Genome-wide DNA methylation profiling reveals a novel hypermethylated biomarker PRKCB in gastric cancer.

Globally, gastric cancer (GC) ranks among the most prevalent forms of malignancy, posing a significant health burden. Epigenetic modifications, predominantly characterized by alterations in DNA methylation patterns, have been linked to a diverse array of neoplastic processes. Here, we undertake a comprehensive analysis of the DNA methylation signature in GC, with the aim to discover the potential diagnostic epigenetic biomarkers. Utilizing the Illumina 935 K BeadChip, we conducted a genome-wide exploration of DNA methylation patterns in four paired samples of GC tissues and adjacent non-cancerous counterparts. The bisulfite-pyrosequencing (n = 7) was employed to the quantification for methylated gene. The pubic databases including GWAS Catalog, TCGA and GEO were used. The immunohistochemistry and qRT-PCR analysis were performed. In contrast to adjacent tissues, GC tissues manifested pronounced hypermethylation patterns specifically within the promoter cytosine-phosphate-guanine (CpG) islands, indicating localized epigenetic alterations. DNA methylome analysis further revealed 4432 differentially-methylated probes (DMPs), with the gene PRKCB exhibited the most prominent average DNA methylation disparity (mean Δß = 0.353). Pyrosequencing validation confirmed three DMPs within the PRKCB promoter (cg08406370, cg00735962, and cg18526361). Notably, the mean methylation levels of PRKCB were inversely correlated with mRNA expression levels in the GWAS Catalog. Furthermore, both mRNA and protein expression levels of PRKCB were significantly reduced in GCs when compared to their adjacent non-cancerous counterparts, verified by TCGA and GEO database. Our study reveals significant DNA methylation alterations in GC and emphasizes the pivotal role of PRKCB gene hypermethylation in conferring GC risk, which offers fresh perspectives for advancing diagnostic approaches and therapeutic strategies for GC.

Single-cell transcriptomic profiling uncovers cellular complexity and microenvironment in gastric tumorigenesis associated with Helicobacter pylori.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is the main risk for gastric cancer (GC). However, the cellular heterogeneity and underlying molecular mechanisms in H. pylori-driven gastric tumorigenesis are poorly understood. OBJECTIVE: Here, we generated a single-cell atlas of gastric tumorigenesis comprising 18 specimens of gastritis, gastric intestinal metaplasia (IM) and GC with or without H. pylori infection. METHODS: Single-cell RNA sequencing (scRNA-seq) was performed. Immunofluorescence, immunohistochemistry and qRT-PCR analysis were applied in a second human gastric tissues cohort for validation. Bioinformatics analyses of public TCGA and GEO datasets were applied. RESULTS: Single-cell RNA profile highlights cellular heterogeneity and alterations in tissue ecology throughout the progression of gastric carcinoma. Various cell lineages exhibited unique cancer-associated expression profiles, such as tumor-like epithelial cell subset (EPC), inflammatory cancer-associated fibroblasts (iCAFs) and Tumor-associated macrophage (TAM). Notably, we revealed that the specific epithelial subset enterocytes from the precancerous lesion GIM, exhibited elevated expression of genes related to lipid metabolism, and HNF4G was predicted as its specific transcription factor. Furthermore, we identified differentially expressed genes in H. pylori-positive and negative epithelial cells, fibroblasts and myeloid cells were identified. Futhermore, H. pylori-positive specimens exhibited enriched cell-cell communication, characterized by significantly active TNF, SPP1, and THY1 signaling networks. CONCLUSIONS: Our study provides a comprehensive landscape of the gastric carcinogenesis ecosystem and novel insights into the molecular mechanisms of different cell types in H. pylori-induced GC.

Risk factors of negative diagnosis of MRCP in acute biliary pancreatitis patients with choledocholithiasis.

