This study is to evaluate the effects of the metformin (Met) on β cell function of diabetic KKAy mice. Female diabetic KKAy mice selected by insulin tolerance test (ITT) were divided randomly into two groups. Con group was orally administered by gavage with water, Met group with metformin hydrochloride at a dose of 0.2 g x kg(-1) for about 12 weeks. ITT and glucose tolerance tests (OGTT) were determined. Beta cell function was assessed by hyperglycemic clamp. Pancreatic biochemical indicators were tested. The changes of gene and protein expression in the pancreas and islets were also analyzed by Real-Time-PCR and immunostaining. Met significantly improved glucose intolerance and insulin resistance in KKAy mice. Fasting plasma glucose and insulin levels were also decreased. In addition, Met markedly increased glucose infusion rate (GIR) and elevated the Ist phase and maximum insulin secretion during clamp. It showed that Met decreased TG content and iNOS activities and increased Ca(2+) -Mg(2+)-ATPase activity in pancreas. Islets periphery was improved, and down-regulation of glucagon and up-regulated insulin protein expressions were found after Met treatment. Pancreatic mRNA expressions of inflammation factors including TLR4, NF-κB, JNK, IL-6 and TNF-α were down-regulated, p-NF-κB p65 protein levels also down-regulated by Met. And mRNA expressions of ion homeostasis involved in insulin secretion including SERCA2 and Kir6.2 were up-regulated by Met. Met increased SIRT5 expression level in pancreas of KKAy mice under the hyperglycemic clamp. These results indicated that chronic administration of Met regulated pancreatic inflammation generation, ion and hormone homeostasis and improved β cell function of diabetic KKAy mice.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; drug therapy ; Down-Regulation ; Female ; Glucose Tolerance Test ; Homeostasis ; Inflammation ; drug therapy ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; Interleukin-6 ; metabolism ; Metformin ; pharmacology ; Mice ; NF-kappa B ; metabolism ; Pancreas ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo study the effect of Mudan Granule (MD) on the glucose metabolism and beta cell function in monosodium glutamate (MSG) induced obese mice with insulin resistance (IR).

METHODSMSG obese mice were induced by subcutaneous injecting MSG (4 g/kg for 7 successive days in neonatal ICR mice). Forty MSG mice with IR features were recruited and divided into four groups according to body weight, fasting blood glucose, triglyceride (TG), total cholesterol (TC), and the percentage of blood glucose decreased within 40 min in the IR test, i.e., the model group (Con), the low dose MD group, the high dose MD group, and the Metformin group (Met). Besides, another 10 ICR mice were recruited as the normal control group (Nor). The water solvent of 2.5 g/kg MD or 5 g/kg MD was respectively administered to mice in the low dose MD group and the high dose MD group. Metformin hydrochloride was given to mice in the Met group at 0.2 g/kg body weight. Equal dose solvent distilled water was administered to mice in the Nor group and the Con group by gastrogavage, once per day. All medication was lasted for 15 weeks. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were performed after 6 weeks of treatment. Beta cell function was assessed by hyperglycemic clamp technique. The morphological changes in the pancreas were evaluated by hematoxylin-eosin (HE) staining. Changes of iNOS, NF-kappaB p65, and p-NF-kappaB p65 in the pancreas were tested.

RESULTSCompared with the Nor group, the blood glucose level, AUC, and fasting blood insulin, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, pNF-kappaB p65 subunit obviously increased; decreased percentage of blood glucose within 40 min in ITT, glucose infusion rate (GIR), Clamp 1 min insulin, and Max-Insulin obviously decreased in the Con group (P < 0.05, P < 0.01). Compared with the Con group, the aforesaid indices could be improved in the Met group (P < 0.05, P < 0.01). In the low dose MD group, AUC, iNOS activities, and the expression of iNOS and p-NF-kappaB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT and GIR obviously increased (P < 0.05, P < 0.01). In the high dose MD group, AUC, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, and p-NF-KB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT, Max-Insulin, and GIR obviously increased (P < 0.05, P < 0.01).

