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Xi-Zheng Li, Yu-Wen Yan, Hui-Zhong Zhang, Yan Zhang School of Nursing and Health, Zhengzhou University, Zhengzhou City, Henan Province, 450001, People’s Republic of ChinaCorrespondence: Yan Zhang, School of Nursing and Health, Zhengzhou University, No.101 Science Avenue, High Tech Zone, Zhengzhou City, Henan Province, 450001, People’s Republic of China, Tel +86 13613804836, Email zhangyanmy@126.comAbstract: Nurses are the largest group in the health care system. The current care shortage remains a global challenge in the healthcare system.The accelerated second-degree nursing (ABSN) program was first proposed by the University of St.Louis in 1971 and then vigorously developed in the United States. Its purpose is to train more nursing talents to solve the medical needs of the poor in the United States. In the past few decades, this project has been carried out by many countries around the world to solve their domestic nursing problems.As a strategy to address severe care shortages, ABSN is continuing to increase rapidly.China as the world’s second most populous country, coupled with aging year by year, the demand for nursing talents, and the ABSN project just gave China effective inspiration.Therefore, this article introduces the basic design of the bachelor’s degree in nursing at the University of Washington, summarizes the characteristics of the training model, and draws on experience from the basic situation, training objectives, courses and evaluation methods. It is urgent to provide guidance and reference for the acceleration of nursing education in China.Keywords: USA, education, nursing, BA, ABSN

Xiaohua Liu,1,2,* Yun Wang,3,* Daihui Peng,3 Huifeng Zhang,3,* Yanqun Zheng,1 Yan Wu,3 Yun-Ai Su,4 Ming Liu,5 Xiancang Ma,6 Yi Li,7 Jianfei Shi,8 Xiaojing Cheng,9 Han Rong,10 Yiru Fang2,3,11 1Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychiatry, Peking University Sixth Hospital, Peking, People’s Republic of China; 5Department of Psychiatry, Harbin First Specific Hospital, Harbin, People’s Republic of China; 6Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, People’s Republic of China; 7Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China; 8Department of Psychiatry, Hangzhou Seventh People’s Hospital, Hangzhou, People’s Republic of China; 9Department of Psychiatry, Shandong Mental Health Center, Shandong, People’s Republic of China; 10Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China; 11CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiru Fang; Daihui PengShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 South Wan Ping Road, Shanghai 200030, People’s Republic of ChinaEmail yirufang@aliyun.com pdhsh@126.comBackground: Major depressive disorder (MDD) is a heterogeneous mental disease that encompasses different subtypes and specifiers. Clinically targeted treatments have not been identified yet, although standardized strategies are recommended by several clinical guidelines. The main aim of this study is to respectively identify the precise treatment for three different subtypes of MDD (ie, melancholic, atypical, and anxious).Methods: An 8-to-12-week, multicenter randomized controlled trial (RCT) with a parallel group design will be conducted to determine the most effective and appropriate treatment. A total of 750 adults diagnosed with MDD will be recruited, categorized into melancholic, atypical or anxious type based on the assessment of the Inventory of Depressive Symptomatology (IDS30) and the Hamilton Anxiety Scale (HAMA), and 1:1 randomly assigned to different intervention groups. Blood draw, EEG test, and MRI scan will be performed at baseline and endpoint. Clinical symptom and side-effects will be evaluated at critical decision points (CDP) including weeks two, four, six, eight, and 12 after treatment. The primary outcome is total score and reduction rate of the 17-Hamilton Depression Rating Scale (17-HDRS). The secondary outcomes include the scores of the Quick Inventory of Depressive Symptomatology-self-report (QIDS-SR), IDS30, HAMA and the Treatment Emergent Symptom Scale (TESS). All the data will be analyzed by SAS software.Discussion: The study commenced recruitment in August 2017 and is currently ongoing.Trial Registration: ClinicalTrials.gov Identifier: NCT03219008 (July 17, 2017).Keywords: major depressive disorder, MDD, subtype, antidepressant, physical therapy, computerized cognitive behavioral treatment, cCBT, randomized controlled trial, RCT

Chun-Hua Wang,1,2,* Li-Li Liu,1,2,* Ding-Zhun Liao,3,* Mei-Fang Zhang,1,2 Jia Fu,1,2 Shi-Xun Lu,1,2 Shi-Lu Chen,1,2 Hong Wang,1,2 Shao-Hang Cai,1,2 Chris Zhiyi Zhang,1,2 Hui-Zhong Zhang,2 Jing-Ping Yun1,2 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; 2Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; 3Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China *These authors contributed equally to this work Introduction: Prenylated Rab acceptor 1 domain family member 2 (PRAF2), a novel oncogene, has been shown to be essential for the development of several human cancers; however, its role in hepatocellular carcinoma (HCC) remains unclear. Materials and methods: PRAF2 mRNA and protein expressions were examined in fresh tissues by quantitative reverse transcription-polymerase chain reaction and Western blot, respectively, and in 518 paraffin-embedded HCC samples by immunohistochemistry. The correlation of PRAF2 expression and clinical outcomes was determined by the Student’s t-test, Kaplan–Meier test, and multivariate Cox regression analysis. The role of PRAF2 in HCC was investigated by cell viability, colony formation, and migration assays in vitro and with a nude mouse model in vivo. Results: In our study, the PRAF2 expression was noticeably increased in HCC tissues at both the mRNA and protein levels compared with that of the nontumorous tissues. Kaplan–Meier analysis indicated that high PRAF2 expression was correlated with worse overall survival in a cohort of 518 patients with HCC. The prognostic implication of PRAF2 was verified by stratified survival analysis. The multivariate Cox regression model revealed PRAF2 as an independent poor prognostic factor for overall survival (hazard ratio = 1.244, 95% CI: 1.039–1.498, P

