Cancer metastasis is the most dangerous stage of tumorigenesis and evolution, the primary cause of death in cancer patients. Clinically, more than 60% of cancer patients have found metastasis at the time of examination. Modern medicine has made significant progress on the mechanisms of cancer metastasis in recent years, from the simple "anatomy and machinery" theory forward to the "seed and soil" theory, then to the "microenvironmental" theory and the "cancer stem cell" theory. The emerging "cancer stem cell" theory successfully explains phenomenon such as tumor genetic heterogeneity, anoikis resistance, tumor dormancy, providing more new targets and ideas for the diagnosis and treatment of cancer metastasis.
Animals ; Humans ; Medicine ; methods ; Neoplasm Metastasis ; Neoplasms ; drug therapy ; pathology

Animals ; Burns ; drug therapy ; metabolism ; physiopathology ; Interleukin-18 ; genetics ; metabolism ; Lactulose ; therapeutic use ; Lipopolysaccharides ; blood ; Liver ; metabolism ; physiopathology ; Lung ; metabolism ; physiopathology ; Male ; Multiple Organ Failure ; prevention & control ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar

Objective To investigate the recent effect of full arthroscopic dual-beam reconstruction of the posterior cruciate ligament(PCL)using tibial Inlay technique.Methods From March 2007 to September 2009,17 PCL injured patients underwent full arthroscopic dual-beam PCL reconstruction using Inlay technique,including 16 males and 1 female,with an average age of 25 years(range,19-54).Of all cases,Lysholm score was(53.4±2.1)points,International Knee Documentation Committee(IKDC)rated C in 7,D in 10,and posterior drawer test(+)in 17.We used self-designed tibia tunnel drill system to produce the deep-limited bone tunnel.Follow-up began at 12 months after operation.Evaluate Lysholm knee score,IKDC rating,and posterior drawer test to compare the knee stability with that of preoperative.Observe the location of the bone block and healing by checking knee X-ray and spiral CT scan.Results Seventeen patients were followed up between 12 to 28 months,with an average of 17.8 months.In the last follow-up study,Lysholm score(93.5±1.7)points compared with that of preoperative was statistically significant different(P=0.016).IKDC rating of A grade in 15 cases,B in 2,compared with that of preoperative was statistically significant different(P=0.021).Posterior drawer test were negative in 15 cases,slight positive in 2.The X-ray and spiral CT scan showed the location of the bone block were perfect and healed well.Conclusion We can accurately produce the deep-limited bone tunnel by the tibia tunnel drill system with minor trauma,and the recent clinical effects of PCL reconstruction were pretty good.

Adult ; Aged ; Analgesics, Opioid ; administration & dosage ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Humans ; Injections, Spinal ; Male ; Middle Aged ; Pupil ; drug effects ; Sufentanil ; administration & dosage ; pharmacology

BACKGROUNDSeveral studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats.

METHODSNinety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-α (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining.

RESULTSThe rats in the I/R group had lower NDSs (P < 0.05), larger infarct volume (P < 0.05), lower HMGB1 levels (P < 0.05), and higher TNF-α levels (P < 0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P < 0.05).

CONCLUSIONSPretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.

Animals ; Blotting, Western ; Brain Ischemia ; drug therapy ; metabolism ; prevention & control ; Injections, Intravenous ; Isoxazoles ; administration & dosage ; therapeutic use ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; metabolism ; prevention & control

The objective of this study was to observe the expression of hoxc4 and hoxc6 genes in the process of differentiation of hematopoietic stem cell (HSC) to colony forming unit-T Lymphocyte (CFU-TL) in vitro. and to explore the possible mechanism of HCMV-induced maldevelopment of human cord blood CFU-TL on genetic level through effecting the differentiation progress by human cytomegalovirus (HCMV) with and/or all-trans retinoic acid (ATRA), Normal CFU-TL culture was used as blank control. After detection with MTT, mRNA expression levels in the human cord blood CFU-TL hoxc4 and hoxc6 genes following HCMV infection and ATRA treatment were detected by fluorogenic quantitative reserve transcription polymerize chain reaction (FQ-RT-PCR) method. HCMV of 10(6) plaque formation unit (PFU)/ml was diluted to 0.1 ml 10(5) PFU/ml and added into the infected group. The results showed that the expression of hoxc4 and hoxc6 genes in the differentiation process increased slightly on day 3, and were up to the most on day 7 (p < 0.05), while became lower on day 12 respectively in normal group, HCMV group and ATRA group. Compared with the expression of hoxc6, the expression of hoxc4 was obviously higher in each group (p < 0.05). Compared with the expression of hoxc4 and hoxc6 genes in normal group, the expressions of hoxc4 and hoxc6 in ATRA group were up-regulated remarkably (p < 0.05), while the expressions of hoxc4 and hoxc6 in group HCMV were down-regulated (p < 0.05). It is concluded that the regular expression of hoxc4 and hoxc6 genes mRNA appeared in each group. A positive co-relationship exits between hoxc4/hoxc6 genes and lymphocytic progenitor hematopoiesis. Compared with the expression of hoxc6 gene, the expression of hoxc4 gene is obviously higher in each group. HCMV can down-regulate the expression of hoxc4 and hoxc6 genes and lead to suppression effect on cell morphology, which confirms that the normal hematopoietic lineage determination and maturation rely on the stable and consistent expression of homeobox gene. At the same condition, ATRA (6 x 10(-8) mol/L at 60 nmol/ml) can up-regulate hoxc4 and hoxc6 genes expression. ATRA can up-regulate the expression of hoxc4 and hoxc6 genes.
Cell Line ; Cell Proliferation ; Cytomegalovirus ; genetics ; Cytomegalovirus Infections ; genetics ; Homeodomain Proteins ; genetics ; Humans ; Lymphoid Progenitor Cells ; cytology ; Tretinoin ; pharmacology

Objective: To investigte the efficacy of docetaxel combined with androgen deprivation therapy for the treatment of metastatic hormone-sensitive prostate cancer based on Chinese population. Methods: A total of 497 patients were enrolled from January 2004 to July 2018 in the Changhai Hospital. 459 patients received androgen deprivation therapy alone and 38 patients received androgen deprivation therapy combined with docetaxel. The mean age was (72.1±8.7)years. The median PSA level was 100.0 ng/ml, ranging 42.3-999.0 ng/ml. Patients of clinical T₂, T₃, T₄ stage were 213(42.9%), 160(32.2%), 124(24.9%), respectively. Patients of clinical N₀, N₁, N_x stage were 319(64.2%), 144(29.0%), 34(6.8%), respectively. Patients of clinical M₀, M_1a, M_1b, M_1c, M_x stage were 100(20.1%), 51(10.3%), 332(66.8%), 9(1.8%), 5(1.0%), respectively. Gleason scores of biopsy showed that 146(29.4%) patients was ≤7, 103(20.7%) was 8 and 248(49.9%)was ≥9. Propensity score matching was used to match the baseline between groups. Caliper value was set at 0.02. SPSS 22 software was used to achieve a 1∶1 match between the two groups. There were no statistical difference in the age(P=0.102), PSA(P=0.713), T stage(P=0.113), N stage(P=0.226), M stage(P=0.514), Gleason score(P=0.612), tumor loading(P=0.812)between the two groups. The castration resistance-free rate and cancer specific survival rate of the two groups were compared by log-rank and breslow-wilcoxon test. Furthermore, forest plots were used to display the analysis results of different subgroups such as age, PSA, clinical stage, Gleason score, tumor load, whether patients had received palliative resection, and the differences in castration resistance-free rate were compared between the subgroups with high tumor load. Results: The median follow-up time was 22.6 months in the androgen deprivation therapy group and 13.7 months in the combined therapy group. The number of patients with castration resistance in the two groups was 23 and 17, respectively. There were 3 and 6 deaths, respectively. There was no statistically significant difference in the overall progression time to castration resistance between the two groups (10.3 m vs. 16.5 m, P>0.05), and no statistically significant difference in the prostate cancer specific survival rate (21.9 m vs.14.8 m, P>0.05). When subgroup analysis was performed, it was found that patients in the high-metastasis-volume subgroup who received the combination therapy had a significantly longer castration resistance free lifetime (10.6 m vs. 7.2 m, P=0.044), but there was no significant difference in the low- metastasis-volume subgroup(10.5 m vs.12.6 m, P>0.05). Conclusion Docetaxel combined with androgen deprivation therapy can improve the castration resistance free rate in patients with high metastasis volume, but not in low metastasis volume group.

