Objective:To evaluate the effect of statins combined with PCSK9 inhibitors on coronary artery atherosclerotic plaque, as well as to verify the lipid-lowering effect of the combined therapy.Methods:A computerized search of PubMed, Embase, Web of Science, Cochrane Library, Wanfang, and CNKI databases was conducted to retrieve published literature from inception to December 20, 2022. The English search terms utilized included "PCSK9 inhibitors," "Alirocumab," "Evolocumab," "plaque," "IVUS," and "OCT." The corresponding Chinese search terms were "PCSK9 inhibitors," "plateau," "intravascular ultrasound," and "optical coherence tomography." The literature that examined the effect of statins alone or in combination with PCSK9 inhibitors on coronary atherosclerotic plaques using intravascular ultrasound or optical coherence tomography was identified. The collected data were subsequently processed using Review Manager (Revman) version 5.4.Results:In the final analysis, nine studies involving 1912 patients were included. The analysis results revealed that compared with statins alone, statins combined with PCSK9 inhibitors significantly reduced the percentage of atherosclerotic volume ( MD: -2.08 mm 3, 95% CI: -2.94 to -1.23 mm 3, P < 0.001), accelerated the regression of atherosclerotic volume ( MD: -1.13 mm 3, 95% CI: -1.49 to -0.77 mm 3, P < 0.001), slightly, but not significantly, reduced the overall atherosclerotic volume ( MD: -6.42 mm 3, 95% CI: -14.34-1.51 mm 3, P = 0.110). Nevertheless, the combined therapy contributed to a significant reduction in atherosclerotic volume ( MD: -5.16 mm 3, 95% CI: -7.09 to -3.23 mm 3, P < 0.001) and significantly increased the fiber cap thickness of thin cap plaques ( MD: 8.46 μm, 95% CI: 5.13-11.79 μm, P < 0.001). Additionally, this combined therapy significantly lowered blood lipid levels. Conclusion:The combination of statins and PCSK9 inhibitors can significantly improve the characteristics and phenotype of atherosclerotic plaques and significantly reduce blood lipid levels. For patients with high cardiovascular risk, it is recommended to initiate treatment with statins combined with PCSK9 inhibitors as soon as possible and maintain it for a long time to ensure more benefits.

Objective To investigate the effect of ultrasound-guided stellate ganglion block(SGB)on intraoperative fentanyl dosage in the patients undergoing open thyroidectomy.Methods A total of 70 patients with elective open thyroidectomy under general anesthesia in the Affiliated Hospital of North Sichuan Medical College from November 2021 to April 2022 were selected as the study subjects and divided into the SGB group(group S,n=35)and the control group(group C,n=33).The group S conducted ultrasound-guided SGB at 15 min before anesthetic induction(injection of 0.25％marcaine 6-8 mL),and group C conducted the stellate ganglion recognition under the ultrasound guidance in 15 min before anesthetic induction without conducting other operations.All patients all received the anesthesia induction and maintenance under the same BIS moni-toring.The fentanyl dosage,recovery time,anesthetic drugs dosage,fluid infusion amounts,bleeding volume,use rate of atropine and ephedrine,operation time and postoperative complications as well as the VAS scores in PACU 30 min,at postoperative 3,6,12,24 h were recorded.Results Compared with group C,the intraopera-tive amount of fentanyl in group S was significantly decreased[(247.9±65.4)μg vs.(295.7±61.5)μg,P=0.003].The propofol dosage,cisatracurium dosage,fluid infusion amounts,bleeding amounts,use rate of atro-pine and ephedrine,recovery time and incidence rate of complications had no statistical differences between the two groups(P＞0.05).The VAS scores at various time points in group S all were lower than those in group C(P＜0.05).Conclusion Ultrasound-guided SGB could reduce the fentanyl use amounts during operation in the patients with open thyroidectomy.

