HELQ suppresses migration and proliferation of non-small cell lung cancer cells by repairing DNA damage and inducing necrosis.

HELQ plays a key role in DNA damage response and cell-cycle checkpoint regulation. It has been implicated in ovarian and pituitary tumors and may play a role in germ cell maintenance. This study investigated the role of HELQ in lung cancer. The expression of HELQ in patients with non-small-cell lung cancer (NSCLC) was downregulated compared with normal human lungs. Clinical prognostic analysis of Kaplan-Meier plots revealed that patients with NSCLC with low HELQ levels had a reduced overall survival. Further, we found that HELQ depletion enhanced lung cancer cell malignancy. Furthermore, overexpression of HELQ in lung cancer cells reduced cell migration in vitro, while DNA damage repair was inhibited. Both in vitro and in vivo studies have shown that HELQ induces cell death. Mechanistically, we found that cells overexpressing HELQ showed a tendency to induce necrosis. After analyzing the database of HELQ interactors. we found that RIPK3 may interact with it and proved this conclusion by immunoprecipitation. Our findings identified the tumor suppressive role of HELQ in malignant human lung cancer and unraveled a potential therapeutic strategy for cancer treatment through HELQ activation. Moreover, HELQ may also be a predictive biomarker for the clinical predisposition, progression, and prognosis of lung cancer.

Sex-Specific Associations Between Preoperative Hemoglobin and Outcomes After Major Noncardiac Surgery: A Retrospective Cohort Study.

BACKGROUND: Preoperative anemia is an established risk factor for morbidity and mortality after surgery. Men and women have different hemoglobin concentrations and are at different risks of postoperative complications. However, sex-stratified analysis on the association between preoperative hemoglobin and outcomes after noncardiac surgery has been limited in previous studies. METHODS: This was a retrospective cohort study of adult patients undergoing elective major noncardiac surgery in a large academic hospital. The primary outcome was a collapsed composite of postoperative mortality or cardiovascular, renal, pulmonary, and infectious complications during hospitalization. Sex-specific univariable associations between preoperative hemoglobin and the composite outcome were visualized using moving-average and cubic-spline smoothing plots. Multivariable regression models adjusting for patient demographics, comorbidities, medication uses, laboratory tests, and anesthesia/surgery features were used to estimate confounder-adjusted associations. Restricted cubic spline and piecewise linear functions were used to assess the possible nonlinear relationships between preoperative hemoglobin and the outcomes. The interaction between patient sex and hemoglobin on outcomes was assessed using a likelihood-ratio test. RESULTS: We included 22,550 patients, with 6.7% (622 of 9268) of women and 9.7% (1293 of 13,282) of men developing the primary outcome. Lower preoperative hemoglobin was associated with a higher incidence of the primary composite outcome in both men and women. Nonlinearity for the association was not statistically significant in either women ( P = .539) or men ( P = .165). The multivariable-adjusted odds ratios per 1 g/dL increase in hemoglobin were 0.93 (95% confidence interval [CI], 0.87-0.98; P = .013) for women and 0.94 (95% CI, 0.90-0.97; P < .001) for men, with no interaction by sex ( Pinteraction = .923). No hemoglobin thresholds were confirmed at which the associations with the primary outcome changed significantly. CONCLUSIONS: Low preoperative hemoglobin was associated with a higher risk of complications or mortality after elective noncardiac surgery in both men and women. No differences in the strength of associations between sexes were found. Further studies are needed to assess whether these associations are linear or there are sex-specific thresholds of preoperative hemoglobin concentrations below which postoperative risks begin to increase.

Outcomes of different zero-profile spacers in the treatment of two-level cervical degenerative disk disease.