BACKGROUND: Assessment of the presence of choledocholithiasis is crucial among acute biliary pancreatitis (ABP). Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasonography (EUS) are widely used to identify the gallstones of common bile duct (CBD). EUS provides better diagnostic accuracy and sensitivity than MRCP but carries a certain risk due to sedation. We investigated the risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis for better selection of MRCP or EUS. METHODS: A total of 2321 ABP patients were retrospectively included in this study. Based on the exclusion criteria, 337 ABP patients with negative MRCP results were ultimately included. Among these patients, 75 patients had positive EUS findings. Univariate and multivariate logistic regression models were used to screen the risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis. RESULTS: Patients with positive EUS findings were older (62.0 vs. 55.0) and had higher rate of cholecystectomy history (18.7% vs. 7.3%) than those with negative EUS findings. The result of univariate logistic regression showed that the history of cholecystectomy, age and sex were potential risk factors (all p < 0.05). Then after adjusting the other potential risk factors (Direct bilirubin (DBIL), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP)), a history of cholecystectomy (OR = 2.859 [1.312,6.23]), older age (1.03 [1.009,1.052]) and male (2.016 [1.152,3.528]) were independent risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis. CONCLUSIONS: The history of cholecystectomy, older age and male are independently associated with an increased risk of negative diagnosis of MRCP in ABP patients with choledocholithiasis. We suggest that patients with these risk factors should undergo EUS first, rather than MRCP.

Elaboration and validation of a novelty nomogram for the prognostication of anxiety susceptibility in individuals suffering from low back pain.

Low back pain (LBP) constitutes a distressing emotional ordeal and serves as a potent catalyst for adverse emotional states, notably anxiety. We dedicated to discerning methodologies for identifying patients who are predisposed to heightened levels of anxiety and pain. A self-assessment questionnaire was administered to patients afflicted with LBP. The pain scores were subjected to analysis in conjunction with anxiety scores, and a clustering procedure was executed using the scientific k-means methodology. Subsequently, six machine learning algorithms, including Logistics Regression (LR), K-Nearest Neighbor (KNN), Decision Tree (DT), Support Vector Machine (SVM), Random Forest (RF), and Extreme Gradient Boosting (XGB), were employed. Next, five pertinent variables were identified, namely Age, Course, Body Mass Index (BMI), Education, and Marital status. Furthermore, a LR model was utilized to construct a nomogram, which was subsequently subjected to assessment for discrimination, calibration, and evaluation of its clinical utility. As a result, 599 questionnaires were valid (effective rate: 99 %). The correlation analysis revealed a significant association between anxiety and pain scores (r = 0.31, P < 0.001). LBP patients could be divided into two clusters, Cluster1 had higher pain scores (P < 0.05) and SAS scores (P < 0.001). The proposed nomogram demonstrated an area under the receiver operating characteristics curve (ROC) of 0.841 (95 %CI: 0.804-0.878) and 0.800 (95 %CI: 0.733-0.867) in the training and test groups, respectively. Briefly, the established nomogram has demonstrated remarkable proficiency in discerning individuals afflicted with LBP who are at a heightened risk of experiencing anxiety.

Macrophage Tim-3 maintains intestinal homeostasis in DSS-induced colitis by suppressing neutrophil necroptosis.

T-cell immunoglobulin domain and mucin domain-3 (Tim-3) is a versatile immunomodulator that protects against intestinal inflammation. Necroptosis is a type of cell death that regulates intestinal homeostasis and inflammation. The mechanism(s) underlying the protective role of macrophage Tim-3 in intestinal inflammation is unclear; thus, we investigated whether specific Tim-3 knockdown in macrophages drives intestinal inflammation via necroptosis. Tim-3 protein and mRNA expression were assessed via double immunofluorescence staining and single-cell RNA sequencing (sc-RNA seq), respectively, in the colonic tissues of patients with inflammatory bowel disease (IBD) and healthy controls. Macrophage-specific Tim3-knockout (Tim-3M-KO) mice were generated to explore the function and mechanism of Tim-3 in dextran sodium sulfate (DSS)-induced colitis. Necroptosis was blocked by pharmacological inhibitors of receptor-interacting protein kinase (RIP)1, RIP3, and reactive oxygen species (ROS). Additionally, in vitro experiments were performed to assess the mechanisms of neutrophil necroptosis induced by Tim-3 knockdown macrophages. Although Tim-3 is relatively inactive in macrophages during colon homeostasis, it is highly active during colitis. Compared to those in controls, Tim-3M-KO mice showed increased susceptibility to colitis, higher colitis scores, and increased pro-inflammatory mediator expression. Following the administration of RIP1/RIP3 or ROS inhibitors, a significant reduction in intestinal inflammation symptoms was observed in DSS-treated Tim-3M-KO mice. Further analysis indicated the TLR4/NF-κB pathway in Tim-3 knockdown macrophages mediates the TNF-α-induced necroptosis pathway in neutrophils. Macrophage Tim-3 regulates neutrophil necroptosis via intracellular ROS signaling. Tim-3 knockdown macrophages can recruit neutrophils and induce neutrophil necroptosis, thereby damaging the intestinal mucosal barrier and triggering a vicious cycle in the development of colitis. Our results demonstrate a protective role of macrophage Tim-3 in maintaining gut homeostasis by inhibiting neutrophil necroptosis and provide novel insights into the pathogenesis of IBD.

