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Yuwei Jiang,1,2,* Wenjun Dang,3,* Lirong Sui,1 Tianci Gao,1 Xiangying Kong,1 Jin Guo,1 Shuang Liu,1 Hong Nie,3 Zhimei Jiang1,2 1College of Rehabilitation Medicine, Jiamusi University, Jiamusi City, Hei longJiang Province, People’s Republic of China; 2Pediatric Cerebral Palsy Prevention and Treatment Center of Heilongjiang Province, Jiamusi City, Hei longJiang Province, People’s Republic of China; 3College of Jiamusi, HeiLongJiang University of Chinese Medicine, Jiamusi City, Hei longJiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhimei Jiang; Shuang Liu, Email 15704601990@163.com; 307692456@qq.comAbstract: We conducted an umbrella evaluation to quantitatively synthesize previous systematic reviews and meta-analyses, thereby collating evidence on the association between vitamin D and core symptoms in people with autism in anticipation of informing clinical vitamin D supplementation. Based on the pre-established protocol, we ended up with 9 studies. Based on rigorous analysis, we found that vitamin D deficiency early in life is a risk factor for the development of ASD and that vitamin D supplementation improves the core symptoms of ASD. Our study concludes that vitamin D supplementation is beneficial for individuals with autism, that vitamin D deficiency early in embryonic life increases the risk of ASD, and that our study supports the idea that prevention begins with vitamin D supplementation early in life. At the same time, we must recognize that our current conclusions support the benefits of vitamin D supplementation for children with ASD, but we are unable to determine the causal relationship, ie, how vitamin D works in ASD, and we need more basic research to explore the mechanisms involved.Keywords: autism spectrum disorders, vitamin D, core symptoms, 25(OH)D, umbrella review

Li Xie,1,* Xiangyi Kong,1,2,* Jidong Gao1,2 1Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, People’s Republic of China; 2Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jidong Gao, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, People’s Republic of China, Email ab168@cicams.ac.cnAbstract: In the vast expanse of restorative surgical procedures, the Deep Inferior Epigastric Perforator (DIEP) flap, originating from the inferior epigastric artery, has emerged as the preferred method of breast reconstruction, attributable to its myriad advantages. The technique provides reliable vascular supply, robust tissue volume for excision, minimal invasiveness to the donor site, with direct closure and concealment of the said site. This paper embarks on an elaborate elucidation of the DIEP surgical procedure, pivoting on the analytical exploration of a particular instance where necrosis of the skin flap occurred following immediate DIEP breast reconstruction in a patient diagnosed with early-stage breast cancer. This patient had previously undergone Nipple Areola Complex Sparing Mastectomy (NSM). We endeavor to extrapolate insights from this singular case of post-NSM DIEP breast reconstruction failure and correlate our findings with current literature dedicated to similar instances of surgical failure in DIEP breast reconstruction.Keywords: breast cancer, NSM, DIEP, breast reconstruction

Arbuscular mycorrhizal fungi (AMF) play an important role on litter decomposition, which is increasing suffering the negative impact of acid deposition. In this study, we investigated the AMF effects on litter decomposition via suppressing AMF and simulating acid deposition in a subtropical Cinnamomum camphora forest. The results showed that acid deposition and AMF suppression decelerated C. camphora leaf litter decomposition, especially at late decomposition stage; soil water content was the main factor restricting early-stage decomposition. The inhibiting effect of acid deposition was enhanced with acid intensity increase and AMF suppression aggravated the negative effect of acid stress on decomposition. Nitrogen-cycling enzymatic activity was significantly higher in later than in early decomposition stage, and acid deposition and AMF suppression significantly decreased microbial activity. Despite the seasonal effect was overwhelming, we still detected the effects of acid deposition and AMF suppression on litter nutrient release. Without or under low acid deposition, AMF suppression significantly increased organic matter and decreased alkali-hydrolyzable nitrogen content of detritusphere soil. Acid deposition significantly reduced soil organic matter content, while high acid deposition intensity increased alkali-hydrolyzable nitrogen content after 2- and 12-month decomposition, and decreased it at other months. Both acid deposition and AMF suppression decreased available phosphorus content, but did not affect phosphatase activity. AMF effects on invertase and nitrogen-release enzyme activities, and alkali-hydrolyzable nitrogen and available phosphorus contents of detritusphere soil were highly sensitive to acid deposition. Our results revealed that AMF effects on microbial activity and nutrient release during litter decomposition are sensitive to acid deposition.

Xu X, Yan Y, Xun Q, et al. Onco Targets Ther. 2019;12:1215-1223. We, the Editor and Publisher of the journal OncoTargets and Therapy have retracted the published article. Following publication of the article, the authors raised concerns about the duplication of images from Figure 2. Specifically, The images for Figure 2D, siVEGF and siANG, have been duplicated. The corresponding author was cooperative and responded to our queries but was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Xing Z, Zhang Z, Gao Y, et al. Onco Targets Ther. 2020;13:3151–3163. We, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figure 3 with images from other unrelated articles. Specifically, Images for Figure 3B have been duplicated with images for Figure 2C from Zhao C, Li Y, Hu X, et al. LncRNA HCP5 Promotes Cell Invasion and Migration by Sponging miR-29b-3p in Human Bladder Cancer. Onco Targets Ther. 2020;13:11827-11838. https://doi.org/10.2147/OTT.S249770 and Figure 3H from Peng Y, Li X, Liu H, et al. RETRACTED ARTICLE: microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway. Nanoscale Res Lett. 2020;15:196. https://doi.org/10.1186/s11671-020-03416-8. The authors did not respond to our queries and were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Hong Li,1 Shuai Meng,2 Weiguang Chen,3 Xuan Lei,4 Xiangyun Kong,5 Huagang Zhu6 1Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Cardiology, 1st Hospital Affiliated of Hebei North University, Zhangjiakou, Hebei Province, People’s Republic of China; 4Department of Cardiology, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of General Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Hong Li, Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13311573539, Email 13311573539@139.comBackground: The clinical value of the Syntax score in patients with non-ST segment elevation myocardial infarction (NSTEMI) has been well established. The neutrophil–lymphocyte ratio (NLR), the platelet–lymphocyte ratio (PLR), the high sensitivity C-reactive protein (hsCRP)-albumin ratio (hsCAR), and systemic immune-inflammatory (SII) index are promising systemic inflammation (SI) biomarkers in coronary artery diseases. However, studies which compare the predicting value of these SI indicators with the Syntax score in NSTEMI patients are limited.Material and Methods: NSTEMI patients who underwent coronary angiography (CAG) in our department were retrospectively enrolled. Both univariable and multivariable logistic regression analyses were performed to evaluate the clinical value between SI biomarkers and Syntax score in these patients. The area under the receiver operating characteristic curve (ROC) was used to compare the clinical values of these parameters in predicting 6-month major cardiovascular events (MACE) and over-all mortality.Results: A total of 429 NSTEMI patients were finally enrolled in this study. The level of NLR, PLR, as well as hsCAR, and SII in patients with high Syntax scores, are significantly higher than patients with the low Syntax score. Multivariable logistic regression analysis demonstrated that all of the SI indicators but not the Syntax score were the independent risk factors of 6-month MACE in NSTEMI patients. ROC showed that all of the SI indicators had better predictive value than the Syntax score in these patients (0.637, 0.592, 0.631, 0.590, 0.559, respectively) in predicting MACE and similar predictive value in over-all mortality (0.530, 0.524, 0.761, 0.553, 0.620, respectively).Conclusion: Novel SI biomarkers including NLR, PLR, hsCAR, and SII have better predictive value in MACE and similar predictive value in over-all mortality compared with Syntax score in NSTEMI patients.Keywords: neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, high-sensitivity C-reactive protein–albumin ratio, non-ST segment elevation myocardial infarction

Tianshui Niu,1,2,&ast; Lihua Guo,2,&ast; Xiaoyang Kong,2,&ast; Fei He,1 Chuhui Ru,1 Yonghong Xiao2 1Department of Respiratory and Critical Care Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Xiao, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel/Fax +86 571 87236421, Email xiaoyonghong@zju.edu.cnBackground: Different sequence types of Acinetobacter baumannii (AB) have their own epidemiological characteristics, drug resistance, and toxicity.Methods: AB bloodstream infection (BSI) in the First Affiliated Hospital of Medical College of Zhejiang University from January 2012 to December 2017 were classified by multilocus sequence typing. Clinical data of patients were retrospectively analyzed, drug resistance and toxicity were respectively studied by drug sensitivity and complement killing tests.Results: 247 unduplicated AB strains were collected, and ST191/195/208, the main epidemic dominant strain, accounted for 70.9%. Patients with ST191/195/208 on infection had higher white blood cell (10.8 vs 8.9, p = 0.004), neutrophil% (89.5 vs 86.9, p = 0.005), neutrophil count (9.5 vs 7.1, p = 0.021), D-dimer (6.7 vs 3.8, p = 0.000), total bilirubin (27.0 vs 21.5, p = 0.038), pronatriuretic peptide (324 vs 164, p = 0.042), C-reactive protein (82.5 vs 56.3, p = 0.048), clinical pulmonary infection score (CPIS; 7.33 ± 2.30 vs 6.50 ± 2.72, p = 0.045), and acute physiology and chronic health evaluation-II (APACHE-II; 19.620 ± 5.1850 vs 17.648 ± 6.1251, p = 0.011). Patients with ST191/195/208 had more complications, including pulmonary infection (p = 0.041), septic shock (p = 0.009), and multiple organ failure (p = 0.019). Patients with ST191/195/208 had higher 3 day mortality (24.6% vs 13.9%, p = 0.043), 14 day mortality (46.8% vs 26.8%, p = 0.003), and 28 day mortality (55.0% vs 32.4%, p = 0.001). ST191/195/208 strains had higher drug resistance to most antibiotics, and higher survival rate at 90% normal serum concentration (p < 0.001).Conclusion: ST191/195/208 strains predominate in the hospital and prevails in patients with severe infections with increased multidrug antimicrobial resistance and excessive mortality compared to any other AB stains.Keywords: Acinetobacter baumannii, bloodstream infection, MLST, mortality, toxicity

Haochen Jiang,1,2,&ast; Zhi Shang,2,&ast; Liping You,1,2,&ast; Jinghao Zhang,1 Junzhe Jiao,2 Yihan Qian,2 Jiacheng Lin,2 Fang Wang,2 Yueqiu Gao,1 Xiaoni Kong,2 Xuehua Sun1 1Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuehua Sun, Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Email susan_sxh@shutcm.edu.cn Xiaoni Kong, Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Email xiaonikong@shutcm.edu.cnBackground and Purpose: Current pharmacological approaches to prevent hepatic ischemia/reperfusion injury (IRI) are limited. To mitigate hepatic injury, more research is needed to improve the understanding of hepatic IRI. Depending on traditional Chinese medicine (TCM) theory, acupuncture therapy has been used for the treatment of ischemic diseases with good efficacy. However, the efficacy and mechanism of acupuncture for hepatic IRI are still unclear.Methods: Blood provided to the left and middle lobe of mice livers was blocked with a non-invasive clamp and then the clamps were removed for reperfusion to establish a liver IRI model. Quantitative proteomics approach was used to evaluate the impact of EA pretreatment on liver tissue proteome in the IRI group. Serum biochemistry was used to detect liver injury, inflammation, and oxidative stress levels. H&E staining and TUNEL staining were used to detect hepatocyte injury and apoptosis. Immunohistochemistry and ELISA were used to detect the degree of inflammatory cell infiltration and the level of inflammation. The anti-inflammatory and antioxidant capacities were detected by Quantitative RT-PCR and Western blotting.Results: We found that EA at Zusanli (ST36) has a protective effect on hepatic IRI in mice by alleviating oxidative stress, hepatocyte death, and inflammation response. Nuclear factor E2-related factor 2 (Nrf2) as a crucial target was regulated by EA and was then successfully validated. The Nrf2 inhibitor ML385 and cervical vagotomy eliminated the protective effect in the EA treatment group.Conclusion: This study firstly demonstrated that EA pretreatment at ST36 significantly ameliorates hepatic IRI in mice by inhibiting oxidative stress via activating the Nrf2 signal pathway, which was vagus nerve-dependent.Keywords: inflammation, liver, proteomics

