BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Objective:To evaluate the short-and medium-term therapeutic efficacy of shockwave balloon therapy for TASCⅡ C/D femoropopliteal artery atherosclerosis obliteration.Methods:This retrospective cohort study included 25 patients who received shockwave balloon therapy in five vascular centers from August 2022 to June 2023. All patients were diagnosed with TASC Ⅱ C/D femoropopliteal arteriosclerosis obliterans (13 cases of type C and 12 cases of type D), and underwent intravascular shock wave lithotripsy (IVL) to treat calcified lesions. The immediate effectiveness (residual stenosis<30% and no flow-limiting dissection), safety (whether there were adverse vascular events during the operation) and the rate of salvage stent implantation were recorded. The observation indexes of patients before operation, early postoperative period (immediately after operation or before discharge) and postoperative follow-up period (3, 6, 12 months after operation) were collected. The observation indexes included ankle-brachial index (ABI), Rutherford classification, and minimum lumen diameter (MLD). Repeated measures ANOVA was used to evaluate the changes of observation indexes in the early postoperative and follow-up stages compared with those before operation; Kaplan-Meier survival analysis was used to evaluate the one-stage patency rate at follow-up and the target lesion revascularization rate free from clinical drive.Results:The immediate effectiveness of surgery was 100% in all patients, with no vascular related adverse events occurred, and no remedial stent implantation was performed. The ABI, Rutherford grade and MLD of the patients in the early postoperative period and each follow-up stage were improved compared with those before operation, with statistically significant differences ( P<0.05). Kaplan-Meier survival analysis showed that the primary patency rate at 12 months after surgery was 0.78 (95% CI 0.64-0.84), and the revascularization rate of target lesions free from clinical drive was 0.87 (95% CI 0.85-0.95). Conclusion:Shockwave balloon therapy for complex calcified femoropopliteal artery lesions is safe and reliable, with satisfactory short-and medium-term efficacy.

Objective To study the effect of stachydrine on cardiomyocyte damage induced by high glucose(HG)and its regulation of Hippo-Yes-associated protein(YAP)signaling pathway.Methods Rat myocardial cells H9C2 were stimulated by HG with 30 mmol/L glucose to establish the myocardial cell injury model,and then treated with 0.05,0.10,0.15,0.20 mmol/L of stachydrine and their activities were detected by CCK-8 method,and the action concentration of stachycarine was screened.Then H9C2 was grouped into control(ctrl)group,HG group,low concentration stachydrine group,high concentration stachydrine group,and high concentration stachydrine+Hippo-YAP signaling pathway inhibitor(TDI-011536)group.Except for the ctrl group cultured with 5 mmol/L glucose,the other 4 groups were cultured with 30 mmol/L glucose,and the low and high concentration stachydrine groups were cultured with 0.05 and 0.10 mmol/L threonine for 24h,respectively.The high concentration stachydrine+TDI-011536 group were cultured with 0.10 mmol/L stachydrine and 3.00 μmol/L TDI-011536 for 24h.CCK-8 method was applied to detect cell proliferation.Flow cytometry was applied to detect apoptosis.ELISA were applied to detect the level of malondialdehyde(MDA)and superoxide dismutase(SOD).Western blot was applied to detect the level of phosphorylated YAP(p-YAP),YAP,proliferating cell nuclear antigen(PCNA),and B-cell lymphoma-2(Bcl-2)proteins.Results Compared with ctrl group,the survival rate of H9C2 cells induced by HG was significantly increased by 0.05,0.10,0.15,0.20 mmol/L stachydrine treatment,and the differences were statistically significant(t=8.32～29.67,all P<0.01).The 50%inhibitory concentration(IC50)value of stachydrine was about 0.09 mmol/L,and the concentrations of 0.05 mmol/L and 0.10 mmol/L close to and lower than IC50 were selected as the concentrations of hydrostachyine for subsequent experiments.Compared with the ctrl group,the survival rate in HG group was significantly decreased(t=44.32,P<0.01).Compared with HG group,the cell survival rate of low concentration stachydrine group and high concentration stachydrine group was significantly increased(t=10.06,21.66,all P<0.01).Compared with the high concentration stachydrine group,the cell survival rate in the high-concentration stachydrine+TDI-011536 group was significantly decreased(t=9.54,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,the apoptosis rate of HG group was significantly increased(t=36.74,P<0.01).Compared with HG group,the apoptosis rate of low concentration stachydrine group and high concentration stachydrine group was significantly decreased(t=11.04,26.78,all P<0.01).Compared with the high concentration threonine group,the apoptosis rate of the high concentration stachydrine+TDI-011536 group was significantly increased(t=9.96,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,SOD level in HG group was significantly decreased,MDA levels were significantly increased(t=18.85,29.12,all P<0.01).Compared with HG group,SOD level were significantly increased in low concentration stachydrine groups and high concentration stachydrine groups(t=6.59,9.86,all P<0.01),MDA level were significantly decreased(t=13.45,23.36,all P<0.01).Compared with the high concentration stachydrine group,the SOD level in the high concentration hydrostatin+TDI-011536 group was significantly decreased.MDA levels were significantly increased,and the differences were statistically significant(t=5.30,6.98,all P<0.01),respectively.Compared with ctrl group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly decreased,and the level of YAP protein was significantly increased(t=15.36～45.00,all P<0.01).Compared with HG group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly increased in low concentration stachydrine group and high concentration stachydrine group,the level of YAP protein levels were significantly decreased(t=5.51～25.15,all P<0.01).Compared with the high concentration stachydrine group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein in the high concentration hydrothreonine+TDI-011536 group were significantly decreased,the level of YAP protein significantly increased,the differences were statistically significant(t=4.27～11.25,all P<0.05).Conclusion Stachydrine may inhibit oxidative stress and apoptosis by activating Hippo-YAP signaling pathway,thereby ameliorating HG-induced myocardial cell damage.

