Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China(RWE-PCSK study)

BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease(ASCVD).METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention(PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events(MACE) over six months were compared between two groups.A propensity score-matched(PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.RESULTS In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol(LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81%(P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group(P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE(hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250).CONCLUSIONS In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Efficacy of cattle encephalon glycoside and ignotin in patients with acute cerebral infarction: a randomized, double-blind, parallel-group, placebo-controlled study

Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a safe and effective treatment for acute cerebral infarction patients,especially for moderate stroke patients.This study was approved by the Ethical Committee of Peking University Third Hospital,China(approval No.2013-068-2)on May 20,2013,and registered in the Chinese Clinical Trial Registry(registration No.ChiCTR1800017937).

BRAF_(V600E)mutant colorectal cancer cells mediate local immunosuppressive microenvironment through exosomal long noncoding RNAs

BACKGROUND BRAF^(V600E) mutated colorectal cancer(CRC)is prone to peritoneal and distant lymph node metastasis and this correlates with a poor prognosis.The BRAF^(V600E) mutation is closely related to the formation of an immunosuppressive microenvironment.However,the correlation between BRAF^(V600E) mutation and changes in local immune microenvironment of CRC is not clear.AIM To explore the effect and mechanism of BRAF^(V600E) mutant on the immune microenvironment of CRC.METHODS Thirty patients with CRC were included in this study:20 in a control group and 10 in a treatment group.The density of microvessels and microlymphatic vessels,and M2 subtype macrophages in tumor tissues were detected by immunohistochemistry.Screening and functional analysis of exosomal long noncoding RNAs(lncRNAs)were performed by transcriptomics.The proliferation and migration of human umbilical vein endothelial cells(HUVECs)and human lymphatic endothelial cells(HLECs)were detected by CCK-8 assay and scratch test,respectively.The tube-forming ability of endothelial cells was detected by tube formation assay.The macrophage subtypes were obtained by flow cytometry.The expression of vascular endothelial growth factor(VEGF)-A,basic fibroblast growth factor(bFGF),transforming growth factor(TGF)-β1,VEGF-C,claudin-5,occludin,zonula occludens(ZO)-1,fibroblast activation protein,andα-smooth muscle actin was assessed by western blot analysis.The levels of cytokines interleukin(IL)-6,TGF-β1,and VEGF were assessed by enzyme-linked immunosorbent assay.RESULTS BRAF^(V600E) mutation was positively correlated with the increase of preoperative serum carbohydrate antigen 19-9(P<0.05),and with poor tumor tissue differentiation in CRC(P<0.01).Microvascular density and microlymphatic vessel density in BRAF^(V600E) mutant CRC tissues were higher than those in BRAF wildtype CRC(P<0.05).The number of CD163+M2 macrophages in BRAF^(V600E) mutant CRC tumor tissue was markedly increased(P<0.05).Compared with exosomes from CRC cells with BRAF gene silencing,the expression of 13 lncRNAs and 192 mRNAs in the exosomes from BRAF^(V600E) mutant CRC cells was upregulated,and the expression of 22 lncRNAs and 236 mRNAs was downregulated(P<0.05).The biological functions and signaling pathways predicted by differential lncRNA target genes and differential mRNAs were closely related to angiogenesis,tumor cell proliferation,differentiation,metabolism,and changes in the microenvironment.The proliferation,migration,and tube formation ability of HUVECs and HLECs induced by exosomes in the 1627 cell group(HT29 cells with BRAF gene silencing)was greatly reduced compared with the HT29 cell group(P<0.05).Compared with the HT29 cell group,the expression levels of VEGF-A,bFGF,TGF-β1,and VEGF-C in the exosomes derived from 1627 cells were reduced.The expression of ZO-1 in HUVECs,and claudin-5,occludin,and ZO-1 in HLECs of the 1627 cell group was higher.Compared with the 1627 cell group,the exosomes of the HT29 cell group promoted the expression of CD163 in macrophages(P<0.05).IL-6 secretion by macrophages in the HT29 cell group was markedly elevated(P<0.05),whereas TGF-β1 was decreased(P<0.05).The levels of IL-6,TGF-β1,and VEGF secreted by fibroblasts in the 1627 cell group decreased,compared with the HT29 cell group(P<0.05).CONCLUSION BRAF^(V600E) mutant CRC cells can reach the tumor microenvironment by releasing exosomal lncRNAs,and induce the formation of an immunosuppressive microenvironment.

Modifications of traditional pressure gloves for improved performance in scar flexion contracture prevention and fingertip circulation inspection

Dear editor,Scar hyperplasia and contracture may occur both during the spontaneous healing process of burn injuries and after surgical correction of burn-injury-related hand dysfunction or deformity such as ulnar claw.[1] Pressure gloves, capable of suppressing local scar hypertrophy and preventing scar contracture formation through scar tissue stretching, are commonly used during the rehabilitation phase in burn patients.[2] Nevertheless, traditional or conventional pressure gloves have significant drawbacks.

