AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

Purpose Based on a variety of combinations of cranial MR Dixon images,the deep learning method is used to generate CT images,and the reconstruction efficiency is evaluated by comparing with the corresponding CT images.Materials and Methods A total of 77 cranial CT and MR images were collected retrospectively in Ruijin Hospital,Shanghai Jiaotong University School of Medicine from June to December 2021.The U-Net neural network was used for network training,with 62 cases in the training set and 15 cases in the test set.CT image reconstruction was performed using four kinds of Dixon images and a total of seven models among the various combinations.Mean absolute error,mean squared error,Pearson correlation coefficient and skull area Dice similarity coefficient were used to evaluate the image reconstruction efficiency.Results The generated CT images of the various Dixon image combination models showed strong correlation with the corresponding CT images(R>0.75,P<0.05),and the CT images reconstructed by the four-channel model had the closest value to the actual CT images[mean absolute error=147.516±30.802,mean squared error=(8.648±3.403)×104],the highest correlation coefficient(R=0.796±0.055),and the highest similarity coefficient in the cranial region(Dice similarity coefficient=0.800±0.036).Conclusion Deep learning training through Dixon images can be used to generate CT images,and the combination of four kinds of Dixon contrast images can improve the CT image reconstruction efficiency.

AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

Purpose Based on a variety of combinations of cranial MR Dixon images,the deep learning method is used to generate CT images,and the reconstruction efficiency is evaluated by comparing with the corresponding CT images.Materials and Methods A total of 77 cranial CT and MR images were collected retrospectively in Ruijin Hospital,Shanghai Jiaotong University School of Medicine from June to December 2021.The U-Net neural network was used for network training,with 62 cases in the training set and 15 cases in the test set.CT image reconstruction was performed using four kinds of Dixon images and a total of seven models among the various combinations.Mean absolute error,mean squared error,Pearson correlation coefficient and skull area Dice similarity coefficient were used to evaluate the image reconstruction efficiency.Results The generated CT images of the various Dixon image combination models showed strong correlation with the corresponding CT images(R>0.75,P<0.05),and the CT images reconstructed by the four-channel model had the closest value to the actual CT images[mean absolute error=147.516±30.802,mean squared error=(8.648±3.403)×104],the highest correlation coefficient(R=0.796±0.055),and the highest similarity coefficient in the cranial region(Dice similarity coefficient=0.800±0.036).Conclusion Deep learning training through Dixon images can be used to generate CT images,and the combination of four kinds of Dixon contrast images can improve the CT image reconstruction efficiency.

BACKGROUND:Traditional scoliosis orthosis has some disadvantages,such as complex manufacturing process,long processing cycle,poor fit and so on.Three-dimensional printed scoliosis orthosis has the advantages of high manufacturing precision and personalization. OBJECTIVE:To evaluate the efficacy of three-dimensional printed scoliosis orthosis for scoliosis based on multi-criteria decision model. METHODS:Clinical data of 72 patients with scoliosis admitted to Chen Xinghai Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to October 2022 were retrospectively collected and divided into two groups according to the treatment of orthosis.Study group(n=23)received three-dimensional printed scoliosis orthosis.Traditional group(n=49)received the traditional polypropylene spine brace treatment.The clinical efficacy and complications were compared between the two groups.A multi-criteria decision model for the treatment of scoliosis with three-dimensional printed scoliosis orthosis was established,and the stability of the benefit value,risk value and decision model of the two groups were evaluated. RESULTS AND CONCLUSION:(1)Compared with the traditional group,there were significant differences in the top vertebral offset distance,Cobb angle,top vertebral rotation,Functional Movement Screen score,visual analog scale score and total effective rate in the study group at 6 months after surgery(P<0.05).(2)Among the benefit indexes,Cobb angle had the greatest impact on the condition of patients,while the risk indexes had the greatest impact on dyspnea.(3)The benefit values of the study group and the traditional group for scoliosis were 79 and 64,and the risk values were 74 and 57,respectively.The combined benefit and risk values found that the benefit-risk value of the study group was 16 higher than that of the traditional group.(4)In the range of 0-100%relative risk weight,the benefit-risk value of the study group was always higher than that of the traditional group,which proved that the multi-criteria decision-making model had good stability.(5)It is indicated that three-dimensional printed scoliosis orthosis can better restore the physiological curvature of scoliosis and improve the efficiency of treatment.

