Sciadopitysin exerts anticancer effects on HepG2 hepatocellular carcinoma cells by regulating reactive oxygen species-mediated signaling pathways

Objectives:Sciadopitysin(SP)is aflavonoid in Ginkgo biloba that exhibits various pharmacological activities.This study aimed to investigate its antitumor effects and the underlying molecular mechanism of SP in hepatocellular carcinoma(HCC)cells.Methods:Network pharmacology was used for target prediction analysis.Cell Counting Kit-8(CCK-8)assay was used to test the cell viability.Flow cytometry was used to test the cell cycle distribution,apoptosis status,and reactive oxygen species(ROS)levels.Transwell and wound-healing assay was used to test the migration effect of SP on HepG2 cells.Western Blot assay was used to test the expression levels of proteins.Results:Network pharmacology analysis results showed that the mitogen-activated protein kinase(MAPK)and other signaling pathways are involved in the SP anti-HCC biological process.CCK-8 assay results demonstrated that SP showed an obvious killing effect on three types of HCC cells and low cytotoxic effect on normal cells.Western Blot andflow cytometry results showed that SP regulated MAPK/signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa-B(NF-κB)signaling pathway to induce mitochondrion-dependent apoptosis in HepG2 cells.Additionally,SP can arrest the G0/G1 phase cell cycle via the protein kinase B(AKT)/p21/p27/cyclin-dependent kinase(CDK)/Cyclin signaling pathway.Wound healing and transwell assays showed that SP inhibited cell motility and invasion through the AKT/glycogen synthase kinase3β(GSK-3β)/vimentin/β-catenin signaling pathway.Conclusion:Thesefindings demonstrated that SP induced mitochondrion-dependent apoptosis,arrested cell cycle in the G0/G1 phase,and inhibited cell migration by regulating the ROS-mediated signaling pathway in HepG2 cells.Thus,SP could serve as a therapeutic agent for the treatment of human HCC.

Study on the expression and prognostic relationship of MYL6B in liver cancer based on bioinformatics

BACKGROUND Primary liver cancer is a prevalent and deadly cancer type.Despite treatment advances,prognosis remains poor,with high recurrence rates.Early detection is crucial but challenging due to the disease’s insidious nature.Myosin proteins play significant roles in cancer development,influencing cell migration,invasion,and tumor suppression.MYL6B,a myosin light chain,is involved in various cellular processes and has been associated with poor prognosis in colorectal adenocarcinoma and potential as a biomarker in breast cancer.AIM To investigate the expression of MYL6B in liver hepatocellular carcinoma(LIHC)and its impact on prognosis and potential mechanisms of action using bioinformatics methods.METHODS The expression of MYL6B in pan-cancer and normal tissues was analyzed using the gene expression profiling interactive analysis 2 and tumor immune estimation resource databases.The expression level of MYL6B in LIHC tissues and its relationship with prognosis were analyzed,immunohistochemical analysis of MYL6B and its effect on immune cell infiltration,and the protein network were further studied.RESULTS MYL6B was highly expressed in diffuse large b-cell lymphoma,LIHC,pancreatic adenocarcinoma,skin cutaneous melanoma,thymoma,uterine corpus endometrial carcinoma,uterine carcinosarcoma,and lowly expressed in kidney chromophobe,acute myeloid leukemia,testicular germ cell tumors.The expression level of MYL6B was significantly different between cancer and normal tissues.It had a significant impact on both overall survival and disease-free survival.MYL6B is highly expressed in hepatocellular carcinoma and its expression level increases with cancer progression.High MYL6B expression is associated with poor prognosis in terms of overall survival and recurrence-free survival.The immunohistochemical level of MYL6B is high in hepatocellular carcinoma tissues,and MYL6B has a high level of immune infiltration inflammation.In protein network analysis,MYL6B is correlated with MYL2,MYL6,MYL9,MYLK4,MYLK2,MYL12A,MYL12B,MYH11,MYH9 and MYH10.CONCLUSION The expression level of MYL6B in LIHC was significantly higher than in normal liver tissues,and it was correlated with the degree of differentiation survival rate,and immune infiltration.MYL6B is a potential target for LIHC treatment.

