Analysis of Angiogenesis-Related Signatures in the Tumor Immune Microenvironment and Identification of Clinical Prognostic Regulators in Lung Adenocarcinoma.

Tumor angiogenesis is considered to be an important part of the mechanism of tumor progression and metastasis, and its specific function in lung adenocarcinoma has not been fully studied. In this study, we used the transcriptome and genome data of lung adenocarcinoma patients to analyze the expression of 36 angiogenesis regulators in lung adenocarcinoma. Consensus clustering analysis divided lung adenocarcinoma samples into 4 subtypes, A, B, C, and D, and the expression of most angiogenesis regulators in subtype B was higher than that in other subtypes. Immunological analysis indicated that subtype B is likely to display the characteristics of a hot tumor with a more active TME. With the help of Lasso-Cox regression analysis, we successfully constructed a risk model involving five Angiogenesis Regulators genes (CCND2, JAG1, MSX1, STC1, TIMP1), which will be helpful for clinical personalized treatment and prognosis prediction. In addition, JAG1 has the highest mutation rate in tumors, and its cancer-promoting function is reflected in a variety of tumors, which provides important clues for the development of new broad-spectrum anti-cancer targets in the future. We successfully constructed a risk model involving five angiogenesis regulators genes (CCND2, JAG1, MSX1, STC1, TIMP1), which may be helpful for clinical personalized treatment and prognosis prediction. In addition, JAG1 has the highest mutation rate in tumors and plays a leading role in the protein interaction network. Its tumor-promoting function is reflected in a variety of tumors and may become a broad-spectrum anti-cancer target in the future.

Tetrahydrocurcumin regulates the tumor immune microenvironment to inhibit breast cancer proliferation and metastasis via the CYP1A1/NF-κB signaling pathway.

The NF-κB signaling pathway is overactivated in tumor cells, and the activation of the NF-κB signaling pathway releases a large number of inflammatory factors, which enhance tumor immunosuppression and promote tumor metastasis. The cytochrome P450 (CYP450) system consists of important metabolic enzymes present in different tissues and progressive tumors, which may lead to changes in the pharmacological action of drugs in inflammatory diseases such as tumors. In this study, the anticancer effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on breast cancer cells and the underlying mechanism were investigated. Result showed that THC selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner. Moreover, THC-induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species (ROS) induction. In addition, THC could affect the CYP450 enzyme metabolic pathway and inhibit the expression of CYP1A1 and activation of the NF-κB pathway, thereby inhibiting the migration and invasion of breast cancer cells. Furthermore, after overexpression of CYP1A1, the inhibitory effects of THC on the proliferation, metastasis, and induction of apoptosis in breast cancer cells were weakened. The knockdown of CYP1A1 significantly enhanced the inhibitory effect of THC on the proliferation, metastasis, and apoptosis induction of breast cancer cells. Notably, THC exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MCF-7 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Collectively, these results showed that TH could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the CYP1A1/NF-κB signaling pathway, indicating that THC serves as a potential candidate drug for the treatment of breast cancer.

Factors Influencing Quality of Life and Functional Outcomes in Patients With Bladder Cancer.

Here, we review the quality of life and functional outcomes of patients with bladder cancer after treatment and assess potential contributing factors. For current scoring systems, we highlighted the most commonly used specificity scores. In addition, we discuss the impact and bias on the quality of life of patients undergoing urinary diversion modalities, robotic surgery, perioperative rehabilitation, and bladder-preserving radiochemotherapy. Through this review, clinicians will gain better insights regarding the importance of improving patients' quality of life with the goal of restoring their patients' normal function and participating in social activities.

Three-dimensional visualization and evaluation of hilar cholangiocarcinoma resectability and proposal of a new classification.

