Pregnane X receptor (PXR), a member of nuclear receptor superfamily, plays an important role in xenobiotic and endogenous metabolism, endocrine balance, and cell proliferation, etc. Previous study has shown that pregnenolone 16α-carbonitrile (PCN), a mouse PXR agonist, could induce liver enlargement. And we found that the change in hepatocytes exhibits regional distribution characteristics: hepatocyte enlargement occurs around the central vein (CV) area, while hepatocyte proliferation occurs around the portal vein (PV) area. In this study, the dynamic changes of hepatocytes during PXR-induced liver enlargement were determined. Serum and liver samples from male C57BL/6 mice were collected for biochemical and pathological analysis after PCN treatment for 1, 2, 3, 5 days, respectively. The animal experiment was approved by the Animal Ethics Committee of Sun Yat-Sen University. The results showed that with the increase in the PCN treatment days, the feature of this regional change of hepatocyte around the CV and PV areas became more and more obvious. At the same time, the factors related to hepatocyte enlargement, such as the expression of PXR downstream genes and the hepatic content of triglyceride (TG), has gradually increased. The upregulation of proliferation-related proteins and downregulation of cyclin-dependent kinases inhibitor proteins were observed in the early stage of PCN treatment, suggesting that hepatocyte proliferation occurs earlier than hepatocyte enlargement during PXR-induced liver enlargement. This study reveals the dynamic change of hepatocytes during PXR-induced liver enlargement and provides a new insight in liver enlargement promoted via PXR activation.

Objective To observe effects of different dosages of moxibustion with ginger-separated moxibustion on expressions of mitogen extracellular kinase (MEK) 1/2 and extracellular regulated protein kinase (ERK) 1/2 of gastric tissue in rats with spleen deficiency; To explore the possible mechanism and the dose-effect relationship. Methods Seventy-five SD rats were randomly divided into blank control group, model group, ginger-separated moxibustion for three zhuang group, six zhuang group and nine zhuang group according to random digits table method, with fifteen rats in each group. The rat model of spleen deficiency was established by intragastric administration with 200% Rhei Radix et Rhizoma infusion at 4 ℃. Ginger-separated moxibustion groups were treated with different dosage of moxibustion at "Zusanli", "Zhongwan" for eight days after the modeling. Pathological changes of gastric tissue by HE staining were observed under light microscope, and immunohistochemistry was used to detect the expressions of MEK1/2 and ERK1/2 protein in gastric tissue of rats. Results Compared with the blank control group rats, the gastric mucosa injury in the model group was obvious, which showed that the damage and abscission was more serious; compared with the model group, the gastric mucosa of rats was partly exfoliated and the damage was improved in three zhuang group, and the surface of gastric mucosa of rats was more complete and damage was improved obviously in six zhuang group and nine zhuang group; compared with the blank control group, the expressions of MEK1/2 and ERK1/2 protein in gastric tissue increased obviously in other groups (P<0.01);compared with three zhuang group, the expressions of MEK1/2 and ERK1/2 protein in gastric tissue increased in six zhuang group and nine zhuang group (P<0.01), but the effects of the two group were similar, without statistical significance (P>0.05). Conclusion Ginger-separated moxibustion can repair gastric mucosa in rats with spleen deficiency, which may be closely associated with its effect in increasing the expressions of MEK1/2 and ERK1/2 protein in gastric tissue and activating the MEK/ERK signal transduction pathway.