Retrospective Case Series on The Enduring Rotational Stability of The AcrySof IQ Toric Intraocular Lens in Cataract Patients Suffering from Myopia

Objective:To analyze the enduring rotational steadiness of AcrySof IQ Toric intraocular lens(IOL)in cataract patients suffering from myopia in a long-term study.Methods:A retrospective study was conducted on a case series involving 78 patients.A total of 120 eyes with an axial length(AL)ranging from 24-30 mm and corneal astigmatism≥1.50 D underwent implantation of AcrySof IQ Toric IOL guided by the version navigation system.The eyes were divided into two groups based on AL.Group A included 60 eyes with high myopia(AL≥26 mm),while Group B consisted of eyes with low to moderate myopia(24 mm≤AL<26 mm).Data on the preoperative AL were collected.Measurements were taken for residual astigmatism,the best corrected visual acuity(BCDVA),corneal astigmatism,and IOL rotation occurring between 24-and 48-months post-surgery.The percentage of eyes with an IOL rotation of under 5°and 10°was analyzed.Results:The mean length of follow-up times was recorded as 34.27±4.98,and the average rotation was 2.73±1.29°.Group A exhibited a slightly higher average rotation of 2.87±1.31°,compared to the rotation of 2.59±1.27°observed in Group B.At both the 24-36 month and 26-48 month post-operation marks,the degree of IOL rotation did not show a statistically significant difference between the two groups,with none of the patients experiencing a rotation exceeding 10°(P>0.05).The percentage of rotation degrees under 5°was recorded as 98.22%.After the procedure,the BCDVA was 0.1322±0.03 LogMAR.There was a substantial increase in theχvalue after the operation as compared to the pre-operativeχ^(2) value(χ^(2)=76.79).The standard deviation of preoperative corneal astigmatism was statistically significant(P<0.05)at 2.17±1.08 D.Following the surgical procedure,the remaining astigmatism was measured at 0.41±0.26 D.The data showed a notable gap in statistical significance(t=4.281,P<0.05).Conclusion:The AcrySof Toric IOL was a reliable solution for managing corneal astigmatism in cataract patients with myopia,demonstrating excellent long-term rotational stability.

Changes in patients' symptoms and gastric emptying after Helicobacter pylori treatment

AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia(FD) patients.METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori(H. pylori)-negative group(28 patients), and H. pylori-positive group(42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group(21 patients) and conventional treatment group(21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half-emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were givenconventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half-emptying time were compared among the 3 groups. RESULTS: The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group(50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group(93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time(P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach(P < 0.05). All were risk factors(odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment(P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group(5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group(P < 0.05). CONCLUSION: FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice.

Expression and significance of MMP-9 and MDM2 in the oncogenesis of lung cancer in rats

Objective:To observe the expression of matrix metalloproteinase-9(MMP-9)and mouse double minute 2 homolog(MDM2)in the oncogenesis of lung cancer in rats and to explore their clinical value.Methods:A total of 140 rats were selected,of which 20 were selected randomly as the control group;and the remaining 120 as the observation group.The observation group was injected with benzopyrene to establish diseases model such as tissue proliferation,abnormal proliferation and lung cancer.Delected the MMP-9 levels of lung tissue by enzyme-linked assay,detected the MDM2 levels of lung tissue by immunochemistry assay.Results:The MMP-9 and MDM2 expression of the lung cancer group and the abnormal proliferation group were significantly higher than that in the tissue proliferation group and the control group,the difference was significant(P<0.05).And the MDM2 expression of the tissue proliferation group was significantly higher than that in the control group,the difference was significant(P<0.05).There was no significant difference in the MMP-9 expression between the tissue proliferation group and the control group(P>0.05).The MDM2 and MMP-9 expression were increased in turn in the small cell carcinoma,squamous cell carcinoma and adenocarcinoma,the difference was statistically significant(P<0.05).The MMP-9 and MDM2 expressions of stageⅢand stageⅣlung cancer tissue in rats were significant higher than that during stageⅠand stageⅡ,the difference was significant(P<0.05).There was no significantly different in the MMP-9 and MDM2 expressions between stageⅢand stageⅣ(P>0.05),and there is no significant difference of the MMP-9and MDM2 expressions between stageⅠand stageⅡ(P>0.05).Conclusions:The expression of MMP-9 and MDM2 in lung tissue was associated with lung disease and lung cancer,both of them may be involved in the development and metastasis of lung cancer.Combined detection can be used as therapy and prognostic indicators for lung cancer.

