1.Effect of umbilical cord blood stem cells on blood glucose levels and PDX-1 and MafA levels in type 1 diabetic rats
Junwen DU ; Tao WU ; Kun ZHANG ; Baiyu SU ; Caiping LU ; Weichao WANG ; Lin LEI ; Jingxia GUO
Chinese Journal of Tissue Engineering Research 2015;(36):5833-5837
BACKGROUND:Type 1 diabetes mel itus is an autoimmune disease, which is characterized as the selective destruction of pancreatic beta cel s in the body, resulting in the lack of insulin secretion. Umbilical cord blood stem cel s have the potential to differentiate into islet cel s in vitro and in vivo, which play a certain hypoglycemic effect. OBJECTIVE:To explore the effects of umbilical cord blood stem cel s on blood glucose levels and PDX-1 and MafA levels in the pancreatic tissue of type 1 diabetic rats. METHODS:Thirty Sprague-Dawley rats were randomly divided into three groups, with 10 rats in each group. In treatment and model groups, type 1 diabetes mel itus modes were established. After modeling, the treatment group was given a single tail vein injection of umbilical cord blood stem cel s;the normal control group was given the same volume of normal saline;the model group was given the same volume of umbilical cord blood stem cel buffer solution. Oral glucose tolerance test was adopted to assess the islet function of rats;hematoxylin-eosin staining was used to observe the pancreatic morphology of rats;western blot and PCR methods were employed to detect expressions of PDX-1 and MafA in pancreatic tissues at protein and mRNA levels. RESULTS AND CONCLUSION:(1) Compared with the normal control group, the levels of blood glucose in the model and treatment groups were significantly higher at 0, 30, 60, 90 minutes (P<0.05). At 120 minutes, the blood glucose level in the model group was significantly higher than that in the normal control group (P<0.05), but there was no difference between the treatment and normal control groups (P>0.05). (2) The number of islets in the model group was decreased, and the boundary was unclear and irregular;in the treatment group, the number of islets was decreased, but the boundary was stil clear. (3) The expressions of PDX-1 and MafA in the treatment group were similar to those in the normal control group (P>0.05), but significantly higher than those in the model group (P<0.05). These findings suggest that the umbilical cord blood stem cel transplantation can significantly reduce the blood glucose levels in type 1 diabetic rats, improve the function of islet and morphology of pancreas, and up-reuglate the expressions of PDX-1 and MafA.
2.Thrombospondin-1 expression in the kidney of a rat model of fibrosis
Junwen DU ; Tao WU ; Kun ZHANG ; Baiyu SU ; Caiping LU ; Weichao WANG ; Lin LEI ; Jingxia GUO
Chinese Journal of Tissue Engineering Research 2016;20(27):4098-4104
BACKGROUND:Thrombospondin-1 is an important endogenous activator of transforming growth factor beta 1 in this experimental inflammatory kidney disease model. Transforming growth factor beta 1 is considered the major cytokine that causes tissue fibrosis in many different inflammatory disease processes, in particular in renal disease.
OBJECTIVE:To investigate the expression of thrombospondin-1 on renal fibrosis in rats.
METHODS:Healthy male Sprague-Dawley rats were randomly divided into sham surgery group and model group. In themodel group, right ureters of rats were ligated to construct models of renal fibrosis. 3 weeks after surgery, blood and urine were obtained weekly. Enzyme linked immunosorbent assay and Bradford method were used to detect the contents of serum creatinine,blood urea nitrogen and urinary protein. After rats were sacrificed, kidneys were fixed. Western blot assay was utilized to identify the expression of vascular endothelial growth factor, transforming growth factor beta 1 and thrombospondin-1 protein. Hematoxylin-eosin staining was applied to detect the changes in pathological structure of the kidney after surgery.
RESULTS AND CONCLUSION:(1) One week after model induction, urinary protein, serum creatinine and urea nitrogen levels were significantly higher in the model group than in the sham surgery group (P< 0.05). Three weeks later, the difference in each index was significant (P< 0.01), which showed that the injury of the kidney was aggravated. (2) Transforming growth factor beta 1 protein and thrombospondin-1 expression was significantly higher in the model group than in the sham surgery group, but vascular endothelial growth factor protein expression was significantly lower in the model group than in the sham surgery group. (3) Hematoxylin-eosin staining results demonstrated that severe pathological changes of renal tissue in rats were detected after ligation of renal tubule. (4) These results confirmed that thrombospondin-1 expression increased in renal tissue, and its expression was strongly associated with vascular endothelial growth factor protein and transforming growth factor beta 1, which may play an important role in the renal fibrosis.
