The paper is to report the study of pharmacokinetics of transdermal administered nicotine in the brain of freely moving rat by using microdialysis with stable labeled isotope as internal standard. The pharmacokinetic behavior of nicotine in Sprague Dawley rat brain was investigated after intranasal administration (3.75 mg). Brain fluid samples were collected by intracerebral microdialysis with DL-nicotine as internal standard. Concentrations of nicotine and DL-nicotine in the sample were measured by HPLC-MS/MS. Main pharmacokinetic parameters were calculated and analyzed by Das 2.0 pharmacokinetic software. The recovery of nicotine and the delivery of DL-nicotine were the same. The fate of absorption and distribution was two compartment model and the values of t1/2alpha was 170.31 min, t1/2beta was 263.30 min and the AUC(0-infinity) was 2.75 x 10(5) microg x L(-1) min separately. DL-nicotine can be used to calibrate the recovery of nicotine, and the new method of stable isotope microdialysis can be used to study the pharmacokinetics of freely moving rat. It will make sense for the treatment of addiction of tobacco and provide a new thought for the research of pharmacokinetics-pharmacodynamic combination.

Objective To investigate the impacts of γ-ray radiation on gene expressions of peripheral blood lymphocytes in SD rats,and to screen differential expression genes and biological pathways closely related to radiation injury.Methods The differential gene expression of peripheral blood lymphocytes in SD rats was selected by microarray at 6 h after 2 Gy 60Co γ-ray exposure in vitro and in vivo.Bioinformatics analysis of the differentially expressed genes was performed by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases.Real-time quantitative PCR was applied to verify the screen results of the microarray.Results Fifty-five genes with three times over-expressed level were screened out from the radiation groups both in vitro and in vivo and they were involved in 6 signaling pathways.There were two differentially expressed genes of microarray assay were verified by PCR assay.Conclusions Differential expressed genes in the peripheral blood lymphocytes of SD rats could be induced by γ-ray radiation and they cooperatively contributed to a variety of biological processes.

Objective To observe the protective effects of different doses of hydrogen-rich water on radiation injury in mice,so as to provide scientific basis for the application of hydrogen-rich water.Methods The ICR mice were randomly divided into control group,irradiation group,amifostine group and hydrogen-rich water of low,medium and high dose groups.The 30 days survival rate,body weight,hematology parameters,serum biochemical parameters,organ weight and coefficient,bone marrow micronucleus rate,bone marrow nucleated cell count were observed after total body irradiation with 9.0 Gy gamma rays.Results After 30 d of irradiation,the hydrogen-rich water showed obvious protective effect on the survival rate and body weight in a dose dependent manner so that the survival was significantly higher than that of irradiation group (t =-2.67,P ＜ 0.05).The biochemical index,such as TP,ALB and CRE in the low dose group,TP,ALB,TBIL and CRE in the medium dose group,and TP,ALB,GLU,TBIL,BUN,GRE and UA in the high dose group also indicated the protective effects of hydrogen-rich water (t =-2.04--4.11,P ＜ 0.05).But the protective effect of hydrogen-rich water was not observed in hematology,organ weight and coefficient,and bone marrow micronucleus induction.Conclusions The hydrogen-rich water has anti-radiation effect,which may depend on the dose of hydrogen.

Objective To investigate the changes of gene expression profile in Beagle dogs' peripheral blood lymphocytes after acute irradiation.Methods Totally 20 male adult Beagle dogs were randomly divided into four groups including non-treatment blank control group and three radiation groups exposed to 0.5,2.0,and 5.0 Gy of γ-rays,respectively.Six hours after radiation,the peripheral blood were collected for lymphocytes isolation.Total RNA was extracted from the lymphocytes and analyzed by microarray hybridization.The differential gene profiles of radiation groups were analyzed by gene ontology (GO) analysis and kyoto encyclopedia of genes and genomes (KEGG) pathways analysis,and the alerted genes were further confirmed by the real time quantitative PCR (qRT-PCR) assay.Results Compared to the blank control group,the expressions of 308 genes in the radiation groups were perturbed over 2-fold of control,including 61 genes up-regulated and 247 genes down-regulated,which were mainly associated with immune response and cancer occurrence.The GO analysis indicated that the differential expressed genes were associated with cell connection,signal transduction,oxidation-reduction reaction and metabolism.The KEGG pathway analysis showed that some physiological and biochemical processes were involved,such as phagocytosis,tumor pathway,p53 signaling pathway,JAK-STAT signal pathway,cell differentiation,and proliferation,oxidative phosphorylation,glycogen dysplasia and other pathways.The microarray data of the alterations of apoptosis enhancing nuclease (AEN) and mitogenactivated protein kinase 13 (MAP3K13) gene expressions were further confirmed by qRT-PCR.Conclusions Exposure to different doses of acute γ-ray irradiation had significant impact on the gene expressions in Beagle dogs' peripheral blood lymphocytes and those differential expressed genes were related to a series of biological processes and pathways including immune response,metabolism and carcinogenesis.

