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Abstract Community correction institutions in China frequently employ the Symptom Checklist-90 (SCL-90) and the health survey brief (SF-12) as primary tools for psychological assessment of community correctional prisoners. However, in practical application, the SCL-90 Checklist faces issues such as complex item numbers, overall low cultural level of the subjects, and insufficient professional level of the administrators. The SF-12 health survey brief, as a preliminary screening tool, although only has 12 questions, to some extent simplifies the evaluation process and improves work efficiency, it is prone to missed screening. The research team collected 17-dimensional basic characteristic data and corresponding SCL-90 and SF-12 data from 25,480 samples of community correctional prisoners in Zhejiang Province, China. This study explored the application of multi-label multi-classification algorithms and oversampling techniques in building machine learning models to delve into the correlation between the psychological health risks of community correctional prisoners and their characteristic data. Inspired by computerized adaptive testing (CAT), we constructed an adaptive and efficient screening model for community correctional prisoners through experimental comparisons, based on the binary relevance algorithm with sample oversampling. This screening model personalize the assessment process by dynamically matching participants with the most relevant subset (s) of the nine dimensions of the SCL-90 based on their individual characteristics. Thus, adaptive dynamic simplification and personalized recommendation of the SCL-90 scale between question groups were achieved for the specific group of community correctional prisoners. As a screening tool for psychological symptoms of community correctional prisoners, this model significantly simplifies the number of questions compared to SCL-90, with a simplification rate of up to 65%. However, it achieves this simplification while maintaining excellent performance. The accuracy reached 0.66, with a sensitivity of 0.754, and an F1 score of 0.649. This innovation simplified the assessment process, reduced the assessment time, improved work efficiency, and enhanced the ability to judge the specificity of community correctional prisoners population. Compared to the SF-12, although the simplification rate and accuracy of the model are slightly lower than those of the SF-12, the sensitivity increased by 42.26%, and the F1 score improved by 15.28%. This means the model greatly reduces the possibility of missed screening, effectively preventing prisoners with abnormal psychological or mental states from losing control due to missed screening, and even committing suicide, self injury, or injuring others.

At present, the in-situ forging devices do not have the ability to flexibly adjust impacting forces over a wide frequency range and cannot be easily integrated, which restricts its application on DED-arc (directed energy deposition-arc) technology for additive manufacturing. A novel method and system of in-situ micro-impacting assisted DED-arc based on a compact high-dynamic linear actuator was proposed, developed and verified in arc deposition of 5B06 aluminum alloy. The terminal impacting head could be sufficiently close to the molten pool to enforce the obtaining of flat surface of the deposited layer. The results show that the in-situ micro-impacting could produce accumulating rapid micro-deformation and thus induce a gradient microstructure. DDRX (discontinuous dynamic recrystallization) and CDRX (continuous dynamic recrystallization) hybrid dynamic recrystallization behavior was observed. The microhardness of impacted samples was increased by 9.5 % and 8.0 % in vertical and horizontal direction, respectively. The process of rapid micro-deformation contributes to the retaining of the in-situ work-hardening effect at high temperatures, which made the proposed in-situ impacting method a preferred option for DED-arc additive manufacturing.

The widespread prevalence of sleep problems in children highlights the importance of timely and accurate sleep staging in the diagnosis and treatment of pediatric sleep disorders. However, most existing sleep staging methods rely on one-dimensional raw polysomnograms or two-dimensional spectrograms, which omit critical details due to single-view processing. This shortcoming is particularly apparent in pediatric sleep staging, where the lack of a specialized network fails to meet the needs of precision medicine. Therefore, we introduce AFSleepNet, a novel attention-based multi-view feature fusion network tailored for pediatric sleep analysis. The model utilizes multimodal data (EEG, EOG, EMG), combining one-dimensional convolutional neural networks to extract time-invariant features and bidirectional-long-short-term memory to learn the transition rules among sleep stages, as well as employing short-time Fourier transform to generate two-dimensional spectral maps. This network employs a fusion method with self-attention mechanism and innovative pre-training strategy. This strategy can maintain the feature extraction capabilities of AFSleepNet from different views, enhancing the robustness of the multi-view model while effectively preventing model overfitting, thereby achieving efficient and accurate automatic sleep stage analysis. A “leave-one-subject-out” cross-validation on CHAT and clinical datasets demonstrated the excellent performance of AFSleepNet, with mean accuracies of 87.5% and 88.1%, respectively. Superiority over existing methods improves the accuracy and reliability of pediatric sleep staging.

ObjectiveThe objective of this study was to investigate the effectiveness of a machine learning algorithm in diagnosing OSA in children based on clinical features that can be obtained in nonnocturnal and nonmedical environments.Patients and methodsThis study was conducted at Beijing Children's Hospital from April 2018 to October 2019. The participants in this study were 2464 children aged 3–18 suspected of having OSA who underwent clinical data collection and polysomnography(PSG). Participants’ data were randomly divided into a training set and a testing set at a ratio of 8:2. The elastic net algorithm was used for feature selection to simplify the model. Stratified 10-fold cross-validation was repeated five times to ensure the robustness of the results.ResultsFeature selection using Elastic Net resulted in 47 features for AHI ≥5 and 31 features for AHI ≥10 being retained. The machine learning model using these selected features achieved an average AUC of 0.73 for AHI ≥5 and 0.78 for AHI ≥10 when tested externally, outperforming models based on PSG questionnaire features. Linear Discriminant Analysis using the selected features identified OSA with a sensitivity of 44% and specificity of 90%, providing a feasible clinical alternative to PSG for stratifying OSA severity.ConclusionsThis study shows that a machine learning model based on children's clinical features effectively identifies OSA in children. Establishing a machine learning screening model based on the clinical features of the target population may be a feasible clinical alternative to nocturnal OSA sleep diagnosis.

Background Obstructive sleep apnea (OSA) is a complex and multi-gene inherited disease caused by both genetic and environmental factors. However, due to the high cost of diagnosis and complex operation, its clinical application is limited. This study aims to explore potential target genes associated with OSA and establish a corresponding diagnostic model. Methods This study used microarray datasets from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) related to OSA and perform functional annotation and pathway analysis. The study employed multi-scale embedded gene co-expression network analysis (MEGENA) combined with least absolute shrinkage and selection operator (LASSO) regression analysis to select hub genes and construct a diagnostic model for OSA. In addition, the study conducted correlation analysis between hub genes and OSA-related genes, immunoinfiltration, gene set enrichment analysis (GSEA), miRNA network analysis, and identified potential transcription factors (TFs) and targeted drugs for hub genes. Finally, the study used chronic intermittent hypoxia (CIH) mouse model to simulate OSA hypoxic conditions and verify the expression of hub genes in CIH mice. Results In this study, a total of 401 upregulated genes and 275 downregulated genes were identified, and enrichment analysis revealed that these differentially expressed genes may be associated with pathways such as vasculature development, cellular response to cytokine stimulus, and negative regulation of cell population proliferation. Through MEGENA combined with LASSO regression, seven OSA hub genes were identified, including C12orf54, FOS, GPR1, OR9A4, MYO5B, RAB39B, and KLHL4. The diagnostic model constructed based on these genes showed strong stability. The expression levels of hub genes were significantly correlated with the expression levels of OSA-related genes and mainly acted on pathways such as the JAK/STAT signaling pathway and the cytosolic DNA-sensing pathway. Drug-target predictions for hub genes were made using the Connectivity Map (CMap) database and the Drug-Gene Interaction database (Dgidb), which identified targeted therapeutic drugs for the hub genes. In vivo experiments showed that the hub genes were all decreasing in the OSA mouse model. Conclusions This study identified novel biomarkers for OSA and established a reliable diagnostic model. The transcriptional changes identified may help to reveal the pathogenesis, mechanisms, and sequelae of OSA.

