MELD 3.0 for adolescent liver transplant candidates.

BACKGROUND AND AIMS: Adolescents constitute a unique waitlist cohort that is distinct from younger children. Model for End-stage Liver Disease (MELD) 3.0, which was developed in an adult population of liver transplant candidates, is planned to replace MELD-Sodium in the current liver allocation system for both adults and adolescents aged 12-17. We evaluated the predictive performance of MELD-Sodium, MELD 3.0, and Pediatric End-stage Liver Disease for 90-day waitlist mortality risk among adolescent liver transplant registrants. APPROACH AND RESULTS: New waitlist registrations for primary liver transplants among individuals aged 12-17 and 18-25 for comparison were identified using Organ Procurement and Transplantation Network (OPTN) data from November 17, 2004, to December 31, 2021. The predictive performance of the current and proposed MELD and Pediatric End-stage Liver Disease scores was assessed using Harrell's concordance ( c ) statistic. There were 1238 eligible listings for adolescents aged 12-17 and 1740 young adults aged 18-25. In the adolescent group, 90-day survival was 97.8%, compared with 95.9% in those aged 18-25 (log-rank p = 0.005), with no significant differences when stratified by sex or indication. Among adolescents, increasing MELD 3.0 was associated with an increased hazard of mortality (HR=1.27, 95% CI: 1.18-1.37), and the c -statistic for 90-day waitlist survival using MELD 3.0 was 0.893 compared with 0.871 using MELD-Sodium and 0.852 using Pediatric End-stage Liver Disease. CONCLUSIONS: The discriminative ability of MELD 3.0 to rank adolescents according to the risk of death within 90 days was robust. Although MELD 3.0 was initially developed and validated in adults, MELD 3.0 may also improve the prediction of waitlist mortality in adolescents and better represent their urgency for liver transplants.

Perovskite light-emitting diodes based on spontaneously formed submicrometre-scale structures.

Light-emitting diodes (LEDs), which convert electricity to light, are widely used in modern society-for example, in lighting, flat-panel displays, medical devices and many other situations. Generally, the efficiency of LEDs is limited by nonradiative recombination (whereby charge carriers recombine without releasing photons) and light trapping1-3. In planar LEDs, such as organic LEDs, around 70 to 80 per cent of the light generated from the emitters is trapped in the device4,5, leaving considerable opportunity for improvements in efficiency. Many methods, including the use of diffraction gratings, low-index grids and buckling patterns, have been used to extract the light trapped in LEDs6-9. However, these methods usually involve complicated fabrication processes and can distort the light-output spectrum and directionality6,7. Here we demonstrate efficient and high-brightness electroluminescence from solution-processed perovskites that spontaneously form submicrometre-scale structures, which can efficiently extract light from the device and retain wavelength- and viewing-angle-independent electroluminescence. These perovskites are formed simply by introducing amino-acid additives into the perovskite precursor solutions. Moreover, the additives can effectively passivate perovskite surface defects and reduce nonradiative recombination. Perovskite LEDs with a peak external quantum efficiency of 20.7 per cent (at a current density of 18 milliamperes per square centimetre) and an energy-conversion efficiency of 12 per cent (at a high current density of 100 milliamperes per square centimetre) can be achieved-values that approach those of the best-performing organic LEDs.

Online-to-offline combined with problem-based learning is an effective teaching modality in the standardized residency training of nephrology.

BACKGROUND: The online-to-offline (O2O) teaching method is recognized as a new educational model that integrates network learning into offline classroom education, while problem-based learning (PBL) is a teaching modality that guides students to apply acquired theoretical knowledge to solve practical problems. However, implementing O2O combined with PBL has not been extensively explored in nephrology residency training. This study aims to explore the efficacy of O2O combined with PBL in the standardized residency training of nephrology by comparing it with the traditional lecture-based teaching (LBT). METHODS: Sixty residency trainees who participated in the standardized training of internal medicine in the nephrology department of the Second Affiliated Hospital of Zhejiang University School of Medicine were equally allocated into O2O combined with PBL (O2O/PBL) or the LBT group demographically matched. Examinations of theory, practice skills, clinical thinking and teaching satisfaction surveys were utilized to assess the teaching effects of the two groups. RESULTS: Participants from the O2O/PBL group outperformed those from the LBT group in the examination of theory (81.233 ± 9.156 vs. 75.800 ± 7.009, mean ± SEM), practice skills (104.433 ± 3.569 vs.100.316 ± 4.628, mean ± SEM) and clinical thinking (88.933 ± 4.473 vs. 86.667 ± 3.844, mean ± SEM). There was no significant difference in the teaching satisfaction between the two groups. CONCLUSION: The current study shows the positive impact of O2O combined with PBL approach on standardized residency training in nephrology without reducing teaching satisfaction.

Development of a risk-stratification scoring system for predicting lymphovascular invasion in breast cancer.

BACKGROUND: Lymphovascular invasion (LVI) is a vital risk factor for prognosis across cancers. We aimed to develop a scoring system for stratifying LVI risk in patients with breast cancer. METHODS: A total of 301 consecutive patients (mean age, 49.8 ± 11.0 years; range, 29-86 years) with breast cancer confirmed by pathological reports were retrospectively evaluated at the authors' institution between June 2015 and October 2018. All patients underwent contrast-enhanced Magnetic Resonance Imaging (MRI) examinations before surgery. MRI findings and histopathologic characteristics of tumors were collected for analysis. Breast LVI was confirmed by postoperative pathology. We used a stepwise logistic regression to select variables and two cut-points were determined to create a three-tier risk-stratification scoring system. The patients were classified as having low, moderate and high probability of LVI. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discrimination ability of the scoring system. RESULTS: Tumor margins, lobulation sign, diffusion-weighted imaging appearance, MRI-reported axillary lymph node metastasis, time to signal intensity curve pattern, and HER-2 were selected as predictors for LVI in the point-based scoring system. Patients were considered at low risk if the score was < 3.5, moderate risk if the score was 3.5 to 6.0, and high risk if the score was ≥6.0. LVI risk was segmented from 0 to 100.0% and was positively associated with an increase in risk scores. The AUC of the scoring system was 0.824 (95% confidence interval [CI]: 0.776--0.872). CONCLUSION: This study shows that a simple and reliable score-based risk-stratification system can be practically used in stratifying the risk of LVI in breast cancer.

Tübingen hip flexion splints for developmental dysplasia of the hip in infants aged 0-6 months.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common disorder in infants. The present study aimed to evaluate the efficacy and safety of the Tübingen hip flexion splints in treating DDH in infants aged 0-6 months. METHODS: This is a retrospective study analyzing 259 hips in 195 infants with DDH of Graf type IIc or worse classifications treated between January 2015 and December 2017. Patients were followed up for at least 6 months. Avascular necrosis of the femoral head was diagnosed using plain radiographs at the last follow-up visit according to the Bucholz-Ogden classification. Successful treatment was defined as an improvement of the Graft classification to type I, or an improvement of the International Hip Dysplasia Institute classification to type I in patients aged > 6 months. RESULTS: Treatment was deemed successful in 128 patients (83.7%). Avascular necrosis occurred in 3 patients (3 hips). Univariate analysis showed that late treatment initiation, family history of DDH, Graf type IV and bilateral involvement were independent risk factors for treatment failure (p < 0.05). The receiver operating characteristic curve showed a cut-off value of 12 weeks for age at treatment initiation regarding successful treatment. Logistic regression analysis showed that gender, breech presentation, firstborn, swaddling, birth weight > 3.5 kg, oligohydramnios, foot deformity and torticollis did not affect the success rate of treatment (p > 0.05). CONCLUSIONS: The Tübingen splint showed good efficacy and safety in treating DDH in infants aged 0-6 months. Family history of DDH, Graf classification of type IV, bilateral involvement and treatment initiation after 12 weeks of age are risk factors of treatment failure. TRIAL REGISTRATION: N/A.

Nationwide Trends in Acute and Chronic Pancreatitis Among Privately Insured Children and Non-Elderly Adults in the United States, 2007-2014.

BACKGROUND & AIMS: Epidemiologic analyses of acute pancreatitis (AP) and chronic pancreatitis (CP) provide insight into causes and strategies for prevention and affect allocation of resources to its study and treatment. We sought to determine current and accurate incidences of AP and CP, along with the prevalence of CP, in children and adults in the United States. METHODS: We collected data from the Truven MarketScan Research Databases of commercial inpatient and outpatient insurance claims in the United States from 2007 through 2014 (patients 0-64 years old). We calculated the incidences of AP and CP and prevalence of CP based on International Classification of Diseases, 9th Revision diagnosis codes. Children were defined as 18 years or younger and adults as 19 to 64 years old. RESULTS: The incidence of pediatric AP was stable from 2007 through 2014, remaining at 12.3/100,000 persons in 2014. Meanwhile, the incidence for adult AP decreased from 123.7/100,000 persons in 2007 to 111.2/100,000 persons in 2014. The incidence of CP decreased over time in children (2.2/100,000 persons in 2007 to 1.9/100,000 persons in 2014) and adults (31.7/100,000 persons in 2007 to 24.7/100,000 persons in 2014). The prevalences of pediatric and adult CP were 5.8/100,000 persons and 91.9/100,000 persons, respectively, in 2014. Incidences of AP and CP increased with age. We found little change in incidence during the first decade of life but linear increases starting in the second decade. CONCLUSIONS: We performed a comprehensive epidemiologic analysis of privately insured, non-elderly adults and children with AP and CP in the United States. Changes in gallstone formation, smoking, and alcohol consumption, along with advances in pancreatitis management, may be responsible for the stabilization and even decrease in the incidences of AP and CP.

Role and Association of Inflammatory and Apoptotic Caspases in Renal Tubulointerstitial Fibrosis.

BACKGROUND/AIMS: Caspases, an evolutionary conserved family of aspartate-specific cystein proteases, play pivotal roles in apoptotic and inflammatory signaling. Thus far, 14 mammalian caspases are identified and categorized into 3 distinct sub-types: inflammatory caspases, apoptotic initiator and apoptotic executioner. Caspase-1 is an inflammatory caspase, while caspase-7 belongs to apoptotic executioner. The roles and association of these two distinct types of caspases in renal tubulointerstitial fibrosis (TIF) have not been well recognized. METHODS: Caspase-1 inhibitor Z-YVAD-FMK and caspase-7 siRNA were used in tubular epithelial cell line NRK-52E (TECs) to test their effects on transforming growth factor-beta1 (TGF-ß1) stimulation. In vivo, Unilateral ureteral obstruction (UUO) animal model was employed in wild-type (WT) and caspase-1 knock out (KO) (caspase-1-/-) mice. RESULTS: In current study, we found that caspase-7 was obviously activated in cultured TECs stimulated by TGF-ß1 and in UUO model of WT mice. While in UUO model of caspase-1 KO mice, the increased caspase-7 activation was suppressed significantly along with reduced trans-differentiation and minimized extracellular matrix (ECM) accumulation, as demonstrated by western blot, Masson trichrome staining and immunohistochemistry. In addition, pharmacological inhibition of caspase-1 dampened caspase-7 activation and TECs' transdifferentiation induced by TGF-ß1 exposure, which was consistent with in vivo study. Notably, caspase-7 gene knock down by specific siRNA abrogated TGF-ß1 driven TECs' trans-differentiation and reduced ECM accumulation. CONCLUSIONS: Our study associated inflammatory and apoptotic caspases in TIF for the first time and we further confirmed that caspase-1 activation is an upstream event of apoptotic caspase-7 induction in TIF triggered by UUO and in TECs mediated by TGF-ß1 induced transdifferentiation.

Spectrally Stable and Bright Red Perovskite Light-Emitting Diodes.

Mixing iodide and bromide in three-dimensional metal-halide perovskites is a facile strategy for achieving red light-emitting diodes (LEDs). However, these devices often face challenges such as instability in electroluminescence spectra and low brightness due to phase segregation in mixed-halide perovskites. Here, we demonstrate spectrally stable and bright red perovskite LEDs by substituting some of the halide ions with pseudohalogen thiocyanate ions (SCN-). We find that SCN- can occupy halogen vacancies, thereby releasing microstrain and passivating defects in the perovskite crystals. This leads to the suppression of mixed-halide phase segregation under electrical bias. As a result, the red perovskite LEDs exhibit a high brightness of >35 000 cd m-2 with stable Commission Internationale de l'Eclairage (CIE) coordinates of (0.713, 0.282). This brightness surpasses that of the best-performing red perovskite LEDs, showing great promise for advancing perovskite LEDs in display and lighting applications.

Bioinspired super-hydrophilic zwitterionic polymer armor combats thrombosis and infection of vascular catheters.

Thrombosis and infection are two major complications associated with central venous catheters (CVCs), which significantly contribute to morbidity and mortality. Antifouling coating strategies currently represent an efficient approach for addressing such complications. However, existing antifouling coatings have limitations in terms of both duration and effectiveness. Herein, we propose a durable zwitterionic polymer armor for catheters. This armor is realized by pre-coating with a robust phenol-polyamine film inspired by insect sclerotization, followed by grafting of poly-2-methacryloyloxyethyl phosphorylcholine (pMPC) via in-situ radical polymerization. The resulting pMPC coating armor exhibits super-hydrophilicity, thereby forming a highly hydrated shell that effectively prevents bacterial adhesion and inhibits the adsorption and activation of fibrinogen and platelets in vitro. In practical applications, the armored catheters significantly reduced inflammation and prevented biofilm formation in a rat subcutaneous infection model, as well as inhibited thrombus formation in a rabbit jugular vein model. Overall, our robust zwitterionic polymer coating presents a promising solution for reducing infections and thrombosis associated with vascular catheters.

Active Dual-Protein Coating Assisted by Stepwise Protein-Protein Interactions Assembly Reduces Thrombosis and Infection.

Universal protein coatings have recently gained wide interest in medical applications due to their biocompatibility and ease of fabrication. However, the challenge persists in protein activity preservation, significantly complicating the functional design of these coatings. Herein, an active dual-protein surface engineering strategy assisted by a facile stepwise protein-protein interactions assembly (SPPIA) method for catheters to reduce clot formation and infection is proposed. This strategy is realized first by the partial oxidation of bovine serum albumin (BSA) and lysozyme (LZM) for creating stable nucleation platforms via hydrophobic interaction, followed by the assembly of nonoxidized BSA (pI, the isoelectric point, ≈4.7) and LZM (pI ≈11) through electrostatic interaction owing to their opposite charge under neutral conditions. The SPPIA method effectively preserves the conformation and functionality of both BSA and LZM, thus endowing the resultant coating with potent antithrombotic and bactericidal properties. Furthermore, the stable nucleation platform ensures the adhesion and durability of the coating, resisting thrombosis and bacterial proliferation even after 15 days of PBS immersion. Overall, the SPPIA approach not only provides a new strategy for the fabrication of active protein coatings but also shows promise for the surface engineering technology of catheters.

Glycocalyx-inspired dynamic antifouling surfaces for temporary intravascular devices.

Protein and cell adhesion on temporary intravascular devices can lead to thrombosis and tissue embedment, significantly increasing complications and device retrieval difficulties. Here, we propose an endothelial glycocalyx-inspired dynamic antifouling surface strategy for indwelling catheters and retrievable vascular filters to prevent thrombosis and suppress intimal embedment. This strategy is realized on the surfaces of substrates by the intensely dense grafting of hydrolyzable endothelial polysaccharide hyaluronic acid (HA), assisted by an amine-rich phenol-polyamine universal platform. The resultant super-hydrophilic surface exhibits potent antifouling property against proteins and cells. Additionally, the HA hydrolysis induces continuous degradation of the coating, enabling removal of inevitable biofouling on the surface. Moreover, the dense grafting of HA also ensures the medium-term effectiveness of this dynamic antifouling surface. The coated catheters maintain a superior anti-thrombosis capacity in ex vivo blood circulation after 30 days immersion. In the abdominal veins of rats, the coated implants show inhibitory effects on intimal embedment up to 2 months. Overall, we envision that this glycocalyx-inspired dynamic antifouling surface strategy could be a promising surface engineering technology for temporary intravascular devices.

Delay-dependent Lurie-Postnikov type Lyapunov-Krasovskii functionals for stability analysis of discrete-time delayed neural networks.

This paper addresses the influence of time-varying delay and nonlinear activation functions with sector restrictions on the stability of discrete-time neural networks. Compared to previous works that mainly focuses on the influence of delay information, this paper devotes to activation nonlinear functions information to help compensate the analysis technique based on Lyapunov-Krasovskii functional (LKF). A class of delay-dependent Lurie-Postnikov type integral terms involving sector constraints of nonlinear activation function is proposed to complement the LKF construction. The less conservative criteria for the stability analysis of discrete-time delayed networks is given by using improved LKF. Numerical examples show that conservatism can be reduced by the delay-dependent integral terms involving nonlinear activation functions.

A Degree-Dependent Polynomial-Based Reciprocally Convex Matrix Inequality and Its Application to Stability Analysis of Delayed Neural Networks.

In this article, several improved stability criteria for time-varying delayed neural networks (DNNs) are proposed. A degree-dependent polynomial-based reciprocally convex matrix inequality (RCMI) is proposed for obtaining less conservative stability criteria. Unlike previous RCMIs, the matrix inequality in this article produces a polynomial of any degree in the time-varying delay, which helps to reduce conservatism. In addition, to reduce the computational complexity caused by dealing with the negative definite of the high-degree terms, an improved lemma is presented. Applying the above matrix inequalities and improved negative definiteness condition helps to generate a more relaxed stability criterion for analyzing time-varying DNNs. Two examples are provided to illustrate this statement.

High-Performance All-Inorganic Architecture Perovskite Light-Emitting Diodes Based on Tens-of-Nanometers-Sized CsPbBr3 Emitters in a Carrier-Confined Heterostructure.

Developing green perovskite light-emitting diodes (PeLEDs) with a high external quantum efficiency (EQE) and low efficiency roll-off at high brightness remains a critical challenge. Nanostructured emitter-based devices have shown high efficiency but restricted ascending luminance at high current densities, while devices based on large-sized crystals exhibit low efficiency roll-off but face great challenges to high efficiency. Herein, we develop an all-inorganic device architecture combined with utilizing tens-of-nanometers-sized CsPbBr3 (TNS-CsPbBr3) emitters in a carrier-confined heterostructure to realize green PeLEDs that exhibit high EQEs and low efficiency roll-off. A typical type-I heterojunction containing TNS-CsPbBr3 crystals and wide-bandgap Cs4PbBr6 within a grain is formed by carefully controlling the precursor ratio. These heterostructured TNS-CsPbBr3 emitters simultaneously enhance carrier confinement and retain low Auger recombination under a large injected carrier density. Benefiting from a simple device architecture consisting of an emissive layer and an oxide electron-transporting layer, the PeLEDs exhibit a sub-bandgap turn-on voltage of 2.0 V and steeply rising luminance. In consequence, we achieved green PeLEDs demonstrating a peak EQE of 17.0% at the brightness of 36,000 cd m-2, and the EQE remained at 15.7% and 12.6% at the brightness of 100,000 and 200,000 cd m-2, respectively. In addition, our results underscore the role of interface degradation during device operation as a factor in device failure.

Strain Engineering and Halogen Compensation of Buried Interface in Polycrystalline Halide Perovskites.

Inverted perovskite solar cells based on weakly polarized hole-transporting layers suffer from the problem of polarity mismatch with the perovskite precursor solution, resulting in a nonideal wetting surface. In addition to the bottom-up growth of the polycrystalline halide perovskite, this will inevitably worse the effects of residual strain and heterogeneity at the buried interface on the interfacial carrier transport and localized compositional deficiency. Here, we propose a multifunctional hybrid pre-embedding strategy to improve substrate wettability and address unfavorable strain and heterogeneities. By exposing the buried interface, it was found that the residual strain of the perovskite films was markedly reduced because of the presence of organic polyelectrolyte and imidazolium salt, which not only realized the halogen compensation and the coordination of Pb2+ but also the buried interface morphology and defect recombination that were well regulated. Benefitting from the above advantages, the power conversion efficiency of the targeted inverted devices with a bandgap of 1.62 eV was 21.93% and outstanding intrinsic stability. In addition, this coembedding strategy can be extended to devices with a bandgap of 1.55 eV, and the champion device achieved a power conversion efficiency of 23.74%. In addition, the optimized perovskite solar cells retained 91% of their initial efficiency (960 h) when exposed to an ambient relative humidity of 20%, with a T80 of 680 h under heating aging at 65 °C, exhibiting elevated durability.

Prognostic value of CD8+ tumor-infiltrating T cells in patients with breast cancer: A systematic review and meta-analysis.

