OBJECTIVETo explore the effects and mechanisms of multi-glycoside of Tripterygium wilfordii (GTW) on improving glomerular inflammatory lesion in rats with diabetic nephropathy (DN).

METHODDN model was induced by unilateral nephrectomy and intraperitoneal injection of STZ (35 mg x kg(-1)) twice. The rats were randomly divided into 3 groups, the sham-operated group (Sham group, n = 5), the vehicle-given group (Vehicle group, n = 5 ) and GTW-treated group (GTW group, n = 5). After the model was successfully established, the rats in GTW group were daily oral administrated with GTW suspension (50 mg x kg(-1) x d(-1)), meanwhile, the rats in Vehicle group were daily oral administrated with distilled water (2 mL) for 8 weeks. From the beginning of the administration, all rats were killed 8 weeks later. Blood and renal tissues were collected,and then UAlb, renal function, glomerular morphology characteristics and glomerular macrophages (ED1 + cells) infiltration, as well as the protein expressions of inflammatory cytokines including tumor necrosis factor(TNF)-α and interleukin(IL)-lβ, and the key molecules in p38MAPK signaling pathway including p38 mitogenactivated protein kinase (MAPK), phosphorylated p38 (p-p38MAPK) and transforming growth factor(TGF)-β1 were investigated respectively.

RESULTGTW not only ameliorated the general state of health and body weight,but also attenuated UAlb, glomerulosclerosis, the infiltration of glomerular ED1 + cells and the protein expressions of TNF-α, IL-1β, p-p38MAPK and TGF-β1 in the kidney in DN model rats.

CONCLUSIONBy means of DN model rats, we demonstrated that GTW has the protective effect on renal inflammatory damage in vivo via inhibiting inflammatory cells infiltration and inflammatory cytokines expression. Furthermore, GTW could improve renal inflammatory lesion through down-regulating the expressions of the key signaling molecules in p38MAPK pathway such as p-p38MAPK and TGF-β1 ,and inhibiting the activation of p38MAPK signaling in the kidney.

Animals ; Diabetic Nephropathies ; drug therapy ; Disease Models, Animal ; Glomerulonephritis ; drug therapy ; Glycosides ; pharmacology ; MAP Kinase Signaling System ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; analysis ; Tripterygium ; chemistry ; p38 Mitogen-Activated Protein Kinases ; physiology

Objective To investigate the application of 293 cells to detect suspected carcinogens and provide experimental evidence by using in vitro cell transformation assay and tumorigenicity study. Methods The transformation systems of cells cultured in vitro have been adopted to clarify the tumor promotive activity of Micrecystin LR (MC-LR). The malignant transformation of 293 cells induced by MC-LR is tested by several methods including clone forming in soft agarose, serum requirement assay and tumor forming in mice to defme the promotive activity of 293 cells. Results 293 cell acted like tumor cells after induced by MC-LR: serum dependence decreased, anchorage independence growth in soft agarose and formed cell clones, malignant tumors appeared in SCID mice. Conclusion 293 cells were easy to culture and sensitive to environmental carcinogens so that can be used in detection of suspicions carcinogens.

BACKGROUNDStudies have reported that patients with human immunodeficiency virus (HIV) have a high incidence of osteonecrosis of the femoral head (ONFH). Total hip arthroplasty (THA) is an effective management of ONFH. However, little data exist regarding the use of THA for the HIV patients with ONFH in China. This study reviewed the outcomes of HIV-positive patients who underwent THA for ONFH, compared with HIV-negative individuals.

METHODSThe patients who underwent THA for ONFH from September 2012 to September 2014 in Beijing Ditan Hospital, Capital Medical University were retrospectively studied. Twenty-eight HIV-positive patients and 35 HIV-negative patients underwent 48 THAs and 45 THAs with cementless components, respectively. Medical records and follow-up data were reviewed. Harris Hip Score (HHS) was applied to evaluate the pain and function of the hips before and after THA. Complications such as wound healing, surgical site infection, deep venous thrombosis, pulmonary embolism, sepsis, mortality, and complications from the prosthesis were reviewed. The operation time, blood loss, and hospital stay were compared between the two groups.