AbstractTo explore the safety and feasibility of wireless thoracoscope in thoracic surgery. A retrospective analysis was made of all the clinical data of 90 patients with thoracoscope lung resection, from April to August 2021, Shanghai changzheng hospital thoracic minimally invasive center. Compared the thoracoscope preparation time, picture resolution, picture delay, surgeon comfort level, assistant comfort level between the wireless thoracoscope group and wired thoracoscope group. The thoracoscopic preparation time of the wireless thoracoscope group was significantly shorter than that of the wired group (26.66 ± 6.04 vs 62.14 ± 10.07, p

Abstract The hepatotoxicity of regorafenib is one of the most noteworthy concerns for patients, however the mechanism is poorly understood. Hence, there is a lack of effective intervention strategies. Here, by comparing the target with sorafenib, we show that regorafenib-induced liver injury is mainly due to its nontherapeutic target Eph receptor A2 (EphA2). EphA2 deficiency attenuated liver damage and cell apoptosis under regorafenib treatment in male mice. Mechanistically, regorafenib inhibits EphA2 Ser897 phosphorylation and reduces ubiquitination of p53 by altering the intracellular localization of mouse double minute 2 (MDM2) by affecting the extracellular signal-regulated kinase (ERK)/MDM2 axis. Meanwhile, we found that schisandrin C, which can upregulate the phosphorylation of EphA2 at Ser897 also has protective effect against the toxicity in vivo. Collectively, our findings identify the inhibition of EphA2 Ser897 phosphorylation as a key cause of regorafenib-induced hepatotoxicity, and chemical activation of EphA2 Ser897 represents a potential therapeutic strategy to prevent regorafenib-induced hepatotoxicity.

BackgroundThe concentrations of disinfection by-products (DBPs) are varied by different water sources, disinfectants, or treatment processes in Wuxi, and the associated health risks are also different. ObjectiveTo understand the levels of trihalomethanes (THMs) and haloacetamides (HAcAms) in drinking water in Wuxi, and their variations by water sources, seasons, disinfectants or treatment processes, aiming to provide technical support for ensuring the safety of drinking water. MethodsIn dry period (December 2019) and wet period (July 2020), the finished water and tap water (from the beginning, middle, and end of the drinking water distribution network) from 12 centralized water treatment plants in Wuxi were collected to detect the concentrations of THMs and HAcAms in water samples. A purge and trap-gas chromatography-mass spectrometry method was applied to detect trichloromethane (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and tribromomethane (TBM), and a solid-phase extraction-gas chromatography-mass spectrometry method to detect dichloroacetamide (DCAcAm), trichloroacetamide (TCAcAm), bromochloroacetamide (BCAcAm), dibromoacetamide (DBAcAm), bromodichloroacetamide (BDCAcAm), dibromochloroacetamide (DBCAcAm), and tribromoacetamide (TBAcAm). Analyses and comparisons were made on the concentrations of THMs and HAcAms in drinking water by water sources (the Yangtze River/the Taihu Lake/reservoir), wet/dry seasons, disinfection methods (liquid chlorine/sodium hypochlorite), and treatment processes (conventional treatment/conventional+advanced treatment). ResultsA total of 96 drinking water samples were collected in Wuxi. THMs were positive in all the water samples (100%), with concentration ranging from 1.027 to 40.225 μg·L−1 and the M (P25, P75) concentration being 24.782 (17.784, 30.932) μg·L−1. None of the 4 THMs exceeded the standard limit of the Standards for drinking water quality (GB 5749-2022 ), and the order of the 4 THMs concentrations from high to low was TCM > BDCM > DBCM > TBM. Five of the 7 HAcAms were detected, the total concentration ranged from 0.137 to 3.288 μg·L−1, and the M (P25, P75) was 0.808 (0.482, 1.704) μg·L−1. The DCAcAm concentration was the highest (2.448 μg·L−1), followed by BCAcAm, while TCAcAm and DBCAcAm were not detected. The M (P25, P75) of the total concentration of THMs in the drinking water from the Taihu Lake was 33.353 (26.649, 36.217) μg·L−1, that of the Yangtze River was 27.448 (24.312, 31.393) μg·L−1, and both were higher than the level of the reservoir [16.359 (2.305, 21.553) μg·L−1] (P0.05). The M (P25, P75) concentrations of THMs and HAcAms in drinking water after advanced treatment process involving ozone, activated carbon, and membrane were 20.565 (3.316, 27.185) μg·L−1 and 0.623 (0.452, 1.286) μg·L−1 respectively, and were lower than the corresponding values after conventional treatment process, 28.740 (23.431, 35.085) μg·L−1 and 0.934 (0.490, 2.116) μg·L−1 respectively (P＜0.05). ConclusionThe concentrations of THMs and HAcAms in drinking water in Wuxi are generally at a low level. The levels of controlled THMs meet the requirements of national standards, and the levels of uncontrolled HAcAms as new DBPs are up to μg·L−1. The concentrations of the two kinds of DBPs in drinking water vary by water sources. The concentrations of THMs and HAcAms produced by the advanced treatment process are lower than that by the conventional treatment process.

Abstract Nephrotoxicity has become prominent due to the increase in the clinical use of nilotinib, a second‐generation BCR‐ABL1 inhibitor in the first‐line treatment of Philadelphia chromosome‐positive chronic myeloid leukemia. To date, the mechanism of nilotinib nephrotoxicity is still unknown, leading to a lack of clinical intervention strategies. Here, it is found that nilotinib could induce glomerular atrophy, renal tubular degeneration, and kidney fibrosis in an animal model. Mechanistically, nilotinib induces intrinsic apoptosis by specifically reducing the level of BCL2 like 1 (Bcl‐XL) in both vascular endothelial cells and renal tubular epithelial cells, as well as in vivo. It is confirmed that chloroquine (CQ) intervenes with nilotinib‐induced apoptosis and improves mitochondrial integrity, reactive oxygen species accumulation, and DNA damage by reversing the decreased Bcl‐XL. The intervention effect is dependent on the alleviation of the nilotinib‐induced reduction in ubiquitin specific peptidase 13 (USP13) and does not rely on autophagy inhibition. Additionally, it is found that USP13 abrogates cell apoptosis by preventing excessive ubiquitin‒proteasome degradation of Bcl‐XL. In conclusion, the research reveals the molecular mechanism of nilotinib's nephrotoxicity, highlighting USP13 as an important regulator of Bcl‐XL stability in determining cell fate, and provides CQ analogs as a clinical intervention strategy for nilotinib's nephrotoxicity.

