OBJECTIVE:To observe clinical efficacy and safety of Shuxuening injection in the adjunctive treatment of traumat-ic subarachnoid hemorrhage. METHODS:96 patients with traumatic subarachnoid hemorrhage were randomly divided into control group and observation group with 48 patients in each group. Control group was given Tranexamic acid injection,Nimodipine injec-tion and Citicoline injection,daily lumbar punctrive and determined intracranial pressure and drained cerebrospinal fluid via lumbar puncture;observation group was additionally given Shuxuening injection 20 ml added into 5% Glucose injection 250 ml,ivgtt,qd. Both group were treated for consecutive 2 weeks. Clinical efficacy of 2 groups were observed,and GCS and MCA were also ob-served before and after treatment;ADR of 2 groups were recorded. RESULTS:Excellent rate of observation group(60.42%)was significantly higher than that of control group(31.25%),with statistical significance(P<0.05). Before treatment,3 and 5 days af-ter treatment,there was no statistical significance in GCS and MCA between 2 groups(P>0.05);7 and 14 days after treatment, GCS of 2 groups increased significantly while MCA decreased significantly,and the observation group was better than the control group,with statistical significance (P<0.05). The incidence of cerebral vasospasm,cerebral infarction and cerebral hemorrhage were 8.33%,4.17%and 4.17%in observation group,and those of control group were 16.67%,12.50%and 16.67%;the observa-tion group was significantly lower than the control group,with statistical significance(P<0.05). CONCLUSIONS:Shuxuening in-jection shows significant therapeutic efficacy in the adjunctive treatment of traumatic subarachnoid hemorrhage,with low incidence of ADR.

The concept of synthetic lethality is defined as a genetic interaction of two non-allelic and non-lethal genes that when mutated simultaneously results in cell death, which has been proposed as a potential way to develop novel antitumor approaches. A new therapeutic approach targeting DNA repair defective genes may remarkably promote the antitumor efficacy based on the mechanism of tumorigenesis induced by DNA repair defects. Previous studies have demontrated that BRCA1 (breast cancer susceptibility gene 1)/BRCA2 or PTEN (phosphatase and tensin homolog deleted on chromosome 10) gene mutation with PARP [poly(ADP-ribose) polymerase] inhibitors could lead to killing effect in cancer cells; deletion of MSH2 (mutS homolog 2) gene with inhibiton of proofreading activity of DNA polβ (polymerase β) and the deletion of MLH1 (mutL homolog 1) gene with inhibiton of proofreading activity of DNA polγ could both lead to killing effect in cancer cells with MMR (mismatch repair) deficiency. PINK1 (PTEN-induced putative kinase 1) may be a potential therapeutic target for the treatment of MMR-deficient cancers with deletion of MSH2, MLH1 or MSH6 gene based on the theory of synthetic lethality. This review descibes the synthetic lethality associated with DNA repair defects. Copyright © 2013 by TUMOR.

Animals ; Female ; Macrophages ; microbiology ; Mice ; Mice, Inbred BALB C ; Microscopy, Electron ; Mycobacteriophages ; physiology ; Mycobacterium tuberculosis ; virology ; Virus Replication

In the etiology study of epidemiology, selection bias will lead to the fact that the research sample cannot represent the general population, the association between exposure and outcome among those selected for analysis differs from the association among those eligible, and the true causal association cannot be inferred. Directed acyclic graphs (DAGs) could visualize complex causality, introduce the Collider-stratification bias using simple graphics language, provide a simple and intuitive way to identify Selection bias, different types of selection bias are verified by the graphic structure of the Collider-stratification bias. In practical studies, there may be multiple biases at the same time, improper adjustment of the collider will lead to Collider-stratification bias, open a backdoor path, even change the size and direction of the confounding bias. In order to obtain an unbiased estimate of the exposure to the outcome, it is necessary to identify the collider and avoid the adjustment to prevent the occurrence of Collider-stratification bias by using DAGs.

OBJECTIVETo explore the effects of Huoxiang Zhengqi liquid (HXZQ) on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea (BSD).

METHODMice were randomly divided into four groups with 10 mice in each group: control group (control), BSD group, Huoxiang Zhengqi liquid treated BSD groups at high dosage and low dosage (HXZQ high, HXZQ low). HXZQ was administrated from the day of diarrhea induction at dosage of 5.21 g kg(-1) and 0.52 g kg (-1) respectively. Peyer's patch and periphery lymphocytes were prepared for flow cytometry, and level of TNF-alpha in periphery and enteric tissue homogenate were determined with ELISA. Student's t-test was used for statistics.

