Objective To explore the valve regurgitation status of left heart after the implantation of left ventricular assist device (LVAD) and its effect on prognosis of patients with LVAD implantation. Methods A total of 35 patients with cardiomyopathy who underwent magnetic levitation LVAD implantation at Zhongshan Hospital, Fudan University from February 2021 to July 2024 were retrospectively selected. Clinical data during hospitalization were collected, including preoperative basic data and postoperative valve regurgitation status. Telephone follow-ups were conducted to monitor patients’ survival status and transthoracic echocardiography was used to assess left valve function. Kaplan-Meier survival curves and log-rank test were employed to compare the survival rate of patients with different levels of valve regurgitation. Results The 35 patients had a mean age of (53.9±11.1) years, with 85.7% male, and 3 patients (8.6%) died during hospitalization. Preoperatively, 17 patients (48.6%) had moderate or greater mitral regurgitation, while all 35 patients had less than moderate aortic regurgitation. One month postoperatively, thirty patients were followed up, among which 24 patients (80%) had less than moderate mitral regurgitation, including 11 cases with alleviated regurgitation compared to pre-surgery; 6 patients (20%) had moderate or greater mitral regurgitation, including 4 cases with stable regurgitation and 2 cases with progression of regurgitation compared to pre-surgery; 2 patients (6.7%) had progression of aortic regurgitation to moderate or greater. The follow-up time was 1.2 (1.0, 2.1) years, with 1-year survival rate of 91.4% and 3-year survival rate of 71.1%. Survival analysis showed that the 3-year survival rate of patients with moderate or greater mitral regurgitation one month postoperatively was significantly lower than that of patients with less than moderate regurgitation (66.7% vs 83.3%, P＝0.046). Conclusions After the implantation of magnetic levitation LVAD, most patients showed improvement in mitral regurgitation, while aortic regurgitation remained unchanged. The degree of mitral regurgitation one month postoperatively is associated with prognosis.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Polygonum cuspidatum polyketide synthase 1 (PcPKS1) has the catalytic activity of chalcone synthase (CHS) and benzylidene acetone synthase (BAS), which can catalyze the production of polyketides naringenin chalcone and benzylidene acetone, and then catalyze the synthesis of flavonoids or benzylidene acetone. In this study, three amino acid sites (Thr133, Ser134, Ser33) that may affect the function of PcPKS1 were identified by analyzing the sequences of PcPKS1, the BAS from Rheum palmatum and the CHS from Arabidopsis thaliana, as well as the conformation of the catalytic site of the enzyme. Molecular modification of PcPKS1 was carried out by site-directed mutagenesis, and two mutants were successfully obtained. The in vitro enzymatic reactions were carried out, and the differences in activity were detected by high performance liquid chromatography (HPLC). Finally, mutants T133LS134A and S339V with bifunctional activity were obtained. In addition to bifunctional activities of BAS and CHS, the modified PcPKS1 had much higher BAS activity than that of the wild type PcPKS1 under the conditions of pH 7.0 and pH 9.0, respectively. It provides a theoretical basis for future use of PcPKS1 in genetic engineering to regulate the biosynthesis of flavonoids and raspberry ketones.
Amino Acid Sequence ; Fallopia japonica/metabolism* ; Polyketide Synthases/chemistry* ; Acetone ; Mutagenesis, Site-Directed ; Flavonoids/metabolism* ; Acyltransferases/metabolism*

With the advantage of high efficiency， low toxicity and targeting， liposomes have become the research hotspot of new drug preparations at home and abroad. In this paper， the research progress in recent years is reviewed from the aspects of preparation methods， classification and clinical application of liposomes. The results showed that in order to obtain more stable and controllable liposomes， scholars improved and optimized the traditional preparation methods and established novel preparation methods such as supercritical fluid methods， freeze-drying method and double-asymmetric centrifugation method. In order to enhance the efficacy and reduce toxicity， the conventional liposomes were optimized to get novel ones such as environmentally sensitive liposomes， long-circulating liposomes and multifunctional liposomes， which had greatly promoted the clinical application of liposomes. For now， liposomes have been used in many fields， such as anti-cancer agents， antimicrobial and vaccines， but most of the new liposomes are still in the early stage of development.

