Search

Background: The current treatments for adjacent two-segment cervical spondylotic myelopathy (CSM) include two-segment anterior cervical discectomy and fusion (ACDF) and single-segment anterior cervical corpectomy and fusion (ACCF). Long-term follow-up has demonstrated that both procedures have complications such as reduced cervical mobility, accelerated degeneration of adjacent segments and loosening of internal fixation screws. The purpose of this study is to demonstrate the feasibility, safety, and efficacy of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) via one vertebra with two bony channels for the treatment of adjacent two-segment CSM and to present our surgical experience., Methods: Anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) via one vertebra with two bony channels was performed for 12 patients with adjacent two-segment CSM with follow-up care for at least 12 months. The Visual analog scale (VAS) and the Japanese Orthopedic Association Score (JOA) were recorded, and modified Macnab criteria were used to evaluate the treatment excellence rate. Radiological examinations, including X-ray, computed tomography (CT) and magnetic resonance imaging (MRI), were used to evaluate spinal cord decompression, intervertebral stability and healing of the bony channel., Results: All 12 patients completed the operation successfully. No postoperative complications, such as dysphagia, Horner's syndrome, or laryngeal recurrent nerve palsy, were found. The postoperative VAS and JOA scores were significantly improved compared with those before surgery(P < 0.001). According to the modified Macnab criteria, the clinical outcome was excellent in 8 cases, good in 3 cases and fine in 1 case at the final follow-up and the excellent and good rate was 91.7%. Postoperative and follow-up imaging showed significant spinal cord decompression, well-healed bony channels and no cervical instability., Conclusions: This study is the first report of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord via one vertebra with two bony channels. This procedure has the advantages of less trauma, faster recovery, fewer complications and no need to implant internal fixators. This is a minimally invasive, feasible and safe surgical procedure for patients with adjacent two-segment CSM., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Nuclear magnetic resonance studies of many physiologically important proteins have long been impeded by the necessity to express such proteins in isotope-labeled form in higher eukaryotic cells and the concomitant high costs of providing isotope-labeled amino acids in the growth medium. Economical routes use isotope-labeled yeast or algae extracts but still require expensive isotope-labeled glutamine. Here, we have systematically quantified the effect of 15 N 2 -glutamine on the expression and isotope labeling of different proteins in insect cells. Sufficient levels of glutamine in the medium increase the protein expression by four to five times relative to deprived conditions. 1 H- 15 N nuclear magnetic resonance spectroscopy shows that the 15 N atoms from 15 N 2 -glutamine are scrambled with surprisingly high (60-70%) efficiency into the three amino acids alanine, aspartate, and glutamate. This phenomenon gives direct evidence that the high energy demand of insect cells during baculovirus infection and concomitant heterologous protein expression is predominantly satisfied by glutamine feeding the tricarboxylic acid cycle. To overcome the high costs of supplementing isotope-labeled glutamine, we have developed a robust method for the large-scale synthesis of 15 N 2 -glutamine and partially deuterated 15 N 2 -glutamine-α,β,β-d 3 from inexpensive precursors. An application is shown for the effective large-scale expression of the isotope-labeled β 1 -adrenergic receptor using the synthesized 15 N 2 -glutamine-α,β,β-d 3 ., Competing Interests: Conflict of interest The authors declare no conflict of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate postoperative clinical outcomes and analyze influencing factors for patients with thymic epithelial tumors over 3 years after operation., Methods: Patients with thymic epithelial tumors (TETs) who underwent surgical treatment in the Department of Thoracic Surgery at Beijing Hospital from January 2011 to May 2019 were retrospectively enrolled in the study. Basic patient information, clinical, pathological, and perioperative data were collected. Patients were followed up by telephone interviews and outpatient records. Statistical analyses were performed using SPSS version 26.0., Results: A total of 242 patients (129 men, 113 women) with TETs were included in this study, of which 150 patients (62.0%) were combined with myasthenia gravis (MG) and 92 patients (38.0%) were not. 216 patients were successfully followed up and their complete information was available. The median follow-up period was 70.5 months (range, 2-137 months). The 3-year overall survival (OS) rate of the whole group was 93.9%, and the 5-year OS rate was 91.1%. The 3-year relapse-free survival (RFS) rate of the whole group was 92.2%, and the 5-year relapse-free survival rate was 89.8%. Multivariable COX regression analysis indicated that recurrence of thymoma was an independent risk factor for OS. Younger age, Masaoka-Koga stage III + IV, and TNM stage III + IV were independent risk factors for RFS. Multivariable COX regression analysis indicated that Masaoka-Koga staging III + IV, WHO type B + C were independent risk factors for postoperative improvement of MG. For patients with MG, the postoperative complete stable remission (CSR) rate was 30.5%. And the result of multivariable COX regression analysis showed that thymoma patients with MG with Osserman staging IIA + IIB + III + IV were not prone to achieving CSR. Compared with patients without MG, MG was more likely to develop in patients with WHO classification type B, and patients with myasthenia gravis were younger, with longer operative duration, and more likely to develop perioperative complications., Conclusions: The 5-year overall survival rate of patients with TETs was 91.1% in this study. Younger age and advanced stage were independent risk factors for RFS of patients with TETs, and recurrence of thymoma were independent risk factors for OS. In patients with MG, WHO classification type B and advanced stage were independent predictors of poor outcomes of MG treatment after thymectomy., (© 2023. The Author(s).)

