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Ming-Zhu Chen,1,&ast; Xiao-Lei Chen,2,&ast; Qin Xu,3 Xiao-Dong Cao,2 Meng-Yu Wang,1 Rong Cao1 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital to Nanjing Medical University, Wuxi, 214001, People’s Republic of China; 2Nursing Department, The Affiliated Wuxi People’s Hospital to Nanjing Medical University, Wuxi, 214001, People’s Republic of China; 3School of Nursing, Nanjing Medical University, Nanjing, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Xu, School of Nursing, Nanjing Medical University, No. 101 of Longmian Road, Jiangning District, Nanijing, 211166, People’s Republic of China, Tel +86 25-86869553, Fax +86 25-86869555, Email qinxu@njmu.edu.cn Xiao-Dong Cao, Email dongdonger99@163.comObjective: To explore the mediating effects of perceived social support between frailty and self-perceived burden (SPB) in elderly patients with diabetes and to provide a theoretical basis for reducing that burden.Methods: A total of 169 elderly patients with diabetes who were hospitalised in the endocrinology department of a third-class hospital in Wuxi between May 2020 and July 2022 were included in this study using the convenience sampling method. Patients were assessed by the general information questionnaire, the Chinese version of the Tilburg frailty inventory (TFI), the Self-Perceived Burden Scale (SPBS) and the Perceived Social Support Scale (PSSS). The SPSS 22.0 software was used for Pearson’s correlation analysis and multiple linear regression analysis. Model four of the SPSS PROCESS was used for mediating the effect analysis.Results: The SPBS of elderly patients with diabetes was positively correlated with the TFI (P < 0.01) and negatively correlated with the PSSS (P < 0.01). The results of the Bootstrap test showed that the mediating effect of the PSSS on the relationship between the TFI and the SPBS in elderly patients with diabetes was 0.296 (95% CI: 0.007, 0.066), and the mesomeric effect accounted for 17.3% of the total effect.Conclusion: The debilitation of elderly patients with diabetes can be reduced by decreasing their SPB through perceived social support. This can be achieved through comprehensive interventions by nurses.Keywords: elderly patients with diabetes, frailty, self-perceived burden, mediating effects

Xiaolu Li,1,&ast; Yizhong Wang,1,2,&ast; Rong Cao,1 Fangfei Xiao,1 Xufei Wang,1 Lin Ye,1 Yongmei Xiao,1 Dan Li,1 Ting Zhang1,2 1Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yizhong Wang; Ting Zhang, Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, 355 Luding Road, Shanghai, 200062, People’s Republic of China, Tel/Fax +86 2152976335, Email wangyz@shchildren.com.cn; zhangt@shchildren.com.cnBackground: Our previous study reported a high rate of recurrence in children with Clostridioides difficile (C. difficile) infection (CDI) after conventional antibiotic therapy. Here, we aimed to explore whether metronidazole and vancomycin resistant C. difficile isolates are circulating in pediatric CDI.Methods: Antimicrobial susceptibility testing (AST) using the agar dilution method according to the Clinical and Laboratory Standard Institute (CLSI) were performed on C. difficile isolates collected from children with CDI between 2019 and 2022 at the Shanghai Children’s Hospital. Whole-genome sequencing (WGS) was performed on all C. difficile isolates, and the presence of antibiotic resistance genes (ARGs) were identified using Resfinder and the Comprehensive Antibiotic Resistance Database (CARD). The presence of plasmid pCD-METRO was detected using SRST2 (v0.2.0) against 8 pCD-METRO coding sequences.Results: A total of 50 C. difficile isolates were collected from stools of CDI children. The overall resistance rate on all isolates was 30.00% for metronidazole, 6.00% for vancomycin, 0% for rifaximin, 2.00% for rifampin, 24.00% for meropenem, 100.00% for ceftriaxone and clindamycin, 86.00% for erythromycin, 30.0% for levofloxacin, and 50.0% for tetracycline. Multidrug-resistant (MDR) was presented in 44 isolates (88.00%). Sixteen reported potential ARGs relating with resistance to antibiotic classes of aminoglycoside (AAC(6’)-Ie-APH(2”)-Ia, aad(6), ANT(6)-Ib, APH(2”)-If, APH(3’)-IIIa), lincosamide-clindamycin-erythromycin (ErmB, ErmQ), fluoroquinolones (CdeA), glycopeptides (vanRG), nucleoside (SAT-4), tetracycline (tetM, tetA(P), tetB(P), tetO), and trimethoprim (dfrF) were identified. However, the pCD-METRO plasmid and vanA/B were not detected in any isolates.Conclusion: C. difficile isolates from children with reduced susceptibility to metronidazole and vancomycin are emerging in pediatric CDI in China. The lack of pCD-METRO plasmid and vanA/B associated with reduced antibiotic susceptibility suggests there are additional mechanisms of resistance.Keywords: Clostridioides difficile, antibiotic resistance, metronidazole, vancomycin, children