Wen-Zhuo He,1,* Qian-Kun Xie,1,* Wan-Ming Hu,2–4,* Peng-fei Kong,1 Lin Yang,1 Yuan-Zhong Yang,2 Chang Jiang,1 Chen-Xi Yin,1 Hui-Juan Qiu,1 Hui-Zhong Zhang,2 Bei Zhang,1 Liang-Ping Xia1 1VIP Region, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: The purpose of the present study was to examine the relationship among the number of negative lymph nodes (LNs), the local and systemic immune response, and survival in patients with colon cancer. Patients and methods: One thousand one hundred and fifty-seven patients with colon cancer who underwent surgery at Sun Yat-sen University Cancer Center between 2009 and 2014 were included. We examined negative LNs in relation to the local and systemic immune response, including percentage carcinoma, neutrophil and lymphocyte infiltration, Crohn’s-like reaction, neutrophil to lymphocyte ratio, platelets, and C-reactive protein (CRP). Disease-free survival and overall survival were also examined. We performed subgroup analysis based on the distribution of negative LNs. Results: An increased number of negative LNs was associated with greater neutrophil invasion (p=0.001), more lymphocyte invasion (p=0.001), and more Crohn’s-like reaction (p=0.001). No significant correlation was observed between negative LNs and the neutrophil to lymphocyte ratio. More than 12 negative LNs were associated with increased platelets and CRP levels. A higher number of negative LNs was independently associated with longer disease-free survival in stage I+II patients (p=0.004) and stage III patients (p=0.015), while negative LNs were also independent prognostic factors in stage IV patients (p=0.007). Conclusion: Our study suggests that negative LNs are indicators of the immune response and are associated with a better prognosis in patients with colon cancer. Keywords: colon cancer, negative lymph nodes, immune response, survival

Qian-Kun Xie,1,* Wen-Zhuo He,1,* Wan-Ming Hu,2–4 Lin Yang,1 Chang Jiang,1 Peng-Fei Kong,1 Yuan-Zhong Yang,2 Qiong Yang,1,5 Hui-Zhong Zhang,2 Bei Zhang,1 Liang-Ping Xia1 1VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; 2Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, SunYat-sen University Cancer Center, Guangzhou, China; 3Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; 4Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; 5Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, China *These authors contributed equally to this work Background: Although tumor-infiltrating lymphocytes (TILs) have been understood for years as a favorable prognostic factor for colorectal cancers (CRCs) after complete surgical resection, its prognostic role in metastatic CRC (mCRC) remains poorly defined, and it is largely unknown how this prognostic benefit relates to the metastatic status and operation modality. Materials and methods: After reviewing 2215 consecutive cases of surgically resected CRC, 332 patients newly diagnosed with stage IV CRC and treated at the Sun Yat-Sen University Cancer Center between 2009 and 2014 were included. H&E-stained (HES) slides from surgical specimens were evaluated for the extent of TILs. The primary end point was overall survival (OS). Cox proportional hazards regression was conducted to determine the prognostic significance of TILs. All statistical tests were 2-sided. Results: HES slides from primary tumor samples were evaluable for 302 of the 332 included cases. Among the 302 patients, 105 patients (34.8%) were classified as high TIL, the remaining 197 (65.2%) were defined as low TIL. In the univariate analysis, TILs were significantly associated with better OS (P=0.015). Multivariable analysis confirmed that high TIL strongly predicted better survival (hazard ratio =0.62, 95% CI: 0.44–0.89, P=0.008), independent of other patients’ clinicopathological characteristics. Stratified analysis revealed a prognostic benefit of high TIL for patients in the subgroup with non-oligometastatic disease (P=0.002), ≥2 metastatic organs (P=0.006), and non-metastasectomy (P=0.005). By contrast, oligometastatic disease, 1 metastatic organ, or metastasectomy fully abrogated the prognostic effect of TIL. Conclusion: Our findings indicate that the level of TILs can be used to predict the outcome for patients with mCRC; however, the operation modality and the metastatic status of patients should also be taken into account. Keywords: colorectal cancer, stage IV, tumor-infiltrating lymphocytes, metastatic status, survival

Longfei Yang,1,* Huanran Liu,2,* Min Long,1 Xi Wang,1 Fang Lin,1 Zhaowei Gao,1 Huizhong Zhang1 1Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi’an, China; 2Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China *These authors contributed equally to this work Background: Targeted therapies have been proven as promising in the treatment of breast cancer and have improved survival and quality of life in advanced breast cancer. We previously identified a novel peptide SA12 which showed significant activity in the inhibition of proliferation and induction of apoptosis in SKBr-3 cells. Methods: The present study investigated the potential antitumor role of SA12 in breast cancer cell lines MDA-MB-231 and MCF-7 through Cell Counting Kit-8 assay and colony formation assay, and examined the cell cycle distribution using flow cytometry analysis. Furthermore, the expression of cell cycle-related genes cyclin D1, CDK4, and tumor suppressor gene p16 were examined by real-time polymerase chain reaction and Western blot to explore the molecular mechanism. Results: We determined that peptide SA12 suppressed the proliferation of MDA-MB-231 and MCF-7 cell lines through the G0/G1 phase cell cycle arrest. Moreover, the expressions of cell cycle-associated genes cyclin D1 and CDK4 were downregulated and the expression of tumor suppressor gene p16 was upregulated after treatment with SA12. MECP2 was required for the enhanced expression of p16 gene induced by SA12, which further inhibits CDK4/CDK6 activation and arrests the cell cycle progression from G0/G1 to S phase.Conclusion: We concluded that SA-12 inhibits the proliferation of MCF-7 and MDA-MB-231 cells through G0/G1 cell cycle arrest. Cell cycle related genes cyclin D1, CDK4, and p16 participate in the process, and MECP2 is essential for the enhanced expression of p16 gene induced by SA-12. Keywords: SA12, breast cancer, G0/G1 arrest, cyclin D1, CDK4, p16

Hangzhou Zhang,1 Yu Sun,1 Ang Tian,2 Xiang Xin Xue,2 Lin Wang,1 Ali Alquhali,1 Xizhuang Bai1 1Department of Sports Medicine and Joint Surgery, First Affiliated Hospital of China Medical University, 2School of Materials and Metallurgy, Northeastern University, Shenyang, People's Republic of China Abstract: The goal for current orthopedic implant research is to design implants that have not only good biocompatibility but also antibacterial properties. TiO2 nanotubes (NTs) were fabricated on the titanium surface through electrochemical anodization, which added new properties, such as enhanced biocompatibility and potential utility as drug nanoreservoirs. The aim of the present study was to investigate the antibacterial properties and biocompatibility of NTs loaded with vancomycin (NT-V), both in vitro and in vivo. Staphylococcus aureus was used to study the antibacterial properties of the NT-V. There were three study groups: the commercially pure titanium (Cp-Ti) group, the NT group (nonloaded vancomycin), and the NT-V group. We compared NT-V biocompatibility and antibacterial efficacy with those of the NT and Cp-Ti groups. Compared with Cp-Ti, NT-V showed good antibacterial effect both in vitro and in vivo. Although the NTs reduced the surface bacterial adhesion in vitro, implant infection still developed in in vivo studies. Furthermore, the results also revealed that both NTs and NT-V showed good biocompatibility. Therefore, the NTs loaded with antibiotic might be potentially used for future orthopedic implants. Keywords: TiO2 nanotubes, biocompatibility, antibacterial properties, osteoblasts, vancomycin

Hongliang Sun,1 Linfeng Xu,1 Tianyuan Fan,2 Hongzhi Zhan,3 Xiaodong Wang,3 Yanfei Zhou,2 Ren-jie Yang3 1Department of Interventional Therapy, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 2Pharmacy School of Beijing University, Beijing, 3Department of Interventional Therapy, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China Background: The purpose of this study was to observe the effect and feasibility of hyperthermia and the influence of heat on surrounding organs in a VX2 rabbit liver model exposed to an alternating magnetic field after embolization with ferromagnetic nanoparticles. Methods: Forty rabbits containing implanted hepatic VX2 carcinomas were divided into four groups, each containing ten rabbits. Fourteen days after tumor transplantation, we opened the abdomen to observe the size and shape of the tumor. A transfemoral retrograde approach was then used for hepatic arterial catheterization in groups B, C, and D to perform angiography and embolization. The next day, three rabbits in group B and all rabbits in group D were exposed to an alternating magnetic field, and the temperature was recorded simultaneously in the center of the tumor, at the edge of the tumor, and in the normal liver parenchyma. On day 28, all animals was euthanized to observe changes in the implanted liver tumor and the condition of the abdomen. A pathologic examination was also done. Results: Before surgery, there was no significant difference in tumor volume between the four groups. Three different temperature points (center of the tumor, edge of the tumor, and in the normal liver parenchyma) of group B under an alternating magnetic field were 37.2°C ± 1.1°C, 36.8°C ± 1.2°C, and 36.9°C ± 2.1°C, none of which were significantly different from pretreatment values. Three points basal temperature in group D showed no significant difference (F = 1.038, P = 0.413). Seven to 26 minutes after hyperthermia, the temperature at the center of the tumor and at the edge of the tumor in group D was significantly different from the corresponding points in group B and from normal liver tissue in group D (FB–D center = 5.431, PB–D center = 0.041, FB–D edge = 9.744, PB–D edge = 0.011; FD = 8.379, PD = 0.002). The highest temperature recorded at the rim of the tumor was 46°C in group D. Fourteen days later, the tumor volume in the four groups was group A 31.4 ± 20.6 cm3, group B 26.7 ± 18.2 cm3, group C 28.7 ± 9.1 cm3, and group D 25.8 ± 13.9 cm3, with no significant difference found between the groups (F = 0.218, P = 0.883). The increase in tumor volume was greatest in group A and least in group D, while that in groups B and D was similar. Conclusion: It is feasible to treat a VX2 tumor in an alternating magnetic field after embolization with magnetic nanoparticles without a significant effect on the surrounding normal liver parenchyma. Keywords: hyperthermia, ferromagnetic nanoparticles, Lipiodol®, hepatocellular carcinoma, animal model

Under the assumption that a quark-gluon plasma (QGP) droplet is produced and its evolution can be described by hydrodynamics in p+A collisions, γ-triggered hadron spectra are studied within a next-to-leading-order perturbative QCD parton model with the medium-modified parton fragmentation functions. The initial conditions and space-time evolution of the small QGP droplet are provided by the superSONIC hydrodynamic model simulations and parton energy loss in such a medium is described by the high-twist (HT) approach. The range of scaled jet transport coefficient q0/T03 in this HT approach is extracted from single hadron suppression in A+A collisions with similar initial medium temperature as in p+A collisions. Numerical results for this scenario show that γ-hadron spectra at pTγ=12-40GeV/c are suppressed by 5-15% in the most central 0-10% p+Pb collisions at sNN=5.02 TeV. The suppression becomes weaker at higher transverse momentum of the γ trigger. As a comparison, γ-hadron suppression in Pb+Pb collisions at sNN=2.76 and 5.02 TeV is also predicted.

Heavy-ion collisions at very high colliding energies are expected to produce a quark-gluon plasma (QGP) at the highest temperature obtainable in a laboratory setting. Experimental studies of these reactions can provide an unprecedented range of information on properties of the QGP at high temperatures. We report theoretical investigations of the physics perspectives of heavy-ion collisions at a future high-energy collider. These include initial parton production, collective expansion of the dense medium, jet quenching, heavy-quark transport, dissociation and regeneration of quarkonia, photon and dilepton production. We illustrate the potential of future experimental studies of the initial particle production and formation of QGP at the highest temperature to provide constraints on properties of strongly interaction matter.

Purpose: To study the additional value of FRONSAC encoding in 2D and 3D wave sequences, implementing a simple strategy to trajectory mapping for FRONSAC encoding gradients., Theory and Methods: The nonlinear gradient trajectory for each voxel was estimated by exploiting the sparsity of the point spread function in the frequency domain. Simulations and in-vivo experiments were used to analyze the performance of combinations of wave and FRONSAC encoding., Results: Field mapping using the simplified approach produced similar image quality with much shorter calibration time than the comprehensive mapping schemes utilized in previous work. In-vivo human brain images showed that the addition of FRONSAC encoding could improve wave image quality, particularly at very high undersampling factors and in the context of limited wave amplitudes. These results were further supported by g-factor maps., Conclusion: Results show that FRONSAC can be used to improve image quality of wave at very high undersampling rates or in slew-limited acquisitions. Our study illustrates the potential of the proposed fast field mapping approach., (© 2024 International Society for Magnetic Resonance in Medicine.)