Abstract Background The complications of postoperative pain, such as hypertension, hypermetabolism, irritability, and postoperative cognitive dysfunction, significantly affect the postoperative rehabilitation of elderly patients. Intrathecal morphine prolongs analgesia after surgery, but has been implicated in nausea and vomiting, pruritus, postoperative respiratory depression, or apneic episodes. The present study explored the effect and safety of low-dose morphine used adjunctively with bupivacaine during single spinal anesthesia or sufentanil patient-controlled intravenous analgesia (PCIA) in elderly patients with hip fracture surgery. Since elderly patients often need anticoagulant therapy in the early postoperative period, single spinal anesthesia was involved in completing the operation in this study. Methods Eighty elderly patients aged 70–85 years who underwent elective hip fracture surgery with single spinal anesthesia were divided into two groups, 12.5 mg of 0.5% hyperbaric bupivacaine with 100 µg of morphine (morphine group, group M) and 12.5 mg of 0.5% hyperbaric bupivacaine with 100 µg of sufentanil PCIA (sufentanil group, group S). The analgesia scores using the visual analogue scale (VAS), the Brinell comfort scale (BCS) were evaluated at 6, 12, 24, and 48 h after operation, and adverse reactions were recorded such as nausea and vomiting, pruritus, sedation, respiratory depression, and POD (postoperative delirium) with Delirium Rating Scale-r 98. Results Within 24 h after operation, the analgesic and BCS scores of group M were better than those of group S (P

ObjectiveTo investigate the safety and efficacy of glasses-free three-dimensional (3D) thoracoscopic surgery in minimally invasive esophagectomy (MIE).MethodsThe clinical data of 98 patients, including 81 men and 17 women aged 45–77 years, with esophageal squamous cell carcinoma who underwent minimally invasive thoracoscopic esophagectomy from January 2017 to December 2019 [3 years, with clinical follow-up time: 1 year~4 years (2017.01–2020.12)] were retrospectively analyzed. Patients were divided into two groups according to different surgical methods including a glasses-free 3D thoracoscopic group (G-3D group: 38 patients) and a two-dimesional (2D) thoracoscopic group (2D group: 60 patients). The clinical outcome of the two groups were compared.ResultsThe operation time of the thoracoscopic part in the G-3D group was significantly shorter than that in the 2D group (P0.05). There was also no significant difference between the two groups on the progression-free survival (P>0.05).ConclusionGlasses-free 3D thoracoscopic surgery for esophageal cancer is a safe and effective surgical procedure. Compared with 2D thoracoscopic MIE, glasses-free 3D thoracoscopic MIE for esophageal cancer has higher safety, more lymph node dissection, and higher operation efficiency through the optimized surgical operations. We believe that glasses-free 3D thoracoscopy for MIE is worthy of clinical promotion.

ObjectivesThe present study aimed to investigate the characteristics of salivary microbiota of children with obstructive sleep apnea (OSA) and to assess longitudinal alterations in salivary microbiota before and after adenotonsillectomy.MethodsA set of cross-sectional samples consisted of 36 OSA children (17 boys and 19 girls, 7.47 ± 2.24 years old) and 22 controls (9 boys and 13 girls, 7.55 ± 2.48 years old) were included in the study, among which eight OSA children (five boys and three girls, 8.8 ± 2.0 years old) who underwent treatment of adenotonsillectomy were followed up after 1 year. Saliva samples were collected, and microbial profiles were analyzed by bioinformatics analysis based on 16S rRNA sequencing.ResultsIn cross-sectional samples, the OSA group had higher α-diversity as estimated by Chao1, Shannon, Simpson, Pielou_e, and observed species as compared with the control group (p < 0.05). β-Diversity based on the Bray–Curtis dissimilarities (p = 0.004) and Jaccard distances (p = 0.001) revealed a significant separation between the OSA group and control group. Nested cross-validated random forest classifier identified the 10 most important genera (Lactobacillus, Escherichia, Bifidobacterium, Capnocytophaga, Bacteroidetes_[G-7], Parvimonas, Bacteroides, Klebsiella, Lautropia, and Prevotella) that could differentiate OSA children from controls with an area under the curve (AUC) of 0.94. Linear discriminant analysis effect size (LEfSe) analysis revealed a significantly higher abundance of genera such as Prevotella (p = 0.027), Actinomyces (p = 0.015), Bifidobacterium (p < 0.001), Escherichia (p < 0.001), and Lactobacillus (p < 0.001) in the OSA group, among which Prevotella was further corroborated in longitudinal samples. Prevotella sp_HMT_396 was found to be significantly enriched in the OSA group (p = 0.02) with significantly higher levels as OSA severity increased (p = 0.014), and it had a lower abundance in the post-treatment group (p = 0.003) with a decline in each OSA child 1 year after adenotonsillectomy.ConclusionsA significantly higher microbial diversity and a significant difference in microbial composition and abundance were identified in salivary microbiota of OSA children compared with controls. Meanwhile, some characteristic genera (Prevotella, Actinomyces, Lactobacillus, Escherichia, and Bifidobacterium) were found in OSA children, among which the relationship between Prevotella spp. and OSA is worth further studies.

BackgroundWith uniportal video-assisted thoracoscopic surgery (VATS) becoming mainstream, how to make the incision cosmetic has attracted much attention. This study aimed to introduce a new traceless method for cosmetic closure of the incision and a special procedure for chest tube fixation after uniportal VATS and to evaluate the feasibility, effectiveness, and safety of this new technique.MethodsIn this retrospective study, a total of 258 consecutive patients who underwent uniportal VATS were included. Among them, 127 patients were treated with a conventional method, and 131 patients were treated with a new method.ResultsPatients in the new method group had a significantly less incidence of subcutaneous emphysema after the chest tube was removed. The incidence of pneumothorax after the chest tube was removed and fat liquefaction of chest incision was not significantly different between the two groups. No differences in the incidence of pneumothorax after chest tube removal and fat liquefaction of postsurgical incision were found between the two groups. Additionally, there was also no significant difference in follow-up items.ConclusionsTaken together, our results showed that this new method for minimally invasive incision closure and chest tube fixation after uniportal VATS was as feasible, effective, and safe as the conventional one but more cosmetic.

A particularly original negative group delay (NGD) theory of $\Delta $ -topology is developed in the present paper. The NGD three-port topology is a passive circuit purely constituted by capacitors network. The model of the proposed $\Delta $ -topology impedance 3-D matrix is analytically established in function of the capacitor elements. Then, the S-matrix model is derived by using the Y-to-S transform. By considering the S-matrix frequency responses, a bandpass (BP) NGD analysis of the capacitive $\Delta $ -topology is originally elaborated. It is theoretically demonstrated that the passive $\Delta $ -topology is susceptible to behave as a BP NGD circuit under an analytical condition between the constituting capacitor values. The design feasibility of the BP NGD function is experimentally verified with lumped capacitor components-based $\Delta $ -circuit proof of concept. An electronic circuit board constituted by purely capacitive-network $\Delta $ -circuit is fabricated as an original $\Delta $ -circuit prototype. The tested board is constituted by arbitrary chosen capacitors, 100 nF, 10 nF and 0.1 nF. As expected, the calculation, simulation and measurement results, which are in very good agreement, confirm the BP NGD behavior. It is observed from measurement that it generates NGD of about −18.1 ns at a frequency of about 0.55 MHz and, lower and upper cut-off frequencies of about 0.33 MHz and 1.71 MHz. It is noteworthy that the transmission and reflection coefficients at very low frequency are independent of the capacitor values and analytically equal to 2/3 and 1/3, respectively.

Congenital muscular dystrophy with early rigid spine, also known as the rigid spine with muscular dystrophy type 1 (RSMD1), is caused by SEPN1 mutation. We investigated the clinical manifestations, pathological features, and genetic characteristics of 8 Chinese RSMD1 patients in order to improve diagnosis and management of the disease. Eight patients presented with delayed motor development, muscle weakness, hypotonia, and a myopathic face with high palatine arches. All patients could walk independently, though with poor running and jumping, and most had a rigid spine, lordosis, or scoliosis. The symptoms of respiratory involvement were present early, and upper respiratory tract infections and pneumonia often occurred. Five patients had severe pneumonia, pulmonary hypertension, and respiratory failure. Lung function tests showed variable restrictive ventilation dysfunction. Polysomnography suggested hypoxia and hypoventilation. The serum creatine kinase (CK) level was normal or mildly increased. Muscle biopsy indicated chronic myopathic changes and minicores. Muscle magnetic resonance imaging (MRI) showed diffuse fatty infiltration of the gluteus maximus and thigh muscle. SEPN1 gene analysis revealed 16 compound heterozygous variants, 81.3% of which are unreported, including 7 exon 1 variants. Our study expands the spectrum of clinical and genetic findings in RSMD1 to improve diagnosis, management, and standards of care. SEPN1 mutations in exon 1 are common and easily missed, and exon 1 should be carefully analyzed when RSMD1 is suspected, which will provide valuable genetic counseling for the family and useful information for future natural history studies and clinical trials.

Abstract Background The known risk factors of childhood OSAS include tonsillar and adenoidhypertrophy, obesity, craniofacial anomalies, neuromuscular disorders and African-American (AA) ancestry. Whether other factors such as allergic rhinitis (AR), premature, environmental tobacco smoking (ETS) are associated with OSAS are inconsistent in different studies. Our study enrolled children of a broad age range and included potential risk factors of OSAS derived from previous studies and our own experience. Our objective is to identify risk factors of OSAS in children in a clinical setting. Methods Children between 2 and 15 years of age exhibiting snoring symptoms who visited the sleep center for polysomnography (PSG) were enrolled. All children completed a questionnaire, physical examination and PSG. The questionnaire included demographic data and information related to potential risk factors for sleep disorders. A physical examination included measurements of height, weight, neck circumference, waist and hip ratio, visual evaluation of the tonsils and the degree of adenoid obstruction. Children with obstructive apnea-hypopnea index (OAHI) ≥ 1 were defined as OSAS. Results A total of 1578 children were enrolled and1009 children exhibited OSAS. Univariate analyses showed that snoring occurring for ≥ 3 months, male gender, preterm birth, breastfeeding, obesity, neck circumference ≥ 30 cm, waist/hip ratio ≥ 0.95, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. The proportion of low educational level was higher in parents who breastfed their babies than those who didn’t. Multivariate analysis showed that snoring for ≥ 3 months, male gender, obesity, breastfeeding, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. Confounders such as socioeconomic status, parental occupation, and health-related behaviors should be explored further to investigate the relationship between breastfeeding and OSAS. Conclusion The independent risk factors for OSAS in children included snoring ≥ 3 months, male gender, obesity, breastfeeding, tonsillar and adenoid hypertrophy. The study was registered on Clinical Trials government (NCT02447614). The name of the trial is “Follow-up Studies of Primary Snoring (PS) and Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in Chinese Children” and the URL is https://clinicaltrials.gov/ .

This paper aims to develop an original circuit theory of inductorless NGD topology. The considered passive cell comprised of resistor and capacitor elements without inductor operates as a bandpass (BP) NGD function. The specifications of NGD functions are defined. Generally, the BP NGD fully lumped circuits available in the literature operate with resonant RLC-network. In the introduced research work, a lumped circuit was first time identified to exhibit the BP behavior without the presence of inductive component. The inductorless BP NGD topology is inspired from the combination of low-pass (LP) and high-pass (HP) NGD passive cells. Therefore, an original LP-HP NGD composite topology is obtained. The identified BP NGD topology is constituted only by passive RC-networks. Then, theoretical development of BP NGD analysis is explored. The inductorless circuit theory starts with the identification of BP NGD canonical form. Then, the expressions of NGD value, center frequency and attenuation in function of RC-network parameters are established. The synthesis equations allowing to determine the resistor and capacitor elements are derived. Proofs-of-concept are designed and prototypes are fabricated to verify the effectiveness of the developed LP-HP NGD composite theory. To validate the developed original circuit theory, two prototypes of RC-network based LP-HP NGD composite were designed, fabricated, simulated and tested. The two prototypes were synthesized with respect to two different NGD center frequencies 13.5 MHz and 22 MHz. As expected, the calculated, simulated and measurement results are in very good agreement with NGD value of about some negative nanoseconds. In the future, the characterized inductorless topology enable to overcome the traditional limitations of RLC-network based BP NGD circuits because of inductance self-effect limitation.

Abstract Introduction Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by alveolar hypoventilation and autonomic system dysregulation secondary to mutations of the PHOX2B gene. Treatment consists of assisted ventilation using positive‐pressure ventilators via tracheostomy, bi‐level positive airway pressure (BPAP) via a noninvasive interface, negative‐pressure ventilators, or diaphragm pacing. The long‐term use of BPAP in younger children at home has been less frequently reported. Case presentation We present a case of a 2‐month‐old infant with CCHS who was successfully managed by BPAP without the need for tracheostomy and followed up for 7 years. Conclusion CCHS is a rare disease that manifests as nocturnal desaturation and carbon dioxide retention in early life. Noninvasive ventilation can be successfully used in young infants via an appropriate mask.

Abstract Importance The incidence of obstructive sleep apnea syndrome (OSAS) in children has increased year by year recently. Blood pressure research of OSAS children can help understand the occurrence of OSAS related complications. Early detection and intervention of blood pressure changes in children with OSAS can reduce the incidence of cardiovascular disease in later adulthood. Objective To investigate the differences in blood pressure among different groups of snoring children and different sleep stages. Methods Habitually snoring children (snoring frequency of ≥ 3 nights per week) aged 3 to 11 years were recruited from Beijing Children's Hospital from 1 January 2017 to 30 June 2018. All children underwent polysomnography, and their blood pressure was monitored and calculated by the pulse transit time. The children were divided into those with primary snoring (PS), mild OSAS, and moderate to severe OSAS according to their obstructive apnea–hypopnea index (OAHI). Results In total, 140 children were included. Ninety‐seven had PS, 24 had mild OSAS, and 19 had moderate to severe OSAS. There were no differences in age, sex, or body mass index z‐score among the groups. Statistically significant differences were found in the OAHI, oxygen desaturation index 3%, respiratory arousal index, and lowest oxygen saturation among the three groups. Children with moderate to severe OSAS had higher systolic and diastolic blood pressure than those with mild OSAS and PS (P < 0.001). In all children, systolic and diastolic blood pressure was higher in the rapid eye movement (REM) sleep stage than in the non‐REM sleep stage (P < 0.05). Interpretation Children with moderate to severe OSAS had higher blood pressure than those with PS and mild OSAS in all sleep stages. Blood pressure in the REM sleep stage was higher than that in other sleep stages in all groups of children.

