Comprehensive biophysical characterization of AAV-AAVR interaction uncovers serotype- and pH-dependent interaction.

After more than two decades of research and development, adeno-associated virus (AAV) has become one of the dominant delivery vectors in gene therapy. Despite the focused research, the cell entry pathway for AAV is still not fully understood. Universal AAV receptor (AAVR) has been identified to be involved in cellular entry of different AAV serotypes. With the unveiling of the high-resolution AAV-AAVR complex structure by cryogenic electron microscopy, the atomic level interaction between AAV and AAVR has become the focus of study in recent years. However, the serotype dependence of this binding interaction and the effect of pH have not been studied. Here, orthogonal approaches including bio-layer interferometry (BLI), size-exclusion chromatography coupled to multi-angle laser scattering (SEC-MALS) and sedimentation velocity analytical ultracentrifugation (SV-AUC) were utilized to study the interaction between selected AAV serotypes and AAVR under different pH conditions. A robust BLI method was developed and the equilibrium dissociation binding constants (KD) between different AAV serotypes (AAV1, AAV5 and AAV8) and AAVR was measured. The binding constants measured by BLI together with orthogonal methods (SEC-MALS and SV-AUC) all confirmed that AAV5 has the strongest binding affinity followed by AAV1 while AAV8 binds the weakest. It was also observed that lower pH promotes the binding between AAV and AAVR and neutral or slightly basic conditions lead to very weak binding. These data indicate that for certain serotypes, AAVR may play a prominent role in trafficking AAV to the Golgi rather than acting as a host cell receptor. Information obtained from these combinatorial biophysical methods can be used to engineer future generations of AAVs to have better transduction efficiency.

A 49-Year-Old Woman With Exertional Dyspnea and Dizziness.

CASE PRESENTATION: A 49-year-old woman with a history of right breast cancer status post radiation therapy presented to our ED with increasing chest pain, exertional dyspnea, fatigue, and dizziness for several weeks. She denied syncope or near-syncope, and she had no personal or family history of cardiac disease. Her outpatient medications included tamoxifen and venlafaxine.

Medical Disruptions During Center-Based Cardiac Rehabilitation: A Necessary Appraisal for the Development of Emerging Remote and Virtual Care Models.

PURPOSE: The purpose of this study is to show that with remote and virtual cardiac rehabilitation (CR) care models rapidly emerging, CR core components must be maintained to prioritize safety and effectiveness. Currently, there is a paucity of data on medical disruptions in phase 2 center-based CR (cCR). This study aimed to characterize the frequency and types of unplanned medical disruptions. METHODS: We reviewed 5038 consecutive sessions from 251 patients enrolled in cCR program from October 2018 to September 2021. Quantification of events was normalized to sessions to control for multiple disruptions that occurred to a single patient. A multivariate logistical regression model was used to predict comorbid risk factors for disruptions. RESULTS: Fifty percent of patients experienced one or more disruptions during cCR. Glycemic events (71%) and blood pressure (12%) abnormalities accounted for most of these while symptomatic arrhythmias (8%) and chest pain (7%) were less frequent. Sixty-six percent of events occurred within the first 12 wk. The regression model showed that a diagnosis of diabetes mellitus was the strongest predictor for disruptions (OR = 2.66: 95% CI, 1.57-4.52; P < .0001). CONCLUSIONS: Medical disruptions were frequent during cCR, with glycemic events being most common and occurring early. A diagnosis of diabetes mellitus was a strong independent risk factor for events. This appraisal suggests that patients living with diabetes mellitus, particularly those on insulin, need to be the highest priority for monitoring and planning and suggests that a hybrid care model may be beneficial in this population.

[Advances in the biomedical application research of halophilic microorganisms].

In recent years, antibiotic resistance has become increasingly serious, and the number of cancer patients keeps increasing. There is an urgent need to develop new drugs with antibacterial and antitumor effects. Halophilic microorganisms are a special group of microorganisms living in extreme environment. They have the characteristics of metabolic diversity, low nutritional requirements and adaptability to harsh conditions, thus can serve as promising candidates for new drug discovery. To date, researchers have isolated a variety of metabolites and enzymes with antibacterial and/or antitumor activities from halophilic microorganisms. This review summarized the functions and potential biomedical applications of halophilic microorganisms and their related products, such as antibacterial, anti-inflammatory, antitumor, antioxidant, biomedical materials and drug carriers. In particular, novel antibacterial and antitumor substances recently discovered in halophilic microorganisms, as well as the biomedical applications of ectoine, a unique metabolite found in halophilic microorganisms, were introduced. Finally, future development and utilization of halophilic microorganisms in biomedical and industrial fields were prospected.

Risk Factors for Nonalcoholic Fatty Liver Disease in Postmenopausal Women with Type 2 Diabetes Mellitus and the Correlation with Bone Mineral Density at Different Locations.

Objective: To explore the risk factors for nonalcoholic fatty liver disease (NAFLD) in postmenopausal women with type 2 diabetes mellitus (T2DM) and the correlation with bone mineral density (BMD) in different areas of the body. Methods: A total of 434 postmenopausal women with T2DM were enrolled and categorized as 198 patients in the NAFLD group and 236 patients in the non-NAFLD group based on color Doppler ultrasound of the liver. The BMD of the lumbar spine, femoral neck, and total hip were measured by dual-energy X-ray absorptiometry. Results: In postmenopausal women with T2DM, the prevalence of NAFLD was 45.6%. The body mass index (BMI), systolic blood pressure (SBP), glycosylated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), triacylglycerol (TG), uric acid (UA), and homeostatic model assessment for insulin resistance (HOMA-IR) C-peptide (CP) were significantly higher in the NAFLD group than in the non-NFALD group, and the duration of diabetes, and high-density lipoprotein cholesterol (HDL-C) were lower than in the non-NAFLD group (P < 0.05). Logistic regression analysis revealed that BMI (odds ratio [OR] = 1.303, 95% confidence interval [CI]: 1.152-1.346), HbA1c (OR = 1.263, 95% CI: 1.095-1.392), TG (OR = 1.263, 95% CI: 1.031-1.601), and SUA (OR = 1.005, 95% CI: 1.001-1.007) were correlated with NAFLD (P < 0.05). The BMD of the total hip and femoral neck in the NAFLD group was higher than in the non-NAFLD group (P < 0.05). Conclusion: Complicated NAFLD in postmenopausal women with T2DM is associated with weight gain, poor blood glucose control, abnormal lipid metabolism, and elevated UA levels. In addition, the NAFLD group had higher femoral neck and total hip BMD than the non-NAFLD group, suggesting NAFLD in postmenopausal women with T2DM may reduce the risk of osteoporosis.

Hemoperitoneum identified by focused assessment with sonography for trauma following cardiopulmonary resuscitation.

It is generally recognized that lives are saved by administering high-quality cardiopulmonary resuscitation (CPR) to patients in cardiac arrest. A focused assessment with sonography for trauma (FAST) examination is an effective and non-invasive method for detecting rare complications of CPR, such as hemorrhage from abdominal visceral injury. We report the case of a 56-year-old female suffering from intra-abdominal hemorrhage caused by a liver laceration following CPR. The hemoperitoneum was diagnosed by a FAST examination. Although severe complications of CPR are rare, they can be easily detected with the use of a FAST examination. A FAST examination should be considered as a post-resuscitation approach to assess for life-threatening complications in all patients following cardiopulmonary resuscitation.

Relationship Between Sexual Activity, Contraceptive Utilization and Biopsychosocial Characteristics Among Homeless Shelter Adolescents.

Objective: To determine whether biopsychosocial factors are associated with sexual activity and contraceptive utilization among homeless shelter adolescents. Methods: A retrospective study of 440 adolescents at a shelter in Pennsylvania between February 2015 and September 2019 was conducted. The cohort was evaluated to determine what relationship age, gender identity, substance use, and trauma history have with sexual activity and contraceptive utilization. Results: Sexual activity was significantly related to age (mean 15.8+1.4 years in sexually active vs. 14.7+1.6 years in abstinent youth, p<0.001); remote history of self-harm behavior (relative risk ratio (RR) 1.23 [95% CI 1.03-1.46]; p=0.02), history of aggressive behavior (RR 1.21 [95% CI 1.01-1.46]; p=0.04), history of trauma (RR 1.24 [95% CI 1.04-1.48]; p=0.03), and substance use (RR 2.27 [95%CI 1.86-2.77]; p<0.001). There were 55.7% sexually active females vs. 42.50% males reporting contraception use (p=0.01). After adjustment, older age and substance use remained significantly associated with sexual activity (adjusted odds ratio (AOR) 1.58 [95% CI 1.36-1.83]; p<0.001 and AOR 5.18 [95% CI 3.28-8.18]; p<0.001, respectively). Conclusions: Females self-reported sexual activity using contraception more than males. After adjustment, older age and substance use were associated with sexual activity. By better understanding the impact these factors can have on contraceptive utilization, informed policy and practice interventions can be developed and implemented to help increase safe sex practices in spaces where homeless adolescents access healthcare.

Changes in the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios before and after percutaneous coronary intervention and their impact on the prognosis of patients with acute coronary syndrome.

OBJECTIVES: This study aimed to prospectively observe the changes in the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) before and after percutaneous coronary intervention (PCI) and their impact on the prognosis of patients with acute coronary syndrome (ACS). METHODS: Blood samples from 205 patients with ACS were collected at admission and at 24h and 30 days post-PCI to observe changes in the complete blood count. The Cox multivariate regression model was used to analyze the factors influencing major adverse cardiac events (MACE) after PCI in patients with ACS. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of inflammation indicators for MACE after PCI. RESULTS: Following PCI, NLR and PLR first increased postoperatively and then decreased within 30 days after PCI. Cox multivariate regression analysis showed that NLR and PLR at 24h post-PCI and acute ST-segment elevation myocardial infarction were independent influencing factors for the incidence of MACE after PCI. The ROC curve analysis showed that the NLR at 24h post-PCI was a better predictor of the incidence of MACE. The NLR at 24h post-PCI was significantly correlated with the number and length of implanted stents and operation duration. CONCLUSIONS: After PCI, patients with ACS had an increased neutrophil proportion and NLR. The NLR at 24h post-PCI was a better predictor of the incidence of postoperative MACE.

The Abuse Characteristics of Amphetamine-Type Stimulants in Patients Receiving Methadone Maintenance Treatment and Buprenorphine Maintenance Treatment.

OBJECTIVE: The purpose of this study was to retrospectively investigate the abuse characteristics of amphetamine-type stimulants (ATS) in patients receiving methadone maintenance treatment (MMT) and buprenorphine maintenance treatment (BMT). METHODS: A total of 58 MMT and 51 BMT patients abusing ATS were recruited from the drug maintenance treatment clinic of Ningbo Addiction Research and Treatment Center from January 2018 to December 2019. They were assessed using the amphetamine abuse questionnaire (AAQ), addiction severity index (ASI) and Barratt impulsiveness scale (BIS). Moreover, 40 MMT control patients, 40 BMT control patients and 20 healthy controls were also assessed using the BIS. All information was collected using the amphetamine abuse questionnaire (AAQ), Chinese version of addiction severity index (ASI-C) and Chinese version of Barratt impulsiveness scale (BIS-C) conducted by qualified psychologists. RESULTS: The interval of amphetamine use in the MMT group was shorter than the BMT group (P < 0.05). The drug use subscale score of ASI was higher in the MMT group than the BMT group (P < 0.05). The respective and total scores of attentional impulsiveness, motor impulsiveness and non-planning impulsiveness in BIS in the MMT group were all higher than the MMT control group (P < 0.05). The scores of motor impulsiveness and non-planning impulsiveness in the BMT group were higher than the BMT control group (P < 0.05). The respective and total scores in BIS in the MMT control group and the BMT control group were all higher than those in the healthy controls. CONCLUSION: The patients showing amphetamine abuse in maintenance therapy had a greater impulsiveness than those having other simple maintenance treatments, and patients under MMT may be more addicted to amphetamines in comparison with those having BMT.

Exploring the chemical space of 1,2,3-triazolyl triclosan analogs for discovery of new antileishmanial chemotherapeutic agents.

Triclosan and isoniazid are known antitubercular compounds that have proven to be also active against Leishmania parasites. On these grounds, a collection of 37 diverse 1,2,3-triazoles based on the antitubercular molecules triclosan and 5-octyl-2-phenoxyphenol (8PP) were designed in search of novel structures with leishmanicidal activity and prepared using different alkynes and azides. The 37 compounds were assayed against Leishmania donovani, the etiological agent of leishmaniasis, yielding some analogs with activity at micromolar concentrations and against M. tuberculosis H37Rv resulting in scarce active compounds with an MIC of 20 µM. To study the mechanism of action of these catechols, we analyzed the inhibition activity of the library on the M. tuberculosis enoyl-ACP reductase (ENR) InhA, obtaining poor inhibition of the enzyme. The cytotoxicity against Vero cells was also tested, resulting in none of the compounds being cytotoxic at concentrations of up to 20 µM. Derivative 5f could be considered a valuable starting point for future antileishmanial drug development. The validation of a putative leishmanial InhA orthologue as a therapeutic target needs to be further investigated.

Relationship Between Vaccination Status and Biopsychosocial Characteristics in Sheltered Adolescents.

Introduction Homeless youth are a vulnerable population. A volunteer clinic supported by medical students in northeastern Pennsylvania provides shelter and healthcare to adolescents seeking refuge. We set out to determine the immunization status of youth in the shelter and evaluate for associations of immunization deficiency with demographics or biopsychosocial factors. Methods After IRB approval, a retrospective cohort study was performed from existing clinical records at the shelter 2/2015-9/2019. Chart abstraction included variables such as demographics (including age, sex, and race/ethnicity), biopsychosocial factors (including childhood trauma/abuse history, substance abuse history, and sexual activity), and immunization history. Results A total of 440 charts were analyzed. When comparing demographics of patients that had complete vaccine regimens versus those who did not, the race was statistically significant (p=.006). The most prominent difference in race was seen for Black/African American patients; only 19.57% had a completed vaccine regimen documented. Regarding immunization history, vaccine schedules of hepatitis B, measles mumps rubella (MMR), inactivated polio vaccine (IPV), and varicella were most likely to be complete; pneumococcal conjugate vaccine (PCV) 13, rotavirus, influenza, and human papillomavirus vaccine (HPV) were least likely. There was no association found between a completed vaccine regimen and biopsychosocial variables. A larger portion of females (37.35%) completed the HPV vaccine compared to males (23.14%) (p=.009). Conclusions In this single-site study, this vulnerable, at-risk population of sheltered adolescents lacked the vaccinations recommended by the Centers for Disease Control and Prevention. Racial disparities further compounded this vulnerability for Black/African American teens. Additionally, a significantly greater number of female patients received the HPV vaccine compared to males.

Changes in the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios before and after percutaneous coronary intervention and their impact on the prognosis of patients with acute coronary syndrome

OBJECTIVES: This study aimed to prospectively observe the changes in the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) before and after percutaneous coronary intervention (PCI) and their impact on the prognosis of patients with acute coronary syndrome (ACS). METHODS: Blood samples from 205 patients with ACS were collected at admission and at 24h and 30 days post-PCI to observe changes in the complete blood count. The Cox multivariate regression model was used to analyze the factors influencing major adverse cardiac events (MACE) after PCI in patients with ACS. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of inflammation indicators for MACE after PCI. RESULTS: Following PCI, NLR and PLR first increased postoperatively and then decreased within 30 days after PCI. Cox multivariate regression analysis showed that NLR and PLR at 24h post-PCI and acute ST-segment elevation myocardial infarction were independent influencing factors for the incidence of MACE after PCI. The ROC curve analysis showed that the NLR at 24h post-PCI was a better predictor of the incidence of MACE. The NLR at 24h post-PCI was significantly correlated with the number and length of implanted stents and operation duration. CONCLUSIONS: After PCI, patients with ACS had an increased neutrophil proportion and NLR. The NLR at 24h post-PCI was a better predictor of the incidence of postoperative MACE.

Activated Oxytocin Neurons in the PVN-DVC Pathway in Asthmatic Rats.

Asthma is a heterogeneous disease, and the central nervous system (CNS) also participates in the pathogenesis of asthma. We previously reported the amygdala might regulate asthmatic attacks via projecting to the paraventricular hypothalamic nucleus (PVN). The dorsal vagal complex (DVC) is a crucial region that modulates respiratory. This study aimed to observe the activity in both PVN and DVC and the connection between PVN and DVC in asthmatic rats. Immunohistochemistry was conducted to observe the changes in Fos and oxytocin (OT) expression. Retrograde tracing using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and double immunohistochemistry for OT and Fos was used to observe the HRP/OT/Fos positive neurons distribution in the PVN. The results showed that during an asthma attack, the Fos positive neurons increased in both PVN and DVC over time. The expression of OT positive neurons in PVN showed a similar trend in parallel to the c-Fos positive neurons in PVN. The HRP retrograde-labeled neurons were densely distributed in the medial and lateral subnucleus in the PVN. OT+/HRP+ and Fos+/OT+/HRP+ accounted for 18.14%, and 2.37% of HRP-labeled neurons, respectively. Our study showed PVN and DVC were activated and the expression of OT positive neurons in PVN were increased over time during an asthma attack. The existence of connection between PVN and DVC suggested the OT neurons in PVN might project to DVC which might be involved in the pathogenesis of asthma.

Aspirin use for cardiovascular disease prevention in the uninsured population.

INTRODUCTION: Aspirin is an effective anti-inflammatory and antiplatelet agent as an irreversible inhibitor of cyclooxygenase. In 2016, the U.S. Preventive Services Task Force recommended aspirin for primary prevention of cardiovascular disease in patients aged 50-69 years with a 10% or greater 10-year cardiovascular disease risk. Current guidelines for patients with prior myocardial infarction or coronary artery disease recommend aspirin use for the secondary prevention of cardiovascular disease. Due to the lack of literature describing adherence to these recommendations in the uninsured patient population, we studied aspirin use for cardiovascular disease prevention in free medical clinics. METHODS: We conducted a cross sectional study of uninsured patients who visited nine free medical clinics in 2016-2017. Data from the records of 8857 patients were combined into a database for analysis. 10-year Framingham risk scores for coronary artery disease were calculated for the 50-69-year-old population to evaluate which patients qualified for aspirin usage. Aspirin use was assessed for patients with prior myocardial infarction or coronary artery disease. RESULTS: In total, 1443 patients met the criteria to take aspirin for primary prevention of cardiovascular disease, but just 17% of these patients aged 50-59 years were on the medication. About 15% of the patients aged 60-69 years were taking aspirin. Of the 297 patients who had prior myocardial infarction or coronary artery disease, 50% were taking aspirin for secondary prevention. CONCLUSION: Among the uninsured population, there are low rates of aspirin use for risk reduction of cardiovascular disease. This study demonstrates that improvements are needed to increase adherence to current guidelines and address barriers uninsured patients may face in maintaining their cardiovascular health.

Inhibition of complement pathway activation with Pozelimab, a fully human antibody to complement component C5.

Complement is a key component of the innate immune system. Inappropriate complement activation underlies the pathophysiology of a variety of diseases. Complement component 5 (C5) is a validated therapeutic target for complement-mediated diseases, but the development of new therapeutics has been limited by a paucity of preclinical models to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) properties of candidate therapies. The present report describes a novel humanized C5 mouse and its utility in evaluating a panel of fully human anti-C5 antibodies. Surprisingly, humanized C5 mice revealed marked differences in clearance rates amongst a panel of anti-C5 antibodies. One antibody, pozelimab (REGN3918), bound C5 and C5 variants with high affinity and potently blocked complement-mediated hemolysis in vitro. In studies conducted in both humanized C5 mice and cynomolgus monkeys, pozelimab demonstrated prolonged PK and durable suppression of hemolytic activity ex vivo. In humanized C5 mice, a switch in dosing from in-house eculizumab to pozelimab was associated with normalization of serum C5 concentrations, sustained suppression of hemolytic activity ex vivo, and no overt toxicity. Our findings demonstrate the value of humanized C5 mice in identifying new therapeutic candidates and treatment options for complement-mediated diseases.

The amygdala via the paraventricular nucleus regulates asthma attack in rats.

AIMS: This study aimed to investigate the functions of the amygdala in rat asthma model. MAIN METHODS: Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was used for tracing from the paraventricular nucleus (PVN) to the amygdala, and nuclear lesions were performed to observe changes in respiratory function and airway inflammation. RESULTS: This study showed that the extracellular neuronal discharged in the medial amygdala (MeA) and central amygdala (CeA), and the expression of Fos significantly increased in asthmatic rat compared to control group. The distribution of Fos- and oxytocin (OT)-positive neurons and Fos/OT dual-positive neurons evidently increased in the PVN. WGA-HRP was injected into the PVN for tracing, and Fos/HRP-dual-positive neurons were observed to be distributed in the MeA. By using kainic acid (KA) to injure the MeA and CeA in asthmatic rats, expiratory and inspiratory times (TE/TI) and airway resistance (Raw) decreased, and minute ventilation volume (MVV) and dynamic pulmonary compliance (Cdyn) increased accordingly. In the bronchoalveolar lavage fluid (BALF), the number of eosinophils and the concentration of IL-4 were lower than those of the control group, and the ratio of Th1/Th2 cells was higher than that of the control group. In the PVN, the distribution of Fos-, OT-positive cells and Fos/OT double-positive cells decreased compared with those of the control group. The activities of the MeA and CeA and of OT neurons in the PVN of the rats were correlated with the occurrence of asthma. CONCLUSIONS: Asthma attack could induce neural activities in the MeA and CeA, and OT neurons in the PVN may be involved in the process of asthma attack.

Knockdown long non-coding RNA PEG10 inhibits proliferation, migration and invasion of glioma cell line U251 by regulating miR-506.

Glioma is a serious malignant tumor without effective therapies till now. lncRNA PEG10 was reported to have some biological activities in cancers. Hence, we explored the effects of PEG10 on the human glioma cell line U251 cells. U251 cells were transfected with sh-PEG10 and/or miR-506 inhibitor. The expression of PEG10 and miR-506 was measured by qRT-PCR. Cell viability, cell apoptosis, cell migration and invasion were detected by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. The cell proliferation and apoptosis related p16, p53, Bcl-2, Bax, and pro-/Cleaved-Caspase-3/9, migration and invasion related-protein: matrix metalloproteinases MMP-2, MMP-9 and vimentin, and Raf/MEK/ERK and JAK1/STAT3 pathways-related proteins were accessed by Western blot. Transfection with sh-PEG10 inhibited cell viability, migration and invasion, and increased cell apoptosis. Meanwhile, PEG10 silence upregulated the expression of p16 and p53, Bax, cleaved-Caspase-3/9 expression, and downregulated Bcl-2 expression. PEG10 silence upregulated miR-506 expression. Co-transfection with sh-PEG10 and miR-506 inhibitor impaired the tumor suppressive effects. PEG10 knockdown decreased the phosphorylation of Raf/MEK/ERK and JAK1/STAT3-related proteins Raf, MEK, ERK, JAK1 and STAT3. PEG10 knockdown inhibited cell viability, migration and invasion, induced cell apoptosis through miR-506 upregulation, as well as inactivation of Raf/MEK/ERK and JAK1/STAT3 signal pathways.

Knockdown of lncRNA-UCA1 inhibits cell viability and migration of human glioma cells by miR-193a-mediated downregulation of CDK6.

BACKGROUND: Long noncoding RNA urothelial carcinoma-associated 1 (lncRNA-UCA1) is generally recognized as an oncogenic molecule in several human malignant tumors. However, the available evidence does not necessarily imply an unequivocal causal function of UCA1 in glioblastoma. The current study was aimed to probe the biological function of lncRNA-UCA1 in human glioblastoma cell lines. Besides, we further investigated the potential mechanisms. METHODS: Cell viability, apoptosis, as well as migration and invasion were measured using a commercial cell counting kit-8, flow cytometry, and 24-Transwell assay, respectively. LncRNA-UCA1, microRNA-193a (miR-193a), and CDK6 at messenger RNA levels were evaluated by quantitative real-time polymerase chain reaction method. Protein level was examined by Western blot analysis. RNA immunoprecipitation was utilized to validate lncRNA-UCA1 associated with miR-193a. Luciferase activity assay was used to identify the miR-193a-targeted CDK6 3'-untranslated region. RESULTS: lncRNA-UCA1 knockdown weakened cell viability, augmented apoptosis progression, as well as suppressed migration and invasion behaviors in glioblastoma cells, whereas lncRNA-UCA1 silence exhibited the opposite functions. lncRNA-UCA1 functioned as an endogenous sponge of miR-193a. miR-193a silence reversed the biological function of lncRNA-UCA1 knockdown on U-118 MG cells. miR-193a negatively regulated the expression of CDK6, and it affected the U-118 MG cells through regulating CDK6 expression. CDK6 overexpression abrogated the blockage of PI3K/AKT, mitogen-activated protein kinase (MAPK), and Notch signaling pathways. Furthermore, lncRNA-UCA1 and miR-193a could affect these signaling cascades through regulating CDK6 expression. The regulatory mechanisms of lncRNA-UCA1 were further consolidated in clinical specimens. CONCLUSION: lncRNA-UCA1 silence reduced cell viability, promoted apoptosis progression, while impeding the migration and invasion of glioblastoma cells by miR-193a-mediated silence of CDK6, with blockage of PI3K/AKT, MAPK, and Notch pathways.

Effect of stress hyperglycaemia on monocyte chemoattractant protein-1 levels and the short-term prognosis of patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

The present study prospectively investigated the effect of blood glucose level at admission on monocyte chemoattractant protein-1 levels at different time points before and after primary percutaneous coronary intervention, and the postoperative 1-year prognosis of patients with acute ST-segment elevation myocardial infarction. The 146 patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention were divided into three groups: Group 1, non-diabetic, non-hyperglycemic group; group 2, stress hyperglycemia group; and group 3, diabetic group. Serum monocyte chemoattractant protein-1 levels before and after percutaneous coronary intervention (PCI), and the incidence of major adverse cardiovascular events 1-year post PCI were observed. The increase in monocyte chemoattractant protein-1 levels 24 h after percutaneous coronary intervention, compared with those before percutaneous coronary intervention, was significantly correlated with the blood glucose level at admission. Furthermore, the 1-year postoperative major adverse cardiovascular events rates were significantly higher in groups 2 and 3 compared with group 1. Logistic regression analysis demonstrated that a high blood glucose level at admission, diabetes, and high preoperative monocyte chemoattractant protein-1 levels were risk factors for major adverse cardiovascular events 1-year post-percutaneous coronary intervention. Stress hyperglycemia and diabetes may contribute to high monocyte chemoattractant protein-1 levels and prolonged inflammation. These symptoms are associated with poor prognosis of acute ST-segment elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention.

Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio are Associated with Lower Extremity Vascular Lesions in Chinese Patients with Type 2 Diabetes.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are inflammatory markers used for prediction of chronic complications of diabetes. Lower extremity arterial disease (LEAD) is one of chronic complications of type 2 diabetes mellitus (T2DM). The correlation between NLR, PLR, and lower extremity vascular lesions was investigated in subjects with T2DM to determine the best predictive marker for LEAD. METHODS: Three hundred thirty-five patients with T2DM (199 males and 136 females; age 54.12 ± 14.07 years) were enrolled. Blood differential counts and anklebrachial index (ABI) were assessed. Patients were divided into the LEAD group (ABI ≤ 0.9, n = 236) and non-LEAD group (ABI > 0.9, n = 99), and NLR and PLR were compared between the two groups. The independent risk factors for LEAD were analyzed using a logistic regression model. Receiver operating characteristic (ROC) curve analysis was used to assess the optimal cutoff values of PLR and NLR for prediction of LEAD. RESULTS: NLR and PLR in the LEAD group were significantly increased compared to non-LEAD group patients. Univariate analyses identified that NLR was positively correlated with age, glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and 2-hours postprandial glucose levels. PLR was positively correlated with age, duration of T2DM, HbA1c, TG, TC, and LDL, but negatively correlated with diastolic blood pressure and fasting C-peptide levels. Binary logistic regression analysis identified that age, total number of white blood cells, PLR, and TC were significant and independent factors of diabetic LEAD. Moreover, ROC curve analysis showed that NLR and PLR were both predictive markers of LEAD in diabetes, and that the area under the PLR curve was larger than NLR. CONCLUSIONS: NLR and PLR are positively correlated with LEAD in diabetes. PLR was superior to NLR as a predictor of LEAD in diabetes.