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Sangsang Xiong,1,* Mingqi Tu,1,* Xiaoting Wu,1 Siying Qu,1 Nisang Chen,1 Junyan Jin,1 Haiqin Rong,1 Shuangyi Pei,2 Jianqiao Fang,1 Xiaomei Shao1 1Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaomei Shao; Jianqiao Fang, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +86 189 5713 0287, Email shaoxiaomei@zcmu.edu.cn; fangjianqiao7532@163.comBackground: Major depressive disorder (MDD) is highly prevalent, affecting more than 300 million individuals worldwide, and its occurrence may be related to the abnormality of the prefrontal cortex and bilateral temporal cortex. Acupuncture, rooted in the theories of acupoints and meridians, has demonstrated its efficacy in regulating cortical blood flow (CBF) in the brains of MDD patients. As one form of acupuncture, intradermal acupuncture (IA) can alleviate clinical symptoms such as depressive mood and insomnia in MDD patients. However, it remains unknown whether IA will have a specific effect on the prefrontal cortex and bilateral temporal cortex in MDD patients.Methods: In total, 60 participants will be recruited: 20 healthy control participants and 40 MDD patients. All healthy control participants will be allocated to the control group, whereas the 40 MDD patients will be randomly divided into two groups: the gallbladder meridian acupoint (GBA) group and the non-acupoint (NA) group, at a 1:1 allocation ratio. All groups will undergo a one-time IA intervention while their cortical activity is monitored using functional near-infrared spectroscopy (fNIRS). Total hemoglobin, oxygenated hemoglobin, and deoxygenated hemoglobin of the prefrontal and bilateral temporal cortices will be measured by fNIRS during the test procedure.Discussion: This trial aims to use fNIRS to compare real-time hemodynamic changes in the prefrontal and bilateral temporal cortices of healthy individuals and MDD patients during IA. The primary objective is to investigate whether MDD patients exhibit specific real-time responses to IA stimulation in these brain regions. The findings from this study will provide clinical data and a possible theoretical basis for the assumption that stimulation of IA may treat MDD by modulating the relevant brain regions.Trial Registration: The study protocol has been registered in the clinicaltrials.gov with the code NCT05707299.Keywords: major depressive disorder, intradermal acupuncture, functional near-infrared spectroscopy, prefrontal cortex, temporal cortex

Heng Rong,1,&ast; Weixin Dai,1,&ast; Yinying Qin,1,&ast; Zhikeng Meng,2 Xia Zou,3 Binbin Wang,4 Qiufeng Wei,1 Yubo Xie1,5 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, The First People’s Hospital of Yulin, Yulin, People’s Republic of China; 3Department of Anesthesiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 5Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yubo Xie, Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuang-Yong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email xybdoctor@163.comPurpose: In this prospective observational study, an ultrasonographic measurement of antral cross-sectional area (ACSA) was conducted to evaluate the gastric content and volume as well as to identify high-risk stomach in non-pregnant adult surgical patients adhering to preanesthetic fasting guidelines.Patients and Methods: Fasted patients undergoing gastrointestinal endoscopy under sedation were included. Ultrasonographic measurements of ACSA were conducted in both semi-recumbent and right lateral decubitus positions before endoscopic procedures. Gastroscopy was employed to guide the measurement of suctioned gastric volume (GV). Ultrasonography was performed to assess gastric contents and identify patients with high-risk stomach. The relationship between ACSA and suctioned GV was also evaluated.Results: ACSA was evaluated in 736 out of 782 patients. A significant positive correlation was discovered between ACSA in the right lateral decubitus position and suctioned GV, which was more reliable than in the semi-recumbent position. To analyze high-risk stomach with a GV > 100 mL, the cutoff value of ACSA in the right lateral decubitus was found to be 7.5 cm2, with the AUC, sensitivity and specificity of 0.80 (95% CI, 0.76– 0.82; P< 0.001), 82.4% and 67.3%, respectively. A novel mathematical model based on ACSA to estimate GV in non-pregnant fasted adults was presented.Conclusion: Ultrasonographic measurement of ACSA can assist anesthesiologists in estimating the risk of pulmonary aspiration of gastric contents during general anesthesia and sedation.Keywords: gastroscopy, antrum, gastric content, pulmonary aspiration, ultrasonography

Pingyi Wang,1– 3 Hongyan Lu,1– 3 Hao Rong,1– 3 Yuhe Wang,1– 4 Li Wang,1– 3 Xue He,1– 3 Dongya Yuan,1– 3 Yongjun He,1– 3 Tianbo Jin1– 3 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of China; 2Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of China; 3School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of China; 4Department of Clinical Laboratory, the Affiliated Hospital of Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of ChinaCorrespondence: Tianbo Jin; Yongjun He, Tel +86-18681940990 ; +86-18691008772, Email jintb@xzmu.edu.cn; 545139647@qq.comBackground: High altitude pulmonary edema (HAPE) is still the most common fatal disease at high altitudes. DNA methylation proceeds with an important role in HAPE progression. This study was designed to investigate the association between CYP39A1 methylation and HAPE.Methods: Peripheral blood samples were enrolled from 106 participants (53 HAPE patients and 53 healthy subjects) to study the association of CYP39A1 methylation with HAPE. DNA methylation site in the promoter region of CYP39A1 was detected by Sequenom MassARRAY EpiTYPER platform.Results: Probability analysis showed that the methylation probabilities of CYP39A1_1_CpG_5 and CYP39A1_3_CpG_21 are significant differences between the cases and controls (p< 0.05). The methylation level analysis indicated that CYP39A1_1_CpG_2.3.4, CYP39A1_5_CpG_6.7, and CYP39A1_5_CpG_9.10 were higher methylation in HAPE compared to the controls (p< 0.05). CYP39A1_3_CpG_21 and CYP39A1_4_CpG_3 exhibited a lower methylation level in HAPE than that in the controls (p< 0.05). The association analysis given that CYP39A1_1_CpG_2.3.4 (OR 2.56, p= 0.035), CYP39A1_5_CpG_6.7 (OR 3.99, p= 0.003), CYP39A1_5_CpG_9.10 (OR 3.99, p= 0.003), CYP39A1_5_CpG_16.17.18 (OR 2.53, p= 0.033), and CYP39A1_5_CpG_20 (OR 3.05, p= 0.031) are associated with an increased risk of HAPE. Whereas CYP39A1_1_CpG_5 (OR 0.33, p= 0.016) and CYP39A1_3_CpG_21 (OR 0.18, p= 0.005) have a protective role in HAPE. Besides, age-stratification analysis showed that CYP39A1_1_CpG_5 (OR 0.16, p= 0.014) and CYP39A1_3_CpG_21 (OR 0.08, p= 0.023) had a protective impact on HAPE in people aged ≤ 32 years. CYP39A1_5_CpG_6.7 (OR 6.70, p= 0.008) and CYP39A1_5_CpG_9.10 (OR 6.70, p= 0.008) were related to an increased susceptibility to HAPE aged > 32 years. Moreover, the diagnostic value of CYP39A1_3_CpG_21 (AUC = 0.712, p< 0.001) was significantly better than other CpG sites.Conclusion: The methylation level of CYP39A1 was associated with a risk of HAPE in the Chinese population, which provided new perspective for preventing and diagnosing of HAPE.Keywords: HAPE, DNA methylation, CYP39A1, CpG, the Chinese population

Yun Wang,1 Xiaohua Liu,2,3 Daihui Peng,2 Yan Wu,2 Yun’ai Su,4 Jia Xu,5 Xiancang Ma,6 Yi Li,7 Jianfei Shi,8 Xiaojing Cheng,9 Han Rong,10 Yiru Fang1,3,11 1Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychiatry, Peking University Sixth Hospital, Peking, People’s Republic of China; 5Department of Psychiatry, Harbin First Specific Hospital, Harbin, People’s Republic of China; 6Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, People’s Republic of China; 7Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China; 8Department of Psychiatry, Hangzhou Seventh People’s Hospital, Hangzhou, People’s Republic of China; 9Department of Psychiatry, Shandong Mental Health Center, Shandong, People’s Republic of China; 10Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China; 11CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of ChinaCorrespondence: Daihui Peng; Yiru Fang Email pdhsh@126.com; yirufang@aliyun.comBackground: Despite the best treatments, about 20% of patients with major depressive disorder (MDD) receiving drugs and psychological intervention show little or no improvement. There is no trial comparing different treatment methods in patients with anxiety/somatic subtype MDD.Aim: To compare the efficacy and safety of various treatments in patients with anxiety/somatic subtype MDD.Methods: This was a preliminary multicenter randomized controlled trial at eight participating hospitals in China (09/2016-06/2019) (ClinicalTrials.gov #NCT03219008). The patients were randomized to mirtazapine/SNRIs, mirtazapine/SNRIs+cognitive behavioral therapy (CBT), mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies (modified electroconvulsive treatment or repetitive transcranial magnetic stimulation). The primary endpoint was the 17-item Hamilton Depression Scale (HAMD-17). The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) and Quality of Life (QOL)-6 were the secondary endpoints. The adverse events (AEs) were monitored. The patients were assessed at baseline (0 weeks), and at the end of the 2nd, 4th, 6th, 8th, and 12th week during treatment.Results: Finally, 107 patients were included: mirtazapine/SNRIs (n=36), mirtazapine/SNRIs+CBT (n=28), mirtazapine+SNRIs (n=29), and mirtazapine+SNRIs+physical therapies (n=14). The 17-HDRS and QIDS-SR scores decreased in all four groups, and the QOL-6 scores increased. There were no differences in the 17-HDRS (P=0.099), QIDS-SR (P=0.407), and QOL-6 (P=0.485) scores among the four groups. There were no differences in the occurrence of AEs among the four groups (P=0.942).Conclusion: This preliminary trial suggests that all four interventions (mirtazapine/SNRIs, mirtazapine/SNRIs+CBT, mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies) achieved similar response and remission rates in patients with anxiety/somatic subtype MDD. The safety profile was manageable.Keywords: major depressive disorder, anxiety, mirtazapine, serotonin-norepinephrine reuptake inhibitor, cognitive behavioral therapy, Hamilton Depression Scale

Yun Wang,1 Xiaohua Liu,2,3 Daihui Peng,2 Yan Wu,2 Yun’ai Su,4 Jia Xu,5 Xiancang Ma,6 Yi Li,7 Jianfei Shi,8 Xiaojing Cheng,9 Han Rong,10 Yiru Fang1,3,11 1Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychiatry, Peking University Sixth Hospital, Peking, People’s Republic of China; 5Department of Psychiatry, Harbin First Specific Hospital, Harbin, People’s Republic of China; 6Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, People’s Republic of China; 7Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China; 8Department of Psychiatry, Hangzhou Seventh People’s Hospital, Hangzhou, People’s Republic of China; 9Department of Psychiatry, Shandong Mental Health Center, Shandong, People’s Republic of China; 10Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China; 11CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of ChinaCorrespondence: Daihui Peng; Yiru Fang Email pdhsh@126.com; yirufang@aliyun.comBackground: Fluoxetine, bupropion, cognitive behavioral therapy (CBT), and physical therapies (modified electroconvulsive treatment or repetitive transcranial magnetic stimulation) can be used to manage melancholic depression.Objective: To compare the efficacy and safety of various treatments in patients with melancholic depression.Methods: This was a preliminary multicenter randomized controlled trial that included patients with depression in their first or recurrent acute episode between September 2016 and June 2019, and randomized to fluoxetine, fluoxetine+CBT, fluoxetine+bupropion, and fluoxetine+bupropion+brain stimulation. The primary endpoint was the decrease in the 17-item Hamilton Depression Rating Scale (17-HDRS). The secondary endpoint included the scores from the Quick Inventory of Depressive Symptomatology (QIDS-SR), QOL-6, and safety. Adverse events (AEs) were monitored. The follow-ups were performed at the end of the 0th, 2nd, 4th, 6th, 8th, and 12th weeks of treatment.Results: Finally, 113 patients were included in the analyses: fluoxetine (n=37), fluoxetine+CBT (n=27), fluoxetine+bupropion (n=34), and fluoxetine+bupropion+brain stimulation (n=15). The 17-HDRS and QIDS-SR scores decreased in all four groups (all P< 0.05). There were no differences in the 17-HDRS scores among the four groups at the end of treatment (P=0.779), except for fluoxetine alone showing a better response regarding self-consciousness than fluoxetine+bupropion. The QOL-6 scores increased in all four groups. The occurrence of AEs among the four groups showed no significant difference (P=0.053).Conclusion: This preliminary trial suggests that all four interventions (fluoxetine, fluoxetine+CBT, fluoxetine+bupropion, and fluoxetine+bupropion+brain stimulation) achieved similar response and remission rates in patients with melancholic depression, but that fluoxetine had a better effect on self-consciousness than fluoxetine+bupropion. The safety profile was manageable.Keywords: major depressive disorder, melancholic depression, fluoxetine, bupropion, cognitive behavioral therapy, brain stimulation

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

Rize Jing,1,2 Tingting Xu,1,3 Hongguo Rong,2 Xiaozhen Lai,1 Hai Fang2,4,5 1School of Public Health, Peking University, Beijing 100083, People’s Republic of China; 2China Center for Health Development Studies, Peking University, Beijing 100083, People’s Republic of China; 3Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Harvard University, Boston, Massachusetts 02115, USA; 4Peking University Health Science Center- Chinese Center for Disease Control and Prevention Joint Center for Vaccine Economics, Peking University, Beijing 100083, People’s Republic of China; 5Key Laboratory of Reproductive Health, National Health Commission of the People’s Republic of China, Peking University, Beijing 10083, People’s Republic of ChinaCorrespondence: Hai FangChina Center for Health Development Studies, Peking University, Xueyuan Road 38, Mailbox 505, Haidian District, Beijing 100083, People’s Republic of ChinaTel +86-108-280-5702Fax +86-108-280-5695Email hfang@hsc.pku.edu.cnAim: This study aimed to evaluate the longitudinal association between sleep duration and depressive symptoms among the elderly in China.Methods: A data set from China Health and Retirement Longitudinal Study (CHARLS) in 2011, 2013 and 2015 was adopted with a total of 22,847 respondents aged ≥ 60-years-old. A linear regression analysis with generalized estimating equations was employed to examine the longitudinal associations between duration of total sleep, nighttime sleep and daytime nap, and depressive symptoms.Results: An extra hour of total sleep including nighttime sleep and daytime nap was associated with lower incidence of depressive symptoms among the elderly after adjusting all confounders (OR=0.83, 95% CI: 0.82– 0.84). In addition, an extra hour of nighttime sleep (OR=0.82, 95% CI: 0.80– 0.83) or daytime nap (OR=0.93, 95% CI: 0.89– 0.97) was also negatively associated with depressive symptoms among the elderly. After controlling the total sleep time, an extra hour of nighttime sleep was negatively associated with depressive symptoms (OR=0.88, 95% CI: 0.84 to 0.92), while an extra hour of daytime nap displayed a positive association with depressive symptoms (OR=0.88, 95% CI: 0.84 to 0.92). Compared with the moderate nappers, only extended nappers had significantly higher incidence of depressive symptoms (OR=1.32, 95% CI: 1.19 to 1.45).Conclusion: For the elderly in China, increasing their total sleep, nighttime sleep, and/or daytime nap duration would reduce the incidence of depressive symptoms. Moreover, after fixing the total sleep time, increasing nighttime sleep was more beneficial to the decrease of the incidence of depressive symptoms than daytime nap.Keywords: sleep duration, daytime nap, depressive symptoms, China, the elderly

Yueshan Fan,1– 3,* Dong Wang1,2 ,* Chenxu Rao,1– 3,* Ying Li,1,2 Hongtao Rong,1,2 Zengguang Wang,1,2 Jianning Zhang1,2 1Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China; 2Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, People’s Republic of China; 3Graduate School, Tianjin Medical University, Tianjin, 300000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianning Zhang; Zengguang Wang Tel +86 22-60817448Email jianningzhang@hotmail.com; wzgforrest@163.comObjective: Our previous study showed that the combination therapy with atorvastatin and low-dose dexamethasone protected endothelial cell function in chronic subdural hematoma (CSDH) injury. In this study, we aimed to investigate the mechanism underlying the effects of this combination therapy on CSDH-induced cell dysfunction.Methods: Monocytes and endothelial cells were cocultured with CSDH patient hematoma samples to mimic the pathological microenvironment of CSDH. Monocytes (THP-1 cells) and endothelial cells (hCMEC/D3 cells) were cocultured in a transwell system for 24 h before stimulation with hematoma samples diluted in endothelial cell medium (ECM) at a 1:1 ratio. Tight junction markers were detected by Western blotting, PCR and immunofluorescence. hCMEC/D3 cells were collected for Western blot and PCR analyses to detect changes in the expression levels of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and Kruppel-like factor 2 (KLF-2). The IL-6, IL-10 and VEGF levels in the supernatant were measured by enzyme-linked immunosorbent assay (ELISA).Results: KLF-2 expression in endothelial cells was decreased after stimulation with CSDH patient hematoma samples, but combination therapy with atorvastatin and low-dose dexamethasone reversed this trend. KLF-2 protected injured cells by increasing the expression of VE-cadherin and ZO-1; attenuating the expression of VCAM-1, ICAM-1, IL-6 and VEGF; and enhancing the expression of IL-10, all of which play pivotal roles in endothelial inflammation. Moreover, the effect of combination therapy with atorvastatin and low-dose dexamethasone was obviously reduced in endothelial cells with KLF-2 knockdown compared with normal cells.Conclusion: Coculture with hematoma samples decreased KLF-2 expression in human cerebral endothelial cells. Combination therapy with atorvastatin and low-dose dexamethasone counteracted hematoma-induced KLF-2 suppression in human cerebral endothelial cells to attenuate robust endothelial inflammation and permeability. KLF-2 plays an important role in drug therapy for CSDH and may become the key factor in treatment and prognosis.Keywords: chronic subdural hematoma, atorvastatin combined with low-dose dexamethasone treatment, endothelial inflammation and permeability, Kruppel-like factor 2

Background: Long non-coding RNAs (lncRNAs), as post-transcriptional regulators, were thought to function in the inductive property of dermal papilla cells (DPCs) in cashmere goat. Previously, lncRNA-599554 was identified in secondary hair follicle (SHF) of cashmere goat, but its functional significance is unknown. Results: In the present investigation, we verified that lncRNA-599554 had significantly higher expression at the anagen dermal papilla of cashmere goat SHF than that at telogen. Based on overexpression and knockdown techniques, we found that lncRNA-599554 contributes the inductive property of DPCs of cashmere goat, which was assessed by detecting the changes in the expression of several typical indictor genes in DPCs including ET-1, SCF, Versican, ALP, Lef1 and Ptc-1. Based on RNA pull-down assay, we verified that lncRNA-599554 directly interacted with chi-miR-15a-5p. Also, we showed that lncRNA-599554 positively regulated the Wnt3a expression in DPCs but which did not appear to involve its modulating of promoter methylation. Based on the use of Dual-luciferase reporter assays, our data indicated that lncRNA-599554 regulated the Wnt3a expression through chi-miR-15a-5p-mediated post-transcriptional level. Conclusions: We showed that lncRNA-599554 contributes the inductive property of DPCs in cashmere goat which might be achieved through sponging chi-miR-15b-5p to promote the Wnt3a expression. The results from the present investigation provided a novel insight into the functional mechanism of lncRNA-599554 in the SHF regeneration of cashmere goat along with the formation and growth of cashmere fiber.How to cite: Yin RH, Wang YR, Zhao SJ, et al. LncRNA-599554 sponges miR-15a-5p to contribute inductive ability of dermal papilla cells through positive regulation of the expression of Wnt3a in cashmere goat. Electron J Biotechnol 2020;45. https://doi.org/10.1016/j.ejbt.2020.03.002

Lirong Liang,1 Changwei Li,2 Ye Shen,2 Hengmo Rong,3 Hang Jing,1 Zhaohui Tong3 1Department of Clinical Epidemiology and Tobacco Dependence Treatment Research, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Epidemiology and Biostatistics, University of Georgia College of Public Health, Athens, GA, USA; 3Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zhaohui TongDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, People’s Republic of ChinaTel +86-10-85231610Fax +86-10-65060167Email tongzhaohuicy@sina.comBackground and Objective: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. We aimed to evaluate the temporal trends in hospitalization and mortality from acute exacerbation of COPD (AECOPD) and the associated financial costs over a 10-year period in Beijing, China.Methods: Hospital admission records from 2008 to 2017 for all patients aged ≥ 20 years with a primary discharge diagnosis of AECOPD were retrieved from the Beijing Public Health Information Center Database. Joinpoint regression was used to analyze trends and calculate the annual percentage change (APC) and average annual percent change (AAPC) for AECOPD hospitalization and mortality.Results: A total of 337,802 AECOPD cases were recorded from 2008 to 2017. An inverse U-shaped trend in the AECOPD hospitalization rate was observed, showing an increase from 150.2 per 100,000 inhabitants in 2008 to 218.7 per 100,000 inhabitants in 2014 (APC: 5.5%, 95% CI: 2.9– 8.2), before declining to 161.13 per 100,000 inhabitants in 2017 (APC: − 9.7%, 95% CI: − 16.0 to-2.9). In-hospital mortality from AECOPD decreased significantly from 3.91% to 2.21% (AAPC: − 11.4%, 95% CI: − 15.5 to− 7.0). A decline in the median length of hospital stay from 13.0 days in 2008 to 12.0 days in 2017 (Ptrend < 0.001) was accompanied by a decrease in the use of mechanical ventilation from 2012 to 2017 (Ptrend < 0.001). However, the total hospitalization cost per case increased from 15953.5 yuan (USD $2281.4) to 19874.5 yuan ($2842.1) during the same period.Conclusion: AECOPD remains a heavy burden on the health care system in Beijing. Strategies to better manage COPD and reduce hospitalizations from AECOPD are needed.Keywords: COPD, exacerbation, hospitalization cost, mortality, outcome research