3.Transplantation of bone marrow mesenchymal stem cells to improve blood glucose and urinary total protein levels in diabetic nephropathy rats
Junwen DU ; Tao WU ; Kun ZHANG ; Baiyu SU ; Caiping LU ; Weichao WANG ; Lin LEI ; Jingxia GUO
Chinese Journal of Tissue Engineering Research 2016;20(6):855-860
BACKGROUND:Common strategies for preventing diabetic nephropathy include effective control of blood sugar and blood pressure, inhibition of the rennin-angiotensin system and lipid-lowering therapy, but it is often difficult to get the desired results. OBJECTIVE:To investigate the effect of transplantation of bone marrow mesenchymal stem cels on levels of blood glucose and urinary total protein in diabetic nephropathy rats. METHODS: Forty-five Sprague-Dawley rats were randomly divided into three groups (n=15 per group): normal control group, diabetic nephropathy group and stem cel transplantation group. Rats in the diabetic nephropathy and stem cel transplantation groups were given single use of 60 mg/kg streptozotocin to make diabetic nephropathy models. The same dose of citric acid-sodium citrate buffer was injected in the normal control group. After modeling, 200μL of bone marrow mesenchymal stem cel solution (2×106) was injected into the left ventricle of rats in the stem cel transplantation group, and then at 7 days after the first transplantation, the cel transplantation was conducted again. The same dose of serum-free L-DMEM was injected intracardialy into the rats in the normal control and diabetic nephropathy groups. Levels of urinary total protein and blood glucose were detected. RESULTS AND CONCLUSION:At 1, 4, 8 weeks after treatment, the urinary total protein and blood glucose levels were significantly higher in the stem cel transplantation group and diabetic nephropathy group than the normal control group (P < 0.05). At 1 week after treatment, the urinary total protein and blood glucose levels were significantly lower in the stem cel transplantation group than the diabetic nephropathy group (P < 0.05). At 4 and 8 weeks after treatment, the total urinary protein and blood glucose levels were slightly higher in the diabetic nephropathy group than the stem cel transplantation group, but there was no significant difference (P > 0.05). These findings indicate that bone marrow mesenchymal stem cel transplantation in diabetic nephropathy rats can get good results in a short period, significantly improve the blood glucose and urinary total protein levels, but the long-term treatment effect is poor.
4.Clinical value of PET /CT imaging of cerebral blood flow and metabolism in patients with chronic disorders of consciousness
Kun SHANG ; Jie LU ; Yusheng SU ; Ze LI ; Dongmei SHUAI ; Zhigang LIANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(12):777-781
Objective To investigate the value of PET/CT imaging of cerebral glucose metabolism (CGM)and cerebral blood flow (CBF)in evaluating chronic disorders of consciousness (CDC).Methods A total of 10 CDC patients (5 males,5 females,age (50.9 ±17.2)years)and 10 healthy controls (5 males,5 females,age (52.0±10.3)years)from January 2016 to March 2017 were recruited to perform brain PET/CT of CGMand CBF.The brain PET imaging using 13 N-Ammonia was performed and followed by 18 F-fluorodeoxyglucose (FDG)PET.The mean standardized uptake values (SUVmean )of frontal,parietal, temporal and occipital lobes as well as basal ganglia,thalamus were obtained.The SUVmean of cerebral re-gions/SUVmean of cerebellum ratios (SUVr )were acquired.The SUVr were compared between the patients and controls.The imaging characteristics of CGM and CBF were investigated,and their relationships with clinical scores were further analyzed.Two-sample t test and Pearson correlation analysis were used to analyze the data.Results The radioactive distribution in the brain of healthy controls was symmetrical.SUVr of cer-ebral regions in the affected side of patients were significantly lower than those of the controls both in CGM imaging and CBF imaging (t values:2.90-5.19,all P<0.05).In 10 CDC patients,there were 9 with hypo-metabolism in basal ganglia and thalamus,8 with hypometabolism in frontal and parietal lobes,and 7 with hypometabolism in temporal and occipital lobes.At the same time,there were 7 with parietal hypoperfusion and 6 with hypoperfusion in other cerebral regions in the CDC patients.In the frontal,parietal lobes and basal ganglia,the CGMand CBF were both correlated with the clinical scores (r values:0.473-0.606,all P<0.05).Abnormal metabolism-perfusion patterns were divided into 3 types.Type Ⅰ included 2 patients and their hypometabolism and hypoperfusion were mismatched completely.Type Ⅱ included 3 patients and their hypometabolism and hypoperfusion were matched in frontal,parietal,occipital and temporal lobes,while mismatched in basal ganglia and thalamus.Type Ⅲ included 5 patients and their hypometabolism and hypoperfusion were matched completely.The clinical scores of typeⅠ,Ⅱand Ⅲ were 10.5,8.3 and 5.6, respectively.Conclusion The PET/CT imaging of cerebral blood flow and metabolism is useful in evalua-ting the disorders of consciousness.