Objective: To study the clinicopathological features, immunohistochemical phenotypes, molecular changes, differential diagnosis and prognosis of isolated intraductal carcinoma of the prostate (iIDC-P). Methods: Three iIDC-P cases were collected retrospectively from 2016 to 2022 at Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinicopathologic features and immunophenotypic profiles were studied using light microscopy and immunohistochemistry. A targeted next-generation sequencing panel was used to analyze cancer-associated mutations. Follow-up and literature review were also performed. Results: The patients' ages were 61, 67 and 77 years, and their preoperative prostate specific antigen (PSA) levels were 7.99, 7.99 and 4.86 μg/L, respectively. Case 1 and 2 were diagnosed on needle biopsy and radical prostatectomy (RP) specimens, and case 3 was diagnosed on a specimen of transurethral resection of the prostate (TURP). The RP specimen was entirely submitted for histologic examination. In the case 1, iIDC-P was found in one tissue core (involving two ducts) in the biopsy specimen, and in 6 sections (diameter, 0.3-1.1 cm) from the radical prostatectomy specimen, and one section had separate foci of low-grade acinar adenocarcinoma (diameter, 0.05 cm). In the case 2, 6 tissue sections from the biopsy specimens showed iIDC-P, and 13 sections from RP specimen showed iIDC-P (diameter, 0.5-1.6 cm), and the other 3 sections had separate low grade acinar adenocarcinoma (diameter, 0.6 cm). In the case 3, 5 tissue blocks from the TURP specimen showed iIDC-P. The case 1 and 2 showed solid architecture with expansile proliferation of neoplastic cells in native ducts and acini. The case 3 showed dense or loose cribriform pattern, with marked cytological atypia, and frequent mitotic figures. Comedonecrosis was found in solid or dense cribriform glands in the case 2. Immunohistochemically, surrounding basal cells were highlighted using high-molecular-weight cytokeratin (34βE12 and CK5/6) and p63, while P504s was positive in the tumor cells. The tumor cells were also positive for AR and prostate markers (NKX3.1, PSA and PSAP), and negative for GATA3. The iIDC-P and acinar adenocarcinoma both showed weak PTEN expression and no ERG (nuclear) expression. In case 2 and 3, targeted sequencing revealed activated oncogenic driver mutations in MAPK and PI3K pathway genes (KRAS, MTOR and PTEN). In addition, pathogenic mutation in TP53 and FOXA1 mutation were found in the case 2 and 3, respectively. No case demonstrated TMPRSS2::ERG translocation. All cases were microsatellite stable and had lower tumor mutation burdens (range, 2.1-3.1 muts/Mb). The patients showed no biochemical recurrence or metastasis after follow-up of 16-91 months. Conclusions: iIDC-P is a special type of intraductal carcinoma of the prostate and differs from intraductal carcinoma within high-grade prostate cancer. iIDC-P has unique molecular characteristics and may represent as a molecularly unique in situ tumor of prostate cancer.

Background: This study investigates the efficacy and safety of bridging intravenous thrombolysis (IVT) before endovascular therapy (EVT) compared with EVT alone in patients with large infarction core., Methods: We conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library from January 2015 to June 2024. Included studies involved patients with acute ischemic stroke with an Alberta Stroke Program Early CT Score of ≤5 or an ischemic core volume of ≥50 mL. Studies were required to provide either 90-day modified Rankin Scale (mRS) score, reperfusion, symptomatic intracranial hemorrhage (sICH), or 90-day mortality., Results: Nine observational studies with 2641 patients were analyzed. The IVT+EVT group had a higher rate of 90-day functional independence (mRS 0-2; OR 1.56, 95% CI 1.31 to 1.87; adjusted OR (aOR) 1.43, 95% CI 1.21 to 1.68) and 90-day functional outcome (mRS 0-3; OR 1.34, 95% CI 1.11 to 1.62; aOR 1.18, 95% CI 1.02 to 1.37) compared with EVT alone. There was no significant difference in successful reperfusion (OR 1.01, 95% CI 0.62 to 1.64; aOR 1.07, 95% CI 0.74 to 1.54) and 90-day mortality (OR 0.86, 95% CI 0.73 to 1.02; aOR 0.89, 95% CI 0.77 to 1.04) between the two groups. Moreover, patients who received IVT+EVT had a higher rate of sICH (OR 1.30, 95% CI 1.03 to 1.64; aOR 2.21, 95% CI 1.22 to 4.01)., Conclusions: In patients with large infarction core, bridging IVT before EVT is associated with favorable functional outcomes compared with EVT, even though bridging therapy entails a higher risk of sICH. Further trials are needed to confirm these findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic obstructive pulmonary disease (COPD) exacerbations accelerate loss of lung function and increased mortality. The complex nature of COPD presents challenges in accurately predicting and understanding frequent exacerbations. The present study aimed to assess the metabolic characteristics of the frequent exacerbation of COPD (COPD‑FE) phenotype, identify potential metabolic biomarkers associated with COPD‑FE risk and evaluate the underlying pathogenic mechanisms. An internal cohort of 30 stable patients with COPD was recruited. A widely targeted metabolomics approach was used to detect and compare serum metabolite expression profiles between patients with COPD‑FE and patients with non‑frequent exacerbation of COPD (COPD‑NE). Bioinformatics analysis was used for pathway enrichment analysis of the identified metabolites. Spearman's correlation analysis assessed the associations between metabolites and clinical indicators, while receiver operating characteristic (ROC) analysis evaluated the ability of metabolites to distinguish between two groups. An external cohort of 20 patients with COPD validated findings from the internal cohort. Out of the 484 detected metabolites, 25 exhibited significant differences between COPD‑FE and COPD‑NE. Metabolomic analysis revealed differences in lipid, energy, amino acid and immunity pathways. Spearman's correlation analysis demonstrated associations between metabolites and clinical indicators of acute exacerbation risk. ROC analysis demonstrated that the area under the curve (AUC) values for D‑fructose 1,6‑bisphosphate (AUC=0.871), arginine (AUC=0.836), L‑2‑hydroxyglutarate (L‑2HG; AUC=0.849), diacylglycerol (DG) (16:0/20:5) (AUC=0.827), DG (16:0/20:4) (AUC=0.818) and carnitine‑C18:2 (AUC=0.804) were >0.8, highlighting their discriminative capacity between the two groups. External validation results demonstrated that DG (16:0/20:5), DG (16:0/20:4), carnitine‑C18:2 and L‑2HG were significantly different between patients with COPD‑FE and those with COPD‑NE. In conclusion, the present study offers insights into early identification, mechanistic understanding and personalized management of the COPD‑FE phenotype.

Osteoarthritis (OA) is one of the leading causes of joint dysfunction and disability in the elderly, posing serious social problems and a huge socio-economic burden. Existing pharmacological treatments have significant drawbacks, and searching for an effective pharmacological intervention is an urgent priority. Recent studies have demonstrated the chondroprotective, anabolic, and anti-catabolic properties of avocado-soybean unsaponifiable (ASU), a natural plant extract made from avocado and soybean oils, consisting of the remainder of the saponified portion of the product that cannot be made into soap. The main components of ASU are phytosterols, beta-sitosterol, canola stanols, and soya stanols, which are rapidly incorporated into cells. Studies have confirmed the anti-inflammatory, antioxidant, and analgesic properties of phytosterols. ASU slows down the progression of OA primarily by inhibiting pathways involved in the development of OA disease. ASU prevents cartilage degradation by inhibiting the release and activity of matrix metalloproteinases and by increasing the tissue inhibition of these catabolic enzymes; ASU is also involved in the inhibition of the activation of nuclear factor κB (NF-κB) which is a transcriptional inhibitor that regulates the inflammatory response of chondrocytes. NF-κB is a transcription factor that regulates the inflammatory response of chondrocytes, and inhibition of the transfer of the transcription factor NF-κB from the cytoplasm to the nucleus regulates the transcription of many pro-inflammatory factors. By appealing to the mechanism of action and thus achieving anti-inflammatory, anti-catabolic, and pro-synthetic effects on cartilage tissues, AUS is clinically responsive to the reduction of acute pain and OA symptom progression. This paper aims to summarize the studies on the use of avocado-soybean unsaponifiable in the pharmacological treatment of osteoarticular., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Abstract: Sepsis-induced myocardial dysfunction commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. This study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. In addition, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NOD-like receptor protein-3 (NLRP3) upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for sepsis-induced myocardial dysfunction therapy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Slow-transmission constipation is a type of intractable constipation with unknown etiology and unclear pathogenesis., Objective: The intention of this study was to evaluate the therapeutic effect and possible mechanism of Modified Zhizhu Pills on loperamide-induced slow transit constipation., Methods: The effects of the Modified Zhizhu Pill were evaluated in a rat model of constipation induced by subcutaneous administration of loperamide. Fecal parameters (fecal count, fecal water content, and fecal hardness) were measured in constipated rats. The substance, target, and pathway basis of the Modified Zhizhu Pill on constipation was investigated using network pharmacology. The microflora in rats was determined. Serum neurotransmitters (acetylcholine and 5-hydroxytryptamine) were measured in rats and their relationship with the gut microbiota was assessed., Results: Modified Zhizhu Pill increased the number of bowel movements and fecal water content, and decreased fecal hardness and transit time. Network pharmacological analysis showed that Modified Zhizhu Pill can target multiple constipation-related targets and pathways through multiple potential active ingredients. Modified Zhizhu Pill alleviated loperamide-induced microbiota dysbiosis. Modified Zhizhu Pill increased serum 5-hydroxytryptamine and acetylcholine. The increase in serum 5-hydroxytryptamine and acetylcholine was associated with rat gut microbiota., Conclusion: These results suggest that Modified Zhizhu Pill may increase intestinal motility and ultimately relieve constipation by improving microecological dysbiosis and neurotransmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Acute appendicitis is a common surgical emergency. It is commonly caused by obstruction of the appendiceal lumen due to fecaliths, tumors, or lymphoid hyperplasia. For over a century, appendectomy has been the primary treatment for acute appendicitis. Abraham Groves performed the first open appendectomy in 1883. In 1983, Kurt Semm completed the first laparoscopic appendectomy, heralding a new era in appendectomy. However, appendectomy is associated with certain complications and a rate of negative appendectomies. Studies have suggested controversy over the impact of appendectomy on the development of inflammatory bowel disease and Parkinson's disease, but an increasing number of studies indicate a possible positive correlation between appendectomy and colorectal cancer, gallstones, and cardiovascular disease. With the recognition that the appendix is not a vestigial organ and the advancement of endoscopic te-chnology, Liu proposed the endoscopic retrograde appendicitis therapy. It is an effective minimally invasive alternative for treating uncomplicated acute appendicitis. Our team has developed an appendoscope with a disposable digital imaging system operated through the biopsy channel of a colonoscope and successfully applied it in the treatment of appendicitis. This article provides an overview of the progress in endoscopic treatment for acute appendicitis and offers a new perspective on the future direction of appendiceal disease treatment., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Patients with acquired immune deficiency syndrome (AIDS) are susceptible to numerous complications, such as sepsis and acute kidney injury (AKI), leading to adverse outcomes. Continuous renal replacement therapy (CRRT) is becoming increasingly popular for treating sepsis and AKI. This study aimed to verify the effectiveness of CRRT in the treatment of patients with AIDS with sepsis and AKI to provide new directions for the treatment of severe AIDS. Data of 74 people with AIDS, sepsis, and AKI were collected. The patients were divided into CRRT and non-CRRT groups. There was no difference in the indicators between the two groups at admission. Vital signs, pH, serum potassium level, renal function, blood lactate level, acute physiology and chronic health evaluation II score, and sequential organ failure assessment score in the CRRT group demonstrated significant improvements over those in the non-CRRT group at both 24 and 72 h after admission (P < 0.05). The levels of interleukin 6 and procalcitonin declined more significantly in the CRRT group at 72 h after admission (P < 0.05). The CRRT group had a higher 28-day survival rate than the non-CRRT group (P < 0.05). CRRT improves the clinical indicators and increases the short-term survival rate of patients with AIDS, sepsis, and AKI.

Background: Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1)., Methods: Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 μg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout (Clec7a -/- ) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons., Results: Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx., Conclusions: Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization., Significance Statement: This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission., (© 2024 European Pain Federation ‐ EFIC ®.)

Alleviating the decomposition of the electrolyte is of great significance to improving the cycle stability of cathodes, especially for LiCoO 2 (LCO), its volumetric energy density can be effectively promoted by increasing the charge cutoff voltage to 4.6 V, thereby supporting the large-scale application of clean energy. However, the rapid decomposition of the electrolyte under 4.6 V conditions not only loses the transport carrier for lithium ion, but also produces HF and insulators that destroy the interface of LCO and increase impedance. In this work, the decomposition of electrolyte is effectively suppressed by changing the adsorption force between LCO interface and EC. Density functional theory illustrates the LCO coated with lower electronegativity elements has a weaker adsorption force with the electrolyte, the adsorption energy between LCO@Mg and EC (0.49 eV) is weaker than that of LCO@Ti (0.73 eV). Meanwhile, based on the results of time of flight secondary ion mass spectrometry, conductivity-atomic force microscopy, in situ differential electrochemical mass spectrometry, soft X-ray absorption spectroscopy, and nuclear magnetic resonance, as the adsorption force increases, the electrolyte decomposes more seriously. This work provides a new perspective on the interaction between electrolyte and the interface of cathode and further improves the understanding of electrolyte decomposition., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

With the popularization of 5G technology and the development of science and technology, flexible and transparent conductive films (TCF) are increasingly used in the preparation of optoelectronic devices such as electromagnetic shielding devices, transparent flexible heaters, and solar cells. Silver nanowires (AgNW) are considered the best material for replacing indium tin oxide to prepare TCFs due to their excellent comprehensive properties. However, the loose overlap between AgNWs is a significant reason for the high resistance. This article investigates a sandwich structured conductive network composed of AgNW and Ti 3 C 2 T x MXene for high-performance EMI shielding and transparent electrical heaters. Polyethylene pyrrolidone (PVP) solution was used to hydrophilic modify PET substrate, and then MXene, AgNW, and MXene were assembled layer by layer using spin coating method to form a TCF with a sandwich structure. One-dimensional AgNW is used to provide electron transfer channels and improve light penetration, while two-dimensional MXene nanosheets are used for welding AgNWs and adding additional conductive channels. The flexible TCF has excellent transmittance (85.1 % at 550 nm) and EMI shielding efficiency (27.1 dB). At the voltage of 5 V, the TCF used as a heater can reach 85.6 °C. This work offers an innovative approach to creating TCFs for the future generation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study innovatively addresses challenges in enhancing upconversion efficiency in lanthanide-based nanoparticles (UCNPs) by exploiting Shewanella oneidensis MR-1, a microorganism capable of extracellular electron transfer. Electroactive membranes, rich in c-type cytochromes, are extracted from bacteria and integrated into membrane-integrated liposomes (MILs), encapsulating core-shelled UCNPs with an optically inactive shell, forming UCNP@MIL constructs. The electroactive membrane, tailored to donate electrons through the inert shell, independently boosts upconversion emission under near-infrared excitation (980 or 1550 nm), bypassing ligand-sensitized UCNPs. The optically inactive shell restricts energy migration, emphasizing electroactive membrane electron donation. Density functional theory calculations elucidate efficient electron transfer due to the electroactive membrane hemes' highest occupied molecular orbital being higher than the valence band maximum of the optically inactive shell, crucial for enhancing energy transfer to emitter ions. The introduction of a SiO 2 insulator coating diminishes light enhancement, underscoring the importance of unimpeded electron transfer. Luminescence enhancement remains resilient to variations in emitter or sensitizing ions, highlighting the robustness of the electron transfer-induced phenomenon. However, altering the inert shell material diminishes enhancement, emphasizing the role of electron transfer. This methodology holds significant promise for diverse biological applications. UCNP@MIL offers an advantage in cellular uptake, which proves beneficial for cell imaging., (© 2024 Wiley‐VCH GmbH.)

Low-field magnetic resonance imaging (MRI) has recently experienced a renaissance that is largely attributable to the numerous technological advancements made in MRI, including optimized pulse sequences, parallel receive and compressed sensing, improved calibrations and reconstruction algorithms, and the adoption of machine learning for image postprocessing. This new attention on low-field MRI originates from a lack of accessibility to traditional MRI and the need for affordable imaging. Low-field MRI provides a viable option due to its lack of reliance on radio-frequency shielding rooms, expensive liquid helium, and cryogen quench pipes. Moreover, its relatively small size and weight allow for easy and affordable installation in most settings. Rather than replacing conventional MRI, low-field MRI will provide new opportunities for imaging both in developing and developed countries. This article discusses the history of low-field MRI, low-field MRI hardware and software, current devices on the market, advantages and disadvantages, and low-field MRI's global potential.

Aeonium arboreum 'Halloween', a popular indoor ornamental succulent in China, changes its leaf colour to red on light exposure. However, the underlying molecular mechanisms is still vague. Comparative analysis of transcriptome data from 'Halloween' leaves treated under dark and light conditions revealed two R2R3-MYB transcription factors, AaMYB113 and AaMYB114, that may mediate anthocyanin accumulation. In this study, we cloned the AaMYB113 and AaMYB114 genes, encoding proteins of 279 and 248 amino acids, respectively. Transcriptional activity analysis revealed that AaMYB113 exhibits strong transcriptional activity, in contrast to AaMYB114, which demonstrates minimal activity. Transient expression studies in tobacco leaves demonstrated that AaMYB113 induced red pigmentation, whereas AaMYB114 did not. Subsequent stable overexpression in Arabidopsis thaliana confirmed that AaMYB113, but not AaMYB114, could similarly turn Arabidopsis leaves red. Further stable transformation of AaMYB113 in tobacco affected multiple floral components, including leaves, petals, calyx, flower tubes, and filaments, turning them red. Quantitative real-time PCR (qRT-PCR) assay in leaves of AaMYB113 stably transformed tobacco and Arabidopsis revealed upregulation of anthocyanin biosynthesis-related structural genes and TT8-like transcription factors. Moreover, the dual luciferase analysis confirmed that AaMYB113 can activate the promoters of 'Halloween' anthocyanin synthesis structural genes, AaCHS, AaCHI, AaF3H, AaDFR and AaANS. The above results indicate that AaMYB113 can promote anthocyanin synthesis, while AaMYB114 does not have this function. This study contributes significantly to the limited body of research on the molecular mechanisms of anthocyanin synthesis in succulents, advancing our understanding of how these pathways are regulated in 'Halloween' succulents and potentially other species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The objective of this study is to explore the patterns of alteration in left ventricular systolic function among patients with severe aortic stenosis (SAS) through the application of automatic myocardial motion quantification (aCMQ) techniques. Furthermore, we seek to ascertain dependable quantitative markers for the assessment of impaired left ventricular function in patients with SAS and an ejection fraction (EF) ≥ 60%., Methods: Seventy patients who underwent echocardiography and received a diagnosis of severe aortic stenosis (SAS) in the hospital from November 2021 to August 2022 were selected for the SAS group and categorized into three subgroups based on ejection fraction (EF)-SAS group with EF ≥ 60%, SAS group with EF ranging from 50% to 59%, and SAS group with EF < 50%. Concurrently, 30 healthy individuals were recruited at the hospital during the same timeframe to serve as the control group. Participants from both groups underwent standard transthoracic echocardiography to assess conventional echocardiographic parameters. Dynamic images were examined using automatic myocardial motion quantification (aCMQ) software to derive longitudinal peak strain (LPS) parameters, which were then subjected to statistical analysis., Results: In comparison to the control group participants, the measurements of ascending aorta diameter (AoD), left atrium diameter (LAD), interventricular septal end diastolic thickness (IVSd), left ventricular posterior wall end diastolic thickness (LVPWd), peak systolic velocity (Vmax), and mean pressure gradient (MPG) were significantly higher in the SAS groups (p < 0.05). When compared to participants in the SAS group with an EF ≥ 60%, the values of IVSd, LVPWd, Vmax, and MPG in the SAS group with EF ranging from 50% to 59% were significantly elevated (p < 0.05). Similarly, left ventricular end-diastolic diameter (LVEDD), the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/e'), and the ratio of early to late diastolic mitral inflow velocities (E/A) in the SAS group with EF < 50% were significantly elevated (p < 0.05). The absolute values of longitudinal peak strain (LPS) in the SAS groups were significantly lower in comparison to those in the control group (p < 0.05). Furthermore, all measurements of left ventricular global longitudinal systolic peak strain (GLPS) showed a positive correlation with MPG, a moderate negative correlation with aortic valve area index (AVAI), and a moderate positive correlation with E/A., Conclusions: Patients with SAS and an EF < 50% exhibited the most profound impairment in left ventricular myocardial function. Utilizing the aCMQ technique enables the precise and quantitative evaluation of the severity of impaired left ventricular systolic function in patients within the SAS group with an EF ≥ 60%., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL - 1 ) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC 50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO 3 - )-1→4-α-L-fucp(2,3-SO 3 - )-1→section), SFcup showed a best inhibitory efficacy against AChE with IC 50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale and Objectives: An accurate prognostic model is essential for the development of treatment strategies for gallbladder cancer (GBC). This study proposes an integrated model using clinical features, radiomics, and deep learning based on contrast-enhanced computed tomography (CT) images for survival prediction in patients with GBC after surgical resection., Methods: A total of 167 patients with GBC who underwent surgical resection at two medical institutions were retrospectively enrolled. After obtaining the pre-treatment CT images, the tumor lesions were manually segmented, and handcrafted radiomics features were extracted. A clinical prognostic signature and radiomics signature were built using machine learning algorithms based on the optimal clinical features or handcrafted radiomics features, respectively. Subsequently, a DenseNet121 model was employed for transfer learning on the radiomics image data and as the basis for the deep learning signature. Finally, we used logistic regression on the three signatures to obtain the unified multimodal model for comprehensive interpretation and analysis., Results: The integrated model performed better than the other models, exhibiting the highest area under the curve (AUC) of 0.870 in the test set, and the highest concordance index (C-index) of 0.736 in predicting patient survival rates. A Kaplan-Meier analysis demonstrated that patients in high-risk group had a lower survival probability compared to those in low-risk group (log-rank p < 0.05)., Conclusion: The nomogram is useful for predicting the survival of patients with GBC after surgical resection, helping in the identification of high-risk patients with poor prognosis and ultimately facilitating individualized management of patients with GBC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients., Methods: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness., Results: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort., Conclusion: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA)., Methods: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22)., Results: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47)., Conclusion: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA., Trial Registration: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016)., (© 2024. The Author(s).)

Senescence, an intricate and inevitable biological process, characterized by the gradual loss of homeostasis and declining organ functions. The pathological features of cellular senescence, including cell cycle arrest, metabolic disruptions, and the emergence of senescence-associated secretory phenotypes (SASP), collectively contribute to the intricate and multifaceted nature of senescence. Beyond its classical interaction with p53, murine double minute gene 2 (MDM2), traditionally known as an E3 ubiquitin ligase involved in protein degradation, plays a pivotal role in cellular processes governing senescence. Histone deacetylase (HDAC), a class of histone deacetylases mainly expressed in the nucleus, has emerged as a critical contributor to renal tissues senescence. In this study we investigated the interplay between MDM2 and HDAC1 in renal senescence. We established a natural aging model in mice over a 2-year period that was verified by SA-β-GAL staining and increased expression of senescence-associated markers such as p21, p16, and TNF-α in the kidneys. Furthermore, we showed that the expression of MDM2 was markedly increased, while HDAC1 expression underwent downregulation during renal senescence. This phenomenon was confirmed in H 2 O 2 -stimulated HK2 cells in vitro. Knockout of renal tubular MDM2 alleviated renal senescence in aged mice and in H 2 O 2 -stimulated HK2 cells. Moreover, we demonstrated that MDM2 promoted renal senescence by orchestrating the ubiquitination and subsequent degradation of HDAC1. These mechanisms synergistically accelerate the aging process in renal tissues, highlighting the intricate interplay between MDM2 and HDAC1, underpinning the age-related organ function decline., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Oral immunotherapy (OIT) is a promising allergen-specific approach in the management of food allergy; however, studies on OIT for allergic rhinitis (AR) have rarely been reported. The purpose of this study is to evaluate the efficacy and safety of OIT using enteric-coated capsules for AR induced by house dust mites., Methods: A total of 49 patients with AR were enrolled, including 25 who received subcutaneous immunotherapy (SCIT) and 24 who received OIT. The clinical efficacy and safety in both groups were evaluated., Results: After 1 year of treatment, both SCIT and OIT demonstrated significant therapeutic effects. OIT was found to be more effective than SCIT in reducing the total AR symptom score and improving the results of nasal provocation tests. Local and systemic adverse reactions were observed in the SCIT group, while none were reported in the OIT group., Conclusion: OIT is an effective and safe treatment for mite-induced AR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Zhang, Xie, Zhou, Chen, Wang, Zhu, Wen and Cheng.)

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 μg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC&#95;(50) of 4.12 μg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.

Background: Although the indoor environment has been proposed to be associated with childhood sleep health, to our knowledge no study has investigated the association between home renovation and childhood sleep problems., Methods: The study included 186,470 children aged 6-18 years from the National Chinese Children Health Study (2012-2018). We measured childhood sleeping problems via the Chinese version of the Sleep Disturbance Scale for Children (C-SDSC). Information on home renovation exposure within the recent 2 years was collected via parent report. We estimated associations between home renovation and various sleeping problems, defined using both continuous and categorized (binary) C-SDSC t-scores, using generalized mixed models. We fitted models with city as a random effect variable, and other covariates as fixed effects., Results: Out of the overall participants, 89,732 (48%) were exposed to recent home renovations. Compared to the unexposed group, children exposed to home renovations had higher odds of total sleep disorder (odd ratios [OR] = 1.3; 95% confidence interval [CI] = 1.2, 1.4). Associations varied when we considered different types of home renovation materials. Children exposed to multiple types of home renovation had higher odds of sleeping problems. We observed similar findings when considering continuous C-SDSC t-scores. Additionally, sex and age of children modified the associations of home renovation exposure with some of the sleeping problem subtypes., Conclusions: We found that home renovation was associated with higher odds of having sleeping problems and that they varied when considering the type of renovation, cumulative exposure, sex, and age differences., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Chemical investigation of a culture broth from the marine-derived fungus Pyrrhoderma noxium HNNU0524 yielded two new compounds including a drimane-type sesquiterpenoid named pyrrnoxin A ( 1 ) and a benzoic acid derivative, pyrrnoxin B ( 5 ), together with three related known analogues ( 2 - 4 ). The chemical structures of 1 and 5 were determined by detailed analysis of spectroscopic data, single-crystal X-ray crystallography, quantum mechanics-based DP4+ and ECD calculations. Compounds 2 and 3 moderately inhibited NO production of lipopolysaccharide-induced microglia cells BV2 with IC 50 values of 26.6 and 60.5 µM, respectively.

Nowadays, flexible multifunctional composites are attracting much attention and are practically being used in various emerging electronic devices. However, most composites suffer from the disadvantages of high loadings of conductive fillers, complicated preparation processes, and low energy conversion efficiency. In this article, Caffeic acid-modified multiwalled carbon nanotubes (C-MWCNTs)/poly(3,4-ethylene dioxythiophene):polystyrene sulfonic acid (PEDOT:PSS)/polyimide (PI) composite films (CPFs) were prepared using a simple layer-by-layer deposition method. The "reinforced concrete" structure of the C-MWCNTs/PEDOT:PSS layer ensures high electrical conductivity of the film, while the PI layer provides excellent mechanical properties (72.69 MPa). The composite film exhibits excellent electrothermal response and thermal stability up to approximately 125 °C at 5 V. In addition, the good conductivity of the film provides its electromagnetic shielding effectiveness (32.69 dB). With these advantages, we expect that flexible CPFs will be widely utilized in wearable devices, electromagnetic interference (EMI) shielding applications, and thermal management of personal or electronic devices.

Patients with locally advanced rectal cancer who undergo neoadjuvant chemoradiotherapy may achieve pathological complete response (pCR). The incidence of recurrence is low among patients with pCR, there is still a lack of consensus on postoperative treatment and follow-up strategy. This review summarizes the recurrence patterns of patients with pCR, including distant metastasis rate, characteristics of distant metastasis time and location, local recurrence rate, and local recurrence time. The aim is to provide reference for the postoperative treatment and follow-up strategy of patients with pCR. Patients with pCR have a low recurrence rate, with infrequent local recurrence. Distant metastasis is the most common recurrence pattern, primarily in the lung and secondly in the regional lymph node. The time of recurrence is delayed which suggests the need for appropriate adjustments to follow-up strategy, extending the follow-up period, and placing emphasis on monitoring sites prone to recurrence.

Purpose: Preoperative anemia increases postoperative morbidity, mortality, and the risk of allogeneic transfusion. However, the incidence of preoperative anemia in patients undergoing total hip arthroplasty and total knee arthroplasty (TKA) and its relationship to postoperative outcomes has not been previously reported., Methods: We conducted a comprehensive literature search through PubMed, Cochrane Library, Web of Sincien, and Embase from inception to July 2023 to investigate the prevalence of preoperative anemia in patients undergoing Total Joint Arthroplasty, comorbidities between anemic and non-anemicpatients before surgery, and postoperative outcomes. postoperative outcomes were analyzed. Overall prevalence was calculated using a random-effects model, and heterogeneity between studies was examined by Cochran's Q test and quantified by the I 2 statistic. Subgroup analyses and meta-regression analyses were performed to identify sources of heterogeneity. Publication bias was assessed by funnel plots and validated by Egger's test., Results: A total of 21 studies with 369,101 samples were included, all of which were retrospective cohort studies. 3 studies were of high quality and 18 studies were of moderate quality. The results showed that the prevalence of preoperative anemia was 22% in patients awaiting arthroplasty; subgroup analyses revealed that the prevalence of preoperative anemia was highest in patients awaiting revision of total knee arthroplasty; the highest prevalence of preoperative anemia was found in the Americas; preoperative anemia was more prevalent in the female than in the male population; and preoperative anemia with a history of preoperative anemia was more common in the female than in the male population. patients with a history of preoperative anemia; patients with joint replacement who had a history of preoperative anemia had an increased risk of infection, postoperative blood transfusion rate, postoperative blood transfusion, Deep vein thrombosis of the lower limbs, days in hospital, readmission within three months, and mortality compared with patients who did not have preoperative anemia., Conclusion: The prevalence of preoperative anemia in patients awaiting total joint arthroplasty is 22%, and is higher in TKA and female patients undergoing revision, while preoperative anemia is detrimental to the patient's postoperative recovery and will increase the risk of postoperative complications, transfusion rates, days in the hospital, readmission rates, and mortality., (© 2024. The Author(s).)

Aim: To investigate the types of bacteria in patients with eye infections in Suzhou and their drug resistance to commonly used antibacterial drugs., Methods: The clinical data of 155 patients were retrospectively collected in this study, and the pathogenic bacteria species and drug resistance of each pathogenic bacteria were analyzed., Results: Among the 155 patients (age from 12 to 87 years old, with an average age of 57, 99 males and 56 females) with eye infections (160 eyes: 74 in the left eye, 76 in the right eye and 5 in both eyes, all of which were exogenous), 71 (45.81%) strains were gram-positive bacteria, 23 (14.84%) strains were gram-negative bacteria and 61 (39.35%) strains were fungi. Gram-positive bacteria were highly resistant to penicillin and erythromycin (78.87% and 46.48% respectively), but least resistant to vancomycin at 0. Gram-negative bacteria were highly resistant to cefoxitin and compound sulfamethoxazole (100% and 95.65% respectively), but least resistant to meropenem at 0. Comparison of the resistance of gram-positive and gram-negative bacteria to some drugs revealed statistically significant differences ( P <0.05) in the resistance of both to cefoxitin, cotrimoxazole, levofloxacin, cefuroxime, ceftriaxone and ceftazidime, and both had higher rates of resistance to gram-negative bacteria than to gram-positive bacteria. The distribution of bacterial infection strains showed that Staphylococcus epidermidis was the most common strain in the conjunctiva, cornea, aqueous humor or vitreous body and other eye parts. Besides, Fusarium and Pseudomonas aeruginosa were also among the most common strains of conjunctival and corneal infections., Conclusion: Gram-positive bacteria are the dominant bacteria in eye infections, followed by gram-negative bacteria and fungi. Considering the resistance of gram-negative bacteria to multiple drugs, monitoring of bacteria should be strengthened in eye bacterial infections for effective prevention and control to reduce complications caused by eye infections., Competing Interests: Conflicts of Interest: Zhang L, None; You HZ, None; Wang GH, None; Xu W, None; Li JS, None; Zhao QL, None; Du S, None., (International Journal of Ophthalmology Press.)