Objective To evaluate the effects of different intensities of treadmill running on changes in tibial bone composition in a rat model.Methods A total of 24 female Wistar rats were randomly assigned into 4 even groups (n =6) of free movement (FM),low-intensity running (LR),medium-intensity running (MR),and high-intensity running (HR).Rats in LR,MR,and HR groups underwent treadmill running with respective intensities (15 m/min and a 0° gradient,20 m/min and a 5° gradient,25 m/min and a 10° gradient) for 8 weeks (1 h/d and 5 d/week).FM group were taken as controls.The cortical and trabecular bone at the left tibial metaphysis was harvested after 8 weeks in each group for Raman spectroscopy to analyze mineral-matrix ratio,carbonate-phosphate ratio and crystallinity.Results In MR group,the mean mineral-matrix ratio was 4.883 ± 0.128 for cortical bone and 4.216 ±0.213 for trabecular bone,both significantly higher than those in FM group (4.113 ±0.132 and 3.773 ±0.122) (P ＜ 0.05).The mean mineral-matrix ratio was 3.222 ± 0.329 for trabecular bone in HR group,significantly lower than that in FM group (P ＜ 0.05).In MR group,the mean carbonate-phosphate ratio was 0.166 ± 0.013 for trabecular bone,significantly lower than that in FM group (0.177 ± 0.011) (P ＜ 0.05).In HR group,the mean carbonate-phosphate ratio was 0.195 ± 0.012 for cortical bone and 0.187 ± 0.010 for trabecular bone,both significantly higher than those in FM group (0.183 ± 0.014 and 0.177 ± 0.011) (P ＜ 0.05).In HR group,the mean crystallinity was 0.0521 ± 0.0012 for cortical bone and 0.0522 ± 0.0017 for trabecular bone,both significantly higher than those in the other 3 groups (P ＜ 0.05).Conclusions Running with medium intensity may increase bone mineralization and turnover,thus enhancing bone quality.However,running with high intensity may decrease bone mineralization and thus bone quality.

Objective:To analyze therapeutic effect of homocysteine (Hcy)‐lowering therapy on serum levels of Hcy and inflammatory factors in patients with coronary heart disease (CHD ) after percutaneous coronary intervention (PCI) .Methods :A total of 82 CHD patients who received PCI in our hospital were selected .According to random number table ,they were randomly and equally divided into routine treatment group (received routine postoperative therapy) and Hcy‐lowering group .Serum levels of Hcy ,inflammatory factors ,N‐terminal pro‐brain natriuretic pep‐tide (NT‐proBNP) and soluble intercellular adhesion molecule‐1 (sICAM‐1) were compared between two groups . Results :1) On six months and one year after treatment ,compared with routine treatment group ,serum Hcy level significantly reduced [after six months: (15.39 ± 1.83) μmol/L vs . (13.21 ± 1.35) μmol/L ,after one year :(15.61 ± 1.62)μmol/L vs . (8.73 ± 0.72)μmol/L] in Hcy‐lowering group ;2) after six‐month treatment ,compared with routine treatment group ,there were significant reductions in serum levels of CRP [ (67.27 ± 7.51) mg/L vs . (37.11 ± 6.32) mg/L] ,IL‐6 [ (87.58 ± 7.21)μg/L vs . (60.17 ± 5.45)μg/L] ,procalcitonin [PCT , (21.34 ± 3.04) ng/L vs .(15.61 ± 2.32) ng/L] ,NT‐proBNP [ (298.37 ± 53.28) pg/ml vs .(104.28 ± 13.17) pg/ml] and sI‐CAM‐1 [ (391.83 ± 75.04) ng/ml vs .(162.18 ± 30.26) ng/ml] in Hcy‐lowering group , P<0.05 all .Conclusion:Hcy‐lowering therapy is help to reduce serum Hcy level ,relieve systemic inflammatory response and protect myocar‐dial function in CHD patients after PCI .

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.

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.

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 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 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.

Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; Gene Editing