复明片联合曲伏前列素滴眼液治疗开角型青光眼的临床研究

目的 探讨复明片联合曲伏前列素滴眼液治疗开角型青光眼的临床疗效。方法 选取2017年10月—2021年1月在洛阳市第三人民医院眼科治疗的142例开角型青光眼患者,根据随机数字法将所有患者分为对照组和治疗组,每组各组71例。对照组外用曲伏前列素滴眼液,睡前1滴/次,1次/d。治疗组在对照组治疗基础上口服复明片,5片/次,3次/d。两组连续用药30 d。观察两组的临床疗效,比较两组临床症状缓解情况,眼动脉血流指标和血清学因子水平。结果 治疗后,治疗组总有效率是98.59%,显著高于对照组的84.51%（P＜0.05）。治疗后,治疗组视力模糊、眼胀、视力下降、头痛缓解时间均显著短于对照组（P＜0.05）。治疗后,两组眼动脉血流阻力指数（RI）、动脉收缩期最大流速（PSV）均较治疗前显著降低,但舒张末期血流速度（EDV）显著升高（P＜0.05）;治疗后,治疗组眼动脉血流指标改善优于对照组（P＜0.05）。治疗后,两组患者血清白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、干扰素-γ（IFN-γ）、内皮素-1（ET-1）水平均较治疗前显著降低（P＜0.05）;治疗后,治疗组血清因子水平低于对照组（P＜0.05）。结论 复明片联合曲伏前列素滴眼液治疗开角型青光眼具有较好的临床疗效,可明显改善眼部血流指标,能有效降低眼部炎症状态,值得临床推广使用。     

Metformin is not just an antihyperglycaemic drug but also has protective effects on the vascular endothelium

Metformin, a synthetic dimethyl biguanide, has been in clinical use for over 55 years, and today is considered the first‐choice drug for the treatment of type 2 diabetes used by an estimated 125 million people worldwide. Metformin is orally effective, not metabolized, excreted unchanged by the kidney, relatively free of side effects and well tolerated by the majority of patients. Of importance is that the United Kingdom Prospective Diabetes Study 20‐year study of type 2 diabetics, completed in 1998, compared patients treated with insulin, sulfonylureas and metformin and concluded that metformin provided vascular protective actions. Cardiovascular disease is the primary basis for the high morbidity and mortality that is associated with diabetes and that metformin proved to be protective resulted in a dramatic increase in its use. The vascular protective actions of metformin are thought to be secondary to the antihyperglycaemic effects of metformin that are mediated via activation of AMP kinase and subsequent inhibition of hepatic gluconeogenesis, fatty acid oxidation as well as an insulin sensitizing action in striated muscle and adipose tissue. As reflected by a number of clinical studies, patients treated with metformin also have improvement in endothelial function as measured by the use of plethysmography and measurement of flow‐mediated vasodilatation. These data as well as data from animal studies are supportive that metformin has a direct protective action on the vascular endothelium. In this review article, we discuss the pharmacology of metformin and critique the literature as to its cellular sites and mechanism(s) of action.     

Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction

Background

Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure–volume loop analysis in HFPEF.

Methods

26 HFPEF patients who showed an increase in LV stiffness by pressure–volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin < 100 μg/l or ferritin of 100–299 μg/l in combination with transferrin saturation < 20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies.

Results

Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p < 0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r = − 0.636, p < 0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency.

Conclusion

In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID.     

Estimation of infarct size using transthoracic Doppler echocardiographic measurement of coronary flow reserve in infarct related and reference coronary artery

Background

Patients in chronic phase of myocardial infarction (MI) have decreased coronary flow reserve (CFR) in infarct related artery (IRA) that is proportional to the extent of microvascular/myocardial damage. We proposed a novel model for the assessment of microvascular damage and infarct size using Doppler echocardiography evaluation of CFRs of the IRA (LAD) and reference artery (RCA).

