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Yanhua Huang,1 Hongwei Qian2,3 1Department of Ultrasound, Shaoxing People’s Hospital, Shaoxing, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, Shaoxing People’s Hospital, Shaoxing, People’s Republic of China; 3Shaoxing Key Laboratory of Minimally Invasive Abdominal Surgery and Precise Treatment of Tumor, Shaoxing, People’s Republic of ChinaCorrespondence: Hongwei Qian, Department of Hepatobiliary and Pancreatic Surgery, Shaoxing People’s Hospital, 568 Zhongxing North Road, Shaoxing, 312000, People’s Republic of China, Email qhwsxsrmyy@163.comAbstract: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is associated with high mortality rates due to late detection and aggressive progression. Peritumoral radiomics, an emerging technique that quantitatively analyzes the tissue surrounding the tumor, has shown significant potential in enhancing the management of HCC. This paper examines the role of peritumoral radiomics in improving diagnostic accuracy, guiding personalized treatment strategies, and refining prognostic assessments. By offering unique insights into the tumor microenvironment, peritumoral radiomics enables more precise patient stratification and informs clinical decision-making. However, the integration of peritumoral radiomics into routine clinical practice faces several challenges. Addressing these challenges through continued research and innovation is crucial for the successful implementation of peritumoral radiomics in HCC management, ultimately leading to improved patient outcomes.Keywords: hepatocellular carcinoma, peritumoral radiomics, diagnostic Imaging, artificial intelligence, precision medicine

Yingli Wang,1,2,* Yalin Jiang,2,* Meiling Xie,1,2,* Bin Qi,2 Kunpeng Pu,2 Wenjie Du,2 Qingqing Zhang,2 Mengmeng Ma,2 Ziyong Chen,2 Yongxia Guo,2 Hui Qian,2 Kaiqin Wang,2 Tulei Tian,2 Lin Fu,3 Xiaofei Zhang2 1Bengbu Medical University Graduate School, Bengbu, Anhui, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Fu, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China, Tel +86 551 6516 7923, Email fulindev@126.com Xiaofei Zhang, Department of Respiratory and Critical Care Medicine, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, 236800, People’s Republic of China, Email zhangxiaofeibz@163.comBackground: Leucine-rich α-2 glycoprotein 1 (LRG1) is associated with various inflammatory lung diseases. Nevertheless, the connection between LRG1 and adult community-acquired pneumonia (CAP) individuals was still not well understood. Through a prospective cohort study, the correlations of serum LRG1 with severity and prognosis were evaluated in CAP patients.Methods: The study encompassed 327 patients who received the diagnosis of CAP. We collected fasting venous blood and clinical features. Serum LRG1 was detected by ELISA. CAP severity was assessed using various scoring systems. The prognostic outcomes were observed through follow-up visits.Results: The level of serum LRG1 at admission was gradually increased with CAP severity scores. Serum LRG1 level shown positive associations with inflammatory indices, including C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). Linear and logistic regression analyses suggested that serum LRG1 at admission was positively associated with severity scores and the risk of death in CAP patients. Serum LRG1 in combination with CAP severity scores significantly increased the predictive powers for severity and death compared with single serum LRG1 or severity scores.Conclusion: The study revealed positive connections of serum LRG1 levels with severity and poor prognosis in CAP patients, suggesting LRG1 partakes into the physiological processes of CAP. Serum LRG1 may be regarded as a potential biomarker in predicting the severity and death among CAP patients.Keywords: community-acquired pneumonia, LRG1, severity, outcomes, cohort study

Quirui Nie,1 Hui Qian,2,3 Shenjian Chen,3 Wenwen Xiang,3 Yu Shen3,4 1Department of Gerontology, Nanchang First Hospital, Nanchang, People’s Republic of China; 2Department of Neurology, Fengxin County People’s Hospital, Fengxin, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Yu Shen, Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China, Email shenyu19950712@sina.comObjective: To compare the differences in risk factors and etiological classification between cerebral infarction in young patients and elderly patients, and explore the correlation between cerebral infarction in young patients and white matter lesions (WMLs).Methods: Sixty young patients with cerebral infarction and 142 elderly patients with cerebral infarction were included. The distributions of risk factors such as hypertension, diabetes, heart disease, smoking status, alcohol consumption status, migraine status, and WMLs in the two groups were carefully investigated and statistically analyzed.Results: According to the univariate analysis, the proportions of males, obese patients, patients with migraine, and patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) in the young group were significantly greater than those in the elderly group. Hypertension, heart disease, and hyperhomocysteinemia were significantly more common in the elderly group than in the young group. According to the TOAST classification, the incidence of stroke of undetermined etiology in the young group was greater than that in the elderly group, whereas the incidence of large-artery atherosclerosis (LAA) in the elderly group was greater than that in the young group. Binary logistic regression analysis revealed that male sex, migraine status, and obstructive sleep apnea-hypopnea syndrome were independently associated with cerebral infarction in young adults, whereas hypertension, heart disease, and hyperhomocysteinemia were independently related to cerebral infarction in elderly individuals. In addition, the incidence of WMLs in the migraine group of young cerebral infarction patients was significantly greater than that in the nonmigraine group.Conclusion: Compared with those in elderly patients with cerebral infarction, the risk factors for cerebral infarction in young patients are relatively controllable. Furthermore, more methods are needed to determine the etiology of unexplained cerebral infarction in young patients. WMLs are thought to have a relatively high incidence in young patients with cerebral infarction and are significantly associated with migraine.Keywords: cerebral infarction, white matter lesions, young people, risk factors, migraine

Xiang Huo,1 Zhongming Tan,1,2 Huimin Qian,1,2 Yuanfang Qin,1,2 Chen Dong,1,2 Chuchu Li,1,2 Xiaoxiao Kong,1,2 Jie Hong1,2 1National Health Commission (NHC) Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 2Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of ChinaCorrespondence: Jie Hong, Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, 172 Jiangsu Road, Gulou Distrct, Nanjing, People’s Republic of China, Email hongjie@jscdc.cnBackground: Streptococcus pneumoniae is a significant etiological agent of infection and commonly inhabits the human nasopharynx, alongside other potentially pathogenic bacteria. In this study, S. pneumoniae strains were obtained from a community population and subjected to investigation of their phenotypes, genotypes, and vaccine coverage.Methods: S. pneumoniae was isolated from nasopharyngeal swab samples of a healthy population in the Guangfu Community. Capsular serotypes and genotypes were identified using Quellung reaction and multilocus sequence typing (MLST), respectively. The antimicrobial susceptibility was tested using minimum inhibitory concentrations.Results: In total, 500 unvaccinated people were sampled. Ninety-four S. pneumoniae strains were identified. Common serotypes were 19F, 6A, and 9V. The strain coverages of PCV13 and PPV23 were 61.7% and 58.5%, respectively. About 27.6% isolates were non-susceptible to penicillin, and over 80% were resistant to erythromycin and doxycycline. Among 27 novel sequence types (STs) identified in all strains, the most common STs were ST236 (6/94, 6.4%) and ST12669 (6/94, 6.4%). Nearly half of the strains were grouped into four clone complexes (CC12665, CC271, CC6011, and CC180), of which CC271 showed the highest resistance to PEN.Conclusion: In our study, various drug-resistant clone complexes of Streptococcus pneumoniae were found in the healthy population, the elderly, and children. Consequently, pneumococcal vaccines should be included in the national immunization schedule to prevent disease spread.Keywords: vaccine, Streptococcus pneumonia, serotype, antibiotics, STs

Guojun Tong,1,2 Hai Qian,1 Dongli Li,2 Jing Li,2 Jing Chen,2 Xiongfeng Li,3 Zhenhua Tan1 1General Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, People’s Republic of China; 2Central Laboratory, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, People’s Republic of China; 3Orthopedic Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, People’s Republic of ChinaCorrespondence: Zhenhua Tan, General Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Sanhuan North Road 1558&num;, Huzhou, People’s Republic of China, Email Tanzh99@163.comAim: This study aims to explore the effect of different doses of antibiotics on rats in order to observe alterations in their fecal microbiota, inflammatory changes in the colonic mucosa and four types of inflammatory markers in blood serum.Methods: Our methodology involved separating 84 female Sprague Dawley rats into groups A-G, with each group consisting of 12 rats. We collected the rat feces for analysis, using a distinct medium for bacterial cultivation and counting colonies under a microscope. On the 11th and 15th days of the experiment, half of the rats from each group were euthanized and 5 mL of abdominal aortic blood and colon tissues were collected. Inflammations changes of colon were observed and assessed by pathological Hematoxylin Eosin (HE) staining. Enzyme-linked immune sorbent assay (ELISA) was adopted for detecting C-reactive protein (CRP), IL-6, IL1-β and TNF-α.Results: Our findings revealed that the initial average weight of the rats did not differ between groups (p> 0.05); but significant differences were observed between stool samples, water intake, food intake and weight (p=0.009, < 0.001, 0.016 and 0.04, respectively) within two hours after the experiment. Additionally, there were notable differences among the groups in nine tested microbiota before and after weighting methods (all p< 0.001). There were no difference in nine microbiota at day 1 (all p> 0.05); at day 4 A/B (p=0.044), A/D (p< 0.001), A/E (p=0.029); at day 8, all p< 0.01, at day 11, only A/F exist significant difference (p< 0.001); at day 14 only A/D has difference (p=0.045). Inflammation changes of colon were observed between groups A-G at days 11 and 15. Significant differences between all groups can be observed for CRP, IL-6, IL1-β and TNF-α (p< 0.001).Conclusion: This study suggests that antibiotics administration can disrupt the balance of bacteria in the rat gut ecosystem, resulting in an inflammatory response in their bloodstream and inducing inflammation changes of colon. Keywords: antibiotics, imbalance of intestinal flora, Sprague Dawley rats, inflammatory bowel disease, IBD, colitis model

Hang Qian,1 Xu Wang,1 Pengbo Wang,1 Guangyang Zhang,1 Jun Liu,1 Xiaoqian Dang,1 Jianbin Guo,2 Ruiyu Liu1 1Department of Orthopedics, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Orthopedics, Honghui Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Ruiyu Liu, Department of Orthopaedics, The Second Affiliated Hospital, Xi’an Jiaotong University, No. 157, Xiwu Road, Xi’an, Shaanxi, 710004, People’s Republic of China, Email liuryu@126.comObjective: Hip ankylosis is a prevalent condition in patients with Ankylosing spondylitis (AS) that can significantly impact their psychological well-being. This study aimed to investigate the impact of Total Hip Arthroplasty (THA) on anxiety and depression among AS patients.Methods: 62 AS patients undergoing primary THA were recruited and separated into two groups based on preoperative hip motion. The 40 patients with hip mobility of 0° were assigned to group A, and others were assigned to group NA. Self-rating Anxiety Scale (SAS), Self-rating Depression scale (SDS), Harris hip scores (HHS) and 36-Item Short Form Survey (SF-36) were obtained one week before and there, six and twelve months after THA.Results: The study found that AS patients in group A had significantly higher levels of anxiety and depression (SAS score = 75.05± 2.79, SDS index score = 0.74± 0.02) compared to group B (SAS score = 54.58± 3.35, SDS index score= 0.64± 0.03, P=0.01). However, both groups showed significant improvements in anxiety and depression scores from there to twelve months after THA (P< 0.001). Correlation analyses revealed that the improvement in group NA was associated with hip pain relief (p< 0.001), while the improvement in group A was related to joint function, disease duration, age at THA and spine imaging lesions (p< 0.001).Conclusion: Some degree of anxiety and depression was present in both groups of AS patients. Levels of depression and anxiety were higher in patients with combined hip ankylosis. And their improvement was associated with improved hip function and quality of life after THA. Hip pain relief played a significant role in patients without hip joint ankylosis. The impact of the degree of lesion on spinal imaging on psychological status needs to be considered in both groups.Keywords: ankylosing spondylitis, depression and anxiety, hip pain, hip joint range of motion, hip ankylosing

Wenwen Wang,1,&ast; Aihua Mei,1,&ast; Hang Qian,1,&ast; Dongfeng Li,1 Hao Xu,1 Jishun Chen,1 Handong Yang,1 Xinwen Min,1 Chunlei Li,1 Li Cheng,1 Jun Chen1,2 1Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China; 2Institute of Virology, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Chen; Li Cheng, Sinopharm General Dongfeng Hospital, Hubei University of Medicine, 16 Daling Road, Shiyan, Hubei, 442000, People’s Republic of China, Email chenjun0121@126.com; 13972468814@163.comAbstract: Chronic obstructive pulmonary disease (COPD) is one of the common diseases of the respiratory system. As the disease recurs, damage to the airways and lung tissue gradually worsens, leading to a progressive decline in lung function, affecting the patient’s workforce and quality of life, and causing a huge social and economic burden. Diabetes is a common comorbidity of COPD and patients with COPD are at increased risk of developing diabetes, while hyperglycemia can also reduce lung function and contribute to the progression and poor prognosis of COPD. Glucagon-like peptide-1 receptor agonist (GLP-1RA) is a new type of hypoglycemic agent that has been shown to regulate blood glucose levels, reduce inflammatory responses and oxidative stress, and regulate lipid metabolism, among other effects. GLP-1RAs may benefit COPD patients by acting directly on the lung from mechanisms such as reducing the inflammatory response, improving oxidative stress, regulating protease/anti-protease imbalance, improving airway mucus homeostasis, and reducing airway remodeling. This study provides a review of the potential role of GLP-1RAs in COPD and offers new ideas for the prevention and treatment of COPD.Keywords: glucagon-like peptide 1 receptor agonist, chronic obstructive pulmonary disease, clinical application

Yanxia Han,1,&ast; Zhenyun Wu,1,&ast; Qian Zhao,1 Bo Jiang,2 Xiaolang Miao,2 Xiangmin Lu,2 Hongying Qian,1 Meie Niu1 1Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2School of Nursing, Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meie Niu, Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, 188th, Shizi Street, Suzhou, 215006, People’s Republic of China, Tel +86 13812671786, Email meniu_123@163.comPurpose: Anthropometric indices are simple indicators of patient nutritional status. However, the association between these indices and skeletal-muscle atrophy in patients with stable chronic obstructive pulmonary disease (COPD) has not been fully investigated. In this study, we evaluated this association.Patients and Methods: We recruited 123 outpatients with stable COPD from a general hospital in China from 2020 to 2021. We recorded their demographic characteristics, including age, sex, course of illness, dyspnea score, body mass index (BMI), force expiratory volume in 1 second (FEV1), forced vital capacity (FVC), smoking status, and severity grading. In addition, patients’ anthropometric indices, including fat-free mass index (FFMI) and appendicular skeletal-muscle mass index (ASMI), were measured using a body composition analyzer, and measurements were taken of the triceps skinfold (TSF), midarm circumference (MAC), and calf circumference (CC). We drew and analyzed a receiver operating characteristic (ROC) curve to identify the best intercept point value for the assessment of skeletal-muscle atrophy.Results: The TSF, MAC, CC, FFMI, and ASMI of COPD patients were 1.08 ± 0.44 cm, 26.39 ± 2.92 cm, 34.5 ± 3.06 cm, 17.49 ± 1.86 kg/m2, and 8.17 ± 0.90 kg/m2, respectively. These anthropometric indices had a significant positive correlation with skeletal-muscle mass (correlation values, 0.481– 0.820). CC was strongly correlated with both FFMI and ASMI. The ROC curve showed an area-under-the-curve (AUC) value of 0.873– 0.959.Conclusion: Anthropometric indices were correlated with skeletal-muscle mass. CC showed the best diagnostic value in COPD patients, suggesting its effectiveness as a simple method for assessing skeletal-muscle atrophy and identifying patients with a noticeable reduction in muscle mass. Such patients require early, multidisciplinary intervention.Keywords: fat-free mass, skeletal-muscle mass, chronic obstructive pulmonary disease, anthropometric index, muscle atrophy

Yi Li, Hongyu Qian, Kewei Yu, Ying Huang Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Yi Li, Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin, People’s Republic of China, Email lisalie5252@hotmail.comBackground: Although the benefits of conventional pulmonary rehabilitation (PR) maintenance are well documented, it is challenged by many difficulties. We investigated whether remote home-based PR maintenance strategy via social media (WeChat) is effective on clinical improvements and reducing the risk for acute exacerbation of chronic obstructive pulmonary disease (COPD).Methods: The eligible stable COPD patients completing an initial 8-week PR were allocated into three groups randomly. Group A: PR maintenance via social media supervision at home. Group B: PR maintenance at hospital. Group C: Usual care. During a 12-month follow-up, the frequency of acute exacerbation of COPD (AECOPD), 6 minutes walking test (6MWT), COPD assessment test (CAT), and modified Medical Research Council scale (mMRC) were evaluated every 3 months.Results: At the end of the follow-up, compared to the decline in the usual care group (n = 49), the clinical improvements of 6MWD, CAT, and mMRC were sustained in both the home-based group (n = 47) and the hospital-based maintenance group (n = 44) (p < 0.001), no difference was observed between these two groups (p > 0.05). In multivariate analysis, the home-based PR maintenance and hospital-based PR maintenance were independent predictors of lower risk for AECOPD (incidence rate ratio (IRR) 0.712, 95% CI 0.595– 0.841, p < 0.001 and IRR 0.799, 95% CI 0.683– 0.927, p = 0.002), respectively.Conclusion: Remote PR maintenance via social media is effective in reducing the risk for AECOPD and keeping the clinical improvement from decline. Remote PR maintenance via social media might be used to deliver alternatives to conventional PR.Keywords: chronic obstructive pulmonary disease, pulmonary rehabilitation, maintenance, exacerbations, home monitoring

Hongyang Qian,1,&ast; Yiqiu Wang,1,&ast; Zehua Ma,1,&ast; Lei Qian,1 Xiaoguang Shao,1 Di Jin,1 Ming Cao,1 Shupeng Liu,2 Haige Chen,1 Jiahua Pan,1 Wei Xue1 1Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China; 2Shanghai Institute for Advanced Communication and Data Science, Key Laboratory of Specialty Fiber Optics and Optical Access Networks, School of Communication and Information Engineering, Shanghai University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Xue; Jiahua Pan, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 1630 Dongfang Road, Shanghai, 200127, People’s Republic of China, Tel +86 21 6838 3375, Email xuewei@renji.com; panjiahua@renji.comObjective: To explore the value of surface-enhanced Raman spectroscopy analysis of pretreated plasma samples in prediction of bladder cancer (BCa) recurrence after neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).Patients and Methods: SERS was used to analyze plasma samples collected before biopsy and treatment in BCa patients undergoing NAC and RC. The value of clinicopathological parameters and distinctive SERS peaks in the prediction of disease recurrence were analyzed in Cox regression proportional hazard analysis and Log rank test. Principal component analysis and linear discriminant analysis (PCA-LDA) were employed to process spectral data and construct diagnostic algorithms.Results: A total of 88 patients with 440 plasma SERS spectra were collected. The SRES spectra from recurrent patients were compared with patients who remained recurrence free. The SERS demonstrated higher levels of circulating free nucleic acid components in recurrent population, which is represented by significantly higher intensities at SERS peaks of 725 cm− 1, 1328 cm− 1 and 1455 cm− 1. The SERS also detected significantly lower levels of tryptophan shown as lower significantly intensities at the 1558 cm− 1, which is proved to be an independent predictor of BCa recurrence. The addition of SERS peaks of 1558 cm− 1 to classic clinicopathological predictors including pathological tumor stage, lymph node metastasis and pathological downstaging can significantly enhance the power of the predictive model from 0.66 to 0.76 in the area under curve (AUC) of receiver operating characteristic (ROC) curves. Meanwhile, the PCA-LDA diagnostic model based on SERS spectra reveals a high accuracy of 85.2% in prediction of disease recurrence and the AUC of 0.92 in the ROC curve. When validated in the leave-one-out cross-validation method, the accuracy of the model remained 84.1%.Conclusion: We show that SERS analysis of plasma before NAC treatment can accurately classify patients with different risks of disease recurrence after surgery and improve the power of clinicopathological predictive models, thus refining clinical decision-making.Keywords: Raman spectroscopy, bladder cancer, cancer recurrence, neoadjuvant chemotherapy, radical cystectomy

Donglan Yuan,1,&ast; Ting Guo,2,&ast; DanDan Zhu,1 Hongshan Ge,1 Yinling Zhao,1 Aihua Huang,1 Xiaosu Wang,1 Xiuhong Cao,3 CuiQin He,1 Hua Qian,1 Hong Yu4 1Department of Obstetrics and Gynecology, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Center for Molecular Medicine, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China; 3Department of Operation, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Pathology, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua QianDepartment of Obstetrics and Gynecology, Taizhou People’s Hospital Affiliated to YangZhou University, 399 Hailing Road, Hailing District, Taizhou, Jiangsu, 225300, People’s Republic of ChinaEmail qianhuayx333@126.comHong YuDepartment of Pathology, Taizhou People’s Hospital Affiliated to YangZhou University, 399 Hailing Road, Hailing District, Taizhou, Jiangsu, 225300, People’s Republic of ChinaEmail Yuhongyuhong1234@126.comBackground: Ovarian cancer is a life-threatening disease with a high mortality rate in women. Our previous work presented that long non-coding RNA (lncRNA) activated by transforming growth factor beta (TGF-β) (lncRNA ATB) played a role of oncogene in ovarian cancer. However, whether exosomal lncRNA ATB from ovarian cancer cells could regulate the tumorigenesis of ovarian cancer remains unclear.Methods: RT-qPCR assay was performed to evaluate the level of lncRNA ATB in cancer cells (SKOV3 and A2780). In addition, ovarian cancer cells-secreted exosomes were collected with ultracentrifugation. CCK8 assay was performed to detect the viability of ovarian cells and HUVECs. Meanwhile, Western blot was performed to detect the expression of mechanism related protein and tube formation assay was used to observe the angiogenesis of HUVECs. Finally, xenograft mice model was used to verify the role of ovarian cancer cell-derived exosomes in vivo.Results: Ovarian cancer cells-derived exosomes promoted the viability, angiogenesis and migration of HUVECs; however, knockdown of lncRNA ATB in HUVECs reversed these phenomena. In addition, exosomal lncRNA ATB promoted the tumorigenesis of ovarian cancer via regulating miR-204-3p/TGFβR2 axis. Furthermore, ovarian cancer cells-secreted exosomal lncRNA ATB increased tumor growth in vivo.Conclusion: Exosomal lncRNA ATB derived from ovarian cancer cells could improve tumor microenvironment via regulating miR-204-3p/TGFβR2 axis. Thus, this study might provide new knowledge for the treatment of ovarian cancer.Keywords: ovarian cancer, exosome, lncRNA ATB, TGFβR2, tumor microenvironment

Hongjie Qian,1,2 Qian Chen,1,2 Liyu Liang,1,2 Yang Zou,1,2 Huahua Pu,1,2 Liang Xin,1,2 Rong Song,1,2 Tingting Li,1,2 Huijuan Zhu,1,2 Yu Wang,3 Guanghui Tian,4 Jingshan Shen,2,3 Hualiang Jiang,2,3 Chen Yu,1,2 Zhen Wang,2,3 Jingying Jia1,2 1Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, 200031, People’s Republic of China; 2Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, 200031, People’s Republic of China; 3CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People’s Republic of China; 4Vigonvita Life Science Co., Ltd., Suzhou, 215123, People’s Republic of ChinaCorrespondence: Jingying JiaShanghai Xuhui Central Hospital, No. 966, Huaihai Road(M), Shanghai, 200031, People’s Republic of ChinaTel/Fax +86 21 54030254Email jyjia@shxh-centerlab.comZhen WangShanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555 Zu Chong Zhi Road, Pudong, Shanghai, 201203, People’s Republic of ChinaTel +86 21 20231000Fax +86 21 20231962Email wangzhen@simm.ac.cnPurpose: TPN171H is a novel, potent and selective phosphodiesterase type 5 (PDE5) inhibitor for the treatment of pulmonary arterial hypertension (PAH). The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of TPN171H in healthy subjects after single and multiple dosing, in addition, to investigate the food effect on pharmacokinetics and safety of TPN171H.Methods: The entire study was comprised of three parts: Part I (single ascending-dose study), Part II (food effect study), and Part III (multiple ascending-dose study). A total of 63 healthy subjects were enrolled in the study. TPN171H tablet or placebo was administered per protocol requirements. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events.Results: In Part I, AUC and Cmax were proved to be linear within the 5– 30 mg dose range. T1/2 of TPN171H was 8.02– 10.88 h. In Part II, we figured out that TPN171H administration under fed condition could decrease Cmax, prolong Tmax, but had no effect on AUC. In Part III, the accumulation ratio at steady-state for AUC and Cmax indicated that TPN171H has a slight accumulation upon repeated dosing. Subjects were generally tolerable after TPN171H administration. Compared with other PDE5 inhibitors, TPN171H was found to have no impact on blood pressure and color discrimination.Conclusion: TPN171H was safe and generally tolerated in healthy subjects. Based on the half-life, food effect, and safety profile of TPN171H, we recommend a once-daily, post-meal administration of TPN171H in subsequent clinical studies in healthy subjects and patients with PAH.Keywords: TPN171H, PDE5 inhibitor, safety, pharmacokinetics, food effect, healthy subjects

Wenbin Xu,* Shangdan Xie,* Xin Chen, Shuya Pan, Hongfei Qian, Xueqiong Zhu Center of Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueqiong ZhuCenter of Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, Zhejiang, 325027, People’s Republic of ChinaTel +86 577 88002796 (office)Fax +86 577 88002796Email zjwzzxq@163.comPurpose: This study aimed to investigate the effects of quercetin on the efficacy of various chemotherapeutic drugs in cervical cancer cells.Methods: All drug experiments were performed in HeLa and SiHa cells. The cell viability was detected by Cell Counting Kit-8 assay, and cell proliferation was estimated by bromodeoxyuridine assay. CompuSyn software was utilized to calculate the combination index (CI) and evaluate the synergistic or antagonistic effect of quercetin with cisplatin, paclitaxel, 5-fluorouracil and doxorubicin on cell viability. Cell migration and invasion abilities were detected by transwell assays, and cell apoptosis was measured by flow cytometry. The expression levels of matrix metallopeptidase 2 (MMP2), ezrin, P-glycoprotein (P-Gp) and methyltransferase-like 3 (METTL3) protein treated with various drugs were analyzed by Western blotting.Results: Quercetin inhibited the viability of HeLa and SiHa cells in a dose- and time-dependent manner. The CI values of quercetin with cisplatin, paclitaxel, 5-fluorouracil and doxorubicin were < 1, > 1, > 1 and > 1, respectively. The effect of combination of quercetin and cisplatin on cell proliferation was stronger than their individual effects. Co-treatment group could inhibit more cell migration and invasion in contrast to single-drug group. Besides, quercetin combined with cisplatin group induced more cell apoptosis in contrast to single-drug group. The results of Western blotting showed that the expression levels of MMP2, ezrin, P-Gp and METTL3 in co-treatment group were lower than in cisplatin group, respectively.Conclusion: Quercetin and cisplatin had synergistic inhibitory effect on cervical cancer cells. Quercetin might enhance the antitumor effect of cisplatin via inhibiting proliferation, migration and invasion and elevating apoptosis through weakening MMP2, ezrin, METTL3 and P-Gp expression of cancer cells.Keywords: quercetin, cisplatin, cervical cancer, chemosensitivity

Lingying Dai,1,* Dan Zhang,2,* Yunzhi Qian,2 Yemin Wan,2 Shuchen Chang,2 Haihua Qian2 1No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, People’s Republic of China; 2Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haihua Qian Tel +86-025-86617141Fax +86-025-86617141Email zyqianhaihua@sina.comIntroduction: Phosphorylation of signal transducer and activator of transcription 6 (STAT6) in the colonic epithelium is elevated in ulcerative colitis (UC) patients, and its inhibition prevents IL-13-associated apoptosis and barrier disruption. Recently, the STAT6 rs324015 polymorphism was reported to be related to genetic susceptibility to UC.Methods: We examined STAT6 rs324015 using the PCR–RFLP method in 268 UC cases and 357 controls. STAT6 expression was determined by quantitative reverse-transcription PCR. The gene–environment interactions were addressed by cross-over analysis.Results: We found that the STAT6 rs324015 polymorphism enhanced the risk of UC under the homozygous, dominant, and allelic models. Further subgroup analyses indicated that this relationship was more evident in alcohol users, smokers, and those younger than 40 years. Cross-over analysis showed strong interactions of STAT6 rs324015 with smoking/alcohol use. In addition, this polymorphism was associated with the severity, and location of UC. The GG genotype was significantly associated with increased STAT6 gene levels.Conclusion: In summary, the STAT6 rs324015 polymorphism is related with predisposition to UC in a Chinese Han population.Keywords: STAT6, ulcerative colitis, case–control study, rs324015 polymorphism

Wanren Peng,1,* Fenglin Zhang,2,* Zishu Wang,3,* Dongliang Li,4,* Yifu He,5,* Zhongliang Ning,6 Lili Sheng,7 Jidong Wang,8 Xiaoyang Xia,9 Changjun Yu,10 Zian Wang,3 Yong Zhao,11 Hui Liang,12 Bing Hu,13 Cuiling Sun,14 Daoqin Wang,15 Yunsheng Cheng,16 Ming Pan,17 Liming Xia,18 Xinglai Guo,19 Yanshun Zhang,20 Zhiqiang Hu,21 Xinzhong Li,22 Lin Lu,23 Jun Zhang,24 Hong Qian,8 Hua Xie,25 Guoping Sun1,* 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People’s Republic of China; 2Department of Oncology, People’s Hospital of Maanshan City, Maanshan, Anhui 243000, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, People’s Republic of China; 4Department of Gastrointestinal Surgery, People’s Hospital of Lu’an City, Lu’an, Anhui 237005, People’s Republic of China; 5Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei, Anhui 230022, People’s Republic of China; 6Department of Gastrointestinal Surgery, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei, Anhui 230022, People’s Republic of China; 7Department of Oncology, Yijishan Hospital of WanNan Medical College, Wuhu, Anhui 340202, People’s Republic of China; 8Department of Oncology, The Navy Anqing Hospital, Anqing, Anhui 246003, People’s Republic of China; 9Department of Oncology, The First People’s Hospital of Chuzhou City, Chuzhou, Anhui 239000, People’s Republic of China; 10Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People’s Republic of China; 11Department of Oncology, People’s Hospital of Lu’an City, Lu’an, Anhui 237005, People’s Republic of China; 12Department of Oncology, Lu’an Hospital of Traditional Chinese Medicine, Lu’an, Anhui 237006, People’s Republic of China; 13Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230022, People’s Republic of China; 14Department of Oncology, People’s Hospital of Fuyang City, Fuyang, Anhui 236047, People’s Republic of China; 15Department of Gastrointestinal Surgery, Wanbei Coal-Electricity Group General Hospital, Suzhou, Anhui 234000, People’s Republic of China; 16Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, People’s Republic of China; 17Department of Oncology, People’s Hospital of Chizhou City, Chizhou, Anhui 247000, People’s Republic of China; 18Department of Oncology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, People’s Republic of China; 19Department of Oncology, Fuyang Cancer Hospital, Fuyang, Anhui 236033, People’s Republic of China; 20Department of Oncology, Huainan First People’s Hospital, Huainan, Anhui 232000, People’s Republic of China; 21Department of Oncology, Huaibei Miners General Hospital, Huaibei, Anhui 235000, People’s Republic of China; 22Department of Oncology, People’s Hospital of Huaibei, Huaibei, Anhui 235000, People’s Republic of China; 23Department of Oncology, The 901 Hospital of the Joint Logistic Support Force of the People’s Liberation Army of China, Hefei, Anhui 230033, People’s Republic of China; 24Department of Oncology, The Second People’s Hospital of Wuhu, Wuhu, Anhui 241001, People’s Republic of China; 25Department of Oncology, The People’s Hospital of Xuancheng City, Xuancheng, Anhui 242000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoping Sun Email sungp@ahmu.edu.cnBackground: In China, gastric cancer (GC) ranks second in incidence and mortality. Over 80% of patients with GC were diagnosed at an advanced stage with poor clinical outcome. Chemotherapy was the mainstream treatment with limited benefit. Apatinib, an inhibitor of targeting vascular endothelial growth factor receptor 2 (VEGFR2), has been approved for third-line treatment of advanced gastric cancer. However, the data of apatinib treatment in the real-world setting are limited. In this real-world study, we aimed to understand the current treatment pattern of apatinib, investigate the effectiveness and safety of apatinib in real-world settings, and explore the potential factors associated with the clinical outcomes.Methods: This was a prospective, multicenter observational study in a real-world setting. Patients aged ≥ 18 years with histologic diagnosis of advanced GC were eligible for enrollment. The eligible patients received either apatinib monotherapy or apatinib plus chemotherapy by physician’s discretion. Apatinib treatment could be used as first-line, second-line, or third-line and above therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), ORR, DCR, and safety profile.Results: A total of 737 patients with advanced gastric cancer treated with apatinib were included in the FAS population. A total of 54.9% patients used apatinib monotherapy and 45.1% patients used apatinib combination therapy. A total of 44.1% patients received apatinib in first-line treatment, 28.2% in second-line, and 27.7% in third-line and above. In first-line treatment, the objective response rate (ORR) was 9.09% and 16.42% in apatinib monotherapy and combination therapy groups, and disease control rate (DCR) was 78.41% and 89.29%, respectively. Patients who received combination therapy achieved significantly longer median progression-free survival (mPFS; 6.18 vs 3.52 months, p< 0.01) and median overall survival (mOS; 8.72 vs 5.92 months, p< 0.01) compared with monotherapy. In second-line and third-line therapy, combination therapy showed a better trend in tumor response and survival outcomes compared with monotherapy. For all patients, apatinib combined with paclitaxel were associated with longer mPFS compared with other combinations (8.88 vs 6.62 months). Multivariate analysis showed that combination with paclitaxel (p=0.02) and experience of apatinib-related specific AEs (p< 0.01) were independent predictors for PFS and OS. The safety profile was tolerable and no unexpected adverse events were reported.Conclusion: In a real-world setting, apatinib showed a favorable effectiveness and safety profile in patients with advanced gastric cancer. Apatinib combination therapy, especially combined with paclitaxel, might lead to better survival benefit in first-line treatment. Combination with paclitaxel and the occurrence of apatinib-specific AEs were independent factors associated with better survival outcomes.Trial Registration: NCT03333967.Keywords: apatinib, combination therapy, real-world, advanced gastric cancer

Lu Lin,1,2 Xiuchen Jing,1,2 Yan Zhang,3 Hongying Qian,1 Jiali Xu,1 Li Tian1,2 1Department of Nursing, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Oncology, School of Nursing, Medical College of Soochow University, Suzhou, People’s Republic of China; 3Department of Oncology, Suzhou Municipal Hospital, Suzhou, People’s Republic of ChinaCorrespondence: Li TianThe First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou 215006, People’s Republic of ChinaTel +86 512 65221481Fax +86 512 65125097Email tianlisz@suda.edu.cnBackground: Patient compliance can influence the effect of auricular acupressure used to manage cancer-related fatigue (CRF).Objective: To explore the barriers and facilitators affecting patients’ compliance with treatment.Methods: The maximum difference sampling method was used to conduct qualitative interviews with 11 CRF patients undergoing auricular acupressure therapy. The interview data were analyzed by Colaizzi’s seven-step analysis.Results: Convenience and acceptability of the therapy, preliminary effects of its implementation, fully believing in the benefits of auricular acupressure and being habituated to the therapy, help and reminder from family members are the facilitating factors to improve patient compliance with auricular acupressure therapy, while the hindering factors include having doubts about the effect of acupressure resulting in interruption, having limited access to medical resources, deterioration of the condition resulting in self-abandonment, and weak family support.Conclusion: In clinical nursing practice, attention should be paid to the analysis of the facilitating and hindering factors during the implementation of auricular acupressure therapy as well as the development of targeted intervention measures to improve patient compliance so as to enhance the effectiveness of auricular acupressure.Keywords: auricular acupressure, compliance, cancer-related fatigue, influencing factors

Qin Liu,1,* Dinghu Zhang,1,2,* Hanqing Qian,1 Yanhong Chu,1 Yan Yang,3 Jie Shao,1 Qiuping Xu,1 Baorui Liu1 1The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China; 2Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 3Department of Oncology, Jiangning Hospital, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baorui LiuThe Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing 210008, People’s Republic of ChinaTel +86 25-83107081Fax +86 25-83317016Email baoruiliu@nju.edu.cnIntroduction: The exhaustion and poor homing of activated lymphocytes are critical obstacles in adoptive cell immunotherapy for solid tumors. In order to effectively deliver immune cells into tumors, we encapsulated interferon-α 2b (IFN-α 2b) into macroporous hydrogels as an enhancement factor and utilized low-dose irradiation (LDI) as a tumoral attractor of T cells.Methods: Hydroxypropyl cellulose hydrogels were prepared by irradiation techniques, and the cross-sectional microstructure was characterized by scanning electron microscopy. The synergistic antitumor mechanism of combination of IFN-α 2b and CIK cells was evaluated by detecting the expression of activation marker CD69 on CIK cell surface and IFN-γ production by CIK cells. The in vivo antitumor activity of IFN-α 2b-incorporated hydroxypropyl cellulose hydrogels combined with CIK and radiation was evaluated in an MKN-45 xenografted nude mice model.Results: The bioactivity of IFN-α 2b was well maintained in ultraviolet-reactive, rapidly cross-linkable hydroxypropyl cellulose hydrogels. In vitro studies demonstrated IFN-α 2b-activated T cells, as evidenced by upregulating early activation marker CD69 and secretion inflammatory cytokine IFN-γ. In vivo real-time image showed our hydrogels kept a higher amount of drug delivery at the tumor site for a long time compared with free drug injection. Low-dose irradiation promoted T cell accumulation and infiltration in subcutaneous tumors. Combination of IFN-α 2b-loaded hydrogels (Gel-IFN) with T cells and LDI exhibited higher efficacy to eradicate human gastric cancer xenograted tumors with less proliferating cells and more necrotic regions compared with IFN-α 2b or T cells alone.Discussion: HPC hydrogels kept the activity of IFN-α 2b and stably release of IFN-α 2b to stimulate T cells for a long time. At the same time, low-dose radiation recruits T cells into tumors. This innovative integration mode of IFN-α 2b-loaded hydrogels and radiotherapy offers a potent strategy to improve the therapeutic outcome of T cell therapy.Keywords: gastric cancer, adoptive cell transfer, interferon-α 2b, hydrogels, low-dose irradiation

Xiaohui Zhang,1,2,* Yanfei Lu,1,2,* Huimin Qian,3 Genyan Liu,1,2 Yaning Mei,1,2 Fei Jin,1,2 Wenying Xia,1,2 Fang Ni1,2 1Department of Laboratory Medicine, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, People’s Republic of China; 2National Key Clinical Department of Laboratory Medicine, Nanjing, People’s Republic of China; 3Key Laboratory of Enteric Pathogenic Microbiology of Ministry of Health, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenying Xia; Fang NiDepartment of Laboratory Medicine, Jiangsu Province Hospital, Guangzhou Street No. 300, 210029, People’s Republic of ChinaTel +8625-6830-6287Fax +8625-8372-4440Email xiawenying21106891@163.com; 13813972378@163.comAbstract: Non-O1, non-O139 Vibrio cholerae (NOVC) does not agglutinate with O1 and O139 antisera and can cause intestinal and extraintestinal infections in immunocompromised individuals. NOVC bacteremia has the highest mortality among NOVC infections, and the number of reports has increased in recent years. Nevertheless, some clinicians are poorly informed about this disease. Herein, we describe a documented case of NOVC bacteremia in a male patient with impaired liver function. Blood cultures revealed the presence of V. cholerae, but this strain showed self-coagulation on the serum agglutination test. To our knowledge, this phenomenon is unreported among cases of NOVC infections. This pathogen was finally confirmed as NOVC via PCR. Because the patient worked as a garbage transporter, he was likely infected after contact with contaminated water through a foot wound. The patient developed septic shock shortly after admission and ultimately died from the illness. This paper reviews 23 cases of NOVC bacteremia from 2015 to 2019. To improve the accuracy of identifying NOVC and analyze its virulence factors, relevant detection methods were reviewed and analyzed.Keywords: bacteremia, non-O1/non-O139 Vibrio cholerae, V. cholerae, virulence factors

Dinghu Zhang,1,2,* Yanhong Chu,1,* Hanqing Qian,1 Lingyu Qian,1 Jie Shao,1 Qiuping Xu,1 Lixia Yu,1 Rutian Li,1 Quanan Zhang,3 Fenglei Wu,4 Baorui Liu,1 Qin Liu1 1The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China; 2Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of China; 3Department of Oncology, Jiangning Hospital, Nanjing, People’s Republic of China; 4Department of Oncology, Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin Liu; Baorui LiuThe Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing 210008, People’s Republic of ChinaTel +86-25-83107081Fax +86-25-83317016Email liuqinxh@126.com; baoruiliu@nju.edu.cnIntroduction: Gambogic acid (GA) is proved to have anti-tumor effects on gastric cancer. Due to poor solubility, non-specific biological distribution, toxicity to normal tissues and short half-life, it is hard to be applied into the clinic. To overcome these issues, we developed a thermosensitive and injectable hydrogel composed of hydroxypropyl cellulose, silk fibroin and glycerol, with short gelling time, good compatibility and sustained release, and demonstrated that the hydrogel packaged with gambogic acid nanoparticles (GA-NPs) and tumor-penetrating peptide iRGD could improve the anti-tumor activity.Methods: The Gelling time and micropore size of the hydrogels were regulated through different concentrations of glycerol. Controlled release characteristics of the hydrogels were evaluated with a real-time near-infrared fluorescence imaging system. Location of nanoparticles from different carriers was traced by confocal laser scanning microscopy. The in vivo antitumor activity of the hydrogels packaging GA-NPs and iRGD was evaluated by investigating tumor volume and tumor size.Results: The thermo-sensitive properties of hydrogels were characterized by 3– 4 min, 37°C, when glycerol concentration was 20%. The hydrogels physically packaged with GA-NPs and iRGD showed higher fluorescence intensity than other groups. The in vivo study indicated that the co-administration of GA-NPs and iRGD by hydrogels had higher antitumor activity than the GA-loaded hydrogels and free GA combining with iRGD. Free GA group showed few antitumor effects. Compared with the control group, the body weight in other groups had no obvious change, and the count of leukocytes and hemoglobin was slightly decreased.Discussion: The hydrogel constructed iRGD and GA-NPs exerted an effective anti-tumor effect possibly due to retention effect, local administration and continuous sustained release of iRGD promoting the penetration of nanoparticles into a deep part of tumors. The delivery system showed little systemic toxicity and would provide a promising strategy to improve anti-gastric cancer efficacy.Keywords: gambogic acid, hydrogel, nanoparticles, iRGD, gastric cancer

Galaxy clusters are the most recently formed and most massive, gravitationally bound structures in the Universe. The number of galaxy clusters formed is highly dependent on cosmological parameters, such as the dark matter density, σ _8 , and Ω _m . The number density is a function of the cluster mass, which can be estimated from the density and temperature profiles of the intracluster medium under the assumption of hydrostatic equilibrium. The temperature of the plasma, hence its mass, is calculated from the X-ray spectra. However, effective-area calibration uncertainties in the soft band result in significantly different temperature measurements from various space-based X-ray telescopes. NuSTAR is potentially less susceptible to these issues than Chandra and XMM-Newton, having larger effective area, particularly at higher energies, enabling high-precision temperature measurements. In this work, we present analyses of Chandra, NuSTAR, and XMM-Newton data of A478 to investigate the nature of this calibration discrepancy. We find that NuSTAR temperatures are on average ∼11% lower than those of Chandra, and XMM-Newton temperatures are on average ∼5% lower than those of NuSTAR. This results in a NuSTAR mass at r _2500,Chandra of ${M}_{2500,\mathrm{NuSTAR}}\,=\,{3.39}_{-0.07}^{+0.07}\times {10}^{14}$ M _⊙ , which is ∼10% lower than that of M _2500,Chandra and ∼4% higher than M _2500,XMM−Newton .

Haiping Zhang,1 Jiani Wu,1 Zhuolin Zhang,2 Haisheng Qian,3 Yifan Wang,1 Miaomiao Yang,1 Yinchu Cheng,4 Shaowen Tang11Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People’s Republic of China; 2Department of Clinical Pharmacy, School of Pharmacy, Nanjing Medical University, Nanjing 211166, Jiangsu, People’s Republic of China; 3Department of Internal Medicine, The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu 210029, People’s Republic of China; 4Department of Pharmacy, Peking University Third Hospital, Beijing 100191, People’s Republic of ChinaPurpose: This study aimed to evaluate Atorvastatin (ATO)-associated hepatotoxicity using prescription sequence symmetry analysis (PSSA), based on a health insurance database of a Chinese population living in Jiangsu Province, China.Methods: Patients prescribed ATO and hepatoprotective drugs in 2017 were identified, and the run-in period was determined based on the “waiting-time” distribution. Adjusted sequence ratio (ASR) and 95% confidence interval (95% CI) were calculated to estimate the risk of ATO-associated hepatotoxicity under different time intervals or based on gender and age stratification.Results: A total of 2,549 patients, with 1,518 filling the ATO prescription first and 1,031 filling the ATO prescription second, were analyzed. After setting the run-in period as 30 days and the time interval as 15, 30, 60, 90, 120, and 180 days, the ASRs were 1.492 (95% CI: 1.367–1.652), 1.399 (95% CI: 1.308–1.508), 1.280 (95% CI: 1.213–1.357), 1.292 (95% CI: 1.234–1.356), 1.278 (95% CI: 1.226–1.336), and 1.274 (95% CI: 1.229–1.323), respectively. No significant difference was observed between different genders and ages (χ2,=0.161, P=0.688; χ2,=1.565, P=0.211, respectively).Conclusion: This is the first study conducted in a real-world setting to evaluate the relationship between ATO and hepatotoxicity using the PSSA in a Chinese population. We found a 1.3- to 1.5-fold increase in risk of hepatotoxicity following ATO, with the greater risk occurring within the first 30 days of treatment.Keywords: atorvastatin, hepatoprotective drug, prescription sequence symmetry analysis, health insurance database

Yongtao Gao,1 Haiyang Qian,2 Xue Tang,1 Xiling Du,3 Gang Wang,2 Hairong Zhang,2 Fei Ye,2 Te Liu41The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 2Department of Imaging, Dahua Hospital, Shanghai, 200237, People’s Republic of China; 3School of Life Science and Technology, Tongji University, Shanghai 200092, People’s Republic of China; 4Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, People’s Republic of ChinaBackground: Previously, our group confirmed the presence of a subset of cancer stem cells in the tissues of endometrial carcinoma (ie, human endometrial carcinoma stem cells [HuECSCs]). However, the mechanisms by which microRNAs regulate the growth of HuECSCs remain elusive.Methods: We loaded miR-326 onto superparamagnetic iron oxide nanoparticles (miR-326@SPION) and transfected them into HuECSCs.Results: In the present study, we found that the expression levels of members of the G-protein coupled receptor 91 (GPR91)/signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor (VEGF) pathway were significantly elevated in CD44+/CD133+ HuECSCs. Luciferase reporter assays indicated that the succinate receptor 1 (SUCNR1) gene, also known as the G-protein coupled receptor 91 (GPR91) gene, was one of the potential targets of miR-326. Transmission electron microscopy revealed that the SPIONs could cross the cell membrane and accumulate in the cytoplasm. The overexpression of miR-326 significantly inhibited the proliferation and cell cycle progression of HuECSCs in vitro. MiR-326 overexpression also effectively inhibited the invasion and angiogenic capacities of HuECSCs in the extracellular matrix. Meanwhile, miR-326 overexpression significantly inhibited the tumorigenicity and tumour neovascularization capacity of HuECSCs in nude mice. Both quantitative real-time PCR and Western blotting confirmed that overexpression of miR-326 significantly reduced the expression of members of the GPR91/STAT3/VEGF pathway in HuECSCs, and the activity (level of phosphorylation) of key molecules in this pathway was also reduced.Conclusion: Collectively, we confirmed that SPIONs are highly efficient nanocarriers for nucleic acids, on which the loading of miR-326 inhibited the activation of the GPR91/STAT3/VEGF signaling pathway and significantly attenuated the activity of stem cells in endometrial carcinoma, both in vitro and in vivo.Keywords: human endometrial carcinoma stem cells, superparamagnetic iron oxide nanoparticles, microRNA, succinate receptor 1

Abstract Background Species diversity is determined by both local environmental conditions that control differentiation and extinction and the outcome of large-scale processes that affect migration. The latter primarily comprises climatic change and dynamic landscape alteration. In the past few million years, both Southeast Asia and Eastern Africa experienced drastic climatic and geological oscillations: in Southeast Asia, especially in China, the Tibetan Plateau significantly rose up, and the flow of the Yangtze River was reversed. In East Africa, lakes and rivers experienced frequent range expansions and regressions due to the African mega-droughts. To test how such climatic and geological histories of both regions relate to their respective regional species and genetic diversity, a large scale comparative phylogeographic study is essential. Bellamya, a species rich freshwater snail genus that is widely distributed across China and East Africa, represents a suitable model system to address this question. We sequenced mitochondrial and nuclear DNA for members of the genus from China and used published sequences from Africa and some other locations in Asia to investigate their phylogeny and distribution of genetic diversity. Results Our phylogenetic analysis revealed two monophyletic groups, one in China and one in East Africa. Within the Chinese group, Bellamya species show little genetic differentiation. In contrast, we observe fairly deep divergence among the East African lakes with almost every lake possessing its unique clade. Our results show that strong divergence does not necessarily depend on intrinsic characteristics of a species, but rather is related to the landscape dynamics of a region. Conclusion Our phylogenetic results suggest that the Bellamya in China and East Africa are independent phylogenetic clades with different evolutionary trajectories. The different climate and geological histories likely contributed to the diverging evolutionary patterns. Repeated range expansions and regressions of lakes likely contributed to the great divergence of Bellamya in East Africa, while reversal of the river courses and intermingling of different lineages had an opposite effect on Bellamya diversification in China.

Xu Zhang,1,2,* Peng Zhang,1,* Meng Shao,1 Xueyan Zang,1 Jiayin Zhang,1 Fei Mao,1 Hui Qian,1,2 Wenrong Xu1,2 1Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China; 2Zhenjiang Key Laboratory of Gastrointestinal Cancer, Jiangsu University, Zhenjiang, Jiangsu 212013, China *These authors contributed equally to this work Background: Increasing evidence suggests that SALL4 plays oncogenic roles in cancer development and progression. We have previously shown that SALL4 is highly expressed in gastric cancer, and its upregulation is associated with lymph node metastasis and poor prognosis. The role of SALL4 in gastric cancer metastasis and the underlying mechanism remain unclear.Materials and methods: The biological roles of SALL4 in gastric cancer cell mobility, migration, and invasion were investigated by wound healing, transwell migration assay, and Matrigel invasion assay. The effects of SALL4 on epithelial–mesenchymal transition (EMT) in gastric cancer cells were examined by quantitative real-time PCR and Western blot. The downstream target genes of SALL4 were identified by microarray. The regulation of TGF-β1 by SALL4 in gastric cancer cells was analyzed by luciferase reporter assay and chromatin immunoprecipitation assay.Results: SALL4 knockdown inhibited, while SALL4 overexpression promoted the motility, migration, and invasion abilities of gastric cancer cells in vitro. SALL4 knockdown also suppressed the peritoneal metastasis of gastric cancer cells in nude mice. SALL4 knockdown suppressed, while SALL4 overexpression induced the activation of TGF-β/SMAD signaling pathway and triggered EMT in gastric cancer cells. TGF-β1 was identified as a direct target gene of SALL4. The results of chromatin immunoprecipitation study and luciferase reporter assay further confirmed that SALL4 bound to the promoter of TGF-β1 gene and activated its expression. TGF-β1 knockdown reversed SALL4-mediated promotion of gastric cancer cell motility, migration, and invasion, indicating that TGF-β1 acts as a downstream effector of SALL4. Furthermore, the expression of TGF-β1 was found to be closely associated with that of SALL4 in gastric cancer tissues.Conclusion: SALL4 promotes the metastasis of gastric cancer, at least partly, by directly activating TGF-β1, suggesting that SALL4 may serve as a new target for gastric cancer therapy. Keywords: gastric cancer, SALL4, TGF-β1, EMT, metastasis

Puyuan Wu, Qin Liu, Qin Wang, Hanqing Qian, Lixia Yu, Baorui Liu, Rutian Li The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China Background: A multi-drug delivery platform is needed as the intra-tumoral heterogeneity of cancer leads to different drug susceptibility. Cancer stem cells (CSCs), a small population of tumor cells responsible for tumor seeding and recurrence, are considered chemotherapy-resistant and have been reported to be sensitive to salinomycin (Sal) instead of paclitaxel (Ptx). Here we report a novel silk fibroin (SF) hydrogel-loading Sal and Ptx by incorporating drug-loaded silk fibroin nanoparticles (SF-NPs) to simultaneously kill CSCs and non-CSCs.Methods: Using the method we have previously reported to prepare Ptx-loaded SF-NPs (Ptx-SF-NPs), Sal-loaded SF-NPs (Sal-SF-NPs) were fabricated under mild and non-toxic conditions. The drug-loaded SF-NPs were dispersed in the ultrasound processed SF solution prior to gelation.Results: The resulting SF hydrogel (Sal-Ptx-NP-Gel) retained its injectable properties, exhibited bio-degradability and demonstrated homogeneous drug distribution compared to the non-NP incorporated hydrogel. Sal-Ptx-NP-Gel showed superior inhibition of tumor growth compared to single drug-loaded hydrogel and systemic dual drug administration in the murine hepatic carcinoma H22 subcutaneous tumor model. Sal-Ptx-NP-Gel also significantly reduced CD44+CD133+ tumor cells and demonstrated the least tumor formation in the in vivo tumor seeding experiment, indicating superior inhibition of cancer stem cells.Conclusion: These results suggest that SF-NPs incorporated SF hydrogel is a promising drug delivery platform, and Sal-Ptx-NP-Gel could be a novel and powerful locoregional tumor treatment regimen in the future. Keywords: silk fibroin, nanoparticle, hydrogel, salinomycin, cancer stem cells

Hong Chen,1–3,* Huizi Sha,2,* Lianru Zhang,2 Hanqing Qian,2 Fangjun Chen,2 Naiqin Ding,2 Liulian Ji,2 Anqing Zhu,2 Qiuping Xu,2 Fanyan Meng,2 Lixia Yu,2 Yan Zhou,3 Baorui Liu1,2 1The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China; 3Department of Oncology, Yixing People’s Hospital, Jiangsu, People’s Republic of China *These authors contributed equally to this work Background: There is currently much interest in cancer cell targeting and tumor penetrating for research and therapeutic purposes.Purpose: To improve targeting delivery of antitumor drugs to gastric cancer, in this study, a tumor-targeting biocompatible drug delivery system derived from erythrocyte membrane for delivering paclitaxel (PTX) was constructed.Methods: Erythrocyte membrane of human red blood cells (RBCs) were used for preparing of erythrocyte membrane-derived vesicles. 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(maleimide[polyethylene glycol]-3400) (DSPE-PEG-MAL), a phospholipid derivative, was used to insert tumor-targeting molecular into erythrocyte membrane-derived vesicles. A lipid insertion method was used to functionalize these vesicles without the need for direct chemical conjugation. Furthermore, a tumor-penetrating bispecific recombinant protein named anti-EGFR-iRGD was used for the first time in this work to enable nanosystem to target and penetrate efficiently into the tumor site.Results: Paclitaxel (PTX)-loaded anti-EGFR-iRGD-modified erythrocyte membrane nanosystem (anti-EGFR-iRGD-RBCm-PTX, abbreviated to PRP) were manufactured. PRP was spheroid, uniformly size, about 171.7±4.7 nm in average, could be stable in vitro for 8 days, and released PTX in a biphasic pattern. PRP showed comparable cytotoxicity toward human gastric cancer cells in vitro. In vivo studies showed that, PRP accumulated in tumor site within 2 h of administration, lasted longer than 48 h, and the tumor volume was reduced 61% by PRP treatment in Balb/c nude mice, without causing severe side effects.Conclusion: PRP has potential applications in cancer treatment and as an adjunct for other anticancer strategies. Keywords: tumor-penetrating bispecific recombinant protein, erythrocyte membrane, biomimetic nanoparticle, drug delivery

Zhen Zhang,1,2 Hanqing Qian,1 Jie Huang,1 Huizi Sha,1 Hang Zhang,1 Lixia Yu,1 Baorui Liu,1 Dong Hua,3 Xiaoping Qian1 1Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Integrated Traditional Chinese Medicine and Western Medicine Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China Background: Red blood cell membrane-coated nanoparticle (RBCm-NP) platform, which consist of natural RBCm and synthetic polymeric core, can extend circulation time in vivo with an improved biocompatibility and stability of this biomimetic nanocarrier. To achieve better bioavailability of antitumor drugs that were loaded in RBCm-NPs, the functionalization of coated RBCm with specific targeting ability is essential. Bispecific recombinant protein anti-EGFR-iRGD, containing both tumor penetrating peptide (internalizing RGD peptide) and EGFR single-domain antibody (sdAb), seems to be an optimal targeting ligand for RBCm-NPs in the treatment of multiple tumors, especially colorectal cancer with high EGFR expression. Materials and methods: We modified the anti-EGFR-iRGD recombinant protein on the surface of RBCm-NPs by lipid insertion method to construct iE–RBCm–PLGA NPs and confirmed the presentation of active tumor-targeting ability in colorectal cancer models with high EGFR expression when compared with RBCm–PLGA NPs. In addition, potential anti- tumor drug gambogic acid (GA) was loaded into the NPs to endow the antitumor efficiency of iE–RBCm–GA/PLGA NPs. It was simultaneously evaluated whether GA can reach better biocompatibility benefiting from the improved antitumor efficiency of iE–RBCm–GA/PLGA NPs in colorectal cancer models. Results: We successfully modified anti-EGFR-iRGD proteins on the surface of biomimetic NPs with integrated and stable “shell–core” structure. iE–RBCm–PLGA NPs showed its improved targeting ability in vitro (multicellular spheroids [MCS]) and in vivo (nude mice bearing tumors). Besides, no matter on short-term cell apoptosis at tumor site (terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling [TUNEL]) and long-term tumor inhibition, iE–RBCm–GA/PLGA NPs achieved better antitumor efficacy than free GA in spite of the similar effects of cytotoxicity and apoptosis to GA in vitro. Conclusion: We expect that the bispecific biomimetic nanocarrier can extend the clinical application of many other potential antitumor drugs similar to GA and become a novel drug carrier in the colorectal cancer treatment. Keywords: biomimetic nanocarrier, anti-EGFR-iRGD recombinant protein, gambogic acid, targeting ability, antitumor efficiency, colorectal cancer

Hong Zhou,1,2 Haixin Qian1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, People’s Republic of China; 2Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, People’s Republic of China Objective: The aim of this study was to develop pH sensitive nanoparticles of budesonide for the treatment of ulcerative colitis.Methods: The NPs system was characterized by the transmission electron microscopy (TEM), particle size, drug loading and encapsulation efficiency. In addition, in vitro drug release properties and pharmacokinetics were also investigated in detail. The optimized formulation was examined for its in-vivo targeting potential using 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in a rat model.Results: Dynamic light-scattering results showed that the particle size of budesonide-Eudragit S100/poly(lactic-co-glycolic acid) nanoparticles was around 110.5 nm, with a polydispersity index of 0.098. Transmission electron microscopy images showed that BUD-ES100/PLGA NPs were spherical with uniform size and relatively smooth surfaces. In vitro release showed that BUD-ES100/PLGA NPs required minimal release of drugs during its transit in the stomach and the upper small intestine to ensure that a maximum dose reached the colon. After the pharmacodynamic treatment, the myeloperoxidase value of BUD-ES100/PLGA NPs was close to the normal group. The histopathological examination of rectum showed that no sign of damages such as epithelial necrosis and sloughing epithelial cells was detected.Conclusion: Our findings suggested that BUD-ES100/PLGA NPs were a promising alternative to single pH-dependent systems for colitis therapy. Keywords: budesonide, nanoparticles, ES100/PLGA, in vitro release, pharmacodynamic

Hong Zhou,1,2 HaiXin Qian1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China; 2Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Objective: To investigate enteral nutrition’s effect on serum inflammatory factors and the cardiac function of malnourished elderly patients with heart failure.Patients and methods: A total of 105 elderly patients with heart failure were randomly divided into 3 groups: Treatment Group A, Treatment Group B, and the Control Group (Group C), each group having 35 patients and being administered conventional heart failure treatment. Group A was treated with 500 mL·d-1 of enteral nutrition for 1 month. Group B was given the same dose of enteral nutrition for 3 months. The Control Group was given free diet. Nutritional risk screening 2002 was used to assess the nutritional status before and after the treatment for each group. New York Heart Association status was recorded as were left ventricular ejection fraction, plasma B-type natriuretic peptide, inteleukin-6, C-reactive protein, and tumor necrosis factor-α.Results: After the treatment, the body mass index, skinfold thickness of upper arm triceps, muscle circumference of the upper arm, upper arm muscle circumference, total protein, albumin, hemoglobin, and left ventricular ejection fraction in the treatment groups all increased, with relatively obvious relief of symptoms of heart failure. The levels of B-type natriuretic peptide, interleukin-6, tumor necrosis factor-α, and C-reactive protein all rose to different extents (P0.05).Conclusion: The use of enteral nutrition in conventional treatment of elderly patients with heart failure could improve not only patients’ nutritional status and cardiac function, but also their immune function, thus reducing the levels of inflammatory factors. The longer the treatment period is, the more obvious the improvement in patients’ cardiac function and inflammatory factors will be observed. Keywords: enteral nutrition, heart failure, elderly, inflammatory factors, cardiac function

Yi Li,1,2 Jing Feng,3,4 Yuechuan Li,2 Wei Jia,2 Hongyu Qian2 1Graduate School, Tianjin Medical University, 2Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, 3Respiratory Department, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 4Neuropharmacology Section, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA Background: The benefit of pulmonary rehabilitation (PR) for patients with COPD diminishes over time. We investigated a new strategy involving home-visit and phone contact and compared this to usual care in maintenance of PR benefits.Methods: A total of 172 stable COPD patients receiving 8-week PR program were recruited for this prospective study. Patients were allocated into usual care group (UC) and PR maintenance group (PRMG) randomly. Patients in PRMG participated in maintenance strategy at home under supervision through home-visit and phone contact. The 6-minute walking test (6MWT), COPD assessment test (CAT), and modified Medical Research Council scale (mMRC) scores were evaluated every 3 months.Results: Of the total, 151 patients completed 8-week PR program with satisfactory PR results (p

Zhenheng Wang,* Kaiwen Xue,* Maosheng Bai, Zhantao Deng, Jingjing Gan, Gang Zhou, Hongbo Qian,* Nirong Bao, Jianning Zhao Department of Orthopaedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Wear particle-induced inflammatory osteolysis is the primary cause of aseptic loosening, which is the most common reason for total hip arthroplasty (THA) failure in the med- and long term. Recent studies have suggested an important role of gut microbiota (GM) in modulating the host metabolism and immune system, leading to alterations in bone mass. Probiotic bacteria administered in adequate amounts can alter the composition of GM and confer health benefits to the host. Given the inflammatory osteolysis that occurs in wear debris-induced prosthesis loosening, we examined whether the probiotic Lactobacillus casei could reduce osteolysis in a mouse calvarial resorption model. In this study, L. casei markedly protected mice from CoCrMo particles (CoPs)-induced osteolysis. Osteoclast gene markers and the number of osteoclasts were significantly decreased in L. casei-treated mice. Probiotic treatment decreased the M1-like macrophage phenotype indicated by downregulation of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and inducible nitric oxide synthase (iNOS) and increased the M2-like macrophage phenotype indicated by upregulation of IL-4, IL-10 and arginase. Collectively, these results indicated that the L. casei treatment modulated the immune status and suppressed wear particle-induced osteolysis in vivo. Thus, probiotic treatment may represent a potential preventive and therapeutic approach to reduced wear debris-induced osteolysis. Keywords: wear particles, gut microbiota, nanotoxicity, macrophage polarization, inflammatory cytokines, aseptic loosening

Lianru Zhang, Rutian Li, Hong Chen, Jia Wei, Hanqing Qian, Shu Su, Jie Shao, Lifeng Wang, Xiaoping Qian, Baorui Liu The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China Abstract: Cell membrane-derived nanoparticles are becoming more attractive because of their ability to mimic many features of their source cells. This study reports on a biomimetic delivery platform based on human cytotoxic T-lymphocyte membranes. In this system, the surface of poly-lactic-co-glycolic acid nanoparticles was camouflaged using T-lymphocyte membranes, and local low-dose irradiation (LDI) was used as a chemoattractant for nanoparticle targeting. The T-lymphocyte membrane coating was verified using dynamic light scattering, transmission electron microscopy, and confocal laser scanning microscopy. This new platform reduced nanoparticle phagocytosis by macrophages to 23.99% (P=0.002). Systemic administration of paclitaxel-loaded T-lymphocyte membrane-coated nanoparticles inhibited the growth of human gastric cancer by 56.68% in Balb/c nude mice. Application of LDI at the tumor site significantly increased the tumor growth inhibition rate to 88.50%, and two mice achieved complete remission. Furthermore, LDI could upregulate the expression of adhesion molecules in tumor vessels, which is important in the process of leukocyte adhesion and might contribute to the localization of T-lymphocyte membrane-encapsulated nanoparticles in tumors. Therefore, this new drug-delivery platform retained both the long circulation time and tumor site accumulation ability of human cytotoxic T lymphocytes, while local LDI could significantly enhance tumor localization. Keywords: cell membrane, drug delivery system, gastric cancer, low-dose irradiation, nanoparticles

BACKGROUND: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome. METHODS: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z-scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale. RESULTS: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10-5) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10-4). Except for inferior parietal lobule volume, these associations were largely mediated by increased severity of positive symptoms and reduced impulse control. CONCLUSIONS: This study provides evidence that the co-occurrence of positive symptoms, poor impulse control and aggressive behaviour in schizophrenia has a neurobiological basis, which may inform the development of therapeutic interventions.

DarkSide-50 at Gran Sasso underground laboratory (LNGS), Italy, is a direct dark matter search experiment based on a liquid argon TPC. DS-50 has completed its first dark matter run using atmospheric argon as target. The detector performances and the results of the first physics run are presented in this proceeding.

In state of the art photoinjector electron sources, thermal emittance from photoemission dominates the final injector emittance. Therefore, low thermal emittance cathode developments and diagnostics are very important. Conventional thermal emittance measurements for the high gradient gun are time-consuming and thus thermal emittance is not measured as frequently as quantum efficiency during the lifetime of photocathodes, although both are important properties for the photoinjector optimizations. In this paper, a single shot measurement of photoemission transverse momentum, i.e., thermal emittance per rms laser spot size, is proposed for photocathode rf guns. By tuning the gun solenoid focusing, the electrons' transverse momenta at the cathode are imaged to a downstream screen, which enables a single shot measurement of both the rms value and the detailed spectra of the photoelectrons' transverse momenta. Both simulations and proof of principle experiments are reported.