Intravitreal injection of anti-vascular endothelial growth factor is considered the first-line treatment for polypoidal choroidal vasculopathy. It has potential risks for circulatory system, which should be particularly carefully evaluated in older patients. In this case study, we aim to discuss the potential impact of this treatment regimen on cardiac health. This case report describes an elderly patient with no prior history of heart disease who exhibited unexpected heart enlargement and dysfunction. Throughout the patient’s hospital stay, various potential causes were investigated, leading to the hypothesis that a 10-year history of intravitreal injections of anti-vascular endothelial growth factor could be related to the observed clinical manifestations. The patient was advised to discontinue this treatment, and after a 2-month follow-up period, there was a gradual improvement in the patient’s cardiac structure and function. This manuscript highlights the importance of conducting cardiac examinations before and after anti-vascular endothelial growth factor treatment, especially for individuals at risk of heart diseases like the elderly. It emphasizes the need to carefully weigh the benefits and risks of treatment regimens to ensure optimal therapeutic outcomes.

Moyamoya disease (MMD) is a rare disorder of the cerebrovascular system. It is a steno-occlusive disease that involves angiogenesis and blood-brain barrier (BBB) disruption. Bradykinin (BK), its metabolite des-Arg9-BK, and receptor (B1R) affect angiogenesis and BBB integrity. In this study, we aimed to investigate the changes in BK, B1R and des-Arg9-BK levels in the serum and brain tissues of patients with MMD and explore the underlying mechanism of these markers in MMD. We obtained the serum samples and superficial temporal artery (STA) tissue of patients with MMD from the Department of Neurosurgery of the Jining First People's Hospital. First, we measured BK, des-Arg9-BK and B1R levels in the serum of patients by means of ELISA. Next, we performed immunofluorescence to determine B1R expression in STA tissues. Finally, we determined the underlying mechanism through Western blot, angiogenesis assay, immunofluorescence, transendothelial electrical resistance and transcytosis assays. Our results demonstrated a significant increase in the BK, des-Arg9-BK and B1R levels in the serum of patients with MMD compared to healthy controls. Furthermore, an increase in the B1R expression level was observed in the STA tissues of patients with MMD. BK and des-Arg9-BK could promote the migratory and proliferative abilities of bEnd.3 cells and inhibited the formation of bEnd.3 cell tubes. In vitro BBB model showed that BK and des-Arg9-BK could reduce claudin-5, ZO-1 and occluding expression and BBB disruption. To the best of our knowledge, our results show an increase in BK and B1R levels in the serum and STA tissues of patients with MMD. BK and Des-Arg9-BK could inhibit angiogenesis, promote migratory and proliferative capacities of cells, and disrupt BBB integrity. Therefore, regulating BK, des-Arg9-BK and B1R levels in the serum and the brain could be potential strategies for treating patients with MMD.

Background:Pylephlebitis refers to an infective suppurative thrombosis that occurs in the portal vein and its branches. Concurrent pylephlebitis and subarachnoid hemorrhage (SAH) are rare but fatal for patients with sepsis. This scenario drives the clinicians into a dilemma of how to deal with coagulation and bleeding simultaneously.Case summary:An 86-year-old man was admitted to hospital for chills and fever. After admission, he developed headache and abdominal distension. Neck stiffness, Kernig's and Brudzinski's sign were present. Laboratory tests discovered decreased platelet count, elevated inflammatory parameters, aggravated transaminitis, and acute kidney injury. Escherichia coli (E. coli) were identified in blood culture. Computed tomography (CT) revealed thrombosis in the superior mesenteric vein and portal veins. Lumbar puncture and Brain CT indicated SAH. The patient had eaten cooked oysters prior to illness. It was speculated that the debris from oyster shell might have injured his intestinal mucosa and resulted in bacterial embolus and secondary thrombosis in portal veins. The patient was treated with effective antibiotics, fluid resuscitation, and anticoagulation. The dose titration of low molecular weight heparin (LMWH) under close monitoring attributed to diminution of the thrombosis and absorption of SAH. He recovered and was discharged after 33-day treatment. One-year follow-up indicated that the post-discharge course was uneventful.Conclusion:This report describes a case of an octogenarian with E. coli septicemia who survived from concurrent pylephlebitis and SAH along with multiple organ dysfunction syndrome. For such patients with life-threatening complications, even in the acute stage of SAH, decisive employment of LMWH is essential to resolve thrombosis and confers a favorable prognosis.

