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Xuan Ma,1,2,&ast; Baolan Ji,2,&ast; Wenhua Du,2 Shuwei Shi,1,2 Hongyan Zhao,1,2 Jie Sheng,1,2 Xinghe Jiang,1,2 Bo Ban,3 Guanqi Gao2 1School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 2Department of Endocrinology, Linyi People’s Hospital Affiliated to Shandong Second Medical University, Linyi, Shandong, 276034, People’s Republic of China; 3Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanqi Gao, Department of Endocrinology, Linyi People’s Hospital, North Side of the Intersection of Wohushan Road and Wuhan Road in Lanshan District, Linyi, Shandong, 276034, People’s Republic of China, Email guanqi_gao@yeah.net Bo Ban, Department of Endocrinology, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272029, People’s Republic of China, Email banbo2011@163.comPurpose: Substantial evidence has established a strong association between non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM) and insulin resistance (IR). Insulin resistance metabolic score (METS-IR) is a new and more effective comprehensive indicator for measuring IR. Our aim was to investigate the relationship between METS-IR and NAFLD in T2DM population.Patients and methods: This cross-sectional study included 1097 adult patients with T2DM. Anthropometric measurements and biochemical indicators were collected, and the NAFLD was diagnosed by ultrasound. The METS-IR was calculated. Based on the presence of NAFLD, the population was divided into non-NAFLD and NAFLD groups. The relationship between METS-IR and NAFLD was evaluated.Results: Compared with the non-NAFLD group, the METS-IR was higher in the NAFLD group (P < 0.001). The incidence rate of NAFLD increased across the quartiles of the METS-IR (P < 0.001). Spearman correlation analysis showed that METS-IR was positively correlated with NAFLD (Correlation Coefficient: 0.441, P < 0.001). The binary logistic regression analysis indicated that METS-IR was independently associated with NAFLD (OR: 1.120, 95% CI 1.080– 1.161). Furthermore, the area under the receiver operating characteristic curve of the METS-IR was 0.781 (95% CI 0.746– 0.817) and relatively higher than other evaluation variables.Conclusion: In patients with T2DM, METS-IR is closely associated with NAFLD, and might be a valuable predictor of NAFLD. Further research is needed to verify this association.Keywords: Type 2 diabetes mellitus, NAFLD, insulin resistance, METS-IR

Han Luo,1,&ast; Xiaofei Wang,1,&ast; Mengqi Fang,1 Huifan Yu,1 Lili Gui,1 Zhengkun Wu,1 Jianyong Sheng,2 Fei Li1 1Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Hubei University of Medicine, 30 Renmin South Road, Shiyan, Hubei, 442000, People’s Republic of China, Email piaopodexinlifei@163.comIntroduction: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.Methods: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.Results: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1± 16.8 nm, zeta potential of about − 23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.Conclusion: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.Keywords: Hydroxyethyl starch, nanocrystals, stabilizer, luteolin, oral bioavailability, anti-hyperuricemia

Hong Zhao,&ast; Huilan Tu,&ast; Xia Yu,&ast; Junwei Su, Xuan Zhang, Kaijin Xu, Yu Shi, Yunqing Qiu, Jifang Sheng State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jifang Sheng; Yunqing Qiu, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel +86 571 8723 6491, Fax +86 571 8723 6491, Email jifang_sheng@zju.edu.cn; qiuyq@zju.edu.cnAim: To analyze the possible risk factors of delayed virus clearance in hospitalized patients with coronavirus disease 2019 (COVID-19).Methods: Retrospective analysis of patients with COVID-19 admitted to the isolation wards from our hospital from 19th Jan 2020 to 18th March 2020. We were collected patient’s data including demographic, epidemiologic, and clinical information, as well as laboratory and radiologic findings. The possible confounding risk factors for prolonged viral RNA shedding of COVID-19 during hospitalization were explored by univariate analysis and any variables with a p value less than 0.05 after univariate analysis were included in a subsequent multivariate logistic regression model analysis.Results: The 104 patients included 30 mild patients and 74 severe or critically ill patients. The median duration of viral RNA positivity in sputum was 11 days, and the longest duration of viral RNA positivity was 49 days after admission. Multivariate analysis shown that the used with darunavir/cobicistat treatment (odds ratio [OR]: 4.25, 95% confidence interval [CI]: 1.25– 14.42, p = 0.020), duration of fever (OR: 1.15, 95% CI: 1.03– 1.30, p = 0.015) and time to radiological improvement (OR: 1.14, 95% CI: 1.01– 1.30, p = 0.033) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients. Then adjusted in the multivariate binary logistic regression analysis model in severe COVID-19 and found that critical COVID-19 patients (OR: 13.25, 95% CI: 1.45– 12.07, p = 0.022), lower virus cycle threshold (CT) values of RT-PCR (OR: 0.96, 95% CI: 0.93– 0.99, p = 0.004) and used with darunavir/cobicistat treatment (OR: 8.44, 95% CI: 2.21– 32.28, p = 0.022) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients.Conclude: Clearance of viral RNA in sputum was delayed in severe COVID-19 patients, especially with lower virus CT value. And antivirals with darunavir/cobicistat has little advantage in eliminating SARS-CoV-2.Keywords: COVID-19, SARS-CoV-2, clearance, critical disease, viral load