Objective:We compared the clinical outcomes between β-blocker with angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in patients with acute myocardial infarction (AMI) without left ventricular systolic dysfunction.Methods:A total of 750 patients who were diagnosed as AMI without left ventricular systolic dysfunction and successfully received percutaneous coronary intervention (PCI) in TEDA International Cardiovascular Hospital from October 2016 to September 2017 were collected retrospectively. We divided the patients into two groups: β-blocker + ACEI group (BB+ ACEI group, n=666) and β-blocker + ARB group (BB+ ARB group, n=84) according to discharge medications. The clinical datas were gathered and the end-point events were followed up. K-M curve was used to describe cumulative survival rate of the two groups. We used Cox regression analysis to compare the clinical outcomes of the two groups. Results:The occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) (8.3% vs 3.4%, HR=2.377, 95% CI: 1.006-5.616, P=0.048), all-cause death (3.6% vs 0.4%, HR=12.951, 95% CI: 1.947-86.159, P=0.008) and non-fatal myocardial infarction (3.6% vs 0.8%, HR=5.231, 95% CI: 1.193-22.934, P=0.028) in the BB+ ARB group was significantly higher than those in the BB+ ACEI group followed up for 13 months. However, there was no difference between the two groups in the incidence of stroke (1.2% vs 1.4%, HR=0.922, 95% CI: 0.117-7.276, P=0.516) and target vessel revascularization (3.6% vs 1.6%, HR=1.607, 95% CI: 0.384-6.729, P=0.516). The cumulative survival rate of BB+ ACEI group was higher than that of BB+ ARB group, with statistically significant difference ( P<0.05). Conclusions:Compared with β-blocker combined with ARB, β-blocker combined with ACEI are more beneficial to reduce the incidence of MACCE, all-cause death and non-fatal myocardial infarction in AMI patients without left ventricular systolic dysfunction after PCI.

Objective:To study the clinical prognosis and related factors affecting optimal medical therapy (OMT) compliance of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).Methods:A prospective study was conducted to select 3 818 patients who were diagnosed with CAD and successfully underwent PCI in TEDA International Cardiovascular Hospital from October 2016 to September 2017. The clinical information and application of OMT during hospitalization and 1 year later were collected for research.The patients were divided into OMT group and non OMT group according to whether they adhered to OMT during follow-up one year after discharge. After comparing the imbalance baseline data of hypertension,diabetes and hyperlipidemia with propensity score,demographic characteristics, coronary revascularization history, CAD, laboratory related laboratory examinations,and the use of OMT drugs were compared between the two groups. Cox regression model was used to analyze the relationship between long-term OMT and clinical prognosis in patients with CAD.Multivariate binary logistic regression was used to analyze the related factors affecting long-term OMT compliance.Results:A total of 3 818 cases of CAD patients were matched by propensity score and 2 596 patients were included in the study. There were 1 609 males and 987 females. The age was (62.51±9.56) years old.One year later,1298 patients (50%) insisted on OMT,including dual antiplatelet therapy(DAPT), statins, β-blockers and ACEI/ARB were 97.0% (2 517/2 596),94.5%(2 454/2 596),69.6% (1 806/2 596) and 64.2% (1 666/2 596), especially angiotensin converting enzyme inhibitors / angiotensin receptor blockers and β Receptor blockers decreased the most.Cox regression analysis showed that after adjusting for other factors, compared with non-adherence to OMT group,OMT after PCI was associated with better prognosis ( HR=0.416,95% CI 0.270-0.641, P<0.001). The prognosis of CAD patients with history of old myocardial infarction ( HR=1.804,95% CI 1.070-3.041, P=0.027),cardiac insufficiency ( HR=2.074,95% CI 1.161-3.702, P=0.014),multivessel coronary disease ( HR=2.211,95% CI 1.228-3.983, P=0.008) and BMI>24 ( HR=1.570,95% CI 1.037-2.377, P=0.033) were related to worse clinical outcomes. Multi-factor binary Logistic regression showed that OMT at hospitalization was a strong influencing factor of long-term adherence to OMT ( OR=41.278,95% CI 29.961-56.871, P<0.001). Patients with higher education,employee medical insurance and with history of PCI tend to persist in OMT. Conclusion:The medication compliance of patients with long-term OMT after PCI is still poor,while the high compliance of OMT is related to the lower incidence of adverse cardiovascular events,including death, nonfatal myocardial infarction and stroke. If there is no obvious contraindication,all patients after PCI should adhere to OMT.

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy.