CONCLUSIONMD could significantly improve IR and functional disorder of 3 cells in MSG obese mice, which might be associated with lowering inflammatory reaction in the pancreas.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; metabolism ; Male ; Metformin ; pharmacology ; Mice ; Mice, Inbred ICR ; Mice, Obese ; Obesity ; chemically induced ; metabolism ; Pancreas ; cytology ; drug effects ; Sodium Glutamate

Objective To investigate the immune protection of dendritic cells(DCs) harboring kinase domain-containing receptor(KDR) fusion gene on mice carrying B16 melanoma.Methods The bone marrow precursor-derived dendritic cells(BMDCs) were induced from bone marrow progenitors of mice by GM-CSF.The KDR fusion gene mRNA was transfected into DCs in vitro.Mice were immunized with the same amount of DCs at 7-day interval and then each mouse was injected with 5?10~5 B16 cells.The mice without tumors were injected with B16 cells again 20 days later.Mice were randomly divided into 4 groups: group A(n=7),group B(n=8),group C(n=8) and group D(n=7).The mice were immunized with DCs one time in group A,2 times in group B,3 times in group C and as controls in group D.Results After one week,all mice in group D had tumors with average survival 15 days.All mice in group A,B and C had no tumors after 20 days later.After the second injection of B16 cells,2 mice in group A and 2 mice in group B had tumors.The mice in group C had no tumor.The average survival periods were calculated from first injection of B16 cells to the study end.The average survival period of group A was 50 days and that of group B was 72 days.Conclusions The dendritic cells vaccine harboring KDR fusion gene has immune protection against melanoma in mice.

OBJECTIVETo observe the effect of traditional Chinese medicine storax on the concentration of combined western medicine sulpiride in brain and blood, discuss the effect of storax in inducing resuscitation and increasing the permeability of the gastrointestinal barrier (GB) and the blood-brain-barrier (BBB), and explore the interaction between storax and sulpiride.

METHODRats were orally administered with the drugs for one week, probes were implanted in their brains and necks by surgery. After balance for 60 min, brain microdialysis and blood microdialysis were adopted for collect dislysates from blood in right atrum and cerebral hippocampus at time periods of 30, 60, 90, 120, 150, 180 min. The concentration of sulpirde in the samples was detected by RP-HPLC. Statistical approaches were adopted to compare the contents of sulpirde in brain and blood of the two groups.

RESULTThe sulpiride combined with storax group showed a significant higher concentration of sulpiride than the pure sulpiride group. The pure sulpiride group showed a concentration ratio between sulpiride in brain and blood of 1:0.2; while the sulpiride combined with storax group increased the concentration ratio between sulpiride in brain and blood to 1:0.3. Compared with the pure sulpiride group, the sulpiride combined with storax group showed an increase of concentration by 39% in brain and 69% in blood.

CONCLUSIONStorax can notably increase the concentration of sulpiride in rat brain and blood, indicating that it can increase the permeation of sulpiride through gastrointestinal barrier and BBB. This study reveals the mechanism of storax in inducing resuscitation by promoting the permeation through gastrointestinal barrier and BBB.

Animals ; Antipsychotic Agents ; pharmacokinetics ; Blood-Brain Barrier ; drug effects ; Brain ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Sulpiride ; pharmacokinetics

Objective To observe the effect and the mechanisms of ferulic acid on radiationinduced damage of mice peripheral blood and bone marrow hematopoietic function.Methods Ninety-six mice were randomly divided into sham irradiation group,irradiation group,positive drug group and 10,30,90 mg·kg-1 ·d-1 ferulic acid group,16 mice per group.Mice were exposed to 3.5 Gy γ-rays 24 h after first drug taken.Then,mice were given drugs for 7 d after irradiation.White blood cells in peripheral blood of 10 mice per group were counted 2 d before irradiation and 3,7,10,15 and 22 days after irradiation.The bone narrow of the other six mice was taken to detect the micronuclei frequency of polychromatic erythrocyte,the hematopoietic progenitor cell colony formation capacity,Thbd and HMGB1 protein expressions in mice bone marrow on the seventh day after irradiation.Results Compared with the irradiation alone group,the treatment of mice with ferulic acid 90 mg· kg-1 · d-1 increased the number of white blood cells in peripheral blood at 3,10,15 and 22 d after irradiation (t =2.267,2.399,1.945,2.828,P ＜ 0.05).Treatment with mice with ferulic acid 90 mg· kg-1 · d 1 decreased the micronuclei rate of erythrocytes in irradiated bone marrow (t =4.013,P ＜ 0.05),increased the clone numbers of CFU-E,BFU-E and CFU-GM of hematopoietic progenitor cells (t =2.366,2.953,3.115,P ＜0.05),improved the relative expression of the Thbd protein in bone marrow and the HMGB1 protein in nuclear (t =17.75,23.39,P ＜ 0.01).Conclusions Ferulilc acid could protect the bone marrow hematopoietic of mice exposed to irradiation by regulating the expressions of Thbd and HMGB1 protein,and then accelerate the peripheral cells recovery.

