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.

To explore the mechanisms by which AKR1C3 induces tumor resistance, human breast cancer cell strain MCF-7/DOX resistant to doxorubicin, MCF-7/ AKR1C3 cells for overexpression of AKR1C3 and MCF-7/DOX-KD cells for knockdown of AKR1C3 in MCF-7/DOX cells were established. Western blot analysis found that AKR1C3 was expressed at a higher level in MCF-7/DOX than MCF-7 wild type cells. Similarly, CCK-8 and DAPI confirmed that MCF-7/ AKR1C3 cells were more resistant to DOX than AKR1C3 wild types as the IC50 was increased 6 times in MCF-7/AKR1C3 cells more than in AKR1C3 wild type cells. Meanwhile, colony formation ability was also enhanced after AKR1C3 was over-expressed in MCF-7 cells.Cytoplasmic/nuclear separation analysis and IF further found that β-catenin nuclear translocation mediated by AKR1C3 was the main reason contributing to the occurrence of DOX-resistant breast cancer cells. β-catenin inhibitor, XAV939, could reverse the AKR1C3 induced doxorubicin resistance in MCF-7 cells.Results indicated that AKR1C3 could be a potential therapeutic target in breast cancer cells.

Tripterygium wilfordii is widely used in the treatment of autoimmune system diseases, but its obvious reproductive toxicity limits the clinical application and promotion of the drug. At present, there is no clear solution to the reproductive injury of Tripterygium wilfordii. TCM believes that its reproductive toxicity lies in its properties of pungent, bitter, and cold. Long-term use can dry liver and blood, hurt liver and yang, consume kidney essence, damage kidney and yang, destroy the balance of qi and blood, yin and yang in the internal organs, and cause infertility. Based on the relationship between liver and kidney and human reproductive function, this article proposed to understand the reproductive toxicity of Tripterygium wilfordii from the perspective of "Yi and Gui homology", and explored the method of reducing the reproductive toxicity of Tripterygium wilfordii according to the thought of "treating liver and kidney together", in order to expand the theoretical thinking of TCM for the safe clinical application of this drug.

Objective:To investigate the risk factors and their warning value for the occurrence of sepsis in patients with severe multiple trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 92 patients with severe multiple trauma admitted to Yuyao People′s Hospital from July 2019 to October 2021. There were 71 males and 21 females, with the age range of 36-55 years [(45.5±13.6)years]. The injury severity score (ISS) was 20-29 points [(25.3±6.4)points]. The patients were divided into sepsis group ( n=32) and non-sepsis group ( n=60) according to whether sepsis occurred during hospitalization. Data were recorded for the two groups, including gender, age, basic diseases, cause of injury, number of injury sites, ISS, post-injury complications, and levels of aryl hydrocarbon receptor (AHR), C-reactive protein (CRP) and procalcitonin (PCT) at 1, 3 and 5 days after injury. The above data were analyzed to identify their correlation with the occurrence of sepsis in patients with severe multiple trauma by univariate analysis. The independent risk factors for sepsis in patients with severe multiple trauma were determined by multivariate Logistic regression analysis. The warning value of the single or combined risk factors for the occurrence of sepsis in patients with severe multiple trauma was evaluated by the receiver operating characteristic (ROC) curve and area under the curve (AUC). Results:By univariate analysis, it was demonstrated that the occurrence of sepsis was correlated with ISS, level of AHR at day 1 after injury, level of CRP at day 3 after injury and level of PCT at day 3 after injury ( P<0.05 or 0.01), but not with age, sex, basic diseases, level of AHR at 3, 5 days after injury, level of PCT at 1, 5 days after injury and level of CRP at 1, 5 days after injury (all P>0.05). By multivariate Logistic regression analysis, higher ISS ( OR=1.12, 95% CI 1.01, 1.24, P<0.05), level of AHR at day 1 after injury ( OR=1.30, 95% CI 1.10, 1.52, P<0.01) and level of PCT at day 3 after injury ( OR=1.81, 95% CI 1.08, 3.03, P<0.05) were found to be strongly correlated with the occurrence of sepsis. ROC curve analysis showed that higher ISS (AUC=0.69, 95% CI 0.57, 0.76) and level of AHR at day 1 after injury (AUC=0.79, 95% CI 0.68, 0.90) had warning value for the occurrence of sepsis, and the warning efficiency of combined panel was much better (AUC=0.86, 95% CI 0.77, 0.95). Conclusions:Higher ISS, level of AHR at day 1 after injury and level of PCT at day 3 after injury are independent risk factors for the occurrence of sepsis in patients with severe multiple trauma. ISS, AHR and combination of both exhibit good warning value for the occurrence of sepsis in patients with severe multiple trauma.

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 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.

[摘 要] 目的：探讨甲状腺滤泡癌（FTC）组织中程序性死亡蛋白1（PD-1）和NOD样受体蛋白3（NLRP3）的表达及其与患者临床病理特征和预后的关系。方法：收集2015年1月至2020年6月福建医科大学附属第二医院手术切除的60例FTC患者的癌和配对癌旁组织标本，采用免疫组织化学染色法检测癌及癌旁组织中PD-1和NLRP3的阳性表达率，χ²检验或者Fisher精确检验法分析PD-1和NLRP3表达与FTC患者临床病理特征的关系，Pearson相关性分析PD-1与NLRP3表达的关系，Kaplan-Meier生存和Logistic回归分析PD-1和NLRP3表达与患者预后的关系。结果：在60例FTC组织中，PD-1和NLRP3均有较高的阳性表达率（46.67%与63.33%）。PD-1表达与FTC患者肿瘤分期、肿瘤大小、血管侵犯、复发与否具有显著相关性（均P<0.05），NLRP3表达与患者肿瘤大小、血管侵犯、甲状腺外浸润以及复发具有显著相关性（均P<0.05）。PD-1与NLRP3的表达成负相关，前者与患者更好的预后相关，后者是FTC复发的独立风险因素。结论：PD-1和NLRP3在FTC组织中有较高的阳性表达率，前者与患者更好的预后相关，后者是FTC复发的独立风险因素，且两者的表达呈负相关。