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As higher education struggles to catch up with the constantly shifting social climate, many modern students are being left overwhelmed by the sheer volume of choices they are being offered in a phenomenon known as the "tyranny of freedom". This issue is exacerbated when they do not have the appropriate guidance from either their parents or universities to build their own identity and find a suitable position in a functional society. Following the innovative education trend, a few top-ranking universities have started self-designed major programs, making themselves pioneers of experimental education in the traditional university system. The purpose of this study aims at discovering how Taiwanese self-designed major students organize their study maps from human and identity capital perspectives. Fifteen research participants were recruited from the three universities providing self-designed major bachelor programs and asked to participate in a semi-structured interview. The content analysis result outlines those students as "learning nomads" who break department or field boundaries to do interdisciplinary learning with clear goals by tracing their learning resources across borders. Three crucial outcomes have been found: first, identity capital mainly influences college entrance channel choices in regards to motivation and has a minor influence on how self-designed major students arrange their learning maps. Second, in regards to human capital, modularized and self-directed learning and the arrangement of theoretical and experiential knowledge do not work alone but together. Finally, learning guidance was found to be essential under the stress of tyranny of freedom.

Tu Li,1 Runting Li,1 Fa Lin,1 Xiaolin Chen1– 3 1Department of Neurosurgery, Beijing Tiantan Hospital, Beijing, People’s Republic of China; 2Stroke Center, Beijing Institute for Brain Disorders, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xiaolin Chen, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Beijing, Fengtai District, 100070, People’s Republic of China, Email chenxiaolin@bjtth.orgPurpose: Early systemic inflammatory changes are increasingly recognized as factors influencing outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Systemic inflammation response index (SIRI), an inflammation biomarker, was thought to be associated with adverse outcomes in many other diseases. However, in aSAH, research on SIRI remains limited. Thus, our objective was to investigate the association between SIRI and poor long-term functional outcomes while evaluating the mediating role of in-hospital complications in this association.Patients and Methods: SIRI was defined as neutrophil count × monocyte count/lymphocyte count. Patients were categorized according to SIRI quartiles. Stabilized inverse probability of treatment weighting (sIPTW) was utilized to minimize group differences. The association between SIRI and in-hospital complications as well as poor 90-day functional outcomes (mRS 3– 6) was estimated by multivariable logistic regression analyses. Mediation analysis was performed to investigate the relationship between SIRI and poor functional outcomes mediated by in-hospital complications.Results: A total of 650 patients were prospectively included. After sIPTW, compared to the lowest quartile, an elevated SIRI was associated with delayed cerebral ischemia (DCI) (OR 2.12, 95% CI 1.20– 3.74), post-operative pneumonia (POP) (OR 2.16, 95% CI 1.29– 3.62) and poor 90-day functional outcomes (OR 3.03, 95% CI 1.55– 5.91). In-hospital complications including DCI (mediation proportion, 18.18% before sIPTW and 20.0% after sIPTW) and POP (mediation proportion, 18.18% before sIPTW and 26.7% after sIPTW) partially mediated the association between SIRI and poor 90-day functional outcomes. Mediation analysis yielded comparable results in subgroups stratified by age and sex.Conclusion: In this study, SIRI was associated with poor long-term functional outcomes in aSAH, which was partially mediated by DCI and POP with a mediation proportion exceeding 18%. Our findings might underscore the potential utility of SIRI in prompting physicians to address systemic inflammatory status timely to prevent in-hospital complications, including DCI and POP, and ultimately improve long-term functional outcomes.Keywords: aneurysmal subarachnoid hemorrhage, systemic inflammation response index, complications, functional outcomes, mediation analysis

Jing Zhang,1,2 Ke Ma,3 Jun Yan,4 Pingsheng Pan,5 Jiangshan Yin,6 Fuqing Lin,7 Hui Chen,8 Weiwei Zhao,1,2 Menglei Chen,1,2 Zhe Zhang,1,2 Minghui Liu,1,2 Xiaoli Gu,1,2 Xinghe Liao,1,2 Chenyue Zhang,1,2 Wenwu Cheng1,2 1Department of Integrated Therapy, Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Oncology, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 5Department of Oncology, Fangta Hospital of Traditional Chinese Medicine in Songjiang District, Shanghai, People’s Republic of China; 6Department of Oncology, Fudan University Shanghai Cancer Center, Minhang Branch, Shanghai, People’s Republic of China; 7Department of Anaesthesiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 8Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Wenwu Cheng, Email cwwxxm@sina.comPurpose: This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in Shanghai.Methods: From 2019 to 2021, a questionnaire survey was conducted among physicians engaged in diagnosis and treatment of cancer pain through the questionnaire WJX network platform in Shanghai, China.Results: A total of 238 responses participated in the survey. This survey reports physicians’ understanding and incidence rate of breakthrough cancer pain (BTCP). The choice of analgesics and satisfaction of analgesic effect were investigated. We also investigated doctors’ knowledge of the diagnostic criteria for RCP and their tendency to choose analgesics. Oral immediate-release morphine and intravenous or subcutaneous morphine injection have been the common treatment approach for transient cancer pain exacerbations. The main barriers to pain management are lack of standardized treatment methods for RCP, lack of knowledge related to RCP, and single drug dosage form. Doctors believe the most necessary measures to improve the current situation of poor cancer pain control include improving medical staff’s understanding and treatment techniques for RCP, updating treatment techniques and methods, and improving the configuration of drug types in medical institutions. Clinicians expect to improve understanding and treatment techniques through systematic training.Conclusion: Despite multiple available analgesic measures, the treatment of RCP remains challenging. Improving the understanding of medical staff towards RCP, improving treatment techniques, and increasing the accessibility of multiple drug types are important ways to improve the satisfaction of cancer pain management in the future.Keywords: refractory cancer pain, breakthrough cancer pain, pain management, opioid drugs

Jin Tu,1– 3,* Feng Jiang,4,* Jieni Fang,2 Luhua Xu,2 Zhicong Zeng,2 Xuanyue Zhang,1 Li Ba,1 Hanjiao Liu,1,3 Fengxia Lin2 1Department of Nursing, Seventh Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 2Department of Cardiovascular, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 3Department of Nursing, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 4School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengxia Lin, Department of Cardiovascular, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China, Email szlinfx@163.com Hanjiao Liu, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China, Email liuhanjiao000@163.comBackground: Dendrobium, with profound botanical importance, reveals a rich composition of bioactive compounds, including polysaccharides, flavonoids, alkaloids, and diverse amino acids, holding promise for skin regeneration. However, the precise mechanism remains elusive. Seeking a potent natural remedy for wound healing, exocyst vesicles were successfully isolated from Dendrobium.Aims of the Study: This investigation aimed to employ bioinformatics and in vivo experiments to elucidate target genes of Dendrobium-derived nanovesicles in skin wound healing, focusing on immune infiltration and senescence characteristics.Materials and Methods: C57 mice experienced facilitated wound healing through Dendrobium-derived nanovesicles (DDNVs). Bioinformatics analysis and GEO database mining identified crucial genes by intersecting immune-related, senescence-related, and PANoptosis-associated genes. The identified genes underwent in vivo validation.Results: DDNVs remarkably accelerated skin wound healing in C57 mice. Bioinformatics analysis revealed abnormal expression patterns of immune-related, senescence-related, and pan-apoptosis-related genes, highlighting an overexpressed IL-1β and downregulated IL-18 in the model group, Exploration of signaling pathways included IL-17, NF-kappa B, NOD-like receptor, and Toll-like receptor pathways. In vivo experiments confirmed DDNVs’ efficacy in suppressing IL-1β expression, enhancing wound healing.Conclusion: Plant-derived nanovesicles (PDNV) emerged as a natural, reliable, and productive approach to wound healing. DDNVs uptake by mouse skin tissues, labeled with a fluorescent dye, led to enhanced wound healing in C57 mice. Notably, IL-1β overexpression in immune cells and genes played a key role. DDNVs intervention effectively suppressed IL-1β expression, accelerating skin wound tissue repair.Keywords: plant-derived nanovesicles, Dendrobium, immune infiltration factors, cellular aging, skin injury recovery

Kangze Wu, Feizhuan Lin Department of Hepatobiliary Surgery, Shaoxing People’s Hospital, Shaoxing, People’s Republic of ChinaCorrespondence: Feizhuan Lin, Department of Hepatobiliary Surgery, Shaoxing People’s Hospital, Shaoxing, People’s Republic of China, Email linfeizhuan@163.comAbstract: Hepatocellular carcinoma (HCC) stands as a severe malignant tumor with a profound impact on overall health, often accompanied by an unfavorable prognosis. Despite some advancements in the diagnosis and treatment of this disease, improving the prognosis of HCC remains a formidable challenge. It is noteworthy that lipid metabolism plays a pivotal role in the onset, development, and progression of tumor cells. Existing research indicates the potential application of targeting lipid metabolism in the treatment of HCC. This review aims to thoroughly explore the alterations in lipid metabolism in HCC, offering a detailed account of the potential advantages associated with innovative therapeutic strategies targeting lipid metabolism. Targeting lipid metabolism holds promise for potentially enhancing the prognosis of HCC.Keywords: cholesterol, fatty acid, hepatocellular carcinoma, lipid uptake, lipid catabolism, lipid synthesis

Fangju Lin,1 Weihua Jia,1 Xuemei Li,2 Ying Chen,1 Min Wan1 1Department of Neurology, Beijing Shijingshan Hospital, Shijingshan Teaching Hospital of Capital Medical University, Beijing, 100043, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, People’s Republic of ChinaCorrespondence: Weihua Jia; Xuemei Li, Email jiawh_sjsh@163.com; lixuemei8806@163.comPurpose: Parkinson’s disease (PD) patients with freezing of gait (FOG) may present with complex and heterogeneous cognitive profiles. Owing to limited access to comprehensive neuropsychological battery in ordinary clinical practice, the Montreal Cognitive Assessment (MoCA) is likely to be easily available cognitive data for comparisons among studies. This study aims to explore the cognitive profiles stratified by education using MoCA in PD patients with FOG.Patients and Methods: PD patients with FOG (FOG+, n = 52) and without FOG (FOG-, n = 71) were included in our study. MoCA items were categorized into five subsections (attention/working memory, executive function, episodic memory, language, and visuospatial function) referring to previously published criteria. Cognitive assessments were compared based on five subsections between groups stratified by three education levels (0– 6 years, 7– 12 years, and > 12 years). The association of cognitive measurements with FOG were analyzed using binary logistic regression models with adjustment for variables.Results: The total scores and subscores of each subsection of MoCA were similar between two groups of each education level. Further detailed analysis showed that a composite measure labeled “Attention/working memory-Composite” (abbreviated to Attention-C), consisting of the scores of four items (target detection task, serial sevens, digit forward and backward, and sentence repetition), were lower significantly in FOG+ group compared with FOG- group in patients with education year ≤ 6 years. The significant association of Attention-C with FOG held true when controlling for disease duration, but not for H-Y stage, MDS-UPDRS III, HAMA, and HAMD.Conclusion: Overall, our findings gave a hint that Attention-C derived from MoCA might be a potential factor associated with FOG in PD patients with lower education level (education year ≤ 6 years), which will need to be validated in future studies.Plain Language Summary: Parkinson’s disease (PD) patients with freezing of gait (FOG) may present with complex and heterogeneous cognitive profiles. Owing to limited access to comprehensive neuropsychological battery in ordinary clinical practice, the Montreal Cognitive Assessment (MoCA) is likely to be easily available cognitive data for comparisons among studies. To the best of our knowledge, our study is the first to investigate the cognitive profiles using MoCA stratified by education in Chinese PD patients with FOG. We proposed a novel composite measure derived from MoCA labeled “Attention/working memory-Composite” (abbreviated to Attention-C), consisting of the scores of four items (target detection task, serial sevens, digit forward and backward, and sentence repetition). We found a significant association of Attention-C with FOG existed in PD patients with education year ≤ 6 years when controlling for disease duration, but disappeared for H-Y stage, MDS-UPDRS III, HAMA, and HAMD. It may be attributed to a large extent to the relatively small size of our study population. Our findings gave a hint that Attention-C derived from MoCA might be a potential factor associated with FOG in PD patients with lower education level (education year ≤ 6 years), which need to be further explored and validated in expanded studies with different international populations. Thus, the present study could provide critical implications for ordinary clinical practice where comprehensive neuropsychological batteries are not easily accessible to clinicians.Keywords: Parkinson’s disease, freezing of gait, Montreal Cognitive Assessment, attention, working memory, executive function

Youli Jiang, Yao Xiong, Yue Chi, Fu Lin, Qingshi Zhao, Yanfeng Li Department of Neurology, People’s Hospital of Longhua, Shenzhen, 518109, People’s Republic of ChinaCorrespondence: Qingshi Zhao; Yanfeng Li, Email 66327285@qq.com; 308114251@qq.comPurpose: Timely medical attention is crucial for patients with Acute Ischemic Stroke (AIS), as delays can significantly impact therapeutic outcomes. These delays are influenced by a combination of socio-cultural, educational, and clinical factors.Patients and Methods: An in-depth analysis was conducted to assess the prevalence and median duration of healthcare-seeking delays in AIS patients. The study specifically investigated the independent impacts of sociocultural and clinical determinants on these delays, with a focus on immigrant status, gender disparities, and educational levels. Multivariate regression analysis was employed to identify these independent effects while controlling for potential confounding factors.Results: Among 1419 AIS patients, 82.52% (n = 1171) experienced delays exceeding 2 hours from symptom onset of symptoms to hospital arrival. The median delay was 12.3 hours. Immigrant populations encountering longer delays compared to native groups. Younger males (< 45 years) and elderly females were more prone to delay in healthcare-seeking. Identified independent risk factors for delay included male gender (OR = 1.65 [95% CI:1.14− 2.48]), self-acknowledged diabetes (OR = 2.50 [95% CI:1.21– 5.17]), small vessel (OR = 2.07 [95% CI:1.27– 3.36]), and wake stroke (OR = 7.04 [95% CI:3.69– 13.44]). Educational background (high school and above), GCS score with 3– 8 points (OR = 0.52 [95% CI:0.09– 0.69]), understanding stroke-related knowledge (OR = 0.26 [95% CI:0.09– 0.44]), conscious disturbance (OR = 0.25 [95% CI:0.10– 0.62]) and limb weakness (OR=0.21[95% CI:0.21– 0.49]) are protective factors for timely treatment.Conclusion: Immigrant populations experienced longer delays from symptom onset to hospital arrival. The crucial roles of education and knowledge about stroke underscore the need for enhanced health literacy campaigns and public awareness, with a targeted focus on younger males and elderly females.Keywords: healthcare-seeking behavior, immigrant population, educational disparity, pre-hospital delay, AIS

Xiaoshuai Ren,1,&ast; Feng Lin,2,&ast; Chaogang Tang,2,&ast; Yao Liu,3 Guolei Liao,2 Jiabi Liang,3 Wenji Luo,3 Lei Zhang,2 Wenli Chen3 1Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, 519000, People’s Republic of China; 2Department of Cerebrovascular Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, 519000, People’s Republic of China; 3Department of Pharmacy, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, 519000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenli Chen; Lei Zhang, Tel +15626471884 ; +13726209240, Email chenwenl@mail3.sysu.edu.cn; zhangl92@mail.sysu.edu.cnPurpose: Stroke is a leading cause of disability and death globally. However, there are few clinical drugs for stroke therapy. Novel and effective neuroprotectants are called on the way.Methods: In this study, 93 steroids from a constructed steroidal library were randomly numbered and blindly evaluated in an L-glutamate-induced HT-22 oxidative stress model. The neuroprotective effects of 5 candidates were further investigated in potassium deprivation-induced apoptosis of cerebellar granule neurons (CGNs), D-glutamate-induced excitotoxicity of CGNs, and cortical neuron (CN) models.Results: Interestingly, unblinding revealed that cholest-4-ene-3,6-dione (78), a cholesterol derivative, was first found to have comprehensive neuroprotective effects in all cell models. 78 administration also decreased the infarction volume and improved motor function in middle cerebral artery occlusion (MCAO) model rats. Additionally, 78 treatment decreased intercellular reactive oxygen species (ROS) and NO production in the HT-22 cell model. Finally, lipidomics and molecular docking results showed that 78 may exert its neuroprotective effects by increasing platelet-activating factor (PAF) analog 1-(9Z-pentadecenoyl)-glycero-3-phosphocholine production.Conclusion: This study indicates that 78, a novel neuroprotectant, is a promising therapeutic candidate with comprehensive neuroprotective effects for the treatment of ischemic stroke by decreasing ROS/reactive nitrogen species (RNS) levels and increasing 1-(9Z-pentadecenoyl)-glycero-3-phospho-choline production. Keywords: neuroprotection, cholest-4-ene-3,6-dione, anti-ROS, lipidomics, molecular docking

Weisheng Xu,1,2,&ast; Wangsheng Xue,1,&ast; Zeyu Zhou,3,&ast; Jiying Wang,1 Hui Qi,1 Shiyu Sun,1 Tong Jin,1 Ping Yao,1 Jian-Yuan Zhao,4 Fuqing Lin1 1Department of Pain Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2School of Medicine, Tongji University, Shanghai, 200331, People’s Republic of China; 3School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China; 4Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200090, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fuqing Lin, Department of Pain Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China, Email fuqinglin@tongji.edu.cn Jian-Yuan Zhao, Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200090, People’s Republic of China, Email zhaojy@vip.163.comBackground: As one of the most frequent complications of type 2 diabetes mellitus (T2DM), diabetic peripheral neuropathy (DPN) shows a profound impact on 50% of patients with symptoms of neuropathic pain, numbness and other paresthesia. No valid serum biomarkers for the prediction of DPN have been identified in the clinic so far. This study is to investigate the potential serum biomarkers for DPN firstly based on 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomics technique.Methods: Thirty-six patients enrolled in this study were divided into two groups: 18 T2DM patients without DPN (T2DM group) and 18 T2DM patients with DPN (DPN group). Serum metabolites were measured via 1H-NMR spectroscopy. Bioinformatic approaches including principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), independent sample t-test, Fisher’s test, Pearson and Spearman correlation analysis, Stepwise multiple linear regression analysis and receiver operating characteristic (ROC) curve analysis were used to identify the potential altered serum biomarkers.Results: A total of 20 metabolites were obtained and further analyzed. Formate was identified as the only potential biomarker that decreased in the DPN group with statistical significance after multiple comparisons (p< 0.05). Formate also displayed a negative relationship with some elevated clinical markers in DPN. ROC curve analysis showed a good discriminative ability for formate in DPN with an area under the curve (AUC) value of 0.981.Conclusion: Formate could be considered a potential serum metabolic biomarker for DPN. The reduced level of formate in DPN may be associated with mitochondrial dysfunction and gut microbiota alteration. Monitoring the level of serum formate would be an important strategy for the early diagnosis of DPN and a supplement of formate may be a promising treatment for DPN in the future.Keywords: diabetic peripheral neuropathy, type 2 diabetes mellitus, 1H-NMR, metabolomics, formate, uric acid

Xiayan Xu,1– 3,&ast; Yun Xie,2– 4,&ast; Xia Gu,5– 7,&ast; Yang Zhou,2,3 Yu Kang,2,3,8 Jin Liu,2,3 Wenguang Lai,2– 4 Hongyu Lu,2,3 Shiqun Chen,2,3 Jun-yan Xu,2,3,9 Feng Lin,10 Yong Liu1– 3 1School of Medicine, South China University of Technology, Guangzhou, 510006, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4School of Biology and Biological Engineering South China University of Technology, Guangzhou, 510006, People’s Republic of China; 5Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 6The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, Heilongjiang, 150086, People’s Republic of China; 7Cardiovascular Imaging Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 8Shantou University Medical College, Shantou, 515041, People’s Republic of China; 9Ministry 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; 10Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Lin, Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China, Email linfeng3085@163.com Yong Liu, South China University of Technology, No. 382, Waihuan East Road, University City, Panyu District, Guangzhou, Guangdong Province, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email liuyong@gdph.org.cnBackground: Blood glucose levels significantly affect the clinical prognosis of patients with coronary artery disease (CAD), and systemic immune inflammation is a common risk factor for both CAD and diabetes. However, the relationship between immune inflammation levels and poor prognosis in patients with CAD with different glucose metabolic statuses remains unclear.Methods: Between January 2007 and December 2020, we recruited 84,645 patients with CAD. The systemic immune inflammation index (SII) was used to comprehensively reflect the immune and inflammatory levels of patients and was calculated using the following formula: neutrophils × platelets/lymphocytes. The patients were classified into nine groups according to their glucose metabolism status (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]). Cox regression models and competing risk Fine and Gray models were used to investigate the association between SII and clinical outcomes.Results: During the follow-up period, 12,578 patients died, including 5857 cardiovascular-related and 1251 cancer-related deaths. The risk of all-cause and cause-specific mortality increased with increasing SII tertiles in CAD patients with NGR, pre-DM, and DM. When considering glucose metabolism status, the multivariate cox regression revealed that CAD patients with DM and SII-H levels had the highest risk of all-cause mortality (1.69 [1.56– 1.83]), cardiovascular mortality (2.29 [2.02– 2.59]), and cancer mortality (1.29 [1.01– 1.66]). Moreover, incorporating the SII into traditional risk factor models significantly improved the C-index for predicting all-cause and cardiovascular mortality.Conclusion: Systemic immune inflammation levels on admission were correlated with a higher risk of all-cause and cause-specific mortality in patients with CAD, particularly in those with DM.Keywords: systemic immune inflammation index, coronary artery disease, type 2 diabetes, prognosis, mortality

Zhenshan Song,1,&ast; Fa Lin,1,&ast; Yu Chen,1 Tu Li,1 Runting Li,1 Junlin Lu,1 Heze Han,1 Ruinan Li,1 Jun Yang,1 Zhipeng Li,1 Haibin Zhang,1 Kexin Yuan,1 Ke Wang,1 Yunfan Zhou,1 Yitong Jia,1 Xiaolin Chen1– 3 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Stroke Center, Beijing Institute for Brain Disorders, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaolin Chen, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Email chenxiaolin@bjtth.orgPurpose: Systemic inflammation plays an important role in the pathophysiology and progression of aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to investigate the association between a new biomarker, the inflammatory burden index (IBI) and the prognosis as well as in-hospital complications of aSAH patients.Patients and Methods: We analyzed data from patients with aSAH between January 2019 and September 2022 who were included in the LongTEAM (Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage) registry study. The IBI was formulated as C-reactive protein × neutrophils/lymphocytes. The unfavorable functional prognosis was assessed by the modified Rankin Scale (mRS). Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values for IBI to distinguish the unfavorable functional prognosis. Multivariate logistic regression was applied to investigate the association between IBI and in-hospital complications. Propensity score matching was adjusted for imbalances in baseline characteristics to assess the effect of IBI on prognosis.Results: A total of 408 consecutive patients with aSAH enrolled in the study, of which 235 (57.6%) were female patients and the mean age was 55.28 years old. An IBI equal to 138.03 was identified as the best cut-off threshold to distinguish the unfavorable prognosis at 3 months (area under the curve [AUC] [95% CI] 0.637 [0.568– 0.706]). ln IBI was independently associated with 3-month functional prognosis (OR [95% CI] 1.362 [1.148– 1.615]; P< 0.001), pneumonia (OR [95% CI] 1.427 [1.227– 1.659]; P< 0.001) and deep venous thrombosis (DVT). (OR [95% CI] 1.326 [1.124– 1.564]; P=0.001). After propensity score matching (57:57), an increased proportion of patients with IBI ≥ 138.03 had a poor functional prognosis at 3 months and in-hospital complications including developed pneumonia and DVT.Conclusion: In patients with aSAH, high IBI level at admission was associated with unfavorable functional prognosis as well as pneumonia and deep vein thrombosis.Keywords: aneurysmal subarachnoid hemorrhage, inflammatory burden index, functional prognosis, complications

Yunxia Wang,1– 3 Wenting Hu,2 Fuquan Lin,2,3 Ai′e Xu2 1Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Dermatology, Hangzhou Clinical College of Anhui Medical University, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Ai′e Xu, Hangzhou Third People’s Hospital, No. 38 Xihu Avenue, Shangcheng District, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86-131 5513 0536, Fax +86+ 571+87827534, Email xuaiehz@msn.comAbstract: Graft versus host disease (GVHD) is a complex immune-mediated pathophysiological process, which is caused by allogenic immune reactions between donors and recipients. No matter ac-ute or chronic GVHD, skin involvement is the most common, severe skin damage can lead to permanent disfigurement, which seriously affects the long-term quality of life of patients. We herein report a patient with generalized vitiligo after allogeneic peripheral hematopoietic stem cell transplantation (allo-HSCT) for aplastic anemia.Keywords: graft versus host disease, vitiligo, aplastic anemia, allogeneic peripheral hematopoietic stem cell transplantation

Qianqian Yao,1,&ast; Kexin Jiang,1,&ast; Fei Lin,2 Tao Zhu,3 Nazeer Hussain Khan,1,4 Enshe Jiang1,4 1Institute of Nursing and Health, Henan University, Kaifeng, People’s Republic of China; 2School of Medicine, Shangqiu Institute of Technology, Shangqiu, People’s Republic of China; 3Department of Geriatrics, Kaifeng Traditional Chinese Medicine Hospital, Kaifeng, People’s Republic of China; 4Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Enshe Jiang, Email esjiang@gmail.comAbstract: Alzheimer’s disease (AD), the most common cause of dementia and the fifth leading cause of death in the adult population has a complex pathophysiological link with hypertension (HTN). A growing volume of published literature on a parallel elevation of blood pressure (BP), amyloid plaques, and neurofibrillary tangles formation in post-middle of human brain cells has developed new, widely accepting foundations on this association. In particular, HTN in elderly life mediates cerebral blood flow dysfunction, neuronal dysfunction, and significant decline in cognitive impairment, primarily in the late-life populace, governing the onset of AD. Thus, HTN is an established risk factor for AD. Considering the impact of AD, 1.89 million deaths annually, and the failure of palliative therapies to cure AD, the scientific research community is looking to adopt integrated approaches to target early modified risk factors like HTN to reduce AD burden. The current review highlights the significance and impact of HTN-based prevention in lowering the AD burden in the elderly by providing a comprehensive overview of the physiological relationship between AD and HTN with an in-detail explanation of the role and applications of pathological biomarkers in this clinical association. The review will gain worth in presenting new insights and providing inclusive discussion on the correlation between HTN and cognitive impairment. It will increase across a wider scientific audience to expand understanding of this pathophysiological association.Keywords: Alzheimer’s disease, hypertension, elderly population, clinical biomarkers

Abstract We examine the spatial distributions of CMIP6‐simulated cloud liquid water path (CLWP) and content (CLWC) against MODIS and CloudSat synthesized data over the tropical and subtropical Pacific. Three subsets of models are categorized based on their treatments of frozen ice‐radiative interactions. CLWP/CLWC are generally well simulated in subset with separately‐calculated radiative effects of cloud ice and falling ice (SON2). Too much warm clouds above 750 hPa are produced in either subset with total frozen ice radiative effects (SON1) or subset without radiative effects of falling ice (NOS) and thus CLWP/CLWC are overestimated over the open ocean including the trade‐wind regions. Stratocumulus clouds off the coasts of North and South America are severely underestimated in NOS models. We attribute the overestimates of clouds above the trade‐wind boundary layers to anomalous ascending motion associated with warmer sea surface temperature and weaker surface wind stress linked to indirect effects of falling ice‐radiation interactions.

Fan Y, Li Z, Wu L, et al. Drug Des Devel Ther. 2021;15:1509–1519. At the author’s request, we, the Editors and Publisher of Drug Design, Development and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 2 and 3 with images from other unrelated articles. Specifically, Images for Figure 2D, have been duplicated with images for Figure 6d from Cheng S, Xia B, Li H, et al. RETRACTED ARTICLE: Long non-coding RNA SATB2-AS1 inhibits microRNA-155-3p to suppress breast cancer cell growth by promoting breast cancer metastasis suppressor 1-like. Cancer Cell Int. 2020;20:321. https://doi.org/10.1186/s12935-020-01411-8; Figure 2B from Wei Y, Liao Y, Deng Y, Zu Y, Zhao B, Li F. MicroRNA-503 Inhibits Non-Small Cell Lung Cancer Progression By Targeting PDK1/PI3K/AKT Pathway. Onco Targets Ther. 2019;12:9005–9016. https://doi.org/10.2147/OTT.S213059; Figure 3B from Qiao Z, Tang J, Wu W, et al. Acteoside inhibits inflammatory response via JAK/STAT signaling pathway in osteoarthritic rats. BMC Complement Altern Med. 2019;19:264. https://doi.org/10.1186/s12906-019-2673-7; Figure 6c from Zhong Q, Huang J, Wei J, et al. Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma. Cancer Cell Int. 2019;19:252. https://doi.org/10.1186/s12935-019-0959-y and Figure 2B from Ma F, Xie Y, Lei Y, et al. The microRNA-130a-5p/RUNX2/STK32A network modulates tumor invasive and metastatic potential in non-small cell lung cancer. BMC Cancer. 2020;20:580. https://doi.org/10.1186/s12885-020-07056-0. Images for Figure 3A and 3B, have been duplicated with images for Figure 2C and Figure 6C from Tantai J, Zhang Y, Zhao H. Heterophyllin B inhibits the adhesion and invasion of ECA‑109 human esophageal carcinoma cells by targeting PI3K/AKT/β‑catenin signaling. Molecular Medicine Reports. 2016;13:1097–1104. https://doi.org/10.3892/mmr.2015.4659 and Figure 5B from Xu G, Lu X, Huang T, Fan J. ARHGAP24 inhibits cell cycle progression, induces apoptosis and suppresses invasion in renal cell carcinoma. Oncotarget. 2016;7:51829–51839. https://www.oncotarget.com/article/10386/text/. The authors were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Editor and Publisher agreed with 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’.

Abstract This study utilized the Coupled Model Intercomparison Project Phase 6 (CMIP6) models to examine the simulations of equatorial ocean currents and explore their substantial influences on the systematic bias of westward‐extended sea surface temperature anomalies (SSTA) pattern during El Niño. The results show that models simulate an excessive westward ocean current field over the equatorial central Pacific in the mean state. It tends to suppress the equatorial eastward ocean current anomalies with their maximum centering over the equatorial western Pacific in the El Niño developing phase. As a consequence, an overestimated zonal advective feedback toward the maritime continent exists, subsequently inducing the biased westward extension of SSTA pattern. Our results show that the mean‐state performance of equatorial ocean currents plays a key role on simulations of El Niño evolution in CMIP6 models.

The impacts of falling ice radiative effects (FIREs) on land‐atmosphere feedback processes were examined, with a focus on the fidelity of land surface properties and their variability as inferred by global climate models (GCMs). We conducted a pair of sensitivity experiments using the National Center for Atmospheric Research (NCAR) Community Earth System Model Version 1 (CESM1) in fully coupled modes with FIREs turned on and off. This allowed us to investigate the seasonal response of land surface properties to changes in radiation fluxes and land surface temperature (LST) associated with FIREs across global land areas. Our findings indicate that during boreal winter, excluding FIREs results in less surface downward longwave and net flux (∼5–15 Wm−2), leading to a colder land surface (∼2–4 K) and air temperatures (∼1–4 K) at mid‐ and high latitudes. Consequently, the surface frozen soil layer and snow cover persist through spring, delaying snowmelt and thawing until summer. This delay reduces liquid soil moisture, thereby suppressing vegetation productivity in subsequent seasons. Conversely, tropical regions, exhibit contrasting responses, with a warmer land surface (∼0.5 K) and warmer air temperatures (∼0.1–0.5 K) due to increased surface downward shortwave and net flux (∼2–10 Wm−2). This enhancement in radiation fosters increased vegetation productivity throughout the seasonal cycle. These findings illustrate a local response of land surface properties to changes in the surface energy balance and LST, highlighting the significant role that FIREs play in land surface modeling within GCMs. Plain Language Summary: We explored the seasonal response of land surface properties to changes in radiation fluxes and land surface temperature across global land areas using the CESM1‐CAM5 coupled model with falling ice radiative effects (FIREs) both turned on and off. During boreal winter, excluding FIREs reduces surface downward longwave and net flux, resulting in a colder land surface and colder air temperatures at mid‐ and high latitudes. These cold conditions lead to the persistence of the surface frozen soil layer and snow cover through spring, delaying snowmelt and thawing until summer, which in turn reduces liquid soil moisture and suppresses vegetation growth in subsequent seasons. In contrast, tropical regions exhibit a warmer land surface and air temperatures due to increased downward shortwave and net flux, promoting vegetation growth throughout the year. Key Points: Most Coupled Model Intercomparison Project Phase 5 models did not consider falling ice radiative effects (FIREs)Excluding FIREs results in cold air, prolonging frozen soil and snow cover, which suppress vegetation growth at mid‐ to high latitudesExcluding FIREs leads to warmer air temperatures and promotes enhanced vegetation growth in tropical latitudes [ABSTRACT FROM AUTHOR]

Background: Adequately evaluating risk and making decisions is vital but understudied for older adults living independently but with compromised cognition, as seen in those with mild cognitive impairment (MCI), specifically those with amnestic MCI (aMCI) which is associated with higher risk of conversion to Alzheimer's disease. Objective: We propose to comprehensively evaluate risk-taking behaviors across domains important for everyday activities between an aMCI group and their cognitively healthy counterparts (HC). Methods: A case-control study design. Data on risk-taking behaviors via the Domain-Specific Risk-Taking Scale (DOSPERT), and candidate confounding mental health factors (i.e., neurodegeneration, depression, and fatigue) were collected. Analyses on group difference and interaction between group and confounding factors on risk-taking behaviors were conducted. Results: The aMCI group showed a higher likelihood of risk-taking than HC (t = 4.38, df = 73, p < 0.001). Moderation analysis showed fatigue (F = 5.91, p = 0.018) and presence of depression (F = 4.52, p = 0.037), but not neurodegeneration, as significant moderators for group and DOSPERT total score, controlling for sex. In post-hoc analyses, there was a significant relationship between both fatigue (B = –7.83, SE = 3.65, t = –2.14, p = 0.036), and presence of depression (B = –20.80, SE = 9.97, t = –2.09, p = 0.041), with DOSPERT total score for HC but not for aMCI. There were no significant relationships between neurodegeneration, fatigue, or depression with any specific risk-taking domains after correction for multiple comparisons. Conclusions: Our results show differences in risk-taking behavior between older adults with and without intact cognition, and overall decision-making is affected by fatigue and depression in HC but not aMCI, together suggesting the importance of cognition in the ability to adjust risk-taking behaviors. [ABSTRACT FROM AUTHOR]

This study investigates the possible linkage of sea surface height anomaly (SSHA), sea surface temperature (SST) and surface wind stress (TAU) with the falling ice radiative effects (FIREs) over the Pacific Ocean under the CMIP5 scenario of 1% CO2 increase per year (1pctCO2) for 140 years. Two sensitivity experiments using the fully-coupled ocean-atmosphere CESM1-CAM5 model are compared: one with FIREs (SON) and the other without (NOS). The warming period of the last 20 year is compared to the control period of the first 20 years. The mean state of the first 20 years exhibits a stronger west-east SSHA gradient in SON than in NOS over the Pacific Ocean, attributed to the stronger prevailing easterly trade winds and the SST pattern of being warmer in the western Pacific but colder in the eastern Pacific. In the last 20 years, SON continues to display a stronger SSHA west-east gradient with higher sea level and SST over the western Pacific Ocean compared to NOS. In the southwest Pacific, stronger trade winds are linked with the wind-evaporation-SST feedback, leading to a more significant decline in SSHA there in SON than in NOS. The CMIP5 ensemble mean shows similar relationships of SSHA with TAU and SST to those of NOS when both are compared against SON, highlighting the importance of FIREs in the SSH projection over the Pacific Ocean and the impact of FIREs on the changing relationships between SSHA, SST and TAU under global warming.