Retrospective Analysis of Diagnosis by Intraoperative Frozen Section and Routine Paraffin Embedded Tissue in 638 Thyroid Disease Patients

OBJECTIVE To summarize a common pathogenefic condition, the pathologic characteristics shown in frozen section and our experience utilizing 2 different common thyroid diseases （TD）. diagnostic methods in cases of METHODS Data from 638 cases with frozen sections from thyroid tissue were retrospectively analyzed. The intraoperative frozen sections of the patients and postoperative diagnostic results of routine paraffin sections were compared. RESULTS In the 683 patients, the gender ratio of females to males was 2.64 ： 1, and the ratio between the patients with nodular goiter （NG） and the patients with thyroid adenoma was 1.5 ： 1. The oldest age group of patients with thyroid cancer （TC） ranged from 40 to 49 years. Frozen section pathologic examination has been employed more and more in the diagnosis of thyroid diseases, and the detection rate of TC has increased year by year, i.e., the rate increased to 6.45%, 7.58%, 14.55% and 16.57%, respectively, in 2005, 2006, 2007 and 2008. Thyroid papillary carcinoma （TPC） was the most commonly seen malignant tumor of the thyroid （MTT）, which accounted for approximately 94.8% of MTTs and 11.44% of the total TDs. Micropapillary carcinoma accounted for 27.4% of TPC, and multifocal carcinomas accounted for 15.58% of TCs. Many of the TCs （19.48%） were complicated by benign diseases such as adenoma, NG and thyroiditis. The coincidence rate of diagnoses made by frozen section and paraffin embedding for thyroid disease was 98.59%. Calcification was rather common in NG and TPC, and there were significant differences in psammoma bodies （PMB） between the calcifications of TPC and NG （P 〈 0.01）. CONCLUSION TPC ranks first in the incidence of MTTs and accounts for 94.8% of all MTTs. About 1/4 of TPCs are micropapillary carcinoma, while 1/5 are accompanied by benign disease, such as adenorna, NG and thyroiditis. PMB are of importance and of significance in the diagnosis of TPC.

The effectiveness and safety of the RESTORE R drug-eluting balloon versus a drug-eluting stent for small coronary vessel disease： study protocol for a multi-center, randomized, controlled trial

bjective Small coronary vessel disease （disease affecting coronary vessels with main branch diameters of 〈 2.75 mm） is a common and intractable problem in percutaneous coronary intervention （PCI）. This study was designed to test the theory that the effectiveness and safety of drug-eluting balloons for the treatment of de novo lesions in small coronary vessels are non-inferior to those of drug-eluting stents. Methods We designed a prospective, multicenter, randomized, controlled clinical trial aiming to assess the effectiveness and safety of the RESTORE R （Cardionovum, Bonn, Germany） drug-eluting balloon （DEB） versus the RESOLUTE R （Medtronic, USA） drug-eluting stent （DES） in the treatment of small coronary vessel disease. This trial started in August 2016. A total of 230 patients with a reference vessel diameter （RVD） 〉 2.25 mm and 〈 2.75 mm were randomly assigned to treatment with a DEB or a DES at a 1：1 ratio. The study was also designed to enroll 30 patients with an RVD 〉 2.00 mm and 〈 2.25 mm in the tiny vessel cohort. Results The key baseline data include demographic characteristics, relative medical history, baseline angiographic values and baseline procedural characteristics. The primary endpoint is in-segment diameter stenosis at nine months after the index procedure. Secondary endpoints include acute success, all-cause death, myocardial infarction, target vessel revascularization, target lesion revascularization and stent thrombosis. Conclusions The study will evaluate the clinical efficacy, angiographic outcomes, and safety of DEBs compared to DESs in the treatment of de novo coronary artery lesions in small vessels.