RESULTSThe mean follow-up period was 19.5 ± 5.8 months (ranging from 6 to 30 months). The mean age of the HIV-positive patients with osteonecrosis at the time of surgery was 35 years old, which was significantly lower than that of the HIV-negative group (42 years old) (P < 0.05). The HIV-positive patients underwent surgery a mean of 2.5 years after their original symptoms, which was significantly shorter than the HIV-negatives' (mean 4 years) (P < 0.05). Among HIV-positive patients, the prevalence of being male and rate of bilateral procedures were significantly higher than those in the HIV-negative group (P < 0.05). The operation time in HIV-positive patients was significantly longer than that in HIV-negative patients (P < 0.05). There were no significant differences in blood loss or hospital stay between the two groups (P > 0.05). The HHSs of two groups significantly improved after THAs (P < 0.05), without significant difference between two groups. No wound complication, sepsis, mortality, prosthesis complication, and occupational exposure occurred, except for two cases of heterotopic ossification and one case of humeral head necrosis.

CONCLUSIONSONFH is more likely to occur bilaterally in younger HIV-positive males. The development of osteonecrosis seems faster in HIV-positive patients than in HIV-negative patients. This should be cautionary for asymptomatic HIV-positive patients with low viral RNA level and in the primary HIV stage. Despite longer operation times in the HIV-positive patients than in the HIV-negative patients, THA is still a safe and efficient approach to treat ONFH in HIV-positive patients. The incidence of complications is much lower than previously reported. However, the long-term follow-up is needed.

Adult ; Arthroplasty, Replacement, Hip ; methods ; China ; Female ; Femur Head Necrosis ; pathology ; surgery ; HIV Infections ; surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo define the clinical features of postoperative chylothorax for lung cancer (PCLC), and to compare them with those for esophageal cancer (PCEC).

METHODWe retrospectively analysed clinical characteristics of 12 patients with chylothorax among 4 084 patients receiving resection of lung cancer, as well as 52 in 4 479 patients having resection of esophageal cancer since 1985 at our hospital.

RESULTSThe incidence of PCLC was 0.29% and that of PCEC was 1.16%. The percentage of diagnosis confirmed within 4 postoperative days was 33.3% for PCLC, and 76.9% for PCEC. The rate of typical chylous pleural effusion was 83.3% for PCLC, and 5.8% for PCEC. Symptoms and signs of PCLC were much milder than those of PCEC. The re-operation rate was 16.7% for PCLC, and 96.2% for PCEC. All patients were discharged uneventfully.

CONCLUSIONThe incidence, causes, clinical manifestations, diagnosis, and treatment of PCLC is different from those of PCEC.

Adult ; Aged ; Chylothorax ; etiology ; therapy ; Esophageal Neoplasms ; surgery ; Female ; Humans ; Lung Neoplasms ; surgery ; Male ; Middle Aged ; Postoperative Complications ; etiology

OBJECTIVETo investigate the clinicopathological features and prognosis of metastatic ovarian tumors from gastric cancer.

METHODSClinical data of 68 patients with metastatic ovarian carcinoma were reviewed retrospectively.

RESULTSThe median age was 46 years. The majority of these patients was in the premenopausal state (67.6%) and had bilateral ovarian involvement (64.7%). Pathological type was signet-ring cell carcinoma in 52.9% of the cases. Most of them underwent surgical treatment or chemotherapy or both. The median overall survival was 14.1 months, and the median progression-free survival was 6.7 months. The survival rates in 1-, 3- and 5-year were 54.8%, 14.9% and 0, respectively. Univariable analysis revealed that resection of gastric cancer, lymphatic metastasis, pathologic type of metastatic ovarian tumor, extent of metastatic lesion, cytoreductive surgery and chemotherapy for metastatic ovarian carcinoma were associated with the prognosis. Multivariable analysis revealed that cytoreductive surgery and extent of metastatic lesion were independent factors. Patients with metastatic lesion confined to the ovaries had a median overall survival of 16.0 months as compared to 8.6 months for those with more extensive metastases (P<0.01), and had a median progression-free survival of 8.2 months as compared to 4.1 months for those with more extensive metastases (P<0.05). Patients who underwent optimal cytoreduction(residual lesion < or =2 cm) had a median overall survival of 16.0 months as compared to 9.7 months for those who received suboptimal cytoreduction (residual lesion >2 cm) ( P<0.01). Optimal cytoreduction was also associated with a significantly longer median progression-free survival (11.0 months) as compared to suboptimal cytoreduction median progression-free survival (3.1 months) (P<0.01).

