Objective:To prepare the nanodrug paclitaxel dimer(PTX2)-loaded nanoparticles(NPs)using the block copolymer 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol 2000,(DSPE-PEG2000),and to explore the killing effect of PTX2 NPs on the human lung cancer A549 cells and its influence on apop to tis.Methods:The PTX2 NPs were prepared using nanoprecipitation method.Dynamic light scattering(DLS)was employed to determine the particle size distribution,and transmission electron microscope(TEM)was used to observe the ultrastructure of the nanoparticles.After treatment of 0 and 10 mmol·L-1 dithiothreitol(DTT),dialysis method was used to evaluate the in vitro drug release profile of PTX2 NPs.The cell counting kit-8(CCK-8)method was used to assess the survival rates of the A549 cells after treated with PTX2 and PTX2 NPs with different concentrations(0.000 1,0.001 0,0.010 0,0.100 0,and 1.000 0 μmol·L-1).The A549 cells were divided into control group,PTX2 group,and PTX2 NPs group.Live/dead staining method was used to detect the survival of the A549 cells in various groups,and flow cytometry was used to detect the apoptotic rates of the A549 cells in various groups.Results:The mean hydrodynamic diameter of PTX2 NPs was determined to be 144.7nmbyDLS.TheTEM imaging confirmed uniform spherical morphology of PTX2 NPs.In a reductive environment,the PTX2 NPs exhibited continuous drug release with total paclitaxel(PTX)release of 84％within 72 h.The results of CCK-8 method showed that both PTX2 and PTX2 NPs inhibited the proliferation of A549 cells in a dose-dependent manner.When the concentrations of PTX＜0.01 μmol·L-1,compared with PTX2 group,the survival rates of A549 cells in PTX2 NPs group were significantly decreased(P＜0.01 or P＜0.001).The live/dead staining results showed that compared with PTX2 group,the number of red fluorescence-labeled dead cells in PTX2 NPs group was increased.The flow cytometry results demonstrated that compared with control group and PTX2 group,the apoptotic rates of the A549 cells in PTX2 NPs group were significantly increased(P＜0.05 orP＜0.01).Conclusion:The PTX2-loaded nanoparticles PTX2 NPs are successfully prepared which exhibits responsive drug release and demonstrates a more significant killing effect on the human lung cancer A549 cells compared to PTX2.

OBJECTIVE To systematically evaluate the efficacy and safety of vonoprazan （VPZ） for Helicobacter pylori （Hp） eradication therapy. METHODS Retrieved from The Cochrane Library， Embase， PubMed， CNKI， VIP and Wanfang database， randomized controlled trials about VPZ for Hp eradication therapy （trial group） versus proton pump inhibitor （PPI） （control group） were collected during the inception to July 2022. After data extraction and quality evaluation with bias risk assessment tool recommended by Cochrane System Evaluation Manual 5.1.0， meta-analysis was performed by using RevMan5.3 software. RESULTS Nine studies with 2 134 patients were included. Compared with control group， the overall Hp eradication rate of trial group increased significantly in either the ITT analysis or PP analysis， being 87.5% vs. 76.2% [RR＝1.14， 95%CI （1.06，1.21）， P＜0.001] and 92.4% vs. 80.5% [RR＝1.11， 95%CI （1.03，1.21）， P＜0.01]， respectively. According to ITT and PP analysis of primary treatment subgroup， compared with control group， the overall Hp eradication rate of trial group increased significantly， being 88.4% vs. 76.5% [RR＝1.15， 95%CI （1.09，1.22）， P＜0.000 01] and 92.8% vs. 80.9% [RR＝1.12， 95%CI（1.03，1.23）， P＜ 0.05]； according to ITT and PP analysis of rescue therapy subgroup， there was no significant difference in the overall Hp eradication rate between control group and trial group （P＞0.05）. According to ITT and PP analysis of triple therapy subgroup， compared with control group， overall Hp eradication rate of trial group increased significantly， being 88.3% vs. 75.6% [RR＝1.16， 95%CI （1.08， 1.25）， P＜0.000 1] and 92.6% vs. 77.6% [RR=1.15， 95%CI （1.04， 1.28）， P＜0.01]； according to ITT and PP analysis of quadruple therapy subgroup， there was no significant difference in the overall Hp eradication rate between control group and trial group （P＞0.05）. Compared with control group， the incidence of adverse events in trial group decreased significantly， being 34.2% vs. 40.9% [RR＝0.84， 95%CI（0.70，0.99）， P＜ 0.05]. There was no statistical significance in the incidence of serious adverse events between 2 groups （P＞0.05）. CONCLUSIONS Compared with PPI therapy， the efficacy of VPZ-based triple therapy is better， particularly in primary treatment patients. However， VPZ has no significant advantage in rescue treatment and bismuth-containing quadruple regimen. And the safety and tolerance of VPZ for Hp eradication therapy are well， even better than PPI.