Rapid Identification and Subtyping of Enterobacter cloacae Clinical Isolates Using Peptide Mass Fingerprinting

Objective To establish a domestic database of Enterobacteria cloacae （E. cloacae）, and improve the identification efficiency using peptide mass fingerprinting. Methods Peptide mass fingerprinting was used for the identification and subtyping of E. cloacae. Eighty-seven strains, identified based on hsp60 genotyping, were used to construct and evaluate a new reference database. Results Compared with the original reference database, the identification efficiency and accuracy of the new reference database was greatly improved at the species level. The first super reference database for E. cloacae identification was also constructed and evaluated. Based on the super reference database and the main spectra projection dendrogram, E. cloacae strains were divided into two clades. Conclusion Peptide mass fingerprinting is a powerful method to identify and subtype E. cloacae, and the use of this method will allow us to obtain more information to understand the heterogeneous organism E. cloacae.

Animal exercise studies in cardiovascular research:Current knowledge and optimal design--A position paper of the Committee on Cardiac Rehabilitation,Chinese Medical Doctors’Association

Growing evidence has demonstrated exercise as an effective way to promote cardiovascular health and protect against cardiovascular diseases However,the underlying mechanisms of the beneficial effects of exercise have yet to be elucidated.Animal exercise studies are widely used to investigate the key mechanisms of exercise-induced cardiovascular protection.However,standardized procedures and well-established evaluation indicators for animal exercise models are needed to guide researchers in carrying out effective,high-quality animal studies using exercise to prevent and treat cardiovascular diseases.In our review,we present the commonly used animal exercise models in cardiovascular research and propose a set of standard procedures for exercise training,emphasizing the appropriate measurements and analysis in these chronic exercise models.We also provide recommendations for optimal design of animal exercise studies in cardiovascular research,including the choice of exercise models,control of exercise protocols,exercise at different stages of disease,and other considerations,such as age,sex,and genetic background.We hope that this position paper will promote basic research on exercise-induced cardiovascular protection and pave the way for successful translation of exercise studies from bench to bedside in the prevention and treatment of cardiovascular diseases.

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.

Investigation of Borrelia spp.in ticks(Acari:Ixodidae) at the border crossings between China and Russia in Heilongjiang Province,China

Objective:To investigate the precise species of tick vector and the Borrelia spirochete pathogen at the Heilongjiang Province international border with Russia.Methods:In dus study,ticks were collected from 12 Heilongjiang border crossings(including grasslands,shrublands,forests,and plantantions) to determine the rate and species type of spirochete-infected ticks and the most prevalent spirochete genotypes.Results:The ticks represented three genera and four species of the Ixodidae family[Ixodes persidcatus,Dermacentor silvarum,Haemapkysalis concinna and Haemaphysalis japonica].Ixodes persulcatus had the highest amount of Borrelia burgdorferi sensu lata infection of 25.6%and the most common species of Borrelia isolated from Ixodes persulcatus mas Borrelia garinii,strain PD91.Conclusions:Our results suggest that Borrelia garinii PD91- infected Ixodes persulcatus may be the principal cause of Lyme disease in the border crossing areas of Heilongjiang Province.