Objective To investigate the feasibility of differentiating lymph node metastases of four types of primary tumors (lymphoma, lung adenocarcinoma, lung squamous cell carcinoma and cholangiocarcinoma) using gemstone spectral imaging (GSI) . Methods Three cases with lymphoma (28 lymph node), five cases with lung adenocarcinoma(30 lymph node), four cases with lung squamous cell carcinoma(24 lymph node) and two cases with cholangiocarcinoma( 10 lymph node) were evaluated by germstona spectra imaging CT scans. Imaging protocol included unenhanced conventional CT scan (120 kVp) ,enhanced GSI (80/140 kVp) on arterial phase and conventional CT scan (120 kVp) on portal phase. CT attenuation values of lymph nodes in the monochromatic images at 11 sets of keV levels (40-140 keV, 10 keV step) and the iodine and water contents of these lymph nodes were measured. All results were analyzed with ANOVA and t test. Results The optimal monochromatic level was 70 keV for the optimal contrast-noise ratio (CNR) of metastatic lymphadenopathy. The CT attenuation values of metastatic lymphadenopathy were (81.36 ±9. 81 ), (58.33 ± 21.55 ), (56. 47 ± 10.62) and (73. 57 ±4. 43 ) HU,respectively, at 70 keV( F = 17.29, P ＜0. 01 ). There were significant differences in CT attenuation values between lymphoma and lung adenocarcinoma, between lymphoma and lung squamous cell carcinoma and between lung squamous cell carcinoma and cholangiocarcinoma (P ＜ 0. 05 ). The differences in CT attenuation values were significant between cholangiocarcinoma and lung squamous cell carcinoma, between cholangiocarcinoma and lymphoma ( P ＜ 0. 05 ). There was no difference in CT attenuation values at all 11 sets of keV levels between lung squamous cell carcinoma and lung adenocarcinoma ( P ＞ 0. 05 ). The iodine contents of lymphoma, lung adenocarcinoma, lung squamous cell carcinoma and cholangiocarcinoma were ( 1. 93 ± 0. 04 ), ( 1.16 ± 0. 15 ), ( 1.25 ± 0. 21 ) and ( 1.44 ± 0. 04 ) g/L, respectively. The water contents of lymphoma, lung adenocarcinoma, lung squamous cell carcinoma and cholangiocarcinoma were (1029.40 ± 20. 85), (1024.98 ± 11.19), (1022.12 ± 12. 94) and (1030.87 ± 10.10) g/L,respectively. Except between lung squamous cell carcinoma and lung adenocarcinoma, the differences in the iodine contents of metastatic lymphadenopathy were significant among tumors ( P ＜ 0. 05 ). There was no difference in the water contents of metastatic lymphadenopathy among tumors ( P ＞ 0. 05 ). Conclusions Although CT spectral imaging fails to differentiate metastatic lymphadenopathy of lung adenocarcinoma and lung squamous cell carcinoma, it is also a promising method of distinguishing metastatic lymphadenopathy of malignant tumors by CT attenuation values in monochromatic images and iodine contents in material density images. The optimal monochromatic level was determined to be at 70 keV for providing the optimal CNR of metastatic lymphadenopathy.

With the popularization and development of lung CT scanning and technology of bronchoscopy in pediatrics,central airway obstruction has been diagnosed more and more.Central airway obstruction can affect airway ventilation and secretion discharge,such children are often hospitalized for repeated pneumonia,and sometimes need mechanical ventilation but may be difficult weaning from it. Malnutrition,hypoxic brain injury and backward growth and development are often associated. In the past,central airway obstruction has been mainly treated by surgery. However,with the development of minimally invasive technology of bronchoscopy in children,airway stent implantation has become an effective and alternative treatment recently. This article reviews the types of pediatric central airway obstruction,indications and contraindication of airway stent implantation,types and selection of stent,and the procedures of stent implantation.

This study is designed to test the agreement in measuring left ventricular systolic function between transthoracic two-dimensional echocardiography (2DTTE) and "gold standard" of non-invasive cardiac imaging, magnetic resonance imaging (CMRI) and their impacts on the classification of patients according to the left ventricular ejection fraction (EF). 32 patients who were suspected with heart disease were evaluated by CMRI and 2DTTE examinations. End diastolic volume (EDV), end systolic volume (ESV), EF and left ventricular function category were then calculated and compared. There was no significant difference (P=0.504) for EDV, while ESV of CMRI was significantly higher than that of 2DTTE (P=0.049), and EF of CMRI was significantly lower than that of 2DTTE (P= 0.018). There was no significant difference (P=0.077) in left ventricular functional category. Bland-Altman analysis of LV volumetric data and EF measurements showed a good agreement between two methods. The 2DTTE over-estimated I (n=5) or II (n=1) degrees of functional classification when compared with the CMRI. Both CMRI and 2DTTE are of great clinical value in evaluating left ventricular systolic function, while CMR may be more beneficial to patients with abnormal LV functions.
Adolescent ; Adult ; Aged ; Echocardiography ; Female ; Heart Diseases ; physiopathology ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Retrospective Studies ; Systole ; physiology ; Ventricular Function, Left ; physiology ; Young Adult