5.Observation on clinical effect of continuous venous-venous hemofiltration combined with hemoperfusion for treatment of hypertriglyceridemia pancreatitis
Kun DING ; Dongdong SU ; Lu ZHOU ; Rengui CHEN ; Na LIU ; Ting YE ; Wenqi ZHAO
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2018;25(1):76-80
Objective To explore the clinical effect of continuous venous-venous hemofiltration (CVVH) combined with hemoperfusion (HP) in treatment of patients with hypertriglyceridemia pancreatitis (HTGP). Methods The clinical data of 33 patients with moderate and severe HTGP who were treated by CVVH combined with HP were retrospectively analyzed from March 2012 to March 2017 in Wuhan general hospital of the people's liberation army. The differences of vital signs and the serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), amylase (AMS), interleukin-6 (IL-6), blood calcium (Ca2+) and white blood cell count (WBC), haemoglobin (Hb), platelet count (PLT) before and 24 hours,72 hours and 1 week after therapy were compared, the changes of recovery time to target serum TG level, frequency of blood purification therapy, time for disease situation becoming stable, days staying in hospital and mortality were observed. Results The levels of LDL were not high in patients with HTGP, the levels of TG and TC were decreased significantly after using CVVH plus HP, and after treatment for 24 hours statistical differences appeared compared with those before treatment [TG (mmol/L):7.14±1.04 vs. 11.90±2.03, TC (mmol/L): 7.47±1.04 vs. 10.20±1.26], the decline persisting to 1 week after treatment;the drop rates of TG and TC were the largest after the first combined treatment, and the TG drop rate was more obvious than that of TC [(51.92±14.18)% vs. (30.09±10.01)%, P < 0.05], an average of (2.58±1.45) days and (2.38±0.98) times of combined blood purification could restore the TG to its safe level (TG < 5.65 mmol/L), the time of disease situation tending to be stable was (7.46±3.05) days and the time of staying in hospital was (20.00±2.12) days. Systemic inflammatory response syndrome (SIRS) related vital signs and inflammatory response indicators were also improved obviously after the combined therapy (all P < 0.05), after treatment for 72 hours, various vital signs and Ca2+reached to their normal reference ranges, after treatment for 24 hours IL-6 began to decline significantly compared with that before treatment (ng/L: 120.85±16.45 vs. 151.05±18.19), and AMS and WBC returned to their normal reference ranges after treatment for 1 week. Conclusion CVVH combined with HP can quickly and effectively eliminate TG in blood in patients with HTGP and in the mean time it may ameliorate and block the early progression of SIRS, resulting in good therapeutic effect on alleviating the disease development and improving its prognosis.
6.Effect of hemodialysis combined with hemoperfusion on sleep quality in maintenance hemodialysis patients
Rengui CHEN ; Na LIU ; Ting YE ; Lu ZHOU ; Wenqi ZHAO ; Kun DING ; Dongdong SU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2018;25(2):181-183
Objective To study the effects of hemodialysis (HD) combined with hemoperfusion (HP) on sleep quality in maintenance hemodialysis (MHD) patients. Methods Sixty MHD patients admitted to Department of Blood Purification of Wuhan General Hospital of PLA from January to December 2016, 30 cases were treated with HD, and the other 30 cases were treated by HD+HP, the course of treatment was 12 weeks in both groups. The changes of serum β2-microglobulin (β2-MG) and parathyroid hormone (iPTH) were observed before treatment and 12 weeks after treatment; the sleep quality of all patients in the two groups were evaluated by Pittsburgh Sleep Quality Index (PSQI) Scale, and the correlations between the sleep quality of MHD patients andβ2-MG level, iPTH level were analyzed by Pearson linear correlation analysis. Results All the 60 patients completed the treatment. The serum β2-MG, iPTH levels and PSQI score after treatment were decreased obviously in HD+HP group compared with those before treatment, and the degrees of decrease in HD+HP group were more significant than those in the HD group [β2-MG (mg/L): 12.34±2.12 vs. 20.27±3.15, iPTH (ng/L): 224.54±100.28 vs. 398.42±155.37, PSQI score:8.56±0.86 vs. 12.45±0.88, all P < 0.05]. Pearson linear correlation analysis showed that the PSQI score was significantly positively correlated with serum β2-MG, iPTH level (r respectively was 0.416 and 0.462, both P < 0.01). Conclusion HD+HP therapy can significantly improve the sleep quality of MHD patients, and the mechanism may be related to the elimination of serum iPTH and β2-MG from the body of MHD patients.