Objective Nerve growth factor (NGF) and tropomyosin kinase receptors A (TrKA) exert a crucial effect on the regulation of autonomic nervous system which contributes to the progress of atrial fibrillation (AF). Valvular heart disease (VHD) patients are more easily to induce the AF. We investigated whether NGF/TrKA could impact the occurrence of AF in VHD patients. Materials and methods Atrial tissues were resected from 30 VHD patients with chronic AF (n = 15, AF >6 months) or sinus rhythm (SR,n = 15). The expression of NGF, TrKA, protein kinase B (PKB/Akt), beta-isoforms of glycogen synthase kinase-3 (GSK3 beta), Serine473 phosphorylation of Akt (p-Ser473 Akt), Serine9 phosphorylation of GSK-3 beta (p-Ser9 GSK3 beta) in right atrial tissues and peripheral blood lymphocyte were quantified by Western blot. The localization of those genes expression was measured by immunohistochemistry. Double sandwich enzyme-linked immunosorbent assay was used to observe the trace changes of NGF-beta in peripheral plasma. Results Our results revealed that the NGF expression was markedly elevated in the tissue of right atrial appendage and peripheral blood lymphocytes from AF patients compared with the SR patients. But, the expression of TrKA, GSK3 beta, p-Akt and p-GSK3 beta were decreased. There was no difference about the expression of Akt from the AF patients and the SR patients. The NGF-beta level in peripheral blood plasma of patients with AF and SR was not statistical difference. Conclusion Thus, we thought that NGF/TrKA signaling pathway may be involved in the AF in the patients with VHD, inactivation of GSK3 beta could increase the incidence of AF, but not relevant to phosphorylation.

Objective To investigate the value of soluble suppression of tumorigenicity 2 ( sST2) and galectin-3 ( Gal-3) in heart failure grading and prognosis by evaluating their levels according to NewYork Heart Association ( NYHA) classification. Methods A total of 191 patients with chronic heart failure treated during Apr. 2015 and Jan. 2016 were chosen randomly, including 115 males and 76 females, average ( 62.36±11.09) years. According to the NYHA criteria and follow-up results, the patients were classified into three groups: non-cardiac events group, rehospitalization groupand death group. Plasma sST2 and Gal-3 levels were measured at admission and every 2 months during follow-up. The incidence of cardiac events were recorded. Results The levels of sST2 and Gal-3 were positively correlated with NYHA classification ( r1= 0.33, P1＜0.001; r2= 0.21, P2= 0.004), and negatively correlated with left ventricular ejection fraction ( LVEF) ( r1=-0.25, P1= 0.001; r2=-0.24, P2= 0.002). There were significant differences in sST2 and Gal-3 levels among the three groups ( F1= 56.76, P1＜ 0.001; F2= 31.08, P2＜ 0.001). The level of sST2 was significantly different between the non-cardiac events group and rehospitalization group, between the non-cardiac events group and death group, and between the rehospitalization group and death group ( t1= 6.15, P1＜0.001; t2= 11.36, P2＜0.001; t3=3.22, P3= 0.003). The level of Gal-3 was significantly different between the non-cardiac events group and rehospitalization group, and between the non-cardiac events group and death group ( t1= 6.28, P1＜ 0.001; t2= 5.91, P2＜ 0.001).Gal-3＜ 15.67 ng/mL and sST2＜ 31.74 ng/mL were the predictive factors of non-cardiac events. sST2＞ 45.031 ng/mL was a predictive factor of recent mortality. Gal-3＞ 21. 90 ng/mL and sST2＞ 45. 03ng/mL were predictors of shortened survival. Conclusion The levels of Gal-3 and sST2 are somewhat positively correlated with NYHA classification, and can indicate the cardiac function of patients with heart failure. The sST2 level is useful to predict patients' prognosis, including death, rehospitalization or non-cardiac events, while Gal-3 level is useful to predict cardiac events. The combined detection of them is valuable for the diagnosis and prognosis of heart failure.