Wen Wei,1,2,&ast; Chengwen Xie,3,&ast; Ronghua Cao,4,&ast; Yanwen Que,3 Xuejing Zhong,5 Zheyuan Chen,6 Fenyan Lv,6 Qianqian Kang,6 Ruiyu Lin,6 Baozhen Cao,7 Xiaomin Lai,7 Mei Tu1 1Department of Endocrinology, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 2Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 3Department of Ultrasonography, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 4Department of Nuclear Medicine, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 5Department of Science and Education, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 6Department of Endocrinology, Fujian Longyan First Hospital, Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Tu, Department of Endocrinology, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China, Tel +86 5972958989, Fax +86 5972292374, Email tm13859596628@163.comObjective: This study aims to examine the clinical significance of ultrasound evaluation of the gastrocnemius muscle (GM) in identifying sarcopenia in patients with type 2 diabetes (T2D).Methods: One hundred and fifty-three patients with T2D were included in this study. We measured the appendicular skeletal muscle mass index (ASMI), handgrip strength, and 6-meter walking speed. The US-derived muscle thickness (MT), cross-sectional area (CSA), and shear wave ultrasound elastography (SWE) of GM were also measured. We assessed the correlations between clinical indicators and US features. The model for screening sarcopenia was established using stepwise logistic regression. Stepwise linear regression was used to identify a set of variables that jointly estimated ASMI. The model’s ability to identify sarcopenia and low muscle mass was assessed by receiver operating characteristic (ROC) curve analysis.Results: The prevalence of sarcopenia in this study was 24.2%. The CSA, MT and SWE values of the patients with sarcopenia were lower than those of patients without sarcopenia (all p < 0.05). ASMI was positively correlated with CSA (r = 0.56, p < 0.001) and MT (r = 0.39, p < 0.001). Handgrip strength was positively correlated with CSA (r = 0.45, p < 0.001), MT (r = 0.25, p < 0.001), and SWE (r = 0.26, p = 0.002). A diagnostic model for sarcopenia was established with a sensitivity of 81.1%, specificity of 75.0%, and an area under the curve (AUC) of 0.800. The estimated ASMI equation was developed and found to have a positive correlation with actual ASMI (r = 0.70, p < 0.001). It was also effective in diagnosing low muscle mass, with an AUC of 0.787 for males and 0.783 for females.Conclusion: Ultrasonographic assessment of the gastrocnemius muscle was found to be a useful and convenient method for detecting sarcopenia in patients with T2D.Keywords: sarcopenia, ultrasound, shear wave elastography, gastrocnemius muscle, T2D

Rui Ma,1,&ast; Yanwen Su,2,3,&ast; Ruomu Cao,1 Kunzheng Wang,1 Pei Yang1 1Department of Bone and Joint Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi, 710004, People’s Republic of China; 2State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 3National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kunzheng Wang; Pei Yang, Email wkzh1955@163.com; yangpei@xjtu.edu.cnBackground: Tissue engineering scaffolds are porous and can be loaded with growth factors to promote osteogenesis and bone repair, which can solve the problem of clinical bone defects. The direct loading of growth factors on scaffolds is hindered by the disadvantages of low loading capacities, and uncontrollable burst release. Zeolitic imidazolate framework-8 (ZIF-8) has osteoinductive activity and drug-loading potential and can be loaded with growth factors to achieve sustained release. In this study, we aimed to establish a sustained release system of composite scaffolds loaded with growth factors to achieve the goal of slow controlled release and effective bone repair.Methods: ZIF‑8 nanoparticles loaded with bone morphogenetic protein-2 (BMP-2) were incorporated into poly-(lactide-co-glycolide)/mesoporous bioactive glass (PLGA/MBG) porous scaffolds by a 3D-printing method. The surface morphology, chemical properties and BMP-2 release of the prepared scaffold were investigated. The osteoblast adhesion, proliferation, spreading, and osteogenic differentiation in vitro and the bone repair ability in vivo of the PLGA/MBG/ZIF-8/BMP-2 (PMZB) scaffold were evaluated, and compared with those of PLGA/MBG (PM) and PLGA/MBG/ZIF-8 (PMZ) scaffolds.Results: The results showed that the PMZB scaffold exhibited a slow and continuous BMP-2 release pattern, enhanced osteoblast adhesion, proliferation, spreading and osteogenic differentiation in vitro, and promoted new bone formation and bone repair in vivo.Conclusion: The PLGA/MBG/ZIF-8/BMP-2 porous scaffold could continuously and slowly release BMP-2, enhance osteogenic activity, and promote new bone formation and bone repair at bone defects. The PMZB scaffold can be used as a bone graft material to repair bone defect at non-weight-bearing sites.Keywords: bone repair, controlled release, zeolitic imidazolate frameworks-8, mesoporous bioactive glass, scaffold

Jing Huang,1,&ast; Mengmeng Dai,1,&ast; Mingxia He,1,&ast; Weicheng Bu,1 Liwen Cao,1 Jing Jing,1 Run Cao,1 Hailong Zhang,1 Ke Men2 1Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital, Henan University, Kaifeng, Henan Province, 475004, People’s Republic of China; 2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hailong Zhang, Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital, Henan University, Kaifeng, Henan Province, 475004, People’s Republic of China, Email hailong6891@163.com Ke Men, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610044, People’s Republic of China, Email mendingbob@hotmail.comPurpose: The abnormal activation of NLRP3 inflammasome is related to the occurrence and development of ulcerative colitis (UC). However, the ideal drug and delivery system remain important factors limiting the targeting of NLRP3 inflammasome in UC therapy. Gene therapy by delivering siRNA is effective in treating various diseases. Therefore, delivering siNLRP3 using an ideal vector for UC treatment is necessary.Materials and Methods: Nanoparticles delivering siNLRP3 were developed based on cationic liposome (CLP/siNLRP3). Their ability to inhibit NLRP3 inflammasome activation was monitored using Western blot (WB) and Enzyme-linked Immunosorbent Assay (ELISA). The ASC oligomerization in LPS-primed peritoneal macrophages (PMs) was detected by WB and immunofluorescence. Moreover, we assessed the role of CLP/siNLRP3 on dextran sodium sulfate (DSS)-induced UC by examining NLRP3 levels, pro-inflammatory cytokines expression, and disease-associated index (DAI). Flow cytometry (FCM) was used to detect the contents of macrophages and T cells. Finally, we assessed the safety of CLP/siNLRP3.Results: The prepared CLP was spherical, with a small particle size (94 nm) and low permeability. The CLP could efficiently protect siNLRP3 from degradation and then deliver siNLRP3 into PMs, inhibiting NLRP3 inflammasome activation. Also, the CLP/siNLRP3 could inhibit the secretion of mature IL-1β and IL-18 from PMs, thereby achieving a favorable anti-inflammation effect. In vivo, CLP/siNLRP3 could effectively alleviate intestinal injury in UC mice, which was attributed to down-regulating levels of IL-1β and IL-18, inhibiting infiltration of macrophages and other immune cells, and the polarization of M1 macrophages. Finally, pathological testing of tissue sections and blood biochemical tests showed no significant toxic effects of CLP/siNLRP3.Conclusion: We introduced a prospective approach for the efficient delivery of siRNA in vitro and in vivo with high safety and stability, which was found to have great potential in treating NLRP3-driven diseases in an RNA-silencing manner.Keywords: cationic liposome, NLRP3, siRNA, macrophage, ulcerative colitis

Jiaoyan Chen, Keke Liu, Juan Zhang, Songhui Liu, Yuanyuan Wang, Ruiyao Cao, Xingwang Peng, Mei Han, Hui Han, Rongying Yao, Lianguo Fu Department of Child and Adolescent Health, School of Public Health, Bengbu Medical College, Bengbu, Anhui, 233030, People’s Republic of ChinaCorrespondence: Lianguo Fu, Department of child and adolescent health, School of Public Health, Bengbu Medical College, 2600 East Sea Avenue, Bengbu, Anhui, People’s Republic of China, Tel +0086-13195529639, Email lianguofu@163.comBackground: Children’s eating behaviors, body shape and body image cognition may be more susceptible to the influence of their parents, but these influences may be weakened with age. There may be different association pathways between parental pressure on children’s body image (PPCBI), body mass index (BMI), body image dissatisfaction (BID) and eating disorders (EDs) among children and adolescents at different developmental stages.Methods: The stratified cluster sampling method (Stratified by grade, and took the classes as clusters) was used to select 486 students aged 8– 15 years in two 9-year schools. Children’s body height, weight, testicular volume and breast development were measured. PPCBI, BID, and EDs were investigated using the Appearance-related Social Stress Questionnaire, Body Size Questionnaire (BID-14), and EDI-1 scale, respectively.Results: The boys before puberty initiation had significantly higher EDs score (182.3± 50.8) than girls before puberty initiation (164.1± 58.1) (P< 0.05). There were significant association pathways of PPCBI→BMI→BID→EDs and PPCBI→BID→EDs in boys before puberty initiation (β=0.035, P< 0.01; β=0.059, P< 0.01), in boys after puberty initiation (β=0.032, P< 0.01; β=0.175, P< 0.001), and in girls after puberty initiation (β=0.026, P< 0.01; β=0.172, P< 0.001). There was a positive association pathway of PPCBI→EDs in boys before puberty initiation (β=0.30, P< 0.001) and PPCBI→BID→EDs in girls before puberty initiation (β=0.176, P< 0.01).Conclusion: Parental pressure on children’s body image may positively associate with children’s eating disorders through BMI and body image dissatisfaction in boys and girls after puberty initiation and directly associate with eating disorders in boys before puberty initiation; however, it may indirectly associate with eating disorders only through BID in girls before puberty initiation.Keywords: parental pressure, body image dissatisfaction, eating disorders, children, path analysis

