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Ji-Rong Yang,1 Ying-Yuan Li,2 Tao-Jia Ran,1 Xiao-Yu Lin,1 Jin-Yan Xu,1 Shao-Li Zhou,1 Pin-Jie Huang1 1Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Anesthesiology, Huadu District People’s Hospital, Guangzhou, Guangdong Province, People’s Republic of ChinaCorrespondence: Pin-Jie Huang; Shao-Li Zhou, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong Province, People’s Republic of China, Email hpjie@126.com; 13610272308@139.comPurpose: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA).Patients and Methods: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine (group ED, n=76), 0.5-μg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications.Results: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P < 0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P < 0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P < 0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P< 0.0001).Conclusion: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.Plain language summary: Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.Keywords: cesarean section, dexmedetomidine, esketamine, CSEA, visceral pain

Li-Chao Ma,1,2 Shi-Ning Lou,3 Xiao-Li Zhu,3 Ruo-Lan Zhang,1 Lin Wu,1 Jiang-Yuan Xu,1 Xiao-Juan Ding,1 Juan Liu,4 Yan Wang1 1School of Nursing, Hebei University, Baoding, Hebei, 071000, People’s Republic of China; 2Operating Room, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Department of Traditional Chinese Medicine, Work’s Hospital of China Lucky Group Corporation, Baoding, Hebei, 07100, People’s Republic of China; 4Department of Rehabilitation Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei, 071000, People’s Republic of ChinaCorrespondence: Juan Liu, Department of Rehabilitation Medicine, Affiliated Hospital of Hebei University, No. 212 of Yuhua East Road, Lianchi District, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13582292161, Email juanliulj07@126.com Yan Wang, School of Nursing, Hebei University, No. 342 of Yuhua East Road, Lianchi District, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13833258628, Email ywang_dr06@163.comObjective: This study aimed to explore the needs and constraints to cardiac rehabilitation (CR) among patients diagnosed with coronary heart disease (CHD) in a community-based setting, and thereby facilitating the implementation of effective CR programs for this population.Methods: Focus group interviews were used as the primary research methodology. A total of 11 community-dwelling individuals diagnosed with CHD were selected from a community hospital to participate in in-depth interviews, aiming to discern and analyze their requirements and constraints experienced concerning medical resources and healthcare agency. The textual data underwent examination using Colaizzi’s method of descriptive data analysis.Results: Deficits existed in the perceptions of patients with CHD within a community-based setting about their condition and CR, and in the social support for this disease. Patients expressed expectations for professional guidance during CR, gained an understanding about the beneficial effects of emotional stability on cognitive function. Patients expressed their thoughts and feelings regarding the diversity of physical exercise options. Two main themes and seven sub-themes were identified: (a) “Insufficient CR resources for patients”: Lack of awareness about CHD; inadequate knowledge about secondary prevention/CR; insufficient support from family and friends. (b) “Patient CR initiative”: Patient self-adjustment; expectation of professional rehabilitation guidance; stable emotions improving cognition; diverse attitudes and awareness of exercise.Conclusion: For more effective CR, community-based medical teams should provide more comprehensive and individualized rehabilitation programs. They should focus on individual variations and preferences of patients, as well as enhance the autonomy of patients and improve their self-care ability through effective empowerment measures.Keywords: coronary heart disease, cardiac rehabilitation, community sanitation service, self-care, patient needs

Zhao-Ting Gong,1 Yu-Yan Xiong,1,2 Yu Ning,1 Rui-Jie Tang,1 Jun-Yan Xu,3 Wen-Yang Jiang,1 Xiao-Song Li,1 Li-Li Zhang,1 Cheng Chen,1 Qi Pan,1 Meng-Jin Hu,1 Jing Xu,1 Yue-Jin Yang1 1State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, People’s Republic of China; 2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Yue-Jin Yang, Email yangyjfw@126.comBackground: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI).Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism.Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway.Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation. Keywords: mesenchymal stem cell, exosomes, nicorandil, macrophage polarization, myocardial infarction