Objective: To observe the effects of different doses of ginger-partitioned moxibustion on serum trefoil factor 1 (TFF1) and mucin 5AC (MUC5AC) levels, as well as the expression of epidermal growth factor receptor (EGFR) in gastric mucosa of rats with spleen deficiency syndrome, therefore, to explore the possible mechanism and the dose-effect characteristics of ginger-partitioned moxibustion in spleen deficiency syndrome. Methods: Seventy-five SPF grade Sprague-Dawley (SD) rats were randomly divided into a blank control group (group A), a model group (group B), a 3 moxa-cone ginger-partitioned moxibustion group (group C1), a 6 moxa-cone ginger-partitioned moxibustion group (group C2) and a 9 moxa-cone ginger-partitioned moxibustion group (group C3) using random number table method, 15 rats in each group. Except group A, rats in the other groups received intragastric administration of 4 ℃200% concentrated Da Huang (Radix et Rhizoma Rhei) to prepare spleen deficiency syndrome model. After successful modeling, rats in group B received no treatment; rats in group C1, C2 and C3 were treated with 3, 6 and 9 moxa-cone ginger-partitioned moxibustion at Zusanli (ST 36) and Zhongwan (CV 12) respectively for 8 continuous days. The general symptom score of rats was observed. The serum levels of TFF1 and MUC5AC were detected by enzyme-linked immunosorbent assay (ELISA). The expression of EGFR protein in gastric mucosa was detected by immunohistochemistry. Results: After the treatment, compared with group A, the spleen deficiency symptom score was increased in group B, the levels of serum TFF1 and MUC5AC, the EGFR protein expression in gastric tissues of group C1, C2 and C3 were significantly increased (all P<0.01); compared with group B, the spleen deficiency scores were decreased in group C1, C2 and C3, and the serum levels of TFF1 and MUC5AC, as well as EGFR protein expression in gastric tissues were increased (all P<0.01). Compared with group C1, the spleen deficiency scores were decreased in group C2 and C3, the serum levels of TFF1 and MUC5AC, and the expression of EGFR protein in gastric tissues were increased (all P<0.01), however, there was no significant difference between group C2 and C3 (all P>0.05). The mechanism may be related to the increase of serum TFF1 and MUC5AC levels and activation of EGFR protein. Conclusion: Ginger-partitioned moxibustion can improve the symptoms, as well as promote the proliferation and repair of gastric mucosa in rats with spleen deficiency. The therapeutic efficacy of 6 or 9 moxa-cone ginger-partitioned moxibustion is better than that of 3 moxa-cone ginger-partitioned moxibustion, while the efficacies are equivalent between 6 and 9 moxa-cone ginger-partitioned moxibustion groups.

OBJECTIVETo evaluate the local risk factors of traumatic brain injury (TBI) patients developing gastrointestinal (GI) bleeding during the early hospitalization in neurosurgery intensive care unit (NICU).

METHODFrom September 2005 to February 2006, 41 patients admitted to NICU and 13 healthy volunteers were involved in our study. Blood samples at 24 hours, 2-3 days and 5-7 days were obtained from each patient via arterial line at 8 a.m. to measure the concentrations of serum adrenocorticotropic hormone (ACTH), total cortisol and gastrin. The collected serum was immersed in an ice bath and tested by the Immulite 1000 systems. Data were analyzed by SPSS 11.5.

RESULTSWithin 24 hours following TBI, the concentrations of total cortisol, ACTH and gastrin increased proportionally to the severity of injury, especially significant in the experimental group (P less than 0.05). The concentrations of ACTH and gastrin were higher in the GI bleeding positive group than in the GI bleeding negative group, (F equal to 1.413, P less than 0.253) for ACTH and (F equal to 9.371, P equal to 0.006) for gastrin. GI bleeding had a positive correlation with gastrin concentration (r equal to 0. 312, P less than 0.05) and a negative correlation with serum hemoglobin (Hb) (r equal to -0.420, P less than 0.01). The clinical incidence of GI bleeding was 24.39% (10/41) in the experimental group. Within 24 hours, GI bleeding had a strong correlation with gastrin concentration (OR equal to 26.643, P less than 0.05) and hematocrit (Hct) (OR equal to 5.385, P less than 0.05). High ACTH concentration ( larger than 100 pg/ml) increased the frequency of GI bleeding. For patients with severe TBI and treated with routine antacids, the incidence of GI bleeding was 40.91% (9/22) and the mortality rate was 20% (2/10).

CONCLUSIONSLow Glasgow coma scale scores, low Hb, high concentrations of gastrin and ACTH (larger than 100 pg/ml) are risk factors and can be predictive values for post-traumatic GI bleeding. Severe TBI patients have high risks of GI bleeding with high mortality.

Adolescent ; Adrenocorticotropic Hormone ; blood ; Adult ; Aged ; Brain Injuries ; blood ; complications ; mortality ; Female ; Gastrins ; blood ; Gastrointestinal Hemorrhage ; blood ; etiology ; mortality ; Glasgow Coma Scale ; Humans ; Logistic Models ; Male ; Middle Aged ; Risk Factors

This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3-vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P < 0.001). For rs696G > A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P < 0.05) and 56.1% (P < 0.001) lower than those containing G allele (pGL3-rs8904C/rs696G and pGL3-rs8904T/rs696G), respectively. For rs8904C > T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity.
3' Untranslated Regions ; Genes, Reporter ; Genetic Vectors ; Humans ; I-kappa B Proteins ; genetics ; Luciferases ; NF-KappaB Inhibitor alpha ; Plasmids ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Transfection

OBJECTIVETo evaluate the clinical outcomes between extreme lateral interbody fusion and conventional posterior operation in the treatment of upper lumbar disc herniation.