High incidence of cutaneous toxicity ranging from 29.2% to 71.2% has been reported during clinical use of vandetanib, which is a multi-target kinase inhibitor indicated for the treatment of unresectable medullary thyroid carcinoma. The cutaneous toxicity of vandetanib has limited its clinical benefits, but the underlying mechanisms and protective strategies are not well studied. Hence, we firstly established an in vivo model by continuously administrating vandetanib at 55 mg/kg/day to C57BL/6 for 21 days and verified that vandetanib could induce skin rash in vivo, which was consistent with the clinical study. We further cultured HaCaT and NHEK cells, the immortalized or primary human keratinocyte line, and investigated vandetanib (0–10 μM, 0–24 h)-caused alteration in cellular survival and death processes. The western blot showed that the expression level of apoptotic-related protein, c-PARP, c-Caspase 3 and Bax were increased, while the anti-apoptotic protein Bcl2 and MCL1 level were decreased. Meanwhile, vandetanib downregulated mitochondrial membrane potential which in turn caused the release of Cytochrome C, excessive production of reactive oxygen species and DNA damage. Furthermore, we found that 5 μM bisdemethoxycurcumin partially rescued vandetanib-induced mitochondria pathway-dependent keratinocyte apoptosis via activation of autophagy in vivo and in vitro, thereby ameliorated cutaneous toxicity. Conclusively, our study revealed the mechanisms of vandetanib-induced apoptosis in keratinocytes during the occurrence of cutaneous toxicity, and suggested bisdemethoxycurcumin as a potential protective drug. This work provided a potentially promising therapeutic strategy for the treatment of vandetanib-induced cutaneous toxicity.

Although previous studies have reported a facial expression classification deficit among adults with SDB, we do not know whether these findings can be generalized to children. In our study, children with sleep-disordered breathing (SDB) were divided into three groups: primary snoring (n = 51), mild obstructive sleep apnea (OSA) (n = 39), and moderate/severe OSA (n = 26). All participants, including 20 healthy controls, underwent an overnight polysomnography recording and the Emotional Expression Recognition Task. Psychosocial problems were evaluated using the parent-reported Strengths and Difficulties Questionnaire (SDQ). There was a borderline significant interaction between expression category and group on reaction times. Further analysis revealed that positive classification advantage (PCA) disappeared in the moderate/severe OSA group, whereas it persisted in the control, primary snoring, and mild OSA groups. Emotional symptoms were positively correlated with OAHI. In both the happy and sad conditions, RT was negatively related to age and body mass index (BMI) but was independent of the obstructive apnea-hypopnea index (OAHI), arterial oxygen (SaO2) and total sleep time. The accuracy of identifying a sad expression was negatively related to conduct problems. Children with moderate/severe OSA exhibited dysfunction in facial expression categorization, which could potentially affect social communication ability.

Renal fibrosis is a failed wound-healing process of the kidney tissue after chronic, sustained injury, which is a common pathway and pathological marker of virtually every type of chronic kidney disease (CKD), regardless of cause. However, there is a lack of effective treatment specifically targeting against renal fibrosis per se to date. The main pathological feature of renal fibrosis is the massive activation and proliferation of renal fibroblasts and the excessive synthesis and secretion of extracellular matrix (ECM) deposited in the renal interstitium, leading to structural damage, impairment of renal function, and eventually end-stage renal disease. In this review, we summarize recent advancements regarding the participation and interaction of many types of kidney residents and infiltrated cells during renal fibrosis, attempt to comprehensively discuss the mechanism of renal fibrosis from the cellular level and conclude by highlighting novel therapeutic targets and approaches for development of new treatments for patients with renal fibrosis.

Congenital central hypoventilation syndrome (CCHS) is characterized by an alteration of the ventilatory response to hypercapnia and hypoxia, and is classically presented in neonates with abnormalities of the autonomic nervous system. Here, we generated human induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) isolated from a male patient clinically diagnosed with CCHS. These iPSC lines carry a heterozygous RET mutation (c.2608-125C > T), express pluripotency markers, have the capacity to differentiate into the normal teratoma tissue, retain the RET mutation and display the normal karyotype, which will also provide a useful resource to study the pathogenesis of CCHS.

Objective. To analyze the clinical and polysomnographic characteristics in children with mild OSA and respiratory events terminated predominantly with arousal. Methods. Children aged 3–10 yrs who had mild obstructive sleep apnea (OSA) were enrolled. All children underwent polysomnography, and patients’ data were collected by using sleep-related breathing disorders (SRBD) questionnaire and OSA-18 quality of life questionnaire. Results. In total, five hundred and seventy-seven children were eligible. Children in arousal predominant group were younger and showed a lower rate of male and obesity. Compared with that of the nonarousal predominant group, the total arousal index, arousal index related to respiratory event, the percentage of NREM stage 1 (N1%), the fraction of respiratory events that were hypopnea, and the mean and minimum oxygen saturation in the arousal predominant group were significantly greater. The percentage of NREM stage 3 (N%), index of obstructive, central, mixed apnea, the fraction of respiratory events that were obstructive, and central and mixed apnea were significantly lower in arousal predominant group. Conclusion. Children with mild OSA in the arousal predominant group had specific characteristics, including younger age, lower rate of male and obesity, worse sleep architecture, higher rates of hypopnea events, and better oxygenation. This trial is registered with NCT02447614.

Numerous protein kinases encoded in the genome have become attractive targets for the treatment of different types of cancer. As of January 2020, a total of 52 small-molecule kinase inhibitors (SMKIs) have been approved by the FDA. With the numerous clinical trials and a heavy focus on drug safety, SMKI-induced cardiotoxicity, which is a life-threatening risk, has greatly attracted the attention of researchers. In this review, the SMKIs with cardiotoxicity incidence were described exhaustively. The data were collected from 42 clinical trials, 25 FDA-published documents, seven meta-analysis/systematic reviews, three case reports and more than 50 other types of articles. To date, 73% (38 of 52) of SMKIs have reported treatment-related cardiotoxicity. Among the 38 SMKIs with known cardiotoxicity, the rates of incidence of cardiac adverse events were QT prolongation: 47% (18 of 38), hypertension: 40% (15 of 38), left ventricular dysfunction: 34% (13 of 38), arrhythmia: 34% (13 of 38), heart failure: 26% (10 of 38) and ischemia or myocardial infarction: 29% (11 of 38). In the development process of novel SMKIs, more attention should be paid to balancing the treatment efficacy and the risk of cardiotoxicity. In preclinical drug studies, producing an accurate and reliable cardiotoxicity evaluation model is of key importance. To avoid the clinical potential cardiotoxicity risk and discontinuation of a highly effective drug, patients treated with SMKIs should be proactively monitored on the basis of a global standard. Moreover, the underlying mechanisms of SMKI-induced cardiotoxicity need to be further studied to develop new therapies for SMKI-induced cardiotoxicity.

Chemotherapy is the only choice for most of the advanced hepatocellular carcinoma (HCC) patients, while few agents were available, making it an urgent need to develop new chemotherapy strategies. A phase II clinical trial suggested that the efficacy of irinotecan in HCC was limited due to dose-dependent toxicities. Here, we found that gefitinib exhibited synergistic activity in combination with SN-38, an active metabolite of irinotecan, in HCC cell lines. And the enhanced apoptosis induced by gefitinib plus SN-38 was a result from caspase pathway activation. Mechanistically, gefitinib dramatically promoted the ubiquitin-proteasome-dependent degradation of Rad51 protein, suppressed the DNA repair, gave rise to more DNA damages, and ultimately resulted in the synergism of these two agents. In addition, the increased antitumor efficacy of gefitinib combined with irinotecan was further validated in a HepG2 xenograft mice model. Taken together, our data demonstrated for the first time that the combination of irinotecan and gefitinib showed potential benefit in HCC, which suggests that Rad51 is a promising target and provides a rationale for clinical trials investigating the efficacy of the combination of topoisomerase I inhibitors and gefitinib in HCC.

Background and objective TLE1 is an important protein in regulating Wnt, Notch and EGFR signaling pathways. The TLE1 N-terminal Q domain regulates the pathways by mediating its oligomerization and interaction with LEF1. The aim of this study is to construct the human TLE1 N-terminal Q domain fragment in prokaryotic expression system, express and purify protein TLE1 N-terminal Q domain and prepare its polyclonal antibody. Methods The sequence of TLE1 N-terminal Q domain obtained by PCR from human lung adenocarcinoma cDNA, was cloned into the prokaryotic expression vector pGEX-4T-1 containing Glutathione S-transferase (GST). Vector pGEX-4T1-TLE1-Q was transformed into E.coli BL21 condon plus. The GST-TLE1-Q(1-136) fusion protein was induced by IPTG, digested by Thrombin, purified with glutathione-sepharose beads and FPLC, identified by SDS-PAGE. Then rabbits were immunized with the purified protein TLE1-Q(1-136) for obtaining the antiserum. The titers and specificity of antibodies were measured by ELISA and Western blot. Results The PCR identification and the sequencing of recombinant plasmid demonstrated that vector pGEX-4T1-TLE1-Q was successfully constructed. The SDS-PAGE shows target protein (14 000 Da) is the interest protein TLE1-Q(1-136). The TLE1 N-terminal Q domain fragment TLE1-Q(1-136) and its polyclonal antibody have been acquired, with an antibody titer of 1:20 000. Conclusion Expression vector pGEX-4T1-TLE1-Q is correctly constructed. The TLE1 N-terminal Q domain fragment TLE1-Q(1-136) and its polyclonal antibody have been acquired. These work established the foundation for further biological study between TLE1 and lung cancers.

Shp2 (Src-homology 2 domain-containing phosphatase 2) was originally reported as an oncogene in kinds of solid tumors and hematologic malignancies. However, recent studies indicated that Shp2 may act as tumor suppressors in several tumor types. We investigated the function of Shp2 in esophageal squamous cell cancer (ESCC). The expression level of Shp2 was analyzed in tumor tissues in comparison with adjacent normal tissues of ESCC patients by immunohistochemistry and Western blot. Shp2 was knocked down by Short hairpin RNA to evaluate its function in ESCC cell lines. The relationship between Shp2 and p-Stat3 (signal transducer and activator of transcription 3) in human ESCC tissues was statistically examined. A significant low expression of Shp2 was found in ESCC tissues. Low expression of Shp2 was related to poorer overall survival in patients from The Cancer Genome Atlas (TCGA) dataset. Knockdown of Shp2 increased the growth of ESCC cell lines both in vivo and vitro. Activation of Stat3 (p-Stat3) was induced by Shp2 depletion. Expression of p-Stat3 was negatively correlated with Shp2 expression in ESCC tissues. Furthermore, knockdown of Shp2 attenuated cisplatin-sensitivity of ESCC cells. Shp2 might suppress the proliferation of ESCC by dephosphorylation of p-Stat3 and represents a novel research field for targeted therapy.

BACKGROUND: McKeown-type esophagectomy combined with retrosternal reconstruction is a common surgical treatment for esophageal cancer. Various enteral feeding options are available post-esophagectomy, but no definitive preference exists. METHOD: "Retrosternal Route Gastrostomy Feeding (RGF)" was developed as an alternative enteral feeding approach that requires few additional surgical interventions. RGF is based on McKeown-type esophagectomy. We retrospectively compared RGF (n = 121) to jejunostomy feeding (JF) (n = 153) in 274 patients at the Department of Cardiothoracic Surgery in Changzheng Hospital (Shanghai, China) between June 2008 and Sept. 2012. Data pertaining to efficacy and procedural complications were compared among patients. RESULTS: RGF had a significantly shorter postoperative hospital stay (11 vs. 15 days, p

Abstract Background Epigenetic modifications that exhibit circadian oscillations also promote circadian oscillations of gene expression. Brassica napus is a heterozygous polyploid species that has undergone distant hybridization and genome doubling events and has a young and distinct species origin. Studies incorporating circadian rhythm analysis of epigenetic modifications can offer new insights into differences in diurnal oscillation behavior among subgenomes and the regulation of diverse expressions of homologous gene rhythms in biological clocks. Results In this study, we created a high-resolution and multioscillatory gene expression dataset, active histone modification (H3K4me3, H3K9ac), and RNAPII recruitment in Brassica napus. We also conducted the pioneering characterization of the diurnal rhythm of transcription and epigenetic modifications in an allopolyploid species. We compared the evolution of diurnal rhythms between subgenomes and observed that the Cn subgenome had higher diurnal oscillation activity in both transcription and active histone modifications than the An subgenome. Compared to the A subgenome in Brassica rapa, the An subgenome of Brassica napus displayed significant changes in diurnal oscillation characteristics of transcription. Homologous gene pairs exhibited a higher proportion of diurnal oscillation in transcription than subgenome-specific genes, attributed to higher chromatin accessibility and abundance of active epigenetic modification types. We found that the diurnal expression of homologous genes displayed diversity, and the redundancy of the circadian system resulted in extensive changes in the diurnal rhythm characteristics of clock genes after distant hybridization and genome duplication events. Epigenetic modifications influenced the differences in the diurnal rhythm of homologous gene expression, and the diurnal oscillation of homologous gene expression was affected by the combination of multiple histone modifications. Conclusions Herein, we presented, for the first time, a characterization of the diurnal rhythm characteristics of gene expression and its epigenetic modifications in an allopolyploid species. Our discoveries shed light on the epigenetic factors responsible for the diurnal oscillation activity imbalance between subgenomes and homologous genes’ rhythmic expression differences. The comprehensive time-series dataset we generated for gene expression and epigenetic modifications provides a valuable resource for future investigations into the regulatory mechanisms of protein-coding genes in Brassica napus.