Objective To explore whether macrophage migration inhibitor factor (MIF)can protect human bone microvascular endothelial cells (HBMECs)from glucocorticoid-induced damage.Methods HUVECs were isolated from human femoral head.After HUVECs were cultured and identified,we constructed the ECs damage model with high-dose hydrocortisone.The cells were randomly divided into blank control group,low-dose MIF group,high-dose MIF group with corresponding treatment.Cell activity was detected by AlamarBlue in each group. The number of viable cells was detected in Live/Dead staining.The cell morphology was observed after cytoskeleton staining.Cell migration ability was compared by scratch test and the level of VEGF expression was detected by ELISA.Results Cell model was successfully constructed.The activity of cells in high-dose MIF group (178.3± 15.2)% was significantly higher than that in the control group (100±8.4)% and low-dose MIF group (149.1± 13.8)% (P<0.05).The number of viable cells in high-dose MIF group (139.5±14.3)% was higher than that in low-dose MIF group (121.3±12.9)% while the two groups had more viable cells than the control group (100± 8.4)% (P<0.05).The scratch test results indicated that cell migration ability in high-dose group was the strongest and the scratch disappeared at 24 hours after scratching.The expression of VEGF at 24 hours after intervention was (170±15.7)pg/mL in normal group,(328±25.3)pg/mL in low-dose group and (405±31.2)pg/mL in high-dose group.VEGF level was lower in low-dose group than in high-dose group (P<0.05),but higher than the normal group (P<0.01).Conclusion MIF can promote the proliferation and migration of ECs in a dose-dependent manner and upregulate the expression of VEGF.MIF can improve ECs damage induced by high-dose glucocorticoid.

Objective · To assess the morphological changes of mitral valve geometry after mitral valve repair by using real-time 3D transesophageal echocardiography. Methods · The clinical data including 3D echocardiography of 36 patients undergoing mitral valve repair for mitral valve prolapse and 56 patients without mitral valve diseases were collected. Parameters of mitral annular and leaflet geometry were acquired and analyzed. Results · The ellipse index of the two-dimensional view (E2D), and non-planar leaflet angle (θNPA) were decreased, while other parameters were increased significantly in patients with mitral valve prolapse compared with controls before mitral valve repair. After repair, patients displayed larger θNPA, and still smaller E2D.Some parameters also get smaller, such as the anterior to posterior diameter of the mitral annulus, the anterolateral to posteromedial coaptation diameter,the minimum circumference of the three-dimensional view of the annulus, the minimum area of the two-dimensional view of the annulus, the exposed area of the anterior leaflet, inter-commissural diameter. Other parameters were not changed significantly. All parameters showed no significant difference between respect group and resect group in posterior valve prolapse before and after mitral valve repair. Conclusion · The repair procedure can restore the function of the mitral valve effectively. In view of the morphology, the geometry of the mitral valve annulus is still different from the normal apparently after the mitral valve repair, but the normal morphology of the leaflets can be regained. It seems to have similar curative effect morphologically for patients with posterior leaflet prolapse to have respect or resect strategy.

Objective:To study the silencing gene expression level of RhoGDI2 small interfering RNA(siRNA)and the colorectal cancer cell malignant behaviors such as cell proliferation,migration,invasion.Methods:Testing RhoGDI2 expression using Westen blot analysis and Real-time reverse transcription polymerase chain reaction(RT-qPCR)in the colorectal cancer cell lines of RKO,HT29,SW620,SW480,HCT116.The siRNA of RhoGDI2 with Lipofecta mineTM2000 was transfected into target cells,as well as negative control and normal control groups.Cell counting kits(CCK-8)to detect proliferation,Wound healing assay and the Transwell plate migration and invasion was detected.The epithelial-mesenchymal transition(EMT)relevant protein E-cadherin/Vimentin expression was detected.Results:Human colon cancer cell lines RhoGDI2 expression levels decreased in the order of RKO,HT29,SW620,SW480,HCT116:siRNA inhibited RhoGDI2 expression rate of RKO cell by 70%;in silence group,negative control group and blank contro1 group,the proliferation rates were(0.683±0.013),(0.866±0.088),(0.905±0.008),P<0.05;Wound healing assay and Transwell assay suggested RhoGDI2 silencing could inhibit migration;siRNA interference of colon cancer cells downregulated Vimentin,but upregulated E-Cadherin protein.Conclusion:RhoGDI2 down-regulation could significantly inhibit the cell proliferation,migration,invasion of colon cancer cell.

