Flavokawain C inhibits glucose metabolism and tumor angiogenesis in nasopharyngeal carcinoma by targeting the HSP90B1/STAT3/HK2 signaling axis.

OBJECTIVE: Over the past decade, heat shock protein 90 (HSP90) inhibitors have emerged as promising anticancer drugs in solid and hematological malignancies. Flavokawain C (FKC) is a naturally occurring chalcone that has been found to exert considerable anti-tumor efficacy by targeting multiple molecular pathways. However, the efficacy of FKC has not been studied in nasopharyngeal carcinoma (NPC). Metabolic abnormalities and uncontrolled angiogenesis are two important features of malignant tumors, and the occurrence of these two events may involve the regulation of HSP90B1. Therefore, this study aimed to explore the effects of FKC on NPC proliferation, glycolysis, and angiogenesis by regulating HSP90B1 and the underlying molecular regulatory mechanisms. METHODS: HSP90B1 expression was analyzed in NPC tissues and its relationship with patient's prognosis was further identified. Afterward, the effects of HSP90B1 on proliferation, apoptosis, glycolysis, and angiogenesis in NPC were studied by loss-of-function assays. Next, the interaction of FKC, HSP90B1, and epidermal growth factor receptor (EGFR) was evaluated. Then, in vitro experiments were designed to analyze the effect of FKC treatment on NPC cells. Finally, in vivo experiments were allowed to investigate whether FKC treatment regulates proliferation, glycolysis, and angiogenesis of NPC cells by HSP90B1/EGFR pathway. RESULTS: HSP90B1 was highly expressed in NPC tissues and was identified as a poor prognostic factor in NPC. At the same time, knockdown of HSP90B1 can inhibit the proliferation of NPC cells, trigger apoptosis, and reduce glycolysis and angiogenesis. Mechanistically, FKC affects downstream EGFR phosphorylation by regulating HSP90B1, thereby regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. FKC treatment inhibited the proliferation, glycolysis, and angiogenesis of NPC cells, which was reversed by introducing overexpression of HSP90B1. In addition, FKC can affect NPC tumor growth and metastasis in vivo by regulating the HSP90B1/EGFR pathway. CONCLUSION: Collectively, FKC inhibits glucose metabolism and tumor angiogenesis in NPC by targeting the HSP90B1/EGFR/PI3K/Akt/mTOR signaling axis.

Label-free colorimetric detection platform based on catalytic hairpin self-assembly and G-quadruplex/hemin DNAzyme for comprehensive biomarker profiling.

The expression level of human apurinic/apyrimidinic endonuclease 1 (APE1) is closely associated with the onset of various diseases, establishing it as a crucial clinical biomarker and a target in anti-cancer efforts. This study accomplished colorimetric and visual detection of APE1 by harnessing its endonuclease activity through catalytic hairpin self-assembly (CHA) and G-quadruplex/hemin DNAzyme. Optimization of the freedom degrees of the G-rich sequence significantly improved the detection performance of the strategy by influencing DNAzyme formation. Additionally, we replaced the signal reporting system with a molecular beacon to develop a fluorescence detection strategy, which served as an extension of the signal amplification system for validation and signal readout. The fluorescent probe method achieved a detection limit of 3.37 × 10-4 U/mL, while the colorimetric method yielded a detection limit of 6.5 × 10-3 U/mL, with a linear range spanning from 0.01 to 0.25 U/mL. Subsequently, the colorimetric approach effectively assessed APE1 activity in biological samples and facilitated the screening of APE1 activity inhibitors. Furthermore, this CHA/G-quadruplex/hemin DNAzyme strategy was adapted for the colorimetric detection of adenosine, showcasing its broad applicability across various biomarkers. The developed colorimetric analytical strategy represents a pivotal biosensing platform for diagnosing and treating diseases.

[Comparation on the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old].

OBJECTIVE: To compare the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old. METHODS: A prospective study was conducted. The febrile infants with less than 90 days old hospitalized in the department of pediatrics of Xuzhou Central Hospital from August 2019 to November 2021 were enrolled. The basic data of the infants were recorded. The infants with high risk or low risk of bacterial infection was evaluated by the step-by-step approach and the lab-score method, respectively. The step-by-step approach was based on clinical manifestations, age, blood neutrophil absolute value or C-reactive protein (CRP), urine white blood cells, blood venous blood procalcitonin (PCT) or interleukin-6 (IL-6) to gradually assess the high risk or low risk of bacterial infection in infants with fever. The lab-score method was based on the levels of laboratory indicators such as blood PCT, CRP and urine white blood cells, which were assigned different scores to evaluate the high risk or low risk of bacterial infection in febrile infants according to the total score. Using clinical bacterial culture results as the "gold standard", the negative predictive value (NPV), positive predictive value (PPV), negative likelihood ratio, positive likelihood ratio, sensitivity, specificity, and accuracy of the two methods were calculated. The consistency of the two evaluation methods was tested by Kappa. RESULTS: A total of 246 patients were enrolled in the analysis, and ultimately confirmed by bacterial culture as non-bacterial infections in 173 cases (70.3%), bacterial infection in 72 cases (29.3%), and unclear in 1 case (0.4%). There were 105 cases with low risk evaluated by the step-by-step approach, and 98 cases (93.3%) were ultimately confirmed as non-bacterial infection; 181 cases with low risk evaluated by the lab-score method, and 140 cases (77.4%) were ultimately confirmed as non-bacterial infection. The consistency of the two evaluation methods was poor (Kappa value = 0.253, P < 0.001). The ability of the step-by-step approach in early identification of non-bacterial infection in febrile infants with less than 90 days old was superior to the lab-score method (NPV: 0.933 vs. 0.773, negative likelihood ratio: 5.835 vs. 1.421), but the sensitivity of the former was lower than that of the latter (0.566 vs. 0.809). The ability of the step-by-step approach in early identification of bacterial infection in febrile infants with less than 90 days old was similar to the lab-score method (PPV: 0.464 vs. 0.484, positive likelihood ratio: 0.481 vs. 0.443), but the specificity of the former was higher than that of the latter (0.903 vs. 0.431). The overall accuracy of the step-by-step approach and the lab-score method was similar (66.5% vs. 69.8%). CONCLUSIONS: The ability of the step-by-step approach in early identification of non-bacterial infections in febrile infants with less than 90 days old is superior to the lab-score method.

Local Feature Matters: Cascade Multi-Scale MLP for Edge Segmentation of Medical Images.

Convolution-based methods are increasingly being used in medical image segmentation tasks and have shown good performance, but there are always problems in segmenting edge parts. These methods all have the following challenges: 1) Previous methods do not highlight the relationship between foreground and background in segmented regions, which is helpful for complex segmentation edges, 2) inductive bias of the convolutional layer leads to the fact that the extracted information is mainly the main part of the segmented area, and cannot effectively perceive complex edge changes and the aggregation of small and many segmented areas,3) different regions around the segmentation edge have different reference values for segmentation, and the ordering of these values is more important when the segmentation task is more complex. To address these challenges, we propose the CM-MLP framework on Multi-scale Feature Interaction (MFI) block and Axial Context Relation Encoder (ACRE) block for accurate segmentation of the edge of medical image. In the MFI block, we propose the Cascade Multi-scale MLP (Cascade MLP) to process all local information from the deeper layers of the network simultaneously, using Squeeze and Excitation in Space(SES) to process and redistribute the weights of all windows in Cascade MLP and utilize a cascade multi-scale mechanism to fuse discrete local information gradually. Then, multiple ACRE blocks cooperate with the deep supervision mechanism to gradually explore the boundary relationship between the foreground and the background, and gradually fine-tune the edges of the medical image. The segmentation accuracy (Dice) of our proposed CM-MLP framework reaches 96.98%, 96.67%, and 83.83% on three benchmark datasets: CVC-ClinicDB dataset, sub-Kvasir dataset, and our in-house dataset, respectively, which significantly outperform the state-of-the-art method. The source code and trained models will be available at https://github.com/ProgrammerHyy/CM-MLP.

Identification of an immune-related genes signature to predict risk of recurrence for patients with laryngeal squamous cell carcinoma.

OBJECTIVE: Numerous studies indicate that immune-related genes (IRGs) are closely related to tumorigenesis and tumor progression. We aimed to establish a robust IRGs-based signature to predict risk of recurrence for patients with laryngeal squamous cell carcinoma (LSCC). METHODS: Gene expression profiles were acquired to select differentially expressed IRGs (DEIRGs) between tumor and adjacent normal tissues. Functional enrichment analysis was performed to explore the biological roles of DEIRGs in LSCC. Univariate Cox analyses and LASSO regression model were used to construct a IRGs-based signature with the ability to predict recurrence for LSCC patients. RESULTS: A total of 272 DEIRGs were identified, of which 20 DEIRGs were significantly associated with recurrence-free survival (RFS). Subsequently, we constructed an eleven-IRGs signature that could classify patients into high-risk or low-risk groups in TCGA-LSCC training cohort. Patients in high-risk groups suffered from shorter RFS (log-rank p = 9.69E-06). Besides, the recurrence rate of high-risk group was significantly higher than that of low-risk group (41.1% vs. 13.7%; Fisher's exact test p < 0.001). The predictive performance was validated in an independent cohort (GSE27020, log-rank p = 1.43E-03). Person correlation analysis showed that the risk scores calculated by eleven-IRGs signature were significantly associated with filtrating immune cells. Furthermore, three immune checkpoint molecules were significantly over-expressed in the high-risk group. CONCLUSION: Our findings for the first time constructed a robust IRGs-based signature to precisely predict risk of recurrence and further provided a deeper understanding of IRGs regulatory mechanism in LSCC pathogenesis.

A multifunctional monolithic interfacial sensor based on gold nanoparticle.

The spatial and temporal uneven distribution of complex biochemical reactions creates the diversity of biological systems. And the microenvironment confers fine regulation of these reactions, a stunning example of which is liquid-liquid phase separation (LLPS). LLPS can form a separate compartment without the physical separation formed by conventional membrane structures, and the reactions within the interface have specific reaction dynamics. Inspired by this, we report an interfacial sensor based on gold nanoparticles showing that interfacial factors have similar properties operating in natural biological environments and sensors. It repels molecules outside the interface and adjusts the DNA conformation within the interface to produce unique dynamics. The sensor adopts a modular design, allowing functional modules assembled on a single nanoparticle to avoid complex designs. We demonstrate the functionality of logical operations, using apurinic/apyrimidinic endonuclease 1 and micro RNA as inputs, showing that the sensor has the ability and potential to become a multifunctional platform with clear interface nature.

Allosteric Nucleic Acid Enzyme: A Versatile Stimuli-Responsive Tool for Molecular Computing and Biosensing Nanodevices.

Allostery is a naturally occurring mechanism in which effector binding induces the modulation and fine control of a related biomolecule function. Deoxyribozyme (DNAzyme) with catalytic activity and substrate recognition ability is ideal to be regulated by allosteric strategies. However, the current regulations frequently confront various obstacles, such as severe activity decay, signal leakage, and limited effectors. In this work, a rational regulation strategy for developing versatile effectors-responsive allosteric nucleic acid enzyme (ANAzyme) by introducing an allosteric domain in response to diverse effectors is established. The enzyme-like activity of this re-engineered ANAzyme can be modulated in a more predictable and fine way compared with the previous DNAzyme regulation strategies. Based on the allosteric strategy, the construction of allosterically coregulatory nanodevices and a series of basic logic gates and logic circuits are achieved, demonstrating that the proposed ANAzyme-regulated strategy showed great potential in molecular computing. Given these facts, the rational design of ANAzyme with the allosteric domain presented here can expand the available toolbox to develop a variety of stimuli-responsive allosteric DNA materials, including molecular machines, computing systems, biosensing platforms, and gene-silencing tools.

Realization of high-dynamic-range broadband magnetic-field sensing with ensemble nitrogen-vacancy centers in diamond.

We present a new magnetometry method integrating an ensemble of nitrogen-vacancy (NV) centers in a single-crystal diamond with an extended dynamic range for monitoring a fast changing magnetic-field. The NV-center spin resonance frequency is tracked using a closed-loop frequency locked technique with fast frequency hopping to achieve a 10 kHz measurement bandwidth, thus allowing for the detection of fast changing magnetic signals up to 0.723 T/s. This technique exhibits an extended dynamic range subjected to the working bandwidth of the microwave source. This extended dynamic range can reach up to 4.3 mT, which is 86 times broader than the intrinsic dynamic range. The essential components for NV spin control and signal processing, such as signal generation, microwave frequency control, data processing, and readout, are integrated in a board-level system. With this platform, we demonstrate a broadband magnetometry with an optimized sensitivity of 4.2 nT Hz-1/2. This magnetometry method has the potential to be implemented in a multichannel frequency locked vector magnetometer suitable for a wide range of practical applications, such as magnetocardiography and high-precision current sensors.

Microfabricated sensor device for CW and pulsed laser power measurements.

On-line measurement is a trend of development toward laser-based applications. We present a fiber-integrated force sensor device for laser power measurement with both CW mode and pulse mode based on laser radiometric heat and radiation force sensing simultaneously. The sensor device is fabricated using a standard microfabrication process. Laser intensity is determined through the displacement of a movable mirror measured by an integrated Fabry-Perot interferometer. Compared with the performance of the device in the ambient condition, a non-linearity error of 0.02% and measurement uncertainty of 2.06% is observed in the quasi-vacuum condition for CW laser illumination. This device can measure a CW laser power with a 46.4 µW/Hz1/2 noise floor and a minimum detection limit of 0.125 mW. For a pulsed laser, a non-linearity error of 0.37% and measurement uncertainty of 2.08% is achieved with a noise floor of 1.3 µJ/Hz1/2 and a minimum detection limit of 3 µJ.

Tragus Perichondrium-Cartilage Island and Temporalis Muscle Fascia for Repairing Tympanic Membrane Perforation Under the Otoendoscope: A Randomized Controlled Trial.

OBJECTIVE: To compare the clinical effects of repairing tympanic membrane perforation (TMP) with the tragus perichondrium-cartilage island and temporalis muscle fascia (TMF) under the otoendoscope. METHODS: The clinical data of 84 patients (total 84 ears) with TMP repaired by otoendoscopy from March 2019 to April 2021 were analyzed. The patients were randomly divided into the control group (n = 42, TMF repair) and the experimental group (n = 42, perichondrium-cartilage island repair). The intraoperative blood loss, operation time, length of hospital stay, success rate of the TMP repair, mean air-conducted sound, and air-bone gap before and after surgery were compared between the two groups. RESULTS: The mean air-bone gap and mean air-conducted hearing threshold in the experimental group were significantly lower after surgery at all frequencies than those of the control group (all P < .05). The reduction of the mean air-conducted hearing threshold in the experimental group was significantly higher than that of the control group (P < .001). The surgery time of the experimental group was significantly shorter than the control group (78.04 ± 2.23 vs. 84.27 ± 1.67 minutes, P < .001). The success rate of the TMP repair was 95.24% (40/42) in the experimental group and 92.86% (39/42) in the control group, indicating that there was no significant difference in the success rate of TMP repair between the two materials (risk ratio = 1.75; 95% confidence interval: .31-12.04; P = .71). CONCLUSION: Repairs with the tragus perichondrium-cartilage island have a short operation time, high healing rate, and more significant postoperative hearing improvement, which makes it a more effective method of TMP repair.

Proteomics analysis of cancer tissues identifies IGF2R as a potential therapeutic target in laryngeal carcinoma.

Background: Laryngeal cancer (LC) is a prevalent head and neck malignancy; however, the essential pathophysiological mechanism underlying its tumorigenesis and progression remains elusive. Due to the perduring scarcity of effective targeted drugs for laryngeal cancer, insights into the disease's pathophysiological mechanisms would substantially impact the treatment landscape of laryngeal cancer. Methods: To ensure quality consistency, 10 tumor and 9 non-tumor samples underwent proteomic analysis on a single mass spectrometer using a label-free technique. Subsequently, gene expression variations between laryngeal squamous cell carcinoma and normal tissues were analyzed using The Cancer Genome Atlas (TCGA) database. Immunohistochemical expressions of insulin-like growth factor 2 receptor (IGF2R), fibronectin (FN), vimentin, and α-smooth muscle actin (SMA) in LC tissues and normal tissues were determined. Results: In the tumor group, significant variations were detected for 433 upregulated and 61 downregulated proteins. Moreover, the heatmap revealed that the expressions of RNA translation-related proteins and proteins involved in RNA metabolism, such as IGF2R, tenascin C (TNC), periostin (POSTN), proteasome 26S subunit ATPase 4 (PSMC4), serpin family A member 3 (SERPINA3), heat shock protein family B (small) member 6 (HSPB6), osteoglycin (OGN), chaperonin containing TCP1 subunit 6A (CCT6A), and chaperonin containing TCP1 subunit 6B (CCT6B), were prominently elevated in the tumor group. Nonsense-mediated RNA decay (NMD), RNA translation, and protein stability were significantly altered in LC tumors. IGF2R was remarkably upregulated in LC tumors. In the TCGA database, the IGF2R mRNA level was significantly upregulated in LSCC tissues. Additionally, IGF2R mRNA expression was lowest in clinical grade 1 samples, with no significant difference between grades 2 and 3. In LSCC patients, a significant positive correlation between IGF2R expression and the stromal score was detected using the ESTIMATE algorithm to estimate the immune score, stromal score, and tumor purity in the tumor microenvironment. Lastly, immunohistochemical analysis revealed that IGF2R is overexpressed in LC. Conclusion: These results demonstrate the vital role of IGF2R in LC carcinogenesis and progression and may facilitate the identification of new therapeutic targets for the prevention and treatment of LC.

A structure change-induced fluorescent biosensor for uracil-DNA glycosylase activity detection based on the substrate preference of Lambda exonuclease.

As one of the initiating DNA glycosylases in the base excision repair pathway, Uracil-DNA glycosylase (UDG) plays a pivotal role in maintaining genomic integrity. The abnormal expression of UDG in the organism is highly relevant to multiple diseases. Thus, rapid and sensitive detection of UDG activity is essential to aid early clinical diagnosis and biomedical research. Here we developed a rapid, sensitive and selective biosensor for UDG activity detection based on the substrate preference of Lambda exonuclease (λ exo). The protruding end in the substrate produced by UDG could be digested at a markedly high rate by λ exo, generating a detectable fluorescence signal. This proposed strategy for UDG detection exhibited high selectivity and high sensitivity (0.0001 U/mL) in a short time. It has also been successfully applied to detect UDG in real biological samples and the screening of UDG inhibitors.

Risk Estimation of Infectious and Inflammatory Disorders in Hospitalized Patients With Acute Ischemic Stroke Using Clinical-Lab Nomogram.

Background: Infections after acute ischemic stroke are common and likely to complicate the clinical course and negatively affect patient outcomes. Despite the development of various risk factors and predictive models for infectious and inflammatory disorders (IAID) after stroke, more objective and easily obtainable predictors remain necessary. This study involves the development and validation of an accessible, accurate nomogram for predicting in-hospital IAID in patients with acute ischemic stroke (AIS). Methods: A retrospective cohort of 2,257 patients with AIS confirmed by neurological examination and radiography was assessed. The International Statistical Classification of Diseases and Health related Problem's definition was used for IAID. Data was obtained from two hospitals between January 2016 and March 2020. Results: The incidence of IAID was 19.8 and 20.8% in the derivation and validation cohorts, respectively. Using an absolute shrinkage and selection operator (LASSO) algorithm, four biochemical blood predictors and four clinical indicators were optimized from fifty-five features. Using a multivariable analysis, four predictors, namely age (adjusted odds ratio, 1.05; 95% confidence interval [CI], 1.038-1.062; p < 0.001), comatose state (28.033[4.706-536.403], p = 0.002), diabetes (0.417[0.27-0.649], p < 0.001), and congestive heart failure (CHF) (5.488[2.451-12.912], p < 0.001) were found to be risk factors for IAID. Furthermore, neutrophil, monocyte, hemoglobin, and high-sensitivity C-reactive protein were also found to be independently associated with IAID. Consequently, a reliable clinical-lab nomogram was constructed to predict IAID in our study (C-index value = 0.83). The results of the ROC analysis were consistent with the calibration curve analysis. The decision curve demonstrated that the clinical-lab model added more net benefit than either the lab-score or clinical models in differentiating IAID from AIS patients. Conclusions: The clinical-lab nomogram predicted IAID in patients with acute ischemic stroke. As a result, this nomogram can be used for identification of high-risk patients and to further guide clinical decisions.

Endonuclease IV-Regulated DNAzyme Motor for Universal Single-nucleotide Variation Discrimination.

Single-nucleotide variation (SNV) detection plays significant roles in disease diagnosis and treatment. Generally, auxiliary probe, restricted design rules, complicated detection system, and repeated experimental parameter optimization are needed to obtain satisfactory tradeoff between sensitivity and selectivity for SNV discrimination, especially when different mutant sites need to be distinguished. To overcome these limitations, we developed a universal, straightforward, and relatively cheap SNV discrimination strategy, which simultaneously possessed high sensitivity and selectivity. The excellent performance of this strategy was ascribed to the SNV discrimination property of endonuclease IV (Endo IV) and the different hydrolysis behavior between free deoxyribozyme (DNAzyme) and the trapped DNAzyme to the substrates modified on gold nanoparticles (AuNPs). When Endo IV recognized the mutant-type target (MT), free DNAzyme was released from the probe, and the DNAzyme motor was activated with the help of cofactor Mn2+ to generate an amplified fluorescence signal. On the contrary, the wild-type target (WT) could not effectively trigger the DNAzyme motor. Moreover, for different SNV types, the corresponding probe could be designed by simply changing the sequence hybridized with the target and retaining the DNAzyme sequence. Thus, the fluorescence signal generation system does not need to change for different SNV targets. Five clinical-related SNVs were determined with the limit of detection (LOD) ranging from 0.01 to 0.05%, which exhibited competitive sensitivity over existing SNV detection methods. This strategy provided another insight into the properties of Endo IV and DNAzyme, expanded the applications of DNAzyme motor, and has great potential to be used for precision medicine.

Discovery of an orally active antitumor agent that induces apoptosis and suppresses EMT through heat shock protein 90 inhibition.

Background Nowadays, lung cancer seriously affects human health in the world. Therefore, it is of great significance to develop effective anti-lung cancer drugs. Methods In this work, chalcone derivative HYQ97 was designed via a molecular hybridization strategy. It was synthesized by the cycloaddition in the presence of sodium ascorbate under mild conditions. Lung cancer cell lines were cultured to investigate its antitumor effects in vitro and in vivo. Results HYQ97 inhibited the proliferation of lung cancer cell lines. Specifically, its IC50 value against lung cancer A549 cells was 74.26 nM. It could inhibit heat shock protein 90 (Hsp90) and degrade its client proteins in a dose-dependent manner. Furthermore, HYQ97 suppressed the epithelial mesenchymal transition process and induced apoptosis of A549 cells. Importantly, HYQ97 also had significant inhibitory effects on tumor growth in vivo. Conclusions Chalcone derivative HYQ97 is a promising candidate for lung cancer treatment.

A sensitive biomolecules detection device with catalytic hairpin assembly and cationic conjugated polymer-assisted dual signal amplification strategy.

A simple, sensitive, selective, and enzyme-free homogeneous fluorescent biosensing device for DNA and protein detection is fabricated based on catalytic hairpin assembly (CHA), cationic conjugated polymer (CCP), and graphene oxide (GO). In this biosensing device, CCP together with CHA, provides dual signal amplification, and GO suppresses the background when the target is absent. Thus, this CHA/CCP/GO-based biosensor shows improved sensitivity compared with conventional CHA-based biosensors. In the biosensor, two 6-carboxyfluorescein (FAM)-labeled hairpin DNA probes (H1 and H2) are designed, and in the initial state, they could absorb on the surface of GO, leading the system to produce a low background fluorescence signal. When the target DNA appears, it continually catalyzes the formation of H1-H2 double-stranded DNA (dsDNA) complex by CHA reaction, which could be regarded as the first-step amplification. At the same time, the H1-H2 dsDNA complex departures from the surface of GO and interacts with CCP through electrostatic interaction. Then, CCP provides the second-step amplification due to its high fluorescence resonance energy transfer (FRET) efficiency from CCP to FAM. The limit of detection (LOD) and the limit of quantification (LOQ) for the target DNA could reach 32 pM and 1 nM, respectively. The linear range was from 0.1 to 40 nM, and relative standard deviation (RSD) for the points on the calibration curve ranged from 2.8% to 13.9%. This strategy could also be applied to protein detection potentially by integrating the aptamer of the target protein into the hairpin DNA. As proof of concept, thrombin was detected, and the LOD and LOQ was 11 pM and 33 pM, respectively. The linear range was from 3 to 54 nM, and RSD ranged from 3.3% to 10.4%. It showed good selectivity for thrombin compared to equal concentrations of interferences. It was also applied to quantify the thrombin (5, 10, 20 nM) in 1% spiked human serum, which showed satisfying recovery in the range of 94.7 ± 5.3 to 103.7 ± 4.9%.

Inflammatory cytokines tumor necrosis factor-α, interleukin-8 and sleep monitoring in patients with obstructive sleep apnea syndrome.

The present study investigated the changes of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and sleep ability in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 684 patients who were admitted to Xuzhou Central Hospital between June 2012 and June 2016 were enrolled to serve as the experimental group and 192 healthy subjects were selected as the control group. Polysomnography was performed on both groups, and serum TNF-α and IL-8 levels were measured by ELISA. Pearson's correlation analysis was used to analyze correlations between factors. Compared with control group, the levels of TNF-α and IL-8, the morning systolic and diastolic pressure in OSAHS group were significantly higher (P<0.01). Furthermore, the mean oxygen saturation (MSaO2) and lowest oxygen saturation (LSaO2) of the OSAHS group were significantly lower compared with those in control group (P<0.01). Results also indicated that TNF-α was positively correlated with apnea-hypopnea index (AHI), morning systolic and diastolic pressure (r=0.621, 0.464, 0.539; P<0.05), and negatively correlated with MSaO2 and LSaO2 (r=-0.526, -0.466; P<0.05). Notably, IL-8 was positively correlated with AHI, morning systolic and diastolic pressure (r=0.337, 0.413 and 0.629; P<0.05), and negatively correlated with MSaO2 and LSaO2 (r=-0.329 and -0.417; P<0.05). Therefore, it was concluded that TNF-α and IL-8 may be involved in the occurrence and development of OSAHS, are closely related to OSAHS and may be important risk factors for cardiovascular disease in patients with OSAHS. The present findings suggest that TNF-α and IL-8 can be used to assess the degree of OSAHS.

The assistance of coblation in arytenoidectomy for vocal cord paralysis.

BACKGROUND: There are many causes for vocal cord paralysis, which can cause difficulty in breathing in serious cases. The common surgical methods for solving vocal cord paralysis include laryngeal splitting or laser surgery, but there are limitations. Plasma radiofrequency ablation is a new treatment with good achievements in clinical applications. OBJECTIVE: To investigate the effect of coblation-assisted arytenoidectomy (CSA) in the treatment of bilateral vocal cord paralysis (BVCP). METHODS: All patients had undergone preoperative electrolaryngoscopic examination of the glottidis rima; electronic laryngoscopy can assess the width of the glottis. The purpose of preoperative electronic laryngoscopic evaluation is to assess the width of the glottis, and arytenoid cartilage movement. Unilateral arytenoid cartilage and a section of the vocal cords were removed in all cases. RESULTS: Of the 14 patients, 13 were successfully extubated after CSA; 1 patient could not be extubated and underwent a second CSA of the contralateral arytenoid cartilage, after which extubation was achieved. All patients were continuously followed up (6 months to 2 years), and all achieved satisfactory results. CONCLUSIONS AND SIGNIFICANCE: CSA can effectively relieve post-CSA dyspnea in patients with BVCP. More patients underwent tracheal cannula extubation after tracheotomy compared with other surgeries.

Proteomic analysis of chondromodulin-I-induced differentiation of mesenchymal stem cells into chondrocytes.

To identify novel proteins that might help clarify the molecular mechanisms underlying chondromodulin-I (ChM-I) induction of mesenchymal stem cells (MSCs) differentiate into chondrocytes. MSCs are triggered to differentiate into chondrocytes, which are recognized as important factors in cartilage tissue engineering. ChM-I is a glycoprotein that stimulates the growth of chondrocytes and inhibits angiogenesis in vitro. In this study, the proteomic approach was used to evaluate protein changes between undifferentiated MSCs and ChM-I-transfected MSCs. The expression of the protein spots was analyzed using two-dimensional gel electrophoresis. Then, 14 protein spots were identified between MSCs and ChM-I-transfected MSCs. 309 proteins were identified using mass spectrometry (MS). The differentially regulated proteins were categorized and annotated using Protein Analysis Through Evolutionary Relationships (PANTHER) analysis with the aid of the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. These proteins are included in a variety of metabolic pathways and signal transduction pathways, such as focal adhesion, glycolysis, actin cytoskeleton regulation, and ribosome. These results demonstrate novel information about the molecular mechanism by which ChM-I induce MSCs to differentiate into chondrocytes. These results also provide a solid foundation for the development of tissue-engineered cartilage.

Chondrogenic differentiation of ChM-I gene transfected rat bone marrow-derived mesenchymal stem cells on 3-dimensional poly (L-lactic acid) scaffold for cartilage engineering.

We have explored the role of Chondromodulin-I (ChM-I) in chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) in 3-dimensional (3D) scaffold for cartilage tissue engineering. BMSCs of Sprague Dawley (SD) rats were cultured on poly-(L-lactic acid) [PLLA] scaffolds with different pore sizes (80-200 µm, 200-450 µm) with or without surface modification by chitosan. Cell viability, proliferation, and morphology were measured using confocal microscope and the CCK-8 method. Untransfected BMSCs, BMSCs expressing pcDNA3.1(+), BMSCs expressing plasmid pcDNA3.1 (+)/ChM-I were cultured on 3D scaffolds in standard growth medium or transforming growth factor-ß1 (TGF-ß1) supplemented chondrogenic induction medium in vitro for 3 weeks and the expression of collagen type II was determined. Cell-scaffolds constructs were implanted subcutaneously for 3 months in vivo. BMSCs had a higher viability and proliferation in PLLA scaffolds of pore size 200-450 µm than that of 80-200 µm, and surface modification with chitosan did not enhance cell attachment. The ChM-I gene enhanced chondrogenesis and increased collagen type II synthesis. Immunohistochemistry from in vivo study showed enhanced cartilage regeneration in BMSCs expressing pcDNA3.1 (+)/ChM-I on 3D PLLA scaffolds. It also demonstrated that TGF-ß1 might promote chondrogenesis of rat BMSCs by synergizing with the ChM-I gene. ChM-I could be beneficial to future applications in cartilage repair.