BackgroundDiabetic retinopathy (DR) is a progressive vision-threatening complication of diabetes mellitus,but its pathogenic mechanism is still unclear. Recent studies showed that it may be associated with the inflammation response of retinal capillary. Cytokines can cause induction of proinflammatory and adhesion molecules and thereby increase monocyte endothelial cell adhesion, which is now accepted as the early key event in the development of DR. ObjectiveThe present study was to determine the relationship between the stages of DR and the levels of serum vascular endothelial growth factor (VEGF) , interleukin-2 ( IL-2 ), tumor necrosis factor-alpha (TNF-α) in diabetic patients. Methods This was a pilot case-controlled study. Ninety patients with type 2 diabetes mellitus were included in this clinical trial and 30 healthy individuals were enrolled as controls. The patients were grouped into the non-diabetic retinopathy(NDR) group,background DR group and proliferative DR(PDR) group according to the results from ophthalmoscopic examination and fundus fluorescein angiography(FFA) ,with 30 patients for each group. The levels of serum VEGF,IL-2,TNF-α were assayed by ELISA and compared among the 4 groups.Written informed consent was obtained from each subject before received any related medical examination to this study. ResultsThe mean serum VEGF levels were(217.35±27. 87)ng/L,(298.31±49.26)ng/L,and(341.23±40. 18)ng/L, respectively, and mean serum IL-2 levels were( 12. 12± 1. 57 )ng/L, (16.43 ±2. 26 )ng/L, and (21.36±0. 86) ng/L,respectively and mean serum TNF-α levels were( 11.63±0. 94) ng/L, ( 17. 52±0. 65) ng/L,and(22. 01±0. 87 ) ng/L respectively in the patients with NDR ,background DR and PDR, showing significant differences from healthy controls with( 193.46±37. 39 ) ng/L for serum VEGF, ( 8. 99 ±0. 57 ) ng/L for serum IL-2 and ( 7.31 ±0. 52 ) ng/L for serum TNF-α ( F =126. 38, P＜0. 0 1 ;F =120. 37, P＜0. 01 ;F =99. 84, P＜0. 01 ). The levels of serum VEGF, IL-2, and TNF-α in the patients with the NDR,background DR and PDR were increased significantly. The level of serum VEGF showed the positively significant correlation with serum IL-2 level and TNF-α level ( r =0. 749, P ＜ 0.01 ; r =0. 631,P＜0. 01 ). The serum levels of VEGF, IL-2 and TNF-α showed a significantly positive correlation with the prolongation and severity of DR(r=0. 791 ,P＜0. 01 ;r=0. 665 ,P＜0. 01 ;r=0. 632,P＜0. 01 ). ConclusionsVEGF, IL-2 and TNF-α play active roles in the generation and development of diabetic retinopathy, and the level of serum VEGF is closely associated with the levels of serum IL-2 and TNF-α. during the development of DR.

In the development of diabetic nephropathy (DN), reactive oxygen specie (ROS) over much in vivo leads to oxidative stress(OS)-related renal injuries, which are characterized by the structural and functional changes in glomerular and renal tubular cells in morphology. The regulative approaches of OS involve the several signaling pathways, in which, both p38 mitogen-activated protein kinase (MAPK) signaling pathway and adenosine monophosphate-activated protein kinase (AMPK) signaling pathway play the important roles as the target of anti-oxidants. The interventional actions of Chinese herbal compound prescriptions and the extracts of single Chinese herbal medicine (CHM) on OS in the kidney in DN include regulating the balance between ROS and antioxidants, reducing the production of AGEs, inhibiting the expression of growth factors and intervening the activity of signaling pathways.
Animals ; Diabetic Nephropathies ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Signal Transduction ; drug effects ; Treatment Outcome