Prediction model of no-response before the first transarterial chemoembolization for hepatocellular carcinoma: TACF score.

Previous clinic models for patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) mainly focused on the overall survival, whereas a simple-to-use tool for predicting the response to the first TACE and the management of risk classification before TACE are lacking. Our aim was to develop a scoring system calculated manually for these patients. A total of 437 patients with hepatocellular carcinoma (HCC) who underwent TACE treatment were carefully selected for analysis. They were then randomly divided into two groups: a training group comprising 350 patients and a validation group comprising 77 patients. Furthermore, 45 HCC patients who had recently undergone TACE treatment been included in the study to validate the model's efficacy and applicability. The factors selected for the predictive model were comprehensively based on the results of the LASSO, univariate and multivariate logistic regression analyses. The discrimination, calibration ability and clinic utility of models were evaluated in both the training and validation groups. A prediction model incorporated 3 objective imaging characteristics and 2 indicators of liver function. The model showed good discrimination, with AUROCs of 0.735, 0.706 and 0.884 and in the training group and validation groups, and good calibration. The model classified the patients into three groups based on the calculated score, including low risk, median risk and high-risk groups, with rates of no response to TACE of 26.3%, 40.2% and 76.8%, respectively. We derived and validated a model for predicting the response of patients with HCC before receiving the first TACE that had adequate performance and utility. This model may be a useful and layered management tool for patients with HCC undergoing TACE.

Rab11a in the spinal cord: an essential contributor to complete Freund's adjuvant-induced inflammatory pain in mice.

Inflammatory pain is a commonly observed clinical symptom in a range of acute and chronic diseases. However, the mechanism of inflammatory pain is far from clear yet. Rab11a, a small molecule guanosine triphosphate enzyme, is reported to regulate orofacial inflammatory pain in our previous works. However, the mechanism of Rab11a's involvement in the regulation of inflammatory pain remains obscure. Here, we aim to elucidate the potential mechanisms through which Rab11a contributes to the development of inflammatory pain in the spinal level. It's shown that neurons, rather than glial cells, were the primary cell type expressing Rab11a in the spinal dorsal horn (SDH). After intra-plantar injection of CFA, both the number of Fos/Rab11a-immunopositive neurons and the expression of Rab11a were increased. Administration of Rab11a-shRNA into the SDH resulted in significantly analgesic effect in mice with CFA injection. Application of Rab11a-shRNA also reduced the NMDA receptor-mediated excitatory post-synaptic current (EPSC) and the spike number of neurons in lamina II of the SDH in mice with CFA injection, without affecting the presynaptic glutamate release and the postsynaptic AMPA receptor-mediated EPSC. Our results thus suggest that the enhanced expression of neuronal Rab11a may be important for the process of inflammatory pain in mice with CFA injection, which is likely mediated by Rab11a's potentiation of the competence of post-synaptic NMDAR and spiking of SDH neurons.

Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice.

Itch is an annoying sensation consisting of both sensory and emotional components. It is known to involve the parabrachial nucleus (PBN), but the following transmission nodes remain elusive. The present study identified that the PBN-central medial thalamic nucleus (CM)-medial prefrontal cortex (mPFC) pathway is essential for itch signal transmission at the supraspinal level in male mice. Chemogenetic inhibition of the CM-mPFC pathway attenuates scratching behavior or chronic itch-related affective responses. CM input to mPFC pyramidal neurons is enhanced in acute and chronic itch models. Specifically chronic itch stimuli also alter mPFC interneuron involvement, resulting in enhanced feedforward inhibition and a distorted excitatory/inhibitory balance in mPFC pyramidal neurons. The present work underscores CM as a transmit node of the itch signal in the thalamus, which is dynamically engaged in both the sensory and affective dimensions of itch with different stimulus salience.

The severity and infection of acute pancreatitis may increase the risk of bleeding in patients undergoing EUS-guided drainage and endoscopic necrosectomy: a large retrospective cohort.

BACKGROUND: There has been great progress in the use of endoscopic ultrasound (EUS)-guided drainage in acute pancreatitis patients using a novel lumen-apposing metal stent (LAMS) in the last decade, but some patients experience bleeding. Our research analyzed the preprocedural risk factors for bleeding. METHODS: From July 13, 2016 to June 23, 2021, we retrospectively analyzed all patients who received endoscopic drainage by the LAMS in our hospital. Univariate and multivariate statistical analyses were used to identify the independent risk factors. We plotted ROC curves based on the independent risk factors. RESULTS: A total of 205 patients were analyzed and 5 patients were excluded. A total of 200 patients were included in our research. Thirty (15%) patients presented with bleeding. In the multivariate analysis, computed tomography severity index score (CTSI) score [odds ratio (OR), 2.66; 95% CI: 1.31-5.38; P = 0.007], positive blood cultures [odds ratio (OR), 5.35; 95% CI: 1.31-21.9; P = 0.02], and Acute Physiology and Chronic Health Evaluation II (APACHE II) score [odds ratio (OR), 1.14; 95% CI: 1. 01-1.29; P = 0.045] were associated with bleeding. The area under the ROC curve of the combined predictive indicator was 0.79. CONCLUSION: Bleeding in endoscopic drainage by the LAMS is significantly associated with the CTSI score, positive blood cultures, and APACHE II score. This result could help clinicians make more appropriate choices.

Projections from the Rostral Zona Incerta to the Thalamic Paraventricular Nucleus Mediate Nociceptive Neurotransmission in Mice.

Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma-aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR-PVT pathway participates in nociceptive modulation is still unclear. Therefore, our investigation utilized anatomical tracing, fiber photometry, chemogenetic, optogenetic and local pharmacological approaches to investigate the roles of the ZIRGABA+-PVT pathway in nociceptive neurotransmission in mice. We found that projections from the GABAergic neurons in ZIR to PVT were involved in nociceptive neurotransmission. Furthermore, chemogenetic and optogenetic activation of the ZIRGABA+-PVT pathway alleviates pain, whereas inhibiting the activities of the ZIRGABA+-PVT circuit induces mechanical hypersensitivity and partial heat hyperalgesia. Importantly, in vivo pharmacology combined with optogenetics revealed that the GABA-A receptor (GABAAR) is crucial for GABAergic inhibition from ZIR to PVT. Our data suggest that the ZIRGABA+-PVT pathway acts through GABAAR-expressing glutamatergic neurons in PVT mediates nociceptive neurotransmission.

Association of alpha-fetoprotein and metastasis for small hepatocellular carcinoma: A propensity-matched analysis.

Metastasis is crucial for the prognosis of hepatocellular carcinoma (HCC). Distinguishing the potential risk factors for distant metastasis in small HCC (diameter ≤ 5 cm) is of great significance for improving the prognosis. HCC patients in the Surveillance, Epidemiology and End Results (SEER) registry with tumors ≤ 5 cm in diameter between January 2010 and December 2015 were retrieved. Demographic and clinicopathological metrics were extracted, including age, sex, race, marital status, tumor size, histological grade, T stage, N stage, M stage, alpha-fetoprotein (AFP), and liver fibrosis score. Univariate and multivariate logistic regression analyses were used to identify independent risk factors correlated with extrahepatic metastasis in small HCC. Propensity score matching (PSM) analysis was performed to balance the confounding factors in baseline characteristics. A total of 4176 eligible patients were divided into a non-metastasis group (n = 4033) and a metastasis group (n = 143) based on metastasis status. In multivariate analysis, larger tumor size, poor histological differentiation, regional lymph node metastasis, and elevated serum AFP levels were identified as independent risk factors for distant metastasis (P < 0.05), while age, sex, race, marital status, and liver fibrosis score were not associated with extrahepatic metastasis. After propensity score analysis, the AFP level was no longer associated with metastatic risk. The present study provided no evidence for a correlation between the clinical threshold of AFP and metastasis in small hepatocellular carcinoma.

Global research trends of immunotherapy and biotherapy for inflammatory bowel disease: a bibliometric analysis from 2002 to 2021.

BACKGROUND: It is known that inflammatory bowel disease is the result of a defective immune system, and immunotherapy and biological therapy have gradually become important means to treat it. This paper focused on the bibliometric statistical analysis of the current research progress to summarize the research status of this field and analyze the research trends in recent years. METHODS: Two visualization tools, CiteSpace and VOSviewer, were used to explore the data of journals, institutions, countries/regions, authors, references, and keywords for the literature included in the Web of Science Core Collection from January 1, 2002, to December 31, 2021. RESULTS: A total of 312 papers were published in 120 journals by 603 institutions from 40 countries/regions, with 9463 co-cited references. The United States has the most publications with the highest total citations in the world. Inflammatory Bowel Diseases published the maximum number of papers, and Gastroenterology devoted the most co-citations to immunotherapy and biological therapy for IBD. In addition, we found that the studies before 2009 mostly focused on clinical trials while researchers have paid more attention to clinical management in therapy for IBD since 2009. Combination therapy and management of the treatment for the disease have become research hotspots. CONCLUSION: The focus of immunotherapy and biotherapy for IBD has shifted from clinical trials to the management of the risks and benefits of immunotherapy.

No significant relationship exists between tumor size and prognosis in distant metastatic hepatocellular carcinoma: a propensity score matching analysis based on SEER database.

BACKGROUND: Previous studies have shown that tumor size has an impact on the prognosis of hepatocellular carcinoma (HCC). Whether tumor size is related to the prognosis of distant metastatic HCC is unclear. The purpose of this study was to investigate the effect of tumor size on the prognosis of distant metastatic HCC. METHODS: Data on patients with HCC were collected from the (SEER) database of surveillance, epidemiology and final results. Propensity score matching (PSM) was used to reduce confounding factors and comprehensively evaluate the clinicopathological features and prognosis of distant metastatic HCC. RESULTS: There were 189 patients with distant metastatic HCC whose tumor size was ≤ 50 mm and 615 patients with a tumor size > 50 mm. The tumor sizes of distant metastatic HCC patients were associated with race, grade, surgical treatment, N and AFP. The Kaplan-Meier analysis showed that the mortality rate of patients with a tumor size > 50 mm was higher than that of patients with a tumor size ≤ 50 mm (p = 0.00062). However, there were no significant differences in mortality rates after adjusting for confounding variables by using propensity score matching (p = 0.23). CONCLUSION: This propensity score matching study provides the best data in support of the following assertions: tumor size is not an independent prognostic factor for distant metastatic HCC.

Identification and Validation of Immune Cells and Hub Genes in Gastric Cancer Microenvironment.

Gastric cancer (GC) is the most common malignant tumor in the digestive system, traditional radiotherapy and chemotherapy are not effective for some patients. The research progress of immunotherapy seems to provide a new way for treatment. However, it is still urgent to predict immunotherapy biomarkers and determine novel therapeutic targets. In this study, the gene expression profiles and clinical data of 407 stomach adenocarcinoma (STAD) patients were downloaded from The Cancer Genome Atlas (TCGA) portal, and the abundance ratio of immune cells in each sample was obtained via the "Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT)" algorithm. Five immune cells were obtained as a result of abundance comparison, and 295 immune-related genes were obtained through differential gene analysis. Enrichment, protein interaction, and module analysis were performed on these genes. We identified five immune cells associated with infiltration and 20 hub genes, of which five genes were correlated with overall survival. Finally, we used Real-time PCR (RT-PCR) to detect the expression differences of the five hub genes in 18 pairs of GC and adjacent tissues. This research not only provides cellular and gene targets for immunotherapy of GC but also provides new ideas for researchers to explore immunotherapy for various tumors.

The Value of Serum Tumor Markers and Blood Inflammation Markers in Differentiating Pancreatic Serous Cystic Neoplasms and Pancreatic Mucinous Cystic Neoplasms.

Although many studies have emphasized the prognostic and diagnostic value of tumor markers and various inflammation-related markers, their clinical significance in differentiating benign and malignant pancreatic cystic neoplasms (PCNs) remains to be clarified. The present study explored the value of serum tumor markers and inflammation-related biomarkers in the differentiation of pancreatic serous cystic neoplasms (SCNs) and pancreatic mucinous cystic neoplasms (MCNs). A total of 79 patients with PCNs were included in this study, including 35 patients with SCNs and 44 patients with MCNs. Comparison of baseline data with preoperative results of serum tumor markers and associated inflammatory markers revealed significant differences in carbohydrate antigen 199 (CA199) and "lymphocyte × ALB" (LA) between the two groups (p = 0.0023, p = 0.0149, respectively). Univariate and multivariate regression analyses showed that an increase in CA199 and a decrease in LA were relevant risk factors for MCNs. Finally, the receiver operating characteristic (ROC) curve was generated, and the area under the ROC curve (AUC) was calculated to evaluate the prediction efficiency of each indicator. The results showed that CA199 and LA had good differential diagnostic efficacy for SCNs and MCNs. This is the first to report to demonstrate that LA can be used for the differential diagnosis of SNCs and MCNs.

Higher Lymph Node Metastasis Rate and Poorer Prognosis of Intestinal-Type Gastric Cancer Compared to Diffuse-Type Gastric Cancer in Early-Onset Early-Stage Gastric Cancer: A Retrospective Study.

Background: The incidence of early-onset gastric cancer (GC) that was diagnosed at <50 years is increasing, but there is a knowledge gap on early-onset early-stage GC (EEGC) that was defined as early-onset GC limited to the mucosa or submucosa. Therefore, we comprehensively analysed the clinical features based on Lauren type. Methods: Logistic and Cox analyses were used to investigate risk factors for lymph node metastasis (LNM) and prognosis, respectively. Propensity score matching (PSM) was used to adjust confounding factors. Protein mass spectrometry analysis was used to explore the molecular mechanism of LNM. Result: Our study included 581 patients with EEGC from the Surveillance, Epidemiology, and End Results (SEER) database and 226 patients with EEGC from our own centre. We identified intestinal type, T1b stage, and tumour size (>3 cm) as risk factors for LNM using SEER and our own data. We also found that the prognosis of patients with intestinal-type EEGC was poorer than patients with diffuse-type EEGC, and T1b stage and positive LNM were hazard factors for survival. After analysing the expression of proteins between positive and negative LNM in the intestinal or diffuse type, we found no similar proteins between these groups. The differentially expressed genes (DEGs) in the intestinal type functioned as epithelial cell signalling in Helicobacter pylori. The DEGs in the diffuse type functioned in the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation. Conclusion: For EEGC, our study was the first report to demonstrate that the intestinal type was a risk factor for LNM and survival compared to the diffuse type, and the oncogenic expression promoting the occurrence of LNM was different. These findings suggest that clinicians should pay more attention to intestinal-type EEGC than diffuse-type EEGC.

Development and validation of a nomogram for predicting the probability of nontraumatic osteonecrosis of the femoral head in Chinese population.

Although corticosteroids and alcohol are two major risk factors for nontraumatic osteonecrosis of the femoral head (NONFH), the effects of other factors have rarely been studied, thereby making early diagnosis and treatment of NONFH difficult. This study aimed to develop and validate a nomogram to NONFH, but patients with alcohol- and steroid-related NONFH are not at all taken into account in this study. A training cohort of 790 patients (n = 434, NONFH; n = 356, femoral neck fractures [non-NONFH]) diagnosed in our hospital from January 2011 to December 2016 was used for model development. A least absolute shrinkage and selection operator (lasso) regression model was used for date dimension reduction and optimal predictor selection. A predictive model was developed from univariate and multivariate logistic regression analyses. Performance characterisation of the resulting nomogram included calibration, discriminatory ability, and clinical usefulness. After internal validation, the nomogram was further evaluated in a separate cohort of 300 consecutive patients included between January 2017 and December 2018. The simple prediction nomogram included five predictors from univariate and multivariate analyses, including gender, total cholesterol levels, triglyceride levels, white blood cell count, and platelet count. Internal validation showed that the model had good discrimination [area under the receiver operating characteristic curve (AUC) = 0.80] and calibration. Good discrimination (AUC = 0.81) and calibration were preserved in the validation cohort. Decision curve analysis showed that the predictive nomogram was clinically useful. The simple diagnostic nomogram, which combines demographic data and laboratory blood test results, was able to quantify the probability of NONFH in cases of early screening and diagnosis.