Microanatomical study of the nutrient artery of the glossopharyngeal nerve root

BACKGROUND： Because the artery leading to the glossopharyngeal nerve is small and complex, insufficient blood supply can occur due to atherosclerosis, occlusion, or injury. This sometimes results in corresponding nerve degeneration, demyelination, and/or arachnoid adhesion. OBJECTIVE： To observe the nutrient artery origin of the glossopharyngeal nerve root in the medulla oblongata region, as well as the relationship between the artery and glossopharyngeal nerve root, to verify dependence of primary glossopharyngeal neuralgia, which is related to contact and compression of the nutrient artery of the glossopharyngeal nerve root. DESIGN, TIME AND SETTING： Repetitive measurement. The experiment was performed at Harbin Medical University and Daqing Oilfields General Hospital between November 2006 and April 2007. MATERIALS： Ten cadaver heads （seven male and three female） were supplied by the Department of Anatomy, Harbin Medical University. A total of 15 patients （nine male and six female）, aged 38-56, that suffered from glossopharyngeal neuralgia were treated at Daqing Oilfields General Hospital and were between 38-56 years old. All cadaver heads were strictly handled according to the Guideline for Medical Ethics Committee. The patients agreed to the criteria set for the study objects. METHODS： （1）The bilateral veins of the nutrient artery were dissected under a surgery microscope. A sliding caliper was used to measure the length of the glossopharyngeal nerve from the oblongata to the jugular foramen. The origin of the nutrient artery was noted, as well as the courser and diameter to explore the relationship between the glossopharyngeal nerve root and the vertebral artery, posterior inferior cerebellar artery, anterior inferior cerebellar artery, as well as the branching veins. （2） A total of 15 patients received glossopharyngeal neuralgia surgery. Contact or oppression of the glossopharyngeal nerve with the posterior inferior cerebellar artery, the anterior inferior cerebellar artery, vertebral artery, and its branches, were evaluated. MAIN OUTCOME MEASURES： The relationship and compression of the glossopharyngeal nerve with the posterior inferior cerebellar artery, anterior inferior cerebellar artery, vertebral artery, and its branches in cadaver sections and the living human body. RESULTS： （1） Cadaver dissection： the nutrient arteries of the glossopharyngeal nerve root originated from three or two branches of the posterior inferior cerebellar artery, anterior inferior cerebellar artery, and dorsolateral medullary artery. During the procedure, four sides of the glossopharyngeal nerve root received contact or compression from the posterior inferior cerebellar artery trunk or thick loop branch. The four sides represented 20% of the area, and the two sides that received glossopharyngeal nerve root contact or compression from the anterior inferior cerebellar artery represented up to 10%. （2） Human living body： during surgery, obvious contact or compression of the glossopharyngeal nerve with three or more branches of the nutrient arteries accounted for 53.3% of the area. CONCLUSION： The cause of a number of primary glossopharyngeal neuralgia is related to contact and pressure of the nutrient artery of the glossopharyngeal nerve root.

Comparison of the safety and efficacy of two types of drug-eluting balloons （RESTORE DEB and SeQuent Please） in the treatment of coronary in-stent restenosis： study protocol for a randomized controlled trial （RESTORE ISR China）

1 Introduction In-stent restenosis （ISR）, characterized by neointimal proliferation and/or neoatherosclerosis in the vessel of the stent, can cause a reduction in lumen diameter after stent implantation, which can directly induce the recurrence of angina symptoms or an acute coronary syndrome in patients and is usually life-threatening.

Analysis of infection and prognosis of extensively drug resistant Acinetobacter baumannii in ICU

