Objective To evaluate the short-term efficacy of transcatheter aortic valve replacement (TAVR) using Venus A-Plus valve delivery system in patients with severe aortic stenosis. Methods The clinical data of patients undergoing TAVR in our hospital from August 2018 to March 2022 were collected and they were divided into a Venus A-Plus and a Venus A group according to the type of valve delivery system used. The perioperative data of the two groups were compared. Results A total of 121 patients were included, including 70 patients in the Venus A-Plus group [45 males and 25 females with a mean age of (67.81±6.62) years], and 51 patients in the Venus A group [33 males and 18 females with a mean age of (68.25±7.01) years]. All patients underwent TAVR, and the postoperative hemodynamic features (left ventricular ejection fraction, mean cross-valve pressure difference, peak flow rate) were significantly improved (P<0.05). There was no statistical difference in surgical success rate, all-cause mortality, conversion to thorax opening, valve-in-valve placement, moderate or above perivalvular regurgitation, new left bundle branch block or new right bundle branch block between the two groups (P>0.05). Conclusion TAVR with Venus A-Plus valve delivery system in patients with severe aortic stenosis shows comparable efficacy to the first-generation Venus A system and is satisfactory, safe and reliable.

ObjectiveTo investigate the regulatory effects and underlying mechanisms of Liuhuang Zhike prescription （LHZK） on blood glucose in type 2 diabetic db/db mice based on the AMP-activated protein kinase/protein kinase B/glycogen synthase kinase-3β （AMPK/Akt/GSK-3β） signaling pathway. MethodsDb/db mice were used as the model animals， and db/m mice served as the blank control. Forty db/db mice were randomly divided into the model group， metformin group （0.14 g·kg^-1）， and low-， medium-， and high-dose （4.11， 8.21， 16.43 g·kg^-1） LHZK groups， with 8 mice in each group. The db/db mice in the metformin and LHZK groups were administered the corresponding drugs by gavage， while the blank control and model groups were given distilled water by gavage once daily for 8 consecutive weeks. Food intake， water consumption， body weight， and fasting blood glucose （FBG） were measured weekly. An automatic biochemical analyzer was used to determine glycated serum protein （GSP）， serum triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels. Hematoxylin-eosin （HE） staining was used to observe pathological morphological changes in the liver and pancreatic tissues. Oil red O staining was used to assess lipid accumulation in liver tissue. The anthrone colorimetric method was used to determine hepatic glycogen content. Real-time quantitative PCR （Real-time PCR） was used to detect the mRNA expression levels of insulin receptor substrate-1 （IRS-1）， Akt2， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6Pase） in liver tissue. Western blot was used to detect the protein expression of AMPKα， phosphorylated AMPKα （p-AMPKα）， GSK-3β， p-GSK-3β， glycogen synthase （GS）， and phosphorylated GS （p-GS） in liver tissue. ResultsCompared with the blank control group， the model group showed significantly increased food intake， water consumption， body weight， FBG， and GSP levels （P<0.01）. Pancreatic islets exhibited marked parenchymal cell hyperplasia and interstitial inflammatory cell infiltration. Liver tissue showed obvious steatosis， accompanied by a compensatory increase in hepatic glycogen content （P<0.01）. Hepatic G6Pase mRNA expression was increased， while IRS-1 and Akt2 mRNA expression levels were significantly decreased （P<0.01）. The p-AMPKα/AMPKα protein expression ratio showed a decreasing trend， whereas the p-GSK-3β/GSK-3β and p-GS/GS protein expression ratios were significantly increased （P<0.01）. Compared with the model group， food intake and water consumption showed decreasing trends in all treatment groups. Food intake was significantly reduced in the low- and high-dose LHZK groups and in the metformin group （P<0.05， P<0.01）， and water consumption was significantly reduced in the low-dose LHZK group and in the metformin group （P<0.05， P<0.01）. No statistically significant differences in body weight were observed among the LHZK groups， whereas body weight in the metformin group was significantly increased （P<0.05， P<0.01）. FBG showed a decreasing trend in all treatment groups， with significant decreases in the low-dose LHZK group and the metformin group （P<0.05， P<0.01）. GSP levels were significantly reduced in the low-dose LHZK group and in the metformin group （P<0.05， P<0.01）. Hepatic steatosis and pancreatic pathological injury were alleviated to varying degrees in all treatment groups. Hepatic glycogen content further increased in all treatment groups， with significant increases in the medium- and high-dose LHZK groups （P<0.05）. Real-time PCR results showed that all treatment groups downregulated the mRNA expression of G6Pase and PEPCK in the liver tissues of db/db mice， with significant downregulation of PEPCK mRNA in the low-dose LHZK and metformin groups （P<0.01）. Meanwhile， all treatment groups upregulated IRS-1 and Akt2 mRNA expression， with the most pronounced upregulation observed in the medium-dose LHZK group （P<0.01）. The p-AMPKα/AMPKα protein expression ratio was significantly increased in the low- and medium-dose LHZK groups （P<0.01）. The p-GSK-3β/GSK-3β protein expression ratio was significantly increased in all treatment groups （P<0.05， P<0.01）， whereas the p-GS/GS protein expression ratio was significantly decreased in all treatment groups （P<0.01）. ConclusionLHZK effectively reduces FBG and GSP levels in type 2 diabetic mice and improves hepatic steatosis and pancreatic islet pathological injury. Its hypoglycemic mechanism may be associated with regulation of the AMPK/Akt/GSK-3β signaling pathway and promotion of hepatic glycogen synthesis.