BACKGROUNDBedtime administration of antihypertensive drugs currently receives more at-tention, but no clear consensus has been reached on the blood pressure (BP)-lowering effect of this strategy.METHODSWe systematically searched literature for clinical trials of ingestion time of anti-hypertensive drugs evaluated by ambulatory blood pressure monitoring (ABPM) to perform a meta-analysis which aimed at determining the difference in diurnal, nocturnal, and 24-h mean of systolic BP (SBP) and diastolic BP (DBP), absolute BP reduction from baseline between bedtime administration group (experimental group) and morning (awaking) administration group (control group).RESULTSThe synthesis analysis showed that the level of BP in bedtime administration group was lower than the morning administration group, which reduced diurnal SBP/DBP by 1.67/1.13 mm Hg (p = 0.36/0.48), 24-h SBP/DBP by 2.78/0.36 mm Hg (p = 0.09/0.62), nocturnal SBP/DBP by 6.32/3.17 mm Hg (p = 0.03/0.007). Furthermore, there was lack of statistically significant differences in the diurnal mean of SBP/DBP reduction from baseline between the two groups (p = 0.94/0.85), but bedtime administration resulted in significant reduction from baseline in the nocturnal mean of SBP/DBP, by -4.72/-3.57 mm Hg (p = 0.01/0.05). Funnel plot demonstrated that there was no evidence of publication bias.CONCLUSIONSAdministration of ≥ 1 antihypertensive drugs at bedtime or evening results in a greater reduction of nocturnal hypertension than dosing in the morning without loss of efficacy of diurnal and 24 h mean BP reduction.

Calpain, calcineurin (CaN), and nuclear factor of activated T cell (NFAT) play a key role in the development of atrial fibrillation. Patients with valvular heart disease (VHD) are prone to develop atrial fibrillation (AF). Thus, our current study was aimed at investigating whether activation of calpain-CaN-NFAT pathway is associated with the incidence of AF in the patients with VHD and diabetes. The expressions of calpain 2 and alpha- and beta-isoforms of CaN catalytic subunit (CnA) as well as NFAT-c3 and NFAT-c4 were quantified by quantitative reverse transcription-polymerase chain reaction in atrial tissues from 77 hospitalized patients with VHD and diabetes. The relevant protein content was measured by Western blot and calpain 2 in human atrium was localized by immunohistochemistry. We found that the expressions of calpain 2, CnA alpha and CnA beta, and NFAT-c3 but not NFAT-c4 were significantly elevated in the samples from patients with AF compared to those with sinus rhythm (SR). Elevated protein levels of calpain 2 and CnA were observed in patients with AF, and so was the enhanced localization of calpain 2. We thereby concluded that CaN together with its upstream molecule, calpain 2, and its downstream effector, NFAT-c3, might contribute to the development of AF in patients with VHD and diabetes.

Current human umbilical cord blood stem cell therapy faces the great challenges, because the stem cells are scarce and cannot survive for a long time. Here we describe how hetrombopag, an orally-active TPO receptor agonists, enhanced ex vivo expansion of human UCB stem cells, and protected cardiac myocytes from the damage caused by oxidative stress.

OBJECTIVE:To investigate the relationship between the protein expression of calpain-2 and calcineurin (CaN) and atrial fibrillation (AF) in patient with valvular heart disease (VHD).METHODS:A total of 40 patients who underwent valve replacement surgery in our hospital from March 2013 to March 2014, right atrial appendages were excised during operation and patients were divided into sinus rhythm (SR) group (n = 17) and AF group (n = 23). The protein expression of calpain-2 and the α-isoform of CaN catalytic subunit (CnA) in the right atrial appendages were determined by Western blot.RESULTS:The protein levels of the full-length CnAa (60,000), the 45,000 fragment of CnAa without autoinhibitory domain, and calpain-2 were significantly upregulated in the AF group compared to the SR group (1.25 ± 0.51 vs. 0.76 ± 0.37, 1.08 ± 0.37 vs. 0.76 ± 0.25, and 0.82 ± 0.44 vs. 0.51 ± 0.19, respectively, all P < 0.05).CONCLUSION:Activated calpain-2-CaN signal pathway might be involved in the pathogenesis of AF.

