Incremental value of non-invasive myocardial work for the evaluation and prediction of coronary microvascular dysfunction in angina with no obstructive coronary artery disease.

Background: Evidence suggests that patients suffering from angina with no obstructive coronary artery disease (ANOCA) experience coronary microvascular dysfunction (CMD). We aimed to understand the diagnosis value of noninvasive myocardial work indices (MWIs) with left ventricular pressure-strain loop (LV PSL) by echocardiography in ANOCA patients with CMD. Methods: 97 patients with ANOCA were recruited. All subjects underwent standard echocardiography with traditional ultrasound parameters, two-dimensional speckle-tracking echocardiography with global longitudinal strain (GLS), LV PSL with MWIs include global work index (GWI), global constructive work (GCW), global waste work (GWW) and global work efficiency (GWE). In addition, all enrolled cases underwent high-dose adenosine stress echocardiography (SE) with coronary flow velocity reserve (CFVR). CMD was defined as CFVR <2.0. Results: Of the 97 patients with ANOCA, 52 were placed in the CMD group and 45 in the control group. GWI and GCW were decreased significantly in the CMD group compared with the control group (P < 0.001 for both). GWI and GCW were moderately correlated with CFVR (r = 0.430, P < 0.001 and r = 0.538, P < 0.001, respectively). In the multiple logistic regression analyses, GCW was identified as the only independent echocardiography parameter associated with CMD after adjusting for age and baseline APV [OR (95%CI) 1.009 (1.005-1.013); P < 0.001]. Moreover, the best predictor of CMD in patients with ANOCA using receiver operating characteristic (ROC) curve was GWI and GCW, with an area under the curve (AUC) of 0.800 and 0.832, sensitivity of 67.3% and 78.8%, specificity of 80.0% and 75.6%, respectively. Conclusion: MWIs with LV PSL is a new method to detect LV systolic function noninvasively in ANOCA patients with CMD.

Diffuse Primary Malignant Pericardial Mesothelioma With Myocardial involvement: A Comprehensive Assessment Using Multimodel Echocardiography.

Diffuse primary malignant pericardial mesothelioma (PMPM) is an extremely rare and highly invasive tumor of pericardium. The tumor can infiltrate myocardium in part of cases, and will contribute to grave prognosis. Herein, we reported a 58-year-old man of diffuse PMPM with myocardial involvement, and summarized 39 cases of diffuse PMPM. Multimodal echocardiography, which combined conventional, tissue Doppler and speckle tracking echocardiography, was applied to diagnose diffuse PMPM with myocardial involvement, and assess the myocardial function. The common features were pericardial effusion, pericardial masses and thickened pericardium. The other echocardiographic characteristics were extensive and heterogenous echo, adhesion with pericardium and myocardium, reduced motion of adhered myocardium, and constriction performance. Diffuse PMPM with myocardial involvement revealed decreased LV diastolic function, and decreased LV and RV systolic function. Especially in systolic function, the unique strain features were reduced longitudinal strains from segmental to global and from epicardial to endocardial, relative 'septal sparing' pattern, and decreased transmural gradient of longitudinal strain. Our findings suggested that multimodal echocardiography not only can identify this disease, but also can provide detailed information of myocardial dysfunction, which provides a reference for clinicians to develop an optimal individualized treatment.

Multimodal Imaging for Total Anomalous Systemic Venous Drainage Diagnosis and Preoperative Planning: A Case Report and Literature Review.

Total anomalous systemic venous drainage (TASVD) is a rare congenital heart malformation. Here, we report a case of a 40-year-old male patient who had a total anomalous systemic venous drainage. It was diagnosed as the TASVD for the first time through multimodal imaging combined Transthoracic (TTE), transesophageal (TEE) and three-dimensional (3D-TTE) echocardiography, contrast echocardiography and computed tomography angiography (CTA). We review 15 published reports on TASVD and summarize the ultrasonographic characteristics. After intracardiac repair through ectopic venous drainage in cardiac surgery, the patient's cyanosis symptoms were alleviated greatly. Echocardiography was the first-line examination for TASVD. Multimodal imaging combined TTE, TEE, 3D TEE, contrast echocardiography and CTA was necessary for confirmed diagnosis of TASVCD.

Catalpol ameliorates diabetes-induced testicular injury and modulates gut microbiota.

AIMS: To explore the mechanisms of diabetes mellitus (DM)-induced testicular injury caused by modulation of testicular glycolysis and gut microbiota (GM), and evaluation of the efficacy of catalpol in reversing testicular morbidity. MAIN METHODS: A model of DM-induced testicular injury was established using a high-fat diet in KK-Ay mice. Microbial communities in the feces of mice in normal, model and catalpol (Cat) groups were analyzed by 16S gene sequencing. Correlations between the GM and lactate metabolism levels, lactate dehydrogenase activity, and indicators of testicular injury were analyzed. KEY FINDINGS: Cat significantly reduced general indicators of diabetes in mice with DM-induced reproductive injury, mitigated damage to the testicular tissue, and increased sperm count and motility. Additionally, the levels of products of glycolysis metabolism (e.g. lactate) increased following Cat treatment compared with the Model group. Disorders in the GM were also reversed in the Cat group. SIGNIFICANCE: Cat ameliorated DM-induced testicular injury in KK-Ay mice by increasing the energy available to germ cells through glycolysis, principally through modulation of the GM and a reduction in the quantities of associated pathogenic bacteria.

Intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain / 中国针灸

OBJECTIVE@#To observe the effect of intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain.@*METHODS@#A total of 60 patients with moderate to severe cancer pain were randomly divided into an observation group and a control group，30 cases in each one. In the control group，opioids were taken to relief pain according to the three-step analgesic method of World Health Organization. On the base of the treatment as the control group, intradermal needling combined with heat-sensitive moxibustion were applied at Neiguan (PC 6), Hegu (LI 4), Zusanli (ST 36), Taichong (LR 3), etc. in the observation group, 14 days of treatment were required. The equivalent morphine consumption at the first day and whole course, the scores of cancer quality of life questionnaire-C30 (QLQ-C30) and Hamilton anxiety scale before and after treatment, and the adverse reaction rate were compared in the two groups. The total analgesic effective rate was evaluated.@*RESULTS@#The total analgesic effective rate was 93.3% (28/30) in the observation group, higher than 73.3% (22/30) in the control group (@*CONCLUSION@#Intradermal needling combined with heat-sensitive moxibustion can reduce the dose of opioids, improve the quality of life, relief the anxiety in patients with moderate to severe cancer pain, and reduce the incidence of common adverse reaction of opioids.

Loganin and catalpol exert cooperative ameliorating effects on podocyte apoptosis upon diabetic nephropathy by targeting AGEs-RAGE signaling.

BACKGROUND/AIMS: Rehmanniae Radix (RR) and Cornus officinalis (CO) are a typical herbal pair used to treat diabetic nephropathy (DN) in clinical practice. DN can be effectively treated by catalpol (Cat) and loganin (Log), the main active components of RR and CO respectively, through combating apoptosis, oxidative stress and inflammation. Herein, a spontaneous DN and podocyte injury model induced by advanced glycation end products (AGEs), i.e. KK-Ay mice, was used to explore the cooperative effects of Log and Cat on DN and the mechanism targeting the AGEs-RAGE (receptor for AGE) pathway. METHODS AND KEY FINDINGS: Log and Cat alone or in combination mitigated diabetic symptoms, decreased the level of fasting blood glucose, and increased that of serum insulin. The two drugs alone or in combination protected renal function from damage, prevented extracellular matrix hyperplasia and glycogen deposition, as well as alleviated the loss of podocytes detected by histological assay and immunohistochemistry. Flow cytometry revealed that Log and Cat alone or in combination relieved the apoptosis of AGEs-induced podocytes in vitro. Silencing RAGE by RNA interference played a protective role in podocyte apoptosis, whereas overexpression of it worked oppositely. Western blot exhibited that Log and Cat alone or in combination inhibited the activation of RAGE/p38 MAPK/p65 NF-κB and RAGE/Nox4/p65 NF-κB pathways in podocytes. The inhibitory effects of drug combination were more evident than those of individual treatments. SIGNIFICANCE: Log and Cat cooperatively resisted the apoptosis of podocytes upon DN by targeting AGEs-RAGE and its downstream pathways p38 MAPK and Nox4.

Loganin alleviates testicular damage and germ cell apoptosis induced by AGEs upon diabetes mellitus by suppressing the RAGE/p38MAPK/NF-κB pathway.

Diabetes mellitus (DM) damages male reproduction at multiple levels, such as endocrine secretion, spermatogenesis and penile erection. We herein investigated the protective effects and mechanism of loganin targeting the advanced glycation end products (AGEs)/receptor for AGEs (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/NF-κB signalling pathway. Loganin relieved the general DM symptoms and decreased the blood glucose level of KK-Ay DM mice. Haematoxylin-eosin staining demonstrated that loganin ameliorated testicular histology and function and enhanced the activities of testis-specific markers lactate dehydrogenase (LDH), acid phosphatase (ACP) and gamma-glutamyl transferase (γ-GT). Loganin also showed evident anti-oxidative stress, anti-apoptotic and anti-inflammatory effects on DM-induced reproductive damage by restoring glutathione (GSH) level and superoxide dismutase (SOD) activity, as well as reducing reactive oxygen species (ROS) level and Bax/Bcl-2 ratio in vivo and in vitro. Western blotting exhibited that loganin significantly inhibited the AGEs/RAGE/p38MAPK/NF-κB signalling pathway. Acridine orange and ethidium bromide staining (AOEB) and Western blotting showed that loganin in combination with inhibitors of RAGE, p38MAPK and NF-κB exerted stronger anti-apoptotic effects on AGE-induced GC-2 cell damage compared with loganin alone. In conclusion, loganin can protect against DM-induced reproductive damage, probably by suppressing the AGEs/RAGE/p38MAPK/NF-κB pathway.

Protective effects of catalpol on diabetes mellitus-induced male reproductive damage via suppression of the AGEs/RAGE/Nox4 signaling pathway.

AIMS: Diabetes mellitus (DM)-induced reproductive damage is an important cause of infertility for male DM patients, we herein evaluated the effects of catalpol on diabetic reproductive damage through the suppression of the AGEs/RAGE/Nox4 signaling pathway. METHODS: KK-Ay diabetic reproductive damage mice were administered with catalpol for 8 weeks, the testis/body weight ratio, testicular histopathology, the levels of endogenous hormone and the activity of testicular marker enzymes were determined. In vitro, the GC-2 cell injury model was induced by advanced glycation end-products (AGEs) and pretreated with catalpol. Cell viability, apoptosis, and oxidative stress markers were detected and the mechanism based on the AGEs/RAGE/Nox4 pathway was explored. KEY FINDINGS: Catalpol showed remarkable capacity on protecting diabetic reproductive damage by improving the histomorphology of the testes, increasing the testis/body weight ratio and activity of acid phosphatase (ACP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (γ-GT). The reduced testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in DM mice were also reversed with catalpol intervention. Moreover, catalpol showed markedly effects of anti-oxidative in vivo and in vitro, which significantly down-regulated reactive oxygen species (ROS) levels and restored superoxide dismutase (SOD) activity, meanwhile decreased GC-2 cell apoptosis and Bax/Bcl-2 ratio. Moreover, the over-expression of receptors for AGEs (RAGE), NADPH oxidase type 4 (Nox4) and phosphorylation of nuclear transcription factor-κB p65 (NF-κB p65) were suppressed by catalpol. SIGNIFICANCE: Catalpol could alleviate DM-induced male reproductive damage by inhibiting oxidative stress-induced apoptosis and inflammation mediated by AGEs/RAGE/Nox4 signaling pathway.

Evidence for the paternal mitochondrial DNA in the crucian carp-like fish lineage with hybrid origin.

In terms of taxonomic status, common carp (Cyprinus carpio, Cyprininae) and crucian carp (Carassius auratus, Cyprininae) are different species; however, in this study, a newborn homodiploid crucian carp-like fish (2n=100) (2nNCRC) lineage (F1-F3) was established from the interspecific hybridization of female common carp (2n=100)×male blunt snout bream (Megalobrama amblycephala, Cultrinae, 2n=48). The phenotypes and genotypes of 2nNCRC differed from those of its parents but were closely related to those of the existing diploid crucian carp. We further sequenced the whole mitochondrial (mt) genomes of the 2nNCRC lineage from F1 to F3. The paternal mtDNA fragments were stably embedded in the mt-genomes of F1-F3 generations of 2nNCRC to form chimeric DNA fragments. Along with this chimeric process, numerous base sites of F1-F3 generations of 2nNCRC underwent mutations. Most of these mutation sites were consistent with the existing diploid crucian carp. Moreover, the mtDNA organization and nucleotide composition of 2nNCRC were more similar to those of the existing diploid crucian carp than those of the parents. The inheritable chimeric DNA fragments and mutant loci in the mt-genomes of different generations of 2nNCRC provided important evidence of the mtDNA change process in the newborn lineage derived from hybridization of different species. Our findings demonstrated for the first time that the paternal mtDNA were transmitted into the mt-genomes of homodiploid lineage, which provided new insights into the existence of paternal mtDNA in the mtDNA inheritance.

Antithrombin III Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Excessive Autophagy in a Phosphoinositide 3-Kinase/Akt-Dependent Manner.

Autophagy is fundamental to myocardial ischemia/reperfusion (I/R) injury. Antithrombin III (AT) has been shown to protect cardiomyocytes against I/R injury; however, it is unknown whether it modulates autophagy. The objective of this study was to investigate whether AT regulates autophagy during I/R injury and, if so, to identify the potential mechanism involved. Our study showed that AT attenuated I/R injury in vivo and hypoxia/reoxygenation (H/R) injury in vitro. Autophagy was increased both in H9C2 cardiomyocytes during H/R injury and in mouse hearts following I/R injury. The stimulation of autophagy by rapamycin attenuated the protective effect of AT against H9C2 cell injury, indicating that autophagy is involved in the protective role of AT. Furthermore, the cardioprotective effects of AT were abolished by A6730, a specific Akt inhibitor. This study shows that AT exhibits cardioprotective effects by modulating autophagy during I/R injury in a phosphoinositide 3-kinase/Akt-dependent manner.

Effects of macrophage migration inhibitory factor on cardiac reperfusion injury in mice with depression induced by constant-darkness.

RATIONALE: Depression is associated with coronary artery disease and increases adverse outcomes and mortality in patients with acute myocardial infarction, but the underlying pathophysiological mechanisms remain unclear. OBJECTIVE: To evaluate the effect of macrophage migration inhibitory factor (MIF) on cardiac ischemia-reperfusion (I/R) injury in mice with constant darkness-induced depression. METHODS AND RESULTS: Twenty C57BL/6 mice (8 weeks old, male) were randomly divided into 2 groups: one group was housed in a 12h light/dark cycle environment (LD) and the other in a constant darkness environment (DD). After 3 weeks, constant darkness-exposed (DD) mice displayed depression-like behavior as indicated by increased immobility in the forced swim test (FST) and lower sucrose preference rate. Western blotting revealed cardiac MIF expression was significantly lower in the DD mice than that in the LD mice. Next, 84 mice were randomly divided into 4 groups: LD sham group, LD I/R group, DD sham group, and DD I/R group. Following ischemia and reperfusion, mice in the DD I/R group had a larger infarct area and lower heart function index than mice in the LD I/R group (P < 0.05 for both). The cardiac pAMPK and pACC expression levels of the DD I/R group were also lower in the DD I/R group (P < 0.05). CONCLUSION: DD-induced depression might cause decreased expression of MIF in the heart, resulting in downregulation of MIF-AMPK signaling and a subsequent adverse outcome after a cardiac I/R injury.

Chimeras Linked to Tandem Repeats and Transposable Elements in Tetraploid Hybrid Fish.

The formation of the allotetraploid hybrid lineage (4nAT) encompasses both distant hybridization and polyploidization processes. The allotetraploid offspring have two sets of sub-genomes inherited from both parental species, and therefore, it is important to explore its genetic structure. Herein, we construct a bacterial artificial chromosome library of allotetraploids, and then sequence and analyze the full-length sequences of 19 bacterial artificial chromosomes. Sixty-eight DNA chimeras are identified, which are divided into four models according to the distribution of the genomic DNA derived from the parents. Among the 68 genetic chimeras, 44 (64.71%) are linked to tandem repeats (TRs) and 23 (33.82%) are linked to transposable elements (TEs). The chimeras linked to TRs are related to slipped-strand mispairing and double-strand break repair while the chimeras linked to TEs benefit from the intervention of recombinases. In addition, TRs and TEs can also result in insertions/deletions of DNA segments. We conclude that DNA chimeras accompanied by TRs and TEs coordinate a balance between the sub-genomes derived from the parents. It is the first report on the relationship between formation of the DNA chimeras and TRs and TEs in the polyploid animals.

Macrophage migration inhibitory factor promoter polymorphisms (-794 CATT5-8): Relationship with soluble MIF levels in coronary atherosclerotic disease subjects.

BACKGROUND: We analyzed the relationship of -794 CATT5-8 MIF polymorphisms with soluble MIF in Coronary Atherosclerotic Disease (CAD) patients. METHODS: A total of 256 patients selected, on which 186 normal-coronary and 70 Coronary artery disease subjects, were recruited in the study (Retrospectively registered). Genotyping of -794 CATT5-8 polymorphisms were performed by PCR and DNA sequencing. Serum MIF levels were measured using an ELISA kit. Patients were classified by coronary angiogram, and CAD based on Gensini's integral degree (angiographic scoring system). RESULTS: The allele frequency and genotype frequency of -794 CATT5-8 did not show any differences in normal-coronary subjects and CAD subjects. In CAD patients, serum MIF levels was lower in CATT (5) subjects than in CATT (7) subjects, while the genotype of -794 CATT5-8 did not show differences in serum MIF levels. In addition, we found a decrease in serum MIF levels in carriers of the (5/5) genotypes the -794 CATT5-8 MIF polymorphisms, although it was not significant. There was no relationship of CAD class and the allele frequency of -794 CATT5-8. CONCLUSIONS: This study found no association between CAD class and -794 CATT5-8 MIF polymorphisms with soluble MIF levels in CAD Subjects. TRIAL REGISTRATION: NCT01750502 (November 2012, Retrospectively registered).

Amifostine Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Apoptosis and Oxidative Stress.

The present study was aimed at investigating the effect of amifostine on myocardial ischemia/reperfusion (I/R) injury of mice and H9c2 cells cultured with TBHP (tert-butyl hydroperoxide). The results showed that pretreatment with amifostine significantly attenuated cell apoptosis and death, accompanied by decreased reactive oxygen species (ROS) production and lower mitochondrial potential (ΔΨm). In vivo, amifostine pretreatment alleviated I/R injury and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase (SOD) and reduced malondialdehyde (MDA) in myocardial tissues, increased Bcl2 expression, decreased Bax expression, lower cleaved caspase-3 level, fewer TUNEL positive cells, and fewer DHE-positive cells in heart. Our results indicate that amifostine pretreatment has a protective effect against myocardial I/R injury via scavenging ROS.

Changing Strabismus Surgery Distribution at Shanxi Province Eye Hospital in Central China.

PURPOSE: To investigate whether there has been a changing trend of strabismus surgery in a provincial eye hospital in the central part of China over the past decade. METHODS: This was a retrospective analysis of data on all strabismus surgery performed in Shanxi Province Eye Hospital in China during the past 10 years. Recorded characteristics included patient demographics, type of strabismus, age, and gender. RESULTS: A total of 12,327 patients received strabismus surgery in the eye hospital from 2005 to 2014. The number of surgeries increased steadily from 800 in 2005 to 1,723 in 2014 (P < .01). Constant exotropia was the most common type among all types of strabismus. Superior oblique muscle palsy was the most common type of paralytic strabismus. Exotropia oblique A- and V-pattern type was the most common type of special strabismus. CONCLUSIONS: The amount of strabismus surgery increased during the past decade. The proportion of patients with intermittent exotropia increased over time compared to those with other types of strabismus. [J Pediatr Ophthalmol Strabismus. 2017;54(2):112-116.].