Objective To study the effect of stachydrine on cardiomyocyte damage induced by high glucose(HG)and its regulation of Hippo-Yes-associated protein(YAP)signaling pathway.Methods Rat myocardial cells H9C2 were stimulated by HG with 30 mmol/L glucose to establish the myocardial cell injury model,and then treated with 0.05,0.10,0.15,0.20 mmol/L of stachydrine and their activities were detected by CCK-8 method,and the action concentration of stachycarine was screened.Then H9C2 was grouped into control(ctrl)group,HG group,low concentration stachydrine group,high concentration stachydrine group,and high concentration stachydrine+Hippo-YAP signaling pathway inhibitor(TDI-011536)group.Except for the ctrl group cultured with 5 mmol/L glucose,the other 4 groups were cultured with 30 mmol/L glucose,and the low and high concentration stachydrine groups were cultured with 0.05 and 0.10 mmol/L threonine for 24h,respectively.The high concentration stachydrine+TDI-011536 group were cultured with 0.10 mmol/L stachydrine and 3.00 μmol/L TDI-011536 for 24h.CCK-8 method was applied to detect cell proliferation.Flow cytometry was applied to detect apoptosis.ELISA were applied to detect the level of malondialdehyde(MDA)and superoxide dismutase(SOD).Western blot was applied to detect the level of phosphorylated YAP(p-YAP),YAP,proliferating cell nuclear antigen(PCNA),and B-cell lymphoma-2(Bcl-2)proteins.Results Compared with ctrl group,the survival rate of H9C2 cells induced by HG was significantly increased by 0.05,0.10,0.15,0.20 mmol/L stachydrine treatment,and the differences were statistically significant(t=8.32～29.67,all P<0.01).The 50%inhibitory concentration(IC50)value of stachydrine was about 0.09 mmol/L,and the concentrations of 0.05 mmol/L and 0.10 mmol/L close to and lower than IC50 were selected as the concentrations of hydrostachyine for subsequent experiments.Compared with the ctrl group,the survival rate in HG group was significantly decreased(t=44.32,P<0.01).Compared with HG group,the cell survival rate of low concentration stachydrine group and high concentration stachydrine group was significantly increased(t=10.06,21.66,all P<0.01).Compared with the high concentration stachydrine group,the cell survival rate in the high-concentration stachydrine+TDI-011536 group was significantly decreased(t=9.54,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,the apoptosis rate of HG group was significantly increased(t=36.74,P<0.01).Compared with HG group,the apoptosis rate of low concentration stachydrine group and high concentration stachydrine group was significantly decreased(t=11.04,26.78,all P<0.01).Compared with the high concentration threonine group,the apoptosis rate of the high concentration stachydrine+TDI-011536 group was significantly increased(t=9.96,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,SOD level in HG group was significantly decreased,MDA levels were significantly increased(t=18.85,29.12,all P<0.01).Compared with HG group,SOD level were significantly increased in low concentration stachydrine groups and high concentration stachydrine groups(t=6.59,9.86,all P<0.01),MDA level were significantly decreased(t=13.45,23.36,all P<0.01).Compared with the high concentration stachydrine group,the SOD level in the high concentration hydrostatin+TDI-011536 group was significantly decreased.MDA levels were significantly increased,and the differences were statistically significant(t=5.30,6.98,all P<0.01),respectively.Compared with ctrl group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly decreased,and the level of YAP protein was significantly increased(t=15.36～45.00,all P<0.01).Compared with HG group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly increased in low concentration stachydrine group and high concentration stachydrine group,the level of YAP protein levels were significantly decreased(t=5.51～25.15,all P<0.01).Compared with the high concentration stachydrine group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein in the high concentration hydrothreonine+TDI-011536 group were significantly decreased,the level of YAP protein significantly increased,the differences were statistically significant(t=4.27～11.25,all P<0.05).Conclusion Stachydrine may inhibit oxidative stress and apoptosis by activating Hippo-YAP signaling pathway,thereby ameliorating HG-induced myocardial cell damage.

