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Jiamin Yu,1 Yongxia Chen,1 Xiaoyan Pan,1 Ji Chen,1 Zhenhua Mai,1 Yuanli Zhang,1 Xiaoyan Wang,2– 4 Gaosheng Zhou,5 Sayed Adam Bukhari,6 Daqing Ma,6,7 Liehua Deng1 1Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, People’s Republic of China; 2Doctoral Scientific Research Center, Lianjiang People’s Hospital, Zhanjiang, 524400, People’s Republic of China; 3Affiliated Lianjiang People’s Hospital, Guangdong Medical University, Zhanjiang, 524400, People’s Republic of China; 4Laboratory of Southern Marine Science and Engineering, Zhanjiang, 524023, People’s Republic of China; 5Department of Critical Care Medicine, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People’s Hospital, Yichang, Hubei, 443003, People’s Republic of China; 6Division of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, SW10 9NH, UK; 7Perioperative and Systems Medicine Laboratory, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of ChinaCorrespondence: Liehua Deng, Email glinson@126.comPurpose: The early diagnosis of septic cardiomyopathy remains a challenge. The present work aims to evaluate the diagnostic and prognostic value of plasma soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in septic cardiomyopathy when compared with traditional myocardial biomarkers.Methods: In the 143 sepsis enrolled patients, 67 and 76 patients were classified as non-septic cardiomyopathy and septic cardiomyopathy, respectively. Their blood samples were harvested up to 14th day after hospital admission for measurements of sTREM-1 and other biomarkers, such as N-terminal pronatriuretic peptide (NT-proBNP), highly sensitive troponin (TNT-HS), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), etc. All the data were collected at 8:00 a.m. The area under the receiver operating characteristic curve was obtained to assess the diagnostic accuracy of those biomarkers. The Log rank test was utilized to evaluate the prognostic value of sTREM-1 on septic cardiomyopathy.Results: Circulating sTREM-1 showed a high specificity (88.1%) and moderate sensitivity (64.5%) to distinguish patients with septic cardiomyopathy in the 143 septic patients. The diagnostic efficiency of sTREM-1 was higher than inflammatory biomarkers and traditional myocardial markers. Logistic regression revealed that plasma sTREM-1 was an independent predictor of septic cardiomyopathy. Furthermore, in the whole septic cardiomyopathy cohorts, the sTREM-1 levels in the non-survivors were significantly higher than those of survivors during ICU stay. In addition, the left ventricular systolic dysfunction had a high odds ratio (3.968) to predict 90-day mortality in septic patients with cardiomyopathy.Conclusion: High plasma sTREM-1 level may be a diagnostic marker in predicting ICU poor outcome of patients with septic cardiomyopathy.Keywords: sepsis, septic cardiomyopathy, diagnosis, sTREM-1

Deying Xiao,1,2,* Long Xie,1,* Wenhong Lin,1 Jinhua Fu,1 Lin Deng,1 Qian Zhuang,2,3 Maobai Liu2,3 1Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 2The School of Pharmacy, Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 3Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Maobai Liu; Qian Zhuang, Department of Pharmacy, Fujian Medical University Union Hospital, No. 29, Xinquan Road, Antai Street, Gulou District, Fuzhou, 350001, People’s Republic of China, Tel +86-591-83357896, Email liumaobai10@163.com; ZhuangQ0591@163.comBackground: This evaluation aims to provide a reference for clinical decision-making regarding the use of SPN in intensive care unit (ICU) patients. The objective of this study is to evaluate the quality of clinical practice guidelines for the use of supplementary parenteral nutrition (SPN) in ICU patients, both domestically and internationally.Patients and Methods: The quality of clinical practice recommendations for SPN use in ICU patients was assessed using a systematic approach.Results: Five nutrition recommendations in total were included for analysis. The average standardized scores for the recommendations across the six domains of the Appraisal of Guidelines for Research and Evaluation II (AGREE II) are as follows: Scope and purpose scored 87.96%, stakeholder Involvement scored 68.52%, rigour of development scored 73.40%, clarity of presentation scored 84.80%, applicability scored 64.72%, and editorial independence scored 91.10%. In the comprehensive evaluation, two guidelines were rated as grade A recommendations, and three were rated as grade B recommendations. Most guidelines recommended against early use of SPN when energy and protein requirements could not be met solely through enteral nutrition (EN) in ICU patients. The guidelines emphasized achieving target energy levels and discontinuing parenteral nutrition (PN) as soon as the energy requirements were met to prevent overfeeding.Conclusion: This study utilized the AGREE II scale to assess the quality of five nutrition guidelines. All 5 guidelines were deemed acceptable Recommendations include focusing on participants, rigour, and applicability to enhance guideline quality. Clinicians should exercise professional judgment when applying guidelines as they complement training and judgment, rather than replacing them.Keywords: ICU, patients, supplementary parenteral nutrition, clinical practice guidelines, guideline evaluation

Juan Li,1,* Ting Zhou,1,* Pei Wang,1,* Ruian Yin,1 Shengqi Zhang,1 Yile Cao,1 Lijuan Zong,1 Ming Xiao,2 Yongjie Zhang,3 Wentao Liu,4 Lingxiao Deng,5 Fei Huang,6 Jianfei Sun,7,* Hongxing Wang1,* 1Department of Rehabilitation Medicine, Zhongda Hospital Southeast University, Nanjing, 210024, People’s Republic of China; 2Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 3Department of Human Anatomy, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 4Department of Pharmacology, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 5Department of Neurological Surgery, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indianapolis, IN, 46202-2266, USA; 6Institute of Neurobiology, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 7State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianfei Sun, State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China, Email sunzaghi@seu.edu.cn Hongxing Wang, Department of Rehabilitation Medicine, Southeast University Zhongda Hospital, Nanjing, 210024, People’s Republic of China, Email 101012648@seu.edu.cnBackground: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms.Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs’ projections and evaluate neurotransmitters’ expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn.Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters’ expression in anterior horn of lumbar spinal cord.Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters’ expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit. Keywords: gigantocellular reticular nucleus, locomotion, magnetic stimulation, spinal cord injury, superparamagnetic iron oxide nanoparticles, treadmill training

Haisong Hou,1,2 Liu Liang,3 Lihong Deng,4 Wanping Ye,5 Yuanzhang Wen,6 Jun Liu1 1Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang, People’s Republic of China; 2Department of Blood Transfusion, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 4Department of Hepatology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 5Department of Gastroenterology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 6Department of Hepatobiliary Surgery, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Jun Liu, Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang, People’s Republic of China, Email liujungd6@163.comBackground: The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk factors associated with HBV-associated HCC, and to provide some references to the diagnosis and treatment of HCC.Methods: This study retrospectively enrolled 730 patients, including 390 patients with chronic hepatitis B (CHB) as controls, and 340 patients with CHB complicated with HCC as patients. Relevant information and medical records of these participants were collected, including age, sex, cigarette smoking, alcoholism, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), cirrhosis, occupation, ascites, HBV-DNA load, the qualitative analysis of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb serological markers, and levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), TNM stage, tumor size and tumor number. The T test, Chi-square test, non-parametric rank-sum test, logistic regression analyses were used to explore the influencing factors and their degree of association with HCC in patients with HBV.Results: The proportion of smoking, alcoholism, married status, DM, hypertension, and the rate of HBV-DNA with a viral load of ≥ 500 copies/mL were significantly higher in the HCC group than in the controls (all p< 0.05). Cirrhosis was more common among patients with CHB+HCC than in controls (p=0.013). The proportion of patients with HBsAg, HBeAb, and HBcAb positive was greater in CHB+HCC group than that in CHB group. Logistic regression analysis indicated that age ≥ 60 years (OR: 1.835, 95% CI: 1.020– 3.302, p=0.043), HBeAb positive (OR: 9.105, 95% CI: 4.796– 17.288, p< 0.001), antiviral treatment with entecavir (OR: 2.209, 95% CI: 1.106– 4.409, p=0.025), and GGT (OR: 1.004, 95% CI: 1.001– 1.007, p=0.002) were risk factors for HCC in patients with CHB.Conclusion: Advanced age, HBeAb positive, antiviral treatment with entecavir, and GGT were independent risk factors for HCC in HBV patients.Keywords: chronic hepatitis B, hepatocellular carcinoma, cirrhosis, hepatitis B virus

Yan Chen,&ast; Xiaohuan Huang,&ast; Hongfei Chen, Junru Tong, Lingling Huang, Junyou Su, Li Deng Department of Obstetrics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Deng; Junyou Su, Email dengli@gxmu.edu.cn; sujunyou@sr.gxmu.edu.cnBackground: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by excessive activation of NK cells and cytotoxic T lymphocytes, subsequently leading to macrophage activation and increased cytokine production. Misdiagnosis due to nonspecific clinical presentations and inadequate understanding of the disease can significantly jeopardize the safety of both the mother and the infant. We report a case of pregnancy combined with HLH and conduct a literature review to provide insights into the diagnosis and treatment of pregnancy-related HLH.Case Presentation: We discussed a case of a pregnant woman with persistent postpartum fever, serum ferritin, and elevated liver function, who failed to respond to repeated anti-infective therapy and was diagnosed with HLH after multidisciplinary diagnostic treatment. We gave dexamethasone treatment, and the patient’s temperature and blood cells quickly returned to normal. Finally, exome sequencing revealed heterozygous variation in UNC13D gene, so we considered this case as pregnancy combined with primary HLH (pHLH).Conclusion: We report the case of HLH diagnosed during pregnancy and show that early diagnosis and timely intervention can prevent rapid disease progression, reduce maternal mortality rates, and improve survival rates. Additionally, molecular genetic testing can confirm pathogenic gene mutations, providing essential genetic counseling for patients with pHLH who plan to conceive a healthy child.Keywords: hemophagocytic lymphohistiocytosis, hemophagocytic syndrome, pregnancy, case report

Liang Deng, Xiaojun Liu, Wei Liu Departmental of Pediatric Intensive Care Unit, The First Affiliated Hospital of Shaoyang University, Shaoyang city, Hunan Province, 422000, People’s Republic of ChinaCorrespondence: Liang Deng, Department of Pediatric intensive care unit, The First Affiliated Hospital of Shaoyang University, 39 Tongheng Street, Shuangqing District, Shaoyang city, Hunan Province, People’s Republic of China, Email Syliangdd28@126.comObjective: To explore the application of serum cardiac troponin T (cTnT), brain natriuretic peptide (BNP) levels, and electrocardiogram changes in the treatment and prognosis evaluation of severe pneumonia in children.Methods: 120 children with severe pneumonia (severe group) admitted to our hospital from June 2020 to December 2022 were selected as the study subjects with prospective study. They were divided into survival group (n=78) and death group (n=42) based on their survival status; 120 children with mild pneumonia were selected as the control group. Compare the levels of serum cTnT and BNP, as well as the changes in electrocardiogram, to analyze their predictive value for the prognosis of pediatric patients and the influencing factors of prognosis.Results: The proportion of children with cTnT, BNP, and abnormal electrocardiogram after treatment was lower than before treatment (P< 0.05). The proportion of children with cTnT, BNP, and abnormal electrocardiogram in the severe group was higher than that in the mild group (P< 0.05). The proportion of children with serum cTnT, BNP levels, and abnormal electrocardiogram in the death group after treatment was higher than that in the survival group (P< 0.05). Bundle branch block, low or inverted T waves, cTnT, and BNP are prognostic factors for children with severe pneumonia (P< 0.05). The combined prediction of serum cTnT and BNP for the prognosis of severe pneumonia in children is better than that of single prediction (Z combined detection - cTnT=2.474, Z combined detection - BNP=2.494, P=0.013, 0.013).Conclusion: The proportion of abnormal cTnT, BNP, and electrocardiogram is increased in patients with severe pneumonia, and those with high expression and abnormalities have poor prognosis. cTnT and BNP have high predictive value for the prognosis of children with severe pneumonia.Keywords: cardiac troponin T, brain natriuretic peptide, severe pneumonia, changes in electrocardiogram, prognosis

Liwei Deng,1,2 Yanyuan Sun,2 Haiqing Wang,3 Changli Liao,2 Deshan Li,2 Guohui Xu,2,&ast; Xuegang Yang2,&ast; 1School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Interventional Therapy, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Chengdu, People’s Republic of China; 3Department of Hepato-Biliary-Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohui Xu; Xuegang Yang, Department of Interventional Therapy, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, 55 Renmin South Road 4th Section, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-13708010123, Fax +86-02885420195, Email xgh0913@hotmail.com; yanggangxue@163.comPurpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus donafenib with immune checkpoint inhibitors (ICIs) (T+D+I) versus TACE plus donafenib (T+D) as the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC).Methods: This retrospective study included patients with unresectable HCC who received T+D+I or T+D between June 2021 and February 2023. The tumor response was analyzed according to the modified Response Evaluation Criteria in Solid Tumors. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) in the two groups were compared before and after propensity score matching (PSM). Cox’s proportional-hazards regression model was used to analyze factors affecting PFS and OS.Results: This study included 69 patients: 41 patients in the T+D group and 28 patients in the T+D+I group. After PSM, 26 patients in each group were analyzed. Patients in the T+D+I group had a higher DCR (96.2% vs 73.1%, P = 0.021), longer median PFS (13.1 vs 7.2 months, P = 0.017), and longer median OS (23.1 vs 14.7 months, P = 0.021) than those in the T+D group. The ORR in the two groups was similar (53.8% vs 50.0%, P = 0.781). Multivariate analyses revealed that T+D+I treatment and total bilirubin levels of < 20 μmol/L were independent prognostic factors for long PFS. T+D+I treatment, Child–Pugh class A, and single-lobe tumor distribution were independent prognostic factors for long OS. The incidence of TRAEs in the two groups was similar (P > 0.05).Conclusion: In comparison with TACE plus donafenib, TACE plus donafenib with ICIs could significantly improve DCR, PFS, and OS as a potential first-line treatment for unresectable HCC with an acceptable safety profile.Keywords: unresectable hepatocellular carcinoma, transarterial chemoembolization, donafenib, immune checkpoint inhibitor, combined therapy

Jie Wang,1,&ast; Lei Deng,2,&ast; Zihao Ding,3,&ast; Yaosheng Zhang,3 Yao Zhang,1 Kangpeng Li,1 Changsong Zhao,1 Qiang Zhang1 1Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Department of First School of Clinical Medicine, Henan University of Chinese Medicine, Henan, 450003, People’s Republic of China; 3Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Zhang, Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Email zhangqianggk@sina.comObjective: The clinical efficacy of perioperative chemotherapy regimen (rifampicin, doxycycline, levofloxacin, ceftriaxone) was evaluated for lumbar brucellosis spondylitis patients with neurological injury.Methods: In Beijing Ditan Hospital affiliated with Capital Medical University, 32 patients with lumbar brucellosis spondylitis underwent surgery and triple perioperative chemotherapy (rifampicin, doxycycline, levofloxacin) between 2011 and 2021 due to neurological injury, and 34 patients matched up with the triple group underwent rifampicin, doxycycline, levofloxacin, and ceftriaxone. Both groups were compared in terms of changes in inflammation index, low back/leg pain, lumbar function, neurological function, and adverse drug reactions.Results: There was no significant difference in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), low back pain visual analogue scale (VAS), leg pain VAS, lumbar Oswestry disability index (ODI) and nerve function injury rate between the two groups before chemotherapy (P> 0.05). The ESR, CRP at 1 week and 2 weeks after chemotherapy and 1 week, 2 weeks, 1 month postoperatively in the quadruple group were significantly lower than those in the triple group, which is the same to ESR 3 months postoperatively (P< 0.05). The low back pain VAS, leg pain VAS and lumbar ODI in the quadruple group were significantly lower than those in the triple group at 1 month and 3 months postoperatively (P< 0.05). The recovery rate of neurological function in the quadruple group was significantly higher than that in the triple group at 3 and 6 months postoperatively (P< 0.05). Both groups did not experience significantly different perioperative and postoperative adverse reactions (P> 0.05).Conclusion: For lumbar brucellosis spondylitis with neurological injury, quadruple perioperative chemotherapy of rifampicin, doxycycline, levofloxacin and ceftriaxone can significantly reduce perioperative inflammation, and improve low back/leg pain, as well as promoting neurological function recovery in the short term.Keywords: lumbar brucellosis spondylitis, neurological injury, perioperative chemotherapy, efficacy

Chunqing Wang, Xiaoyao Jiang, Di Wu, Mengjun Ge, Li Deng Department of General Practice, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of ChinaCorrespondence: Chunqing Wang, Department of General Practice, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Email yamail@126.comObjective: Discussing the relationship between geriatric nutritional risk index (GNRI) and platelet-to-lymphocyte ratio (PLR) on stroke-associated pneumonia (SAP) in acute ischemic stroke (AIS) patients, developing and validating a web-based dynamic nomogram.Methods: A total of 996 AIS patients admitted to the Department of General Medicine and Neurology at Xuzhou Medical University Affiliated Hospital were collected. They were divided into Non-SAP group and SAP group based on the occurrence of SAP. The data was randomly divided into training set and validation set in a ratio of 7:3. LASSO regression and multivariable logistic regression analysis were used to screen for independent risk factors and develop a dynamic nomogram. Area under the receiver operating characteristic curve (AUC-ROC), calibration curve, and decision curve analysis (DCA) curve were used to validate the model’s discriminative ability, calibration, and clinical value, respectively.Results: Among AIS patients, a total of 221 cases (22.19%) developed SAP. Age, NIHSS score, comorbid atrial fibrillation, dysphagia, PLR, and GNRI were identified as independent factors influencing the occurrence of SAP in AIS patients. A web-based dynamic nomogram was developed based on these six variables. The training set showed an AUC-ROC of 0.864 (95% CI: 0.828– 0.892), while the validation set showed an AUC-ROC of 0.825 (95% CI: 0.772– 0.882), indicating good predictive ability and discrimination of the model. The calibration curve demonstrated good calibration of the model, and the DCA curve showed its clinical value. This model can be accessed and utilized by anyone on the website (https://moonlittledoctor.shinyapps.io/ANADPG/).Conclusion: PLR and GNRI are independent factors influencing the occurrence of SAP in AIS patients, and a dynamic nomogram was constructed to predict the risk of SAP in AIS patients. It can guide clinical decision-making and improve patient prognosis.Keywords: GNRI, PLR, dynamic nomogram, acute ischemic stroke, stroke-associated pneumonia

Xiuxian Huang,1,&ast; Licai Deng,1,&ast; Jianhao Huang,1,&ast; Jingxia Sun,1 Qiu Wang,1 Jiacheng Mo,2 Zhenwei Zhai,1 Yuechou Nong,1 Wensheng Lu1,&ast; 1Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 2Information Network Center of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Email Lws2613676@sohu.comAim: To clarify the relationship between serum uric acid (UA) and glycosylated hemoglobin (UA/HbA1c) ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs).Methods: A total of 172 inpatients with DFUs (PEDIS grades 2– 4) were eligible for inclusion in this study from 2018 to 2023. This was a retrospective, longitudinal cohort study. All subjects were followed up every 6 months for a median of 60 months. According to the cutoff value of the UA/HbA1c ratio of 39.07 obtained from ROC analysis, the participants were divided into two groups: low-level (≤ 39.07, n = 107) and high-level (> 39.07, n = 65) groups. The correlation between UA/HbA1c ratio and all-cause mortality was also evaluated by Cox regression analysis TheKaplan-Meier survival curve analysis and Log rank tests were used to assess the incidence rates of all-cause mortality. The contribution rate of risk factors was estimated by the population-attributable risk percentage (PAR%) analysis.Results: ROC analysis showed that the optimal cutoff values for UA and the UA/HbA1c ratio were 372 μmol/L and 39.07, respectively. Multivariate Cox regression analysis indicated that a high UA/HbA1c ratio (HR =4.63; 95% CI = 2.004– 10.7, P < 0.001) was independently associated with a high risk of all-cause mortality in patients with DFUs. Stratified analysis indicated that subjects aged ≥ 60 years had a greater risk of all-cause mortality associated with a high UA/HbA1c ratio (HR = 4.450; 95% CI = 1.711– 11.574, P = 0.002). Kaplan-Meier survival analysis showed that all-cause mortality had a significant positive association with a high UA/HbA1c ratio (log-rank, P < 0.001) and a significant negative correlation with the lowered HbA1c level (< 6.5%) after a follow-up of 32 months (log-rank, P < 0.001). The population attributable risk percentage (PAR%) analysis suggested that the contribution rate of the high-level UA/HbA1c ratio to all-cause mortality was 33.7%, which was much greater than the 19.69% of UA.Conclusion: In brief, our study showed that for every 1.0% increase in the UA/HbA1c ratio, the all-cause mortality rate in elderly patients with DFUs aged ≥ 60 years increased by 3.45-fold. For elderly patients with DFUs, a safe and effective strategy to reduce all-cause mortality is to strictly control serum UA levels to < 372 μmol/L and appropriately loosen the control goal of HbA1c to ≥ 6.5%.Keywords: diabetic foot ulcer, uric acid to glycosylated hemoglobin ratio, all-cause mortality

Limin Deng,1 Huiming Jiang2 1Department of Urology, Meizhou Academy of Medical Sciences, Meizhou People’s Hospital, Guangdong Medical University, Meizhou, Guangdong Province, People’s Republic of China; 2Department of Urology, Meizhou Academy of Medical Sciences, Meizhou People’s Hospital, Meizhou, Guangdong Province, People’s Republic of ChinaCorrespondence: Huiming Jiang, Department of Urology, Meizhou Academy of Medical Sciences, Meizhou People’s Hospital, No. 63, Huang Tang Road, Meizhou, Guangdong Province, 514031, People’s Republic of China, Tel +86-13560990839, Email jianghm0228@163.comBackground: GLYATL1 is a member of the glycine-N-acyltransferase family, which catalyses acyl group transfer. The role of GLYATL1 in cancer is largely unknown; therefore, the potential value of GLYATL1 in clear cell renal cell carcinoma (ccRCC) was explored.Methods: The ccRCC gene expression profiles and clinical data were obtained from the University of California Santa Cruz Xena platform. Differential expression and survival analysis were performed using R software. Samples from the TIMER public database and real-world were used for validation. The potential molecular mechanism of GLYATL1 in ccRCC was explored using gene set enrichment analysis (GSEA).Results: GLYATL1 was downregulated, indicating a poor prognosis in ccRCC. Low expression of GLYATL1 was significantly associated with advanced stage and higher histological grade ccRCC. The differential expression of GLYATL1 was validated at the protein level using clinical samples and tissue microarray. The results of GSEA showed that multiple crucial signalling pathways including fatty acid metabolism, adipogenesis, oxidative phosphorylation and epithelial–mesenchymal transition were enriched.Conclusion: This study demonstrated that GLYATL1 downregulation has an unfavourable impact on the survival of patients with ccRCC. The resulting data indicated that GLYATL1 could be a potential new target for ccRCC therapy, which may be helpful for the personalized treatment of such individuals.Keywords: clear cell renal cell carcinoma, glycine-N-acyltransferase-like 1, GLYATL1, prognosis, biomarker

Yuanli Li,1,&ast; Xiaoyi He,2,&ast; Ling Deng,2 Hai Chen,1 Xi Chen,1 Xuhu Mao,2 Yang Xiang2 1Department of Clinical Laboratory, Sanya People’s Hospital, Sanya, Hainan, People’s Republic of China; 2Department of Clinical Microbiology and Immunology, College of Pharmacy and Laboratory Medicine Science, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Xiang, Email xiangyang@tmmu.edu.cnAbstract: Burkholderia pseudomallei, the causative agent of melioidosis can be responsible for a wide spectrum of clinical manifestations and heterogeneous prognoses, with a high mortality in the acute onset. We report a case of a deep abdominal abscess with sepsis secondary to melioidosis in a young farmer from a non-high-risk population. Emergency medical treatment was administered according to the detection of serum antibodies against Hcp1, the results of which provided etiological evidence of B. pseudomallei infection for the timely and properly antimicrobial therapy in the absence of direct evidence of melioidosis. To our knowledge, this is the first reported case of serodiagnosis of acute exacerbation of melioidosis in China.Keywords: melioidosis abscess, serodiagnosis, Burkholderia pseudomallei, antibody detection, Hcp-1

You Zhou,&ast; Lixiang Deng,&ast; Zhe Wang,&ast; Yiqing Hu, Zhangwei Chen, Hao Lu, Juying Qian, Junbo Ge Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Lu, Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-64041990, Email lu.hao@zs-hospital.sh.cn Juying Qian, Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, 1609 Xietu Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-64041990 ext 2728, Email qian.juying@zs-hospital.sh.cnBackground: The tip-in technique, which involves advancing an antegrade microcatheter cross the lesion over a retrograde guidewire, is an elaborated maneuver in the recanalization of coronary chronic total occlusion (CTO). We seek to assess the efficiency of a guide extension catheter-facilitated tip-in technique in comparison to the traditional retrograde approach, which is accomplished by an externalization wire.Methods: Thirty-three CTO patients successfully revascularized using guide extension catheter-facilitated “tip-in” were included and matched with another 33 patients by J-CTO score and operators, whose CTO was recanalized using an externalized wire. The manipulation time from the first retrograde wire entering the antegrade guide to the first antegrade balloon inflation in the occlusion was calculated.Results: Compared with the wire-externalization group, the manipulation time in the tip-in group was significantly shortened [389s; interquartile range (IQR), 272– 478 vs 706s; IQR, 560– 914; p < 0.001]. There was a trend in decreasing total operation time and radiation dose, but it did not reach statistical significance.Conclusion: Guide extension catheter-facilitated tip-in is an efficient method to achieve the recanalization of CTO in a retrograde way, which would be pivotal when the retrograde microcatheter could not be advanced into the antegrade guide catheter.Keywords: chronic total occlusion, extension guide catheter, tip-in, retrograde