PURPOSE: The purpose of this study was to analyze the clinical and radiological outcomes of two different zero-profile spacers (ROI-C and anchor-C) in contiguous two-level ACDF for CDDD patients. METHODS: We retrospectively analyzed patients who underwent contiguous two-level ACDF due to CDDD between January 2015 and December 2020 in our hospital. Patients who received ROI-C and anchor-C were included as the study groups, and those who underwent plate-cage construct (PCC) were included as the control group. The primary outcome measures were radiographical parameters, and the secondary outcome measures were dysphagia, JOA scores and VAS scores for these patients. RESULTS: A total of 91 patients were enrolled in the study; there were 31, 21 and 39 patients in the ROI-C, anchor-C and PCC groups, respectively. The mean follow-up duration was 24.52 months (range, 18-48 months) in the ROI-C group, 24.38 months (range, 16-52 months) in the anchor-C group and 25.18 months (range, 15-54 months) in the PCC group. The loss of the intervertebral space height and cage subsidence rate in the ROI-C group were significantly higher than those in the anchor-C group and PCC group at the final follow-up (P < 0.05). The ROI-C group showed a lower incidence of adjacent segment degeneration than the anchor-C group and PCC group, but the difference was not significant. The fusion rates were not different among these three groups. The early dysphagia rate was significantly lower in the patients with zero-profile spacers than in the PCC group (P < 0.05), but the difference was not significant at the last follow-up. No relevant differences were found in the JOA scores and VAS scores. CONCLUSIONS: Zero-profile spacers showed promising clinical outcomes in CDDD patients having contiguous two-level ACDF. However, ROI-C resulted in a higher intervertebral space height loss and a higher cage subsidence rate than anchor-C during the follow-up.

Machine learning for the prediction of postoperative nosocomial pulmonary infection in patients with spinal cord injury.

PURPOSE: The purpose of this study was to establish the best prediction model for postoperative nosocomial pulmonary infection through machine learning (ML) and assist physicians to make accurate diagnosis and treatment decisions. METHODS: Patients with spinal cord injury (SCI) who admitted to a general hospital between July 2014 and April 2022 were included in this study. The data were segmented according to the ratio of seven to three, 70% were randomly selected to train the model, and the other 30% were used for testing. We used LASSO regression to screen the variables, and the selected variables were used in the construction of six different ML models. Shapley additive explanations and permutation importance were used to explain the output of the ML models. Finally, sensitivity, specificity, accuracy and area under receiver operating characteristic curve (AUC) were used as the evaluation index of the model. RESULTS: A total of 870 patients were enrolled in this study, of whom 98 (11.26%) developed pulmonary infection. Seven variables were used for ML model construction and multivariate logistic regression analysis. Among these variables, age, ASIA scale and tracheotomy were found to be the independent risk factors for postoperative nosocomial pulmonary infection in SCI patients. Meanwhile, the prediction model based on RF algorithm performed best in the training and test sets. (AUC = 0.721, accuracy = 0.664, sensitivity = 0.694, specificity = 0.656). CONCLUSION: Age, ASIA scale and tracheotomy were the independent risk factors of postoperative nosocomial pulmonary infection in SCI. The prediction model based on RF algorithm had the best performance.

Role of magnetic resonance imaging features in diagnosing and localization of disc rupture related to cervical spinal cord injury without radiographic abnormalities.

