OBJECTIVE To investigate the ameliorative effects and potential mechanism of total secondary ginsenosides （TSG） on hypertrophic changes of primary cardiomyocytes stimulated by angiotensin Ⅱ （Ang Ⅱ）. METHODS Primary cardiomyocytes were isolated from the hearts of neonatal SD rats and divided into the following groups： control group， AngⅡ group （2 µmol/L）， TSG group （7.5 µg/mL）， PFK-015 group [6-phosphofructo-2-kinase/fructose-2， 6-bisphosphatase 3 （PFKFB3） inhibitor， 10 nmol/L]， and TSG+PFK-015 group （TSG 7.5 µg/mL+PFK-015 10 nmol/L）. The surface area， protein synthesis， energy metabolism-related indicators [free fatty acid （FFA）， coenzyme A （CoA）， acetyl coenzyme A （acetyl-CoA）]， and the expressions of glycolysis-related factors [hypoxia-inducible factor 1α （HIF-1α）， glucose transporter protein 4 （GLUT-4）， lactate dehydrogenase A （LDHA）， pyruvate dehydrogenase kinase 1 （PDK1） and PFKFB3] in primary cardiomyocytes of each group were measured. RESULTS Compared with the control group， the surface area of primary cardiomyocytes and protein synthesis were significantly increased， the content of FFA， protein and mRNA expressions of HIF-1α， LDHA， PDK1 and PFKFB3 were significantly increased or up-regulated in the AngⅡ group， while the contents of CoA and acetyl-CoA， the protein and mRNA expressions of GLUT-4 were significantly decreased or down-regulated （P＜0.05）. Compared with the AngⅡ group， both TSG group and PFK-015 group showed significant improvements in these indexes， with the TSG+PFK-015 group generally demonstrating superior effects compared to either treatment alone （P＜0.05）. CONCLUSIONS TSG can reduce the surface area of AngⅡ-induced primary cardiomyocytes， decrease protein synthesis， and inhibit their hypertrophic changes. These effects may be related to improving energy metabolism and the inhibition of glycolysis activity.

Objective:To explore the effects of Tongdu Tiaoshen acupuncture on vascular endothelial function and inflammatory factors in patients with mild cognitive impairment (MCI) after ischemic stroke (IS).Methods:A retrospective analysis was performed on the clinical data of 71 patients with MCI after IS in the hospital between January 2020 and September 2022. According to different treatment methods, they were divided into Tongdu Tiaoshen acupuncture group ( n=31, Tongdu Tiaoshen acupuncture + oral nimodipine tables) and routine body-acupuncture group ( n=40, routine body-acupuncture group + oral nimodipine tables). Both groups were treated for 2 courses (14 d/course). Before and after treatment, levels of serum NO and endothelin-1 (ET-1) were detected by radioimmunoassay, and levels of serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), plasma homocysteine (Hcy) and IL-6 were detected by ELISA. The cognitive function of patients was evaluated and intelligence level by Montreal Cognitive Assessment Scale (MoCA), Mini-Mental State Examination(MMSE) and the clinical curative effect was also evaluated. Results:The total response rates in Tongdu Tiaoshen acupuncture group and routine body-acupuncture group were 90.32% (28/31) and 70.00% (28/40), and the difference between the two groups was statistically significant ( χ2=4.33, P=0.037). After treatment, levels of plasma Hcy and IL-6 in Tongdu Tiaoshen acupuncture group were lower than those in the routine body-acupuncture group ( t=2.57, 9.36, P<0.05 or P<0.01). After treatment, levels of serum bFGF, VEGF and NO in Tongdu Tiaoshen acupuncture group were significantly higher than those in the routine body-acupuncture group ( t=10.03, 9.29, 8.17, P<0.01), while ET-1 level was significantly lower than that of the routine body-acupuncture group ( t=2.41, P=0.019). After treatment, MoCA score [(28.24±4.45) vs. (25.32±4.34), t=2.78], MMSE score [(28.73±1.44) vs. (28.02±1.22), t=2.25] in Tongdu Tiaoshen acupuncture group were higher than those in the routine body-acupuncture group ( P<0.01). Conclusion:Tongdu Tiaoshen acupuncture is beneficial to improve vascular endothelial function, reduce levels of inflammatory factors, promote the recovery of cognitive function and improve curative effect in patients with MCI after IS.

