Hepatic ischemia/reperfusion injury (HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI. Ischemia/reperfusion surgery was performed to establish a murine model of HIRI. 16S rRNA gene sequencing and metabolomics were used for microbial analysis. Transcriptomics and proteomics analysis were employed to study the host cell responses. Our results establish HIRI was significantly increased when surgery occurred in the evening (ZT12, 20:00) when compared with the morning (ZT0, 08:00); however, antibiotic pretreatment reduced this diurnal variation. The abundance of a microbial metabolite 3,4-dihydroxyphenylpropionic acid was significantly higher in ZT0 when compared with ZT12 in the gut and this compound significantly protected mice against HIRI. Furthermore, 3,4-dihydroxyphenylpropionic acid suppressed the macrophage pro-inflammatory response in vivo and in vitro. This metabolite inhibits histone deacetylase activity by reducing its phosphorylation. Histone deacetylase inhibition suppressed macrophage pro-inflammatory activation and diminished the diurnal variation of HIRI. Our findings revealed a novel protective microbial metabolite against HIRI in mice. The potential underlying mechanism was at least in part, via 3,4-dihydroxyphenylpropionic acid-dependent immune regulation and histone deacetylase (HDAC) inhibition in macrophages.

Objective To investigate the clinical values of NT-proBNP in left ventricular enlargement(LVE) and left ventricular dysfunction(LVD) of the patients with essential hypertension(EH) to provide a diagnostic basis for their diagnosis .Methods Plas-ma NT-proBNP concentrations in 120 patients with EH and in 29 normal controls were measured ,then the echocardiography exami-nation was performed to determine the left ventricular ejection fraction ( LVEF) ,left ventricular end-diastolic diameter(LVEDD) , left atrium(LA) and left ventricular systolic diameter(LVSDD) .The correlation between plasma NT-proBNP with LVE and LVD was analyzed .The diagnostic accuracy of NT-proBNP was analyzed by using receiver operating characteristic (ROC) curve .Results There were no statistically significant differences in the aspects of age ,sex and serum creatinine between the EH group and con-trol group ,but plasma NT-proBNP level of the former was significantly higher than that of the latter .The NT-proBNP level in the patients with LVE was significantly higher than that in the patients with normal left ventricle (P<0 .05) .The NT-proBNP level in the LVD patients was significantly higher than that in the patients with normal left ventricular function (P<0 .05) .The plasma NT-p roBNP level was positively correlated with LA ,LVEDD and LVSDD(r=0 .518 ,0 .58 ,0 .48 ,P<0 .01) while negatively crrelated with LVEF(r= -0 .61 ,P<0 .01) .The ROC curve showed that when the NT-proBNP was set at 380 pg/mL ,the sensitivity and specificity of NT-proBNP for diagnosing LVE were 80 .6% and 72 .4% ;which for diagnosing LVD were 80 .8% and 77 .4% ,re-spectively .Conclusion NT-proBNP is closely correlated with multiple ultrasonic indicators reflecting the left ventricular function and its level can reliably reflect the left ventricular contraction function ,which can serve as the marker for screening LVE and LVD in the patients with EH .

Objective To investigate the effects of osthole on neural stem cells ( NSCs) differentiation and explore the potential mechanism. Methods Brain-derived NSCs from newborn mice were isolated and cultured in vitro and determined by immunofluorescence. The P5 generations of NSCs were placed in culture solution with osthole at concentrations of (0,10,50, 100 μmol·L-1 ) . The neuron, astrocyte and oligodendroglia cell differentiation were determined by immunofluorescence. The mRNA expression of Notch 1 and its target genes Mash 1 and Neurogenin 2 were assessed by RT-PCR. Results The neurosphere displayed Nestin and Sox 2-postive by immunofluorescence, suggesting that the cultured cells were NSCs. Osthole promoted NSCs differentiating into more neuron(P<0. 01) and oligodendrocyte(P<0. 05), but not astrocyte. Meanwhile, osthole significantly reduced the mRNA expression of Notch 1(P<0. 01) and increased Ngn 2(P<0. 01)at the dose of 100 μmol·L-1. Conclusion Osthole enhances NSCs differentiating into more neuron and oligodendrocyte via probablly inhibiting Notch signal pathway.