STUDY DESIGN: A retrospective study. OBJECTIVE: Traumatic cervical spinal cord injury (TSCI) is often associated with disc rupture. It was reported that high signal of disc and anterior longitudinal ligament (ALL) rupture on magnetic resonance imaging (MRI) were the typical signs of ruptured disc. However, for TSCI with no fracture or dislocation, there is still difficult to diagnose disc rupture. The purpose of this study was to investigate the diagnostic efficiency and localization method of different MRI features for cervical disc rupture in patient with TSCI but no any signs of fracture or dislocation. SETTING: Affiliated hospital of University in Nanchang, China. METHODS: Patients who had TSCI and underwent anterior cervical surgery between June 2016 and December 2021 in our hospital were included. All patients received X-ray, CT scan, and MRI examinations before surgery. MRI findings such as prevertebral hematoma, high-signal SCI, high-signal posterior ligamentous complex (PLC), were recorded. The correlation between preoperative MRI features and intraoperative findings was analyzed. Also, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these MRI features in diagnosing the disc rupture were calculated. RESULTS: A total of 140 consecutive patients, 120 males and 20 females with an average age of 53 years were included in this study. Of these patients, 98 (134 cervical discs) were intraoperatively confirmed with cervical disc rupture, but 59.1% (58 patients) of them had no definite evidence of an injured disc on preoperative MRI (high-signal disc or ALL rupture signal). For these patients, the high-signal PLC on preoperative MRI had the highest diagnostic rate for disc rupture based on intraoperative findings, with a sensitivity of 97%, specificity of 72%, PPV of 84% and NPV of 93%. Combined high-signal SCI with high-signal PLC had higher specificity (97%) and PPV (98%), and a lower FPR (3%) and FNR (9%) for the diagnosis of disc rupture. And combination of three MRI features (prevertebral hematoma, high-signal SCI and PLC) had the highest accuracy in diagnosing traumatic disc rupture. For the localization of the ruptured disc, the level of the high-signal SCI had the highest consistency with the segment of the ruptured disc. CONCLUSION: MRI features, such as prevertebral hematoma, high-signal SCI and PLC, demonstrated high sensitivities for diagnosing cervical disc rupture. High-signal SCI on preoperative MRI could be used to locate the segment of ruptured disc.

[Key Prediction Genes of Nasopharyngeal Carcinoma:Screening Based on Systematic Bioinformatics and Validation by Cell Experiments].

Objective To screen out the potential prediction genes for nasopharyngeal carcinoma(NPC)from the gene microarray data of NPC samples and then verify the genes by cell experiments.Methods The NPC dataset was downloaded from Gene Expression Omnibus,and limma package was employed to screen out the differentially expressed genes.Weighted correlation network analysis package was used for weighted gene co-expression network analysis,and Venn diagram was drawn to find the common genes.The gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment were then performed for the common genes.The biomarkers for NPC were further explored by protein-protein interaction network,LASSO regression,and non-parametric tests.Real-time quantitative PCR and Western blotting were employed to determine the mRNA and protein levels of key predictors of NPC,so as to verify the screening results.Results There were 622 up-regulated genes and 351 down-regulated genes in the GSE12452 dataset.A total of 116 common genes were obtained by limma analysis and weighted gene co-expression network analysis.The common genes were mainly involved in the biological processes of cell proliferation and regulation and regulation of intercellular adhesion.They were mainly enriched in Rap1,Ras,and tumor necrosis factor signaling pathways.Six key genes were screened out,encoding angiopoietin-2(ANGPT2),dual oxidase 2(DUOX2),coagulation factor Ⅲ(F3),interleukin-15(IL-15),lipocalin-2,and retinoic acid receptor-related orphan receptor B(RORB).Real-time quantitative PCR and Western blotting showed that the NPC cells had up-regulated mRNA and protein levels of ANGPT2 and IL-15 and down-regulated mRNA and protein levels of DUOX2,F3,and RORB,which was consistent with the results predicted by bioinformatics.Conclusion ANGPT2,DUOX2,F3,IL-15 and RORB are potential predictive molecular markers and therapeutic targets for NPC,which may be involved in Rap1,Ras,tumor necrosis factor and other signaling pathways.

[Significance of high expression of C5orf46 in gastric cancer and potential intervention of tarditional Chinese medicine based on bioinformatics, molecular docking, and cell experiments].

This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 µmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.

Effects of the linewidth enhancement factor on the microwave linewidth of the period-one oscillations of optically injected semiconductor lasers.