Many studies have indicated possible associations between a polymorphism of adiponectin receptor 1 (ADIPOR1) rs1342387 and risk of cancer, but contradictory results have been reported. The main aim of this study was to draw a reliable conclusion about the relationship between the rs1342387 polymorphism and cancer incidence, by conducting a literature search of Pubmed, Embase, Wanfang and Cochrane libraries. Eleven studies including 3, 738 cases and 4, 748 controls were identified in this meta-analysis. The ADIPOR1 rs1342387 polymorphism was associated with risk of colorectal cancer for all genetic comparison models (GG vs AA, OR: 1.44, 95%CI: 1.21-1.70; G carriers vs A carriers, OR: 1.23, 95%CI: 1.11-1.36; dominant model, OR: 1.28, 95%CI: 1.10-1.49 and recessive model, OR: 1.31, 95%CI: 1.12-1.55). Stratified by ethnicity, the rs1342387 polymorphism was significantly associated with risk of colorectal cancer in Asian ancestry for all genetic comparison models (GG vs AA, OR: 1.56, 95%CI: 1.26-1.92; G carriers vs. A carriers OR: 1.30, 95%CI: 1.18-1.43; dominant model OR: 1.31, 95%CI: 1.08-1.60 and recessive model OR: 1.44, 95%CI: 1.26-1.64), but not in Caucasian or mixed (Caucasian mainly) groups. In summary, the ADIPOR1 rs1342387 polymorphism is significantly associated with risk of colorectal cancer among individuals of Asian ancestry.

患者老年男性,冠状动脉造影植入支架治疗后长期口服双联抗血小板药物,出现急性上消化道出血后诱发急性前壁心肌梗死,止血与抗凝治疗存在矛盾;心肌梗死急性期出现交感风暴,应用多种抗心律失常药物治疗和多次电除颤,最终静脉应用短效艾司洛尔使恶性心律失常得到控制.

BACKGROUND:The calmodulin-independent pathway is thought to involve the activation of calcineurin by calpain. However, the effect of endogenous calpain on calcineurin in human heart is not well known.METHODS:Proteolysis and activation of recombinant calcineurin by purified calpain isozymes I and II as well as endogenous calcineurin by calpains in the human heart were investigated by Western blot. Activation of calpain and calcineurin in the human heart was examined using zymography and a calcineurin activity assay.RESULTS:Calpains I and II caused limited proteolysis of full-length calcineurin in a Ca(2+)-dependent manner, and the degradation fragment(s) were constitutively active in the absence of calmodulin. Calpain I and calcineurin were expressed in ventricular myocardium from patients with heart failure, with no difference in expression levels in the left and right heart chambers. Human heart calpains I and II degraded the specific substrate casein in gels which were incubated in medium containing Ca2+, but not in Ca(2+)-free medium. Calpain inhibitor-sensitive calcineurin activity was stimulated in the human ventricular myocardium in the presence of concentrations of Ca2+ that were found to activate calpain I.CONCLUSIONS:Proteolysis of calcineurin A by endogenous calpain I leads to the formation of constitutively active calcineurin in the human heart, which may contribute to the pathogenesis of myocardial disease.

Objective:To investigate the relationship among serum adiponectin,hs-CRP and IMT of carotid in type 2 diabetic patients.Methods:287 cases of type 2 diabetes included 148 males and 139 females.We collected the related clinical data,measured the fasting serum adiponectin by ELISA,by immuno-turbidimetry and measured the level of hs-CRP by finally,type 2 diabetic subjects were divided into two groups depending on the carotid ultrasound results: IMT normal group and IMT thickening or plaque group.The relationship among serum adiponectin,hs-CRP and IMT was analyzed.Results: ① In categorical analysis,the mean level of serum adiponectin and HDL-C in IMT thickening or plaque group was significantly lower than that in the other group;② In pearson correlation analysis,APN as the dependent variable and the index for the independent variable,the results showed that BMI,WHR,TG,hs-CRP and APN were negatively correlated;HDL-C and APN levels were positively correlated;③ In multiple stepwise regression analysis,serum adiponectin,hs-CRP and HDL-C were related to the formation of diabetic IMT.Conclusion:APN may be the protective factor to atherosclerosis of diabetic patients.