Yan Zhou,1,2,&ast; Zekun Zhou,3,&ast; Xiaojuan Wu,2 Zefeng Wang,2 Wangdan Qi,1 Jing Yang,1 Liming Qing,3 Juyu Tang,3 Le Deng1 1State Key Laboratory of Developmental Biology of Freshwater Fish, Department of Microbiology, College of Life Science, Hunan Normal University, Changsha, Hunan, People’s Republic of China; 2State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecule Engineering of Hunan Province, Changsha, Hunan, People’s Republic of China; 3Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Le Deng, State Key Laboratory of Developmental Biology of Freshwater Fish, Department of Microbiology, College of Life Science, Hunan Normal University, Changsha, Hunan, People’s Republic of China, Email dengle@hunnu.edu.cn Juyu Tang, Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Email tangjuyu@csu.edu.cnPurpose: We aimed to develop an oxidative-stress-activated palladium-copper nanozyme to reduce bacterial’s heat sensitivity by down-regulating heat shock proteins to overcome the shortcomings of conventional photothermal antimicrobial therapy and achieve mild photothermal bactericidal efficacy.Methods: We first synthesized palladium-copper nanozymes (PC-NPs) by hydration and used transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy to demonstrate their successful preparation. Their photothermal therapy (PTT) and chemo-dynamic therapy (CDT) activities were then determined by a series of photothermal performance tests and peroxidase-like performance tests, and the destruction of heat shock proteins by reactive oxygen species (ROS) was verified at the protein level by Western Blotting tests, providing a basis for the effective bacteria-killing by the mild-temperature photothermal treatment subsequently applied. We also validated this promising programmed and controlled antimicrobial treatment with palladium-copper nanozymes by in vivo/in vitro antimicrobial assays. A hemolysis assay, MTT cytotoxicity test and histopathological analysis were also performed to assess the in vivo safety of PC-NPs.Results: In the micro-acidic environment of bacterial infection, PC-NPs showed peroxidase-like activity that broke down the H2O2 at the wound into hydroxyl radicals and down-regulated bacterial heat shock proteins. The application of PC-NPs increased bacteria’s sensitivity to subsequent photothermal treatment, enabling the elimination of bacteria via mild photothermal treatment.Conclusion: The programmed synergistic catalytic enhancement of CDT and mild photothermal therapy achieves the most efficient killing of bacteria and their biofilms, which brings future thinking in the relationship between heat shock proteins and oxidative stress damage in bacteria.Keywords: nanozyme, mild-temperature photothermal therapy, DnaK, reactive oxygen species, ROS, antibiofilm

Jinjie Yu,1,2,* Mengwen Liu,3,* Xiaokaiti Mijiti,4,* Haican Liu,2,* Quan Wang,4 Chunjie Yin,3 Aiketaguli Anwaierjiang,5 Miao Xu,4 Machao Li,2 Lele Deng,2,6 Hui Xiao,3 Xiuqin Zhao,2 Kanglin Wan,2 Guilian Li,2 Xiuqin Yuan1 1School of Public Health, University of South China, Hengyang, 421001, People’s Republic of China; 2State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 3School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 4The Eighth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830049, People’s Republic of China; 5College of Xinjiang Uyghur Medicine, Hetian, 848000, People’s Republic of China; 6National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guilian Li, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China, Email liguilian@icdc.cn Xiuqin Yuan, School of Public Health, University of South China, Hengyang, 421001, People’s Republic of China, Email wtjysh@126.comBackground: The aim of the present study was to investigate the association between vitamin D receptor (VDR) gene polymorphism and tuberculosis susceptibility, as well as the potential interaction of host genetic factors with the heterogeneity of Mycobacterium tuberculosis in the population from Xinjiang, China.Methods: From January 2019 to January 2020, we enrolled 221 tuberculosis patients as the case group and 363 staff with no clinical symptoms as the control group from four designated tuberculosis hospitals in southern Xinjiang, China. The polymorphisms of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in the VDR were detected by sequencing. M. tuberculosis isolates were collected from the case group and identified as Beijing or non-Beijing lineage by multiplex PCR. Propensity score (PS), univariate analysis and multivariable logistic regression models were used to perform the analysis.Results: Our results showed that the allele and genotype frequencies of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in VDR were not correlated with tuberculosis susceptibility or lineages of M. tuberculosis. Two out of six loci of the VDR gene formed one haplotype block, and none of the haplotypes was found to correlate with tuberculosis susceptibility or lineages of M. tuberculosis infected.Conclusion: Polymorphisms in the VDR gene may not indicate susceptibility to tuberculosis. There was also no evidence on the interaction between the VDR gene of host and the lineages of M. tuberculosis in the population from Xinjiang, China. Further studies are nonetheless required to prove our conclusions.Keywords: vitamin D receptor, VDR, polymorphism, tuberculosis, Mycobacterium tuberculosis, Beijing lineage

Yuandi Wang,1,2,&ast; Lijuan Xing,2,&ast; Lexiu Deng,1,2 Xinsheng Wang,2 Dandan Xu,2 Bu Wang,2 Zhihua Zhang2,&ast; 1Graduate School, Hebei North University, Zhangjiakou City, Hebei Province, People’s Republic of China; 2Department of Respiratory and Critical Care Clinical Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihua Zhang, Department of Respiratory and Critical Care Clinical Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei Province, People’s Republic of China, Tel +86 0313 8033598, Email zzh19641229@163.comPurpose: The efficacy of immunotherapy for non-small cell lung cancer (NSCLC) is limited owing to cold tumors and drug resistance. Therefore, it is important to identify the molecular mechanisms underlying immune evasion in NSCLC. Spontaneous ferroptosis of neutrophils has been suggested as a key mechanism of immunosuppression in cancer. Insulin-like growth factor binding protein 1 (IGFBP1) plays an important role in immune infiltration in several cancers. However, the role of IGFBP1 in NSCLC is unknown. Therefore, in this study, we aimed to investigate the association of IGFBP1 mRNA expression with infiltration of myeloid-derived suppressor cells and prognosis in NSCLC.Patients and Methods: Retrospective RNA-seq data from 990 patients in the Cancer Genome Atlas (TCGA) database were analyzed in relation to patient clinical characteristics. The Timer2 database was used to assess immune infiltration, and the FerrDb V2 database was used to obtain ferroptosis-related genes. Finally, the results were validated by the proteomic analysis of serum samples collected from six patients with NSCLC and six healthy individuals.Results: IGFBP1 expression was enriched in lung adenocarcinoma samples and positively correlated with the pathological grade of NSCLC. IGFBP1 expression was an independent prognostic factor for the overall survival of patients with NSCLC. In addition, IGFBP1 expression correlated with myeloid-derived suppressor cell infiltration. Notably, Gene Ontology analysis of IGFBP1-related genes revealed that the major molecular functions of their protein products were related to NADP+ 1-oxidoreductase activity. Furthermore, expression levels of multiple ferroptosis suppressor genes positively correlated with IGFBP1 expression.Conclusion: High IGFBP1 expression indicates a poor prognosis in patients with NSCLC, which may be related to tumor immunosuppression caused by neutrophil ferroptosis.Keywords: immune infiltration, immunotherapy, lung adenocarcinoma, lung squamous cell carcinoma, myeloid-derived suppressor cells

Lin Deng,1 Beilei He,2 Kamran Ali,1,3 Zhangyu Bu1 1Department of Dermatology Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of the Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Dermatology, International Education College of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of ChinaCorrespondence: Zhangyu Bu, Department of Dermatology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, No. 261, Huansha Road, Hangzhou, People’s Republic of China, Tel +8657156006617, Email buzyhz@163.comAbstract: Acute generalized exanthematous pustulosis (AGEP) is generally caused by drugs and is characterized by the rapid development of numerous non-follicular sterile pustules on an erythematous base, fever, and neutrophilia. We report an association between terbinafine, with AGEP, and adalimumab treatment. A 24-year-old teenage female patient with a history of onychomycosis was treated with terbinafine. On the second day of the first dose, multiple edematous and erythematous lesions appear with pinhead pustules. Neutrophilia was observed in the blood report. The clinical history, lesions, and laboratory evaluations were consistent with AGEP. We discontinued the terbinafine therapy, and the systemic corticosteroid was initiated; however, the patient’s condition worsened. Adalimumab subcutaneously was initiated, and the symptoms cleared up in weeks. The European Study of Severe Cutaneous Adverse Reactions (EuroSCAR) scoring system and Naranjo’s algorithm scale were used to check the possibility of a drug-induced adverse reaction. The Association of AGEP with the terbinafine drug is not rare. However, there are no reports or literature of drug-related rash or exanthematous eruptions unresponsive to corticosteroids and treated with adalimumab.Keywords: acute generalized exanthematous pustulosis, AGEP, adalimumab, terbinafine, drug-induced adverse reaction, Naranjo’s algorithm scale, EuroSCAR

Lin Deng,1,&ast; Yingzhi Luo,1,&ast; Binyi An,2 Ming Su,1 Hong Sang,3 Fang Liu3 1Department of Dermatology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 2Department of Dermatology, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, People’s Republic of China; 3Department of Dermatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Liu; Hong Sang, Department of Dermatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, People’s Republic of China, Tel +86-25-80860092, Fax +86-25-84815775, Email liufangndyx@163.com; sanghong@nju.edu.cnBackground: Palmar-plantar atopic dermatitis is a common and debilitating condition with significant diagnostic and management challenges.Case Presentation: The paper presents the successful treatment of dupilumab in five female patients with recalcitrant palmar-plantar atopic dermatitis.Methods: The Hand Eczema Severity Index (HECSI) and the Foot Eczema Severity Index (FECSI), eosinophils and IgE levels were evaluated before and after the treatment.Results: Five recalcitrant palmar-plantar atopic dermatitis patients had substantial responses to dupilumab and the persistent pruritus was soon alleviated during the therapy. By week 16, all patients’ palmar-plantar eczema has been almost clear, with significant decrease of HECSI and FECSI. The count of eosinophils and IgE levels returned to normal in all patients.Conclusion: Dupilumab significantly improves disease severity and reduces eosinophils and IgE in refractory palmar-plantar AD patients.Keywords: atopic dermatitis, dupilumab, palmar-plantar

Dongmei Deng,1,&ast; Mu Niu,1,&ast; Jie Yang,1 Lijun Deng2 1Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, People’s Republic of China; 2Department of Dermatovenereology, Wuzhong People’s Hospital, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Yang, Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, People’s Republic of China, Email 13337564169@163.com Lijun Deng, Department of Dermatovenereology, Wuzhong People’s Hospital, Suzhou, 215128, People’s Republic of China, Email 474974283@qq.comAbstract: As scrotal simple lymphangioma is a rare benign proliferation of lymphatic vessels in the scrotum, a few reports were documented. A 68-year-old man gradually developed vesicles on the scrotum for ten years and easily ruptured due to friction. Physical examination showed diffuse millet-sized vesicles on the scrotum with milky white fluids and chyle-like exudates. Histopathological examination revealed proliferating and dilated lymphatic vessels with various sizes of lumens in the dermis. An immunohistochemical study showed positive staining for D2-40 and CD31. Therefore, the patient was diagnosed with scrotal lymphangioma and received carbon dioxide laser therapy. After the treatment, the vesicles markedly decreased, and no apparent exudates were observed. During one year of the follow-up, no relapse, scars, or other complications occurred.Keywords: lymphangioma, scrotum, carbon dioxide laser

Zhi-Hui Wang,1 Lili Deng2 1Department of Medical Oncology, The Fifth People’s Hospital of Shenyang, Shenyang, People’s Republic of China; 2Department of Medical Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Lili Deng, Department of Medical Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email dengdoctor@126.comBackground: Surgical procedure is the preferred option for people with early-stage non-small cell lung cancer (NSCLC), while nearly 30% of patients experienced metastatic or recurrent tumor after operation. The primary intention of this context is to summarize high-risk prognostic factors and set up a novel nomogram to predict the overall survival of individuals with stage I NSCLC after resection.Methods: Research objects, 10,218 patients with stage I NSCLC after operation from 2010 to 2015, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Independent prognostic factors, confirmed by Cox regression analyses, were integrated into a nomogram, to predict the 3-and 5-year overall survival of these individuals. The model experienced internal validation of testing cohorts above and external validation crewed by 160 patients from China. Finally, the nomogram was evaluated through several verification methods such as concordance index (C-index), calibration plots and receiver operating characteristic curve (ROC).Results: Multivariate analysis identified that age, gender, histologic type, differentiation class, type of operation, T stage and treatment were significant predictive factors for the survival of stage I NSCLC. Based on these factors, a nomogram was constructed to predict the 3- and 5-year overall survival of these individuals. Meanwhile, in the training set, this nomogram displayed excellent superiority over the TNM staging system with abroad application, especially in C-index (0.669 vs 0.580) and the AUC (the Area Under ROC Curve) for the 3- and 5-year survival (0.678 vs 0.582; 0.650 vs 0.576). In the calibration curve, the curve representing predicted survival tended to align with the line representing actual survival as well.Conclusion: A nomogram was successfully created and verified to achieve the goal that made a rounded accurate prediction on the survival of postoperative I NSCLC patients in terms of the SEER database.Keywords: NSCLC, nomogram, prognosis, SEER, survival