We investigate the microwave linewidth of the period-one (P1) nonlinear dynamics of an optically injected semiconductor laser as a function of the linewidth enhancement factor. Under proper conditions of optical injection, the destabilizing effect of a large value of the linewidth enhancement factor of the injected semiconductor laser is found to be unexpectedly suppressed in the P1 oscillation of the laser, thus resulting in a narrow P1 linewidth equal to that generated by a laser of a small linewidth enhancement factor. By properly choosing the operating point, P1 oscillations with microwave linewidths that are an order of magnitude narrower than the free-running optical linewidths of the master and slave lasers are observed.

LRIG2 regulates cell proliferation, migration and apoptosis of osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is one of the malignant bone tumors with strong aggressiveness and poor prognosis. Leucine-rich repeats and immunoglobulin-like domains2 (LRIG2) is closely associated with the poor prognosis of a variety of tumors, but the role of LRIG2 in osteosarcoma and the underlying molecular mechanism remains unclear. OBJECTIVE: The aim of this study was to determine the function of LRIG2 in OS and the related molecular mechanism on cell proliferation, apoptosis and migration of OS. METHODS: The mRNA and protein expression of LRIG2 in OS tissues and cells was detected by qRT-PCR, western blot (WB) assay and immunohistochemistry (IHC). The cell counting Kit-8 (CCK-8), clone formation, transwell, TdT-mediated dUTP Nick-End Labeling (TUNEL) and WB assay were applied to determine the proliferation, migration and apoptosis abilities of OS cells and its molecular mechanisms. Spontaneous metastasis xenografts were established to confirm the role of LRIG2 in vivo. RESULTS: LRIG2 exhibited high expression in OS tissues and OS cell lines and the expression of which was significantly correlated with Enneking stage of patients, knockdown LRIG2 expression significantly inhibited OS cell proliferation, migration and enhanced apoptosis. Silencing LRIG2 also suppressed the growth of subcutaneous transplanted tumor in nude mice. Further, the mechanism investigation revealed that the protein level of cell proapoptotic proteins (Bax, caspase9 and caspase3) all increased attributed to LRIG2 deficiency, whereas expression of anti-apoptotic protein BCL2 decreased. LRIG2 silencing led to the decrease phosphorylation of AKT signaling, a decrease expression of vimentin and N-cadherin. Additionally, silencing LRIG2 significantly decreased the rate of tumor growth and tumor size. CONCLUSIONS: LRIG2 acts as an oncogene in osteosarcoma, and it might become a novel target in the treatment of human OS.

MiR-325-3p Alleviates Acute Pancreatitis via Targeting RIPK3.

BACKGROUND AND AIMS: Acute pancreatitis (AP) is an acute inflammatory disease that can lead to death. Mir-325-3p is strongly and abnormally expressed in many diseases, necessitating exploration of its function and mechanism in AP. METHODS: Blood samples from AP patients and mice were analyzed. The expression levels of miR-325-3p in AP patients and mouse were detected. Whether miR-325-3p targets RIPK3 gene was predicted by TargetScan online database and dual luciferase reporter assay. In vitro experiments verified the effect of miR-325-3p overexpression on caerulein-induced MPC83 pancreatic acinar cancer cell line. In vivo experiments verified the effect of overexpression of miR-325-3p on the disease degree of pancreatic tissues in AP mice. RESULTS: Analysis of blood samples from AP patients and experiments in mice demonstrated that expression of miR-325-3p was significantly reduced during the process of AP in humans and mice. Predicted using the TargetScan online database and through dual luciferase reporter assay detection, miR-325-3p directly targets the RIPK3 gene. In vitro experiments revealed that overexpression of miR-325-3p reversed caerulein-induced apoptosis and necroptosis in MPC83 pancreatic acinar cancer cell line. We used Z-VAD-FMK to assess necroptosis and demonstrated that miR-325-3p targets necroptosis to reduce cell damage. In subsequent experiments in mice, we verified that overexpression of miR-325-3p reduces inflammation, edema, hemorrhage, and necrosis in acute pancreatitis. Characteristic western blot, immunohistochemistry, and transmission electron microscopy results revealed that overexpression of miR-325-3p reduces the severity of acute pancreatitis by inhibiting pancreatic necroptosis in AP mice. CONCLUSIONS: The current research results indicate that miR-325-3p directly targets RIPK3 and exerts a protective role in mouse AP. Necroptosis is still the primary mechanism of RIPK3 regulation. MiR-325-3p inhibits acute pancreatitis by targeting RIPK3-dependent necroptosis, which may represent a novel treatment method for acute pancreatitis.