AIM:Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury(MIRI).METHODS:Firstly,the rat MIRI related dataset GSE122020,E-MEXP-2098,and E-GEOD-4105 were downloaded from the database.Secondly,differentially expressed genes(DEGs)were screened from each dataset using the linear models for microarray data(limma)package,and robust DEGs were filtered using the robust rank aggregation(RRA)method.In addition,the surrogate variable analysis(SVA)package was used to merge all datas-ets into one,and merged DEGs were screened using the limma package.The common DEGs were obtained by taking the intersection of the two channels of DEGs.Next,the protein-protein interaction(PPI)network of common DEGs was con-structed,and the hub genes were identified using the density-maximizing neighborhood component(DMNC)algorithm.The receiver operating characteristic curve(ROC)was plotted to evaluate the diagnostic performance of the hub gene.Then,the mRNA and protein expression levels of hub genes were detected in the rat MIRI model,and the literature re-view analysis was carried out on the involvement of hub genes in MIRI.Finally,the gene set enrichment analysis(GSEA)was performed on hub gene to further reveal the possible mechanism in mediating MIRI.RESULTS:A total of 143 robust DEGs and 48 merged DEGs were identified.After taking the intersection of the two,48 common DEGs were obtained.In the PPI network of common DEGs,5 hub genes were screened out,namely MYC proto-oncogene bHLH transcription fac-tor(MYC),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),caspase-3(CASP3),and plasminogen activator urokinase receptor(PLAUR).The ROC results showed that the area under the curve values for all hub genes were greater than 0.8.MYC,PTGS2,CASP3,and PLAUR showed high mRNA and protein expression in rat MIRI,while there was no difference in mRNA and protein expression for HMOX1.The literature review revealed that among the 5 hub genes,only PLAUR has not been reported to be involved in MIRI.The GSEA results for PLAUR indicat-ed that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway,P53 signaling pathway,Toll-like receptor signaling pathway,apoptosis,and fatty acid metabolism.CONCLUSION:MYC,PTGS2,CASP3,HMOX1,and PLAUR are involved in the pathological process of MIRI.PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling,P53 signaling,Toll like receptor signaling,cell apoptosis,and fatty acid metabolism.The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI.

Purpose/Significance To solve the problem that regional clinical research data are difficult to integrate efficiently,and to promote"Chinese evidence"and"Chinese protocol"in the global clinical research community.Method/Process Based on the standard-ization theory,the data standardization system is proposed,and the construction and application methods of the regional clinical research data platform are explored with the integration of multi-center clinical research data as the starting point.Result/Conclusion The theo-retical framework of the regional clinical research data platform has been preliminarily established,and the clinical research capabilities of tertiary hospitals in Shanghai have been significantly improved.

Objective To discover 5-HT2A receptor antagonist molecules with novel structures and explore their structure-activity relationship through structure-and mechanism-based drug design,synthesis and activity evaluation.Methods The way in which pimovanserin interacted with 5-HT2A receptor was analyzed via molecular docking,molecular dynamics simulation and binding free energy calculations.Based on the results of this study,the 5-HT2A receptor antagonist target compounds with novel structures were designed using pimovanserin as the lead molecule.According to the structures of target compounds,corresponding synthetic routes were designed.The heterocyclic methylamine intermediates were obtained by reductive amination or reduction reaction from heterocyclic formaldehyde or heterocyclic methanonitrile before being reacted with 4-(4-fluorobenzylamino)-1-methylpiperidine to obtain the target compounds using CDI urea synthesis method.The inhibitory activity of the target compounds against 5-HT2A receptor was tested at the cellular level,and the anti-hallucinogenic effects of the target compounds were tested in the mouse head twitch response model.Results Twelvenovel compounds were synthesized and their structures were confirmed by HR-MS,1H-NMR and 13C-NMR.The results of the activity assay showed that compounds 6a,6c and 6d exhibited better 5-HT2Areceptor inhibitoryactivity with IC50 values of 120,152 and 285 nmol/L,respectively while compounds 6c and 6d exhibited better anti-hallucinogenic activity in mice with inhibition rates of 97.0％and 82.9％(10 mg/kg),respectively.Conclusion The novel compound 6c and 6d have shown strong 5-HT2A receptor inhibitoryactivity and anti-hallucinogenic activity and deserve more research.Structure-activity relationship analyses of target compounds indicate that the repulsion of the heterocyclic ring with basic N atoms and the accommodation of the heterocyclic ring without basic N atoms by the side extended pocket of the 5-HT2A receptor could significantly affect the ex vivo and in vivo effects of antagonists.