Liuying Li,1 Lanying Yang,2 Biao Luo,2 Lvyu Deng,2 Yue Zhong,2 Daohui Gan,2 Xiaohan Wu,2 Peimin Feng,1 Fengya Zhu2 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Traditional Chinese Medicine Department, Zigong First People’s Hospital, Zigong, People’s Republic of ChinaCorrespondence: Peimin Feng; Fengya Zhu, Email fpmmed@cdutcm.edu.cn; notfounds@foxmail.comBackground: Post-stroke cognitive impairment (PSCI) is one of the most common complications after stroke. In recent years, as a complementary alternative therapy, many systematic reviews (SRs) and meta-analysis (MAs) have reported the efficacy and safety of acupuncture in improving cognitive function in patients with PSCI, but the quality of evidence is unknown and therefore needs to be evaluated comprehensively.Aim: We aimed to evaluate the SRs of acupuncture for patients with PSCI, to summarize the evidence quality of SRs to provide scientific evidence.Methods: We searched for relevant SRs and MAs in seven databases up to March 22, 2022. Two reviewers independently completed literature retrieval, screening, and data extraction. We used A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) to evaluate the methodological quality; the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to determine the strength of evidence; and the ROBIS tool to assess RoB.Results: We identified 14 SRs. The methodological quality of all SRs was low (2/14) or very low (12/14). GRADE results showed 13 were moderate quality (26%), 5 were low quality (10%), and 32 were very-low quality (64%). RoB showed that one SR had a low risk and 13 had a high risk. Moderate quality results showed that combined acupuncture therapy was superior to western medicine or cognitive rehabilitation training in improving cognitive function, the total response rate, and the daily living ability of patients with PSCI.Conclusion: Based on the evidence, acupuncture appears to be effective and safe in improving cognitive function for patients with PSCI, but the overall quality of SRs is not high. High-quality randomized controlled trials are needed to confirm the effectiveness and safety of acupuncture on the cognitive function of patients with PSCI.Systematic Review Registration: PROSPERO CRD42022315441.Keywords: acupuncture, PSCI, overview, AMSTAR-2, GRADE

Yanqiu He,1,&ast; Cheng Hu,1,&ast; Shiyu Liu,1 Mingjie Xu,1 Ge Liang,2 Dan Du,3 Tingting Liu,1 Fei Cai,1 Zhiyao Chen,1 Qingyuan Tan,1 Lihui Deng,1 Qing Xia1 1Pancreatitis Centre, Department and Laboratory of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Clinical Proteomics and Metabolomics, Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihui Deng, Pancreatitis Centre, Department and Laboratory of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, Email denglihui@scu.edu.cnBackground: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas without specific treatment. Shenmai injection (SMI) was reported to eliminate the severity of experimental AP. This study aimed to explore the mechanisms underlying the synergistic protective effects of SMI on AP based on network pharmacology and experimental validation.Methods: Network pharmacology analysis and molecular docking based on identified components were performed to construct the potential therapeutic targets and pathways. The principal components of SMI were detected via ultra-high-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Effect of SMI and the identified components on cellular injury and IL6/STAT3 signaling was assessed on mouse pancreatic acinar cell line 266– 6 cells. Finally, 4% sodium taurocholate (NaT) was used to induce AP model to assess the effects of SMI in treating AP and validate the potential molecular mechanisms.Results: By searching the TCMSP and ETCM databases, 119 candidate components of SMI were obtained. UHPLC-QTOF/MS analysis successfully determined the representative components of SMI: ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D. Fifteen hub targets and eight related pathways were obtained to establish the main pharmacology network. Subnetwork analysis and molecular docking indicated that the effects of these four main SMI components were mostly related to the interleukin (IL) 6/STAT3 pathway. In vitro, SMI, ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D increased the cell viability of NaT-stimulated mouse pancreatic acinar 266– 6 cells and decreased IL6 and STAT3 expression. In vivo, 10 mL/kg SMI significantly alleviated the pancreatic histopathological changes and the expression of IL6 and STAT3 in the AP mice.Conclusion: This study demonstrated SMI may exert anti-inflammatory effects against AP by suppressing IL6/STAT3 activation, thus providing a basis for its potential use in clinical practice and further study in treating AP.Keywords: acute pancreatitis, Shenmai injection, network pharmacology, molecular docking, IL6/STAT3 signaling pathway

Hao Liu, Quan Zhou, Xiaofeng Shao, Junxin Zhang, Lei Deng, Tao Liu, Huilin Yang Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of ChinaCorrespondence: Tao Liu; Huilin Yang, Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 899 Pinhai Road, Suzhou, 215006, People’s Republic of China, Email liutao821108@163.com; szyhlspine@163.comPurpose: To comparatively analyze the clinical and radiographic outcomes of percutaneous kyphoplasty (PKP) in patients with severe osteoporotic vertebral compression fracture (sOVCF) with or without intravertebral cleft (IVC).Methods: We enrolled a total of 75 patients with sOVCF receiving PKP between January 2016 and December 2018. The patients were divided into the following two groups based on their radiographic findings: with IVC (IVC group) and without IVC (NIVC group). The following radiographic outcomes were determined: anterior vertebral height (AVH), kyphotic angle (KA), lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI), and pelvic tilt (PT). The clinical functional assessment included Oswestry disability index (ODI) and visual analog scale (VAS) scores.Results: No significant difference was found between the demographic data of the two groups (P > 0.05). AVH, KA, and LL in both groups were significantly corrected one month after surgery (P < 0.05). There was statistical difference between the two groups in AVH and KA one year and three years after surgery, and in LL and PT three years after surgery (P < 0.05). Compared with the results one month after surgery, AVH, KA, and LL of the IVC group deteriorated significantly one year and three years after surgery, whereas AVH, KA, and LL of the NIVC group deteriorated significantly three years after surgery (P < 0.05). The VAS and ODI scores in both groups decreased significantly one month, one year, and three years after surgery than preoperative results (P < 0.05), and a statistical difference was observed between the two groups three years after surgery (P < 0.05).Conclusion: PKP can give satisfactory outcomes for the treatment of sOVCF with or without IVC. However, the NIVC group showed better clinical outcomes and could maintain spinal sagittal balance better than the IVC group during long-term follow-up.Keywords: kyphoplasty, severe osteoporotic vertebral compression fracture, intervertebral cleft, sagittal balance

Shanshan Hou,1,2 Xiaokang Wang,3 Fang Wang,4 Zhongliang Li,5 Hui Wang,6 Jiahui Li,7 Jing Wang,8 Haiying He,9 Liping Deng,10 Yushu Feng,11 Xiufang Fan,12 Wen Li,13 Qinghua Lu,14 Yanying Ma,15 Guoying Zhao,16 Simmy Reddy,17 Yanqiu Wu,2,&ast; Yonghui Yu1,3,&ast; 1Department of Neonatology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, People’s Republic of China; 2Department of Pediatric, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, People’s Republic of China; 3Department of Neonatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 4Department of Neonatology, Liaocheng People’s Hospital, Liaocheng, 252000, People’s Republic of China; 5Department of Neonatology, W.F. Maternal and Child Health Hospital, Weifang, 261011, People’s Republic of China; 6Department of Neonatology, Hebei PetroChina Central Hospital, Langfang, 065000, People’s Republic of China; 7Department of Neonatology, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, People’s Republic of China; 8Department of Neonatology, Women and Children’s Healthcare Hospital of Linyi, Linyi, 276000, People’s Republic of China; 9Department of Neonatology, Baogang Third Hospital of Hongci Group, Baotou, 014010, People’s Republic of China; 10Department of Neonatology, Heze Municipal Hospital, Heze, 274031, People’s Republic of China; 11Department of Neonatology, Linyi People’s Hospital, Linyi, 276000, People’s Republic of China; 12Department of Neonatology, Jinan Maternity and Child Health Care Hospital, Jinan, 250001, People’s Republic of China; 13Department of Neonatology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 14Department of Neonatology, Shandong Maternal and Child Health Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, People’s Republic of China; 15Department of Neonatology, Jinan Second Maternal and Child Health Care Hospital, Jinan, 271100, People’s Republic of China; 16Department of Neonatology, Binzhou Medical University Hospital, Binzhou, 256603, People’s Republic of China; 17Cheeloo College of Medicine, Shandong University, Jinan, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghui Yu, Department of Neonatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 234, Jingwu, Road, Huai Yin District, Jinan, Shandong, 250021, People’s Republic of China, Tel +86-0531-66953201, Email alice20402@126.com; yuyonghui6888@126.com Yanqiu Wu, Department of Pediatric, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuhuangding East Road, Zhi fu District, Yantai, 264000, People’s Republic of China, Tel +86-0535-6691999, Email yqwu76@126.comPurpose: Significant antibiotic overuse due to prolonged antibiotic duration has not draw enough attention in developing countries with high antibiotic consumption. We aimed to describe the current status of prolonged early antibiotic duration in very-low-birth-weight (VLBW) infants in a large regional multicenter cohort in China.Patients and Methods: Institution-based prospective cohort study was conducted in all VLBW infants admitted to 16 Grade A tertiary hospitals between January 1, 2019 and December 31, 2020. Early antibiotic use was defined as antibiotic initiation within the first 3 days of life. Prolonged early antibiotic course was defined as early antibiotic initiation for more than 7 days in infants with early-onset sepsis (EOS) or more than 3 days in infants with unlikely EOS. Antibiotic use was described as days of therapy (DOT) per 1000 patient days (PD).Results: Among 1684 eligible VLBW infants, 1544 (91.7%) infants were prescribed with prolonged early antibiotic course, including 618 infants with EOS and 926 infants with unlikely EOS. The median duration of early antibiotic course was 13 (IQR 8;20) days, with 78.0% of courses > 7 days and 43.6% of courses > 14 days. Total early antibiotic use was 408.3DOT/1000Pd, of which prolonged antibiotic courses accounted for 98.2% of all antibiotic use days. More than three antibiotics used, escalation antibiotic therapy, antibiotics for special use and the use of third generation cephalosporins and carbapenems were significantly common in prolonged courses compared to short courses in both infants with EOS and unlikely EOS group (P< 0.05).Conclusion: A large proportion of VLBW infants had excessively prolonged early antibiotic durations in the regional multicenter in China. Timely discontinuation of antibiotics in VLBW infants according to standardized guidelines and limit on the use of third-generation cephalosporins and carbapenems may be key drivers in reducing the antibiotic overuse in developing countries like ours.Keywords: very-low-birth-weight infants, early antibiotic use, prolonged antibiotic course, days of therapy

Louis Tong,1– 4 Lei Zhou,3– 5 Siew Kwan Koh,5 Yan Gao,5 Hla Myint Htoon,1,3 AiHua Hou,1,3 Lu Deng,6 Qi-Ping Wei,7 Pat Lim8 1Ocular Surface Research Group, Singapore Eye Research Institute, Singapore; 2Corneal and External Eye Disease Service, Singapore National Eye Centre, Singapore; 3Eye-Academic Clinical Program, Duke-National University of Singapore (NUS) Medical School, Singapore; 4Department of Ophthalmology, Yong Loo Lin School of Medicine, NUS, Singapore; 5Ocular Proteomics Platform, Singapore Eye Research Institute, Singapore; 6Department of Statistics and Applied Probability, Faculty of Science, NUS, Singapore; 7Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 8Singapore Chung Hwa Medical Institution, SingaporeCorrespondence: Louis TongSingapore National Eye Centre, 11, Third Hospital Avenue, 168751, SingaporeTel +65 9818 6221Fax +65 62252568Email Louis.tong.h.t@singhealth.com.sgLei ZhouSingapore Eye Research Institute, The Academia, 20 College Road, Level 6, 169856, SingaporeEmail zhou.lei@seri.com.sg

Shanping Wang,1 Jiandong Huang,1 Fei Liu,1 Keai Sinn Tan,2,3 Liangjun Deng,1 Yue Lin,1 Wen Tan3,4 1Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, People’s Republic of China; 2College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China; 3Post-Doctoral Innovation Site, Jinan University, Yuanzhi Health Technology Co, Ltd, Zhuhai, People’s Republic of China; 4Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, MalaysiaCorrespondence: Wen TanPost-Doctoral Innovation Site, Jinan University, Yuanzhi Health Technology Co, Ltd, Hengqin New District, Zhuhai, People’s Republic of ChinaTel/Fax +86 20-85827854Email uscnwt@163.comPurpose: Inflammatory bowel diseases (IBDs) are global health problems that are associated with immune regulation, but clinical IBDs treatment is currently inadequate. Effective preventive or therapeutic methods for immune disorders rely on controlling the function of immune cells. Isosteviol sodium (STV-Na) has antioxidant activity, but the therapeutic effect of STV-Na against IBD remain undocumented. Herein, we investigated the therapeutic effect of STV-Na in mice models with IBDs.Methods: Mice received 3.5% DSS for 7 days to establish IBD models. Intraperitoneal STV-Na was given 2 days before DSS and lasted for 9 days. Commercially available drugs used in treating IBDs (5-aminosalicylic acid, dexamethasone, and infliximab) were used as positive controls. Samples were collected 7 days after colitis induction. Histopathological score, biochemical parameters, molecular biology methods, and metabolomics were used for evaluating the therapeutic effect of STV-Na.Results: Our data revealed that STV-Na could significantly alleviate colon inflammation in mice with colitis. Specifically, STV-Na treatment improved body weight loss, increased colon length, decreased histology scores, and restored the hematological parameters of mice with colitis. The untargeted metabolomics analysis revealed that metabolic profiles were restored by STV-Na treatment. Furthermore, STV-Na therapy suppressed the number of CD68 macrophages and F4/80 cell infiltration. And STV-Na suppressed M1 and M2 macrophage numbers along with the mRNA expressions of proinflammatory cytokines. Moreover, STV-Na administration increased the number of regulatory T (Treg) cells while decreasing Th1/Th2/Th17 cell counts in the spleen. Additionally, STV-Na treatment restored intestinal barrier disruption in DSS-triggered colitis tissues by ameliorating the TJ proteins, increasing goblet cell proportions, and mucin protein production, and decreasing the permeability to FITC-dextran, which was accompanied by decreased plasma LPS and DAO contents.Conclusion: These results indicate that STV-Na can ameliorate colitis by modulating immune responses along with metabolic reprogramming, and could therefore be a promising therapeutic strategy for IBDs.Keywords: inflammatory bowel disease, isosteviol sodium, macrophage polarization, Th cells, barrier function, metabolomics

Yaqin Zhang, 1,* Ruofei Chen, 1,* Lili Deng, 2 Zongwen Shuai, 1 Mingwei Chen 2 1Department of Rheumatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zongwen Shuai; Mingwei Chen Email shuaizongwen@ahmu.edu.cn; chmw1@163.comObjective: To explore whether metformin (MET) can affect the biological behaviour and CD133 mRNA expression of CD133+ colon cancer stem cells (CCSCs) through miR-342-3p.Methods: The direct immunomagnetic bead method was used to select CD133+ CCSCs from the SW480 and HCT116 cell lines, and miRNA-tailing qRT-PCR was used to detect the expression changes of tumor suppressor-related miRNAs (miR-34a, miR-126, miR-143, miR-145, miR-342-3p, miR-342-5p) after MET intervention. Then, miR-342-3p with markedly significant differential expression was selected as the target miRNA. The lentiviruses LV16-hsa-miR-342-3p inhibitor and LV16-NC were used for the transfection inhibition test. CCK-8, flow cytometry, and qRT-PCR were used to detect the cell viability, apoptosis rate, and CD133 mRNA expression of CD133+ CCSCs.Results: Under the high-glucose environment, the expression of tumor suppressor-related miRNAs in CCSCs changed differently (p < 0.05), MET also had different effects on the expression of tumor suppressor-related miRNA under different glucose concentrations (p< 0.05). Among them, MET upregulates the expression of miR-342-3p in CCSCs for the first time. The results of the lentiviruses transfection inhibition test showed that after miR-342-3p was inhibited, the cell viability and apoptosis rate of CD133+ CCSCs did not change significantly compared with before inhibition (p> 0.05), but the expression of CD133 mRNA markedly increased (p< 0.05). Meanwhile, after MET intervention, the apoptosis rate and the expression of CD133 mRNA of CD133+ CCSCs was significantly increased, and the proliferation of CD133+ CCSCs was obviously inhibited (p< 0.05).Conclusion: MET upregulating the expression of miR-342-3p may not have a significant effect on the proliferation and apoptosis of CD133+ CCSCs, but it can reduce the expression of CD133 mRNA in CD133+ CCSCs.Keywords: metformin, colon cancer stem cells, tumor suppressor-related miRNAs, CD133

Cong Wei,1,&ast; Xiaoting Zhang,1,&ast; Dan Liang,1 Jilong Yang,1 Jingwen Du,1 Chunyan Yue,1 Lan Deng1,2 1Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 2Department of Hematology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan DengDepartment of Hematology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of ChinaTel +86 13724862939Email denglan_76@126.comChunyan YueDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of ChinaTel +86 15521117300Email doctor_yy@126.comBackground: Graft-versus-host disease (GVHD) is a main complication following allogeneic hematopoietic stem cell transplantation and is a leading cause of non-relapse-related death. Unsatisfactory response to standard first-line therapy with glucocorticoids is a predictor of a poor prognosis in patients with GVHD. Ruxolitinib is a selective Janus kinases 1/2 inhibitor which has been shown to control acute (a) and chronic (c) GVHD while maintaining graft-versus-tumor effects.Objective: This study aims to evaluate the efficacy and safety of ruxolitinib in the treatment of steroid-refractory GVHD (SR-GVHD) in a population of Chinese patients.Methods: We report the results of 55 patients, including 23 patients with aGVHD and 32 patients with cGVHD, who were treated with ruxolitinib as salvage therapy between August, 2017 and December, 2020.Results: In patients with aGVHD, the overall response rate (ORR) was 86.9%, and the 1-year overall survival (OS) was 82.6% (95% CI, 67.1– 98.1%). The 1-year OS was significantly improved in responders than in non-responders (90.0% vs 33.3%, P=0.004). In patients with cGVHD, the ORR was 78.1%, and the 1-year OS was 81.3% (95% CI, 67.8– 94.8%). There was no significant difference in the 1-year OS between responders and non-responders (84.0% vs 71.4%, P=0.327). Cytopenia, cytomegalovirus-reactivation and infections were common adverse events, particularly in patients with aGVHD.Conclusion: Our real-world data from Chinese patients further confirm that ruxolitinib is a safe and effective treatment for SR-GVHD.Keywords: ruxolitinib, allogeneic hematopoietic stem cell transplantation, graft-versus-host disease, steroid-refractory

Jinman Zhong,1,&ast; Jianke Ding,2,&ast; Lei Deng,1 Ying Xiang,1 Duoduo Liu,1 Yanyan Zhang,1 Xin Chen,1 Quanxin Yang1 1Department of Radiology, The Second Affiliated Hospital, Xi’ an Jiaotong University, Xi’an, Shaanxi Province, 710004, People’s Republic of China; 2Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Quanxin Yang; Xin ChenDepartment of Radiology, The Second Affiliated Hospital, Xi’ an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi Province, 710004, People’s Republic of ChinaEmail quanxin1962@163.com; chen_x129@163.comBackground: The sensitive and specific detection of pathogenic cells is important in tumor diagnosis at an early stage. Aptamers are short single-stranded oligonucleotides evolved from systematic evolution of ligands by exponential enrichment (SELEX). It has been proved that aptamers can interact with cognate target molecules with high affinity and specificity and have great potential in the development of medical imaging at molecular level.Purpose: To select epithelial cell adhesion molecule (EpCAM) specific aptamers targeting prostate cancer and further to conjugate aptamers with GoldMag nanoparticles (a typical iron oxide core/gold shell structure) to construct magnetic molecular probes for medical imaging.Methods: EpCAM-specific aptamers were selected by Cell-SELEX. The enrichment of specific aptamer candidates was monitored by flow cytometric analysis. Aptamers were further conjugated with GoldMag nanoparticles to construct magnetic molecular probes. The affinity and specificity of aptamer candidates and aptamer-conjugated GoldMag nanoparticles were evaluated. The MR imaging of aptamer-conjugated GoldMag nanoparticles to prostate cancer was further explored in vitro and in vivo.Results: After 12 rounds of selection, aptamer candidates Eppc6 and Eppc14 could specifically target three types of prostate cancer cells, revealing a high affinity of Eppc6 and Eppc14. Moreover, aptamer-conjugated GoldMag nanoparticles not only exhibited good affinity to different prostate cancer cells but also produced strong T2WI signal intensity reduction distinguished from peritumoral tissue in MRI, indicating that the molecular probes possess both the affinity properties of EpCAM-specific aptamer and the superparamagnetic features of iron oxide.Conclusion: Our study indicates that aptamer Eppc6 and Eppc14 can recognize prostate cancer cells and tissues. The aptamer-conjugated GoldMag nanoparticles constructed in the study can be used as a molecular imaging agent for detection of PCa in MRI.Keywords: EpCAM, aptamer, Cell-SELEX, prostate cancer

Shanshan Jia,1,* Pin Guo,2,* Junhua Lu,1 Xujun Huang,3 Laming Deng,4 Yan Jin,5 Lanyan Zhao,6 Xiaofang Fan7 1Department of Respiration, Hengdian Wenrong’s Hospital, Dongyang, People’s Republic of China; 2Lithotriptic Section, Dongyang Red Cross Hospital, Dongyang City, People’s Republic of China; 3Intensive Care Unit, Hengdian Wenrong’s Hospital, Dongyang, People’s Republic of China; 4Department of Emergency, Hengdian Wenrong’s Hospital, Dongyang, People’s Republic of China; 5Department of Nursing, Hengdian Wenrong’s Hospital, Dongyang, People’s Republic of China; 6Department of Respiration, Dongyang People’s Hospital, Dongyang City, People’s Republic of China; 7School of Basic Medicine, Wenzhou Medical University, Wenzhou City, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shanshan JiaDepartment of Respiration, Hengdian Wenrong’s Hospital, No. 99, Guest-Meeting Avenue, Hengdian Town, Dongyang, 322118, People’s Republic of ChinaEmail jiashsh_ssjias@163.comBackground: Curcumol exhibits anti-inflammatory effect, but its effect on chronic asthma lacked research. Therefore, this study explored the role of curcumol in asthma.Methods: A chronic asthmatic mice model was established by ovalbumin induction. After treatment with curcumol, airway resistance in mice was detected by forced oscillation technique. The histopathological features of airway tissues, pulmonary inflammation, and inflammation cell recruitment in the bronchoalveolar lavage fluid (BALF) of mice were detected by hematoxylin-eosin staining. Collagen deposition in the airways of mice was examined by Masson staining. The secretion of ovalbumin-IgE, IL-4, IL-5, IL-13 in mouse serum and VEGFA secretion in BALF were analyzed by ELISA. Finally, the expressions of β-catenin, Wnt5a, VEGFA, TGF-β 1, Fibronectin, and MMP-9 in mice lung tissues were determined by Western blot or immunohistochemical.Results: Curcumol attenuated airway hyperresponsiveness, airway remodeling, and pulmonary inflammation in chronic asthmatic mice. Curcumol relieved collagen deposition in airway tissues, inflammation cell recruitment in BALF, and reduced the up-regulation of serum ovalbumin-IgE, IL-4, IL-5, and IL-13 and BALF VEGFA in chronic asthmatic mice. In addition, curcumol attenuated the up-regulated expressions of β-catenin, Wnt5a, VEGFA, TGF-β 1, Fibronectin, and MMP-9 in the lung tissues of chronic asthmatic mice, but curcumol treatment did not show such effects on healthy mice.Conclusion: Our findings revealed that curcumol could ameliorate lung inflammation and airway remodeling by inhibiting the abnormal activation of the Wnt/β-catenin pathway in chronic asthmatic mice, indicating that curcumol could be used as a novel anti-asthma drug for basic and clinical research.Keywords: curcumol, chronic asthma, inflammation, airway remodeling, Wnt/β-catenin

Ping Li,1– 3,* Chang Liu,4– 6,* Shuang Wu,2,3,7 Lin Deng,2,3,8 Guangyuan Zhang,2,3,8 Xin Cai,1– 3 Silong Hu,4– 6 Jingyi Cheng,2,3,6,9 Xiaoping Xu,4– 6 Bin Wu,2,3,10 Xiaomao Guo,2,3,7 Yingjian Zhang,4– 6 Shen Fu,5,11 Qing Zhang1– 3 1Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Radiation Oncology, Shanghai, People’s Republic of China; 3Shanghai Engineering Research Center of Proton and Heavy ion Radiation Therapy, Shanghai, People’s Republic of China; 4Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 5Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People’s Republic of China; 6Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, People’s Republic of China; 7Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, People’s Republic of China; 8Department of Radiology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China; 9Department of Nuclear Medicine, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, People’s Republic of China; 10Department of Radiology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, People’s Republic of China; 11Department of Radiation Oncology, Shanghai Concord Cancer Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing ZhangDepartment of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of ChinaTel +86 139 1737 4609Fax +86 2138296518Email qing.zhang@hotmail.comShen FuDepartment of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of ChinaEmail shen_fu@hotmail.comPurpose: The purpose of this study was to assess the potential of 99mTc-labeled PSMA-SPECT/CT and diffusion-weighted image (DWI) for predicting treatment response after carbon ion radiotherapy (CIRT) in prostate cancer.Patients and Methods: We prospectively registered 26 patients with localized prostate cancer treated with CIRT. All patients underwent 99mTc-labeled PSMA-SPECT/CT and multiparametric magnetic resonance imaging (MRI) before and after CIRT. The tumor/background ratio (TBR) and mean apparent diffusion coefficient (ADCmean) were measured on the tumor and the percentage changes before and after therapy (ΔTBR and ΔADCmean) were calculated. Patients were divided into two groups: good response and poor response according to clinical follow-up.Results: The median follow up time was 38.3months. The TBR was significantly decreased (p=0.001), while the ADCmean was significantly increased compared with the pretreatment value (p< 0.001). The ΔTBR and ΔADCmean were negatively correlated with each other (p = 0.002). On ROC curve analysis for predicting treatment response, the area under the ROC curve (AUC) of ΔTBR (0.867) for predicting good response was higher than that of ΔADCmean (0.819). The AUC of combined with ΔTBR and ΔADCmean (0.895) was higher than that of either ΔADCmean or ΔTBR alone. The combined use of ΔTBR and ΔADCmean showed 91.4% sensitivity and 95.2% specificity.Conclusion: Our preliminary data indicate that the changes of TBR and ADCmean maybe an early bio-marker for predicting prognosis after CIRT in localized prostate cancer patients. In addition, the ΔTBR seems to be a more powerful prognostic factor than ΔADCmean in prostate cancer treated with CIRT.Keywords: PSMA, DWI, prostate cancer, carbon ion radiotherapy

Zhaojun Yu,1– 3 Jianbiao Huang,1– 3 Huanhuan Deng,1,3 Zhihua Zeng,1 Leihong Deng,4 Xiangda Xu,1 Haichao Chao,1 Tao Zeng1 1Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 2Department of Urology, The People’s Hospital Affiliated to Nanchang University, Nanchang, 330006, People’s Republic of China; 3Medical Department, Nanchang University, Nanchang, 330006, People’s Republic of China; 4Department of Ultrasound, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of ChinaCorrespondence: Tao ZengDepartment of Urology, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi Province, 330006, People’s Republic of ChinaTel +8613607919171Email Taozeng40709@sina.comPurpose: To explore the application of the neobladder-urethral drag-and-bond anastomosis technique in laparoscopic radical cystectomy (LRC) with ileal orthotopic neobladder (IONB) reconstruction.Patients and Methods: This is a retrospective cohort study on a procedure performed by a single surgeon. From January 2014 to December 2018, we identified 43 male bladder cancer patients who received LRC with IONB reconstruction. These patients were divided into two groups, with 22 patients undergoing neobladder-urethral drag-and-bond anastomosis (NUDA) and 21 patients undergoing neobladder-urethral anastomosis under laparoscopy (NUAL). Anastomosis time, catheter removal time, postvoid residual (PVR), maximum urinary flow rate (Q-max), urine leakage and anastomotic stenosis were used to evaluate the simplicity and surgical effect of the two groups.Results: Both groups demonstrated similar tumor characteristics. A significant difference in neobladder-urethral anastomosis time was found between the NUDA group and the NUAL group (14.6 ± 0.4 vs 70 ± 2.5 min, P< 0.0001), and there was no significant difference in other characteristics.Conclusion: The neobladder-urethral drag-and-bond anastomosis technique in LRC and IONB reconstruction, with its shorter learning curve, was easier and more convenient than neobladder-urethral anastomosis under laparoscopy.Keywords: drag-and-bond anastomosis, neobladder-urethral anastomosis, laparoscopic radical cystectomy, ileal orthotopic neobladder, bladder cancer

Xiongwei Liu,1,* Kuizhong Shan,2,* Xiaxia Shao,1 Xianqing Shi,3 Yun He,4 Zhen Liu,1 Joe Antony Jacob,5 Lichun Deng1 1Department of Oncology, Affiliated Jiangyin Hospital of Medical College, Southeast University, Jiangyin, People’s Republic of China; 2Department of Oncology, The Second People’s Hospital of Kunshan, Kunshan, People’s Republic of China; 3Department of Oncology, Liyang People’s Hospital, Liyang, People’s Republic of China; 4Department of Oncology, Affiliated Hospital of Chinese Medicine of Changshu City, Nanjing University of Chinese Medicine, Changshu, People’s Republic of China; 5Nanosynthesis Unit, Nanome Consulting, Salem, Tamil Nadu, India*These authors contributed equally to this workCorrespondence: Lichun DengDepartment of Oncology, Affiliated Jiangyin Hospital of Medical College, Southeast University, No. 163 Shoushan Road, Jiangyin, 214400, Jiangsu Province, People’s Republic of ChinaTel +86 510 8061 5131Email 18921233265@163.comJoe Antony JacobNanosynthesis Unit, Nanome Consulting, No. 11, Kannankurichi Road, Salem, 636008, Tamil Nadu, IndiaTel +91-9443861940Email joeantonyjacob@gmail.comPurpose: Biomimetic approaches for the synthesis of silver nanoparticles (AgNPs) had created a substantial impression among the research community that focuses on nano-bio interactions. In this study, an eco-friendly method using Rhizophora apiculata aqueous leaf extract as a reductant-rich hydrosol was followed to synthesize AgNPs and test its cytotoxicity.Methods: To optimise the parameters for the synthesis of AgNPs, central composite design based on response surface methodology was used. The particles synthesized at a nano-scale were characterized in our previously published report. The present report further characterizes the nanoparticles by X-ray diffraction, SEM and TEM at varying sites and magnifications. The characterized AgNPs were tested for their cytotoxic effects on HEK-293 and HeLa cells.Results: The cytotoxicity on the cell lines was dose-dependent. At a concentration of 2.5 μL/mL of the AgNPs-containing hydrosol, 100% inhibition of HEK-293 cells and 75% inhibition of the HeLa cells were observed. The IC50 value for AgNPs on HEK-293 was 0.622 μL/mL (12.135 ng), whereas, for HeLa cells, it was 1.98 μL/mL (38.629 ng).Conclusion: The nanoparticles were three-fold toxic towards the HEK-293 cells in comparison to the HeLa cells. Therefore, the therapeutic index is low for R. apiculata derived AgNPs on HeLa cells when tested in comparison with the HEK-293 cells. The nanotoxicity profile of the synthesized AgNPs seems more prominent than the nanotherapeutic index. According to our knowledge, this is the first-ever report on the optimization of synthesis of AgNPs using response surface methodology and identifying the therapeutic index of mangrove leaf-derived AgNPs.Keywords: AgNPs, XRD, HEK-293, HeLa, nanotoxicity

Lijun Deng,1 Rubo Sui,1 Lei Zhang2 1Department of Neurology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 2School of Nursing, Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of ChinaCorrespondence: Rubo SuiDepartment of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of ChinaTel +8613204525199Email 627079227@qq.comPurpose: To analyze the changes in white matter tracts in patients with post-stroke depression (PSD), and the correlation between these changes and the depressive state.Patients and Methods: The numbers of white matter tracts and corresponding fractional anisotropy (FA) in the acute phase (the onset time < 72 hours) were examined in each subject by diffusion tensor tractography (DTT). Diffusion tensor imaging (DTT), a new development of diffusion tensor imaging (DTI), enables visualization of white matter fiber tracts, which are thought to be closely related to the occurrence of PSD, According to the scores of Hamilton Depression Scale (HAMD) recorded at the 2nd week, 1st month, 3rd month, 6th month, and 12th month, forty patients were randomly selected and were classified into PSD group (n=20), non-depression post-stroke group (N-PSD, n=20), and control normal group (NORM, n=20), respectively. Correlations between the number of bundles (lines) in the white matter tract and corresponding FA, and HAMD score were finally assessed.Results: 1) FAs of the ipsilesional crossed corticocerebellar tract, the corticospinal tract, and the anterior thalamic radiation in PSD group were significantly lower than those in N-PSD and NORM groups (P< 0.01); 2) Lines in the three areas in the PSD group were significantly lower than those in the N-PSD and NORM groups (P< 0.01); and 3) FA and lines in the three areas of PSD patients were negatively correlated to HAMD scores (correlation coefficient=− 0.586, − 0.793, − 0.626, − 0.533, − 0.642, and − 0.524, respectively, all P< 0.05).Conclusion: FA and lines of the ipsilesional crossed corticocerebellar tract, the corticospinal tract, and the anterior thalamic radiation in PSD patients are significantly correlated to the depressive state. The crossed corticocerebellar tract, the corticospinal tract and the anterior thalamic radiation are involved in the development of PSD.Keywords: post-stroke depression, white matter tracts, diffusion tensor imaging, diffusion tensor tractography

Lifen Peng,1 Hailan Yan,2 Shuyi Qi,3 Lifei Deng4 1Department of Otolaryngology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, People’s Republic of China; 2Department of Clinical Medicine, Xi’an Jiaotong University Health Science Center, Xi’an, People’s Republic of China; 3Department of Pathology, Jiangxi Provincial Cancer Hospital, Nanchang, People’s Republic of China; 4Head and Neck Cancer Surgery, Jiangxi Provincial Cancer Hospital, Nanchang, People’s Republic of ChinaCorrespondence: Lifei DengHead and Neck Cancer Surgery, Jiangxi Provincial Cancer Hospital, Nanchang 330006, People’s Republic of ChinaTel +86 13657099876Email denglifei@126.comAim: To investigate the role of CAB39 in nasopharyngeal carcinoma (NPC) development and examine its expression level in NPC tumor samples.Methods: Immunohistochemistry staining of NPC tissue microarray was conducted to detect the expression of CAB39 protein in NPC tissues, and the clinical significance of CAB39 was evaluated. Lentivirus-mediated over-expression of CAB39 was designed to increase CAB39 expression in CNE-1 cells. Cell colony formation, cell cycle and CCK-8 proliferation experiments were performed to compare the proliferation ability of CNE-1 cells with or without CAB39 over-expression. Western blotting was conducted to examine downstream targets of CAB39.Results: CAB39 expression was higher in tumor samples compared to normal tissue and the higher CAB39 expression was positively correlated to higher TNM stage and distant metastasis rate and non-keratinized state. Further, CAB39 over-expression dramatically increased the proliferation and colony formation of CNE-1 cells. Finally, higher p-JNK protein level was found in CAB39 over-expressing cells.Conclusion: CAB39 promotes the proliferation of CNE-1 cells via up-regulating p-JNK.Keywords: CAB39, proliferation, nasopharyngeal carcinoma, p-JNK

Shuyi He,1– 3,* Jingyu Li,1– 3,* Mingjian Chen,1– 3 Liehua Deng,4 Yuxin Yang,1– 3 Zhaoyang Zeng,1– 3 Wei Xiong,1– 3 Xu Wu1– 3 1NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science, Central South University, Changsha, People’s Republic of China; 2Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China; 4Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu WuCentral South University, 110 Xiangya Road, Kaifu District, Changsha City, Hunan Province 410078, People’s Republic of ChinaEmail wuxu1028@csu.edu.cnIntroduction: Near-infrared (NIR) hyperthermia agents are promising in cancer photothermal therapy due to their deeper penetration ability and less side effects. Spherical gold nanoshell and graphene-based nanomaterials are two major NIR hyperthermia agents that have been reported for photothermal therapy of cancer. Herein, we constructed a two-dimensional graphene oxide-template gold nanosheet (GO@SiO2@AuNS) hybrid that could destruct cancer cells with efficient photothermal effect.Methods: Graphene oxide was coated with a layer of mesoporous silica, which provided binding sites for gold seeds. Then, seed-growth method was utilized to grow a layer of gold nanosheet to form the GO@SiO2@AuNS hybrid, which possessed great biocompatibility and high photothermal conversion efficiency.Results: With the irradiation of NIR laser (808 nm) with low power density (0.3 W/cm2), GO@SiO2@AuNS hybrid showed a photothermal conversion efficiency of 30%, leading to a temperature increase of 16.4 °C in water. Colorectal cancer cells (KM12C) were killed with the treatment of GO@SiO2@AuNS hybrid under NIR irradiation.Conclusion: The GO@SiO2@AuNS hybrid may expand the library of the 2D nanostructures based on gold for cancer photothermal therapy.Keywords: graphene oxide, gold nanosheets, photothermal therapy, near-infrared

Lian Deng,1,* Xiongjie Zhu,1,* Zhongjian Yu,1 Ying Li,1 Lingyu Qin,1 Zhile Liu,1 Longbao Feng,2 Rui Guo,2 Yanfang Zheng1 1Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China; 2Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China*These authors contributed equally to this workCorrespondence: Yanfang Zheng; Rui Guo Tel +86 18665000236Email 18665000236@163.com; guorui@jnu.edu.cnBackground: Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side-effects, poor bioavailability, and drug-resistance. Increasing attention has been paid to nanomedicines because of their good biological safety, targeting capabilities, and high-efficiency loading of multiple drugs. Herein, we have developed a novel T7 peptide-modified pH-responsive targeting nanosystem co-loaded with docetaxel and curcumin for the treatment of esophageal cancer.Methods: Firstly, CM-β-CD-PEI-PEG-T7/DTX/CUR (T7-NP-DC) was synthesized by the double emulsion (W/O/W) method. The targeting capacity of the nanocarrier was then investigated by in vitro and in vivo assays using targeted (T7-NP) and non-targeted nanoparticles (NP). Furthermore, the anti-tumor efficacy of T7-NP-DC was studied using esophageal cancer cells (KYSE150 and KYSE510) and a KYSE150 xenograft tumor model.Results: T7-NP-DC was synthesized successfully and its diameter was determined to be about 100 nm by transmission electron microscopy and dynamic light scattering. T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively, had good colloidal stability and exhibited pH-responsive drug release. Good biosafety was observed, even when the concentration was as high as 800 μg/mL. Significant enhancement of T7-NP uptake was observed 6 hours after intravenous injection compared with NP. In addition, the therapeutic efficacy of T7-NP-DC was better than NP-DC and docetaxel in terms of growth suppression in the KYSE150 esophageal cancer model.Conclusion: The findings demonstrated that T7-NP-DC is a promising, non-toxic, and controllable nanoparticle that is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor and exerts a synergistic anti-tumor effect. The data indicate that the nanomaterials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.Keywords: nanocarrier, T7 peptide, pH-responsive, docetaxel, esophageal cancer

Pinyi Zhang,1 Jianlong Bu,2 Xiaohong Wu,1 Lin Deng,1 Meng Chi,1 Chao Ma,3 Xiaoding Shi,1 Guonian Wang3 1Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 2Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 3Department of Anesthesiology, The Fourth Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Guonian WangDepartment of Anesthesiology, The Fourth Hospital of Harbin Medical University, Nangang District, Harbin 150081, People’s Republic of ChinaTel +86 15804616023Email wangguonian609cn@aliyun.comBackground: Sustained morphine treatment for cancer pain has been limited due to analgesic tolerance. Opioid receptor internalization and desensitization mediated by downregulation of mu-opioid receptor (MOR) expression have been confirmed as one of the mechanisms of chronic morphine tolerance. In addition to the opiate system, the α 2-adrenergic system is involved in the development of morphine tolerance. Several studies reported that co-administration of α 2-adrenoceptor agonist dexmedetomidine inhibits morphine tolerance in normal or neuropathic pain animals. However, the effect of dexmedetomidine on morphine tolerance has not been studied in cancer pain. Therefore, we investigated the effect of intrathecal injection of dexmedetomidine on the development of morphine tolerance in cancer pain and on the expression of MOR in the spinal cord of morphine-tolerant cancer pain rats.Methods: The model was established using a rat’s right hind paw injection of Walker 256 cancer cells. Subcutaneous morphine (10mg/kg) was administrated twice daily for 7 days; meanwhile, the rats received intrathecal α 2-adrenoceptor agonist dexmedetomidine (10μ/kg) or antagonist MK-467 (0.25mg/kg) in test groups. Rats receiving drug vehicle served as the control group. Antinociception was detected by von Frey filaments and hot-plate tests. The expression of MOR in the spinal cord was examined through real-time reverse transcription polymerase chain reaction and Western blotting. The data were analyzed via analysis of variance followed by Student t-test with Bonferroni correction.Results: Seven-day chronic morphine administration elicited notable analgesic tolerance in the rats with cancer pain. Co-administration of α 2-adrenoceptor agonist dexmedetomidine enhanced morphine analgesia and attenuated morphine tolerance, which could be blocked by α 2-adrenoceptor antagonist MK-467. Furthermore, pre-treatment of dexmedetomidine significantly upregulated MOR protein expression without a notable change in MOR mRNA expression in the spinal cord.Conclusion: Our findings suggest that intrathecal injection of dexmedetomidine enhanced morphine analgesia and attenuated morphine tolerance in cancer pain, potentially by upregulating MOR expression in the spinal cord. The α 2-adrenoceptor agonist may provide a more versatile analgesia option for morphine treatment for cancer pain.Keywords: μ-opioid receptor, MOR, α 2-adrenoceptor, α 2-AR, dexmedetomidine, DEX, morphine tolerance, cancer pain

Lin Deng,1,* Shikong Guo,2,* Hong Li,1 Xianghui You,1 Yang Song,1 Haichuan Su1 1Department of Oncology, Tangdu Hospital, Air Force Military Medical University, Xi’an, Shaanxi, China; 2Department of Orthopedics, Tangdu Hospital, Air Force Military Medical University, Xi’an, Shaanxi, China*These authors contributed equally to this workCorrespondence: Yang Song; Haichuan Su Email songyang212212@163.com; suhaic_1@163.comBackground: This study explored the value of ascites and serum CA125, CEA, and CA19-9 levels and ascites DNA ploidy analysis for the diagnosis of peritoneal carcinomatosis (PC) in patients with gastrointestinal and ovarian malignancies, which can cause ascites and may disseminate peritoneally.Methods: We measured ascites and serum levels of CA125, CEA, CA19-9 and performed an ascites DNA ploidy analysis in 58 patients with PC and 44 patients without PC.Results: We found that a high expression level of CA125 in ascites fluid was associated with the occurrence of PC in patients with gastrointestinal and ovarian malignancies (P< 0.001), and that high CEA and CA19- 9 levels in ascites fluid were associated with PC in patients with gastrointestinal malignancies (P=0.001, P=0.002). But, these tumor marker expression levels in ascites fluid were not significantly associated with the PC stage (P> 0.05). We found similar serum levels of CA125, CEA, and CA19-9 between patients with gastrointestinal and ovarian malignancies and PC and those without PC (P> 0.05). We found that the presence of three or more cells with heteroploid in the ascites samples was significantly associated with PC in gastrointestinal and ovarian malignancies (P< 0.001). In addition, the best ROC curves and highest AUCs were achieved by combining the CA125 level and heteroploid cell analysis results (AUC for gastrointestinal and ovarian malignancies, 0.815, AUC for gastrointestinal malignancies, 0.873). Moreover, the combined ascites CA125 level and result of heteroploid cell analysis provided the best diagnostic sensitivity and specificity for PC (75.9% and 79.5%, respectively, in gastrointestinal and ovarian malignancies; 85.0% and 86.7%, respectively, in gastrointestinal malignancies).Conclusion: Ascites levels of CA125, CEA, CA19-9, and heteroploid cells can be considered valuable markers for the diagnosis of PC in patients with gastrointestinal and ovarian cancer.Keywords: peritoneal carcinomatosis, tumor marker, ascites, heteroploid cell

Fan Yang,1 Lu Deng,2 JinPeng Li,3 MuHu Chen,1 Ying Liu,1 YingChun Hu,1 Wu Zhong1 1Department of Emergency Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 2Department of Thyroid Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 3Department of Thyroid and Breast Surgery, Wuhan University Zhongnan Hospital, Wuhan, Hubei 430071, People’s Republic of ChinaCorrespondence: Wu Zhong Department of Emergency MedicineAffiliated Hospital of Southwest Medical University, 25 Taiping Street, Luzhou, Sichuan 646000, People’s Republic of ChinaEmail zhongwu3987@126.comBackground: Renal fibrosis is a frequently occurring type of chronic kidney disease that can cause end-stage renal disease. It has been verified that emodin or HGF can inhibit the development of renal fibrosis. However, the antifibrotic effect of emodin in combination with HGF remains unclear.Methods: Cell viability was detected with CCK8. Gene and protein expression in HK2 cells was detected by qRT-PCR and Western blot, respectively. Moreover, a unilateral ureteral obstruction–induced mouse model of renal fibrosis was established for investigating the antifibrotic effect of emodin in combination with HGF in vivo.Results: HGF notably increased the expression of collagen II in TGFβ-treated HK2 cells. In addition, HGF-induced increase in collagen II expression was further enhanced by emodin. In contrast, fibronectin, αSMA and Smad2 expression in TGFβ-stimulated HK2 cells was significantly inhibited by HGF and further decreased by combination treatment (emodin plus HGF). Moreover, we found that combination treatment exhibited better antifibrotic effects compared with emodin or HGF in vivo.Conclusion: These data demonstrated that emodin plus HGF exhibited better antifibrotic effects compared with emodin or HGF. As such, emodin in combination with HGF may serve as a new possibilty for treatment of renal fibrosis.Keywords: fibrosis, combination, emodin, TGFβ

Lei Deng,1,2 Xiaoli Pan,1 Yulong Zhang,1 Sujing Sun,1 Liping Lv,1 Lei Gao,1 Ping Ma,1 Huisheng Ai,2 Qianqian Zhou,1 Xiaohui Wang,1 Linsheng Zhan1 1Department of Emerging Transfusion Technology, Institute of Health Service and Transfusion Medicine, Academy of Military Medical Sciences, Beijing, People’s Republic of China; 2Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiaohui Wang; Linsheng ZhanDepartment of Emerging Transfusion Technology, Institute of Health Service and Transfusion Medicine, Academy of Military Medical Sciences, Beijing, People’s Republic of ChinaEmail lszhan91@yahoo.com; lovechina1980@163.comBackground: Due to their extraordinary physical and chemical properties, MoS2 nanosheets (MSNs) are becoming more widely used in nanomedicine. However, their influence on immune systems remains unclear.Materials and Methods: Two few-layered MSNs at sizes of 100– 250 nm (S-MSNs) and 400– 500 nm (L-MSNs) were used in this study. Bone marrow-derived dendritic cells (DCs) were exposed to both MSNs at different doses (0, 8, 16, 32, 64, 128 μg/mL) for 48 h and subjected to analyses of surface marker expression, cytokine secretion, lymphoid homing and in vivo T cell priming.Results: Different-sized MSNs of all doses did not affect the viability of DCs. The expression of CD40, CD80, CD86 and CCR7 was significantly higher on both S-MSN- and L-MSN-treated DCs at a dose of 128 μg/mL. As the dose of MSN increased, the secretion of IL-12p70 remained unchanged, the secretion of IL-1β decreased, and the production of TNF-α increased. A significant increase in IL-6 was observed in the 128 μg/mL L-MSN-treated DCs. In particular, MSN treatment dramatically improved the ex vivo movement and in vivo homing ability of both the local resident and blood circulating DCs. Furthermore, the cytoskeleton rearrangement regulated by ROS elevation was responsible for the enhanced homing ability of the MSNs. More robust CD4+ and CD8+ T cell proliferation and activation (characterized by high expression of CD107a, CD69 and ICOS) was observed in mice vaccinated with MSN-treated DCs. Importantly, exposure to MSNs did not interrupt LPS-induced DC activation, homing and T cell priming.Conclusion: Few-layered MSNs ranging from 100 to 500 nm in size could play an immunostimulatory role in enhancing DC maturation, migration and T cell elicitation, making them a good candidate for vaccine adjuvants. Investigation of this study will not only expand the applications of MSNs and other new transition metal dichalcogenides (TMDCs) but also shed light on the in vivo immune-risk evaluation of MSN-based nanomaterials.Keywords: MoS2 nanosheets, dendritic cells, migration, vaccine adjuvant

Peixian Zhang,* Lan Shi,* Linjing Song, Yi Long, Kehua Yuan, Wanbao Ding, Lei Deng Department of Oncology, Yan’an Hospital of Kunming City & Yan’an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of China *These authors contributed equally to this workCorrespondence: Lei Deng; Wanbao DingDepartment of Oncology, Yan’an Affiliated Hospital of Kunming Medical University. No. 245 East of Renmin Road, Kunming, Yunnan 650051, People’s Republic of ChinaEmail leidengkm@163.com; wabading@163.comPurpose: Synchronous colorectal liver metastasis (SCLM) had limited availability of tools to predict survival and tumor recurrence. LncRNA CRNDE and lncRNA SNHG7 have been proven to be closely related to cancer progression. However, the predictive value of lncRNA CRNDE and lncRNA SNHG7 in cancer prognosis is still unclear. The purpose of this study was to investigate whether lncRNA CRNDE and lncRNA SNHG7 could be used as promising biomarkers for prognosis prediction of SCLM patients who underwent hepatectomy.Methods: The expression profile of lncRNA CRNDE and lncRNA SNHG7 in serum of SCLM patients was examined by qRT-PCR. The relationship between lncRNA expression and clinicopathological characteristics was analyzed. The Cox proportional-hazards regression model and Kaplan-Meier analysis were performed to analyze the association between lncRNA expression and overall survival (OS) and tumor recurrence of SCLM patients.Results: Levels of lncRNA CRNDE and lncRNA SNHG7 in patients who underwent recurrence or death were significantly higher than that of patients with recurrence-free or survival (P< 0.01). Both lncRNA CRNDE high level and lncRNA SNHG7 high level showed a significant correlation with differentiation of primary tumor, invasion depth of primary focus, lymph node metastases, number of liver metastases, and liver metastasis grade. High levels of lncRNA CRNDE or lncRNA SNHG7 predicted shorter recurrence time, shorter OS time, higher recurrence rate and lower OS rate. Furthermore, lncRNA CRNDE and lncRNA SNHG7 were independent risk factors for high recurrence and poor OS in SCLM underwent hepatectomy.Conclusion: Taken together, lncRNA CRNDE and lncRNA SNHG7 could be promising biomarkers for prediction of OS and tumor recurrence in SCLM underwent hepatectomy.Keywords: lncRNA CRNDE, lncRNA SNHG7, prognosis, recurrence, synchronous colorectal liver metastasis, SCLM

Yun Du,1,2 Wentong Zhang,3 Feng Lei,4 Xia Yu,1 Zhuming Li,1 Xiaodong Liu,1 Yanan Ni,1 Li Deng,4 Mingfang Ji1 1Cancer Research Institute of Zhongshan City, Zhongshan City People’s Hospital, Zhongshan 528400, People’s Republic of China; 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Stockholm, Sweden; 3Department of Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Radiotherapy, Zhongshan City People’s Hospital, Zhongshan, People’s Republic of ChinaCorrespondence: Mingfang JiCancer Research Institute of Zhongshan City, Zhongshan City People’s Hospital, No. 2. Sunwen Road East, Zhongshan 528400, Guangdong, People’s Republic of ChinaTel +86 135 3206 2222Fax +86 076488822698Email jmftbh@sina.comPurpose: NPC is a malignant and invasive tumor with the incidence rate of 19/100,000 per year in Zhongshan City, a prefecture city in southern China. Long-term survival analysis on intensity-modulated radiotherapy (IMRT)-based treatment in local prefecture-level hospitals have not been investigated. We aimed to evaluate the 5-year clinical outcomes and prognostic factors of NPC treated with IMRT in Zhongshan City People’s Hospital (ZSPH), a prefecture-level hospital in South China.Patients and Methods: The number of 149 newly diagnosed non-metastatic NPC cases treated with IMRT were included from Zhongshan City People’s Hospital between January 2010 and December 2011. The survival outcomes, treatment toxicities and prognostic factors were analyzed by Kaplan-Meier method and Cox proportional hazards model.Results: With a median follow-up period of 65 months for the cohort, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) and overall survival (OS) were 86.80%, 94.80%, 86.10% and 80.50%, respectively. The 5-year OS rates were 100%, 95.2%, 87% and 67.2% for stage I, II, II and IVa-b, respectively (P=0.004). The 5-year LRFS rates were 97.2%, 96.0%, 90.4% and 72.0% for T1, T2, T3 and T4, respectively (P=0.001); the 5-year DMFS rates were 100% for T1, 96.8% for T2, 81.9% for T3 and 74.6% for T4 (P=0.022). A multivariate analysis revealed tumor stage as an independent prognostic factor for LRFS, DMFS and OS. No patients died from acute toxicities. Late toxicities were observed for 130 (87.2%) patients, and most late toxicities were graded I/II.Conclusion: NPC treatment effect in a prefecture-level hospital in South China was comparable to international results and toxicities were tolerable. Tumour stage was an independent prognostic factor for survival outcome. More NPC survival data from local and remote places are needed.Keywords: nasopharyngeal carcinoma, intensity-modulated, radiotherapy, prognosis, long-term survival results

Xiaopeng Sun,1,2 Hao Xue,1,3 Ye Xiong,4 Rui Yu,5 Xiao Gao,1 Mingyu Qian,1 Shaobo Wang,1 Huizhi Wang,1 Jianye Xu,1 Zihang Chen,1 Lin Deng,1,3 Gang Li1,3 1Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012, People’s Republic of China; 2Department of Neurosurgery, Dezhou People’s Hospital, Dezhou, Shandong Province 253014, People’s Republic of China; 3Institute of Brain and Brain-Inspired Science, Shandong Provincial Key Laboratory of Brain Function Remodeling, Shandong University, Jinan, Shandong Province, People’s Republic of China; 4Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People’s Republic of China; 5Department of Neurosurgery, The Second Hospital of Shandong University, Jinan 250033, People’s Republic of ChinaCorrespondence: Gang Li; Lin DengDepartment of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012, People’s Republic of ChinaEmail ligangqiluhospital@163.com; denglinqilu@163.comPurpose: Glioma is the most common and lethal type of brain tumor. While GALE (UDP-galactose-4-epimerase) has been shown to be overexpressed in some kinds of cancers, its expression in gliomas has not been reported. MicroRNAs (miRNAs) function as tumor suppressors in many cancers, and online datasets can be used to predict whether GALE is regulated by miR-let-7i-5p. In this investigation, we explored the effect and regulatory mechanisms of GALE on glioblastoma growth via miR-let-7i-5p.Methods: We used a Cox proportional hazards model and publicly available datasets to examine the relationship between GALE and the survival rates of glioma patients. Bioinformatics predicted the targeting of GALE by miR-let-7i-5p. The proliferation, migration, cell cycle and apoptosis of human glioblastoma cells were assessed by relevant assays. We also demonstrated the effect of GALE on glioblastoma multiforme [GBM] tumor growth using an in vivo orthotopic xenograft model.Results: GALE was upregulated in human gliomas, especially in high-grade gliomas (e.g., GBM). An obvious decline in GALE expression was observed in human glioblastoma cell lines (U87 and U251) following treatment with a small interfering RNA (siRNA) targeting GALE or miR-let-7i-5p mimics. Knockdown of GALE or overexpression of miR-let-7i-5p (with miR-let-7i-5p mimics) inhibited U87 and U251 cell growth. miR-let-7i-5p significantly restrained the migration ability of human glioblastoma cells in vascular mimic (VM), wound healing and transwell assays, and GALE promoted glioblastoma growth in vivo.Conclusion: Our findings confirm that GALE plays an important role in promoting the development of human glioma and that GALE can be regulated by miR-let-7i-5p to inhibit human glioblastoma growth.Implications for cancer survivors: Our data show that cancer survivors have low GALE expression, which indicates that GALE may be a diagnostic biomarker and a promising therapeutic target in glioblastoma.Keywords: glioblastoma, GALE, miR-let-7i-5p, proliferation, migration

Yuanyuan Li,1,* Yueqi Song,1,* Leqing Zhu,1,* Xiao Wang,1 Bin Yang,2 Ping Lu,2 Quan Chen,3 Lianghua Bin,4 Liehua Deng5 1Biomedical Translational Research Institute, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 3Division of Research Informatics Services, Department of Medicine, National Jewish Health, Denver, CO, USA; 4Department of Pediatrics, National Jewish Health, Denver, CO, USA; 5Department of Dermatology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lianghua BinDepartment of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USATel +1-303-270-2055Email binl@njhealth.orgLiehua DengDepartment of Dermatology, The First Affiliated Hospital, Jinan University, West Huangpu Dadao, No 605, Tianhe Qu, Guangzhou, Guangdong Province, People’s Republic of ChinaTel +86-137-25356728Email liehuadeng@126.comPurpose: There is increased type I interferon signature in psoriasis patients. Interferon-kappa (IFN-κ) is a member of type I interferon family that is constitutively expressed by keratinocytes. In this study, we investigate whether IFN-κ is involved in psoriasis etiology.Patients and methods: Twenty healthy individuals, 20 psoriasis vulgaris patients and 10 atopic dermatitis (AD) were included for this study. Immunohistochemistry staining, normal human epidermal keratinocytes (NHEK) culture, Ca2Cl-induced differentiation, quantitative reverse transcription (qRT-PCR), ELISA and murine experiments were performed.Results: We found IFN-κ protein expression was extremely low in the epidermis of normal skin, but it was significantly increased in the suprabasal layers of epidermal keratinocytes in psoriatic skin lesions. However, its expression in the skin lesions of AD was similar to normal skin. Additionally, IFN-κ protein was detected in sera from psoriasis patients, but not in sera from normal subjects and AD. We further investigated the regulation of IFNk gene expression in NHEK. We found that IFNk was significantly induced by types of nucleic acid pathogen recognition receptor (PRR) agonists in NHEK. While its expression was significantly induced by itself and IFN-γ, it was inhibited by type 2 immunity cytokines IL4 and IL13; other inflammatory cytokines including IL1 super-family members and IL17A did not alter its expression. Addition of recombinant IFN-κ did not affect keratinocytes differentiation. Using the murine experimental model, we demonstrated that subcutaneous administration of recombinant IFN-κ did not increase skin thickness, but significantly increased the transcription of TNFA and IL17A in mice skin.Conclusion: Increased IFN-κ in psoriasis may be caused by injured cells-released nucleic acids, increased IFN-γ and self-activation. Its enhancement may contribute to the etiology of the disease by enhancing TNFA and IL17A gene expression.Keywords: IFN-κ, psoriasis, TNFA, IL17A, atopic dermatitis

Taiyuan Li,1,* Li Deng,2,* Xin He,1 Gongan Jiang,1 Fang Hu,1 Shanping Ye,1 Yu You,3 Jinzhong Duanmu,1 Hua Dai,4 Guodong Huang,1 Cheng Tang,1 Xiong Lei1 1Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China; 2Department of Diagnostic Medical Sonography, Jiangxi Pingxiang People’s Hospital, Pingxiang 337000, Jiangxi, People’s Republic of China; 3Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China; 4Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiong LeiDepartment of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of ChinaTel +86-791-88694893Fax +86-791-88692745Email leixionglinty@126.comBackground: Metastasis is the main cause for gastric cancer (GC)-related deaths. Better understanding of GC metastatic mechanism would provide novel diagnostic markers and therapeutic targets. Though it has been reported that mammalian sterile-20-like kinase 4 (MST4) exerts the oncogenic role in other tumors, the prognostic value and biological role of MST4 in GC are still unknown.Methods: The expression level of MST4 in GC was analyzed by using TCGA database. Then, Western blot and polymerase chain reaction (PCR) were used to determine the MST4 expression in GC tissues and cell lines. Immunohistochemistry was performed to investigate the expression of proteins in human GC tissues, and its correlation with clinicopathologic parameters as well as the prognosis for patients with GC was analyzed. In addition, the biological function and its molecular mechanism of MST4 in GC were investigated by in vitro and in vivo assays.Results: It demonstrated that MST4 expression was significantly upregulated in GC tissues and cell lines. High expression of MST4 was correlated with aggressive clinicopathological parameters such as lymph node metastasis, lymphovascular invasion (all P < 0.05). GC patients with high MST4 expression had both shorter overall survival (OS) and disease-free survival (DFS) than those with low MST4 expression (all P < 0.05). MST4 expression was an independent and significant risk factor for OS and DFS of GC patients (all P < 0.05). Results of functional experiments showed that MST4 could promote GC cells migration, invasion in vitro and metastasis in vivo. In terms of mechanism, MST4 promoted metastasis by facilitating epithelial–mesenchymal transition (EMT) through activating Ezrin pathway in GC. Further studies indicate that down-regulated miR-124-3p expression contributes to upregulated MST4 expression in GC.Conclusion: Our data showed that MST4 predicts poor prognosis and promotes metastasis by facilitating epithelial–mesenchymal transition in GC. Therefore, our study suggests that MST4 can be used as a valuable prognostic biomarker and a potential therapeutic target in GC.Keywords: MST4, gastric cancer, prognosis, epithelial-mesenchymal transition, metastasis

Xinwei Huang,1,2,* Xi Mu,3,* Li Deng,4 Aili Fu,5 Endong Pu,6 Tao Tang,2 Xiangyang Kong21Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming City, Yunnan Province, People’s Republic of China; 2Medical School, Kunming University of Science and Technology, Kunming City, Yunnan Province, People’s Republic of China; 3Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming City, Yunnan Province, People’s Republic of China; 4The Pathology Department, First People‘s Hospital of Yunnan Province, Kunming City, Yunnan Province, People’s Republic of China; 5Department of Oncology, Yunfeng Hospital, Xuanwei City, Yunnan Province, People’s Republic of China; 6Department of Thoracic Surgery, Yunfeng Hospital, Xuanwei City, Yunnan Province, People’s Republic of China *These authors contributed equally to this workAbstract: COPD, characterized by long-term poorly irreversible airway limitation and persistent respiratory symptoms, has resulted in enormous challenges to human health worldwide, with increasing rates of prevalence, death, and disability. Although its origin was thought to be in the interactions of genetic with environmental factors, the effects of environmental factors on the disease during different life stages remain little known. Without clear mechanisms and radical cure for it, early screening and prevention of COPD seem to be important. In this review, we will discuss the etiologic origins for poor lung function and COPD caused by specific adverse effects during corresponding life stages, as well as try to find new insights and potential prevention strategies for this disease.Keywords: chronic obstructive pulmonary disease, COPD, early origins, risk factors, air pollution, cigarette smoking

Chan Wu,1,* Yang Zhang,1,2,* Daoqiu Yang,3,* Jinfeng Zhang,4 Juanjuan Ma,1 Dan Cheng,1 Jianming Chen,1,5 Li Deng1 1Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, People’s Republic of China; 2Department of Pharmacy, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai 200072, People’s Republic of China; 3Department of Dermatology, 107th Hospital of PLA, Yantai 264000, People’s Republic of China; 4Department of Traditional Chinese Medicine, Shanghai Hospital of Chinese Integrative Medicine, Shanghai, People’s Republic of China; 5Tasly Diyi Pharmaceutical Group Co., Ltd, Jiangsu 223002, People’s Republic of China *These authors contributed equally to this work Background: Many novel drug delivery systems have been extensively studied to exploit the full therapeutic potential of SN38, which is one of the most potent antitumor analogs of camptothecins (CPTs), whose clinical application is seriously hindered by poor water solubility, low plasmatic stability, and severe toxicity, but results are always unsatisfactory.Methods: In this study, combining the advantages of prodrug and nanotechnology, a lipophilic prodrug of SN38, SN38-PA, was developed by conjugating palmitic acid to SN38 via ester bond at C10 position, and then the lipophilic prodrug was encapsulated into a long-circulating liposomal carrier by film dispersion method.Results: The SN38-PA liposomes were characterized as follows: an average particle size of 80.13 nm, an average zeta potential of -33.53 mv, and the entrapment efficiency of 99%. Compared with CPT-11, SN38-PA liposome was more stable in close lactone form, more efficient in conversion rate to SN38, and more potent in cytotoxicity against tumor cells. Pharmacokinetic study showed that SN38-PA liposome had significantly enhanced plasma half-life (t1/2) value of SN38 and increased area under the curve (AUC) of SN38, which was 7.5-fold higher than that of CPT-11. Biodistribution study showed that SN38-PA liposome had more active metabolite SN38 in each tissue. Finally, the pharmacodynamic study showed that SN38-PA liposome had higher antitumor effect with the antitumor inhibition rate of 1.61 times than that of CPT-11.Conclusion: These encouraging data merit further investigation on this novel SN38-PA liposome. Keywords: SN38, lipophilic prodrug, long-circulating liposome, pharmacokinetics, biodistribution, pharmacodynamics, CPT-11