Objective To construct lentiviral vectors containing peptide P1-GFP fusion genes.Umbilical cord derived mesenchymal stem cells were infected with lentivirus carrying peptide P1 and GFP fusion genes.To inject the targeted umbilical cord derived mesenchymal stem cells into mice and to detect GFP expression in the spleen.Methods Umbilical cord derived mesenchymal stem cells were cultured with adhered tissues of umbilical cord smaller than 1 mm3 . Lentiviral vector containing P1-GFP fusion genes with engineering technology was constructed and infected the umbilical cord derive mesenchymal stem cells.Targeted umbilical cord derived mesenchymal stem cells were intravenously injected in the mouse tail vein and after 18 hours GFP expression was detected with immunohistochamical staining of the spleen tissues.Results Harvested umbilical cord derived mesenchymal stem cells grew well in culture medium. Green fluorescence on umbilical cord derived mesenchymal stem cells were observed under fluorescence microscope at 18 hours after infected with lentivirus.Green fluorescence intensity of umbilical cord derived mesenchymal stem cells was increasing over time and reached a peak at 72 hours.Umbilical cord derived mesenchymal stem cells highly expressed CD105 (90.0%)/CD44 (98%) and CD73 (85.0%)/CD90 (98.5%) molecules.GFP expression was detected in the spleen after intravenous injection of targeted umbilical cord derived mesenchymal stem cells in the mice 18 hours later.GFP expressing cells intimately contacted with lymphocytes.Conclusions Targeted umbilical cord derived mesenchymal stem cells contain P1-GFP fusion genes are constructed.Targeted umbilical cord derived mesenchymal stem cells can be targeted to mouse spleen and intimately contact with lymphocytes after intravenous injection.Our results lay the groundwork for further studies.

OBJECTIVETo investigate the effect of aluminum exposure on neuronal apoptosis of rats hippocampus and the correlation of and synaptic plasticity.

METHODSThere were 40 SPF grade SD rats which were randomly divided into four groups: the control group, the low dose group, the medium dose group and the high dose group, 10 rats in each group. The rats were daily gavaged with aluminum lactate for 30 days. The hippocampal fEPSPs in rat was measured by electrophysiological grapher and the neuronal apoptosis in hippocampus was detected by Flow cytometer. In addition, the relative expression of gene which includes caspase-3, 8, 9 was measured by Real-time PCR.

RESULTSCompared to the control group, the average of fEPSPs which after HFS 10, 20, 30, 40, 50, 60 min was decreased at different time point in the low dose group, the medium dose group and the high dose group (P < 0.05). Compared with the control group, the rate of apoptosis was significantly increased in the medium dose group and the high dose group (P < 0.05). Compared to the control group, the relative expression of caspase-3 in the medium dose group and the high dose group was significantly increased in Real-time PCR (P < 0.05), and the relative expression of caspase-8 in the high dose group was significantly increased (P < 0.05).

CONCLUSIONAluminum exposure may induced neuronal apoptosis in rats, and then affect hippocampal synaptic plasticity.

Aluminum ; toxicity ; Aluminum Compounds ; toxicity ; Animals ; Apoptosis ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Hippocampus ; cytology ; drug effects ; Lactates ; toxicity ; Neuronal Plasticity ; drug effects ; Neurons ; cytology ; drug effects ; Rats ; Rats, Sprague-Dawley

Objective:To explore the intervention effect of Shumu Peitu herb-partitioned moxibustion on clinical signs and symptoms and negative emotions of diarrhea-predominant irritable bowel syndrome (IBS-D) patients with liver-stagnation and spleen-deficiency pattern.Methods:A total of 72 patients with IBS-D of liver-stagnation and spleen-deficiency pattern treated in the Department of Gastroenterology of Nanjing Vniversity of Chinese Medicine from September 2021 to June 2022 were selected for randomized controlled trial. The patients were randomly divided into the observation group (2 cases dropped off, 34 cases in total) and control group (1 case dropped off, 35 cases in total) by random number table method. The patients in control group were treated with Tongxieyaofang (TXYF). The patients in observation group were treated with oral administration of TXYF and Shumu Peitu herb-partitioned moxibustion, and both groups were treated for 4 weeks. The clinical efficacy, Traditional Chinese Medicine (TCM) syndrome integral, IBS Quality of Life Questionnaire (IBS-QOL), IBS Symptom Severity Scale (IBS-SSS), Bristol Stool Form Scale and Hospital Anxiety and Depression Scale (HADS) were compared before and after treatment.Results:After treatment, the total effective rate of the observation group was 94.12%(32/34), which was higher than the 71.43%(25/35) in the control group, the difference was significant ( χ2 = 6.18, P<0.05). After treatment, the TCM syndrome integral in the observation group was (7.62 ± 4.08), which was lower than the (9.89 ± 4.71) in the control group, the difference was significant ( t = 2.14, P<0.05). After treatment of 3 days, the scores of quality of life in the five dimensions of dysthymia, behavior disorder, health worry, avoidance of eating and social function in the observation group were (82.44 ± 11.46), (80.25 ± 11.67), (76.23 ± 12.67), (59.80 ± 15.14) and (79.23 ± 11.59) points, which were different with the (73.57 ± 12.39), (72.35 ± 15.48), (69.76 ± 13.11), (50.00 ± 16.17) and (73.04 ± 13.11) points in the control group, the difference were significant ( t values were -3.09 - -2.08, all P<0.05). Three days after treatment, the score of IBS-SSS and Bristol fecal character in the observation group were (118.24 ± 40.64) and (5.09 ± 0.62) points, which were lower than the (146.86 ± 60.09) and (5.51 ± 0.66) points in the control group, the difference were significant ( t = 2.31 and 2.76, both P<0.05). After treatment, the score of HADS-A and HADS-D in the observation group were (6.26 ± 1.75) and (5.29 ± 1.47), which were different with the (7.26 ± 2.19) and (6.17 ± 2.11) in the control group, the difference were significant ( t = 2.08 and 2.00, both P<0.05). Conclusions:Shumu Peitu herb-partitioned moxibustion can effectively improve IBS-D patients with liver-stagnation and spleen-deficiency pattern, relieve clinical symptoms, reduce negative emotions, and improve quality of life.