Objective To detect the expression of matrix metalloproteinase-9 (MMP-9) gene in peripheral blood of patients with oral paraquat (PQ) poisoning and evaluate its predictive value for their prognosis.Methods Thirty-seven cases of oral PQ poisoning admitted to Linyi People's Hospital from January 2013 to June 2014 were enrolled,and they were divided into survival group (26 cases) and death group (11 cases) according to the survival sitnation in 28 days after poisoning;a healthy control group included 10 healthy people selected in the same period.The peripheral blood 3 mL was collected from each PQ patient on the 1st and 3rd day after admission,and in the healthy control group,3 mL peripheral venous blood was obtained under fast on the day for physical examination.The MMP-9 gene expression of peripheral blood mononuclear cells (PBMCs) was detected by reverse transcription-polymerase chain reaction (RT-PCR) methods;the serum MMP-9 concentration was determined by using enzyme-linked immunosorbent assay (ELISA);the serum PQ level was detected by high performance liquid chromatography (HPLC),and the amount of poison orally taken was recorded.The correlations between PQ amount orally taken,serum PQ level and MMP-9 expression were analyzed by Spearman correlation analysis.A receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of peripheral blood MMP-9 level for the 28-day prognosis of PQ poisoning patients.Results After admission the 1 day serum PQ level was (2.60 ± 1.29) mg/L,and the amount of poison taken was 50.0 (7.5,60.0) mL in the 37 patients with oral PQ poisoning.The MMP-9 gene expression level in PBMCs and serum MMP-9 protein level of both PQ poisoning groups were significantly higher than those of healthy control group,and the levels were gradually increased with the extension of poisoning time;the degrees of elevation in death group were more significant [the PBMCs' MMP-9 gene expression (A value):2.84± 1.16 vs.0.95 ± 0.23 on the 1st poisoning day,4.22± 1.75 vs.1.29 ±0.30 on the 3rd poisoning day;serum MMP-9 concentration (μg/L):2791.48± 1 230.88 vs.807.81±279.86 on the 1st poisoning day,4384.21 ± 1 781.97 vs.1 131.14±291.76 on the 3rd poisoning day,all P ＜ 0.05].Correlation analysis showed:there were significant positive correlations of oral PQ amount,serum PQ concentration to the MMP-9 gene expression in PBMCs and serum MMP-9 protein concentration in patients with oral PQ poisoning (all P =0.000).ROC curve analysis showed:the MMP-9 gene expression in PBMCs on the 1st day and the serum MMP-9 content on the 3rd day after admission had predictive value for 28-day prognosis in patients with oral PQ poisoning,and the ROC areas under the curve (AUC) was 0.820 and 0.776 respectively.When the cutoff value of MMP-9 gene expression level on the 1st day after admission was 0.90,the predictive sensitivity and specificity were 80.00％ and 63.64％ respectively;when the cutoff value of serum MMP-9 protein content on the 3rd day after admission was 904.36 μg/L,the predictive sensitivity and specificity were 80.00％ and 72.73％ respectively.Conclusion Oral PQ poisoning can lead to the MMP-9 gene expression in PBMCs and elevation of serum MMP-9 protein level in the body,and the MMP-9 gene expression has predictive value for the prognosis of patients with oral PQ poisoning.

Objective To evaluate the role of (99)Tc(m)-MDP SPECT/CT bone fusion imaging in diagnosis and treatment strategy establishment of patients with bone metastatic malignancy.Methods Retrospective study was carried out on 66 patients (55 patients with primary malignant tumors,11 patients with primary benign bone disease) chosen from 117 patients who had undergone whole body bone scintigraphy and SPECT/CT fusion imaging examination.Comparison was carried out on diagnostic efficacy for bone metastases and changes of treatment between SPECT/CT fusion imaging and other anatomical imaging (CT and/or MR).Cases excluded are extensive bone metastases and no final diagnosis of patients.Results For diagnosis of patient with bone metastasis and bone metastasis lesion,the sensitivity of SPECT/CT fusion imaging was (90.62％,93.88％),specificity (79.41％,89.47％) and accuracy (84.84％,90.97％),while sensitivity of simple anatomical imaging was (59.38％,51.02％),specificity (94.11％,94.73％) and accuracy (77.27％,79.86％),with a significant difference (P ＜ 0.05).SPECT/CT fusion imaging changed 30.31％ (20/66) the patient's treatment plan,while 16.67％ (11/66) for simple anatomical imaging,with a significant difference (P ＜ 0.05).Conclusions SPECT/CT fusion imaging could increase the accuracy of diagnosis of bone metastases and have an important role in establishing the treatment strategy.