OBJECTIVE: To investigate the effect of NBI assisted white light transurethral resection of bladder tumor (TURBT) in the treatment of bladder urothelial carcinoma and to summarize the experience of narrow band imaging (NBI) operation. METHODS: Patients with bladder urothelial carcinoma were selected, and TURBT was performed after anesthesia. First of all, the bladder tumor was found and resected under white light. Then we replaced with NBI, looked for suspicious lesions and resected them, The specimens excised under white light and NBI were collected separately. The number, location and pathological results of the lesions under white light were recorded, and the residual lesions under NBI were also recorded. To evaluate the effect of NBI, the ratio of residual bladder tumor was calculated. The cases were divided into three groups according to the time sequence. The clinical data of each group were collected and the learning curve of TURBT under NBI assisted white light was observed. RESULTS: A prospective study of 45 patients with bladder tumor from April 2018 to January 2020, including 32 males and 13 females, aged from 23 to 89 years, with an average age of 65.2 years. All the operations were successfully completed, without obvious complications after operation. Nine cases were single and 36 cases were multiple. The maximum diameter of the tumors was 0.5 to 4.0 cm, with an average of 2.2 cm. The histopathology of the resected tissue under white light was urothelial carcinoma, and 19 cases (42.2%) were pathologically positive by NBI resection. The 45 cases were divided into three groups according to the time sequence, 15 cases in each group. The true positive rate of NBI was 33.3%, 46.7% and 46.7%, respectively, and the false positive rate was 60.0%, 46.7% and 26.7%, respectively in the three groups. CONCLUSION TURBT is an effective way to treat bladder urothelial cancer, NBI is an effective supplement of white light, which can increase the detection rate of bladder cancer and reduce post-operative recurrence. The NBI light source has a certain learning curve. With the increase of cases, the false-positive rate of NBI is gradually reduced. After the NBI operator has rich experience, the recognition degree of flat tumor is gradually improved under white light, and the residual rate of NBI is reduced after the removal under white light.
Adult ; Aged ; Aged, 80 and over ; Cystoscopy ; Female ; Humans ; Male ; Middle Aged ; Narrow Band Imaging ; Neoplasm Recurrence, Local ; Prospective Studies ; Self-Control ; Urinary Bladder Neoplasms/surgery* ; Young Adult

ObjectiveTo measure the iodine content of normal thyroid and the sternocleidomastoid muscle with gemstone spectral imaging (GSI),in order to offer diagnostic reference for iodine excess or iodine deficiency disorders.MethodsA total of 226 cases of patients with suspected neck or cervical disease underwent GSI of the neck,the thyroid and the sternocleidomastoid muscle.One hundred and nineteen cases were male and 107 female,aged 18 to 77 years,average age(46 ± 17) years.Data were transmitted to AW 4.4 workstation and processed using GSI Viewer software to obtain the best contrast-to-noise ratio(CNR) of thyroid to sternocleidomastoid muscle and corresponding singe-energy images.Iodine content of left and right thyroid lobes and both sides of sternocleidomastoid muscle as well as iodine content ratio of thyroid to sternocleidomastoid muscle were calculated in the iodine-based images.ResultsTotal iodine content of the left and the right lobes of the thyroid was (1.5233 ±0.4318)mg/cm3,of the left lobe was (1.5230 ± 0.4271 )mg/cm3,of the right lobe was (1.5236 ± 0.4365 )mg/cm3,there was no significant difference statistically between the two(t =0.0084,P ＞ 0.05).The iodine content of the male was (1.6395 ± 0.4105)mg/cm3,and of the female was (1.4238 ± 0.3832)mg/cm3,there was statistically a significant difference between the two(t =3.4743,P ＜ 0.01 ).Iodine content ratio of thyroid to sternocleidomastoid muscle was 96.6271 ± 33.2442,the ratio in male was 94.6250 ± 37.3621 and in female was 98.0000 ± 29.0737,there was no statistical difference between the two(t =0.3817,P ＞ 0.05).The iodine content of thyroid decreased gradually with age,the difference between groups was statistically significant(F =9.66,P ＜ 0.01 ).The iodine content in ＜ 40 age group[(1.7256 ± 0.4631)mg/cm3] was higher than that in 40 - 60 age group[(1.4517 ±0.3643)mg/cm3] and ＞ 60 age group [(1.4368 ± 0.3465)mg/cm3; q =5.6195,5.4158,all P ＜ 0.01).Conclusions It is easy to calculate thyroid iodine content with gemstone spectral imaging,which can reflect the iodine level of our body,and is helpful for the diagnosis of iodine excess or iodine deficiency disorders.