Incidences and reasons of postoperative surgical site infection after lumbar spinal surgery: a large population study.

PURPOSE: The purpose of this study was to determine the incidences of postoperative acute surgical site infection (SSI) after lumbar spinal surgery and its possible reasons in our hospital during the past 9 years. METHODS: This is a retrospective study with a large sample size. The medical records of all included patients were reviewed, and patients with acute SSI were identified. The incidence and possible reasons of SSI were determined. RESULTS: A total of 7240 patients who underwent posterior lumbar spinal surgery were included in this study, and the total incidence of postoperative SSI was 1.53% (111/7240). Gram-negative bacteria were found to be dominant in postoperative wound infections after lumbar spinal surgery. And Escherichia coli were the most common pathogen in patients with SSI. The rate of postoperative SSI following lumbar spinal surgery was increased at first and then decreased during the past 9 years. Additionally, from 2011 to 2014, it was mainly deep infection in these patients, and then was mainly superficial infection from 2015 to 2019. Patients with lumbar spinal stenosis had the highest incidence of postoperative SSI (2.39%, P < 0.001). There was also a significant difference for the number of SSI cases among different surgeons. CONCLUSION: Based on a large population analysis, Gram-negative bacteria were the most common pathogen in postoperative SSI after lumbar spinal surgery. And patients with lumbar spinal stenosis had the highest incidence of SSI. Increasing the intervention of Gram-negative may be an important step to reduce the postoperative SSI after lumbar spinal surgery.

Long disease-free interval diminishes the prognostic value of primary tumor stage for patients with colorectal cancer liver metastases.

BACKGROUND: It is assumed that the impact of primary tumor stage (PTS) on prognosis gradually weakens with increasing disease-free interval (DFI) from colorectal cancer resection to liver metastases. METHODS: Data from 733 patients undergoing hepatectomy in the Hepato-pancreato-biliary Surgery Department I of Peking University Cancer Hospital were retrospectively analyzed. Early and late metastases were defined as DFI ≤ and >12 months, respectively. RESULTS: In early metastases group, patients with T4 stage had a significantly worse recurrence-free survival (RFS) and overall survival (OS) than those with T1-3 stage (P = 0.002 and P < 0.001, respectively). Patients with N1-2 stage disease also demonstrated a worse RFS and OS than those with N0 stage (P = 0.006 and P = 0.007, respectively). In late metastases group, patients with T4 and T1-3 stages as well as patients with N1-2 and N0 stages, had comparable RFS (P = 0.395 and P = 0.996, respectively) and OS (P = 0.387 and P = 0.684, respectively). T and N stages were independent prognostic predictors only in patients with early metastases. CONCLUSION: The impact of PTS on prognosis is diminished with increasing DFI and limited only to patients with early metastases.

Ultra-broadband supercontinuum covering a spectrum from visible to mid-infrared generated by high-power and ultrashort noise-like pulses.

To facilitate a fiber-based supercontinuum generation system, single-mode fibers with different cutoff wavelengths are introduced to serve as shortpass filters to replace conventional reflective or transmissive filters. Meanwhile, an ytterbium-doped fiber amplifier is adopted to amplify the filtrated pulses, scaling their average power to the watt level up to 4.33 W. Through this approach, ultrashort high-power laser pulses of 1.56 µm and 1.06 µm wavelengths, which are commonly used in optical communications and industrial applications, can be generated by this single system. Furthermore, it is found that the noise-like pulses still maintain their temporal features, even after they undergo multiple optical processes including amplification, supercontinuum generation, and filtration. After that, the generated pulses at 1.06 µm were launched into a photonic crystal fiber to generate a supercontinuum of 1.85 W covering a spectral range from 560 nm in the visible region to 3.5 µm in the mid-infrared region. This is one of the widest records of spectrum in broadband supercontinuum generation.

