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Yan Chen,1,* Yanmei Zhu,1,* Cong Huang,2 Youyang Qu,1 Yulan Zhu1 1Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150080, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yulan Zhu, Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin, Heilongjiang, 150081, People’s Republic of China, Email ylz1111@outlook.comBackground: This research utilized a combination of gene databases associated with ferroptosis and online gene expression data from ischemic stroke samples to pinpoint ferroptosis-related genes (FRGs) in ischemic stroke cases.Methods: By employing Random Forest (RF) and Support Vector Machine (SVM) models based on these genes, an overlap of genes from both models was identified as “Hub” genes. Through consensus clustering analysis using Hub genes, two distinct clusters of FRGs were revealed in ischemic stroke samples. Examination of the correlation between these molecular subtypes and the immune microenvironment highlighted a close link between gene expression levels and immune cell infiltration. Significantly different gene expression and functions within the FRG clusters underscored the pivotal role of Hub genes in the immune microenvironment. A gene diagnostic model related to ferroptosis was developed and validated to elucidate the significance of the identified genes.Results: The results demonstrated that the Hub gene-based classification model effectively differentiated between ischemic stroke patients and normal samples, achieving an AUC of 0.900, signifying clinical relevance.Conclusion: This study successfully identified ferroptosis-related genes in ischemic stroke, offering insights that could contribute to the formulation of future comprehensive treatment approaches.Keywords: Ischemic Stroke, Ferroptosis Related Genes, Peripheral Immune Landscape

Hong-Jing Zhu,1,&ast; Sheng-Yu Zhou,1,&ast; Yang Qu,1 Ying-Ying Sun,1 Ke-Jia Zhang,1 Shu-Yan Pang,1 Yi Yang,1 Zhen-Ni Guo1,2 1Stroke Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, People’s Republic of China; 2Neuroscience Research Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen-Ni Guo; Yi Yang, Stroke Center, Department of Neurology, The First Hospital of Jilin University, Xinmin Street 1&num;, Changchun, 130021, People’s Republic of China, Tel +86-18186872986 ; +86-13756661217, Fax +86-431-88782378, Email zhen1ni2@163.com; yang_yi@jlu.edu.cnPurpose: Although recombinant tissue plasminogen activator (rt-PA) treatment is efficient in patients with acute ischemic stroke (AIS), a significant percentage of patients who received rt-PA intravenous thrombolysis (IVT) do not achieve a good prognosis. Therefore, the factors that affect the poor prognosis of patients with IVT are needed. The Fibrosis-4 (FIB-4) index has been used as a liver fibrosis biomarker. We aimed to investigate the relationship between the FIB-4 index and functional outcomes in patients with AIS receiving IVT.Patients and Methods: This study prospectively included consecutive patients with AIS receiving IVT between April 2015 and May 2022. We collected clinical and laboratory data and calculated the FIB-4 index. Clinical outcome was poor functional outcome (mRS ≥ 3) at 3 months after IVT. Multivariate logistic regression analysis was used to analyze the association between FIB-4 and outcome. We explored the interactive effect of FIB-4 and dyslipidemia on poor outcomes, and subgroup analysis was performed. Furthermore, an individualized prediction model based on the FIB-4 for functional outcome was established in the dyslipidemia group.Results: A total of 1135 patients were included, and 41.50% had poor 3-month outcomes. After adjusted by other variants that P value < 0.05 in univariable analysis, FIB-4 was independently associated with poor outcomes (OR=1.420; 95% CI: 1.113– 1.812; P=0.004). There was a significant interaction between FIB-4 and dyslipidemia on poor outcome (P=0.036), and the independent association between FIB-4 and poor outcome was maintained in the dyslipidemia subgroup (OR=1.646; 95% CI: 1.228– 2.206; P=0.001). Furthermore, in the dyslipidemia group, the FIB-4-based prediction model had good predictive value (the AUC of the training and validation sets were 0.767 and 0.708, respectively), good calibration (P-values for the Hosmer–Lemeshow test > 0.05), and clinical usefulness.Conclusion: FIB-4 is an independent risk factor for poor outcomes in IVT patients with dyslipidemia, which can be used as a simple predictor of their prognosis.Keywords: Fibrosis-4, acute ischemic stroke, intravenous thrombolysis, prognosis, dyslipidemia

Jiechu Wang,1– 3,&ast; Yao Yu,1,&ast; Ya Gao,1– 3,&ast; Tingting Wan,1– 3 Zhukai Cong,1– 3 Zhengqian Li,1– 3 Yang Zhou,1– 3 Xiaoxiao Wang,4 Luyang Feng,1– 3 Yongzheng Han,1– 3 Jing Zhang,1– 3 Yinyin Qu,1– 3 Xiangyang Guo1– 3 1Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Beijing Center of Quality Control and Improvement on Clinical Anesthesia, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Anesthesia and Perioperative Medicine Branch of China International Exchange and Promotive Association for Medical and Health Care (CPAM), Beijing, 100191, People’s Republic of China; 4Research Center for Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Guo; Yinyin Qu, Department of Anesthesiology, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, 100191, People’s Republic of China, Email puthmzk@hsc.pku.edu.cn; quyinyin@bjmu.edu.cnBackground: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists’ understanding of MH in China.Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants’ perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study.Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P< 0.001), hospital classification (P< 0.001), and urban hierarchy (P< 0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH.Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.Keywords: malignant hyperthermia, dantrolene, China, anesthesiologists, survey

Yuzhu Qu,1– 3,&ast; Ying Peng,4,&ast; Yan Xiong,5 Xiaohui Dong,3 Peihong Ma,6 Shirui Cheng2,3 1Post-Doctoral Scientific Research Workstation of Affiliated Sport Hospital, Chengdu Sport University, Chengdu, Sichuan, People’s Republic of China; 2Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 3Acupuncture and Brain Science Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 4Medical Aesthetics Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 5Department of Osteoporosis, West China Fourth Hospital Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Medical Technology School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shirui Cheng, Chengdu University of Traditional Chinese Medicine, 1166 &num; Liutai Avenue, Chengdu, Sichuan, 611137, People’s Republic of China, Email csr1190@163.com Peihong Ma, Tianjin University of Traditional Chinese Medicine, 10 &num; Poyanghu Road, Tuanpo Xincheng West District, Jinghai District, Tianjin, 301617, People’s Republic of China, Email acu_madai@163.comAbstract: Acupuncture has been widely applied for treating knee osteoarthritis (KOA). Numerous studies have found that acupuncture can effectively alleviate KOA symptoms. With the advancement of neuroimaging techniques, integrating neuroimaging with in-depth investigations of acupuncture mechanisms has emerged as a hot topic in traditional Chinese medical neuroscience research. This review aimed to analyze the study design and main findings from neuroimaging studies of acupuncture-related therapy for KOA to provide a reference for future research. Original studies were sourced from English databases (PubMed, Embase, and Cochrane Library) and Chinese databases (Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, the Chongqing VIP database, and Wanfang database). As a result, thirteen articles were ultimately included in this review. Functional magnetic resonance imaging was the most frequently used neuroimaging technique to explore cerebral responses to acupuncture-related therapy for KOA. Findings suggested that acupuncture-related therapy could regulate some brain regions in patients with KOA. Specifically, for acupuncture, it showed that the medial pain pathway and the limbic system were involved in the regulation of KOA. Meanwhile, moxibustion induced a wide range of functional activity throughout the entire brain.Keywords: acupuncture-related therapy, knee osteoarthritis, cerebral response, neuroimaging study

Zheng Xiang,&ast; Yueyuan Wang,&ast; Yuchen Qu, Bo Lv, Junping Han, Delai Xu, Kai Fan, Cunjin Su, Zhu Shen Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cunjin Su; Zhu Shen, Email sucjgh@vip.163.com; jsdxsz@163.comObjective: To assess the key factors influencing the effectiveness of nirmatrelvir/ritonavir in treating elderly patients with COVID-19.Methods: This study was conducted on patients aged ≥ 60 who were admitted to the Second Affiliated Hospital of Soochow University for COVID-19 infection and were treated with nirmatrelvir/ritonavir. Clinical information was collected from patients and steady-state blood concentrations of nirmatrelvir and ritonavir were measured. Factors associated with treatment effects were searched by univariate and multivariate analysis.Results: A total of 68 (51 males and 17 females) patients had a median age of 80 (73.0– 84.8) years were enrolled in this study. The blood concentration measurements (trough concentrations) of nirmatrelvir and ritonavir were 5.1 (2.6– 7.1) and 0.4 (0.2– 0.9) μg/mL, respectively. Adverse drug reaction was reported in 4 (5.9%) patients. Univariate analysis showed that age, clinical classification, APACHE II score, total bilirubin (TBil), aspartate transaminase (AST), lactate dehydrogenase (LDH), and total cholesterol (TC) were significantly associated with the effectiveness of treatment (P value < 0.05). Concentration of nirmatrelvir was also associated with treatment outcome (P value < 0.1). Based on the results of univariate analysis, the above factors were introduced into the multiple linear regression equation as independent variables, and the results showed that clinical classification was included in the regression equation model and was the most important factor affecting the treatment outcome. By receiver operating characteristic curve analysis, the area under curve of age + biochemical indicators + APACHE II score + clinical classification was 0.968 (95% CI = 0.919– 1.000; P < 0.0001). Among the 68 patients included in the study, 4 cases experienced adverse drug reactions.Conclusion: Age, clinical classification, APACHE II score, TBil, AST, LDH, and TC were significantly associated with the effectiveness of treatment in elderly patients with COVID-19.Keywords: nirmatrelvir/ritonavir, COVID-19, elderly patients, effectiveness