METHODSAmong 60 patients with upper lumbar disc herniation were treated with extreme lateral interbody fusion(XLIF) or conventional posterior operation from June 2010 to December 2014, 30 patients(19 males and 11 females) were treated with XLIF (XLIF group); and the other 30 patients(17 males and 13 females) were treated with conventional posterior operation (conventional group). In XLIF group, the lesions occurred at T₁₂L₁ segments in 2 patients, at L₁,₂ segments in 6 patients, at L₂,₃ segments in 10 patients, and at L₃,₄ segment in 12 patients. In conventional group, the lesions occurred at T₁₂L₁ segments in 1 patient, at L₁,₂ segments in 6 patients, at L₂,₃ segments in 8 patients, and at L₃,₄ segment in 15 patients. Operative incision lengths, time, blood loss, postoperative draining volume, hospital stays were recorded. Pre-and post-operative visual analogue score(VAS) and Japanese Orthopedic Association(JOA) were compared between two groups. According to the image data, the intervertebral fusion device was observed to be displaced and the rate of interbody fusion was analyzed.

RESULTSAll the patients were followed up, and the duration ranged from 12 to 48 months, with an average of 29 months. The complications included 2 femoral nerve damage in XLIF group (postoperative recovery within 3 months) and superficial incision infection in conventional group(cured by anti-infection). There were no patients with cerebrospinal fluid leakage(CSFL), cauda equina injuries or functional deterioration in the nerve root of lower limbs. In the XLIF group: the operative time was (65.6±20.5) minutes, blood loss was (48.8±15.3) ml, postoperative draining volume was 0 ml. In the conventional group: the operative time was (135.2±33.9) minutes, blood loss was (260.3±125.7) ml, postoperative draining volume was (207.1±50.2) ml. The operative time, blood loss, postoperative draining volume in XLIF group were less than those in the conventional group(<0.05). The JOA and VAS score were significantly improved in both groups during the follow-up period compared with those before operation(<0.05). But the difference of the JOA and VAS score between the two groups 1, 6, and 24 months after surgery had not significant differences(>0.05). There were no significant differences in the fusion rate between the two groups 6 and 12 months after operation(>0.05).

CONCLUSIONSThe XLIF fusion for the treatment of upper lumbar disc herniation has several advantages such as minimal invasive, stable vertebral plate, less complications and postoperative fusion rate, which has a better clinical effect.

OBJECTIVETo investigate the expression of integrin-linked kinase (ILK) in kidneys of mice with unilateral ureteral obstruction and its relevance with the epithelial-mesenchymal transition.

METHODSMice were randomly divided into two groups, sham operation (C, n = 20) and unilateral ureteral obstruction (UUO, n = 40). The animals were sacrificed at day 1, 3, 7 and 14 respectively after the surgery. Tubulointerstitial fibrosis (TIF) was graded according to Masson staining. The protein level of ILK was examined by Western blot. Tissue/cytological expression for ILK, alpha-SMA and E-cadherin were investigated by immunohistochemistry. The mRNA levels of ILK, alpha-SMA and E-cadherin were analyzed by quantitative real-time PCR.

RESULTSIn the control animals (group C), weak staining for ILK was detected mainly in the podocytes. Significant increase of staining for ILK in the experimental mice (UUO group) was detected from day 1 onward (t = 16.5, P < 0.01), reaching the peak at day 7. The protein expression of E-cadherin was continuously down-regulated from day 3 onward after surgery (t = 21.0, P < 0.01), while expression for alpha-SMA was up-regulated. From day 1 to day 7, the protein expression of ILK was positively correlated with alpha-SMA (R = 0.88, P < 0.01), but negatively correlated with E-cadherin (R = -0.87, P < 0.01). The mRNA expression of ILK and alpha-SMA analyzed by real-time PCR increased from postoperative day 1 and 3 respectively, but the mRNA expression of E-cadherin decreased from day 3 onward.

CONCLUSIONIncreasing expression of ILK occurs in the early phase of UUO mouse and may play an important role in the process of TIF through mediating the epithelial-mesenchymal transition.