BACKGROUND/AIMS: High-fat diets contribute to pancreatic fibrogenesis, but the pathogenesis remains unclear. This study investigated the role of nuclear factor kappa B (NF-kappaB) in high-fat diet-induced pancreatic fibrosis in rats. METHODS: Male Wistar rats were fed a high-fat diet or standard normal chow for 20 weeks. Pancreatic fibrosis was determined by Sirius red staining. Immunohistochemical staining, reverse transcription-polymerase chain reaction and Western blotting were used to identify NF-kappaB-associated genes or protein expressions. RESULTS: Inflammation, fat deposition, pancreatic stellate cell activation and fibrosis were observed in the pancreases of the high-fat diet group. NF-kappaB subunit p65 (NF-kappaB/p65) expression was localized to the nucleus, and intercellular adhesion molecule 1 (ICAM-1) was over-expressed. Pancreatic gene expression levels of NF-kappaB/p65, ICAM-1 and tumor necrosis factor alpha were all elevated significantly in rats fed a high-fat diet compared with control rats. Western blotting also revealed significantly increased levels of ICAM-1 and nuclear NF-kappaB/p65 in rats fed high-fat diets comparison with control rats. CONCLUSIONS: NF-kappaB is involved in high-fat diet-related pancreatic fibrosis.
Animals ; Blotting, Western ; Diet, High-Fat ; Fibrosis ; Gene Expression ; Humans ; Inflammation ; Intercellular Adhesion Molecule-1 ; Male ; NF-kappa B ; Pancreas ; Pancreatic Stellate Cells ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha

OBJECTIVETo investigate the feasibility and reliability on the quantitative evaluation of Colles' fracture by multislice CT (MSCT) multiplanner reconstruction (MPR).

METHODSA total of 36 patients with Colles' fracture from July 2011 to July 2014 were investigated in this study. There were 11 males and 25 females with a mean age of (42.5 ± 5.4) years old (ranged 35 to 72 years). All the patients underwent anteroposterior and lateral X-ray films and MSCT scans on wrist joints within 2 days after trauma. Images were sent to the workstation through picture archiving and conserving system (PACS). One associate chief physician independently and respectively measured the dorsal intercalation depth of distal fracture block, palmar angle and dislocation degree of wrist articular surface collapse on anteroposterior and lateral X-ray film and MSCT-MPR. The time interval between the two measurements was 2 weeks. All the data between the first and second measurement on X-ray and MPR and the mean value between the X-ray and MPR was examined with paired t-test. The pearson analyzed their correlation.

RESULTSAmong the 35 cases, 35 cases of palmar angle, 21 cases of intercalation depth and 16 cases of dislocation of wrist articular surface collapse could be measured on both X-ray and MPR. For the above parameters, the first measurement results were (12.5 ± 3.6)°, (4.5 ± 2.1) mm, (3.7 ± 1.6) mm and the second measurement results were (4.8 ± 2.2)°, (6.4 ± 3.6) mm, (2.5 ± 1.2) mm on X-ray films respectively. The first measurement results on MPR were (14.5 ± 5.3)°, (4.2 ± 1.2) mm, (5.7 ± 2.3) mm, and the results were (13.2 ± 2.6)°, (4.7 ± 2.2) mm, (4.6 ± 2.1) mm for the second measurement respectively. The three parameters between the first and second measurement on plain film had statistical difference and low correlation (r = 0.681, 0.640, 0.345, P < 0.05). The data between the first and second measurement on MPR showed that the dislocation degree of wrist articular surface collapse had statistical difference (P < 0.05) and no statistical significance was found for the other two parameters (P > 0.05), with the moderate correlation (r = 0.954, 0.854, 0.642). The three parameters had low or moderate correlation with each other on X-ray (r = 0.454, 0.532, 0.378, P < 0.05), compared with the mean value on MPR.

CONCLUSIONUsing MSCT MPR images may carry on the multiple parameter measurement of Colles fracture, to make quantitative evaluation, and repeated measurement is better reliability.

Adult ; Aged ; Colles' Fracture ; diagnostic imaging ; Feasibility Studies ; Female ; Humans ; Image Processing, Computer-Assisted ; Male ; Middle Aged ; Multidetector Computed Tomography ; methods

OBJECTIVETo investigate the frequencies and distribution of CD4+ T cells and CD8+ T cells as well as the changes of immune activation in gastric mucosa of HIV-infected individuals.