Xiangshu Kong, Kuiran Liu Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Kuiran Liu, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 1100001, People’s Republic of China, Tel +86 18940251585, Email liukr0412@163.comPurpose: To study the early predictive value of WBC, CRP and PCT on infectious complications after epithelial ovarian cancer surgery, draw ROC curves, and construct a nomogram prediction model.Patients and Methods: The clinical data of patients with epithelial ovarian cancer in Shengjing Hospital from August 2019 to August 2022 were included. The levels of WBC, CRP and PCT were statistically analyzed on the first, third and fifth days after surgery, and the ROC was plotted. Multivariate logistic regression analysis determined independent influencing factors, individualized nomogram model for predicting the occurrence of postoperative infectious complications was constructed, and the correction curve was used for verification.Results: A total of 116 patients were enrolled. The postoperative test levels of WBC, CRP and PCT were compared between two groups, and the differences on POD3 and POD5 were statistically significant. The ROC area on POD5 was 0.739, 0.838 and 0.804, respectively, better than that on POD3. Among them, CRP has the greatest value; The predicted value of the combined test of WBC, CRP and PCT on POD5 was greater than that of a single index on POD5. The nomogram model on POD5 was constructed, and the ROC analysis showed that it had a good degree of differentiation.Conclusion: WBC, CRP and PCT can effectively predict the occurrence of postoperative infectious complications, among which CRP alone has the greatest diagnostic value on POD5, and the combined test value of the three indicators is higher than that of a single index. The nomogram model constructed by the combined indicators on POD5 can assess the risk individually.Keywords: surgery, epithelial ovarian cancer, postoperative infectious complications, prediction

Sha Peng,1,2 Xiaoya Kong,1,2 Guiyuan Ma,1,2 Jianmei Hou,1 Lingxia Luo,1 Ran Xu,1,2 Yuhua Fan,1 Jinghui Zhang1– 3 1Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Xiangya Nursing School, Central South University, Changsha, Hunan, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jinghui Zhang, Email zhangjh-1206@163.comPurpose: The present study aims to evaluate the current situation of knowledge, attitude and practice of clinical nurses in catheter-related thrombosis, analyze its influencing factors, enhance the attention of nursing managers and clinical nurses about catheter-related thrombosis, and provide a basis for formulating catheter-related thrombosis training plan.Patients and Methods: The research was conducted from January 1 to February 31, 2022, we recruited 549 nurses from two hospitals in Hunan province in this cross-sectional study using a two-stage random sampling method. We used a self-designed questionnaire with good reliability and validity to measure clinical nurses’ knowledge, attitudes, and practice toward catheter-related thrombosis. We used χ2 test, Welch t-test, and multiple linear regression analysis to analyze the data.Results: The knowledge of clinical nurses about catheter-related thrombosis was insufficient (55.00%), while the attitude was positive (88.49%) and the practice was inadequate (68.62%). Knowledge of clinical nurses was significantly associated with job title (β: 1.069, P< 0.001), educational level (β: 0.094, P< 0.05), and training times (β: 0.085, P< 0.05), which were positive factors while whether they are specialized nurses in intravenous therapy (β: − 0.126, P< 0.05), and hospital level (β: − 0.101, P< 0.05) were negative factors. Training times (β: 0.166, P< 0.001), job title (β: 0.099, P< 0.019), and hospital level (β: 0.090, P< 0.05) were associated factors of attitude. Moreover, training times (β: 0.255, P< 0.001) was the only factor associated with the practice.Conclusion: Although clinical nurses hold a positive attitude towards catheter-related thrombosis, their knowledge level was unsatisfactory and their practice was affected by many factors, suggesting that nursing managers should strengthen the training and skill assessment of catheter-related thrombosis. At the same time, the hospital can formulate relevant rules, regulations, and guidelines to reduce the incidence of catheter-related thrombosis.Keywords: knowledge, attitude, practice, clinical nurses, catheter-related thrombosis

Yubo Liu,1,2,&ast; Shuai Zhang,2,3,&ast; Chao Li,2,4,&ast; Mingyang Ma,2,3 Minzhi Yang,1,2 Renwen Guo,2,3 Xiangpeng Kong,2,4 Wei Chai2,4 1School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China; 2Senior Department of Orthopedics, the Fourth Medical Center of PLA General Hospital, Beijing, 100048, People’s Republic of China; 3Medical School of Chinese People’s Liberation Army, Beijing, 100853, People’s Republic of China; 4National Clinical Research Center for Orthopaedics, Sports Medicine & Rehabilitation, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangpeng Kong; Wei Chai, Email 18810999609@163.com; chaiweiguanjie@sina.comAim: Subtrochanteric shortening osteotomy (SSO) is often applied during total hip arthroplasty (THA) in high hip dislocations. The aim of the present paper was to evaluate the results of fixation by autogenous cortical plate technique on sites of SSO in THA for patients with Crowe type IV developmental dysplasia of the hip (DDH).Methods: We conducted a historical prospective cohort study and reviewed 67 patients (82 THAs) with SSO performed between March 2016 and May 2020. Thirty-nine patients (48 hips) obtained stability by intramedullary pressure provided by the S-ROM modular prostheses and with or without prophylactic binding by stainless-steel wire after osteotomy and before stem implantation (group A). Twenty-eight patients (34 hips) were fixed with autogenous cortical plate technique and stainless-steel wire or cables (group B). Time of operations, complications, radiographic results and clinical scores were compared.Results: One intraoperative fracture and a dislocation occurred, while component loosening, ectopic ossification and osteolysis were not observed. Group B had a higher union rate at the 4th month than group A (P = 0.015) while there were no significant differences of union rates at the 8th (P = 0.811) and the 12th month (P = 0.722) and of the average healing time (P = 0.181). No significant differences were found in hip function scores (HHS and WOMAC Osteoarthritis Index) between two groups.Conclusion: Fixation with autogenous cortical plate from the cylinder of femoral bone contributes to early bone union of osteotomy ends in Crowe type IV DDH patients compared to those who do not apply the technique. Besides of application of autogenous cortical strut grafts, relevant measures are as well recommended to prevent nonunion after SSO.Keywords: developmental dysplasia of the Hip, subtrochanteric shortening osteotomy, autogenous cortical plate technique, bone union, total Hip arthroplasty

Xiaojuan Dai,1 Jinghua Wang,1 Xiao Zhang,1 Li Wang,1 Sifan Wu,1 Huiyong Chen,1 Ying Sun,1 Lili Ma,1 Lingying Ma,1 Xiufang Kong,1 Lindi Jiang1,2 1Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Center of Clinical Epidemiology and Evidence-Based Medicine, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Lindi Jiang; Xiufang Kong, Email zsh-rheum@hotmail.com; kongxiufang2007@163.comObjective: This study aimed to analyze biomarker changes in patients with TAK following treatment with glucocorticoids (GCs) and tofacitinib (TOF).Methods: Seventeen patients from a prospective TAK cohort treated with GCs and TOF and 12 healthy individuals were recruited. TAK associated cytokines, chemokines, growth factors, and MMPs were analyzed in these patients before and after GCs and TOF treatment, and healthy controls. Molecular signatures associated with clinical features were evaluated.Results: Patients’ cytokines (PTX3, IL-6, IFN-γ), chemokines (IL-16, CCL22, CCL2), growth factors (VEGF), and MMP9 levels were significantly higher at baseline (all p < 0.05), while patients’ FGF-2 levels were significantly lower (p = 0.02). After treatment, IL-10 was significantly increased at 6 months (p=0.007), and inflammatory cytokines such as PTX3, IL-6 demonstrated a downward trend. Patients without vascular occlusion had higher baseline CCL22 levels than patients with it (p = 0.05), which remained persistently higher after treatment. Radar plot analysis demonstrated that PTX3 was closely correlated with disease activity. In addition, patients without imaging improvement had relatively higher baseline levels of CCL22, FGF-2, and PDGF-AB (p = 0.056, p = 0.06 and p = 0.08 respectively) and lower baseline levels of TNFα, ESR, and CRP (p=0.04, p=0.056, p=0.07, respectively) compared with patients without it.Conclusion: GCs and TOF are effective in decreasing inflammatory molecules but have limited efficacy in regulating multiple other markers involved in TAK. PTX3 is a prominent marker for disease activity, and CCL22 may have a predictive value for vascular progression.Keywords: Takayasu arteritis, tofacitinib, molecular signature, biomarker changes

Shan Sun,1 Kai Chen,2 Xuehua Kong,2 Wenjun Tian,3,&ast; Siqiang Niu1,&ast; 1Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Clinical Laboratory Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Tian; Siqiang Niu, Email twenjun708@163.com; siqiangniu@cqmu.edu.cnPurpose: This study aimed to understand the distribution characteristics of carbapenemase genes and assess the antimicrobial activities of aztreonam/avibactam (ATM/AVI) and ceftazidime/avibactam (CAZ/AVI) against carbapenem-resistant Enterobacterales (CRE) isolates in Chongqing, Southwest China.Methods: CRE isolates and their clinical information were collected from 22 hospitals covering all the five regions across Chongqing between January 1, 2016 and December 31, 2017. PCR was used to screen for common carbapenemase genes. And minimum inhibitory concentrations (MICs) were determined by broth microdilution method.Results: A total of 312 unduplicated CRE isolates (eg, 206 Klebsiella pneumoniae, 43 Escherichia coli, and 42 Enterobacter cloacae) were collected during the two-year study period. Among these CRE isolates, 92.3% carried carbapenemase genes, with a majority of isolates carrying single blaKPC-2 (47.1%) or single blaNDM/IPM (36.2%) and 8.9% of isolates carrying two or three carbapenemase genes. Notably, 95.6% (197/206) K. pneumoniae, 86.0% (37/43) E. coli and 88.1% (37/42) E. cloacae harbored carbapenemase genes. In addition, blaKPC-2 was prevalent in K. pneumoniae (70.4%), while blaNDM was predominant in E. coli (83.7%) and E. cloacae (78.6%). Besides, only metallo-β-lactamase (MBL) genes were detected in the CRE isolates from children. Overall, 0.0%, 48.1%, 59.0%, 61.5% and 63.1% of the CRE isolates were resistant to ATM/AVI, CAZ/AVI, nitrofurantoin, amikacin and trimethoprim/sulfamethoxazole, respectively. 99.7% of the total 312 isolates could be killed by ATM/AVI with the MIC 1 μg/mL, whereas CAZ/AVI showed good antibacterial activity (98.0% susceptible) against the blaKPC-2-carriers with the MIC50/90 values of 1/4 μg/mL.Conclusion: The distribution features of carbapenemase genes in Chongqing were comprehensively illustrated in terms of species and sources of CRE for the first time in this multi-center study that covered all the geographical locations across Chongqing. ATM/AVI showed superior activity against all CRE isolates regardless of their genotype, whereas CAZ/AVI was active against almost all KPC-producers.Keywords: carbapenem-resistant Enterobacterales, carbapenemase genes, aztreonam/avibactam, ceftazidime/avibactam

Ping Song,1– 3,&ast; Xiangpeng Kong,2,3,&ast; Minzhi Yang,2,3 Mingyang Ma,1– 3 Wei Chai2,3 1Graduate School, Chinese PLA Medical School, Beijing, People’s Republic of China; 2Senior Department of Orthopedics, the Fourth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center for Orthopedics, Sports Medical and Rehabilitation, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Chai, Tel +8610-66938304, Email chaiweiguanjie@sina.comBackground: This study aims to investigate the course and anatomical characteristics of sciatic and femoral nerves in unilateral Crowe type-IV developmental dysplasia of the hip (DDH) patients.Methods: We conducted a retrospective own-control study of patients with unilateral Crowe type-IV DDH. Bilateral hip computed tomography (CT) of 21 female patients was reviewed in our institute from February 2018 to February 2020. The distances between nerves and bony landmarks were measured in different CT sections (anterior superior iliac spine, acetabular inner wall, teardrop, and ischial tuberosity) to analyze the anatomical position and course of sciatic and femoral nerves between bilateral hips.Results: In the section of the acetabular inner wall, the distance between the femoral nerve and the acetabular anterior wall in affected hip (13.20 ± 3.59 mm) was significantly smaller than that in the healthy hip (16.58 ± 5.12mm) (p < 0.001). In other sections, the distances between nerves and bony landmarks in affected hips were significantly larger than or equal to those in the healthy hips.Conclusion: In female patients with unilateral Crowe type-IV DDH, the femoral nerve in the affected hip runs closer to the anterior acetabular wall than that in the healthy hip.Keywords: developmental dysplasia of the hip, total hip arthroplasty, nerve injury, nerve course, sciatic nerve, femoral nerve

Jianmei Hou,1,2 Binbin Xu,1 Jinghui Zhang,1,3,4 Lingxia Luo,1,5 Xiaobei Pen,1,6 Shujie Chen,1,4 Guiyuan Ma,1,4 Zixing Hu,1,4 Xiaoya Kong1,4 1Teaching and Research Section of Clinical Nursing, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 2Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, People’s Republic of China; 4Xiangya Nursing School, Central South University, Changsha, Hunan, People’s Republic of China; 5Emergency Department, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 6Intensive Care Unit, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaCorrespondence: Jinghui Zhang, Tel +86 15874032339, Email zhangjh-1206@163.comPurpose: Investigating psychological status and job burnout of nurses working in the frontline of the novel coronavirus in Zhangjiajie city in China during the Delta variant outbreak, comparing differences and analyzing factors of these two variables between the nurses from different nucleic acid testing (NAT) sites.Patients and methods: This survey was conducted from August 1 to 31, 2021. The participants were 512 nurses, 198 nurses of whom were from temporary NAT sites in communities/towns in Zhangjiajie city, and the rest were from NAT sites inside hospitals. The psychological status and the job burnout were measured by the Symptom Checklist-90 (SCL-90) and the Maslach Burnout Inventory-General Scale (MBI-GS).Results: The prevalence of the SCL-90 positive result and job burnout were 49.4% and 61.1%, respectively. The factors influencing the psychological status of nurses included the contact with COVID-19 patients or their body fluids and specimens, working seniority and the duration of working in the frontline of the novel coronavirus. The independent risk factors of nurses’ job burnout included the following four factors. Firstly, the contact with COVID-19 patients or their body fluids and specimens (OR=150.95, 95% CI=(44.87,507.77), P< 0.001). Secondly, five to nine years of working seniority (OR=8.91, 95% CI=(3.59,22.14), P< 0.001). Thirdly, 10 to 19 days (OR=2.63, 95% CI=(1.19,5.82), P=0.017), 20 to 29 days (OR=161.31, 95% CI=(49.48,525.9), P< 0.001). Lastly, more than 30 days (OR=92.05, 95% CI=(33.88,250.14), P< 0.001) of working in the frontline of the novel coronavirus.Conclusion: The prevalence of psychological problems and job burnout were at a high level among nurses working in the frontline of the novel coronavirus in different NAT sites. The nurses from NAT sites inside hospitals and temporary NAT sites in communities/towns in Zhangjiajie city had an equal risk of developing psychological problems and job burnout. Interventions need to be immediately implemented to promote psychological well-being and decrease job burnout of nurses.Keywords: psychological status, job burnout, specimen collection, nucleic acid testing, the novel coronavirus, the Delta variant

Mengliu Zhu,1,&ast; Li Chen,1,2,&ast; Xiangyi Kong,1,&ast; Xiangyu Wang,1,&ast; Xingrui Li,2 Yi Fang,1 Jing Wang1 1Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Jing Wang; Yi Fang, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email wangjing@cicams.ac.cn; fangyi@cicams.ac.cnPurpose: The current investigation examines the potential clinical value and prognostic significance of a systemic immune-inflammation index (SII) in patients with breast cancer.Patients and Methods: A total of 477 individuals underwent neoadjuvant chemotherapy, and 308 individuals did not at our center between January 1998 and December 2016 were selected. An optimized SII threshold was generated using a receiver operating characteristic curve (ROC). The relationship between various factors and breast cancer in predicting disease-free survival (DFS) and overall survival (OS) were analyzed.Results: The SII < 560 group (Low SII group) and SII ≥ 560 group (High SII group) are divided according to the threshold value. SII was an independent predictor for breast cancer DFS and OS based on univariate and multivariate analyses. Low SII patients had higher mean DFS and OS in contrast to those in the high SII groups (46.65 vs 27.37 months and 69.92 vs 49.53 months). Those in the low SII cohort who also had early or advanced breast cancer, different molecular subtypes, and with or without lymph vessel invasion all had higher mean survival time of DFS and OS in contrast to those with raised SII values (P< 0.05). The mean DFS and OS durations also varied based on different Miller and Payne grades (MPG) (P < 0.005), and different response groups (P< 0.05).Conclusion: SII can be used as an easily accessible and minimally invasive potential prognostic factor in individuals with breast cancer and may also guide clinicians in treating and prognosticating patients with breast cancer.Keywords: breast cancer, neoadjuvant chemotherapy, systemic immune-inflammation index, SII, prognosis, inflammation

Yong Chen,1,&ast; Anzhou Peng,2,&ast; Yiqing Chen,1 Xianghua Kong,2 Linyang Li,2 Guangxiao Tang,3 Huifen Li,2 Yu Chen,4 Fan Jiang,2 Peibo Li,5 Qiu Zhang1 1Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Department of the Fifth Tuberculosis, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China; 3Department of Radiology, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China; 4Department of Medical Record Statistics Room, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China; 5Department of Physician Assistant, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiu Zhang; Peibo Li Tel +8613965015060; +8618709843713Email zhangqiu@ahmu.edu.cn; lipeibo013@163.comBackground: The purpose of this study was to investigate the association of the triglyceride glucose (TyG) index, a surrogate marker of insulin resistance (IR) with a high sensitivity of 96.5% and a specificity of 85.0% for the diagnosis of IR, with computed tomography (CT) features in patients with tuberculosis and diabetes mellitus.Methods: A total of 247 subjects were enrolled from July, 2020 to May, 2021. The basic clinical features and CT features were analyzed. In addition, multivariate logistic regression analysis models were employed to evaluate the association of the TyG indicator with CT features in participants.Results: In the quartile groups of TyG index, air bronchial sign detection rate was 11.7%, 14.5%, 23.2%, and 44.1%; large segmented leafy shadow detection rate was 27.9%, 40.6%, 46.4%, and 66.2%; thick-walled cavity was found in 38.2%, 43.4%, 57.9%, and 69.1%; the rate of multiple cavities was 17.6%, 27.5%, 36.2%, 52.9%; the rate of lymph node enlargement was 22.1%, 17.4%, 28.9%, and 38.2%, respectively. In addition, the positive relation with the TyG index and the prevalence of abnormal CT signs was observed in the fully adjusted model: TyG, per one-unit increase: air bronchial sign: adjusted odds ratio (AOR) 3.92, 95% CI 1– 15.35, P = 0.049; multiple cavities: AOR 4.1, 95% CI 1.26– 13.31, P = 0.019; thick-walled cavity: AOR 2.89, 95% CI 1.05– 8.03, P = 0.041. In quartile of TyG index, compared with patients in quartile 1, the AOR (95% CI) values for air bronchial sign in quartile 4 was 8.1 (1.7– 44), p = 0.011; multiple cavities was 7.1 (1.7– 32), p = 0.008; thick-walled cavity was 7.8 (1.9– 34.7), p = 0.005.Conclusion: The present study showed that an increased TyG index was positively related to the severity of patients with T2DM-PTB.Keywords: CT features, insulin resistance, triglyceride glucose index, pulmonary tuberculosis, T2DM

Zhihong Gong,1 Jinghui Zhang,1– 3 Jianmei Hou,1,4 Shujie Chen,1 Zixin Hu,1 Xiaoya Kong,1 Guiyuan Ma,1 Lingxia Luo1,5 1Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Xiangya Nursing School, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Thoracic Oncology, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Emergency Medicine, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jinghui ZhangTeaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, 87 Xiangya St, Kaifu District, Changsha, 410008, Hunan, People’s Republic of ChinaTel +86 15874032339Email zhangjh-1206@163.comBackground and Aim: Drug extravasation is one of the most common complications of intravenous therapy, which can lead to severe tissue injury if inappropriately treated. This study analyzes the current situation of extravasation and the risk factors affecting the severity of extravasation to provide a theoretical basis for carrying out prospective research, reducing the severity of drug extravasation, and strengthening the management of drug extravasation.Materials and Methods: We retrieved the data on extravasation from January 2016 to December 2020 from the hospital’s safe infusion management system. We used nonparametric tests to assess the differences in the severity of drug extravasation among each variable and performed a multivariate analysis using multivariate ordered logistic regression.Results: Extravasation occurred in 0.038% (263/694,043) of patients, including 203 cases of mild extravasation (77.2%), 57 cases of moderate extravasation (21.7%), and 3 cases of severe extravasation (1.1%). The main diseases of the patients with extravasation were cancer (24.7%), neurological-related diseases (19.4%), circulatory-related diseases (14.8%), and digestive-related diseases (14.1%); the main extravasated drugs were hypotonic or hypertonic drugs (31.9%) and contrast media (27.8%); the infusion tools of extravasation were indwelling needles (92.0%) and steel needles (8.0%). The multi-factor analysis showed that close to joints, patients’ age ≤ 6 or age > 65, cancer, neurological-related diseases, circulatory-related diseases, antineoplastic agents, hypotonic or hypertonic drugs and strong acid or alkali drugs were independent risk factors for more severe extravasation. The nurses’ age and first identified by nurse were nurse-related factors that influenced the severity of drug extravasation.Conclusion: To prevent the occurrence of drug extravasation and reduce its severity, the nurses should strengthen the learning of emergency plans related drug extravasation, strengthen inspections of high-risk patients. Besides, the managers should strengthen the risk warning management of high-risk extravasated drugs.Keywords: extravasation, risk factors, retrospective cohort study, the severity level