CD8+ tumor-infiltrating lymphocytes have been regarded as potential biomarkers for cancer prognosis, while the prognostic effect of CD8+ tumor-infiltrating T cells remains controversial in breast cancer. In the present study, a meta-analysis was performed to evaluate the prognostic value of CD8+ T cells in breast cancer and the associations between CD8+ T cells and the pathological characteristics. The PubMed, Embase and the Cochrane Library were systematically searched entries added from the establishment of the database to November 2021 and prospective or retrospective studies of patients with breast cancer were included. The Newcastle-Ottawa Scale was used to assess the quality of evidence for each study. STATA 15.1 was used for the data analysis. A total of 14 studies comprising 22,222 patients were included in the final analysis and the pooled results suggested that a high CD8+ T-cell infiltration level was significantly related to better overall survival [hazard ratio (HR)=0.70, 95% confidence interval (CI): 0.60-0.82, P<0.001] and disease-free survival (HR=0.63, 95% CI: 0.49-0.81, P<0.001) for patients with breast cancer. In addition, a high CD8+ T-cell infiltration level was significantly associated with decreased expression of estrogen receptor [odds ratio (OR)=1.92, 95% CI: 1.30-2.85, P=0.001] and progesterone receptor (OR=1.66, 95% CI: 1.14-2.42, P=0.008), and increased human epidermal growth factor receptor 2 expression (OR=0.79, 95% CI: 0.66-0.94, P=0.010) in patients with breast cancer, while there was no significant association between CD8+ T-cell infiltration and age, tumor size or lymph node status of patients with breast cancer (P>0.05). In conclusion, CD8+ T-cell infiltration is of prognostic value in patients with breast cancer. High levels of CD8+ T-cell infiltration were related to improved prognosis, including OS and DFS, in patients with breast cancer.

Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity.

PURPOSE: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. MATERIALS AND METHODS: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). RESULTS: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. CONCLUSIONS: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

Temporal Analysis of Inflammatory Bowel Disease and Pancreatitis Co-Occurrence in Children and Adults in the United States.

INTRODUCTION: Pancreatitis in inflammatory bowel disease has been attributed to peripancreatic intestinal disease and/or drug-induced pancreatic toxicity. We used large cohort analyses to define inflammatory bowel disease and pancreatitis temporal co-occurrence with a detailed descriptive analysis to gain greater insight into the pathophysiological relationship between these 2 diseases. METHODS: Truven Health MarketScan private insurance claims from 141,017,841 patients (younger than 65 years) and 7,457,709 patients from 4 academic hospitals were analyzed. We calculated the prevalence of Crohn's disease or ulcerative colitis (UC) with acute pancreatitis or chronic pancreatitis (CP) and performed temporal and descriptive analyses. RESULTS: Of 516,724 patients with inflammatory bowel disease, 12,109 individuals (2.3%) had pancreatitis. Acute pancreatitis (AP) was 2-6x more prevalent than CP. In adults, AP occurred equally among Crohn's disease and UC (1.8%-2.2% vs 1.6%-2.1%, respectively), whereas in children, AP was more frequent in UC (2.3%-3.4% vs 1.5%-1.8%, respectively). The highest proportion of pancreatitis (21.7%-44.7%) was at/near the time of inflammatory bowel disease diagnosis. Of them, 22.1%-39.3% were on steroids during pancreatitis. Individuals with CP or recurrent pancreatitis hospitalizations had increased risk of a future inflammatory bowel disease diagnosis (odds ratio = 1.52 or 1.72, respectively). DISCUSSION: Pancreatitis in inflammatory bowel disease may not simply be a drug adverse event but may also involve local and/or systemic processes that negatively affect the pancreas. Our analysis of pancreatitis before, during, and after inflammatory bowel disease diagnosis suggests a bidirectional pathophysiologic relationship between inflammatory bowel disease and pancreatitis, with potentially more complexity than previously appreciated.

CDCA8 Contributes to the Development and Progression of Thyroid Cancer through Regulating CDK1.

Background: This study aims to reveal regulatory role of cell division cycle associated 8 (CDCA8) in thyroid cancer progression and metastasis. Methods: A series of experiments in vivo and in vitro were performed to explore the function of CDCA8 in thyroid cancer. Results: Immunohistochemical analysis showed that CDCA8 expression levels were upregulated in thyroid cancer tissues compared with normal tissues, and were statistically correlated with tumor stage. Results of in vitro loss-of-function assay showed that downregulation of endogenous expression of CDCA8 could significantly inhibit cell proliferation, colony formation, cell migration, and promote apoptosis. Thyroid cancer cells lacking CDCA8 expression also had reduced tumorigenicity in vivo. Further, results of preliminary mechanistic exploration showed that CDK1 may be a potential downstream molecule of CDCA8 in regulating thyroid cancer progression. We subsequently confirmed that CDK1 itself exerted a significant regulatory function in thyroid cancer by loss- and gain-of-function experiments. Moreover, overexpression of CDK1 could weaken the tumor suppressive effect caused by CDCA8 knockdown. Conclusions: CDCA8 functions as an oncogene in thyroid cancer, and CDCA8 knockdown suppresses cancer development in vitro and in vivo. Additionally, CDK1 was further identified as a potential target of CDCA8 in thyroid cancer.