OBJECTIVE:To examine the relationship between single nucleotide polymorphism (SNP) of adiponectin (APN) locus +45T/G and Han male patients with premature coronary artery heart disease (pCAD).METHODS:A total of 423 male patients of Han ethnic group (< 55 yr old) undergoing coronary arteriography were recruited. Among them, 358 patients were diagnosed as pCAD while another 65 normal control (NC). All subjects were genotyped for adiponectin gene SNP +45 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.RESULTS:Statistical differences of TG/GG genotype ratio were observed between two groups. The TG/GG genotype ratio in the pCAD group was 51.1% versus 35.4% in the NC group (χ(2) = 5.45, P = 0.022). After an adjustment of conventional risk factors, such as age, body mass index (BMI) and hypertension, the adiponectin gene SNP +45TG/GG genotype was strongly associated with Han ethnic group male pCAD by binary logistic regression analysis (OR = 1.843, P = 0.035, 95%CI: 1.045 ∼ 3.250). And there were statistical differences between TT genotype and TG/GG genotype among pCAD subjects in the following factors: BMI, total cholesterol (TC), low-density lipoprotein-C (LDL-C) and APN level (P < 0.05). By Pearson correlation analysis, APN was negatively correlated with TC, LDL-C and SNP +45T/G polymorphism.CONCLUSION:The SNP of adiponectin locus +45T/G is associated with male pCAD. And TG/GG genotype is a possible predisposing gene for Han ethnic group male pCAD.

Objective To study the association of adiponectin concentration in patients with heart failure(HF) and cachexia with body mass index(BMI) and B-type natriuretic peptide(BNP).Methods A total of 80 patients with coronary artery disease(CHD) were included into 3 groups: group A(HF and cachexia,n=20),group B(HF without cachexia,n=40),group C(no HF,n=20);and a control group of 14 healthy persons were studied as well.BMI were calculated and adiponectin,BNP and LVEF were tested for all subjects.The associations of ADP with BMI and BNP were studied.Results Patients with HF and cachexia had higher concentrations of adiponectin and BNP than the other groups.Adiponectin was correlated negatively with BMI,and positively with BNP.Conclusion Cachexia in HF is associated with an increase in adiponectin concentration.This may indicate a possible cause and effect relationship between increased adiponcetin concentration and cachexia in HF.The positive correlation between BNP and adiponectin also raises the possibility that the former might increase the secretion of the latter.

目的探讨冠状动脉粥样硬化患者血浆瘦素、脂联素水平及其与动脉粥样硬化的关系。方法选择242例冠状动脉粥样硬化患者,按冠脉造影结果分为对照组(冠脉狭窄<50%)107例、冠心病(CHD)组135例,分别检测两组患者血浆瘦素、脂联素水平,并分析其与动脉粥样硬化的关系。结果 CHD组血浆脂联素水平[(4.81±0.96)mg/L]显著低于对照组[(6.04±0.98)mg/L](P<0.01);血浆瘦素水平[(1.71±0.36)μg/L]显著高于对照组[(1.32±0.31)μg/L](P<0.01)。Pearson相关分析显示,血浆瘦素与脂联素水平呈显著负相关(r=-0.672,P<0.01),且随着Gensini积分增高,血浆瘦素水平逐渐增高,而脂联素水平逐渐下降(P<0.01)。结论冠状动脉粥样硬化患者冠脉病变程度与血浆瘦素和脂联素水平均有相关性;血浆瘦素与脂联素水平存在相互抑制调节的关系。

