BACKGROUND: This study aimed to determine the plasma levels of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), D-dimer, IL-6 and TNF-α, and observe the relations among uPA, uPAR, D-dimer, IL-6 and TNF-α in patients with systemic inflammatory response syndrome (SIRS). METHODS: A prospective, clinical case-control study was conducted in patients with SIRS at age of more than 55 years old treated during 2008-2010 at Wuhan Central Hospital. Venous blood samples were collected by routine venipuncture. Eighty-five patients were divided into two groups according to diagnostic criteria of SIRS: SIRS patients from intensive care units (n=50), and non-SIRS patients from medical wards (n=35). Thirty healthy blood donors who visited the General Health Check-up Division at Wuhan Central Hospital served as controls. Excluded from the study were (1) those patients with pregnancy; (2) those with cancer; (3) those died after admission into the ICU in 7 days; (4) those received cardiopulmonary resuscitation; (5) those who had previous blood system diseases; and (6) those with SIRS before admission into the ICU. The levels of uPA, uPAR, D-D, IL-6 and TNF-α in blood were detected by commercial enzyme-linked immunosorbent assay (ELISA) kit. The data were analyzed using SPSS version 17.0 and expressed as mean ± standard. Student's t test and the Mann-Whitney U test were used in the analysis. The relations of uPA, uPAR and D-dimer, IL-6 TNF-α levels were analyzed using Spearman's rank-order correlation coefficient test. RESULTS: The plasma levels of uPA , uPAR, D-dimer,IL-6 and TNF-α in the patients with SIRS were obviously higher than those in the non-SIRS patients and controls (P<0.001). Correlation analysis showed a positive correlation between uPAR and IL-6 levels (r=0.395, P=0.004) and between uPAR and TNF-α levels (r=0.606, P<0.001), but no correlation between uPAR and D-dimer levels (r=0.069, P=0.632). No correlation was observed between uPA, D-dimer, IL-6 and TNF-α levels (P>0.05). The establishment of ROC curve was based on the levels of uPAR, D-dimer, IL-6 and TNF-αin 24 hours for the diagnosis of multiple organ dysfunction syndrome (MODS), and the ROC areas under the curve were 0.76, 0.58, 0.86 and 0.83, respectively. CONCLUSIONS: uPA and uPAR play a major role in patients with SIRS in the process of coagulation disorder, but the mechanism of SIRS is not the same. uPAR may play a central role in the development of SIRS to MODS.

BACKGROUND:Urokinase-type plasminogen activator (uPA) and urokinase-type plasminogen activator receptor (uPAR) are known as important factors, which mediate a variety of functions in terms of vascular homeostasis, inflammation and tissue repair. However, their role in systemic inflammatory response syndrome (SIRS) has been less well studied. This study aimed to test the hypothesis that the abnormalities of fibrinolysis and degradation of extracellular matrix mediated by uPA and uPAR are directly related to the patients with SIRS. We therefore analyzed their role and clinicopathological significance in patients with SIRS.METHODS:A case-control study was conducted with 85 patients who were divided into two groups according to the diagnostic criteria of SIRS:SIRS group (n=50) and non-SIRS group (n=35). The SIRS group was divided into MODS group (n=26) and non-MODS group (n=24) by their severity, and survival group (n=35) and non-survival group (n=15) by their prognosis. Another 30 healthy adults served as normal controls. uPA and uPAR in plasma were detected by commercial enzyme-linked immunosorbent assay (ELISA) kits.RESULTS:The plasma level of uPA was lower in the SIRS group than in the non-SIRS group and controls (P<0.001 andP<0.001). It was lower in sepsis patients and the MODS group than in the non-sepsis patients and the non-MODS patients (allP<0.05). However, there was no difference in uPA level between survivors and non-survivors (P>0.05). The plasma level of uPAR increased in the SIRS group compared with the non-SIRS group and controls (P<0.001 andP<0.001). There was a significant elevation of uPAR in sepsis patients, MODS patients and non-survivors as compared with non-sepsis patients, non-MODS patients and survivors respectively (allP<0.05). Plasma uPAR levels were positively correlated with APACHE II score (r=0.575,P<0.001) and SOFA score (r=0.349,P=0.013). AUCs for the prediction of SIRS mortality were 0.67 and 0.51, respectively, for uPA and uPAR.CONCLUSION:uPAR could be a predictor of poor outcome in patients with SIRS.

OBJECTIVETo reverse the multidrug resistant (MDR) phenotype of human breast carcinoma cells by small hairpin RNA (shRNA) technique targeting hypoxia-inducible factor (HIF)-1alpha gene.