Objective To investigate the risk factors for pulmonary fibrosis in patients with paraquat (PQ) poisoning.Methods A total of 120 patients with PQ poisoning who were admitted from January 2012 to December 2014 were enrolled.According to the presence or absence of pulmonary fibrosis,the patients were divided into non-pulmonary fibrosis group (67 patients) and pulmonary fibrosis group (53 patients).The Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE II) score was obtained on days 1 and 3 of poisoning.Routine blood test results,blood biochemical parameters,and radiological parameters were recorded,and the patients with PQ poisoning were followed up for survival and pulmonary fibrosis.Results A total of 39 patients with PQ poisoning died,resulting in a mortality rate of 32.5％.There were 53 patients who developed pulmonary interstitial fibrosis,yielding an incidence rate of 44.2％.Compared with the non-pulmonary fibrosis group,the pulmonary fibrosis group had a significantly higher age,a significantly higher dose of PQ,and significantly higher APACHE II scores on days 1 and 3 of poisoning(P＜0.01),as well as significantly higher white blood cell (WBC) count and neutrophil count on day 1,significantly higher levels of urea nitrogen,creatinine,and blood glucose on days 1 and 3,and significantly higher activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT)(P＜0.01).The logistic regression analysis showed that the dose of PQ,WBC count and neutrophil count on day 1,APACHE II scores on days 1 and 3 of poisoning,levels of urea nitrogen,creatinine,and blood glucose,and activities of AST and ALT were associated with the development of pulmonary fibrosis in patients with PQ poisoning.Conclusion Oral dose of PQ,APACHE Ⅱ scores on days 1 and 3 of poisoning,levels of urea nitrogen,creatinine,and blood glucose,activities of AST and ALT,and WBC count and neutrophil count on day 1 are risk factors for pulmonary fibrosis in patients with paraquat poisoning.

Objective To investigate the risk factors for pulmonary fibrosis in patients with paraquat (PQ) poisoning.Methods A total of 120 patients with PQ poisoning who were admitted from January 2012 to December 2014 were enrolled.According to the presence or absence of pulmonary fibrosis,the patients were divided into non-pulmonary fibrosis group (67 patients) and pulmonary fibrosis group (53 patients).The Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE II) score was obtained on days 1 and 3 of poisoning.Routine blood test results,blood biochemical parameters,and radiological parameters were recorded,and the patients with PQ poisoning were followed up for survival and pulmonary fibrosis.Results A total of 39 patients with PQ poisoning died,resulting in a mortality rate of 32.5％.There were 53 patients who developed pulmonary interstitial fibrosis,yielding an incidence rate of 44.2％.Compared with the non-pulmonary fibrosis group,the pulmonary fibrosis group had a significantly higher age,a significantly higher dose of PQ,and significantly higher APACHE II scores on days 1 and 3 of poisoning(P＜0.01),as well as significantly higher white blood cell (WBC) count and neutrophil count on day 1,significantly higher levels of urea nitrogen,creatinine,and blood glucose on days 1 and 3,and significantly higher activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT)(P＜0.01).The logistic regression analysis showed that the dose of PQ,WBC count and neutrophil count on day 1,APACHE II scores on days 1 and 3 of poisoning,levels of urea nitrogen,creatinine,and blood glucose,and activities of AST and ALT were associated with the development of pulmonary fibrosis in patients with PQ poisoning.Conclusion Oral dose of PQ,APACHE Ⅱ scores on days 1 and 3 of poisoning,levels of urea nitrogen,creatinine,and blood glucose,activities of AST and ALT,and WBC count and neutrophil count on day 1 are risk factors for pulmonary fibrosis in patients with paraquat poisoning.

Objective:To investigate the effect of activin A and nerve growth factor ( NGF) NGF on stimulating neurite outgrowth of dorsal root ganglia(DRG)of the embryonic chicken.Methods:In this study,we observed that activin A and NGF together induced neurite outgrowth of DRG and kept survival of DRG neurons by the primary cultured DRGs from embryonic day 8 ( E8 ) chicken.calcitonin gene-related peptide(CGRP)CGRP mRNA expressions were analyzed by RT-PCR.Results: The DRG treated with activin A +NGF had obvious neurite outgrowth ,compared with only NGF group on day 3,and the number of living DRG neurons also increased.Activin A +NGF up-regulated the mRNA expressions of CGRP in DRG.Conclusion:The Data demonstrated that activin A with NGF can synergistically stimulate DRG neurite outgrowth and maintain the DRG neurons survival , suggesting that it is more effective that NGF and activin A together treat the associated disease of nerve system.