Objective:To evaluate the short-and medium-term therapeutic efficacy of shockwave balloon therapy for TASCⅡ C/D femoropopliteal artery atherosclerosis obliteration.Methods:This retrospective cohort study included 25 patients who received shockwave balloon therapy in five vascular centers from August 2022 to June 2023. All patients were diagnosed with TASC Ⅱ C/D femoropopliteal arteriosclerosis obliterans (13 cases of type C and 12 cases of type D), and underwent intravascular shock wave lithotripsy (IVL) to treat calcified lesions. The immediate effectiveness (residual stenosis<30% and no flow-limiting dissection), safety (whether there were adverse vascular events during the operation) and the rate of salvage stent implantation were recorded. The observation indexes of patients before operation, early postoperative period (immediately after operation or before discharge) and postoperative follow-up period (3, 6, 12 months after operation) were collected. The observation indexes included ankle-brachial index (ABI), Rutherford classification, and minimum lumen diameter (MLD). Repeated measures ANOVA was used to evaluate the changes of observation indexes in the early postoperative and follow-up stages compared with those before operation; Kaplan-Meier survival analysis was used to evaluate the one-stage patency rate at follow-up and the target lesion revascularization rate free from clinical drive.Results:The immediate effectiveness of surgery was 100% in all patients, with no vascular related adverse events occurred, and no remedial stent implantation was performed. The ABI, Rutherford grade and MLD of the patients in the early postoperative period and each follow-up stage were improved compared with those before operation, with statistically significant differences ( P<0.05). Kaplan-Meier survival analysis showed that the primary patency rate at 12 months after surgery was 0.78 (95% CI 0.64-0.84), and the revascularization rate of target lesions free from clinical drive was 0.87 (95% CI 0.85-0.95). Conclusion:Shockwave balloon therapy for complex calcified femoropopliteal artery lesions is safe and reliable, with satisfactory short-and medium-term efficacy.

Objective:To analyze the status quo and influencing factors of accidental prolapse of peripherally inserted central catheter (PICC) in children, so as to provide references for formulating preventive measures.Methods:Using the convenient sampling method, a total of 1 268 pediatric patients who underwent catheterization at Intravenous Catheter Nursing Studio of Beijing Children's Hospital, Capital Medical University from January to December 2021 were selected as the research objects to analyze the incidence of PICC accidental prolapse. Logistic regression was used to analyze the influencing factors of PICC accidental prolapse.Results:Of the 1 268 children included in this study, 29 were excluded from follow-up and 1 239 children were eventually included. A total of 1 339 PICCs were implanted in 1 239 children, and the incidence of PICC accidental prolapse was 5.60% (75/1 339). Logistic regression analysis showed that whether the children had skin rash, time, location and catheter indentation time were the influencing factors for the occurrence of PICC accidental prolapse ( P<0.05) . Conclusions:The incidence of children's PICC accidental prolapse is at a high level, which is affected by many factors. Nursing staff should formulate effective preventive measures according to the influencing factors of PICC accidental prolapse, reduce the occurrence of children's accidental catheterization and extend the retention time of PICC.

