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Boyong Qiu,1,2,* Siyu Qiao,2,* Xiujuan Shi,2 Lin Shen,2 Bing Deng,2 Zilin Ma,2 Duan Zhou,2 Yihong Wei2 1Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan, People’s Republic of China; 2Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yihong Wei; Duan Zhou, Email weiyihong2022@shutcm.edu.cn; zhouduan@126.comBackground: In China, Shen’ge formula (SGF), a Traditional Chinese Medicine blend crafted from ginseng and gecko, holds a revered place in the treatment of cardiovascular diseases. However, despite its prevalent use, the precise cardioprotective mechanisms of SGF remain largely uncharted. This study aims to fill this gap by delving deeper into SGF’s therapeutic potential and underlying action mechanism, thus giving its traditional use a solid scientific grounding.Methods: In this study, rats were subjected to abdominal aortic constriction (AAC) to generate pressure overload. Following AAC, we administered SGF and bisoprolol intragastrically at specified doses for two distinct durations: 8 and 24 weeks. The cardiac function post-treatment was thoroughly analyzed using echocardiography and histological examinations, offering insights into SGF’s influence on vital cardiovascular metrics, and signaling pathways central to cardiac health.Results: SGF exhibited promising results, significantly enhanced cardiac functions over both 8 and 24-week periods, evidenced by improved ejection fraction and fractional shortening while moderating left ventricular parameters. Noteworthy was SGF’s role in the significant mitigation of myocardial hypertrophy and in fostering the expression of vital proteins essential for heart health by the 24-week mark. This intervention markedly altered the dynamics of the Akt/HIF-1α/p53 pathway, inhibiting detrimental processes while promoting protective mechanisms.Conclusion: Our research casts SGF in a promising light as a cardioprotective agent in heart failure conditions induced by pressure overload in rats. Central to this protective shield is the modulation of the Akt/HIF-1α/p53 pathway, pointing to a therapeutic trajectory that leverages HIF-1α promotion and p53 nuclear transport inhibition. Keywords: Shen’ge formula, heart failure, hypertrophy, apoptosis, angiogenesis

Yunpeng Feng,1 Shifeng Qiao,1 Jie Chen,1 Xin Wen,2 Yanlei Chen,3 Xiaoyu Song,1 Jiaxin Xu,1 Xiucheng Qiao,1 Jing Yang,2 Shenshen Zhang,1 Yang Feng,1 Yu Gao4 1The Second Ward of Colorectal Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of China; 3The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of ChinaCorrespondence: Yu Gao, School of Basic Medical Sciences, Jinzhou Medical University, No. 40, Section 3 Songpo Road, Jinzhou, Liaoning, 121000, People’s Republic of China, Tel +86 15904161717, Email jzykdxgy@163.comPurpose: This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells.Methods: The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases.Results: 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis.Conclusion: M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.Keywords: M2-type macrophages, cancer-associated fibroblasts, colorectal cancer, liver metastasis

Shan Qiao,1,2,&ast; Haiyun Li,3,&ast; Caisan Cui,4 Chong Zhang,1 Aihua Wang,1 Wenjing Jiang,3 Shanchao Zhang1,5 1Department of Neurology, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 4Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 5School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanchao Zhang, Email zhangshanchao2012@163.com; Wenjing Jiang, Email jiangwenjing@qiluhospital.comPurpose: CSF inflammation in subtypes of antibody-defined autoimmune encephalitis (AE) ranges in intensity from moderate to severe. In a retrospective, cross-sectional study, we characterized CSF findings in Chinese patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E), anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1-E), and anti-gamma aminobutyric acid-B receptor encephalitis (GABABR-E).Patients and Methods: The AE cases, including 102 NMDAR-E, 68 LGI1-E and 15 GABABR-E, were included. CSF inflammatory parameters consisted primarily of CSF leukocytes, oligoclonal bands (OCBs), and CSF/serum albumin ratios (QAlb). Ten serum cytokines were evaluated in order to classify AE subtypes.Results: 88% of NMDAR-E, 80% of GABABR-E, and 51% of LGI1-E patients had aberrant CSF features. In NMDAR-E, the CSF leukocyte count, CSF protein concentration, and age-adjusted QAlb were significantly higher than in LGI1-E, but did not differ from GABABR-E. Blood-CSF barrier dysfunction was less common in NMDAR-E patients with > 40 years old. On admission, inflammatory CSF response was more prevalent in NMDAR-E patients with a higher CASE score. With age < 60 years, CSF inflammatory changes were less frequent in LGI1-E patients, but more common in GABABR-E patients. MCP-1, IL-10, IL-1β, and IL-4 were potential classifiers for NMDAR-E, LGI1-E, and GABABR-E, and correlated substantially with CSF leukocyte count and QAlb.Conclusion: Subtype-specific patterns are formed by the various inflammatory CSF parameters in NMDAR-E, LGI1-E, and GABABR-E, and their correlation with disease severity, age, and disease duration. CSF inflammatory characteristics associated with MCP-1, IL-10, IL-1β, and IL-4 may be potential immunopathogeneses targeting markers for these AE subtypes.Keywords: autoimmune encephalitis, cytokines, neuroinflammation, cerebrospinal fluid

Shina Qiao, Xiaoming Zhang, Weilan Xiang, Linyan Yao, Xuemei Xian Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Shina Qiao, Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel +86 13575764508, Email qiaoshina08@zju.edu.cnBackground: Compared to Western countries, palliative and hospice care services are used less often in Asian countries. While both types have been implemented in mainland China in recent years, their utilization rates have not increased satisfactorily. Moreover, few hospitals in mainland China implement hospice care using the hospice shared care model.Objective: This study investigated a case in which the hospice shared care model was implemented for one patient with advanced colon cancer who had received treatment at a general tertiary hospital in mainland China.Methods: Critical points of care included pain symptom management, nutritional support, application of the SHARE model for disease notification, family meetings to assist medical decision-making, relaxation therapy to relieve depressive symptoms, provisions to address end-of-life wishes, and support for primary caregivers.Results: The patient’s basic pain was controlled (Numeric Rating Scale, NRS2-3), and the score of the Depression Screening Scale (PHQ-9) decreased from 15 to 10 after intervention during hospitalization. In the end, the patient died comfortably and peacefully at home.Conclusion: The hospice shared care team helped the patient with her physical and psychological pain, met her end-of-life wishes, and provided support for the families.Keywords: advanced colon cancer, palliative care, symptom management, hospice share care, case report

Gaigai Bai,1,2 Yue Zhou,1,2 Qing Rong,1,2 Sijing Qiao,1,2 Hongluan Mao,1,2,&ast; Peishu Liu1,2,&ast; 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Shandong Engineering Laboratory for Urogynecology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongluan Mao; Peishu Liu, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, People’s Republic of China, Tel +86-18560081988 ; +86-18560082027, Email peishuliu@126.com; hongluanmao@126.comPurpose: Nutritional and inflammatory states are crucial in cancer development. The purpose of this study is to construct a scoring system grounded on peripheral blood parameters associated with nutrition and inflammation and explore its value in stage, overall survival (OS), and progression-free survival (PFS) prediction for epithelial ovarian cancer (EOC) patients.Patients and Methods: Four hundred and fifty-three EOC patients were retrospectively identified and their clinical data and relevant peripheral blood parameters were collected. The ratio of neutrophil to lymphocyte, lymphocyte to monocyte, fibrinogen to lymphocyte, total cholesterol to lymphocyte and albumin level were calculated and dichotomized. A scoring system named peripheral blood score (PBS) was constructed. Univariate and multivariate Logistic or Cox regression analyses were used to select independent factors; these factors were then used to develop nomogram models of advanced stage and OS, PFS, respectively. The internal validation and DCA analysis were performed to evaluate models.Results: Lower PBS indicated a better prognosis and higher PBS indicated inferior. High PBS is associated with advanced stage, high CA125, serous histological type, poor differentiation, and accompanied ascites. The logistic regression showed age, CA125, and PBS were independent factors for the FIGO III–IV stage. The nomogram models for advanced FIGO stage based on these factors showed good efficiency. FIGO stage, residual disease, and PBS were independent factors affecting OS and PFS, the nomogram models composed of these factors had good performance. DCA curves revealed the models augmented net benefits.Conclusion: PBS can be a noninvasive biomarker for EOC patients’ prognosis. The related nomogram models could be powerful, cost-effective tools to provide information of advanced stage, OS, and PFS for EOC patients.Keywords: inflammation, nutrition, ovarian cancer, predict model, peripheral blood

Xuejie Fu,1,&ast; Shuangjian He,2,&ast; Liang Wang,2 Yangyang Xue,2 Shigang Qiao,1 Jianzhong An,1 Tingting Xia1 1Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Suzhou, JiangSu, People’s Republic of China; 2Department of Orthopedics, Suzhou Science & Technology Town Hospital, Suzhou, JiangSu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingting Xia, Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Suzhou, 215153, JiangSu, People’s Republic of China, Tel +86 18523986726, Email xtt_92@126.comPurpose: Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment besides late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Madecassic acid (MA) is the first native triterpenoid compound extracted from Centella asiatica, which has a variety of anti-inflammatory effects. However, the role of MA in OA therapy has not been reported. This study aimed to explore whether MA could suppress the inflammatory response, preserve and restore chondrocyte functions, and ameliorate the progression of OA in vitro and in vivo.Methods: Rat primary chondrocytes were treated with IL-1β to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of MA at concentrations ranging from 0 to 200 μM on the viability of rat chondrocytes and selected 10 μM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and Western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with MA into the knee articular cavity.Results: We found that MA could down-regulate the IL-1β-induced up-regulation of COX-2, iNOS and IL-6 and restore the cytoskeletal integrity of chondrocytes treated with IL-1β. Moreover, MA protects chondrocytes from IL-1β-induced ECM degradation by upregulating ECM synthesis related protein expression, including collagen-II and ACAN, and further down-regulating ECM catabolic related protein expression, including MMP-3 and MMP-13. Furthermore, we found that NF-κB/IκBα and PI3K/AKT signaling pathways were involved in the regulatory effects of MA on the inflammation inhibition and promotion of ECM anabolism on IL-1β-induced chondrocytes.Conclusion: These findings suggest that MA appears to be a potentially small molecular drug for rat OA.Keywords: osteoarthritis, madecassic acid, inflammatory responses, cartilage degradation

Yan Wu,1– 3,&ast; Shuaifeng Liu,4,&ast; Liuxi Chu,1– 3 Quan Zhang,5,6 Jin Yang,3,7 Shan Qiao,5 Xiaoming Li,5 Yuejiao Zhou,4 Huihua Deng,1– 3 Zhiyong Shen4 1Department of Brain and Learning Science, School of Biological Science & Medical Engineering, Southeast University, Nanjing, People’s Republic of China; 2Key Laboratory of Child Development and Learning Science (Southeast University), Ministry of Education, Nanjing, People’s Republic of China; 3Institute of Child Development and Education, Research Center for Learning Science, Southeast University, Nanjing, People’s Republic of China; 4Unit of AIDS Prevention and Control, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, People’s Republic of China; 5Department of Health Promotion, Education and Behavior, South Carolina SmartState Center for Healthcare Quality (CHQ), Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; 6College of Graduate Health Sciences, The University of Tennessee Health Science Center, Memphis, TN, USA; 7Department of Preventive Medicine, School of Public Health, Southeast University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huihua Deng, Department of Brain and Learning Science, School of Biological Science & Medical Engineering, Southeast University, No. 2 Sipailou, Nanjing, 210096, People’s Republic of China, Tel +86 25 8379 5664, Fax +86 25 8379 3779, Email dengrcls@seu.edu.cn Zhiyong Shen, Unit of AIDS Prevention and Control, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, No. 18 Jinzhou Road, Nanning, 530028, People’s Republic of China, Tel +86 771 251 8838, Email shenzhiyong99999@sina.comBackground: Hair antiretroviral concentrations are an objective and non-invasive measure of adherence to long-term antiretroviral therapy (ART) and can further predict virologic outcomes among people living with HIV/AIDS (PLWH). Zidovudine, one of the mainstream antiretrovirals in China, has been verified to have high reliability in adherence assessment, especially for its hair concentrations. However, data are limited in its predicting virologic outcomes. Therefore, this study aimed to characterize whether hair zidovudine concentrations can predict virologic suppression among Chinese PLWH compared with hair lamivudine concentrations and two self-reported measures, the overall frequency of adherence behaviors and percentage adherence.Methods: This cross-sectional study randomly recruited 564 PLWH currently treated with zidovudine, lamivudine, and other ART agents (efavirenz, nevirapine, or lopinavir/ritonavir) in Guangxi, China. Hair antiretroviral concentrations were determined using the LC-ESI+-MS/MS method. Receiver operating characteristic (ROC) curves were used to estimate the optimal classification thresholds of hair concentrations of zidovudine and lamivudine, and the two self-reported measures. Based on those optimal classification thresholds, logistic regression was used to examine whether those four adherence measures can predict virologic suppression (HIV-1 RNA < 200 copies/mL).Results: ROC curves demonstrated good classification performance for association with virologic suppression of zidovudine with the optimal threshold at 58 pg/mg and lamivudine at 255 pg/mg but no self-reported measures. PLWH with hair zidovudine concentrations > 58 pg/mg had an adjusted odds ratio (aOR) of 43.191 (95% confidence interval (CI) = 10.171‒183.418, p < 0.001) for virologic suppression. Hair lamivudine concentrations were also associated with virologic suppression (aOR = 10.656, 95% CI = 3.670‒30.943, p < 0.001). However, two self-reported measures did not predict virologic suppression (aORs = 1.157 and 2.488, ps > 0.149).Conclusion: Hair zidovudine concentrations can be served as an alternative tool for clinically predicting virologic suppression among PLWH in China.Keywords: hair antiretroviral concentrations, zidovudine, virologic suppression, PLWH, LC-MS/MS

Shan Qiao,1,2,* Quan-Ye Sun,3,* Shan-Chao Zhang,1 Ran-Ran Zhang,4 Yu-Jiao Wu,4 Zhi-Hao Wang,4 Xue-Wu Liu4,5 1Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China; 2Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 4Department of Neurology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 5Institute of Epilepsy, Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue-Wu Liu, Email snlxw1966@163.comPurpose: Syncytin-1 may play a role in several neuropsychiatric disorders, but its function in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is unknown. The purpose of this study was to examine the possible mechanism of action of syncytin-1 in patients with anti-NMDAR encephalitis.Patients and Methods: Twenty patients with anti-NMDAR encephalitis and eight controls were recruited. The protein levels of syncytin-1 in serum were determined using an enzyme-linked immunosorbent assay, and the transcript levels of syncytin-1 were determined using real-time quantitative PCR. Flow cytometry was used for peripheral blood lymphocyte subset detection. Further, the relationship between syncytin-1 levels and clinical features of anti-NMDAR encephalitis and peripheral blood lymphocyte subsets was analyzed.Results: Compared with those in controls, higher syncytin-1 levels and percentage of B cells (CD3-CD19+) were observed in patients with anti-NMDAR encephalitis. Among anti-NMDAR encephalitis patients, the level of syncytin-1 positively correlated with the proportion of B cells and modified Rankin scale score at onset and after immunotherapy and negatively correlated with the proportion of CD3+ T cells.Conclusion: An increased expression of Syncytin-1 is associated with the pathogenesis of anti-NMDAR encephalitis, providing evidence for elucidating the pathogenesis of the disease and suggesting novel therapeutic targets. Further, this study clarifies the role of syncytin-1 in neuroimmune disorders.Keywords: autoimmune encephalitis, neuroinflammation, syncytin-1, B cells, pathogenesis

Yufei Gu, Fengyu Zheng, Yingxuan Zhang, Shishi Qiao Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, People’s Republic of ChinaCorrespondence: Shishi Qiao, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, No. 50 Jianshe East Road, Erqi District, Zhengzhou City, Henan Province, People’s Republic of China, Tel +86 18595811956, Email qiaoshishiv@163.comPurpose: We aimed to develop and to validate a novel nomogram based on inflammatory markers to preoperatively predict microvascular invasion (MVI) in patients with solitary primary hepatocellular carcinoma (HCC).Patients and Methods: Data from 658 patients with solitary primary HCC who underwent hepatectomy at the First Affiliated Hospital of Zhengzhou University from June 2018 to October 2021 were retrospectively analyzed. Patients were divided into training (n=441) and validation (n=217) cohorts according to surgical data. Independent risk factors for MVI were identified via univariate and multivariate logistic regression analyses in the training cohort. A novel nomogram was developed based on the independent risk factors identified. Its accuracy was evaluated using a calibration curve and concordance index (C-index). The predictive value was evaluated using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA).Results: Preoperative alpha-fetoprotein > 969 μg/L (P< 0.001), tumor size (P=0.002), neutrophil > 1.8× 109/L (P=0.002), gamma-glutamyl transpeptidase-to-platelet ratio (GPR) > 0.32 (P=0.001), aspartate aminotransferase-to-platelet ratio (APR) > 0.18 (P< 0.001), gamma-glutamyl transpeptidase-to-albumin ratio (GAR) > 2.30 (P=0.001), and gamma-glutamyl transpeptidase-to-lymphocyte ratio > 29.58 (P< 0.001) were identified as preoperative independent risk factors for MVI and were used to establish the nomogram. The C-index of the training and validation cohorts were 0.788 (95% confidence interval [CI]: 0.744– 0.831) and 0.735 (95% CI: 0.668– 0.802), respectively. The calibration curve analysis revealed that the standard curve fit well with the predicted curve. ROC curve analysis demonstrated high efficiency of the nomogram. DCA verified that the nomogram had notable clinical value.Conclusion: Preoperative GPR > 0.32, APR > 0.18, and GAR > 2.30 were independent risk factors for MVI in patients with solitary primary HCC, suggesting their utility as preoperative predictors of MVI. The novel nomogram developed and validated in this study may aid in determining optimal therapeutic approaches for patients with solitary HCC at risk for MVI.Keywords: hepatocellular carcinoma, microvascular invasion, preoperative prediction, nomogram

Xueqian Ma,1 Yu Gao,2 Yanlei Chen,1 Jinhao Liu,1 Chunyu Yang,3 Cuifen Bao,4 Yanping Wang,1 Yang Feng,1 Xiaoyu Song,1 Shifeng Qiao1 1The Second Ward of Colorectal Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, Liaoning, People’s Republic of China; 2Computer Teaching and Research Section, Jinzhou Medical University, Jinzhou, 121000, Liaoning, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, Liaoning, People’s Republic of China; 4Basic Medical Experimental Teaching Center, Jinzhou Medical University, Jinzhou, 121000, Liaoning, People’s Republic of ChinaCorrespondence: Shifeng QiaoThe Second Ward of Colorectal Surgery, The First Affiliated Hospital of Jinzhou Medical University, No. 2 Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People’s Republic of ChinaTel +86 15904161717Email shifengqiao2020@163.comPurpose: The increase of both M2-type macrophages and Tregs is closely associated with the development of colorectal cancer. However, the mechanism of their interaction is still unclear. In this study, we investigated the correlation of M2-type macrophages with Tregs and the possible mechanisms between them.Methods: Using immunohistochemistry, we analysed Smad3 (a key protein in the TGF-β/Smad signalling pathway) expression in colorectal cells, as well as infiltrating numbers of CD163 (a marker for M2-type macrophages), Foxp3 (a marker for Tregs) in 250 surgically resected colorectal cancer tissues, matched normal and paracancerous tissues. The relation of CD163 and Foxp3 was investigated in CRC with clinicopathological characteristics and preoperative tumour markers.Results: CD163, Foxp3 and Smad3 were upregulated in CRC tissues compared to matched normal and paracancerous tissues. Interestingly, CD163 and Foxp3 were significantly positively correlated in CRC, and both were significantly positively correlated with Smad3. Both CD163 and Foxp3 were upregulated with increasing tumour TNM staging, increasing number of lymph node metastases and increasing vascular invasion. Additionally, CD163 was upregulated with increasing depth of infiltration. The number of M2-type macrophages and the expression levels of preoperative CEA, CA19-9 and CA72-4 were significantly positively correlated. The number of Tregs was significantly positively correlated with the expression levels of preoperative CEA and CA19-9.Conclusion: M2-type macrophages may induce Tregs generation through activation of the TGF-β/Smad signalling pathway, which can promote the development of colorectal cancer.Keywords: M2-type macrophages, Tregs, TGF-β/Smad signalling pathway, CD163, Foxp3, colorectal cancer, CRC

Xueyao Huang,1,2 Xuan Wei,1 Sijing Qiao,1,2 Xue Zhang,1,2 Rui Li,1 Shunxue Hu,3 Hongluan Mao,1,2 Peishu Liu1,2 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Peishu Liu; Hongluan MaoDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No. 107 Wen Hua Xi Road, Jinan, Shandong, 250012, People’s Republic of ChinaTel +8618560081988; Tel +8618560082027Email peishuliu@126.com; hongluanmao@126.comPurpose: The efficacy of post-surgery platinum-based chemotherapy, the primary choice for the treatment of ovarian cancer (OC), is greatly reduced by the development of drug-resistance. In this study, we investigated the association of expression low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), two cholesterol metabolism-related proteins, in OC tissues and chemoresistance and patient prognosis.Methods: Survival analysis using LDLR and HMGCR expression in the ovarian cancer patients using the dataset of Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was carried out online. A retrospective study was performed on 65 patients who had undergone surgery for ovarian cancer. In addition, patients were divided into 2 groups: platinum resistance group and platinum sensitivity group. Serum lipid metabolism data were collected and analyzed. Protein expressions of LDLR and HMGCR in ovarian cancer tissue were detected by immunohistochemistry.Results: Online survival analysis showed that patients with higher LDLR expression had poorer prognosis than those with lower LDLR expression in ovarian cancer cells, while a higher HMGCR expression was associated with better OC prognosis. Overall survival (OS) and disease-free survival (DFS) were lower in patients with higher LDLR levels (OS: P=0.046, DFS: P=0.009). Platinum-resistant patients had higher levels of low-density lipoprotein (LDL) and cholesterol in serum as compared with platinum-sensitive patients (P< 0.001). Immunohistochemistry showed that LDLR expression was high and HMGCR was low in platinum-resistant patients.Conclusion: The expression of LDLR and HMGCR proteins, involved in the regulation of cholesterol metabolism and the plasma LDL and cholesterol levels were significantly different in platinum-resistant and platinum-sensitive ovarian cancer patients. We postulate that cholesterol metabolic reprogramming might play a role in platinum resistance in ovarian cancer.Keywords: LDLR, HMGCR, ovarian cancer, platinum resistance, cholesterol metabolism

Xiaowei Jiang,1,2 Shubin Qiao2 1Cardiology Department, Xiangya Hospital, Central South University; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of ChinaCorrespondence: Shubin QiaoState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of ChinaEmail qsbfw@sina.comObjective: Percutaneous transluminal septal myocardial ablation (PTSMA) is one of the septal reduction therapies without all satisfactory results in hypertrophic obstructive cardiomyopathy (HOCM) patients. Initial r-wave in leads V1 and aVR on the surface electrocardiography is the sign of ventricular septal base depolarization. Whether the initial r-wave in leads V1 and aVR is predictive of good mid-term response to PTSMA in patients with HOCM remains unknown.Design, Settings, and Participants: Among 546 consecutive patients evaluated in Fuwai Hospital (Beijing, China), we selected HOCM patients who underwent PTSMA. During the 3-year follow-up after PTSMA, primary outcomes included death, surgical myectomy, syncope, and NYHA classification III/IV.Results: At last, 85 patients were selected, and were assigned to 3 groups based on the presence of initial r-wave in leads V1 and aVR. Through multivariable Cox and Kaplan–Meier method, patients with initial r-wave in both leads V1 and aVR were independently associated with a decreased risk of primary outcomes (HR: 0.112; 95% CI: 0.024 to 0.518; p = 0.005) during 3-years’ follow-up.Conclusion: The results suggest that the presence of initial r-wave in both leads V1 and aVR on the surface 12-lead ECG is highly predictive of good mid-term response to PTSMA in patients with HOCM.Keywords: hypertrophic obstructive cardiomyopathy, percutaneous transluminal septal myocardial ablation, electrocardiography

Quan Zhang,1,2,* Xiaoming Li,1 Shan Qiao,1 Shuaifeng Liu,3 Zhiyong Shen,3 Yuejiao Zhou3,* 1South Carolina SmartState Center for Healthcare Quality (CHQ), Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; 2Institute of Pedagogy and Applied Psychology, School of Public Administration, Hohai University, Nanjing, Jiangsu, People’s Republic of China; 3Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quan ZhangSouth Carolina SmartState Center for Healthcare Quality (CHQ), Arnold School of Public Health, University of South Carolina, Discovery I, 915 Greene Street, Columbia, SC, 29028, USATel +1 803 777 8615Fax +1 803 777 6290Email quanz@mailbox.sc.eduZhiyong ShenGuangxi Zhuang Autonomous Region Center for Disease Control and Prevention, No. 18 Jinzhou Road, Nanning, Guangxi, 530028, People’s Republic of ChinaTel +86 771 251 8838Email shenzhiyong99999@sina.comBackground: Hair concentrations of antiretrovirals are an innovative and non-invasive method for measuring cumulative antiretroviral exposure and assessing long-term antiretroviral adherence. This study aimed to examine hair concentrations of antiretrovirals in relation to virologic outcomes among PLHIV in Guangxi, China.Methods: Cross-sectional data of hair concentrations of antiretrovirals and HIV viral load were collected from 215 PLHIV in Guangxi, China. Multivariate logistic regression analyses were used to examine the association of hair concentrations of antiretrovirals with virologic outcomes.Results: Of the 215 participants, 215, 67, and 163 PLHIV are receiving lamivudine, zidovudine, and efavirenz, respectively. Multivariate analysis revealed that hair concentrations of lamivudine [odds ratio = 16.52, 95% CI 2.51– 108.60, p = 0.004] and efavirenz [odds ratio = 14.26, 95% CI 1.18– 172.01, p = 0.036], but not zidovudine [odds ratio = 1.77, 95% CI 0.06– 56.14, p = 0.747], were the strongest independent predictor of virologic suppression when controlling for sociodemographic and other HIV-related characteristics.Conclusion: Hair concentrations of lamivudine and efavirenz were the strongest independent predictor of virologic suppression among Chinese PLHIV. Hair analysis of antiretrovirals may provide a non-invasive, cost-effective tool that predicts virologic suppression among PLHIV in China.Keywords: hair concentrations, antiretroviral, viral load, people living with HIV

Quan Zhang,1,2 Xiaoming Li,1 Shan Qiao,1 Shuaifeng Liu,3 Zhiyong Shen,3 Yuejiao Zhou3 1South Carolina SmartState Center for Healthcare Quality (CHQ), Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; 2Institute of Pedagogy and Applied Psychology, School of Public Administration, Hohai University, Nanjing, Jiangsu, People’s Republic of China; 3Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Quan ZhangSouth Carolina SmartState Center for Healthcare Quality (CHQ), Arnold School of Public Health, University of South Carolina, Discovery I, Suite 408, 915 Greene Street, Columbia, SC, 29028, USATel +1 803 777 8615Fax +1 803 777 6290Email quanz@mailbox.sc.eduYuejiao ZhouGuangxi Zhuang Autonomous Region Center for Disease Control and Prevention, No. 18 Jinzhou Road, Nanning, Guangxi, 530028, People’s Republic of ChinaTel +86 771 251 8838Email gxcdcj2013@163.comBackground: Pain is a common occurrence and persistent symptom, which has an adverse impact on individual well-being and quality of life among people living with HIV (PLHIV). Alteration in the activity of the Hypothalamic-Pituitary-Adrenal (HPA) axis resulting in abnormal glucocorticoid levels had been proposed to play important roles in those associations.Purpose: This study aimed to investigate whether pain severity was associated with hair glucocorticoid levels, a novel method of measuring long-term glucocorticoid exposure, among a large cohort of Chinese PLHIV.Methods: A measure of pain severity and hair samples were collected from 431 adults PLHIV in Guangxi, China. Glucocorticoid (cortisol and cortisone) in hair were quantified by liquid chromatography-tandem mass spectrometry. The general linear model was used to test the associations of pain severity with hair glucocorticoid levels after adjusting for potential confounding factors.Results: Of the 431 PLHIV, 273 reported none pain, 87 reported mild pain, and 71 reported moderate-severe pain. Hair cortisone, but not hair cortisol, was found to differ significantly among the three pain severity groups (F=3.90, p=0.021). PLHIV reported moderate-severe pain had higher hair cortisone than those reported mild (p=0.070) or none pain (p=0.014), with no differences between the latter two pain severity groups.Conclusion: Greater pain severity is associated with higher hair cortisone levels among Chinese PLHIV. In order to reduce the long-term glucocorticoid levels, interventions managing pain should be considered for PLHIV with moderate-severe pain.Keywords: pain, hair cortisol, hair cortisone, HIV

Shan Qiao,1 Huai-kuan Wu,1 Ling-ling Liu,2 Mei-ling Wang,3 Ran-ran Zhang,4 Tao Han,5 Xue-wu Liu4 1Department of Neurology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong Province 250014, People’s Republic of China; 2Department of Neurology, Liaocheng People’s Hospital, Liaocheng, Shandong Province 252000, People’s Republic of China; 3Department of Neurology, Binzhou Medical University Hospital, Binzhou, Shandong Province 256603, People’s Republic of China; 4Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, People’s Republic of China; 5Department of Neurology, Shandong Provincial Hospital, Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Xue-wu LiuDepartment of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 Wen Hua Xi Road, Jinan 250012, Shan Dong, People’s Republic of ChinaTel + 86 0531-82169114Email snlxw1966@163.comPurpose: To describe the clinical manifestation, immunotherapy, and long-term outcomes of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.Patients and Methods: This study was a retrospective analysis of 117 patients with a diagnosis of anti-LGI1 encephalitis identified from the databases of multiple clinical centers between September 2014 and December 2019. The clinical features, ancillary test results, and details of long-term outcomes were evaluated.Results: Among the 117 patients with anti-LGI1 encephalitis, 69.2% (81/117) were male and 30.8% (36/117) were female. The median age of all patients at the onset of the disease was 57 years (interquartile range [IQR], 52– 67). The median time from symptom onset to diagnosis was 8.7 weeks (IQR, 4.2– 25). The main clinical features identified were seizures, cognitive impairment, and mental and behavioral abnormalities. Of the 117 patients, 109 were treated with immunotherapy. Symptoms including memory, mental ability, and behavior improved in all 109 patients after 3– 5 days of treatment. The median time of follow-up for the treated patients was 33 months (IQR, 17– 42). Of the treated patients, 16.2% (19/117) experienced a relapse, with a median delay of 5 months (IQR, 2.1– 17) between onset and the first relapse. There were no mortalities over the follow-up period.Conclusion: The long-term outcome of patients with anti-LGI1 encephalitis was mostly favorable, although some patients continued to experience cognitive dysfunction. Early recognition is important for prompt initiation of immunotherapy that can improve clinical symptoms of anti-LGI1 encephalitis.Keywords: anti-LGI1 encephalitis, autoimmune epilepsy, follow-up, immunotherapy, relapse

Jinhao Liu,1 Jikun Wang,2 Xueqian Ma,1 Yang Feng,1 Yanlei Chen,1 Yanping Wang,1 Dong Xue,1 Shifeng Qiao1 1The Second Ward of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 2Oncology Department, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of ChinaCorrespondence: Shifeng QiaoThe Second Ward of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, No. 2 Section 5, Renmin Street, Guta District, Jinzhou City, Liaoning 121001, People’s Republic of ChinaTel +86 15904161717Email shifengqiao2020@163.comPurpose: Lymph node metastasis is one of the important prognostic factors of colorectal cancer, and an important index of individualized treatment. The purpose of this study is to use metabonomics to identify potential molecular markers of lymph node metastasis in colorectal cancer (CRC).Patients and Methods: Peripheral blood samples of 223 CRC patients were collected. The metabolic levels of amino acids and carnitine in peripheral blood of CRC patients, with and without lymph node metastasis, were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).Results: The results show that there were significant differences in the levels of serum amino acids and carnitine between lymph node metastatic patients and lymph node non-metastatic patients. The diagnostic model that was constructed by 9 types of serum metabolites has a high diagnostic ability.Conclusion: LC-MS/MS is a detection method that has a broad application in predicting CRC prognosis, individualized treatment, and in studying the mechanism of lymph node metastasis.Keywords: colorectal cancer, lymph node metastasis, metabonomics, amino acid, liquid chromatography-mass spectrometry

Shang Qiao, Wen Gao, Shujun Guo Department of Cardiology, Bayan Nur Hospital of the Nei Monggol Autonomous Region, Bayan Nur City 015000, People’s Republic of ChinaCorrespondence: Shujun GuoDepartment of Cardiology, Bayan Nur Hospital of the Nei Monggol Autonomous Region, Bayan Nur Hospital, No. 98 Wulanbuhe Road, Linhe District, Bayan Nur City 015000, People’s Republic of ChinaEmail zuiailicip@126.comBackground: Cardiovascular diseases (CVD) combined with Type 2 diabetes mellitus (T2DM) frequently occurred. In this study, we aimed at exploring the prognostic significance of blood neutrophil–lymphocyte ratio (NLR) in these types of patients.Patients and Methods: Between June 30, 2010 and August 30, 2017, 1454 patients with CVD were enrolled in this study. Kaplan and Meier methodology was used for survival analysis. We also used propensity score matching (PSM) to further compare survival in patients with or without T2DM.Results: Among all patients, we applied ROC curve analysis to stratify all patients into two different groups including NLR > 2.5 (n=432) and NLR≤ 2.5 (n=1022) groups. After that, we further performed survival analysis between different groups. We found that patients with NLR ≤ 2.5 had significantly favorable OS compared with the overall survival in patients with NLR > 2.5. We further built the PSM using 242 pairs of patients who have CVD and with or without T2DM. After adjusting for competing risk factors, we performed Cox proportional hazards models to identify the independent prognostic factors in multivariable adjustment. We found that NLR ≤ 2.5 (HR: 2.576, 95% CI: 1.241– 4.583, P =0.001) and extent of coronary artery disease (HR: 2.432, 95% CI: 1.189– 4.392, P =0.005) remained independent predictors of OS.Conclusion: In conclusion, we have established an PSM model and found that a high NLR value was an independent prognostic factor for survival, predicting in patients with both CAD and T2DM. The NLR value would be a valuable biomarker to evaluate the outcomes of patients and give them opportunities for choosing alternative therapies.Keywords: neutrophil–lymphocyte ratio, NLR, cardiovascular diseases, CVD, type 2 diabetes mellitus, T2DM

Yue Yang,1 Yunjian Li,1 Kai Chen,1 Ling Zhang,2 Sen Qiao,1 Guoxin Tan,1 Fen Chen,1,3,4 Weisan Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 3Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, People’s Republic of China; 4Zhejiang Jingxin Pharmaceutical Co., Ltd, Zhejiang 312500, People’s Republic of ChinaCorrespondence: Weisan PanSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of ChinaTel/ Fax +86 24 4352 0533Email pppwwwsss@163.comFen ChenKey Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, People’s Republic of ChinaTel/ Fax +86 24 3120 7125Email chenfen1121@163.comPurpose: Poor site-specific delivery and insufficient intracellular drug release in tumors are inherent disadvantages to successful chemotherapy. In this study, an extraordinary polymeric micelle nanoplatform was designed for the efficient delivery of paclitaxel (PTX) by combining dual receptor-mediated active targeting and stimuli response to intracellular reduction potential.Methods: The dual-targeted redox-sensitive polymer, folic acid-hyaluronic acid-SS-vitamin E succinate (FHSV), was synthesized via an amidation reaction and characterized by 1H-NMR. Then, PTX-loaded FHSV micelles (PTX/FHSV) were prepared by a dialysis method. The physiochemical properties of the micelles were explored. Moreover, in vitro cytological experiments and in vivo animal studies were carried out to evaluate the antitumor efficacy of polymeric micelles.Results: The PTX/FHSV micelles exhibited a uniform, near-spherical morphology (148.8 ± 1.4 nm) and a high drug loading capacity (11.28% ± 0.25). Triggered by the high concentration of glutathione, PTX/FHSV micelles could quickly release their loaded drug into the release medium. The in vitro cytological evaluations showed that, compared with Taxol or single receptor-targeted micelles, FHSV micelles yielded higher cellular uptake by the dual receptor-mediated endocytosis pathway, thus leading to significantly superior cytotoxicity and apoptosis in tumor cells but less cytotoxicity in normal cells. More importantly, in the in vivo antitumor experiments, PTX/FHSV micelles exhibited enhanced tumor accumulation and produced remarkable tumor growth inhibition with minimal systemic toxicity.Conclusion: Our results suggest that this well-designed FHSV polymer has promising potential for use as a vehicle of chemotherapeutic drugs for precise cancer therapy.Keywords: micelles, paclitaxel, dual-targeted, redox-sensitive, cytotoxicity, antitumor

Shina Qiao*, Leiwen Tang*, Weibo Zhang, Suming Tian, Minjun Liu, Lili Yang, Zhihong YeAffiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this work Background: Recently, cancer pain management has come increasingly to be provided in outpatient settings, requiring health-care providers and outpatients to take on responsibilities. Pain is among the most distressing symptoms of cancer.Objectives: To compare the effectiveness of nurse-led telephone calls plus WeChat versus telephone calls only for the pain management of outpatients with cancer.Methods: 231 outpatients with cancer pain were classified into two groups (group 1, N=125; group 2, N=106). Group 1 was followed up with weekly telephone calls for eight weeks, and group 2 with weekly telephone calls combined with the booklets through WeChat for eight weeks. Differences between groups in pain level, side effects, medication adherence, and satisfaction with pain management were analyzed, and statistical differences were tested usingan independent-sample t-test and a chi-squared test.Results: Group 2 had a significantly lower rest pain (p

Li-Hua Yang,1,2,* Ye Wang,1,3,* Shi Qiao,1,* Min-Jun Wang,1 Fei Chen,1 Xiao-Yuan Zi,1 Jian-Xiu Li,1 Hai-Bin Zhang,4 Bing Yu,1,4 Yi-Ping Hu1 1Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, Shanghai, People’s Republic of China; 2Department of Cell Biology and Neurobiology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 4Department of Hepatic Surgery V, Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: Liver cancer stem cells (CSCs) are known to be associated with the development, survival, proliferation, metastasis, and recurrence of liver tumors. The aim of this study was to investigate the association of liver-enriched activator protein 1 (LAP1) with hepatocellular carcinoma (HCC) and liver CSCs (LCSCs) and explore the impact of LAP1 on LCSCs. Materials and methods: Differences in LAP1 expression in liver cancer tissues versus matched para-tumoral liver tissues and LCSCs versus non-CSCs were analyzed by Western blotting, real-time polymerase chain reaction, immunohistochemistry, and flow cytometry. The effect of LAP1 on liver cancer cells was evaluated by the expression of CSC markers, oncosphere formation, proliferation, migration, and invasion in vitro. Cell cycle distribution and the number of apoptotic cells were analyzed to assess cell cycle and cell apoptosis. Furthermore, a mouse subcutaneous tumor implant model was established to explore the role of LAP1 in the development of HCC in vivo. Finally, the expression of CSC markers in paraffin-embedded sections was evaluated by immunofluorescence. Results: LAP1 was weakly expressed in HCC tumors and cell lines and even weaker in LCSCs. LAP1 inhibited the expression of stem cell–associated genes and reduced the abilities of oncosphere formation, proliferation, migration, and invasion in vitro. Cell cycle assay revealed that LAP1 induced G1/G0 arrest. Furthermore, LAP1 decreased subcutaneous tumor-formation ability and the expression of CSC markers and Ki67 in vivo. Conclusion: LAP1 suppressed the stem cell features of HCC, indicating that it possessed an antitumor effect in liver cancer, both in vitro and in vivo; therefore, LAP1 may prove to be a potential target in liver CSC-targeted therapy. Keywords: LAP1, liver-enriched activator protein 1, hepatocellular carcinoma, HCC, liver cancer stem cell

Shupei Qiao,1,* Yufang Zhao,1,* Shuai Geng,2,* Yong Li,1,* Xiaolu Hou,1,3 Yi Liu,1 Feng-Huei Lin,4,5 Lifen Yao,6 Weiming Tian1 1School of Life Science and Technology, Harbin Institute of Technology, 2Department of Pharmacology, Harbin Medical University, 3Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; 5Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan; 6Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China *These authors contributed equally to this work Abstract: Instead of killing cancer stem cells (CSCs), the conventional chemotherapy used for cancer treatment promotes the enrichment of CSCs, which are responsible for tumor growth, metastasis, and recurrence. However, most therapeutic agents are only able to kill a small proportion of CSCs by targeting one or two cell surface markers or dysregulated CSC pathways, which are usually shared with normal stem cells (NSCs). In this study, we developed a novel nondrug delivery system for the dual targeting of CSCs by conjugating hyaluronic acid (HA) and grafting the doublecortin-like kinase 1 (DCLK1) monoclonal antibody to the surface of poly(ethylene glycol) (PEG)–poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which can specifically target CD44 receptors and the DCLK1 surface marker – the latter was shown to possess the capacity to distinguish between CSCSs and NSCs. The size and morphology of these NPs were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). This was followed by studies of NP encapsulation efficiency and in vitro drug release properties. Then, the cytotoxicity of the NPs was tested via Cell Counting Kit-8 assay. Finally, the 4T1 CSCs were obtained from the alginate-based platform, which we developed as an in vitro tumor model. Tumor-bearing nude mice were used as in vivo models to systematically detect the ability of NPs to target CSCs. Our results showed that the DCLK1–HA–PEG–PLGA NPs exhibited a targeting effect toward CSCs both in vitro and in vivo. These findings have important implications for the rational design of drug delivery systems that target CSCs with high efficacy. Keywords: alginate, CD44, PEG–PLGA, DCLK1, hyaluronic acid

Rui Fang,1,2 Shupei Qiao,1 Yi Liu,1 Qingyuan Meng,3 Xiongbiao Chen,2,4 Bing Song,5 Xiaolu Hou,6 Weiming Tian1 1Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin, People’s Republic of China; 2Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, SK, Canada; 3State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Department of Mechanical Engineering, University of Saskatchewan, Saskatoon, SK, Canada; 5College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK; 6Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Abstract: Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization. Keywords: myocardial infarction, gelatin nanoparticle, cardiomyocyte proliferation, injectable hydrogel

An uneven mixing of hydrogen-blended natural gas will lead to hydrogen embrittlement in distribution pipelines, thereby affecting the quality of terminal gas, and thus highlighting the importance of ensuring the uniformity of hydrogen and natural gas mixing. In this study, FLUENT software was used to simulate three different hydrogen filling modes, namely, T-tube, bending-tube, and static mixer, and the mechanisms underlying the mixing of hydrogen and natural gas under different filling modes were analyzed. In addition, we assessed the influences of gas velocity, hydrogen blending ratio, and mixer length and blade angle on the mixing effects of a static mixer. The results revealed that among the three mixing methods assessed, the static mixer has the best overall mixing effect. Increasing gas velocity was found to have no significant effect on the mixing of hydrogen and natural gas. With an increase of hydrogen blending ratio, the mixing uniformity of hydrogen and natural gas increased from 99.49% to 99.95%, whereas there was an increase from 84.12% to 99.05% when the length of static mixer was increased, and an increase from 59.53% to 99.78% in response to an increase in blade angle. Our findings in this study can provide a methodological reference for increasing the mixing uniformity of hydrogen and natural gas in hydrogen-blended natural gas pipeline networks, and thereby contribute to the safe and rapid development of the hydrogen energy industry. [ABSTRACT FROM AUTHOR]

All commercial electron spin polarimeters work in single channel mode, which is the bottleneck of researches by spin-resolved photoelectron spectroscopy. By adopting the time inversion antisymmetry of the magnetic field, we developed a multichannel spin polarimeter based on normal incident very low energy electron diffraction (VLEED). The key point to achieve the multi-channel measurements is the spatial resolution of the electron optics. The test of the electron optics shows that the designed spatial resolution can be achieved and an image type spin polarimeter with 100 times 100, totally ten thousand channels is possible to be realized.

Magnetic topological semimetals have been at the forefront of condensed matter physics due to their ability to exhibit exotic transport phenomena. Investigating the interplay between magnetic and topological orders in systems with broken time-reversal symmetry is crucial for realizing non-trivial quantum effects. We delve into the electronic structure of the rare-earth-based antiferromagnetic Dirac semimetal EuMg2Bi2 using first-principles calculations and angle-resolved photoemission spectroscopy. Our calculations reveal that the spin–orbit coupling (SOC) in EuMg2Bi2 prompts an insulator to topological semimetal transition, with the Dirac bands protected by crystal symmetries. The linearly dispersive states near the Fermi level, primarily originating from Bi 6 p orbitals, are observed on both the (001) and (100) surfaces, confirming that EuMg2Bi2 is a three-dimensional topological Dirac semimetal. This research offers pivotal insights into the interplay between magnetism, SOC and topological phase transitions in spintronics applications. [ABSTRACT FROM AUTHOR]