Adult ; Femur Head Necrosis ; chemically induced ; drug therapy ; Glucocorticoids ; therapeutic use ; Humans ; Male ; Paraquat ; poisoning

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Paraquat ; poisoning

Bridged-Ring Compounds ; poisoning ; Humans ; Male ; Middle Aged ; Poisoning ; therapy ; Treatment Outcome

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.

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

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.

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.

OBJECTIVETo investigate the clinical significance of dynamic changes of blood urea nitrogen (BUN), serum creatinine (Cr), serum cystatin (Cys C) and urinary protein on renal injury with paraquat poisoning.

METHODSAccording to the clinical manifestation and curative effect, the clinical information was analyzed retrospectively in 35 cases of acute paraquat poisoning, survival after eight weeks as the standard. Poisoning patients were taken a fasting blood 5 ml and the middle of urinary on the 1st day, 3rd day, 7th day, 14th day, 21st day and 8 weeks after the poisoning. Then the levels of serum BUN, Cr, Cys C and urinary protein were detected by automatic biochemistry analyzer. 30 cases healthy subjects were randomly selected as normal control group, and discharged kidney disease and other diseases of urinary system history. The same laboratory subjects have been done.

RESULTSThe level of serum Bun, Cr, Cys C of survival group increased significantly compared with control group within 21 days (P < 0.05). The level of serum BUN, Cr Cys C decreased on the 14th day. The decreased level of serum Cys C was lower than that of serum BUN and Cr. The renal function of 29 cases among 35 cases survival patients recovered on 21st day. The renal function of 31 cases among 35 cases survival patients recovered 8 weeks late. The positive rate of urinary protein of survival patients was high in the early intoxication (76.9%).

CONCLUSIONSerum Cys C is sensitive indicator to reveal the kidney injury on paraquat poisoning patients and have higher value of clinical applications in the diagnosis of the kidney injury of paraquat poisoning, which sensitivity is higher than serum BUN and Cr. The kidney injury caused by paraquat poisoning is reversible.

Acute Kidney Injury ; blood ; chemically induced ; Adolescent ; Adult ; Blood Urea Nitrogen ; Case-Control Studies ; Creatinine ; blood ; Cystatin C ; blood ; Female ; Humans ; Male ; Middle Aged ; Paraquat ; poisoning ; Young Adult

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

BACKGROUNDOssification of the posterior longitudinal ligament (OPLL) has a strong genetic background. Previous studies have shown that bone morphogenetic protein-2 (BMP2) and BMP2 mRNA are expressed in ossifying matrix and chondrocytes adjacent to cartilaginous areas of OPLL tissues and mesenchymal cells with fibroblastic features in the immediate vicinity of the cartilaginous areas. It is suggested that BMP2 plays different roles in the different stages of development of OPLL. However, it remains unknown which factors induce ligament cells to produce BMP2.

METHODSOPLL patients (n = 192) and non-OPLL controls (n = 304) were studied. Radiographs of the cervical spine were analyzed for extent of OPLL. We investigated whether single nucleotide polymorphisms of exons 3 (-726) T/C and 3 (-583) A/G in the BMP2 gene are statistically associated with genetic susceptibility to OPLL in Chinese Han subjects.

RESULTSThere was no statistical difference between the occurrence of exons 3 (-726) T/C and 3 (-583) A/G and the occurrence of OPLL in the cervical spine. However, there was a significant association between occurrence of exon 3 (-726) T/C polymorphism and occurrence of OPLL in males of cases and controls in the cervical spine. In addition, no significant association was found between the exons 3 (-726) T/C and 3 (-583) A/G with number of ossified cervical vertebrae in OPLL patients.

CONCLUSIONSExon 3 (-583) A/G polymorphism in BMP2 gene is not associated with the occurrence and the extent of OPLL in the cervical spine. Chinese Han male patients with TC and CC genotypes in exon 3 (-726) T/C have genetic susceptibility to OPLL but not to more extensive OPLL in the cervical spine.

Asian Continental Ancestry Group ; genetics ; Bone Morphogenetic Protein 2 ; genetics ; China ; Exons ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; Neck ; Ossification of Posterior Longitudinal Ligament ; genetics ; Polymorphism, Genetic