Yan Ting Wang,1,&ast; Ya Qin Tang,2 Jia Yuan Xu,1 Xue Mei Bian2,&ast; 1School of Nursing, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Nursing, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Mei Bian, Department of Nursing, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Tel +8613588492353, Email bxm7013@126.comBackground: The incidence of granulomatous lobular mastitis (GLM) is increasing year by year, and the breast wounds of women patients with GLM can develop into abscesses, fistulas, sinuses, and sometimes orange-like degeneration similar to malignant tumors, which seriously affects the quality of life of women patients with GLM. In China, breast wounds in women patients with GLM have not been better managed. Therefore, the purpose of this study is to explore the disease experience of women patients with GLM, to provide a basis for the development of precise intervention and support strategies for women patients with GLM, and to further improve the quality of nursing management and enrich the research types of GLM.Methods: In this study, 10 cases of GLM women patients from a tertiary hospital in Hangzhou, Zhejiang Province were selected by purposive sampling. After obtaining the informed consent of GLM women patients, semi-structured interviews were conducted with GLM women patients using the interview outline to collect qualitative data. The interview was recorded, transcribed verbatim in the local language, and then translated into English, and the content analysis method was used to analyze the data. The Consolidated Criteria for Reporting Qualitative Research (CORE-Q) checklist follows the report ‘s findings.Results: Our study identified six themes: (a) Perception of the disease, (b) Emotional discomfort (c) Variety of changes (d) Lack of specific skills (e) Coping strategies adopted to rebuild health, (f) Expectation.Conclusion: The experience of women with GLM is characterized by diversity and specificity. After experiencing physical trauma, most patients use support systems to change negative attitudes and rebuild physical and mental health. Family, hospital and society should be fully linked to strengthen the prevention of GLM and the popularization of nursing management knowledge; nurses should provide targeted nursing services. Nursing leaders should improve the medical security system, broaden the medical channels, and reduce the pain experience and pressure of patients.Keywords: granulomatous lobular mastitis, non-puerperal mastitis, qualitative study, nursing

Yuan-yuan Wu,1 Wen-Hui Liao,1 Zong-ling Niu,1 Si-Han Zhou,1 Tian-Tian Wu,1 Zhe Li,2 Qi-Hua Zhao,1 Jing-Yuan Xu,2 Ming-jin Xie1 1School of Chemical Science and Technology, Yunnan University, Kunming, People’s Republic of China; 2Department of Chemical Biology and Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Ming-jin Xie, Email mjxie@ynu.edu.cnBackground: Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach.Methods: Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex.Results: Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models.Conclusion: The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.Graphical Abstract: Keywords: gallium complex, nanomedicine, anticancer, colorectal cells, drug delivery, in vivo imaging

Wenguang Lai,1,2,&ast; Xiaoli Zhao,3,&ast; Zhidong Huang,1,&ast; Yun Xie,1,2,&ast; Sijia Yu,1,4 Jiabin Tu,5 Dachuan Guo,6 Jiaming Xiu,5 Ziling Mai,1,2 Qiang Li,1 Haozhang Huang,1,4 Huanqiang Li,1 Jun-Yan Xu,1,7 Hongyu Lu,1 Guanzhong Chen,1 Shiqun Chen,1 Jin Liu,1 Yong Liu1 1Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2School of Biology and Biological Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 3Department of Cardiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Cardiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 6Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 7Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Liu; Jin Liu, Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Email liuyong@gdph.org.cn; ljaw397017568@163.comBackground: Inflammation and immune responses play an important role in the pathophysiology of contrast-associated acute kidney injury (CA-AKI), and systemic immune inflammation index (SII) has recently emerged as a new parameter for immune and inflammatory response evaluation. However, limited research has been undertaken to explore the relationship between SII and CA-AKI following coronary angiography (CAG).Patients and Methods: From January 2007 to December 2020, 46,333 patients undergoing CAG were included from 5 Chinese tertiary hospitals. SII was calculated as total peripheral platelets count × neutrophil-to-lymphocyte ratio. Patients were categorized by preprocedural SII quartiles: Q1 ≤ 404.5, Q2 > 404.5 and ≤ 631.7, Q3 > 631.7 and ≤ 1082.8, Q4 > 1082.8. Univariable and multivariable logistic regression were used to reveal the link between preprocedural SII and CA-AKI.Results: A total of the 46,333 patients (62.9 ± 11.5 years, female 28.1%) were included in the study. The incidence of CA-AKI was 8.4% in Q1 group, 8.7% in Q2 group, 9.4% in Q3 group, 15.1% in Q4 group. In the multivariable model, comparing the highest (Q4 group) to lowest (Q1 group) SII level categories, preprocedural SII was related to a higher risk of CA-AKI after fully adjusting for well-known confounders, and there was no statistically difference in the other two SII level categories (Q2 and Q3 groups) compared with Q1 group (adjusted model 3: Q2 group: OR: 0.98, 95% CI: 0.87– 1.11, P = 0.771; Q3 group: OR: 1.04, 95% CI: 0.92– 1.18, P = 0.553; Q4: OR: 1.65, 95% CI: 1.45– 1.88, p < 0.001; P for trend < 0.001). Similar results were found for all the subgroups analysis except for patients undergoing PCI, and the interaction analyses for age, PCI and AMI were significant. In addition, Kaplan–Meier curves demonstrated that the lowest quartile group showed the worst all-cause mortality in a significant SII level-dependent manner among the four groups (Log rank test; p < 0.0001).Conclusion: Elevated preprocedural SII level was a significant and independent risk factor for CA-AKI following CAG. Higher-quality prospective studies are needed to validate the predictive value of SII for CA-AKI.Keywords: systemic immune inflammation index, contrast-associated acute kidney injury, coronary angiography, preprocedural

Wen-Gang Chen,1,&ast; Sa-Sa Zhang,1– 3,&ast; Shu Pan,1– 3 Zhong-Fang Wang,1 Jin-Ying Xu,1 Xue-He Sheng,1 Qin Yin,1,2 Yi-Jin Wu1,3 1Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China; 2Graduate School, Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China; 3Xin’An Medicine Research Center, Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Yin; Yi-Jin Wu, Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China, Tel +86 13905530299 ; +86 17318531920, Email yq0553@163.com; yijinwu1224@163.comBackground: Studies have found that α-mangostin (MG) can relieve experimental arthritis by activating cholinergic anti-inflammatory pathway (CAP). It affects the polarization of macrophages and the balance of related immune cell subpopulations, but the specific mechanism is still unclear. It has been found that silent information regulator 1 (SIRT1) is closely related to macrophage activity. The purpose of this study is to explore the mechanism of MG intervening in macrophage polarization during treatment of early adjuvant-induced (AIA) rats through the CAP-SIRT1 pathway.Methods: We investigated the polarization of M1 macrophages and the differentiation of Th1 in AIA rats by flow cytometry. Activity of acetylcholinesterase (AChE) and the level of nicotinic adenine dinucleotide (NAD+) in serum were also detected, and immunohistochemical was used to detect the levels of α 7 nicotinic cholinergic receptor (α 7nAChR) and SIRT1. Then in macrophages, the molecular mechanism of MG regulating the abnormal activation of macrophages in rats with early AIA through the CAP-SIRT1 pathway was studied.Results: MG can significantly inhibit the polarization of M1 macrophages and the differentiation of Th1 in AIA rats in the acute phase of inflammation. MG can significantly inhibit the activity of AChE and increase the level of NAD+, thereby further up-regulated the expression levels of α 7nAChR and SIRT1. Meanwhile, MG inhibited nuclear factor-κB (NF-κB)-mediated inflammation by activating the CAP-SIRT1 pathway in macrophages.Conclusion: In summary, the stimulation of MG induced CAP activation, which up-regulated SIRT1 signal, and thereby inhibited M1 polarization through the NF-κB pathway, and improved the pathological immune environment of early-stage AIA rats.Keywords: α-mangostin, rheumatoid arthritis, choline anti-inflammatory pathway, silent information regulator 1, macrophages

Jing-Yong Xu,1 Chen Li,2 He Zhang,3 Yuan Liu,2 Jun-Min Wei1 1Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 2Department of Sonography, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 3Community Health Service Administration Center of Dongcheng District, Beijing 100006, People’s Republic of ChinaCorrespondence: Jun-Min Wei Tel +86-13810351797Email weijunminsci@163.comBackground and Aim: Sarcopenia has been proven to be a risk factor after pancreatoduodenectomy (PD). We aimed to evaluate if decreased psoas muscle area and density shown in CT scan, as measures for sarcopenia, were associated with postoperative major complications and adverse outcomes in patients who underwent PD.Patients and Methods: We analyzed 152 consecutive patients who underwent open PD. Total psoas area and muscle attenuation were measured on CT images at the level of the third lumbar vertebra. Total psoas area index (TPAI) was calculated, the cut-off values of TPAI were estimated and validated. The relationship between radiographic characters and outcomes was analyzed.Results: The optimal cut-off values of TPAI were 4.78 cm2/m2 for males and 3.46 cm2/m2 for females. The values were validated by outcomes with significant differences in the rate of major complications, re-operation, length of stay, and total cost. The prevalence of TPAI-defined sarcopenia and sarcopenic overweight/obesity was 38.8% and 17.1% in total. In multivariate logistic regression, rate of major complications was associated with TPAI [OR=0.605, 95% CI (0.414, 0.883), P=0.009], TPAI-defined sarcopenia [OR=8.256, 95% CI (2.890, 23.583), P=0.000] and sarcopenic overweight/obesity [OR=7.462, 95% CI (2.084, 26.724), P=0.002]; meanwhile, NRS2002-defined nutritional risk and GLIM-defined malnutrition did not show relationship with major complications.Conclusion: Both sarcopenia and sarcopenic overweight/obesity determined by new TPAI cut-off values were associated with a higher rate of major complications and adverse outcomes in Chinese patients undergoing open PD whereas usual nutritional assessment was not.Keywords: psoas muscle area index, CT scan, sarcopenia, sarcopenic obesity, pancreatoduodenectomy

Yao-Dan Liang,1,2 Yao-Nan Zhang,3 Yan-Ming Li,4 Yu-Hui Chen,5 Jing-Yong Xu,6 Ming Liu,7 Jing Li,8 Zhao Ma,9 Lin-Lin Qiao,10 Zi Wang,11 Jie-Fu Yang,1 Hua Wang1 1Department of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 2Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Orthopedics; 4Department of Pulmonary and Critical Care Medicine; 5Department of Neurology; 6Department of General Surgery; 7Department of Urology; 8Department of Geriatrics; 9Department of Rehabilitation; 10Department of Traditional Chinese Medicine; 11Department of Cardiac Surgery, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of ChinaCorrespondence: Hua Wang; Jie-Fu YangDepartment of Cardiology, Beijing Hospital, National Center of Gerontology, No. 1, Dahua Road, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel +86 13911680467; +86 13601292259Fax +86-010-58115035Email wh74220@aliyun.com; yangjiefu2011@126.comObjectives: To survey the difference of frailty prevalence in elderly inpatients amongdifferent wards; to compare the diagnostic performance of five frailty measurements (Clinical Frailty Scale [CFS], FRAIL, Fried, Edmonton, Frailty Index [FI]) in identifying frailty; and to explore the risk factors of frailty in elderly inpatients.Participants and methods: This was a cross-sectional study including 1000 inpatients (mean age 75.2±6.7 years, 51.5% male; 542, 229, and 229 patients from cardiology, non-surgical, and surgical wards, respectively) in a tertiary hospital from September 2018 to February 2019. We applied the combined index to integrate the five frailty measurements mentioned above as the gold standard of frailty diagnosis. Multivariate logistic regression models were used to determine the independent risk factors of frailty.Results: Frailty prevalence was 32.3% (Fried), 36.2% (CFS), 19.2% (FRAIL), 25.2% (Edmonton), 35.1% (FI) in all patients. The frailty was more common in non-surgical wards, regardless of the frailty assessment tools used (non-surgical wards: 27.5% to 51.5%; cardiology ward: 14.9% to 29.3%; surgical wards: 18.8% to 41.9%). CFS≥5 showed a sensitivity of 94.1% and a specificity of 85.2% for all patients. FI≥0.25 showed a sensitivity of 94.8% and a specificity of 87.0% for all patients. Age [odds ratio (OR) = 1.089, P

Yun Liu,1,* Li-Zhi Deng,2,3,* Hai-Peng Sun,1 Jia-Yun Xu,1 Yi-Ming Li,1 Xin Xie,1 Li-Ming Zhang,2,3 Fei-Long Deng1 1Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2PCFM Lab, 3GDHPPC Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: To compare the direct osteogenic effect between placental growth factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2). Methods: Three groups of PlGF-2/BMP-2-loaded heparin–N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 µg PlGF-2; with 1.0 µg BMP-2; and with 0.5 µg PlGF-2 combined with 1.0 µg BMP-2. The loading efficiencies and release profiles of these growth factors (GFs) in this nanocomplex system were quantified using enzyme-linked immunosorbent assay, their biological activities were evaluated using cell counting kit-8, cell morphology, and cell number counting assays, and their osteogenic activities were quantified using alkaline phosphatase and Alizarin Red S staining assays. Results: The loading efficiencies were more than 99% for the nanocomplexes loaded with just PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex loaded with just BMP-2, the loading efficiency was more than 97%. About 83%–84% of PlGF-2 and 89%–91% of BMP-2 were stably retained on the nanocomplexes for at least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects comparable to those of BMP-2 despite its dose in the experiments being lower than that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes encapsulating two GFs have enhanced potential in the enhancement of osteoblast function. Conclusion: PlGF-2-loaded heparin–HTCC nanocomplexes may constitute a promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and BMP-2 appears to have greater potential in bone tissue regeneration than the delivery of either GFs alone. Keywords: placental growth factor-2, bone morphogenic protein-2, heparin, nanocomplexes, osteogenesis

Yong-yan Bei1, Xiao-yan Chen1, Yang Liu1, Jing-yu Xu1, Wen-juan Wang1, Zong-lin Gu1, Kong-lang Xing1, Ai-jun Zhu1, Wei-liang Chen1, Lin-seng Shi1, Qin Wang1, Xue-nong Zhang1, Qiang Zhang21College of Pharmaceutical Science, Soochow University, Suzhou, 2Department of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing, People's Republic of ChinaAbstract: In this paper, two novel liver-targeting nanoparticles, norcantharidin-loaded chitosan nanoparticles (NCTD-CS-NPs) and norcantharidin-associated galactosylated chitosan nanoparticles (NCTD-GC-NPs), were prepared using ionic cross-linkage. The physical properties, particle size, encapsulation efficiency, and drug release characteristics of the nanoparticles were investigated in vitro. To investigate the intestinal absorption mechanisms of the two preparations, a series of experiments was carried out, including in situ circulation method, in vitro everted gut sacs, and Ussing chamber perfusion technique. The absorption rate constants (Ka) of NCTD at different segments were found to be duodenum > jejunum > ileum > colon. The concentration had no distinctive effect on absorption kinetics, suggesting that drug absorption is not dose-dependent. The transport of NCTD was found to be inhibited by P-glycoprotein (P-gp) inhibitor, indicating that NCTD might be the substrate of P-gp. The order of the absorption enhancer effects were as follows: low molecular weight chitosan (CS-8kDa) . high molecular weight chitosan (CS-30kDa) > Poloxamer > sodium dodecyl sulfate (SDS) > sodium deoxycholate (SDCh). The results indicate that the chitosan nanoparticles can improve intestinal absorption of NCTD.Keywords: P-glycoprotein, absorption enhancers

Oral Diseases (2010) 16, 299-304 Objective: To explore a potential causal contribution of the transcription factor HIF-1[alpha] and its target gene, RTP801 and VEGF, to the development of oral lichen planus (OLP). Design relevant: Twenty-two adult OLP patients were enrolled in this study. All OLP diagnoses were verified by histopathological characteristics. Normal mucous specimens were collected from 12 controls after various oral surgeries. Material and method: RNA was isolated from OLP and control specimens. Microarray was performed using BiostarH-40s gene chip. Expression of HIF-1[alpha], VEGF and RTP801 was evaluated using quantitative real-time polymerase chain reaction (qPCR). Unpaired t-test and one-way ANOVA was used for statistical analysis. Results: Microarray results showed that RTP801 expression was lower in OLP than in controls (779 vs 3090). qPCR further confirmed that expression of RTP801 was similarly lower in OLP than in controls (0.363 vs 1.473, P < 0.001); expression of VEGF was also lower in OLP (0.448 vs 1.74, P = 0.012). In contrast, expression of HIF-1[alpha] was higher in OLP than in controls (11.12 vs 1.628, P < 0.001). Conclusion: The oral mucosa of OLP is hypoxic. Genes that are activated by hypoxia, such as RTP801 and VEGF, and their signal cascades may be novel potential therapeutic targets for OLP. [ABSTRACT FROM AUTHOR]

Oral Diseases (2010) 16, 299–304 Objective: To explore a potential causal contribution of the transcription factor HIF-1α and its target gene, RTP801 and VEGF, to the development of oral lichen planus (OLP). Design relevant: Twenty-two adult OLP patients were enrolled in this study. All OLP diagnoses were verified by histopathological characteristics. Normal mucous specimens were collected from 12 controls after various oral surgeries. Material and method: RNA was isolated from OLP and control specimens. Microarray was performed using BiostarH-40s gene chip. Expression of HIF-1α, VEGF and RTP801 was evaluated using quantitative real-time polymerase chain reaction (qPCR). Unpaired t-test and one-way ANOVA was used for statistical analysis. Results: Microarray results showed that RTP801 expression was lower in OLP than in controls (779 vs 3090). qPCR further confirmed that expression of RTP801 was similarly lower in OLP than in controls (0.363 vs 1.473, P < 0.001); expression of VEGF was also lower in OLP (0.448 vs 1.74, P = 0.012). In contrast, expression of HIF-1α was higher in OLP than in controls (11.12 vs 1.628, P < 0.001). Conclusion: The oral mucosa of OLP is hypoxic. Genes that are activated by hypoxia, such as RTP801 and VEGF, and their signal cascades may be novel potential therapeutic targets for OLP. [ABSTRACT FROM AUTHOR]

Background: Rapid response to antidepressant therapy is desirable and may be particularly critical in elderly patients with major depressive disorder (MDD).Methods: Findings are based on post-hoc analyses from a double-blind trial of elderly patients with MDD > or = 65 years, randomly assigned 2:1 to duloxetine 60 mg QD (N = 207) or placebo (N = 104) for 8 weeks. Depression and pain measures included the Geriatric Depression Scale (GDS), 17-item Hamilton Depression Scale (HAMD17), CGI-Severity, and Visual Analog Scale (VAS) for overall pain. The time to response and remission for duloxetine compared with placebo was evaluated using Cox proportional hazards (PH) modeling, Kaplan-Meier estimation, and categorical repeated measures analysis.Results: Significant improvements of estimated HAMD17 response and remission rates for duloxetine started at week 2 (P = 0.022 and P = 0.033, respectively). Time to HAMD17 response and remission were significantly shorter for duloxetine versus placebo (P 0.10 for all PH treatment-by-age interactions). The placebo-referenced duloxetine HR for time to 50% reduction in overall pain was 1.75 (P = 0.024) for patients with moderate to severe pain.Conclusion: Duloxetine demonstrated a faster time to antidepressant response and improvement in self-reported pain as compared with placebo. CLINICAL TRIAL REGISTRY NUMBER FOR THIS STUDY: NCT00062673, at www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy, limiting the clinical application of this treatment. Evidence shows the potential benefits of dietary restriction in improving metabolic profiles and age-related diseases. The present study investigated the effects and mechanisms of dietary restriction in radiation-induced intestinal injury. The mice were randomly divided into the control group, 10 Gy total abdominal irradiation (TAI) group, and groups pretreated with 30% caloric restriction (CR) for 7 days or 24 h fasting before TAI. After radiation, the mice were returned to ad libitum. The mice were sacrificed 3.5 days after radiation, and tissue samples were collected. CR and fasting reduced radiation-induced intestinal damage and promoted intestinal recovery by restoring the shortened colon length, improving the impaired intestinal structure and permeability, and remodeling gut microbial structure. CR and fasting also significantly reduced mitochondrial damage and DNA damage, which in turn reduced activation of the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) pathway and the production of type I interferon and other chemokines in the jejunum. Since the cGAS/STING pathway is linked with innate immunity, we further showed that CR and fasting induced polarization to immunosuppressive M2 macrophage, decreased CD8 + cytotoxic T lymphocytes, and downregulated proinflammatory factors in the jejunum. Our findings indicated that CR and fasting alleviate radiation-induced intestinal damage by reducing cGAS/STING-mediated harmful immune responses., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The increasing prevalence of zinc pollution in marine ecosystems, primarily from industrial sources, has become a global environmental concern. This study addresses zinc toxicity in Chinese coastal waters, emphasizing the importance of considering environmental factors like salinity and temperature in establishing water quality criteria (WQC). Data collected from various marine regions underwent meticulous analysis, incorporating salinity corrections to derive more precise criteria values. The short-term criteria for the Bohai Sea, Yellow Sea, East China Sea, and South China Sea were 94.0, 77.6, 84.2, and 118 μg/L under the salinity correction, respectively, and the long-term criteria was 4.10 μg/L. Ecological risk assessments employing diverse methodologies revealed varying levels of risk across sea areas, underscoring the nuanced nature of zinc pollution's impact on marine ecosystems. Greater acute and chronic risk of zinc ions observed in the Yellow Sea region. These findings underscore the imperative need for tailored management strategies to protect local marine life from the environmental threats posed by zinc., Competing Interests: Declaration of competing interest The authors declare no competing financial interests related to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Immune rejection caused by mismatches in human leucocyte antigens (HLAs) remains a major obstacle to the success of allogeneic cell therapies. Current strategies for the generation of 'universal' immune-compatible cells, particularly the editing of HLA class I (HLA-I) genes or the modulation of proteins that inhibit natural killer cells, often result in genomic instability or cellular cytotoxicity. Here we show that a β 2 -microglobulin super-enhancer (B2M-SE) that is responsive to interferon-γ is a critical regulator of the expression of HLA-I on mesenchymal stromal cells (MSCs). Targeted epigenetic repression of B2M-SE in MSCs reduced the surface expression of HLA-I below the threshold required to activate allogenic T cells while maintaining levels sufficient to evade cytotoxicity mediated by natural killer cells. In a humanized mouse model, the epigenetically edited MSCs demonstrated improved survival by evading the immune system, allowing them to exert enhanced therapeutic effects on LPS-induced acute lung injury. Targeted epigenetic repression of B2M-SE may facilitate the development of off-the-shelf cell sources for allogeneic cell therapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Perillae Folium (PF) is a well-known food and herb containing different chemotypes, which affect its quality. Herein, a method was proposed to classify and quantify PF chemotypes using gas chromatography-mass spectrometry (GC-MS) and Fourier transform-near infrared spectroscopy (FT-NIR). GC-MS results revealed that PF contains several chemotypes, including perilla ketone (PK) type, α -asarone (PP-as) type, and dillapiole (PP-dm) type, with the PK type being the predominant chemotype. Based on FT-NIR data, different chemotypes were accurately classified. The random forest algorithm achieved >90 % accuracy in chemotype classification. Furthermore, the main components of perilla ketone and isoegomaketone in PF were successfully quantified using partial least squares regression models, with prediction to deviation values of 3.76 and 2.59, respectively. This method provides valuable insights and references for the quality supervision of PF and other foods., Competing Interests: 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., (© 2024 The Authors.)

Printer source prediction is an important task when examining questioned documents. While some research has provided methods to predict the source printer of documents, with the advent of compatible consumables, printer prediction could become more complex and difficult. Predicting the source printer after replacing cartridges and identifying the source of printer cartridges are unresolved issues that are rarely addressed in current research. Herein, we introduce a novel technique to predict the manufacturer, model, and cartridges of laser printers (i.e., compatible, and original cartridges) used to produce a given document. Document samples produced using eight laser printers and 247 cartridges were collected to establish a dataset. Common manufacturers included HP, Canon, Lenovo, and Epson. After obtaining white-light images and three-dimensional profile images of printed characters, a morphological analysis was conducted by questioned document examiners (QDEs) using microscopy. Microscopic image features across a series of images were also extracted and analyzed using algorithms. Then, six high-dimensional reduction algorithms were used to obtain between- and within-printer variations as well as between- and within-cartridge variations. Finally, we conducted principal component analysis (PCA) and discriminant analysis. For 40 % of the samples, mixed discrimination analysis (MDA) and fixed discrimination analysis (FDA) were employed to predict the manufacturer, model and cartridge of laser printers used to produce the questioned printed document; the remaining 60 % samples comprised the training dataset. In the prediction of manufacturer, model and cartridge, our method achieved mean accuracies of 95.5 %, 97.5 %, and 90.2 %, respectively. Hence, this technique could reasonably aid in predicting the manufacturer, model, and cartridge of a laser printer, even if different cartridges are loaded into printers., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: There is an urgent need to develop an efficient therapeutic strategy for heart failure with preserved ejection fraction (HFpEF), which is mediated by phenotypic changes in cardiac macrophages. We previously reported that vitamin B-6 inhibits macrophage-mediated inflammasome activation., Objectives: We sought to examine whether the prophylactic use of vitamin B-6 prevents HFpEF., Methods: HFpEF model was elicited by a combination of high-fat diet and N ω -nitro-l-arginine methyl ester supplement in mice. Cardiac function was assessed using conventional echocardiography and Doppler imaging. Immunohistochemistry and immunoblotting were used to detect changes in the macrophage phenotype and myocardial remodeling-related molecules., Results: Co-administration of vitamin B-6 with HFpEF mice mitigated HFpEF phenotypes, including diastolic dysfunction, cardiac macrophage phenotypic shifts, fibrosis, and hypertrophy. Echocardiographic improvements were observed, with the E/E' ratio decreasing from 42.0 to 21.6 and the E/A ratio improving from 2.13 to 1.17. The exercise capacity also increased from 295.3 to 657.7 min. However, these beneficial effects were negated in downstream of kinase (DOK) 3-deficient mice. Mechanistically, vitamin B-6 increased DOK3 protein concentrations and inhibited macrophage phenotypic changes, which were abrogated by an AMP-activated protein kinase inhibitor., Conclusions: Vitamin B-6 increases DOK3 signaling to lower risk of HFpEF by inhibiting phenotypic changes in cardiac macrophages., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

The development of acute respiratory distress syndrome (ARDS) in sepsis is associated with substantial morbidity and mortality. However, the molecular pathogenesis underlying sepsis-induced ARDS remains elusive. Neutrophil heterogeneity and dysfunction contribute to uncontrolled inflammation in patients with ARDS. A specific subset of neutrophils undergoing reverse transendothelial migration (rTEM), which is characterized by an activated phenotype, is implicated in the systemic dissemination of inflammation. Using single-cell RNA sequencing (scRNA-seq), it identified functionally activated neutrophils exhibiting the rTEM phenotype in the lung of a sepsis mouse model using cecal ligation and puncture. The prevalence of neutrophils with the rTEM phenotype is elevated in the blood of patients with sepsis-associated ARDS and is positively correlated with disease severity. Mechanically, scRNA-seq and proteomic analys revealed that inflamed endothelial cell (EC) released extracellular vesicles (EVs) enriched in karyopherin subunit beta-1 (KPNB1), promoting abluminal-to-luminal neutrophil rTEM. Additionally, EC-derived EVs are elevated and positively correlated with the proportion of rTEM neutrophils in clinical sepsis. Collectively, EC-derived EV is identified as a critical regulator of neutrophil rTEM, providing insights into the contribution of rTEM neutrophils to sepsis-associated lung injury., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Alzheimer's disease (AD) is a neurodegenerative disorder frequently accompanied by neuroinflammation and oxidative stress. The medicine and food homology (MFH) has shown potential for treating neuroinflammation and oxidative stress. This study aimed to provide a safe and efficient therapy for AD based on MFH. In this study, we develop a MFH formula consisting of egg yolk oil, perilla seed oil, raphani seed oil, cinnamon oil, and noni puree (EPRCN). To evaluate the ameliorative effects of EPRCN on AD-related symptoms, a mouse model of AD was constructed using intraperitoneal injection of scopolamine in ICR mice. Experimental results demonstrated that EPRCN supplement restored behavioral deficits and suppressed neuroinflammation and oxidative stress in the hippocampus of scopolamine-induced mice. An in vitro study was then performed using induction of Aβ (25-35) in glial (BV-2 and SW-1783) and neuron (SH-SY5Y) cell lines to examine the improvement mechanism of EPRCN on cognitive deficits. Multi-omics and in vitro studies demonstrated that these changes were driven by the anandamide (AEA)-Trpv1-Nrf2 pathway, which was inhibited by AM404 (an AEA inhibitor), AMG9810 (a Trpv1 inhibitor), and BT (an Nrf2 inhibitor). Consequently, EPRCN is an effective therapy on preventing cognitive deficits in mouse models of AD. In contrast to donepezil, EPRCN exhibits a novel modes action for ameliorating neuroinflammation. The mechanism of EPRCN on preventing cognitive deficits is mediated by improving neuroinflammation and oxidative stress via activating the AEA-Trpv1-Nrf2 pathway., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Stability-issues of organic light-emitting diodes (OLEDs) employing thermally activated delayed fluorescence (TADF) require further advancements, especially in pure-blue range of CIE y < 0.20, existing a dilemma between color purity and device lifetime. Though improving bond-dissociation-energy (BDE) can effectively improve material intrinsic stability, strategies to simultaneously improve BDE and photophysical performances are still lacking. Herein, it is disclosed that synergistic intramolecular non-covalent interactions (Intra-NI) can achieve not only the highest C─N BDE among blue TADF materials, but enhanced molecular-rigidity, near-unity photoluminescent quantum yields and short delayed lifetime. Pure-blue TADF-OLEDs based on proof-of-concept TADF material realize high external-quantum-efficiency and record-high LT 80 @500 cd m -2 of 109 h with CIE y = 0.16. Furthermore, deep-blue TADF-sensitized devices exhibit high LT 80 @500 cd m -2 of 81 h with CIE y = 0.10. The findings provide new insight into the critical role of Intra-NI in OLED materials and open the way to tackling vexing stability issues for developing robust pure-blue organic emitters and other functional materials., (© 2024 Wiley‐VCH GmbH.)

Herein, chiral metal-organic frameworks (MOFs), DCF-20 and LCF-20, were utilized as matrices for both chirality transfer and energy transfer. HBT1@MOFs and HBT2@MOFs emit excitation-dependent circularly polarized luminescence (CPL) due to excited-state intramolecular proton transfer (ESIPT). HBT1/C152/NIR@MOFs exhibit full-color and white CPL. The luminescence dissymmetry factors ( g lum ) were significantly increased, benefiting from the efficient chirality space transfer and high luminescence efficiency.

As a prerequisite for the success of embryo development, embryonic genome activation (EGA) is an important biological event in which zygotic gene products in the embryo are activated to replace maternal-derived transcripts. Although EGA has been extensively studied in a large number of vertebrates and invertebrates, there is a lack of information regarding this event in crustacean crab. In this study, the timing of EGA was confirmed by examining a transcriptomic dataset of early embryonic development, including mature oocytes and embryos through six early developmental stages, and signaling pathways associated with EGA were identified in the mud crab, S. paramamosain. The comprehensive transcriptomic data identified a total of 53,915 transcripts from these sequencing samples. Notable transcriptomic change was evident at the 1-cell stage, indicated by a 36% transcript number shift and a reduction in transcript fragment length, compared to those present in the mature oocytes. Concurrently, a substantial increase in the expression of newly transcribed transcripts was observed, with gene counts reaching 3485 at the 1-cell stage, indicative of the onset of EGA. GO functional enrichment revealed key biological processes initiated at the 1-cell stage, such as protein complex formation, protein metabolism, and various biosynthetic processes. KEGG analysis identified several critical signaling pathways activated during EGA, including the "cell cycle," "spliceosome," "RNA degradation", and "RNA polymerase", pathways. Furthermore, transcription factor families, including zinc finger, T-box, Nrf1, and Tub were predominantly enriched at the 1-cell stage, suggesting their pivotal roles in regulating embryonic development through the targeting of specific DNA sequences during the EGA process. This groundbreaking study not only addresses a significant knowledge gap regarding the developmental biology of S. paramamosain, especially for the understanding of the mechanism underlying EGA, but also provides scientific data crucial for the research on the individual synchronization of seed breeding within S. paramamosain aquaculture. Additionally, it serves as a reference basis for the study of early embryonic development in other crustacean species., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)