Objective To systematically review the efficacy of hydromorphone hydrochloride injection for treatment of chronic pain.Methods Web of Science Proceedings and PubMed were searched for clinical trials involving the efficacy of hydromorphone for treatment of chronic pain, with no language or time limit.Evaluation indexes included visual analogue scale (VAS) score and the rate of pain control or relief.The studies were screened independently, and the data were extracted by two researchers.Meta-analysis was conducted using the Stata 10 software.Results Eleven studies involving 452 patients were included in our meta-analysis.VAS score was significantly decreased after treatment compared with that before treatment.For the patients with cancer pain, VAS score was significantly decreased after treatment with hydromorphone hydrochoride injection, and the rate of pain control or relief was increased when compared with the other opioid analgesics.Conclusion Hydromorphone hydrochloride injection can treat chronic pain, and it may provide better therapeutic effect than the other opioid analgesics for the patients with cancer pain.

Objective To investigate the influence of in vitro artificial CO 2 cavity on matrix metallopro-teinase 2(MMP-2), adhesion molecule vascular cell adhesion molecule 1(VCAM-1), and intercellular adhesion molecule 1(ICAM-1)expression in MDA-MB-231 cell.Methods An in vitro artificial CO2 cavity model was es-tablished.MDA-MB-231 cells were exposed to CO2 under the pressure of 7 mmHg for 1, 2 and 4 hours, respective-ly.MMP-2 concentration was measured by enzyme linked immunosorbent assay (ELISA).VCAM-1 and ICAM-1 ex-pression were measured by flow cytometry 0, 24, 48 and 72 hours after CO2-insufflation.Hypoxia group was ex-posed to 0 mmHg helium for 1 h, and the control group was exposed to 37℃incubator only .Results Compared with that in the control group , MMP-2 expression in the 1, 2 and 4 hours treatment group was significantly elevat-ed at 0 hour(F=15.045, P<0.05), and the MMP-2 expression in the 2 hours CO2 treatment group was signifi-cantly elevated after 24 hours compared with that in the control group and 1, and 4 hours CO2 treatment group (F=5.976, P<0.05).The VCAM-1 expression was significantly elevated at 0 hour and after 24 hours in the 1, 2 and 4 hours CO2 treatment group compared with that in the control group ( F1 =18.321, F2 =20.443, P<0.05), and significantly declined after 72 hours in the 4 hours CO2 treatment group compared with that in 1, and 2 hours CO2 treatment group(F=15.045,P<0.05).ICAM-1 expression was significantly elevated at 0 hour in hypoxia group and 1, 2, 4 hours CO2 treatment group compared with that in the control group , Meanwhile it was higher in 2 hours CO2 treatment group than in 1 hours and 4 hours CO2 treatment group(F=73.765, P<0.05). ICAM-1 expression was significantly elevated after 24 hours in 2 and 4 hours CO2 treatment group compared with that in the control group and 1 hour CO2 treatment group(F=46.322, P<0.05), and it was significantly elevat-ed after 48 hours in 2 hours CO2 treatment group compared with that in the control group and 1, and 4 hours CO2 treatment group(F=22.315, P<0.05).Conclusion The expression of MMP-2, adhesion molecule VCAM-1, and ICAM-1 in MDA-MB-231 cells is elevated after exposure to artificial 7 mmHg CO2 cavity, and CO2 cavity of mastoscopy may modulate the metastasis capacity of breast tumor cells .

BACKGROUNDA variety of inflammatory mediators and effector cells participate together in acute lung injury, and lead to secondary injury that is due to an inflammatory cascade and secondary diffuse lung parenchyma injury. Inflammation is associated with an oxidative stress reaction, which is produced in the development of airway inflammation, and which has positive feedback on inflammation itself. Resolvin D1 can reduce the infiltration of neutrophils, regulate cytokine levels and reduce the inflammation reaction, and thereby promote the resolution of inflammation. The purpose of this study is to investigate the effects of resolvin D1 on an inflammatory response and oxidative stress during lipopolysaccharide (LPS)-induced acute lung injury.