Objective:To investigate the changes of intraventricular pressure differences (IVPDs) and intraventricular pressure gradients (IVPGs) in different diastolic phases of hypertensive patients with different left ventricular configurations by relative pressure imaging (RPI) based on vector flow mapping (VFM), and to explore its diagnostic value for diastolic function in hypertensive patients with different left ventricular configurations.Methods:Totally 180 patients with hypertension were selected from April 2020 to March 2021 in the Outpatient Clinic of the Second Affiliated Hospital of Harbin Medical University. According to the relative wall thickness (RWT) and left ventricular mass index (LVMI), the patients were divided into normal geometry group (NG group, n=62), concentric remodeling group (CR group, n=62) and concentric hypertrophy group (CH group, n=56). Sixty-one healthy volunteers were selected as the control group. Clinical data and echocardiographic parameters were collected and the differences of each parameter among 4 groups were compared. IVPDs and IVPGs in four diastolic phases were obtained by RPI, including isovolumic relaxation (IR), rapid filling (RF), slow filling (SF) and atrial contraction (AC). The differences of IVPDs and IVPGs in each phase of diastole among 4 groups and their correlations with echocardiographic parameters were analyzed, and the diagnostic efficacy of RPI parameters in NG group patients with reduced diastolic function was analyzed by the ROC curve. Results:The absolute values of IVPDs and IVPGs were greater in all subgroups of hypertension than those of the control group at each diastole phase( P<0.001). Pairwise comparisons showed statistically significant differences of IVPDs-IR and IVPGs-IR among 4 groups( P<0.001). They were correlated with E/e′( rs=-0.615, -0.605; all P<0.001). IVPDs-IR and IVPGs-IR had good diagnostic efficacy for the decrease of diastolic function of patients in NG group, the cutoff values were <-0.705 mmHg (AUC=0.935, P<0.001) and <-0.130 mmHg/cm (AUC=0.926, P<0.001). Conclusions:RPI can precisely assess different degrees of diastolic function changes in hypertensive patients with different configurations. IVPDs-IR and IVPGs-IR can be used as potential new indicators for non-invasive early diagnosis of hypertensive patients with reduced diastolic function, which is of great significance for timely clinical intervention and treatment of reversing ventricular remodeling.

Objective:To evaluate the short- and medium-term clinical efficacy of TIPS approach combined with AngioJet thrombus aspiration technology treatment in acute portal vein thrombosis.Methods:63 cases with acute portal vein thrombosis treated in our center from May 2017 to July 2019 were studied retrospectively, including 49 males and 14 females, aged 35-61 (46 ± 5) years. TIPS approach (with/without) combined with Angiojet thrombus aspiration and gastroesophageal varices embolization was performed simultaneously according to the patient's condition. Regular follow-up for 3-33 (22 ± 3) months after surgery was used to observe the curative effect.Results:The technical success rate was 100%. Portal vein and superior mesenteric vein blood flow were returned to normal after the operation. Two cases of biliary tract injury were untreated. Simultaneously, two cases of intrahepatic arteriovenous fistula were treated with superselective arterial embolization. During the follow-up period, 47 cases (74.61%) had complete portal vein recanalization, 13 cases (20.63%) had partial recanalization, 3 cases (4.76%) had complete portal cavernoma, 7 cases (11.11%) had symptomatic hepatic encephalopathy, 1 case had received artificial liver treatment (1.59%), 1 case had peptic ulcer (11.11%), 6 cases (9.52%) had lost to follow-up, and there was no portal hypertension-related bleeding or death.Conclusion:TIPS approach combined with AngioJet thrombus aspiration technology is safe, effective and feasible in the treatment of acute portal vein thrombosis, and the short- and medium-term clinical effects are satisfactory.

Objective:To investigate the effect of miR-218 on the proliferation and invasion of breast cancer cells.Methods: The expression of miR-218 in breast cancer tissues and breast cancer cell lines was detected by qPCR.The relationship between the expression of miR-218 and the clinicopathological parameters of breast cancer were analyzed.Double luciferase assay was used to detect the relationship between miR-218 and SNX4.MTT assay and invasion assay were used to detect the proliferation and invasion of breast cancer cells after overexpression of miR-218.MTX assay and invasion assay were used to detect the recovery level of SNX4 on the proliferation and invasion of breast cancer cells.The effect of miR-218 on the tumorigenesis of breast cancer cell lines was examined by tumorigenesis in nude mice.Results: The expression level of miR-218 in breast cancer tissue and MCF-7 cell line was higher.The expression of miR-218 was associated with pathological stage of breast cancer and lymph node metastasis.SNX4 may be the target of miR-218.Overexpression of miR-21 could inhibit the proliferation and invasion of breast cancer cells.Overexpression of SNX4 could reverse the inhibitory effect of miR-218 on breast cancer cells.Overexpression of miR-218 could inhibit the breast cancer cell line in nude mice tumorigenic ability.Conclusion: miR-218 can up-regulate the expression of miR-218 in breast cancer,and miR-218 can regulate the expression of SNX4 in breast cancer cell proliferation and invasion.