Preoperative CA19-9: a competitive predictor of recurrence in patients with colorectal cancer liver metastases after hepatectomy.

PURPOSE: The role of preoperative carbohydrate antigen 19-9 (CA19-9) in colorectal cancer liver metastases (CRLM) patients is still unclear. The present study aimed to explore the prognostic significance of preoperative CA19-9 in those patients. METHODS: A total of 691 CRLM patients were included in this study. X-tile analyses were performed to determine the optimal cut-off values of CA19-9 and carcinoembryonic antigen (CEA). Prognostic predictors were identified by multivariate analyses. RESULTS: The optimal cut-off values of CA19-9 and CEA for 5-year recurrence-free survival (RFS) were 35.24 U/ml and 20.4 ng/ml, respectively. Patients with high-level CA19-9 had significantly worse RFS and overall survival (OS) than those with low-level CA19-9 (P = 0.001 and P = 0.002, respectively). In addition, patients with high-level CA19-9 had poor RFS and OS (P = 0.028 and P = 0.011, respectively) at low-level CEA. Multivariate analyses confirmed that preoperative CA19-9 was an independent predictor for RFS (hazard ratio [HR] 1.295; 95% confidence interval [CI] 1.043-1.607; P = 0.019) but not for OS (HR 1.213; 95% CI 0.902-1.631; P = 0.201). CONCLUSION: CA19-9 is a promising predictor of recurrence for CRLM patients undergoing hepatectomy, and an effective supplement for patients with low-level CEA.

Recurrent colorectal liver metastasis patients could benefit from repeat hepatic resection.

BACKGROUND: Local treatment remains the best option for recurrent colorectal liver metastasis (CRLM). The current study aimed to investigate predictive factors of survival outcomes and select candidates for local treatment for CRLM at first recurrence. METHODS: Data were collected retrospectively from CRLM patients who underwent hepatic resection and developed first recurrence between 2000 and 2019 at our institution.A nomogram predicting overall survival was established based on a multivariable Cox model of clinicopathologic factors. The predictive accuracy and discriminative ability of the nomogram were determined by the concordance index and calibration curve. RESULTS: Among 867 patients who underwent curative hepatic resection, 549 patients developed recurrence. Three hundred patients were evaluated and had resectable and liver-limited disease. Among them, repeat liver resection and percutaneous radiofrequency ablation were performed in 88 and 85 patients, respectively. The other 127 patients received only systemic chemotherapy. Multivariable analysis identified primary lymph node positivity, tumor size > 3 cm, early recurrence, RAS gene mutation and no local treatment as independent risk factors for survival outcomes. Integrating these five variables, the nomogram presented a good concordance index of 0.707. Compared with patients who received only systemic chemotherapy, radical local treatment did not significantly improve survival outcomes (median OS: 21 vs. 15 months, p = 0.126) in the high-risk group (total score ≥ 13). CONCLUSION: Radical local treatment improved the survival of recurrent CRLM patients. The proposed model facilitates personalized assessments of prognosis for patients who develop first recurrence in the liver.

Linewidth characteristics of period-one dynamics induced by optically injected semiconductor lasers.

