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Yan Lu,1 Wei Gou,1,2 Hai Feng Zhang,3 Yi Ying Li3 1Department of Clinical Medicine, Qingdao University, Qingdao City, Shandong Province, People’s Republic of China; 2Department of Metabolic Liver Disease, Qingdao Sixth People’s Hospital, Qingdao City, Shandong Province, People’s Republic of China; 3Medical Department, Qingdao Sixth People’s Hospital, Qingdao City, Shandong Province, People’s Republic of ChinaCorrespondence: Wei Gou, Email gouwei@qdu.edu.cnBackground: Patients with chronic hepatitis B (CHB) and cirrhosis often have impaired fasting glucose (IFG). This study sought to investigate the impact of liver fibrosis on islet function in individuals diagnosed with CHB and IFG.Material and Methods: Patients with chronic hepatitis B (CHB) and impaired fasting glucose (IFG) were selected for this study. They were divided into low-risk (L-R), intermediate-risk (M-R), and high-risk (H-R) liver fibrosis groups based on the FIB-4 score. The study compared islet function among different risk groups of liver fibrosis and analyze the correlation between liver fibrosis and islet function. Additionally, the patients were divided into a diabetes mellitus (DM) group and a non-DM (NDM) group based on the development of DM. The cumulative risk of progression to DM in patients with L-R, M-R, and H-R liver fibrosis was analyzed using the Kaplan–Meier method. Hazard ratios (HRs) and confidence intervals (CIs) were calculated for DM development through Cox regression analysis.Results: In this study of 228 individuals, higher FIB-4 scores were observed in the DM group compared to the NDM group. Patients with H-R liver fibrosis displayed lower islet function and had a significantly higher risk of developing DM. The FIB-4 score and fasting plasma glucose (FPG) were identified as independent risk factors for DM progression in CHB patients with IFG.Conclusion: Among patients with CHB and IFG, the severity of liver fibrosis is associated with islet function, and the FIB-4 score is a significant risk factor for DM development.Keywords: chronic hepatitis B, FIB-4, impaired fasting glucose, islet function, diabetes mellitus

Xiao-Pei Hou,1 Yan-Yang Zhang,1 Hong-Feng Zhang,1 Shan Wang,1 Yun-Li Xing,1 Hong-Wei Li,2 Ying Sun1 1Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Ying Sun, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, No. 95 of Yong’an Road, Xicheng District, Beijing, People’s Republic of China, Tel +86-010-63137740, Email ysun15@163.comPurpose: Many older patients with acute myocardial infarction (AMI) have impaired ability for activities of daily living (ADL). Impaired ADL leads to poor prognosis in elderly patients. The Global Registry of Acute Coronary Events (GRACE) score is widely used for risk stratification in AMI patients but does not consider physical performance, which is an important prognosis predictor for older adults. This study assessed whether the Barthel Index (BI) score combine the GRACE score would achieve improved one-year mortality prediction in older AMI patients.Patients and Methods: This single-center retrospective study included 688 AMI patients aged ≥ 65 years who were divided into an impaired ADL group (BI ≤ 60, n = 102) and a normal ADL group (BI > 60, n = 586) based on BI scores at discharge. The participants were followed up for one year. Cox survival models were constructed for BI score, GRACE score, and BI score combined GRACE score for one-year mortality prediction.Results: Patients had a mean age of 76.29 ± 7.42 years, and 399 were men (58%). A lower BI score was associated with more years of hypertension and diabetes, less revascularization, longer hospital stays, and higher one-year mortality after discharge. Multivariable Cox regression analysis identified BI as a significant risk factor for one-year mortality in older AMI patients (HR 0.977, 95% CI, 0.963– 0.992, P = 0.002). BI (0.774, 95% CI: 0.731– 0.818) and GRACE (0.758, 95% CI: 0.704– 0.812) scores had similar predictive power, but their combination outperformed either score alone (0.810, 95% CI: 0.770– 0.851).Conclusion: BI at discharge is a significant risk factor for one-year mortality in older AMI patients, which can be better predicted by the combination of BI and GRACE scores.Keywords: older adults, acute myocardial infarction, Barthel Index, GRACE, prognosis

Zheng RP, Ma DK, Li Z, Zhang HF. Cancer Manag Res. 2020;12:6165–6175. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors were cooperative but were unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were informed of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Li-Jun Chen,1,2 Wang Xu,1 Ya-Ping Li,3 Li-Ting Ma,1 Hui-Fang Zhang,1 Xiao-Bo Huang,1 Geng-Geng Yu,1 Xiu-Qin Ma,1 Chao Chen,1 Yan-Hong Liu,1 Jie Wu,4 Li-Jun Wang,4 Yuan Xu4 1Department of Respiratory and Critical Medicine, The First People’s Hospital of Yinchuan City, Yinchuan, Ningxia, People’s Republic of China; 2Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 3Department of Respiratory Medicine, Weihai Municipal Hospital of Shandong Province, Weihai, Shandong, People’s Republic of China; 4Department of Clinical Institute, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of ChinaCorrespondence: Li-Jun ChenDepartment of Respiratory and Critical Medicine, The Second Affiliated Hospital of Ningxia Medical University, No. 2, Liqun West Street, Xingqing District, Yinchuan, Ningxia 750001, People’s Republic of ChinaTel +86-13895016600Fax +86-951-6192235Email ycchenlj@163.comBackground: Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease characterized by irreversible airflow obstruction. Pathogenic mechanisms underlying COPD remain largely unknown.Objective: The current study was designed to explore serum concentration of hypoxia-inducible factor 1α (HIF-1α) in stable COPD patients and the potential effect of Lycium barbarum polysaccharides (LBP) on HIF-1α protein expression.Methods: Serum HIF-1α was quantified by ELISA in 102 stable COPD patients before and after 2-week orally taken LBP (100 mL/time, twice daily, 5– 15 mg/mL). Correlation of serum LBP and lung function (FEV1%) or blood gas (PO2 and PCO2) was also analyzed. As a control, 105 healthy subjects were also enrolled into this study.Results: Serum concentration of HIF-1α was significantly higher in the stable COPD patients (37.34 ± 7.20 pg/mL) than that in the healthy subjects (29.55 ± 9.66 pg/mL, P< 0.001). Oral administration of LBP (5 mg/mL, 100 mL, twice daily for 2 weeks) not only relieved COPD symptoms but also significantly reduced serum HIF-1α concentration (36.94 ± 9.23 vs 30.49 ± 6.42 pg/mL, P< 0.05). In addition, level of serum HIF-1α concentration was significantly correlated with PCO2 (r = 0.283, P< 0.001), but negatively and significantly correlated with PO2 (r = − 0.490, P=0.005) or FEV1%(r = − 0.420, P=0.018).Conclusion: These findings suggested that activation of HIF-1 signaling pathway may be involved in the pathophysiology of COPD and that stabilization of serum HIF-1α concentration by LBP might benefit the stable COPD patients.Keywords: chronic obstructive pulmonary disease, COPD, hypoxia-induced factor 1, HIF-1, Lycium barbarum polysaccharides, LBP

Jing-Jing Jin,1 Tian-Tian Xu,1 Yan-Fang Li,2 Hong-Yang Wang,1 Dan Zhang,1 Pan-Pan Zhang,1 Li-Xin Xu,1 Chun-Xiu Wang,1 Zhu Fan,1 Ling Wang,1 Chen Liu,1 Shuang Wang,1 Hao-Tian Shi,1 Cai-Hong Li,1 Hai-Fang Zhang,1 Yan Huang1 1Department of Respiratory Medicine, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei 063000, People’s Republic of China; 2Department of Pediatric Medicine, Hebei People’s Hospital Affiliated to North China University of Science and Technology, Shijiazhuang, Hebei 050000, People’s Republic of ChinaCorrespondence: Yan HuangDepartment of Respiratory Medicine, North China University of Science and Technology Affiliated Hospital, No. 73 of Jianshe Road, Lubei District, Tangshan, Hebei 063000, People’s Republic of ChinaTel +86 18713877946Email huangy95201@163.comObjective: This study investigates the effect of the standardized management of cancer pain on patients with bone metastasis of lung cancer in China.Patients and Methods: A total of 123 patients with bone metastasis of lung cancer were selected from the Respiratory Department of the Affiliated Hospital of North China University of Science and Technology. Among these patients, 62 patients who had not received standardized management of cancer pain from March 12, 2018, to September 11, 2018, were selected as the control group. In contrast, 61 patients who had received the standardized management of cancer pain from September 12, 2018, to March 11, 2019, were selected as the observation group. The former cohort accepted the conventional management of cancer pain, while the latter accepted the strict, standardized management of cancer pain. The demographic statistics, disease characteristics, and painkiller application of patients in these two groups were analyzed. Then, the analgesic effect and level of satisfaction were compared between these two groups.Results: No significant differences were noticed between these two groups in terms of age, gender, smoking status, type of pathology, education level, previous treatment, and the Eastern Cooperative Oncology Group score, as well as other demographic and disease characteristics. As for the use of painkillers, opioid analgesics accounted for a higher proportion in the observation group than in the control group. Compared with the control group, pain improvement and patient satisfaction after analgesic treatment were significantly higher in the observation group (p < 0.05).Conclusion: The standardized management of cancer pain can considerably alleviate the pain of patients with bone metastasis of lung cancer and improve their quality of life. Furthermore, this type of management can increase satisfaction.Keywords: standard management, lung cancer, cancer pain, bone metastasis, analgesic effect

Rui-Peng Zheng,1 Dong-Kai Ma,2 Zhuo Li,3 Hai-Feng Zhang1 1Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Gastroenterology and Hepatology, Qian Wei Hospital of Jilin Province, Changchun, Jilin Province 130012, People’s Republic of China; 3Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaCorrespondence: Hai-Feng ZhangDepartment of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaTel +86 13756696677Email HaifengZhang159@outlook.comBackground: 5-fluorouracil (5-FU) is a common drug for hepatic carcinoma (HCC), but the drug resistance of clinical chemotherapy restricts its use. Studies have demonstrated that miRNA molecules can act as a chemoresistance regulator in drug resistance of tumors, whereas the role of miR-145 in the 5-FU-resistant HCC remains unclear.Objective: To explore the prognostic value of miR-145 in HCC and its molecular mechanism in 5-FU-resistant HCC cells.Methods: A qRT-PCR assay was conducted to quantify miR-145 in HCC tissues and 5-FU-resistant HCC cells. The Cell Counting Kit-8 (CCK-8) and flow cytometry were adopted to analyze the proliferation and apoptosis of 5-FU-resistant HCC cells. The Western blot was adopted to quantify toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and apoptosis-related proteins. Moreover, an in vivo tumor xenotransplantation of nude mice was conducted to determine the effect of miR-145 on 5-FU-resistant HCC cells.Results: MiR-145 was expressed lowly in HCC tissues and cells, and linked to high TNM staging and lymph node metastasis of HCC patients. Down-regulation of miR-145 indicated a poorer prognosis and it promoted drug resistance of HCC cells and inhibited cell apoptosis. In contrast, miR-145 overexpression improved the sensitivity of HCC cells to 5-FU and enhanced the inhibition of 5-FU on tumor growth. The luciferase reporter gene assay showed that TLR4 was the direct target of miR-145, and the Western blot assay revealed that overexpression of TLR4 reversed the inhibitory effect of miR-145 overexpression on TLR4 and MyD88 protein and the effects of it on apoptosis-related proteins.Conclusion: MiR-145 is an inhibiting factor in HCC and can target TLR4 to mediate the chemoresistance of HCC, which may provide novel ideas for treating HCC.Keywords: hepatic carcinoma, miR-145, toll-like receptor 4, TLR4, 5-fluorouracil, drug resistance

Zheng RP, Ma DK, Li Z, Zhang HF. Cancer Manag Res. 2020;12:6165–6175. The Editor and Publisher of Cancer Management and Research wish to issue an Expression of Concern for the published article. Following publication, concerns were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. However, the authors did not provide the requested files and could not satisfy our requirements to confirm the authenticity of some types of data. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. Read the original article

Hua-feng Zhang,1 Chen-guang Wang,1 Hui Li,1 Yu-ting Huang,2 Zhi-jun Li1 1Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Cancer & Immunology Research, Children’s Research Institute, Children’s National Medical Center, Washington DC, USA Purpose: Platelet-rich plasma (PRP) and hyaluronic acid (HA) have been increasingly used in recent years to treat knee osteoarthritis (OA). However, whether PRP is superior to HA is controversial.Methods: We conducted an electronic search of PubMed, Embase, ScienceDirect, and Cochrane library. The pooled data were analyzed using RevMan 5.1.Results: Three prospective and ten randomized trials were identified. PRP injections reduced pain more effectively than HA injections in OA of the knee at 6 months (mean difference [MD]=-14.18; 95% confidence interval [CI]: -26.12 to -2.23; P=0.02; I2=95%) and 12 months (MD=-15.25; 95% CI: -22.17 to -8.32; P

Hufei Zhang,1,* Xinhe Liu,2,* Hongye Jiang,3 Zimeng Liu,4 Xu-Yu Zhang,1 Hong-Zhe Xie,3 1Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 2Department of Anesthesiology, Shenzhen Hospital, University of Hong Kong, Shenzhen, 3Department of Obstetrics and Gynecology, 4Surgical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objectives: Postlaparoscopic shoulder pain (PLSP) remains a common problem after laparoscopies. The aim of this study was to investigate the correlation between pressure pain threshold (PPT) of different muscles and PLSP after gynecologic laparoscopy, and to explore the effect of parecoxib, a cyclooxygenase-2 inhibitor, on the changes of PPT.Materials and methods: The patients were randomly allocated into two groups; group P and group C. In group P, parecoxib 40 mg was intravenously infused at 30 minutes before surgery and 8 and 20 hours after surgery. In group C, normal saline was infused at the corresponding time point. PPT assessment was performed 1 day before surgery and at postoperative 24 hours by using a pressure algometer at bilateral shoulder muscles (levator scapulae and supraspinatus) and forearm (flexor carpi ulnaris). Meanwhile, bilateral shoulder pain was evaluated through visual analog scale score at 24 hours after surgery. Results: Preoperative PPT level of the shoulder, but not of the forearm, was significantly and negatively correlated with the intensity of ipsilateral PLSP. In group C, PPT levels of shoulder muscles, but not of forearm muscles, decreased after laparoscopy at postoperative 24 hours. The use of parecoxib significantly improved the decline of PPT levels of bilateral shoulder muscles (all P

Yang-Yang He,1,2,* Yu Yan,1,3,* Hui-Fang Zhang,1,3 Yi-Huang Lin,3 Yu-Cai Chen,1,3 Yi Yan,4 Ping Wu,1,3 Jian-Song Fang,5 Shu-Hui Yang,2 Guan-Hua Du1,3 1Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 3State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 4Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 5Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Systemic lupus erythematosus (SLE), with a high incidence rate and insufficient therapy worldwide, is a complex disease involving multiple organs characterized primarily by inflammation due to deposition of immunocomplexes formed by production of autoantibodies. The mechanism of SLE remains unclear, and the disease still cannot be cured. We used pristane to induce SLE in female BALB/c mice. Methyl salicylate 2-O-β-D-lactoside (MSL; 200, 400, and 800 mg/kg) was orally administered 45 days after pristane injection for 4.5 months. The results showed that MSL antagonized the increasing levels of multiple types of antibodies and cytokines in lupus mice. MSL was found to suppress joint swelling and have potent inhibitory effect on arthritis-like symptoms. MSL also significantly decreased the spleen index and expression of inflammatory markers in the lupus mice. MSL protected the kidneys of lupus mice from injury through inhibiting the expression of inflammatory cytokines and reducing the IgG and C3 immunocomplex deposits. Further Western blot assays revealed that the downregulation of the intracellular inflammatory signals of NFκB and JAK/STAT3 might be the potential molecular mechanisms of the pharmacological activity of MSL against SLE in vivo. These findings may demonstrate that MSL has the potential to be a useful and highly effective treatment for SLE. Keywords: methyl salicylate 2-O-β-D-lactoside, systemic lupus erythematosus, inflammatory response, lupus nephritis, signal transduction

Background: De novo malignancies are serious complications in the late postoperative period after liver transplantation. The most common de novo tumors are skin malignancies, posttransplantation lymphoproliferative disorder, tumors of the head and neck, and Kaposi's sarcoma. Such posttransplant de novo malignancies are apparently rarely found in bone.Case Description: We describe a patient with a low-grade, aggressive fibrous histiocytoma of the scapula. The patient had undergone liver transplantation 6 years earlier. En bloc resection of the tumor and limb salvage was performed. At the 2-year followup the patient had no signs of local recurrence or metastatic spread; the patient had a Musculoskeletal Tumor Society (MSTS) score of 87.Literature Review: A literature review suggests the main predisposing factors to such malignancies are immunosuppression and its length of use. According to the literature, tumors apparently are rare in bone after liver transplantation, with no clearly documented cases. However, in the presence of such a finding, our study might be the first clearly documented case study of this kind of bone tumor.Clinical Relevance: We describe a patient with a bone tumor after liver transplantation. Our literature review suggests liver transplantation and long-term immunosuppression played a role in this patient's tumor. [ABSTRACT FROM AUTHOR]

Stroke, a major neurological disorder and a leading cause of disability and death, often inflicts damage upon other organs, particularly the kidneys. While chronic kidney disease (CKD) has long been established as a significant risk factor for cerebrovascular disease, stroke can induce renal dysfunction, manifesting as acute kidney injury (AKI) or CKD. Mounting clinical and basic research evidence supports the existence of a bidirectional brain-kidney crosstalk following stroke, implicating specific mechanisms and pathways in stroke-related renal dysfunction. This review analyzes pertinent experimental studies, elucidating the underlying mechanisms of this cerebro-renal interaction following stroke. Additionally, we summarize the current landscape of clinical research investigating brain-kidney interplay and discuss potential challenges in the future. By enhancing our understanding of the scientific underpinnings of brain-kidney crosstalk, this review paves the way for improved treatment strategies and outcomes for stroke patients. Recognizing the intricate interplay between the brain and kidneys after stroke holds profound clinical implications., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Power flow calculation plays a significant role in the operation and planning of modern power systems. Traditional numerical calculation methods have good interpretability but high time complexity. They are unable to cope with increasing amounts of data in power systems; therefore, many machine learning based methods have been proposed for more efficient power flow calculation. Despite the good performance of these methods in terms of computation speed, they often overlook the importance of transmission lines and do not fully consider the physical mechanisms in the power systems, thereby weakening the prediction accuracy of power flow. Given the importance of the transmission lines as well as to comprehensively consider their mutual influence, we shift our focus from bus adjacency relationships to transmission line adjacency relationships and propose a physics-informed line graph neural network framework. This framework propagates information between buses and transmission lines by introducing the concepts of the incidence matrix and the line graph matrix. Based on the mechanics of the power flow equations, we further design a loss function by integrating physical information to ensure that the output results of the model satisfy the laws of physics and have better interpretability. Experimental results on different power grid datasets and different scenarios demonstrate the accuracy of our proposed model., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Acute mesenteric vein thrombosis (MVT) accounts for only 2%-10% of all cases of acute mesenteric ischaemia, with an incidence rate of ~0.1% in Europe and the United States. It represents < 10% of mesenteric infarction cases and is seen predominantly in older adults. In younger individuals, MVT is uncommon, with 36% of cases having unidentified mechanisms and causes., Case Summary: A 27-year-old man presented to the emergency department on February 29, 2024, with a chief complaint of intermittent abdominal pain for 3 day. He was previously in good health. As the abdominal pain was not alleviated by conventional treatment, an abdominal computed tomography (CT) scan was performed, which showed increased density in the portal and mesenteric veins. Further imaging, including portal vein ultrasound, mesenteric CT angiography, and enhanced abdominal CT, revealed widespread thrombosis of the portal vein system (including the main portal vein, left and right branches, proximal mesenteric vein, and splenic vein). After 10 day of thrombectomy and anticoagulation therapy, the patient's abdominal pain had improved significantly. Follow-up assessments indicated that portal venous blood flow had largely returned to normal. He was discharged on March 9, 2024. During a follow-up exam 2 months later, repeat abdominal enhanced CT showed that the previously detected thrombi were no longer visible., Conclusion: Clinicians should remain vigilant for acute MVT in young patients presenting with abdominal pain, to prevent misdiagnosis of this fatal condition., Competing Interests: Conflict-of-interest statement: All authors declare that they have no competing interests to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD. Methods: This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality. Results: A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC =0. 698,95% CI :0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC =0.596, 95% CI : 0.523-0.669) and DPG ( AUC =0.526, 95% CI : 0.452-0.601) (all P <0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P <0.05), while DPG did not showed significance ( P >0.05). Multivariate Cox regression analysis showed that age, PVR and log 2 N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P <0.05). Conclusion: Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Background: Stem cell transplantation has been regarded as a promising therapeutic strategy for myocardial regeneration after myocardial infarction (MI). However, the survival and differentiation of the transplanted stem cells in the hostile ischaemic and inflammatory microenvironment are poor. Recent studies have focused on enhancing the survival and differentiation of the stem cells, while strategies to suppress the senescence of the transplanted stem cells is unknown. Therefore, we investigated the effect of growth differentiation factor 11 (GDF11) on attenuating oxidative stress-induced senescence in the engrafted endothelial progenitor cells (EPCs)., Methods: Rat models of oxidative stress were established by hydrogen peroxide conditioning. Oxidative stress-induced senescence was assessed through senescence-associated β-galactosidase expression and lipofuscin accumulation. The effects of GDF11 treatment on senescence and autophagy of EPCs were evaluated 345, while improvement of myocardial regeneration, neovascularization and cardiac function were examined following transplantation of the self-assembling peptide (SAP) loaded EPCs and GDF11 in the rat MI models., Results: Following hydrogen peroxide conditioning, the level of ROS in EPCs decreased significantly upon treatment with GDF11. This resulted in reduction in the senescent cells and lipofuscin particles, as well as the damaged mitochondria and rough endoplasmic reticula. Concurrently, there was a significant increase in LC3-II expression, LC3-positive puncta and the presence of autophagic ultrastructures were increased significantly. The formulated SAP effectively adhered to EPCs and sustained the release of GDF11. Transplantation of SAP-loaded EPCs and GDF11 into the ischaemic abdominal pouch or myocardium resulted in a decreased number of the senescent EPCs. At four weeks after transplantation into the myocardium, neovascularization and myocardial regeneration were enhanced, reverse myocardial remodeling was attenuated, and cardiac function was improved effectively., Conclusions: This study provides novel evidence suggesting that oxidative stress could induce senescence of the transplanted EPCs in the ischemic myocardium. GDF11 demonstrates the ability to mitigate oxidative stress-induced senescence in the transplanted EPCs within the myocardium by activating autophagy., (© 2024. The Author(s).)

Aim: Coronary artery calcium (CAC) progression is a strong predictor of cardiovascular disease. This study aims to develop and validate a practical tool for predicting individual CAC progression in the general population., Materials and Methods: Data were utilized from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, comprising 5486 participants (47.3% male, mean ± SD age: 61.9 ± 10.2 years), who were randomly assigned to either a training set or an internal validation set at a 7:3 ratio. Additionally, a separate cohort of 2447 participants (44.6% male, mean ± SD age: 40.4 ± 3.5 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) study served as the external validation set. A nomogram was developed based on a Cox regression model incorporating 10 variables selected by the least absolute shrinkage and selection operator (LASSO) method to predict CAC progression., Results: From the 61 features considered, 10 key variables were identified: age, male sex, smoking status, waist circumference, systolic blood pressure, fasting glucose, lipid abnormalities, and the use of antihypertensive, glucose-lowering, and lipid-lowering medications. The nomogram demonstrated good discrimination with a C-statistic of 0.682 (95% confidence interval [CI], 0.665-0.699) in the training set and 0.750 (95% CI, 0.729-0.771) in the external validation set. Decision curve analysis further confirmed the nomogram's clinical utility in predicting the risk of CAC progression., Conclusion: Our nomogram offers a practical tool for individualized prediction of CAC progression potentially aiding in the primary prevention of cardiovascular disease in clinical practice. REGISTRATION URL: https://www., Clinicaltrials: gov; Unique identifier: NCT00005130 (CARDIA), NCT00005487 (MESA)., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Statins are well-tolerated and widely available lipid-lowering medications with neuroprotective effects against traumatic brain injury (TBI). However, whether delayed statin therapy starting in the subacute phase promotes recovery after TBI is unknown. Elongation of the very long-chain fatty acid protein 1 (ELOVL1) is involved in astrocyte-mediated neurotoxicity, but its role in TBI and the relationship between ELOVL1 and statins are unclear. We hypothesized that delayed simvastatin treatment promotes neurological functional recovery after TBI by regulating the ELOVL1-mediated production of very long-chain fatty acids (VLCFAs). ICR male mice received daily intragastric administration of 1, 2 or 5 mg/kg simvastatin on Days 1-14, 3-14, 5-14, or 7-14 after cryogenic TBI (cTBI). The results showed that simvastatin promoted motor functional recovery in a dose-dependent manner, with a wide therapeutic window of at least 7 days postinjury. Meanwhile, simvastatin inhibited astrocyte and microglial overactivation and glial scar formation, and increased total dendritic length, neuronal complexity and spine density on day 14 after cTBI. The up-regulation of ELOVL1 expression and saturated VLCFAs concentrations in the cortex surrounding the lesion caused by cTBI was inhibited by simvastatin, which was related to the inhibition of the mTOR signaling. Overexpression of ELOVL1 in astrocytes surrounding the lesion using HBAAV2/9-GFAP-m-ELOVL1-3xFlag-EGFP partially attenuated the benefits of simvastatin. These results showed that delayed simvastatin treatment promoted functional recovery and brain tissue repair after TBI through the downregulation of ELOVL1 expression by inhibiting mTOR signaling. Astrocytic ELOVL1 may be a potential target for rehabilitation after TBI., Competing Interests: Declaration of Competing Interest None. The authors declare no competing interest!, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study., Research Design and Methods: This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time., Results: During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time., Conclusions: Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D., (© 2024 by the American Diabetes Association.)

Purpose: Effective therapies for metastatic osteosarcoma (OS) remain a critical unmet need. Targeting mRNA translation in metastatic OS offers a promising option, as selective translation drives the synthesis of cytoprotective proteins under harsh microenvironmental conditions to facilitate metastatic competence., Experimental Design: We assessed the expression levels of eukaryotic translation factors in OS, revealing the high expression of the eukaryotic initiation factor 4A1 (EIF4A1). Using a panel of metastatic OS cell lines and patient-derived xenograft (PDX) models, EIF4A1 inhibitors were evaluated for their ability to block proliferation and reduce survival under oxidative stress, mimicking harsh conditions of the lung microenvironment. Inhibitors were also evaluated for their antimetastatic activity using the ex vivo pulmonary metastasis assay and in vivo metastasis models. Proteomics was performed to catalog which cytoprotective proteins or pathways were affected by EIF4A1 inhibition., Results: CR-1-31B, a rocaglate-based EIF4A1 inhibitor, exhibited nanomolar cytotoxicity against all metastatic OS models tested. CR-1-31B exacerbated oxidative stress and apoptosis when OS cells were co-treated with tert-butylhydroquinone, a chemical oxidative stress inducer. CR-1-31B potently inhibited OS growth in the pulmonary metastasis assay model and in experimental and spontaneous models of OS lung metastasis. Proteomic analysis revealed that tert-butylhydroquinone-mediated upregulation of the NRF2 antioxidant factor was blocked by co-treatment with CR-1-31B. Genetic inactivation of NRF2 phenocopied the antimetastatic activity of CR-1-31B. Finally, the clinical-grade EIF4A1 phase-1-to-2 inhibitor, zotatifin, similarly blocked NRF2 synthesis and the OS metastatic phenotype., Conclusions: Collectively, our data reveal that pharmacologic targeting of EIF4A1 is highly effective in blocking OS metastasis by blunting the NRF2 antioxidant response., (©2024 The Authors; Published by the American Association for Cancer Research.)

Changes in microcirculation lead to the progression of organ pathology in diabetes. Although neuroimmune interactions contribute to a variety of conditions, it is still unclear whether abnormal neural activities affect microcirculation related to diabetes. Using laser speckle contrast imaging, we examined the skin of patients with type 2 diabetes and found that their microvascular perfusion was significantly compromised. This phenomenon was replicated in a high-fat diet-driven murine model of type 2 diabetes-like disease. In this setting, although both macrophages and mast cells were enriched in the skin, only mast cells and associated degranulation were critically required for the microvascular impairment. Sensory neurons exhibited enhanced TRPV1 activities, which triggered mast cells to degranulate and compromise skin microcirculation. Chemical and genetic ablation of TRPV1+ nociceptors robustly improved skin microcirculation status. Substance P (SP) is a neuropeptide and was elevated in the skin and sensory neurons in the context of type 2 diabetes. Exogenous administration of SP resulted in impaired skin microcirculation, whereas neuronal knockdown of SP dramatically prevented mast cell degranulation and consequently improved skin microcirculation. Overall, our findings indicate a neuron-mast cell axis underlying skin microcirculation disturbance in diabetes and shed light on neuroimmune therapeutics for diabetes-related complications., (© 2024 by the American Diabetes Association.)

T-cell death-associated gene 8 (TDAG8), a G-protein-coupled receptor sensing physiological or weak acids, regulates inflammatory responses. However, its role in traumatic brain injury (TBI) remains unknown. Our recent study showed that delayed CO 2 postconditioning (DCPC) has neuroreparative effects after TBI. We hypothesized that activating astrocytic TDAG8 is a key mechanism for DCPC. WT and TDAG8 -/- mice received DCPC daily by transiently inhaling 10% CO 2 after controlled cortical impact (CCI). HBAAV2/9-GFAP-m-TDAG8-3xflag-EGFP was used to overexpress TDAG8 in astrocytes. The beam walking test, mNSS, immunofluorescence and Golgi-Cox staining were used to evaluate motor function, glial activation and dendritic plasticity. DCPC significantly improved motor function; increased total dendritic length, neuronal complexity and spine density; inhibited overactivation of astrocytes and microglia; and promoted the expression of astrocytic brain-derived neurotrophic factor in WT but not TDAG8 -/- mice. Overexpressing TDAG8 in astrocytes surrounding the lesion in TDAG8 -/- mice restored the beneficial effects of DCPC. Although the effects of DCPC on Days 14-28 were much weaker than those of DCPC on Days 3-28 in WT mice, these effects were further enhanced by overexpressing astrocytic TDAG8. Astrocytic TDAG8 is a key target of DCPC for TBI rehabilitation. Its overexpression is a strategy that broadens the therapeutic window and enhances the effects of DCPC., 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. Published by Elsevier Inc.)

Background & Aims: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear., Methods: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysM cre OXCT1 f/f (OXCT1 conditional knockout in macrophages) mice., Results: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8 + T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8 + T-cell exhaustion and increasing CD8 + T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8 + T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC., Conclusions: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer., Impact and Implications: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: Preeclampsia is a pregnancy-specific disorder characterized by de novo development of hypertension and proteinuria over 20 weeks gestation that has been associated with the dysfunction of trophoblasts. Current evidence suggests that syncytin-1 plays an important role in the non-fusogenic biological activity of trophoblasts, except for specific fusogenic function. However, the underlying mechanism remains unclear., Methods: The expression and location of syncytin-1 in normal and the late-onset preeclampsia placentas were detected by quantitative real-time PCR, western blotting and immunofluorescence. Morphological and apoptosis analysis were processed in placentas. The ex vivo extravillous explant culture model was used to explore the effect of syncytin-1 on EVT outgrowths. Real-time quantitative PCR and immunoblotting were used to calculate syncytin-1 levels in the trophoblast cells before and after syncytin-1 knockdown or overexpression. CCK-8 assay was used to detect the cell viability. TUNEL staining and immunoblotting were processed in trophoblast cells. Transwell assays and wound healing assays were utilize to assess the invasion and migration of trophoblastic cells. Conditional knockout of syncytin-a mouse model was conducted to present the change of placentas in vivo. The ex vivo extravillous explant culture model was used to explore the effect of syncytin-1 on EVT outgrowths. Western blotting was used to identify the key proteins of PI3K/Akt pathways and invasion-related proteins in trophoblast cells., Results and Discussion: Here, reduced syncytin-1 was identified in the late-onset preeclampsia placentas. Reduced syncytin-1 may attenuates the EMT process by promoting apoptosis, inhibiting proliferation and invasion by suppressed PI3K/Akt pathway in trophoblast cells. Our findings provide novel insights into the non-fusogenic biological function of reduced syncytin-1 that may be involves in the pathogenesis of preeclampsia., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To use robotic visible-light OCT (vis-OCT) to study circumferential segmental Schlemm's canal (SC) anatomy in mice after topical pilocarpine administration., Methods: Anterior segment imaging was performed using a vis-OCT sample arm attached to a 6-degree-of-freedom robotic arm to maintain normal (perpendicular) laser illumination aimed at SC around the limbus. Sixteen mice were studied for repeatability testing and to study aqueous humor outflow (AHO) pathway response to topical drug. Pharmaceutical-grade pilocarpine (1%; n = 5) or control artificial tears (n = 9) were given, and vis-OCT imaging was performed before and 15 minutes after drug application. After SC segmentation, SC areas and volumes were measured circumferentially in control- and drug-treated eyes., Results: Circumferential vis-OCT provided high-resolution imaging of the anterior segment and AHO pathways, including SC. Segmental SC anatomy was visualized with the average cross-sectional area greatest temporal (3971 ± 328 μm 2 ) and the least nasal (2727 ± 218 μm 2 ; p = 0.018). After pilocarpine administration, the iris became flatter, and SC became larger (pilocarpine: 26.8 ± 5.0% vs. control: 8.9 ± 4.6% volume increase; p = 0.030). However, the pilocarpine alteration was segmental as well, with a greater increase observed superior (pilocarpine: 31.6 ± 8.9% vs. control: 1.8 ± 5.7% volume increase; p = 0.023) and nasal (pilocarpine: 41.1 ± 15.3% vs. control: 13.9 ± 4.5% volume increase; p = 0.045)., Conclusion: High-resolution circumferential non-invasive imaging using AS-OCT of AHO pathways is possible in living animals with robotic control. Segmental SC anatomy was seen at baseline and was consistent with the known segmental nature of trabecular AHO. Segmental SC anatomical response to a muscarinic agonist was seen as well. Segmental glaucoma drug response around the circumference of AHO pathways is a novel observation that may explain the variable patient response to glaucoma treatments.

In this paper, a kind of layered metastructure (LMS) is proposed by stacking multi-layer dielectric plates. By adjusting the dielectric constant of medium A (set as ε i ), the Brewster angle (BA) of incident electromagnetic waves (EMWs) has been directly selected. At the same time, the operating band of the above angle selection (AS) can be extended to the whole visible light band (VLB) which covers 400 nm to 700 nm according to Bragg reflection. After careful design, two ranges of BAs that cross 0° to 42° and 0° to 60° have been realized in the VLB, which is defined as privacy protection (PP) in this paper. Compared with previous reports, this accomplishment improves transmissivity at small angles and covers a large band. Also, the gradient thickness of the proposed LMS can be changed arbitrarily according to the needs of operating bands, which undoubtedly expands the actual operating scenarios. The obtained results can offer some help to the design of directional devices in industry production, the PP of daily life, and so on.