7.An observation of curative effect of cinacalcet combined with activated vitamin D for treatment of patients with secondary hyperparathyroidism undergoing maintenance hemodialysis
Lu ZHOU ; Wenqi ZHAO ; Ting YE ; Kun DING ; Rengui CHEN ; Na LIU ; Dongdong SU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2017;24(6):650-653
Objective To observe the clinical curative effect of cinacalcet combined with activated vitamin D for treatment of patients with secondary hyperparathyroidism (SHPT) undergoing maintenance hemodialysis (MHD).Methods Eighty-six patients with SHPT undergoing MHD admitted to the Blood Purification Center of Wuhan General Hospital of Chinese People's Liberation Army from April 2014 to April 2016 were enrolled, and they were divided into an observation group and a control group by random number table, 43 cases in each group. The patients in control group were given cinacalcet whose initial dose was 25 mg/d and maximum dose should not exceed 75 mg/d, and the calcium acetate orally; on the basis of control group, the patients in observation group were additionally given activated vitamin D therapy, and both groups were treated for consecutive 12 weeks. After treatment, the clinical therapeutic effect, serum calcium, serum phosphorus, calcium phosphorus product, intact parathyroid hormone (iPTH) levels and the incidence of adverse reactions were compared between the two groups.Results The total effective rate in observation group was higher than that of the control group [90.70% (39/43) vs. 74.42% (32/43),P < 0.05]. After treatment, the difference of the serum calcium, calciumphosphorus product were higher than those before treatment in both groups [serum calcium (mmol/L): the control group was 2.24±0.25 vs. 1.99±0.26, observation group was 2.60±0.21 vs. 2.03±0.24; calcium phosphorus product (mmol2/L2): the control group was 4.05±0.34 vs. 3.79±0.35, observation group was 4.25±0.37 vs. 3.86±0.36, allP < 0.05], serum phosphorus, iPTH were lower than those before treatment in both groups [phosphorus (mmol/L): the control group was 1.69±0.14 vs. 2.09±0.12, observation group was 1.15±0.18 vs. 2.03±0.16; iPTH (ng/L): the control group was 297.36±59.73 vs. 499.54±69.32, observation group was 198.53±57.32 vs. 492.92±67.54, allP < 0.05], the degrees of changes in observation group were more significant than those in control group [serum calcium (mmol/L): 2.60±0.21 vs. 2.24±0.25, serum phosphorus (mmol/L): 1.15±0.18 vs. 1.69±0.14, calcium phosphorus product (mmol2/L2): 4.25±0.37 vs. 4.05±0.34, iPTH (ng/L): 198.53±57.32 vs. 297.36±59.73, allP < 0.05]; and the incidence of adverse reactions was significantly lower in observation group than that of the control group [4.65% (2/43) vs. 20.93% (9/43),P < 0.05].Conclusion Cinacalcet combined with activated vitaminD for treatment of SHPT patients undergoing maintenance hemodialysis shows obvious curative effect, reduces the whole segment of iPTH, and simultaneously has less adverse reactions.
8.Efficacy of early treatment via fiber bronchoscope in children with Mycoplasma pneumoniae pneumonia complicated by airway mucus obstruction.
Li-Jie CAO ; Jian-Hua LIU ; Jin-Feng SHUAI ; Bo NIU ; Su-Kun LU ; Kun-Ling HUANG
Chinese Journal of Contemporary Pediatrics 2018;20(4):298-302
OBJECTIVETo study the efficacy of early treatment via fiber bronchoscope in children with Mycoplasma pneumoniae pneumonia (MPP) complicated by airway mucus obstruction.
METHODSAccording to the time from admission to the treatment via fiber bronchoscope, the children with MPP who were found to have airway mucus obstruction under a fiber bronchoscope were randomly divided into early intervention group (≤3 days; n=40) and late intervention group (>3 days; n=56). The two groups were compared in terms of clinical data and imaging recovery.The children were followed for 1-3 months.
