Aim To observe the effects of receptor interacting protein 2(RIP2)on macrophage inflammatory ac-tivation and polarity transformation,and to explore the mechanism of RIP2 in macrophage phagocytosis of oxidized low den-sity lipoprotein(ox-LDL).Methods THP-1 derived macrophages were treated with different doses(10,25 and 50 mg/L)of ox-LDL for 24 hours,and treated with 50 mg/L ox-LDL for 8,16 and 24 hours.Real-time quantitative PCR and Western blot were used to detect the expression of RIP2 mRNA and protein in THP-1 derived macrophages,and ELISA was used to detect the secretion of tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein-1(MCP-1).Three pairs of RIP2 siRNA were designed,transfecting them into cells using hiperfict transfection reagent,real-time quanti-tative PCR and Western blot were used to detect the expression of RIP2 mRNA and protein in THP-1 derived macrophages after transfection,in order to screen for the optimal siRNA transfection concentration and the most effective pair of siRNA.After transfection with the most effective RIP2 siRNA,cells were treated with 50 mg/L ox-LDL for 24 hours,ELISA was used to detect the secretion of TNF-α,MCP-1,interleukin-10(IL-10)and interleukin-12(IL-12),real-time quantitative PCR was used to detect the expression of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1),flow cytometry was used to detect the expression of cell surface antigens CD86,CD80 and CD163.Results Ox-LDL induced the ex-pression of RIP2 in macrophages in a dose-dependent and time-dependent manner.With the increase of ox-LDL treatment dose and time,the expression of RIP2 mRNA and protein increased.Among them,the expression of RIP2 protein in the 50 mg/L group was 7.6 times of the control group,and the expression of RIP2 protein in the 24 h group was 17.9 times of the control group(P＜0.001).The ELISA results showed that with the increase of ox-LDL treatment dose and time,the secretion of TNF-α and MCP-1 increased(P＜0.05).After transfection of RIP2 siRNA into cells,ELISA results showed that the secretion of TNF-α,MCP-1 and IL-10 in the ox-LDL group was 2.4 times,2.9 times and 1.8 times of the control group(P＜0.01),and the secretion of IL-12 decreased by 34.2％compared to the control group(P＜0.01);the secretion of TNF-α,MCP-1 and IL-10 in the siRNA+ox-LDL group decreased by 37.4％,45.3％and 27.4％,respectively,com-pared to the ox-LDL group(P＜0.01),while the secretion of IL-12 increased by 31.4％(P＜0.05).The results of flow cytometry and real-time quantitative PCR showed that the expression of CD86,CD80 and iNOS mRNA in the ox-LDL group was 14.2 times,33.8 times and 4.5 times of those of the control group,respectively,while the expression of CD163 and Arg-1 mRNA decreased by 33.4％and 43.0％,respectively,compared with the control group(P＜0.05);the expression of CD86,CD80 and iNOS mRNA in the siRNA+ox-LDL group decreased by 27.6％,29.3％and 34.3％,respectively,compared to the ox-LDL group,while the expression of CD163 and Arg-1 mRNA increased by 30.3％and 38.6％,respec-tively(P＜0.05).Conclusion RIP2 expression in macrophages can be induced by ox-LDL in a dose-dependent and time-dependent manner.RIP2 gene silencing can inhibit ox-LDL induced M1 macrophage transformation.

Aim To observe the effects of receptor interacting protein 2(RIP2)on macrophage inflammatory ac-tivation and polarity transformation,and to explore the mechanism of RIP2 in macrophage phagocytosis of oxidized low den-sity lipoprotein(ox-LDL).Methods THP-1 derived macrophages were treated with different doses(10,25 and 50 mg/L)of ox-LDL for 24 hours,and treated with 50 mg/L ox-LDL for 8,16 and 24 hours.Real-time quantitative PCR and Western blot were used to detect the expression of RIP2 mRNA and protein in THP-1 derived macrophages,and ELISA was used to detect the secretion of tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein-1(MCP-1).Three pairs of RIP2 siRNA were designed,transfecting them into cells using hiperfict transfection reagent,real-time quanti-tative PCR and Western blot were used to detect the expression of RIP2 mRNA and protein in THP-1 derived macrophages after transfection,in order to screen for the optimal siRNA transfection concentration and the most effective pair of siRNA.After transfection with the most effective RIP2 siRNA,cells were treated with 50 mg/L ox-LDL for 24 hours,ELISA was used to detect the secretion of TNF-α,MCP-1,interleukin-10(IL-10)and interleukin-12(IL-12),real-time quantitative PCR was used to detect the expression of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1),flow cytometry was used to detect the expression of cell surface antigens CD86,CD80 and CD163.Results Ox-LDL induced the ex-pression of RIP2 in macrophages in a dose-dependent and time-dependent manner.With the increase of ox-LDL treatment dose and time,the expression of RIP2 mRNA and protein increased.Among them,the expression of RIP2 protein in the 50 mg/L group was 7.6 times of the control group,and the expression of RIP2 protein in the 24 h group was 17.9 times of the control group(P＜0.001).The ELISA results showed that with the increase of ox-LDL treatment dose and time,the secretion of TNF-α and MCP-1 increased(P＜0.05).After transfection of RIP2 siRNA into cells,ELISA results showed that the secretion of TNF-α,MCP-1 and IL-10 in the ox-LDL group was 2.4 times,2.9 times and 1.8 times of the control group(P＜0.01),and the secretion of IL-12 decreased by 34.2％compared to the control group(P＜0.01);the secretion of TNF-α,MCP-1 and IL-10 in the siRNA+ox-LDL group decreased by 37.4％,45.3％and 27.4％,respectively,com-pared to the ox-LDL group(P＜0.01),while the secretion of IL-12 increased by 31.4％(P＜0.05).The results of flow cytometry and real-time quantitative PCR showed that the expression of CD86,CD80 and iNOS mRNA in the ox-LDL group was 14.2 times,33.8 times and 4.5 times of those of the control group,respectively,while the expression of CD163 and Arg-1 mRNA decreased by 33.4％and 43.0％,respectively,compared with the control group(P＜0.05);the expression of CD86,CD80 and iNOS mRNA in the siRNA+ox-LDL group decreased by 27.6％,29.3％and 34.3％,respectively,compared to the ox-LDL group,while the expression of CD163 and Arg-1 mRNA increased by 30.3％and 38.6％,respec-tively(P＜0.05).Conclusion RIP2 expression in macrophages can be induced by ox-LDL in a dose-dependent and time-dependent manner.RIP2 gene silencing can inhibit ox-LDL induced M1 macrophage transformation.

Objective To investigate the efficacy and safety of interventional therapy for bronchopleural fistula(BPF).Methods A total of 172 patients with confirmed BPF were treated with continuous negative pressure drainage(CNPD)and/or airway stent occlusion therapy.The clinical data were collected,and its effectiveness and safety were analyzed.Results In 5-7 days after interventional treatment,the pneumonia severity index(PSI)decreased significantly,and successful drainage was achieved in 166 patients(96.5％).One month after interventional therapy,the lung volume was remarkably increased.The median clinical healing time of interventional therapy was 9.0 months(95％CI=6.18-1 1.83).Multivariate analysis of the Cox proportional hazards model showed that the diagnosis time(HR=0.53,95％CI=0.38-0.74,P＜0.01)and fistula size(HR=0.74,95％CI=0.55-0.99,P=0.04)were significantly correlated with the clinical healing time.Conclusion For the treatment of BPF,CNPD and/or airway stent occlusion has several advantages such as accurate operation,minimally invasive,safe and effective.It can quickly improve the symptoms and quality of life,and prolong survival,therefore,it is worthy of clinical promotion and application.(J Intervent Radiol,2024,33:641-645)

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Objective:To investigate the effect of 1M3S nursing management mode combined with transcatheter arterial chemoembolization (TACE) on intestinal microecological distribution in patients with primary liver cancer.Methods:A total of 115 patients with primary liver cancer in Hai′an people′s Hospital from January 2017 to January 2020 were enrolled. Patients were divided into two groups according to the admission time. Patients ( n=56) receiving routine nursing care from January 2017 to December 2018 were set as control group, patients ( n=59) receiving 1M3S nursing management from January 2019 to January 2020 were set as observation group. Another 34 healthy individuals were set as healthy group from January 2017 to January 2020 in Hai′an People′s Hospital. The general data were collected in all three groups, and the serum levels of endotoxin (ET), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Fecal samples were collected, and 16S rDNA sequencing method was used to analyze the fecal flora structure and species relative abundance among groups, and alpha diversity was analyzed. Results:At the level of phylum, the dominant phylum of the three groups were Bacteroidetes, Proteobacteria and Firmicutes. After TACE, the ET, ALT and AST levels were (9.67±2.12) ng/L, (53.24±8.47) U/L, (55.48±8.15) U/L in the control group, (4.36±2.15) ng/L, (45.31±8.36) U/L, (47.25±8.21) U/L in the observation group ( t value was 13.328, 5.052, 5.392, P<0.05). Compared with the control group, there was an increase in the relative abundance percentage of Firmicutes( t value was 16.426, P<0.01) and Lachnospiraceae in the observation group ( t value was 4.527, P<0.01), and a decrease in the relative abundance percentage of Proteobacteria ( t value was 8.462, P<0.001) after intervention. Conclusions:TACE can affect the intestinal bacteria in patients with primary liver cancer, resulting in a decrease in the relative abundance of Proteobacteria, Lachnospiraceae, and an increase in the relative abundance of Firmicutes, while application of 1M3S nursing management mode can effectively reduce the level of endotoxin, improve liver function, and reduce the imbalance of intestinal flora caused by TACE.

Objective: The consistency of 24-hour oropharyngeal Dx-pH monitoring and proton pump inhibitor(PPI) test in the diagnosis of laryngopharyngeal reflux disease (LPRD) was investigated. Methods: Sixty patients with laryngopharyngeal reflux (LPR) related symptoms who had never received PPI treatment were assessed by reflux symptom index (RSI) and reflux finding score (RFS) between October 2017 and October 2018, including 28 males and 38 females, aged from 16 to 72 years, with a medium age of 38 years. Prior to treatment, all patients were evaluated with 24 hours oropharyngeal Dx-pH monitoring(Restech). After empiric therapy with PPI twice-daily for 8 weeks, the efficacy was evaluated according to posttreatment RSI score.The data was analysed with Kruskal-Wallis test, Student Newman Keuls test and consistency check. Results: (1)Among all 60 patients,13 patients (21.7%) had pathologic Ryan score and all resulted responsive to PPI;27 patients (45.0%) with a negative Ryan score were unresponsive to PPI; 20 patients (33.3%) despite a negative Ryan score resulted responsive to PPI therapy. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of Ryan score were 39.4%, 100%, 100% and 57.4% respectively. The Kappa value was 0.369 (P<0.01). (2)Among 34 patients (56.7%) with positive Dx-pH results (24-hour oropharyngeal acid reflux events≥ 3 times), 29 patients were positive and 5 patients were negative in PPI test. Among 26 patients with negative Dx-pH results (24-hour oropharyngeal acid reflux events<3 times), 4 patients were positive and 22 patients were negative in PPI test. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of 24-hour oropharyngeal acid reflux events were 87.9%, 81.5%, 85.3% and 84.6% respectively. The Kappa value was 0.696(P<0.01). Conclusions There is a positive correlation between 24-hour oropharyngeal Dx-pH monitoring positive results (24-hour oropharyngeal acid reflux events≥3 times) and PPI test in the diagnosis of LPRD. The 24-hour oropharyngeal Dx-pH monitoring can be a promising tool for the diagnosis of suspected LPRD patients, and more sensitive and accurate Dx-pH diagnostic index will be required in the clinic.

Objective To explore the development of the cross sign of olivepontocerebellar atrophy(OPCA) and its diagnostic value.Methods The clinical and imaging data of 8 patients with OPCA were analyzed retrospec-tively.MRI imaging used SE sequence,plain T1 WI,T2 WI,axial,coronal,sagittal imaging.Results All patients were hide onset.The major clinical presentation was cerebellar atsxia and autonomic nerve dysfunction.Positive radiographic findings were consistent with clinical presentation,mainly for the brain stem atrophy,8 patients of the group had this performance,followed by cerebellar atrophy,6 patients had symmetrical atrophy and 2 patients had asymmetric atro-phy.6 patients after onset of 1.5 -3 years showed a typical cross.Conclusion The cross sign gradually appears at a certain stage of development,and it has high specificity.So the combination of clinical and MRI is valuable for the diagnosis and differential diagnosis of OPCA.

Objective:To evaluate the effectiveness and safety of most common used regimens against brucellosis.Methods: Search PubMed and CENTRAL database of Cochrane library for all literatures written in English about treatment of brucellosis and CBM database for all RCTs for Brucellosis in Chinese from the year 1985 till now.Assess the quality of the included literatures using Cochrane Collaboration Risk of Bias form.Combine data of relapse,total therapeutic failure,and adverse reaction of regimens for treating human brucellosis.Results: 17 literatures were included.Combined antibiotic therapeutic regimens such as DR,DS,QR and DG were compared.Rate of total therapeutic failure(RRcb:2.53,95%CI:1.51-4.23) and relapse(RRcb:2.69,95%CI:1.46-4.98) of DS regimen was lower than those of DR regimen,while adverse reaction did not show any significant differences between them(RRcb:1.40,95%CI:0.97-2.01).No significant differences were seen in rate of relapse(RRcb:1.24,95%CI:0.67-2.30) and total therapeutic failure(RRcb:1.41,95%CI:0.86-2.32) between QR and DR regimen.QR regimen had lower rate of adverse reaction than DR regimen(RRcb:1.79,95%CI:1.17-2.74).Conclusion: DS regimen priors to DR regimen.QR equals DR in treatment outcome,has fewer adverse reactions meanwhile.Triple antimicrobial based on double regimens seemed to provide better outcomes without a significant increase in adverse reaction,but more clinical evidences are still needed.

Objectives To evaluate the effects of "disease-characteristics nursing quality improvement" program(DNQIP)combined with targeted monitoring in reducing the incidence of ventilator associated pneumonia (VAP)among patients with mechanical ventilation and to provide evidence for the prevention of VAP. Methods This was a prospective intervention study. All mechanical ventilation patients admitted in stroke intensive care unit(SICU)of our hospital from 2007 to 2015 were selected as the research object. Targeted monitoring was implemented in patients admitted from 2007 to 2011,and DNQIP was formed based on the monitoring results. DNQIP combined with targeted monitoring was implemented from 2012 to 2013 as the first phase,and the second phase was from 2014 to 2015.Results From 2007 to 2015,the number of new patients per year and the total time of using breathing machine in SICU presented a tendency of increasing while the number of patients with VAP and the incidence of VAP presented a tendency of decreasing year by year. The implementation of DNQIP in the first phase from 2012 to 2013(incidence of VAP was 5.4 ‰),compared with the data before implementation from 2007 to 2011(incidence of VAP was 13.8‰),the incidence of VAP was significantly reduced(χ2=9.029,P=0.003). The incidence of VAP(5.3‰)in the second phase from 2014 to 2015,was significantly reduced compared with the incidence of VAP(13.8‰)from 2007 to 2011(χ2=9.559, P=0.002).Conclusions The implementation of targeted monitoring is helpful in finding problems existing in the prevention of VAP. DNQIP in patients with mechanical ventilation can effectively reduce the incidence of VAP and can refine professional assessment and health education. It is also good for the standardization and evidence-based care in the whole process provided for patients. DNQIP combined with targeted monitoring can realize the continuous quality improvement on the basis of evidence-based theory.

Objective:To establish an ion chromatography method for the determination of methane sulfonic acid in betahistine me-sylate and evaluate the uncertainty in the measurement. Methods: An ion chromatographic column IonPac AS11-HC ( 25 mm × 4. 0 mm,5 μm) was used with 12 mmol·L-1 NaOH as the eluent and an electrical conductivity detector with the suppressor of 30 mV. Results:The results showed that methane sulfonic acid could be detected without any interference. The calibration curve was linear within the range of 10-30 μg·ml-1(r=0.999 9)and the LOQ was 0.116 μg·ml-1. The average recovery was 100.8% (RSD=1. 2%, n=9). Based on the results of experiments, the influencing factors of uncertainty in the measurement were quantitatively eval-uated. The expanded uncertainty was obtained. Conclusion:The method is simple, accurate and selective. It can be used for the de-termination of methane sulfonic acid in betahistine mesylate. Based on the evaluation of uncertainty, the analysis can help reduce the uncertainty in the measurement and improve the accuracy and reliability of the determination.