Animals ; DNA Methylation ; Female ; Genes, Tumor Suppressor ; Genes, ras ; Humans ; Lung Neoplasms ; genetics ; metabolism ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; Signal Transduction ; Tumor Suppressor Proteins ; genetics ; metabolism ; Uterine Cervical Neoplasms ; genetics ; metabolism

OBJECTIVE To investigate the effect of phosphotyrosine interaction domain containing 1 (PID1, NYGGF4) onpromotion of IR and HCC, and explore its underlying mechanisms. METHODS Lentivirus were used to mediate the knockdown of PID1 in HFD induced IR mouse model as well as ob/ob mice. Intraperitoneal glucose and insulin tolerance were performed 4 weeks after lentivirus injection. Hydrodynamics-based transfection was applied to induce the liver specific overexpression of PID1. Flow cytometry was exerted to detect the proportion and function of immune cells.qRT-PCR and Western blot were used to detect the expression of downstream pathways of PID1. Liquid chromatography-mass spectrometry (LC-MS) and co-immunoprecipitation (Co-IP) were conducted to identify proteins interacting with PID1.Chromatin immunoprecipitation(ChIP)was operated to measure the modification of H3K4me3 of PID1 promoter.RESULTS PID1 restriction improved insulin resistance,hyperglycemia and fatty liver. Conversely, hepatic knockdown of PID1 attenuated liver xenografted tumor growth. Moreover,PID1 liver-specific protooncogenes via hydrodynamics-based transfection established a primary hepatocellular carcinoma mouse model,induced an immunosuppressive environment,with the reduction of CD3+,CD4+,CD8+T cells,retarded maturation of dendritic cells(DCs),pronounced differentiation of regulatory T cells(Tregs),and recruitment of MDSC.In addition,PID1 overexpression activated prolifer-ation related genes, promoted anti-inflammatory genes, suppressed pro-inflammatory genes, induced glycolysis and lipid metabolism genes to facilitate tumorigenesis in liver. Importantly, PID1 exerted its tumor-promoting function through binding to epidermal growth factor receptor(EGFR)and activation of downstream KRAS/ERK pathway.As such,PID1 exist trimethylation of histone H3 at lysine 4(H3K4me3) modification and IR up-regulated the expression of PID1 by activation the H3K4me3 modification. CONCLUSION PID1 is a new gene that exerts both liver cancer-promoting and insulin resistance inducing function.IR accelerates liver cancer development and progression partially dependent on the activation of PID1.

Child ; Ectodermal Dysplasia ; diagnosis ; genetics ; Family Health ; Genes, Recessive ; genetics ; Humans ; Male ; Sex Factors

ObjectiveTo observe the spatial-temporal distribution of mouse leptomeningeal lymphatic endothelial cells and their effects on behavior. MethodsImmunofluorescence was used to detect the number of Lyve-1⁺and CD68⁺ cells in the dorsal， temporal， ventral， and lateral paraventricular leptomeningeal of 1-week， 2-week， 4-week， 10-week， 15-week， and 15-month-old wild-type C57BL mice and 15-week-old APP/PS1 transgenic mice. Two-week-old C57BL mice were randomly grouped as follows： PBS-injected group， anti-Lyve-1-injected group and SAR131675-injected group， which were injected with corresponding reagents into lateral ventricle. Two weeks after injection （i.e.， 4 weeks old）， the three groups of mice were subjected to the open field experiment， the three-chamber social interaction experiment， and the novel object recognition experiment. Then their ratio of leptomeningeal lymphatic cells were detected by immunofluorescence. ResultsThere was no statistical difference in the distribution of leptomeningeal lymphatic endothelial cells in different regions （F=0.8700， P=0. 4668， df=3）. The percentage of Lyve-1⁺ cells in the leptomeninges of mice decreased with ages （F=17.30， P<0.0001， df=5）. There was no statistical difference in the proportion of Lyve-1⁺ and CD68⁺ cells in the dorsal leptomeninges of mice of different ages （F=0.2686， P=0.9244， df=5）. Proportion of Lyve-1⁺ cells in the leptomeninges of 15-week-old APP/PS1 transgenic mice was lower than that of wild-type C57BL/6 mice （t=6.381，P=0.0078）. The ratio of Lyve-1⁺ cells was lower in the leptomeningeal of anti-Lyve-1-injected mice than that in the control group （M_PBS=0.4513， M_anti-Lyve-1=0.2692， q=8.726， P<0.0001）. The ratio of Lyve-1⁺ cells in the leptomeningeal of SAR131675-injected mice was lower than that in the control group （M_SAR131675=0.3230， q=5.588， P=0.0006）. In the open field tests， SAR131675-injected mice showed reduced exploratory locomotion， but increased willingness to explore the central area. The anti-Lyve-1-injected mice showed an increased willingness to explore the central area. In the social interaction tests， the anti-Lyve-1-injected mice showed no reduction in social behavior or social preference. The SAR131675-injected mice showed reduced social behavior in terms of frequency of interaction but no social preference， suggesting that the SAR131675-injected mice had a social interaction decrease. In the novel object recognition tests， the anti-Lyve-1-injected mice showed no change in frequency， time and distance， indicating that the anti-Lyve-1-injected mice showed no change in short-term memory. The SAR131675-injected mice showed a decrease in short-term memory. ConclusionLeptomeningeal lymphatic endothelial cells play an important role in the early development of mice， which can be related to their phagocytosis of macromolecular substances.