METHODSLPS (3 mg/kg) was used to induce the acute lung injury model. Pretreatment resolvin D1 (100 ng/mouse) was given to mice 30 minutes before inducing acute lung injury. Mice were observed at 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days and 7 days after LPS was administrated, then they were humanely sacrificed. We collected bronchoalveolar lavage fluid (BALF) and the lung tissues for further analysis. Paraffin section and HE staining of the lung tissues were made for histopathology observations. Parts of the lung tissues were evaluated for wet-to-dry (W/D) weight ratio. tumor necrosis factor (TNF)-α, inter leukin (IL)-1β, IL-10 and myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA). A lipid peroxidation malondialdehyde (MDA) assay kit was used to detect MDA. A total superoxide dismutase assay kit with WST-1 was used to analyze superoxide dismutase (SOD). We determined the apoptosis of neutrophils by Flow Cytometry. A real-time quantitative PCR Detecting System detected the expression of mRNA for heme oxygenase (HO)-1.

RESULTSPretreatment with resolvin D1 reduced the pathological damage in the lung, decreased the recruitment of neutrophils and stimulated their apoptosis. It markedly decreased the expressions of TNF-α, IL-1β and increased the expressions of IL-10, and decreased the production of MDA and increased the expressions of SOD. The mRNA expression of HO-1 was also significantly increased.

CONCLUSIONSResolvin D1 displays potent anti-inflammatory actions by regulating cytokines, inhibiting aberrant neutrophil recruitment and stimulating apoptosis of neutrophils. Resolvin D1 can also relieve the injury due to oxidative stress. The mechanisms might be related to increase HO-1 expression.

Acute Lung Injury ; chemically induced ; drug therapy ; immunology ; Animals ; Bronchoalveolar Lavage Fluid ; immunology ; Docosahexaenoic Acids ; therapeutic use ; Interleukin-10 ; metabolism ; Interleukin-1beta ; metabolism ; Lipopolysaccharides ; toxicity ; Male ; Mice ; Mice, Inbred BALB C ; Oxidative Stress ; drug effects ; Peroxidase ; metabolism ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Objective To reduce birthrate of severe thalassemia children of this area and improve population diathesis.Methods The red blood cell indices analysis was carried out on all of the samples of 2 218 couples.GapPCR and RDB method were used for α-thalassemia genotyping and β-thalassemia genotyping.Results 277 cases of thalassemia (12.49％) were identified among the total cases.220 cases were with α-thalassemia(9.92％),which including 198 cases of--SEA/αα,11 cases of-α37/,7 cases of-α4.2/αα,57 cases were with β-thalassemia(2.57％),the types of mutation were CD41/42 (-TTCT),IVS2nt-654 (C→T),CD17 (A→T),-28 (A→G),TATAbox29 (A→G),CD71/72(+ A).42 carrier couples were detected for thalassemia and the fetuses were subjected prenatal diagnosis:3cases of Bart's edema,7 cases of β-thalassemia homozygote.Conclusions Neonates with major thalassemia can be clarified and even avoided by screening the incidence and types of genicmutations.Thus setting up the system of prenatal screening-prenatal diagnosis-selective abortion is effective to avoid the birth of neonates.And it is vital to improve the quality of human being.