Objective To evaluate the effects of mindfulness training on diabetes-related distress and quality of life in patients with type 2 diabetes mellitus, so as to provide evidence for nursing interventions. Methods A total of 90 inpatients with type 2 diabetes mellitus were randomly assigned to a control group and an observation group of 45 cases. The control group received routine health education, while the observation group received mindfulness training by the mindfulness training team composed of seven members including psychological counselors and nurse educators. Both groups were followed up for 6 months, and the scores of diabetes-related distress and quality of life were measured before and 6 months after the intervention. t-test was adopted to compare the difference between the two groups. Results After the intervention, the total score and scores of each dimension of diabetes-related distress in the observation group were (1.81±0.40), (1.99±0.45), (1.45±0.20), (2.01±0.27), and (1.51±0.21) respectively. Correspondingly, the scores of the control group were (2.07±0.24), (2.21±0.40), (1.61±0.19), (2.57±0.25) and (2.20±0.23), which were all higher than the observation group, with statistical differences (t=3.54, 2.32, 3.69, 9.68, 14.11;P<0.05). The scores of quality of life in disease dimension, physiological dimension, psychological dimension, social dimension and satisfaction dimension were (28.41±5.40), (21.05±4.16), (21.08±5.16), (19.04±3.30) and (22.84±3.79) in the observation group, which were all lower than those in the control group respectively [(36.08±5.20), (23.80±5.00), (24.11±5.22), (21.34±3.47), (24.64±3.50)], the differences were statistically significant (t=6.51, 2.69, 2.63, 3.06, 2.22;P< 0.05). Conclusions Mindfulness training can reduce the degree of diabetes-related distress and improve the quality of life in patients with type 2 diabetes mellitus.

Objective To evaluate the effect of rational-emotive therapy on coping style and self-management behaviors among patient with type 2 diabetes .Methods Ninety in-patients with type 2 diabetes were assigned to the control group and the intervention group according to the random number table method , with 45 cases each .The control group received routine diabetic education , while the intervention group was given the education of Rational-emotive therapy.Both groups were followed up for 3 months.Their coping style and self-management behaviors were measured before and 3 months after the intervention .Results There was no statistically significant differences of the scores of coping style and self-management behaviors between two groups before the intervention (P>0.05).The score of facing was (22.44 ±3.33) in the intervention group, higher than (19.36 ±2.87) in the control group.The score of avoidance was (13.33 ±2.53) in the intervention group, lower than (14.93 ±2.61) in the control group.The score of yield was (10.00 ±2.63) in the intervention group, lower than (11.93 ±3.03) in the control group.The differences were statistically significant (t=-4.63, 2.91, 3.17, respectively;P<0.05).The score of self-management behaviors was (108.19 ±7.48) in the intervention group, higher than (100.95 ±6.24) in the control group after the intervention, and the difference was statistically significant (t=-4.90;P<0.05).Conclusions Rational-emotive therapy can improve the coping style and self-management behaviors of patients with type 2 diabetes.

By binding alpha-particle to ligands, targeted alpha-particle therapy illuminates the diseased tissue, using the radiographic energy and the range in the tissues of nuclides, and avoids damage to normal tissue to obtain the expected therapeutic effect, which is mainly used for tumor treatment. Targeted ligands are ideal drug carriers to deliver alpha-particle to the target to kill tumor cells accurately. In recent years, there have been some progresses in the research of α-radionuclide drug-based targeted ligands in nanomaterials, which have improved drug delivery and off-target effects. By summarizing the current research status, it is expected to provide reference for the development of alpha-particle drug delivery in the industry.