Objective:To explore the expression and clinical significance of RhoGDI2 in colorectal cancer. Methods:Immuno-histochemistry was used to identify RhoGDI2 expression in clinical samples of colorectal cancer tissues,para-tumorous tissues and lymph node metastasis tissues. The relationships between CRC clinical factors and survival were analyzed. Results: RhoGDI2 expression contributed positively with tumor progression and metastasis in clinical tissues. It was associated with the stage of the tumor,lymph node metastasis, remote metastasis, venous invasion and vessel invasion. Patients with higher RhoGDI2 expression had poorer overall survival. Conclusion:RhoGDI2 showed high expression in colorectal cancer and it was associated with the stage of the tumor,lymph node metastasis,remote metastasis, venous invasion and vessel invasion. Patients with higher RhoGDI2 expression had poorer overall survival.

Objective To study the effects of low calcium dialysate on bone mineral density (BMD) in old patients with low turnover renal osteodystrophy under maintenance hemodialysis.Methods Totally 72 elderly patients aged≥ 60 years under MHD for 6 months or more with parathyroid hormone(iPTH)＜100 ng/L were selected and randomly divided into treatment group(n=36,calcium 1.25 mmol/L in dialysate)and a control group(n =36,calcium 1.5 mmol/L in dialysate),for 12 months of treatment.The changes of albumin-corrected calcium and phosphorus,calciumphosphorus product,iPTH level,bone mineral density,and other indicators as well as related adverse events were observed before and 12 months after the study.Results There was no statistically significant difference in general conditions and the correlated laboratory examinations between the two groups before and after treatment (P ＞ 0.05).After dialytic treatments with dialysate containing calcium 1.25 mmol/L for 12 months,the therapy group versus pre-therapy and control group showed statistically significant decrease in parameters of mean arterial pressure(MAP) [(88.6 ± 9.2) vs.(92.6±10.4)and(93.7±8.8)mmHg],serum calcium[(2.4±0.1)vs.(2.6±0.3)and(2.6±0.2)mmol/L,t =5.061,5.074],phosphorus[(2.0±0.2)vs.(2.1 ±0.2)and(2.1±0.3)mmol/L,t=2.276,2.271],calcium-phosphorus product[(4.7 ± 0.5) vs.(5.3 ± 0.6) and (5.4 ± 0.7) mmol2 / L2,t =4.682,4.627](all P＜0.05),and showed statistically significant increase in parameters of iPTH levels[(132.6 ±37.8) vs.(71.3 ± 11.48) and (69.7 ± 16.0) ng/L;t value 8.824 and 9.048,respectively],bone mineral density values(Lumbar:0.8±0.9 vs.-1.2±1.1 and-1.2±1.1;t value 2.170 and 2.170,respectivly.Femoral neck:-0.8± 1.0 vs.1.3±1.2 and-1.3±1.3;t value 2.258 and 2.243,respectively) (all P＜0.05).In the control group after 12 months of treatment with calcium 1.5mmol/L dialysate,there was no significant difference in related parameters (P＞ 0.05).There was no significant difference in the adverse reactions between study and control groups (P ＞ 0.05).Conclusions The low calcium dialysate(calcium 1.25 mmol/L)used in elderly patients with iPTH＜100 ng/L under MHD can effectively improve the excessive depression of parathyroid function and the decreased BMD,and better control the albumin corrected calcium,phosphorus,calcium-phosphorus product level,and has a good security.

The chalcone synthase (CHS) superfamily of the type III polyketide synthases (PKSs) generates backbones of a variety of plant secondary metabolites. Benzalacetone synthase (BAS) catalyzes a condensation reaction of decarboxylation between the substrates of 4-coumaric coenzyme A and malonyl coenzyme A to generate benzylidene acetone, whose derivatives are series of compounds with various biological activities. A BAS gene Pcpks2 and a bifunctional CHS/BAS PcPKSI were isolated from medicinal plant P. cuspidatum. Crystallographic and structure-based mutagenesis studies indicate that the functional diversity of the CHS-superfamily enzymes is principally derived from small modifications of the active site architecture. In order to obtain an understanding of the biosynthesis of polyketides in P. cuspidatum, which has been poorly described, as well as of its activation mechanism, PcPKS2 was overexpressed in Escherichia coli as a C-terminally poly-His-tagged fusion protein, purified to homogeneity and crystallized, which is helpful for the clarification of the catalytic mechanism of the enzyme and lays the foundation for its genetic engineering manipulation.
Butanones ; Catalytic Domain ; Crystallization ; Fallopia japonica ; enzymology ; Polyketide Synthases ; genetics ; metabolism