CONCLUSIONSPrognosis of patients with metastatic ovarian carcinoma from gastric cancer is quite poor. Extent of metastatic lesion is an independent factor. Optimal cytoreduction is associated with improved survival.

Adult ; Aged ; Female ; Humans ; Middle Aged ; Ovarian Neoplasms ; pathology ; secondary ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; diagnosis ; pathology

OBJECTIVETo investigate the functional role of hippocampal mossy fiber sprouting in the pathophysiologic mechanism of initiation and propagation of epilepsy.

METHODSThe authors examined hippocampal mossy fiber synaptic reorganization and the changes of hippocampal neurons in P77PMC rats at different stages in the course of recurrent seizures using Timm's method of silver sulfide staining and Nissl staining and observed the effects of recurrent audiogenic seizures (AGSs) on seizure behavior of P77PMC rats.

RESULTSFrequent recurrent AGSs could cause neuronal loss in CA(1) region of hippocampus and hippocampal mossy fiber sprouting got into the inner molecular layer of dentate gyrus in P77PMC rats, and could decrease the latency of IV/V grade of AGSs, increase the durations of AGSs. The mean A of CA(1) region of hippocampus in Nissl staining after 50 times of AGSs was 35.3 +/- 0.8, which was markedly lower than that of the control (44.1 +/- 0.5; F = 333.89, P < 0.001). The mean A of the inner molecular layer of dentate gyrus in Timm's staining after 50 times of AGSs was 49.3 +/- 4.6, which was markedly higher than that of the control (26.8 +/- 1.7; F = 76.83, P < 0.001). After 30 and 50 times of AGSs, the latent periods of IV/V grade of AGSs were 12 +/- 8 (t = 3.805; P < 0.02) and 17 +/- 7 (t = 5.927; P < 0.002) seconds shorter than the initial period of stimulation respectively on average, and the durations of AGSs were 19 +/- 18 (t = 2.644; P < 0.05) and 10 +/- 7 (t = 3.780; P < 0.02) seconds longer.

CONCLUSIONHippocampal mossy fiber sprouting and neuronal loss not only presents in limbic seizure, but also in AGS, the seizure can be initiated in brainstem but rapidly generalized;in AGS-prone rats, recurrent AGSs can cause mossy fiber synaptic reorganization and neuronal loss in hippocampus, and can also enhance seizure susceptibility of P77PMC rats. In the course of recurrent AGSs, enhanced seizure susceptibility happened before hippocampal mossy fiber sprouting. Their temporal relationships indicate that the anatomical changes may be preceded by functional changes of elevated excitability in the brain.

Acoustic Stimulation ; adverse effects ; Animals ; Epilepsy ; pathology ; Mossy Fibers, Hippocampal ; pathology ; Rats ; Rats, Wistar ; Seizures ; etiology ; pathology

OBJECTIVETo investigate the clinicopathological characteristics, diagnosis, treatment and prognostic factors of gastric gastrointestinal stromal tumors(GIST) in the stomach.

METHODSThe clinicopathological data of 132 patients with gastric GIST between January 1998 and December 2008 were analyzed retrospectively, and the prognostic factors were evaluated.

RESULTSTumor locations were the cardia or fundus (50, 37.9%), the stomach body (62, 47%),the antrum (13, 9.8%), and two regions were found in 6 cases (4.5%), three regions in 1 cases (0.8%). Tumor size ranged from 1.0 to 27.0 cm with an average of 9.4 cm. All the patients underwent complete tumor resection, including multi-organ resection in 41 cases. Thirty-four cases underwent lymph node dissection. All the lymph nodes were negative. The positive rate was 93.2% (23/132) for CD 117 and 82.6% (109/132) for CD34. The 1-,3- and 5-year survival rates of the 118 cases with follow up were 94.7%, 80.2%, and 56.6%, respectively. Univariate analysis revealed that the differences in Fletcher classification, tumor size, infiltration to surrounding tissue, preoperative metastasis, and adjuvant postoperative therapy with imatinib were related to the survival rates. Multivariate analysis demonstrated that Fletcher classification, preoperative metastasis and adjuvant postoperative therapy with imatinib were independent poor prognostic factors for survival.