Objective To investigate the effects of selective cyclooxygenase 2 inhibitor on the hyperplasia of parathyroid glands from uremic rats. Methods Sixty-five 5/6-nephrectomized (Nx) and fifteen sham operated rats were assigned to 4 groups: (1)Sham group (n=14):shamoperated +normal phosphate diet (P 0.8％,Ca 1.2％)； (2) Nx-HP group (n=17):Nx+high phosphate(HP) diet (P 1.2％,Ca 1.2％)； (3)Prophylactic COX2 inhibition group (Prey group,n=18):Nx+HP+celecoxib 100 mg· kg-1·d-1 for 3 months； (4)Therapeutic group (Ther group,n=18):Nx+HP+celecoxib 100 mg·kg-1·d-1 starting at the second month of the 5/6 nephrectomy.At the end of 3 month,blood,urine and parathyroid samples were collected.The expressions of COX2 and PCNA were determined by immunohistochemistry,Western blotting and real-time PCR. Results All of the Nx rats fed with high phosphate diet for 3 months manifested progressively increasing serum creatinine,serum iPTH as well as augmentation of parathyroid gland volume,suggesting that secondary parathyroid hyperplasia animal model was established successfully.Celecoxib significantly decreased serum iPTH levels [Sham (34.77±0.83),Nx-HP(100.73±4.35),Prey (87.36±2.18),Ther (87.47±1.76) ng/L,P＜0.05],the size of the parathyroid glands in Nx rats [Sham (0.461±0.089),Nx-HP (2.436±0.372),Prey (0.987±0.254),Ther (1.27±0.305) mm2/kg,P＜0.05] and PCNA expression in PG determined by Western blotting (decreased to 52.91％ in Prev group and 34.68％ in Ther group respectively,P＜0.05).No significant difference was observed between the two COX2 inhibition groups.The levels of COX2 expression in parathyroid gland were greatly increased in three Nx groups compared with that in sham group (2.47-fold in Nx-HP,2.34-fold in Prey group,3.04-fold in Ther group,P＜0.05).COX2 inhibitor had no effects on COX2 expression in PGs.Real-time PCR analysis demonstrated the same trends of mRNA expression of COX2 and PCNA in PGs of rats. Conclusion Selective inhibition of COX2 may help to suppress the hyperplasia of parathyroid glands in uremic rats.

Objective To identify a locus for hereditary symmetrical dyschromatosis(HSD).Methods A genome-wide scan was performed with402microsatellite markers in two large Chinese HSD families to map the chromosome location of the susceptible gene.The LINKAGE software(Version5.10)and CYRILLIC soft-ware(Version2.01)were used for linkage and haplotype analysis.Results A locus was identified at chro-mosome1q11-1q21with a cumulative maximum two-point LOD score of8.85at microsatellite marker D1S2343(?=0.00).Haplotype analysis indicated that the candidate gene was located within11.6cM region between markers D1S2696and D1S2635.This was the first locus identified for HSD.This study provided a map location for isolation of the candidate genes causing HSD.Conclusion Chromosome1q11-1q21contains the candidate gene susceptible for dyschromatosis symmetrica hereditaria.

OBJECTIVETo evaluate the optimal timing of hepatectomy for intrahepatic lithiasis complicated with acute cholangitis.

METHODSOne hundred and twenty-six patients with hepatolithiasis who had a history of acute cholangitis and underwent hepatectomy were reviewed retrospectively. According to the period between the surgery and last attack of acute cholangitis, 126 patients were divided into 3 groups: > 3 months (group A, n = 73), 1 approximately 3 months (group B, n = 28), < 1 month (group C, n = 25). The operation time, blood loss, hospital stay, postoperative complications and stone residual rate were compared among the groups.

RESULTSThe intraoperative blood loss of C group was (644.0 +/- 625.7) ml, which was significantly higher than those of A and B group [(409.2 +/- 250.7) ml and (423.2 +/- 237.1) ml, respectively]. The numbers of patients who needed transfusion and the amount of blood transfusion in group C were also higher than those of group A and B. The incidence rate of complications, residual stone in group C were all markedly higher than those of group A and B. The period of hospital stay in group C was much longer than that in group A and B.

CONCLUSIONSThe optimal timing of hepatectomy for hepatolithiasis complicated with acute cholangitis is at least one month after subsidence of cholangitis.

Adult ; Aged ; Bile Ducts, Intrahepatic ; Cholangitis ; complications ; Cholelithiasis ; complications ; surgery ; Female ; Hepatectomy ; methods ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Time Factors

OBJECTIVETo investigate the effect of Lupus Recipe (LR) on IL-6 and IL-10 secretion of splenic cells in vitro in lupoid model mice and on anti-dsDNA antibody.