Background: Disc herniation (DH) is a fragment of the disc nucleus that is pushed out of the annulus into the spinal canal due to a tear or rupture in the annulus. It is a common cause of lumbar and leg pains. Substantial advancements have been made to determine the cause of DH and to ensure accurate diagnosis, imaging, and treatment of this condition. Total endoscopic discectomy is an alternative surgical technique that is less invasive., Aim: To study the optimal approach for a total endoscopic discectomy and its influence on lumbar and leg function in DH patients., Methods: This prospective study enrolled 120 patients with lumbar DH who were treated in our hospital from February 2018 to January 2021. All patients were randomly divided into the following two groups: The observation group, comprising 62 patients who underwent surgery using the interlaminar approach, and the control group, comprising 58 patients who were operated through the foramina approach. The treatment effects, perioperative indicators, functional recovery, pain, and quality of life were compared between the two groups., Results: The treatment effect in the observation group (93.55%) was significantly better than that in the control group (77.59%). There was no difference in the operative time and intraoperative blood loss amount between the two groups ( P > 0.05). The hospitalization time of the observation group (4.34 ± 1.33 d) was significantly shorter than that of the control group (5.38 ± 1.57 days) ( P < 0.05). The Japanese Orthopaedic Association and Oswestry Disability Index scores decreased significantly in both groups after treatment, but the scores were lower in the observation group than in the control group. The visual analog scale scores of the lower back and legs of the two groups were significantly reduced after treatment, but scores were lower in the observation group (2.18 ± 0.88 in the lower back and 1.42 ± 0.50 in the leg) than in the control group (3.53 ± 0.50 in the lower back and 2.21 ± 0.52 in the leg). A short form of the Arthritis Impact Measurement Scales 2 measurement scale (AIMS2-SF) score and Barthel index of the lower back of the two groups increased significantly after treatment, with the observation group having a significantly higher AIMS2-SF score (95.16 ± 1.74) and Barthel index (97.29 ± 1.75) than the control group (84.95 ± 2.14 and 89.16 ± 2.71, respectively) ( P < 0.05)., Conclusion: Through total endoscopic discectomy with the interlaminar approach, the degree of pain in the waist and leg was reduced, and the lumbar function considerably recovered., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: TGF-β superfamily signaling is indispensable for bone homeostasis. However, the global expression profiles of all the genes that make up this signaling module in bone and bone-related diseases have not yet been well characterized., Methods: Transcriptomic datasets from human bone marrows, bone marrow-derived mesenchymal stem cells (MSCs) and MSCs of primary osteoporotic patients were used for expression profile analyses. Protein treatments, gene quantification, reporter assay and signaling dissection in MSC lines were used to clarify the interactive regulations and feedback mechanisms between TGF-β superfamily ligands and antagonists. Ingenuity Pathway Analysis was used for network construction., Results: We identified TGFB1 in the ligand group that carries out SMAD2/3 signaling and BMP8A, BMP8B and BMP2 in the ligand group that conducts SMAD1/5/8 signaling have relatively high expression levels in normal bone marrows and MSCs. Among 16 antagonist genes, the dominantly expressed TGF-β superfamily ligands induced only NOG, GREM1 and GREM2 via different SMAD pathways in MSCs. These induced antagonist proteins further showed distinct antagonisms to the treated ligands and thus would make up complicated negative feedback networks in bone. We further identified TGF-β superfamily signaling is enriched in MSCs of primary osteoporosis. Enhanced expression of the genes mediating TGF-β-mediated SMAD3 signaling and the genes encoding TGF-β superfamily antagonists served as significant features to osteoporosis., Conclusion: Our data for the first time unveiled the transcription landscape of all the genes that make up TGF-β superfamily signaling module in bone. The feedback mechanisms and regulatory network prediction of antagonists provided novel hints to treat osteoporosis. Video Abstract., (© 2022. The Author(s).)

Medical records scoring is important in a health care system. Artificial intelligence (AI) with projection word embeddings has been validated in its performance disease coding tasks, which maintain the vocabulary diversity of open internet databases and the medical terminology understanding of electronic health records (EHRs). We considered that an AI-enhanced system might be also applied to automatically score medical records. This study aimed to develop a series of deep learning models (DLMs) and validated their performance in medical records scoring task. We also analyzed the practical value of the best model. We used the admission medical records from the Tri-Services General Hospital during January 2016 to May 2020, which were scored by our visiting staffs with different levels from different departments. The medical records were scored ranged 0 to 10. All samples were divided into a training set ( n = 74,959) and testing set ( n = 152,730) based on time, which were used to train and validate the DLMs, respectively. The mean absolute error (MAE) was used to evaluate each DLM performance. In original AI medical record scoring, the predicted score by BERT architecture is closer to the actual reviewer score than the projection word embedding and LSTM architecture. The original MAE is 0.84 ± 0.27 using the BERT model, and the MAE is 1.00 ± 0.32 using the LSTM model. Linear mixed model can be used to improve the model performance, and the adjusted predicted score was closer compared to the original score. However, the project word embedding with the LSTM model (0.66 ± 0.39) provided better performance compared to BERT (0.70 ± 0.33) after linear mixed model enhancement ( p < 0.001). In addition to comparing different architectures to score the medical records, this study further uses a mixed linear model to successfully adjust the AI medical record score to make it closer to the actual physician's score.

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infection rates continue to rise. Screening guidelines have largely focused on sexually active female individuals and men who have sex with men populations. Health care system testing and infection rates, particularly among heterosexual male individuals, are poorly understood. Our aim was to evaluate CT and GC testing and prevalence among 12- to 24-year-old patients in an urban federally qualified health center system., Methods: This retrospective study analyzed electronic health record data from 2017 to 2019 in a large system of federally qualified health centers in Denver, CO. Abstracted data included demographics, sexual activity, sexual orientation, and laboratory results. χ2 Tests were used to evaluate differences between groups., Results: Of the 44,021 patients included, 37.6% were tested, 15.0% were positive for CT, and 3.4% were positive for GC. Heterosexual male patients had a testing rate of 22.8% and positivity rates of CT and GC at 13.1% and 3.0%, respectively. Among tested patients documented as not sexually active, 7.5% were positive for CT. Multiple or reinfections were detected in 29% of patients., Conclusions: This study shows low testing rates and high rates of CT and GC infections among all patients, including heterosexual male patients and those documented as not sexually active. Improved screening of these populations in the primary care setting may be key to combating the sexually transmitted disease epidemic., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no conflicts of interest to disclose. H.M.F. received salary support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under Award Number K23HD099925. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (Copyright © 2020 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Tracheal stenosis is able to lead to airway obstruction., Objective: To evaluate the efficacy and safety profile of Montgomery T-tube implantation in patients with tracheal stenosis., Methods: Fifty-two patients with tracheal stenosis diagnosed between 2016 and 2019 were included in this retrospective cohort study. The patients were divided into observation group ( n  = 25 cases) and control group ( n  = 27). The therapeutic effect, arterial blood gas analysis, arterial oxygen partial pressure (PaO 2 ), arterial carbon dioxide partial pressure (PaCO 2 ), shortness of breath score, airway diameter change, dyspnea score, quality of life, and safety were compared between the two groups before and after treatment., Results: The therapeutic effect of the observation group gained better results than that of the control group (84.00% vs. 62.96%). One week after operation, the pH value, SaO 2 , PaCO 2 , shortness of breath score, airway diameter change, dyspnea score, life quality, and incidence of postoperative complications in the observation group exerted better results as compared to the control group., Conclusion: The implantation of Montgomery T-tube has effective function in terms of improving the symptoms of dyspnea and the life quality of patients with safety profile in patients harboring tracheal stenosis., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Feng-Jie Wu et al.)

G protein-coupled receptors (GPCRs) use a series of conserved microswitches to transmit signals across the cell membrane via an allosteric network encompassing the ligand-binding site and the G protein-binding site. Crystal structures of GPCRs provide snapshots of their inactive and active states, but poorly describe the conformational dynamics of the allosteric network that underlies GPCR activation. Here, we analyzed the correlation between ligand binding and receptor conformation of the α 1A -adrenoreceptor, a GPCR that stimulates smooth muscle contraction in response to binding noradrenaline. NMR of [ 13 C ϵ H 3 ]methionine-labeled α 1A -adrenoreceptor variants, each exhibiting differing signaling capacities, revealed how different classes of ligands modulate the conformational equilibria of this receptor. [ 13 C ϵ H 3 ]Methionine residues near the microswitches exhibited distinct states that correlated with ligand efficacies, supporting a conformational selection mechanism. We propose that allosteric coupling among the microswitches controls the conformation of the α 1A -adrenoreceptor and underlies the mechanism of ligand modulation of GPCR signaling in cells., (© 2020 Wu et al.)

Objectives: The administration of androgen deprivation therapy (ADT) to patients with metastatic prostate cancer might be associated with some adverse effects such as anaemia; however, few studies have been performed in East Asian populations. This study aimed to investigate the association between ADT and iron-deficiency anaemia (IDA) among patients with prostate cancer in a population-based nationwide cohort., Design: Cohort study., Setting: Taiwan., Participants: Data for the cohort study were retrieved from the Taiwan National Health Insurance Research Database. Propensity score matching was used to select 7262 patients with prostate cancer who received ADT as the study group and 3631 patients who did not receive ADT as the control group., Primary and Secondary Outcome Measures: This study individually tracked patients over a 3-year study period and identified those who were subsequently diagnosed with IDA following the index date., Results: The incidence rates of IDA in the study and control groups were 1.66 (95% CI CI 1.45 to 1.86) and 1.01 per 100 person-years (95% CI 0.78 to 1.25), respectively. Furthermore, proportional Cox regression revealed an HR of 1.62 (95% CI 1.24 to 2.12) for IDA in the study group after adjusting for patients' age, monthly income, geographic location, residential urbanisation level and incidence of hyperlipidaemia, diabetes, hypertension, coronary heart disease, inflammatory bowel disease, other cancers and gastrointestinal bleeding., Conclusion: Compared with its non-use among patients with prostate cancer, ADT use was associated with a higher risk of IDA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bone morphogenetic proteins (BMPs) are known to play an indispensable role in preventing the precocious luteinization of granulosa cells within growing ovarian follicles. In this study, we found that the transcripts of BMP8 genes are enriched in the ovaries of humans and rodents. When analyzing transcriptomic datasets obtained from human mature granulosa cells, we further found that the BMP8 transcripts not only show the highest abundance among the searchable BMP-related ligands but also decrease significantly in women of advanced age or women with polycystic ovarian syndrome. The correlation between the BMP8 levels in granulosa cells and the decline in ovarian function in these subjects suggests that BMP8 protein may be involved in the regulation of granulosa cell function(s). Using a rat model, we demonstrated that human BMP8A protein activates the SMAD1/5/8 and the SMAD2/3 pathways simultaneously in both immature and mature granulosa cells. Furthermore, the expression of potential type I and type II receptors used by BMP8 in rat granulosa cells was characterized. We found that BMP8A treatment can significantly inhibit gonadotropin-induced progesterone production and steroidogenesis-related gene expression in granulosa cells. Pathway dissection using receptor inhibitors further revealed that such inhibitory effects occur specifically through the BMP8-activated SMAD1/5/8, but not SMAD2/3, pathway. Taken together, considering its abundance and possible functions in granulosa cells, we suggest that BMP8 may act as a novel luteinization inhibitor in growing follicles.

Objective: To analyze the features of chest CT imaging in adult patients with bronchiectasis and explore its correlation with clinical characteristics. Methods: From January 2010 to December 2017, patients with bronchiectasis diagnosed by chest high-resolution CT (HRCT) and aged at or above 18 years old in 5 general hospitals of Shandong province were included in the study. The correlations between the HRCT imaging features and etiology, clinical manifestations, lung function, sputum culture, prognosis and other characteristics were analyzed. Results: There were 410 bronchiectasis patients included in the study. The chest HRCT imaging of bronchiectasis were divided into three types, including columnar 46.8%, cystic 45.9% and varicose 7.3%, respectively. The HRCT imaging score was [6.0 (4.0, 7.0)]. In addition, the most common etiology of bronchiectasis was idiopathic (262, 69.3%). The proportion of idiopathic bronchiectasis in cystic bronchiectasis patients was significantly higher than that in columnar and varicose bronchiectasis (71.8% vs 58.3%, 50.0%; both P< 0.017). Compared with columnar bronchiectasis, patients with cystic bronchiectasis were more likely to suffer from clinical manifestations such as cough, dyspnea, fever and wet rales ( P< 0.017). Compared with patients with HRCT scores of 1 to 4, patients with scores ≥8 were more likely to suffer from cough, dyspnea, fever, wet rales and clubbing ( P< 0.017). The proportions of pulmonary ventilatory dysfunction were significantly greater in patients with cystic bronchiectasis and varicose bronchiectasis than columnar bronchiectasis (86.7%, 86.7% vs 51.0%; both P< 0.017). The HRCT scores were significantly negatively correlated with pulmonary function ( P< 0.001). The number of acute exacerbations, hospitalizations, and bronchiectasis severe index scores in patients with cystic bronchiectasis were significantly higher than those with columnar bronchiectasis ( P< 0.017). There was a significantly positive correlation between HRCT scores and the number of acute exacerbations, hospitalizations and the bronchiectasis severity index scores ( P< 0.001). The mortality of patients with cystic and varicose bronchiectasis was significantly higher than that of patients with columnar bronchiectasis (9.0%, 10.0% vs 2.1%; both P< 0.017). Compared with patients with HRCT scores of 1 to 4, patients with scores ≥8 had a higher mortality rate (15.9% vs 0.9%; P< 0.017). Conclusions: There is a correlation between HRCT findings and clinical manifestations in patients with bronchiectasis. The clinical manifestations, lung function and prognosis of patients with cystic bronchiectasis are worse than those of the columnar bronchiectasis; the higher the HRCT scores are, the worse the clinical manifestations, lung function and prognosis of the patients are.

Peritoneal dissemination is the most frequent metastatic route of ovarian cancer. However, due to the high heterogeneity in ovarian cancer, most conventional studies lack parental tumor controls relevant to metastases and, thus, it is difficult to trace the molecular changes of cancer cells along with the selection by the abdominal microenvironment. Here, we established an in vivo mouse peritoneal dissemination scheme that allowed us to select more aggressive sublines from parental ovarian cancer cells, including A2780 and SKOV-3. Microarray and gene profiling analyses indicated that autophagy-related genes were enriched in selected malignant sublines. Detection of LC3-II, p62 and autophagic puncta demonstrated that these malignant variants were more sensitive to autophagic induction when exposed to diverse stress conditions, such as high cell density, starvation and drug treatment. As compared with parental A2780, the selected variant acquired the ability to grow better under high-density stress; however, this effect was reversed by addition of autophagic inhibitors or knockdown of ATG5. When analyzing the clinical profiles of autophagy-related genes identified to be enriched in malignant A2780 variant, 73% of them had prognostic significance for the survival of ovarian cancer patients. Taken together, our findings indicate that an increase in autophagic potency among ovarian cancer cells is crucial for selection of metastatic colonies in the abdominal microenvironment. In addition, the derived autophagic gene profile can not only predict prognosis well but can also be potentially applied to precision medicine for identifying those ovarian cancer patients suitable for taking anti-autophagy cancer drugs., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Accumulating evidence suggests a role of bisphenol A (BPA) in non-alcoholic fatty liver disease (NAFLD), and its mechanism may be related to the up-regulation of lipogenic genes, but the mechanism of BPA induced lipogenic gene expression remains unknown. The aim of this study was to investigate the effects of perinatal exposure to BPA on NAFLD and its mechanisms. Pregnant Sprague-Dawley rats had access to drinking water containing 1 or 10 μg/ml BPA from gestational day 6 to post-natal day 21. For 5 weeks after weaning, offspring drank normal water without BPA. Body weight, lipid profile and the expression of genes or proteins involved in mTOR mediated lipid metabolism and autophagy, as well as inflammatory response were investigated in the 8-wk-old offspring of different genders. The results showed that body weight was increased only in females, however, males, and females from dams treated with BPA had significantly excess visceral adipose tissue, which was consistent with adipocyte hypertrophy. Elevated TG levels and up-regulation of lipogenic genes or proteins in liver, such as sterol regulatory element binding protein 1 (SREBP1), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS) were consistent with increased liver lipid droplets in offspring exposed to BPA. Compared with controls, the protein levels of InsR, p-IRS-1, IRS-1, TSC1, and TSC2 were decreased, p-PI3K, p-Akt (S473), p-Akt (T308), p-mTOR, and mTOR were increased, and the impaired autophagic degradation was evidenced by increased protein levels of p62, although the levels of p-ULK1, Beclin1, and LC3B proteins were increased in liver of BPA-exposed offspring. The levels of TLR4 and NF-κB proteins were also significantly increased, and ERα protein was significantly decreased in BPA-exposed offspring. Our findings indicate that perinatal exposure to BPA causes the development of NAFLD in both female and male offspring, which is associated with up-regulation of lipogenic genes, dysregulated autophagy and activated inflammatory response involving the PI3K/Akt/mTOR and TLR4/NF-κB pathways.

Objective: With the improvement of surgical operation, increasing incidence of secondary benign airway stenosis, as a complication of long-term tracheal intubation and tracheotomy, leads to significant increases in morbidity and mortality. Previous treatment of secondary benign airway stenosis was mainly based on surgical resection and reconstruction. There is an urgent need for new treatment methods except surgery, especially for those inoperable patients. Methods: This study retrospectively reviewed 20 patients who had treatments of secondary benign airway stenosis after tracheotomy with Montgomery T-tube. The clinical data including clinical features, efficacy, complications and prognosis were retrospectively evaluated. Results: Complete airway obstruction was 12/20, partial stenosis was 8/20, combined with airway granuloma and endoscopic granulation resection was 16/20, combined with scar stenosis and endoscopic balloon dilatation was 18/20. Plugging successfully was 19/20. Complications included mucous accumulation (20/20), secondary granulation tissue formation (13/20), subcutaneous soft tissue infection (1/20), and T-tube re-implantation (3/20). Conclusions: Montgomery T-tube implantation under rigid bronchoscopy is a safe, feasible and effective tracheal forming method with well tolerance for patients with benign airway stenosis. Secondary benign airway stenosis after tracheal intubation and tracheotomy is an indication of Montgomery T-tube implantation. Compared with the traditional tracheotomy, the advantage of Montgomery T-tube implantation is easy to make the patient phonate, significantly improving the quality of life of patients. T-tube implantation is safe, and the postoperative complications include mucous accumulation and formation of secondary T-tube granulation tissue.