Period-one (P1) nonlinear dynamics of optically injected semiconductor lasers exhibit periodic intensity fluctuations with operating frequencies that are tunable in the micro/millimeter-wave range. Through numerical experiments, the characteristics of the microwave linewidth of the P1 oscillation and the linewidths of its optical frequency components due to intrinsic laser noise sources are investigated. The field noise and carrier noise of the master and slave lasers are systematically considered. The contribution of the field noise of the master laser is significant; it considerably broadens the microwave linewidth of the P1 oscillation. When the operating conditions in the regions of high microwave power are properly adjusted, the microwave linewidth of the P1 oscillation becomes narrower than the free-running optical linewidths of the master and slave lasers. Regions with low sensitivity to time-dependent fluctuations in an operating parameter show reduced microwave linewidth of the P1 oscillation.

Aurora-B knockdown inhibits osteosarcoma metastasis by inducing autophagy via the mTOR/ULK1 pathway.

BACKGROUND: Autophagy plays an essential role in metastasis of malignancies. Although our studies showed that Aurora-B facilitate pulmonary metastasis in OS, the mechanism of Aurora-B kinase on autophagy and metastasis in OS has not been explored. METHODS: Clinical-pathological parameters and follow-up information was collected in OS patients. Immunohistochemical staining was performed to detect Aurora-B and LC3 protein in OS tissues. Short hairpin RNA transfection was used to silence Aurora-B in OS cells. Real-time quantitative PCR (RT-qPCR) was performed to detect Aurora-B mRNA expression in OS cells. Aurora-B and autophagy related protein were measured by Western blot. Transmission electron microscopy and laser scanning confocal microscopy were performed to observe the formation of autophagosomes and autolysosomes. Migratory and invasive ability of OS cells were measured by Wound healing and transwell assays. Orthotopic xenograft model was used to evaluate the effect of autophagy mediated by Aurora-B inhibition on pulmonary metastasis of OS. RESULTS: The elevated expression of Aurora-B protein in OS tissues negatively associated with the overall survival of OS patients. Further investigation has found that Aurora-B expression was negatively correlative with autophagy related protein LC3 in OS patient tissues. Knockdown Aurora-B stimulates autophagy and inhibits migratory and invasive ability of OS cells. Mechanistically, Aurora-B knockdown suppressed the mTOR/ULK1 signaling pathway and reactivation of the mTOR/ULK1 pathway decreased autophagy level. Furthermore, the inhibition effect of silencing Aurora-B on migration and invasion of OS was reversed by chloroquine and mTOR activator in vitro and vivo. CONCLUSIONS: Our results suggest that silencing of Aurora-B stimulate autophagy via decreasing mTOR/ULK1 and result in inhibiting OS metastasis. Targeted Aurora-B/mTOR/ULK1 pathway may be a promising treatment strategy for OS patients.

Use of Blood Lipid Indicators as a Screening Tool of Insulin Resistance among Individuals in Low-Income Country Sides of China: A Multiethnic Region Study.

OBJECTIVE: This study is aimed at evaluating the diagnostic value of blood lipid indicators (BLIs) for insulin resistance (IR) among major ethnic groups in Xinjiang, China, to identify the most valuable indicators and appropriate cut-off points for each ethnic group and to lay the foundation for the early detection, diagnosis, and treatment of metabolic diseases in remote rural areas. METHODS: Overall, 418 Uygurs, 331 Kazakhs, and 220 Hans were randomly included in our study. The homeostasis model assessment was the gold standard for identifying IR. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value, and the nomogram was utilized to analyze the predictive value. The size of the area under the curve (AUC) reflected the accuracy of screening and prediction. RESULTS: Differences in races were observed in terms of IR and BLIs, and the Kazakhs had the highest IR level at 5.27 mmol/L. The correlation between IR and BLIs differed among the three races. For the Kazakhs and Hans, all BLIs, except total cholesterol (TC), were correlated to IR. However, for the Uygurs, only the triglyceride (TG) level, TG/high-density lipoprotein cholesterol (HDL-C) ratio, and TC/HDL-C ratio were associated with IR. After further adjustment of confounding factors, these indicators were still correlated to IR. BLIs that independently correlated to IR in the three nationalities had a certain diagnostic value for IR. In terms of the AUC size, the TG level was the highest in Uygurs, the TG/HDL-C ratio was the highest for Kazakhs and Hans, and the corresponding best cut-off points for IR were 1.515, 1.230, and 1.495 mmol/L, respectively. In addition, for each race, when the indicators with a certain diagnostic value were combined, the diagnostic value for IR was higher. CONCLUSION: BLIs had a certain diagnostic value for IR and could be used as a screening tool for IR among Uygurs, Kazakhs, and Hans in Xinjiang. These findings are extremely important for the prevention and treatment of IR and metabolic diseases in remote rural areas.

