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.

OBJECTIVE To explore the ameliorative effect of Tiaozhi Xiaoban Mixture on atherosclerosis and the potential role of long non-coding RNA(Linc RNA)in anti-atherosclerosis.METHODS A model of atherosclerosis was established in SD rats subjec-ted to a high-fat diet.At 4 weeks post-modeling,thoracic aortic tissues from atherosclerotic rats were collected for hematoxylin-eosin(HE)staining to systematically evaluate the anti-atherosclerotic effects of Tiaozhi Xiaoban Mixture at different doses.Biochemical kits were utilized to assess relevant indices related to blood lipid levels as well as liver and kidney function,thereby evaluating the impact of Tiaozhi Xiaoban Mixture on these parameters.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum inflam-mation markers influenced by Tiaozhi Xiaoban Mixture.Additionally,TUNEL staining and Western blot analysis were conducted to ex-amine the apoptotic effects of Tiaozhi Xiaoban Mixture on thoracic aorta tissue.Finally,qPCR was used to detect the expression levels of Line-HC,MALAT1,etc.,in order to evaluate how Tiaozhi Xiaoban Mixture affecting these specific RNA molecules.RESULTS Following treatment with Tiaozhi Xiaoban Mixture,the blood lipid profiles indicated that total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)were significantly down-regulated(P＜0.05,P＜0.01),while high-density lipopro-tein cholesterol(HDL-C)levels were up-regulated in the atherosclerotic rats.Moreover,serum levels of liver and kidney function markers such as aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN),and creatinine(Cr)exhibited down-regulation(P＜0.05,P＜0.01).Additionally,pro-inflammatory factors including interleukin-6(IL-6),interleukin-1 beta(IL-1β),tumor necrosis factor-alpha(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and matrix metallopeptidase 9(MMP-9)were also reduced(P＜0.01),whereas the anti-inflammatory factor interleukin-10(IL-10)was found to be elevated(P＜0.01).Furthermore,after oral administration of Tiaozhi Xiaoban Mixture,expression levels of apoptosis-related factors NLRP3,ASC,Cleaved Caspase-1,Cleaved IL-1 β,Puma,Bax,Noxa,and MDM2 in thoracic aorta tissues from the atherosclerotic rats showed sig-nificant down-regulation(P＜0.05,P＜0.01).Notably,following treatment with Tiaozhi Xiaoban Mixture,mRNA levels of Linc-HC decreased while mRNA expression of MALAT1 increased(P＜0.05,P＜0.01).CONCLUSION Tiaozhi Xiaoban Mixture may inhibit the expression of Linc-HC and up-regulate the expression of MALAT1 to reduce the formation of atherosclerotic plaque,improve ab-normal blood lipids and liver and kidney function,alleviate inflammation and inhibit apoptosis.

Objective:To explore the effects of age and gender on the sagittal spinal-pelvic parameters during the natural aging process of healthy adults.Methods:A total of 647 Chinese healthy adults who underwent health check-ups at the Second Affiliated Hospital of Zhejiang University School of Medicine and Songyang County People's Hospital, from January 2017 to September 2024 were collected. There were 277 males and 370 females, aged 18-93 years. Anteroposterior and lateral X-ray films of the whole spine were taken to evaluate the spinal-pelvic sagittal morphology. The following parameters were measured: thoracic kyphosis (TK), lumbar lordosis(LL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT), global tilt (GT), T 1-pelvic angle (TPA), sagittal vertical axis (SVA), thoracic Cobb angle (T-Cobb), lower end vertebra of thoracic Cobb angle (T-LEV), apex vertebra of thoracic Cobb angle (T-Apex), lumbar Cobb angle (L-Cobb). Compare the differences in spine-pelvis parameters among patients of different genders and age groups (in this study, the subjects were subdivided into the 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-93 years groups according to the age range). Results:The results showed that GT, SVA, TPA, and PT increased with age ( P<0.05). For males aged 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-93 years, PT values were 8.58°±6.47°, 9.60°±5.63°, 12.65°±7.13°, 11.00°±6.99°, 13.01°±8.63°, 15.77°±8.02°, and 18.47°±10.03° respectively; for females in the same age groups, the PT values were 8.44°±6.83°, 9.00°±6.44°, 11.84°±7.35°, 12.07°±7.51°, 15.44°±9.39°, 19.26°±8.28°, and 18.17°±9.43° respectively. For males in these age groups, the global tilt (GT) values were 6.37°±7.20°, 8.77°±6.51°, 10.38°±9.07°, 8.80°±7.49°, 10.80°±8.62°, 16.07°±10.42°, and 21.99°±12.65° respectively; for females, the GT values were 4.46°±8.09°, 5.96°±7.83°, 8.17°±6.88°, 9.41°±8.03°, 9.96°±1.39°, 17.89°±9.39°, and 19.55°±12.34° respectively. The sagittal vertical axis (SVA) values for males in the age groups were -7.94±25.57 mm, -2.98±25.69 mm, -4.63±20.90 mm, -6.43±32.81 mm, 7.85±43.39 mm, 36.49±53.89 mm, and 55.57±51.10 mm respectively; for females, they were -24.12±31.35 mm, -17.49±25.12 mm, -17.88±22.72 mm, -8.25±30.91 mm, 8.80±27.45 mm, 28.67±38.22 mm, and 23.23±35.19 mm respectively. For males, the thoracic pelvic angle (TPA) values across the age groups were 4.46°±5.94°, 6.05°±5.38°, 9.58°±9.35°, 7.52°±7.64°, 11.23°±9.59°, 16.32°±12.38°, and 18.49°±11.70° respectively; for females, the TPA values were 2.72°±6.88°, 3.68°±6.26°, 7.30°±6.11°, 7.44°±6.75°, 12.64°±9.79°, 19.08°±10.39°, and 16.79°±13.19° respectively. T-Cobb, T-LEV, and T-Apex increased slowly with age ( P<0.05). The pelvic incidence (PI) remained relatively constant in males ( P>0.05), while it increased slowly with age in females ( P<0.05). Conclusions:Sagittal anteversion of the spinal-pelvis increases with age. Gender differences are reflected in specific changes in the fluctuation amplitude of certain parameters (such as PI), and the fluctuations of indicators like T-Cobb, T-LEV, and T-Apex are closely related to the natural aging process of the spine.

OBJECTIVE To explore the ameliorative effect of Tiaozhi Xiaoban Mixture on atherosclerosis and the potential role of long non-coding RNA(Linc RNA)in anti-atherosclerosis.METHODS A model of atherosclerosis was established in SD rats subjec-ted to a high-fat diet.At 4 weeks post-modeling,thoracic aortic tissues from atherosclerotic rats were collected for hematoxylin-eosin(HE)staining to systematically evaluate the anti-atherosclerotic effects of Tiaozhi Xiaoban Mixture at different doses.Biochemical kits were utilized to assess relevant indices related to blood lipid levels as well as liver and kidney function,thereby evaluating the impact of Tiaozhi Xiaoban Mixture on these parameters.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum inflam-mation markers influenced by Tiaozhi Xiaoban Mixture.Additionally,TUNEL staining and Western blot analysis were conducted to ex-amine the apoptotic effects of Tiaozhi Xiaoban Mixture on thoracic aorta tissue.Finally,qPCR was used to detect the expression levels of Line-HC,MALAT1,etc.,in order to evaluate how Tiaozhi Xiaoban Mixture affecting these specific RNA molecules.RESULTS Following treatment with Tiaozhi Xiaoban Mixture,the blood lipid profiles indicated that total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)were significantly down-regulated(P＜0.05,P＜0.01),while high-density lipopro-tein cholesterol(HDL-C)levels were up-regulated in the atherosclerotic rats.Moreover,serum levels of liver and kidney function markers such as aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN),and creatinine(Cr)exhibited down-regulation(P＜0.05,P＜0.01).Additionally,pro-inflammatory factors including interleukin-6(IL-6),interleukin-1 beta(IL-1β),tumor necrosis factor-alpha(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and matrix metallopeptidase 9(MMP-9)were also reduced(P＜0.01),whereas the anti-inflammatory factor interleukin-10(IL-10)was found to be elevated(P＜0.01).Furthermore,after oral administration of Tiaozhi Xiaoban Mixture,expression levels of apoptosis-related factors NLRP3,ASC,Cleaved Caspase-1,Cleaved IL-1 β,Puma,Bax,Noxa,and MDM2 in thoracic aorta tissues from the atherosclerotic rats showed sig-nificant down-regulation(P＜0.05,P＜0.01).Notably,following treatment with Tiaozhi Xiaoban Mixture,mRNA levels of Linc-HC decreased while mRNA expression of MALAT1 increased(P＜0.05,P＜0.01).CONCLUSION Tiaozhi Xiaoban Mixture may inhibit the expression of Linc-HC and up-regulate the expression of MALAT1 to reduce the formation of atherosclerotic plaque,improve ab-normal blood lipids and liver and kidney function,alleviate inflammation and inhibit apoptosis.

Objective:To explore the feasibility and preliminary clinical experience of robot-assisted pelvic exenteration (PE) in the treatment of locally advanced (LARC) and recurrent (LRRC) rectal cancer.Method:A descriptive case series research method was adopted. Inclusion criteria included: (1) Age 18-80 years old; (2) Preoperative puncture biopsy performed through endoscopy, and a pathological diagnosis of rectal malignant tumor; (3) Preoperative imaging examinations confirming locally advanced (cT4b stage) or locally recurrent rectal cancer, with tumor location in the pelvic cavity; (4) Physical condition: ECOG score ≤1 point, and radical resection being feasible after assessment. The data for five patients with LARC or LRRC who underwent pelvic exenteration (PE) using the da Vinci robotic surgical system in the Department of Anorectal Surgery, the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) from January, 2024 to January, 2025 were collected retrospectively. The mean age was (46.8±7.7) years, with 3 males and 2 females, who comprised 2 cases of LARC and 3 cases of LRRC. Two patients received preoperative radiotherapy, and 4 patients received preoperative chemotherapy. The average body mass index was (21.5±2.7) kg/m2. According to the American Society of Anesthesiologists (ASA) classification, 2 cases were grade II and 3 cases were grade III.Results:All patients with LARC or LRRC successfully underwent robot-assisted PE. The average operation time was (496.4±139.5) minutes; the average intraoperative blood loss was (72.0±29.5) ml; the average postoperative exhaust time was (50.0 ±13.6) hours; and the average postoperative defecation time was(64.2±15.3) hours. Mean early postoperative VAS pain scores was (3.6±1.5) points. Three patients underwent primary intestinal anastomosis, and 2 patients underwent colonic single-lumen ostomy. All 5 patients underwent urinary system reconstruction, among which 2 underwent ureterovesical reimplantation, 1 underwent percutaneous ureterostomy, 1 underwent ileal conduit replacement of bladder, and 1 underwent direct bladder suture. After surgery, except for 1 case of pelvic infection with effusion (Clavien-Dindo grade IIIa), there were no obvious postoperative complications. Postoperative pathological results showed that all patients achieved R0 resection, including 1 case of T4a stage and 4 cases of T4b stage (all involving urogenital organs or tissues), and 3 cases of N0 stage and 2 cases of N1 stage, with a maximum tumor diameter of (4.7±1.9) cm. The median postoperative follow-up time was 11 (range 7 to 17) months, and no patient experienced local recurrence.Conclusion:The above short-term preliminary results of robot-assisted PE in the treatment of LARC or LRRC within the pelvic cavity indicate that it is both safe and feasible.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

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*

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.