METHODSSmall hairpin RNA (shRNA) eukaryotic expression vector targeting HIF-1alpha gene, named pSilencer-HIF, was constructed and transfected into MCF-7/ADR human breast cancer cells by liposome technique. Tumor cell livability (TCL) and Rhodamine 123 efflux assay were used to monitor the biological changes of the transfected cells. The mRNA and protein expression of HIF-1alpha and mdr-1 were investigated by RT-PCR and Western blot.

RESULTSThe successful construction of pSilencer-HIF plasmid was confirmed by DNA sequencing. HIF-1alpha mRNA and protein levels were significantly decreased in MCF-7/ADR cells after the transfection and there was a direct correlation between HIF-1alpha and mdr-1 expression. By comparing the cells transfected with control vector and the MCF-7/ADR cells transfected with pSilencer-HIF, a reduced TCL from 76% to 43%, and an increased Rhodamine 123 fluorescence intensity from 22.0% to 86.6% were observed.

CONCLUSIONSpSilencer-HIF-1alpha has been successfully constructed. The inhibition of HIF-1alpha expression through shRNA technique can significantly reverse the multidrug resistance phenotype of MCF-7/ADR cells.

Breast Neoplasms ; pathology ; Cell Line, Tumor ; Drug Resistance, Multiple ; drug effects ; physiology ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; RNA Interference ; RNA, Small Interfering ; pharmacology

BACKGROUNDEndogenous hydrogen sulfide (H(2)S) plays an important role in hypertension. The aim of this study was to investigate the role of erythrocyte and serum H(2)S in patients with untreated essential hypertension.

METHODSWe recruited 62 patients (age 22 - 74 years) with untreated prehypertension or hypertension, and 64 normotensive subjects (age 18 - 64 years). We assessed the 3-mercaptopyruvate sulphurtransferase (MPST) protein expression in erythrocytes and measured the H(2)S production from erythrocytes and serum H(2)S levels, then analyzed the association of erythrocytic or serum H(2)S content and blood pressure or cardiovascular risk factors (e.g., age, body mass index (BMI) and dyslipidemia). A stepwise regression analysis was used to evaluate the possible relationship of erythrocytic H(2)S in hypertension.

RESULTSIn hypertensive patients, erythrocyte H(2)S production ((111.04 ± 29.20) nmol/min per 10(8) erythrocytes) was higher than that in controls ((78.85 ± 19.38) nmol/min per 10(8) erythrocytes), and serum H(2)S was also higher. The erythrocytic H(2)S production was associated with increased systolic blood pressure (sBP), diastolic blood pressure (dBP), age, BMI, level of C-reactive protein (CRP), as well as triglycerides (TG) and high density lipoprotein cholesterol (HDL-C). Serum H(2)S was not associated with age or CRP. Stepwise regression analysis showed that erythrocytic H(2)S production was correlated with sBP, TG, HDL-C, low density lipoprotein cholesterol (LDL-C) and blood urea nitrogen (BUN) and serum H(2)S was correlated with dBP and TG. Results of receiver-operating characteristic curve analysis suggested that erythrocytic H(2)S production was a more sensitive predictor of hypertension development than serum H(2)S.

CONCLUSIONErythrocytic or serum H(2)S production is sensitive predictor of hypertension.

Adolescent ; Adult ; Aged ; Erythrocytes ; metabolism ; Female ; Humans ; Hydrogen Sulfide ; blood ; Hypertension ; blood ; metabolism ; Male ; Middle Aged ; Young Adult

Carcinoma, Hepatocellular ; genetics ; DNA Methylation ; DNA-Binding Proteins ; genetics ; Histone-Lysine N-Methyltransferase ; Humans ; Liver Neoplasms ; genetics ; Nuclear Proteins ; genetics ; Promoter Regions, Genetic ; genetics ; Transcription Factors ; genetics

We investigated the fatty acid profiles of muscle from large yellow croaker (Pseudosciaena crocea R.) of different age. One- and two-year-old fish were cultured in floating net cages and sampled randomly for analysis. Moisture, protein, lipid and ash contents were determined by methods of Association of Analytical Chemist (AOAC) International. Fatty acid profile was determined by gas chromatography. Crude protein, fat, moisture and ash contents showed no significant differences between the two age groups. The contents of total polyunsaturated fatty acids and docosahexaenoic acid (DHA) were significantly higher and eicosapentaenoic acid (EPA) content was significantly lower in the two-year-old large yellow croaker than in the one-year-old (P<0.05). No significant differences were observed in the contents of total saturated fatty acids and monounsaturated fatty acids, or the ratio of n-3/n-6 fatty acids among the large yellow croakers of the two age groups. We conclude that large yellow croakers are good food sources of EPA and DHA.
Age Factors ; Animals ; Fatty Acids ; analysis ; Muscles ; chemistry ; Perciformes ; metabolism

OBJECTIVETo investigate the qualitative diagnosis method of atlanto-axial tuberculosis and the corresponding therapeutic strategy.