Objective To investigate the new-onset conduction block after transcatheter aortic valve replacement (TAVR) and summarize the relevant experience. Methods The perioperative data of TAVR patients in the Second Hospital of Hebei Medical University from January 2016 to February 2023 were collected, and the new-onset incidence of conduction block after TAVR was analyzed retrospectively. Results Finally 352 patients were included, including 225 males and 127 females, with an average age of (67.2±5.1) years, among whom 256 patients were treated with Venus-A valves, 69 patients with Vita-Flow valves, and 27 patients with J-Valve valves. There were 38 (10.8%) patients of new-onset postoperative block. There were 6 (1.7%) patients of new-onset postoperative grade Ⅲ atrioventricular block, including 5 (2.0%) patients of Venus-A and 1 (1.4%) patient of Vita-Flow. Conduction function was restored in 2 patients within 14 days after surgery, and failed to be restored in 4 patients, who then received permanent pacemaker implantation in the Department of Cardiology. There were 27 (7.7%) patients of new left bundle branch block after surgery, including 22 (8.6%) patients of Venus-A, 4 (5.8%) patients of Vita-Flow and 1 (3.7%) patient of J-Valve; and conduction function was restored within 7 days after surgery in 23 patients, and 5 (1.4%) patients developed new right bundle branch blocks after surgery including 4 (1.5%) patients of Venus-A and 1 (1.4%) patient of Vita-Flow. Conclusion New-onset conduction block is a common complication after TAVR, and the new-onset rate of left bundle branch block is the highest, followed by the grade Ⅲ atrioventricular block. Mastering reasonable methods and applying appropriate strategies can effectively reduce the new-onset rate of postoperative conduction block and improve the overall success rate of TAVR surgery.

Cucumber (Cucumis sativus L.) is one of the most widely cultivated vegetables in the world. High temperature and other stress conditions can affect the growth and development of this plant, even leading to the decreases in yield and quality. The mitogen-activated protein kinase (MAPK) family plays a crucial role in plant stress responses. However, the role of MPK4 in the stress response of cucumber remains to be reported. In this study, we cloned CsMPK4, which encoded 383 amino acid residues. The qRT-PCR results showed that the expression level of CsMPK4 was the highest in leaves and flowers, moderate in roots, and the lowest in stems and tendrils. CsMPK4 was located in the nucleus and cytoplasm, and it had a close relationship with CmMPK4 in muskmelon. The cucumber plants overexpressing CsMPK4 became stronger and shorter, with reduced length and quantity of tendrils. Moreover, the transgenic seedlings were more resistant to high temperatures, with decreased malondialdehyde (MDA) content and increased activities of peroxidase (POD) and superoxide dismutase (SOD) in young leaves. Furthermore, the protein-protein interaction between CsMPK4 and CsVQ10, a member of the valine-glutamine family, was confirmed by yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays. The results suggested that CsVQ10 cooperated with CsMPK4 in response to the high temperature stress in cucumber. This study laid a foundation for the further study on the stress response mechanism of CsMPK4 and the breeding of stress-resistant cucumber varieties.
Cucumis sativus/metabolism* ; Mitogen-Activated Protein Kinases/physiology* ; Plant Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Gene Expression Regulation, Plant ; Stress, Physiological/genetics* ; Cloning, Molecular