OBJECTIVE To explore the mechanism of Tingli dazao xiefei decoction on ventricular remodeling in model rats with heart failure after myocardial infarction. METHODS The rat model of heart failure after myocardial infarction was established by ligation of anterior descending branch of left coronary artery， which was divided into 8 groups： sham operation group， model group， A779 group （1 mg/kg）， A779 （1 mg/kg）+Tingli dazao xiefei decoction equivalent-dose group （0.8 g/kg）， A779 （1 mg/kg） +Tingli dazao xiefei decoction high-dose group （1.6 g/kg）， Tingli dazao xiefei decoction equivalent-dose group （0.8 g/kg）， Tingli dazao xiefei decoction high-dose group （1.6 g/kg） and losartan potassium group （10 mg/kg）. Each group was given equal volume of distilled water or corresponding drugs intragastrically for 4 weeks. Masson staining was used to determine the distribution of collagen fibers in rat myocardium. The content of hydroxyproline （Hyp） in myocardium was determined by alkaline hydrolyzation. The expressions of type Ⅰ and Ⅲ collagen （COLⅠ， COLⅢ）in myocardium were detected by immunohisto-chemistry. Myocardial fibrosis-related indexes such as matrix metalloproteinase-2 （MMP-2）， MMP-9， tissue inhibitor of metalloproteinase-1 （TIMP-1） and soluble suppression of tumorigenicity-2 （sST-2） were detected by ELISA. The protein expressions of angiotensin converting enzyme 2-angiotensin-（1-7）-Mas [ACE2-Ang-（1-7）-Mas] axis were detected by Western blot. RESULTS Compared with sham operation group， myocardial cells in model group and A779 group were disordered， collagen fiber deposition was significantly increased and myocardial fibrosis was obvious； the Hyp content and MMP-2， MMP-9， sST-2 levels were increased， and COL Ⅰ and COL Ⅲ positive expressions were significantly enhanced； TIMP-1 level， protein expressions of ACE2， Ang-（1-7） and Mas were significantly decreased （P＜0.05）. Compared with model group， above indexes of Tingli dazao xiefei decoction equivalent-dose and high-dose groups were improved to different extents. Compared with A779 group， A779+Tingli dazao xiefei decoction equivalent-dose and A779+high-dose groups could improve myocardial arrangement and collagen distribution， reduce the Hyp content and MMP-2， MMP-9 levels， reduce positive expressions of COL Ⅰ and COL Ⅲ （P＜0.05）， but couldn’t improve Ang-（1-7） and Mas protein expression. CONCLUSIONS Tingli dazao xiefei decoction can improve ventricular remodeling in myocardial failure model rats after myocardial infarction by improving the expression of ACE2- Ang（- 1-7）-Mas axis proteins.