In this paper, new bridged-T network operating with bandpass (BP) negative group delay (NGD) function is introduced. The circuit design is innovatively based on an inductorless passive RCnetwork. The innovative bridged-T topology is implemented with a R-shunt configuration. The analytical transfer function of voltages and equivalent impedance-matrix are carefully calculated. The BP NGD analysis and design of the bridged-T topology is developed. The BP NGD properties and specifications are analytically investigated. A proof of concept of R-shunt bridged-T prototype with a surface-mounted device printed circuit board is designed, fabricated, and measured to verify the BP NGD behavior from theoretical equations and simulations. As expected, the theoretical, simulation, and measurements results are in very good agreement. From measurement results, the fabricated BP NGD C-shunt bridged-T reaches a delay of about -45 ns and a center frequency of about 0.5 MHz over a -3 dB attenuation. [ABSTRACT FROM AUTHOR]

Objective: While most studies on Central Sleep Apnea (CSA) have focused on breathing and metabolic disorders, the neuronal dysfunction that causes CSA remains largely unknown. Here, we investigate the underlying neuronal mechanism of CSA by studying the sleep-wake dynamics as derived from hypnograms. Methods: We analyze sleep data of seven groups of subjects: healthy adults (n = 48), adults with obstructive sleep apnea (OSA) (n = 29), adults with CSA (n = 25), healthy children (n = 40), children with OSA (n = 18), children with CSA (n = 73) and CSA children treated with CPAP (n = 10). We calculate sleep-wake parameters based on the probability distributions of wake-bout durations and sleep-bout durations. We compare these parameters with results obtained from a neuronal model that simulates the interplay between sleep- and wake-promoting neurons. Results: We find that sleep arousals of CSA patients show a characteristic time scale (i.e., exponential distribution) in contrast to the scale-invariant (i.e., power-law) distribution that has been reported for arousals in healthy sleep. Furthermore, we show that this change in arousal statistics is caused by triggering more arousals of similar durations, which through our model can be related to a higher excitability threshold in sleep-promoting neurons in CSA patients. Conclusions: We propose a neuronal mechanism to shed light on CSA pathophysiology and a method to discriminate between CSA and OSA. We show that higher neuronal excitability thresholds can lead to complex reorganization of sleep-wake dynamics. Significance: The derived sleep parameters enable a more specific evaluation of CSA severity and can be used for CSA diagnosis and monitor CSA treatment. [ABSTRACT FROM AUTHOR]

This paper introduces a tensorial analysis of networks (TAN) applied to a tree asymmetrical structure. To illustrate the TAN concept easily, the present investigation is applied to a three-port structure represented by a Y -tree topology. The unfamiliar method of TAN circuit modelling is elaborated from the graph topology. The fast formulation of the Y -matrix model of the structure is established from branch and mesh space TAN analyses. The TAN model is validated with commercial tool simulation and measurements from DC up to 0.5 GHz in the frequency domain and two different waveform signals in the time domain. The proof of concept circuit is implemented in microstrip technology on an FR4-epoxy dielectric substrate. Mapping sensitivity analysis with respect to the Y -tree RLC-parameters is realized by showing that local variations around initial set of R, L, and C do not equally influence reflection and transmission coefficients over the frequency bandwidth. If a similar impact is observed at the lowest frequency, maximum variations up to 250% show the importance of parameters ranking to improve both microstrip design and modelling. [ABSTRACT FROM AUTHOR]

Objective To systematically investigate and validate the survey methodology for the epidemiological study of childhood sleep-disordered breathing (SDB) in mainland China using the Mandarin version of the Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder (PSQSRBD). Design A cross-sectional study using randomised, stratified, multistage, cluster sampling method. Setting A total of 11 kindergartens, 7 primary schools and 8 middle schools from 7 districts of Beijing, China. Participants A total of 9198 children with valid questionnaires (4736 boys and 4462 girls; age range 3.0-14.4 years) were included. Primary and secondary outcome measures Data on sociodemographic characteristics and PSQ-SRBD were collected. The score on PSQ-SRBD and the included factors were calculated with the effective data after data cleaning. Logistic regression and factor analysis with the principal components method were used to evaluate the validity of the questionnaire; reliability was assessed by retesting 5% of the respondents after 2±4 weeks of the initial test, and the intraclass correlation coefficient was calculated. Results The effective response rate of80.54% matched the sociodemographic characteristics of the respondents with respect to age group ratio and sex ratio in Beijing. With regard to construct validity of the PSQ-SRBD, the item score, except that of 'delayed growth', was highly correlated to the SRBD score as assessed by the logistic regression model. The exploratory factor analysis displayed a credible construct validity, with majority of the items grouped as the original dimensions. The test-retest reliability coefficient of each dimension's score ranged from 0.758 to 0.901, with an SRBD score of 0.730 indicating significant retest reliability. Conclusions This study conducted and validated a successful survey methodology for investigation of childhood SDB in Beijing, China. The questionnaire demonstrated credible construct validity and retest reliability, thereby supporting the applicability and generalisability of the PSQ-SRBD in a large epidemiological survey of childhood SDB in China. [ABSTRACT FROM AUTHOR]

Rationale: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA.Methods: Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA.Measurements and Main Results: The automatically estimated apnea-hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively).Conclusions: Neural network-based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes. [ABSTRACT FROM AUTHOR]

The measurement of surface curvature is of great significance in aerospace, structural health monitoring, energy batteries, etc. In this paper, a fiber-optic surface curvature sensor, based on intracavity sensing of fiber ring laser (FRL), is experimentally demonstrated. A no-core fiber- based filter performs as the sensing head of the FRL sensor. The response between the curvature of the NCF and the output wavelength of the FRL was investigated. In the measurement of curvature, the sensor system showed a narrow 3-dB bandwidth of 0.08 nm, with a high signal-to-noise ratio of about 60 dB. The curvature sensitivities were measured as −0.348 nm/m−1 within 0.2 m−1, and −3.185 nm/m−1 from 0.2 m−1 to 0.475 m−1. The performance of the surface curvature sensor was characterized by parameters, including output stability, temperature cross-sensitivity, and detection limit.

Background: Chemotherapy is the only therapy option for the majority of AML patients, however, there are several limitations for this treatment. Our aim was to find a new chemotherapy strategy that is more effective and less toxic. Methods: MTT assays and a xenograft mouse model were employed to evaluate the synergistic activity of all-trans retinoic acid (ATRA) combined with topotecan (TPT). Drug-induced DNA damage and apoptosis were determined by flow cytometry analysis with PI and DAPI staining, the comet assay and Western blots. Short hairpin RNA (shRNA) and a RARα plasmid were used to determine whether RARα expression influenced DNA damage and apoptosis. Results: We found that ATRA exhibited synergistic activity in combination with Topotecan in AML cells, and the enhanced apoptosis induced by Topotecan plus ATRA resulted from caspase pathway activation. Mechanistically, ATRA dramatically down regulated RARα protein levels and led to more DNA damage and ultimately resulted in the synergism of these two agents. In addition, the increased antitumor efficacy of Topotecan combined with ATRA was further validated in the HL60 xenograft mouse model. Conclusions: Our data demonstrated, for the first time, that the combination of TPT and ATRA showed potential benefits in AML, providing a novel insight into clinical treatment strategies. [ABSTRACT FROM AUTHOR]