Methods

Our study included 34 consecutive patients (28 men, mean age 50 ± 11 years) with first anterior STEMI and single vessel disease successfully treated with primary PCI. All patients underwent SPECT MPI for the assessment of infarct size (expressed as a percentage of myocardium with fixed perfusion abnormalities) and CFR evaluation of LAD and RCA. CFR derived percentage of microvascular damage (CFR PMD) was calculated as: CFR PMD = (CFR RCA − CFR LAD) / (CFR RCA − 1) × 100 (%).

Results

CFR PMD correlated significantly with all parameters evaluating the severity of myocardial damage including: peak CK activity (r = 0.632, p < 0.001), WMSI (r = 0.857, p < 0.001), ejection fraction (r = − 0.820, p < 0.001), left ventricular end diastolic (r = 0.757, p < 0.001) and end systolic volume (r = 0.794, p < 0.001). Most importantly, CFR PMD (22 ± 17%) correlated significantly with infarct size by SPECT MPI (21 ± 17%) (r = 0.874, p < 0.001).

Conclusions

CFR PMD derived from the proposed model was significantly related to echocardiographic and enzymatic parameters of infarct size, as well as to myocardial damage assessed by SPECT MPI in patients with successfully reperfused first anterior STEMI.     

Multi-Modality Imaging in the Assessment of Cardiovascular Toxicity in the Cancer Patient

Cancer therapy can be associated with both cardiac and vascular toxicity. Advanced multi-modality imaging can be used to stratify patient risk, identify cardiovascular injury during and after therapy, and forecast recovery. Echocardiography continues to be the mainstay in the evaluation of cardiac toxicity. Particularly, echocardiography-based strain imaging is useful for risk stratification of patients at baseline, and detection of subclinical left ventricle (LV) dysfunction during therapy. Cardiac magnetic resonance (CMR) serves a complementary role in the patient with poor echocardiographic or equilibrium radionuclide angiographic image quality or in situations where a more accurate and precise LV ejection fraction measurement is needed to inform decisions regarding discontinuation of chemotherapy. New CMR techniques like T1 and T2 mapping and positron emission tomography (PET) imaging will help us better understand the structural, pathological, and metabolic myocardial changes associated with ventricular dysfunction or release of serum biomarkers. CMR may also be helpful in the evaluation of vascular complications of cancer therapy. Stress echocardiography, stress CMR, computed tomography, and PET are excellent imaging options in the evaluation of ischemia in patients receiving therapies that could potentially cause vasospasm or accelerated atherosclerosis.     

Ablation of p21-activated kinase-1 in mice promotes isoproterenol-induced cardiac hypertrophy in association with activation of Erk1/2 and inhibition of protein phosphatase 2A

Earlier investigations in our lab indicated an anti-adrenergic effect induced by activation of p21-activated kinase (Pak-1) and protein phosphatase 2A (PP2A). Our objective was to test the hypothesis that Pak-1/PP2A is a signaling cascade controlling stress-induced cardiac growth. We determined the effects of ablation of the Pak-1 gene on the response of the myocardium to chronic stress of isoproterenol (ISO) administration. Wild-type (WT) and Pak-1-knockout (Pak-1-KO) mice were randomized into six groups to receive either ISO, saline (CTRL), or ISO and FR180204, a selective inhibitor of Erk1/2. Echocardiography revealed that hearts of the Pak-1-KO/ISO group had increased LV fractional shortening, reduced LV chamber volume in diastole and systole, increased cardiac hypertrophy, and enhanced transmitral early filling deceleration time, compared to all other groups. The changes were associated with an increase in relative Erk1/2 activation in Pak-1-KO/ISO mice versus all other groups. ISO-induced cardiac hypertrophy and Erk1/2 activation in Pak-1-KO/ISO were attenuated when the selective Erk1/2 inhibitor FR180204 was administered. Immunoprecipitation showed an association between Pak-1, PP2A, and Erk1/2. Cardiac myocytes infected with an adenoviral vector expressing constitutively active Pak-1 showed a repression of Erk1/2 activation. p38 MAPK phosphorylation was decreased in Pak-1-KO/ISO and Pak-1-KO/CTRL mice compared to WT. Levels of phosphorylated PP2A were increased in ISO-treated Pak-1-KO mice, indicating reduced phosphatase activity. Maximum Ca²⁺-activated tension in detergent-extracted bundles of papillary fibers from ISO-treated Pak-1-KO mice was higher than in all other groups. Analysis of cTnI phosphorylation indicated that compared to WT, ISO-induced phosphorylation of cTnI was blunted in Pak-1-KO mice. Active Pak-1 is a natural inhibitor of Erk1/2 and a novel anti-hypertrophic signaling molecule upstream of PP2A.     

