Current experimental and computational methods have limitations in accurately and efficiently classi-fying ion channels within vast protein spaces.Here we have developed a deep learning algorithm,GPT2 Ion Channel Classifier(GPT2-ICC),which effectively distinguishing ion channels from a test set con-taining approximately 239 times more non-ion-channel proteins.GPT2-ICC integrates representation learning with a large language model(LLM)-based classifier,enabling highly accurate identification of potential ion channels.Several potential ion channels were predicated from the unannotated human proteome,further demonstrating GPT2-ICC's generalization ability.This study marks a significant advancement in artificial-intelligence-driven ion channel research,highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data.Moreover,it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

Objective:To evaluate the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated by gemcitabine and nab-paclitaxel (AG) or AG combined with pro-grammed death-1 (PD-1) inhibitor regimen and application value of the Cleveland Clinic Foundation (CCF) risk score.Methods:The retrospective cohort study was conducted. The clinicopathological data of 151 PDAC patients who were treated by AG regimen or AG combined with PD-1 inhibitor regimen in Zhejiang Cancer Hospital from January 2013 to March 2024 were collected. There were 84 males and 67 females, aged (64±9)years. Observation indicators: (1) comparison of clinical characteristics among resectable PDAC patients with different CCF risk score; (2) analysis of influencing factors for overall survival time of resectable PDAC patients; (3) survival of resectable PDAC patients. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regression model. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. Results:(1) Comparison of clinical characteristics among resectable PDAC patients with different CCF risk score. Based on CCF risk score, 102 of 151 patients were classified as low risk and 49 cases were classified as intermediate-to-high risk. There were signi-ficant differences in sex, age, smoking status, alcohol consumption, hypertension, and diabetes between the two categories ( P<0.05). (2) Analysis of influencing factors for overall survival time of resectable PDAC patients. Results of multivariate analysis showed that the treatment regimen was an indepen-dent influencing factor for overall survival time of resectable PDAC patients ( hazard ratio=1.976, 95% confidence interval as 1.065?3.666, P<0.05). (3) Survival of resectable PDAC patients. The follow-up time of 151 patients was 21.8(18.7,24.2)months, and the median overall survival time was 23.3(19.0,32.4)months. The follow-up time was 22.1(18.9,30.7)months of patients treated by AG regimen and 11.2(8.1,23.3)months of patients treated by AG combined with PD-1 inhibitor regimen, respectively. The median overall survival time of the two types of patients was 24.4(17.2,31.7)months and 16.9(8.9,24.9)months. The 1-year overall survival rates were 79.1% and 60.0%, and the 2-year overall survival rates were 53.4% and 28.5%, respectively. There was a significant difference in the overall survival between the two types of patients ( hazard ratio=1.913, 95% confidence interval as 1.041?3.516, P<0.05). Of the intermediate-to-high risk patients, the follow-up time was 18.5(8.8,28.1)months of 37 patients treated by AG regimen and 8.1(7.3,9.0)months of 12 patients treated by AG combined with PD-1 inhibitor regimen. The median overall survival time of the two types of patients was 32.4(15.7,49.0)months and 8.9(5.7,12.1)months, respectively. The 1-year overall survival rates were 82.7% and 31.3%, and the 2-year overall survival rates were 66.5% and 0, respectively. There was a significant difference in the overall survival between the two types of patients ( hazard ratio=5.402, 95% confidence interval as 1.811?16.118, P<0.05). Conclusions:The treatment regimen is an independent influencing factor for overall survival in patients with resectable PDAC. Compared with the AG combined with PD-1 inhibitor regimen, AG regimen is associated with good survival of patients with resectable PDAC. For patients classified as intermediate-to-high risk based on the CCF risk score, AG regimen is assiociated with a better overall survival compared to AG combined with PD-1 inhibitor regimen.

Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces. Here we have developed a deep learning algorithm, GPT2 Ion Channel Classifier (GPT2-ICC), which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins. GPT2-ICC integrates representation learning with a large language model (LLM)-based classifier, enabling highly accurate identification of potential ion channels. Several potential ion channels were predicated from the unannotated human proteome, further demonstrating GPT2-ICC's generalization ability. This study marks a significant advancement in artificial-intelligence-driven ion channel research, highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data. Moreover, it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Objective:To investigate the role and underlying mechanism of parthanatos death in neonatal SD rats with bilirubin encephalopathy(BE).Methods:Eighty 3-day-old neonatal SD rats were selected and randomly divided into control group and BE group.The BE model was established by intraperitoneal injection of bilirubin solution,and the pathological changes in the hippocampus were observed by hematoxylin-eosin(HE)staining and Nissl staining.The protein expressions of the phosphorylation of the core histone protein H2AX(termed gamma H2AX),poly ADP-ribose polymerasw-1(PARP-1)and apoptosis-inducing factor(AIF)in hippocampus were detected by Western blot.Immuno-fluorescence staining was used to detect the expression and distribution of AIF in hippocampus.Results:Compared with the control group,neonatal SD rats developed jaundice 12 hours after bilirubin injection,accompanied by slow weight gain.HE staining and Nissl staining showed that the hippocampus in BE group were damaged and the content of Nissl bodies was decreased.Western blot results showed that the expression of γ-H2AX protein in hippocampus began to increase at 72 h after modeling(P＜0.05),and the levels of PARP-1 and AIF protein in hippocampus increased signif-icantly at 72 h after modeling(P＜0.05).Immunofluorescence staining showed increased AIF expression and nuclear translocation.Conclusion:Intraperitoneal injection of bilirubin can induce DNA damage in hippocampal neurons of neonatal SD rats and activate the PARP-1/AIF pathway to cause parthanatos death of hippocampal neurons.

Objective:To investigate the role and underlying mechanism of parthanatos death in neonatal SD rats with bilirubin encephalopathy(BE).Methods:Eighty 3-day-old neonatal SD rats were selected and randomly divided into control group and BE group.The BE model was established by intraperitoneal injection of bilirubin solution,and the pathological changes in the hippocampus were observed by hematoxylin-eosin(HE)staining and Nissl staining.The protein expressions of the phosphorylation of the core histone protein H2AX(termed gamma H2AX),poly ADP-ribose polymerasw-1(PARP-1)and apoptosis-inducing factor(AIF)in hippocampus were detected by Western blot.Immuno-fluorescence staining was used to detect the expression and distribution of AIF in hippocampus.Results:Compared with the control group,neonatal SD rats developed jaundice 12 hours after bilirubin injection,accompanied by slow weight gain.HE staining and Nissl staining showed that the hippocampus in BE group were damaged and the content of Nissl bodies was decreased.Western blot results showed that the expression of γ-H2AX protein in hippocampus began to increase at 72 h after modeling(P＜0.05),and the levels of PARP-1 and AIF protein in hippocampus increased signif-icantly at 72 h after modeling(P＜0.05).Immunofluorescence staining showed increased AIF expression and nuclear translocation.Conclusion:Intraperitoneal injection of bilirubin can induce DNA damage in hippocampal neurons of neonatal SD rats and activate the PARP-1/AIF pathway to cause parthanatos death of hippocampal neurons.

Objective:To evaluate the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated by gemcitabine and nab-paclitaxel (AG) or AG combined with pro-grammed death-1 (PD-1) inhibitor regimen and application value of the Cleveland Clinic Foundation (CCF) risk score.Methods:The retrospective cohort study was conducted. The clinicopathological data of 151 PDAC patients who were treated by AG regimen or AG combined with PD-1 inhibitor regimen in Zhejiang Cancer Hospital from January 2013 to March 2024 were collected. There were 84 males and 67 females, aged (64±9)years. Observation indicators: (1) comparison of clinical characteristics among resectable PDAC patients with different CCF risk score; (2) analysis of influencing factors for overall survival time of resectable PDAC patients; (3) survival of resectable PDAC patients. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regression model. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. Results:(1) Comparison of clinical characteristics among resectable PDAC patients with different CCF risk score. Based on CCF risk score, 102 of 151 patients were classified as low risk and 49 cases were classified as intermediate-to-high risk. There were signi-ficant differences in sex, age, smoking status, alcohol consumption, hypertension, and diabetes between the two categories ( P<0.05). (2) Analysis of influencing factors for overall survival time of resectable PDAC patients. Results of multivariate analysis showed that the treatment regimen was an indepen-dent influencing factor for overall survival time of resectable PDAC patients ( hazard ratio=1.976, 95% confidence interval as 1.065?3.666, P<0.05). (3) Survival of resectable PDAC patients. The follow-up time of 151 patients was 21.8(18.7,24.2)months, and the median overall survival time was 23.3(19.0,32.4)months. The follow-up time was 22.1(18.9,30.7)months of patients treated by AG regimen and 11.2(8.1,23.3)months of patients treated by AG combined with PD-1 inhibitor regimen, respectively. The median overall survival time of the two types of patients was 24.4(17.2,31.7)months and 16.9(8.9,24.9)months. The 1-year overall survival rates were 79.1% and 60.0%, and the 2-year overall survival rates were 53.4% and 28.5%, respectively. There was a significant difference in the overall survival between the two types of patients ( hazard ratio=1.913, 95% confidence interval as 1.041?3.516, P<0.05). Of the intermediate-to-high risk patients, the follow-up time was 18.5(8.8,28.1)months of 37 patients treated by AG regimen and 8.1(7.3,9.0)months of 12 patients treated by AG combined with PD-1 inhibitor regimen. The median overall survival time of the two types of patients was 32.4(15.7,49.0)months and 8.9(5.7,12.1)months, respectively. The 1-year overall survival rates were 82.7% and 31.3%, and the 2-year overall survival rates were 66.5% and 0, respectively. There was a significant difference in the overall survival between the two types of patients ( hazard ratio=5.402, 95% confidence interval as 1.811?16.118, P<0.05). Conclusions:The treatment regimen is an independent influencing factor for overall survival in patients with resectable PDAC. Compared with the AG combined with PD-1 inhibitor regimen, AG regimen is associated with good survival of patients with resectable PDAC. For patients classified as intermediate-to-high risk based on the CCF risk score, AG regimen is assiociated with a better overall survival compared to AG combined with PD-1 inhibitor regimen.

Tricuspid regurgitation(TR) is a malocclusion of the tricuspid lobes during systole, resulting in blood returning from the right ventricle to the right atrium during systole. Functional TR is not associated with clear tricuspid valve disease, but is secondary to left heart disease and is often accompanied by dilation of the tricuspid ring. The main treatment for TR is to reduce the enlarged ring with tricuspid valvuloplasty or to replace the diseased valve with tricuspid valve replacement. Tricuspid valvuloplasty is the most common and safest surgical method for functional TR, but the specific treatment strategies for TR are still controversial. This article reviews the diagnostic evaluation, surgical strategy and prognosis of TR treated by tricuspid valvuloplasty.

Patients with hepatocellular carcinoma (HCC) and bone metastasis (BM) suffer from greatly reduced life quality and a dismal prognosis. However, BM in HCC has long been overlooked possibly due to its relatively low prevalence in previous decades. To date, no consensus or guidelines have been reached or formulated for the prevention and management of HCC BM. Our narrative review manifests the increasing incidence of HCC BM to sound the alarm for additional attention. The risk factors, diagnosis, prognosis, and therapeutic approaches of HCC BM are detailed to provide a panoramic view of this disease to clinicians and specialists. We further delineate an informative cancer bone metastatic cascade based on evidence from recent studies and point out the main factors responsible for the tumor-associated disruption of bone homeostasis and the formation of skeletal cancer lesions. We also present the advances in the pathological and molecular mechanisms of HCC BM to shed light on translational opportunities. Dilemmas and challenges in the treatment and investigation of HCC BM are outlined and discussed to encourage further endeavors in the exploration of underlying pathogenic and molecular mechanisms, as well as the development of novel effective therapies for HCC patients with BM.
Bone Neoplasms/secondary* ; Carcinoma, Hepatocellular/therapy* ; Humans ; Liver Neoplasms/therapy* ; Prognosis

Objective To investigate the characteristics of gut microbiota in patients with schizophrenia. Methods The composition of the fecal microbiota in 16 schizophrenia patients and 20 healthy controls was analyzed by 16S rRNA sequencing. Results At the phylum level, TM7 was increased in the patients (P<0.05). At the class level, the abundance of Peptostreptococcaceae, Lactobacillaceae and Actinomycetaceae in the patients increased (P<0.05), whereas the abundance of Tissierellaceae decreased relative to health controls (P<0.05). At the genus level, Actinomyces, Scardovia, Atopobium, Moryella, G07 and Lactobacillus were increased in the patients relative to healthy controls (P<0.05). Prediction of functional properties of bacterial flora showed that the metabolic pathways of fatty acids and pyruvate were different between the patients and healthy controls (P<0.05). Conclusion The present study reveals an alteration in the characteristics of gut microbiota in schizophrenia patients which may be an auxiliary diagnosis marker for clinical diagnosis of schizophrenia.