METHODSChronic graft-versus-host disease model was used in the experiment. The model mice were divided into four groups, the model group was un-treated and the other three groups treated with LR, prednisone and combined treatment (prednisone + LR) respectively. The serum level of ds-DNA antibody, the ConA induced splenic cell proliferation in mice's splenic cell culture as well as the IL-6, IL-10 level in the supernatant of culture were determined after treatment and compared with those of normal controls.

RESULTS(1) The splenic cell proliferative reaction in the model group splenic cells was obviously higher than that of the normal control (P < 0.05); but that in the three treated groups was different from the control insignificantly (P > 0.05); (2) The serum anti-dsDNA in the model group was higher than that in the normal control, 1.75 +/- 0.25 vs 1.20 +/- 0.21 (P < 0.01), while the difference in comparison of the treated groups with the normal control was insignificant, (P > 0.05); (3) Splenic cell IL-6 and IL-10 secretion in the model group induced by ConA was higher than those in the treated groups and the controls significantly (P < 0.05).

CONCLUSIONLR reveals the effect of immunosuppressor, which could inhibit the activation of T- and B-cells, reduce the Th2 cytokine formation and auto-antibody production so as to treat lupus erythematosus effectively.

Animals ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Female ; Graft vs Host Disease ; immunology ; Immunosuppressive Agents ; pharmacology ; Interleukin-10 ; biosynthesis ; Interleukin-6 ; biosynthesis ; Lupus Erythematosus, Systemic ; immunology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Spleen ; cytology ; immunology

OBJECTIVETo improve diagnosis and therapeutic efficacy for pancreatic trauma.

METHODSWe retrospectively analyzed 71 cases of pancreatic injuries received in our department from 1987 to 2004. Different surgical procedures were performed according to different patterns of pancreatic injuries. Among them, 31 cases were defined as Grade I or II injury according to the pancreatic organ injury score developed by American Association for the Surgery of Trauma and were performed pancreas debridement and drainage; 26 cases belonged to Grade III injury and were performed distal pancreatectomy plus external drainage; 10 cases of Grade IV injury in whom 8 were performed distal Roux-en-Y pancreaticojejunostomy and 2 were performed Whipple operation; 4 cases of Grade V injury in whom 1 was performed restoration of duodenal damage, suture of proximal pancreatic laceration and distal Roux-en-Y pancreaticojejunostomy, and 3 were performed Whipple operation.

RESULTSSixty-six cases were cured, of whom 14 had postoperative complications, and 5 cases died. The causes of death were of pancreatic fistula in 2 cases, upper gastrointestinal bleeding in 1 case, ARDS in 1 case, and serious abdominal infection in 1 case.

CONCLUSIONSPreoperative diagnosis for pancreatic trauma is rather challenging. Prompt explorative laparotomy is still a reliable diagnostic method for pancreatic trauma. In order to improve curative rate, different surgical procedures should be undertaken according to different sites and grades of pancreatic traumas.

Abdominal Injuries ; diagnosis ; epidemiology ; therapy ; Adolescent ; Adult ; Aged ; China ; epidemiology ; Emergency Service, Hospital ; statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Outcome and Process Assessment (Health Care) ; Pancreas ; injuries ; Postoperative Complications ; epidemiology ; Retrospective Studies ; Treatment Outcome

This study was purposed to investigate the inhibitory effect of bactericidal permeability-increasing protein (BPI) on lipopolysaccharide (LPS)-mediated activation of platelets. Venous blood samples were obtained from 10 healthy volunteers and were prepared into platelet-rich plasma (PRP, 1 × 10(8)/ml). Experiments were divided into four groups: normal platelet group (untreated group); LPS group, BPI group and BPI+LPS group. PRP were stimulated by LPS (10 µg/ml) in the presence and absence of BPI (100 µg/ml) or BPI alone. Then platelets were harvested and determined for Toll-like receptor-4 (TLR-4) with flow cytometry (FCM), the supernatant was used for detection of cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) with enzyme-linked immunosorbent assay (ELISA). The results showed that as compared with normal platelet group, TLR-4 expression on platelets was significantly increased under LPS stimulation (P < 0.001); the levels of TNF-α and IL-6 in the supernatant were also remarkably elevated (P < 0.001). However, either TLR-4 expression or the cytokine levels significantly decreased in the presence of BPI when platelets underwent LPS-challenge (P < 0.05), but still were higher than that in normal platelet group. Stimulating the platelets with BPI alone could not enhance the TLR-4 expression and cytokine levels. It is concluded that BPI has the ability to inhibit the LPS-induced platelet activation.
Antimicrobial Cationic Peptides ; pharmacology ; Blood Proteins ; pharmacology ; Humans ; Inflammation ; Lipopolysaccharides ; adverse effects ; Platelet Activation ; drug effects ; Platelet-Rich Plasma ; metabolism ; Toll-Like Receptor 4 ; metabolism