WeiHong Ren,1,2 XuRan Zhang,2 WenBo Li,2 Qian Feng,2 HuiJie Feng,2 Yan Tong,2 Hao Rong,2 Wei Wang,2 Dai Zhang,2 ZhenQiang Zhang,3 ShiChun Tu,4 XiaoYan Zhu,1 QinXian Zhang11Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 3Immunology Laboratory of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 4Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA, USABackground: Myeloid-derived suppressor cells (MDSCs) promote immunosuppression in the tumor microenvironment, support tumor growth and survival, and may contribute to immunotherapy resistance. Recent studies showed that tumor-derived exosomes (TDEs) can induce MDSCs accumulation and expansion, the mechanisms of which are largely unknown.Methods: The morphologies and sizes of the exosomes was observed by using a JEM-1400 transmission electron microscope. MicroRNA(miR)-107 and ARG1, DICER1, PTEN, PI3K, AKT, mTOR, and NF-kB mRNAs were quantified by quantitative reverse tanscription PCR. Dual-Luciferase Reports Assay were used to examine the expression of genes which was targeted by miR-107. The expression of proteins were analyzed by using western blot.Results: MiR-107 was not only overexpressed in gastric cancer cells but also enriched in their secreted TDEs. Also, these miR-107 enriched TDEs could be taken up by HLA-DR-,CD33+,MDSCs, where miR-107 was able to target and suppress expression of DICER1 and PTEN genes. Dampened DICER1 expression supported expansion of MDSCs , while decreased PTEN led to activation of the PI3K pathway, resulting in increased ARG1 expression. Furthemore, gastric cancer-derived miR-107 TDEs, when dosed intravenously into mice, were also capable of inducing expansion of CD11b+,Gr1+/high ,MDSCs in mouse peripheral blood and altering expression of DICER1, PTEN, ARG1, and NOS2 in the MDSCs.Conclusions: Our findings demonstrate for the first time that gastric cancer-secreted exosomes are able to deliver miR-107 to the host MDSCs where they induce their expansion and activition by targeting DICER1 and PTEN genes, thereby may provide novel cancer therapeutics target for gastric cancer.Keywords: exosome, miRNA-107, myeloid-derived suppressor cell, arginase 1, gastric cancer

Circular RNAs (CircRNAs) are a type of non-coding RNAs, which contain a covalently closed loop structure without 5′ to 3′ free ends. CircRNAs play essential roles in the regeneration of secondary hair follicle (SHF) and cashmere growth in goats. CircRNA-1926 was previously identified in SHF of cashmere goats, but its potential roles are unclear. In this study, we confirmed the expression of circRNA-1926 in SHF bulge of nine cashmere goats with a significantly higher level at anagen than that of telogen. Through the use of both overexpression and siRNA interference, we showed that circRNA-1926 promoted the differentiation of SHF stem cell into hair follicle lineage in cashmere goats which was evaluated via indictor genes Keratin 7 and Keratin 17. Using RNA pull-down, we found that circRNA-1926 bound with miR-148a/b-3p. Additionally, our data indicated that circRNA-1926 promoted the expression of the CDK19 gene. Using dual-luciferase reporter assays, it was revealed that circRNA-1926 positively regulated the CDK19 expression through miR-148a/b-3p. The results from this study demonstrated that circRNA-1926 contributes the differentiation of SHF stem cells into hair follicle lineages in cashmere goats via sponging miR-148a/b-3p to enhance CDK19 expression.

Ying Hu,1,2 Hai Bo Tan,1 Xin Mei Wang,3 Hua Rong,1 Hong Ping Cui,1 Hao Cui2 Departments of Ophthalmology, 1Shanghai East Hospital of Tongji University, Shanghai, 2First Affiliated Hospital, 3Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China Abstract: Glaucoma is a common eye disease in the aged population and has severe consequences. The present study examined the therapeutic effects of bone marrow mesenchymal stem cell (BMSC) transplantation in preventing loss of visual function in aged rats with glaucoma caused by laser-induced ocular hypertension. We found that BMSCs promoted survival of retinal ganglion cells in the transplanted eye as compared with the control eye. Further, in swimming tests guided by visual cues, the rats with a BMSC transplant performed significantly better. We believe that BMSC transplantation therapy is effective in treating aged rats with glaucoma. Keywords: glaucoma, stem cell, transplantation, cell therapy, aging

An approach for colorimetric and fluorescent sensing of thiocyanate (SCN-) hasbeen proposed based on the competitive-displacement strategy betweenmeso-tetraphenylporphyrin (TPP) and meso-tetraphenylporphyrin cobalt(II) (CoTPP). InTHF-water solution, TPP emits strong fluorescence at 651 nm; however, the fluorescence wasquenched stepwise by CoTPP, and then restored by SCN-, the detection limit is 6.0 × 10-4 M.The recognition of SCN- could also be easily achieved by visual way since the assemblysystem showed significant color change by the anion. Both the fluorescence and the colorchange of the system exhibits remarkably high selectivity to SCN- over a large series ofanions. The interaction mechanisms among TPP, CoTPP and SCN- were primarilyinvestigated by fluorescence lifetime. The quenching of TPP fluorescence is attributed to theformation of TPP/CoTPP aggregates, and the fluorescence restoration is due to the binding ofCoTPP with SCN-, releasing the free TPP. This simple system has the potential to be used asa latent fluorescent sensing approach for SCN- for environmental analysis.

Abstract Irrigation with saline groundwater has become necessary to overcome freshwater scarcity in the agricultural industry in arid areas. However, the effects of long-term saline groundwater irrigation on soil salinity and bacterial diversity have rarely been examined. In this study, a Lycium ruthenicum field was divided into two parts and subjected to flooding irrigation with saline groundwater (pH 7.81, total salinity 0.95 g L−1) and surface water (pH 7.76, total salinity 0.36 g L−1) for 8 years. After 8 years of irrigation, the soil salinity and salt ion content (i.e., Na+, Mg2+, K+, Ca2+, Cl− and CO3 2−) in the groundwater irrigation group were significantly greater than those in the surface water irrigation group (p

Abstract Chemotherapy resistance has been a great challenge in pancreatic ductal adenocarcinoma(PDAC) treatments. Current first-line chemotherapy regimens for PDAC include gemcitabine-based regimens such as AG regimen (albumin paclitaxel and gemcitabine), fluorouracil-based regiments such as FOLFIRINOX regimen ((5-fluorouracil5-FU), oxaliplatin, Irinotecan) and platinum-based regimens for patients with BRCA mutations. large amounts of work have been done on exploring the mechanism underlying resistance of gemcitabine-based and platinum-based regimens, while little research has been achieved on the mechanism of FOLFIRINOX regimens resistance. Hence, we identified Polypeptide N-Acetylgalactosaminyltransferase 5, (GALNT5) as a vital regulator and a potential therapeutic target in FOLFIRINOX regimens resistance. Colony formation assays and flow cytometry assays were performed to explore the roles of GALNT5 in cell proliferation and apoptosis in PDAC treated with FOLFIRINOX. IC50 alterations were calculated in GALNT5 knockdown and overexpressed cell lines. RNA-seq followed by GSEA (gene set enrichment analysis) was displayed to explore the potential mechanism. WB (western blotting), real-time PCR, and IF (immunofluorescence) were performed to validate relative pathways. The mouse orthotopic xenograft PDAC model was established to examine GALNT5 functions in vivo. GALNT5 was highly expressed in PDAC tissues and predicted poor prognosis in PDAC. Upregulation of GALNT5 in PDAC cells conferred FOLFIRINOX resistance on PDAC by inhibiting DNA damage. Moreover, GALNT5 interacted with MYH9, thus participating in the activation of the NOTCH pathways, resulting in hampering FOI-induced DNA damage. Functions of GALNT5 promoting FOLFIRINOX resistance were validated in vivo. In this study, we found that aberrantly overexpressed GALNT5 in PDAC took part in the activation of the NOTCH pathway by interacting with MYH9, thus inhibiting the DDR to achieve FOLFIRINOX resistance and causing poor prognosis. We identified GALNT5 as a potential therapeutic target for PDAC patients resistant to FOLFIRINOX chemotherapy.

Abstract Background The effect of supplements on mortality risk in patients with cancer remains uncertain and has scarcely been investigated in subgroups of patients with varying characteristics. This study aimed to investigate the association between two popular supplements, fish oil and glucosamine, and mortality risk in a large population-based cohort and determine whether cardiovascular health and clinical prognosis influence these associations. Methods This prospective cohort study analyzed the data of UK Biobank participants who were diagnosed with cancer. The associations of fish oil and glucosamine consumption with mortality were analyzed using Cox proportional hazards models. Subgroup analyses were performed to assess the effects of Life Essential 8 [LE8] scores (a measure of cardiovascular health) and cancer prognosis (grouped according to the survival rates of specific cancer types) on the associations between supplement use and mortality. Results This analysis included 14,920 participants (mean age = 59.9 years; 60.2% female). One third (34.1%) of the participants reported using fish oil, and one fifth (20.5%) reported using glucosamine. Over a median follow-up of 12.0 years, 2,708 all-cause deaths were registered. The use of fish oil was associated with reduced risks of all-cause mortality (adjusted hazard ratio [aHR] = 0.89, 95% Confidence Interval [CI] = 0.81–0.97) and cancer mortality (aHR = 0.89, 95% CI = 0.81–0.98). Similarly, glucosamine use was associated with reduced risks of all-cause mortality (aHR = 0.83, 95% CI = 0.74–0.92) and cancer mortality (aHR = 0.83, 95% CI = 0.74–0.93) in the fully adjusted model. Subgroup analyses revealed that the protective effects of fish oil and glucosamine against mortality risk were only observed in patients with LE8 scores lower than the mean score or a poor cancer prognosis. Additionally, the association between glucosamine use and a reduced risk of CVD-related mortality was only observed in patients with lower LE8 scores. Conclusions This large cohort study identified the potential differential impact of LE8 scores and cancer prognosis on the associations of fish oil and glucosamine supplementation with survival in patients with cancer. This suggests the importance of considering these factors in future research on supplements and in the provision of personalized integrative cancer care.

Abstract Latexin (LXN) is abundant in macrophages and plays critical roles in inflammation. Much is known about macrophages in atherosclerosis, the role of macrophage LXN in atherosclerosis has remained elusive. Here, the expression of LXN in human and mouse atherosclerotic lesions was examined by immunofluorescence and immunohistochemistry. LXN knockout and LXN/ApoE double-knockout mice were generated to evaluate the functions of LXN in atherosclerosis. Bone marrow transplantation (BMT) experimentation was carried out to determine whether macrophage LXN regulates atherosclerosis. We found that LXN is enriched in human and murine atherosclerotic lesions, mainly localized to macrophages. LXN deletion ameliorated atherosclerosis in ApoE -/- mice. BMT demonstrate that deletion of LXN in bone marrow protects ApoE -/- mice against atherosclerosis. Mechanistically, we found that LXN targets and inhibits JAK1 in macrophages. LXN deficiency stimulates the JAK1/STAT3/ABC transporter pathway, thereby enhancing the anti-inflammatory and anti-oxidant phenotype, cholesterol efflux, subsequently minimizing foam cell formation and atherosclerosis. Gene therapy by treatment of atherosclerotic mice with adeno-associated virus harbouring LXN-depleting shRNA attenuated the disease phenotype. In summary, our study provides new clues for the role of LXN in the pathological regulation of atherosclerosis, and determines that LXN is a target for preventing atherosclerosis, which may be a potential new anti-atherosclerosis therapeutic target.

Abstract Background Transfusion-dependent β-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors. Methods Adult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants’ WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion. Results The analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of $198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of $70.4 per unit (95% CI [62.0, 78.9]). Estimated WTP for temporary anemia alleviation per transfusion totaled $260.6, exceeding monthly income by 1.32 times. Higher WTP was observed among males, higher-income households, and those with at least junior education. Lower WTP was noted among patients with lower transfusion volumes and those needing to travel for transfusion or during hospitalization for blood transfusion. Conclusion High WTP indicated a strong desire for temporary anemia relief. Most TDT patients faced significant economic and transfusion burden. The evident gap in meeting clinical needed underscores the urgent demand for innovative treatments to reduce transfusion dependency, potentially transforming TDT care and improving socioeconomic well-being and clinical outcomes. These findings supported evidence-based decision-making for TDT pharmacoeconomics and efficient healthcare resource allocation in China.

Abstract Background The increasing prevalence of cognitive impairment poses substantial risks to older adults, particularly those with chronic diseases. While existing studies have examined the connection between the empty nest phenomenon and cognitive function, few have attempted to consider endogeneity issues within this relationship, with limited attention given to older adults with chronic diseases. This study investigates the impact of empty nest status on cognitive function among rural Chinese older adults with chronic diseases and explores the possible mechanisms underlying this effect. Methods A cross-sectional study involved 365 older adults aged 60 or above with chronic diseases in rural areas of Shaanxi province, northwest China. Cognitive function was measured using the Mini-Mental State Examination. Multiple regression models and the instrumental variable (IV) method were employed to examine the association between empty nest and cognitive function. Results Among the 365 older adults aged 60 or above with chronic diseases, 43% experienced cognitive impairment. Results from both multiple regression and IV analyses consistently demonstrate a significant association between empty nest status and higher cognitive function scores (β = 1.757, p = 0.007; β = 3.682, p = 0.034, respectively). Mechanism analysis further supports that the positive association may arise from empty nesters receiving more social support from children and friends, and perceiving loneliness experiences as inadequate. Heterogeneity analysis reveals that the association between empty nest status and cognitive function is more pronounced among male adults with chronic diseases. Conclusions This study challenges the notion that empty nest status is a risk factor for cognitive decline in older adults with chronic diseases in rural China. The positive impact is attributed to the robust social relationships of empty nesters, encompassing sustained support from their social network, and the absence of an increase in loneliness. Therefore, future interventions aimed at improving cognitive function in older adults may benefit from promoting the development of social relationships.

Abstract Background Muscle invasive bladder cancer (MIBC) is a life-threatening malignant tumor characterized by high metastasis rates, poor prognosis, and limited treatment options. Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 represent an emerging treatment for MIBC immunotherapy. However, the characteristics of patients likely to benefit from immunotherapy remain unclear. Methods We performed single-cell mass cytometry (CyTOF) analysis of 179,483 single cells to characterize potential immunotherapy-related cancer stem cells (CSCs)-like populations in the tumor microenvironment of 38 MIBC tissues. The upregulated expression of IGF2BP3 in CD274 + ALDH + CSC-like cells, which was associated with poor clinical prognosis, was analyzed by bulk RNA-sequencing data from an in-house cohort. The functional role of IGF2BP3 was determined through cell proliferation, colony formation, cell apoptosis and sphere formation assays. The regulation of SPHK1 expression by IGF2BP3 was investigated using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and bulk RNA-sequencing (bulk RNA-seq). We further utilized single-nucleus RNA sequencing (snRNA-seq) data from 67,988 cells of 25 MIBC tissues and single-cell RNA sequencing (scRNA-seq) data from MIBC patient-derived organoids to characterize the molecular features of bladder cancer cells co-expressing IGF2BP3 and SPHK1. Spatial transcriptomics (ST) and co-detection by indexing (CODEX) analysis were used to describe the spatial distribution and interactions of IGF2BP3 + SPHK1 + bladder cancer cells and immune cells. Results A subset of CD274 + ALDH + CSC-like cells was identified, associating with immunosuppression and low survival rates in MIBC patients. IGF2BP3, an m6A reader gene, was found to be upregulated in the CD274 + ALDH + CSC-like cell population and linked to poor clinical prognosis in MIBC. Knockout of IGF2BP3 dramatically promoted cell apoptosis and reduced cell proliferation in T24 cells. By integrating MeRIP-seq and bulk RNA-seq analyses, we identified SPHK1 served as a substrate for IGF2BP3 in an m6A-dependent manner. Further snRNA-seq, scRNA-seq, ST, and CODEX analysis revealed a closer topographical distance between IGF2BP3 + SPHK1 + bladder cancer cells and exhausted CD8 + T cells, providing one explanation for the superior response to immunotherapy in IGF2BP3 + SPHK1 + bladder cancer cells-enriched patients. Finally, an ICI-associated signature was developed based on the enriched genes of IGF2BP3 + SPHK1 + bladder cancer cells, and its potential ability to predict the response to immunotherapy was validated in two independent immunotherapy cohort. Conclusions Our study highlighted the critical involvement of the IGF2BP3/SPHK1 signaling in maintaining the stemness of CSCs and promoting MIBC progression. Additionally, these findings suggested that the IGF2BP3/SPHK1 signaling might serve as a biomarker for prognosis and immunotherapy response in MIBC.

Objective The transverse tibial transfer technique is employed primarily to treat diabetic foot ulcers (DFUs), aiming to enhance leg circulation and promote new blood vessel growth. This technique is also beneficial for various conditions associated with poor blood flow in the lower extremities. However, there is no clear molecular mechanism to explain the relationship between the transverse tibial transfer technique and angiogenesis in patients with diabetic foot. This study aims to preliminarily explore the change of IL‐6 and related cytokines in promoting angiogenesis during transverse tibial transplantation, providing a direction for future research. Methods We retrospectively assessed a study from April 2022 to November 2023 on 76 patients with severe DFUs at Wagner stages 3–4. Flow cytometry was used to detect the levels of 12 cytokines in serum before the operation and 3, 7, 14, 21, and 35 days after the operation. Ankle‐brachial index (ABI), transcutaneous oxygen tension (TcPO2), and glycosylated hemoglobin (Hba1c) were recorded at admission and discharge. We examined the variations in cytokine levels, wound healing duration, amputation rates, infection incidence, and other key outcomes. Results In our investigation, a total of 76 individuals participated, comprising 49 males and 27 females. These subjects had an average age of 64.7 years, with a standard deviation of 13 years. The mean ulcer healing time was 74 ± 31 days, amputation occurred in 3 patients, pin tract infection occurred in one patient (1.3%), and incision infection occurred in one patient (1.3%). By day 35 following the surgery, both the ABI and TcPO2 values showed a significant increase from their preoperative levels. HbA1c significantly improved compared with presurgery (p

Abstract Objective To explore the distribution of thrombin–antithrombin complex (TAT), plasmin-α2-antiplasmin inhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) in healthy older Chinese adults, and establish the reference intervals (RIs). Methods The Biotech Shine i2900 chemiluminescence immune assay was used to measure the plasma concentrations of TAT, PIC, TM, and t-PAIC in 1628 adults ≥ 60 years. The RIs were established using the 2.5th and 97.5th percentiles of the distribution. Results TAT levels were lower in males than females across all ages. Differences between the ages of 60–79 and ≥ 80 in both sex groups were statistically significant, with an upward trend with age. PIC levels showed no difference between the sexes but increased with age in both groups. TM levels did not differ between the sex groups, with slight fluctuation with age. The level in females aged 60–69 was slightly higher than that in the other groups; the difference was statistically significant. T-PAIC levels were not significantly different between the sex groups, with less fluctuation with sex and age. The level in males ≥ 80 years old was slightly lower than that in the other groups; the difference was statistically significant. The RIs for all markers in healthy older Chinese adults were determined and statistically reported by age and sex. For TAT, the RIs for males aged 60–79 and ≥ 80 are 0.51–2.30 ng/mL and 0.88–3.72 ng/mL, respectively, whereas for females aged 60–79 and ≥ 80, the RIs are 0.68–2.82 ng/mL and 1.02–3.67 ng/mL, respectively. For PIC, the RIs for the age groups 60–69, 70–79, and ≥ 80 are 0.10–0.89 µg/mL, 0.12–1.00 µg/mL, and 0.21–1.04 µg/mL, respectively. The RI of TM for females aged 60–69 is 3.32–13.22 TU/mL, whereas it is 2.96–13.26 TU/mL for the other groups. The RI of t-PAIC for males aged ≥ 80 is 1.63–10.68 ng/mL, whereas it is 2.33–11.34 ng/mL for the other groups. Conclusions Discrepancies exist in thrombus markers among different sex and age groups. The RIs of TAT, PIC, TM and t-PAIC for healthy older Chinese adults were successfully established.