Objective:To explore the efficacy and safety of Ganhai Weikang capsule (GWC) in the treatment of functional dyspepsia (FD).Methods:A randomized, double-blind, placebo-controlled parallel, multi-center, superiority clinical trial was conducted. From March 2018 to April 2020, totally 324 patients with dyspepsia symptoms, who were diagnosed as chronic non-atrophic gastritis by endoscopy and pathology and met the Rome Ⅳ diagnostic criteria for FD from 7 top hospitals were enrolled, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Heilongjiang Hospital of Traditional Chinese Medicine, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Qilu Hospital of Shandong University, the First Affiliated Hospital of Zhejiang University, Beijing Hospital of Traditional Chinese Medicine of Capital Medical University and the Third Xiangya Hospital of Central South University. The patients were randomly divided into the GWC group and the placebo group according to the ratio of 1∶1. The patients of GWC group were given GWC and the patients of placebo group were given GWC capsule simulant. The patients of both groups orally took capsules before meals, 2.4 g each time and 3 times per day, and the course of treatment was 4 weeks. The main efficacy index was the total clinical effective rate after 4 weeks, and the secondary efficacy index was the changes of clinical symptom scores of upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety. The safety index included laboratory tests and adverse events. Chi-square test and Wilcoxon rank sum test were used for statistical analysis.Results:A total of 320 FD patients were enrolled in the full analysis set (FAS), which included 161 cases in GWC group and 159 cases in placebo group. A total of 298 cases were in the per-protocol set (PPS), 149 cases each in GWC group and placebo group. The results of FAS and PPS both showed that the total clinical effective rates of the GWC group were higher than those of the placebo group (84.5%, 136/161 vs. 44.0%, 70/159 and 83.9%, 125/149 vs. 46.3%, 69/149), and the differences were statistically significant ( χ2=57.07 and 46.32, both P<0.001). In addition, the differences of the total score of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (FAS: 10 (7, 14) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 3); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs. 1 (0, 3). PPS: 10 (7, 13) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 2); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs.1 (0, 3)), and the differences were statistically significant (FAS: Z=5.80, 5.91, 3.19, 3.72 and 3.30; PPS: Z=5.14, 5.11, 2.86, 3.21 and 2.84; all P<0.01). The results of FAS and PPS indicated that the improvement rates of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) of GWC group were all higher than those of the placebo group (FAS: 77.8% (54.6%, 91.3%) vs. 42.9% (28.6%, 61.5%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 60.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 41.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%). PPS: 77.8% (54.2%, 89.5%) vs. 44.0% (28.6%, 65.0%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 46.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%)), and the differences were statistically significant (FAS: Z=8.60, 7.72, 4.98, 4.24 and 5.61; PPS: Z=7.90, 7.03, 4.49, 3.88 and 4.83; all P<0.001). After 2 weeks of treatment, the differences of the total score of main symptoms and score of each symptom (upper abdominal pain, upper abdominal burning and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (5.0 (3.0, 8.0) vs. 4.0 (2.0, 6.0); 2.0 (1.0, 2.0) vs. 2.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0)), and the differences were statistically significant ( Z=2.95, 3.44, 2.43 and 2.79, all P<0.05). There was no significant difference in the incidence of adverse events between the GWC group and the placebo group (0.6%, 1/163 vs. 0, 0/159). Conclusion:The clinical total effective rate of GWC in the treatment of FD is superior to that of placebo and it has good safety.

Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs (miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34c-5p on cardiac hypertrophy and the mechanism involved. The expression of miR-34c-5p was proved to be elevated in heart tissues from isoprenaline (ISO)-infused mice. ISO also promoted miR-34c-5p level in primary cultures of neonatal rat cardiomyocytes (NRCMs). Transfection with miR-34c-5p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor (Anf) and β-myosin heavy chain (β-Mhc) in NRCMs. In contrast, treatment with miR-34c-5p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34c-5p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34c-5p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34c-5p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4B (ATG4B) was identified as a direct target of miR-34c-5p, and miR-34c-5p was certified to interact with 3' untranslated region of Atg4b mRNA by dual-luciferase reporter assay. miR-34c-5p reduced the expression of ATG4B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34c-5p abolished the detrimental effects of ISO by restoring ATG4B and increasing autophagy. In conclusion, our findings illuminate that miR-34c-5p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4B and autophagy. It suggests that regulation of miR-34c-5p may offer a new way for handling hypertrophy-related cardiac dysfunction.

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8