Objective:To explore the feasibility and clinical efficacy of oblique lateral interbody fusion (OLIF) in the treatment of adjacent segment disease (ASDis).Methods:Retrospective analysis was conducted on the data of 31 patients with ASDis treated by OLIF in four medical centers from June 2015 to December 2018. There were 17 males and 14 females. The average age was (65.7±3.4) years (range, 59 to 75 years). 19 cases received single-segment fixed fusion, 11 cases received double-segment fixed fusion and 1 case received three-segment fixed fusion. Original fixed fusion site: 1 case of L 1, 2, 3 cases of L 3, 4, 11 cases of L 4, 5, 4 cases of L 5S 1, 6 cases of L 3-L 5, 5 cases of L 4-S 1, and 1 case of L 3-S 1. The time from the initial fixation and fusion to this admission was 82.5±45.5 months (rang, 24 to 180 months). ASDis occurred at the proximal end of the fixed fusion segment in 28 cases and at the distal end in 3 cases. The types of ASDis: degenerative disc disease in 11 cases, lumbar spinal stenosis in 15 cases, degenerative spondylolisthesis in 2 cases, and degenerative scoliosis in 3 cases. The location of ASDis: 6 cases of L 2, 3, 12 cases of L 3, 4, 6 cases of L 4, 5, 3 cases of L 1-L 3, 1 case of L 2-L 4, and 3 cases of L 1-L 4. At admission, 3 cases of lumbar internal fixation had been removed and 28 cases of internal fixation remained. Stand-alone OLIF was performed in 19 cases, OLIF combined with pedicle screw fixation in 8 cases, and OLIF combined with cortical screw fixation in 4 cases. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate the low back pain and lumbar function before operation and at the last follow-up, and the imaging results and complications were observed. Results:All patients were followed up. The follow-up time was 23.6±9.6 months (range, 12 to 60 months). The operation time was 73.8±25.3 mins (range, 40 to 180 min), and the intraoperative blood loss was 86.2±67.4 ml (range, 20 to 310 ml). The average blood loss in each segment was 24.8 ml. During the operation, there were 1 case of segmental vein injury, 7 cases of endplate injury, 2 cases of transient iliopsoas muscle weakness, 1 case of thigh pain and numbness, and 1 case of incomplete intestinal obstruction. There was no incision necrosis and infection. The VAS score of low back pain decreased from 5.9±1.9 before operation to 1.4±0.6 at the last follow-up, with a statistically significant difference ( t=8.47, P<0.001). The ODI index recovered from 45.2%±5.7% before operation to 13.8%±4.7% at the last follow-up, with a statistically significant difference ( t=7.92, P<0.001). The height of intervertebral space increased from 8.7±1.6 mm before operation to 11.4±1.9 mm after operation and 9.9±1.8 mm at the last follow-up. There was a statistically significant difference between postoperative and preoperative height of intervertebral space ( F=4.15, P=0.007). There was a statistically significant difference between the last follow-up and postoperative height of intervertebral space ( P=0.011). During the follow-up, there were 13 cases of fusion cage subsidence, 1 case of fusion cage displacement, and no case of internal fixation loosening or fracture. The intervertebral fusion rate was 94%(29/31) and the complication rate was 42%(13/31). Conclusion:ASDis is a common complication after lumbar fixation and fusion, and requires surgical treatment. OLIF is a reliable method to treat ASDis as it has advantages of small trauma, high fusion rate and low complication rate.

Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10
Aneurysm, Dissecting/genetics* ; Case-Control Studies ; Cluster Analysis ; Cohort Studies ; Collagen Type III/genetics* ; Computational Biology ; Genetic Predisposition to Disease ; Humans