METHODS42 HIV-infected individuals were recruited into this investigation, and 36 patients had definite diagnosis of clinical stage. Biopsy of gastric mucosal tissues was performed by fiberoptic gastroscope including 10 normal people as a control group. Then, immunohistochemistry was used to detect expression of CD4, CD8 and CD38 in gastric mucosa, and the distinctions among three groups were analyzed with LEICA Qwin image analysis system.

RESULTS(1) Compared with asymptomatic HIV carriers and control group, CD4 T cells remarkably decreased in the gastric mucosa of AIDS patients (P < 0.01). In gastric mucosa of asymptomatic HIV carriers, there were still some CD4+ T cells in lymphoid follicles and stroma where CD4+ T cells were unevenly distributed, the frequency of CD4+ T cells was not significantly different between asymptomatic HIV carriers and control group (P > 0.05); (2) Phenomenon of CD8+ T cells infiltrating mucosal epithelium and gland was general in HIV-infected individuals. CD8+ T cells took on local excessive hyperplasia in gastric mucosa of some individuals. As compared with control group, CD8+ T cells markedly increased in gastric mucosa of infected individuals (P < 0.01), but the distinction of asymptomatic HIV carriers and AIDS patients was not significant (P > 0.05); (3) CD38-expressing cells mainly distributed over gastric mucosal surface to superficial layer(1/3-2/3 layer) of HIV-infected individuals, and was more intensive than control group (P < or = 0.01), but there was not noticeable difference between asymptomatic HIV carriers and AIDS patients (P > 0.05).

CONCLUSIONThe frequencies and distribution of gastric mucosal CD4+ T cells of HIV-infected individuals were closely correlated with progression of disease. Disfunction of mucosal immune system which was resulted from HIV infection and injury of CD4+ T cells could be an important cause of CD8+ T cells increasing and CD38-expressing enhancement.

ADP-ribosyl Cyclase 1 ; genetics ; immunology ; Adult ; CD4-Positive T-Lymphocytes ; cytology ; immunology ; CD8-Positive T-Lymphocytes ; cytology ; immunology ; Female ; Gastric Mucosa ; immunology ; Gene Expression ; HIV Infections ; genetics ; immunology ; HIV-1 ; immunology ; Humans ; Lymphocyte Count ; Male ; Middle Aged

OBJECTIVETo explore whether there exists coincidence of the most appearing time of clinical features of liver cancer at different longitude and latitude, according to the law of field equation and the theory of warpage of space time by Einstein.

METHODSThree regions with different longitude and latitude were selected randomly and sampled. There were 36 items altogether, including 12 clinical items, which were used to imitate the yearly cycle cosine curve. The acorphases and the ratioes of amplitudes and means were compared to justifying whether they were in the same range.

RESULTSAll the acorphases of 36 items appeared between -90.1degrees to -207.5 degrees (from april to july), existing in one third of the same range, in which 13 items occurred rhythmly (P<0.05). The image acorphases of liver cancer at the early and middle stage and gamma-glutamyl transpeptidase acorphase appeared between -98.5 degrees to -148.2 degrees (from april to may), in which 5 items occurred rhythmly (P<0.05).

CONCLUSIONIt is the same mode of the yearly biologcal cycle for liver cancer malignant growth within the most appearing time (from april to july). It will increase the detecting rate of liver cancer at the early and middle stage during this time (especially from april to may).

Carcinoma, Hepatocellular ; pathology ; Cell Cycle ; physiology ; Chronobiology Phenomena ; Hepatocytes ; physiology ; Humans ; Liver Neoplasms ; pathology ; Mathematical Computing ; Periodicity

OBJECTIVEThe effect of mesenchymal stem cells (MSCs) transplantation is poor because of the harsh environment post infarction. Our previous studies have proven that Statins could enhance the implanted bone marrow MSCs survival, but the exact mechanism remained to be clarified. We hypothesized that atorvastatin (Ator) could protect MSCs from hypoxia and serum-free (H/SF) induced apoptosis and investigated the potential mechanisms.