Objective:To investigate the infection of patients in the ICU with extensively drug-resistant Acinetobacter baumannii(XDRAB)and analyse the effect of tigecycline therapy for XDRAB.Methods:Seventy-one patients admitted to the ICU with XDRAB infection from January 2013 to July 2017 were divided into the tigecycline group(combination therapy with 50 mg tigecycline and 0.1 g minocycline every 12 hours)or the control group(no tigecycline treatment).Patient data,including age,sex,history of malignant tumour,body temperature,APACHE Ⅱ score,ALT,AST,GGT,TB,ALB,TBIL,DBIL,IBIL,BUN,Cr,absolute neutrophil count,procalcitonin(PCT),site positive for XDRAB infection,length of stay,and prognosis,were collected and compared between the two groups.Binary logistic regression was used to analyse the prognostic risk factors for XDRAB.Results:A total of 61.6% of the patients infected with XDRAB had multiple sites of XDRAB colonization.The cure rate achieved in the tigecycline group was higher than that of the control group(70.7%vs 41.9%).Multivariate analysis showed that older age,a high level of PCT after treatment and the absence of tigecycline treatment were poor prognostic factors for XDRAB infection.Conclusion:Combination therapy with tigecycline and minocycline is effective for XDRAB infection and reduces the cost of treatment.Combined therapy with tigecycline is a predictor of good prognosis for patients infected with XDRAB,whereas older age and increased PCT levels after treatment are predictors of poor prognosis.

Efficacy and safety of dual antiplatelet therapy in the elderly for stroke prevention: a subgroup analysis of the CHANCE- 2 trial

Objectives Evidence of the optimal antiplatelet therapy for elderly patients who had a stroke is limited,especially those elder than 80 years.This study aimed to explore the efficacy and safety of dual antiplatelet therapy(DAPT)in old-old patients compared with younger patients in the ticagrelor or Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events-II(CHANCE-2)trial.Methods CHANCE-2 was a randomised,double-blind,placebo-controlled trial in China involving patients with high-risk transient ischaemic attack or minor stroke with CYP2C19 loss-of-function alleles.In our substudy,all enrolled patients were stratified by age:old-old(≥80 years),young-old(65–80 years)and younger(<65 years).The primary outcomes were stroke recurrence and moderate to severe bleeding within 90 days,respectively.Results Of all the 6412 patients,406(6.3%)were old-old,2755(43.0%)were young-old and 3251(50.7%)were younger.Old-old patients were associated with higher composite vascular events(HR 1.41,95%CI 1.00 to 1.98,p=0.048),disabling stroke(OR 2.43,95%CI 1.52 to 3.88,p=0.0002),severe or moderate bleeding(HR 8.40,95%CI 1.95 to 36.21,p=0.004)and mortality(HR 7.56,95%CI 2.23 to 25.70,p=0.001)within 90 days.Ticagrelor-aspirin group was associated with lower risks of stroke recurrence within 90 days in younger patients(HR 0.68,95%CI 0.51 to 0.91,p=0.008),which was no differences in old-old patients.Conclusion Elderly patients aged over 80 in CHANCE-2 trial had higher risks of composite vascular events,disabling stroke,severe or moderate bleeding and mortality within 90 days.Genotype-guided DAPT might not be as effective in old-old patients as in younger ones.Trial registration number NCT04078737.

Nerve Growth Factor Promotes Angiogenesis and Skeletal Muscle Fiber Remodeling in a Murine Model of Hindlimb Ischemia

Background： Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion.Nerve growth factor （NGF） has been reported to play an important role in both physiological and pathological angiogenesis.This study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor （VEGF） in angiogenesis.Methods： Twenty-four mice were randomly allocated to normal control group （n =6）, blank control group （n =6）, VEGF gene transfection group （n =6）, and NGF gene transfection group （n =6）.The model of left hindlimb ischemia model was established by ligating the femoral artery.VEGF165 plasmid （125 μg） and NGF plasmid （125 μg） was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, respectively.Left hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia induction.The gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase staining.NGF and VEGF protein expression was detected by enzyme-linked immunosorbent assay.Results： On the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control group.The endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group （P 〈 0.05）.The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group （P 〈 0.05）.Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group （P 〈 0.05）, but there was no significant difference of the NGF protein expression between VEGF group and blank control group （P 〉 0.05）.The type Ⅰ skeletal muscle fiber proportion in gastrocnemius of NGF group and VEGF group was significantly higher than that of blank control group （P 〈 0.05）.Conclusions： NGF transfection can promote NGF and VEGF protein expression which not only can induce angiogenesis but also induce type Ⅰ muscle fiber expression in ischemic limbs.