Yuanyuan Wang,1,* Li Zhang,1,* Lu Wu,2 Ruiyao Cao,1 Xingwang Peng,1 Lianguo Fu1 1Department of Children and Adolescent Health, School of Public Health, Bengbu Medical College, Bengbu, People’s Republic of China; 2Graduate School of Wannan Medical College, Wuhu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lianguo Fu, Department of Children and Adolescent Health, School of Public Health, Bengbu Medical College, Bengbu, 233000, People’s Republic of China, Tel +8613195529639, Fax +86-5523175215, Email lianguofu@163.comBackground: Fibronectin type III domain containing protein 5 (FNDC5) gene encodes irisin that regulates adipose tissue metabolism. Peroxide-proliferator-activated receptor γ coactivator 1α (PGC-1α) is a powerful promoter of mitochondrial biosynthesis and oxidative metabolism, which plays an important role in inducing heat production and energy consumption of brown fat. PGC1-α expression stimulated an increase in expression of FNDC5.Purpose: The aims of this study were to analyze the association between FNDC5, PGC-1α genetic variants and overweight or obesity in Chinese children and adolescents.Methods: A total of 198 children and adolescents with overweight or obesity and 198 children and adolescents with normal weight were screened according to gender and age 1:1. The healthy eating behaviors, moderate-to-vigorous physical activity time were surveyed using food frequency questionnaire and CLASS questionnaire, respectively. Genotypes of FNDC5 and PGC-1α gene were detected using SNaPshot method.Results: GT genotype of FNDC 5 (rs16835198) increased the risk of overweight or obesity in boys (OR (95% CI): 1.68 (1.00, 2.93)) based on overdominant model; GG genotype of FNDC 5 (rs16835198) decreased the risk of overweight or obesity in girls and boys (OR (95% CI): 0.45 (0.21,0.97), 0.45 (0.24, 0.83), respectively) based on dominant model; TT genotype of FNDC 5 (rs16835198) increased the risk of overweight or obesity in girls based on recessive model (OR (95% CI): 2.46 (1.19, 5.05)), and based on the additive model (OR (95% CI): 3.82 (1.49, 9.80)). There was significant interaction between FNDC 5 (rs16835198) and PGC-1α (rs3755863, rs8192678), healthy eating behaviors, moderate-to-vigorous physical activity time, interaction between PGC-1α (rs8192678) and moderate-to-vigorous physical activity time in the occurrence of overweight or obesity in Chinese children and adolescents.Conclusion: FNDC5 (rs16835198) played an independent or interactive role with PGC-1α (rs3755863, rs8192678), healthy eating behaviors, moderate-to-vigorous physical activity time in the occurrence of overweight or obesity in Chinese children and adolescents.Keywords: children, adolescents, FNDC 5, PGC-1α, gene polymorphism

An experimental study is described on the fracture toughness and micro-mechanisms associated with the initiation and propagation of cracks in metallic nickel containing marked gradients in grain size, ranging from ∼30 nm to ∼4 μm. Specifically, cracks are grown in a gradient structured (GS) nickel with grain-size gradient ranging from the coarse macro-scale to nano-scale (CG → NG) and vice versa (NG → CG), with the measured crack-resistance R-curves compared to the corresponding behavior in uniform nano-grained (NG) and coarse-grained (CG) materials. It is found that the gradient structures display a much-improved combination of high strength and toughness compared to uniform grain-sized materials. However, based on J-integral measurements in the gradient materials, the crack-initiation toughness is far higher for cracks grown in the direction of the coarse-to-nano grained gradient than vice versa, a result which we ascribe primarily to excessive crack-tip blunting in the coarse-grained microstructure. Both gradient structures, however, display marked rising R-curve behavior with exceptional crack-growth toughnesses exceeding 200 MPa.m½.

Xingwang Peng, Ruiyao Cao, Yuanyuan Wang, Rongying Yao, Hui Han, Mei Han, Lianguo Fu Department of Child and Adolescent Health, School of Public Health, Bengbu Medical College, Bengbu, Anhui, 233030, People’s Republic of ChinaCorrespondence: Lianguo Fu, Tel +86-13195529639, Fax +86-05523175215, Email lianguofu@163.comBackground: Body image dissatisfaction and aggressive behavior have become important public health problem in children and adolescents, and body image dissatisfaction may increase the occurrence of aggressive behavior. The aim of this study was to explore the correlation between body image dissatisfaction and aggressive behavior among Chinese children in different developmental stages.Methods: The stratified cluster sampling method was used to effectively survey 518 children aged 8– 15 years. The Body Shape Questionnaire and the Buss-Warren Aggressive Questionnaire scale were used to measure body image dissatisfaction and aggressive behavior. Pubertal development stages were divided into three stages according to Tanner criteria.Results: There was a main correlation path of body image dissatisfaction - hostility - anger - indirect aggression - physical aggression in boys with stage I and stage II and in girls with stage I and stage III. In addition, there were direct paths of hostility - indirect aggression, hostility - verbal aggression, anger - physical aggression, and anger - verbal aggression in boys with stage I; hostility - indirect aggression, hostility - verbal aggression, and anger - physical aggression in boys with stage II and in girls with stage I; and anger - physical aggression, and anger - verbal aggression in girls with stage III.Conclusion: Body image dissatisfaction might positively correlate with aggression through hostility among Chinese children and adolescents, and their association paths were different in different puberty stages.Keywords: aggressive behavior, body image dissatisfaction, puberty, children, adolescents

Yu Cui,1,&ast; Yu Wang,2,&ast; Jing Yang,1,&ast; Longqing Ran,1,&ast; Qianqian Zhang,1 Qinghua Huang,1 Tianqing Gong,1 Rong Cao,1 Xiao Yang3 1Department of Anesthesiology, The Affiliated Hospital, School of Medicine, UESTC Chengdu Women’s & Children’s Central Hospital, Chengdu, People’s Republic of China; 2Department of Anesthesiology, No.363 Hospital, Chengdu, People’s Republic of China; 3Department of Hospital Management, The Affiliated Hospital, School of Medicine, UESTC Chengdu Women’s & Children’s Central Hospital, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao Yang, Tel/Fax +86 13882288881, Email yczar@126.comStudy Objective: Pain management plays a pivotal role in enhanced recovery after surgery (ERAS). Erector spinae plane block (ESPB) is widely used in many regions to treat perioperative pain, but its benefits are still somewhat controversial. We, therefore, intent to systematically review the available literature on ESPB, to elucidate its effects on opioid-sparing analgesia, and summarize its potential complications.Design: Systematic review of randomized controlled trials (RCTs) with meta-analysis.Setting: Postoperative opioid consumption for various surgeries.Patients: Patients undergoing various surgeries.Intervention: We searched relevant studies in PubMed, EMBASE, Medline, and the Cochrane Library up to May 16, 2021. All prospective and RCTs that compared ESPB and sham block or no block were enrolled.Measurements: The primary outcomes were postoperative opioid consumption during the first 24 hours. The secondary outcomes were the requirement of rescue analgesia, time to first rescue analgesic and ESPB-related adverse events.Results: We included 52 trials that reported postoperative opioid consumption during the first 24 hours. The results presented that compared to control group (ie, no intervention or a sham block), ESPB reduced the accumulated opioid consumption during the first 24 h after surgery [mean difference (MD) of − 12.83 (95% CI: − 17.29 to − 8.38; p < 0.001) mg; I2 = 100%]. Besides, ESPB could prolong time to first rescue analgesia after surgery [SMD = 5.31; 95% CI 4.01– 6.61; p < 0.001; I2 = 97%]. The number of patients who received rescue analgesia after surgery in the ESPB group was less than that in the control group (OR 0.13; 95% CI 0.09, 0.21; p < 0.001; I2 = 54%), and the incidence of PONV was lower in the ESPB group (OR 0.51; 95% CI 0.43, 0.62; p < 0.001; I2 = 19%).Conclusion: ESPB is an effective technique on pain management with few complications.Keywords: erector spinae plane block, ESPB, opioid consumption, postoperative nausea and vomiting, PONV

Xin Feng,1,* Gengfan Ye,1,* Ruoyao Cao,1 Peng Qi,2 Jun Lu,2 Juan Chen,2 Daming Wang1 1Department of Neurosurgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences; Graduate School of Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Neurosurgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Daming WangDepartment of Neurosurgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences; Graduate School of Peking Union Medical College, No. 1 DaHua Road, Dong Dan, Beijing 100730, People’s Republic of ChinaTel +86 10-85136281Fax +86 10-85132621Email dm.wang@bjhmoh.cnPurpose: This study aimed to identify independent predictors for the risk of hemorrhagic transformation (HT) in arterial ischemic stroke (AIS) patients.Methods: Consecutive patients with AIS due to large artery occlusion in the anterior circulation treated with mechanical thrombectomy (MT) were enrolled in a tertiary stroke center. Demographic and medical history data, admission lab results, and Circle of Willis (CoW) variations were collected from all patients.Results: Altogether, 90 patients were included in this study; among them, 34 (37.8%) had HT after MT. The final pruned decision tree (DT) model consisted of collateral score and platelet to lymphocyte ratios (PLR) as predictors. Confusion matrix analysis showed that 82.2% (74/90) were correctly classified by the model (sensitivity, 79.4%; specificity, 83.9%). The area under the ROC curve (AUC) was 81.7%. The DT model demonstrated that participants with collateral scores of 2– 4 had a 75.0% probability of HT. For participants with collateral scores of 0– 1, if PLR at admission was < 302, participants had a 13.0% probability of HT; otherwise, participants had an 75.0% probability of HT. The final adjusted multivariate logistic regression analysis indicated that collateral score 0– 1 (OR, 10.186; 95% CI, 3.029– 34.248; p < 0.001), PLR (OR, 1.005; 95% CI, 1.001– 1.010; p = 0.040), and NIHSS at admission (OR, 1.106; 95% CI, 1.014– 1.205; p = 0.022) could be used to predict HT. The AUC for the model was 0.855, with 83.3% (75/90) were correctly classified (sensitivity, 79.4%; specificity, 87.3%). Less patients with HT achieved independent outcomes (mRS, 0– 2) in 90 days (20.6% vs. 64.3%, p < 0.001). Rate of poor outcomes (mRS, 4– 6) was significantly higher in patients with HT (73.5% vs. 19.6%; p < 0.001).Conclusion: Both the DT model and multivariate logistic regression model confirmed that the lower collateral status and the higher PLR were significantly associated with an increased risk for HT in AIS patients after MT. PLR may be one of the cost-effective and practical predictors for HT. Further prospective multicenter studies are needed to validate our findings.Keywords: acute ischemic stroke, mechanical thrombectomy; MT, hemorrhagic transformation; HT, decision tree model; DT

