A Cellular Mechanism to Detect and Alleviate Reductive Stress.

Metazoan organisms rely on conserved stress response pathways to alleviate adverse conditions and preserve cellular integrity. Stress responses are particularly important in stem cells that provide lifetime support for tissue formation and repair, but how these protective systems are integrated into developmental programs is poorly understood. Here we used myoblast differentiation to identify the E3 ligase CUL2FEM1B and its substrate FNIP1 as core components of the reductive stress response. Reductive stress, as caused by prolonged antioxidant signaling or mitochondrial inactivity, reverts the oxidation of invariant Cys residues in FNIP1 and allows CUL2FEM1B to recognize its target. The ensuing proteasomal degradation of FNIP1 restores mitochondrial activity to preserve redox homeostasis and stem cell integrity. The reductive stress response is therefore built around a ubiquitin-dependent rheostat that tunes mitochondrial activity to redox needs and implicates metabolic control in coordination of stress and developmental signaling.

Chlorogenic acid can improve spermatogenic dysfunction in rats with varicocele by regulating mitochondrial homeostasis and inhibiting the activation of NLRP3 inflammasomes by oxidative mitochondrial DNA and cGAS/STING pathway.

In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to testicular spermatogenic function has attracted extensive attention in recent years. Among them, overexpressed ROS and high levels of inflammation may play a key role in VC-induced testicular damage. As the key mediated innate immune pathways, cGAS-STING shaft under pathological conditions, such as in cell and tissue damage stress can be cytoplasmic DNA activation, induce the activation of NLRP3 inflammatory corpuscle, triggering downstream of the inflammatory cascade reaction. Chlorogenic acid (CGA), as a natural compound from a wide range of sources, has strong anti-inflammatory and antioxidant activities, and is a potential effective drug for the treatment of varicocele infertility. The aim of this study is to investigate the role of CGA in the spermatogenic dysfunction of the rat testis induced by VC and the potential mechanisms. The results of this study have shown that CGA gavage treatment ameliorated the pathological damage of seminiferous tubules, increased the number of sperm in the lumen, and increased the expression levels of Occludin and ZO-1, which indicated the therapeutic effect of CGA on spermatogenic dysfunction in the testis of VC rats. Meanwhile, the damage of mitochondrial structure was alleviated and the expression levels of ROS, NLRP3 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-18) were significantly reduced in the testicular tissues of model rats after CGA treatment. In addition, we demonstrated for the first time the high expression status of cGAS and STING in testicular tissues of VC model rats, and this was ameliorated to varying degrees after CGA treatment. In conclusion, this study suggests that CGA can improve the spermatogenic function of the testis by reducing mitochondrial damage and inhibiting the activation of the cGAS-STING axis, inhibiting the activation of the NLRP3 inflammasome, and improving the inflammatory damage of the testis, highlighting the potential of CGA as a therapeutic agent for varicocele infertility.

Assessing the Feasibility of Simplifying the Scanning Protocol for Spinal Metastases With Vertebral Compression Fractures Using Only the Dixon T2-Weighted Sequence.

OBJECTIVE: Conventional imaging protocols, including sagittal T1-weighted imaging (T1WI) and water-only T2-weighted imaging (T2WI), are time consuming when screening for spinal metastases with vertebral compression fractures (VCFs). In this study, we aimed to assess the accuracy of using only the Dixon T2-weighted sequence in the diagnosis of spinal metastases with VCFs to determine its suitability as a simplified protocol for this task. METHODS: This retrospective study included 27 patients diagnosed with spinal metastases and VCFs. Qualitative analysis was performed separately by two musculoskeletal radiologists, who independently performed diagnostic evaluations of each vertebra using both conventional and simplified protocols. McNemar's test was then used to compare the differences in diagnostic results, and Cohen's kappa coefficient was used to assess interobserver and interprotocol agreement. Diagnostic performance values for both protocols, including sensitivity, specificity, and area under the curve, were then determined based on the reference standard. Quantitative image analysis was performed randomly for 30 metastases on T1WI and fat-only T2WI to measure the signal intensity, signal-to-noise ratio, and contrast-to-noise ratio. RESULTS: The diagnosis of VCFs by both radiologists was in full agreement with the reference standard. The classification of spinal metastases and diagnostic performance values determined by both radiologists were not significantly different between the two protocols (all P > 0.05), and the consistency between observers and protocols was excellent (κ = 0.973-0.991). The contrast-to-noise ratio of fat-only T2WI was significantly higher than that of T1WI (P < 0.001). CONCLUSIONS: The Dixon T2-weighted sequence alone performed well in diagnosing spinal metastases with VCFs, performing no worse than the conventional protocol (T1WI and water-only T2WI). This suggests that the Dixon T2-weighted sequence alone can serve as a simplified protocol for the diagnosis of spinal metastases with VCFs, thereby avoiding the need for more intricate scanning procedures.

Unconventional hcp/fcc Nickel Heteronanocrystal with Asymmetric Convex Sites Boosts Hydrogen Oxidation.

Developing non-platinum group metal catalysts for the sluggish hydrogen oxidation reaction (HOR) is critical for alkaline fuel cells. To date, Ni-based materials are the most promising candidates but still suffer from insufficient performance. Herein, we report an unconventional hcp/fcc Ni (u-hcp/fcc Ni) heteronanocrystal with multiple epitaxial hcp/fcc heterointerfaces and coherent twin boundaries, generating rugged surfaces with plenty of asymmetric convex sites. Systematic analyses discover that such convex sites enable the adsorption of *H in unusual bridge positions with weakened binding energy, circumventing the over-strong *H adsorption on traditional hollow positions, and simultaneously stabilizing interfacial *H2O. It thus synergistically optimizes the HOR thermodynamic process as well as reduces the kinetic barrier of the rate-determining Volmer step. Consequently, the developed u-hcp/fcc Ni exhibits the top-rank alkaline HOR activity with a mass activity of 40.6 mA mgNi-1 (6.3 times higher than fcc Ni control) together with superior stability and high CO-tolerance. These results provide a paradigm for designing high-performance catalysts by shifting the adsorption state of intermediates through configuring surface sites.

Predicting pathological complete response of neoadjuvant radiotherapy and targeted therapy for soft tissue sarcoma by whole-tumor texture analysis of multisequence MRI imaging.

OBJECTIVES: To construct effective prediction models for neoadjuvant radiotherapy (RT) and targeted therapy based on whole-tumor texture analysis of multisequence MRI for soft tissue sarcoma (STS) patients. METHODS: Thirty patients with STS of the extremities or trunk from a prospective phase II trial were enrolled for this analysis. All patients underwent pre- and post-neoadjuvant RT MRI examinations from which whole-tumor texture features were extracted, including T1-weighted with fat saturation and contrast enhancement (T1FSGd), T2-weighted with fat saturation (T2FS), and diffusion-weighted imaging (DWI) sequences and their corresponding apparent diffusion coefficient (ADC) maps. According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) and non-pCR (N-pCR) groups. pCR was defined as less than 5% of residual tumor cells by postoperative pathology. Delta features were defined as the percentage change in a texture feature from pre- to post-neoadjuvant RT MRI. After data reduction and feature selection, logistic regression was used to build prediction models. ROC analysis was performed to assess the diagnostic performance. RESULTS: Five of 30 patients (16.7%) achieved pCR. The Delta_Model (AUC 0.92) had a better predictive ability than the Pre_Model (AUC 0.78) and Post_Model (AUC 0.76) and was better than AJCC staging (AUC 0.52) and RECIST 1.1 criteria (AUC 0.52). The Combined_Model (pre, post, and delta features) had the best predictive performance (AUC 0.95). CONCLUSION: Whole-tumor texture analysis of multisequence MRI can well predict pCR status after neoadjuvant RT and targeted therapy in STS patients, with better performance than RECIST 1.1 and AJCC staging. KEY POINTS: • MRI multisequence texture analysis could predict the efficacy of neoadjuvant RT and targeted therapy for STS patients. • Texture features showed incremental value beyond routine clinical factors. • The Combined_Model with features at multiple time points showed the best performance.

High Protonic Conductivity of Three Highly Stable Nanoscale Hafnium(IV) Metal-Organic Frameworks and Their Imidazole-Loaded Products.

Attracted by the exceptional structural rigidity and inherent porous structures of the Hf-based metal-organic frameworks (MOFs), we adopted a rapid synthesis approach to preparing three nanoscale MOFs, Hf-UiO-66 (1), Hf-UiO-66-(OH)2 (2), and Hf-UiO-66-NH2 (3), and systematically explored the water-assisted proton conductivities of the original ones and the post-modified products. Interestingly, the proton conductivities (σ) of all three MOFs exhibit significant temperature and humidity dependence. At 98% RH and 100 °C, their optimal σ values can reach up to 10-3 S·cm-1. Consequently, imidazole units are loaded into 1-3 to obtain related MOFs, Im@1, Im@2, and Im@3, and the σ values of the imidazole-loaded products are boosted to 10-2 S·cm-1. Note that these modifications not only do not change the frameworks of the pristine MOFs but also do not affect their high chemical and water stability. The proton-conductive mechanisms of these MOFs before and after modification have been thoroughly discussed based on structural analyses, N2 and H2O vapor adsorptions, and activation energy values. The excellent structural stability as well as the durability and stability of their proton conduction ability indicate that these MOFs can be used in the field of fuel cells and so on.

Biocompatible Au-Fe3O4 Nanoparticle-based Magnetic Resonance Imaging in the Diagnosis of Liver Tumor.

The study aimed to analyze the value and significance of magnetic resonance imaging (MRI) using biocompatible Au-Fe3O4 nanomaterials in the diagnosis of liver tumors. In this study, 124 patients with liver tumors were selected to perform MRI scanning based on Au-Fe3O4 nanoparticles. The coincidence rate between MRI scanning results and pathological examination results, the detection rate of tumor focus between MRI scanning results and CT detection results were analyzed, to evaluate the diagnostic performance of MRI scanning based on Au-Fe3O4 nanoparticles. The results showed that in the detection of primary tumors, secondary tumors, and focal nodular hyperplasia, the coincidence rate between MRI scanning results and pathological examination results was high, and Kappa values were all greater than 0.8. Compared with the results of CT, the detection rate of tumor lesions smaller than 1 cm by MRI was significantly higher (P<0.05), but there was no significant difference between the two diagnostic methods for tumor lesions larger than 1 cm (P>0.05). Additionally, the accuracy, specificity, and sensitivity of MRI in diagnosing liver tumors were 86.81, 84.29, and 77.27, respectively. Clinically, MRI scanning based on Au-Fe3O4nanoparticles can provide a practical and effective reference for the differential diagnosis of liver tumors.

Discovery of Novel Potential Aphid Repellents: Geranic Acid Esters Containing Substituted Aromatic Rings.

Aphids are one of the most damaging agricultural pests. For the sake of novel eco-friendly compounds with good activity for aphid control, a series of novel geranic acid esters containing substituted aromatic rings were designed by inverting ester groups of lead compounds. All compounds were characterized by HRMS, 1H-NMR, and 13C-NMR. In order to identify the effect of inversion ester groups on activity, a bioassay was conducted. The results showed that the repellent activity against Acyrthosiphon pisum (A. pisum) and the binding affinity with the odorant-binding protein 9 from A. pisum (ApisOBP9) of the compounds were increased after inversion of the ester groups. Particularly, 5f showed the best repellent activity (repellency proportion: 55.6%) and binding affinity (1/Ki: 0.49 µM). Meanwhile, the structure-activity relationships revealed that the introduction of meta-substitution of the benzene ring and halogen atoms, such as Cl and Br, facilitated the biological activity. The further molecular docking results demonstrated that hydrogen bonding interactions and hydrophobic interactions were vital for the binding affinity with ApisOBP9. Additionally, all compounds were predicted to be eco-friendly and their volatile physicochemical properties have been enhanced compared to the leads. The present results provide valuable clues for the further rational design of aphids' behavioral control agents.

Association of a Clinician's Antibiotic-Prescribing Rate With Patients' Future Likelihood of Seeking Care and Receipt of Antibiotics.

BACKGROUND: One underexplored driver of inappropriate antibiotic prescribing for acute respiratory illnesses (ARI) is patients' prior care experiences. When patients receive antibiotics for an ARI, patients may attribute their clinical improvement to the antibiotics, regardless of their true benefit. These experiences, and experiences of family members, may drive whether patients seek care or request antibiotics for subsequent ARIs. METHODS: Using encounter data from a national United States insurer, we identified patients <65 years old with an index ARI urgent care center (UCC) visit. We categorized clinicians within each UCC into quartiles based on their ARI antibiotic prescribing rate. Exploiting the quasi-random assignment of patients to a clinician within an UCC, we examined the association between the clinician's antibiotic prescribing rate to the patients' and their spouses' rates of ARI antibiotic receipt in the subsequent year. RESULTS: Across 232,256 visits at 736 UCCs, ARI antibiotic prescribing rates were 42.1% and 80.2% in the lowest and highest quartile of clinicians, respectively. Patient characteristics were similar across the four quartiles. In the year after the index ARI visit, patients seen by the highest-prescribing clinicians received more ARI antibiotics (+3.0 fills/100 patients (a 14.6% difference), 95% CI 2.2-3.8, P < 0.001,) versus those seen by the lowest-prescribing clinicians. The increase in antibiotics was also observed among the patients' spouses. The increase in patient ARI antibiotic prescriptions was largely driven by an increased number of ARI visits (+5.6 ARI visits/100 patients, 95% CI 3.6-7.7, P < 0.001), rather than a higher antibiotic prescribing rate during those subsequent ARI visits. CONCLUSIONS: Receipt of antibiotics for an ARI increases the likelihood that patients and their spouses will receive antibiotics for future ARIs.

Declining Use of Primary Care Among Commercially Insured Adults in the United States, 2008-2016.

Background: Primary care is known to improve outcomes and lower health care costs, prompting recent U.S. policy efforts to expand its role. Nonetheless, there is early evidence of a decline in per capita primary care visit rates, and little is understood about what is contributing to the decline. Objective: To describe primary care provider (PCP) visit trends among adults enrolled with a large, national, commercial insurer and assess factors underlying a potential decline in PCP visits. Design: Descriptive repeated cross-sectional study using 100% deidentified claims data from the insurer, 2008-2016. A 5% claims sample was used for Poisson regression models to quantify visit trends. Setting: National, population-based. Participants: Adult health plan members aged 18 to 64 years. Measurements: PCP visit rates per 100 member-years. Results: In total, 142 million primary care visits among 94 million member-years were examined. Visits to PCPs declined by 24.2%, from 169.5 to 134.3 visits per 100 member-years, while the proportion of adults with no PCP visits in a given year rose from 38.1% to 46.4%. Rates of visits addressing low-acuity conditions decreased by 47.7% (95% CI, -48.1% to -47.3%). The decline was largest among the youngest adults (-27.6% [CI, -28.2% to -27.1%]), those without chronic conditions (-26.4% [CI, -26.7% to -26.1%]), and those living in the lowest-income areas (-31.4% [CI, -31.8% to -30.9%]). Out-of-pocket cost per problem-based visit rose by $9.4 (31.5%). Visit rates to specialists remained stable (-0.08% [CI, -0.56% to 0.40%]), and visits to alternative venues, such as urgent care clinics, increased by 46.9% (CI, 45.8% to 48.1%). Limitation: Data were limited to a single commercial insurer and did not capture nonbilled clinician-patient interactions. Conclusion: Commercially insured adults have been visiting PCPs less often, and nearly one half had no PCP visits in a given year by 2016. Our results suggest that this decline may be explained by decreased real or perceived visit needs, financial deterrents, and use of alternative sources of care. Primary Funding Source: None.

Establishment of an anti-inflammation-based bioassay for the quality control of the 13-component TCM formula (Lianhua Qingwen).

CONTEXT: Owing to the complexity of chemical ingredients in traditional Chinese medicine (TCM), it is difficult to maintain quality and efficacy by relying only on chemical markers. OBJECTIVE: Lianhua Qingwen capsule (LHQW) was selected as an example to discuss the feasibility of a bioassay for quality control. MATERIALS AND METHODS: Network pharmacology was used to screen potential targets in LHQW with respect to its anti-inflammatory effects. An in vitro cell model was used to validate the prediction. An anti-inflammatory bioassay was established for the quality evaluation of LHQW in 40 batches of marketed products and three batches of destructed samples. RESULTS: The tumor necrosis factor/interleukin-6 (TNF/IL-6) pathway via macrophage was selected as the potential target of LHQW. The IC50 value of LHQW on RAW 264.7 was 799.8 µg/mL. LHQW had significant inhibitory effects on the expression of IL-6 in a dose-dependent manner (p < 0.05). The anti-inflammatory biopotency of LHQW was calculated based on the inhibitory bioactivity on IL-6. The biopotency of 40 marketed samples ranged from 404 U/µg to 2171 U/µg, with a coefficient of variation (CV) of 37.91%. By contrast, the contents of forsythin indicated lower CV (28.05%) than the value of biopotency. Moreover, the biopotencies of destructed samples declined approximate 50%, while the contents of forsythin did not change. This newly established bioassay revealed a better ability to discriminate the quality variations of LHQW as compared to the routine chemical determination. CONCLUSIONS: A well-established bioassay may have promising ability to reveal the variance in quality of TCM.

Noninvasive treatment of pectus excavatum with a vacuum bell combined with a three-dimensional scanner.

PURPOSE: Our aim was to evaluate the effect of a vacuum bell (VB) combined with a three-dimensional (3D) scanner for the noninvasive treatment of pectus excavatum (PE). METHODS: A VB was used to create a vacuum at the anterior chest wall with a patient-activated hand pump, and it should be applied regularly for more than 2 h each day at home. Eighty-two patients required to be followed up every three months were included in this retrospective study and distributed into four stages (stage 1: treated for 3 months, stage 2: treated for 6 months, stage 3: treated for 9 months, and stage 4: treated for 12 months). In addition, the deformity in the chest wall was scanned by a 3D scanner at the clinic, and the 3D depth (3D-DE) and 3D Haller index (3D-HI) of PE were calculated through Geomagic studio 2013 software. RESULTS: Eighty-two patients (12/2017-12/2019) met the criteria at the clinic, and 24 patients (29.3%) achieved excellent correction (3D-DE ≤ 3 mm). When comparing the improvement in 3D-DE and 3D-HI of PE to the patient's treatment time, a statistically significant difference was observed between stages 2 and 1 (3D-DE p < 0.01, 3D-HI p < 0.01), stages 3 and 2 (3D-DE p < 0.01, 3D-HI p < 0.01) and stages 4 and 3 (3D-DE p < 0.01, 3D-HI p < 0.01). There was a statistically significant difference in sternum elevation between patients aged < 10 years and those aged ≥ 10 years (3D-DE p = 0.006, 3D-HI p = 0.045) and patients with symmetrical and asymmetric PE (3D-DE p = 0.042, 3D-HI p = 0.032). However, there was no statistically significant difference in sternal elevation between males and females (3D-DE p = 0.27, 3D-HI p = 0.495). The main side effects were moderate subcutaneous hematoma, petechial bleeding, thoracalgia and chest tightness. CONCLUSIONS: With controllable side effects, noninvasive treatment for PE with a VB combined with a 3D scanner is safe, objective and radiation free, and the initial results to date are encouraging. Patients aged < 10 years, with symmetrical PE and treated for over 12 months may achieve a better outcome.

National Trends in Primary Care Visit Use and Practice Capabilities, 2008-2015.

PURPOSE: Recent evidence shows a national decline in primary care visit rates over the last decade. It is unclear how changes in practice-including the use and content of primary care visits-may have contributed. METHODS: We analyzed nationally representative data of adult visits to primary care physicians (PCPs) and physician practice characteristics from 2007-2016 (National Ambulatory Medical Care Survey). United States census estimates were used to calculate visits per capita. Measures included visit rates per person year; visit duration; number of medications, diagnoses, and preventive services per visit; percentage of visits with scheduled follow-up; and percentage of physicians with practice capabilities including an electronic medical record (EMR). RESULTS: Our weighted sample represented 3.2 billion visits (83,368 visits, unweighted). Visits per capita declined by 20% (-0.25 visits per person, 95% CI, -0.32 to -0.19) during this time, while visit duration increased by 2.4 minutes per visit (95% CI, 1.1-3.8). Per visit, PCPs addressed 0.30 more diagnoses (95% CI, 0.16-0.43) and 0.82 more medications (95% CI, 0.59-1.1), and provided 0.24 more preventive services (95% CI, 0.12-0.36). Visits with scheduled PCP followup declined by 6.0% (95% CI, -12.4 to 0.46), while PCPs reporting use of EMR increased by 44.3% (95% CI, 39.1-49.5) and those reporting use of secure messaging increased by 60.9% (95% CI, 27.5-94.3). CONCLUSION: From 2008 to 2015, primary care visits were longer, addressed more issues per visit, and were less likely to have scheduled follow-up for certain patients and conditions. Meanwhile, more PCPs offered non-face-to-face care. The decline in primary care visit rates may be explained in part by PCPs offering more comprehensive in-person visits and using more non-face-to-face care.

Hepatocyte-specific deletion of BAP31 promotes SREBP1C activation, promotes hepatic lipid accumulation, and worsens IR in mice.

Conditional knockout mice with targeted disruption of B-cell associated protein (BAP)31 in adult mouse liver were generated and challenged with a high-fat diet (HFD) for 36 or 96 days and markers of obesity, diabetes, and hepatic steatosis were determined. Mutant mice were indistinguishable from WT littermates, but exhibited increased HFD-induced obesity. BAP31-deletion in hepatocytes increased the expression of SREBP1C and the target genes, including acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1, and increased hepatic lipid accumulation and HFD-induced liver steatosis. Immunoprecipitation assay showed that BAP31 interacts with SREBP1C and insulin-induced gene 1 (INSIG1), and BAP31-deletion reduces INSIG1 expression, suggesting that BAP31 may regulate SREBP1C activity by modulating INSIG1 protein levels. Additionally, BAP31-deletion induced glucose and insulin intolerance, decreased Akt and glycogen synthase kinase 3ß phosphorylation, and enhanced hepatic glucose production in mice. Expression of endoplasmic reticulum (ER) stress markers was significantly induced in BAP31-mutant mice. HFD-induced inflammation was aggravated in mutant mice, along with increased c-Jun N-terminal kinase and nuclear factor-κB activation. These findings demonstrate that BAP31-deletion induces SREBP activation and promotes hepatic lipid accumulation, reduces insulin signaling, impairs glucose/insulin tolerance, and increases ER stress and hepatic inflammation, explaining the protective roles of BAP31 in the development of liver steatosis and insulin resistance in HFD-induced obesity in animal models.

Incidence of interval colorectal cancer attributable to an endoscopist in clinical practice.

BACKGROUND AND AIMS: Endoscopists who encounter an interval colorectal cancer (I-CRC) may be concerned about the implications because I-CRCs may represent a lapse in colonoscopy quality and a missed opportunity for prevention. We wanted to determine the I-CRC rate per colonoscopy examination and to examine the effect of colonoscopy volume and adenoma detection rate (ADR) on the number of I-CRCs attributable to an endoscopist. METHODS: We determined the rate of I-CRC diagnosis per outpatient colonoscopy examination by measuring the incidence of CRC diagnosis in practice and by assessing, via literature review, the percentage of cancers that are interval. We also estimated the number of attributable I-CRCs as a function of ADR and colonoscopy volume. RESULTS: Among 93,562 colonoscopies performed in 2013 to 2015 by 120 physicians in 4 diverse U.S. medical centers, 526 CRCs were diagnosed (.6%). Of 149,556 CRCs in the published literature, 7958 were I-CRCs (5.25% ± .94%). With rates of .6% (CRC per colonoscopy) and 5.25% (I-CRC per CRC), the rate of I-CRC is 1 per 3174 colonoscopies (95% confidence interval, 1 per 2710 to 1 per 3875). An endoscopist at the median of outpatient colonoscopy volume (316/year) in the lowest ADR quintile of detection (7%-19%) would have an I-CRC attributed every 8.2 years, or 4.2 I-CRCs in a 35-year career, versus every 16.7 years, or 2.0 I-CRCs in a 35-year career, for an endoscopist in the highest ADR quintile (33%-52%). CONCLUSIONS: An average-volume endoscopist will have 2 to 4 attributable I-CRCs in a 35-year career, but the frequency will vary depending on colonoscopy volume and ADR.

Endoscopist factors that influence serrated polyp detection: a multicenter study.

BACKGROUND: Serrated polyps are important colorectal cancer precursors that are variably detected during colonoscopy. We measured serrated polyp detection rate (SPDR) in a large, multicenter, cross-sectional study of colonoscopy quality to identify drivers of SPDR variation. METHODS: Colonoscopy and pathology reports were collected for a 2-year period (10/2013-9/2015) from four sites across the United States. Data from reports, including size, location, and histology of polyps, were abstracted using a validated natural language processing algorithm. SPDR was defined as the proportion of colonoscopies with ≥ 1 serrated polyp (not including hyperplastic polyps). Multivariable logistic regression was performed to determine endoscopist characteristics associated with serrated polyp detection. RESULTS: A total of 104 618 colonoscopies were performed by 201 endoscopists who varied with respect to specialty (86 % were gastroenterologists), sex (18 % female), years in practice (range 1 - 51), and number of colonoscopies performed during the study period (range 30 - 2654). The overall mean SPDR was 5.1 % (SD 3.8 %, range 0 - 18.8 %). In multivariable analysis, gastroenterology specialty training (odds ratio [OR] 1.89, 95 % confidence interval [CI] 1.33 - 2.70), fewer years in practice (≤ 9 years vs. ≥ 27 years: OR 1.52, 95 %CI 1.14 - 2.04)], and higher procedure volumes (highest vs. lowest quartile: OR 1.77, 95 %CI 1.27 - 2.46)] were independently associated with serrated polyp detection. CONCLUSIONS: Gastroenterology specialization, more recent completion of training, and greater procedure volume are associated with serrated polyp detection. These findings imply that both repetition and training are likely to be important contributors to adequate detection of these important cancer precursors. Additional efforts to improve SPDR are needed.

Analyzing gene expression profiles with preliminary validations in cardiac hypertrophy induced by pressure overload.

The aim of this study was to identify the key genes involved in the cardiac hypertrophy (CH) induced by pressure overload. mRNA microarray data sets GSE5500 and GSE18801 were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were screened using the Limma package; then, functional and pathway enrichment analysis were performed for common DEGs using the Database for Annotation, Visualization and Integrated Discovery database. Furthermore, the top DEGs were further validated using quantitative PCR in the hypertrophic heart tissue induced by isoprenaline. A total of 113 common DEGs with absolute fold change > 0.5, including 60 significantly upregulated DEGs and 53 downregulated DEGs, were obtained. Gene ontology term enrichment analysis suggested that common upregulated DEG were mainly enriched in neutrophil chemotaxis, extracellular fibril organization, and cell proliferation; and the common downregulated genes were significantly enriched in ion transport, endoplasmic reticulum, and dendritic spine. Kyoto Encyclopedia of Genes and Genomes pathway analysis found that the common DEGs were mainly enriched in extracellular matrix receptor interaction, phagosome, and focal adhesion. Additionally, the expression of Mfap4, Ltbp2, Aspn, Serpina3n, and Cnksr1 were upregulated in the model of CH, while the expression of Anp32a was downregulated. The current study identified the key deregulated genes and pathways involved in the CH, which could shed new light to understand the mechanism of CH.

[Application of cameral-type three-dimensional scan in assessment of funnel chest].

OBJECTIVE: To evaluate the application of cameral-type three-dimensional (3D) scan in the assessment of funnel chest. METHODS: Eighty children with funnel chest were collected from the Children's Hospital, Zhejiang University School of Medicine during June 2016 and December 2017. All patients underwent routine CT scan. In the same selected mediastinal window, the lowest point of the depression to the front of the spine was the anteroposterior diameter (A1), and the maximum left to right diameter was B1 (which was perpendicular to A1). The ratio B1/A1 was calculated to get CT Haller index (CT-HI). In the same period, the chest wall scan was performed by EinScan-Pro 3D scanner, and the image was analyzed by GeoMedic image software. On the plane of the most concave point of the sternum, the distance from the lowest point of the skin to the back skin was the anteroposterior diameter (A2), the maximum plane diameter was measured on the same plane (B2), and the ratio B2/A2 was the 3D-Haller index (3D-HI). Pearson correlation analysis was used to analyze the consistency of the two measurements. Kappa test was used to analyze the consistency of surgical indication based on cutoff value of CT-HI and 3D-HI. RESULTS: All children were able to cooperate with CT and 3D chest wall surface scan. The mean value of CT-HI was 3.82±0.96, and that of 3D-HI was 1.82±0.23. Pearson correlation analysis showed that the correlation coefficient between CT-HI and 3D-HI was 0.823 (P<0.01). When CT-HI > 3.2 and 3D-HI > 1.7 were set as cutoff values for indication of operation, the sensitivity and specificity of 3D-HI were 90.48% and 100.0%, respectively. 3D-HI was well consistent with CT-HI in surgical indication (Kappa=0.801). CONCLUSIONS: s 3D scan can be used to assess the funnel chest in children, and 3D-HI>1.7 can be used as the cutoff value for surgical indication.

[Efficacy of percutaneous atrial septal defect closure guided by transesophageal echocardiography in children].

OBJECTIVE: To compare the efficacy of percutaneous atrial septal defect (ASD) closure guided by transesophageal echocardiography (TEE) or guided by fluoroscopy in pediatric patients. METHODS: Medical records of patients who underwent percutaneous ASD closure in the Children's Hospital, Zhejiang University School of Medicine from January 2017 to March 2018 were reviewed. There were 120 patients whose procedures were guided by TEE (TEE group), and 125 patients who had their procedures guided by fluoroscopy (fluoroscopy group). The performance of surgery, efficacy and postoperative complications were compared between two groups. RESULTS: Percutaneous ASD closure was successful in all patients. The operation time was shorter in the TEE group than that in fluoroscopy group[(20±14) min vs. (29±11) min, t=-7.939, P<0.05]. The size of the defect was larger in the TEE group than that of fluoroscopy group[(11±4) mm vs. (9±4) mm, t=2.512, P<0.05], but there was no significant difference in the sizes of occluder and occluder sheath between two groups (all P>0.05). No residual shunt, occluder shedding or displacement, severe arrhythmia or pericardial effusion were observed in either group. The incidence rates of fever, cough and diarrhea were not statistically different between two groups (all P>0.05). CONCLUSIONS: There was no significant difference in the outcome of percutaneous ASD closure guided by TEE or by fluoroscopy, but the procedure guided by TEE may reduce the operation time and can evaluate the size of ASD more accurately without involving radiation exposure, contrast agents use and large digital subtraction equipment.