A drug-eluting Balloon for the trEatment of coronarY bifurcatiON lesions in the side branch:a prospective multicenter ranDomized (BEYOND)clinical trial in China

Background:Treatment of coronary bifurcation lesions remains challenging;a simple strategy has been preferred as of late,but the disadvantage is ostium stenosis or even occlusion of the side branch(SB).Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported.This prospective,multicenter,randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon(PEB)compared with regular balloon angioplasty(BA)in the treatment of non-left main coronary artery bifurcation lesions.Methods:Between December 2014 and November 2015,a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers.Patients were randomly allocated at a 1:1 ratio to a PEB group(n=113)and a BA group(n=109).The primary efficacy endpoint was angiographic target lesion stenosis at 9 months.Secondary efficacy and safety endpoints included target lesion revascularization,target vessel revascularization,target lesion failure,major adverse cardiac and cerebral events(MACCEs),all-cause death,cardiac death,non-fatal myocardial infarction,and thrombosis in target lesions.The main analyses performed in this clinical trial included case shedding analysis,base-value equilibrium analysis,effectiveness analysis,and safety analysis.SAS version 9.4 was used for the statistical analyses.Results:At the 9-month angiographic follow-up,the difference in the primary efficacy endpoint of target lesion stenosis between the PEB(28.7%±18.7%)and BA groups(40.0%±19.0%)was-11.3%(95%confidence interval:-16.3%to-6.3%,Psuperiority<0.0001)in the intention-to-treat analysis,and similar results were recorded in the per-protocol analysis,demonstrating the superiority of PEB to BA.Late lumen loss was significantly lower in the PEB group than in the BA group(-0.06±0.32 vs.0.18±0.34 mm,P<0.0001).For intention-to-treat,there were no significant differences between PEB and BA in the 9-month percentages of MACCEs(0.9%vs.3.7%,P=0.16)or non-fatal myocardial infarctions(0 vs.0.9%,P=0.49).There were no clinical events of target lesion revascularization,target vessel revascularization,target lesion failure,all-cause death,cardiac death or target lesion thrombosis in either group.Conclusions:In de novo non-left main coronary artery bifurcations treated with provisional T stenting,SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis.Trial registration:ClinicalTrials.gov,NCT02325817;https://clinicaltrials.gov.

Mini-culotte stenting for bifurcation coronary disease

Coronary bifurcation lesions remain a challenging subset of lesions for percutaneous coronary intervention （PCI） with use of drug-eluting stents.Side branch （SB）is the most problematic lesion with higher rates of instent restenosis leading to the need for revascularization.1The current consensus based on clinical studies have reported that two-stent strategies are required in only a small number of patients.Of currently used complex stenting techniques,culotte stenting is comparable with the others.2-4 Unfortunately,the culotte technique has some limitations,of which double layers of metal struts is reported to be related to the occurrence of stent thrombosis （ST）.Stenting sequences of culotte stenting shares features with provisional T stenting,indicated by a jailed wire in a SB at risk of SB loss after stenting the main vessel （MV）.Accordingly we reported our modified mini-culotte stenting technique in 2008,5 but we found that mini-culotte is not always correctly used in China.As a result,it is crucial to systematically describe the tips and pitfalls of mini-culotte techniques in details.

The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats

Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor （CaSR） is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin （STZ, 40 mg kg-1） in Wistar rats. Animals then received GdCl3 （an agonist of CaSR, 8.67 mg kg-1）, NPS-2390 （an antagonist of CaSR, 0.20 g kg-~）, or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde （MDA）, lower superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH2-terminal protein kinase （JNK）, p38, and extracellular signaling-regulated kinase （ERK） 1/2. The above parameters could be further increased or aggravated by the administration of GdCI3, but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.