RESULTMice in BSD group started showing continuous diarrhea at the day of induction till the fourth day when the mice were sacrificed. Diarrhea in the mice of HXZQ high and low groups lasted for 36 and 54 h respectively. There were more CD4+ and CD8+ cells in periphery, less CD4+ cells in peyer's patch in BSD mice comparing to normal mice. In peyer's patch, there were more CD8+ cells in mice in HXZQ high and low groups and more CD4+ in mice in HXZQ high group. Higher level TNF-alpha in periphery and intestinal tissue homogenate in BSD group were observed. Mice in HXZQ high group showed the decreased level TNF-alpha in periphery and enteric tissue homogenate.

CONCLUSIONThe immune regulation on peyer's patch CD4+ and CD8+ cells and suppression on TNF-alpha level in enteric homogenate might partially explain the effect of HXZQ on improvement of BSD.

Animals ; CD4-CD8 Ratio ; Colon ; immunology ; metabolism ; pathology ; Diarrhea ; immunology ; metabolism ; microbiology ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Dysentery, Bacillary ; immunology ; metabolism ; microbiology ; Immunity, Mucosal ; drug effects ; Intestinal Mucosa ; immunology ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Peyer's Patches ; drug effects ; immunology ; pathology ; Plants, Medicinal ; chemistry ; Random Allocation ; Salmonella Infections ; immunology ; metabolism ; microbiology ; Salmonella typhimurium ; immunology ; Shigella dysenteriae ; immunology ; T-Lymphocyte Subsets ; drug effects ; immunology ; pathology ; Tumor Necrosis Factor-alpha ; blood ; metabolism

OBJECTIVETo screen out the HAb18G/CD147 binding peptides and find out an antagonist against hepatoma invasion.

METHODSHAb18G/CD147 was purified by affinity chromatographic method and the antigen binding peptides acquired by bio-panning a phage-displayed 12-peptide library. After obtaining the sequence of the selected phage-displayed peptides, all the 9 peptides were synthesized by solid-phase method and identified by mass spectrograph. The peptides' anti-metastatic function was tested by Boyden Chamber assay.

RESULTSThe purified HAb18G/CD147, identified by Western blot (molecular weight about 65 kd) could be used to bio-pan the phage-displayed peptide library. After 3 rounds of bio-panning, 9 positive phage clones were selected and sequenced. The synthesized peptides had uneven inhibitory activities and three of them were able to markedly inhibit the hepatoma cell invasion (P < 0.01). The most effective peptide decreased by 90.1% of hepatoma cells migrating through the Boyden Chamber membrane as compared with the control.

CONCLUSIONBio-panning the phage-displayed peptide library can be used successfully to screen out the antigen binding peptides. Hepatoma metastatic potential can be inhibited by peptide antagonist which could be a good foundation of developing peptide therapeutic agent against hepatoma metastasis.

Animals ; Antibodies, Monoclonal ; therapeutic use ; Basigin ; metabolism ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; Mice ; Neoplasm Invasiveness ; Peptide Library ; Peptides ; therapeutic use

In recent years,the incidence of age-related macular degeneration (AMD) gradually increased,but the definite cause of AMD is still unclear,and the recent study have found that the immune and inflammation in retinal play an important role in the occurrence and development of AMD,so this article will give a brief review of the latest advances in immune and inflammatory mechanisms of AMD.

AIMTo investigate the effects of NPPB, a chloride channel blocker, on proliferation of mesangial cells.

METHODSCell proliferation was determined by measuring cell number and 3H-thymidine incorporation. The LDH activity released from these cells was measured as evaluation of cell viability. The phase of cell cycle was detected by flow cytometry.

RESULTSCell proliferation assays showed that treatment with both NPPB (50 and 25 micromol x L(-1)) and in hypertonic media (100% increased osmolarity with D-mannitol ) significantly reduced the number of human MC and 3H-thymidine incorporation in a dose-dependent manner. But the LDH activity was not significantly altered in the treatment with 50 micromol x L(-1) NPPB. Flow cytometry experiments showed that 50 and 25 micromol x L(-1) NPPB arrested (84.2 +/- 2.4) % and (80.8 +/- 2.9) % of cells at G0/G1 stage, versus (70.5 +/- 1.4) % of control cells. Conclusion NPPB suppresses cell proliferation and produces growth arrest at G0/G1 phase in human MC by a mechanism probably associated with changes in cell volume.

Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Chloride Channels ; antagonists & inhibitors ; Dose-Response Relationship, Drug ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Mesangial Cells ; cytology ; metabolism ; Nitrobenzoates ; administration & dosage ; pharmacology

OBJECTIVETo construct an cell penetrating peptide-based expression vector capable of targeted delivery of proteins into the cell nuclei and study its function of protein transduction.

METHODSThe fusion protein expression vector pET14b-HC(L)NE (pET14-b-His-CPP-Linker-NLS-EGFP) incorporating cell penetrating peptide (CPP), nuclear localization signal(NLS), linker and enhanced green fluorescent protein (EGFP) was constructed based on His-tagged pET14b-HE (pET14b-His-EGFP) by site-directed mutagenesis PCR method. After identification by enzyme digestion and DNA sequencing, the recombinant plasmid was transformed into BL21(DE(3)) strain. The HC(L)NE fusion protein was expressed following IPTG induction and purified with Ni(2+)-NTA affinity chromatography. After dialysis and filtration, the HC(L)NE fusion protein was added into cultured eukaryotic cells. The protein transduction in the living cells was observed under fluorescence microscope and analyzed by Western blotting.

RESULTSEnzyme digestion and DNA sequencing confirmed successful construction of the pET14b-HC(L)NE vector, and the fusion protein efficiently expressed in E. coli. Protein transduction experiments in eukaryotic cells revealed that the fusion protein could rapidly penetrate the cell membrane and reach the cell nucleus, and this internalization was time- and concentration-dependent.

CONCLUSIONThe cell penetrating peptide-based expression vector for targeted protein delivery to the cell nucleus has been successfully constructed, and a transport system that can delivery exogenous proteins or polypeptides into the cytoplasm and cell nucleus is established, which provides an economical and efficient means for functional study of the proteins and polypeptide in cells and targeted drug delivery.

Animals ; Blotting, Western ; COS Cells ; Cell Line ; Cell Membrane ; metabolism ; Cell Nucleus ; metabolism ; Cercopithecus aethiops ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; HeLa Cells ; Humans ; Mice ; Microscopy, Fluorescence ; NIH 3T3 Cells ; Nuclear Localization Signals ; genetics ; Peptides ; genetics ; metabolism ; Protein Transport ; Recombinant Fusion Proteins ; genetics ; metabolism ; Transfection

BACKGROUNDRecent studies have discovered that nuclear translocation of nerve growth factor (NGF) and its receptor fragments function differently from the traditional model. This study aimed to uncover the nuclear expression of NGF in astrocytoma and its biological significance.

METHODSNinety-four paraffin-embedded astrocytoma specimens were subjected to immunohistochemical (IHC) and hemotoxylin & eosin (HE) staining. Preoperative cerebrospinal fluid (CSF) specimens and intraoperative snap-frozen astrocytoma tissues were assayed for NGF expression by ELISA and Western blotting. The outcome of patients who contributed samples was tracked. Each ten tissue samples from patients with traumatic brain injury who had received decompression surgery and CSF samples from patients undergoing spinal anesthesia but with no history of nervous system disease were taken as control.

RESULTSNGF-positive immunoreactive products were distributed in both the cytoplasm and nucleus of astrocytoma, but were only located in the cytoplasm of traumatic brain injury (TBI) tissue. NGF nuclear-positive rate (NPR) of grades III - IV astrocytomas (70.0%) was higher than that of grades I - II astrocytoma (28.6%, P < 0.05). NGF-NP expression positively correlated with the NGF concentration in cerebrospinal fluid (CSF) (r = 0.755, P < 0.01). Kaplan-Meier survival analysis indicated that the median survival time was 25 months for NGF-NP astrocytoma grade I - II patients and 42 months in NGF nuclear negative (NGF-NN) astrocytoma grade I - II patients (P < 0.05). In astrocytoma III - IV patients, the median survival was 7 months for NGF-NP patients and 24 months for NGF-NN patients (P < 0.01). Two types of NGF with molecular weights of 13 and 36 kDa were present in astrocytoma, but only the 36 kDa NGF was found in the CSF. NGF expression elevated as the malignancy increased.

CONCLUSIONSNGF-NP expression and NGF level in CSF were significant prognostic factors in astrocytoma patients. Because of the easy access of CSF, it may be developed as an index for early diagnosis and surveillance of astrocytoma.

Astrocytoma ; metabolism ; Biomarkers ; metabolism ; Blotting, Western ; Cerebrospinal Fluid ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Nerve Growth Factor ; metabolism ; Prognosis