Peng Guo,1,&ast; Chi Huang,2,&ast; Qin Yang,1 Guofeng Zhong,1 Junbo Zhang,1 Mengyu Qiu,1 Rui Zeng,3 Kaijun Gou,3 Chen Zhang,1 Yan Qu1 1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2Department of Pharmacy, Jiang’an Hospital of Traditional Chinese Medicine, Yibin, 644200, People’s Republic of China; 3Institute of Tibetan Plateau, Southwest Minzu University, Chengdu, 610225, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Qu; Chen Zhang, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, People’s Republic of China, Email quyan028@126.com; chenzhang_1990@126.comAbstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation, eventually leading to severe disability and premature death. At present, the treatment of RA is mainly to reduce inflammation, swelling, and pain. Commonly used drugs are non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs). These drugs lack specificity and require long-term, high-dose administration, which can cause serious adverse effects. In addition, the oral, intravenous, and intra-articular injections will reduce patient compliance, resulting in high cost and low bioavailability. Due to these limitations, microneedles (MNs) have emerged as a new strategy to efficiently localize the drugs in inflamed joints for the treatment of RA. MNs can overcome the cuticle barrier of the skin without stimulating nerves and blood vessels. Which can increase patient compliance, improve bioavailability, and avoid systemic circulation. This review summarizes and evaluates the application of MNs in RA, especially dissolving MNs (DMNs). We encourage the use of MNs to treat RA, by describing the general properties of MNs, materials, preparation technology, drug release mechanism, and advantages. Furthermore, we discussed the biological safety, development prospects, and future challenges of MNs, hoping to provide a new strategy for the treatment of RA. Keywords: rheumatoid arthritis, dissolving microneedles, transdermal delivery system, degradability, biosafety

Dong Zhang,1 Yan Qu,2 Changlin Sui,2 Meiling Li,1 Yanmei Yuan,1 Ningning Wang,1 Weiyuan Ma1 1Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Dermatology, Yantai Yuhuangding Hospital, Yantai, Shandong, People’s Republic of ChinaCorrespondence: Weiyuan Ma, Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China, Email fymaweiyuan@wfmc.edu.cnBackground: Condyloma cuminata (CA) is a sexually transmitted disease caused by human papillomavirus (HPV) infection, which is prone to recurrence and difficult to cure in the short term. CD207 is a C-type lectin receptor that is specifically expressed on the surface of Langerhans cells (LCs) and is considered as an LC-specific immunohistochemical marker. The main purpose of this study is to explore the correlation between the expression of CD207 in CA skin lesions and the duration of CA disease course and frequency of recurrence, in order to provide new prognostic markers for CA to clinicians.Materials and Methods: A total of 40 male patients with CA and their skin lesions were collected, as well as 40 healthy male penile tissue samples. The skin lesions of CA were clinically and histologically confirmed by acetic acid test. The expression of CD207 in epidermal tissues was detected using immunohistochemistry. The difference in the number of CD207 positive cells between CA skin lesions and healthy skin controls was compared, and the association between the number of CD207 positive cells in CA skin lesions and the duration of disease course and the frequency of recurrence was determined through Spearman correlation analysis.Conclusion: In CA skin lesions, CD207 positive cells were found to have morphological abnormalities and the number of cells was significantly reduced compared to healthy skin, suggesting that there may be antigen presentation dysfunction in CA skin lesions, which may be the reason for the prolonged and unresolved condition of the disease. The fewer CD207 positive cells in CA skin lesions, the longer the disease course and the more frequent the recurrence, therefore, the expression level of CD207 can be used as a new prognostic marker for predicting the outcome of CA.Keywords: condyloma acuminata, CD207, langerhans cells, prognosis, biomarker

Liwei Wang,1,&ast; Yinyin Qu,1,&ast; Ying Deng,1 Jun Li,1 Yanqing Liu,2 Changyi Wu1 1Department of Anesthesiology, Peking University Third Hospital, Peking University, Beijing, 100191, People’s Republic of China; 2Department of Orthopaedics, Peking University Third Hospital, Peking University, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changyi Wu, Department of Anesthesiology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86-13522028771, Email wuchangyitougao@sina.com Yanqing Liu, Department of Orthopaedics, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86-13611346532, Email yanqing_liu@sohu.comPurpose: The location of the sciatic nerve deep within the thigh tissue makes it challenging to locate while the patient is in a supine position. The posterior intermuscular septum of the thigh, which encircles the posterior surface of the adductor magnus muscle (AMM), is where the sciatic nerve is located. Our hypothesis was that administering local anesthetic injections into this area could block the sciatic nerve. Therefore, our aim was to evaluate the effectiveness of sciatic nerve block achieved by injecting local anesthetic into the posterior intermuscular septum of the thigh, named the AMM approach.Methods: Twenty-six patients undergoing total knee arthroplasty were included in the study. We performed an ultrasound-guided sciatic nerve block by injecting 20 mL of 0.25% ropivacaine into the posterior surface of the adductor magnus muscle, using the AMM approach. Additionally, we administered a femoral nerve block with 20 mL of 0.4% ropivacaine. We assessed the sensory and motor effects of the blockade in the operated lower limb and recorded postoperative pain scores at 0, 4, 8, 12, 24, and 48 hours after the operation.Results: The AMM approach successfully block the sciatic nerve in all 26 patients. The onset of the sensory and motor blockades was achieved within 5.4 ± 1.9 min and 8.7 ± 3.5 min, respectively. We achieved a satisfactory position with the first puncture in 19 of 26 patients (73.1%). The muscle strength of the tibialis anterior immediately after surgery was 4 (ranging from 2 to 5). Additional rescue analgesics were required in 5 of the 26 patients (19.2%) during the first 24 hours postoperatively.Conclusion: The AMM approach is an innovative and effective method for sciatic nerve block. When combined with simultaneous femoral nerve block in patients undergoing total knee arthroplasty, it provides a useful analgesic treatment option.Keywords: sciatic nerve block, adductor magnus muscle, tibialis anterior, femoral nerve block

Weiqiang Xiao,1,&ast; Xiaokun Wang,1,&ast; Yuanye Qu,1 Mingyue Sun,1 Yanmin Chang,1 Wenjiao Li,1 Yong Shen,1,2 Xiufang Shi,3 Min Jing,1 Qingxia Xu1,4 1Department of Clinical Laboratory, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Institute of Biophysics, Chinese Academy of Sciences, Foshan, People’s Republic of China; 3School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 4Zhengzhou Key Laboratory for Diagnosis of Digestive System Tumor Markers, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingxia Xu; Xiufang Shi, Email zlyyxuqingxia0575@zzu.edu.cn; xfshi@zzu.edu.cnBackground: Emergence of blaKPC and blaNDM co-harboring Klebsiella pneumoniae has escalated the threat of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to healthcare. It remains unknown the prevalence and molecular characteristics of CRKP co-producing KPC and NDMs carbapenemases in Henan.Methods and Results: Twenty-seven CRKP strains isolated from different times were selected randomly in affiliated cancer hospital of Zhengzhou University from January 2019 to January 2021, among which one KPC-2 and NDM-5 positive CRKP named K9 was isolated from an abdominal pus sample of a 63-year-old male patient with leukemia. Sequencing of K9 determined that K9 belonged to ST11-KL47, which is resistant to antibiotics such as meropenem, ceftazidime-avibactam and tetracycline. K9 carried two different plasmids that contained blaNDM− 5 and blaKPC− 2. Both plasmids were shown to be novel hybrid plasmids and IS 26 played an important role in generation of two plasmids. Gene blaKPC-2 was flanked by the NTEKPC-Ib-like genetic structure (IS 26-ΔTn 3-ISKpn8-blaKPC-2-ISKpn6-IS 26) and was located on a conjugative IncFII/R/N type hybrid plasmid.Conclusion: The resistance gene blaNDM− 5 located on a region organized as IS 26-blaNDM– 5-ble-trpF-dsbD-ISCR1-sul1-aadA2-dfrA12-IntI1-IS 26 was carried by a phage-plasmid. We described a clinical CRKP co-producing KPC-2 and NDM-5 and emphasized an urgent need to control their further spread.Keywords: carbapenem-resistant Klebsiella pneumoniae, KPC-2, NDM-5, beta-lactamases, hybrid plasmid, IS 26