Gang Wang,1– 4,* Rui Cao,5,* Kaiyu Qian,1– 4,* Tianchen Peng,6 Lushun Yuan,6 Liang Chen,6 Songtao Cheng,6 Yaoyi Xiong,6 Lingao Ju,1– 4 Xinghuan Wang,6 Yu Xiao1– 4,6 1Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Human Genetics Resource Preservation Center of Wuhan University, Wuhan, People’s Republic of China; 3Human Genetics Resource Preservation Center of Hubei Province, Wuhan, People’s Republic of China; 4Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Wuhan, People’s Republic of China; 5Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Xiao; Xinghuan Wang Tel +86-27-6781-2689; +86-27-6781-3104Fax +86-27-6781-2892Email yu.xiao@whu.edu.cn; wangxinghuan@whu.edu.cnIntroduction: Based on accumulating evidence, transient receptor potential (TRP) ion channels may play important roles in the occurrence and the progression of cancer. TRP melastatin 8 (TRPM8), a member of the TRP family, functions as a Ca2+-permeable channel and regulates various physiological and pathological processes. However, the effects of TRPM8 on bladder cancer (BCa) and its underlying mechanisms have not been elucidated.Methods: BCa tissues and matched noncancerous tissues were collected to examine the expression of the TRPM8 mRNA and protein using qRT-PCR, Western blotting and immunofluorescence staining. Meanwhile, the effect of knockdown or inhibition of the activity of the TRPM8 protein on the proliferation, migration and ROS metabolism of bladder cancer cells was detected using the MTT assay, clonogenic survival assay, Transwell chamber migration assay, and reactive oxygen species (ROS) detection, respectively. Furthermore, a mouse model transplanted with BCa cells was established to assess tumor growth after TRPM8 expression was inhibited in vivo.Results: Compared with the noncancerous tissues, the levels of TRPM8 in BCa tissues were significantly increased. Knockdown or inhibition of the activity of the TRPM8 protein in BCa cells reduced cell proliferation and migration. Moreover, the production of ROS was increased in cells treated with siTRPM8, which was accompanied by increased levels of Catalase, HO-1 and SOD2. Furthermore, a mouse model transplanted with the stable TRPM8-deficient T24 cell line was established, demonstrating that knockdown of TRPM8 delayed tumor growth in vivo.Discussion: TRPM8 might play an essential for BCa tumor progression and metastasis by interfering with BCa cell proliferation, motility, ROS metabolism and migration.Keywords: bladder cancer, TRPM8, proliferation, migration, reactive oxygen species

Qingliang Shao,1 Zhiqiang Zhang,1 Rongxian Cao,2 Hui Zang,1 Wanting Pei,2 Tian Sun2 1Department of General Surgery, The Peoples’ Hospital of Liaoning Province, Shenyang City, Liaoning Province, People’s Republic of China; 2Graduate School of China Medical University, Shenyang City, Liaoning Province, People’s Republic of ChinaCorrespondence: Hui Zang Email Drzanghui0320@163.comBackground: Carboxypeptidase A4 (CPA4), as a novel tumor biomarker, is prevalently observed in various cancers. However, the potential role of CPA4 in pancreatic cancer (PC), to our knowledge, has not been fully clarified.Materials and Methods: We systematically explored the detailed function of CPA4 in epithelial to mesenchymal transition (EMT) stimulated PC in human clinical samples and in vitro.Results: CPA4 was overexpressed in clinical PC samples that was positively related with tumor size (P=0.026), T stage (P=0.011), lymph-node metastasis (P=0.026) and a worse prognosis for PC patients (P=0.001). Interestingly, CPA4 was inversely correlated with E-cadherin (r=− 0.372, P=0.003) in clinical samples and PC cell lines which cooperatively contributed to a worse prognosis (P=0.005) for PC patients. CPA4 overexpression enhanced EMT in AsPC-1 and Capan-2 cells, which promoted EMT-like cellular morphology and cell invasion and migration. Meanwhile, CPA4 overexpression activated EMT and PI3K-AKT-mTOR signaling, following with the downregulation of E-cadherin and β-catenin, and the upregulation of N-cadherin, vimentin, p-PI3K (Tyr458), p-AKT (Ser473) and p-mTOR (Ser2448). However, PI3K inhibitor LY294002 reversed CPA4 overexpression-stimulated EMT in vitro. Moreover, CPA4 was co-immunoprecipitated with AKT in two PC cells with CPA4 high expression. Conversely, CPA4 silencing inhibited EMT in PANC-1 cells. CPA4 overexpression or silencing promoted or inhibited cell proliferation and drug resistance in Capan-2 and PANC-1 cells via regulating Bcl2/Bax and cleaved-caspase3 signaling. However, LY294002 reversed CPA4 overexpression-stimulated cell proliferation and drug resistance in vitro in Bcl2/Bax and caspase3-dependent apoptosis.Conclusion: CPA4 overexpression contributes to aggressive clinical stage of PC patients and promotes EMT in vitro via activation of PI3K-AKT-mTOR signaling.Keywords: CPA4, EMT, pancreatic cancer, PI3K-AKT-mTOR signaling