BACKGROUND:Studies have shown that atorvastatin can up-regulate the expression of heme oxygenase-1 and enhance the anti-inflammation and anti-oxidative damage ability of cells.However,whether atorvastatin can regulate macrophage polarization,inhibit inflammation and reduce cholesterol accumulation by inducing heme oxygenase-1 expression remains unclear. OBJECTIVE:To investigate the effect of atorvastatin on polarization,inflammation and cholesterol content of oxidized low-density lipoprotein stimulated RAW264.7 macrophages by inducing heme oxygenase-1 expression and its related mechanism. METHODS:Firstly,RAW264.7 cells were randomly divided into six groups and incubated with different concentrations of atorvastatin for 24 hours.The expression of heme oxygenase-1 protein and cell activity were detected to explore the optimal dose of atorvastatin for subsequent studies.RAW264.7 cells were randomly divided into control group,atorvastatin group and heme oxygenase-1 inhibition group.Cells were preincubated with pure medium,atorvastatin 20 μmol/L and atorvastatin 20 μmol/L + zinc protoporphyrin IX 10 μmol/L for 24 hours,and then oxidized low-density lipoprotein 50 mg/L was added for 48 hours.The polarization of macrophages was detected by flow cytometry.The secretion of inflammatory factors such as transforming growth factor β,interleukin 10,interleukin 1β,and tumor necrosis factor α was detected by ELISA.The expression levels of heme oxygenase-1,LC3II,LC3I,P62,PPARγ and ABCA1 were detected by western blot assay.The intracellular cholesterol content was measured with the oxidose method and the accumulation degree of intracellular lipid droplets was evaluated by oil red O staining. RESULTS AND CONCLUSION:(1)Atorvastatin could induce the expression of heme oxygenase-1 protein in macrophages in a dose-dependent manner.(2)Oxidized low-density lipoprotein could induce macrophages to polarize towards M1,secrete proinflammatory factors,and increase the accumulation of intracellular cholesterol.(3)Compared with the control group,the heme oxygenase-1 protein expression of macrophages was increased after atorvastatin intervention,and the cells turned to M2-type polarization and mainly secreted anti-inflammatory factors such as transforming growth factor-β and interleukin-10.PPARγ,ABCA1,LC3II/I and other signal molecules reflecting cholesterol efflux and autophagy increased,and the contents of intracellular cholesterol and lipid droplets decreased significantly(P<0.05).(4)The heme oxygenase-1 inhibition group treated with zinc protoporphyrin IX significantly reversed the above changes in the atorvastatin group.(5)The results have shown that atorvastatin may promote the polarization of macrophages stimulated by oxidized low-density lipoprotein to M2 type and inhibit inflammation by up-regulating the expression of heme oxygenase-1 and by up-regulating PPARγ/ABCA1 signaling pathway and enhancing autophagy.Atorvastatin can increase the outflow of intracellular cholesterol and reduce the accumulation of intracellular lipids.

Objective    To evaluate the clinical outcomes of  pulmonary valve replacement (PVR) in patients with tetralogy of Fallot (TOF) after re-PVR surgery. Methods    PubMed, EMbase, the Cochrane Controlled Trials Register databases, CNKI, CBM disc and VIP datebases were searched, and study eligibility and data abstraction were determined independently and in duplicate. Literature searches from database establishment to December 2018. The heterogeneity and data were analyzed by the software of Stata 11.0. Results    Of 4 831 studies identified, 26 studies met eligibility criteria, and invovled with a total of 3 613 patients. The combined 30-day mortality for PVR was 2.2% (95% CI 1.5%-3.1%) and follow-up mortality was 3.4% (95% CI 2.4%-4.9%), re-PVR rate was 6.8% (95% CI 5.1%-9.2%), and the rate of intervention was 11.4% (95% CI 8.0%-16.4%). Subgroup analysis showed that the patient's age range may be a heterogeneous source of mortality during the follow-up period, and there was no statistical heterogeneity for adult patients (P=0.63, I2=0%), with a lower incidence than those including adolescents patients. The type of valve was likely to be a source of retrospective PVR. There was no statistical heterogeneity in bioprosthetic valves and allograft lobes (P=0.24, I2=25%). And the incidence of re-PVR was lower than that of the mechanical valve patients. Heart function classification (NYHA) of patients with TOF after PVR was statistically improved (P<0.05). Electrocardiogram QRS change was not statistically differently (P>0.05). Postoperative MRI findings showed a decrease in RVEDV, an increase in RVEF, a decrease in RV/LV ratio, and a decrease in pulmonary valve (all P<0.05). Funnel map monitoring, Begg test and Egger's test both indicated that there was no publication bias. Conclusions    According to the results of the analysis, PVR after TOF surgery is a more mature surgery, the clinical effect was significant, with lower early and long-term mortality. The long-term mortality rate of adolescent patients undergoing PVR is higher than that of adult patients. Long-term outocme of re-PVR or re-intervention is still the main problem affecting the effect of the operation. Indications for surgery and choice of valve need further investigation.