RESULTSOf the 96 children, 38 were found to have the formation of plastic bronchial tree, among whom 10 were in the early intervention group and 28 were in the late intervention group (P=0.01). Compared with the late intervention group, the early intervention group had a shorter duration of fever, length of hospital stay, and time to the recovery of white blood cell count and C-reactive protein (P<0.05), as well as a higher atelectasis resolution rate (P<0.05). Compared with the late intervention group, the early intervention group had a higher percentage of children with a ≥ 60% absorbed area of pulmonary consolidation at discharge. After 3 months of follow-up, the early intervention group had a higher percentage of children with a ≥ 90% absorbed area of pulmonary consolidation than the late intervention group (80% vs 55%; P=0.01), and the early intervention group had a lower incidence rate of atelectasis than the late intervention group (P<0.05).
CONCLUSIONSEarly treatment via fiber bronchoscope can shorten the course of the disease and reduce complications and sequelae in MPP children with airway mucus obstruction.
Airway Obstruction ; therapy ; Bronchoscopes ; Child ; Child, Preschool ; Female ; Fiber Optic Technology ; Humans ; Male ; Mucus ; Pneumonia, Mycoplasma ; complications
9.18F-FDG PET/CT imaging in temporal lobe epilepsy and extratemporal lobe epilepsy caused by focal cortical dysplasia
Yaqin HOU ; Kun GUO ; Kun SHANG ; Jingjuan WANG ; Zhenming WANG ; Haiqin ZHANG ; Yusheng SU ; Jie LU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(10):607-612
Objective:To analyze the differences in 18F-fluorodeoxyglucose (FDG) PET/CT imaging and preoperative localization between patients with temporal lobe epilepsy (TLE) and extratemporal epilepsy (ETLE) caused by focal cortical dysplasia (FCD). Methods:From April 2015 to August 2018, a total of 71 patients (45 males, 26 females, age (24.3±9.1) years) with refractory epilepsy who underwent 18F-FDG PET/CT imaging before surgery and confirmed as FCD by pathology in Xuanwu Hospital were retrospectively analyzed. Patients were divided into TLE and ETLE groups based on pathological results. 18F-FDG PET/CT images were analyzed qualitatively and compared with the operation result, then region of interest (ROI) was used to calculate the asymmetry index (AI), and evaluated the hypometabolism of every cerebral region by |AI| semi-quantitatively. Engle classification were followed-up after surgery. Independent-sample t test and χ2 test were used to analyze data. Results:Of 71 FCD patients, 35 were TLE and 36 were ETLE. The onset age of ETLE patients were younger than TLE patients ((10.1±6.5) vs (14.9±9.7) years; t=2.48, P=0.02). In TLE group, 54.29%(19/35) were completely consistent with the operation results, and 42.86%(15/35) showed hypometabolized brain regions in extratemporal lobe. In ETLE group, 27.78%(10/36) were completely consistent with the operation results, and 47.22%(17/36) showed hypometabolized brain regions in temporal lobe. There were significant differences in the lateral accuracy and positioning accuracy of 18F-FDG PET/CT between TLE and ETLE patients (97.14%(34/35) vs 75.00%(27/36), 54.29%(19/35) vs 27.78%(10/36); χ2 values: 7.19, 6.27, both P<0.05). There was no significant difference in |AI| values between the brain regions of TLE and ETLE patients ( z values: from -1.25 to -0.06, all P>0.05). Conclusion:The lateral accuracy and positioning accuracy of 18F-FDG PET/CT in TLE patients are better than that in ETLE patients.
10.Alterations of FHIT gene and P16 gene in nickel transformed human bronchial epithelial cells.
Wei-Dong JI ; Jia-Kun CHEN ; Jia-Chun LU ; Zhong-Liang WU ; Fei YI ; Su-Mei FENG
Biomedical and Environmental Sciences 2006;19(4):277-284
OBJECTIVETo study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis.
METHODS16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting.
RESULTSNiS-treated cells exhibited overlapping growth. Compared with that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases (P < 0.01) and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in p16 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8.
CONCLUSIONSThe FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.
Acid Anhydride Hydrolases ; chemistry ; genetics ; metabolism ; Animals ; Base Sequence ; Bronchi ; cytology ; Cell Line ; Cell Transformation, Neoplastic ; chemically induced ; DNA Damage ; Exons ; Gene Deletion ; Genes, p16 ; Humans ; Mice ; Mice, Nude ; Molecular Sequence Data ; Mutagenicity Tests ; Neoplasm Proteins ; chemistry ; genetics ; metabolism ; Nickel ; toxicity ; RNA, Messenger ; metabolism ; Respiratory Mucosa ; cytology ; drug effects ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA