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Yaduo Li,1,* Ningning Fan,1,* Xu He,2,* Jianjun Zhu,3,* Jie Zhang,1 Ligong Lu1,2 1Medical Imaging Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital), Zhuhai, People’s Republic of China; 2Department of Interventional Medicine, Guangzhou First People’s Hospital, Guangzhou, People’s Republic of China; 3R&D Department, Hanglok-Tech Co., Ltd., Hengqin, People’s Republic of China; Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ligong Lu, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital), Zhuhai, Guangdong, 519000, People’s Republic of China & Guangzhou First People’s Hospital, Guangzhou, Guangdong, 510180, People’s Republic of China, Tel +020-81048888, Email lu_ligong@163.com Jie Zhang, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital), Zhuhai, Guangdong, 519000, People’s Republic of China, Tel +86-756-15916221984, Email zhangjie201806@sina.comAbstract: Hepatocellular Carcinoma (HCC) is a condition associated with significant morbidity and mortality. The presence of Portal Vein Tumour Thrombus (PVTT) typically signifies advanced disease stages and poor prognosis. Artificial intelligence (AI), particularly Machine Learning (ML) and Deep Learning (DL), has emerged as a promising tool for extracting quantitative data from medical images. AI is increasingly integrated into the imaging omics workflow and has become integral to various medical disciplines. This paper provides a comprehensive review of the mechanisms underlying the formation and progression of PVTT, as well as its impact on clinical management and prognosis. Additionally, it outlines the advancements in AI for predicting the diagnosis of HCC and the development of PVTT. The limitations of existing studies are critically evaluated, and potential future research directions in the realm of imaging for the diagnostic prediction of HCC and PVTT are discussed, with the ultimate goal of enhancing survival outcomes for PVTT patients.Keywords: hepatocellular carcinoma, portal vein tumour thrombus, imaging omics, prediction, artificial intelligence

Shuo Yuan,&ast; Xuanyu Lu,&ast; Lei Zang, Yuqi Mei, Ning Fan, Peng Du Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zang, Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, 5 JingYuan Road, Shijingshan District, Beijing, 100043, People’s Republic of China, Email zanglei@ccmu.edu.cnPurpose: Percutaneous transforaminal endoscopic discectomy (PTED) was used as a minimally invasive treatment option for lumbar disc herniation (LDH). However, studies focusing on the clinical outcomes of PTED for elderly patients with adjacent segment disease (ASD) were limited. This study aims to compare the clinical outcomes of PTED between ASD and LDH in elderly patients.Patients and Methods: This retrospective study enrolled 39 patients with ASD and 39 patients with LDH. Both groups had undergone PTED in Beijing Chaoyang Hospital from July 4, 2016 to July 30, 2021. Visual analog scale for back pain (VAS-BP) and leg pain (VAS-LP) and Oswestry disability index (ODI) were used to value the clinical outcomes of patients preoperatively, immediately postoperatively, 12, and 24 months postoperatively, and at final follow-up. Patients’ satisfaction was evaluated based on the MacNab criteria.Results: All operations were completed. The excellent or good clinical outcomes at final follow-up was demonstrated by 87.15% (34/39) and 89.74% (35/39) in ASD and non-ASD patients, respectively. Clinical improvement was observed immediately postoperatively in both groups and sustained stability during the postoperative follow-up. The ASD group demonstrated significantly longer hospital stays (p = 0.02) and operative time (p < 0.01) than the non-ASD group.Conclusion: PTED is an effective and minimally invasive treatment option for revision surgery of ASD, especially for elderly patients. However, the long-term prognosis of PTED treating ASD still needs further exploration.Keywords: adjacent segment degeneration, percutaneous transforaminal endoscopic discectomy, clinical outcomes, geriatric patients, minimally invasive

Lihe Ma,1 Rui Yan,1 Xiang Wang,2 Xiaohong Gao,1 Na Fan,1 Linmei Liu,3 Haifen Kang3 1Nursing College of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Foreign Language, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of General Surgery, First Affiliated Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Rui Yan, Nursing College of Shanxi Medical University, No. 56 of Xinjian Road, Yingze District, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel +86 13934168679, Email yanruifl29@outlook.comBackground: Surgical nursing is a high-risk, high-pressure, and complex field. Nurses need extensive knowledge, skills, and abilities. Problem-Based Learning (PBL) and Simulation-Based Learning (SBL) are effective student-centered methods. Which method is better for surgical nurse training? More research is needed to determine the best approach for undergraduate surgical nurse education.Purpose: To compare the impact of PBL and SBL on undergraduate nursing students’ performance and improve learning outcomes in surgical nursing education.Methods: We used a pretest/post-test design with 318 nursing undergraduates randomly assigned to two groups. Participants completed three progressive scenarios focused on surgical nursing cases. Experts blindly reviewed video recordings using the 70-item Korean Nurses’ Core Competence Scale (KNCCS) to assess performance. The 13-item Satisfaction and Self-confidence in learning Scale (SSS) measured learning confidence and satisfaction. SBL participants also completed the 16-item Educational Practices in Simulation Scale (EPSS) and 20-item Simulation Design Scale (SDS).Results: The study found significant positive effects on both groups, with noticeable improvements in post-test, retention, and follow-up test results (P < 0.001). The SBL group showed higher competency levels in nurses (P < 0.001). The Cohen’s d and effect size (r) for various skills were as follows: clinical performance (0.84767 and 6.39023), critical thinking (0.31017 and 0.15325), professional attitude (0.85868 and 0.39452), and communication skills (1.55149 and 0.61294). The satisfaction and self-confidence of nurses were higher in the SBL group (4.53± 0.596; 4.47± 0.611) compared to the PBL group (4.32± 0.689; 4.25± 0.632) in all dimensions of SSS (all P < 0.05). The SBL group also scored high in simulation design and EPSS. However, improvements are needed in fidelity, objectives, information, and students’ expectations.Conclusion: SBL and PBL improve nurses’ core competence, satisfaction, and self-confidence. SBL is superior. This study promotes student-centered education, enhancing surgical nursing professionals’ quality and ensuring future patient safety.Keywords: baccalaureate nursing, education, problem-based learning, simulation training, surgical nursing