METHODSChinese mini-swine's bone marrow derived MSCs were cultured in vitro and exposed to hypoxia and H/SF, Ator of various concentrations (0.001 - 10 µmol/L), AMPK inhibitor-compound C (CC), PI3K inhibitor-LY294002 (LY), Ator + CC and Ator + LY. Cell apoptosis was assessed using Annexin V/Prospidine Iodine kit by flow cytometry. Phosphorylation of AMPK, Akt, endothelial nitric oxide synthase (eNOS) level and phosphorylation were tested with Western blot. Real Time-PCR was performed to analyze the gene expression of AMPK, Akt and eNOS.

RESULTSMSCs apoptosis in Ator (0.01 - 10 µmol/L) treated H/SF groups was significantly reduced compared with H/SF group (1.94% - 6.10% vs. 10.94%, P < 0.01 or 0.05). Apoptosis was higher in Ator + CC group than in 1 µmol/L Ator group (4.94% ± 0.98% vs. 2.59% ± 0.84%, P < 0.01) and similar between Ator + LY and 1 µmol/L Ator group (2.02% ± 0.45% vs. 2.59% ± 0.84%, P > 0.05). The gene expressions of AMPK, Akt and eNOS were significantly upregulated in atorvastatin treated groups. Meanwhile, phosphorylation of AMPK and eNOS increased in MSCs treated with atorvastatin (P < 0.01 or 0.05). Phosphorylation of eNOS significantly correlated with AMPK phosphorylation (r = 0.599, P = 0.004), but not with Akt phosphorylation (P = 0.263).

CONCLUSIONSAtorvastatin can protect MSCs from H/SF induced apoptosis through AMPK pathway, which resulting in activation of eNOS.

Adenylate Kinase ; metabolism ; Animals ; Apoptosis ; drug effects ; Atorvastatin Calcium ; Bone Marrow Cells ; cytology ; metabolism ; Culture Media, Serum-Free ; Heptanoic Acids ; pharmacology ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Pyrroles ; pharmacology ; Signal Transduction ; Swine

OBJECTIVETo observe the therapeutic effect of acupuncture and moxibustion on takayasu arteritis of brachiocephalic artery type and the mechanism.

METHODSThirty-one cases were treated by acupuncture and moxibustion at main acupoint Renying (ST 9) and adjuvant acupoints selected according to the symptoms. The therapeutic effect and changes of color Doppler's ultrasonic flow image (CDFI) of relevant arteries in patients before and after treatment were investigated.

RESULTSThe clinical total effective rate was 90.3%. Of the 31 cases, 5 cases were clinically cured, 16 cases were markedly effective, 7 cases improved and 3 cases were ineffective; and it was showed that acupuncture and moxibustion could enlarge the inner diameter of the injured blood vessel, increase the volume of blood flow and the elastic index of the injured blood vessel, and improve the abnormal velocity and the abnormal crest form of blood flow.

CONCLUSIONAcupuncture and moxibustion has a good therapeutic effect on takayasu arteritis of brachiocephalic artery type; acupuncture and moxibustion can improve the stenotic degree of the injured blood vessel and abnormal hemodynamics of blood flow in the limb and brain.

Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Blood Flow Velocity ; Blood Vessels ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Takayasu Arteritis ; physiopathology ; therapy ; Treatment Outcome

OBJECTIVETo focus on the study of the effect on proliferation and apoptosis of human aortic smooth muscle cells (ASMC) by adeno-associated virus (AAV) vector carrying antisense thrombin receptor (ATR) and p21 double gene co-expression system.

