Identification of key genes of diabetic cardiomyopathy in hiPSCs-CMs based on bioinformatics analysis.

Diabetic cardiomyopathy (DbCM) is one of the most common vascular complications of diabetes, and can cause heart failure and threaten the life of patients. The pathogenesis is complex, and key genes have not fully identified. In this study, bioinformatics analysis was used to predict DbCM-related gene targets. Published datasets from the NCBI Gene Expression Omnibus with accession numbers GSE62203 and GSE197850 were selected for analysis. Differentially expressed genes (DEGs) were identified by the online tool GEO2R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID online database. Protein-protein interaction network construction and hub gene identification were performed using STRING and Cytoscape. We used 30 mM and 1 µM hydrocortisone-stimulated AC16 cells as an in vitro model of diabetic cardiomyopathy. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression levels of hub genes. A total of 73 common DEGs were identified in both datasets, including 47 upregulated and 26 downregulated genes. GO and KEGG pathway enrichment analyses revealed that the DEGs were significantly enriched in metabolism, hypoxia response, apoptosis, cell proliferation regulation, and cytoplasmic and HIF signalling pathways. The top 10 hub genes were LDHA, PGK1, SLC2A1, ENO1, PFKFB3, EGLN1, MYC, PDK1, EGLN3 and BNIP3. In our in vitro study, we found that PGK1, SLC2A1, PFKFB3, EGLN1, MYC, EGLN3 and BNIP3 were upregulated, ENO1 was downregulated, and LDHA was unchanged. Except for PGK1 and ENO1, these hub genes have been previously reported to be involved in DbCM. In summary, we identified DEGs and hub genes and first reported PGK1 and ENO1 in DbCM, which may serve as potential candidate genes for DbCM targeted therapy.

Age-adjusted D-Dimer Thresholds Combined with the Modified Wells Score as a Predictor of Lower Extremity Deep Venous Thrombosis.

BACKGROUND: Neurosurgical patients are at an increased risk of deep venous thrombosis (DVT), which, if not properly managed, can lead to pulmonary embolism. This study aimed to investigate the accuracy of age-adjusted D-dimer thresholds combined with the modified Wells score as a predictor for lower extremity DVT diagnosis. METHODS: We conducted a study among patients aged >50 years with suspected lower extremity DVT in the neurosurgery intensive care unit between December 2019 and December 2020. Receiver operating characteristic curve analysis was performed to examine the diagnostic capacity of age-adjusted D-dimer combined with the modified Wells score. RESULTS: A total of 233 participants, with an average age of 71.81 ± 12.59 years, were enrolled in the study. The mean D-dimer levels were 0.73 ± 0.39 mg/L. Among the participants, 57 (57.9%, 33 males) were diagnosed with DVT. The age-adjusted D-dimer combined with the modified Wells score had the highest area under the curve for diagnosing lower extremity DVT compared to D-dimer and age-adjusted D-dimer alone, with an AUC of 0.858. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the age-adjusted D-dimer combined with the modified Wells score for DVT diagnosis were 78.95%, 80.68%, 57%, 92.2%, and 80.26%, respectively. When analyzing subgroups, the accuracy was 79.55% for participants with cerebral hemorrhage, 81.69% for those with craniocerebral injury, 74.99% for participants with intracranial infection, and 88.89% for those with craniocerebral tumor. CONCLUSION: The combination of the age-adjusted D-dimer thresholds with the modified Wells score might effectively predict lower extremity DVT.

Improvements of the Tada formula in estimating the intracerebral hemorrhage volume based on computed tomography.

Background: The Tada formula has been used widely for assessing intracerebral hemorrhage (ICH) volume. However, it is only suitable for calculating regular and small volume hematomas. Therefore, we attempted to improve the formula to increase its accuracy and maintain its efficiency. Methods: Computed tomography (CT) data of 15 balls of different shapes filled with predetermined volumes of water were collected to verify the high accuracy of FireVoxel in measuring the volume. CT data from 329 patients with ICH from two different hospitals grouped by hematoma shape and volume were retrospectively reviewed. The distinctly shaped ICH volumes of 245 patients from one of the hospitals were estimated using FireVoxel and the Tada formula grouped by the hematoma shape and volume. Taking the hematoma volumes measured by FireVoxel as the reference standard, the accuracy and reliability of the Tada formula were evaluated. Polynomial fitting was employed to determine the associations of the values calculated between the Tada formula and FireVoxel. Then, a corrected Tada formula (C-Tada formula) was produced, and the limits of agreement between the C-Tada formula and Tada formula were analyzed with Bland-Altman analysis. The C-Tada formula was validated by the CT data of 84 patients from another hospital. Results: The volume measured by FireVoxel can be set as the reference standard. The ICH volume calculated by the Tada formula was significantly greater than that calculated by FireVoxel for different shapes and volumes. The percentage deviation between the volumes calculated by FireVoxel and the Tada formula was also statistically significant and influenced by ICH shape and volume. The limits of agreement between the C-Tada formula and FireVoxel were tighter than those between the Tada formula and FireVoxel. The percentage deviation of the C-Tada formula calculation from the FireVoxel estimate was greatly reduced relative to that for the Tada formula for each group. Conclusions: The C-Tada formula is more clinically valuable than the Tada formula, given its sufficient efficiency and greater accuracy and reliability in ICH volume calculation.

Differences in Physiological Characteristics, Seed Germination, and Seedling Establishment in Response to Salt Stress between Dimorphic Seeds in the Halophyte Suaeda liaotungensis.

Soil salinization is an increasing agricultural problem around the world, affecting crop productivity and quality. Seed germination and seedling establishment are susceptible to salt stress. Suaeda liaotungensis is a halophyte with strong salt tolerance that produces dimorphic seeds to adapt to the saline environment. Differences in physiological characteristics, seed germination, and seedling establishment in response to salt stress between dimorphic seeds in S. liaotungensis have not been reported. The results showed that brown seeds had significantly higher H2O2 and O2-. levels and betaine content, as well as POD and CAT activities, while they had significantly lower MDA and proline contents and SOD activity than black seeds. Light promoted the germination of brown seeds in a certain temperature range, and brown seeds could reach a higher germination percentage in a wide temperature range. However, light and temperature had no effect on the germination percentage of black seeds. Brown seeds had higher germination than black seeds under the same NaCl concentration. The final germination of brown seeds was significantly decreased as salt concentration increased, whereas this had no effect on the final germination of black seeds. POD and CAT activities, as well as MDA content, in brown seeds were significantly higher than those in black seeds during germination under salt stress. Additionally, the seedlings from brown seeds were more tolerant to salinity than those from black seeds. Therefore, these results will give an in-depth understanding of the adaptation strategies of dimorphic seeds to a salinization environment, and better exploitation and utilization of S. liaotungensis.

Evaluation of Platelet Parameters in Patients With Secondary Failure of Platelet Recovery and Cytomegalovirus Infection After Hematopoietic Stem Cell Transplantation.

OBJECTIVE: To investigate the clinical significance of changes in platelet parameters in patients with secondary failure of platelet recovery (SFPR) and cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT). METHODS: In this retrospective study, 79 patients who had undergone allogeneic HSCT (allo-HSCT), including 40 patients with SFPR and 39 patients without SFPR, were recruited. The evaluated parameters were platelet count (PLT), plateletcrit (PCT), platelet-large cell ratio (P-LCR), mean platelet volume (MPV), platelet distribution width (PDW), the incidence of CMV infection after allo-HSCT, and the correlation of SFPR and CMV infection in patients who had undergone allo-HSCT. The control group included 107 healthy donors. RESULTS: The SFPR group had significantly lower megakaryocyte counts, PLT, and PCT and significantly higher P-LCR, MPV, and PDW than the healthy donor and non-SFPR groups. The incidence of CMV infection was higher in SFPR patients than in non-SFPR patients. Among the patients with SFPR, P-LCR, MPV, and PDW were lower in those with CMV DNA >8000 copies/mL than in those with CMV DNA <8000 copies/mL (P < .05 for all); the CMV viral load was slightly negatively correlated with MPV (P = .0297) and P-LCR (P = .0280). CONCLUSION: We demonstrate for the first time that the level of platelet activation in SFPR patients, which was closely related to CMV infection, was higher than that in that in non-SFPR patients, and higher CMV load was associated with the inhibition of platelet activation.

Craniocervical Manual Lymphatic Drainage Increases the Efficiency of Atorvastatin-Based Treatment of Chronic Subdural Hematoma.

The objective of this study is to explore whether craniocervical manual lymphatic drainage (cMLD) can promote hematoma absorption and increase the efficiency of atorvastatin-based conservative treatment in chronic subdural hematoma (CSDH) patients. All CSDH patients treated with atorvastatin-based therapy between October 2020 and February 2022 in our department were retrospectively screened for enrollment. The patients were divided into the control and cMLD groups according to whether cMLD was performed. Head CT or MR images in both groups were obtained before the treatment and 2 weeks and 4 weeks after the treatment. MR images of the deep cervical lymphatic nodes (dCLNs) in 23 patients were obtained in the cMLD group before and approximately 2 weeks after treatment. The volumes of the dCLNs and hematoma were calculated. The primary outcomes are the differences in hematoma volume reduction after 4 weeks of treatment. The secondary outcomes were (1) the differences in hematoma volume reduction between the patients in these two groups in the 2nd week, (2) the dCLN volume change in the cMLD group before and after 2 weeks of treatment, and (3) the percentage of patients who transitioned to surgery because of failure to the conservative treatment. A total of 106 consecutive patients were enrolled in this study for analysis; 54 patients received atorvastatin-based treatment (control group), and 52 were treated with both atorvastatin-based treatment and cMLD (cMLD group). At baseline, the mean hematoma volume was 76.53 ± 42.97 ml in the control group and 88.57 ± 49.01 ml in the cMLD group (p = 0.181). In the 4th week, the absolute number of hematoma reductions (20.79 ± 34.73 ml vs. 37.28 ± 28.24 ml, p = 0.009) and percentage of hematoma reductions (22.58% ± 60.01% vs. 46.43% ± 30.12%, p = 0.012) in the cMLD group were greater than those in the control group. After 2 weeks of treatment, the absolute number of hematoma reductions showed no difference in the two groups, while the percentage of hematoma reduction was higher in the cMLD group (18.18% ± 24.61% vs. 2.08% ± 25.72%, p = 0.001). One patient in cMLD and 8 patients in the control group were transitioned to receive surgical treatment. The dCLN volumes in 23 experimental patients increased significantly after 2 weeks of treatment in the cMLD group (p = 0.032). There were no severe side effects that needed to be reported. Combined with atorvastatin-based therapy, cMLD can promote hematoma absorption and decrease the surgery rate, which provides a new therapeutic strategy for CSDH.

Establishment and validation of a prediction model for self-absorption probability of chronic subdural hematoma.

Background: Chronic subdural hematoma (CSDH) is common in elderly people with a clear or occult traumatic brain injury history. Surgery is a traditional method to remove the hematomas, but it carries a significant risk of recurrence and poor outcomes. Non-surgical treatment has been recently considered effective and safe for some patients with CSDH. However, it is a challenge to speculate which part of patients could obtain benefits from non-surgical treatment. Objective: To establish and validate a new prediction model of self-absorption probability with chronic subdural hematoma. Method: The prediction model was established based on the data from a randomized clinical trial, which enrolled 196 patients with CSDH from February 2014 to November 2015. The following subjects were extracted: demographic characteristics, medical history, hematoma characters in imaging at admission, and clinical assessments. The outcome was self-absorption at the 8th week after admission. A least absolute shrinkage and selection operator (LASSO) regression model was implemented for data dimensionality reduction and feature selection. Multivariable logistic regression was adopted to establish the model, while the experimental results were presented by nomogram. Discrimination, calibration, and clinical usefulness were used to evaluate the performance of the nomogram. A total of 60 consecutive patients were involved in the external validation, which enrolled in a proof-of-concept clinical trial from July 2014 to December 2018. Results: Diabetes mellitus history, hematoma volume at admission, presence of basal ganglia suppression, presence of septate hematoma, and usage of atorvastatin were the strongest predictors of self-absorption. The model had good discrimination [area under the curve (AUC), 0.713 (95% CI, 0.637-0.788)] and good calibration (p = 0.986). The nomogram in the validation cohort still had good discrimination [AUC, 0.709 (95% CI, 0.574-0.844)] and good calibration (p = 0.441). A decision curve analysis proved that the nomogram was clinically effective. Conclusions: This prediction model can be used to obtain self-absorption probability in patients with CSDH, assisting in guiding the choice of therapy, whether they undergo non-surgical treatment or surgery.

MicroRNA alteration in cerebrospinal fluid from comatose patients with traumatic brain injury after right median nerve stimulation.

Electrical stimulation of the right median nerve can aid coma arousal after traumatic brain injury (TBI). This study aimed to confirm the efficacy further and explore possible mechanisms of right median nerve electrical stimulation (RMNS). Five comatose patients after severe TBI from May to September 2020 in the Tianjin Medical University General Hospital received RMNS for 2 weeks besides standard management. After the 2-week treatment, the mean Glasgow Coma Scale (GCS) and neurophysiological examination were used. We then investigated the alterations in microRNA (miRNA) expression in cerebrospinal fluid (CSF) by high-throughput whole transcriptome sequencing, analyzed the data by Gene Ontology (GO) and pathway analysis, and constructed the miRNA-target gene network. Patient awareness and brain function showed a more rapid increase after treatment. We also found 38 differently expressed miRNAs, 34 of which were upregulated and 4 downregulated. GO analysis showed a relation of these differentially expressed miRNAs with neuronal growth, repair, and neural signal transmission. The most highly correlated pathways were primarily associated with the tumor necrosis factor (TNF) signaling pathway and dopaminergic synapse. The application of RMNS effectively promoted early awakening in comatose patients with severe TBI. Moreover, differentially expressed miRNAs might reduce neuronal apoptosis and increase dopamine levels by regulating target gene expression, thus participating in the specific biological process after arousal therapy. Our study provided novel targets for further research on the molecular mechanisms of RMNS arousal treatment and a new way to treat neurotraumatic diseases.

Atorvastatin Plus Low-Dose Dexamethasone May Be Effective for Leukemia-Related Chronic Subdural Hematoma but Not for Leukemia Encephalopathy: A Report of Three Cases.

We are not aware of any reports regarding conservative treatment for leukemia-related chronic subdural hematoma (CSDH). We report our experience with 3 men who were admitted with subdural masses and abnormal leukocyte counts. In two patients, leukemia and CSDH were confirmed on the basis of medical records, mild head trauma, and neuroimaging features. Both patients experienced reduced CSDH and neurological symptoms after receiving atorvastatin (20 mg/day) plus low-dose dexamethasone. However, this combined conservative treatment was ineffective in the third patient, who was diagnosed as having leukemia and showed an increased hematoma volume after two weeks of therapy. Magnetic resonance imaging findings suggested dural metastasis, which prompted a switch from statin-based conservative treatment to chemotherapy. Complete remission of the leukemia and resolution of the subdural mass were observed after chemotherapy, which supported a diagnosis of leukemia encephalopathy. The 5-month follow-ups did not reveal CSDH relapse in all 3 cases. Thus, atorvastatin-based conservative treatment may be effective for leukemia-related CSDH but not for leukemia encephalopathy.

High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata (Zhiheshouwu) by UHPLC-Q-Exactive Orbitrap-MS.

Polygoni Multiflori Radix Praeparata (PMRP), as the processed product of tuberous roots of Polygonum multiflorum Thunb., is one of the most famous traditional Chinese medicines, with a long history. However, in recent years, liver adverse reactions linked to PMRP have been frequently reported. Our work attempted to investigate the chemical constituents of PMRP for clinical research and safe medication. In this study, an effective and rapid method was established to separate and characterize the constituents in PMRP by combining ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Based on the accurate mass measurements for molecular and characteristic fragment ions, a total of 103 compounds, including 24 anthraquinones, 21 stilbenes, 15 phenolic acids, 14 flavones, and 29 other compounds were identified or tentatively characterized. Forty-eight compounds were tentatively characterized from PMRP for the first time, and their fragmentation behaviors were summarized. There were 101 components in PMRP ethanol extract (PMRPE) and 91 components in PMRP water extract (PMRPW). Simultaneously, the peak areas of several potential xenobiotic components were compared in the detection, which showed that PMRPE has a higher content of anthraquinones and stilbenes. The obtained results can be used in pharmacological and toxicological research and provided useful information for further in vitro and in vivo studies.

Successful Treatment of a Nail Gun Injury in Right Parietal Region and Superior Sagittal Sinus.

BACKGROUND INTRODUCTION: Nail injuries are important causes of penetrating craniocerebral injuries. Theirs incidence is very low, but the injuries can be fatal. Since the nail gun was gradually popularized in 1959, the incidence of nail injuries has been increasing. Here we report a case of nail gun injury to superior sagittal sinus and review the literature of the past 60 years to find out what are the possible factors of nail gun injury and what are their respective ratios? CLINICAL REPORT: An 18-year-old male patient was accidentally injured in the head by the worker's nail gun, accompanied by scalp pain, no physical sensation disorder, and consciousness disorder. A computed tomography scan of his skull showed the penetrating site at the right frontal area, near the superior sagittal sinus. Seven days later, the patient underwent a successful surgery without neurological sequelae. DISCUSSION: Nail injuries are rare, but can be potentially fatal. We found that nail guns were the main cause of nail injuries, and other causes include occupational injury, violence, lack of supervision of young children (potential for domestic violence, and child abuse), mental illness, and suicide attempts. While paying attention to the anatomical location of trauma, clinicians should also think more about the possibility of injury so as to provide better help to patients in time.

Mouse nerve growth factor promotes neurological recovery in patients with acute intracerebral hemorrhage: A proof-of-concept study.

BACKGROUND: ew drugs were confirmed to be effective in the treatments of neurological dysfunction caused by acute intracerebral hemorrhage (ICH). The present prospective clinical trial aims to evaluate the effect of mouse nerve growth factor (mNGF) on neurological function in patients with acute ICH. METHODS: 60 patients with acute spontaneous ICH were randomized to receive mNGF (mNGF group) and citicoline (control group) for 4 weeks within 24-72 h after onset, respectively. The primary outcome was difference in the neurological functional outcome at 3 months by the modified Rankin Scale score (mRS). The secondary outcomes were the changes in hematoma volume at 4 weeks and 3 months. RESULTS: There were 55 patients receiving treatment (29 patients in the mNGF group, 26 patients in the control group). Among the patients, 46 patients finished the trial at 3 months; the odds of a shift towards death or dependence (mRS > 3) at 3 months in the mNGF group were lower than that in the control group with adjustment for age, sex, NIHSS at admission, and hematoma volume at admission (adjusted OR, 0.185; 95%CI, 0.059-0.582; P = 0.0039). The hematoma was gradually reduced in all 46 patients and absorbed after non-surgical treatment at 3 months. There was no significant difference in hematoma volume between the two groups. No serious adverse event was found. CONCLUSIONS: The administration of mNGF and citicoline was well-tolerated in patients with acute ICH. mNGF was associated with improved neurological function and less disability in patients with ICH. Therefore, the quality of life of patients with ICH may be improved by mNGF. TRIAL REGISTRATION: The trial is registered with the Chinese Clinical Trial Registry, number ChiCTR1800020258.

Fingolimod Attenuates Lung Injury and Cardiac Dysfunction after Traumatic Brain Injury.

Acute lung injury (ALI) and cardiac dysfunction are common in traumatic brain injury (TBI) patients and always indicate poor outcomes. Inflammatory responses play important roles in TBI-induced cardiac and pulmonary damage. Fingolimod, an immunomodulatory agent, alleviates brain edema, restores the integrity of the blood-brain barrier (BBB), and improves functional deficits by inhibiting multiple inflammatory responses. Fingolimod (1 mg/kg) was injected intraperitoneally at 2 h after the controlled cortical impact (CCI) model was established in adult male mice. The concentration of inflammatory cytokines in the lung and heart after TBI was measured with a cytokine array. The lung wet/dry weight ratio and Evans blue dye leakage were used to quantify pulmonary edema and capillary leakage. Immunofluorescence, electron microscopy, and echocardiographic examination were used to assess the pathology and functional deficits in hearts. We found that TBI caused significant heart and lung damage. The administration of fingolimod significantly reduced the elevated inflammatory cytokine production, neutrophil infiltration, the leakage of protein in bronchoalveolar lavage fluid (BALF), and the wet/dry weight ratio in lung tissue at 3 days after TBI. In addition, fingolimod treatment also alleviated the inflammatory response in the heart; decreased cardiac apoptosis, fibrosis, and histological microstructural changes; and improved cardiac function from 3 days after TBI and maintained it for 30 days after TBI as measured by echocardiography. These results suggest that TBI resulted in significant cardiac and pulmonary damage accompanied by significant inflammatory responses in heart and lung tissue. Fingolimod treatment reduced the inflammatory response and alleviated TBI-induced lung and heart injury.

An acute kidney injury prediction nomogram based on neurosurgical intensive care unit profiles.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication with high mortality within the neural-critical care unit, and can limit the treatment of osmotic diuresis and body fluid equilibrium. Given its seriousness, it is necessary to find a tool to predict the likelihood of AKI and to prevent its occurrence. METHODS: In this retrospective study, patients' clinical profiles, laboratory test results, and doctors' prescriptions were collected. Least absolute shrinkage and selection operator (LASSO) regression was used to select variables, and a logistic regression model was then applied to find independent risk factors for AKI. Based on the results of multivariate analysis, we established a nomogram to evaluate the probability of AKI, which was verified through the use of a receiver operating characteristic (ROC) curve and its calibration curves. RESULTS: Risk factors given by logistic regression were Glasgow Coma Scale (GCS) classification (1.593; 95% CI: 0.995-2.549; P=0.0523), coefficient of variation (CV) of GCS (1.017; 95% CI: 0.995-1.04; P=0.1367), hypertension (2.238; 95% CI: 1.124-4.456; P=0.0219), coronary heart disease (2.924; 95% CI: 1.2-7.126; P=0.0182), pneumonia within 7 days (3.032; 95% CI: 1.511-6.085; P=0.0018), heart failure within 7 days (6.589; 95% CI: 2.235-19.42; P=0.0006), furosemide (1.011; 95% CI: 1.005-1.016; P<0.0001), torasemide (1.028; 95% CI: 0.976-1.082; P=0.297), dopamine (1; 95% CI: 1-1.001, P=0.3297), and norepinephrine (1.007; 95% CI: 1-1.015; P=0.0474). The area under the curve (AUC) of the prediction model was 0.8786, and the calibration curves showed that the model had a good ability to predict AKI occurrence. CONCLUSIONS: This study presents an AKI prediction nomogram based on LASSO, logistic regression, and clinical risk factors. The clinical use of the nomogram may allow for the timely detection of AKI occurrence and thus improve the prognosis of patients.

Low-temperature laminar flow ward for the treatment of multidrug resistance Acinetobacter baumannii pneumonia.

This study was designed to investigate the effect of low-temperature laminar flow ward (LTLFW) on the Acinetobacter baumannii pneumonia (MDR-ABP) in neurosurgical intensive care unit (NICU) patients. We evaluated whether patients in a LTLFW had significantly improved clinical outcomes as compared to those in nonconstant-temperature NICU (room temperature). The association of temperature with the prevalence of ABP and A. baumannii isolates (ABI) found in NICU patients was specifically investigated. In vitro microbiological experiments were conducted to measure the proliferation, antibiotic sensitivity, and genomic profiles of A. baumannii (AB) that grew in variable temperatures. MDR-ABP patients in LTLFW had significantly improved outcomes than those in the room temperature NICU. In addition, the numbers of ABI were positively associated with mean ambient outdoor temperatures (P = 0.002), with the incidence of ABP and average numbers of ABI among NICU patients being substantially lower in the winter as compared to other seasons. However, there were no significant seasonal variations in the other strains of the top five bacteria. Consistent with these clinical observations, AB growing at 20°C and 25°C had significantly reduced viability and antibiotic resistance compared to those growing at 35°C. The expression of genes related to AB survival ability, drug resistance, and virulence also differed between AB growing at 20°C and those at 35°C. LTLFW is effective in promoting the recovery of MDR-ABP patients because low temperatures reduced the density and virulence of AB and enhanced the efficacy of antibiotics, likely at the genetic level.

Effects of microRNA-195 on the Prognosis of Glioma Patients and the Proliferation and Apoptosis of Human Glioma Cells.

Glioma is the most common and aggressive intracranial malignant tumor with poor prognosis. Acts as a tumor suppressor, microRNA-195 (miR-195) plays important roles in a variety of cancers. However, the expression of miR-195 and role of miR-195 in glioma are still not well understood. 186 patients with glioma were enrolled and the follow-up period ranges from 1 to 69 months. MiR-195 was exogenously transfected into human glioma U87 cell line. The cell proliferation assay (CCK-8), colony formation assay, cell cycle analysis and cell apoptosis analysis were examined to investigate miR-195 effect on U87 cells. MiR-195 levels were reversely correlated with pathological grades (r = -0.487, p = 0.003). For patients with low miR-195 levels, their median survival time was 15 months, whereas the median survival time in patients with high miR-195 levels was 56.53 months. Multi-factor Cox regression analysis showed that high level of miR-195 (Odds ratio (OR): 0.347, 95% CI: 0.121-0.992) was associated with decreased mortality risk of patients. Moreover, overexpression of miR-195 inhibits proliferation and colony formation, and induces apoptosis of U87 cells. MiR-195 could block the glioma cells in G0/G1 phase, reducing S phase cells and regulating apoptosis related proteins (Caspase-3, Caspase-8, Caspase-9 and Bcl-2). Downregulation of miR-195 was associated with poor prognosis in human glioma. MiR-195 acted as tumor suppressor through inhibiting cell proliferation and promoting cell apoptosis via blockade of cell cycle and regulation of apoptosis related proteins.

Hematoma-derived exosomes of chronic subdural hematoma promote abnormal angiogenesis and inhibit hematoma absorption through miR-144-5p.

Exosomes are small (30-150 nm diameter) lipid bilayer-enclosed vesicles found in all bodily fluids. We investigated whether exosomes play a role in chronic subdural hematoma (CSDH). Exosomes were identified and characterized using transmission electron microscopy and NanoSight particle tracking. The functions of hematoma-derived exosomes were evaluated in a rat model of acute subdural hematoma (SDH). The hematoma-derived exosomes inhibited hematoma absorption and exacerbated neurological deficits in SDH rats. We examined the effects of the exosomes on angiogenesis and cell permeability in human umbilical vein endothelial cells (HUVECs). Co-culture of exosomes with HUVECs revealed that the hematoma-derived exosomes were taken-in by the HUVECs, resulting in enhanced tube formation and vascular permeability. Additionally, there was a concomitant increase in ANG-2 expression and decrease in ANG-1 expression. Exosomes were enriched with microRNAs including miR-144-5p, which they could deliver to HUVECs to promote angiogenesis and increase membrane permeability. Overexpression of miR-144-5p in HUVECs and in SDH rats promoted abnormal angiogenesis and reduced hematoma absorption, which mimicked the effects of the hematoma-derived exosomes both in vitro and in vivo. Thus, hematoma-derived exosomes promote abnormal angiogenesis with high permeability and inhibit hematoma absorption through miR-144-5p in CSDH.

Exosomal transfer of miR-501 confers doxorubicin resistance and tumorigenesis via targeting of BLID in gastric cancer.

Exosomal transfer of oncogenic miRNAs can enhance recipient cell growth, metastasis and chemoresistance. Currently we found that microRNA-501-5p (miR-501) was overexpressed in doxorubicin-resistant gastric cancer (GC) SGC7901/ADR cell-secreted exosomes (ADR Exo) than that in SGC7901 cell-secreted exosomes (7901 Exo). ADR Exo was internalized by SGC7901, and a Cy3-miR-501 mimic was transferred from SGC7901/ADR to SGC7901 via exosomes. ADR Exo conferred doxorubicin resistance, proliferation, migration and invasion abilities to negative control miRNA inhibitor-expressing GC cells, whereas it inhibited apoptosis. MiR-501 knockdown or BH3-like motif-containing protein, cell death inducer (BLID) overexpression could reverse the effects of ADR Exo on recipient cells. SGC7901 cells cocultured with SGC7901/ADR prior to treatment with GW4869 or transfection of a miR-501 inhibitor were sensitive to doxorubicin and exhibited attenuated proliferation, migration and invasion and increased apoptosis. The intratumoral injection of ADR Exo into negative control miRNA inhibitor-expressing SGC7901 cells induced rapid subcutaneous tumor growth and resistance to doxorubicin compared to that of miR-501 knockdown or BLID-overexpressing cells. This effect is possibly achieved by exosomal miR-501-induced downregulation of BLID, subsequent inactivation of caspase-9/-3 and phosphorylation of Akt. Exosomal miR-501 might be a therapeutic target for GC.

Clinical Outcomes of Myocardial Bridging versus No Myocardial Bridging in Patients with Apical Hypertrophic Cardiomyopathy.

OBJECTIVE: To determine the prevalence and clinical effects of myocardial bridging (MB) in patients with apical hypertrophic cardiomyopathy (AHCM). METHODS: Angiograms from 212 AHCM patients were reviewed to identify MB. The patients were classified into 2 groups: AHCM with and AHCM without MB. We reviewed patient records on cardiovascular (CV) risk factors, symptoms, CV events, and CV mortality. RESULTS: In all, 60 patients with MB and 100 without MB were included. Rates of angina (61.7 vs. 40%; p = 0.008), mimicking non-ST-segment elevation myocardial infarction (15 vs. 3%, p = 0.013), and Canadian Cardiovascular Society class III/IV angina (18.3 vs. 4%; p = 0.003) were higher in patients with MB than in those without. Mean follow-up periods (65.5 ± 50.5 vs. 64.4 ± 43.6 months, p = 0.378) and CV mortality (3.3 vs. 1%; p = 0.652) were similar in the 2 groups. Kaplan-Meier estimates demonstrated that CV event-free survival rates were lower in patients with MB than in those without (71.7 vs. 88%; p = 0.022). MB, late gadolinium enhancement, and female sex were independent risk factors for CV events in a multivariate Cox regression analysis adjusted for other risk factors. CONCLUSION: More serious symptoms and a higher risk of CV events were observed in AHCM patients with MB than in those without MB. CV mortality was similar in these 2 groups.