OBJECTIVE:To investigate the effects of carvedilol and metoprolol on the expression of autoantibodies against cardiac β(1), β(2) and α(1) adrenergic receptors in aged patients with chronic heart failure (CHF) and ventricular arrhythmia (VA).METHODS:Sixty-eight patients with CHF and VA were randomly divided metoprolol treatment group or carvedilol treatment group on the basis of digoxin and diuretic treatment. All patients were followed up for six months cardiac function was monitored by echocardiography, VA by Holter and the three autoantibodies by enzyme-linked immunosorbent assay (ELISA).RESULTS:(1) Systolic blood pressure and brain natriuretic peptide (BNP) were significantly lower in carvedilol group than that in metoprolol group (P < 0.05). (2) The positive ratio of autoantibodies against the cardiac β(1) adrenergic receptor was significantly decreased compared with that of pre-treatment (P < 0.05) in metoprolol group. The positive ratios of autoantibodies against cardiac β(1), β(2) and α(1)-adrenergic receptors were all significantly decreased compared with that of pre-treatment (P < 0.01) in carvedilol group. Moreover, the incidence of VA was significantly decreased in carvedilol group (P < 0.05) but not in metoprolol group.CONCLUSION:Carvedilol is superior to metoprolol on decreasing the incidence of VA in aged patients with chronic heart failure and ventricular arrhythmia.

Objective:To study the relationship of the postprandial metablism after daily meal and atherosclerosis with the use of color Doppler ultrasound examination of carotid windows.Methods:The elderly hypertentive patients whose fasting blood glucose(FBG)6.1mmol/L and fasting triglyceride8.1mmol/L were studied.Color Doppler ultrasonography of carotid ateries were used to examine all subjects group A and B were divided according to the cut-off point of 2-hour postprandial blood glucose ≥7.8mmol/L.Blood glucose,cholesterol,carotid atery intima-media thickness(IMT),atheromatous plaque and other indicators were compared.Results:There was no significant difference of fasting blood glucose between group A and B.But 2-hour postprandial blood glucose and triglyceride levers were signifcantly higher in group B(P0.05).And carotid artery IMT atheromtous plague were improved as well.Conclusion:Postprandial hyperglycemia,hyperlipidemia occurs on about 58%(33/57 vs) eldly hypertensive patients with normal fasting blood glucose.The IMT and plaque rate in the postprandial metabolism are significantly higher than normal.The relationship of daily postprandial metabolism and ateroclerosis was closely related in elderly hypertensive patients.

Objective:To explore the advantages of combined treatment of Benalapril plus Lorsartan for target organ protection in elderly patients.Methods:Three groups of elderly patients with grade 1-2 hypertension were treated with Benalapril(group B),Lorsartan(group L),and Benalapril plus Lorsartan(group C) for 1 year,respectively.The differences in the following indicators among three groups were investigated:mean blood pressure(MBP),left ventricle mass index(LVMI),intima-media thickness(IMT) of cervical arteries,fast blood glucose(FBG),serum lipids,renal function,serum uric acid(SUA),plasma angiotensin II(Ang II) and aldosterone,urine 2-microalbumin(2-MG).Results:After antihypertension intervention,no significant difference was observed in MBP,FBG,total cholesterol,blood urine nitrogen(BUN),creatinine and aldosterone among groups.LVMI and IMT in group C were dramatically lower than those in groups A and B,but there was no significant difference between groups B and L.SUA and 2-MG in group B was higher than those in group L and C.There was significant difference in the levels of Ang II among three groups,the highest in group B,medium in group C and the lowest in group L.Conclusion:Combined use of Benalapril and Lorsartan can prevent the target organ from damage by multiple mechanisms in the elderly patients with hypertension and its effect is superior to that used alone.

Objective: To investigate the short-term prognostic value of plasma Nterminal pro-brain natriuretic peptide(NT-proBNP) on acute myocardial infarction.Method: A total of 132 subjects,including 30 healthy subjects and 102 patients with a first AMI were selected into the study.The plasma NT-proBNP was measured at 48 to 96 hours after infarction.Total mortality and the risk for major adverse cardiac events(MACE,including death,recurrent MI,recurrent angina,heart failure,readmission for any reason) were analyzed.Results: Six months later,plasma NT-proBNP was much higher in patients with AMI than that in health controls(326.1±193.4 pmol/L vs 73.5±58.3(pmol/L,) P0.01).With the increasing of NT-proBNP,the 6-month mortality and the incidence of MACE had been raising.Multivariate logistic regression analyses showed that the plasma NT-proBNP concentration predicted 6-month mortality((r=)0.943?7,P0.01)and incidence of MACE(r=0.607?2,P0.01).Conclusion: The plasma NT-proBNP level has relation with short-term prognosis of AMI.