BACKGROUND: As digital medicine has exerted profound influences upon diagnosis and treatment of hepatobiliary diseases, our study aims to investigate the accuracy of three-dimensional visualization and evaluation (3DVE) system in assessing the resectability of hilar cholangiocarcinoma (hCCA), and explores its potential clinical value. MATERIALS AND METHODS: The discovery cohort, containing 111 patients from April 2013 to December 2019, was retrospectively included to determine resectability according to revised criteria for unresectability of hCCA. 3D visualization models were reconstructed to evaluate resectability parameters including biliary infiltration, vascular involvement, hepatic atrophy and metastasis. Evaluation accuracy were compared between contrast-enhanced CT and 3DVE. Logistic analysis was performed to identify independent risk factors of R0 resection. A new comprehensive 3DVE classification of hCCA based on factors influencing resectability was proposed to investigate its role in predicting R0 resection and prognosis. The main outcomes were also analyzed in cohort validation, including 34 patients from January 2020 to August 2022. RESULTS: 3DVE showed an accuracy rate of 91% (95%CI 83.6-95.4%) in preoperatively evaluating hCCA resectability, significantly higher than 81% (95%CI 72.8-87.7%) of that of CT (p = 0.03). By multivariable analysis, hepatic artery involvement in 3DVE was identified an independent risk factor for R1 or R2 resection (OR = 3.5, 95%CI 1.4,8.8, P < 0.01). New 3DVE hCCA classification was valuable in predicting patients' R0 resection rate (p < 0.001) and prognosis (p < 0.0001). The main outcomes were internally validated. CONCLUSIONS: 3DVE exhibited a better efficacy in evaluating hCCA resectability, compared with contrast-enhanced CT. Preoperative 3DVE demonstrated hepatic artery involvement was an independent risk factor for the absence of R0 margin. 3DVE classification of hCCA was valuable in clinical practice.

Independent and combined associations of dietary antioxidant intake with bone mineral density and risk of osteoporosis among elderly population in United States.

BACKGROUND: The influence of dietary antioxidant intake on the occurrence and progression of osteoporosis may be significant. However, to date, evidence on the link between combined effect of dietary antioxidants on bone mineral density (BMD) level and risk of osteoporosis is limited. We aimed to assess the independent and combined association of dietary antioxidant intake with BMD level and risk of osteoporosis among elderly population in United States through analysis of data in the National Health and Nutrition Examination Survey. METHODS: The dietary antioxidant intake was assessed based on six antioxidants, including vitamin A, vitamin C, vitamin E, zinc, selenium, and total carotenoid. A composite dietary antioxidant index (CDAI) was used to evaluate the combined exposure of dietary antioxidant intake. RESULTS: A total of 5618 participants were included. Higher dietary vitamin A, vitamin C, vitamin E, zinc, selenium, and total carotenoid, were positively associated with BMD level. Compared with participants in the first quartile, those in the higher quartile of vitamin E (Q4: OR 0.652; 95% CI 0.463-0.918), zinc (Q4: OR 0.581; 95% CI 0.408-0.826), and selenium (Q3: OR 0.673; 95% CI 0.503-0.899) were associated with decreased risk of overall osteoporosis. Furthermore, compared to those in the first quartile, participants in the highest quartile of CDAI were associated with increased total femur (ß 0.019; 95% CI 0.007-0.032), femur neck (ß 0.020; 95% CI 0.009-0.032), trochanter (ß 0.012; 95% CI 0.001-0.023), and intertrochanter BMD level (ß 0.022; 95% CI 0.007-0.037); participants in the highest quartile of CDAI were associated with decreased risk of overall osteoporosis (OR 0.536; 95% CI 0.376-0.763). Furthermore, the associations of CDAI with the BMD level and osteoporosis risk were more significant among female participants. CONCLUSION: Our study provides evidence that a combination of dietary antioxidants intake was associated increased BMD level and decreased osteoporosis risk.

A Four Autophagy-Related Gene-Based Prognostic Signature for Pancreatic Cancer.

This study aimed to screen autophagy-related genes (ARGs) that affect the prognosis of pancreatic cancer patients based on The Cancer Genome Atlas (TCGA) gene expression data and genotype-tissue expression (GTEx) databases. The expression data of pancreatic cancer and normal pancreas were downloaded from TCGA and GTEx databases. Human ARGs list was obtained through the Human Autophagy Database (HADB) and GeneCards database. The Wilcox test was performed to screen differentially expressed ARGs. Differentially expressed ARGs were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. The CIBER-SORT algorithm was utilized to analyze immune cell infiltration in samples. A total of 21 up-regulated ARGs and 11 down-regulated ARGs were screened in the TCGA-GTEx integrated data set. The enrichment analysis of GO and KEGG showed that 32 differentially expressed ARGs were significantly enriched in autophagy-related pathways. Univariate Cox regression analysis showed that 12 candidate ARGs were significantly related to the prognosis of pancreatic cancer patients. Multivariate Cox regression analysis found that ATG16L2, GNAI3, APOL1, and PTK6 genes may be the key ARGs affecting the prognosis of pancreatic cancer patients. Based on these four key ARGs, a prognostic risk assessment model was constructed, and pancreatic cancer patients were classified into the high-risk and low-risk group according to the risk value. Survival analysis and ROC analysis confirmed that the prognostic risk assessment model can accurately predict the prognosis of patients with pancreatic cancer. Immune infiltration analysis found that B cells naive, B cells memory, plasma cells, T cells CD8, T cells CD4 memory resting, monocytes and macrophages M0 were significantly different in tissue samples of pancreatic cancer patients in the high and low risk groups. Pearson's correlation coefficient showed that the four key ARGs may affect the development of pancreatic cancer by affecting immune cell components in the tumor micro-environment. In conclusion, ATG16L2, GNAI3, APOL1, and PTK6 may be related to the prognosis of pancreatic cancer patients. The prognostic risk assessment model constructed based on these four key ARGs could accurately predict the prognosis of pancreatic cancer patients.

Down-regulation of EGFL8 regulates migration, invasion and apoptosis of hepatocellular carcinoma through activating Notch signaling pathway.

BACKGROUND: Our previous studies have reported the down-regulation of EGFL8 correlates to the development and prognosis of colorectal and gastric cancer. The present study is carried out to explore the expression pattern and role of EGFL8 in hepatocellular carcinoma (HCC). METHODS AND MATERIALS: EGFL8 expression in 102 cases of HCC tissues matched with adjacent non-tumorous liver tissues, a normal liver cell line and three liver cancer cell lines with different metastatic capacity was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Moreover, the clinicopathological features and prognosis of HCC patients were correlated with expression of EGFL8. Subsequently, the gain-and loss-of-function experiments were carried out to investigate the biological function of EGFL8 in HCC. We also used N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-(S)- phenylglycine t-butyl ester (DAPT), an inhibitor for Notch signaling pathway, in these experiments to verify the involvement of Notch signaling pathway in the effects of EGFL8. Additionally, a mouse model was established to investigate the effect of EGFL8 on metastasis of HCC cells. The expression of Notch signaling pathway in HCC cells and xenograft mouse tumors were detected by Western blot and immunohistochemistory. RESULTS: The expression of EGFL8 was significantly decreased in HCC tissues and cell lines and EGFL8 down-regulation correlated to multiple nodules, vein invasion, high TNM stage and poor prognosis of HCC. Interestingly, the expression levels of EGFL8 in three liver cancer cell lines were negatively associated with their metastatic capacity. In vitro and in vivo experiments indicated that EGFL8 obviously suppressed metastasis and invasion of HCC cells but slightly promoted apoptosis. Meanwhile, the expression of Notch signaling pathway was obviously suppressed in EGFL8 overexpressed HCCLM3 cells and xenograft mouse tumors generated from these cells but markedly elevated in EGFL8 depleted Hep3B cells. Furthermore, the up-regulated expression of Notch signaling pathway and effects induced by EGFL8 knockdown in Hep3B cells could be counteracted by DAPT treatment. CONCLUSION: The down-regulation of EGFL8 was correlated to progression and poor prognosis of HCC and regulates HCC cell migration, invasion and apoptosis through activating the Notch signaling pathway, suggesting EGFL8 as a novel therapeutic target and a potential prognostic marker for HCC.

Isoliquiritigenin ameliorates caerulein-induced chronic pancreatitis by inhibiting the activation of PSCs and pancreatic infiltration of macrophages.

Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Currently, the clinical therapeutic scheme of CP is mainly symptomatic treatment including pancreatic enzyme replacement, glycaemic control and nutritional support therapy, lacking of specific therapeutic drugs for prevention and suppression of inflammation and fibrosis aggravating in CP. Here, we investigated the effect of isoliquiritigenin (ILG), a chalcone-type dietary compound derived from licorice, on pancreatic fibrosis and inflammation in a model of caerulein-induced murine CP, and the results indicated that ILG notably alleviated pancreatic fibrosis and infiltration of macrophages. Further in vitro studies in human pancreatic stellate cells (hPSCs) showed that ILG exerted significant inhibition on the proliferation and activation of hPSCs, which may be due to negative regulation of the ERK1/2 and JNK1/2 activities. Moreover, ILG significantly restrained the M1 polarization of macrophages (RAW 264.7) via attenuation of the NF-κB signalling pathway, whereas the M2 polarization was hardly affected. These findings indicated that ILG might be a potential anti-inflammatory and anti-fibrotic therapeutic agent for CP.

Electrospun cellulose-based conductive polymer nanofibrous mats: composite scaffolds and their influence on cell behavior with electrical stimulation for nerve tissue engineering.

The fabrication of scaffolds with suitable chemical, physical, and electrical properties is critical for nerve cell adhesion and proliferation. Recently, electrical stimulation on conductive polymers has been applied to construct functional nerve cell scaffolds. Herein, we prepared natural polymer (cellulose)/conductive polymer nanofibrous mats, i.e., electrospun cellulose (EC)/poly N-vinylpyrrole (PNVPY) and EC/poly(3-hexylthiophene) (P3HT) through an efficient in situ polymerization method. The surface immobilization was characterized by optical microscopy (OM), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, hydrophilicity, porosity, and cyclic voltammetry. The OM and SEM images showed that PNVPY formed polymer coatings and aggregated nanoparticles on the EC nanofibers, while P3HT only produced polymer coatings. Compared with pure EC mats, both the composite mats had increased thickness, higher porosity, and higher conductivity. Also, an increase in hydrophilicity was found for EC/P3HT. In vivo cytocompatibility of the undifferentiated PC12 cells showed that the EC/PNVPY and EC/P3HT scaffolds exhibited favorable cell activity, adhesion, and proliferation. Furthermore, the results of electrical stimulation experiments indicated that the EC/P3HT mats could effectively promote the proliferation of the PC12 cells more than the EC and EC/PNVPY mats. The findings suggest a positive outcome regarding the conductive polymer-modified EC/PNVPY and EC/P3HT nanofibrous mats in neural tissue engineering.

Risk factors and nomogram for diabetes mellitus in idiopathic chronic pancreatitis.

BACKGROUND AND AIM: Diabetes mellitus (DM) is a common complication of idiopathic chronic pancreatitis (ICP), which impairs the quality of life for patients. This study aimed to identify risk factors and develop nomogram for DM in ICP to help early diagnosis. METHODS: Idiopathic chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were included. Cumulative rates of DM were calculated by Kaplan-Meier method. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on training cohort, risk factors for DM were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: Totally, 1633 patients with ICP were finally enrolled. The median follow-up duration was 9.8 years. DM was found in 26.3% (430/1633) of patients after the onset of CP. Adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct were identified risk factors for DM development. The nomogram achieved good concordance indexes in the training and validation cohorts, respectively, with well-fitted calibration curves. CONCLUSIONS: Risk factors were identified, and nomogram was developed to determine the risk of DM in ICP patients. Patients with one or more of the risk factors including adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct have higher incidence of DM.

Risk Factors and Nomogram for Pancreatic Stone Formation in Chronic Pancreatitis over a Long-Term Course: A Cohort of 2,153 Patients.

BACKGROUND: Pancreatic stones are pathognomonic of chronic pancreatitis (CP). This study aimed to determine the incidence, identify risk factors, and develop a nomogram for pancreatic stones in CP patients. METHODS: Patients with CP admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic stones after the onset of CP and after the diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 2,153 CP patients, pancreatic stones were detected in 1,626 (75.5%) patients, with a median follow-up of 7.8 years. Age at the onset of CP, body mass index, smoking, diabetes mellitus, pancreatic pseudocyst, biliary stricture, severe acute pancreatitis, and type of pain were identified risk factors for pancreatic stones development. The nomogram with these 8 factors achieved good accuracy. CONCLUSIONS: The nomogram achieved an individualized prediction of pancreatic stones development in CP. It may help the management of pancreatic stones.

Risk Factors and Nomogram for Common Bile Duct Stricture in Chronic Pancreatitis: A Cohort of 2153 Patients.

GOALS: To identify the risk factors and develop nomograms for common bile duct (CBD) stricture in chronic pancreatitis (CP) patients. BACKGROUND: CBD stricture is a common complication in CP and has a variable clinical presentation ranging from asymptomatic to overt jaundice and cholangitis. STUDY: Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of CBD stricture after onset and diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. On the basis of the training cohort, risk factors for CBD stricture and symptomatic CBD stricture were identified through Cox proportional hazards regression model, and nomograms was developed, respectively. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 2153 patients, the median duration of follow-up was 7.0 years. CBD strictures were detected in 340 (15.8%) patients, whereas 159 of them were symptomatic. Male gender, age at onset of CP, smoking, body mass index, and morphology of main pancreatic duct were identified risk factors for CBD stricture development. Age at onset of CP, body mass index, and type of pain were identified risk factors for symptomatic CBD stricture development. Both nomograms achieved good concordance indexes with well-fitted calibration curves. CONCLUSIONS: The nomogram achieved an individualized prediction of symptomatic CBD stricture development in CP patients. It may help the early diagnosis and intervention of symptomatic CBD stricture and reduce the rates of severe adverse events.

Colonic hematoma after extracorporeal shock wave lithotripsy for pancreatic stones: a case report.

BACKGROUND: Despite pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is a minimally invasive treatment for pancreatic stones, complications exist. CASE PRESENTATION: A 37-year-old male was diagnosed with chronic pancreatitis and admitted to our hospital for recurrent acute pancreatitis. After the first P-ESWL session, the patient complained of a new type of pain different from the previous pain pattern. Computerized tomography and colonoscopy were arranged and colonic hematoma was found. Since the patient had stable vital signs, no special treatment was given focusing on the colonic hematoma. Five days later, P-ESWL treatment was repeatedly performed for four consecutive days. Two days after the last P-ESWL session, the patient underwent endoscopic retrograde cholangiopancreatography. At the three-month follow up visit, the colonic hematoma disappeared and pancreatic stones decreased significantly. CONCLUSIONS: To the best of our knowledge, colonic hematoma after P-ESWL for pancreatic stones has never been reported. Here, we present the only case of colonic hematoma after P-ESWL, which was coincidentally found in more than 6000 P-ESWL sessions in our hospital. As the symptoms of colonic hematoma are mild, we believe the incidence of colonic hematoma has been underestimated. Many people with colonic hematoma after P-ESWL may be undiagnosed or misdiagnosed. Treatment for colonic hematoma depends on whether there is severe clinical state. Exploration of more precise location method for pancreatic stones may reduce the probability of P-ESWL complication.

Autoantibody detection is not recommended for chronic pancreatitis: a cross-sectional Study of 557 patients.

BACKGROUND: Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown. METHODS: Hospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis. RESULTS: In a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-ß2-glycoprotein I (ß2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum ß2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P < 0.05). Multivariate logistic regression analysis result showed that diabetes mellitus (OR = 2.515) and common bile duct stricture (OR = 2.844) were the risk factors of positive ß2-GPI antibody in patients while diabetes mellitus in first-/second-/third-degree relatives (OR = 0.266) was the protective factor. There were no related factors for other three differentially expressed autoantibodies. CONCLUSIONS: Four autoantibodies were expressed differentially between patients with non-AIP CP and historial healthy controls. Due to limited significance for diagnosis and treatment of chronic pancreatitis, autoantibodies detection is not recommended conventionally unless suspected of AIP.

Extracorporeal shock wave lithotripsy is safe and effective for geriatric patients with chronic pancreatitis.

BACKGROUND AND AIM: Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is a first-line treatment for chronic pancreatitis (CP) patients with pancreatic stones. However, the performance of P-EWSL in geriatric patients remains unclear. We aimed to evaluate the safety and efficacy of P-ESWL for them. METHODS: This prospective study was conducted in painful CP patients who underwent P-ESWL. Patients aged over 65 years were included in geriatric group; patients aged under 65 years were assigned to control group. For the long-term follow-up investigation, geriatric patients were matched with patients from the control group in a 1:1 ratio. Primary outcomes were complications of P-ESWL and pain relief. Secondary outcomes included stone clearance, physical and mental health, quality of life score, changes in exocrine and endocrine pancreatic function, and survival. RESULTS: From March 2011 to March 2016, P-ESWL was performed in 1404 patients (72 in the geriatric group and 1332 in the control group). No significant differences were observed in complications of P-ESWL between the two groups (P = 0.364). Among the 67 (67/72, 93.1%) geriatric patients who underwent follow up for 4.02 years, complete pain relief was achieved in 53 patients, which was not significantly different from that of matched controls (54/70; P = 0.920). The death in the geriatrics was significantly higher (P = 0.007), but none of them were correlated with P-ESWL. CONCLUSIONS: P-ESWL is safe and effective for geriatric CP patients with pancreatic stones. It can promote significant pain relief and stone clearance and improve quality of life and mental and physical health.

Risk factor for steatorrhea in pediatric chronic pancreatitis patients.

BACKGROUND: Pediatric patients always suffer from chronic pancreatitis (CP), especially those with steatorrhea. This study aimed to identify the incidence of and risk factors for steatorrhea in pediatric CP. To our best knowledge, there is no pediatric study to document the natural history of steatorrhea in CP. METHODS: CP patients admitted to our center from January 2000 to December 2013 were enrolled. Patients were assigned to the pediatric (< 18 years old) and adult group according to their age at onset of CP. Cumulative rates of steatorrhea in both groups were calculated. Risk factors for both groups were identified, respectively. RESULTS: The median follow-up duration for the whole cohort was 7.6 years. In a total of 2153 patients, 13.5% of them were pediatrics. The mean age at the onset and the diagnosis of CP in pediatrics were 11.622 and 19.727, respectively. Steatorrhea was detected in 46 patients (46/291, 15.8%) in the pediatric group and in 447 patients (447/1862, 24.0%) in the adult group. Age at the onset of CP (hazard ratio [HR], 1.121), diabetes mellitus (DM, HR, 51.140), and severe acute pancreatitis (SAP, HR, 13.946) was identified risk factor for steatorrhea in the pediatric group. CONCLUSIONS: Age at the onset of CP, DM and SAP were identified risk factors for the development of steatorrhea in pediatric CP patients. The high-risk populations were suggested to be followed up closely. They may benefit from a full adequate pancreatic exocrine replacement therapy.

Painful Schmorl's nodes treated by discography and discoblock.

PURPOSE: To determine the efficacy of discography and discoblock in the treatment of low back pain (LBP) associated with painful Schmorl's nodes (SNs). METHODS: Between January 2010 and February 2015, 46 patients were studied who had LBP suspected to be secondary to SNs. There were 34 men and 12 women, and mean age was 54.2 years (range 42-68 years). All patients underwent provocation discography, and discoblock was given to positive patients (confirmed to have painful SNs). Visual analogue scores (VAS) and the Oswestry Disability Index (ODI) were evaluated at 4 h and 1, 3, 6, and 12 months post-operatively. MRI was also used to evaluate the SNs at 12 months. RESULTS: Discography was performed on a total of 60 discs without infection or other complications. Positive findings were found in 71.7% discs; 20.0% were negative, and 8.3% were indeterminate. Among the positive patients who underwent discoblock, 89.2% reported an improvement in their LBP, and none reported worsening symptoms. VAS and ODI scores decreased significantly after discoblock, and there were no significant differences between 4 h and 1, 3, 6, and 12 months post-operatively. In patients with painful SNs, the vertebral body bone marrow surrounding the SN was characterized by low T1 and high T2 signals on MRI. At 12 months, the node demonstrated either high T1 and T2 signals or low T1 and T2 signals. The SNs tended to remain stable in size over time. CONCLUSIONS: Painful SNs refractory to medical or physical therapy should be an indication for treatment with discography and discoblock.

The endoplasmic reticulum adaptor protein ERAdP initiates NK cell activation via the Ubc13-mediated NF-κB pathway.

NK cells play a pivotal role in innate immune responses against pathogenic infections. However, the underlying mechanisms driving defined NK functions remain largely elusive. In this study, we identified a novel endoplasmic reticulum (ER) membrane protein, ER adaptor protein (ERAdP), which is constitutively expressed in human and mouse NK cells. ERAdP is expressed at low levels in peripheral NK cells of hepatitis B virus-associated hepatocellular carcinoma patients. We show that ERAdP initiates NK cell activation through the NF-κB pathway. Notably, ERAdP interacts with ubiquitin-conjugating enzyme 13 (Ubc13) to potentiate its charging activity. Thus, ERAdP augments Ubc13-mediated NF-κB essential modulator ubiquitination to trigger the Ubc13-mediated NF-κB pathway, leading to NK cell activation. Finally, ERAdP transgenic mice display hyperactivated NK cells that are more resistant to pathogenic infections. Therefore, understanding the mechanism of ERAdP-mediated NK cell activation will provide strategies for treatment of infectious diseases.

Risk factors and nomogram for pancreatic pseudocysts in chronic pancreatitis: A cohort of 1998 patients.

BACKGROUND AND AIM: Pancreatic pseudocyst is a common complication of chronic pancreatitis. The identification of risk factors and development of a nomogram for pancreatic pseudocysts in chronic pancreatitis patients may contribute to the early diagnosis and intervention of pancreatic pseudocysts. METHODS: Patients with chronic pancreatitis admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic pseudocysts after the onset of chronic pancreatitis and after the diagnosis of chronic pancreatitis were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 1998 patients, pancreatic pseudocysts were detected in 228 (11.41%) patients. Age at the onset of chronic pancreatitis, smoking, and severe acute pancreatitis were identified risk factors for pancreatic pseudocysts development while steatorrhea and pancreatic stones were protective factors. Incorporating these five factors, the nomogram achieved good concordance indexes of 0.735 and 0.628 in the training and validation cohorts, respectively, with well-fitted calibration curves. CONCLUSION: The nomogram achieved an individualized prediction of pancreatic pseudocysts development in chronic pancreatitis. It may help the early diagnosis and management of pancreatic pseudocysts.