METHODSCultured human AMSC was infected with recombinant AAV containing ATR, p21 single gene and AP double gene respectively. The integration and expression of genes were confirmed by semi-quantitative RT-PCR. The anti-proliferation effect was determined by MTT assay. Cell cycle and apoptotic cell counts were measured through Flow Cytometry. The rate of apoptotic cells was examined with acridine orange/ethidium bromide(AO/EB) stain.

RESULTSRT-PCR indicated that the exogenous genes had been integrated into ASMC. The rates of cell survival were decreased by 16.67%, 21.60%, and 29.4% and the cell counts of G0/G1 phase were (61.8 +/- 2.9)%, (82.5 +/- 4.0)%, (80.4 +/- 6.1)% in ATR, p21 and AP group respectively after rAAV infected 4 days. The level and area of apoptotic peak were greater in AP double gene than ATR and p21 single gene. Cell stain indicated that apoptotic cells were (7.2 +/- 3.3)%, (10.7 +/- 5.6)%, and (18.3 +/- 2.7)% in each transgene group compared with (1.5 +/- 0.8)% in control group.

CONCLUSIONAP double gene co-expression system has powerful effect for inhibiting proliferation and inducing apoptosis ASMC than ATR and p21 single gene and that is a superior way for gene therapy to restenosis.

Adenoviruses, Human ; genetics ; Antisense Elements (Genetics) ; Aorta ; cytology ; Apoptosis ; Cell Division ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins ; biosynthesis ; genetics ; Fetus ; Genetic Vectors ; Humans ; Muscle, Smooth, Vascular ; cytology ; Receptors, Thrombin ; biosynthesis ; genetics

OBJECTIVETo study the molecular genetic mechanism of mucopolysaccharidosis type IV A(MPS IV A), and reveal the relationship between the genotype and phenotype, and provide a basis for prenatal gene diagnosis in the future.

METHODSA preliminary diagnosis was made by qualitative detection of urinary glycosaminoglycans of the suspected MPS IV A proband. Then, mutation detection was performed on the proband and her family members with PCR and direct sequencing of the PCR products. After a novel c.1567T to G mutation was detected, Xsp I restriction enzyme digestion and amplification refractory mutation system (ARMS) fast specific identification were established to analyze the sequences of exon 14 in GALNS gene, including 110 randomly selected healthy controls, the proband and other pedigree members. At the same time, bioinformatic approaches for protein secondary, tertiary structure prediction were applied to identify the novel pathologic mutation.

RESULTSThe proband's urine GAGs test was a weak positive(± ), and a c.1567T to G heterozygous termination codon mutation in exon 14 and a c.374C to T heterozygous missense mutation in exon 4 were found. The proband was compound heterozygous of the two mutations, so was her younger sister. Her mother was a carrier with only a c.1567T to G heterozygous mutation in exon 14. Her father had a heterozygous mutation of c.374C to T in exon 4. After Xsp I restriction enzyme digestion, healthy controls had three bands including 28 bp, 120 bp and 399 bp, while the proband and her mother had four bands consisting of 28 bp, 120 bp, 148 bp and 399 bp. For amplification by ARMS specific primers, it was negative for the controls, while it was positive for the proband and the carrier. The results of protein secondary and tertiary structure prediction showed that the c.1567T to G mutation located in the stop codon, resulted in stop codon (TAG) changing to glutamic acid (GAG), with the peptide chain extending 92 amino acid residues, and secondary and tertiary protein structure change, which were not found in the controls. The result of enzyme assay showed that the activity of GALNS enzyme in the affected child was 8.3 nmol/17h/mg pr, which was obviously lower than the normal value (the normal range is 41.9-92.1 nmol/17h/mg pr).

CONCLUSIONThese results illustrate that the c.1567 T to G is a novel pathologic mutation, which is the main cause of the disease in this family.

Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Chondroitinsulfatases ; chemistry ; genetics ; metabolism ; Female ; Genotype ; Humans ; Infant ; Molecular Sequence Data ; Mucopolysaccharidosis IV ; enzymology ; genetics ; Mutation ; genetics ; Pedigree ; Protein Conformation ; Sequence Alignment