Objective To explore the value of 3D printing technology in transcatheter aortic valve replacement(TAVR)for bicuspid aortic stenosis.Methods We retrospectively analyzed the clinical data of patients who underwent TAVR for bicuspid aortic stenosis at the Department of Cardiac Surgery of the Second Hospital of Hebei Medical University between January 2020 and January 2023.Seven-ty patients were divided into 3D printing and non-3D printing groups of 35 each,based on whether or not 3D printing technology was applied,and the perioperative clinical data of the two groups were compared.Results The patients' postoperative symptoms signifi-cantly improved compared with those before the operation,and the left ventricular ejection fraction increased to varying degrees.Compared with the non-3D printing group,the operation time,X-ray irradiation time.and transvalvular time in the 3D printing group were signifi-cantly shortened,and the probabilities of the occurrence of postoperative"flap-to-flap"implantation and conduction block were signifi-cantly reduced,with statistically significant differences(P＜0.05).There was no statistically significant difference(P＞0.05)in the inci-dence of moderate and above perivalvular leakage,valve displacement,or conversion to thoracotomy between the two groups after surgery.Conclusion 3D printing technology can effectively guide the TAVR treatment of bicuspid aortic stenosis.While significantly shortening the operation time,it can effectively increase the success rate of TAVR and reduce the risk of adverse events,providing a new approach for the transcatheter treatment of bicuspid aortic stenosis.

Objective To explore the value of 3D printing technology in transcatheter aortic valve replacement(TAVR)for bicuspid aortic stenosis.Methods We retrospectively analyzed the clinical data of patients who underwent TAVR for bicuspid aortic stenosis at the Department of Cardiac Surgery of the Second Hospital of Hebei Medical University between January 2020 and January 2023.Seven-ty patients were divided into 3D printing and non-3D printing groups of 35 each,based on whether or not 3D printing technology was applied,and the perioperative clinical data of the two groups were compared.Results The patients' postoperative symptoms signifi-cantly improved compared with those before the operation,and the left ventricular ejection fraction increased to varying degrees.Compared with the non-3D printing group,the operation time,X-ray irradiation time.and transvalvular time in the 3D printing group were signifi-cantly shortened,and the probabilities of the occurrence of postoperative"flap-to-flap"implantation and conduction block were signifi-cantly reduced,with statistically significant differences(P＜0.05).There was no statistically significant difference(P＞0.05)in the inci-dence of moderate and above perivalvular leakage,valve displacement,or conversion to thoracotomy between the two groups after surgery.Conclusion 3D printing technology can effectively guide the TAVR treatment of bicuspid aortic stenosis.While significantly shortening the operation time,it can effectively increase the success rate of TAVR and reduce the risk of adverse events,providing a new approach for the transcatheter treatment of bicuspid aortic stenosis.

Objective To investigate the expression of the ubiquitination enzyme UBE2S in different cell types in hepatocellular carcinoma(HCC)microenvironment and its impact on proliferation and stemness of HCC cells.Methods TCGA and CPTAC database were used to analyze the transcriptional and promoter methylation levels and protein expressions of UBE2S in HCC.Specific expression patterns of UBE2S,intercellular communication and key transcription factors in different cell types were analyzed based on single-cell sequencing data from TISCH website.We further examined UBE2S expressions in clinical samples of HCC tissues,HCC cells and T cells using immunohistochemistry and immunofluorescence staining.We also tested the effects of UBE2S knockdown on stemness of HCC-LM3 and HepG2 cells using clone formation experiments and sphere formation assay.Results Analysis based on TCGA database suggested significant overexpression of UBE2S in both paired and non-paired tumor tissues(P<0.001),and its transcriptional level increased with tumor grades.The methylation level of UBE2S promoter was significantly decreased in HCC(P<0.001),and its transcription level increased obviously in HCC with TP53 mutation(P<0.001).Analysis of CPTAC database also demonstrated overexpression of UBE2S protein in HCC tissues(P<0.001).Three prognostic models suggested that HCC patients with high UBE2S expression had poorer prognosis(P<0.001).Single-cell sequencing data analysis revealed high expressions of UBE2S in T cells and high intensities of interaction between endothelial cells,epithelial cells and fibroblasts in HCC microenvironment.Immunohistochemistry and immunofluorescence staining demonstrated high UBE2S expressions in clinical samples of HCC tissues,HCC cells and T cells.In HCC-LM3 and HepG2 cells,UBE2S knockdown significantly inhibited cell clone formation and tumor sphere formation(P<0.05).Conclusion UBE2S is highly expressed in T cells in HCC microenvironment in close correlation with a poor prognosis.High UBE2S expression promotes the stemness of HCC cells.

