OBJECTIVETo investigate the differential gene expression profile of the lung tissues in experimental silicosis rats and to screen for and identify the key signal transduction pathways in pulmonary silicotic fibrosis.

METHODSA total of 80 rats were randomly divided into control group (n = 40) and silica-instilled group (n = 40). Each group was equally divided into five subgroups, and each subgroup was treated at 1, 7, 14, 21, or 28 d. Intratracheal instillation was used to give 1 ml of silica suspension (50 mg/ml) in the silica-instilled group and normal saline in the control group. Silicotic nodules and type I and III collagen were observed through hematoxylin and eosin staining and Sirius red staining, respectively. Differentially expressed genes in pulmonary silicotic fibrosis were selected by the rat whole-genome gene expression RatRef-12 BeadChip (Illumina, USA), and a fold change cutoff was applied. Quantitative real-time polymerase chain reaction (qRT-PCR) was also used to verify differentially expressed genes. Through bioinformatics databases such as Visualization and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG), preliminary research was performed on the biological pathways of differential genes, key biological signal transduction pathways were identified, and key differentially expressed genes in each pathway at different time points were searched for.

RESULTSA total of 2694 genes were differentially expressed and changed dynamically. The KEGG pathway analysis showed that 141 signal transduction pathways were involved in the development and progression of pulmonary silicotic fibrosis, among which 48 pathways were more significant than others (P < 0.01), with the mitogen-activated protein kinase (MAPK) pathway exceptionally significant. The differentially expressed genes interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and transforming growth factor beta (TGF-β) in the MAPK pathway were up-regulated at different time points after silica instillation. The results of real-time PCR showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was over-expressed at 4 time points and under-expressed at 1 time point compared with the control group.

CONCLUSIONThe MAPK signal transduction pathway plays a very important role in the development of pulmonary silicotic fibrosis. Both IL-1R and TNFR may play major roles during inflammation phase through the P38/Jun N-terminal kinase (JNK) pathway, and TGF-β may have important function through the extracellular-signal-regulated kinase (ERK) pathway in the formation of fibrosis.

Animals ; Gene Expression ; Lung ; metabolism ; pathology ; Male ; Pulmonary Fibrosis ; genetics ; metabolism ; pathology ; Rats ; Rats, Wistar ; Signal Transduction ; Silicosis ; genetics ; metabolism ; pathology

Toxicity of Chinese materia medica (CMM) is an important part of Chinese herbal nature theory. In clinical application, the dosage, time limitation and compatibility of CMM is mainly determined by toxicity. At present, there is no uniform toxicity classification standard for the evaluation of Chinese herbal toxicity. Therefore, it is significant to research toxicity classification of CMM. The current situation of toxicity classification of CMM is reviewed in this paper, and proposed research thoughts are as follows: the measurement of toxicity parameters, the confirmation of poisoning target organs, the investigation on toxic mechanism by serum pharmacology and toxicokinetics, the comprehensive evaluation on toxicity based on quantitative theory.
Animals ; Biomedical Research ; China ; Drugs, Chinese Herbal ; analysis ; classification ; history ; toxicity ; History, Ancient ; Humans ; Materia Medica ; analysis ; classification ; history ; toxicity ; Medicine, Chinese Traditional ; adverse effects ; Mice ; Rats

OBJECTIVETo investigate the clinical efficacy of laparoscopic ventriculoperitoneal shunt with temporary external drainage in the treatment of hydrocephalus.

METHODSFifty-two cases of hydrocephalus randomized into two groups to receive laparoscopic assisted ventriculoperitoneal shunt with temporary external drainage (19 male and 7 female patients) and conventional ventriculoperitoneal shunt (20 male and 6 female patients). The catheterization time in the abdominal cavity, release time of intracranial hypertension, average hospital stay, postoperative pains, and postoperative complications were compared between the two groups.

RESULTSLaparoscopic ventriculoperitoneal shunt with temporary external drainage was performed successfully in all the cases without intraoperative conversion to open surgery. Compared with the conventional ventriculoperitoneal shunt, laparoscopic ventriculoperitoneal shunt with temporary external drainage was associated with significantly shortened catheterization time in the abdominal cavity, release time of intracranial hypertension, and average hospital stay (P<0.01) as well as lowered postoperative pain score at 4, 8, 16, and 24 h after the operation. The pain scores at 48 and 72 h postoperatively were comparable between the two groups. During the follow-up 3 months, the patients receiving laparoscopic ventriculoperitoneal shunt were found to have significantly lower rates of peritoneal end obstruction and abdominal cavity infection than those having conventional shunt (3.8% vs 19.2%, P<0.01; 1.0% vs 23.1%, P<0.01).

CONCLUSIONLaparoscopic ventriculoperitoneal shunt with temporary external drainage is feasible and produces better clinical therapeutic effect for management of hydrocephalus.