Neuron-specific enolase, histopathological types, and age as risk factors for bone metastases in lung cancer.

Lung cancer is a malignant tumor with high metastatic ability and bone is the most common site of distant metastasis of it. However, the independent risk factors for bone metastases of lung cancer remain largely to be elucidated. Here, we conducted a retrospective study to evaluate the correlation between clinical-pathological parameters, serum levels of neuron-specific enolase and CYFRA21-1, and bone metastases in lung cancer patients. The results revealed that patients with bone metastases were younger than those without metastases. Adenocarcinoma was the most frequent type of histopathology in patients with bone metastases. And the incidence of bone metastasis in patients with adenocarcinoma was significantly higher than those with other histopathological subtypes ( p < 0.001). Furthermore, the serum concentration of neuron-specific enolase was significantly higher in patients with bone lesions than those without bone metastases. Multivariate logistic regression analysis showed that patients' age (odds ratio = 1.024, p < 0.001), concentrations of neuron-specific enolase (odds ratio = 1.212, p = 0.004), and histopathological types (odds ratio = 0.995, p = 0.001) were the independent risk factors for bone metastases in patients with lung cancer. Thus, physicians should pay attention to these factors in order to identify bone metastasis earlier while patient was primarily diagnosed as having lung cancer.

Cytokines Interleukin 4 (IL-4) and Interleukin 10 (IL-10) Gene Polymorphisms as Potential Host Susceptibility Factors in Virus-Induced Encephalitis.

BACKGROUND This study aimed to analyze and explore the relationship between the cytokines IL-4 and IL-10 in relation to gene polymorphism and their respective effects on the susceptibility to virus-induced encephalitis. MATERIAL AND METHODS From January 2012 to June 2013, 112 patients with virus-induced encephalitis (the case group and 109 healthy individuals (the control group) were recruited for the purposes of this study. The functional variations that IL-4 and IL-10 genes exhibit were detected through the use of a function analysis and selection tool for single-nucleotide polymorphisms (FASTSNP). The genotypes of IL-4 were rs2227283 and IL-4 rs2227288, and the genotypes of IL-10 were rs1800871 and IL-10 rs1800872. These genotypes were respectively assessed using direct sequencing. RESULTS IL-4 rs2227283 and IL-10 rs1800871 have no correlation in with risk of virus-induced encephalitis (both P>0.05) GA and AA genotypes were related to IL-4 rs2227288 and GT, while TT and GT + TT genotypes were related to IL-10 rs1800872. These were highlighted as being risk factors in virus-induced encephalitis (all P<0.05). However, the duration of fever, white blood cell (WBC) count, C-reactive protein (CRP), neutrophils, and lymphocytes and monocytes of virus-induced encephalitis patients with IL-4 rs2227288 and IL-10 rs1800872 all displayed significant differences (all P<0.05). Frequencies of GAGT and CAGT haplotypes were evaluated and deemed to be of statistical significance and subsequently were highlighted as being risk factors in virus-induced encephalitis (all P<0.05). CONCLUSIONS IL-4 rs2227288 and IL-10 rs1800872 may contribute to an increased risk for virus-induced encephalitis. Through use of direct sequencing, we showed that genotypes of IL-4 rs2227288 and IL-10 rs1800872 may have particular host susceptibility to virus-induced encephalitis.