CONCLUSIONSPreoperative metastasis is an independent factor predicting poor prognosis of gastric GIST. Fletcher classification can be used to evaluate the biological behaviors and prognosis, while surgery is the main therapy and targeted therapy can improve survival of gastric GIST.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Gastrointestinal Stromal Tumors ; diagnosis ; pathology ; therapy ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; diagnosis ; pathology ; therapy ; Young Adult

This paper was designed to observe the colocalization of 11beta-HSD1 and GR, and its significance in the rat hippocampus. Immunocytochemical dual-staining showed that not only 11beta-HSD1 but also GR immunoreactive substances were present in the cultured rat hippocampal neurons. Moreover, they were colocalized in the same hippocampal neuron. Synthetic glucocorticoid dexamethasone (DEX) up-regulated the protein expression and activity of 11beta-HSD1 in the cultured hippocampal neurons, as determined by Western blot and thin layer chromatography (TLC) respectively. The transfection of PC12 cells with the plasmid containing promoter sequence of 11beta-HSD1 gene and the reporter gene of CAT enzyme was conducted. DEX up-regulated the reporter gene expression in the system described above. The up-regulation of 11beta-HSD1 and reporter gene expression induced by DEX were both blocked by GR antagonist RU38486. Our study suggests that the colocalization of 11beta-HSD1 and GR in the hippocampus may be implicated in the up-regulation of 11beta-HSD1 expression by glucocorticoids combining to its promoter region, which in turn produces more biologically active glucocorticoids necessary for the binding of low affinity of GR.
11-beta-Hydroxysteroid Dehydrogenases ; genetics ; metabolism ; Animals ; Animals, Newborn ; Dexamethasone ; pharmacology ; Gene Expression Regulation ; Hippocampus ; cytology ; metabolism ; Mifepristone ; pharmacology ; Neurons ; chemistry ; metabolism ; PC12 Cells ; Promoter Regions, Genetic ; Rats ; Receptors, Glucocorticoid ; genetics ; metabolism ; Transfection

Objective The purpose of this study was to approach the relation of SNP43,SNP44 locus, main haplotypes and haplotype combinations with type 2 diabetes mellitus(T2DM).Methods According to the theory and principles of systematic review,data from case-control studies regarding the association between calpain-10(CAPN10) gene and T2DM were derived through electronic search of PubMed and Chinese journals databases.To gain a more precise estimation of the relationship,a stratified Meta-analysis with four subgroups was pertbrmed according to the races.Publication bias Was also assessed.Results The association with T2DM in different races was evaluated.In Mongoloid race,SNP43-G allele,G/G genotype and 111/221 haplotype combination showed notable association with T2DM with Ors (95%CI) as 1.368(1.155-1.620),1.437(1.186-1.741) and 2.762 (1.287-5.927) respectively.In Caucasoid race,SNP44-C allele,111/111 hapotype combination showed strong relationship with T2DM with Ors(95%CI) as 1.144(1.023-1.278),1.291(1.050-1.586) respectively.In Hybrid race,only one positive finding Was obtained which Was SNP44-C allele with OR(95%CI)as 1.653(1.025-2.665).Conclusion SNP43-G allele,G/G genotype,111/221 were risk factors to Mongoloid race.And SNP-C allele,111/111 haplotype combination were risk factors to Caucasoid race,and SNP44-C allele to Hybrid race.

To explore the gene-based principal component logistic regression model and its application in genome-wide association study.Using the simulated genome-wide single nucleotide polymorphism (SNPs) genotypes data,we proposed a practical statistical analysis strategy-'the principal component logistic regression model',based on the gene levels to assess the association between genetic variations and complex diseases.The simulation results showed that the P value of genes in related diseases was the smallest among the results from all the genes.The results of simulation indicated that not only it could reduce the degree of freedom through hypothesis testing but could also better understand the correlations between SNPs.The gene-based principal component logistic regression model seemed to have certain statistical power for testing the association between genetic genes and diseases in the genome-wide association studies.