Abdominal Cavity ; Adult ; Female ; Humans ; Hydrocephalus ; surgery ; Laparoscopy ; Male ; Treatment Outcome ; Ventriculoperitoneal Shunt ; methods

BACKGROUNDGensing Rg3 is an active component from ginseng. The aim of this study is to observe the clinical anticancer effect of Rg3 in combination with chemotherapy regimen NP (vinorelbine+cisplatin) in advanced non-small cell lung cancer (NSCLC).

METHODSStage III-IV NSCLC patients confirmed by pathology or cytology all received vinorelbine plus cisplatin for at least two cycles, and were randomized into two groups: patients in arm A also received placebo twice a day, while patients in arm B received two tablets of Rg3 twice a day for at least two months. The endpoints of the study were the efficacy, survival and tolerance of patients.

RESULTSFrom July 2000 to May 2002, 115 patients were enrolled into the trial. The patients' characteristics were well balanced in the two groups. Sex of patients: male, 79; female 36. Types of pathology: adenocarcinoma, 71; squamous cell carcinoma, 29; adenosquamous carcinoma, 8; others, 7. TNM stage: stage III, 45; stage IV, 70. Prior chemotherapy: with, 17; without, 98. Prior radiotherapy: with, 15; without, 100. Prior surgical treatment: with, 23; without, 92. Nine patients discontinued from the trial due to severe adverse effects (5) and other reasons (4), so there were 106 patients evaluable for clinical efficacy. The response rate was 14.5% (8/55) in arm A, and 33.3% (17/51) in arm B (P=0.011). The survival time in arm A was 9.7 months (mean) and 8.0 months (median), and 15.3 months (mean) and 10.0 months (median) in arm B (P=0.0088).

CONCLUSIONSPreliminary results show improvements in response rate and survival time (median and mean) in Rg3 arm compared with placebo arm. It is worthy to confirm the results in further clinical trials.

OBJECTIVETo study the effects of skeletal muscle satellite cells implanted into infarcted myocardium on the volume of remnant myocytes.

METHODSThirty-six adult mongrel canines were divided randomly into implantation group and control group. In the implantation group, skeletal muscle satellite cells taken from the gluteus maximus muscles of the dogs were cultured, proliferated and labeled with 4',6-diamidino-2-phenylindone (DAPI) in vitro. In both groups, a model of acute myocardial infarction was established in every dog. In the implantation group, each dog was injected with M199 solution containing autologous skeletal muscle satellite cells. The dogs in the control group received M199 solution without skeletal muscle satellite cells. The dogs of both groups were killed 2, 4 and 8 weeks after implantation (six dogs in a separate group each time). Both infarcted myocardium and normal myocytes distal from the infracted regions isolated were observed under optical and fluorescent microscope. Their volumes were determined using a confocal microscopy image analysis system and analyzed using SAS. A P < 0.05 was considered significant.

RESULTSA portion of the implanted cells differentiated into muscle fiber with striations and were connected with intercalated discs. Cross-sectional area and cell volume were increased in normal myocardium. Hypertrophy of remnant myocytes in the infarcted site after skeletal muscle cell implantation was much more evident than in the control group. Cross-sectional area, cell area and cell volume differed significantly from those of the control group (P < 0.05). Hypertrophy of the cells occurred predominantly in terms of width and thickness, whereas cell length remained unchanged.

CONCLUSIONSkeletal muscle satellite cells implanted into infarct myocardium, could induce the hypertrophy of remnant myocyte cells in the infarcted site and could also aid in the recovery of the contractile force of the infarcted myocardium.

Animals ; Cell Size ; Dogs ; Myocardial Infarction ; pathology ; Myocardium ; pathology ; Myocytes, Cardiac ; cytology ; Random Allocation ; Satellite Cells, Skeletal Muscle ; cytology ; physiology

OBJECTIVETo study the effect of different access routes on autologous satellite cell implantation to stimulate myocardial regeneration.

METHODSSatellite cells were procured from skeletal muscle (gluteus max) of adult mongrel canine, cultured, proliferated and labeled with 4', 6-diamidino-2-phenylindone (DAPI) in vitro. The cells were autologously implanted into the site of acute myocardial infarction by local injection or perfusion through the ligated distal left anterior descending coronary artery. Specimens were harvested 2, 4 and 8 weeks later for histological study.

RESULTSThe labeling efficiency of satellite cells with DAPI was close to 100%. Fluorescent cells were found at the infarcted zone, papillary muscle and local injection site. Some of these cells had progressively differentiated into striated muscle fibers connected to intercalated discs. The infant cells appeared different from the mature myocardium under an electron microscope. Satellite cells implanted by perfusion through the coronary artery were arranged in order of consistency with host myocardial fibers. The satellite cells, implanted by local injection, were found growing in a disordered way.

CONCLUSIONSatellite cells, implanted by coronary artery perfusion, can progressively differentiate into striated muscle fibers, arranging in order and disseminating over the infarcted zone. This approach seems more favorable for the recovery of myocardial contractile function than that of local injection.

Animals ; Cell Differentiation ; physiology ; Dogs ; Myocardial Infarction ; pathology ; therapy ; Myocardium ; cytology ; Regeneration ; Satellite Cells, Skeletal Muscle ; cytology ; transplantation ; Transplantation, Autologous