Li Jiang,1,&ast; Wei Sun,2,&ast; Mi Zhang,3,&ast; Yaqing Wang,2 Yunfan Tian,2 Peng Li,2 Yan Lu,2 Tianhua Xu,2 Ming Qiu,2 Yun Yang,2 Xuemei Jia,3 Xiangqing Kong2 1Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Gynecological Tumor, Nanjing Maternity and Child Health Hospital, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangqing KongThe First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of ChinaTel +86 25 83718836Fax +86 25 83724440Email kongxq@njmu.edu.cnXuemei JiaThe Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Hospital), 123 Tianfeixiang, Mochou Road, Nanjing, Jiangsu Province, 210004, People’s Republic of ChinaTel/Fax +86 25 84460507Email xmjia@njmu.edu.cnAim: Several studies have demonstrated that increased omental adipose is a risk factor for obesity and metabolic syndrome. It remains unclear whether it is responsible for hypertension as an independent risk. This study was designed to assess the impact of omental adipose removal by surgery on blood pressure in cancer patients with or without hypertension.Methods and Results: In this prospective observational study, 133 patients with gastric or gynecological cancer were divided into 3 groups: non-hypertensive and omentum removed (NH&OR), hypertensive and omentum removed (H&OR), and hypertensive and omentum present (H&OP). Patients were followed up with systolic and diastolic blood pressure (SBP and DBP), changes in related body mass index and metabolic indices. The time points of the 2 follow-up visits were 1 month ± 7 days after the operation before the start of chemotherapy and the endpoint of 8 ± 1 month. Omental adipose tissues from both non-hypertensive and hypertensive patients in surgery were collected. We included 133 patients (84.2% female, 20.3% malignant gastric cancer and 79.7% malignant gynecological cancer, 78.2% omentum removal, 48.9% hypertensive), and all completed follow-up. H&OR group showed significant reductions in systolic and diastolic blood pressure compared with the baseline at 1-m (− 16.94/-10.50 mmHg, both P < 0.001) and 8-m end point (− 16.00/-5.50 mmHg, P < 0.001 and P = 0.004). Little reductions were observed with the body mass index of patients in 3 groups till the endpoint of study (H&OR group: 24.60 kg/m2 to 23.57 kg/m2, NH&OR group: 23.45 kg/m2 to 23.25 kg/m2, H&OP group: 25.74 kg/m2 to 25.24 kg/m2, all P > 0.05). No correlation was found between the baseline body mass index and 8-m change of systolic and diastolic blood pressure in omentum removed groups. In both groups, triglyceride levels were significantly increased at 4 ± 1 week after surgery (NH&OR 0.32 mmol/L, P = 0.006; H&OR 0.40 mmol/L, P = 0.010).Conclusion: Resection of omental adipose tissue represents an effective strategy for reducing systolic and diastolic blood pressure at 8 months in hypertensive patients, even in the non-obese hypertensive population.Keywords: hypertension, omentum adipose, mRNA microarray

Lulu Song,1 Xiaomu Kong,2 Zhaojun Yang,1 Jinping Zhang,1 Wenying Yang,1 Bo Zhang,1 Xiaoping Chen,1 Xin Wang1 1Department of Endocrinology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Clinical Laboratory, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xin WangDepartment of Endocrinology, China-Japan Friendship Hospital, 2 Yinghua East Road, Beijing, 100029, People’s Republic of ChinaTel +86 1084205254Email xiangpian11@163.comPurpose: To assess the effect of acarbose in lowering low-grade albuminuria compared to metformin in newly diagnosed Chinese type 2 diabetes (T2DM) patients.Patients and Methods: The Metformin and AcaRbose Clinical Trial was a randomized, open-label trial in newly diagnosed T2DM patients. Participants received 48 weeks of monotherapy with acarbose (100 mg three times a day) or metformin (1500 mg once a day). As the hypoglycemic effect of acarbose and metformin has been evaluated in previous reports. This analysis studied the effect of the two antidiabetic drugs on reducing urinary albumin. The percent change in the urinary albumin/creatinine ratio (uACR) from baseline to week 48 was analyzed, and ANCOVA was employed to establish whether the effect in decreasing uACR was mediated by metabolic improvement.Results: Acarbose reduced the adjusted mean percent uACR by − 31.5% (95% confidence interval [CI] − 48.4 to − 7.5) compared with metformin. When adjusting for changes in glycated hemoglobin, body weight, systolic blood pressure and triglycerides or changes in area under the curve of glucagon-like peptide 1 (AUCGLP-1) in the standard meal test, the uACR-lowering effect was not attenuated. If stratified by eGFR, blood glucose level, sex or uACR level, the effect of acarbose versus metformin was consistent across subgroups. The proportion of patients with a reduction in uACR of at least 70% was 48.6% in the acarbose group and 34.1% in the metformin group.Conclusion: Acarbose lowered the uACR compared to metformin in newly diagnosed T2DM patients independent of improvements in hyperglycemia, blood pressure, body weight and triglycerides.Keywords: diabetes mellitus, type 2, diabetic nephropathies, hypoglycemic agents

Chang Yu,1,&ast; Xiaojun Zhu,1,&ast; Chao Zheng,1 Yichun Luo,1 Fang Wang,1 Yueqiu Gao,1 Hailong Wu,2 Xuehua Sun,1 Xiaoni Kong1 1Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoni Kong; Xuehua SunCentral Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, 528 Zhangheng Road, Shanghai, 201203, People’s Republic of ChinaTel +86 21 20256838Email xiaoni-kong@126.com; susan_sxh@sina.comIntroduction: Mortality of sepsis is caused by an inappropriately amplified systemic inflammatory response and bacteremia. Methyl diet has been shown to associate with greater inflammation response in different diseases. This study aimed to determine whether dietary supplementation with methyl donors affects the inflammation response and mortality in sepsis and to investigate the underlying mechanisms.Methods: Four-week-old male C57BL/6 mice were fed with a high-methyl diet (HMD) or a regulator diet (RD) till the experiment time. Mice septic model was induced by Cecal ligation and puncture (CLP), lipopolysaccharide (LPS), or E.coli. Inflammatory cytokine was analyzed by ELISA and qRT-PCR. Immune cell infiltration was evaluated by H&E and IHC. The composition of gut microbiota was determined by 16S rRNA sequencing. The effect of gut microbiota on sepsis was further verified by fecal microbiome transplantation.Results: Our results showed that the diet riches in methyl donors exacerbated mortality, organ injury, and circulating levels of inflammatory mediators in CLP-induced septic mice model, compared to the control diet group. However, no significant differences have been observed in the inflammatory responses in the LPS-induced septic model and macrophages activation between the two groups of mice. There was a higher bacterial burden in CLP-induced HMD mice suggested that methyl diet might modulate gut microbiota. Bacterial 16S rRNA sequencing results showed that the composition of gut microbiota was altered. The high methyl donor diet reduced the abundance of Akkermansia and Lachnospiraceae, which were associated with protective effects in sepsis, in the gut. Moreover, fecal microbiome transplantation experiment showed that the transfer of feces, which obtained from high methyl diet mice, aggravated the mortality and inflammation responses in recipient mice.Discussion: Methyl diet enhanced CLP-induced septic mortality and inflammatory responses through altering the composition of gut microbiota. This result indicated that diet-based gut microbiota may be a new therapeutic strategy for sepsis patients.Keywords: sepsis, DNA methylation, gut microbiota, Akkermansia, Lachnospiraceae

Wenqing Zhu,1,2 Xiangmei Kong,1,2,* Ying Huang,1,2,* Mingshui Fu,3 Xi Shen,4 Fang Wang,5 Xinghuai Sun1,2,6 1Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, People’s Republic of China; 3Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 4Ruijin Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of China; 6State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangmei Kong; Ying HuangDepartment of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of ChinaTel +86-21-64377134Email kongxm95@163.com; 13661763815@163.comPurpose: To investigate the agreement of optic nerve head evaluations and initial diagnoses of primary open-angle glaucoma (POAG) by general ophthalmologists and glaucoma specialists in Shanghai, China.Methods: This multicenter, cross-sectional study involved the outpatients from the general ophthalmology departments of four top eye hospitals in Shanghai. The participants underwent ocular examinations, including intraocular pressure, fundus photography, corneal thickness, refractometry, visual acuity, visual field and gonioscopy. General ophthalmologists and glaucoma specialists performed the diagnoses and classified them as non-glaucoma, POAG suspects, and POAG. The consistency of initial diagnosis between general ophthalmologists and glaucoma specialists was measured using the weighted kappa coefficient. Logistic regression analysis was used to detect the risk factors for the reliability of POAG diagnosis.Results: In 922 participants, the initial diagnosis rates of POAG and non-glaucoma were much higher in the glaucoma specialist group than in the general ophthalmologist group, while the initial diagnosis rates of POAG suspects were higher in the general ophthalmologist group. The weighted kappa coefficient between the two groups was 0.831± 0.027 (95% confidence interval, 0.779– 0.884). Logistic regression analysis of the risk factors for the reliability of POAG diagnosis showed that the independent risk factors were intraocular pressure (OR 8.363, 95% CI: 4.27– 16.37) and vertical cup-to-disc ratio (OR 3.459, 95% CI: 1.54– 7.76).Conclusion: The diagnosis consistency between the general ophthalmologists and the glaucoma specialists was similar among outpatients in the area of Shanghai. However, general ophthalmologists tended to classify the indefinite subjects as POAG suspects, and their accuracy in diagnosing POAG was low. By paying more attention to the risk factors of POAG diagnosis, general ophthalmologists could improve the diagnosis accuracy.Keywords: primary open-angle glaucoma, initial diagnosis, risk factor, intraocular pressure, vertical cup-to-disc ratio

Yubo Yan, Xiangyuan Jin, HaoBo Sun, Sainan Pang, Xianglong Kong, Jianlong Bu, Shidong Xu Department of Thoracic Surgery, Harbin Medical University Tumer Hospital, Harbin, Heilongjiang Province, 150000, People’s Republic of ChinaCorrespondence: Shidong XuDepartment of Thoracic Surgery, Harbin Medical University Tumer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150000, People’s Republic of ChinaTel +86-13903611962Email shidongxushi@sina.comObjective: To explore relevant mechanisms of miR-139-5p in alleviating the metastasis of non-small cell lung cancer cells (NSCLC) and their resistance against cisplatin.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) assays were carried out to determine the protein levels of miR-139-5p and YAF2, and cisplatin (DDP)-resistant NSCLC cell strains were established. Subsequently, an MTT assay was employed to evaluate the viability of the cell strains, a Transwell assay to evaluate cell invasion activity, and flow cytometry to analyze cell apoptosis rate. Finally, a Western blot assay was carried out to determine the protein levels of P-PI3K and p-p38.Results: NSCLC tissues showed lower miR-139-5p expression and higher YAF2 expression than paracancerous tissues and human normal lung epithelial cells, and miR-139-5p was related to the prognosis of NSCLC patients. Overexpression of miR-139-5p or knock-down of YAF2 inhibited the proliferation and invasion of NSCLC cells and induced their apoptosis. Additionally, the dual-luciferase reporter assay verified a targeting relationship between miR-139-5p and YAF2. Overexpression of miR-139-5p and knockdown of YAF2 reversed the resistance of A549/DDP cells against DDP, inactivated p38 and Akt proteins, and inhibited the AKT/p38 MAPK signaling pathway. Furthermore, inhibiting the AKT/p38 MAPK signaling pathway with MK2206 resisted the effects of knock-down of miR-139-5p on DDP resistance in NSCLC cells.Conclusion: MiR-139-5p targetedly regulates YAF2 and mediates the AKT/p38 MAPK signaling pathway to alleviate the metastasis of NSCLC cells and their resistance against cisplatin, which may be a novel target for improving the therapeutic effect on NSCLC.Keywords: miR-139-5p, YAF2, AKT/p38 MAPK, non-small cell lung cancer, cisplatin

