant (t = 10.13, P < 0.01).
CONCLUSIONCXCR4 is closely correlated to metastasis of nasopharyngeal carcinoma. CXCR4/SDF-1alpha axis may play an important role in organ-specific metastasis of NPC.
Adult ; Aged ; Bone Marrow ; metabolism ; Cell Differentiation ; Chemokine CXCL12 ; genetics ; metabolism ; Female ; Humans ; Liver ; metabolism ; Lung ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Metastasis ; Neoplasm Staging ; RNA, Messenger ; metabolism ; Receptors, CXCR4 ; genetics ; metabolism ; Young Adult
9.The significance of serum GM and BG antigens assay for invasive fungal infections in hematological malignancies patients.
Shu-ying ZENG ; Ting LIU ; Wen-tong MENG ; You-nan CHEN
Chinese Journal of Hematology 2011;32(1):43-46
OBJECTIVETo evaluate the diagnostic value of serum galactomannan antigen (GM) and (1→3)-β-D-glucan antigen (BG) assay in invasive fungal infections (IFI) in the patients with hematologic malignancies and the role in monitoring therapeutic response.
METHODSFifty one patients with hematological malignancies met the criteria for inclusion: (1) body temperature above 38°C for 48 hours, (2) failure to respond to broad-spectrum antibiotic treatment, or (3) temperature rose again after the responded drop. Blood samples were collected twice at the first week, then once a week in at least four weeks. The double antibody sandwich enzyme-linked immunosorbent assay (ELISA) and colorimetric assay were used for detecting GM and BG. The positive GM test is defined as two consecutive tests at different time GM value > 0.5 or > 0.8 and the positive G test is defined as BG value > 80 pg/ml. The patients were assigned into four groups as proven, probable, possible, and non-fungal infection respectively, and 21 normal volunteers were as controls.
RESULTSTwo hundred and forty serum samples were collected from 51 patients including 2 of proven IFI, 26 probable IFI, 17 possible IFI and 6 non-fungal infection. The true-positive group including the proven and probable groups, and true negative group was the non-fungal infection group. GM tests were positive in 21 of 28 cases in true positive group, and only one of 6 cases in non-fungal infection. The sensitivity, specificity, positive predictive value and negative predictive value were 75%, 83.3%, 95.5% and 41.7%, respectively. G tests were positive in all 28 cases of the true positive group, and 4 in 6 non-fungal infection cases. The sensitivity, specificity, positive predictive value and negative predictive value were 100%, 33.3%, 87.5% and 100%, respectively. G test is more sensitive than GM test (P = 0.015), but there was no significant difference in specificity of the two tests (P = 0.242). In 19 of 21 patients with GM test positive, anti-fungal treatment was effective, and GM value gradually decreased to negative, two invalid patients were persistent with GM test positive. After two weeks treatment, the average GM value was significantly lower in the effective group than in the ineffective group (P < 0.05). BG values in the responded patients showed a gradual decline similar to that of GM values, but not to negative. The changes of BG value in ineffective group varied with a trend upward. The changes in BG value had no relation with treatment effectiveness.
CONCLUSIONSSerum GM and BG antigens detection provides strong evidence for early diagnosis of IFI. Combination of GM and G tests can improve the diagnostic specificity and reduce the false positive GM test seems superior to G test for monitoring GM and BG values during treatment.
Adult ; Aged ; Aged, 80 and over ; Antigens, Fungal ; blood ; immunology ; Female ; Hematologic Neoplasms ; immunology ; microbiology ; Humans ; Male ; Mannans ; immunology ; Middle Aged ; Mycoses ; blood ; immunology ; Young Adult ; beta-Glucans ; immunology
10.Prophylactic treatment with growth hormone improves intestinal barrier function and alleviates bacterial translocation in stressed rats.
Lian-an DING ; Jie-shou LI ; You-sheng LI ; Fang-nan LIU ; Li TAN
Chinese Medical Journal 2004;117(2):264-269
BACKGROUNDDamage to the gut barrier often occurs during critical illnesses. In such cases, it is very important to alleviate impairment of the intestinal barrier and protect intestinal barrier function. This study investigated the protective effect of growth hormone on intestinal barrier function in rats under stress.
METHODSThis study consisted of prospective, randomized, and controlled animal experiments. Twenty-five Sprague-Dawley rats served as total parenteral nutrition (TPN) models and were divided into three groups: TPN group, sepsis (Sep) group, and growth hormone (GH) group. Another 8 rats served as normal controls. Each group received different stress stimuli. Rats were fed for 7 days, and samples were taken for examination 24 hours after gavaging with dual saccharides.
RESULTSThe architecture of the small intestinal mucosa in the Sep group showed the most severe damage among all groups. Nitric oxide levels in blood plasma and immunoglobulin A levels in the intestinal mucosa of the GH group were significantly lower than in the Sep group (P < 0.02). There were no significant changes in CD3 counts and in the CD4/CD8 ratio between the four groups. Dual sugar tests and bacteriological examinations revealed that intestinal permeability and rate of bacterial translocation in the GH group were lower than in the Sep group (P < 0.01, respectively).
CONCLUSIONProphylactic treatment with growth hormone can alleviate damage to intestinal barrier function caused by trauma and endotoxemia in rats under stress.
Animals ; Bacterial Translocation ; drug effects ; Growth Hormone ; therapeutic use ; Intestinal Mucosa ; drug effects ; physiology ; Parenteral Nutrition, Total ; adverse effects ; Prospective Studies ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological ; physiopathology