Background: The reconstruction of large bone defects, including rib defects, remains a challenge for surgeons. In this study, we used biodegradable polydioxanone (PDO) cages to tissue engineer ribs for the reconstruction of 4cm-long costal defects. Methods: PDO sutures were used to weave 6cm long and 1cm diameter cages. Demineralized bone matrix (DBM) which is a xenograft was molded into cuboids and seeded with second passage bone marrow mesenchymal stem cells (BMSCs) that had been osteogenically induced. Two DBM cuboids seeded with BMSCs were put into the PDO cage and used to reconstruct the costal defects. Radiographic examination including 3D reconstruction, histologic examination and mechanical test was performed after 24 postoperative weeks. Results: All the experimental subjects survived. In all groups, the PDO cage had completely degraded after 24 weeks and been replaced by fibrous tissue. Better shape and radian were achieved in PDO cages filled with DBM and BMSCs than in the other two groups (cages alone, or cages filled with acellular DBM cuboids). When the repaired ribs were subjected to an outer force, the ribs in the PDO cage/DBMs/BMSCs group kept their original shape while ribs in the other two groups deformed. In the PDO cage/DBMs/BMSCs groups, we also observed bony union at all the construct interfaces while there was no bony union observed in the other two groups. This result was also confirmed by radiographic and histologic examination. Conclusions: This study demonstrates that biodegradable PDO cage in combination with two short BMSCs/DBM cuboids can repair large rib defects. The satisfactory repair rate suggests that this might be a feasible approach for large bone repair [ABSTRACT FROM AUTHOR]

Background: The purpose of the present study was to explore the clinicopathological characteristics and operative therapeutic efficacy of thoracic esophageal cancer after gastrectomy and compare with those without gastrectomy.Methods: From January 2000 to June 2007, 28 esophageal cancer patients with a history of distal gastrectomy underwent subtotal esophagectomy. Vascularized pedicle colonic conduit was most commonly used for esophageal substitution. Six hundred seventeen patients without a history of gastrectomy treated in the same period form the control group. After the operation, pathological characteristic, tumor staging, and survival statistics were analyzed.Results: Of those patients with esophageal cancer associated with gastric remnant, the majority were male. There was an average of 16.5 years for diagnosing esophageal cancer from the initial partial gastrectomy, 75% (21/28) of them were patients with Billroth I anastomosis. The proportion of lower-third tumors in patients after gastrectomy (12 of 28 patients, 43%) was significantly higher compared with that of the patients with intact stomachs (124 of 617 patients, 20%; P = 0.004). After surgical treatment, the overall 1-, 3-, and 5-year survival rates of gastrectomized and nongastrectomized patients were 100%, 35.00%, and 23.33% versus 98.93%, 59.42%, and 30.85% in stages I-II and 80.00%, 30.00%, and 0% versus 98.59%, 62.03%, and 21.03% in stages III-IV. The log rank test of equality of survival distribution for the gastrectomized vs nongastrectomized patients was not significant in stages I-II (P = 0.5692) but was significant in stages III-IV (P = 0.0166).Conclusions: The patients with partial gastrectomy for more than 5 years, having upper gastrointestinal symptoms, should be considered having the risk of esophageal cancer associated with gastric remnant. For patients with a history of distal gastrectomy, a vascularized pedicle colonic conduit was most commonly used for esophageal substitution. Surgical efficacy was similar with the no-gastrectomy group in early stages I-II of esophageal cancer associated with gastric remnant but was lower compared with the no-gastrectomy group in stages III-IV. So, early diagnosis and an aggressive surgical approach may be crucial to achieve better outcomes for esophageal cancer patients with gastrectomy. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive transhiatal esophagectomy for esophageal cancer includes mediastinoscopic and laparoscopic transhiatal esophagectomy. It is inadequate in both two techniques. It is impossible to dissect the lower esophagus with single mediastinoscopy or the upper and middle esophagus with single laparoscopy. We use mediastinoscopy combined with laparoscopy to dissect the whole esophagus and stomach including lymph node dissection. In addition, laparoscopic gastric mobilization leads to less trauma than an open gastroplasty. Methods: 40 cases of video-assisted mediastinoscopic transhiatal esophagectomy were performed and divided into two groups.32 patients were received surgical therapy of single mediastinoscopic esophagectomy with open gastroplasty in group A, while 8 patients were received surgical therapy of mediastinoscopic esophagectomy combined with laparoscopic lower esophageal and gastric dissection in group B. The perioperative complications were recorded. Results: Video-assisted mediastinoscopic transhiatal esophagectomy was performed successfully both in group A and B. It suggested that mediastinoscopy combined with laparoscopy be better than single mediastinoscopy because of less blood loss, less pain, shorter ICU stay and complete lower mediastinal lymph nodes resection. Conclusions: Video-assisted mediastinoscopic transhiatal esophagectomy combined with laparoscopy is a safe and minimally invasive technique with whole esophagus and mediastinal lymph node dissection in the clear visualization of the mediastinum, reducing the abdominal trauma. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to explore the efficacy of an extended operation for locally advanced non-small cell lung cancer invading the left atrium and intrapericardial pulmonary vein. From January 2000 to January 2006, lobectomy or pneumonectomy combined with extended resection of the left atrium was carried out in 46 patients. The operations included left lower lobectomy in 6 cases, left pneumonectomy in 14 cases, right middle and lower lobectomy in 8 cases, right lower lobectomy in 2 cases, and right pneumonectomy in 16 cases; these cases accounted for 4.9% of the lung cancer patients who underwent surgical treatment in the Changzheng Hospital, Second Military Medical University, during the study period. There were no surgery-related deaths, and the overall 1-, 3-, and 5-year survival rates were 71.77%, 37.79%, and 22.04%, respectively; the 1-, 3-, and 5-year survival rates of patients with no lymph node involvement (N0) were 77.16%, 43.40%, and 28.94%, respectively; the 1-, 3-, and 5-year survival rates of N1 patients were 75.94%, 41.88%, and 27.92%, respectively; the 1- and 3-year survival rates of N2 patients were 53.85% and 17.95%, respectively. Surgical treatment of T4 lung cancer invading the left atrium or the base of the pulmonary vein is feasible, particularly in N0 and N1 patients with a ≤3 cm maximum diameter of primary lung cancer. It can improve the quality of life and increase long-term survival. Surgical management should be considered in selected lung cancer patients. [ABSTRACT FROM AUTHOR]

The article reports on a study to determine the occurrence of obstructive sleep apnea-hypopnea syndrome (OSAHS) in children and the role of obesity in OSAHS. The results from the study, involving 99 obese children and 99 controls, indicated that obesity is a contributing factor to OSAHS and the degree of obesity is positively linked to the gravity of OSAHS.

The article discusses the factors being applied when predicting obstructive sleep apnea (OSA) in children. Some of the factors used are parents' observation, clinical examination and lateral upper airway radiograph. On the other hand, the symptoms of OSA include apnea during sleep, nocturnal enuresis, intrusive naps, mouth breathing, enlarged tonsils and upper airway narrowing. The authors conclude that the use of combined clinical and radiologic findings might be helpful in screening OSA.

Four patients with diffuse emphysema and a giant bulla were treated by a modified Brompton technique using a mushroom catheter and low suction. There was no mortality although one patient developed a troublesome pulmonary infection. All the patients had significant symptomatic improvement with a mean dyspnoea index changing from 3.5 before operation to 2.25 afterwards. We concluded that the modified Brompton technique is a safe and simple alternative in treating a giant bulla associated with diffuse emphysema. [ABSTRACT FROM AUTHOR]

BSTRACT [ABSTRACT FROM AUTHOR]