Objective To evaluate the role of inositol triphosphate receptor (IP3 R) in the fractalkine-induced activation of p38MAPK signaling pathway in BV-2 microglial cells.Methods BV-2 microglial cells were seeded in 3.5 cm diameter dishes (5 ml/dish),50 ml culture flasks (8 ml/flask) or 24-well plates (1 ml/hole) with a density of 1 × 105/ml and randomly divided into 5 groups (n =25 each) ∶ control group (group C),fractalkinegroup (group F),CX3C chemokine receptor 1 (CX3CR1) antibody anti-CX3CR1 + fractalkine group (group CF),IP3R antagonist 2-APB + fractalkine group (group AF) and p38 mitogen-activated protease (p38MAPK) inhibitor SB203580 + fractalkine group (group SF).Fractalkine 10 nmol/L was added to the culture medium in groups F,CF,AF and SF.The anti-CX3CR1 15 μmol/L,2-APB 50 μmol/L and SB203580 10 μmol/L were added to the culture medium in groups CF,AF and SF,respectively,1 h before addition of fractalkine.The cells were then cultured for 24 h.The intracellular Ca2+ concentration ([Ca2+]i) was measured during the 10 min incubation with fractalkine.The phosphorylation of p38MAPK was measured at 0,30,60,120 and 240 min of incubation with fractalkine.The concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in theculture medium were determined at 24 h of incubation with fractalkine.Results Compared with group C,[Ca2+]i,and the phosphorylation of p38MAPK and concentrations of IL-1β and TNF-α were significantly increased in groups F,CF,AF and SF (P ＜ 0.05).[Ca2+]i was significant lower in groups AF and CF and phosphorylation of p38MAPK and concentrations of IL-1β and TNF-α were significantly lower in groups CF,AF and SF than in group F (P ＜ 0.05).Conclusion IP3 R is involve in the fractalkine-induced activation of p38MAPK signaling pathway in BV-2 microglial cells.

Objective To determine whether p38 mitogen-activated protein kinase (p38MAPK) signaling pathway is involved in cerebral fractalkine-induced hyperalgesia in mice.Methods Two hundred and twenty-five male Kunming mice weighing 30-40 g were randomly divided into 4 groups:group control ( group C,n =55 ) ;group fractalkine (group F,n =60); group anti-CX3CR1 + fractalkine (group CF,n =55) and group SB203580 (p38MAPK inhibitor) + fractalkine (group SF,n =55).Fractalkine 100 ng was injected into cerebral lateral ventricle (i.c.v.) in groups F,CF and SF.Anti-CX3CR1 1 μg and SB203580 1 μg were injected i.c.v.at 1 h before fractalkine injection in groups CF and SF respectively.Paw withdrawal latency to a thermal nociceptive stimulus (PWL) was measured at 30 min before the drugs were injected into cerebral lateral ventricle and 30,60,120 and 240 min after fractalkine injection.Five animals were sacrificed after PWL measurement at each time point and their brains were removed for determination of phosphorylated p38MAPK protein expression (by Western blot analysis).Five animals were sacrificed at 30 min before the drugs were injected into cerebral lateral ventricle and 6,12 and 24 h after fractalkine injection for determination of IL-1β and TNF-α contents in the brain (by ELISA) in all the 4 groups.In group F 5 animals were sacrificed at 4 h after fractalkine injection for determination of action of fractalkine on microglia or astrocyte (by immunofluorescence).Results Fractalkine i.c.v.injection significantly reduced PWL and increased phosphorylated 38MAPK,IL-1β and TNF-α levels in group F as compared with group C.Pretreatment with anti-CX3CR1 or SB203580 significantly decreased fractalkine-induced hyperalgesia and phosphorylated-p38MAPK,IL-1β and TNF-α levels in groups CF and SF as compared with group F.Fractalkine was localized at microglia.Conclusion p38MAPK signal transduction pathway is involved in cerebral fractalkine-induced hyperalgesia in mice.

Objective To detect the expression of osteopontin (OPN) in cervical local tissues of patients with chronic cervicitis, cervical intraepithelial neoplasia (CIN), cervical cancer. To investigate the possibility that OPN is used as tumor marker of cervical cancer. Methods The expression of OPN in 25 cases of chronic cervicitis, 18 cases of CIN and 21 cases of cervical cancer was detected by immuohistochemistry SP method. Results The positive expression rates of OPN in the chronic cervicitis, CIN and the cervical cancer had a rising trend (48 %, 77.78 % and 80.95 %, respectively) and their differences had statistical significant (P <0.05). The OPN expression level in cervical cancer had no statistical correlation with age, tumor size, clinical stage and other clinical pathological features (P >0.05). Although OPN expression level in cervical cancer wasn' t related with tumor clinical stage, positive expression rates of OPN had a gradually increased trend along with the clinical stage. Conclusion High expression of OPN is found in cervical cancer and may be related to the occurrence and development of cervical cancer.