Kai Li,1 Yuan Jiao,1 Xuli Ren,1 Di You,1 Rangjuan Cao2 1Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of China; 2Department of Hand-Surgery, China-Japan Union Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of ChinaCorrespondence: Rangjuan Cao Department of Hand-SurgeryChina-Japan Union Hospital of Jilin University, 126th Xiantai Avenue, Changchun 130021, Jilin, People’s Republic of ChinaTel/ Fax +86-431-89876551Email caorj@jlu.edu.cnObjective: Neuropathic pain (NP) is a debilitating condition caused by nervous system injury and chronic diseases. LncRNA H19 is upregulated in many human diseases, including NP. Cyclin-dependent kinase 5 (CDK5) aggressively worsens inflammatory action and nerve damage to cause severe NP. Phosphorylated cAMP response element binding protein (CREB) is detrimental to nerves and promotes NP progression. Herein, aim of our study was to assess the mechanism of lncRNA H19.Methods: The NP rat model was established using chronic constriction injury (CCI). Paw withdrawal threshold (PWT) tests and paw withdrawal latency (PWL) tests were performed. Then, small interfering (si)RNA against H19 was intrathecally injected into rats to suppress H19 expression. Schwann cells were isolated from NP rats and transfected with siRNA-H19 or a lentivirus (LV)-based vector expressing H19. Inflammatory factors and glial fibrillary acidic protein (GFAP) were detected. Western blot analysis was conducted to detect CDK5/p35 and p-CREB expression. Finally, H19, CDK5 and CREB phosphorylation were tested with the combination of the CDK5 inhibitor roscovitine and transfection of LV-H19 and siRNA-H19. Finally, we investigated the binding relationships between H19 and miR-196a-5p and between miR-196a-5p and CDK5 and detected the mRNA expression of miR-196a-5p and CDK5 in rats with H19 knockdown and in Schwann cells with H19 knockdown.Results: Highly expressed H19, CDK5/p-35 and p-CREB were observed in NP rats, accompanied by obviously decreased PWT and PWL, upregulated inflammatory factors and GFAP levels, and reduced 5-HT2A and GABAB2 expression. siRNA-H19 restored NP-related indexes and downregulated CDK5/p35 and p-CREB phosphorylation. siRNA-H19, together with the CDK5 inhibitor roscovitine, reduced CDK5 and p-CREB expression in Schwann cells isolated from NP rats. Binding sites between H19 and miR-196a-5p and between miR-196a-5p and CDK5 were identified. Silencing H19 upregulated miR-196a-5p expression and downregulated CDK5 levels.Conclusion: Our study demonstrated that silencing H19 inhibited NP by suppressing CDK5/p35 and p-CREB phosphorylation via the miR-196a-5p/CDK5 axis, which may provide new insight into NP treatment.Keywords: neuropathic pain, long noncoding RNA H19, cyclin-dependent kinases 5, cAMP response element binding protein phosphorylation, roscovitine

Yijia Guo, Rui Cao, Xiangyan Zhang, Letian Huang, Li Sun, Jianzhu Zhao, Jietao Ma, Chengbo Han Department of Oncology, Shengjing Hospital of China Medical University, China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Chengbo HanDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, People’s Republic of ChinaTel +86 189 4025 9860Email hanchengbo@sj-hospital.orgAbstract: Non-small cell lung cancer (NSCLC) is frequently associated with oncogenic driver mutations, which play an important role in carcinogenesis and cancer progression. Targeting epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase rearrangements has become standard therapy for patients with these aberrations because of the greater improvement of survival, tolerance, and quality-of-life compared to chemotherapy. Clinical trials for emerging therapies that target other less common driver genes are generating mixed results. Here, we review the literature on rare drivers in NSCLC with frequencies lower than 5% (e.g., ROS1, RET, MET, BRAF, NTRK, HER2, NRG1, FGFR1, PIK3CA, DDR2, and EGFR exon 20 insertions). In summary, targeting rare oncogenic drivers in NSCLC has achieved some success. With the development of new inhibitors that target these rare drivers, the spectrum of targeted therapy has been expanded, although acquired resistance is still an unavoidable problem.Keywords: non-small cell lung cancer, oncogenic driver, targeted therapy