Effects of calorie restriction on cardioprotection and cardiovascular health

Multiple health benefits of calorie restriction (CR) and alternate day fasting (ADF) regimens are widely recognized. Experimental data concerning the effects of calorie restriction on cardiac health are more controversial, ranging from evidence that ADF protects heart from ischemic damage but results in developing of diastolic dysfunction, to reports that CR ameliorates the age-associated diastolic dysfunction. Here we investigated the effects of chronic CR on morphology and function of the cardiovascular system of aged rats and cardioprotective effect of CR against ischemic damage in the experimental rat model of MI. Cardiovascular fitness of 24-month old Fisher 344 rats maintained through life on ad libitum (AL) or CR diets was extensively evaluated via echocardiography, dobutamine stress test, pressure-volume loop analyses, pulse wave velocity measurements, and histology. Groups of 2-month old AL and 29-month old CR rats were studied for comparison. Myocardial infarction (MI) was induced by a permanent ligation of the anterior descending coronary artery in 5-month old rats maintained for 3 months on CR or AL. MI size was evaluated histologically 24 hrs following coronary ligation. Cardiac remodeling was followed-up via echocardiography. Age-associated changes in 24-month old rats consisted of 33% increase of fibrosis in the myocardium and more than 2 fold increase of the collagen in the tunica media of the aorta. There was a significant decrease in the density and total number of cardiomyocytes, while their size was increased. These morphological changes were manifested in a decline of systolic and diastolic cardiac function, increase of left ventricular and aortic stiffness, and arterio-ventricular uncoupling. Tachycardic response to dobutamine challenge was absent in the old rats. Compared to AL rats, 24-month old CR rats had reduced levels of cardiac and aortic fibrosis, increased density of cardiomyocytes that were smaller in size, attenuated diastolic dysfunction, normal systolic function and arterio-ventricular coupling. Tachycardic response to dobutamine was also intact in CR 24-month old rats and aortic stiffness was reduced. Adjustment for body weight differences through ratiometric or allometric scaling did not affect the overall pattern of differences between AL and CR rats. Attenuation of morphological and functional age-associated changes in 24-month old CR rats either was not observed at all or was smaller in 29-month old CR rats. Size of MI induced by a permanent coronary ligation as well as post-MI cardiac remodeling and function were similar in CR and AL rats. CR does not increase tolerance of myocardium to ischemic damage, but attenuates the age-associated changes in the heart and major vessels. The attenuation of age-associated changes by CR cannot be explained by the effect of lower body weight but are attributable to more intimate cellular mechanisms of CR itself. Attenuation of age-associated changes by CR waned with advancing age, and is consistent with the idea that CR postponed senescence.     

调经促孕丸联合地屈孕酮治疗黄体功能不全性不孕症的疗效观察

目的探讨调经促孕丸联合地屈孕酮片治疗黄体功能不全性不孕症临床疗效。方法选取2015年4月—2017年4月在中国航天科工集团七三一医院治疗的黄体功能不全性不孕症患者82例,根据用药差别分为对照组(41例)和治疗组(41例)。对照组口服地屈孕酮片,首剂量40 mg,之后10 mg/次,1次/8 h;治疗组在对照组基础上口服调经促孕丸,5 g/次,2次/d。两组均治疗3个月。观察两组患者临床疗效,同时比较治疗前后两组患者性激素水平、Salle评分、HPS评分和PNI指数及子宫内膜容受性指标。结果治疗后,对照组和治疗组临床有效率分别为80.49%和95.12%,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清黄体生成激素(LH)、促卵泡成熟激素(FSH)、孕酮(P)、雌二醇(E_2)水平均显著升高(P0.05),且治疗组患者FSH、LH、E_2、P水平明显高于对照组(P0.05)。治疗后,两组Salle评分、HPS评分和PNI指数均明显升高(P0.05),且治疗组患者Salle评分、HPS评分和PNI指数明显高于对照组(P0.05)。治疗后,两组子宫内膜厚度显著增加(P0.05),搏动指数(PI)和阻力指数(RI)显著降低(P0.05),卵巢基质血流收缩期峰值血流速度(PSV)和舒张末期流速(EDV)显著升高(P0.05),且治疗组患者这些指标明显好于对照组(P0.05)。结论调经促孕丸联合地屈孕酮片治疗黄体功能不全性不孕症能够显著改善黄体功能及性激素水平,改善子宫内膜容受性,降低卵巢血流阻力,进而提高妊娠率,具有一定的临床推广应用价值。     

Incorporation of RG1 epitope concatemers into a self-adjuvanting Flagellin-L2 vaccine broaden durable protection against cutaneous challenge with diverse human papillomavirus genotypes

AimTo achieve durable and broad protection against human papillomaviruses by vaccination with multimers of minor capsid antigen L2 using self-adjuvanting fusions with the toll-like receptor-5 (TLR5) ligand bacterial flagellin (Fla) instead of co-formulation with alum.MethodsFla fusions with L2 protective epitopes comprising residues 11-200, 11-88 and/or 17-38 of a single or multiple HPV types were produced in E. coli and their capacity to activate TLR5 signaling was assessed. Immunogenicity was evaluated serially following administration of 3 intramuscular doses of Fla-L2 multimer without exogenous adjuvant, followed by challenge 1, 3, 6 or 12 months later, and efficacy compared to vaccination with human doses of L1 VLP vaccines (Gardasil and Cervarix) or L2 multimer formulated in alum. Serum antibody responses were assessed by peptide ELISA, in vitro neutralization assays and passive transfer to naïve rabbits in which End-Point Protection Titers (EPPT) were determined using serial dilutions of pooled immune sera collected 1, 3, 6 or 12 months after completing active immunization. Efficacy was assessed by determining wart volume following concurrent challenge at different sites with HPV6/16/18/31/45/58 ‘quasivirions’ containing cottontail rabbit papillomavirus (CRPV) genomes.ResultsVaccination in the absence of exogenous adjuvant with Fla-HPV16 L2 11-200 fusion protein elicited durable protection against HPV16, but limited cross-protection against other HPV types. Peptide mapping data suggested the importance of the 17-38 aa region in conferring immunity. Indeed, addition of L2 residues 17-38 of HPV6/18/31/39/52 to a Fla-HPV16 L2 11-200 or 11-88 elicited broader protection via active or passive immunization, similar to that seen with vaccination with an alum-adjuvanted L2 multimer comprising the aa 11-88 peptides of five or eight genital HPV types.ConclusionsVaccination with flagellin fused L2 multimers provided lasting (>1 year) immunity without the need for an exogenous adjuvant. Inclusion of the L2 amino acid 17-38 region in such multi-HPV type fusions expanded the spectrum of protection.     

42 a. Datengerechte Befunderhebung,Organisation und Archivierung in einer mittleren chirurgischen Abteilung — Konzeption einer Standardisierung

Zusammenfassung Eine standardisierte chirurgische Dokumentation sollte in folgenden Stufen realisiert werden: I. Zentrales I-Zahl-Archiv, gleichzeitig sind fortan alle Routinedokumente mit der 1-Zahl zu kennzeichnen. 2. Einführung des verschlüsselbaren standardisierten Krankenblattes. 3. Für spezielle Probleme Einführung der zugehörigen erweiterten Basisdokumentation. 4. Einsatz abteilungsinterner EDV-Anlagen unter Beachtung international gültiger Schlüsselsysteme.