Yiting Huang,1,2 Siyi Yu,2 Georgia Wilson,2 Joel Park,2 Ming Cheng,2 Xuejun Kong,3 Tao Lu,1 Jian Kong2 1School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 3Martino Imaging Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Tao LuSchool of Life Sciences, Beijing University of Chinese Medicine, No. 11 East Road, North 3rd Ring Road, Beijing, 100029, People’s Republic of ChinaEmail taolu@bucm.edu.cnJian KongDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 120 2nd Ave, Room 101C, Charlestown, MA, 02129, USAEmail jkong2@mgh.harvard.eduIntroduction: Previous studies have suggested that cerebral projections of the norepinephrine (NE) and dopamine (DA) systems have important etiology and treatment implications for autism spectrum disorder (ASD).Methods: We used functional magnetic resonance imaging to evaluate spontaneous resting state functional connectivity in boys aged 7– 15 years with ASD (n=86) and age-, intelligence quotient-matched typically developing boys (TD, n=118). Specifically, we investigated functional connectivity of the locus coeruleus (LC) and ventral tegmental area (VTA), the main source projection of neurotransmitters NE and DA, respectively.Results: 1) Both the LC and VTA showed reduced connectivity with the postcentral gyrus (PoCG) in boys with ASD, reflecting the potential roles of NE and DA in modulating the function of the somatosensory cortex in boys with ASD. 2) The VTA had increased connectivity with bilateral thalamus in ASD; this alteration was correlated with repetitive and restrictive features. 3) Altered functional connectivity of both the LC and VTA with brain regions such as the angular gyrus (AG), middle temporal gyrus visual area (MT/V5), and occipital face area (OFA) in ASD group.Discussion: Our findings implicate the role of LC-NE and VTA-DA systems from the perspective of functional neuroimaging and may shed light on pharmacological studies targeting NE and DA for the treatment of autism in the future.Keywords: autism spectrum disorder, locus coeruleus, ventral tegmental area, norepinephrine, dopamine, functional connectivity

Jingsun Wei,1,2,* Yucheng Qian,1,2,* Yang Tang,1,2 Xiaoxu Ge,1,2 Kai Jiang,1,2 Yimin Fang,1,2 Dongliang Fu,1,2 Xiangxing Kong,1 Qian Xiao,1 Kefeng Ding1,2 1Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kefeng DingDepartment of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, People’s Republic of ChinaTel/Fax +86-571-87784820Email dingkefeng@zju.edu.cnPurpose: N6-methyladenosine (m6A) modifications represent one of the most common methylation modifications, and they are mediated by m6A RNA methylation regulators. However, their functions in renal cell carcinoma (RCC) are not completely understood. The aim of this study was to investigate the effects of the regulators in RCC.Materials and Methods: The expression levels of the 13 main m6A RNA methylation regulators in RCC were detected and consensus clustering was performed to explore their relationships with RCC. Thereafter, a risk signature based on the regulators was established. This risk model was fully verified by conducting prognostic analyses using two datasets (The Cancer Genome Atlas [TCGA] and Gene Expression Omnibus [GEO] datasets) and a ROC curve analysis.Results: Of the 13 main m6A regulators, six were significantly upregulated and four were significantly downregulated in 893 RCC cases compared to 128 normal controls in the TCGA database. Consensus clustering based on the regulators identified two clusters of RCC cases, which were significantly associated with a pathological characteristic (T status). Thus, these results indicated that m6A RNA methylation regulators were associated with RCC. Thereafter, a risk model involving two of the regulators (METTL14 and WTAP) was established. The alterations in the mRNA and protein expression levels of these two regulators were further confirmed based on Human Protein Atlas data and real-time PCR in RCC and normal cell lines. The results indicated that the risk model may serve as an independent prognostic marker of overall survival, and it was also associated with clinicopathological characteristics (T status, M status, pathological stage, and gender) in RCC.Conclusion: Collectively, the results of this study indicated that the risk model (based on two m6A RNA methylation regulators) may serve as an independent prognostic indicator of RCC, which may aid further investigation into m6A RNA modification in RCC.Keywords: renal cell carcinoma, m6A methylation, TCGA, prognostic signature

Jianming Gong,* Xiangdong Kong,* Jinhui Qi, Jiangkun Lu, Shaofeng Yuan, Ming Wu Department of Surgery, Tinglin Hospital of Jinshan District, Shanghai 201505, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming WuDepartment of Surgery, Tinglin Hospital of Jinshan District, No. 80 Siping North Road, Jinshan District, Shanghai 201505, People’s Republic of ChinaTel + 86-18121367005Email wum7005@126.comBackground: Thyroid cancer is one of the most common cancers with rising incidence worldwide, and papillary thyroid carcinoma (PTC) accounts for 80– 85% of thyroid malignancy. Although it has been reported that many genes relate to the carcinogenesis of PTC, the molecular mechanisms remain mostly unclear.Methods: QRT-PCR assay was performed to detect circRNA_104565, miR-134 and ELF2 expression. CCK8 assay was exercised to examine cell proliferation. Western blot was used to detect ELF2 expression.Results: We found that circRNA_104565 was highly expressed in PTC tissue and cell and promoted cell proliferation in vitro and in vivo. In addition, circRNA_104565 promoted cell proliferation in PTC by regulating the miR-134/ELF2 axis.Conclusion: Hence, revealing the function of circRNA_104565 in PTC is important for understanding the molecular mechanism of carcinogenesis and providing new biomarkers or therapeutic targets for PTC.Keywords: circRNA_104565, cell proliferation, PTC, miR-134, ELF2

Peng Gao, Zhongzhao Wang, Xiangyi Kong, Xiangyu Wang, Yi Fang, Jing Wang Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of ChinaCorrespondence: Yi Fang; Jing WangDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of ChinaEmail fangyi@cicams.ac.cn; wangjing@cicams.ac.cnBackground: Biological matrix can provide coverage of compromised muscle and augment the subpectoral pocket in the one-stage reconstruction. However, few studies compared one stage implant-based breast reconstruction with and without biological matrix. The primary endpoint of our study was to assess the patient-reported outcomes (PROs) based on BREAST-Q version 2.0 and analyze complications between SIS matrix-assisted implant-based breast reconstruction (IBBR) and no-matrix-assisted IBBR.Methods: This retrospective single-center study was conducted from May 2015 to April 2019, and we analyzed 155 patients who underwent one-stage IBBR with at least 1 year of follow-up. Seventy-nine patients underwent one-stage IBBR with SIS matrix group and 76 patients underwent one-stage IBBR without SIS matrix group were evaluated of PROs with BREAST-Q version 2.0 (from 3 different domains) and compared with complications. Complications occurred in patients were divided into major complications and minor complications.Results: In the satisfaction domain, the mean score for satisfaction with breasts was 60.27 (17.71) in the SIS matrix group and 54.49 (14.76) in the no-matrix group, p=0.045. The multivariate logistic regression for postoperative complications in the whole series pointed out a statistical significance for age> 40 years old (odds ratio 3.314, 95% CI 1.012– 10.854, p=0.048) and patients with endocrine therapy (odds ratio 0.260, 95% CI 0.092– 0.736, p=0.011).Conclusion: Patients who underwent SIS matrix-assisted one-stage IBBR yield better results in PROs of satisfaction with breasts. Other domains and complications between the two groups had no significant difference.Keywords: breast cancer, one-stage implant-based breast reconstruction, biological matrix, BREAST-Q version 2.0

Yumin Wu,1,* Weifeng Shi,1,* Honghai Wang,2,* Jiawei Yue,2 Yijie Mao,1 Wei Zhou,1 Xinagmin Kong,1 Qiqiong Guo,1 Lirong Zhang,1 Pengxiao Xu,1 Yuyue Wang1 1Department of Laboratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, People’s Republic of China; 2Department of Orthopaedics, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, People’s Republic of China*These authors contributed equally to this workCorrespondence:Yuyue WangThe Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, People’s Republic of ChinaEmail wangyuyue1085@126.comBackground: Asthma has been regarded as an inflammatory disease, and group 2 innate lymphoid cells (ILC2s) are implicated in asthma pathogenesis. However, no strategy is available to block ILC2s function. Efficiency is also limited due to the use of systemic or subcutaneous routes of administration. The purpose of this study was to investigate the effects of nanoparticles targeting suppression of tumorigenicity 2 (ST2), which is the ILC2 receptor, to alleviate lung inflammation in the murine model of asthma.Methods: The ultra-small SPIO nanoparticles were firstly synthesized, OVA-induced mice were administered by anti-ST2-conjugated nanoparticles. The inflammatory degree of the lung was investigated by H&E. The percentages of ILC2s and CD4+T cells in bronchoalveolar lavage fluid (BALF) and lung tissue were determined by FACS. Th2-cytokine and OVA-IgE levels were detected by real-time PCR and ELISA, respectively.Results: Treatment with anti-ST2-conjugated nanoparticles significantly alleviated airway inflammation, IL-33 and IL-13 levels and the percentage of CD4+T cells. The percentage of ILC2s was increased, whereas the levels of IL-13 and IL-5 expressed by ILC2s were reduced.Conclusion: In the present study, we demonstrated that anti-ST2-conjugated nanoparticles can efficiently control lung inflammation in OVA-induced mice by reducing the ability of ILC2s to produce IL-5 and IL-13, thereby reducing CD4+T cells. Our study also demonstrated that the nanoparticle delivery system could improve the performance of anti-ST2, which may be used as a strategic tool to expand the current drug market.Keywords: anti-ST2, asthma, group 2 innate lymphoid cells, (ILC2s), CD4+T cells, nanoparticle

Lisa Su,1,* Genhao Zhang,2,* Xiangdong Kong1 1Department of Genetic and Prenatal Diagnosis Center, Zhengzhou University First Affiliated Hospital, Zhengzhou, People’s Republic of China; 2Department of Blood Transfusion, Zhengzhou University First Affiliated Hospital, Zhengzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangdong Kong Email kongxdprenatal@163.comAim: Human pregnancy zone protein (PZP) is a pregnancy-related protein which is increased dramatically during pregnancy. However, the expression of PZP and its prognostic value, association with tumor-infiltrating immune cells (TIICs) in microenvironment and potential biological process in HCC were unclear.Methods: The PZP expression, clinicopathology analysis and its influence on survival were analyzed by GEPIA and HPA. Fifty-nine HCC samples and 30 corresponding noncancerous tissues were collected and retrospectively analyzed to verify the results of bioinformatics analysis. Further, TIMER and CIBERSORT were performed to identify the significantly alerted biological process and affections of PZP expression on the immune system in patients with HCC. Finally, IHC assay of CD4+ T cells and Treg cells was performed to confirm the results of immune infiltrates analysis by TIMER and CIBERSORT.Results: PZP expression was downregulated in HCC tissues and its low level was substantially correlated with poor prognosis in patients with HCC. TIMER analysis showed that PZP expression had a positive correlation with the levels of macrophage and neutrophil. Furthermore, CIBERSORT analysis showed that resting memory CD4 T cells were increased in high PZP expression group, while the results of Tregs were the opposite. Finally, the IHC results of CD4+ T cells and Treg cells showed that only Tregs were negatively associated with PZP expression.Conclusion: PZP was identified as a novel prognosis biomarker of HCC and might play a vital role in the regulation and recruitment of TIICs in HCC immune microenvironment.Keywords: PZP, prognosis, TIICs