METHODSTwenty-two cases with atlanto-axial tuberculosis proven by histopathologic diagnosis were observed. Three cases and 17 cases underwent trans-oral biopsy and CT-guide percutaneous biopsy respectively, 2 cases were conformed by frozen section in operation. Thirteen of the 22 cases underwent surgical therapy: 1 case with anterior trans-oral radical eradication and fusion under Halo-vest immobilization, 7 cases with anterior cervical radical eradication, 1 case with anterior interbody fusion and titanic plate fixation, 2 cases were with posterior atlantoaxial interlaminar fusion and 2 cases with posterior cervical occipito-axial titanic plate internal fixation and fusion. Other 9 cases accepted nonsurgical therapy: 8 cases with Halo-vest immobilization and 1 case with head halter traction. All cases were given appropriate antituberculotic chemotherapy for 12-18 months.

RESULTSAll of the 22 cases were followed up, and the average time was 37 month. The lesion focus showed reparation and fusion in X-ray, and the results were satisfactory.

CONCLUSIONSBiopsy can acquire the qualitative diagnosis on atlanto-axial tuberculosis. The choice of therapy is made on the situation of cold abscess, pathological fracture, atlanto-axial dislocation and spinal cord compression.

Adolescent ; Adult ; Antitubercular Agents ; therapeutic use ; Atlanto-Axial Joint ; pathology ; Biopsy, Needle ; methods ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Fracture Fixation, Internal ; Humans ; Male ; Middle Aged ; Spinal Fusion ; Tuberculosis, Spinal ; diagnosis ; pathology ; therapy

Objective:To evaluate the clinical outcomes of digital technique-aided occlusal rehabilitation based on implant-supported fixed prostheses (ISFP), and to provide some information for clinical application of digital technique.Methods:Retrospectively reviewed the cases which had used neuromuscular system and condylar movement tracing device to reconstruct occlusion in one or double jaw fully edentulous ISFP from January, 2013 to January, 2020. A total of 6 eligible patients were enrolled in the present study with 56 implants and 8 ISFP, including 4 male patients and 2 female patients, aged from 43 to 74 years. The clinical outcomes were evaluated in four aspects, including implant survival rate, implants success rate, marginal bone loss and the occurrence of prosthesis complications.Results:The follow-up time was (4.0±2.2) years (1-7 years). The implant survival rate was 100% (56/56) and the implant success rate was 98% (55/56), with an average missal and distal marginal bone loss of (0.04±0.11) mm/year. Veneer chipping occurred at incisal edge of 2 adjacent incisors in only one prosthesis 3 years after rehabilitation.Conclusions:Combination of digital techniques of neuromuscular system and condylar movement tracing device to assist occlusal rehabilitation based on ISFP showed a high implant success rate. The complication seldom happened. Long and stable occlusion has been observed. The clinical outcomes were favorable.

Porcine circovirus 3 (PCV3) has been detected in major pig-producing countries around the world since its first report in the US in 2016. Most current studies have focused on epidemiological investigations and detection methods of PCV3 because of lack of live virus strains for research on its pathogenesis in porcine cells or even in pigs. We constructed a recombinant plasmid pCMV-Cap carrying the PCV3 orf2 gene to investigate the effects of capsid (Cap) protein expression on autophagic response in human embryonic kidney cell line 293T (HEK293T). We demonstrate that PCV3 Cap protein induced complete autophagy shown as formation of autophagosomes and autophagosome-like vesicles as well as LC3-II conversion from LC3-I via inhibiting phosphorylation of the mammalian target of rapamycin (mTOR) in HEK293T cells. The ubiquitin-proteasome pathway is also involved in the autophagy process. These findings provide insight for further exploration of PCV3 pathogenetic mechanisms in porcine cells.

Objective To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC).
Methods In this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival.
Results The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75;P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48;95%confidence interval, 0.35-0.68;P<0.001). The main adverse effect of sorafenib was rash and acne of the skin (in 51.7%patients). The incidences of severe rash, diarrhea, and dry skin were 5.6%, 5.6%, and 2.2%in the sorafenib group. One patient reached partial response in the sorafenib group.
Conclusions Sorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.