The prognostic value of gender in gastric gastrointestinal stromal tumors: a propensity score matching analysis.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) of the stomach are the most common GISTs. The risk, incidence, and outcome of cancer are different between the sexes. Whether gender is related to the prognosis of gastric stromal tumors is unclear. Therefore, this study aims to explore the relationship between gender and gastric GIST prognosis. METHODS: Data from gastric GIST patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to reduce confounding factors, and the clinicopathological features and prognosis of GIST patients were comprehensively evaluated. RESULTS: There were 512 male patients and 538 female patients with gastric GIST. The gender of gastric GIST patients was associated with marital status, surgical treatment, tumor size, and mitotic index (P < 0.05). The Kaplan-Meier analysis and log-rank test revealed that male patients had a higher mortality rate than female patients (P = 0.0024). After matching all the potential confounding factors, the survival of the female gastric GIST patients was better than that of the male gastric GIST patients (P = 0.042). Cox regression analysis revealed that gender was an independent risk factor for overall survival. The risk of death was higher for males than for females (HR 1.677, 95% CI 1.150-2.444, P = 0.007). CONCLUSION: Gender could be a prognostic factor for gastric GIST survival, and male patients had a higher risk of death.

Cytoskeleton-associated membrane protein 4 is upregulated in tumor tissues and is associated with clinicopathological characteristics and prognosis in hepatocellular carcinoma.

The role of cytoskeleton-associated membrane protein 4 (CKAP4) in hepatocellular carcinoma (HCC) is controversial. The present study aimed to investigate the association between tumor CKAP4 mRNA expression and clinicopathological characteristics and prognosis in patients with HCC. Data relating to CKAP4 mRNA expression in HCC tumor and normal adjacent liver tissues, and clinicopathological characteristics, were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The CKAP4 mRNA levels in tumor tissues were compared with those in normal adjacent liver tissues, their association with clinicopathological parameters was analyzed, and diagnostic and prognostic values were evaluated in patients with HCC. In all 4 datasets (total samples, n=693), CKAP4 mRNA levels were significantly higher in tumor tissues compared with adjacent tissues (all P<0.001), with the area under the receiver operating characteristic curve ranging from 0.799-0.898 for HCC diagnosis. In patients with HCC with available clinical data (n=361), the low-level CKAP4 mRNA group exhibited a lower body mass index (P=0.005), higher α-fetoprotein level (P<0.001), more frequent adjacent liver tissue inflammation (P<0.001), poorer tumor histological grade (P<0.001), higher Ishak fibrosis score (P=0.035) and a more advanced tumor node metastasis (TNM) stage (P=0.014) compared with the high-level CKAP4 mRNA group. Patients stratified by all the above parameters, except for TNM stage, exhibited significantly different expression of tissue CKAP4 mRNA (P<0.05-0.001). Furthermore, higher CKAP4 mRNA levels were observed in patients who died within one year following diagnosis compared with those who survived >3 years (P=0.003). The high-level CKAP4 mRNA group also exhibited lower overall survival (OS) and disease-free survival (DFS) rates compared with the low-level group [hazard ratio (HR)=1.494; 95% confidence interval (CI), 1.044-2.138; P=0.028] for OS and (HR=1.616; 95% CI, 1.022-2.555; P=0.040) for DFS. The results of the present study suggest that CKAP4 mRNA is upregulated in HCC tumor tissues compared with normal adjacent tissues, and is associated with poor clinical prognosis, pathological features and survival in patients with HCC. Thus, CKAP4 is a potential biomarker for HCC diagnosis and prognosis.