Actins ; biosynthesis ; genetics ; Animals ; Blotting, Western ; Cadherins ; biosynthesis ; genetics ; Epithelial Cells ; metabolism ; pathology ; Fibrosis ; Immunohistochemistry ; Kidney Tubules ; metabolism ; pathology ; Male ; Mesoderm ; metabolism ; pathology ; Mice ; Muscle, Smooth ; chemistry ; Protein-Serine-Threonine Kinases ; biosynthesis ; genetics ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Ureteral Obstruction ; genetics ; metabolism ; pathology

Objective To analyze the genetic etiology of lateral ventriculomegaly fetal on the genome-wide level with chromosomal microarray analysis (CMA),and investigate the relationship between copy number variations (CNVs) and lateral ventriculomegaly and the application value of CMA in prenatal diagnosis of fetuses with lateral ventriculomegaly.Methods Seventy fetuses with lateral ventriculomegaly but normal or uncertain karyotype were selected and invasive prenatal diagnosis was performed in Xi Jing Hospital of the Fourth Military Medical University from Jan.2015 to Nov.2016.Microarray testing was performed using Affymetrix CytoScanTM 750k arrays and the results were analyzed according to biological information science database.The fetal development was regularly inspected,and follow up was conducted to find out the pregnancy outcome and fetal postnatal conditions.Results In 70 cases of lateral ventriculomegaly fetuses,there were 9 fetuses with pathogenic copy number variations (CNVs),3 fetuses with likely pathogenic CNVs and 1 fetus with likely pathogenic 1 oss of heterozygosity (LOH).During the 70 fetuses with lateral ventriculomegaly,2 pathogenic CNVs were detected in 6 fetuses with severe and non isolated lateral ventriculomegaly (33.3％).Pathogenic CNVs was not detected but 1 likely pathogenic CNV was detected in 3 fetuses with severe and isolated lateral ventriculomegaly (33.3％).Six pathogenic CNVs were detected in 31 mild and non isolated lateral ventriculomegaly (19.4％),and 2 likely pathogenic CNVs were also detected in these group (6.5％).One pathogenic CNV and 1 likely pathogenic CNV were detected in 30 fetuses with mild and isolated fetal lateral ventriculomegaly.Conclusions CMA can identify chromosome abnormality microdeletion/microduplication which was unrecognizable by conventional karyotyping analysis.The application of CMA may increase the detection rate of pathogenic CNVs in fetuses with lateral ventriculomegaly,and benefit evaluation of fetal prognosis in prenatal genetic counselling.

The effects of human insulin 70/30 and insulin lispro 75/25 were compared in improving postprandial blood glucose excursions in 106 patients with type 1 or 2 diabetes in a one-month,open-labelled,self- controlled trial .The results showed that treatment of diabetic patients with insulin lispro 75/25 significantly improved 2 h postprandial blood glucose excursion compared to pre-study with human insulin 70/30 (baseline) without any significant adverse events or sustained hypoglycemic episodes.These physiological benefits were associated with a patient preference for insulin lispro 75/25.

OBJECTIVEThe aim of this study was to evaluate the therapeutic efficacy and to determine the prognostic factors of TACE in patients with colorectal liver metastases (CRLM).

METHODSThe clinical data of 183 patients with unresectable CRLM treated with TACE from Jan. 2002 to Dec. 2008 were retrospectively reviewed. Log-rank method was used for univariate analysis and Cox proportional hazard model was used for multivariate analysis of the prognostic factors.

RESULTSThe median survival time was 22 months, and the 0.5-, 1-, 2-, 3-, 5-year survival rates were 93.9%, 81.1%, 39.8%, 18.2%, and 3.9%, respectively. Multivariate analysis showed that tumor involved more than one lobe of the liver, and elevated CEA and CA19-9 levels were independent risk factors for the overall survival (P < 0.01). Females, more times of TACE, combination with regional therapy and received phase II resection were related with a good survival (P < 0.01) in CRLM patients after TACE treatment.

CONCLUSIONSTranscatheter arterial chemoembolization is an effective therapy for unresectable colorectal liver metastases. Patients with tumor spread more than one lobe of the liver, high CEA and CA19-9 levels are independent poor prognostic factors. Females, patients received more times of TACE, combined with regional therapy and received phase II resection may have a good survival.

Adult ; Aged ; Aged, 80 and over ; Antigens, Tumor-Associated, Carbohydrate ; blood ; Carcinoembryonic Antigen ; blood ; Chemoembolization, Therapeutic ; Colonic Neoplasms ; pathology ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Iodized Oil ; administration & dosage ; Liver Neoplasms ; blood ; secondary ; surgery ; therapy ; Male ; Middle Aged ; Mitomycin ; administration & dosage ; Organoplatinum Compounds ; administration & dosage ; Proportional Hazards Models ; Rectal Neoplasms ; pathology ; Retrospective Studies ; Survival Rate