The traditional Chinese herb Lonicerae Japonicae Flos has shown significant clinical benefits in the treatment of heart failure, but the mechanism remains unclear. As the main active ingredient found in the plasma after oral administration of Lonicerae Japonicae Flos, chlorogenic acid (CGA) has been reported to possess anti-inflammatory, anti-oxidant and anti-apoptosis function. We firstly confirmed the cardioprotective effects of CGA in transverse aortic constriction (TAC)-induced heart failure mouse model, through mitigating the TNF-α-induced toxicity. We further used TNF-α-induced cardiac injury in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to elucidate the underlying mechanisms. CGA pre-treatment could reverse TNF-α-induced cellular injuries, including improved cell viability, increased mitochondrial membrane potential and inhibited cardiomyocytes apoptosis. We then examined the NF-κB/p65 and major mitogen-activated protein kinases (MAPKs) signalling pathways involved in TNF-α-induced apoptosis of hiPSC-CMs. Importantly, CGA can directly inhibit NF-κB signal by suppressing the phosphorylation of NF-κB/p65. As for the MAPKs, CGA suppressed the activity of only c-Jun N-terminal kinase (JNK), but enhanced extracellular signal-regulated kinase1/2 (ERK1/2) and had no effect on p38. In summary, our study revealed that CGA has profound cardioprotective effects through inhibiting the activation of NF-κB and JNK pathway, providing a novel therapeutic alternative for prevention and treatment of heart failure., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

All of the objects in the real world are envisioned to be connected and/or represented, through an infrastructure layer, in the virtual world of the Internet, becoming Things with status information. Services are then using the available data from this Internet-of-Things (IoT) for various social and economical benefits which explain its extreme broad usage in very heterogeneous fields. Domain administrations of diverse areas of application developed and deployed their own IoT systems and services following disparate standards and architecture approaches that created a fragmentation of things, infrastructures and services in vertical IoT silos. Coordination and cooperation among IoT systems are the keys to build "smarter" IoT services boosting the benefits magnitude. This article analyses the technical trends of the future IoT world based on the current limitations of the IoT systems and the capability requirements. We propose a hyper-connected IoT framework in which "things" are connected to multiple interdependent services and describe how this framework enables the development of future applications. Moreover, we discuss the major limitations in today's IoT and highlight the required capabilities in the future. We illustrate this global vision with the help of two concrete instances of the hyper-connected IoT in smart cities and autonomous driving scenarios. Finally, we analyse the trends in the number of connected "things" and point out open issues and future challenges. The proposed hyper-connected IoT framework is meant to scale the benefits of IoT from local to global.

The interrelationships between ventilation rate, indoor air quality, and energy consumption in operation rooms at rest are yet to be understood. We investigate the effect of ventilation rate on indoor air quality indices and energy consumption in ORs at rest. The study investigates the air temperature, relative humidity, concentrations of carbon dioxide, particulate matter (PM), and airborne bacteria at different ventilation rates in operation rooms at rest of a medical center. The energy consumption and cost analysis of the heating, ventilating, and air conditioning (HVAC) system in the operation rooms at rest were also evaluated for all ventilation rates. No air-conditioned operation rooms had very highest PM and airborne bacterial concentrations in the operation areas. The bacterial concentration in the operation areas with 6-30 air changes per hour (ACH) was below the suggested level set by the United Kingdom (UK) for an empty operation room. A 70% of reduction in annual energy cost by reducing the ventilation rate from 30 to 6 ACH was found in the operation rooms at rest. Maintenance of operation rooms at ventilation rate of 6 ACH could save considerable amounts of energy and achieve the goal of air cleanliness.

Objective: Besides pulmonary arteriography, a number of imaging techniques, such as magnetic resonance imaging (MRI) and computed tomography (CT), were adopted in the detection of identifying pulmonary embolism (PE). However, the contrast of sensitivity and specificity in these methods was studied little in a statistical way. To compare the effects of MRI and CT, this study used a series of methods to analyze data in included researches., Methods: A comprehensive computer search was conducted through internet up to July 2016. The quality assessment was performed by the Quality Assessment Tool for Diagnostic Accuracy Studies, version 2 tool. The diagnostic value of comparison between MRI and CT was evaluated by using the pooled estimate of sensitivity, specificity, and summary receiver operating characteristic (SROC) curve. In addition, sensitivity analysis and bias analysis were applied to ensure the accuracy of the results., Results: Ten studies with 590 cases were involved in the study. Only 2 trials had high risk regarding bias while other trials were supposed to be at low risk of applicability. Heterogeneity existed in analysis of both CT and MRI. The pooled sensitivity of CT was 0.90 (95% CI: 0.85-0.93), pooled specificity was 0.88 (95% CI: 0.77 to 0.95), the pooled sensitivity of MRI was 0.92 (95% CI: 0.89-0.94), and pooled specificity was 0.91 (95% CI: 0.77-0.97). The Q index of sensitivity and specificity for CT and MRI were 71.38, 19.67, 47.14, and 12.35, respectively. The SROC curve area under the curve of CT and MRI were 0.94 (95% CI: 0.91-0.96) and 0.93 (95% CI: 0.91-0.95), respectively., Conclusion: This meta-analysis demonstrates that MRI has better sensitivity and specificity in detecting subsegmental artery PE. MRI is a relatively better detection technique for PE. This conclusion is consistent with many published researches., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The objective was to assess the safety and outcome of cold snare technique used by flexible bronchoscopy in the treatment of airway benign neoplasms. The clinical data of 21 patients, who had airway benign neoplasm and were treated through the cold snare method in Sir Run Run Shaw Hospital, affiliated with the Zhejiang University, were retrospectively analyzed. The relief of the symptoms and occurrence of complications were observed and evaluated. All the tumors were benign and removed by cold snare. Postoperatively, we found that the treatment was completely effective in 12 patients, and there was a significant improvement in 7 patients and a moderate improvement in 2 patients, and no recurrence in follow-up visit. In conclusion, the cold snare technique is an economically feasible, safe, and effective method in the treatment of airway neoplasms.

In this study, we assessed whether the down-regulation of Yes-associated protein (YAP) is involved in the pathogenesis of extracellular matrix (ECM) mechanical stress-induced Stanford type A aortic dissection (STAAD). Human aortic samples were obtained from heart transplantation donors as normal controls and from STAAD patients undergoing surgical replacement of the ascending aorta. Decreased maximum aortic wall velocity, ECM disorders, increased VSMC apoptosis, and YAP down-regulation were identified in STAAD samples. In a mouse model of STAAD, YAP was down-regulated over time during the development of ECM damage, and increased VSMC apoptosis was also observed. YAP knockdown induced VSMC apoptosis under static conditions in vitro , and the change in mechanical stress induced YAP down-regulation and VSMC apoptosis. This study provides evidence that YAP down-regulation caused by the disruption of mechanical stress is associated with the development of STAAD via the induction of apoptosis in aortic VSMCs. As STAAD is among the most elusive and life-threatening vascular diseases, better understanding of the molecular pathogenesis of STAAD is critical to improve clinical outcome., Competing Interests: No conflicts of interest, financial or otherwise, are declared by the authors.

Gonadotropin signaling plays an indispensable role in ovarian cancer progression. We previously have demonstrated that thyrostimulin and thyroid-stimulating hormone receptor (TSHR), the most ancient glycoprotein hormone and receptor pair that evolved much earlier than the gonadotropin systems, co-exist in the ovary. However, whether thyrostimulin-driven TSHR activation contributes to ovarian cancer progression in a similar way to gonadotropin receptors has never been explored. In this study, we first found that TSHR is expressed in both rat normal ovarian surface epithelium and human epithelial ovarian cancers (EOCs). Using human NIH:OVCAR-3 as a cell model, we demonstrated that thyrostimulin promotes EOC cell proliferation as strongly as gonadotropins. Thyrostimulin treatment not only activated adenylyl cyclase and the subsequent PKA, MEK-ERK1/2 and PI3K-AKT signal cascades, but also trans-activated EGFR signaling. Signaling dissection using diverse inhibitors indicated that EOC cell proliferation driven by thyrostimulin-TSHR signaling is PKA independent, but does require the involvement of the MEK-ERK and PI3K-AKT signal cascades, which are activated mainly via the trans-activation of EGFR. Thus, not only have we proved that this ancient glycoprotein hormone system is involved in NIH:OVCAR-3 cell proliferation for the first time, but also that it may possibly become a novel oncotarget when studying ovarian cancer.

Neuromedin U (NMU) was originally named based on its strong uterine contractile activity, but little is known regarding its signaling/functions in utero. We identified that NMU and one of its receptors, NMUR2, are not only present in normal uterine endometrium but also co-expressed in endometrial cancer tissues, where the NMU level is correlated with the malignant grades and survival of patients. Cell-based assays further confirmed that NMU signaling can promote cell motility and proliferation of endometrial cancer cells derived from grade II tumors. Activation of NMU pathway in these endometrial cancer cells is required in order to sustain expression of various adhesion molecules, such as CD44 and integrin alpha1, as well as production of their corresponding extracellular matrix ligands, hyaluronan and collagen IV; it also increased the activity of SRC and its downstream proteins RHOA and RAC1. Thus, it is concluded that NMU pathway positively controls the adhesion signaling-SRC-Rho GTPase axis in the tested endometrial cancer cells and that changes in cell motility and proliferation can occur when there is manipulation of NMU signaling in these cells either in vitro or in vivo. Intriguingly, this novel mechanism also explains how NMU signaling promotes the EGFR-driven and TGFβ receptor-driven mesenchymal transitions. Through the above axis, NMU signaling not only can promote malignancy of the tested endometrial cancer cells directly, but also helps these cells to become more sensitive to niche growth factors in their microenvironment.

The high quality of induced pluripotent stem cells (iPSCs) has been determined to be high-grade chimeras that are competent for germline transmission, and viable mice can be generated through tetraploid complementation. Most of the high-quality iPSCs described to date have been male. Female iPSCs, especially fully pluripotent female iPSCs, are also essential for clinical applications and scientific research. Here, we show, for the first time, that a gender-mixed induction strategy could lead to a skewed sex ratio of iPSCs. After reprogramming, 50%, 70%, and 90% female initiating mouse embryonic fibroblasts at different male ratios resulted in 14.1 ± 6.8% (P < 0.05), 31.8 ± 5.4% (P < 0.05), and 80.1 ± 2.8% (P < 0.05) female iPSCs, respectively. Furthermore, these female iPSCs had pluripotent properties typical of embryonic stem cells. Importantly, these fully pluripotent female iPSCs could generate viable mice by tetraploid complementation. These findings indicate that high-quality female iPSCs could be derived effectively, and suggest that clinical application of female iPSCs is feasible., (© 2015 by the Society for the Study of Reproduction, Inc.)

Unlabelled: Preeclampsia (PE) is a pregnancy-specific syndrome that occurs in a previously normotensive woman. Some data suggested that the activation parameters of platelets in preeclampsia. The aim of this study is to determine whether the levels of GPIbα and GPIIb for patients with preeclampsia were enhanced after cesarean section. In this study, detecting levels of GPIbα and GPIIb by flow cytometry (FCM). The venous blood of 48 severe preeclampsia women, 16 mild preeclampsia and 22 normotensive women, were collected before operation and 72 hours after the operation. Blood samples were obtained also from 20 non-pregnant women., Results: The level of GPIbα of the normotensive pregnancy was lower than the control group, but there was no significance (P > 0.05). The level of GPIbα of the severe preeclampsia group was much lower than other groups (P < 0.01). In the severe preeclampsia group, the level of GPIbα of postoperative patients was higher than preoperative patients (P < 0.01). There was no significance of GPIIb levels between each group (P > 0.05). In conclusion, GPIbα was an important index of reflecting the change of severe preeclampsia. Detecting the levels of GPIbα plays an important role in observing the development of this disease and guiding clinical treatment.

Leucine-rich repeat containing G protein-coupled receptor 4 (LGR4) promotes the Wnt signaling through interaction with R-spondins or norrin. Using PCR amplification from rat ovarian cDNAs, we identified a naturally occurring Lgr4 splice variant encoding only the ectodomain of Lgr4, which was named Lgr4-ED. Lgr4-ED can be detected as a secreted protein in the extracts from rodent and bovine postnatal gonads, suggesting conservation of Lgr4-ED in mammals. Recombinant Lgr4-ED purified from the conditioned media of transfected 293T cells was found to dose-dependently inhibit the LGR4-mediated Wnt signaling induced by RSPO2 or norrin, suggesting that it is capable of ligand absorption and could have a potential role as an antagonist. Intraperitoneal injection of purified recombinant Lgr4-ED into newborn mice was found to significantly decrease the testicular expression of estrogen receptor alpha and aquaporin 1, which is similar to the phenotype found in Lgr4-null mice. Administration of recombinant Lgr4-ED to superovulated female rats can also decrease the expression of estrogen receptor alpha, aquaporin 1, LH receptor and other key steroidogenic genes as well as bring about the suppression of progesterone production. Thus, these findings suggest that endogenously expressed Lgr4-ED may act as an antagonist molecule and help to fine-tune the R-spondin/norrin-mediated Lgr4-Wnt signaling during gonadal development.

Neuromedin U (NMU) was originally identified as an anorexigenic peptide that modulates appetite as well as energy homeostasis through the brain-gut axis. Although growing evidence has linked NMU activity with the development of female reproductive organs, no direct expression of and function for NMU in these organs has been pinpointed. Using a superovulated rat model, we found that NMU is directly expressed in the ovary, where its transcript level is tightly regulated by gonadotropins. Ovarian microdissection and immunohistochemical staining showed clearly that NMU is expressed mainly in theca/interstitial cells and to a moderate extent in granulosa cells. Primary cell studies together with reporter assays indicated the Nmu mRNA level in these cells is strongly induced via cAMP signaling, whereas this increase in expression can be reversed by the degradation message residing within its 3'-untranslated region, which recruits cis-acting mRNA degradation mechanisms, such as the gonadotropin-induced zinc finger RNA-binding protein Zfp36l1. This study also demonstrated that NMUR2, but not NMUR1, is the dominant NMU receptor in the ovary, where its expression is restricted to theca/interstitial cells. Treatment with NMU led to induction of the early response c-Fos gene, phosphorylation of extracellular signal-regulated kinase 1/2, and promotion of progesterone production in both developing and mature theca/interstitial cells. Taken as a whole, this study demonstrates that NMU and NMU receptor 2 compose a novel autocrine system in theca/interstitial cells in which the intensity of signaling is tightly controlled by gonadotropins.

Although differential screening-selected gene aberrative in neuroblastoma (DAN, official symbol NBL1) is the founding member of the DAN subfamily of bone morphogenetic protein (BMP) antagonists, its antagonizing targets, gene regulation, and physiological functions remain unclear. Using diverse cell expression systems, we found that the generation of bioactive DAN is likely to be cell type specific. Unlike other phylogenetically close members, which are covalently linked homodimers, DAN forms a noncovalently linked homodimer during folding. Purified recombinant DAN specifically blocked signaling of BMP2 and BMP4 but not that of other ovarian-expressed transforming growth factor-beta members. Although widely distributed in many organs, DAN transcript level was periodically regulated by gonadotropins. Ovarian microdissection indicated that NBL1 (DAN) mRNA is mainly expressed in granulosa cells, where its transcript level is up-regulated by the gonadotropin-driven cAMP cascade. We further investigated the local regulation and ovarian functions of DAN. NBL1 (DAN) mRNA expression in granulosa cells was up-regulated by oocyte-derived growth differentiation factor 9 (GDF9), whereas treatment with DAN significantly reversed the inhibitory effect of BMP4 on follicle-stimulating hormone-induced progesterone production in cultured granulosa cells. Our findings suggest the DAN gradient in granulosa cells, established by oocyte-derived GDF9, may serve as an antagonist barrier that modulates the actions of theca-derived BMP4 and granulosa/theca-derived BMP2 during folliculogenesis both spatially and temporally.

The thyroid-stimulating hormone receptor (TSHR), activated by either TSH or the newly discovered glycoprotein hormone thyrostimulin, plays a central role in the control of body metabolism. Interestingly, in addition to its thyroid expression, we discovered that the mRNA level of TSHR is periodically regulated in rat ovary by gonadotropins. Ovarian microdissection followed by real-time PCR analysis indicated that granulosa cells show the highest level of TSHR expression. Cultures of follicles and primary granulosa cells demonstrated that the level of TSHR is up-regulated and decreased by the gonadotropin-driven cAMP cascade and estradiol production, respectively. Furthermore, in contrast to the negligible expression of TSH in the ovary, we also found by real-time PCR and immunohistochemical analysis that thyrostimulin is expressed mainly in oocytes. Evolving before the appearance of gonadotropins, thyrostimulin is considered the most ancestral glycoprotein hormone. Therefore, the presence of thyrostimulin in the ovary suggests that it may have a primitive function in reproduction when it activates ovarian TSHR. Next, we generated recombinant thyrostimulin protein and characterized its non-covalent heterodimeric nature. Using purified recombinant thyrostimulin, we show that the human ovarian cell line NIH:OVCAR-3 also expresses endogenous and functional TSHR. Using cultured rat granulosa cells isolated from different ovarian stages, we found that treatments with thyrostimulin significantly increase cAMP production and the c-fos gene response in the presence of gonadotropins. Thus, this study demonstrates that oocyte-derived thyrostimulin and granulosa cell-expressed TSHR compose a novel paracrine system in the ovary, where the activity is tightly controlled by gonadotropins.

The present study examines duration-sensitive neurons in the inferior colliculus (IC) of the least horseshoe bat, Rhinolophus pusillus, from China. In contrast to other bat species tested for duration selectivity so far, echolocation pulses emitted by horseshoe bats are generally longer and composed of a long constant-frequency (CF) component followed by a short downward frequency-modulated (FM) sweep (CF-FM pulse). We used combined CF-FM pulses to analyze the differential effects that these two pulse components had on the duration tuning in neurons of the horseshoe bat's IC. Consistent with results from other mammals, duration-sensitive neurons found in the least horseshoe bat fall into three main classes: short-pass, band-pass, and long-pass. Using a CF stimulus alone, 54% (51/95) of all IC neurons showed at least one form of duration selectivity at one or more stimulus intensities. In 65 of the 95 IC neurons tested with CF pulses, we were also able to test their duration selectivity for a combined CF-FM pulse, which increased the ratio of duration-sensitive neurons to 66% (43/65). Seven to 15 neurons that failed to show duration tuning for CF bursts became duration sensitive for CF-FM pulses, with most of them exhibiting short-pass (depending on stimulus intensity, between 4 and 8 neurons) or band-pass tuning (1-3 neurons). Increasing stimulus intensities did not affect the duration tuning in 53% (23/43) of duration-sensitive neurons for CF bursts and in about 26% (7/27) for CF-FM stimuli. In the remaining neurons, increasing sound levels generally reduced the ratio of duration-sensitive neurons to 33% for CF and 37% for CF-FM stimulation. In those that remained duration sensitive, louder CF bursts shortened best durations in band-pass neurons and cutoff durations in short- and long-pass neurons, whereas louder CF-FM stimuli reduced the cutoff durations only in short-pass neurons. Bandwidths of band-pass neurons were not significantly affected by any stimulus configuration, with only a slight trend for increasing bandwidths for louder CF bursts (but not CF-FM stimuli). Best durations and cutoff durations reached higher values than those in the other bat species examined so far and roughly match the longer durations of echolocation pulses emitted by horseshoe bats. Therefore presentation of a CF-FM stimulus improved the duration sensitivity in IC neurons by increasing the ratio of duration-tuned neurons and making them less susceptible to changes in signal intensity.

A batch photoreactor was used to evaluate the UV/H2O2 oxidation process for the removal of humic acids in water. A 450-W UV lamp with high-pressure mercury vapor was employed as the light source. The residues of humic acids and hydrogen peroxide were measured for assessment of process performance and understanding of process reaction behavior. The UV photolysis alone can play an important role in the degradation of humic acids. The presence of hydrogen peroxide was found to promote the degradation efficiency. However, excessive dosage of H2O2 does not further improve the degradation of humic acids. On the contrary, the lower the H2O2 dosage the higher the amount of humic acids which can be removed. Aeration with air does not favor the removal efficiency of humic acids as the oxidation lasts for a sufficiently long time. The presence of carbonate species deteriorates the humic acids' removal, whereas it results in a larger amount of H2O2 decomposition.

Liver failure is a major cause of mortality. A bioartificial liver (BAL) employing isolated hepatocytes can potentially provide temporary support for liver failure patients. We have developed a bioartificial liver by entrapping hepatocytes in collagen loaded in the luminal side of a hollow fiber bioreactor. In the first phase of development, liver-specific metabolic activities of biosynthesis, biotransformation and conjugation were demonstrated. Subsequently anhepatic rabbits were used to show that rat hepatocytes continued to function after the BAL was linked to the test animal. For scale-up studies, a canine liver failure model was developed using D-galactosamine overdose. In order to secure a sufficient number of hepatocytes for large animal treatment, a collagenase perfusion protocol was established for harvesting porcine hepatocytes at high yield and viability. An instrumented bioreactor system, which included dissolved oxygen measurement, pH control, flow rate control, an oxygenator and two hollow fiber bioreactors in series, was used for these studies. An improved survival of dogs treated with the BAL was shown over the controls. In anticipated clinical applications, it is desirable to have the liver-specific activities in the BAL as high as possible. To that end, the possibility of employing hepatocyte spheroids was explored. These self-assembled spheroids formed from monolayer culture exhibited higher liver-specific functions and remained viable longer than hepatocytes in a monolayer. To ease the surface requirement for large-scale preparation of hepatocyte spheroids, we succeeded in inducing spheroid formation in stirred tank bioreactors for both rat and porcine hepatocytes. These spheroids formed in stirred tanks were shown to be morphologically and functionally indistinguishable from those formed from a monolayer. Collagen entrapment of these spheroids resulted in sustaining their liver-specific functions at higher levels even longer than those of spheroids maintained in suspension. For use in the BAL, a mixture of spheroids and dispersed hepatocytes was used to ensure a proper degree of collagen gel contraction. This mixture of spheroids and dispersed cells entrapped in the BAL was shown to sustain the high level of liver-specific functions. The possibility of employing such a BAL for improved clinical performance warrants further investigations.

Freshly harvested rat hepatocytes form spheroids on uncoated positively charged polystyrene surfaces. Time lapse microscopy revealed that cell movement and reorganization were involved in spheroid formation. Ultrastructural evaluation using scanning and transmission electron microscopy indicated polarized cellular morphology and extensive cell-cell communication within spheroids. Bile canalicular structures were observed to surround each individual hepatocyte, forming an intricate three-dimensional continuous network of channels that appeared to end as pores/holes on the surface of the spheroid. The maintenance of differentiated cellular morphology coincided with preservation of hepatocyte viability and enhanced levels of tissue specific functions in spheroids.

Azotobacter vinelandii cells grew well in a medium made from soil and distilled water which contained little or no carbohydrate. They utilized p-hydroxybenzoic acid and other phenolic acids, soil nitrogen, and water-soluble mineral substances. Seventeen soils which supported excellent growth of A. vinelandii contained 11 to 18 different phenolic acids each, including p-hydroxybenzoic, m-hydroxybenzoic, vanillic, p-coumeric, syringic, cis- and trans-ferrulic, and other unidentified aromatic acids. Three white, chalky "caliche" soils which were taken from areas where no plants grew failed to support the growth of A. vinelandii, and these contained no, two, and three phenolic acids, respectively. A. vinelandii did not fix nitrogen when growing in dialysates of soils which contained numerous phenolic acids. Growth was ample and rapid in most of the soils tested, but cell morphology was different from that usually seen in chemically defined, nitrogen-free media which contain glucose.