Objective To investigate the change and clinical value of serum cystain C(CysC)level in the patients with HBeAg-negative chronic hepatitis B(CHB).Methods 212 cases of CHB in our hospital were selected and divided into the HBeAg-negative group and the HBeAg-positive group according to the HBeAg status.105 healthy individuals at the same time were enrolled as the control group.The levels of serum CysC,ALT,AST,Cr,BUN and HBV DNA in 3 groups were detected and compared.The corre-lations between serum CysC with AST,AST,Cr,Bun,HBV DNA were analyzed by the Pearson correlation analysis.Results The mean CysC level in the HBeAg-negative group was (1 .40±0.36)mg/L,which was higher than (0.93±0.12)mg/L in the control group and (0.96±0.18)mg/L in the HBeAg-positive group,the differences between them was statistically significant(P <0.05). The CysC was significantly positively correlated with serum Cr level in the HBeAg-negative group(r=0.840,P <0.01).Conclusion The CysC level might be used as an effective index for monitoring the early kidney injury in the patients with HBeAg-negative CHB,which has important significance in the prevention and treatment of HBeAg-negative CHB.

Objective To explore the role of resolvin D1 in reducing brain injury after porcine cardiopulmonary resuscitation and its potential mechanisms.Methods Twenty-eight male domestic pigs weighing (36 ±3)kg were utilized.The animals were randomly divided into 4 groups (n =7 each):sham operation group (group S),cardiopulmonary resuscitation group (group CPR),low-dose resolvin D1 gToup (group LRD),and high-dose resolvin D1 group (group HRD).The animals in group S only got the general preparation without the procedure of cardiac arrest and resuscitation.The pig model was established by 8 mins of untreated ventricular fibrillation and then 5 mins of cardiopulmonary resuscitation.At 5 min post-resuscitation,the doses of resolvin D10.3 μg/kg,and 0.6 μg/kg were correspondingly injected via the femoral vein in LRD and HRD groups,and meanwhile the same amount of vehicle was given into the animals inthe other two groups.At 3 h,6 h and 24 h post-resuscitation,the concentrations of neuron specific enolase (NSE) and S100B protein (S100B) in serum was measured.At 24 h post-resuscitation,neurological deficit score (NDS) was evaluated;thereafter the pigs were sacrificed,and cerebral cortex was obtained for the determination of tumor necrosis factor-alpha (TNF-α),interleukin-6 (IL-6),and malondialdehyde (MDA) contents,and superoxide dismutase (SOD) activity.Results Compared to group S,post-resuscitation brain injury was observed in the other three groups,which was indicated by significantly increased NDS score,and markedly elevated concentrations of serum NSE and S100B.Compared to group CPR,the NDS was significantly decreased at 24 h post-resuscitation,and the concentrations of serum NSE and S100B were significantly reduced at 6 h and 24 h post-resuscitation in LRD and HRD groups.Compared to group LRD,the NDS score and its serum markers were further significantly decreased in group HRD.The inflammatory response and oxidative stress in brain tissue were observed in all the animals experiencing cardiac arrest and resuscitation,which were indicated by increased contents of TNF-α,IL-6 and MDA and decreased SOD activity.Compared to group CPR,the contents of TNF-α,IL-6 and MDA were significantly decreasedwhile SOD activity was significantly increased in LRD and HRD groups.The indicators of inflammatory response and oxidative stress in brain tissue were further significantly improved in group HRD when compared to group LRD.Conclusions Resolvin D1 can reduce post-resuscitation brain injury in a dose-dependent manner in swine,and the mechanism is related to the inhibition of inflammatory response and oxidative stress.