Objective To investigate the risk factors of prolonged postoperative mechanical ventilation for adult patients with atrioventricular septal defect (AVSD). Methods We retrospectively analyzed the clinical data of 76 patients with AVSD aged more than 18 years in our hospital from January 1, 2011 to December 31, 2017. The patients ventilated longer than 24 hours were described as a prolonged ventilation group (n=27) and the others as a normal group (n=49). There were 9 males and 18 females aged 32.22±9.64 years in the prolonged ventilation group, and 16 males and 33 females aged 35.98±11.34 years in the normal group. Perioperative variables between the two groups were compared and selected, and then analyzed by logistic regression analysis. Results The result of univariate analysis showed that there was a statistical difference in weight, preoperative pulmonary artery systolic pressure, duration of cardiopulmonary bypass, the level of postoperative platelet, hemoglobin, blood glucose, lactic acid and serum creatinine, postoperative maximum heart rate and postoperative infection rate between the prolonged ventilated group and the normal group. Multivarable logistic regression showed that preoperative pulmonary artery hypertension (OR=1.056, 95%CI 1.005 to 1.110, P=0.030), prolonged duration of cardiopulmonary bypass (OR=1.036, 95%CI 1.007 to 1.066, P=0.016) and the low postoperative hemoglobin level (OR=0.874, 95%CI 0.786 to 0.973, P=0.014) were the risk factors of prolonged postoperative mechanical ventilation. Conclusion Preoperative pulmonary artery hypertension, long duration of cardiopulmonary bypass and postoperative anaemia are the risk factors associated with prolonged postoperative mechanical ventilation.

Objective To explore application of our self-designed U-shaped transdermal surgical navigator based on three-dimensional reverse design in cannulated screwing for femoral neck fracture Methods A retrospective study was done of 5 patients with femoral neck fracture who had been treated from August 2016 to March 2017.They were 3 men and 2 women,aged from 33 to 60 years (average,46.5 years).Thin layer CT scanning was conducted on the patients' affected hip (at the left side in 2 cases and at the right side in 3).Based on their CT data,3D design software and 3D printing technique were used to manufacture the U-shaped transdermal surgical navigator and a real-sized model of the fracture.Operations were simulated using the U-shaped transdermal surgical navigator on the fracture model to determine the angle,depth and location of the screwing.Fixation of the fracture with cannulated screws was conducted after confirmation of satisfactory surgical parameters.The postoperative X-ray films of the patients were reviewed.Evaluations were conducted of the screw position,operating time,volume of operative bleeding,and number of intraoperative X-ray shots.Results The screw positions in the 5 patients were consistent with their preoperative design.Four patients had only one shot of fluoroscopy and one patient 3 shots.Their operating time ranged from 15 to 30 minutes,averaging 22.5 minutes;their bleeding ranged from 5 to 10 mL,averaging 7.5 mL.The 5 patients were followed up for an average of 4.5 months (from 3 to 6 months).By the Harris scoring at their final follow-ups,one was excellent,3 good and one fair.No complications like pain,functional impairment of the joint,or collapse or necrosis of the femoral head occurred during the follow-up.Conclusions Our self-designed U-shaped transdermal surgical navigator based on three-dimensional reverse design can significandy improve the accuracy and safety of the cannulated screwing for femoral neck fractures.The operation is minimally invasive,reducing operating time and intraoperative blood loss.

Objective To summarize 500 cases of surgical experience in restoration of adult congenital heart disease ( ACHD) treatment and early postoperative.Methods During January 2012 to December 2014 in Fuwai Hospital, 500 cases of ACHD treated by operation were chosen to collect the clinical data .We divided the groups according to whether the case was a complex malformation and whether the case had an ICU retention time is more than the 5 days.Results The average age was 35, the average weight was 59 kg.The operation average cardiopulmonary bypass(CPB) time was 102min.The average ICU treatment time was 2 days, the average duration of mechanical ventilation was 23 hours, 3 early deaths occurred.The complex malformation group had younger age and less weight than the simple malformation group , the complex malformation group had longer time of cardiopulmonary bypass time, aortic cross clamping time, mechanical ventilation time and ICU treatment time, had higher rate of complication and blood transfusion peri-operative period than the simple malformation group.(P<0.05) The group of ICU retention time less than 5 days had higher rate of the male proportion, had younger age and less weigh, had longer time of cardiopulmonary bypass time , mechanical ventilation time and ICU treatment time , had higher rate of complication and blood transfusion peri-operative period than the control group(P <0.01).Conclusion Although ACHD patients have long medical history and complicated pathological and physiological changes , when they get proper surgical operation and periopera-tive treatment, they should obtain satisfied effect.Professional medical team or organization service for the ACHD patient is very important and urgent to build.