Yulan Huang,&ast; Shitong He,&ast; Yitian Chen, Junli Sheng, Yuling Fu, Xialin Du, Yalong Yang, Honglin Liu, Zhenyu Han, Yingqi Huang, Qian Wen, Chaoying Zhou, Xinying Zhou, Shengfeng Hu, Li Ma Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Ma; Shengfeng HuInstitute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email mali_61648322@smu.edu.cn; hushengfeng@smu.edu.cnBackground: As deubiquitinases (DUBs), ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to play a crucial role in regulating diverse biological processes. However, its function in macrophage polarization remains unclear.Methods: We performed in vivo and in vitro experiments to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a kind of DUBs, in macrophage differentiation by using UCHL1-deficiency mice.Results: We demonstrated that LPS stimulation induced UCHL1 expression in macrophages. The deficiency of UCHL1 expression decreased the expression of CD80 and CD86 but increased the expression of CD206. The expression of TNF-α, IL-6, iNOS, and IL-10 was downregulated, while that of Arg1, Ym1, and Fizz1 was upregulated in UCHL1 deficient macrophages. Moreover, we observed that UCHL1 promoted the degradation of p110α through autophagy, but paradoxically increased the activity of AKT, thereby promoting polarization of macrophages into pro-inflammatory states.Conclusion: In this study, we identified UCHL1 as a positive regulator of M1 macrophage polarization. Our findings may help in developing therapeutic interventions for the treatment of inflammatory diseases and pathogenic infections.Keywords: UCHL1, macrophages, AKT, p110α, autophagy

The level structures of 92Mo have been investigated using the shell model code nushellx @ msu within two large model spaces containing neutron core excitations across the N = 50 closed shell. The calculated results are compared with the available experimental data, and reasonable agreements are obtained. The level structures of 92Mo, especially the levels come from neutron core excitations, are interpreted by the present calculations. The systematic features of neutron core excitations in the even–even N = 50 isotones have also been investigated. [ABSTRACT FROM AUTHOR]

Motor developmental delay (MDD) usually affects the inter-joint coordination for limb movement. However, the mechanism between the abnormal inter-joint coordination and MDD is still unclear, which poses a challenge for clinical diagnosis and motor rehabilitation of MDD in infant’s early life. This study aimed to explore whether the joint activities of limbs during infant crawling are represented with kinematic synergies of joint angles, and evaluate the impacts of MDD on the inter-joint coordination using those synergies. 20 typically developing infants, 16 infants at risk of developmental delay, 11 infants at high risk of developmental delay and 13 infants with confirmed developmental delay were recruited for self-paced crawling on hands and knees. A motion capture system was employed to trace infants’ limbs in space, and angles of shoulder, elbow, hip and knee over time were computed. Kinematic synergies were derived from joint angles using principal component analysis. Sample entropy and Spearman’s rank correlation coefficients were calculated among those synergies to evaluate the crawling complexity and the symmetry of bilateral limbs, respectively. We found that the first two synergies with different contributions to the crawling movements sufficiently represented the joint angular profiles of limbs. MDD further delayed the development of motor function for lower limbs and mainly increased the crawling complexity of joint flexion/extension to some extent, but did not obviously change the symmetry of bilateral limbs. These results suggest that the time-varying kinematic synergy of joint angles is a potential index for objectively evaluating the abnormal inter-joint coordination affected by MDD.

Jianhong Ji,1,&ast; Li Wang,2,&ast; Haiyang Guan,2 Yaqiong Jiang,1 Sanlian Zhou,2 Junhua Sheng,3 Lihua Wang4 1Intensive Care Unit, The Second Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 3Department of Medical, The Second Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 4Department of Nursing, The Second Affiliated Hospital of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua WangDepartment of Nursing, The Second Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of ChinaTel +86 13815219995Email lihua_wangdr@outlook.comObjective: This study was designed to verify the effect of group random quality control on the first aid ability of ward doctors and nurses with regard to the resuscitation of patients with in-hospital cardiac arrest (IHCA).Methods: The first aid quality control team of our hospital was established in December 2018, when the number, qualifications, organizational structure, quality control methods, and responsibilities of the team and team members were determined. The baseline data and assessment results of examinees, the rates of return of spontaneous circulation (ROSC), and the discharge survival rate of IHCA patients in 2019 and 2020 were compared.Results: There were no significant differences in the baseline data of examinees at each stage (p > 0.05). As time went on, the results of the four practical examinations were significantly improved (pairwise comparison, p < 0.05). The number of problems in examinations was significantly higher for physicians than for nurses. After guidance in department relearning, the incidence of related problems was significantly reduced, but the mastery of the frequency and depth of extracorporeal cardiac compression were not always up to standard. The proportion of critically ill patients and the incidence of IHCA in the hospital in 2020 was higher than in 2019 (p < 0.05), and the ROSC rate was also significantly higher than it was in 2019 (p < 0.05), but the difference in the survival rate at discharge was not statistically significant (p > 0.05).Conclusion: Group random quality control meets the needs of IHCA emergencies, and it can improve the first aid skills and organizational coordination of doctors and nurses on the ward through continuous discovery and problem solving so that the ultimate goal of improving the success rate of resuscitation can be achieved.Keywords: in-hospital cardiac arrest, cardiopulmonary resuscitation, quality control, patient outcomes, survival, ability

Leyi Liu,1 Ting Dong,2 Jun Sheng3 1Department of Anesthesiology, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, 241000, People’s Republic of China; 2Yijishan Hospital, First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of China; 3Department of Oncology, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, 241000, People’s Republic of ChinaCorrespondence: Jun ShengDepartment of Oncology, Wuhu Hospital of Traditional Chinese Medicine, No. 430, Jiuhua South Road, Yijiang District, Wuhu, 241000, People’s Republic of ChinaEmail sj6785@126.comBackground: Propofol is a common intravenous anesthetic that exerts an antitumor role in human cancers. Circular RNAs (circRNAs) play crucial roles in the progression of various cancers. However, the relationship between propofol and circRNA decaprenyl diphosphate synthase subunit 1 (circPDSS1) in gastric cancer (GC) remains unclear.Methods: Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8), colony formation, and 5-ethynyl-2ʹ-deoxyuridine (EdU) assays. Cell migration and invasion were assessed by transwell assay. Cell apoptosis was determined by flow cytometry. All protein levels were detected by Western blot assay. The expression levels of circPDSS1, microRNA-1324 (miR-1324), and SRY-box transcription factor 4 (SOX4) mRNA were determined by quantitative real-time PCR (qRT-PCR). The interaction between miR-1324 and circPDSS1 or SOX4 was confirmed by dual-luciferase reporter and RNA pull-down assays. The mice xenograft model was established to investigate the role of propofol and circPDSS1 in vivo.Results: Propofol inhibited cell proliferation, migration and invasion and induced apoptosis in GC cells, which could be reversed by upregulating circPDSS1. MiR-1324 was a target of circPDSS1, and circPDSS1 promoted cell proliferation, migration and invasion and reduced apoptosis in propofol-treated cells by sponging miR-1324. Moreover, SOX4 was a direct target of miR-1324, and miR-1324 exerted anticancer role by targeting SOX4 in propofol-treated cells. CircPDSS1 acted as a sponge of miR-1324 to regulate SOX4 expression. Additionally, circPDSS1 overexpression weakened the anticancer role of propofol in vivo.Conclusion: Propofol exerted anticancer role in GC through regulating circPDSS1/miR-1324/SOX4 axis, indicating that propofol might be an effective therapeutic medicine for GC treatment.Keywords: gastric cancer, propofol, circPDSS1, miR-1324, SOX4

Huashan Li,1,* Jianying Sheng,1,* Jing Wang,1 Haiting Gao,1 Jing Yu,2 Guoxian Ding,2 Ning Ding,1 Weiqi He,1,3 Juanmin Zha1 1Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Geriatrics, Division of Geriatric Endocrinology, The First Affiliated Hospital to Nanjing Medical University, Nanjing, People’s Republic of China; 3State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiqi He; Juanmin ZhaCambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Department of Oncology, The First Affiliated Hospital of Soochow University, 199 Ren-Ai Road, Suzhou, 205123, People’s Republic of ChinaTel +86-512-6588-3545Fax +86-6588-3562Email whe@suda.edu.cn; zhajuanmin@suda.edu.cnIntroduction: The effect of 11β-hydroxysteroid dehydrogenase type1 (11β-HSD1) inhibition on hepatic steatosis is incompletely understood. Here, we aimed to determine the therapeutic effect of BVT.2733, a selective 11β-HSD1 inhibitor, on hepatic steatosis.Materials and Methods: C57B/6J mice were randomly divided into a low-fat diet (LFD) fed group and a high-fat diet (HFD) fed group. Mice were fed with HFD for 28 weeks which induced obesity and severe hepatic steatosis. The two groups were further divided into four groups as follows: LFD, LFD with BVT.2733, HFD, and HFD with BVT.2733. Mice in LFD+BVT and HFD+BVT groups were intraperitoneally injected with BVT.2733 daily for 30 days. Effects of BVT.2733 on mice body weight, serum lipid profile, serum free fatty acids (FFAs), glucocorticoid levels, gene expression in adipose and liver tissues were assessed.Results: Injection of a low dose of BVT.2733 (50 mg/kg/day) reduced body weight and hyperlipidemia, but did not improve glucose tolerance and insulin resistance in diet-induced obese mice. The low dose of BVT.2733 attenuated hepatic steatosis, liver injury, and liver lipolytic gene expression in diet-induced obese mice. Besides, the low dose of BVT.2733 reduced fat mass and lipolysis in visceral adipose tissues, hepatic FFAs, and serum corticosterone levels in diet-induced obese mice.Conclusion: Our study shows that moderate inhibition of 11β-HSD1 by BVT.2733 reduces FFAs and corticosterone synthesis in fatty tissues, thereby attenuates the delivery of corticosterone and FFAs to the liver. Collectively, this prevents high-fat diet-induced hepatic steatosis.Keywords: 11β-HSD1, hepatic steatosis, inhibitor, adipose tissue, free fatty acids

Ying Chen,1– 3 Lei Zhang,1– 3 Fangxuan Li,4 Jindong Sheng,1 Changxiao Xu,1 Dan Li,1 Hu Yu,1 Wenxin Liu1 1Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of China; 2Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060; 3National Clinical Research Centre of Cancer, Tianjin, 300060, People’s Republic of China; 4Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of ChinaCorrespondence: Ying ChenDepartment of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin, 300060, People’s Republic of ChinaEmail lychenying2004@126.comIntroduction: Photodynamic therapy (PDT) has been widely researched by cancer therapists in recent years. This study aims to establish a drug delivery system combining PDT and chemotherapy to show that chemotherapeutic drugs provide oxygen to PDT, while PDT promotes the release of chemotherapeutic drug.Methods: Firstly, poly(ethylene glycol)-lysine(Ce6)-block-poly(L-glutamate)-imidazole (mPEG-lys(Ce6)-PGA-AIM) was synthesized and self-assembled into micelles that exhibited pH- and ROS-responsiveness and buffering capacity. Perfluorohexanoate-modified cisplatin (FCP), as oxygen carriers, was encapsulated into mPEG-lys(Ce6)-PGA-AIM micelles. Then, the properties of micelles and their biological functions in vivo and in vitro were investigated.Results: The micelles exhibited remarkabe stability, pH regulated drug release, good biocompatibility and effective tumor penetration. Cellular uptake demonstrated the efficient endosome/lysosome escape of CFMs, which facilitates the intracellular drug release. Both in vitro and in vivo experiments reflected that CFMs with laser irradiation showed significantly improved therapeutic activity compared with single PDT or chemotherapy.Conclusion: Chemotherapy and PDT were combined in the form of mutual assistance to provide a promising strategy for clinical treatment.Keywords: chemotherapy, photodynamic therapy, dual-responsiveness, oxygen carriers

Jiayu Sheng, Chunyang Li, Mengting Dong, Ke Jiang Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Ke JiangDepartment of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Shanghai 200437, People’s Republic of ChinaTel +86 21-65161782Email surgeonjk@163.comBackground: Previous studies have shown that kinesin family proteins (KIFs) play an indispensable roles in several types of cancer. However, the expression and clinical significance of KIFs in triple-negative breast cancer remain unclear.Methods: In this study, the role of KIF15, including gene expression analysis, methylation characteristic, CNV characteristic, and miRNA target regulation, was evaluated using multiple bioinformatic tools based on TCGA database. Quantitative real-time PCR and Western blot were used to determine the expression level of KIF15 in triple-negative breast cancer cell lines. Then, functional experiments were employed to explore the effects of KIF15 on tumor growth and metastasis in triple-negative breast cancer.Results: Our data showed that KIF15 was significantly upregulated in triple-negative breast cancer (TNBC). Functionally, downregulation of KIF15 significantly facilitated apoptosis and G2/M phase arrest, and inhibited the migration and invasion of TNBC cells. The mechanism of action of KIF15 was closely related to DNA replication checkpoint and cell cycle regulation in TNBC based on GSEA. In addition, bioinformatics analysis demonstrated that high expression of KIF15 in TNBC was correlated with copy number aberration and DNA methylation levels.Conclusion: Our findings suggest that KIF15 is a novel oncogene in TNBC and provide us a strong evidence that it might be served as a potential clinical target and biomarker in triple-negative breast cancer.Keywords: kinesin family proteins, bioinformatics analysis, biomarker, triple-negative breast cancer

Zhaochen Zhu, Jieyuan Zhang, Jiagen Sheng, Changqing Zhang, Zongping Xie Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Zongping XieShanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, People’s Republic of ChinaTel +86 18930173155Fax +86 21-64369181Email x91034@qq.comBackground: Low back pain is a prevalent symptom that occurs in all age of people, whereas the pathogenesis is unknown. Iliopsoas tendinopathy is an increasingly recognized hip disorder that may contribute to low back pain. Our purpose is to evaluate the effect of ultrasound-guided local injection of anesthetic and steroid into the trigger point of iliopsoas tendon in treating low back pain caused by iliopsoas tendinopathy.Materials and Methods: This retrospective study reviewed 45 patients diagnosed with iliopsoas tendinopathy treated by B-ultrasound guided injection of 2 mL 2% lidocaine and 1 mL (5 mg) triamcinolone acetonide into the trigger point of iliopsoas tendon from March 2016 to June 2016. Medical records were collected to analyze the clinical presentation. Numerical Rating Scale (NRS) measuring low back pain and Harris Hip score (HHS) measuring hip pain and function were administered to determine patient outcomes. Telephone follow-up was conducted, and the mean follow-up was 11 months.Results: We observed that most patients with iliopsoas tendinopathy also complain about chronic low back pain except for groin pain. After injection of anesthetic and corticosteroid into the iliopsoas tendon, the NRS of patients with low back pain fell from 7.68± 1.31 to 2.58± 1.16 immediately after the injection and 0.75± 0.73 at follow-up. The HHS improved from 43.02± 16.81 to 98.15± 2.56 at follow-up. Statistically significant difference (P< 0.001) was observed. All patients returned to their original level of function, and only five patients presented with mild low back pain at the follow-up.Conclusion: Low back pain is a prevalent presentation for iliopsoas tendinopathy. Diagnosis of iliopsoas tendinopathy should be considered in patients with low back pain with tenderness over the iliopsoas tendon. Ultrasound-guided local injection of anesthetic and steroid lead to satisfactory effect in relieving low back and groin pain and improving joint function.Keywords: low back pain, iliopsoas tendinopathy, spine, ultrasound

T-cell acute lymphoblastic leukemia (T-ALL) is a high-risk subset of acute leukemia, characterized by frequent activation of Notch1 or AKT signaling, where new therapeutic approaches are needed. We showed previously that cyclin-dependent kinase 6 (CDK6) is required for thymic lymphoblastic lymphoma induced by activated AKT. Here, we show CDK6 is required for initiation and maintenance of Notch-induced T-ALL. In a mouse retroviral model, hematopoietic stem/progenitor cells lacking CDK6 protein or expressing kinase-inactive (K43M) CDK6 are resistant to induction of T-ALL by activated Notch, whereas those expressing INK4-insensitive (R31C) CDK6 are permissive. Pharmacologic inhibition of CDK6 kinase induces CD25 and RUNX1 expression, cell cycle arrest and apoptosis in mouse and human T-ALL. Ablation of Cd25 in a K43M background restores Notch-induced T leukemogenesis, with disease that is resistant to CDK6 inhibitors in vivo. These data support a model whereby CDK6-mediated suppression of CD25 is required for initiation of T-ALL by activated Notch1, and CD25 induction mediates the therapeutic response to CDK6 inhibition in established T-ALL. These results both validate CDK6 as a molecular target for therapy of this subset of T-ALL and suggest that CD25 expression could serve as a biomarker for responsiveness of T-ALL to CDK4/6 inhibitor therapy.

