4.PID1 based connection of insulin resistance to hepatocellular carcinogenesis
Ming XIANG ; Qian-Qian XU ; Sen-Lin LI ; Bao-Tian WANG ; Ya-Li TUO
Chinese Journal of Pharmacology and Toxicology 2018;32(4):316-316
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.
5.Investigate on rational lymph-node dissection for gastric cardia cancer.
Xiang HU ; Da-yu TIAN ; Quan BAO
Chinese Journal of Gastrointestinal Surgery 2007;10(2):127-129
OBJECTIVETo investigate the rule of lymph-node metastasis in gastric cardia cancer and the rational extent of lymph node dissection.
METHODSClinicopathological data of 77 patients with gastric cardia cancer were reviewed and the relationship between extent of lymph-node dissection and prognosis was analyzed retrospectively.
RESULTS(1) The lymph node metastasis rates were 64.9% for N(1), 14.3% for N(2) and 10.4% for N(3). (2) No lymph node metastasis was detected in T(1) stage tumor and maximum diameter of less than 2.0 cm. The lymph node metastasis rates were 20% for T(2), 68.2% for T(3) and 82.8% for T(4) respectively. (3) Lymph node No.1, 3, 2 were often involved in the metastasis of lymph node group 1, and No.7, 8, 10, 9 in Group 2. In lymph node group 3, lymph node metastasis rates were 6.5% for No.5, 1.3% for No.6, 1.3% for No.16 and 2.6% for No.107-110. (4) The five-year survival rates were 36.5% for D(3), 31.3% for D(2), and 22.7% for D(1) lymphadenectomy respectively. The survival rates of patients undergone D(2) and D(3) lymphadenectomy were significantly higher than that undergone D(1) dissection (P<0.05).
CONCLUSIOND(2) or more than D(2) lymphadenectomy associated with enlargement of esophageal hiatus via laparotomy, lower partial esophagectomy and total gastrectomy is able to achieve surgical resectability and improve the survival rate of gastric cardia cancer patients.
Cardia ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Stomach Neoplasms ; pathology ; surgery
6.Determination of serum progesterone by isotope dilution gas chromatography mass spectrometry
Tian-Jiao ZHANG ; Rui-Feng XU ; Wei-Hua WANG ; Xin-Hua DAI ; Chuan-Bao ZHANG ; Wen-Xiang CHEN ;
Chinese Journal of Laboratory Medicine 2001;0(03):-
Objective To develop a candidate reference method for the measurement of progesterone in human serum.Methods The serum sample is mixed with the internal standard [3,4-~(13)C_2] progesterone.After extraction with n-hexane and purified by a aqueous solution of 2-Hydroxypropyl-?- cyclodextrin (HP-?-CD),the serum progesterone and labeled progesterone are converted to the 3-enol heptafluorobutyrate and analyzed by gas chromatography mass spectrometry (GC/MS) with selected ion monitoring.The concentration of serum progesterone is calculated by bracketing method.Results The results gave coefficients of variation (CVs) of 0.69% to 2.12%.The analytical recoveries ranged from 98.3% to 100.1%.The results of measuring certified reference materials of serum progesterone are agree with the target value.Conclusion The procedure for measuring progesterone in serum is a highly accurate and precise method and may be used as a candidate reference method for serum progesterone assays.
7.Application of Monte Carlo simulation to optimize the dosage regimen of norvancomycin
Gan-Bin WU ; Xiang-Yu TIAN ; Lian-Qi HAO ; Ying ZHANG ; Bao-Luo WAN ; Xiao-Tian LI ; Mao-Wen GUO
The Chinese Journal of Clinical Pharmacology 2014;(5):442-444
Objective To assess and optimize the dosage regimens of nor-vancomycin in patients with different renal functions.Methods The minimum inhibitory concentration ( MIC ) distribution was determined by agar dilution method with the target value of AUC 0-24/MIC≥638.Ten thousand cases in virtue of Monte Carlo simulation were performed in dif-ferent doses to obtain probabilities of target attainment ( PTA) and cumu-lative fractions of response ( CFR ) in patients with different renal func-tions.Results For the patients with normal renal function , when En-terococcus faecium and Enterococcus faecalis were treated with recommen-ded dose , from 0.8 to 1.6 g· d-1 , the CFR were lower than 59.77%.The CFR could reach to 83.95%and 73.10%when the dose was adjus-ted to 2.5 g· d -1.For the patients with moderate renal function insuffi-ciency , the CFR could reach to 82.81% at the dose of 0.8 g · d -1 against Enterococcus faecalis.The CFR could reach from 73.10% to 86.84%at the dose from 0.8 to 2.5 g · d-1 in the process of treating Enterococcus faecium.For the patients with severe renal function insuffi-ciency , the CFR could reach to 97.77% and 85.90% respectively a-gainst Enterococcus faecalis and Enterococcus faecium.Conclusion Monte Carlo simulation provides dosage regimens and the norvancomycin regimen is complemented and optimized.
8.Changes of serum cytokine caused by acute paraquat poisoning.
Xiang-dong JIAN ; Hong SUI ; Zhong-hua CHU ; Zheng-wei ZHANG ; Bao-tian KAN ; Ling ZHANG ; Hai-ting ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2007;25(4):230-232
OBJECTIVETo observe the change of cytokine interleukin IL-1 beta, IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha) occurred in acute paraquat (PQ) poisoning rats and to investigate the mechanism of acute lung injury caused by paraquat (PQ) poisoning.
METHODSAll 72 healthy adult Wistar rats were random assigned into normal control groups, paraquat high dose group (120 mg/kg), paraquat middle dose (60 mg/kg) group, paraquat low dose group (30 mg/kg). Three observing periods of time included 8, 24, 72 h and the standards of TNF-alpha, IL-1 beta, IL-6, IL-10 were determined.
RESULTSEvery index of the PQ group was significantly higher than that in the NS group at the same period of time (P<0.05 or P<0.01). In the 72 h group, the high dose group was significantly higher than the middle and low dose group (P<0.05), and there was no significantly difference between the middle and low dose group (P>0.05). For the comparison of index in the same dose group, the group of 72 h was much higher than 8 h group and 24 h group (P<0.05), and there was no difference between the 8h group and 24 h group (P>0.05).
CONCLUSIONThe cytokine may play an important role in paraquat-induced acute lung tissue injury.
Acute Disease ; Animals ; Cytokines ; blood ; Disease Models, Animal ; Female ; Interleukin-10 ; blood ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Male ; Paraquat ; poisoning ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood
9.T allele at site 6007 of bone morphogenetic protein-4 gene increases genetic susceptibility to ossification of the posterior longitudinal ligament in male Chinese Han population.
Xiang-long MENG ; Hao WANG ; Hui YANG ; Yong HAI ; Bao-peng TIAN ; Xin LIN
Chinese Medical Journal 2010;123(18):2537-2542
BACKGROUNDSeveral candidate genes of ossification of the posterior longitudinal ligament (OPLL) susceptibility have been identified, but their polymorphisms account for only a small percent of the total variance. Bone morphogenetic protein-4 (BMP4) is a potent ectopic ossification inducing factor. BMP4 protein and mRNA are present in cells from OPLL patients, but not non-OPLL controls. A single nucleotide polymorphism of 6007C>T(rs17563) of BMP4 has been reported to affect bone density in postmenopausal women. Thus, BMP4 may function in OPLL development. Appropriately, the relationship between BMP4 polymorphisms and OPLL was investigated.
METHODSA case-control association study investigated the genetic etiology in 179 OPLL patients and 298 non-OPLL controls. Extent of OPLL was analyzed by radiologic examinations. Whether single nucleotide polymorphism (SNP) of -5826G>A(rs1957860) 5' of the transcription start site and 6007C>T(rs17563) in exon 4 of the BMP4 gene were statistically associated with genetic susceptibility to OPLL in Chinese Han subjects was assessed.
RESULTSA significant statistical difference in genotype of 6007C>T polymorphism between male OPLL patients and male controls was evident, and the frequency of "TT" genotype in male OPLL patients was significantly higher than in male controls (P = 0.039). The frequency of the "T" allele was also significantly higher in male OPLL subjects than in male controls (P = 0.014, OR = 1.57). A significant difference was also observed between the 6007C>T polymorphism and the number of ossified cervical vertebrae in OPLL patients, while no statistical difference was apparent between the -5826G>A polymorphism and OPLL occurrence.
CONCLUSIONSThe T allele in the 6007C>T polymorphism may be a risk factor for male Han Chinese with ossification of the posterior longitudinal ligament in the cervical spine. Chinese Han male patients with CT and TT 6007C>T genotypes have a genetic susceptibility to OPLL and more extensive OPLL in the cervical spine.
Alleles ; Asian Continental Ancestry Group ; genetics ; Bone Morphogenetic Protein 4 ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Ossification of Posterior Longitudinal Ligament ; genetics ; Polymorphism, Single Nucleotide ; genetics
10.Study on antiinflammatory effect of a compound TCM agent containing ant extractive in animal models.
Ri-bao WEI ; Hai-ru HUO ; Xiao-qin LI ; Ai-xiang ZHOU ; Hong SHEN ; Jia-li TIAN
China Journal of Chinese Materia Medica 2002;27(3):215-218
OBJECTIVETo study the antiinflammatory effect of a compound TCM (Traditional Chinese Medicine) agent on animal models. The agent contains ant extractive and a blent of three herbal products, herba epimedii, fructus cnidii, and fructus lycii.
METHODThree animal models to induce experimental inflammation in rats, including carrageenin--induced paw edema, cotton-ball granuloma and adjuvant induced arthritis, were chosen to study the antiinflammatory effect of the TCM agent.
RESULTThe TCM agent showed a marked inhibitory effect on edema induced by all three types of inflammation in rats, the inhibitory rate of the TCM agent at the dose of 0.20, 0.40 and 0.80 g.kg-1 in granuloma model bing over 25% at 1 hour post oral administration, and being 23.8%, 22.7%, 39.7% at 6 hour. In addition, the TCM agent also showed a significant preventive as well as therapeutic effect on adjuvant induced arthritis in rats, and improved the pathological changes of the animal joints with the induced arthritis.
CONCLUSIONTCM agent has significant antiinflammatory effects on the three above mentioned animal models.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Ants ; Arthritis ; drug therapy ; Capsules ; Cnidium ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; therapeutic use ; Edema ; drug therapy ; Epimedium ; chemistry ; Granuloma, Foreign-Body ; drug therapy ; Lycium ; chemistry ; Male ; Materia Medica ; therapeutic use ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar