Effect of Continuous Positive Airway Pressure on Blood Pressure in Patients with Resistant Hypertension and Obstructive Sleep Apnea: An Updated Meta-analysis.

PURPOSE OF REVIEW: The effect of continuous positive airway pressure (CPAP) on resistant hypertension in patients at high risk with obstructive sleep apnea (OSA) needs further investigation. We aimed to determine the effect of CPAP on blood pressure in patients with resistant hypertension and OSA. Databases including PubMed, EMBASE, MEDLINE, the Cochrane Library, and CMB were searched. Data were pooled using a random-effects or fixed-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals (CIs). RECENT FINDINGS: A total of 12 trials and 718 participants were included. Compared with control, CPAP significantly reduced 24-h systolic blood pressure (SBP) (WMD: - 5.92 mmHg [ - 8.72, - 3.11]; P＜0.001), 24-h diastolic blood pressure (DBP) (WMD: - 4.44 mmHg [- 6.26 , - 2.62]; P ＜0.001),  daytime SBP (WMD: - 5.76 mmHg [ - 9.16, - 2.36]; P ＜0.001),  daytime DBP (WMD: - 3.92 mmHg [- 5.55, - 2.30];  nighttime SBP (WMD: - 4.87 mmHg [ - 7.96 , - 1.78]; P = 0.002), and nighttime DBP (WMD: - 2.05 mmHg [- 2.99, - 1.11]; P＜0.001) in patients with resistant hypertension and OSA. CPAP improved the blood pressure both in the short (＜3 months) and long term (≥ 3 months). No significant impact on mean heart rate was noted (WMD: -2.76 beats per min [- 7.50, 1.97]; P = 0.25). CPAP treatment was associated with BP reduction in patients with resistant hypertension and OSA.

Prediction of miRNA-disease associations by neural network-based deep matrix factorization.

MicroRNA(miRNA) is a class of short non-coding RNAs with a length of about 22 nucleotides, which participates in various biological processes of cells. A number of studies have shown that miRNAs are closely related to the occurrence of cancer and various human diseases. Therefore, studying miRNA-disease associations is helpful to understand the pathogenesis of diseases as well as the prevention, diagnosis, treatment and prognosis of diseases. Traditional biological experimental methods for studying miRNA-disease associations have disadvantages such as expensive equipment, time-consuming and labor-intensive. With the rapid development of bioinformatics, more and more researchers are committed to developing effective computational methods to predict miRNA-disease associations in roder to reduce the time and money cost of experiments. In this study, we proposed a neural network-based deep matrix factorization method named NNDMF to predict miRNA-disease associations. To address the problem that traditional matrix factorization methods can only extract linear features, NNDMF used neural network to perform deep matrix factorization to extract nonlinear features, which makes up for the shortcomings of traditional matrix factorization methods. We compared NNDMF with four previous classical prediction models (IMCMDA, GRMDA, SACMDA and ICFMDA) in global LOOCV and local LOOCV, respectively. The AUCs achieved by NNDMF in two cross-validation methods were 0.9340 and 0.8763, respectively. Furthermore, we conducted case studies on three important human diseases (lymphoma, colorectal cancer and lung cancer) to validate the effectiveness of NNDMF. In conclusion, NNDMF could effectively predict the potential miRNA-disease associations.

GmMKK4-activated GmMPK6 stimulates GmERF113 to trigger resistance to Phytophthora sojae in soybean.

Phytophthora root and stem rot is a worldwide soybean (Glycine max) disease caused by the soil-borne pathogen Phytophthora sojae. This disease is devastating to soybean production, so improvement of resistance to P. sojae is a major target in soybean breeding. Mitogen-activated protein kinase (MAPK) cascades are important signaling modules that convert environmental stimuli into cellular responses. Compared with extensive studies in Arabidopsis, the molecular mechanism of MAPK cascades in soybean disease resistance is barely elucidated. In this work, we found that the gene expression of mitogen-activated protein kinase 6 (GmMPK6) was potently induced by P. sojae infection in the disease-resistant soybean cultivar 'Suinong 10'. Overexpression of GmMPK6 in soybean resulted in enhanced resistance to P. sojae and silencing of GmMPK6 led to the opposite phenotype. In our attempt to dissect the role of GmMPK6 in soybean resistance to phytophthora disease, we found that MAPK kinase 4 (GmMKK4) and the ERF transcription factor GmERF113 physically interact with GmMPK6, and we determined that GmMKK4 could phosphorylate and activate GmMPK6, which could subsequently phosphorylate GmERF113 upon P. sojae infection, suggesting that P. sojae can stimulate the GmMKK4-GmMPK6-GmERF113 signaling pathway in soybean. Moreover, phosphorylation of GmERF113 by the GmMKK4-GmMPK6 module promoted GmERF113 stability, nuclear localization and transcriptional activity, which significantly enhanced expression of the defense-related genes GmPR1 and GmPR10-1 and hence improved disease resistance of the transgenic soybean seedlings. In all, our data reveal that the GmMKK4-GmMPK6-GmERF113 cascade triggers resistance to P. sojae in soybean and shed light on functions of MAPK kinases in plant disease resistance.

Helicobacter pylori-induced aberrant demethylation and expression of GNB4 promotes gastric carcinogenesis via the Hippo-YAP1 pathway.

BACKGROUND: Helicobacter pylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an aberrant methylation level of GNB4 in H. pylori-induced GC in our previous bioinformatic analysis; however, its expression and underlying molecular mechanisms are poorly understood. METHODS: The expression, underlying signaling pathways, and clinical significance of GNB4 were analyzed in a local cohort of 107 patients with GC and several public databases. H. pylori infection was induced in in vitro and in vivo models. Methylation-specific PCR, pyrosequencing, and mass spectrometry analysis were used to detect changes in methylation levels. GNB4, TET1, and YAP1 were overexpressed or knocked down in GC cell lines. We performed gain- and loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, and invasion assays. Nude mice were injected with genetically manipulated GC cells, and the growth of xenograft tumors and metastases was measured. Real-time quantitative PCR, western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and co-immunoprecipitation experiments were performed to elucidate the underlying molecular mechanisms. RESULTS: GNB4 expression was significantly upregulated in GC and correlated with aggressive clinical characteristics and poor prognosis. Increased levels of GNB4 were associated with shorter survival times. Infection with H. pylori strains 26695 and SS1 induced GNB4 mRNA and protein expression in GC cell lines and mice. Additionally, silencing of GNB4 blocked the pro-proliferative, metastatic, and invasive ability of H. pylori in GC cells. H. pylori infection remarkably decreased the methylation level of the GNB4 promoter region, particularly at the CpG#5 site (chr3:179451746-179451745). H. pylori infection upregulated TET1 expression via activation of the NF-κB. TET binds to the GNB4 promoter region which undergoes demethylation modification. Functionally, we identified that GNB4 induced oncogenic behaviors of tumors via the Hippo-YAP1 pathway in both in vitro and in vivo models. CONCLUSIONS: Our findings demonstrate that H. pylori infection activates the NF-κB-TET1-GNB4 demethylation-YAP1 axis, which may be a potential therapeutic target for GC.

Nomogram based on clinical and preoperative CT features for predicting the early recurrence of combined hepatocellular-cholangiocarcinoma: a multicenter study.

PURPOSE: To establish and validate a multiparameter prediction model for early recurrence after radical resection in patients diagnosed with combined hepatocellular-cholangiocarcinoma (cHCC-CC). MATERIALS AND METHODS: This study reviewed the clinical characteristics and preoperative CT images of 143 cHCC-CC patients who underwent radical resection from three institutions. A total of 110 patients from institution 1 were randomly divided into training set (n = 78) and testing set (n = 32) in the ratio of 7-3. Univariate and multivariate logistic regression analysis were used to construct a nomogram prediction model in the training set, which was internally and externally validated in the testing set and the validation set (n = 33) from institutions 2 and 3. The area under the curve (AUC) of receiver operating characteristics (ROC), decision curve analysis (DCA), and calibration analysis were used to evaluate the model's performance. RESULTS: The combined model demonstrated superior predictive performance compared to the clinical model, the CT model, the pathological model and the clinic-CT model in predicting the early postoperative recurrence. The nomogram based on the combined model included AST, ALP, tumor size, tumor margin, arterial phase peritumoral enhancement, and MVI (Microvascular invasion). The model had AUCs of 0.89 (95% CI 0.81-0.96), 0.85 (95% CI 0.70-0.99), and 0.86 (95% CI 0.72-1.00) in the training, testing, and validation sets, respectively, indicating high predictive power. DCA showed that the combined model had good clinical value and correction effect. CONCLUSION: A nomogram incorporating clinical characteristics and preoperative CT features can be utilized to effectively predict the early postoperative recurrence in patients with cHCC-CC.

Pbrm1 intrinsically controls the development and effector differentiation of iNKT cells.

Under static condition, the pool size of peripheral invariant natural killer T (iNKT) cells is determined by their homeostatic proliferation, survival and thymic input. However, the underlying mechanism is not fully understood. In the present study, we found that the percentage and number of iNKT cells were significantly reduced in the spleen, but not in the thymus of mice with deletion of polybromo-1 (Pbrm1) compared to wild type (WT) mice. Pbrm1 deletion did not affect iNKT cell proliferation and survival, instead significantly impaired their development from stage 1 to stage 2. Importantly, loss of Pbrm1 led to a dysfunction of RORγt expression and iNKT17 cell differentiation, but not iNKT1 and iNKT2 proportion. Collectively, our study reveals a novel mechanism of Pbrm1 controlling the peripheral size of iNKT cells through regulating their development and differentiation.

CircPrkcsh, a circular RNA, contributes to the polarization of microglia towards the M1 phenotype induced by spinal cord injury and acts via the JNK/p38 MAPK pathway.

Spinal cord injury (SCI) is a complex pathological change that includes primary SCI and gradually evolves into secondary SCI. Accumulating evidence demonstrates that circular RNAs (circRNAs) are involved in the pathology of a variety of neurological diseases and injuries. However, the characteristics and function of circRNAs in SCI have yet to be elucidated. Although previous research demonstrated that circPrkcsh induces astrocytes to produce inflammatory factors and chemokines, the precise function and mechanism of circPrkcsh in microglia after SCI remains unknown. In this study, we constructed a mouse model of SCI by applying a SCI impactor. Quantitative Real-time PCR and Fluorescence in situ hybridization analysis revealed that circPrkcsh was upregulated in the microglia of SCI mice when compared to sham-operated mice. Gain- or loss-of-function experiments and in vivo assays further indicated that circPrkcsh promotes microglia M1 polarization both in vivo and in vitro. Furthermore, bioinformatics analysis, dual-luciferase assays, and RNA immunoprecipitation assays, confirmed that circPrkcsh serves as a competing endogenous RNA (ceRNA) to promote the expression of MEKK1 mRNA by sponging miR-488. Double knockout rescue experiments further showed that circPrkcsh regulates the MEKK1/JNK/p38 MAPK pathway via miR-488. Our research provides a better understanding of the mechanism of circPrkcsh in SCI and demonstrates that the circPrkcsh/miR-488/Mekk1 axis is a promising regulatory method for the treatment of SCI.

Asenapine maleate inhibits angiotensin II-induced proliferation and activation of cardiac fibroblasts via the ROS/TGFß1/MAPK signaling pathway.

BACKGROUND: Cardiac fibrosis will increase wall stiffness and diastolic dysfunction, which will eventually lead to heart failure. Asenapine maleate (AM) is widely used in the treatment of schizophrenia. In the current study, we explored the potential mechanism underlying the role of AM in angiotensin II (Ang II)-induced cardiac fibrosis. METHODS: Cardiac fibroblasts (CFs) were stimulated using Ang II with or without AM. Cell proliferation was measured using the cell counting kit-8 assay and the Cell-Light EdU Apollo567 In Vitro Kit. The expression levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were detected using immunofluorescence or western blotting. At the protein level, the expression levels of the components of the transforming growth factor beta 1 (TGFß1)/mitogen-activated protein kinase (MAPK) signaling pathway were also detected. RESULTS: After Ang II stimulation, TGFß1, TGFß1 receptor, α-SMA, fibronectin (Fn), collagen type I (Col1), and collagen type III (Col3) mRNA levels increased; the TGFß1/MAPK signaling pathway was activated in CFs. After AM pretreatment, cell proliferation was inhibited, the numbers of PCNA -positive cells and the levels of cardiac fibrosis markers decreased. The activity of the TGFß1/MAPK signaling pathway was also inhibited. Therefore, AM can inhibit cardiac fibrosis by blocking the Ang II-induced activation through TGFß1/MAPK signaling pathway. CONCLUSIONS: This is the first report to demonstrate that AM can inhibit Ang II-induced cardiac fibrosis by down-regulating the TGFß1/MAPK signaling pathway. In this process, AM inhibited the proliferation and activation of CFs and reduced the levels of cardiac fibrosis markers. Thus, AM represents a potential treatment strategy for cardiac fibrosis.

Silencing miR-21 induces polarization of astrocytes to the A2 phenotype and improves the formation of synapses by targeting glypican 6 via the signal transducer and activator of transcription-3 pathway after acute ischemic spinal cord injury.

Ischemic spinal cord injury (ISCI) results in the motor sensory dysfunction of the limbs below the injury site. In response to the injury, astrocytes develop into neuroprotective astrocytes [(neurotrophic reactive astrocytes (A2s)] to mitigate the damage. MicroRNA (miR)-21 can promote the development of neuroinflammation in previous studies. Our aim was to investigate the effect of miR-21 on its polarization. We used the abdominal aortic occlusion model in vivo. Immunohistochemistry was used to detect the distribution of A2s in the spinal cord. We used an oxygen glucose deprivation method to model astrocytes ischemia in vitro and tested proliferation, migration, and excitability of A2s using an 5-ethynyl -2'-deoxyuridine kit, wound scratch assay, and calcium-ion probe. After adjustment, we detected the model and target genes of A2s using PCR, Western blot, immunofluorescence, and chromatin immunoprecipitation. We demonstrated in vivo that naive astrocytes were transformed into A2s by ischemia. And in vitro miR-21, which can regulate the signal transducer and activator of transcription-3 pathway, can transform neurotoxic reactive astrocyte into A2. Moreover, we also verified the mechanism of A2s promoting synaptic formation and nerve growth. miR-21 is a switch to regulate the polarization of reactive astrocyte, and it promoted synapsis formation and nerites growth after acute ISCI.-Su, Y., Chen, Z., Du, H., Liu, R., Wang, W., Li, H., Ning, B. Silencing miR-21 induces polarization of astrocytes to the A2 phenotype and improves the formation of synapses by targeting glypican 6 via the signal transducer and activator of transcription-3 pathway after acute ischemic spinal cord injury.

Patient satisfaction of radiofrequency ablation for symptomatic benign solid thyroid nodules: our experience for 2-year follow up.

BACKGROUND: The patient satisfaction of symptoms improvement and disease factors that may affect long-term treatment efficacy of radiofrequency ablation (RFA) for non-functioning solid benign thyroid nodules (TNs) over a 2-year follow up study was investigated. METHODS: This retrospective study evaluated 194 non-functioning solid benign TNs of 103 patients. The TNs were categorized as small (≤5 ml), medium (5.1 to 13 ml), intermediate (13.1 to 30 ml) and large (over 30 ml) according to the initial volume of TNs before ablation. Clinical evaluation and contrast-enhanced ultrasound (CEUS) were carried out before ablation and the follow up at 1, 3, 6 months and every 6 months after ablation. All patients were asked to assess the cosmetic score (1-4 scores) and symptom score (0-10 scores) before ablation and every follow up after ablation. RESULTS: All patients underwent RFA without any major complications. The mean treatment sessions were 1.5 ± 0.6. 98 nodules required a single session (98/194, 50.5%), 87 required two sessions (87/194, 44.9%), 9 required three sessions (9/194, 4.6%). The average follow up months were 16.3 ± 5.6 (range, 6-24 months) and no nodule regrew in our study. After RFA treatment, the TNs volume significantly decreased (P < 0.001). The small group of nodules shrunk larger compared to the medium, intermediate and large groups (P < 0.001). Cosmetic signs and pressure symptoms were significantly improved, particularly in the intermediate and large groups (P < 0.05). CONCLUSIONS: RFA is effective for treating non-functioning solid benign TNs and controlling clinical symptoms with a low complication rate during 2 years follow up. The reduction rate was related to the initial volume of nodules. Patients were satisfied with cosmetic signs and pressure symptoms improvement, particularly in the intermediate and large groups. However, multiple RFA treatments should be used in larger nodules to achieve the desired clinical outcomes.

Iodine-catalyzed guanylation of amines with N,N'-di-Boc-thiourea.

Herein, we report that iodine-catalyzed guanylation of primary amines can be accomplished with N,N'-di-Boc-thiourea and TBHP to afford the corresponding guanidines in 40-99% yields. Oxidation of the HI byproduct by TBHP eliminates the need for an extra base to prevent the protonation of substrates and makes the reaction especially useful for both electronically and sterically deactivated primary anilines.

Reorganization of the brain in spinal cord injury: a meta-analysis of functional MRI studies.

PURPOSE: Reorganization of the brain is considered the key mechanism of functional recovery in patients after spinal cord injury (SCI). This meta-analysis assessed abnormal brain activation in SCI patients to understand the pattern of reorganization in the brain after SCI. METHODS: Functional magnetic resonance imaging (fMRI) studies that compared SCI patients with controls and were published before August 30, 2018, were extracted from the PubMed, Web of Science, and EMBASE databases. Voxel-wise whole-brain meta-analysis and region-of-interest meta-analysis of group differences were separately performed. Then, meta-regression analysis was conducted with several clinical characteristics as regressors. RESULTS: Sixteen studies that met the inclusion criteria were identified. Compared with control individuals, SCI patients showed increased activation in the sensorimotor cortex in both whole-brain and region-of-interest (ROI) analyses. In addition, whole-brain meta-analysis revealed increased activation in the cerebellum, and this increase was positively correlated with lesion level and injury severity. CONCLUSION: Our results demonstrated that reorganization occurred mainly in the sensorimotor system of the brain after SCI, implying that brain functions involved in sensorimotor demands can still be preserved in this condition. These findings provide opportunities for future studies in terms of therapeutic strategies and prognosis assessment.

MicroRNA-21a-5p promotes fibrosis in spinal fibroblasts after mechanical trauma.

Traumatic spinal cord injury (SCI) causes permanent disability to at least 180,000 people per year worldwide. Early regulation of spinal fibroblast proliferation may inhibit fibrotic scar formation, allowing the creation of a favorable environment for neuronal regeneration and thereby enhancing recovery from traumatic SCIs. In this study, we aimed to identify the role of microRNA-21a-5p (miR-21a-5p) in regulating spinal fibroblasts after mechanical trauma and to investigate the dysregulation of miR-21a-5p in the pathological process of spinal SCI. We investigated the differential expression of microRNAs in primary spinal fibroblasts after mechanical trauma and found that the expression of miR-21a-5p was higher in spinal fibroblasts after scratch damage (SD). In addition, mouse spinal fibroblasts were transfected with miR-21a-5p mimics/inhibitor, and the role of miR-21a-5p in spinal fibrogenic activation was analyzed. These experiments demonstrated that miR-21a-5p overexpression promoted fibrogenic activity in spinal fibroblasts after mechanical trauma, as well as enhancing proliferation and attenuating apoptosis in spinal fibroblasts. Finally, the potential role of miR-21a-5p in regulating the Smad signaling pathway was examined. MiR-21a-5p activated the Smad signaling pathway by enhancing Smad2/3 phosphorylation. These results suggest that miR-21a-5p promotes spinal fibrosis after mechanical trauma. Based on these findings, we propose a close relationship between miR-21a-5p and spinal fibrosis, providing a new potential therapeutic target for SCI.

The association between body mass index and in-hospital outcome among patients with acute myocardial infarction-Insights from China Acute Myocardial Infarction (CAMI) registry.

BACKGROUND: The relationship between body mass index (BMI) and in-hospital mortality risk among patients with acute myocardial infarction (AMI) remains controversial. METHODS AND RESULTS: We included 35,964 patients diagnosed with AMI in China Acute Myocardial Infarction registry between January 2013 and December 2016. Patients were categorized into 4 groups according to BMI level: BMI <18.5, 18.5-24.9, 25-30, and ≥30 kg/m2 for underweight, normal, overweight, and obese groups, respectively. Clinical data were extracted for each patient, and multivariable logistic regression analysis was used to examine the association between BMI level and in-hospital mortality. Compared with normal-weight patients, obese patients were younger, more often current smokers, and more likely to have hypertension, hyperlipidemia, and diabetes. Multivariable regression analysis results demonstrated that compared with normal group, underweight group had significantly higher in-hospital mortality (odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.06-1.69; p = 0.016), while overweight group (OR: 0.86; 95% CI: 0.77-0.97; p = 0.011) and obese group (OR: 0.65; 95% CI: 0.46-0.91; p = 0.013) had lower mortality. All subgroups showed a trend toward lower in-hospital mortality risk as BMI increased. CONCLUSIONS: Our study provided robust evidence supporting "obesity paradox" in a contemporary large-scale cohort of patients with AMI and demonstrated that increased BMI was independently associated with lower in-hospital mortality.

Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury.

To assess the therapeutic effects of microRNA-21 (miR-21) knockdown (KD) for acute thoracic spinal cord contusion using a mouse model. Forty C57/BL6 mice were randomly divided into four groups: mice in the sham-operated (Sham) group received surgical procedure without spinal cord contusion; the spinal cord injury (SCI) group mice underwent spinal cord contusion without treatment; mice in the miR-21 KD group underwent spinal cord contusion followed by a single dose subdural injection of miR-21 KD vectors (1 × 107 TU); and the negative control (NC) group mice were given subdural injection of comparable amount of NC vectors (1 × 107 TU) after spinal cord contusion. The Basso Mouse Scale (BMS) was employed to assess hindlimb motor functions. Hematoxylin-eosin and Luxol fast blue staining were performed to evaluate pathologic changes in spinal cord tissues. Peripheral blood serum levels of tumor necrosis factor α (TNFα), transforming growth factor ß (TGF-ß) and interleukin-1ß (IL-1ß) were determined by the enzyme-linked immunosorbent assay, and mRNA expression of Brain derived neurotrophic factor (BDNF) was examined by reverse transcription-polymerase chain reaction (RT-PCR). Western blotting was performed to analyze the AKT signaling pathway. KD of miRNA-21 effectively improved the BMS scores at day 14 post-surgery compared with the SCI group (p < 0.01). The spinal cord tissue in the miR-21 KD group displayed the most overt histologic signs of recovery, with axonal regeneration and the recovery of neuronal morphology at day 14 post-surgery. Significantly alleviation of TGF-ß1, TNF-α and IL-1ß was also found in sera from the miR-21 inhibition group in comparison to others, whereas BDNF gene expression was upregulated following miR-21 KD (p < 0.01). Further, significantly decreased AKT phosphorylation activity was illustrated in the miR-21 KD group (p < 0.001). The data suggest that miR-21 KD significantly reduces the inflammatory response at the damaged spinal cord site and promotes motor functional recovery. The treatment also elevated expression of BDNF, a neurotrophin participating in nerve regeneration.

Macrophage Polarization in IL-10 Treatment of Particle-Induced Inflammation and Osteolysis.

This study investigated the therapeutic influence and potential mechanism of IL-10 in ameliorating orthopedic debris particle-induced inflammation and osteolysis. A murine air pouch with bone implantation and polyethylene particles was also used to evaluate the therapeutic effects of IL-10. The data suggested that the particle challenges significantly promoted macrophage activation and osteoclastogenesis, with dramatically increased macrophage infiltration into the pouch membranes and elevated tartrate-resistant acid phosphatase-positive cell deposition. Immunohistochemical stains revealed a significantly higher ratio of induced nitric oxide synthase-expressing cells in the particle-challenged group; treatment with IL-10 resulted in marked switching to CD163(+) cells. Also, IL-10 effectively reduced tartrate-resistant acid phosphatase-positive stained cells in the pouch membranes, and minimized the bone mineral density loss compared with untreated samples. Real-time PCR and Western blot examination indicated that IL-10 treatment significantly diminished the particle-induced IL-1ß expression but promoted expression of CD163, transforming growth factor-ß1, and CCR2. Furthermore, IL-10 significantly inhibited the ultra-high-molecular-weight polyethylene particle-elevated phospho-STAT1 and phospho-NF-κB p65 productions, and promoted phospho-STAT3 expression. Overall, the data indicate the pivotal effects of IL-10 on macrophage polarization. The effects of IL-10 in ameliorating local inflammation and osteolysis may be associated with macrophage polarization through the up-regulation of the Janus activating kinase/STAT3 signaling pathway, and the down-regulation of NF-κB and Janus activating kinase/STAT1 expression.

GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis.

Observational studies have reported controversial results on the association between GSTT1 and GSTM1 genotypes and treatment outcome of breast cancer. The purpose of this study is to evaluate the association between GSTT1 and GSTM1 and treatment outcome in breast cancer patients. Eligible studies were searched in PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases. A random-effect model or fixed-effect model was used to calculate the overall combined risk estimates. Twenty-one studies with a total of 4990 patients were included in this meta-analysis. The GSTM1 null genotype (odds ratio (OR) = 1.33, 95 % confidence interval (CI) 1.01-1.75, P = 0.046) and GSTT1/GSTM1 double null genotype (OR = 2.22, 95 % CI 1.02-4.84, P = 0.045) were significantly associated with an increased tumor response. A reduced overall survival (hazard ratio (HR) = 0.84, 95 % CI 0.72-0.98, P = 0.024) was observed in GSTM1 null genotype, especially in mixed descent (HR = 0.77, 95 % CI 0.61-0.96, P = 0.018) and large sample size (HR = 0.85, 95 % CI 0.72-0.99, P = 0.033). Evidence of publication bias was observed in GSTM1 genotype rather than in GSTT1 genotype. This meta-analysis suggests that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response. However, the GSTM1 null genotype might be significantly associated with a reduced overall survival. Future studies are warranted to confirm these findings.

Biventricular pacing cardiac contractility modulation improves cardiac contractile function via upregulating SERCA2 and miR-133 in a rabbit model of congestive heart failure.

OBJECTIVE: To compare the effects of biventricular electrical pacing and conventional single-ventricular pacing for cardiac contractility modulation (CCM) on cardiac contractile function and to delineate the underlying molecular mechanisms. METHODS: Forty rabbits were divided into four groups before surgery: healthy control, HF sham, HF left ventricular pacing CCM (LVP-CCM), and HF biventricular pacing CCM (BVP-CCM) groups with n=10 for each group. A rabbit model of chronic heart failure was established by ligating ascending aortic root of rabbits. Then electrical stimulations during the absolute refractory period were delivered to the anterior wall of left ventricle in the LVP-CCM group and on the anterior wall of both left and right ventricles in the BVP-CCM group lasting six hours per day for seven days. Changes in ventricular structure, cardiac function and electrocardiogram were monitored before and after CCM stimulation. RESULTS: Compared with the sham-operated group, heart weight, heart weight index, LV end-systolic diameter (LVESD), LV end-diastolic diameter (LVEDD) in the LVP-CCM and BVP-CCM groups were significantly decreased (p<0.05), while LV ejection fraction (LVEF) and fractional shortening fraction (FS) were increased (p<0.05). Notably all these changes were consistently found to be greater in BVP-CCM than in LVP-CCM. Moreover, plasma BNP levels were highest in the HF sham-control group, followed by the LVP-CCM group, and lowest in the BVP-CCM group (p<0.05). Furthermore, sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) protein levels were upregulated by 1.7 and 2.4 fold, along with simultaneous upregulation of a cardiac-enriched microRNA miR-133 levels by 2.6 and 3.3 fold, in LVP-CCM and BVP-CCM, respectively, compared to sham. CONCLUSIONS: Biventricular pacing CCM is superior to conventional monoventricular pacing CCM, producing greater improvement cardiac contractile function. Greater upregulation of SERCA2 and miR-133 may account, at least partially, for the improvement by BVP-CCM.

Comparison of transcranial color-coded real-time sonography and contrast-enhanced color-coded sonography for detection and characterization of intracranial arteriovenous malformations.

OBJECTIVES: To compare the diagnostic value of transcranial color-coded real-time sonography and contrast-enhanced color-coded sonography in detection and characterization of intracranial arteriovenous malformations. METHODS: Thirty-one patients highly suspected to have an intracranial arteriovenous malformation were imaged with real-time and contrast-enhanced sonography. With digital subtraction angiography as the reference standard, the ability to detect the malformations and accurately determine their size and location was compared between the two imaging techniques. RESULTS: One cavernous hemangioma and 30 intracranial arteriovenous malformations were imaged with real-time and contrast-enhanced sonography, which were confirmed by angiography. The detectability of contrast-enhanced sonography, especially for optimizing visualization of malformations located in the frontal, parietal, and occipital lobes, was higher than that of real-time sonography, although the overall number of malformations was too small to demonstrate significance. The sizes of the malformations (6 in the frontal lobe, 1 in the parietal lobe, and 1 in the occipital lobe) were underestimated by real-time sonography compared to angiography, whereas there was agreement in the sizes between contrast-enhanced sonography and angiography. The detection rates for the 30 arteriovenous malformations on contrast-enhanced and real-time sonography were 96.7% (29 of 30) and 70.0% (21 of 30), respectively (P = .008). Moreover, contrast-enhanced sonography was significantly superior to real-time sonography for detection of feeding arteries (59.5% [22 of 37] versus 83.7% [31 of 37]; P = .004). Although the feeding arteries showed increased peak systolic and end-diastolic velocities after contrast agent injection, there were no statistically significant differences in the velocities before and after injection. CONCLUSIONS: Transcranial contrast-enhanced color-coded sonography is superior to color-coded real-time sonography for detection of intracranial arteriovenous malformations, particularly for lesions located in the frontal, parietal, and occipital lobes of the brain.

Mismatch of AO anatomically shaped distal humeral plate with humeral shaft forward flexion angulation in adult Chinese population.

BACKGROUND: LCP extra-articular distal humerus plate (LCPEA) designed by AO has been introduced as an anatomically shaped plate that improves the results of surgical fixation in extra-articular distal humeral shaft fractures. However, no study analyzed whether LCPEA matches humeral shaft forward flexion angulation (FFA). OBJECTIVE: The aims of this study were to evaluate the morphological discrepancies between LCPEA and the humeral shaft FFA in Chinese cadaveric dried adult humeri and to propose a further design of pre-contoured plates to accommodate the FFA. MATERIALS AND METHODS: Forty-four Chinese cadaveric dried adult humeri were used for this study. An eight-hole LCPEA was applied to the posterior aspect of the distal humerus according to the contour. Mismatches between the bone and the plate were recorded. The distance between the inner surface of the plate and the underlying humeral dorsal cortex was measured at the sites of mismatch. The humeral shaft FFA was measured from the intersection angle between tangent lines placed on the dorsal aspect of the 1/3 distal humeral shaft and the dorsal ridge of the 2/3 proximal humeral shaft. The location of the apex of the FFA was determined by measuring the distance from the most distal point of trochlea of humerus to the point of intersection of the FFA tangent lines. The distance was defined as forward flexion distance (FFD). RESULTS: Mismatch was found at the level of proximal 3-6 holes of LCPEA with an average distance of 6.9 ± 3.1 mm (range 2.3-14.0 mm) at the tip of the plate. The FFA was present in all specimens. The average FFA was 8.2° ± 2.2° (range 4°-13°), the average FFD was 99.9 ± 9.6 mm (range 79.2-117.9 mm), and the average ratio of FFD to humerus length was 0.33 ± 0.03 (range 0.27-0.39). CONCLUSIONS: A rather consistent pattern of mismatch was found at the proximal part of LCPEA. An attempt to fit the plate to the bone at this level may cause a gap of the fracture at the opposite cortex. The main reason for the mismatch is the existence of the humeral shaft FFA. LCPEA is usually made a bend of about 8° between the fourth and the fifth dynamic-compression portion of the combination hole in the distal-to-proximal direction.