Fan Yang,1,2 Mo Xu,1 Shiqing Wang,1 Le Song,1 Dandan Yu,1 Yao Li,1 Rui Cao,1 Zhang Xiong,1,2 Zhijun Chen,1 Qian Zhang,1 Bing Zhao,2 Siying Wang1 1School of Basic Medical Sciences, Anhui Medical University, Hefei, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Siying WangSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui Province 230032, People’s Republic of ChinaTel +86 551 6516 1215Email sywang@ahmu.edu.cn Bing ZhaoDepartment of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province 230601, People’s Republic of China Tel +86 551 6386 9502Email aydzhb@126.comPurpose: The aim of this study was to investigate the effects of gain-of-function (GOF) E76K-mutant Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) on the biological behaviors of glioblastoma (GBM) cells, and explore the molecular mechanisms of GBM progression.Methods: Firstly, a negative control vector and vectors overexpressing SHP2 and E76K-mutant SHP2 were transduced into GBM cells (U87 and A172) using a lentivirus. The effect of GOF-mutant SHP2 on proliferation was measured using the MTT assay, flow cytometry, colony formation assay, and soft agar assay. Moreover, the migration and invasion of GBM cells were determined through the transwell assay. Related proteins of the extracellular signal-regulated kinase/cAMP response element binding protein (ERK/CREB) pathway were detected by Western blotting analysis. A xenograft model was established to confirm the tumor-promoting effect of GOF-mutant SHP2 in vivo. Finally, ERK was inhibited using a mitogen-activated protein kinase/ERK kinase inhibitor (U0126) to further explore the molecular mechanism of GOF-mutant SHP2 affecting GBM cells.Results: After transduction, the expression of SHP2 in the SHP2-mutant and SHP2-overexpression groups was higher than that observed in the control and normal groups. Our data indicated that GOF-mutant SHP2 enhanced the abilities of GBM cells for proliferation, migration, and invasion in vitro, and promoted tumor growth in vivo. Mechanistically, the ERK/CREB pathway was activated, and the levels of relevant proteins were increased in the SHP2-mutant group. Furthermore, following inhibition of ERK in the GOF-SHP2 mutant group, the activation of CREB was also depressed, and the malignant biological behaviors were weakened accordingly.Conclusion: The GOF-mutant SHP2 promoted GBM cell proliferation, metastasis, and tumor growth through the ERK/CREB pathway, providing a promising target for the treatment of GBM.Keywords: glioblastoma, E76K mutation, SHP2, malignant behavior, ERK, CREB, cancer

A rapid switch from hyperbolic to isokinetic cycling allows the velocity-specific decline in maximal power to be measured, i.e., fatigue. We reasoned that, should the baseline relationship between isokinetic power (Piso) and electromyography (EMG) be reproducible, then contributions to fatigue may be isolated from 1) the decline in muscle activation (muscle activation fatigue); and 2) the decline in Piso at a given activation (muscle fatigue). We hypothesized that the EMG-Piso relationship is linear, velocity dependent, and reliable for instantaneous fatigue assessment at intolerance during and following whole body exercise. Healthy participants (n = 13) completed short (5 s) variable-effort isokinetic bouts at 50, 70, and 100 rpm to characterize baseline EMG-Piso. Repeated ramp incremental exercise tests were terminated with maximal isokinetic cycling (5 s) at 70 rpm. Individual baseline EMG-Piso relationships were linear (r(2) = 0.95 ± 0.04) and velocity dependent (analysis of covariance). Piso at intolerance (two legs, 335 ± 88 W) was ∼45% less than baseline [630 ± 156 W, confidence interval of the difference (CIDifference) 211, 380 W, P < 0.05]. Following intolerance, Piso recovered rapidly (F = 44.1; P < 0.05; η(2) = 0.79): power was reduced (P < 0.05) vs. baseline only at 0-min (CIDifference 80, 201 W) and 1-min recovery (CIDifference 13, 80 W). Activation fatigue and muscle fatigue (one leg) were 97 ± 55 and 60 ± 50 W, respectively. Mean bias ± limits of agreement for reproducibility were as follows: baseline Piso 1 ± 30 W; Piso at 0-min recovery 3 ± 35 W; and EMG at Piso 3 ± 14%. EMG power is linear, velocity dependent, and reproducible. Deviation from this relationship at the limit of tolerance can quantify the "activation" and "muscle" related components of fatigue during cycling.

Li K, Jiao Y, Ren X, You D, Cao R. J Pain Res. 2020;13:2113–2124. At the request of the authors, the Editor-in-chief and Publisher of Journal of Pain Research wish to retract the following article. In the reported study the authors found that Long noncoding RNA H19 was highly expressed in the spinal dorsal horn after chronic constriction injury in rats, and the silencing of H19 could ameliorate neuropathic pain via the von Frey filament test. Recently, the authors performed another batch of experiments using the same neuropathic pain model, and knockdown of H19 by siRNA served as a positive control, which was supposed to inhibit neuropathic pain. However, the authors found that the silencing of H19 by the siRNA did not ameliorate the neuropathic pain and despite several attempts the behavioral test previously described could not be reproduced and the authors cannot clearly explain the reason for this. As they are unable to support their findings the authors wish to retract the published paper and the editor has agreed with this request. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper