Airway hillocks are injury-resistant reservoirs of unique plastic stem cells.

Airway hillocks are stratified epithelial structures of unknown function1. Hillocks persist for months and have a unique population of basal stem cells that express genes associated with barrier function and cell adhesion. Hillock basal stem cells continually replenish overlying squamous barrier cells. They exhibit dramatically higher turnover than the abundant, largely quiescent classic pseudostratified airway epithelium. Hillocks resist a remarkably broad spectrum of injuries, including toxins, infection, acid and physical injury because hillock squamous cells shield underlying hillock basal stem cells from injury. Hillock basal stem cells are capable of massive clonal expansion that is sufficient to resurface denuded airway, and eventually regenerate normal airway epithelium with each of its six component cell types. Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signalling inhibition, a known cause of squamous metaplasia2,3. Here we show that mouse hillock expansion is the cause of vitamin A deficiency-induced squamous metaplasia. Finally, we identify human hillocks whose basal stem cells generate functional squamous barrier structures in culture. The existence of hillocks reframes our understanding of airway epithelial regeneration. Furthermore, we show that hillocks are one origin of 'squamous metaplasia', which is long thought to be a precursor of lung cancer.

Analysis of antimicrobial biological activity of a marine Bacillus velezensis NDB.

A new strain of Bacillus velezensis NDB was isolated from Xiangshan Harbor and antibacterial test revealed antibacterial activity of this strain against 12 major pathogenic bacteria. The whole genome of the bacterium was sequenced and found to consist of a 4,214,838 bp circular chromosome and a 7410 bp circular plasmid. Furthermore, it was predicted by AntiSMASH and BAGEL4 to have 12 clusters of secondary metabolism genes for the synthesis of the inhibitors, fengycin, bacillomycin, macrolactin H, bacillaene, and difficidin, and there were also five clusters encoding potentially novel antimicrobial substances, as well as three bacteriocin biosynthesis gene clusters of amylocyclicin, ComX1, and LCI. qRT-PCR revealed significant up-regulation of antimicrobial secondary metabolite synthesis genes after 24 h of antagonism with pathogenic bacteria. Furthermore, MALDI-TOF mass spectrometry revealed that it can secrete surfactin non-ribosomal peptide synthase and polyketide synthase to exert antibacterial effects. GC-MS was used to analyze methanol extract of B. velezensis NDB, a total of 68 compounds were identified and these metabolites include 16 amino acids, 17 acids, 3 amines, 11 sugars, 11 alcohols, 1 ester, and 9 other compounds which can inhibit pathogenic bacteria by initiating the antibiotic secretion pathway. A comparative genomic analysis of gene families showed that the specificity of B. velezensis NDB was mainly reflected in environmental adaptability. Overall, this research on B. velezensis NDB provides the basis for elucidating its biocontrol effect and promotes its future application as a probiotic.

Radioiodine therapy in advanced differentiated thyroid cancer: Resistance and overcoming strategy.

Thyroid cancer is the most prevalent endocrine tumor and its incidence is fast-growing worldwide in recent years. Differentiated thyroid cancer (DTC) is the most common pathological subtype which is typically curable with surgery and Radioactive iodine (RAI) therapy (approximately 85%). Radioactive iodine is the first-line treatment for patients with metastatic Papillary Thyroid Cancer (PTC). However, 60% of patients with aggressive metastasis DTC developed resistance to RAI treatment and had a poor overall prognosis. The molecular mechanisms of RAI resistance include gene mutation and fusion, failure to transport RAI into the DTC cells, and interference with the tumor microenvironment (TME). However, it is unclear whether the above are the main drivers of the inability of patients with DTC to benefit from iodine therapy. With the development of new biological technologies, strategies that bolster RAI function include TKI-targeted therapy, DTC cell redifferentiation, and improved drug delivery via extracellular vesicles (EVs) have emerged. Despite some promising data and early success, overall survival was not prolonged in the majority of patients, and the disease continued to progress. It is still necessary to understand the genetic landscape and signaling pathways leading to iodine resistance and enhance the effectiveness and safety of the RAI sensitization approach. This review will summarize the mechanisms of RAI resistance, predictive biomarkers of RAI resistance, and the current RAI sensitization strategies.

Relationship between self-reported sleep and cognitive function: a specification curve analysis.

The relationship between self-reported sleep and cognitive function is complex; it is unclear whether self-reported sleep is a robust correlate of people's cognitive function. We address this gap by using a comprehensive large-scale dataset (N = 1054) coupled with a novel modeling approach, specification curve analysis (SCA), to test the association between self-reported sleep and cognitive function. The results of the SCA showed robust correlations between self-reported sleep and cognitive function, with poorer sleep associated with worse cognitive function. Furthermore, the correlations between sleep components and cognitive function were heterogeneous, with differences emerging across cognitive measures and domains. Specifically, daytime dysfunction was associated with the strongest effect on subjective cognitive function, whereas sleep duration and sleep efficiency had the strongest effect on objective cognitive function. Therefore, the relationship between self-reported sleep and cognition depends largely on what and how cognitive function is measured. Our findings guide measurement and domain selection for future research on the role of sleep in cognitive function.

[Accurate tissue flap reconstruction method based on the quadratic surface developability for head and neck soft tissue defects].

Soft tissue defects resulting from head and neck tumor resection seriously impact the physical appearance and psychological well-being of patients. The complex curvature of the human head and neck poses a formidable challenge for maxillofacial surgeons to achieve precise aesthetic and functional restoration after surgery. To this end, a normal head and neck volunteer was selected as the subject of investigation. Employing Gaussian curvature analysis, combined with mechanical constraints and principal curvature analysis methods of soft tissue clinical treatment, a precise developable/non-developable area partition map of the head and neck surface was obtained, and a non-developable surface was constructed. Subsequently, a digital design method was proposed for the repair of head and neck soft tissue defects, and an in vitro simulated surgery experiment was conducted. Clinical verification was performed on a patient with tonsil tumor, and the results demonstrated that digital technology-designed flaps improved the accuracy and aesthetic outcome of head and neck soft tissue defect repair surgery. This study validates the feasibility of digital precision repair technology for soft tissue defects after head and neck tumor resection, which effectively assists surgeons in achieving precise flap transplantation reconstruction and improves patients' postoperative satisfaction.

Glymphatic dysfunction correlates with severity of small vessel disease and cognitive impairment in cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is characterized by ß-amyloid deposition in cortical and leptomeningeal arterioles, which might result from glymphatic dysfunction. The aim was to explore glymphatic function in CAA using the non-invasive diffusion tensor image analysis along the perivascular space method. METHODS: Sixty-three patients with CAA were prospectively recruited together with seventy age- and sex-matched normal controls. The Mini-Mental State Examination and Montreal Cognitive Assessment were applied to screen global cognitive status. Magnetic resonance imaging scans were conducted to calculate the index for diffusivity along the perivascular space (ALPS index), and linear regression models were used to assess its relationships with cerebral small vessel disease (CSVD) markers, cognitive status and blood biomarkers. Cox proportional hazard models were applied to explore the role of the baseline ALPS index in disease recurrence. RESULTS: Patients with CAA exhibited a lower ALPS index than controls globally (p < 0.001). In addition, a lower ALPS index was related to more enlarged perivascular space in basal ganglia (p = 0.026), more lacunes (p < 0.001), higher white matter hyperintensity Fazekas score (p = 0.049), elevated total magnetic resonance imaging burden of CSVD (p = 0.034) and lower Mini-Mental State Examination (p = 0.001) as well as Montreal Cognitive Assessment (p < 0.001) in CAA. During a median follow-up of 4.1 years, a higher ALPS index was associated with lower disease recurrence (p = 0.022). The ALPS index was also negatively correlated with serum soluble intercellular adhesion molecule-1, neurofilament light and chitinase-3-like protein 1 in CAA. CONCLUSIONS: Patients with CAA showed impaired glymphatic function. The ALPS index was significantly related to CSVD severity, cognitive impairment and disease recurrence in CAA.

Tibial nerve stimulation increases vaginal blood perfusion and bone mineral density and yield load in ovariectomized rat menopause model.

INTRODUCTION AND HYPOTHESIS: Human menopause transition and post-menopausal syndrome, driven by reduced ovarian activity and estrogen levels, are associated with an increased risk for symptoms including but not limited to sexual dysfunction, metabolic disease, and osteoporosis. Current treatments are limited in efficacy and may have adverse consequences, so investigation for additional treatment options is necessary. Previous studies have demonstrated that percutaneous tibial nerve stimulation (PTNS) and electro-acupuncture near the tibial nerve are minimally invasive treatments that increase vaginal blood perfusion or serum estrogen in the rat model. We hypothesized that PTNS would protect against harmful reproductive and systemic changes associated with menopause. METHODS: We examined the effects of twice-weekly PTNS (0.2 ms pulse width, 20 Hz, 2× motor threshold) under ketamine-xylazine anesthesia in ovariectomized (OVX) female Sprague-Dawley rats on menopause-associated physiological parameters including serum estradiol, body weight, blood glucose, bone health, and vaginal blood perfusion. Rats were split into three groups (n = 10 per group): (1) intact control (no stimulation), (2) OVX control (no stimulation), and (3) OVX stimulation (treatment group). RESULTS: PTNS did not affect serum estradiol levels, body weight, or blood glucose. PTNS transiently increased vaginal blood perfusion during stimulation for up to 5 weeks after OVX and increased areal bone mineral density and yield load of the right femur (side of stimulation) compared to the unstimulated OVX control. CONCLUSIONS: PTNS may ameliorate some symptoms associated with menopause. Additional studies to elucidate the full potential of PTNS on menopause-associated symptoms under different experimental conditions are warranted.

Interleukin-10-Modified Adipose-Derived Mesenchymal Stem Cells Prevent Hypertrophic Scar Formation via Regulating the Biological Characteristics of Fibroblasts and Inflammation.

Hypertrophic scar causes serious functional and cosmetic problem, but no treatment method is known to achieve a satisfactory therapeutic effect. However, mesenchymal stem cells show a possible cure prospect. Here, we investigated the effect of interleukin-10-modified adipose-derived mesenchymal stem cells (IL-10-ADMSC) on the formation of hypertrophic scar. In vitro, IL-10-ADMSC could highly express IL-10 and exhibited stronger inhibition of hypertrophic scar fibroblasts (HSFs) proliferation, migration, and extracellular matrix synthesis (the expression of collagen I, collagen III, FN, and α-SMA protein) than ADMSC. In vivo, we found that IL-10-ADMSC speeded up wound healing time and reduced scar area and scar outstanding height. Same as in vitro, IL-10-ADMSC also exhibited stronger inhibition of extracellular matrix synthesis (the expression of collagen I, collagen III protein) in wound than ADMSC. In addition, we also found that IL-10-ADMSC is also a stronger inhibitory effect on inflammation in wound than ADMSC, and IL-10-ADMSC inhibited TGF-ß/Smads and NF-κB pathway. In conclusion, IL-10-ADMSC demonstrated the ability to prevent hypertrophic scar formation. And its possible molecular mechanism might be related to IL-10-ADMSC inhibiting the proliferation and migration of the synthesis of extracellular matrix of HSFs, and IL-10-ADMSC inhibited the inflammation during the wound healing.

Novel computer-aided reconstruction of soft tissue defects following resection of oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: Reconstruction of soft tissue defects following surgical tumor resection is important for quality of life in cancer patients with oral and oropharyngeal squamous cell carcinoma (SCC). This study presents a novel computer-aided reconstruction of soft tissue (CARST) technology employed with these patients. METHODS: We first described the CARST technology in detail in a report of a 34-year-old male patient with locally invasive right-sided tongue SCC following a nearly total glossectomy and reported the postoperative outcomes. This digital technology was applied to construct a 3D model from CT images, which was used to delineate surgical resection boundaries and design a personalized reconstruction of the soft tissue defect. A nonuniform rational B-spline (NURBS) was generated and applied to transform the 3D model into a 2D flap-cutting guide printed out using a 3D printer. We then reported a case-series study on oral and oropharyngeal SCC patients who were randomly assigned to receive the CARST (n = 15) or a traditional soft tissue reconstruction (n = 15). Clinicopathological features and short- and long-term postoperative outcomes between the two groups were compared. RESULTS: The patient with the tongue SCC had a successful CARST following surgical tumor resection without any complications. His speech and swallowing functions recovered well after surgery and he experienced no significant changes to his appearance following recovery. There was no recurrence within a 3-year follow-up period. Results of the case-series study showed that the CARST group had significantly shorter operative and post-operation hospital-stay time, a higher flap utilization rate, and a trend of less and milder postoperative complications, and they experienced no significant difference in intraoperative blood loss and long-term outcomes compared to the traditional group. CONCLUSION: CARST is a safer and more efficient personalized technology of soft tissue reconstruction following surgical tumor resection in patients with oral and oropharyngeal SCC.

Diagnosis of cardiac abnormalities based on phonocardiogram using a novel fuzzy matching feature extraction method.

BACKGROUND: The diagnosis of cardiac abnormalities based on heart sound signal is a research hotspot in recent years. The early diagnosis of cardiac abnormalities has a crucial significance for the treatment of heart diseases. METHODS: For the sake of achieving more practical clinical applications of automatic recognition of cardiac abnormalities, here we proposed a novel fuzzy matching feature extraction method. First of all, a group of Gaussian wavelets are selected and then optimized based on a template signal. Convolutional features of test signal and the template signal are then computed. Matching degree and matching energy features between template signal and test signal in time domain and frequency domain are then extracted. To test performance of proposed feature extraction method, machine learning algorithms such as K-nearest neighbor, support vector machine, random forest and multilayer perceptron with grid search parameter optimization are constructed to recognize heart disease using the extracted features based on phonocardiogram signals. RESULTS: As a result, we found that the best classification accuracy of random forest reaches 96.5% under tenfold cross validation using the features extracted by the proposed method. Further, Mel-Frequency Cepstral Coefficients of phonocardiogram signals combing with features extracted by our algorithm are evaluated. Accuracy, sensitivity and specificity of integrated features reaches 99.0%, 99.4% and 99.7% respectively when using support vector machine, which achieves the best performance among all reported algorithms based on the same dataset. On several common features, we used independent sample t-tests. The results revealed that there are significant differences (p < 0.05) between 5 categories. CONCLUSION: It can be concluded that our proposed fuzzy matching feature extraction method is a practical approach to extract powerful and interpretable features from one-dimensional signals for heart sound diagnostics and other pattern recognition task.

Visuospatial dysfunction is associated with posterior distribution of white matter damage in non-demented cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a well-recognized contributor to cognitive decline in the elderly. The posterior cortical predilection of CAA pathology would cause visuospatial dysfunction, which is still underexplored. We aimed to investigate whether the visuospatial dysfunction in CAA is associated with the posterior distribution of small vessel disease (SVD) imaging markers. METHODS: We recruited 60 non-demented CAA cases from a Chinese prospective cohort and 30 cases with non-CAA SVD as controls. We used the Visual Object and Space Perception (VOSP) battery to evaluate visuospatial abilities, and multivariable regression models to assess their associations with SVD imaging markers. RESULTS: There was visuospatial dysfunction, especially visual object perception impairment, in CAA compared to controls (Z-score of VOSP: -0.11 ± 0.66 vs. 0.22 ± 0.54, p = 0.023). The VOSP score in CAA was independently related to the fronto-occipital gradient of white matter hyperintensity volumes (coefficient = 0.03, 95% confidence interval [CI] = 0.003-0.05, p = 0.030) and mean fractional anisotropy values on diffusion tensor imaging (coefficient = 4.72, 95% CI = 0.97-8.48, p = 0.015), but not the severity of global SVD imaging markers or the gradient of lobar cerebral microbleeds with adjustments for age and global cognition score. CONCLUSIONS: This finding suggests that the damage of posterior white matter rather than global disease severity may be a major contributor to visuospatial dysfunction in CAA.

Direct Medium-Chain Carboxylic Acid Oil Separation from a Bioreactor by an Electrodialysis/Phase Separation Cell.

Medium-chain carboxylic acids (MCCAs) are valuable platform chemicals and can be produced from waste biomass sources or syngas fermentation effluent through microbial chain elongation. We have previously demonstrated successful approaches to separate >90% purity oil with different MCCAs (MCCA oil) by integrating the anaerobic bioprocess with membrane-based liquid-liquid extraction (pertraction) and membrane electrolysis. However, two-compartment membrane electrolysis unit without pertraction was not able to separate MCCA oil. Therefore, we developed a five-compartment electrodialysis/phase separation cell (ED/PS). First, we tested an ED/PS cell in series with pertraction and achieved a maximum MCCA-oil flux of 1.7 × 103 g d-1 per projected area (m2) (19 mL oil d-1) and MCCA-oil transfer efficiency [100% × moles MCCA-oil moles electrons-1] of 74% at 15 A m-2. This extraction system at 15 A m-2 demonstrated a ∼10 times lower electric-power consumption (1.1 kWh kg-1 MCCA oil) than membrane electrolysis in series with pertraction (9.9 kWh kg-1 MCCA oil). Second, we evaluated our ED/PS as a stand-alone unit when integrated with the anaerobic bioprocess and demonstrated that we can selectively extract and separate MCCA oil directly from chain-elongating bioreactor broth with just an abiotic electrochemical cell. However, the electric-power consumption increased considerably due to the lower MCCA concentrations in the bioreactor broth compared to the pertraction broth.

Development of Mast Cell and Eosinophil Hyperplasia and HLH/MAS-Like Disease in NSG-SGM3 Mice Receiving Human CD34+ Hematopoietic Stem Cells or Patient-Derived Leukemia Xenografts.

Immunocompromised mouse strains expressing human transgenes are being increasingly used in biomedical research. The genetic modifications in these mice cause various cellular responses, resulting in histologic features unique to each strain. The NSG-SGM3 mouse strain is similar to the commonly used NSG (NOD scid gamma) strain but expresses human transgenes encoding stem cell factor (also known as KIT ligand), granulocyte-macrophage colony-stimulating factor, and interleukin 3. This report describes 3 histopathologic features seen in these mice when they are unmanipulated or after transplantation with human CD34+ hematopoietic stem cells (HSCs), virally transduced hCD34+ HSCs, or a leukemia patient-derived xenograft. The first feature is mast cell hyperplasia: unmanipulated, naïve mice develop periductular pancreatic aggregates of murine mast cells, whereas mice given the aforementioned human cells develop a proliferative infiltrative interstitial pancreatic mast cell hyperplasia but with human mast cells. The second feature is the predisposition of NSG-SGM3 mice given these human cells to develop eosinophil hyperplasia. The third feature, secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)-like disease, is the most pronounced in both its clinical and histopathologic presentations. As part of this disease, a small number of mice also have histiocytic infiltration of the brain and spinal cord with subsequent neurologic or vestibular signs. The presence of any of these features can confound accurate histopathologic interpretation; therefore, it is important to recognize them as strain characteristics and to differentiate them from what may be experimentally induced in the model being studied.

Craniofacial and Upper Airway Development in Patients With Treacher Collins Syndrome.

ABSTRACT: This study evaluated age-associated morphology changes in the cranial base, facial development, and upper airway of patients with Treacher Collins syndrome (TCS). A total of 33 preoperative computed tomographic images (TCS, n = 14; control, n = 19) were included in the study and divided into three age-related subgroups (2-6 years, 7-18 years, and older than 18 years). Linear, angular cephalometric measurements and upper airway volumes were collected. All measurements were analyzed using ProPlan CMF software (version 3.0; Materialize, Leuven, Belgium). The association between aging and upper airway morphology was analyzed. Compared to control subjects, TCS patients had a smaller cranial base, maxilla, and nose; they also had reduced upper airway volume compared to control subjects. The observed differences were most significant in patients between the ages of 7 and 18 years. This study used computed tomography-based three-dimensional analyses to provide a detailed description of age-related changes that occur in craniofacial measurements and upper airway volumes in children, adolescents, and young adult patients with TCS in China. These data can be used to evaluate individual patients with TCS and to select treatment to improve the growth of the craniofacial region.

Genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis.

Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland, with a relatively high cure rate. Distant metastasis (DM) of PTC is uncommon, but when it occurs, it significantly decreases the survival of PTC patients. The molecular mechanisms of DM in PTC have not been systematically studied. We performed whole exome sequencing and GeneseeqPrime (425 genes) panel sequencing of the primary tumor, plasma and matched white blood cell samples from 20 PTC with DM and 46 PTC without DM. We identified somatic mutations, gene fusions and copy number alterations and analyzed their relationships with DM of PTC. BRAF-V600E was identified in 73% of PTC, followed by RET fusions (14%) in a mutually exclusive manner (P < 0.0001). We found that gene fusions (RET, ALK or NTRK1) (P < 0.01) and chromosome 22q loss (P < 0.01) were independently associated with DM in both univariate and multivariate analyses. A nomogram model consisting of chromosome 22q loss, gene fusions and three clinical variables was built for predicting DM in PTC (C-index = 0.89). The plasma circulating tumor DNA (ctDNA) detection rate in PTC was only 38.9%; however, it was significantly associated with the metastatic status (P = 0.04), tumor size (P = 0.001) and invasiveness (P = 0.01). In conclusion, gene fusions and chromosome 22q loss were independently associated with DM in PTC and could serve as molecular biomarkers for predicting DM. The ctDNA detection rate was low in non-DM PTC but significantly higher in PTC with DM.

Interleukin-10 modified bone marrow mesenchymal stem cells prevent hypertrophic scar formation by inhibiting inflammation.

This study was performed to examine the effect of Interleukin-10 (IL-10) modified bone marrow mesenchymal stem cells (BMSCs) on hypertrophic scar formation on the rabbit ear hypertrophic scar model. Rabbit BMSCs were obtained by whole bone marrow adherence method and IL-10-modified BMSCs (IL-10BMSCs) were established by transfecting BMSCs with an adenovirus. We treated the rabbit ear hypertrophic scar with BMSCs and IL-10-BMSCs, then evaluated the area and measured the height of the hypertrophic scar, and detected expression using real-time PCR and western blot. Compared with wild type BMSCs, the proliferative capability of IL-10 modified BMSCs was significantly reduced, but the expression of IL-10 in IL-10-BMSCs was significantly increased. After treating with a local injection of BMSCs or IL-10-BMSCs in the rabbit ear hypertrophic scar, we found that the time of wound healing, the area and height of scar were all significantly reduced in the IL-10-BMSCs group when compared to those in the BMSCs group. Moreover, the expression of Collagen-I, α-SMA, TNF-α, IL-6 and IL-1ß mRNA, the number of CD45-positive cells, CD3-positive cells and ED-1-positive cells, and the expression of p-IKBα / IKBα, p-p65 / p65, p-JNK / JNK and p-c-JUN / c-JUN in the scar of the IL-10-BMSCs group were significantly lower than those in BMSCs group. IL-10 modified BMSCs prevented hypertrophic scar formation in the rabbit ear hypertrophic scar model, and the results suggest this could be due to the inhibition of inflammation by IL-10 modified BMSCs through the JNK / NF-κB pathway.

How the health institution combinative contracting mechanism influences community residents' patient experiences in Shanghai: A comparative study of data from two cross-sectional surveys.

OBJECTIVE: To understand the effect of the health institution combinative contracting mechanism (which make participating residents make a "combinative contracting" involving family doctor of community health center, one secondary hospital, and one tertiary hospital) on community residents' patient experiences in Shanghai, China. METHODS: We conducted two questionnaire surveys (2016 and 2018) on the patient experiences of 1200 permanent residents of 12 subdistricts of Shanghai, who were selected via stratified random sampling. Of these, 926 participants were included after propensity score matching. We compared five dimensions of patient experience-accessibility, environment and facilities, service attitude and emotional support, communication and patient engagement, and service integration-before and after implementation of the health institution combinative contracting mechanism in June 2016. Furthermore, logistic regression analysis was used to explore the factors related to residents' overall experience. RESULTS: The health institution combinative contracting mechanism influenced most dimensions of residents' patient experience, such as accessibility, service attitude and emotional support, communication and patient participation, and service integration. The mechanism in general helped contracted residents obtain a better patient experience than before its implementation. Referral had a significant effect on participants' overall experience. CONCLUSION: Contracted family doctors play active roles in improving nearly every dimension of residents' service experience, as well as their overall experience of services. The health institution combinative contracting mechanism not only increases interaction and strengthens trust between doctors and patients but also makes it possible for residents to obtain integrated health services.

Correlation Between Mandible and External Ear in Patients with Treacher-Collins Syndrome.

BACKGROUND: Patients with Treacher-Collins syndrome (TCS) are frequently affected by congenital ear deformities. The external ear in patients with TCS tends to have both abnormal morphology and reduced overall volume. Previous studies considered a correlation exists between TCS mandibular skeletal features and external ear volume. The purpose of this study was to assess the external ear volume in patients with TCS 3-dimensionally. Furthermore, this study evaluated the relationship between mandibular morphology, external ear profile, and external ear volume. METHODS: A total of 36 nonoperated patients with TCS were compared to 39 age- and gender-matched normal controls. Morphologic variables of the mandible and the external ear were compared between TCS group and controls by 3-dimensional cephalometrics. The external ear volume and morphologic variables were analyzed with independent sample T-tests and Pearson correlation coefficient analyses (level of evidence: level III). RESULTS: The external ear volume was reduced by approximately 50% in patients with TCS compared to controls (P < 0.001). External ear length and width were positively correlated with external ear volume (length: r = 0.809, P < 0.001 on left and r = 0.732, P < 0.001 on right; width: r = 0.518, P = 0.001 on left and r = 0.447, P < 0.010 on right). A negative correlation of right ear inclination angle and external ear volume was shown in patients with TCS (r = -0.396, P = 0.027). However, no correlation was shown for the mandibular anatomic variables. CONCLUSIONS: Three-dimensional analysis confirmed that external ear volume is significantly reduced in patients with TCS. The external ear dimensions and orientation correlated significantly with ear volume. There was no intrinsic association between the severity of mandibular deformity and external ear volume.

The Landscape of Circular RNA Expression Profiles in Papillary Thyroid Carcinoma Based on RNA Sequencing.

BACKGROUND/AIMS: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. However, the molecular mechanisms responsible for its tumorigenesis and progression remain largely unknown. Circular RNA (circRNA) is a novel type of noncoding RNA that can serve as an ideal biomarker due to its stability. Recent evidence suggests that circRNAs play important roles in tumorigenesis. This study aims to investigate circRNA expression profiles and their potential biological functions in PTC. METHODS: High-throughput RNA sequencing was used to assess circRNA expression profiles in PTC, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate dysregulated circRNAs. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of circRNAs for PTC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to determine the biological functions of differentially expressed circRNAs. Bioinformatic analyses were applied to predict interactions between circRNAs and microRNAs (miRNAs), and a circRNA-miRNA-mRNA network was constructed using Cytoscape software. RESULTS: We identified a number of differentially expressed circRNAs in PTC tissues compared with paired normal thyroid tissues, with chr5: 160757890-160763776-, chr12: 40696591-40697936+, chr7: 22330794-22357656-, and chr21: 16386665-16415895- being upregulated, and chr7: 91924203-91957214+, chr2: 179514891-179516047-, chr9: 16435553-16437522-, and chr22: 36006931-36007153- being downregulated. These findings were confirmed by qRT-PCR, and ROC curves indicated that they can serve as potential biomarkers for PTC. GO and KEGG pathway analyses showed that some of these circRNAs are related to cancers. Additionally, bioinformatic analyses revealed a potential competing-endogenous-RNA-regulating network among circRNAs, miRNAs, and mRNAs. CONCLUSIONS: Our study results depict the landscape of circRNA expression profiles in PTC and also provide potential biomarkers for PTC. Further functional and mechanistic studies of these circRNAs may improve our understanding of PTC tumorigenesis.

Loss of PIM1 correlates with progression and prognosis of salivary adenoid cystic carcinoma (SACC).

BACKGROUND: Increasing evidence indicates that PIM1 is a potential prognostic marker and target for cancer treatment but its precise mechanisms of action remain to be determined in salivary adenoid cystic carcinoma (SACC). This study aims to decipher the prognostic and mechanistic role of PIM1 in progression of SACC cells and tumor tissues. METHODS: A SACC cell line (ACC-M) was transfected with shRNA plasmids targeting the PIM1 gene. The expression levels of PIM1, RUNX3 and p21 were measured by quantitative real-time PCR and western blot. Subcellular translocalization of RUNX3 and p21 proteins was assessed using immunofluorescence, and cell cycle phase was quantified using flow cytometry. A total of 97 SACC patients were retrospectively analyzed by clinicopathologic characteristics and survival outcomes. RESULTS: After down-regulation of PIM1 in ACC-M cells, RUNX3 and p21 proteins were translocated from cytoplasm to nucleus, with a decrease of p21 expression and increase of G0/G1 phase cells. PIM1 and RUNX3 levels show a distinct covariance. PIM1 is associated with T-status, lymph node involvement, nerve invasion, and distant metastasis in SACC tissues. Patients with low PIM1 level had a better outcome than those with higher PIM1 level. CONCLUSIONS: PIM1 is multifunctional in ACC-M cells and it serves as a neoteric therapeutic target and potential prognostic marker for SACC patients.