Shubin Wang,1,* Juan An,2,* Weiwei Dong,3,* Xin Wang,4 Jianqiu Sheng,4 Yan Jia,4 Yuqi He,4 Xianzong Ma,4 Jiheng Wang,4 Dedong Yu,1 Xiuqin Jia,1 Bingyu Wang,5 Wenbo Yu,5 Kejia Liu,5 Yuanyuan Zhao,6 Yun Wu,1 Wei Zhu,1 Yuanming Pan1,4,6 1Department of Oncology, Baotou City Central Hospital, Baotou 014040, People’s Republic of China; 2Department of Basic Research Medical Sciences, Qinghai University, Xining 810001, People’s Republic of China; 3Department of Oncology, General Hospital of Chinese People’s Liberation Army, Beijing 100085, People’s Republic of China; 4Department of Gastroenterology, The 7th Medical Center of Chinese PLA General Hospital, Beijing 100700, People’s Republic of China; 5Yidu Cloud (Beijing) Technology Co. Ltd 8F, Health Work, Beijing 100083, People’s Republic of China; 6National Center for Nanoscience and Technology, Zhongguancun, Beijing 100190, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanming PanNational Center for Nanoscience and Technology, Zhongguancun, Beijing 100190, People’s Republic of ChinaTel +86-10-6406-9831Fax +86-10-6401-2266Email panym@nanoctr.cnWei ZhuDepartment of Oncology, Baotou City Central Hospital, Baotou, Inner Mongolia 01404, People’s Republic of ChinaTel +86-472-6955473Fax +86-472-6955708Email 18686111667@163.comIntroduction: Glioma is the primary malignant brain tumor with poor prognosis. Berberine (BBR) was the potential drug for anti-tumor in glioma cells. Based on its limitation of poor aqueous solubility and instability, little information of BBR nanoparticles is reported in glioma.Methods: Different solutions including 5% glucose, 1*PBS, ddH2O, 0.9% NaCl, cell culture medium were selected, and only 5% glucose and ddH2O exhibited BBR-related nanoparticles. After heating for a longer time or adding a higher concentration of glucose solution, BBR nanoparticles were detected by TEM analysis. The uptake of BBR-Glu or BBR-Water nanoparticles were detected by immunofluorescence analysis for BBR autofluorescence. Cell viability was measured by MTT assay and Western blotting analysis. Apoptosis was performed with flow cytometric analysis and was detected by cleaved caspase-3 immuno-fluorescent staining. Cell cycle was used by flow cytometric analysis. Cytoskeleton was observed by confocal analysis using the neuron specific Class III ß-tubulin and ß-tubulin antibodies. Mitochondrial-related proteins were detected by Western blotting analyses and mito-tracker staining in live cells. Mitochondrion structures were observed by TEM analysis. ROS generation and ATP production were detected by related commercial kits. The tracking of BBR-Glu or BBR-Water nanoparticles into blood–brain barrier was observed in primary tumor-bearing models. The fluorescence of BBR was detected by confocal analyses in brains and gliomas.Results: BBR-Glu nanoparticles became more homogenized and smaller with dose- and time-dependent manners. BBR-Glu nanoparticles were easily absorbed in glioma cells. The IC50 of BBR-Glu in U87 and U251 was far lower than that of BBR-Water. BBR-Glu performed better cytotoxicity, with higher G2/M phase arrest, decreased cell viability by targeting mitochondrion. In primary U87 glioma-bearing mice, BBR-Glu exhibited better imaging in brains and gliomas, indicating that more BBR moved across the blood–brain tumor barrier.Discussion: BBR-Glu nanoparticles have better solubility and stability, providing a promising strategy in glioma precision treatment.Keywords: berberine, glioma, glucose-nanocarrier, nanoparticles, mitochondria

Xiao Wei,1,* Zhiwei Fang,2,* Jing Sheng,1 Yu Wang,3 Ping Lu1 1Department of Geriatrics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China; 2Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China; 3Department of Cardiology, Shidong Hospital of Yangpu District, Shanghai 200438, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Wang; Ping Lu Email 1300941009@qq.com; pinglushanghai@163.comIntroduction: The main pathological mechanism of restenosis after percutaneous coronary intervention (PCI) is intimal hyperplasia, which is mainly caused by proliferation and migration of vascular smooth muscle cells (VSMCs). Our previous study found that honokiol (HNK), a small-molecule polyphenol, can inhibit neointimal hyperplasia after balloon injury, but its specific mechanism is still unclear. Moreover, poor water solubility as well as low bioavailability of honokiol has limited its practical use.Methods: We used mesoporous silica nanoparticles (MSNPs) as a standard substance to encapsulate HNK and then assemble into honokiol-mesoporous silica nanoparticles, and we investigated the effect of these nanoparticles on the process of restenosis after common carotid artery injury in rats.Results: We report a promising delivery system that loads HNK into MSNPs and finally assembles it into a nanocomposite particle. These HNK-MSNPs not merely inhibited proliferation and migration of VSMCs by reducing phosphorylation of Smad3, but also showed a higher suppression of intimal thickening than the free-honokiol-treated group in a rat model of balloon injury.Conclusion: To sum up, this drug delivery system supplies a potent nano-platform for improving the biological effects of HNK and provides a promising strategy for preventing vascular restenosis.Keywords: mesoporous silica nanoparticles, honokiol, vascular smooth muscle cells, TGF-β pathway, balloon injury, intimal thickening, restenosis

Hua Xiao,* Chongxiang Xiong,* Xiaofei Shao,* Peichun Gao, Haishan Chen, Jing Ning, Yunying Chen, Ziliang Zou, Guobao Hong, Xiaolin Li, Xu You, Jieli Sheng, Fan Wu, Xin Wang, Hequn Zou Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China *These authors contributed equally to this workCorrespondence: Hequn ZouDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaTel +86 20 6278 4391Email hequnzou@hotmail.comPurpose: To investigate the correlation between visceral obesity and pathogenesis of chronic kidney disease (CKD) among non-diabetic individuals, and to evaluate the potential of visceral adiposity index (VAI) as a predictor of CKD.Patients and Methods: From December 2017 to March 2018, 1877 non-diabetic participants (male n=699, female n=1208) in southern China were recruited for a cross-sectional survey. Males and females were divided into four groups according to gender-specific quartiles of VAI scores. A logistic regression model was established to analyze the correlation between visceral adiposity index and CKD.Results: Visceral adiposity index was positively correlated with CKD and was negatively associated with estimated glomerular filtration rate (eGFR). Using group one as the control, odds ratios (ORs) were calculated to determine the risk of developing CKD as VAI increased (male: group four 2.73 [P< 0.005]; female: Group three 1.76 [P< 0.05], Group four 2.88 [P< 0.005]). When related factors such as history of hypertension, smoking, alcohol use, and physical inactivity were normalized in the logistic model before calculation, ORs became 2.73 (male: P< 0.05), and 2.18 (female: P< 0.05), respectively. The results differed after normalizing further for systolic blood pressure (SBP), diastolic blood pressure (DBP), hypersensitive c-reactive protein (hsCRP), interleukin-6 (IL-6), homocysteine (Hcy), superoxide dismutase (SOD), and retinol-binding protein (RBP). There were no significant differences in ORs among the female groups.Conclusion: Visceral adiposity index was significantly associated with CKD in non-diabetic individuals. It may be a good predictor of the pathogenesis of CKD and was dependent on hsCRP, IL-6, Hcy, SOD, RBP, and blood pressure levels in females and males with VAI scores of 1.41 and higher. Visceral adiposity index may be used to predict CKD in males with VAI less than 0.983.Keywords: visceral adiposity index, chronic kidney disease, non-diabetic population