Objective To analyze the short-term clinical efficacy and prognosis of one-stop transcatheter aortic valve replacement (TAVR)+percutaneous coronary intervention (PCI) in the treatment of aortic valve disease with coronary heart disease. Methods The clinical data of patients with aortic valve disease complicated with coronary heart disease who underwent one-stop TAVR+PCI treatment at the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University from January 2018 to June 2023 were retrospective analyzed. The preoperative and postoperative clinical data were compared, and 1-month follow-up results were recorded. Results A total of 37 patients were enrolled, including 22 males and 15 females, with an average age of 69.14±6.47 years. Thirty-six patients recovered and were discharged after the surgery, and 1 (2.7%) patient died during the surgery. Self-expanding TAVR valves were implanted through the femoral artery in all patients. One coronary artery was opened by PCI in 35 (94.6%) patients, and two coronary arteries were opened by PCI in 2 (5.4%) patients. All PCI opened arteries had a stenosis>70%. During the postoperative hospitalization, the complications included pulmonary infection in 11 (30.6%) patients, severe pneumonia in 10 (27.8%) patients, liver function injury in 14 (38.9%) patients, renal function injury in 5 (13.9%) patients, cerebral infarction in 1 (2.8%) patient, atrial fibrillation in 1 (2.8%) patient, ventricular premature beats in 2 (5.6%) patients, atrioventricular block in 2 (5.6%) patients, and complete left bundle branch block in 5 (13.9%) patients. The median postoperative ventilation assistance time was 12.0 (0.0, 17.0) h, the ICU monitoring time was 1.0 (0.0, 2.0) d, and the postoperative hospitalization time was 5.0 (4.0, 7.0) d. There was a significant improvement in the New York Heart Association cardiac function grading after surgery (P<0.001). After surgery, there were 21 (58.3%) patients had minor perivalve leakage, 6 (16.7%) patients had minor to moderate perivalve leakage, and no moderate or above degree of perivalve leakage. After one month of postoperative follow-up, 36 patients showed significant improvement in heart function. There were no patients with recurrent acute coronary syndrome, re-PCI, or cardiovascular system disease related re-hospitalization. Conclusion The one-stop TAVR+PCI treatment for patients with aortic valve disease and coronary heart disease can obtain satisfactory short-term clinical efficacy, which is worth further trying and studying.

Objective To investigate the expression of the ubiquitination enzyme UBE2S in different cell types in hepatocellular carcinoma(HCC)microenvironment and its impact on proliferation and stemness of HCC cells.Methods TCGA and CPTAC database were used to analyze the transcriptional and promoter methylation levels and protein expressions of UBE2S in HCC.Specific expression patterns of UBE2S,intercellular communication and key transcription factors in different cell types were analyzed based on single-cell sequencing data from TISCH website.We further examined UBE2S expressions in clinical samples of HCC tissues,HCC cells and T cells using immunohistochemistry and immunofluorescence staining.We also tested the effects of UBE2S knockdown on stemness of HCC-LM3 and HepG2 cells using clone formation experiments and sphere formation assay.Results Analysis based on TCGA database suggested significant overexpression of UBE2S in both paired and non-paired tumor tissues(P<0.001),and its transcriptional level increased with tumor grades.The methylation level of UBE2S promoter was significantly decreased in HCC(P<0.001),and its transcription level increased obviously in HCC with TP53 mutation(P<0.001).Analysis of CPTAC database also demonstrated overexpression of UBE2S protein in HCC tissues(P<0.001).Three prognostic models suggested that HCC patients with high UBE2S expression had poorer prognosis(P<0.001).Single-cell sequencing data analysis revealed high expressions of UBE2S in T cells and high intensities of interaction between endothelial cells,epithelial cells and fibroblasts in HCC microenvironment.Immunohistochemistry and immunofluorescence staining demonstrated high UBE2S expressions in clinical samples of HCC tissues,HCC cells and T cells.In HCC-LM3 and HepG2 cells,UBE2S knockdown significantly inhibited cell clone formation and tumor sphere formation(P<0.05).Conclusion UBE2S is highly expressed in T cells in HCC microenvironment in close correlation with a poor prognosis.High UBE2S expression promotes the stemness of HCC cells.

Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.