A miRNA-7704/IL2RB/AKT feedback loop regulates tumorigenesis and chemoresistance in ovarian cancer.

Ovarian cancer is one of the most common gynecological tumors worldwide. Despite the availability of multiple treatments for ovarian cancer, its resistance to chemotherapy remains a significant challenge. miRNAs play crucial roles in the initiation and progression of cancer by affecting processes such as differentiation, proliferation, and chemoresistance. According to microarray and qPCR analyses, miR-7704 is significantly downregulated in cisplatin-resistant cells compared to parental cells. In this study, we found that miR-7704 inhibited the proliferation and promoted cisplatin sensitivity of ovarian cancer cells in vitro and in vivo. Moreover, ectopic expression of miR-7704 had the same effect as IL2RB knockdown. Further mechanistic studies revealed that miR-7704 played an inhibitory role by regulating IL2RB expression to inactivate the AKT signaling pathway. Furthermore, IL2RB reversed the miR-7704 mediated resistance to cisplatin in ovarian cancer. Based on these findings, miR-7704 and IL2RB show the potential as novel therapeutic targets for ovarian cancer.

Genetic perturbation of IL-6 receptor signaling pathway and risk of multiple respiratory diseases.

Dysregulation of inflammation can lead to multiple chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Interleukin-6 (IL6) is crucial in regulating the inflammatory cascade, but the causal link between IL6 signaling downregulation and respiratory diseases risk is unclear. This study uses Mendelian randomization to examine the effects of IL6R blockade on respiratory diseases. Analyzing data from 522,681 Europeans, 26 genetic variants were obtained to mimic IL6R inhibition. Our findings show that IL6R blockade significantly reduces the risk of COPD (OR = 0.71, 95% CI = 0.60-9.84) and asthma (OR = 0.82, 95% CI = 0.74-0.90), with protective trends for bronchitis, pulmonary embolism, and lung cancer. Results were consistent across methods, with no significant heterogeneity or pleiotropy. These insights suggest IL6R downregulation as a potential therapeutic target for respiratory diseases, meriting further clinical investigation.

From hepatitis B virus infection to acute-on-chronic liver failure: The dynamic role of hepatic macrophages.

Acute-on-chronic liver failure (ACLF) is a progressive disease that is associated with rapid worsening of clinical symptoms and high mortality. A multicentre prospective study from China demonstrated that patients with hepatitis B virus-related ACLF (HBV-ACLF) exhibited worse clinical characteristics and higher mortality rates compared to non-HBV-ACLF patients. Immune dysregulation is closely linked to the potential mechanisms of initiation and progression of ACLF. Innate immune response, which is represented by monocytes/macrophages, is up-regulated across ACLF development. This suggests that monocytes/macrophages play an essential role in maintaining the immune homeostasis of ACLF. Information that has been published in recent years shows that the immune status and function of monocytes/macrophages vary in ACLF precipitated by different chronic liver diseases. Monocytes/macrophages have an immune activation effect in hepatitis B-precipitated-ACLF, but they exhibit an immune suppression in cirrhosis-precipitated-ACLF. Therefore, this review aims to explain whether this difference affects the clinical outcome in HBV-ACLF patients as well as the mechanisms involved. We summarize the novel findings that highlight the dynamic polarization phenotype and functional status of hepatic macrophages from the stage of HBV infection to ACLF development. Moreover, we discuss how different HBV-related liver disease tissue microenvironments affect the phenotype and function of hepatic macrophages. In summary, increasing developments in understanding the differences in immune phenotype and functional status of hepatic macrophages in ACLF patients will provide new perspectives towards the effective restoration of ACLF immune homeostasis.

Investigating causal associations between pneumonia and lung cancer using a bidirectional mendelian randomization framework.

BACKGROUND: Pneumonia and lung cancer are both major respiratory diseases, and observational studies have explored the association between their susceptibility. However, due to the presence of potential confounders and reverse causality, the comprehensive causal relationships between pneumonia and lung cancer require further exploration. METHODS: Genome-wide association study (GWAS) summary-level data were obtained from the hitherto latest FinnGen database, COVID-19 Host Genetics Initiative resource, and International Lung Cancer Consortium. We implemented a bidirectional Mendelian randomization (MR) framework to evaluate the causal relationships between several specific types of pneumonia and lung cancer. The causal estimates were mainly calculated by inverse-variance weighted (IVW) approach. Additionally, sensitivity analyses were also conducted to validate the robustness of the causalty. RESULTS: In the MR analyses, overall pneumonia demonstrated a suggestive but modest association with overall lung cancer risk (Odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.01 - 1.44, P = 0.037). The correlations between specific pneumonia types and overall lung cancer were not as significant, including bacterial pneumonia (OR: 1.07, 95% CI: 0.91 - 1.26, P = 0.386), viral pneumonia (OR: 1.00, 95% CI: 0.95 - 1.06, P = 0.891), asthma-related pneumonia (OR: 1.18, 95% CI: 0.92 - 1.52, P = 0.181), and COVID-19 (OR: 1.01, 95% CI: 0.78 - 1.30, P = 0.952). Reversely, with lung cancer as the exposure, we observed that overall lung cancer had statistically crucial associations with bacterial pneumonia (OR: 1.08, 95% CI: 1.03 - 1.13, P = 0.001) and viral pneumonia (OR: 1.09, 95% CI: 1.01 - 1.19, P = 0.037). Sensitivity analysis also confirmed the robustness of these findings. CONCLUSION: This study has presented a systematic investigation into the causal relationships between pneumonia and lung cancer subtypes. Further prospective study is warranted to verify these findings.

Free water alterations in different inflammatory subgroups in schizophrenia.

BACKGROUND: Accumulating evidence suggests that inflammatory dysregulation both in blood and the brain is implicated in the pathogenesis of schizophrenia. Alterations in peripheral cytokines are not evident in all patients and there may be discrete altered inflammatory subgroups in schizophrenia. Recent studies using a novel and in vivo free-water imaging to detect inflammatory processes, have shown increased free water in white matter in schizophrenia. However, no studies to date have investigated the free water alterations in different inflammatory subgroups in schizophrenia. METHODS: Forty-four patients with schizophrenia and 49 controls were recruited. The serum levels of interleukin-1 beta (IL-1ß), IL-6, IL-10, and IL-12p70 were measured and used for cluster analysis with K-means and hierarchical algorithms. Diffusion tensor imaging (DTI) images were collected for all participants and voxel-wise free water and fractional anisotropy of tissue (FA-t) were compared between groups with Randomise running in FSL. Partial correlation analysis was employed to explore the association of the peripheral cytokine levels with free water. RESULTS: We identified two statistically quantifiable discrete subgroups of patients based on the cluster analysis of cytokine measures. The peripheral levels of IL-1ß (P < 0.001), IL-10 (P = 0.041), and IL-12p70 (P < 0.001) showed significant differences between the two different inflammatory subgroups. In the inflammatory subgroup with a predominantly higher IL-1ß level, increased free water values in white matter were found mainly in the left posterior limb of the internal capsule, posterior corona radiata, and partly in the left sagittal stratum. These affected areas did not overlap with the regions that showed significant free water differences between patients and healthy controls. In the inflammatory subgroup with lower IL-1ß levels, peripheral IL-1ß was significantly associated with free water values in white matter while no such association was detected in the patient group. CONCLUSIONS: Localized free water differences were demonstrated between the two identified inflammatory subgroups in our data, and free water appears to be a feasible in vivo neuroimaging biomarker guiding the target of inflammatory intervention and development of new therapeutic strategies in an individualized manner in schizophrenia.

Preoperative H. pylori Eradication Therapy Facilitates Precise Delineation in Early Gastric Cancer with Current H. pylori Infection.

INTRODUCTION: Early gastric cancer with current Helicobacter pylori infection (HpC-EGC) is common, but it is still unclear whether H. pylori eradication therapy (Hp-ET) or endoscopic submucosal dissection (ESD) should be performed first. We evaluated Hp-ETs short-term effects on horizontal boundary delineations of HpC-EGC in ESD. METHODS: Prospectively enrolled HpC-EGC patients were randomly assigned to eradication or control groups. Operation scopes of HpC-EGC lesions were delineated with marking dots at 5 mm out of the endoscopic demarcation line by an independent endoscopist, unaware of eradication status, before formal circumferential incision. As representatives, precise delineation rate, the shortest distance of all marking dots to the pathological demarcation line in all slices of one intact resected specimen (Dmin), and negative marking dot specimen rate were examined. RESULTS: Twenty-three HpC-EGC patients (25 lesions) were allocated to eradication group and 26 patients (27 lesions) were allocated to the control group with similar eradication success rates and all were differentiated type. With improving background mucosa inflammation after Hp-ET and similar gastritis-like epithelium rates, 10 lesions (40.0%) in the eradication group were of precise delineation compared to control group with 2 lesions (7.4%) (relative risk = 5.40, 95% CI 1.31-22.28). Dmin of eradication and control groups were 4.17 ± 2.52 mm and 2.67 ± 2.30 mm (p = 0.029), accompanied by 4 (14.8%) and none (0.0%) specimens that exhibited positive marking dots (p = 0.11), respectively. CONCLUSION: For HpC-EGC patients, administrating eradication medication before ESD is beneficial for the precise delineation of lesions and reducing the risk of positive horizontal resection margins.

Deep learning pneumoconiosis staging and diagnosis system based on multi-stage joint approach.

BACKGROUND: Pneumoconiosis has a significant impact on the quality of patient survival due to its difficult staging diagnosis and poor prognosis. This study aimed to develop a computer-aided diagnostic system for the screening and staging of pneumoconiosis based on a multi-stage joint deep learning approach using X-ray chest radiographs of pneumoconiosis patients. METHODS: In this study, a total of 498 medical chest radiographs were obtained from the Department of Radiology of West China Fourth Hospital. The dataset was randomly divided into a training set and a test set at a ratio of 4:1. Following histogram equalization for image enhancement, the images were segmented using the U-Net model, and staging was predicted using a convolutional neural network classification model. We first used Efficient-Net for multi-classification staging diagnosis, but the results showed that stage I/II of pneumoconiosis was difficult to diagnose. Therefore, based on clinical practice we continued to improve the model by using the Res-Net 34 Multi-stage joint method. RESULTS: Of the 498 cases collected, the classification model using the Efficient-Net achieved an accuracy of 83% with a Quadratic Weighted Kappa (QWK) score of 0.889. The classification model using the multi-stage joint approach of Res-Net 34 achieved an accuracy of 89% with an area under the curve (AUC) of 0.98 and a high QWK score of 0.94. CONCLUSIONS: In this study, the diagnostic accuracy of pneumoconiosis staging was significantly improved by an innovative combined multi-stage approach, which provided a reference for clinical application and pneumoconiosis screening.

Inhibition of Bromodomain Proteins Enhances Oncolytic HAdVC5 Replication and Efficacy in Pancreatic Ductal Adenocarcinoma (PDAC) Models.

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive type of pancreatic cancer, which rapidly develops resistance to the current standard of care. Several oncolytic Human AdenoViruses (HAdVs) have been reported to re-sensitize drug-resistant cancer cells and in combination with chemotherapeutics attenuate solid tumour growth. Obstacles preventing greater clinical success are rapid hepatic elimination and limited viral replication and spread within the tumour microenvironment. We hypothesised that higher intratumoural levels of the virus could be achieved by altering cellular epigenetic regulation. Here we report on the screening of an enriched epigenetics small molecule library and validation of six compounds that increased viral gene expression and replication. The greatest effects were observed with three epigenetic inhibitors targeting bromodomain (BRD)-containing proteins. Specifically, BRD4 inhibitors enhanced the efficacy of Ad5 wild type, Ad∆∆, and Ad-3∆-A20T in 3-dimensional co-culture models of PDAC and in vivo xenografts. RNAseq analysis demonstrated that the inhibitors increased viral E1A expression, altered expression of cell cycle regulators and inflammatory factors, and attenuated expression levels of tumour cell oncogenes such as c-Myc and Myb. The data suggest that the tumour-selective Ad∆∆ and Ad-3∆-A20T combined with epigenetic inhibitors is a novel strategy for the treatment of PDAC by eliminating both cancer and associated stromal cells to pave the way for immune cell access even after systemic delivery of the virus.

[A survey on the application of convolutional neural networks in the diagnosis of occupational pneumoconiosis].

Pneumoconiosis ranks first among the newly-emerged occupational diseases reported annually in China, and imaging diagnosis is still one of the main clinical diagnostic methods. However, manual reading of films requires high level of doctors, and it is difficult to discriminate the staged diagnosis of pneumoconiosis imaging, and due to the influence of uneven distribution of medical resources and other factors, it is easy to lead to misdiagnosis and omission of diagnosis in primary healthcare institutions. Computer-aided diagnosis system can realize rapid screening of pneumoconiosis in order to assist clinicians in identification and diagnosis, and improve diagnostic efficacy. As an important branch of deep learning, convolutional neural network (CNN) is good at dealing with various visual tasks such as image segmentation, image classification, target detection and so on because of its characteristics of local association and weight sharing, and has been widely used in the field of computer-aided diagnosis of pneumoconiosis in recent years. This paper was categorized into three parts according to the main applications of CNNs (VGG, U-Net, ResNet, DenseNet, CheXNet, Inception-V3, and ShuffleNet) in the imaging diagnosis of pneumoconiosis, including CNNs in pneumoconiosis screening diagnosis, CNNs in staging diagnosis of pneumoconiosis, and CNNs in segmentation of pneumoconiosis foci to conduct a literature review. It aims to summarize the methods, advantages and disadvantages, and optimization ideas of CNN applied to the images of pneumoconiosis, and to provide a reference for the research direction of further development of computer-aided diagnosis of pneumoconiosis.

A Competing Risk Model Nomogram to Predict the Long-Term Prognosis of Lung Carcinoid.

BACKGROUND: The prediction of long-term, cancer-specific survival of lung carcinoid remains controversial. We aimed to build a prognostic model by using competing-risk analysis to predict the long-term, cancer-specific survival of lung carcinoid patients. METHODS: Patients were retrospectively enrolled from the SEER database, and clinicopathological data were collected. Univariable and multivariable competing-risk analyses were conducted to identify prognostic factors. A competing-risk model and a nomogram were developed by using independent prognostic factors. The model was assessed by using concordance index and calibration curves. RESULTS: A total of 2496 patients were enrolled, of which 267 (10.7%) died of diagnosed carcinoma; 316 (12.7%) died because of other reasons. The 5-year, 10-year, and 15-year cancer-specific survival of carcinoid patients were 91.35%, 86.60%, and 84.39%, respectively. Multivariable analysis demonstrated that increasing age, male, larger tumor size, higher N stage, M1, atypical carcinoid, and undergoing no surgery were independent risk factors. A competing-risk model based on the risk factors and a corresponding nomogram were developed. Concordance index of the developed model for 5-year, 10-year, and 15-year were 0.891, 0.856, 0.836 respectively in the training cohort and 0.876, 0.841, 0.819 respectively in the validation cohort after bootstrap adjustment. The calibration curves of 5-year, 10-year, and 15-year showed good agreement. CONCLUSIONS: Increasing age, male, larger tumor size, higher N stage, M1, atypical carcinoid, and undergoing no surgery were independent risk factors. A competing risk model of excellent performance in predicting long-term survival was developed, and a nomogram was established.

A Clinical Prediction Model for Postoperative Pneumonia After Lung Cancer Surgery.

INTRODUCTION: Postoperative pneumonia (POP) is a common complication following lung cancer surgery and is associated with increased hospitalization costs and mortalities. We aimed to identify risk factors associated with POP and to develop a reliable predictive model. METHODS: Patients who underwent lung cancer surgery between January 2015 and December 2021 in our hospital were enrolled. Least absolute shrinkage and selection operator regression analysis was used to select predictors of POP. Multivariable logistic regression was performed to construct the nomogram. Bootstrap resampling was conducted for internal validation. The performance of the model was evaluated by discrimination and calibration. RESULTS: A total of 5269 consecutive patients were enrolled. POP occurred in 1.7% of patients (92/5269). Five independent predictors were identified: age, predicted forced expiratory volume in 1 s, predicted diffusing capacity of the lungs for carbon monoxide, tuberculosis history, and surgery duration. The multivariable regression model showed good discrimination (C-index: 0.821, 95% confidence interval, 0.783-0.859), which was well validated by internal validation. The calibration curve illustrated good agreement between the predicted probability and observed probability of POP. CONCLUSIONS: Based on the easily available risk factors, our nomogram could predict the risk of POP with good discrimination and calibration. The model has good clinical practicability, enabling precise and targeted interventions to reduce the incidence of POP in high-risk patients.

Endoscopic ultrasound-guided tissue acquisition with or without rapid on-site evaluation for solid pancreatic lesions: five years of experience from a single center.

BACKGROUND: Endoscopic ultrasound (EUS)-guided tissue acquisition (TA) by EUS-guided fine needle aspiration (FNA) or fine needle biopsy (FNB) is a standard diagnostic procedure for solid pancreatic lesions. Whether rapid on-site evaluation (ROSE) should be used to support EUS-TA remains controversial. Here we assessed the diagnostic performance of EUS-TA with or without self-ROSE for solid pancreatic masses. METHODS: Three hundred and seventy EUS-TA cases with self-ROSE and 244 cases without ROSE were retrospectively enrolled between August 2018 and June 2022. All procedures including ROSE were performed by the attending endoscopist. Clinical data, EUS characteristics, and diagnostic performance for distinguishing benign from malignant solid pancreatic masses including accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared between groups. RESULTS: Self-ROSE improved the diagnostic accuracy of solid pancreatic lesions by 16.7% in the EUS-TA group (p < 0.001) and by 18.9% in the EUS-FNA alone group (p < 0.001). Self-ROSE also improved the diagnostic sensitivity by 18.6% in the EUS-TA group (p < 0.001) and by 21.2% in the EUS-FNA alone group (p < 0.001). Improvements in the diagnostic accuracy by self-ROSE in the EUS-FNB group were not significant. 2.2 ± 0.7, 2.4 ± 0.9, 2.3 ± 0.7, 2.5 ± 0.9, 2.1 ± 0.6, and 2.1 ± 0.7 needle passes were required in the EUS-TA, EUS-FNA, and EUS-FNB with or without self-ROSE groups, respectively. CONCLUSIONS: Self-ROSE significantly improved the accuracy and sensitivity of EUS-FNA alone and EUS-TA diagnosis of solid pancreatic lesions and helped to reduce needle passes during the procedure. Whether self-ROSE benefits EUS-FNB and whether EUS-FNB alone is comparable to EUS-FNA with self-ROSE require further clarification.

A Novel in Duck Myoblasts: The Transcription Factor Retinoid X Receptor Alpha (RXRA) Inhibits Lipid Accumulation by Promoting CD36 Expression.

Retinoid X receptor alpha (RXRA) is a well-characterized factor that regulates lipid metabolism; however, the regulatory mechanism in muscle cells of poultry is still unknown. The overexpression and the knockdown of RXRA in myoblasts (CS2 cells), RT-PCR, and western blotting were used to detect the expression levels of genes and proteins related to PPAR-signaling pathways. Intracellular triglycerides (TGs), cholesterol (CHOL), and nonesterified free fatty acids (NEFAs) were detected by the Elisa kit. Fat droplets were stained with Oil Red O. The double-fluorescein reporter gene and chromatin immunoprecipitation (CHIP) were used to verify the relationship between RXRA and candidate target genes. The RXRA gene was highly expressed in duck breast muscle, and its mRNA and its protein were reduced during the differentiation of CS2 cells. The CS2 cells, with the overexpression of RXRA, showed reduced content in TGs, CHOL, NEFAs, and lipid droplets and upregulated the mRNA expression of CD36, ACSL1, and PPARG genes and the protein expression of CD36 and PPARG. The knockdown of RXRA expression in CS2 cells enhanced the content of TGs, CHOL, NEFAs, and lipid droplets and downregulated the mRNA and protein expression of CD36, ACLS1, ELOVL6, and PPARG. The overexpression of the RXRA gene, the activity of the double-luciferase reporter gene of the wild-type CD36 promoter was higher than that of the mutant type. RXRA bound to -860/-852 nt, -688/-680 nt, and -165/-157 nt at the promoter region of CD36. Moreover, the overexpression of CD36 in CS2 cells could suppress the content of TGs, CHOL, NEFAs, and lipid droplets, while the knockdown expression of CD36 increased the content of TGs, CHOL, NEFAs, and lipid droplets. In this study, the transcription factor, RXRA, inhibited the accumulation of TGs, CHOL, NEFAs, and fat droplets in CS2 cells by promoting CD36 expression.

Biliary inflammation scoring for immunoglobulin G4-related sclerosing cholangitis: an endoscopic approach with endoscopic ultrasound.

BACKGROUND AND AIMS: The differential diagnosis of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma (CC) remains a clinical challenge. Imaging modalities play critical roles in the diagnosis of IgG4-SC. The present study aimed to evaluate the differential diagnosis of IgG4-SC and CC based on images of endoscopic ultrasound (EUS). METHODS: The biliary inflammation scoring (BIS) method for EUS was developed based on the comparison between images of IgG4-SC and that of cholangiocarcinoma (CC) and other acute or chronic cholangitis. In the BIS diagnostic phase, the EUS images from 66 IgG4-SC patients and 44 CC patients were blindly evaluated using the BIS methods. RESULTS: The sensitivity, specificity, and accuracy of the newly established BIS in distinguishing IgG4-SC from CC were 86% [95% confidence interval (CI) 75-93%], 95% (95% CI 83-99%), and 90% (95% CI 83-94%), respectively. CONCLUSION: EUS should be considered to be added to the workup algorithm in patients with suspected IgG4-SC as a useful diagnostic procedure. BIS is a promising diagnostic method to discriminate IgG4-SC during the ongoing endoscopy.

Gastrointestinal endoscopy infection control strategy during COVID-19 pandemic: Experience from a tertiary medical center in China.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) has spread globally and become a pandemic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not only infects the gastrointestinal (GI) tract and causes GI symptoms, but also increases nosocomial transmission risk during endoscopic procedures for aerosol generation. We hereby share our infection control strategies aiming to minimize COVID-19 transmission in the endoscopy center. METHODS: We established our infection control strategies based on the guidance of Chinese Society of Digestive Endoscopy and inputs from hospital infection control experts: admission control through the procedure and patient triage, environmental control to reduce possible virus exposure, proper usage of personal protective equipment (PPE), and scope disinfection and room decontamination. All endoscopic procedures accomplished during COVID-19 outbreak and progress of stepwise resumption of elective endoscopy procedures were retrospectively reviewed. RESULTS: Only urgent or semi-urgent procedures were performed during COVID-19 outbreak. After no local new-onset COVID-19 case in Beijing for four weeks, we reopened the endoscopy center for elective procedures and monitored the outbreak continuously while maintaining a sustainable endoscopy service. CONCLUSIONS: It is imperative that all endoscopy centers should establish standard infection control strategies in order to fight COVID-19 pandemic based on national guidance and academic society guidelines and tailor them to individual resources. These measures and setup can also be reserved for future pandemics.

Intraneural Injection of ATP Stimulates Regeneration of Primary Sensory Axons in the Spinal Cord.

Injury to the peripheral axons of sensory neurons strongly enhances the regeneration of their central axons in the spinal cord. It remains unclear on what molecules that initiate such conditioning effect. Because ATP is released extracellularly by nerve and other tissue injury, we hypothesize that injection of ATP into a peripheral nerve might mimic the stimulatory effect of nerve injury on the regenerative state of the primary sensory neurons. We found that a single injection of 6 µl of 150 µm ATP into female rat sciatic nerve quadrupled the number of axons growing into a lesion epicenter in spinal cord after a concomitant dorsal column transection. A second boost ATP injection 1 week after the first one markedly reinforced the stimulatory effect of a single injection. Single ATP injection increased expression of phospho-STAT3 and GAP43, two markers of regenerative activity, in sensory neurons. Double ATP injections sustained the activation of phospho-STAT3 and GAP43, which may account for the marked axonal growth across the lesion epicenter. Similar studies performed on P2X7 or P2Y2 receptor knock-out mice indicate P2Y2 receptors are involved in the activation of STAT3 after ATP injection or conditioning lesion, whereas P2X7 receptors are not. Injection of ATP at 150 µm caused little Wallerian degeneration and behavioral tests showed no significant long-term adverse effects on sciatic nerve functions. The results in this study reveal possible mechanisms underlying the stimulation of regenerative programs and suggest a practical strategy for stimulating axonal regeneration following spinal cord injury.SIGNIFICANCE STATEMENT Injury of peripheral axons of sensory neurons has been known to strongly enhance the regeneration of their central axons in the spinal cord. In this study, we found that injection of ATP into a peripheral nerve can mimic the effect of peripheral nerve injury and significantly increase the number of sensory axons growing across lesion epicenter in the spinal cord. ATP injection increased expression of several markers for regenerative activity in sensory neurons, including phospho-STAT3 and GAP43. ATP injection did not cause significant long-term adverse effects on the functions of the injected nerve. These results may lead to clinically applicable strategies for enhancing neuronal responses that support regeneration of injured axons.

[Medication regularity of combination of traditional Chinese medicine and Western medicine in treating Helicobacter pylori-related gastropathy based on literatures].

The medication rules of combination of traditional Chinese medicine( TCM) and Western medicine in treating Helicobacter pylori-related gastropathy are analyzed to provide reference for clinical Helicobacter pylori-related gastropathy. Relevant literatures on integrated traditional Chinese and Western medicine in the treatment of Helicobacter pylori-related gastropathy were collected in CNKI,Wan Fang,VIP and CBM. Excel software and traditional Chinese medicine inheritance support system were used to establish a prescription database for data mining and analysis of the medication rules. A total of 178 literatures were selected,77 of them indicated TCM syndromes,and the syndrome of dampness-heat in the spleen and stomach had the highest frequency. A total of 207 prescriptions were used,including 100 classic prescriptions,and Banxia Xiexin Decoction had the highest frequency. Traditional Chinese medicine materials were used for 3 027 times,involving 207 herbs,and the top three mostly frequently used herbs were Glycyrrhiza uralensis,Coptis chinensis,and Pinellia ternata. The herbs mostly featured cold and warm properties in four natures,and bitterness and pungent in five flavors,and enter spleen,stomach and liver meridians. Totally 21 core drug combinations and 12 new prescriptions were obtained. According to data mining,the treatment of Helicobacter pylori-related gastropathy gives priority to " dispelling evil" " tonifying deficiency" and regulating Qi. The medication rules were the combination of cold and warm herbs and the compatibility of acrid opening and bitter down-bearing herbs. This provides a certain reference for optimizing clinical prescriptions,improving efficacy,and developing new drugs.

Increased expression of colony-stimulating factor-1 in mouse spinal cord with experimental autoimmune encephalomyelitis correlates with microglial activation and neuronal loss.

Microglia contribute to pathophysiology at all stages of multiple sclerosis. Colony-stimulating factor-1 (CSF1) is crucial for microglial proliferation and activation. In this study we measured the CSF1 levels and studied its cellular expression in the mouse spinal cords with experimental autoimmune encephalomyelitis (EAE) to explore the potential contribution of CSF1 in neuronal death. ELISA data showed that CSF1 levels were significantly higher in the spinal cords with acute and chronic EAE than those of normal and adjuvant-injected mice. Immunohistochemical studies demonstrated that CSF1 was expressed in astrocytes and neurons in normal mouse spinal cord. In acute EAE, CSF1 expression was significantly increased, especially in astrocytes in peripheral white matter and large motoneurons. High density of activated microglia was observed in the gray matter where motoneurons expressed high-level CSF1 in acute EAE. Significant large motoneuron loss was seen in chronic EAE and the remaining motoneurons with high-level CSF1 were enwrapped by microglia. Viral vector mediated over-expression of CSF1 in spinal neurons induced profound proliferation and activation of microglia at the injection site and microglia enwrapped CSF1-transduced neurons and their neurites. Significant loss of large CSF1-transduced neurons was seen at 2 and 3 weeks post-viral injection. Demyelination in the CSF1-transduced areas was also significant. These results implicate that CSF1 upregulation in CNS may play an important role in the proliferation and activation of microglia in EAE, contributing to neuroinflammation and neurodegeneration. © 2018 Wiley Periodicals, Inc.

Model to identify early-stage gastric cancers with deep invasion of submucosa based on endoscopy and endoscopic ultrasonography findings.

BACKGROUND: Conventional endoscopy and endoscopic ultrasonography (EUS) are used to estimate the invasion depth of early-stage gastric cancers (EGCs), but estimates made by either technique are often inaccurate. We developed a model to determine the invasion depth of EGCs using conventional endoscopy and EUS findings, with pathology results as the reference. METHODS: We performed a retrospective study of 195 patients (205 lesions) diagnosed with gastric cancers who underwent endoscopy and EUS followed by resection. Based on pathology analyses, lesions (n = 205) were assigned to categories of: mucosa invasion or minute invasion into the submucosal layer less than 500 µm from the muscularis mucosae (M-SM1) or penetration of 500 µm or more (≥SM2). The lesions were randomly assigned to derivation (138 lesions) and validation sets (67 lesions). A depth predictive model was proposed in the derivation set using multivariate logistic regression analyses. The discriminative power of this model was assessed in both sets. RESULTS: Remarkable redness (OR 5.42; 95% CI 1.32-22.29), abrupt cutting of converging folds (OR 8.58; 95% CI 1.65-44.72), lesions location in the upper third of the stomach (OR 10.26; 95% CI 2.19-48.09), and deep invasion based on EUS findings (OR 16.53; 95% CI 4.48-61.15) significantly associated with ≥SM2 invasion. A model that incorporated these 4 variables discriminated between M-SM1 and ≥SM2 lesions with the area under the ROC curve of 0.865 in the derivation set and 0.797 in the validation set. In the derivation set, a cut-off score of 8 identified lesions as ≥SM2 with 54% sensitivity and 97% specificity. The model correctly predicted the invasion depth 89.86% of lesions; it overestimated the depth of 2.17% of lesions. CONCLUSIONS: We developed a model to identify EGCs with invasion depth ≥SM2 based on endoscopy and EUS findings. This model might reduce overestimation of gastric tumor depth and prevent unnecessary gastrectomy.