Wei Yu,1,* Dulei Xiang,1,* Houjun Jia,2,* Xin He,1 Jie Sheng,1 Yuxiang Long,1 Shujuan Zhu,1 Kejian Wang,1 Qian Liu1 1Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Liu Tel +86 186 2355 1357Email qianliu@cqmu.edu.cnIntroduction: Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) are deregulated in many cancers and exert their functions through multiple cancer-related biological processes. Glioma is the most common primary malignant central nervous system tumor and has a high fatality rate in adults. In current study, we aimed to determine the role and functional mechanism of the lncRNA BCYRN1 in glioma.Methods: Gain-of-function and loss-of function approaches were used to investigate the function of BCYRN1. The effects of BCYRN1 on glioma cell proliferation, migration and invasion were evaluated using MTS, Transwell and wound-healing assays. The correlation between the expression of BCYRN1 and miR-125a-5p was verified by quantitative real-time PCR.Results: The upregulation of BCYRN1 promoted the proliferation, migration and invasion of glioma cells. Meanwhile, the knockdown of BCYRN1 had the opposite effects. BCYRN1 was negatively correlated with miR-125a-5p. Additionally, TAZ, the endogenous target of miR-125a-5p, could be regulated by BCYRN1 in RNA and protein levels. A miR-125a-5p inhibitor restored BCYRN1 siRNA function in glioma.Conclusion: The present study indicates that BCYRN1 promotes glioma cell proliferation, invasion and migration in vitro. Mechanistically, upregulated expression of BCYRN1 in glioma acts as a sponge to sequester the endogenous tumor suppressor miR-125a-5p and to further increase the expression TAZ. Our findings suggest that BCYRN1 is a novel oncogene and a new therapeutic target for glioma.Keywords: BCYRN1, glioma, miR-125a-5p, ceRNA, TAZ

Haishan Chen,* Chongxiang Xiong, Xiaofei Shao,* Jing Ning, Peichun Gao, Hua Xiao, Yunying Chen, Ziliang Zou, Guobao Hong, Xiaolin Li, Mengjiao Shao, Jieli Sheng, Xingyan Yang, Xu You, Hequn Zou Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hequn ZouDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183 Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaEmail Hequnzou@hotmail.comPurpose: Metabolic syndrome (MetS), which is a global public health problem, is a state of chronic low-grade inflammation. This study looked at the changes in hematological parameters and the predictive value of the lymphocyte to high-density lipoprotein cholesterol (HDL-C) ratio (LHR) as a new index in subjects with and without MetS in coastal cities in southern China.Patients and methods: In this cross-sectional study, there were 852 participants (n = 598 with MetS and n = 254 without MetS). MetS was defined in accordance with the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATP III) criteria.Results: MetS was positively correlated with white blood cell count, total lymphocyte count, neutrophil count, red blood cell count, hematocrit, hemoglobin, and high-sensitivity C-reactive protein levels (p

Beibei Ma,1,* Jie Sheng,1,2,* Ping Wang,1 Zhongying Jiang,1,2 Entomack Borrathybay31College of Electronic and Information Engineering, Yili Normal University, Micro-nano Electric Sensing Technology and Bionic Devices Key Laboratory, Yining 835000, People’s Republic of China; 2Physics School of Nanjing University, Laboratory of Solid State Microstructures, Nanjing 210093, People’s Republic of China; 3College of Biology and Geography Sciences, Yili Normal University, Yining, Xinjiang, 835000, People’s Republic of China*These authors contributed equally to this work Background: Tumor metastasis is responsible for most cancer death worldwide, which lacks curative treatment.Purpose: The objective of this study was to eliminate tumor and control the development of tumor metastasis.Methods: Herein, we demonstrated a smart nano-enabled platform, in which 2-[2-[2-chloro-3-[(1,3-dihydro-3,3-dimethyl-1-propyl-2h-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-1-propylindolium iodide (IR780) and tirapazamine (TPZ) were co-loaded in poly(ϵ-caprolactone)-poly(ethylene glycol) (PEG-PCL) to form versatile nanoparticles (PEG-PCL-IR780-TPZ NPs).Results: The intelligence of the system was reflected in the triggered and controlled engineering. Specially, PEG-PCL not only prolonged the circulation time of IR780 and TPZ but also promoted tumor accumulation of nanodrugs through enhanced permeability and retention (EPR) effect. Moreover, reactive oxygen species (ROS) generated by IR780 armed by an 808 nm laser irradiation evoked a cargo release. Meanwhile, IR780, as a mitochondria-targeting phototherapy agent exacerbated tumor hypoxic microenvironment and activated TPZ for accomplishing hypoxia-activated chemotherapy. Most significantly, IR780 was capable of triggering immunogenic cell death (ICD) during the synergic treatment. ICD biomarkers as a “danger signal” accelerated dendritic cells (DCs) maturation, and subsequently activated toxic T lymphocytes.Conclusion: Eventually, antitumor immune responses stimulated by combinational phototherapy and hypoxia-activated chemotherapy revolutionized the current landscape of cancer treatment, strikingly inhibiting tumor metastasis and providing a promising prospect in the clinical application.Keywords: phototherapy, hypoxia-activated chemotherapy, IR780, tirapazamine, antitumor immune responsive, metastasis