Liqin Ma,1,* Fei Chen,2,* Xiangquan Kong,3,* Ting Xu,2 Zhaodong Fei,1 Weining Fang,1 Binyi Wang,1 Haixia Wu2 1Department of Radiation Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, People’s Republic of China; 2Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Radiation Oncology, Fujian Medical University Affiliated Xiamen Humanity Hospital, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liqin MaDepartment of Radiation Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, No. 420, Fuma Road, Fuzhou, Fujian 350014, People’s Republic of ChinaTel +8613609537603Fax +86 591-83660063Email maliqin3@126.comPurpose: Nasopharyngeal carcinoma (NPC) is more common among women in Southeast Asia. An important issue is whether it is safe for them to bear children after treatment and when it is safe to do so. We conducted this study to explore the relation between fertility and prognosis in child-bearing women with NPC.Patients and Methods: Child-bearing women were defined as young women between the ages of 18 and 30. A total of 127 eligible child-bearing NPC patients were identified from December 2003 to December 2014. The patients were divided into two groups, depending on whether or not they had post-therapeutic births. The Kaplan–Meier method was used for survival analyses. The Log rank test was used to compare two survival curves and the independent significances of different prognostic factors were assessed by Cox proportional hazards regression analysis.Results: The 5-year overall survival (OS) and disease-free survival (DFS) in the Childbirth group were significantly higher than those in the Non-Childbirth group (100% vs 88.8%, P = 0.026 and 100% vs 77.5%, P = 0.007, respectively). In the Childbirth group, no difference was found in the 5-year DFS between different birth interval times, from 1 to 5 years after treatment. The clinical stage was identified as the risk factor of OS (HR = 101.725, 95% CI: 2.160– 4790.910, P = 0.019), and consequent childbirth after treatment was associated with favorable DFS (HR = 0.148, 95% CI: 0.034– 0.643, P = 0.011).Conclusion: Post-therapeutic birth did not increase the mortality risk of child-bearing women with NPC. There was no significant correlation between the subsequent birth time window after treatment and the prognosis.Keywords: nasopharyngeal carcinoma, fertility, child-bearing mortality risk, post-treatment

Jingyi Cheng,1– 3,* Yujing Yang,1– 3,* Xiehe Kong,4 Li Zeng,1– 3 Zhi Chen,1– 3 Jianjiang Xu,1– 3 Chaoran Zhang1– 3 1Department of Ophthalmology and Visual Science, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College of Fudan University, Shanghai, People’s Republic of China; 2Key Laboratory of Myopia, Ministry of Health (Fudan University), Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, People’s Republic of China; 4Shanghai Research Institute of Acupuncture and Meridian, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaoran ZhangDepartment of Ophthalmology and Visual Science, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College of Fudan University, 83 Fenyang Road, Shanghai 200031, People’s Republic of ChinaTel/ Fax +86 2164377134Email zhangchaoran@hotmail.comPurpose: To evaluate the effect of 0.01% atropine eye drops on the ocular surface in children for the control of myopia.Methods: A total of 72 participants were recruited for this prospective study. Prior to and after 1, 3, and 6 months of 0.01% atropine administration, an ocular surface disease index (OSDI) questionnaire was obtained, Keratograph 5M was used for the measurement of the tear meniscus height (TMH), noninvasive keratographic tear film break-up time (NK-BUT, the first keratographic break-up time, [NK-BUTfirst] and the average keratographic break-up time, [NK-BUTave]), bulbar redness (BR), meiboscore (MS), and anterior segment optical coherence tomography (AS-OCT) was used to calculate the inferior tear meniscus area (TMA).Results: After using the 0.01% atropine eye drops for 1 month, 9 subjects complained of discomfort immediately after administration, but this quickly subsided, and 1 subject was temporarily dazzled. All the ocular surface symptoms were mild and occurred rarely. After 3 months, these complaints no longer occurred. Compared with the baseline values, the OSDI scores (0.08 ± 0.28), values of TMH (0.23 ± 0.04 mm), TMA (0.0420 ± 0.0444 mm2), NK-BUTfirst (9.39 ± 5.25 s), NK-BUTave (10.49 ± 4.94 s), BR (0.63 ± 0.37), and MS (0.89 ± 0.70) did not change significantly after 6 months of 0.01% atropine eye drop administration (P > 0.05).Conclusion: In this 6-month prospective study, no side effects were observed on the ocular surface after using 0.01% atropine in children.Keywords: 0.01% atropine eye drops, ocular surface, children, myopia control

Xiangpeng Kong,1 Minzhi Yang,1,2 Renwen Guo,1 Jiying Chen,1 Wei Chai,1 Yan Wang1 1Department of Orthopaedics, Chinese PLA General Hospital, Beijing, People’s Republic of China ; 2Nankai University, Tianjin, People’s Republic of ChinaCorrespondence: Wei Chai; Yan Wang Email chaiweiguanjie@sina.com; wangyanguanjie@sina.comBackground: The study focusing on the tissue adhesive in total knee arthroplasty (TKA) was rare. This study aimed to evaluate the clinical outcomes and economic costs of tissue adhesive when acting as the adjunct to standard incision closure in TKA.Patients and Methods: From September 2019 to November 2019, we prospectively enrolled the consecutive patients who underwent simultaneous bilateral TKA in our institute. The allocation using the tissue adhesive was done after the subcuticular suture in right knee first and another method was applied in the left knee automatically. The patients’ demographics, length of stay (LOS), times of dressing changes and incision-related cost, range of motion (ROM), incision-related complications and incision evaluation scores were recorded.Results: Thirty-two patients were enrolled in this study and followed at two months after surgery. In the knees of tissue adhesive, the times of dressing change and patient scar assessment scores (PSAS) were significantly less than those standard skin closure (p=0.000; p=0.003). Although there were no significant differences of the delayed discharge, incision-related cost, ROM, incision-related complications and Vancouver scar score (VSS) between two groups, 65.6% (21/32) patients preferred the tissue adhesive and only 15.6% (5/32) patients preferred the standard incision closure.Conclusion: Tissue adhesive could effectively reduce postoperative wound drainage and improve patients’ satisfaction rate with no difference in medical costs and ROM in TKA. The application of tissue adhesive and subcuticular sutures might be one safe and convenient method of skin closure in TKA.Chinese Clinical Trial Registry: ChiCTR1900025730; Registered 6 September 2019.Keywords: total knee arthroplasty, tissue adhesive, incision closure, dressing change

Wei Chai,1 Xiangpeng Kong,1 Minzhi Yang,1,2 Ken Lee Puah,3 Peifu Tang,1 Jiying Chen1 1Department of Orthopedics, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Medical College, Nankai University, Tianjin, People’s Republic of China; 3Department of Orthopedic Surgery, Singapore General Hospital, SingaporeCorrespondence: Jiying Chen; Peifu Tang Tel +8610-66938404; +8610-66938304Email chenjiyingjoint@sina.com; pftang301@126.comBackground: Conversion of arthrodesed hips to total hip arthroplasty (THA) remains technically demanding. This study aims to evaluate the safety and efficacy of robot-assisted THA in arthrodesed hips.Methods: We retrospectively analyzed 45 ankylosing spondylitis patients with hip arthrodesis in the Chinese PLA General Hospital between August 2018 and August 2019. All surgeries were carried out by one single surgeon. The patients were followed at 3 months after surgery. Gender, body mass index, angle of hip arthrodesis, operating time, intraoperative fluoroscopic times, postoperative length of hospitalization, cup positioning, postoperative leg length discrepancy, offset discrepancy, intraoperative and postoperative complications, and postoperative Harris Hip Score were collected for all patients.Results: Twenty-two patients (35 hips) who underwent robot-assisted THA and 23 patients (37 hips) who underwent manual THA were enrolled in this study. There were no significant differences in demographics and arthrodesed angles between the two groups. The fluoroscopic times during manual THA were significantly higher than those during robot-assisted THA (2.16± 1.61 vs 0.47± 0.61, respectively, p=0.000). In the robotic group, the percentage of acetabular cups within the safe zone was significantly greater than in the manual group (94.29% vs 67.56%, respectively, p=0.042). For manual THA, the anteversions were significantly different between the left and right sides (21.14± 7.86 vs 16.00± 6.32, respectively, p=0.042); however, no such significant difference was found in robot-assisted THA.Conclusion: Compared with manual THA for arthrodesed hips, robot-assisted THA had significant advantages in improving the frequency of achieving cup positioning within the target zone with diminished radiation dose and no increase in operating time.Keywords: total hip arthroplasty, robot-assisted surgery, cup positioning, hip arthrodesis

Zhiwei Xing,1 Zhihua Zhang,2 Yanjun Gao,3 Xun Zhang,3 Xianglong Kong,3 Jianwu Zhang,3 Hongzhong Bai2 1Department of Blood Transfusion, Hebei Chest Hospital, Shijiazhuang City, Hebei Province 050041, People’s Republic of China; 2Department of Radiology, Hebei Chest Hospital, Shijiazhuang City, Hebei Province 050041, People’s Republic of China; 3Department of Laboratory, Hebei Chest Hospital, Shijiazhuang City, Hebei Province 050041, People’s Republic of ChinaCorrespondence: Jianwu ZhangDepartment of Laboratory, Hebei Chest Hospital, No. 372 Shengli North Street, Shijiazhuang City, Hebei Province 050041, People’s Republic of ChinaEmail jianwuzhang123@163.comHongzhong BaiDepartment of Radiology, Hebei Chest Hospital, No. 372 Shengli North Street, Shijiazhuang City, Hebei Province 050041, People’s Republic of ChinaTel +86-0311 86911072Email wwqlghecqfsd78@163.comBackground: This experimental design was based on lncRNA LINC01194 to explore the pathogenesis of NSCLC.Methods: RT-qPCR was used to detect the expression of lncRNA LINC01194 and miR-486-5p in NSCLC tissues and cell lines. CCK-8, colony formation, and transwell assays were used to examine the effects of lncRNA LINC01194 and miR-486-5p on NSCLC cell proliferation and migration invasiveness. For target gene prediction and screening, luciferase reporter assays were used to verify downstream target genes for lncRNA LINC01194 and miR-486-5p. The protein expression of CDK4 was detected using Western blotting. The tumor changes in mice were detected by in vivo experiments in nude mice.Results: LncRNA LINC01194 was highly expressed in NSCLC tissues and NSCLC lines (A549, H1299, H460 cells, H1975), and lncRNA LINC01194 significantly promoted cell proliferation and migration of NSCLC cells. MiR-486-5p was identified as a potential target for LINC01194, and miR-486-5p was expressed at a low level in NSCLC tissues and NSCLC lines (A549, H1299, H460 cells, H1975). CDK4 was identified as a potential target for miR-486-5p. LncRNA LINC01194 was able to inhibit miR-486-5p expression and upregulate the expression level of CDK4. Finally, the results of in vivo animal models confirmed that lncRNA LINC01194 promoted NSCLC progression by modulating the miR-486-5p/CDK4 axis.Conclusion: LncRNA LINC01194 promoted the progression of NSCLC by modulating the miR-486-5p/CDK4 axis.Keywords: lncRNA LINC01194, miR-486-5p, CDK4, non-small cell lung cancer, proliferation, invasion

Li Li,1,2,* Xiang’an Kong,2,* Mousheng Zang,2 Bin Hu,2 Xing Fang,2 Binjie Gui,1 Yong Hu1 1Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Orthopedics, The Second People’s Hospital of Hefei, The Affiliated Hefei Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Hu Tel +86-551-62923605Email huyong121613@163.comBackground: Osteosarcoma (OS), an aggressive malignant neoplasm, exhibits osteoblastic differentiation. Cisplatin (DDP) and taxanes are among the most effective drugs for OS patients. Nevertheless, the drug resistance remains a main limitation to efficacious chemotherapy in OS. The current report sets to explore the biological function of microRNA-584 (miR-584) and the potential mechanism underlying OS cells resistance to these two drugs.Materials and Methods: The expression profiles of miR-584 and connective tissue growth factor (CTGF, CCN2) in OS tissue samples and cell lines were tested by means of reverse transcription-quantitative polymerase chain reaction and Western blot. U2OS and MG63 cell lines were delivered with miR-584 mimic alone or plus CCN2 to excavate theirs functions by cell counting kit-8 and EdU, flow cytometric analysis, as well as transwell assay, severally. Western bot analysis was conducted to examine the expression of IκBα, pIκBα, NF-κB and pNF-κB. Dual-luciferase reporter gene assay was carried out to assess the targets of miR-584.Results: The downregulation of miR-584 was identified in OS tissues and cells, which was closely linked to the dismal prognosis of OS patients. Overexpression of miR-584 repressed cell viability, migration as well as invasion, potentiated apoptosis and sensitized OS cells to DDP and taxanes. Mechanism investigation specified a direct targeting relationship between CCN2 and miR-584 in OS.Conclusion: In conclusion, miR-584 has the potency to act as a therapeutic maneuver for OS mainly by inducing the chemosensitivity of OS cells to DDP and taxanes.Keywords: osteosarcoma, microRNA-584, CCN2, the IκBα/NF-κB signaling pathway, chemoresistance

Li Chen, Xiangyi Kong, Zhongzhao Wang, Xiangyu Wang, Yi Fang, Jing Wang Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of ChinaCorrespondence: Jing Wang; Yi FangDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of ChinaEmail Wangjing19682019@163.com; Fangyi19772019@163.comBackground and Objective: Systemic inflammation response index (SIRI=N×M/L), based on neutrophil (N), monocyte (M), and lymphocyte (L) counts, is used to predict the survival of patients with malignant tumors and can fully evaluate the balance between host immune and inflammatory condition. The present study is aimed to evaluate the potential prognostic significance of SIRI in patients with breast cancer undergoing neoadjuvant chemotherapy.Subjects and Methods: A total of 262 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of SIRI by receiver operating characteristic curve stratified patients into low SIRI (< 0.85× 109/L) group and high SIRI (≥ 0.85× 109/L) group. The associations between breast cancer and clinicopathological variables by SIRI were determined by chi-square test or Fisher’s exact test. Kaplan–Meier plots and log-rank test were used to evaluate the clinical outcomes of disease-free survival (DFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of SIRI. The toxicity of neoadjuvant chemotherapy was evaluated by the National Cancer Institute Common Toxicity Criteria (NCICTC).Results: The results were shown that SIRI had prognostic significance by optimal cutoff value of 0.85× 109/L on DFS and OS in univariate and multivariate Cox regression survival analyses. Compared with patients who had high SIRI, patients with low SIRI had longer DFS and OS (41.27 vs 30.45 months, HR: 1.694, 95% CI: 1.128– 2.543, P=0.011; 52.86 vs 45.75 months, HR: 1.288, 95% CI: 0.781– 3.124, P=0.002, respectively). The patients with low SIRI had better 3-, 5-, and 10-year rates of DFS and OS than those with high SIRI. The common toxicities after neoadjuvant chemotherapy were hematologic and gastrointestinal reaction, and the SIRI had no significance on toxicities of all enrolled patients, excepted diarrhea. In patients without neural invasion, those with low SIRI had better prognosis and lower recurrence rates than those with high SIRI.Conclusion: Pretreatment SIRI with the advantage of repeatable, convenient, and non-invasive is a useful prognostic indicator for breast cancer patients who received neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.Keywords: systemic inflammation response index, SIRI, breast cancer, neoadjuvant chemotherapy, survival, prognosis

Li Chen,1,* Xiangyi Kong,1,* Chengrui Yan,2,* Yi Fang,1 Jing Wang1 1Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 2Department of Neurosurgery, Peking University International Hospital, Beijing 100021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wang; Yi FangDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of ChinaEmail Wangjing19682019@163.com; Fangyi19772019@163.comAbstract: Breast carcinoma is one of the most malignant tumors, severely influencing the physical and mental health of people. The latest epidemiological and clinical studies have found that breast tumor and inflammation are determinate relationships with each other. Inflammation is an essential component of the tumor microenvironment, and the change of inflammatory cells might influence tumor progression, such as neoplastic cell proliferation, migration, invasion, the collapse of antitumor immunity, metastasis and so forth. Peripheral blood tests at the time of diagnosis and treatment can reflect inflammatory conditions within the neoplasm. Evaluation of peripheral blood parameters including white blood cell, neutrophil, lymphocyte, monocyte, platelet counts, as well as neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR) (neutrophil count divided by the result of white blood cell count minus neutrophil count), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), which are indicators of systematic inflammatory response, have been widely proposed as prognostic factors for many malignancies. To intensively study the relationship between the common markers in peripheral blood and the treatment or prognosis of breast cancer will have critical clinical significance and application prospect, and can provide useful information for the clinicians. Herein, we review the research progress in the prognostic role of the peripheral blood in breast cancer to provide a new method for the treatment and prognosis of breast cancer.Keywords: breast cancer, prognosis, neutrophil-to-lymphocyte ratio, NLR, platelet to lymphocyte ratio, PLR, lymphocyte-to-monocyte ratio, LMR

Deguo Zhang,1,2 Ping Zhang,3 Luan Li,2 Nan Tang,1,2 Fei Huang,2,4 Xianguo Kong,5 Xueying Tan,2,* Guangjun Shi,2,* 1Department of Hepatobiliary Surgery, The Affiliated Qingdao Chengyang District People’s Hospital of Qingdao University, Qingdao 266109, Shandong Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao 266000, Shandong Province, People’s Republic of China; 3Department of Gynecology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao 266000, Shandong Province, People’s Republic of China; 4Department of Gastrointestinal Hernia Surgery, Qianxinan People’s Hospital, Xingyi 562400, Guizhou Province, People’s Republic of China; 5Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia 19107, PA, USA*These authors contributed equally to this workCorrespondence: Xueying Tan; Guangjun ShiDepartment of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, No 1, Jiao Zhou Road, Shibei District, Qingdao 266000, Shandong Province, People’s Republic of ChinaTel +86 185 6269 2818; Tel +86 186 6167 5603Email sgjzp@hotmail.com; gdxbsys@163.comIntroduction: Irisin is a newly identified cytokine that has gained increasing attention because of its potential therapeutic applications in metabolic diseases and human cancers. Recently, accumulating evidence indicates that irisin plays an important role in the development and metastasis of various tumors. The aim of this study was to evaluate the effects and underlying mechanisms of irisin on malignant growth of pancreatic cancer cells.Materials and methods: The anti-proliferative effect of irisin was examined using the CCK-8 assay. Irisin-induced apoptosis was determined by the annexin V-FITC/PI staining assay. The effects of irisin on cell migration and invasion were assessed using the scratch-induced wound healing assay and transwell invasion assay, respectively. The expression and phosphorylation of signaling proteins were detected by Western blot analysis.Results: Our results showed that irisin inhibited cell proliferation and induced apoptosis of pancreatic cancer cells in a dose-dependent manner. In addition, irisin decreased the migration and invasion of pancreatic cancer cells. Finally, Western blot analysis revealed that irisin downregulated the PI3K/AKT signaling pathway.Conclusion: Our findings suggest that irisin is a novel therapeutic agent for pancreatic cancer.Keywords: irisin, pancreatic cancer, cell growth, migration, apoptosis

Xiangyi Kong,1,2,* Kai Zhang,3,* Xiangyu Wang,1,4,* Xue Yang,1,* Yalun Li,5 Jie Zhai,1 Zeyu Xing,1 Yihang Qi,1 Ran Gao,1 Xiaoli Feng,6 Jing Wang,1 Yi Fang11Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 2Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, MA 02114-3117, USA; 3Department of Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 4Department of Laboratory Medicine, Mayo Clinic, Rochester, MN 55902, USA; 5Department of Breast Surgery, Yantai Yuhuangding Hospital, Yantai 264000, People’s Republic of China; 6Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China*These authors contributed equally to this workBackground: Trastuzumab is an effective drug for the treatment of Her2-positive breast cancer. But, primary or secondary resistances to trastuzumab have become an important factor influencing the curative effect. The mechanisms of trastuzumab resistance are somewhat complex. The present work aims to explore the mechanism of trastuzumab resistance caused by HER-2 mutation in breast carcinomas.Methods: Firstly, the HER2 wild type (WT) and HER2 mutant (HER2 Q429R, HER2 Q429H and HER2 T798M are the commonest 3 types of mutations) MCF7 cell lines were established. Cell proliferation inhibition was then assessed by the Cell Counting Kit-8 assay and BrdU assay. Transwell invasion assays were also conducted to investigate the metastatic potential influenced by the HER2 mutation. Furthermore, Western blotting and co-immunoprecipitation were conducted to detect protein levels and the physical interaction of HER2 and trastuzumab.Results: The results showed that the mutant MCF7 cells were less sensitive to trastuzumab than the WTMCF7 cells. The mutation of HER2 almost had no influence on the expression of HER2 and the interaction of HER2 and trastuzumab. Finally, the mutation of HER2 weakened the inhibition of trastuzumab in the PI3K/AKT pathways. In addition, the inhibition of PI3K/AKT signaling-pathway increased the trastuzumab-sensitivity of HER2-mutant MCF7 cells.Conclusions: Dysregulation of the PI3K-AKT signaling-pathway was a key mechanism inducing the trastuzumab-resistance to HER2 mutant breast cancer cells.Keywords: HER2, trastuzumab, resistance, PI3K

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

Shai N Gozani, Thomas C Ferree, Martin Moynihan, Xuan Kong NeuroMetrix, Inc., Waltham, MA 02451, USA Objective: The purpose of this study was to determine if transcutaneous electrical nerve stimulation (TENS) improves sleep in chronic low back pain (CLBP).Background: There is uncertainty over the effectiveness of TENS in CLBP. In most studies, pain intensity has been the primary outcome measure. Although sleep abnormalities are common in CLBP, sleep outcomes have not been evaluated in most studies of TENS effectiveness. Subjective and objective sleep measures are often inconsistent in CLBP, suggesting that perception of sleep and actual sleep may differ.Methods: This retrospective cohort study evaluated TENS for CLBP over 10 weeks. The source database included demographics, pain characteristics, pain intensity and interference on an 11-point numerical rating scale, adherence and actigraphic sleep data from real-world TENS users. Key inclusion criteria were CLBP with self-reported history of back injury and baseline pain interference with sleep ≥4. Study participants were stratified into improved and unimproved groups based on changes in pain interference with sleep (improved ≥1-point decrease). Actigraphic sleep metrics were compared between the two groups for weeks 1–2 and weeks 9–10.Results: The inclusion criteria were met by 554 TENS users. There were 282 (50.9%) participants in the improved group and 272 (49.1%) in the unimproved group. The two groups had similar baseline characteristics and high TENS adherence. At the weeks 1–2 assessment, there were no differences among actigraphic sleep. At the weeks 9–10 assessment, there was a difference in total sleep time, with the improved group sleeping 29 minutes longer. In addition, the periodic leg movement (PLM) index was lower in the improved group.Conclusion: Regular TENS improved self-reported and objective sleep measures in individuals with CLBP. When compared to the unimproved group, the improved group had longer total sleep time and fewer PLMs. Sleep may be an important outcome for TENS effectiveness in CLBP. Keywords: chronic pain, chronic low back pain, transcutaneous electrical nerve stimulation, sleep, actigraphy, periodic leg movements, total sleep time

