OBJECTIVEThe B7-H1/PD-1 co-signaling pathway has recently been found to play a pivotal role in the immune evasion of tumor cells from host immune system. The aim of this study was to examine the B7-H1 and PD-1 expression and TILs status in gastric cancer and to elucidate the clinical relevance of B7-H1 and PD-1 to the pathogenesis of gastric carcinoma.

METHODSImmunohistochemistry and ANAE histochemical staining were used to investigate the in situ expression of B7-H1 and PD-1 and TILs status in the gastric tissues. RT-PCR was used to explore B7-H1 and PD-1 expression at the transcriptional level. The B7-H1 expression at protein level was detected by Western blot.

RESULTSExpression of B7-H1 and PD-1 was found to be increased in gastric carcinoma, but absent in normal gastric tissue. B7-H1 expression in gastric carcinoma was inversely correlated with TILs infiltration. B7-H1 but not PD-1 expression in tumor tissue was significantly correlated with some clinicopathhological variables including depth of invasion, lymph node metastasis and distant metastasis.

CONCLUSIONB7-H1 and PD-1 expressions are increased in gastric carcinoma. This signaling pathway may inhibit antitumor immune responses in gastric carcinoma. B7-H1 expression plays a critical role in the pathogenesis of human gastric carcinoma,and might be a promising prognostic marker and therapeutic target in the treatment of this disease.

Adult ; Aged ; Antigens, CD ; genetics ; metabolism ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; B7-H1 Antigen ; CD4-Positive T-Lymphocytes ; immunology ; Female ; Humans ; Lymphatic Metastasis ; Lymphocyte Subsets ; immunology ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Programmed Cell Death 1 Receptor ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; genetics ; immunology ; pathology

OBJECTIVETo gain an insight into large genomic deletions in mismatch repair genes MSH2 and MLH1 in Chinese hereditary nonpolyposis colorectal cancer (HNPCC) patients in order to improve genetic detections of HNPCC kindreds.

METHODSFourteen peripheral blood DNA samples were obtained from 14 unrelated HNPCC patients, and fluorescent labeled quantitative multiplex PCR was used to detect large genomic deletions in MSH2 and MLH1 genes.

RESULTSOne of the fourteen probands, a man, was found to have MSH2 exon 1-7 deletions. His cancer-distressed son was also found to have the mutations. Additionally, three normal members of the family had the same mutations.

CONCLUSIONLarge genomic deletions which mainly present to MSH2 account for 20% of general pathological sequence changes of MSH2 and MLH1 genes in Chinese HNPCC patients, and large genomic detections of mismatch repair genes should be included in the regular genetic detections of Chinese HNPCC kindreds.

Adaptor Proteins, Signal Transducing ; genetics ; Asian Continental Ancestry Group ; genetics ; China ; Colorectal Neoplasms, Hereditary Nonpolyposis ; ethnology ; genetics ; pathology ; Female ; Humans ; Male ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; genetics ; Nuclear Proteins ; genetics ; Pedigree ; Polymerase Chain Reaction ; Sequence Deletion

OBJECTIVESTo establish DHPLC method in detecting mutations of mismatch repair genes, hMLH1 and hMSH2, and to identify germline mutations of hMLH1 and hMSH2 in HNPCC kindreds fulfilling Chinese HNPCC criteria.

METHODSFourteen peripheral blood DNA samples from 14 unrelated HNPCC probands fulfilling Chinese HNPCC criteria were obtained respectively. PCR amplified 35 exons of two main mismatch repair genes, hMLH1 and hMSH2. DHPLC followed by DNA sequencing was used to detect and confirm mutations.

RESULTSa total of 41 colorectal cancers and 19 extracolonic tumors were developed in 14 HNPCC kindreds, and gastric cancer was the most common extracolonic tumor type. Twelve single nucleotide changes were identified by DHPLC in 14 probands. Among them, three were missense mutations, one was a nonsense mutation. Other single nucleotide changes included five single nucleotide polymorphisms, two intron single nucleotide changes, one synonymous mutation. hMLH1 EXON19 CODON749 TAC-->TAG (Tyr-->X), hMSH2 EXON12 CODON629 CAA-->CGA (Gln-->Arg) and hMSH2 EXON15 CODON839 CAT-->CGT (His-->Arg) were new discovered mutations.

CONCLUSIONS(1) DHPLC was considered to be highly effective, convenient technique with consistent results for the mutation detection of hMLH1 and hMSH2 genes. (2) Valid mutations of hMLH1 and hMSH2 genes were identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria and missense mutation was the most common mutational types in this cohort of families.

Adaptor Proteins, Signal Transducing ; Asian Continental Ancestry Group ; genetics ; Base Pair Mismatch ; Carrier Proteins ; genetics ; Chromatography, High Pressure Liquid ; Codon, Nonsense ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; DNA Mutational Analysis ; Female ; Genetic Testing ; Germ-Line Mutation ; Humans ; Male ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; genetics ; Mutation, Missense ; Nuclear Proteins ; genetics ; Pedigree

Aged ; Bone Neoplasms ; secondary ; Carcinoma, Hepatocellular ; pathology ; Humans ; Liver Neoplasms ; pathology ; Male ; Paranasal Sinus Neoplasms ; secondary

Objective To study and analyze the efficacy of Methylprednisolone and gamma globulin in the treatment of acute myelitis. Methods 100 cases of acute myelitis in the second affiliated hospital of Xi'an Jiaotong University were selected as the research objects, and the control group was treated with Dexamethasone. The experimental group was treated with Methylprednisolone combined with gamma globulin. The clinical efficacy, adverse reactions and related clinical indicators of the experimental group and the control group were compared and analyzed. Results The effective rate of the experimental group (92.0 %) was significantly better than (82.0 %) of the control group with statistical difference (P<0.05). There were no obvious adverse reactions in the two groups, the incidence rate was 8.0% and 10.0 % respectively, and there was no significant difference. Time of muscle strength improved two level in the control group (18.90±5.23) d was significantly longer than that (10.87±4.30) d of the experimental group, the experimental group hospitalization time, sensory recovery time and recovery of urinary function and other indicators are better than the control group, with statistical difference (P<0.05). Conclusion Methylprednisolone combined with gamma globulin in the treatment of acute myelitis has ideal efficacy, could significantly improve the patient's muscle strength with high safety.

OBJECTIVETo investigate the characteristics of microglial activation of hippocampus in experimental epileptic rats.

METHODSMorphological changes and proliferation of OX-42 positive cells were compared at different time points after status of epilepticus (SE) in lithium-pilocarpine induced epileptic rats.

RESULTSOX-42 positive cells were activated after SE, which increased to a peak at 3-7 d and in a relatively stable state at 7-14 d; then gradually decreased after 14d and returned to slightly higher level than previously at 21 d.

CONCLUSIONInflammatory injury, microglial activation and cell proliferation are closely related after seizures, microglial activation may be an important mechanism in the inflammatory injury of epilepsy.

Animals ; Cell Proliferation ; Disease Models, Animal ; Hippocampus ; cytology ; pathology ; Male ; Microglia ; pathology ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; pathology

OBJECTIVETo observe the distribution of hypoxia inducible factor-1alpha (HIF-1alpha) in different brain regions in aged rats and investigate the role of HIF-1alpha in the aging process of the nervous system.

METHODSThe Nissl bodies and HIF-1alpha expression in different brain regions were observed in rats aged 3 and 30 months using Nissl staining and immunohistochemical method, respectively.

RESULTSIn the 30-month-old rats, the neural cells in 4 different brain regions presented with large cell body and loose alignment, containing reduced Nissl bodies in the cytoplasm. Compared with the 3-month-old rats, the aged rats showed greater number of HIF-1alpha-positive cells in the brain (P < 0.01), and the number varied significantly between the different brain regions (P < 0.01). The CA3 region contained the greatest number of positive cells, which were fewer in the motor cortex and cerebellum.

CONCLUSIONThe capacity for protein synthesis in the neural cells is weakened but the expression of HIF-1alpha increased in aged rats, suggesting the important role that HIF-1alpha may play in the aging process of the nervous system, especially in hypomnesis.