Objective:To evaluate the clinical efficacy of staged surgery in treatment of calf Gustilo-Anderson type IIIC fracture.Methods:A retrospective case series was conducted to analyze clinical data of 16 patients with calf Gustilo-Anderson type IIIC fracture admitted to Shanghai Jiao Tong University Affiliated Sixth People's Hospital from January 2017 to December 2019. There were 12 males and 4 females, with the age of (38.6±8.2)years (range, 18-53 years). All patients had limb salvage treatment at one stage in the emergency department. The survival of the limb and the occurrence of vascular crisis were examined within one week after limb salvage. The second stage involved the repair of skin and soft tissue defects with the defect area from 12.0 cm×5.0 cm to 20.0 cm×8.0 cm using free flaps. The survival of the flap, vascular crisis, and donor site healing within two weeks after the flap procedure. The third stage used bone graft revision and bone lengthening technology to repair bone tissue. The lower extremity functional scale (LEFS) and Mazur ankle joint function score were used to evaluate the function of the affected limb before bone repair and at the last follow-up. The fracture healing and related complications were observed at the last follow-up.Results:All patients were followed up for (14.2±4.6)months (range, 8-20 months). At one stage, the limb-saving surgery was successful in all patients, among which one had vascular crisis. At second stage, free flaps survived in all patients, among which two had vascular crisis. All donor areas were healed by first intention. At third stage, the LEFS of the affected limb was increased from (32.0±7.4)points before bone repair to (48.0±10.2)points at the last follow-up ( P<0.01) and the Mazur score was increased from (50.9±15.3)points before bone repair to (73.8±11.9)points at the last follow-up ( P<0.01). All bone defects were repaired and healed without complications such as infection or osteomyelitis at the last follow-up. Conclusion:For calf Gustilo-Anderson type IIIC fracture, the staged strategy can effectively save limbs and restore limb function.

Objective:To compare the clinical outcomes and complications of oblique lateral interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach and posterior interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach by channel for lumbar spinal stenosis.Methods:A retrospective study was conducted on 73 patients who underwent surgical treatment for lumbar spinal stenosis from Jun 2015 to Jun 2017, including 33 males and 40 females. The average age was 66.8±7.94 years (from 39-85 years). These diseases occured at L 3/4 in 5 patients and L 4/5 in 68 patients. Random according to the time of admission, 38 cases were treated with oblique lateral interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach (oblique lateral fusion group), and 35 cases with posterior interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach by channel (posterior fusion group). The clinical results, image data and complications were compared between the two groups. Results:All patients in both groups had operation performed smoothly. The operation time was 99±8.96 min in the oblique lateral fusion group and 96.8±9.57 min in the posterior fusion group, and there was no significant difference between the two groups. The intraoperative bleeding in the oblique lateral fusion group 80±24.72 ml was significantly less than that in the posterior fusion group 261±52.87 ml ( t=9.621, P<0.05). No incision infection occurred after surgery. The VAS score of lumbar incision 72h after operation in the oblique lateral fusion group 1.21±0.55 was significantly less than that in the posterior fusion group 1.70±0.86 ( t=3.723, P=0.028). The follow-up period lasted for 12-24 months, averagely 17.5±2.58 months. There was statistically significant difference between preoperative and postoperative in the two groups, whether it was the area of the foraminal canal or the area of the spinal canal. There wboth the foraminal area and the spinal canal area were enlarged. The intervertebral space height in the two groups recovered significantly after surgery, the difference was statistically significant. But the intervertebral space height were partly lost at the last follow-up, and there was significant difference compared with postoperative. During the follow-up, no pedicle screw loosening, displacement, rupture, or anterior and lateral displacement of cage occurred. The fusion rate was 97.1% in the posterior fusion group and 100% in the oblique lateral fusion group. There was no statistical difference between the two groups.In terms of ODI index: the posterior fusion group recovered from 48.6±6.1 preoperative to 10.2±2.2 at the last follow-up, and the oblique lateral fusion group recovered from 49.0±5.7 preoperative to 9.3±1.8 at the last follow-up. There was statistically difference between last follow-up and preoperative in the two groups. The incidence of complications in the posterior fusion group was 22.86%, and the incidence in the oblique lateral fusion group was 23.68%. There was no significant difference between the two groups. Conclusion:Both the two decompression and fusion methods have achieved good clinical results in the treatment of lumbar spinal stenosis, with the advantages of less trauma, good stability, fast recovery, and high fusion rate. Compared with posterior decompression and fusion methods, the advantages of OLIF are more obvious, such as less bleeding,lower risk of nerve injury and good indirect decompression of spinal canal. Therefore, the OLIF technique can be a better choice for surgical treatment of lumbar spinal stenosis.