Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis patients admitted to intensive care unit (ICU) have a high mortality rate. AIM: To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis. METHODS: We extracted demographic, etiological, vital sign, laboratory test, comorbidity, complication, treatment, and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and electronic ICU (eICU) collaborative research database (eICU-CRD). Predictor selection and model building were based on the MIMIC-IV dataset. The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors. The final predictors were included in the multivariate logistic regression model, which was used to construct a nomogram. Finally, we conducted external validation using the eICU-CRD. The area under the receiver operating characteristic curve (AUC), decision curve, and calibration curve were used to assess the efficacy of the models. RESULTS: Risk factors, including the mean respiratory rate, mean systolic blood pressure, mean heart rate, white blood cells, international normalized ratio, total bilirubin, age, invasive ventilation, vasopressor use, maximum stage of acute kidney injury, and sequential organ failure assessment score, were included in the multivariate logistic regression. The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases, respectively. The calibration curve also confirmed the predictive ability of the model, while the decision curve confirmed its clinical value. CONCLUSION: The nomogram has high accuracy in predicting in-hospital mortality. Improving the included predictors may help improve the prognosis of patients.

An interpretable machine learning model for predicting 28-day mortality in patients with sepsis-associated liver injury.

Sepsis-Associated Liver Injury (SALI) is an independent risk factor for death from sepsis. The aim of this study was to develop an interpretable machine learning model for early prediction of 28-day mortality in patients with SALI. Data from the Medical Information Mart for Intensive Care (MIMIC-IV, v2.2, MIMIC-III, v1.4) were used in this study. The study cohort from MIMIC-IV was randomized to the training set (0.7) and the internal validation set (0.3), with MIMIC-III (2001 to 2008) as external validation. The features with more than 20% missing values were deleted and the remaining features were multiple interpolated. Lasso-CV that lasso linear model with iterative fitting along a regularization path in which the best model is selected by cross-validation was used to select important features for model development. Eight machine learning models including Random Forest (RF), Logistic Regression, Decision Tree, Extreme Gradient Boost (XGBoost), K Nearest Neighbor, Support Vector Machine, Generalized Linear Models in which the best model is selected by cross-validation (CV_glmnet), and Linear Discriminant Analysis (LDA) were developed. Shapley additive interpretation (SHAP) was used to improve the interpretability of the optimal model. At last, a total of 1043 patients were included, of whom 710 were from MIMIC-IV and 333 from MIMIC-III. Twenty-four clinically relevant parameters were selected for model construction. For the prediction of 28-day mortality of SALI in the internal validation set, the area under the curve (AUC (95% CI)) of RF was 0.79 (95% CI: 0.73-0.86), and which performed the best. Compared with the traditional disease severity scores including Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Systemic Inflammatory Response Syndrome (SIRS), and Acute Physiology Score III (APS III), RF also had the best performance. SHAP analysis found that Urine output, Charlson Comorbidity Index (CCI), minimal Glasgow Coma Scale (GCS_min), blood urea nitrogen (BUN) and admission_age were the five most important features affecting RF model. Therefore, RF has good predictive ability for 28-day mortality prediction in SALI. Urine output, CCI, GCS_min, BUN and age at admission(admission_age) within 24 h after intensive care unit(ICU) admission contribute significantly to model prediction.

Gender disparity between first and senior authors on liver cancer research in the top journals of Gastroenterology and Hepatology.

BACKGROUND: Gender disparity is pervasive in academic medicine. This study aimed to assess the disparity between men and women with regard to first and senior author positions in primary studies on liver cancer over the last two decades. METHODS: We conducted a review of articles published in high-impact factor journals of the field of Gastroenterology and Hepatology in 2005, 2010, 2015 and 2020. First and senior authors of all ages were considered as the study population. The authors' genders were determined using the online artificial intelligence tool genderize.io (https://genderize.io/). The disparity between men and women authors was assessed using the linear-by-linear association test. RESULTS: 665 original articles from 10 journals were reviewed. The point prevalence of first women authors was 25.0% compared with 75.0% for men. The point prevalence of senior women authors was 16.3% compared with 83.7% for men. From 2000 to 2020, the proportion of first women authors increased 14.4% to 26.8% compared with 85.6%-73.2% for men (P = 0.009), and the proportion of senior women authors increased from 7.4% to 19.5%, compared with 92.6%-80.5% for men (P = 0.035). The factor independently associated with a reduced representation of women among first authors was the region of author. The factor independently associated with a reduced representation of women among senior authors was the impact factor of journals. CONCLUSION: The findings indicated a remarkable increase in the proportion of women, both first and senior authors, over the past two decades in the field of liver cancers. However, the representation of women authors in this area is far less than that of men.

Rational design of a near-infrared fluorescent probe for monitoring butyrylcholinesterase activity and its application in development of inhibitors.

Butyrylcholinesterase (BChE) is widely expressed in multiple tissues and has a vital role in several key human disorders, such as Alzheimer's disease and tumorigenesis. However, the role of BChE in human disorders has not been investigated. Thus, to quantitatively detect and visualize dynamical variations in BChE activity is essential for exploring the biological roles of BChE in the progression of a number of human disorders. Herein, based on the substrate characteristics of BChE, we customized and synthesized three near-infrared (NIR) fluorescent probe substrates with cyanine-skeleton, and finally selected a NIR fluorescence probe substrate named CYBA. The CYBA demonstrated a significant increase in fluorescence when interacting with BChE, but mainly avoided AChE. Upon the addition of BChE, CYBA could be specifically hydrolyzed to TBO, resulting in a significant NIR fluorescence signal enhancement at 710 nm. Systematic evaluation revealed that CYBA exhibited exceptional chemical stability in complex biosamples and possessed remarkable selectivity and sensitivity towards BChE. Moreover, CYBA was successfully applied for real-time imaging of endogenous BChE activity in two types of nerve-related living cells. Additionally, CYBA demonstrated exceptional stability in the detection of complex biological samples in plasma recovery studies (97.51%-104.01%). Furthermore, CYBA was used to construct a high-throughput screening (HTS) method for BChE inhibitors using human plasma as the enzyme source. We evaluated inhibitory effects of a series of natural products and four flavonoids were identified as potent inhibitors of BChE. Collectively, CYBA can serve as a practical tool to track the changes of BChE activity in complicated biological environments due to its excellent capabilities.

Acute Pancreatitis in Pregnancy: A Propensity Score Matching Analysis and Dynamic Nomogram for Risk Assessment.

BACKGROUND: Acute pancreatitis is easily confused with abdominal pain symptoms, and it could lead to serious complications for pregnant women and fetus, the mortality was as high as 3.3% and 11.6-18.7%, respectively. However, there is still lack of sensitive laboratory markers for early diagnosis of APIP and authoritative guidelines to guide treatment. OBJECTIVE: The purpose of this study was to explore the risk factors of acute pancreatitis in pregnancy, establish, and evaluate the dynamic prediction model of risk factors in acute pancreatitis in pregnancy patients. STUDY DESIGN: Clinical data of APIP patients and non-pregnant acute pancreases patients who underwent regular antenatal check-ups during the same period were collected. The dataset after propensity matching was randomly divided into training set and verification set at a ratio of 7:3. The model was constructed using Logistic regression, least absolute shrinkage and selection operator regression, R language and other methods. The training set model was used to construct the diagnostic nomogram model and the validation set was used to validate the model. Finally, the accuracy and clinical practicability of the model were evaluated. RESULTS: A total of 111 APIP were included. In all APIP patients, hyperlipidemic pancreatitis was the most important reason. The levels of serum amylase, creatinine, albumin, triglyceride, high-density lipoprotein cholesterol, and apolipoprotein A1 were significantly different between the two groups. The propensity matching method was used to match pregnant pancreatitis patients and pregnant non-pancreatic patients 1:1 according to age and gestational age, and the matching tolerance was 0.02. The multivariate logistic regression analysis of training set showed that diabetes, triglyceride, Body Mass Index, white blood cell, and C-reactive protein were identified and entered the dynamic nomogram. The area under the ROC curve of the training set was 0.942 and in validation set was 0.842. The calibration curve showed good predictive in training set, and the calibration performance in the validation set was acceptable. The calibration curve showed the consistency between the nomogram model and the actual probability. CONCLUSION: The dynamic nomogram model we constructed to predict the risk factors of acute pancreatitis in pregnancy has high accuracy, discrimination, and clinical practicability.

Comparing clinical outcomes of peroral endoscopic myotomy for achalasia between Eastern and Western countries: a systematic review and meta-analysis.

Peroral endoscopic myotomy (POEM) has revolutionized the therapeutic strategy for achalasia with promising results. We conducted this meta-analysis to compare clinical outcomes between Eastern and Western countries. A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library databases to query for studies that assessed the efficacy of POEM for achalasia. All articles published from inception to December 31, 2021 were included. The primary outcome was the pooled clinical success rate. The secondary outcomes included the pooled technical success rate, incidence of adverse events, procedure time and hospital stay. Eighteen Eastern studies involving 5962 patients and 11 Western studies involving 1651 patients were included. The pooled clinical success rate and technical success rate for POEM was equal in the Eastern studies compared to Western studies. The pooled incidence of procedure adverse events for POEM was a little lower in the Eastern studies compared to Western studies (6.6% vs. 8.7%). Similarly, the incidence of reflux-related adverse events was lower in Eastern studies than that in Western studies. The pooled procedure time of POEM was shorter in Eastern studies compared to Western studies (61 minutes vs. 80 minutes), while the length of hospital stay was longer in Eastern studies compared to Western studies (5.8 days vs. 2.4 days). Overall, Eastern countries have the similar POEM outcomes compared to Western countries. However, Eastern countries still need to do more to reduce the length of hospital stay.

Trends of hospitalisation among new admission inpatients with oesophagogastric variceal bleeding in cirrhosis from 2014 to 2019 in the Affiliated Hospital of Southwest Medical University: a single-centre time-series analysis.

OBJECTIVES: This study aimed to assess the internal law and time trend of hospitalisation for oesophagogastric variceal bleeding (EGVB) in cirrhosis and develop an effective model to predict the trend of hospitalisation time. DESIGN: We used a time series covering 72 months to analyse the hospitalisation for EGVB in cirrhosis. The number of inpatients in the first 60 months was used as the training set to establish the autoregressive integrated moving average (ARIMA) model, and the number over the next 12 months was used as the test set to predict and observe their fitting effect. SETTING AND DATA: Case data of patients with EGVB between January 2014 and December 2019 were collected from the Affiliated Hospital of Southwest Medical University. OUTCOME MEASURES: The number of monthly hospitalised patients with EGVB in our hospital. RESULTS: A total of 877 patients were included in the analysis. The proportion of EGVB in patients with cirrhosis was 73% among men and 27% among women. The peak age at hospitalisation was 40-60 years. The incidence of EGVB varied seasonally with two peaks from January to February and October to November, while the lowest number was observed between April and August. Time-series analysis showed that the number of inpatients with EGVB in our hospital increased annually. The sequence after the first-order difference was a stationary series (augmented Dickey-Fuller test p=0.02). ARIMA (0,1,0) (0,1,1)12 with a minimum Akaike Information Criterion value of 260.18 could fit the time trend of EGVB inpatients and had a good short-term prediction effect. The root mean square error and mean absolute error were 2.4347 and 1.9017, respectively. CONCLUSIONS: The number of hospitalised patients with EGVB at our hospital is increasing annually, with seasonal changes. The ARIMA model has a good prediction effect on the number of hospitalised patients with EGVB in cirrhosis.

Prediction and evaluation of a nomogram model for recurrent acute pancreatitis.

OBJECTIVE: The purpose of this study was to investigate the influencing factors for recurrent acute pancreatitis and construct the nomogram model to predict the risk of recurrent acute pancreatitis. METHODS: Patients diagnosed with acute pancreatitis in the Affiliated Hospital of Southwest Medical University were enrolled. We collected these patients' basic information, laboratory data, imaging information. Using Logistic regression and least absolute shrinkage and selection operator regression to select risk factor for Cross-Validation Criterion. To create nomogram and validated by receiver operator characteristic curve, calibration curves and decision curve analysis. RESULTS: A total of 533 patients with acute pancreatitis were included, including 99 recurrent acute pancreatitis patients. The average age of recurrent acute pancreatitis patients was 49.69 years old, and 67.7% of them were male. At the same time, in all recurrent acute pancreatitis patients, hypertriglyceridemic pancreatitis is the most important reason (54.5%). Regression analysis and least absolute shrinkage and selection operator regression showed that smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis were identified and entered into the nomogram. The area under the receiver operator characteristic curve of the training set was 0.747. The calibration curve showed the consistency between the nomogram model and the actual probability. CONCLUSION: In conclusion, some high-risk factors like smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis may predict recurrent pancreatitis and their incorporation into a nomogram has high accuracy in predicting recurrence.

Early Predictive Value of Different Indicators for Persistent Organ Failure in Acute Pancreatitis: A Systematic Review and Network Meta-Analysis.

GOALS: In this study, we conducted this network meta-analysis (based on the ANOVA model) to evaluate the predictive efficacy of each early predictor. BACKGROUND: Persistent organ failure (POF) is one of the determining factors in patients with acute pancreatitis (AP); however, the diagnosis of POF has a long-time lag (>48 h). It is of great clinical significance for the early noninvasive prediction of POF. STUDY: We conducted a comprehensive and systematic search in PubMed, Cochrane library, Embase, and Web of Science to identify relevant clinical trials, case-control studies, or cohort studies, extracted the early indicators of POF in studies, and summarized the predictive efficacy of each indicator through network meta-analysis. The diagnostic odds ratio (DOR) was used to rank the prediction efficiency of each indicator. RESULTS: We identified 23 studies in this network meta-analysis, including 10,393 patients with AP, of which 2014 patients had POF. A total of 10 early prediction indicators were extracted. The mean and 95% CI lower limit of each predictive indicator were greater than 1.0. Albumin had the largest diagnostic odds ratio, followed by high-density lipoprotein-cholesterol (HDL-C), Ranson Score, beside index for severity in acute pancreatitis Score, acute physiology and chronic health evaluation II, C-reactive protein (CRP), Interleukin 6 (IL-6), Interleukin 8 (IL-8), Systemic Inflammatory Response Syndrome (SIRS) and blood urea nitrogen. CONCLUSIONS: Albumin, high-density lipoprotein-cholesterol, Ranson Score, and beside index for severity in acute pancreatitis Score are effective in the early prediction of POF in patients with AP, which can provide evidence for developing effective prediction systems. However, due to the limitations of the extraction method of predictive indicators in this study, some effective indicators may not be included in this meta-analysis.

Tumor-infiltrating mast cells stimulate ICOS+ regulatory T cells through an IL-33 and IL-2 axis to promote gastric cancer progression.

INTRODUCTION: In solid tumors, regulatory T cell (Treg) and mast cell perform different roles depending on the microenvironment. Nevertheless, mast cell and Treg-mediated interactions in gastric cancer (GC) are unclear, as are their regulation, function, and clinical significance. OBJECTIVE: The present study demonstrated the mechanism of tumor-infiltrating mast cells stimulating ICOS+ regulatory T cells via the IL-33/IL-2 axis to promote the growth of gastric cancer. METHODS: Analyses of 98 patients with GC were conducted to examine mast cell counts, ICOS+ Tregs, and the levels of IL-33 or IL-2. Isolated ICOS+ Treg and CD8+ T cell were stimulated, cultured and tested for their functional abilities in vitro and in vivo. RESULTS: GC patients exhibited a significantly more production of IL-33 in tumors. Mast cell stimulated by tumor-derived IL-33 exhibited a prolonged lifespan through IL-33 mediated inhibition of apoptosis. Moreover, mast cells stimulated by tumor-derived IL-33 secreted IL-2, which induced Treg expansion. These inducible Tregs displayed an activated immunosuppressive phenotype with positive expression for the inducible T cell co-stimulator (ICOS). In vitro, IL-2 from IL to 33-stimulated mast cells induced increased numbers of ICOS+ Tregs with increased immunosuppressive activity against proliferation and effector function of CD8+ T cell. In vivo, ICOS+ Tregs were treated with anti-IL-2 neutralizing antibody followed by co-injection with CD8+ T cells in GC mouse model, which showed an increased CD8+ T cell infiltration and effector molecules production, meanwhile tumor growth and progression were inhibited. Besides, reduction in GC patient survival was associated with tumor-derived ICOS+ Tregs. CONCLUSION: Our results highlight a crosstalk between GC-infiltrating mast cells and ICOS+ Tregs and provide a novel mechanism describing ICOS+ Treg expansion and induction by an IL-33/mast cell/IL-2 signaling axis in GC, and also provide functional evidence that the modulation of this immunosuppressive pathway can attenuate GC-mediated immune tolerance.

Genome analysis of the mpox (formerly monkeypox) virus and characterization of core/variable regions.

Since smallpox was eradicated in 1980, the monkeypox virus (MPXV) has emerged as the most threatening orthopoxvirus in the world. In this study, we conducted a comprehensive analysis of the currently published complete genome sequences of the monkeypox virus. The core/variable regions were identified through core-pan analysis of MPXV. Besides single-nucleotide polymorphisms, our study also revealed that specific genes, multi-copy genes, repeat sequences, and recombination fragments are primarily distributed in the variable region. This result suggests that variable regions are not only more susceptible to single-base mutations, but also to events such as gene loss or gain, as well as recombination. Taken together, our results demonstrate the genomic characteristics of the core/variable regions of MPXV, and contribute to our understanding of the evolution of MPXV.

Identification of ACBD3 as a new molecular biomarker in pan-cancers through bioinformatic analysis: a preclinical study.

BACKGROUND: Acyl-CoA-binding domain-containing 3 (ACBD3) is a multifunctional protein, that plays essential roles in cellular signaling and membrane domain organization. Although the precise roles of ACBD3 in various cancers remain unclear. Thus, we aimed to determine the diverse roles of ACBD3 in pan-cancers. METHODS: Relevant clinical and RNA-sequencing data for normal tissues and 33 tumors from The Cancer Genome Atlas (TCGA) database, the Human Protein Atlas, and other databases were applied to investigate ACBD3 expression in various cancers. ACBD3-binding and ACBD3-related target genes were obtained from the STRING and GEPIA2 databases. The possible functions of ACBD3-binding genes were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also applied the diagnostic value and survival prognosis analysis of ACBD3 in pan-cancers using R language. The mutational features of ACBD3 in various TCGA cancers were obtained from the cBioPortal database. RESULTS: When compared with normal tissues, ACBD3 expression was statistically upregulated in eleven cancers and downregulated in three cancers. ACBD3 expression was remarkably different among various pathological stages of tumors, immune and molecular subtypes of cancers, cancer phosphorylation levels, and immune cell infiltration. The survival of four tumors was correlated with the expression level of ACBD3, including pancreatic adenocarcinoma, adrenocortical carcinoma, sarcoma, and glioma. The high accuracy in diagnosing multiple tumors and its correlation with prognosis indicated that ACBD3 may be a potential biomarker of pan-cancers. CONCLUSION: According to our pan-cancer analysis, ACBD3 may serve as a remarkable prognostic and diagnostic biomarker of pan-cancers as well as contribute to tumor development. ACBD3 may also provide new directions for cancer treatment targets in the future.

A disulfidptosis-related lncRNA index predicting prognosis and the tumor microenvironment in colorectal cancer.

Colorectal cancer (CRC) is a common and deadly cancer worldwide with a high lethality rate. Disulfidptosis has been found to be an emerging mode of death in cancer, and the purpose of this study was to explore the relationship between disulfidptosis-related lncRNAs (DRLs) and CRC and to develop a prognostic model for CRC and DRLs. The gene expression data and clinicopathologic information of colorectal cancer patients were obtained from The Cancer Genome Atlas (TCGA) and screened for DRLs based on correlation analysis. The least absolute shrinkage and selection operator (LASSO) and Cox regression were used to construct the prognostic model, and its validation was carried out by PCA and receiver operating characteristic (ROC) curves. We constructed nomograms combined with the model. Finally, the possible mechanisms by which lncRNAs affect CRC were explored by functional enrichment analysis, immune infiltration and immune escape analysis. In summary, we developed a prognostic marker consisting of lncRNAs associated with disulfidptosis to help clinicians predict the survival of different CRC patients and use different targeted therapies and immunotherapies depending on the condition.

Application of a Machine Learning Predictive Model for Recurrent Acute Pancreatitis.

BACKGROUND AND AIM: Acute pancreatitis is the main cause of hospitalization for pancreatic disease. Some patients tend to have recurrent episodes after experiencing an episode of acute pancreatitis. This study aimed to construct predictive models for recurrent acute pancreatitis (RAP). METHODS: A total of 531 patients who were hospitalized for the first episode of acute pancreatitis at the Affiliated Hospital of Southwest Medical University from January 2018 to December 2019 were enrolled in the study. We confirmed whether the patients had a second episode until December 31, 2021, through an electronic medical record system and telephone or WeChat follow-up. Clinical and follow-up data of patients were collected and randomly allocated to the training and test sets at a ratio of 7:3. The training set was used to select the best model, and the selected model was tested with the test set. The area under the receiver operating characteristic curves, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, decision curve, and calibration plots were used to assess the efficacy of the models. Shapley additive explanation values were used to explain the model. RESULTS: Considering multiple indices, XGBoost was the best model. The area under the receiver operating characteristic curves, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model in the test set were 0.779, 0.763, 0.883, 0.647, 0.341, and 0.922, respectively. According to the Shapley additive explanation values, drinking, smoking, higher levels of triglyceride, and the occurrence of ANC are associated with RAP. CONCLUSION: The XGBoost model shows good performance in predicting RAP, which may help identify high-risk patients.

Gender authorship trends of gastric cancer in the top journals of gastroenterology: A 20-year perspective.

Gender authorship trends have been explored in varied medical specialties, and no study had observed in the field of gastric cancer. Therefore, we aimed to access whether the "gender gap" in authorship existed in gastric cancer in the leading gastroenterological journals over the last 2 decades. All original articles published from 2000 to 2020 in 9 leading gastroenterological journals were collected. Information on the first and senior author's gender, country of author's institution, and impact factor of journals were collected. Chi-square tests and multivariable logistic regression were used for data analysis. A total of 5785 original articles were included and analyzed, of which 440 (7.61%) were articles on gastric cancer and 5345 (92.39%) covered other topics. Fewer female authors published original articles as first (19.32%, 85/440) and senior authors (14.32%, 63/440) compared with males. Remarkably, a significant increase in female authorship was discovered. The proportion of female first authors grown from 12.99% to 30.89% during the last 20 years (P < .001), but not in senior authors (P = .175). Multivariable logistic analysis showed that female first authors demonstrated a higher percentage when senior authors were female (odds ratio, 2.040; 95% confidence interval, 1.105-3.769). Although a statistically ascending tendency in female first authors on gastric cancer has been going on over the last 20 years, the exorbitant gender gap still exists. This gap may help explain the continued underrepresentation of women within both clinical work and academic research, and prompt us to look further for the underlying causes.

Trends in gender disparity in the field of Helicobacter pylori research from 2000 to 2020: A cross-sectional study.

Many studies have investigated gender disparity in scientific publications, but this has been poorly studied in the field of digestive diseases. This study aimed to determine the gender difference of first and senior authors in publications related to Helicobacter pylori (H. pylori) during the past 20 years. Data were derived from original articles published in the main journals of digestive diseases (Journal of Hepatology, Gut, Gastroenterology, American Journal of Gastroenterology, Endoscopy, Gastrointestinal Endoscopy, Alimentary Pharmacology and Therapeutics, Digestive Endoscopy, Journal of Gastroenterology, Helicobacter, and Gastric Cancer) in 2000, 2005, 2010, 2015, and 2020. These original articles were classified according to the gender and nationality of the first and senior (last listed) authors. Linear-by-linear association test was used to analyze the proportion of women authors over time. Multivariable logistic regression was applied to explain the factors impacting authorship difference of first and senior authors. A total of 561 original articles on H. pylori were collected for this study, accounting for 10.70% in 2000 to 7.60% in 2020 among all articles. In these original articles, the percentage of women first authors increased from 14.60% in 2000 to 45.0% in 2020 (P < .001). The percentage of women senior authors increased from 5.60% in 2000 to 18.80% in 2020 (P < .001). Women first authors were more likely to perform research with women senior authors (18.42%) than with men senior authors (10.23%, P < .001). The proportion of women first authors from Oceania were higher than that from North and South America (P = .004), whereas there was no statistical difference regarding women senior authors. In the past 2 decades, although the percentage of women authors among both first and senior authors in the field of H. pylori research has increased significantly, women are still a minority in original research.

Morusinol Extracted from Morus alba Inhibits Cell Proliferation and Induces Autophagy via FOXO3a Nuclear Accumulation-Mediated Cholesterol Biosynthesis Obstruction in Colorectal Cancer.