Xiaofeng Xu,1,* Yuhua Yan,1,2,* Qingying Xun,3 Jiayu Shi,1,4 Xiangyi Kong,1 Jun Wu,1 Huaijun Zhou1 1Department of Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, China; 2Department of Gynecology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, China; 3Department of Physiology, Medical College, Southeast University, Nanjing, Jiangsu 210009, China; 4Department of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450008, China *These authors contributed equally to this work Background: Angiogenesis is critical for the growth and metastasis of solid tumors and is, therefore, an important therapeutic target. Despite the great research advances in tumor therapies targeting vascular endothelial growth factor (VEGF), drug resistance frequently occurs, and further strategies targeting the tumor vasculature are of primary concern. Purpose: The present study aimed to determine whether a combination of small interfering RNAs (siRNAs) targeting VEGF-A and angiopoietin-2 (Ang-2) inhibited the biologic mechanisms of endometrial cancer more effectively compared to either one alone, in vitro and in vivo. Methods: VEGF-A and Ang-2 were silenced by siRNA in Ishikawa endometrial cancer cells. Cell growth, apoptosis, metastasis, and tumor angiogenesis were measured in vitro and in vivo. Results: There was no difference observed in cell apoptosis rate; however, combined silencing of VEGF-A and Ang-2 resulted in a stronger inhibition of cell proliferation and invasion (P

Xin You,1,2,* Sheng Yang,3,* Jing Sui,3 Wenjuan Wu,3 Tong Liu,3 Siyi Xu,3 Yanping Cheng,3 Xiaoling Kong,3 Geyu Liang,3 Yongzhong Yao1,2 1Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China; 2Department of General Surgery, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Purpose: Papillary thyroid carcinoma (PTC), the most frequent type of malignant thyroid tumor, lacks novel and reliable biomarkers of patients’ prognosis. In the current study, we mined The Cancer Genome Atlas (TCGA) to develop lncRNA signature of PTC.Patients and methods: The intersection of PTC lncRNAs was obtained from the TCGA database using integrative computational method. By the univariate and multivariate Cox analysis, key lncRNAs were identified to construct the prognostic model. Then, all patients were divided into the high-risk group and low-risk group to perform the Kaplan–Meier (K–M) survival curves and time-dependent receiver operating characteristic (ROC) curve, estimating the prognostic power of the prognostic model. Functional enrichment analysis was also performed. Finally, we verified the results of the TCGA analysis by the Gene Expression Omnibus (GEO) databases and quantitative real-time PCR (qRT-PCR).Results: After the comprehensive analysis, a three-lncRNA signature (PRSS3P2, KRTAP5-AS1 and PWAR5) was obtained. Interestingly, patients with low-risk scores tended to gain obviously longer survival time, and the area under the time-dependent ROC curve was 0.739. Furthermore, gene ontology (GO) and pathway analysis revealed the tumorigenic and prognostic function of the three lncRNAs. We also found three potential transcription factors to help understand the mechanisms of the PTC-specific lncRNAs. Finally, the GEO databases and qRT-PCR validation were consistent with our TCGA bioinformatics results.Conclusion: We built a three-lncRNA signature by mining the TCGA database, which could effectively predict the prognosis of PTC. Keywords: The Cancer Genome Atlas, long noncoding RNAs, overall survival, risk score

Wei X, Yu L, Kong K. Onco Targets Ther. 2018;11:2205–2216. The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. It came to the journals attention that the article contained instances of alleged image manipulation. Specifically: Figure 3A panel 786-O miR-NC appears to be duplicated with panel A498 miR-NC which has been rotated clockwise by ~90°. Figure 3B panel 786-O miR-NC appears to be duplicated with panel A498 miR-NC which has been rotated clockwise by ~45° and had some elements altered. Figure 3B panel 786-O miR-488 appears to be duplicated with panel A498 miR-488 which has been rotated clockwise by ~90°. The western blots for Figure 5A panel 786-O HMGN5 appear to be duplicated with Figure 5F panel 786-O N-cadherin. The western blots for Figure 5A panel A498 HMGN5 appear to be duplicated with Figure 5F panel A498 N-cadherin. We tried to contact the authors but despite several attempts received no response. The Editor has determined the findings of the study are no longer valid and requested for the article to be retracted. 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”. Read the original article

Xiangyi Kong,1,2,* Shun Gong,3–5,* I-Ting Lee6,7,* Yi Yang1 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Neurosurgery, The General Hospital of Shenyang Military, Army Institute of Neurology, Shenyang, People’s Republic of China; 4Department of Neurosurgery, Shanghai Institute of Neurosurgery, PLA Institute of Neurosurgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 5Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 6Peking University Health Science Center, Peking University, Beijing, People’s Republic of China; 7Department of Dermatology, Beijing Hospital of the Ministry of Health, Beijing, People’s Republic of China *These authors contribute equally to this work Objective: To discuss the diagnosis, operation methods, and clinical effects of parafalcine meningiomas. Methods: The clinical and preoperative imaging characteristics, operative methods, and effects of operations of 126 cases of parafalcine meningiomas were respectively discussed. Results: G1 resection was achieved in 13 cases, G2 in 105 cases, G3 in four cases, and G4 in four cases, with no deaths. Among these, there were 16 patients with dyskinesia of the contralateral extremities after surgery, but they recovered after several months. Conclusion: In order to avoid postoperative complications, we consider it vital to analyze the patients’ condition, the anatomy of venous drainage in by digital subtractional angiography, the relationship between tumor location and brain tissue according to MRI, and to remove the tumor in an adequately exposed surgical field. Keywords: parafalcine meningioma, image-based types, microsurgery

Xiangyi Kong,1,2,* Shun Gong,3–5,* Tao Yan,6,* Yi Yang1 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 2Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 3Department of Neurosurgery, The General Hospital of Shenyang Military, Army Institute of Neurology, Shenyang 110016, People’s Republic of China; 4Department of Neurosurgery, Shanghai Institute of Neurosurgery, PLA Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 5Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 6Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China *These authors contributed equally to this work Aim: To elucidate the clinical implication of microRNA (miRNA)-200b in the pathological grading of gliomas.Methods: We searched the Chinese National Knowledge Infrastructure, Web of Knowledge, Embase, and PubMed databases. Related articles were assessed, and ORs with 95% CIs were calculated to examine the relationship between miRNA-200b expression levels and the World Health Organization (WHO) glioma grade, patients’ sex and age, tumor size, and extent of surgical resection. Heterogeneity, publication bias, and stability of the pooled results of the included studies were also analyzed. MiR-200b expression in 87 human glioma tissues (50 high grade and 37 low grade) and matched 41 non-neoplastic brain tissues was measured by real-time quantitative RT-PCR assay.Results: Five eligible studies involving 630 patients were included in the present meta-analysis. The miRNA-200b expression in glioma tissues was negatively associated with the WHO glioma grade (OR, 0.070; 95% CI, 0.007–0.678; P=0.022). No significant correlations were found between miRNA-200b and sex (P=0.858), age (P=0.776), tumor size (P=0.134), or extent of resection (P=0.778). In our own test, compared with non-neoplastic brain tissues, the expression level of miR-200b was significantly decreased in glioma tissues (tumor vs normal: 4.29±1.90 vs 10.45±2.34, P

Jie Zhai,* Xiangyi Kong,* Xue Yang,* Jidong Gao, Lixue Xuan, Xiang Wang, Jing Wang, Yi Fang Department of Breast Surgical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Granulocytic sarcoma (GS) is an uncommon extramedullary manifestation of acute myeloid leukemia. GS is often likely to be clinically misdiagnosed as another type of primary breast cancer due to its rarity. We report an uncommon case of breast GS in a patient and review the relevant literature. Keywords: granulocytic sarcoma, breast, misdiagnosis, immunohistochemistry

Xin Wei, Lili Yu, Xiangbo Kong Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, China Purpose: microRNAs are thought to play crucial roles in tumorigenesis. Dysregulation of miR-488 has been implicated to be involved in several cancer progressions. However, the biological functions of miR-488 in renal cell carcinoma (RCC) remain unclear. This study aimed to explore the molecular mechanism underlying the role of miR-488 in RCC development. Materials and methods: The expression levels of miR-488 were detected in 38 paired RCC tumor samples and cell lines by quantitative real-time polymerase chain reaction method. miR-488 was upregulated by mimics transfection in RCC cell lines. MTT, colony formation, transwell assay, flow cytometry assay, and a xenograft model were performed to determine cell proliferation, invasion, migration, epithelial-to-mesenchymal transition, and apoptosis in vitro and in vivo. Moreover, the potential target of miR-488 was verified by dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and Western blot. The correlation between miR-488 expression and its target gene expression was confirmed by Spearman’s correlation analysis in 38 selected RCC tissue samples. Results: We found that miR-488 was remarkably downregulated in human RCC samples and cell lines compared with paired normal tissues and cell lines. Functional investigations revealed that overexpression of miR-488 significantly suppressed cell proliferation, invasion, and migration, and promoted cell apoptosis in RCC cells. Nucleosome binding protein 1 (high-mobility group nucleosome binding domain 5 [HMGN5]) was identified as a direct target of miR-488, and an inverse relationship was found between miR-488 expression and HMGN5 mRNA levels in RCC specimens. Rescue experiments suggested that restoration of HMGN5 partially abolished miR-488-mediated cell proliferation and invasion inhibition in RCC cells through regulating phosphatidylinositol 3-kinase/protein kinase B/the mammalian target of rapamycin and epithelial-to-mesenchymal transition signaling pathways. Conclusion: These data indicated that miR-488 acted as a tumor suppressor in RCC proliferation and invasion by targeting HMGN5, which might provide potential therapeutic biomarker for RCC patients. Keywords: renal cell carcinoma, miRNA-488, HMGN5, metastasis, proliferation

Xuan Kong, Shai N Gozani NeuroMetrix, Inc., Waltham, MA, USA Objective: The objective of this study was to assess the effectiveness of fixed-site high-frequency transcutaneous electrical nerve stimulation (FS-TENS) in a real-world chronic pain sample. Background: There is a need for nonpharmacological treatment options for chronic pain. FS-TENS improved multisite chronic pain in a previous interventional study. Large observational studies are needed to further characterize its effectiveness. Methods: This retrospective observational cohort study examined changes in chronic pain measures following 60 days of FS-TENS use. The study data were obtained from FS-TENS users who uploaded their device utilization and clinical data to an online database. The primary outcome measures were changes in pain intensity and pain interference with sleep, activity, and mood on an 11-point numerical rating scale. Dose–response associations were evaluated by stratifying subjects into low (≤30 days), intermediate (31–56 days), and high (≥57 days) utilization subgroups. FS-TENS effectiveness was quantified by baseline to follow-up group differences and a responder analysis (≥30% improvement in pain intensity or ≥2-point improvement in pain interference domains). Results: Utilization and clinical data were collected from 11,900 people using FS-TENS for chronic pain, with 713 device users meeting the inclusion and exclusion criteria. Study subjects were generally older, overweight adults. Subjects reported multisite pain with a mean of 4.8 (standard deviation [SD] 2.5) pain sites. A total of 97.2% of subjects identified low back and/or lower extremity pain, and 72.9% of subjects reported upper body pain. All pain measures exhibited statistically significant group differences from baseline to 60-day follow-up. The largest changes were pain interference with activity (−0.99±2.69 points) and mood (−1.02±2.78 points). A total of 48.7% of subjects exhibited a clinically meaningful reduction in pain interference with activity or mood. This proportion increased to 57.1% for the high utilization subgroup. Conclusion: FS-TENS is a practical option for treating multisite chronic pain. The greatest impact is on pain interference with activity and mood. FS-TENS utilization and effectiveness exhibit a dose–response association, suggesting that daily use maximizes pain relief. Keywords: chronic pain, multisite, widespread, transcutaneous electrical nerve stimulation, wearable, pain relief devices