Objective To investigate the effects of dexmedetomidine postconditioning on brain injury after cardiac arrest and resuscitation in a swine model.Methods Twenty-eight healthy male domestic pigs,weighing 36±2 kg,were randomized (random number) into 4 groups (n=7 each group):sham operation group (S group),cardiopulmonary resuscitation group (CPR group),low-dose dexmedetomidine postconditioning group (LDP group),and high-dose dexmedetomidine postconditioning group (HDP group).Animals in the S group only underwent the surgical preparation.In the other three groups,the experimental model was established by 8 mins of electrically induced ventricular fibrillation and then 5 mins of cardiopulmonary resuscitation.At 5 min after resuscitation,a loading dose of dexmedetomidine of 0.25 μg/kg was intravenously infused followed by continuous infusion at a rate of 0.25 μg/(kg·h) for 6 h in the LDP group,and a loading dose of dexmedetomidine of 0.5 μ.g/kg was infused followed by continuous infusion at a rate of 0.5 μg/(kg·h) for 6 h in the HDP group.The same amount of normal saline was administered in the S and CPR groups.At 1 h,3 h,6 h and 24 h after resuscitation,the levels of serum neuron specific enolase (NSE) and S100B protein were measured.At 24 h after resuscitation,neurologic deficit score (NSD) was evaluated.After that,the animals were euthanized and cerebral cortex was obtained for the determination of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6)and malondialdehyde (MDA) contents,superoxide dismutase (SOD) activity,cell apoptosis and caspase-3 expression.Results Compared with the S group,post-resuscitation neurologic dysfunction and brain injury were observed in the other three groups,which were indicated by significantly higher NDS and markedly greater levels of serum NSE and S 100B (all P＜0.05).Compared with the CPR group,the score of NDS at 24 h post-resuscitation were significantly lower and the levels of serum NSE and S100B at 6 h and 24 h post-resuscitation were significantly less in the LDP and HDP groups [NDS:194±26,103±16 vs 278±23 at 24 h;NSE (ng/mL):32.4±1.8,28.6±3.7 vs 36.2±2.8 at 6 h,39.9±4.2,35.1±1.5 vs 45.1±3.0 at 24 h;S100B (pg/mL):2 534±207,2 382±170 vs 2 825±113 at 6 h,3 719±164,3 246±176 vs 4 085±161 at 24 h,all P＜0.05].Compared with the LDP group,neurologic dysfunction and brain injury at 24 h postresuscitation were further significantly alleviated in the HDP group (all P＜0.05).Pathological analysis indicated that brain inflammation,oxidative stress and cell apoptosis were observed after resuscitation in the CPR,LDP and HDP groups.However,the contents of TNF-α,IL-6 and MDA were significantly lower while the activity of SOD was significantly higher,and cell apoptosis and caspase-3 expression were significantly reduced in the brain after resuscitation in the LDP and HDP groups compared with the CPR group (all P＜0.05).In addition,those pathological injuries mentioned above were further significantly alleviated in the brain after resuscitation in the HDP group compared to the LDP group (all P＜0.05).Conclusions Dexmedetomidine postconditioning significantly alleviated the severity of postresuscitation brain injury in a dose-dependent manner,in which the protection was produced possibly through reducing tissue inflammation,oxidative stress and cell apoptosis.

Objective To establish a porcine model of cardiopulmonary resuscitation to explore the effectiveness of resolvin D1 in improving post-resuscitation myocardial dysfunction and its potential mechanisms.Methods Twenty-eight male domestic pigs weighing 36 ± 3 kg were utilized.The pig model was established by 8 mins of untreated ventricular fibrillation and then 5 mins of cardiopulmonary resuscitation.The animals were randomly divided into 4 groups (n =7 each):sham operation group (group S),cardiopulmonary resuscitation group (group CPR),low-dose resolvin D1 group (group LRD),and high-dose resolvin D1 group (group HRD).The animals in group S only got the general preparation without the procedure of cardiac arrest and resuscitation.At 5 min after resuscitation,the doses of resolvin D1 0.3 μg/kg and 0.6 μg/kg were respectively injected via the femoral vein of pigs in LRD and HRD groups,and meanwhile the equal volume of vehicle was given into the animals in the other two groups.At 3 h,6 h