Objective:To investigate the regulatory effect of serum containing Buyang Huanwu Tang on endothelial-to-mesenchymal transition(EndMT) in human pulmonary artery endothelial cells (HPAEC), and make further analysis on its mechanism from the perspective of the signal transduction of Jagged1/Notch1. Method:Rabbit serum containing Buyang Huanwu Tang was prepared by gavage with dosage of 53.36 g·kg^-1·d^-1, and blank serum was prepared by gavage with same volume of normal saline. The HPAECs cultured in vitro, EndMT model was established by the transforming growth factor-β₁(TGF-β₁) induced, which were divided into five groups:the control group (10%blank serum), the model group (10%blank serum+TGF-β₁), the serum containing high-dose Buyang Huanwu Tang group (10%medicated serum + TGF-β₁), the medium-dose group (5%medicated serum + 5%blank serum medicated + TGF-β₁) and the low-dose group(2.5%medicated serum+7.5%blank serum+ TGF-β₁). Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) method. Cell migration was detected by transwell and scratch assay. The endothelial markers platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), vascular endothelial cadherin (VE-cadherin) and the mesenchymal markers fibroblast-specific protein 1 (FSP1), α-smooth muscle actin (α-SMA) were observed by immunofluorescence assay. The expression levels of Notch1, Jagged1 and CBF1 were detected by Western blot assay. Result:Compared with the control group, the proliferation and migration abilities of the HPAEC cells in model group were enhanced (P<0.01), and the expressions of CD31 and VE-cadherin were decreased, while the expressions of FSP1 and α-SMA were increased. Further study found that the expressions of Notch1, Jagged1 and CBF1 were up-regulated (P<0.01). After the intervention of the serum containing Buyang Huanwu Tang, compared with model group, the proliferation and migration abilities of cells were decreased (P<0.05,P<0.01), and the expressions of CD31 and VE-cadherin were on the rise, while the expressions of FSP1and α-SMA were on the decline. The expressions of Notch1, Jagged1 and CBF1 were also significantly lower than those in model group (P<0.05,P<0.01). With the increase of serum concentration, the effect was more obvious. Conclusion:The serum containing Buyang Huanwu Tang can partly inhibit the EndMT in human pulmonary artery endothelial cells, which may be related to the regulation effect of Jagged1/Notch1 signaling.

BACKGROUNDIn-hospital medical complications are associated with poorer clinical outcomes for stroke patients after disease onset. However, few studies from China have reported the effect of these complications on the mortality of patients with acute ischemic stroke. In this prospective work, the China National Stroke Registry Study, we investigated the effect of medical complications on the case fatality of patients with acute ischemic stroke.

METHODSFrom September 2007 to August 2008, we prospectively obtained the data of patients with acute stroke from 132 clinical centers in China. Medical complications, case fatality and other information recorded at baseline, during hospitalisation, and at 3, 6, and 12 months after stroke onset. Multivariable Logistic regression was performed to analyze the effect of medical complications on the case fatality of patients with acute ischemic stroke.

RESULTSThere were 39 741 patients screened, 14 526 patients with acute ischemic stroke recruited, and 11 560 ischemic stroke patients without missing data identified during the 12-month follow-up. Of the 11 560 ischemic patients, 15.8% (1826) had in-hospital medical complications. The most common complication was pneumonia (1373; 11.9% of patients), followed by urinary tract infection and gastrointestinal bleeding. In comparison with patients without complications, stroke patients with complications had a significantly higher risk of death during their hospitalization, and at 3, 6 and 12 months post-stroke. Having any one in-hospital medical complication was an independent risk factor for death in patients with acute ischemic stroke during hospital period (adjusted OR = 6.946; 95%CI 5.181 to 9.314), at 3 months (adjusted OR = 3.843; 95%CI 3.221 to 4.584), 6 months (adjusted OR = 3.492; 95%CI 2.970 to 4.106), and 12 months (adjusted OR = 3.511; 95%CI 3.021 to 4.080). Having multiple complications strongly increased the death risk of patients.

CONCLUSIONShort-term and long-term outcomes of acute stroke patients are affected by in-hospital medical complications.

Aged ; China ; Female ; Gastrointestinal Hemorrhage ; complications ; Hospital Mortality ; Hospitalization ; statistics & numerical data ; Humans ; Male ; Middle Aged ; Pneumonia ; complications ; Prospective Studies ; Registries ; statistics & numerical data ; Stroke ; mortality ; Urinary Tract Infections ; complications

Brain Injuries ; pathology ; surgery ; China ; Craniotomy ; Earthquakes ; Hematoma, Epidural, Cranial ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Time Factors ; Treatment Outcome