Aging ; metabolism ; Animals ; Brain ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; biosynthesis ; Male ; Rats ; Rats, Sprague-Dawley

PURPOSE: Urapidil is putatively effective for patients with hypertension and acute heart failure, although randomized controlled trials thereon are lacking. We investigated the efficacy and safety of intravenous urapidil relative to that of nitroglycerin in older patients with hypertension and heart failure in a randomized controlled trial. MATERIALS AND METHODS: Patients (>60 y) with hypertension and heart failure were randomly assigned to receive intravenous urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters, cardiac function, and safety outcomes were compared. RESULTS: Patients in the urapidil group had significantly lower mean systolic blood pressure (110.1±6.5 mm Hg) than those given nitroglycerin (126.4±8.1 mm Hg, p=0.022), without changes in heart rate. Urapidil was associated with improved cardiac function as reflected by lower N terminal-pro B type natriuretic peptide after 7 days (3311.4±546.1 ng/mL vs. 4879.1±325.7 ng/mL, p=0.027) and improved left ventricular ejection fraction (62.2±3.4% vs. 51.0±2.4%, p=0.032). Patients given urapidil had fewer associated adverse events, specifically headache (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and all-cause mortality rates were similar. CONCLUSION: Intravenous administration of urapidil, compared with nitroglycerin, was associated with better control of blood pressure and preserved cardiac function, as well as fewer adverse events, for elderly patients with hypertension and acute heart failure.
Acute Disease ; Aged ; Antihypertensive Agents/*administration & dosage ; Blood Pressure/drug effects ; Cause of Death ; Female ; Heart Failure/*drug therapy/physiopathology ; Heart Rate/drug effects/physiology ; Hemodynamics ; Humans ; Hypertension/*drug therapy/physiopathology ; Injections, Intravenous ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Nitroglycerin/administration & dosage ; Peptide Fragments/blood ; Piperazines/*administration & dosage ; Ventricular Function, Left/drug effects/physiology

OBJECTIVETo explore the effect of recombinant human erythropoietin (rhEPO) on expression of brain-derived neurotrophic factor (BDNF) in different brain regions of aging rats.

METHODSForty male SD rats were randomized equally into negative control group, D-galactose group, EPO treatment group, and positive control group. Rat models of subacute aging were established by continuous subcutaneous injection of 5% D-galactose. Immunohistochemical staining was used to analyze the variation of BDNF expressions in different brain regions of the aging rats with different treatments.

RESULTSSignificant brain region-specific differences in BDNF expression were found among the rats in different groups. Compared with those in the negative control group, the numbers of BDNF-positive cells in the hippocampal CA1 region, CA3 region, dentate gyrus (DG) and frontal cortex were all decreased obviously in D-galactose group (P<0.05) but increased in both EPO group and the positive control group (P<0.05) without significant differences between the latter two groups. In the rats in the same group, the number of BDNF-positive cells varied markedly in different brain regions (P<0.05), and the expression level of BDNF was the highest in the frontal cortex followed by the hippocampal CA3 region and the dentate gyrus, and was the lowest in the hippocampal CA1 region.

CONCLUSIONTreatment with rhEPO enhances the expression of BDNF in rat neural cells, suggesting that rhEPO may protect the nervous system from aging by regulating the BDNF pathway.

Aging ; Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; CA1 Region, Hippocampal ; metabolism ; CA3 Region, Hippocampal ; metabolism ; Dentate Gyrus ; metabolism ; Erythropoietin ; pharmacology ; Frontal Lobe ; metabolism ; Galactose ; Humans ; Male ; Neurons ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology

Objective To compare the clinical features between cryptogenic stoke(CS)with and without right-to-left shunt(RLS)so as to determine whether shunt severity determined by control-enhanced transcranial Doppler(c-TCD)is correlated with the risk of paradoxical embolism(RoPE)score.Methods We made a retrospective analysis of clinical characteristics of 138 CS patients with and without RLS admitted to our department between January 2014 and November 2016.For patients documented by c-TCD,we evaluated whether there was a correlation between RLS severity and RoPE score. RLS was diagnosed by c-TCD and contrast-enhanced transthoracic echocardiography(c-TTE).We compared every modality for detecting RLS with and without Valsalva maneuver.For patients found with RLS in c-TCD and c-TTE,we judged whether there was an agreement in grading RLS between two modalities.Results For patients with CS,shunt severity by c-TCD was positively correlated with RoPE score(r= 0.26,P= 0.05).The clinical features were different between CS patients with RLS and without RLS.Compared with the positive results of c-TCD and c-TTE at rest,the positive rate was higher in Valsalva maneuver,respectively(P＜0.01).There was a moderate agreement between shunt grades identified by the two techniques(Kappa=0.428).Conclusion There is a positive correlation between RoPE score and RLS severity determined by c-TCD in CS patients.Valsalva maneuver can significantly increase the positive rate of RLS detected by c-TCD and c-TTE.