and 24 h after resuscitation,the changes of stroke volume (SV) and global ejection fraction (GEF) were evaluated by a PiCCO monitor,and meanwhile the concentration of cardiac troponin I (cTNI) in serum was measured.At 24 h after resuscitation,the pigs were sacrificed,and myocardial tissue was obtained for the determination of tumor necrosis factor-alpha (TNF-α),interleukin-6 (IL-6),malondialdehyde (MDA),and superoxide dismutase (SOD) activity.Results Compared with group S,significantly decreased SV and GEF and markedly increased concentration of serum cTNI were observed in the other three groups with post-resuscitation myocardial dysfunction (all P ＜ 0.05).Compared with group CPR,the values of SV and GEF were significantly increased while the concentration of serum cTNI was significantly decreased in LRD and HRD groups [SV (ml):28 ±5,31 ±5 vs.23 ±4 at 3 hrs,32 ±3,36 ±6 vs.27 ± 6 at6 hrs,35 ±5,41 ±5 vs.29±5 at24 hrs;GEF (％):17±2,19±2 vs.14±1 at3 hrs,20±2,23 ± ±3 vs.16 ±3 at 6 hrs,23 ±2,26 ±3 vs.20 ±2 at 24 hrs;cTNI (pg/ml):247 ±34,230 ±26 vs.324 ± 56 at 3 hrs,553 ± 37,501 ± 34 vs.611 ± 44 at 6 hrs,436 ± 23,371 ± 29 vs.553 ± 47 at 24 hrs,all P ＜ 0.05].Compared with group LRD,myocardial function and serum markers were further significantly improved in group HRD (all P ＜ 0.05).The inflammation and oxidative stress in myocardial tissue were observed in all the animals experiencing cardiac arrest and resuscitation,which were indicated by increased levels of TNF-α,IL-6 and MDA and decreased SOD activity.Compared with group CPR,the levels of TNF-α,IL-6 and MDA were significantly decreased while SOD activity was significantly increased in LRD and HRD groups [TNF-α (pg/ml):442 ±87,218 ±55 vs.653 ± 112;IL-6 (pg/ml):563 ± 68,403±61vs.824±117;MDA (nmol/mg):3.95±0.96,2.54±1.21vs.6.37±1.26;SOD (U/mg):2.27±0.93,3.36±0.74vs.0.89±0.31,all P＜0.05].The morbidity of myocardial inflammation and oxidative stress were further significantly ameliorated in group HRD evidenced by the figure of biomarkers compared with group LRD (all P ＜ 0.05).Conclusions Resolvin D1 can improve post-resuscitation myocardial dysfunction in a dose-dependent manner in swine,and the mechanism is related to the inhibition of inflammation and oxidative stress.

OBJECTIVE To investigate the effects and mechanism of luteolin on osteogenic repair of bone defects. METHODS The targets and potential pathways of luteolin in the treatment of bone defects were screened by network pharmacology method， and then the top 2 targets were selected by Hub gene screening for molecular docking verification， with binding energy as the evaluation standard. In vitro experiments were conducted on rat bone mesenchymal stem cells （BMSC） and rat umbilical vein endothelial cells （RUVEC）. Phenotypic validation was performed using alkaline phosphatase staining， alizarin red S staining， and in vitro angiogenesis experiments. Western blot assay was used to detect the protein expressions of phosphatidylinositol 3 kinase （PI3K） and protein kinase 1 （Akt1）， so as to validate the mechanism of luteolin on osteogenic differentiation of BMSC and angiogenesis of RUVEC in vitro. RESULTS The results of network pharmacology showed that the effects of luteolin on vascular formation and bone repair in bone defects were mainly related to Akt1， SRC， estrogen receptor 1， epidermal growth factor receptor， cyclooxygenase 2， matrix metalloproteinase 9 targets， and were closely related to PI3K-Akt signaling pathway. The results of molecular docking showed that luteolin binding to Akt1 and SRC proteins was stable. The results of in vitro experiments showed that luteolin could significantly improve the expressions and activities of alkaline phosphatase in BMSC， increased the number of calcium salt deposits and calcified nodules， and promoted calcification of BMSC. Compared with luteolin 0 μmol/L group， the angiogenesis ability of RUVEC was enhanced significantly in luteolin 1， 10 μmol/L groups， the length of blood vessels and the protein expressions of PI3K and Akt1 were significantly increased （P＜0.05 or P＜0.01）； the higherthe concentration， the better the effect. CONCLUSIONS Luteolin may play a role in promoting angiogenesis and bone repair at the fracture site by activating PI3K/Akt signaling pathway and promoting the protein expressions of PI3K and Akt1.