The incidence rate of colorectal cancer (CRC) has been increasing significantly in recent years, and it is urgent to develop novel drugs that have more effects for its treatment. It has been reported that many molecules extracted from the root bark of Morus alba L. (also known as Cortex Mori) have antitumor activities. In our study, we identified morusinol as a promising anticancer agent by selecting from 30 molecules extracted from Morus alba L. We found that morusinol treatment suppressed cell proliferation and promoted apoptosis of CRC cells in vitro. Besides this, we observed that morusinol induced cytoprotective autophagy. The GO analysis of differentially expressed genes from RNA-seq data showed that morusinol affected cholesterol metabolism. Then we found that key enzyme genes in the cholesterol biosynthesis pathway as well as the sterol regulatory element binding transcription factor 2 (SREBF2) were significantly downregulated. Furthermore, additional cholesterol treatment reversed the anti-CRC effect of morusinol. Interestingly, we also found that morusinol treatment could promote forkhead box O3 (FOXO3a) nuclear accumulation, which subsequently suppressed SREBF2 transcription. Then SREBF2-controlled cholesterol biosynthesis was blocked, resulting in the suppression of cell proliferation, promotion of apoptosis, and production of autophagy. The experiments in animal models also showed that morusinol significantly impeded tumor growth in mice models. Our results suggested that morusinol may be used as a candidate anticancer drug for the treatment of CRC.

FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma.

BACKGROUND: Ferroptosis is related to the immunosuppression of tumors and plays a critical role in cancer progression. Fanconi anemia complementation group D2 (FANCD2) is a vital gene that regulates ferroptosis. However, the mechanism of action of FANCD2 in Hepatitis B-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the prognostic significance and mechanism of action of FANCD2 in Hepatitis B-related HCC. METHODS: The expression of FANCD2 in Hepatitis B-related HCC was explored using The Cancer Genome Atlas (TCGA) and validated using the Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox regression analyses and Kaplan-Meier survival curves were used to analyze the relationship between FANCD2 expression and the overall survival of patients with Hepatitis B-related HCC. Protein-protein interaction networks for FANCD2 were built using the STRING website. In addition, correlations between FANCD2 expression and the dryness index, tumor mutational burden, microsatellite instability (MSI), immune pathways, genes involved in iron metabolism, and sorafenib chemotherapeutic response were analyzed. RESULTS: Our results indicated that FANCD2 was significantly overexpressed in Hepatitis B-related HCC and demonstrated a strong predictive ability for diagnosis (Area Under Curve, 0.903) and prognosis of the disease. High FANCD2 expression was associated with poor prognosis, high-grade tumors, high expression of PDL-1, high MSI scores, and low sorafenib IC50 in Hepatitis B-related HCC. BRCA1, BRCA2, FAN1, and FANCC were vital proteins interacting with FANCD2. The expression level of FANCD2 significantly correlated with the infiltration levels of Treg cells, B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells, and NK cells in Hepatitis B-related HCC. FANCD2 was positively correlated with the tumor proliferation signature pathway, DNA repair, and cellular response to hypoxia. CONCLUSION: Our study indicated that FANCD2 was a potential novel biomarker and immunotherapeutic target against Hepatitis B-related HCC, which might be related to the chemotherapeutic response to sorafenib.

Research hotspots and trend of a emerging novel endoscopic technique of peroral endoscopic myotomy from 2010 to 2022: A bibliometric analysis.

Peroral endoscopic myotomy (POEM), which has been used to treat achalasia and other esophageal motility disorders for the past 10 years, has proven to be secure and efficient. Every year, more and more essays on this subject are published. We sought to investigate the global scientific outputs and hotspots of POEM produced by various nations, organizations, and authors. From 2010 to October 2022, there were 875 papers on POEM that were found in the Web of Science Core database. The bibliometric visualization analyses of nations/regions, institutions, authors, journals, references, and keywords were conducted by CiteSpace V.5.8.R3. Eight hundred seventy-five publications were included in this analysis. With 68 publications, Inoue H had the highest output. While Showa University in Japan was the most productive institution, the United States was the most productive nation. Among the journals, Surgical Endoscopy published the highest number of articles, followed by Gastrointestinal Endoscopy and Endoscopy. The top 10 keywords that appeared most frequently were achalasia, peroral endoscopic myotomy, POEM, myotomy, esophageal achalasia, dysphagia, heller myotomy, endoscopy, gastroparesis and peroral endoscopic myotomy. Seven frontiers, including meta-analysis, high-resolution esophageal manometry, geriatric patient, third space endoscopy, adverse event, endoscopic submucosal dissection, and gastric peroral endoscopic myotomy, had an impact on future research on POEM. The previous 10 years have seen a considerable rise in POEM research, and this trend will continue. The most recent research frontiers, which require more attention, are meta-analysis, high-resolution esophageal manometry, geriatric patient, third space endoscopy, adverse event, and gastric peroral endoscopic myotomy.