Effect of prolonging interval time between coronary angiography and percutaneous coronary intervention on X-ray-induced DNA double-strand breaks in blood lymphocytes

Background It is desirable to minimize the risk of adverse radiation effects associated with percutaneous coronary intervention.The aim of this study was to determine the impact of prolonging the interval between coronary angiography and percutaneous coronary intervention on X-ray-induced DNA double-strand breaks in blood lymphocytes using γ-H2AX immunofluorescence microscopy.Methods Blood samples of eight patients were taken before the first exposure to ionizing radiation,10 minutes,20 minutes,30 minutes,1 hour,and 24 hours after the last exposure to determine the γ-H2AX foci repair kinetics.Fifty-eight patients undergoing percutaneous coronary intervention were randomized to an intermittent radiation exposure group and a continuous radiation exposure group.Blood samples were taken before coronary angiography and 15 minutes after the last exposure.By enumerating γ-H2AX foci,the impact of prolonging the interval on DNA double-strand breaks was investigated.Student t-test was used to compare the difference in DNA double-strand breaks between the two groups.Results An increase in foci was found in all patients received percutaneous coronary intervention.The maximum number of γ-H2AX foci was found 10-20 minutes after the end of the last exposure.There was no statistically significant difference between the two groups in γ-H2AX foci at baseline.On average there were （0.79±0.15） γ-H2AX foci induced by interventional X-rays per lymphocyte in the continuous radiation exposure group and （0.66±0.21） in the intermittent radiation exposure group after exposure （P〈0.05）.Conclusions A significant number of γ-H2AX foci develop following the percutaneous coronary intervention procedures.The number of X-ray-induced DNA double-strand breaks may be decreased by prolonging the interval time between coronary angiography and percutaneous coronary intervention to 30 minutes.

针刺联合MOTOmed智能运动训练对痉挛型脑瘫患儿的影响

目的:观察针刺联合MOTOmed智能运动训练治疗痉挛型脑瘫患儿的疗效,分析其对患儿下肢运动功能、智力发育水平、免疫功能及脑血流动力学的影响.方法:选择42例痉挛型脑瘫患儿作为研究对象,纳入观察组.选取同期治疗的42例作为对照组.两组患儿均接受MOTOmed智能运动训练,观察组加用针刺治疗,对照组加用常规康复治疗.连续治疗2个疗程后观察两组患儿中国儿童发展研究中心(CDCC)量表的心理运动发育指数(PDI)与智力发育指数(MDI)、粗大运动功能测定(GMFM)量表、改良Ashworth量表(MAS)评分及CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)的变化,观测患儿大脑前动脉(ACA)、大脑中动脉(MCA)及大脑后动脉(PCA)的收缩期流速峰值(PSV)与平均血流速度(MFV)的变化,并评估两组疗效.结果:与同组治疗前比较,治疗后两组患儿GMFM、PDI及MDI评分,CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)及ACA、MCA、PCA的PSV和MFV均显著升高(均P<0.05),CD8^(+)水平均无显著变化(均P>0.05).治疗后,观察组下肢痉挛的总有效率90.5%,明显高于对照组的71.4%(P<0.05);观察组患儿GMFM、PDI及MDI评分,CD3^(+)、CD4^(+)水平及ACA、MCA、PCA的PSV和MFV均显著高于对照组(均P<0.05),CD8^(+)及CD4^(+)/CD8^(+)的组间差异均无统计学意义(均P>0.05).结论:针刺加MOTOmed智能运动训练治疗痉挛型脑瘫患儿临床疗效优于常规康复加MOTOmed智能运动训练;前者在改善患儿的下肢运动功能,提升患儿的智力发育水平方面亦优于后者;其作用机制可能与改善患儿脑血流动力学有关.

不同形式三伏贴防治慢性支气管炎疗效比较

目的:通过分析近5年传统三伏贴与曼吉磁贴防治慢性支气管炎(CB)缓解期的临床效果,探究三伏贴防治CB的作用原理及适宜有效的刺激量,为穴位贴敷法防治CB提供临床依据.方法:应用回顾性研究方法,选择符合纳入标准的CB患者405例,均为2013年至2017年间采用三伏贴或曼吉磁贴防治的患者,对405患者的临床资料进行统计分析,比较三伏贴与曼吉磁贴的防治效果,以及三伏贴不同刺激量的防治效果.结果:三伏贴组中,轻刺激量组总有效率为63.6%,中刺激量组总有效率为93.1%,重刺激量组总有效率为94.8%.轻刺激量组与中刺激量组和重刺激量组的总有效率差异均具有统计学意义(均P<0.05),中刺激量组与重刺激量组总有效率差异无统计学意义(P>0.05).三伏贴组总有效率为83.9%,曼吉磁贴组总有效率为45.4%,两组总有效率有统计学差异(P<0.05).结论:三伏贴防治CB的疗效优于曼吉磁贴;刺激量是保证三伏贴防治CP效果的基础,以中、重度刺激量为宜.