Qichao Wu,&ast; Shuo Yuan,&ast; Lei Zang, Tianyi Wang, Xuanyu Lu, Aobo Wang, Fangda Si, Ning Fan, Peng Du Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zang, Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email zanglei@ccmu.edu.cnObjective: To investigate the correlation between postoperative imaging parameters and clinical outcomes in patients with foraminal stenosis (FS) and lateral recess stenosis (LRS) who underwent percutaneous endoscopic transforaminal decompression (PETD).Methods: The study included 104 eligible patients who underwent PETD, and the mean follow-up time was 2.4 years (range 2.2– 3.6 years). Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) scores, and the modified MacNab criteria were used to evaluate the clinical outcomes. The related parameters of the FS and LRS based on computed tomography and magnetic resonance imaging were measured before and after surgery. Correlations between the imaging parameters and clinical outcomes were investigated.Results: The proportion of excellent and good results following MacNab evaluation was 82.6%. In the treatment of LRS, VAS-back, VAS-leg, and ODI at the 2-year follow-up were negatively correlated with postoperative facet joint length based on computed tomography. In the treatment of FS, the above clinical results were positively correlated with the variation of foraminal width and nerve root-facet distance before and after surgery based on magnetic resonance imaging.Conclusion: PETD can achieve good clinical outcomes in the treatment of patients with LRS or FS. Postoperative facet joint length was negatively correlated with clinical outcomes of LRS patients. In FS patients, the variation in foraminal width and nerve root-facet distance before and after surgery were positively correlated with their clinical outcomes. These findings may help surgeons optimize treatment strategies and selection of surgical candidates.Keywords: lumbar spinal stenosis, clinical outcomes, percutaneous endoscopic transforaminal decompression, microsurgery, spinal endoscopy

Luyuan Bai,1 Weiye Liang,1 Yongqian Wang,2 Ning Fan,1 Qi zhang,3 Yun Bian,1 Fude Yang1 1Peking University Huilongguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People’s Republic of China; 2Office of Scientific Research, Peking University Health Science Center, Beijing, People’s Republic of China; 3Department of Psychology, Wuxi Mental Health Center, Wuxi, People’s Republic of ChinaCorrespondence: Fude Yang; Yun Bian, Peking University Huilongguan Clinical Medical School, 7, Nandian Road, Huilongguan, Changping District, Beijing, 100096, People’s Republic of China, Tel +86-010-83024456 ; +86-010-83024572, Email yangfd_200@163.com; ihqihqajjq@163.comObjective: This study aims to explore the ability of betahistine to inhibit weight gain and abnormal lipid metabolism in patients with chronic schizophrenia.Methods: A comparison study of betahistine or placebo therapy was conducted for 4 weeks in 94 patients with chronic schizophrenia, who were randomly divided into two groups. Clinical information and lipid metabolic parameters were collected. Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms. Treatment Emergent Symptom Scale (TESS) was used to evaluate treatment-related adverse reactions. The differences in lipid metabolic parameters before and after treatment between the two groups were compared.Results: Repeated measures analysis of variance (ANOVA) revealed that after 4 weeks of betahistine/placebo treatment, the interaction effect of time and group was statistically significant on low-density lipoprotein cholesterol (F = 6.453, p = 0.013) and waist-to-hip ratio (F = 4.473, p = 0.037), but did not reveal any significant interaction effect of time and group on weight, body mass index or other lipid metabolic parameters, as well as the time main effect and group main effect (all p > 0.05). Betahistine had no significant impact on PANSS, and no side effects related to betahistine were detected.Conclusion: Betahistine may delay metabolic abnormalities in patients with chronic schizophrenia. It does not affect the efficacy of the original antipsychotics. Thus, it provides new ideas for the treatment of metabolic syndrome in patients with chronic schizophrenia.Keywords: schizophrenia, lipid metabolism, betahistine, histamine, H3-receptor antagonist

Lei Wang, Tianyi Wang, Ning Fan, Shuo Yuan, Peng Du, Fangda Si, Aobo Wang, Lei Zang Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Lei Zang, Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, 5 JingYuan Road, Shijingshan District, Beijing, 100043, People’s Republic of China, Tel +86 13601252787, Email zanglei@ccmu.edu.cnPurpose: To evaluate the efficacy of repeat percutaneous endoscopic lumbar decompression (PELD) in lumbar spinal stenosis (LSS) reoperation.Patients and Methods: This study included patients with LSS who relapsed following treatment with PELD therapy between March 2017 and March 2020. Visual analog scale (VAS) scores and Oswestry Disability Index (ODI) were analyzed preoperatively, postoperatively at 3, 6, 12, and 24 months, and at final follow-up. The modified MacNab criteria were used to assess clinical effects. All complications were recorded.Results: At a mean follow-up of 3 years, 24 patients with LSS who underwent repeat PELD were identified. The patients’ mean operative time was 122.3± 29.2 min, blood loss was 12.5± 5.3 mL, and mean hospital stay was 7.0± 1.9 days. VAS leg-pain score improved from 6.1± 1.0 to 2.0± 1.2 (P< 0.001), VAS back-pain score improved from 6.2± 0.8 to 2.1± 1.1 (P< 0.001), and ODI improved from 68.9± 6.0 to 20.9± 5.6 (P < 0.001). According to the modified MacNab criteria, the good-to-excellent rate was 83.3%. Postoperative complications, including hematoma, nerve root injury, and dural injury, developed in four patients.Conclusion: Repeat PELD for reoperation in patients with LSS has a good clinical effect, and is recommended in routine clinical practice. Careful intraoperative manipulation is recommended to prevent complications.Keywords: lumbar spinal stenosis, percutaneous endoscopic lumbar decompression, reoperation, complication

Aobo Wang,&ast; Fangda Si,&ast; Tianyi Wang, Shuo Yuan, Ning Fan, Peng Du, Lei Wang, Lei Zang Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zang, Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, 5 JingYuan Road, Shijingshan District, Beijing, 100043, People’s Republic of China, Tel +86 13601252787, Email zanglei@ccmu.edu.cnPurpose: To identify the incidence rates and risk factors for early readmission and reoperation after percutaneous transforaminal endoscopic decompression (PTED) for degenerative lumbar spinal stenosis (DLSS).Patients and Methods: A total of 1011 DLSS patients who underwent PTED were retrospectively evaluated. Of them, 58 were readmitted, and 31 underwent reoperation. The patients were matched with 174 control patients to perform case-control analyses. The clinical and preoperative imaging data of each patient were recorded. Univariate analyses were performed using independent sample t-tests and Fisher’s exact tests. Furthermore, the risk factors for early readmission and reoperation were analyzed using multivariate logistic regression analyses.Results: The incidence rates of readmission and reoperation within 90 days after PTED were 5.7% and 3.1%, respectively. Age (odds ratio [OR]=1.054, p=0.001), BMI (OR=1.104, p=0.041), a history of lumbar surgery (OR=3.260, p=0.014), and the number of levels with radiological lumbar foraminal stenosis (LFS, OR=2.533, p< 0.001) were independent risk factors for early readmission. The number of levels with radiological LFS (OR=5.049, p< 0.001), the grade of surgical-level facet joint degeneration (OR=2.010, p=0.023), and a history of lumbar surgery (OR=10.091, p< 0.001) were independent risk factors for early reoperation.Conclusion: This study confirmed that aging, a higher BMI, a history of lumbar surgery, and more levels with radiological LFS were associated with a higher risk of early readmission. More levels with radiological LFS, a higher grade of surgical-level facet joint degeneration, and a history of lumbar surgery were predictors of early reoperation. These results are helpful in patient counseling and perioperative evaluation of PTED.Keywords: spinal stenosis, minimally invasive, readmission, reoperation, risk factor

Aobo Wang,&ast; Tianyi Wang,&ast; Lei Zang, Shuo Yuan, Ning Fan, Peng Du, Qichao Wu Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zang, Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, 5 JingYuan Road, Shijingshan District, Beijing, 100043, People’s Republic of China, Tel +86 13601252787, Email zanglei@ccmu.edu.cnPurpose: This study aimed to evaluate the degeneration patterns of the facet joints (FJs) in patients with lumbar foraminal stenosis (LFS) and investigate the correlation between quantitative parameters and FJ osteoarthritis (FJ OA).Patients and Methods: A total of 171 patients with LFS at the L4/5 level and 146 control patients were enrolled in this study. The severity of FJ OA was graded according to the Weishaupt classification. The FJ orientation, FJ tropism, superior articular process cross-sectional area (SAPA), and FJ area were measured at the L3/4, L4/5, and L5/S1 spinal levels. Associations among the parameters were assessed using Pearson’s correlation coefficients. Independent sample t-tests and Pearson’s chi-square tests were used for univariate analyses. The association between LFS and the quantitative parameters was also analyzed using multivariate logistic regression models adjusted for age, gender, and body mass index.Results: Patients with LFS had more sagittal FJ orientation (37.9 vs 45.0, p < 0.001), more FJ tropism (5.6 vs 3.8, p < 0.001), larger SAPA (129.0 vs 97.8, p < 0.001), and less FJ area (21.7 vs 23.3, p = 0.016). Logistic regression analysis showed that LFS was significantly associated with FJ tropism (odds ratio [OR]: 1.153; p = 0.003) and SAPA (OR: 1.113; p < 0.001). The SAPA showed the largest area under the curve (0.908, 95% confidence interval: 0.875– 0.942) for the diagnosis of LFS. The optimal cutoff value was 114.75 mm2 with 85.4% sensitivity and 87.0% specificity. Additionally, a significant correlation was observed between FJ OA and SAPA and FJ area at each studied spinal level.Conclusion: This study confirmed that LFS is significantly associated with FJ hypertrophy and tropism. FJ hypertrophy and joint space narrowing correlated with the severity of FJ OA. These results are helpful in understanding the morphology and pathology of FJs.Keywords: spinal stenosis, facet joint, articular process, osteoarthritis

Fangda Si,&ast; Shuo Yuan,&ast; Lei Zang, Ning Fan, Qichao Wu, Tianyi Wang, Aobo Wang Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zang, Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China, Tel +86-13601252787, Email zanglei@ccmu.edu.cnBackground: The paraspinal muscle is essential for maintaining normal spine function and structure, which degeneration is closely related to various spinal diseases. The main objective of this study was to identify the potential role of paraspinal muscle degeneration in the occurrence of new vertebral compression fractures (NVCF) and develop a clinically applicable nomogram for prospective NVCF risk prediction.Methods: A total of 202 patients with single-level osteoporotic vertebral compression fractures (OVCF) who underwent percutaneous kyphoplasty treatment between January 2016 and March 2019 were included in this study. Demographic, clinical, radiological, and treatment data were collected and analyzed. The paraspinal muscle cross-sectional area (CSA) and fat signal fraction (FSF) were measured to quantify the extent of muscle degeneration. Multivariate binary logistic regression analysis was performed to select risk factors to build a nomogram that predicted the occurrence of NVCF. The concordance index (C-index) and calibration curve were used to evaluate the discriminative capacity and predictive accuracy of the nomogram.Results: NVCF occurred in 54 of 202 patients (26.7%). The erector spinae FSF (OR = 1.064; P = 0.001), psoas major FSF (OR = 1.326; P < 0.001), and the difference index of the muscle CSA between multifidus and psoas major (OR = 1.048; P < 0.001) were independent risk factors for the occurrence of NVCF. The nomogram performance was good after evaluation using the calibration curves and C-index (95% confidence interval, 0.854– 0.943).Conclusion: Paraspinal muscle degeneration is a potential risk factor for NVCF occurrence. A nomogram was designed to precisely predict the risk of NVCF. This predictive nomogram may help clinicians to make better clinical decisions and provide more accurate functional exercise protocol for OVCF patients.Keywords: paraspinal muscle degeneration, new vertebral compression fractures, percutaneous kyphoplasty, risk factors, nomogram

Fu He,1,2 Kangjian Song,1,2 Ge Guan,3 Junyu Huo,1,2 Yang Xin,1 Tianxiang Li,3 Chao Liu,1 Qingwei Zhu,1,2 Ning Fan,1 Yuan Guo,1 Liqun Wu1 1Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People’s Republic of China; 2Department of Clinical Medicine, Qingdao University, Qingdao, 266071, Shandong, People’s Republic of China; 3Organ Transplant Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People’s Republic of ChinaCorrespondence: Liqun WuLiver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, 266003, Shandong Province, People’s Republic of ChinaTel +86 18661809789Email wulq5810@126.comPurpose: Gene rearrangements (GRs) have been reported to be related to adverse prognosis in some tumours, but the relationship in hepatocellular carcinoma (HCC) remains less studied. The objective of our study was to explore the clinicopathological characteristics and prognosis of HCC patients (HCCs) with GRs (GR-HCCs).Patients and Methods: This retrospective study included 297 HCCs who underwent hepatectomy and had their tumours sequenced by next-generation sequencing. Categorical variables between groups were compared by the chi-square test. The impact of variables on disease-free survival (DFS) and survival after relapse (SAR) was analysed by the Kaplan–Meier method and Cox regression.Results: We observed four repetitive GR events in 297 HCCs: BRD9/TERT, ARID2/intergenic, CDKN2A/intergenic and OBSCN truncation. GR-HCCs frequently presented with low tumour differentiation, tumour necrosis, microvascular invasion, elevated AFP and gene mutations (TP53, NTRK3 and BRD9). The 1-, 2-, and 3-year cumulative DFS rates in GR-HCCs were 45.1%, 31.9%, 31.9%, respectively, which were significantly lower than those of GR-negative HCCs (NGR-HCCs) (72.5%, 57.9%, and 49.0%, respectively; P = 0.001). GR was identified as an independent risk factor for inferior DFS in HCCs (HR = 1.980, 95% CI = 1.246– 3.147; P = 0.004). However, there was no significant difference in SAR between GR-HCCs and NGR-HCCs receiving targeted therapy or immunotherapy.Conclusion: GR is frequently associated with TP53 mutations and significantly affects DFS following radical resection for HCC. We recommend that GR-HCCs should be closely followed up as a high-risk group for postoperative recurrence.Keywords: hepatocellular carcinoma, gene rearrangement, next-generation sequencing, prognosis, risk factors

Kangjian Song, Fu He, Yang Xin, Ge Guan, Junyu Huo, Qingwei Zhu, Ning Fan, Yuan Guo, Yunjin Zang, Liqun Wu Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of ChinaCorrespondence: Liqun WuLiver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao, Shandong, 266003, People’s Republic of ChinaTel +86 15315328331Email wulq5810@126.comPurpose: To explore the value of Tuberous sclerosis complex 2 (TSC2) mutations in evaluating the early recurrence of hepatocellular carcinoma (HCC) patients underwent hepatectomy.Patients and Methods: A total of 183 HCC patients were enrolled. Next-generation sequencing was performed on tumor tissues to analyze genomic alterations, tumor mutational burden and variant allele fraction (VAF). The associations between TSC2 mutations and recurrence rate within 1 year, RFS and OS after hepatectomy were analyzed.Results: Our results showed that TSC2 mutation frequency in HCC was 12.6%. Compared to patients without TSC2 mutation, the proportion of microvascular invasion (MVI) and Edmondson grade III–IV was significantly higher in patients with a TSC2 mutation (p< 0.05). The VAF of mutated TSC2 was higher in patients with maximum diameter of tumor > 5cm or MVI than that of other patients (p< 0.05). The frequency of TP53 mutation was significantly higher in patients with a TSC2 mutation than those without TSC2 mutation (p=0.003). Follow-up analysis showed that patients with a TSC2 mutation had significantly higher recurrence rate within 1 year (p=0.015) and poorer median recurrence-free survival (RFS) (p=0.010) than patients without TSC2 mutation. TSC2 mutations did not significantly affect overall survival of patients (p=0.480). The multivariate analysis results showed that the Barcelona Clinic Liver Cancer (BCLC) B-C stage, TSC2 mutations and preoperative serum alpha-fetoprotein level ≥ 400μg/L were independently associated with recurrence within 1 year after hepatectomy (HR=8.628, 95% CI: 3.836– 19.405, p=0.000; HR=3.885, 95% CI: 1.295– 11.653, p=0.015; HR=2.327, 95% CI: 1.018– 5.323, p=0.045; respectively), and poorer RFS after hepatectomy (HR=3.070, 95% CI: 1.971– 4.783, p=0.000; HR=1.861, 95% CI: 1.061– 3.267, p=0.030; HR=1.715, 95% CI: 1.093– 2.693, p=0.019; respectively).Conclusion: TSC2 mutations were significantly associated with MVI in liver para-carcinoma tissue and Edmondson grade III–IV in patients with HCC and were independently associated with recurrence within 1 year and poorer RFS after hepatectomy. The TSC2 mutation may be a potential predictor for early recurrence in HCC patients underwent hepatectomy.Keywords: hepatocellular carcinoma, tuberous sclerosis complex 2, next-generation sequencing, gene mutation, early recurrence

Ningbo Fan,1,* Dongni Chen,1,* Jiabo Zheng,2 Zhesheng Wen,1 Peng Lin11Department of Thoracic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China*These authors contributed equally to this workPurpose: The inflammatory microenvironment and hemostatic system are involved in several stages of tumor progression. The aim of this study was to assess the prognostic effect of fibrinogen-to-lymphocyte ratio (FLR) in esophageal squamous cell carcinoma (ESCC) patients who underwent radical esophagectomy.Patients and methods: We retrospectively reviewed 673 consecutive patients with ESCC who underwent radical esophagectomy from January 2009 to December 2012 at a major cancer hospital in Guangzhou, southern China. The cutoff points were defined by the X-tile software. The prognostic value of FLR for overall survival (OS), disease-free survival (DFS), and first-year mortality after surgery were analyzed using Cox proportional hazard regression model and logistic regression model. Survival was estimated by the Kaplan–Meier estimator and compared using the log-rank test.Results: The optimal cutoff point of FLR was 3.03. Compared with the FLR-low (≤3.03) group, the FLR-high (>3.03) group included older patients (χ2=7.267, P=0.007), showed higher postoperative overall morbidity (24.7% vs 14.8%, χ2=5.414, P=0.020) and tended to die within one year (23.5% vs 10.9%, χ2=10.871, P=0.001). The FLR-high group showed significant lower 5-year OS rates (41.2% vs 53.7%, log-rank=6.827, P=0.009) and 5-year DFS rates (35.3% vs 48.0%, log-rank=5.954, P=0.015) than the FLR-low group. Multivariate analyses suggested that high FLR was an independent negative predictor of OS (HR: 1.448, 95%CI: 1.073–1.952, P=0.015), DFS (HR: 1.445, 95%CI: 1.084–1.925, P=0.012) and first-year mortality (HR: 2.123, 95%CI: 1.157–3.898, P=0.015).Conclusion: The preoperative FLR level could be used as a simple, noninvasive, inexpensive, and potentially effective indicator to evaluate the prognosis of ESCC patients following radical esophagectomy.Keywords: esophageal squamous cell carcinoma, prognostic indicator, fibrinogen, lymphocyte

Al2O3/TiAl composites were successfully fabricated from powder mixtures of Ti, Al, TiO2, Cr2O3 and Nb2O5 by a hot-press-assisted exothermic dispersion method. The effect of the Cr2O3 and Nb2O5 addition on the microstructures and mechanical properties of Al2O3/TiAl composites was characterized. The results showed that the specimens are mainly composed of TiAl, Ti3Al, Al2O3, NbAl3 and Cr2Al. The Vicker-hardness and density of Al2O3/TiAl composites increase gradually with the increase of Nb2O5 content. When the Nb2O5 content was 6.54 wt %, the flexural strength and fracture toughness of the composites have a maximum values of 789.79 MPa and 9.69 MPa•m1/2, respectively. The improvement of mechanical properties is discussed in detail.

Abstract Motivation Retrosynthesis planning poses a formidable challenge in the organic chemical industry, particularly in pharmaceuticals. Single-step retrosynthesis prediction, a crucial step in the planning process, has witnessed a surge in interest in recent years due to advancements in AI for science. Various deep learning-based methods have been proposed for this task in recent years, incorporating diverse levels of additional chemical knowledge dependency. Results This paper introduces UAlign, a template-free graph-to-sequence pipeline for retrosynthesis prediction. By combining graph neural networks and Transformers, our method can more effectively leverage the inherent graph structure of molecules. Based on the fact that the majority of molecule structures remain unchanged during a chemical reaction, we propose a simple yet effective SMILES alignment technique to facilitate the reuse of unchanged structures for reactant generation. Extensive experiments show that our method substantially outperforms state-of-the-art template-free and semi-template-based approaches. Importantly, our template-free method achieves effectiveness comparable to, or even surpasses, established powerful template-based methods. Scientific contribution We present a novel graph-to-sequence template-free retrosynthesis prediction pipeline that overcomes the limitations of Transformer-based methods in molecular representation learning and insufficient utilization of chemical information. We propose an unsupervised learning mechanism for establishing product-atom correspondence with reactant SMILES tokens, achieving even better results than supervised SMILES alignment methods. Extensive experiments demonstrate that UAlign significantly outperforms state-of-the-art template-free methods and rivals or surpasses template-based approaches, with up to 5% (top-5) and 5.4% (top-10) increased accuracy over the strongest baseline.

Understanding the function of sleep requires studying the dynamics of brain activity across whole-night sleep and their transitions. However, current gold standard polysomnography (PSG) has limited spatial resolution to track brain activity. Additionally, previous fMRI studies were too short to capture full sleep stages and their cycling. To study whole-brain dynamics and transitions across whole-night sleep, we used an unsupervised learning approach, the Hidden Markov model (HMM), on two-night, 16 hr fMRI recordings of 12 non-sleep-deprived participants who reached all PSG-based sleep stages. This method identified 21 recurring brain states and their transition probabilities, beyond PSG-defined sleep stages. The HMM trained on one night accurately predicted the other, demonstrating unprecedented reproducibility. We also found functionally relevant subdivisions within rapid eye movement (REM) and within non-REM 2 stages. This study provides new insights into brain dynamics and transitions during sleep, aiding our understanding of sleep disorders that impact sleep transitions.

BackgroundOASL (Oligoadenylate Synthetase-Like), an interferon-induced protein in the OAS family, plays a significant role in anti-viral response. Studies have demonstrated its association with prognosis of certain tumors. However, the mechanism through which OASL affects tumors is unclear. A systemic pan-cancer study of OASL needs to be illustrated.MethodsAnalysis of OASL expression across 33 tumors was conducted utilizing TCGA, GTEx and CPTAC databases. COX and Log-Rank regressions were employed to calculate the prognosis. We validated the impact of OASL on apoptosis, migration, and invasion in pancreatic cancer cell lines. Moreover, we employed seven algorithms in bulk data to investigate the association of OASL expression and immune cell infiltration within tumor immune microenvironment (TIME) and ultimately validated at single-cell transcriptome level.ResultsWe discovered elevated expression of OASL and its genetic heterogeneity in certain tumors, which link closely to prognosis. Validation experiments were conducted in PAAD and confirmed these findings. Additionally, OASL regulates immune checkpoint ligand such as programmed death ligand 1 (PD-L1), through IFN-γ/STAT1 and IL-6/JAK/STAT3 pathways in tumor cells. Meanwhile, OASL affects macrophages infiltration in TIME. By these mechanisms OASL could cause dysfunction of cytotoxic T lymphocytes (CTLs) in tumors.DiscussionMulti-omics analysis reveals OASL as a prognostic and immunological biomarker in pan-cancer.

Abstract As the world's first oral nuclear export inhibitor, selinexor is increasingly being used in clinical applications for malignant tumors. However, there is no extensive exploration on selinexor's adverse events (ADEs), necessitating a real-word assessment of its clinical medication safety. FAERS data (July 2019–June 2023) were searched for selinexor ADE reports across all indications. Use the system organ class (SOC) and preferred terms (PT) from the medical dictionary for regulatory activities (MedDRA) to describe, categorize, and statistic ADEs. Disproportionality analysis was employed through calculation of reporting odds ratio (ROR) and proportional reporting ratio (PRR). Based on total of 4392 selinexor related ADE reports as the primary suspect (PS), of which 2595 instances were severe outcomes. The predominant ADEs included gastrointestinal disorders, myelosuppression symptoms, and various nonspecific manifestations. 124 signals associated with selinexor ADE were detected, and 10 of these top 15 signals were not included into the instructions. Our study provides real-world evidence regarding the drug safety of selinexor, which is crucial for clinicians to safeguard patients’ health.

Abstract Background Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH. Methods We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug’s water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes’ surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug’s impact on AML targets. Results We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells. Conclusion The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy.

Abstract The high sequencing error rate has impeded the application of long noisy reads for diploid genome assembly. Most existing assemblers failed to generate high-quality phased assemblies using long noisy reads. Here, we present PECAT, a Phased Error Correction and Assembly Tool, for reconstructing diploid genomes from long noisy reads. We design a haplotype-aware error correction method that can retain heterozygote alleles while correcting sequencing errors. We combine a corrected read SNP caller and a raw read SNP caller to further improve the identification of inconsistent overlaps in the string graph. We use a grouping method to assign reads to different haplotype groups. PECAT efficiently assembles diploid genomes using Nanopore R9, PacBio CLR or Nanopore R10 reads only. PECAT generates more contiguous haplotype-specific contigs compared to other assemblers. Especially, PECAT achieves nearly haplotype-resolved assembly on B. taurus (Bison×Simmental) using Nanopore R9 reads and phase block NG50 with 59.4/58.0 Mb for HG002 using Nanopore R10 reads.

BackgroundThe treatment of multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) remains challenging due to the limited availability of effective drugs. Linezolid has emerged as a promising therapeutic option for these cases. However, its long-term use can lead to complications such as peripheral and optic neuropathies. Acupuncture, a cornerstone of traditional Chinese medicine, has been shown to be effective in the treatment of peripheral neuropathy (PN). This study examines the potential benefits of acupuncture in the treatment of linezolid-induced peripheral neuropathy (LIPN).MethodsFour patients, aged 27 to 60 years, diagnosed with LIPN, underwent daily acupuncture treatments. The main endpoint was to assess the efficacy of acupuncture in reducing neuropathic pain associated with LIPN in patients. This was primarily measured using changes in the Short Form McGill Pain Questionnaire (SF-MPQ) scores before and after acupuncture treatment.ResultsThree of the patients experienced significant symptom remission, while one experienced marginal improvement. Treatments ranged from 7 to 18 sessions. Specifically, the first patient reported substantial relief with a score reduction from 33 to 13; the second patient observed minimal change; the third patient’s score decreased dramatically from 10 to 2 after eight sessions; the last patient had a score reduction from 21 to 12 after five sessions, but did not continue treatment for a second assessment.ConclusionAcupuncture is a promising therapeutic approach for LIPN. However, larger and more thorough studies are needed to determine its full potential.

Congenital disorder of glycosylation type Ia (CDG-Ia) is an autosomal recessive genetic disease caused by a mutation in the phosphomannomutase 2 (PMM2) gene. We have identified a 13-month-old boy who has been diagnosed with CDG-Ia. He displays several characteristic symptoms, including cerebellar hypoplasia, severe developmental retardation, hypothyroidism, impaired liver function, and abnormal serum ferritin levels. Through whole-exome sequencing, we discovered novel complex heterozygous mutations in the PMM2 gene, specifically the c.663C > G (p.F221L) mutation and loss of exon 2. Further analysis revealed that the enzymatic activity of the mutant PMM2 protein was significantly reduced by 44.97% (p

Objective: To effectively solve the difficulty of observing the electron microstructure of samples with high water content. Methods: A series of samples with high water content were observed by conventional scanning electron microscope with a new mode instrument combination of semiconductor cold cooling table. Results: Under the conditions of conductive tape as matrix, voltage 5 kV, electron beam spot of 50 or 60, and cold table temperature of 4 ℃, the sample with high water content did not need to be fixed and dehydrated, and its microstructure could be directly imaged under the scanning electron microscope to observe its microstructure. The microstructure of the sample hadd no deformation phenomena such as shrinkage, stretching and distortion, which could reflect the original appearance of the sample more realistically. Conclusion: The new mode of free combination of conventional scanning electron microscope with semiconductor cold cooling table is an effective means to solve the microstructure observation of high water content samples, and is an economical, cost-effective and widely adaptable mode.

Abstract Private universities play an important role in many countries worldwide. Approximately one-third of university students worldwide are enrolled in private universities. In countries with a large proportion of private universities, the quality of private universities determines the quality of higher education in the country as a whole. In some developed countries, the quality is high; however, in most developing countries, the quality of private universities is significantly lower than that of public universities. In many countries, private universities are managed in either a “not-for-profit” or a “for-profit” manner. The management type of private universities that best supports high-quality development has become an important issue in the field of higher education in many developing countries, but there are only a few related quantitative studies. Taking one private university in China as an example, this study aims to reveal the path that best supports high-quality development for a private university regarding the choice between the not-for-profit and for-profit orientations. Based on a literature review, a system dynamics model of development for private universities is developed, and the case data are simulated and analyzed based on the model. It is concluded that the rapid development path with a not-for-profit orientation, which enjoys government financial allocation, is more conducive to the high-quality development of private universities. Finally, the study proposes the strategies of encouraging private universities to choose the not-for-profit orientation, increasing government investment in not-for-profit private universities, and strengthening the financial supervision of not-for-profit private universities to promote their high-quality development.

Abstract Citrus melanose, caused by Diaporthe citri, is one of the most important and widespread fungal diseases of citrus. Previous studies demonstrated that the citrus host was able to trigger the defense response to restrict the spread of D. citri. However, the molecular mechanism underlying this defense response has yet to be elucidated. Here, we used RNA-Seq to explore the gene expression pattern at the early (3 days post infection, dpi) and late (14 dpi) infection stages of citrus leaves in response to D. citri infection, and outlined the differences in transcriptional regulation associated with defense responses. The functional enrichment analysis indicated that the plant cell wall biogenesis was significantly induced at the early infection stage, while the callose deposition response was more active at the late infection stage. CYP83B1 genes of the cytochrome P450 family were extensively induced in the callus deposition-mediated defense response. Remarkably, the gene encoding pectin methylesterase showed the highest upregulation and was only found to be differentially expressed at the late infection stage. Genes involved in the synthesis and regulation of phytoalexin coumarin were effectively activated. F6’H1 and S8H, encoding key enzymes in the biosynthesis of coumarins and their derivatives, were more strongly expressed at the late infection stage than at the early infection stage. Collectively, our study profiled the response pattern of citrus leaves against D. citri infection and provided the transcriptional evidence to support the defense mechanism.

In traditional cardiac ultrasound diagnostics, the process of planning scanning paths and adjusting the ultrasound window relies solely on the experience and intuition of the physician, a method that not only affects the efficiency and quality of cardiac imaging but also increases the workload for physicians. To overcome these challenges, this study introduces a robotic system designed for autonomous cardiac ultrasound scanning, with the goal of advancing both the degree of automation and the quality of imaging in cardiac ultrasound examinations. The system achieves autonomous functionality through two key stages: initially, in the autonomous path planning stage, it utilizes a camera posture adjustment method based on the human body’s central region and its planar normal vectors to achieve automatic adjustment of the camera’s positioning angle; precise segmentation of the human body point cloud is accomplished through efficient point cloud processing techniques, and precise localization of the region of interest (ROI) based on keypoints of the human body. Furthermore, by applying isometric path slicing and B-spline curve fitting techniques, it independently plans the scanning path and the initial position of the probe. Subsequently, in the autonomous scanning stage, an innovative servo control strategy based on cardiac image edge correction is introduced to optimize the quality of the cardiac ultrasound window, integrating position compensation through admittance control to enhance the stability of autonomous cardiac ultrasound imaging, thereby obtaining a detailed view of the heart’s structure and function. A series of experimental validations on human and cardiac models have assessed the system’s effectiveness and precision in the correction of camera pose, planning of scanning paths, and control of cardiac ultrasound imaging quality, demonstrating its significant potential for clinical ultrasound scanning applications.

Quantitative structure-activity relationship (QSAR) is a cost-effective solution to directly and accurately estimating the environmental safety thresholds (ESTs) of pollutants in the ecological risk assessment due to the lack of toxicity data. In this study, QSAR models were developed for estimating the Predicted No-Effect Concentrations (PNECs) of petroleum hydrocarbons and their derivatives (PHDs) under dietary exposure, based on the quantified molecular descriptors and the obtained PNECs of 51 PHDs with given acute or chronic toxicity concentrations. Three high-reliable QSAR models were respectively developed for PHDs, aromatic hydrocarbons and their derivatives (AHDs), and alkanes, alkenes and their derivatives (ALKDs), with excellent fitting performance evidenced by high correlation coefficient (0.89–0.95) and low root mean square error (0.13–0.2 mg/kg), and high stability and predictive performance reflected by high internal and external verification coefficient (Q2LOO, 0.66–0.89; Q2F1, 0.62–0.78; Q2F2, 0.60–0.73). The investigated quantitative relationships between molecular structure and PNECs indicated that 18 autocorrelation descriptors, 3 information index descriptors, 4 barysz matrix descriptors, 6 burden modified eigenvalues descriptors, and 1 BCUT descriptor were important molecular descriptors affecting the PNECs of PHDs. The obtained results supported that PNECs of PHDs can be accurately estimated by the influencing molecular descriptors and the quantitative relationship from the developed QSAR models, that provided a new feasible solution for ESTs derivation in the ecological risk assessment.

Abstract The concept of lateral optical force (LOF) is of general interest in optical manipulation as it releases the constraint of intensity gradient in tightly focused light, yet such a force is normally limited to exotic materials and/or complex light fields. Here, we report a general and controllable LOF in a nonchiral elongated nanoparticle illuminated by an obliquely incident plane wave. Through computational analysis, we reveal that the sign and magnitude of LOF can be tuned by multiple parameters of the particle (aspect ratio, material) and light (incident angle, direction of linear polarization, wavelength). The underlying physics is attributed to the multipolar interplay in the particle, leading to a reduction in symmetry. Direct experimental evidence of switchable LOF is captured by polarization-angle-controlled manipulation of single Ag nanowires using holographic optical tweezers. This work provides a minimalist paradigm to achieve interface-free LOF for optomechanical applications, such as optical sorting and light-driven micro/nanomotors.

Bistatic interferometric Synthetic Aperture Radar (SAR) overcomes the baseline length limit of the configuration of single-station interferometric SAR with two antennas and has become the primary method of terrain mapping using spaceborne interferometric SAR. To reduce the cost of surveying and mapping while promoting the development and application of Unmanned Aerial Vehicle (UAV)-borne bistatic interferometric SAR, the Aerospace Information Research Institute, Chinese Academy of Sciences took the lead in designing and developing a UAV-borne bistatic interferometric SAR processing system and performed flight experiments at Bailing Airport in Inner Mongolia. Herein, the system design, composition, and performance are introduced, and the scheme and implementation of the first flight experiment, along with the preliminary data processing results, are presented. In addition, the key performance metrics of the system, such as 0.5 m-elevation measurement accuracy, are verified in this study. The system serves as a foundation for future research topics, such as distributed InSAR using a multiaviation platform and tomography data acquisition and processing.

Abstract Long single-molecular sequencing technologies, such as PacBio circular consensus sequencing (CCS) and nanopore sequencing, are advantageous in detecting DNA 5-methylcytosine in CpGs (5mCpGs), especially in repetitive genomic regions. However, existing methods for detecting 5mCpGs using PacBio CCS are less accurate and robust. Here, we present ccsmeth, a deep-learning method to detect DNA 5mCpGs using CCS reads. We sequence polymerase-chain-reaction treated and M.SssI-methyltransferase treated DNA of one human sample using PacBio CCS for training ccsmeth. Using long (≥10 Kb) CCS reads, ccsmeth achieves 0.90 accuracy and 0.97 Area Under the Curve on 5mCpG detection at single-molecule resolution. At the genome-wide site level, ccsmeth achieves >0.90 correlations with bisulfite sequencing and nanopore sequencing using only 10× reads. Furthermore, we develop a Nextflow pipeline, ccsmethphase, to detect haplotype-aware methylation using CCS reads, and then sequence a Chinese family trio to validate it. ccsmeth and ccsmethphase can be robust and accurate tools for detecting DNA 5-methylcytosines.

Ginkgolic acid is a natural plant antifungal substance with important biological activities, present in the testa of Ginkgo biloba. This research aims to analyse the antifungal action of ginkgolic acid against pathogenic fungi. Ginkgolic acid was analyzed by HPLC and FTIR, and the in vitro inhibitory activities of ginkgolic acid against pathogenic fungi has been investigated. Results showed that ginkgolic acid was a small hydrophobic molecule composed of five ginkgolic acids and their derivatives, with the alkyl and phenolic hydroxyl groups being located on the skeleton of the aromatic ring. Among Nigrospora oryzae (N. oryzae), Alternaria alternata (A. alternata) and Penicillium expansum (P. expansum), ginkgolic acid showed the strongest inhibition against N. oryzae, and the inhibition rate of ginkgolic acid at 5 mg · mL-1 reached 65.82%. Ginkgolic acid lysed the cell membrane of N. oryzae, causing the leaking of the mycelial protein and enhancement of the permeability of the cell membrane, which caused the electrical conductivity of the liquid medium to increase. In addition, it also decreased the activities of superoxide dismutase and catalase in the mycelium of N. oryzae, thereby weakening the cell’s protective function by damaging the integrity of the biomembrane. Furthermore, ginkgolic acid can effectively protect the leaves of Epipremnum aureum from infection by N. oryzae. It was concluded that ginkgolic acid effectively inhibited the activity of N. oryzae.

BackgroundThymectomy is an efficient and standard treatment strategy for patients with myasthenia gravis (MG), postoperative myasthenic crisis (POMC) is the major complication related to thymectomy and has a strongly life-threatening effect. As a biomarker, whether the bilirubin level is a risk factor for MG progression remains unclear. This study aimed to investigate the association between the preoperative bilirubin level and postoperative myasthenic crisis (POMC).MethodsWe analyzed 375 patients with MG who underwent thymectomy at Tangdu Hospital between January 2012 and September 2021. The primary outcome measurement was POMC. The association between POMC and bilirubin level was analyzed by restricted cubic spline (RCS). Indirect bilirubin (IBIL) was divided into two subgroups based on the normal upper limit of IBIL, 14 μmol/L.ResultsCompared with non–POMC group, IBIL levels were significantly higher in patients with POMC. Elevated IBIL levels were closely associated with an increased risk of POMC (p for trend = 0.002). There was a dose-response curve relationship between IBIL levels and POMC incidence (p for non–linearity = 0.93). However, DBIL levels showed a U-shaped association with POMC incidence. High IBIL level (≥14 μmol/L) was an independent predictive factor for POMC [odds ratio = 3.47, 95% confidence interval (CI): 1.56–7.8, p = 0.002]. The addition of high IBIL levels improved the prediction model performance (net reclassification index = 0.186, 95% CI: 0.039–0.334; integrated discrimination improvement = 0.0345, 95% CI: 0.005–0.065).ConclusionHigh preoperative IBIL levels, especially those exceeding the normal upper limit, could independently predict the incidence of POMC.

Introduction: Risk of adverse effects and exacerbation in autoimmune neurological conditions (ANC)are frequently cited reasons for COVID-19 vaccine hesitancy. This study evaluates the ANC safety of COVID-19 vaccines in the real world. Methods: Electronic databases were searched to identify studies reporting the use of the COVID-19 vaccine in ANC. We selected studies that provided data on adverse effects and worsening conditions related to ANC after vaccination. The pooled incidence rates for various adverse effects, stratified for the disease category, dosage, and type of vaccine, were estimated. Results: Twenty-eight studies (31 vaccination cohorts) were included. The pooled incidence rate of general adverse events was 0.35 (95%CI, 0.27–0.43, I2 = 100 %). The pooled incidence rates of local injection reaction, fatigue, weakness, myalgia, fever, headache, and chills were 0.27 (0.18–0.36, I2 = 98 %), 0.16(0.11–0.21, I2 = 93 %), 0.15(0.00–0.31, I2 = 97 %), 0.13(0.08–0.19, I2 = 97 %), 0.11(0.07–0.15, I2 = 95 %), 0.11(0.07–0.16, I2 = 97 %), and 0.09 (0.03–0.16, I2 = 96 %), respectively. The pooled incidence rate of exacerbation adverse events was 0.05 (95%CI, 0.04–0.07, I2 = 84 %). Conclusion: According to available evidence, the administration of COVID-19 vaccines in individuals with autoimmune neurological disorders seems well-tolerated, with few reports of adverse events. Furthermore, exacerbation of autoimmune neurological conditions following vaccination appears to be infrequent.

Spallation behaviour of TC4 titanium alloy under laser irradiation was investigated in our work. Here we present numerical and experimental study methods including X-ray diffraction (XRD) and a scanning electron microscope (SEM) with the particular laser shock conditions. Experiments have been manipulated by laser pulses with reconfigurable laser parameters of thin foils of TC4 titanium alloy. The experimental results show the spallation behaviour on the surface of TC4 titanium alloy, which reveals the underlying relation between the dynamic failure of materials and the laser parameters. The spallation mechanism of TC4 titanium alloy were determined by fitting the numerical simulations to the experimental data. The results could have important implications for the modification of TC4 titanium alloy. [ABSTRACT FROM AUTHOR]

Abstract Background N6-methyladenosine (m6A) modification has been recognized to play fundamental roles in the development of autoimmune diseases. However, the implication of m6A modification in myasthenia gravis (MG) remains largely unknown. Thus, we aimed to systematically explore the potential functions and related immune characteristics of m6A regulators in MG. Methods The GSE85452 dataset with MG and healthy samples was downloaded from Gene Expression Omnibus (GEO) database. m6A modification regulators were manually curated. The targets of m6A regulators were obtained from m6A2Target database. The differential expressed m6A regulators in GSE85452 dataset were identified by “limma” package and were validated by RT-PCR. Function enrichment analysis of dysregulated m6A regulators was performed using “clusterProfiler” package. Correlation analysis was applied for analyzing the relationships between m6A regulators and immune characteristics. Unsupervised clustering analysis was used to identify distinct m6A modification subtypes. The differences between subtypes were analyzed, including the expression level of all genes and the enrichment degree of immune characteristics. Weighted gene co-expression network analysis (WGCNA) was conducted to obtain modules associated with m6A modification subtypes. Results We found that CBLL1, RBM15 and YTHDF1 were upregulated in MG samples of GSE85452 dataset, and the results were verified by RT-PCR in blood samples from19 MG patients and 19 controls. The targeted genes common modified by CBLL1, RBM15, and YTHDF1 were mainly enriched in histone modification and Wnt signaling pathway. Correlation analysis showed that three dysregulated m6A regulators were closely associated with immune characteristics. Among them, RBM15 possessed the strongest correlation with immune characteristics, including CD56dim natural killer cell (r = 0.77, P = 0.0023), T follicular helper cell (r = − 0.86, P = 0.0002), Interferon Receptor (r = 0.78, P = 0.0017), and HLA-DOA (r = 0.64, P = 0.0200). Further two distinct m6A modification patterns mediated by three dysregulated m6A regulators was identified. Bioinformatics analysis found that there were 3029 differentially expressed genes and different immune characteristics between two m6A modification patterns. Finally, WGCNA analysis obtained a total of 12 modules and yellow module was the most positively correlated to subtype-2. Conclusion Our findings suggested that m6A RNA modification had an important effect on immunity molecular mechanism of MG and provided a new perspective into understanding the pathogenesis of MG.

IntroductionOAS1(2’-5’-oligoadenylate synthetase 1) is a member of the Interferon-Stimulated Genes which plays an important role in the antiviral process. In recent years, the role of OAS1 in tumors has attracted attention, and it was found to be associated with prognosis in several tumors. However, the mechanism by which OAS1 affects tumors is unclear and pan-cancer study of OAS1 is necessary to better understand its implication in cancers.MethodsThe expression, prognostic value, genetic alteration, alternative splicing events of OAS1 in pan-cancers were analyzed using TCGA, GTEx, HPA, GEPIA and OncoSplicing databases. OAS1 associated immune cell infiltration was evaluated using the ESTIMATE, xCell, CIBERSORT and QUANTISEQ algorithm. Single cell transcriptome data download using TISH database. Finally, the roles of the OAS1 on apoptosis, migration and invasion were investigated in two pancreatic cancer cells.ResultsOur results revealed significant differences in OAS1 expression among various tumors, which had prognostic implications. In addition, we investigated the impact of OAS1 on genomic stability, methylation status, and other factors across different types of cancer, and the effects of these factors on prognosis. Notably, our study also demonstrated that OAS1 overexpression can contribute to CTL dysfunction and macrophage M2 polarization. In addition, cell experiments showed that the knockdown of OAS1 could reduce the invasive ability and increased the apoptosis rate of PAAD cells.DiscussionThese results confirmed that OAS1 could be a prognostic biomarker and therapeutic target for its potential role in CTL dysfunction and macrophage M2 polarization.