Renjie Li,1 Tingting Li,1 Yang Xie,1 Shuang Zhai,1 Yang Qu,1 Dan Zhang,1 Liwei Zou,2 Yajuan Yang,2 Xiaoyan Wu,1,2 Fangbiao Tao,1,2 Shuman Tao2,3 1Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2MOE Key Laboratory of Population Health Across Life Cycle; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei, 230032, People’s Republic of China; 3Department of Ophthalmology, The Second Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaCorrespondence: Shuman Tao, Email Shumantao@126.comPurpose: Smartphone use could lead to being physically inactive and a greater risk for health problems, such as inflammation. However, the associations between smartphone use, physical activity (PA), and systemic low-grade inflammation remained unclear. This study aimed to examine the potential mediating effect of PA on the association between smartphone use and inflammation.Patients and Methods: A two-year follow-up study was conducted between April 2019 and April 2021. Duration of smartphone use, smartphone dependence and PA were assessed by a self-administered questionnaire. Laboratory analysis of blood samples was performed to evaluate the levels of TNF-α, IL-6, IL-1β, and CRP as biomarkers of systemic inflammation. The correlations between smartphone use, PA, and inflammation were analyzed using Pearson correlation. Structural equation modelling was used to analyze the potential mediating effect of PA on the associations between smartphone use and inflammation.Results: A total of 210 participants were included with a mean (standard deviation) age of 18.7 (1.0) years, 82 (39%) of whom were males. Smartphone dependence was negatively associated with the total PA level (r=− 0.18, P< 0.01). PA mediated the associations between the duration of smartphone use and smartphone dependence with inflammatory markers. Specifically, as PA decreased, the duration of smartphone use was more negatively associated with TNF-α (ab=− 0.027; 95% CI: − 0.052, − 0.007) and more positively correlated to IL-6 (ab=0.020; 95% CI: 0.001, 0.046) and CRP (ab=0.038; 95% CI: 0.004, 0.086); smartphone dependency was more negatively associated with TNF-α (ab=− 0.139; 95% CI: − 0.288, − 0.017) and more positively related to CRP (ab=0.206; 95% CI: 0.020, 0.421).Conclusion: Our study illustrates that there are no direct associations between smartphone use and systemic low-grade inflammation, however, PA level plays a weak but significant mediating effect on the associations between smartphone use and inflammation among college students.Keywords: smartphone, inflammation, physical activity, mediating role, follow-up

Jiongdi Lu,1,2,&ast; Zhi Zheng,3,&ast; Yixuan Ding,1,2 Yuanxu Qu,1,2 Wentong Mei,1,2 Zhen Fang,1,2 Chang Qu,1,2,&ast; Yulu Feng,4 Yulin Guo,1,2 Chongchong Gao,1,2 Feng Cao,1,2 Fei Li1,2 1Clinical Center of Acute Pancreatitis, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Chui Yang Liu Hospital Affiliated Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Clinical Center of Acute Pancreatitis, Department of General Surgery, Department of Surgery, Xuanwu Hospital of Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-10-83198731, Fax +86-10-83198868, Email feili36@ccmu.edu.cn Feng Cao, Clinical Center of Acute Pancreatitis, Department of General Surgery, Xuanwu Hospital of Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Email f.cao@xwhosp.orgObjective: To clarify the incidence of colonic complications in patients with NP and their impact on prognosis.Methods: The clinical data of NP patients admitted to the Department of General Surgery of Xuanwu Hospital, Capital Medical University from January 2014 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of colonic complications, and the clinical prognosis of the two groups was analyzed after matching using a 1:1 propensity score, The primary study endpoint was patient mortality during hospitalization. Data are reported as median (range) or percentage of patients (%).Results: A total of 306 patients with NP were included in this study, and the incidence of colonic complications was 12.4%, including 15 cases of colonic obstruction, 17 cases of colonic fistula, and 9 cases of colonic hemorrhage. Before matching, patients in the colonic group had severe admissions and poor clinical outcomes (P< 0.05). After matching, the baseline data and clinical characteristics at admission were comparable between the two groups of patients. In terms of clinical outcomes, although the mortality was similar in the two groups (P> 0.05), but patients in the colonic group were more likely to have multiorgan failure, length of nutrition support, number of minimally invasive interventions, number of extra-pancreatic infections, length of ICU stay and total length of stay were significantly higher than those of patients in the group without colonic complications (P< 0.05). During long-term follow-up, patients in the colonic group were more likely to develop recurrent pancreatitis.Conclusion: About 12.4% of NP patients developed colonic complications, and after PSM it was found that colonic complications only led to a longer hospital stay and an increased number of clinical interventions in NP patients and did not increase the mortality.Keywords: necrotizing pancreatitis, colon involvement, propensity score match

Jiongdi Lu,1,2 Yixuan Ding,1,2 Yuanxu Qu,1,2 Wentong Mei,1,2 Yulin Guo,1,2 Zhen Fang,1,2 Chang Qu,1,2 Chongchong Gao,1,2 Feng Cao,1,2,&ast; Fei Li,1,2,&ast; Yulu Feng3 1Clinical Center of Acute Pancreatitis, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pediatric, Chui Yang Liu Hospital Affiliated Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li; Feng Cao, Clinical Center of Acute Pancreatitis, Capital Medical University, Department of General Surgery, Department of Surgery, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-10-83198731, Fax +86-10-83198868, Email feili36@ccmu.edu.cn; f.cao@xwhosp.orgObjective: The incidence of acute pancreatitis (AP) is increasing. Twenty percent of AP patients with developing necrotizing pancreatitis (NP), while ~40– 70% of NP patients develop potentially fatal infectious complications. When patients are suspected or confirmed infected pancreatic necrosis (IPN), antibiotics should be administered timeously to control the infection, but long-term use of antibiotics can lead to multidrug-resistant bacteria (MDRB) infection and eventually to increased mortality. Our study aimed to determine the incidence of MDRB infection and evaluate the risk factors for MDRB infection in IPN patients.Methods: Clinical data of IPN patients admitted to the general surgery department of Xuanwu Hospital of Capital Medical University between January 1, 2014, and December 31, 2021, were retrospectively analyzed.Results: IPN patients (n = 267) were assigned to MDRB infection (n = 124) and non-MDRB infection (n = 143) groups. On admission, patients in the MDRB group had a higher modified computer tomography severity index (CTSI) score (P < 0.05), pancreatic necrosis degree, and PCT level (P < 0.05) than those in the non-MDRB group, and the prognosis of patients in MDRB group was poor. The most common gram-negative bacteria were Acinetobacter baumannii (n = 117), the most common gram-positive bacteria were Enterococcus faecium (n = 98), and the most common fungal infection was Candida albicans (n = 47). Multivariable analysis showed that complications of EPI (OR: 4.116, 95% CI: 1.381– 12.271, P = 0.011), procalcitonin (PCT) level at admission (OR: 2.728, 95% CI: 1.502– 4.954, P = 0.001), and degree of pancreatic necrosis (OR: 2.741, 95% CI: 1.109– 6.775, P = 0.029) were independent risk factors for MDRB infection in IPN patients.Conclusion: We identified common infectious strains and risk factors for MDRB infection in IPN patients.Keywords: infected pancreatic necrosis, extra-pancreatic infection, multidrug-resistant bacteria, risk factor analysis

Guo P, Huang C, Yang Q, et al. Int J Nanomedicine. 2023;18:7759-7784. The authors have advised the correspondence section on page 7759 is incorrect. The correct correspondence address is as follows. Correspondence: Yan Qu, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, People’s Republic of China, Email quyan028@126.com The authors apologize for this error.

Yunfeng Qu, Ruiyang Liu School of Law, Hainan University, Haikou, People’s Republic of ChinaCorrespondence: Ruiyang Liu, School of Law, Hainan University, No. 58 Renmin Road, Meilan District, Haikou, 570228, People’s Republic of China, Email lawliuruiyang@163.comAbstract: With the advent of 5G network technology and the maturity of medical applications associated with 5G, the Internet medical service industry is gradually developing. Given the COVID-19 pandemic crisis occasionally happened in China, hospitals were taken up most of the medical resources, the Internet medical care is seen as the alternative way for patients to access medical care and treatment. With the aid of 5G, patients nowadays can seek remote medical care, diagnosis, and surgery. However, this is not without any problems. The current legal supervision system in the Internet medical service industry is still incomplete, and ought to be augmented. This essay serves to identify and evaluate the loopholes existing in the legal supervision system in the Internet medical service industry, in the hope to improve the current system and ensure the safety of patients who are seeking Internet medical services.Keywords: internet medical care, legal supervision, 5G technology, remote surgery

Suipeng Chen,1,&ast; Mengjiao Kuang,1,&ast; Ying Qu,1,2 Shirui Huang,1 Binbin Gong,1 Suzhen Lin,1 Huiyan Wang,1 Guiye Wang,1 Hongqun Tao,1 Jian Yu,1 Zuqin Yang,3 Minghua Jiang,1 Qipeng Xie1 1Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 2Department of Clinical Laboratory, Wenzhou People’s Hospital, The Third Affiliated Hospital of Shanghai University, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 3Newborn Department of Pediatrics, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qipeng Xie, Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86 15157787159, Email pandon2002@163.comObjective: Sepsis remains a major cause of neonatal death. To better characterize the inflammatory response during neonatal sepsis, we compared the differences in serum cytokines and chemokines between full-term neonates with sepsis and without infection.Methods: We enrolled 40 full-term neonates with sepsis and 26 full-term neonates without infection as controls between October 2016 and June 2018. Forty cytokines /chemokines in serum were analyzed using the Luminex Bead Immunoassay System.Results: Our results showed that serum IL-6, IL-8, TNF-α, IL-1β, MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, and CX3CL1 levels were significantly increased in neonates with sepsis compared to those in the control group (all p< 0.05). The levels of serum CCL20, and IL-17 were higher in late-onset sepsis (LOS) than those in early-onset sepsis (EOS) (all p< 0.05). Conversely, serum CXCL16 was lower in LOS than that in EOS (p< 0.05).Conclusion: Our findings revealed that excessive pro-inflammatory cytokines might be involved in neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but this could lead to damage.Keywords: neonatal sepsis, cytokines, chemokines

Xiaoxiao Qu,1,&ast; Shishi Wang,1,&ast; Ying Qu,2 Huiyan Wang,1 Xuanmei Ye,1 Luming Tang,3 Qipeng Xie1 1Department of Clinical Laboratory, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2Department of Clinical Laboratory, Wenzhou People’s Hospital, The Third Affiliated Hospital of Shanghai University, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 3Emergency Department, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qipeng Xie, Department of Clinical Laboratory, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86 151 577 87159, Email pandon2002@163.comPurpose: To clarify the distribution of pathogenic bacteria by analyzing the bacterial susceptibility characteristics and risk factors for adult sepsis in The Wenzhou city, Zhejiang province, China, and to aid early diagnosis, monitoring, and prognosis prediction in cases of bacterial sepsis.Patients and Methods: We retrospectively analyzed 329 patients with sepsis admitted to the Second Affiliated Hospital of Wenzhou Medical University between January 2018 and March 2021. Laboratory data were collected before and after treatment; moreover, the bacterial susceptibility characteristics and risk factors for sepsis were comprehensively analyzed using the Sequential Organ Failure Assessment (SOFA) score.Results: The SOFA score was negatively correlated with the prognosis (P < 0.05). We isolated 47 pathogenic strains from blood culture samples, including 29 gram-positive strains, 18 gram-negative strains. The most common gram-negative pathogens in blood cultures are Klebsiella pneumoniae and Escherichia coli, while the most common gram-positive pathogens are Staphylococcus aureus and Staphylococcus hominis. Gram-negative pathogens had resistance rates of 77% and 62.5% to ciprofloxacin and ceftriaxone, respectively. Gram-positive bacteria had a high resistance to penicillin at 100%. Prognostic factors for sepsis included patients’ consciousness, SOFA score, prothrombin time, international normalized ratio, fibrinogen, D-dimer, and aspartate aminotransferase (P < 0.05). Of these, the D-dimer level could predict the outcome of patients with sepsis (AUC = 0.661, P < 0.05).Conclusion: The pathogens detected in adult sepsis in Wenzhou are mainly Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Staphylococcus hominis. The pathogens exhibited differences in drug susceptibility. The optimal antibiotics should be chosen based on the principles of rational use and drug susceptibility. Combined with D-dimer levels, these parameters can be used to determine the optimal strategy for preventing and treating pathogenic bacteria.Keywords: adult sepsis, drug susceptibility characteristics, risk factors, D-dimer

Zihan Wei, Ying Zhang, Sizhen Yang, Chenhui Cai, Jiawen Ye, Hao Qiu, Xu Hu, Yiyun Qu, Xuan Wen, Tongwei Chu Department of Orthopedics, Xinqiao Hospital of Chongqing, Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Tongwei Chu, Department of Orthopedics, Xinqiao Hospital of Chongqing, Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China, Tel/Fax +8613708388336, Email chtw@sina.comObjective: To compare the cervical sagittal balance parameters and clinical efficacy of three fusion devices after short-segment anterior cervical discectomy and fusion.Patients and Methods: Retrospectively analyzed 516 patients with cervical spondylosis who underwent surgery at our hospital from May 2013 to May 2019. All patients had complete data and were divided into three groups according to the selected fusion cage. Neck and upper limb pain were assessed by the visual analog scale (VAS) score. Neurological function was evaluated by the modified Japanese Orthopedics Society (mJOA) score. Also, the curvature of the cervical spine and the occurrence of dysphagia were observed.Results: There were no significant differences in the general information, thoracic inlet angle, T1 slope, or surgical data among the groups (p> 0.05). There were significant differences in the scores between pre- and postoperatively in the different groups (p< 0.05). There were no significant differences in the C2-C7 Cobb angle or C2-C7 sagittal vertebral axis before the operation among the groups (p> 0.05). There was a significant difference in the correction and loss of correction among the groups postoperatively and on follow-up (p> 0.05). Dysphagia was less likely in the Zero-P VA fusion group than in the other two groups.Conclusion: Different fusion instruments can relieve the symptoms. In the Prodisc-C Vivo group, no significant improvement in cervical sagittal balance was achieved. A good effect on improving sagittal balance was observed in both the Zero-P VA fusion and Skyline anterior cervical titanium plate groups, but a better effect on preventing dysphagia was observed in the Zero-PVA fusion group.Keywords: retrospective analyze, cervical spondylosis, anterior cervical discectomy and fusion, cervical sagittal balance parameters, fusion devices

Yongjie Xiong,1 Yi Qu,1 Zhe Min,1 Jun Wu,2 Suming Zhang,1 Zheng Xue1 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic Of ChinaCorrespondence: Zheng Xue, Department of Neurology, Tongji Hospital, Tongji College of Medicine, Huazhong University of Science and Technology, Wuhan, 430000, People’s Republic of China, Tel +86 1 404 234 5433, Email xuezheng@hust.edu.cnPurpose: Magnetic resonance imaging (MRI) is a promising technique for detecting amyloid beta (Aβ) deposits in Alzheimer’s disease (AD). Contrast agents can reduce the scanning time and provide specific images to identify various structures. This study aimed to develop an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle coupled with a functional protein as a targeted MRI contrast agent to detect Aβ deposits.Methods: The targeted MRI contrast agent USPIO nanoparticle was coupled with Aβ(16– 20) (KLVFF) and HIV-1 trans-activating transcriptor-protein transduction domain (Tat-PTD) to produce the Tat-PTD-USPIO-Aβ(16– 20) structure to better penetrate the blood–brain barrier (BBB). In vitro studies were conducted to measure the coupling efficiency, including bicinchoninic acid protein assays, potassium ferrocyanide staining of cardiac microvascular endothelial cells, 1.5T MRI, and toxicity assessments. The contrast agent was injected into five transgenic mice and five age-matched wild-type mice for MRI and histological studies. The targeted agent was diluted, and all mice were scanned with a 7.0 Tesla MRI-scanner. The brain tissues were processed as frozen sections for Thioflavin-S staining to detect Aβ.Results: The coupling efficiency reached 97.75%. The developed MRI contrast agent successfully passed through biological membranes, bound to Aβ deposits, and decreased the MRI signal of tissue in vitro and in vivo. Compared with Aβ(16– 20) or Aβ(1– 40) alone, there was no significant toxicity of Tat-PTD or Aβ(16– 20) when coupled with USPIO nanoparticles.Conclusion: Our novel MRI contrast agent USPIO nanoparticle coupled with functional protein can pass through biological membranes in vitro and visualize Aβ deposits in AD animal models by MRI.Keywords: Alzheimer’s disease, transgenic mice, contrast agent, magnetic resonance imaging, nanomolecular imaging

Self-thinning due to density-dependent mortality usually occurs during the forest development. To improve predictions of such processes during forest successions under climate change, reliable stand-level models are needed. In this study, we developed an integrated system of tree- and stand-level models by deriving tree diameter and survival models from stand growth and survival models based on climate-sensitive self-thinning rule of Chinese fir plantations in subtropical China. The resulting integrated system, having a unified mathematical structure, should provide consistent estimates at both tree and stand levels. Predictions were reasonable at both stand and tree levels. Because stand-level values aggregated from the tree model outputs are different from those predicted directly from the stand models, the disaggregation approach was applied to provide numerical consistency between models of different resolutions. Compared to the unadjusted approach, predictions from the disaggregation approach were slightly worse for tree survival but slightly better for tree diameter. Because the stand models were developed under the climate-sensitive self-thinning trajectory, the integrated system could offer reasonable predictions that could aid in managing Chinese fir plantations under climate change.

Shuang Zhai,1 Shuman Tao,2,3 Xiaoyan Wu,1,3 Liwei Zou,1 Yajuan Yang,4 Yang Xie,1 Tingting Li,1 Dan Zhang,1 Yang Qu,1 Fangbiao Tao1,3 1Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 2Department of Nephrology, The Second Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3MOE Key Laboratory of Population Health Across Life Cycle/NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, People’s Republic of China; 4School of Nursing, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Shuman TaoDepartment of Nephrology, The Second Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaTel +86 15077927106Email shumantao@126.comPurpose: Sleep insufficiency and circadian rhythm disturbances in college students have become prominent. Current findings show that sleep insufficiency is closely related to inflammation. Studies on the correlation between chronotype and inflammatory factors are still lacking. Therefore, this research intended to examine the relationships between sleep duration, chronotype and inflammatory cytokines in young adults, and to estimate the correlation between chronotype and inflammatory cytokines stratified by sleep duration.Patients and Methods: We conducted a cross-sectional study in April and May 2019. Participants were recruited from two colleges located in central China. The Pittsburgh Sleep Quality Index (PSQI) and the Morning and Evening Questionnaire-5 (MEQ-5) were administered to assess sleep duration and chronotype. Sleep duration less than 7 hours was defined as insufficient sleep. Fasting venous blood was collected to measure plasma levels of inflammatory markers including IL-1β, IL-6, TNF-α and IL-10.Results: A total of 723 participants were included in this study, with a mean age of 18.68 years (standard deviation=0.99). After adjusting for confounding factors, the results of generalized linear model showed that sleep insufficiency was positively correlated with IL-1β, TNF-α and IL-10; and evening-types (E-types) were positively associated with the levels of IL-1β and IL-6 (p< 0.05). Compared to the control group (sleep sufficiency and M-types), there were positive interaction effects of sleep insufficiency and neutral-types (N-types) on the levels of IL-1β, IL-6, TNF-α and IL-10 (p< 0.05). The hierarchical regression model showed that N-types and E-types were positively correlated to the levels of IL-1β, IL-6, TNF-α and IL-10 among college students with sleep insufficiency (p< 0.05).Conclusion: The levels of inflammatory markers were higher among college students with sleep insufficiency and E-types. N-types and E-types were positively correlated with IL-1β, IL-6, TNF-α and IL-10 among college students with sleep insufficiency.Keywords: sleep duration, circadian rhythm, chronic inflammation, young adults

Yan Qu,1 Xien Feng,2 Jin’ning Liang,2 Junru Liu,3 Dong Gao2 1Department of Dermatology, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, People’s Republic of China; 2Department of Dermatology, Yantai Yuhuangding Hospital, Yantai, 264003, Shandong, People’s Republic of China; 3Department of Dermatology, Yantai Yuhuangding Hospital Laishan Branch, Yantai, 264003, Shandong, People’s Republic of ChinaCorrespondence: Dong Gao Email gaodong_yhd@163.comObjective: We aimed to investigate picosecond laser effects regarding rat tattoo removals. We systematically detected the metabolic pathways considering tattoo pigment particles in rat models.Materials and Methods: We employed fluorescein to mark the tattoo dye and utilized a pattern needle to prepare tattoo on rat so as to establish the tattoo removal effects of picosecond laser methods employing animal models. We applied a picosecond laser to process the tattoo and observed the effects along with metabolic pathways for tattoo removal via pathology and imaging approaches.Results: Based on the results of characterization, pathology and fluorescence, we discovered that the picosecond laser could effectively remove the pigment particles on rat skin, part of which would be metabolized out of the body through the circulatory system. After picosecond laser treatment, the fluorescence intensity of the rat skin engraved part was gradually weakened. At 8 h after the treatment, the metabolic organs had weak fluorescence, and there was no fluorescence in the metabolic organs at 12 h and 24 h after the treatment.Conclusion: The picosecond laser had perfect tattoo removal effects, which could be utilized as a reference for clinical tattoo removal.Keywords: tattoo, picosecond laser, pattern engraving, dye

Chunmei Wang,1,2,* Jun Liu,3,* Xiaoye Shi,1 Shaoze Ma,1 Guangqin Xu,1 Tingwei Liu,1 Tingting Xu,3 Bo Huang,3 Ying Qu,4 Xiaozhong Guo,1 Xingshun Qi1 1Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, People’s Republic of China; 2Graduate School, Jinzhou Medical University, Jinzhou, People’s Republic of China; 3Military Joint Teaching and Research Office, The 32684 Troop of Chinese PLA, Shenyang, People’s Republic of China; 4Department of Health Care, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xingshun Qi; Xiaozhong GuoDepartment of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), No. 83 Wenhua Road, Shenyang, Liaoning Province, 110840, People’s Republic of ChinaTel +86-24-28897603Fax +86-24-28851113Email xingshunqi@126.com; guo_xiao_zhong@126.comPurpose: Helicobacter pylori infection is an important cause of peptic ulcer disease and gastric cancer. Current knowledge regarding epidemiology of H. pylori infection in military personnel has insufficiently been updated. This cross-sectional study aimed to estimate the prevalence of H. pylori infection in military personnel and to compare the prevalences in military and civilian groups.Patients and Methods: We retrospectively enrolled the subjects who underwent 14C-urea breath tests at the Department of Gastroenterology of the General Hospital of Northern Theater Command between January 2017 and July 2020. Subjects were divided into military and civilian groups. H. pylori infection and major endoscopic findings were reviewed.Results: Overall, 23,496 subjects were eligible, including 2282 subjects in the military group and 21,214 subjects in the civilian group. In the overall analysis, the prevalence of H. pylori infection was not significantly different between military and civilian groups (33.9% versus 34.4%, P=0.592). In the population aged 17– 25 years, the prevalence of H. pylori infection was significantly higher in the military group than in the civilian group (35.6% versus 25.9%, P=0.001). Both 14C-UBT and endoscopy were performed in 547 inpatients, including 83 military inpatients and 464 civilian inpatients. There was a significantly higher prevalence of H. pylori in inpatients with peptic ulcer and/or gastric cancer than in those without (65.5% versus 41.4%, P=0.001).Conclusion: Among the adolescent population, H. pylori infection may be more common in military personnel as compared to the civilians. Well-designed prospective studies should be required to validate such a high prevalence and to explain its potential causes.Keywords: Helicobacter pylori, prevalence, military, epidemiology, endoscopy

Changcong Wang,1 Yangming Qu,1 Huikun Niu,1 Yingan Pan,1 Yinghua He,2 Jianwei Liu,2 Nan Yao,1 Han Wang,1 Yinpei Guo,1 Yang Pan,2,3 Bo Li1 1Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 2Jilin Provincial Center for Disease Control and Prevention, Changchun, Jilin, 130062, People’s Republic of China; 3Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Bo LiDepartment of Epidemiology and Biostatistics, Jilin University School of Public Health, 1163 Xinmin Street, Changchun, Jilin, 130021, People’s Republic of ChinaTel/Fax +86 43185619451Email li_bo@jlu.edu.cnYang PanJilin Provincial Center for Disease Control and Prevention, Changchun, Jilin, 130062, People’s Republic of ChinaTel +86 18844504063Email 18844504063@163.comPurpose: Respiratory disease is a major and increasingly global epidemic that has a great impact on humans, especially children. The purpose of this study was to identify environmental risk factors for respiratory diseases and pulmonary function in children.Patients and Methods: A population-based, cross-sectional survey of respiratory diseases and environmental risk factors was conducted in Jilin Province, China. Complete questionnaire information was available for 2419 children, while adequate pulmonary function data were available for a subgroup of 627 children.Results: Our study found that environmental risk factors for respiratory health in children were mainly concentrated indoors. After adjusting for demographic factors, insecticide exposure and passive smoking were risk factors for respiratory disease and industrial pollutant sources, insecticide exposure and the use of a fume exhauster may be independent risk factors for recurrent respiratory infections. The main fuel for cooking in the winter and passive smoking were the main influencing factors of pulmonary function indicators.Conclusion: The primary risk factors differ in different respiratory diseases. Passive smoking remains a critical adverse factor for respiratory illness and pulmonary function in children, and it is important to reduce children’s exposure to passive smoking to increase pulmonary health. Insecticide exposure may be a neglected environmental risk factor, and further investigations are still needed to explore the relationship and mechanisms between insecticide exposure and children’s respiratory health.Keywords: respiratory diseases, lung function, environmental risk factors

Jinge Zhou,1,* Zekang Xiong,1,* Man Liu,2 Liang Yang,1 Sheng Yao,1 Kaifang Chen,1 Keda Yu,1 Yanzhen Qu,1 Tingfang Sun,1 Xiaodong Guo1 1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China; 2Department of Gastroenterology and Hepatology, Taikang Tongji Hospital, Wuhan 430050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong Guo; Tingfang Sun Tel +8615327216660; +8613554435801Email xiaodongguo@hust.edu.cn; tingfangsun@163.comIntroduction: Decellularized matrix from porcine small intestinal submucosa (SIS) endows scaffolds with an ECM-like surface, which enhances stem cell self-renewal, proliferation, and differentiation. Mesoporous bioactive glass (MBG) is extensively recognized as an excellent bio-ceramic for fabricating bone grafts.Materials and Methods: In the current study, SIS was doped on an MBG scaffold (MBG/SIS) using polyurethane foam templating and polydopamine chemistry method. To mimic the bony environment of a natural bone matrix, an ECM-inspired delivery system was constructed by coupling the BMP2-related peptide P28 to a heparinized MBG/SIS scaffold (MBG/SIS-H-P28). The release of P28 from MBG/SIS-H-P28 and its effects on the proliferation, viability, and osteogenic differentiation of bone marrow stromal stem cells were investigated in vitro and in vivo.Results: Our research indicated that the novel tissue-derived ECM scaffold MBG/SIS has a hierarchical and interconnected porous architecture, and superior biomechanical properties. MBG/SIS-H-P28 released P28 in a controlled manner, with the long-term release time of 40 d. The results of in vitro experiments showed improvements in cell proliferation, cell viability, alkaline phosphatase activity, and mRNA expression levels of osteogenesis-related genes (Runx-2, OCN, OPN, and ALP) compared to those of MBG/SIS or MBG/SIS-P28 and MBG/SIS-H-P28. The in vivo results demonstrated that MBG/SIS-H-P28 scaffolds evidently increased bone formation in rat calvarial critical-sized defect compared to that in controls.Conclusion: MBG/SIS-H-P28 scaffolds show potential as ideal platforms for delivery of P28 and for providing a bony environment for bone regeneration.Keywords: small intestinal submucosa, mesoporous bioactive glass, microenvironment, osteogenesis, BMP2-related peptide

Xince Shen,1 Yunfeng Qu,1 Qiuzi Wu2 1School of Law, Hainan University, Haikou, Hainan, People’s Republic of China; 2Graduate Institute of Interpretation and Translation, Beijing Foreign Studies University, Beijing, People’s Republic of ChinaCorrespondence: Xince ShenSchool of Law, Hainan University, No. 58 Renmin Road, Meilan District, Haikou City, Hainan Province, People’s Republic of ChinaEmail shlxce@foxmail.comAbstract: While China’s medical tourism industry is increasingly standardized and institutionalized, the relevant research assessing its legal risks is still absent. This paper aims to evaluate the risks of medical tourism from the legal perspective by exploring the conflict between the developing new practice and the existing legal system, summarizing the legal risks in medical tourism, and proposing measures and suggestions to mitigate such risks. The empirical research method is employed to review the legal risks in Boao Lecheng International Medical Tourism Pilot Zone, which is the pioneering project of China’s development within the medical tourism industry. These research methods include collecting the latest medical tourism policies and regulations, judicial decisions, and on-the-spot investigation of the Pilot Zone. It is found that the legal risks in medical tourism activities are mainly concentrated in the administrative, civil and litigious legal relations, and concern four major subjects which are regulators, medical operators, tourism operators and consumers. For regulators, their administrative supervision has not been well in place before and during medical tourism activities, and there remain legal gaps in regulation. In terms of the protection of consumers’ substantive rights, service providers and operators may evade their responsibilities by exploring the vacuum area during the transition from the old laws to the new ones, and the conflicting provisions exist between the special laws and general ones. Concerning the protection of consumers’ litigation rights, there are many obstacles for consumers to safeguard their interests through litigation in a foreign land. In this paper, medical tourism activities are identified among four legal subjects and involving three types of legal risks, in the hope to help improve the overall understanding of medical tourism from the legal perspective, and put forward targeted suggestions on the potential legal risks.Keywords: medical tourism, legal risk, Boao Lecheng International Medical Tourism Pilot Zone, Free Trade Port

Huili Wang, Runye Wu, Xiaodong Huang, Yuan Qu, Kai Wang, Qingfeng Liu, Xuesong Chen, Ye Zhang, Shiping Zhang, Jianping Xiao, Junlin Yi, Guozhen Xu, Li Gao, Jingwei Luo National Cancer Center/National Cancer Clinical Medical Research Center/Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jingwei LuoNational Cancer Center/National Cancer Clinical Medical Research Center/Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Hospital, Beijing, People’s Republic of ChinaTel +86 13601181202Email jingwei-luo@outlook.comBackground: This study was to determine the patterns of regional lymph node (LN) spread and the risk factors of retropharyngeal lymph node (RPLN) metastasis based on magnetic resonance imaging (MRI) in hypopharyngeal squamous carcinoma (HPC) to improve clinical target volume (CTV) delineation.Methods: A cohort of 326 consecutive patients of HPC in a single institute were retrospectively reviewed. All patients underwent MRI prior to initial treatment, and the diagnosis based on MRI of the LN metastasis was confirmed by all radiation oncologists in the head and neck group during twice weekly chat rounds. Statistical analysis of data was using chi-square test and multivariant logistic regression model in SPSS 22.0 software.Results: The LN metastasis rate of all patients in this cohort was 90.5% (295/326). Level IIa/b and level III were the most frequently involved regions followed by level IV and retropharyngeal region. Skip metastasis only occurred in 6.4% (19/295). Univariate and multivariate analysis demonstrated that primary tumor subsites were located in the posterior pharyngeal wall (P=0.002), bilateral cervical LN metastasis (P=0.020), larger volume of primary gross target (GTVp, P=0.003), and larger volume of LN gross target (GTVnd, P=0.023) were significantly associated with RPLN metastasis.Conclusion: The regional LN spread of HPC follows an ordered pattern as level II is the most frequently involved area followed by level III, level IV, and RPLN. RPLN metastasis is more likely to occur in patients with primary site of posterior pharyngeal wall, large tumor burden, or bilateral neck LN metastasis. Therefore, it is highly recommended that the RPLN should be included into CTV for patients who have these risk factors.Keywords: hypopharyngeal carcinoma, lymph node metastasis, risk factors, retropharyngeal lymph node, metastasis

Ling An,1,* Dongde Ji,2,* Wenbo Hu,1 Jianrong Wang,1 Xiuzhen Jin,3 Yunfei Qu,4 Ning Zhang5 1Department of Nephrology, Qinghai Provincial People’s Hospital, Xining 810007, People’s Republic of China; 2Department of Gastroenterology, Qinghai Provincial People’s Hospital, Xining 810007, People’s Republic of China; 3Department of Nursing, Qinghai Institute of Health Sciences, Xining 810007, People’s Republic of China; 4Department of Cardiovascular Surgery, Chongqing University Three Gorges Hospital, Chongqing 404000, People’s Republic of China; 5Department of General Practice, Chongqing University Three Gorges Hospital, Chongqing 404000, People’s Republic of China*These authors contributed equally to this work.Correspondence: Yunfei Qu; Ning ZhangChongqing University Three Gorges Hospital, No. 165, Xincheng Road, Wanzhou District, Chongqing 404000, People’s Republic of ChinaEmail yunfeiqu0521@163.com; zhangnning667@163.comBackground: Diabetic nephropathy (DN) is a severe end-stage kidney disease developed from diabetes mellitus. The involvement of circular RNA (circRNAs) in the regulation of DN pathogenesis has been implied, but the underlying mechanism of DN is still lacking. This study aimed to investigate the effect of hsa_circ_0003928 on the inflammation and apoptosis of high glucose (HG)-induced renal tubular cells.Methods: The expression of hsa_circ_0003928, miR-151-3p and Anxa2 in blood samples from DN patients and healthy controls was detected by RT-qPCR. Human renal epithelial cells HK-2 were incubated with D-glucose (30 mmol/l) to establish DN model in vitro. RT-qPCR analysis confirmed the transfection effects and detected the expressions of TNF-α, IL-6 and IL-1β. Western blotting analysis determined the protein expression of Anxa2, Bcl-2, Bax, cleaved caspase-3 and caspase-3. The production of ROS was detected by DCF-DA method and production of inflammatory cytokines was verified by ELISA assay. CCK-8 assay and TUNEL assay were performed to determine cell viability and apoptosis, respectively. Dual-luciferase reporter assay was performed to confirm the relationship between miR-151-3p and hsa_circ_0003928 or Anxa2.Results: Hsa_circ_0003928 and Anxa2 mRNA levels were increased, whereas miR-151-3p was decreased in both HG-induced HK-2 cells and patients with DN. Hsa_circ_0003928 knockdown could decrease cell viability loss and apoptosis, increase Bcl-2 expression, and decrease Bax and cleaved caspase-3 expression. Besides, hsa_circ_0003928 knockdown suppressed HG-induced overproduction of ROS, TNF-α, IL-6 and IL-1β. However, the effects made by miR-151-3p inhibition were opposite to those made by hsa_circ_0003928 knockdown. Furthermore, the binding sites between miR-151-3p and hsa_circ_0003928 or Anxa2 were predicted and verified. Protein expression of Anxa2 was suppressed by hsa_circ_0003928 knockdown, which was rescued by miR-151-3p inhibition.Conclusion: These results demonstrated that hsa_circ_0003928 could act as a sponge of miR-151-3p and regulate HG-induced inflammation and apoptosis partly through regulating Anxa2.Keywords: diabetic nephropathy, hsa_circ_0003928, miR-151-3p, Anxa2

Li Liu,1 Di Wu,2 Lulu Wang,1 Yunting Qu,1 Hui Wu1 1Department of Social Medicine, School of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2School of Fundamental Sciences, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Hui WuDepartment of Social Medicine, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, People’s Republic of ChinaTel +86 189 0091 0568Email hwu@cmu.edu.cnPurpose: Fatigue undermines nurses’ well-being and work performance worldwide. Work stress is a critical factor that causes nurses’ fatigue, but the solutions are not well known. This study aimed to identify the moderated mediation model of fatigue involving effort-reward imbalance (ERI), resilience and perceived organizational support (POS) in Chinese nurses.Methods: In a cross-sectional investigation conducted in Liaoning Province of China, 996 nurses completed the self-administered measurements of fatigue, ERI, resilience and POS. Moderated mediation was tested using the PROCESS procedure. The “pick-a-point” method was adopted to assess conditional effect on fatigue.Results: The indirect effect of ERI on fatigue through resilience was significant (a×b = 0.119, BCa 95% CI: 0.094 to 0.146), indicating a partial mediation of resilience. POS moderated the association of resilience with fatigue (β = − 0.056, p = 0.006). The higher the level of POS was, the stronger the resilience-fatigue association became. Thus, the mediating role of resilience in the ERI-fatigue association was gradually increased with the increase of POS level (low POS: 0.073; moderate POS: 0.095; high POS: 0.116).Conclusion: Resilience could partially mediate the ERI-fatigue association. POS could act as a moderator that enhanced the association of resilience with fatigue. A moderated mediation model of fatigue was demonstrated in Chinese nurses. Managers should establish a balanced social reciprocity, and improve nurses’ resilience and POS in order to decrease nurses’ fatigue.Keywords: fatigue, effort-reward imbalance, resilience, perceived organizational support, nurses

Yan Qu,* Zhihua Wen,* Si Mi, Pengxiang Chen, Jianbo Wang, Yibin Jia, Yufeng Cheng Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yufeng ChengDepartment of Radiation Oncology, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan, 250012, People’s Republic of ChinaTel +86 1 876 978 5399Email qlchengyf@163.comPurpose: To clarify the effect of 12-lipoxygenase/12-hydroxyeicosatetraeonic acid (12-LOX/12-HETE) on progress of esophageal squamous cell carcinoma (ESCC) and the possible mechanism.Patients and methods: We performed cell experiments including chemical treatment, transfection, Western blotting and transwell assay to investigate the function of 12-LOX/12-HETE. Slices of tumor tissues were obtained from ESCC patients treated in Qilu Hospital of Shandong University. Immunohistochemical (IHC) staining was done to find their correlation with prognosis and clinicopathological characteristics.Results: In ESCC cells, inhibition of 12-LOX caused a decrease in transforming growth factor-β1 (TGF-β1)-mediated epithelial-mesenchymal transition (EMT) level, and abilities of migration and invasion were also inhibited. Nevertheless, the inhibition could be partly relieved when treated with 12-HETE or TGF-β1. Analyses of IHC staining indicated a positive correlation between the expression of 12-LOX and EMT level, and an inverse correlation between 12-LOX and overall survival (OS). Univariate and multivariate analyses further suggested that 12-LOX was an independent prognostic factor for ESCC patients.Conclusion: In conclusion, our study proved that 12-LOX/12-HETE-promoted tumor migration and invasion might partly be through TGF-β1-mediated EMT in ESCC, and 12-LOX could be a promising biomarker for predicting prognosis in ESCC patients.Keywords: 12-LOX, 12-HETE, Baicalein, tumor metastasis, overall survival

Ye Tao,*,1,2 Miao He,*,3 Qinghua Yang,1 Zhao Ma,3 Yingxin Qu,1 Wen Chen,3 Guanghua Peng,1 Dengke Teng41Department of Physiology, Basic Medical College, Zhengzhou University, Zhengzhou 450001, People’s Republic of China; 2Lab of Visual Cell Differentiation, Basic Medical College, Zhengzhou University, Zhengzhou 450001, People’s Republic of China; 3Department of Neurosurgery, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, People’s Republic of China; 4Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China*These authors contributed equally to this workObjective: Retinitis pigmentosa causes progressive photoreceptor degeneration in the subjects while no clinical therapy exists. The present study sought to evaluate the potential protective effects of taurine on a pharmacologically induced RP animal model.Methods: Photoreceptor degeneration in mice was induced by an intraperitoneal injection of N-methyl-N-nitrosourea (MNU). The MNU-administrated mouse received taurine treatment and then they were examined by electroretinography, spectral-domain optical coherence tomography, optokinetic test, and histological and immunohistochemistry assay.Results: Prominent taurine deficiency was found in the retinas of MNU-administered mice. Intravenous taurine treatment increased significantly the retinal taurine level. Morphological studies showed that taurine could alleviate the retinal disorganizations in the MNU-induced mice. Taurine also ameliorated the visual impairments in the MNU-induced mice as evidenced by functional examinations. Immunostaining experiments demonstrated that both the M-cone and S-cone populations in the degenerative retinas are rescued by taurine. In particular, the M-cone photoreceptors in superior-temporal quadrant and the S-cone photoreceptors in inferior-nasal quadrant were preferentially rescued. Mechanism study showed that the photoreceptor apoptosis and oxidative stress in the degenerative retina were effectively alleviated by taurine treatment.Conclusion: Taurine is protective against the MNU-induced photoreceptor degeneration. Systemic taurine administration may act as a promising therapeutic potion for retinopathies with chronic cycle.Keywords: neural degeneration, retina, therapeutics

Li Qiao1,2, Chunjiang Yu,1 Hongwei Zhang,1 Mingshan Zhang,1 Yanming Qu,1 Ming Ren,1 Chunyu Gu,1 Haoran Wang11Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, Gansu Provincial Hospital, Lanzhou, Gansu Province, People’s Republic of ChinaPurpose: The relationship of clinical results and survival analysis of operative patients with petroclival meningioma (PCM) was studied.Patients and methods: Data from a total of 176 PCM patients receiving surgical resection were retrospectively collected. Follow-up was conducted through outpatient review by reexamination telephone calls and letters. Clinical outcomes, survival, and Karnofsky Performance Scale (KPS) data were analyzed.Results: Seventy-two percent of patients (127/176) received only surgery, 8.5% (15/176) received surgery and adjuvant radiation therapy (RT) (surgery + RT), and 19.3% (34/176) received surgery and adjuvant gamma knife surgery (GKS) (surgery + GKS). Gross total resection (GTR) was performed in 34.7% of patients (61/176), subtotal resection (STR) in 58.0% (102/176), and partial resection (PR) in 7.4% (13/176). Recent follow-up KPS was higher than preoperative (80 vs 70, P

Lijun Yang,* Yafei Ye,* Jie Chu, Jinlin Jia, Yunhui Qu, Ting Sun, Huiqing Yin, Liang Ming, Junhu Wan, Fucheng HeDepartment of Medical Laboratory, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China*These authors contributed equally to this workBackground: Long noncoding RNAs (lncRNAs), a class of noncoding RNA nucleotides >200 bp, has been demonstrated to play vital role in the development of cancer. FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) has been reported as an lncRNA which acts as a tumor-promoting effect in some cancers. However, the role of it in esophageal squamous cell carcinoma (ESCC) and its potential regulatory mechanism was unclear now.Methods: qRT-PCR was used to detect the levels of FEZF1-AS1 and mRNA CTNNB1 (β-catenin) in ESCC tissues and cells. Cell transfection experiments were used to knock down or overexpress the level of FEZF1-AS1 in EC1 and EC9706 cell lines. WST-1 assays, cell cycle assays, scratch wound assays, migration, and invasion assays were used to evaluate the function of FEZF1-AS1 in ESCC progression.Results: FEZF1-AS1 was remarkably upregulated in ESCC tissues and cell lines. Silencing of FEZF1-AS1 significantly inhibited the migration and invasion of ESCC cells, while overexpression of FEZF1-AS1 notably accelerated ESCC migration and invasion. Meanwhile, the levels of FEZF1-AS1 had no effect on ESCC cell proliferation and cell cycle. We also found that β-catenin was upregulated in ESCC tissues, and the level of it was positively correlated with the expression of FEZF1-AS1. Silencing of FEZF1-AS1 could decrease the mRNA and protein level of β-catenin, while overexpression FEZF1-AS1 could lead to the contrary.Conclusion: Our results suggested that the expression of lncRNA FEZF1-AS1 played an important role in ESCC progression, especially the motility of the tumor. FEZF1-AS1 may provide us with a new sight for ESCC treatment.Keywords: esophageal squamous cell carcinoma, lncRNA, FEZF1-AS1, biological function, β-catenin

Jianda Xu,1,* Yuxing Qu,1 Huan Li,2 Tao Jiang,1,* Chong Zheng,1 Bin Wang,1 Pengfei Shen1 1Department of Orthopaedics, Changzhou Traditional Chinese Medical Hospital, Changzhou, Jiangsu 213003, China; 2Department of Arthroplasty, The First People’s Hospital of Changzhou, Changzhou, Jiangsu 213003, China *These authors contributed equally to this work Background: To date, a regional approach using local anesthetics has become a popular analgesic method for arthroscopy. The optimal postoperative analgesia method for shoulder arthroscopy is still debated. Objective: This study was designed to evaluate the effect and safety of using ketorolac in combination with a multimodal drug regime (ropivacaine, morphine, and triamcinolone acetonide) after shoulder arthroscopy. Methods: A total of 60 patients were included in a pilot study and patients were randomized into an experimental group (n=30) and a control group (n=30). The following parameters were used to evaluate pain relief levels postoperatively: the Visual Analog Scale (VAS) at 1, 3, 6, 12, 24, and 48 hours postoperatively, morphine consumption, and initial analgesic desired time. Complications were also recorded. Results: Except for 1 hour postoperatively, patients in the experimental group experienced lower VAS scores during the first 48 hours postoperatively (P

Xin Jiang,1 Ye Liu,2 Lixin Ma,1 Rui Ji,3 Yaqin Qu,1 Ying Xin,4 Guoyue Lv5 1Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; 2Department of Pathobiology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, China; 3Department of Internal Medicine, Florida Hospital, Orlando, FL, USA; 4Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China; 5Department of General Surgery, The First Hospital of Jilin University, Changchun 130021, China Abstract: Cancer is one of the major causes of morbidity and mortality in the world. Carcinogenesis is a multistep process induced by genetic and epigenetic changes that disrupt pathways controlling cell proliferation, apoptosis, differentiation, and senescence. In this context, many bioactive dietary compounds from vegetables and fruits have been demonstrated to be effective in cancer prevention and intervention. Over the years, sulforaphane (SFN), found in cruciferous vegetables, has been shown to have chemopreventive activity in vitro and in vivo. SFN protects cells from environmental carcinogens and also induces growth arrest and/or apoptosis in various cancer cells. In this review, we will discuss several potential mechanisms of the chemopreventive activity of SFN, including regulation of Phase I and Phase II drug-metabolizing enzymes, cell cycle arrest, and induction of apoptosis, especially via regulation of signaling pathways such as Nrf2-Keap1 and NF-κB. Recent studies suggest that SFN can also affect the epigenetic control of key genes and greatly influence the initiation and progression of cancer. This research may provide a basis for the clinical use of SFN for cancer chemoprevention and enable us to design preventive strategies for cancer management, reduce cancer development and recurrence, and thus improve patient survival. Keywords: sulforaphane, tumor, chemoprevention, Phase I and Phase II drug-metabolizing enzymes, apoptosis, anti-inflammatory, cell cycle progression, epigenetics

Xiao Liu,1,* Jingge Qu,2,* Weixiao Xue,1 Liangai He,1 Jun Wang,3 Xuejiao Xi,1 Xiaoxia Liu,1 Yunhong Yin,1 Yiqing Qu1 1Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Department of Rheumatology, Second Hospital of Harbin Medical University, Harbin, People’s Republic of China; 3Department of Respiratory Medicine, Second Hospital of Shandong Traditional Chinese Medicine University, Jinan, People’s Republic of China *These authors contributed equally to this work Objectives: MicroRNAs (miRNAs) play essential roles in the development of COPD. In this study, we aimed to identify and validate potential miRNA biomarkers in frequent and non-frequent exacerbators of COPD patients using bioinformatic analysis.Materials and methods: The candidate miRNA biomarkers in COPD were screened from Gene Expression Omnibus (GEO) dataset and identified using GEO2R online tool. Then, we performed bioinformatic analyses including target prediction, gene ontology (GO), pathway enrichment analysis and construction of protein–protein interaction (PPI) network. Furthermore, the expression of the identified miRNAs in peripheral blood monocular cells (PBMCs) of COPD patients was validated using quantitative real-time polymerase chain reaction (qRT-PCR).Results: MiR-23a, miR-25, miR-145 and miR-224 were identified to be significantly downregulated in COPD patients compared with healthy controls. GO analysis showed the four miRNAs involved in apoptotic, cell differentiation, cell proliferation and innate immune response. Pathway analysis showed that the targets of these miRNAs were associated with p53, TGF-β, Wnt, VEGF and MAPK signal pathway. In healthy controls, the miR-25 and miR-224 levels were significantly decreased in smokers compared with nonsmokers (P

Ying Zhang,1,* Xiaowen Wu,1,* Chenxi Hou,1 Kun Shang,1 Kui Yang,1 Zhimin Tian,2 Zhichao Pei,1 Yongquan Qu,2 Yuxin Pei1 1Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Yangling, Shaanxi, People’s Republic of China; 2Center for Applied Chemical Research, Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, People’s Republic of China *These authors contributed equally to this work Objective: The aim was to produce the first report of assembling degradable stimuli-responsive dithio-polydopamine coating with a cancer target unit for synergistic and targeted drug delivery. Methods: A multifunctional drug delivery system was constructed by coating a dual-responsive dithio-polydopamine (PDS) on porous CeO2 nanorods and subsequent conjugation of lactose derivative, where the PDS was formed by self-polymerization of dithio-dopamine (DOPASS). Results: The multifunctional drug delivery system displayed excellent cancer targeted ability resulting from the conjugation of lactose derivative, which could specifically recognize the overexpressed asialoglycoprotein receptors on the surface of HepG2 cells. It also showed a dual-responsive property of glutathione and pH, achieving controllable drug release from the cleavage of disulfide bond and subsequent degradation of PDS in cancer cells. Moreover, the degradation of PDS led to the exposure of CeO2 nanorods, which has a synergistic anticancer effect due to its cytotoxicity to cancer cells. Conclusion: This work presents a good example of a rational design towards synergistic and targeted DDS for cancer chemotherapies. Keywords: degradable polydopamine, cerium oxide nanoparticles, dual-responsiveness, targeted drug delivery, synergistic anticancer

Yinyin Qu,1 Qing Zheng,1 Cheng Ni,1 Zhongqi Cui,2 Xiangyang Guo1 1Department of Anesthesiology, 2Department of Cardiac Surgery, Peking University Third Hospital, Beijing, People’s Republic of China Introduction: Lung metastasis of leiomyosarcoma that protrudes into the left atrium is an extremely rare condition. Severe complications may occur that prominently increase the mortality during the perioperative period. Currently, the anesthetic management reports are limited and there is no generally acknowledged algorithm available.Case presentation: A 67-year-old man presented with cough and dyspnea for 10 days. Workup revealed bilateral pulmonary effusion. Transthoracic echocardiography showed a large mass in the left atrium. Urgent surgical resection under cardiopulmonary bypass was performed. We focused on oxygenation improvement and cardiac function management by applying protective ventilation with low positive end expiratory pressure, low dose inotropic agents, and other methods to maintain stable homeostasis. Results of biopsy established a diagnosis of metastatic leiomyosarcoma.Conclusion: We reported a case of metastatic leiomyosarcoma presenting as a lung mass with left atrial extension and anesthetic management during surgical resection. Treating acute heart failure and refractory hypoxemia was the key focus perioperatively. Keywords: leiomyosarcoma, metastatic, anesthesia, acute heart failure, hypoxemia

Yang Qu, Zhengming Wang, Haohan Zhou, Mingyang Kang, Rongpeng Dong, Jianwu Zhao Department of Orthopedics, The Second Hospital of Jilin University, Changchun, People’s Republic of China Abstract: Degenerative lumbar disease (DLD) is a significant issue for public health. Posterior lumbar intervertebral fusion with cages (PLIFC) has high-level fusion rate and realignment on DLD. However, there are some complications following the surgery. Alginate oligosaccharides (AOS) have antioxidant and anti-inflammatory activities and may be suitable for infection therapy. MiR-155 is a biomarker associated with inflammatory and oxidative stress. AOS may promote PLIFC therapy by regulating miR-155. Pluronic nanoparticles and oligosaccharide nanomedicine of alginate sodium (ONAS) were prepared with ampicillin at size

Mengjie Rui, Yang Qu, Tong Gao, Yanru Ge, Chunlai Feng, Ximing Xu Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang, People’s Republic of China Abstract: The development of drug resistance in cancer cells is one of the major obstacles to achieving effective chemotherapy. We hypothesized that the combination of a doxorubicin (Dox) prodrug and microRNA (miR)21 inhibitor might show synergistic antitumor effects on drug-resistant breast cancer cells. In this study, we aimed to develop new high-density lipoprotein-mimicking nanoparticles (HMNs) for coencapsulation and codelivery of this potential combination. Dox was coupled with a nuclear localization signal (NLS) peptide to construct a prodrug (NLS-Dox), thereby electrostatically condensing miR21 inhibitor (anti-miR21) to form cationic complexes. The HMNs were formulated by shielding these complexes with anionic lipids and Apo AI proteins. We have characterized that the coloaded HMNs had uniformly dispersed distribution, favorable negatively charged surface, and high coencapsulation efficiency. The HMN formulation effectively codelivered NLS-Dox and anti-miR21 into Dox-resistant breast cancer MCF7/ADR cells and wild-type MCF7 cells via a high-density-lipoprotein receptor-mediated pathway, which facilitated the escape of Pgp drug efflux. The coloaded HMNs consisting of NLS-Dox/anti-miR21 demonstrated greater cytotoxicity with enhanced intracellular accumulation in resistant MCF7/ADR cells compared with free Dox solution. The reversal of drug resistance by coloaded HMNs might be attributed to the suppression of miR21 expression and the related antiapoptosis network. Furthermore, the codelivery of anti-miR21 and NLS-Dox by HMNs showed synergistic antiproliferative effects in MCF7/ADR-bearing nude mice, and was more effective in tumor inhibition than other drug formulations. These data suggested that codelivery of anti-miR21 and chemotherapeutic agents by HMNs might be a promising strategy for antitumor therapy, and could restore the drug sensitivity of cancer cells, alter intracellular drug distribution, and ultimately enhance chemotherapeutic effects. Keywords: drug resistance, microRNA21 inhibitor, doxorubicin prodrug, nuclear localization signal peptide, lipoprotein-mimicking nanoparticles, breast cancer therapy

Dominik Gonnissen,1 Ying Qu,1,2 Klaus Langer,3 Cengiz Öztürk,4 Yuliang Zhao,2 Chunying Chen,2 Guiscard Seebohm,5 Martina Düfer,6 Harald Fuchs,1 Hans-Joachim Galla,7 Kristina Riehemann11Center for Nanotechnology, Institute of Physics, University of Münster, Münster, Germany; 2National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 3Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Münster, 4chemicell GmbH, Berlin, 5Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases, University Hospital Münster, 6Department of Pharmacology, Institute of Pharmaceutical and Medicinal Chemistry, 7Department of Cell Biology/Biophysics, Institute of Biochemistry, University of Münster, Münster, GermanyAbstract: Within the last years, progress has been made in the knowledge of the properties of medically used nanoparticles and their toxic effects, but still, little is known about their influence on cellular processes of immune cells. The aim of our comparative study was to present the influence of two different nanoparticle types on subcellular processes of primary monocytes and the leukemic monocyte cell line MM6. We used core-shell starch-coated superparamagnetic iron oxide nanoparticles (SPIONs) and matrix poly(lactic-co-glycolic acid) (PLGA) nanoparticles for our experiments. In addition to typical biocompatibility testing like the detection of necrosis or secretion of interleukins (ILs), we investigated the impact of these nanoparticles on the actin cytoskeleton and the two voltage-gated potassium channels Kv1.3 and Kv7.1. Induction of necrosis was not seen for PLGA nanoparticles and SPIONs in primary monocytes and MM6 cells. Likewise, no alteration in secretion of IL-1β and IL-10 was detected under the same experimental conditions. In contrast, IL-6 secretion was exclusively downregulated in primary monocytes after contact with both nanoparticles. Two-electrode voltage clamp experiments revealed that both nanoparticles reduce currents of the aforementioned potassium channels. The two nanoparticles differed significantly in their impact on the actin cytoskeleton, demonstrated via atomic force microscopy elasticity measurement and phalloidin staining. While SPIONs led to the disruption of the respective cytoskeleton, PLGA did not show any influence in both experimental setups. The difference in the effects on ion channels and the actin cytoskeleton suggests that nanoparticles affect these subcellular components via different pathways. Our data indicate that the alteration of the cytoskeleton and the effect on ion channels are new parameters that describe the influence of nanoparticles on cells. The results are highly relevant for medical application and further evaluation of nanomaterial biosafety. Keywords: actin cytoskeleton, cell elasticity, AFM, ion channels, patch clamp, TEVC

Zhaohui Xie,1 Yine Qu,2 Yanli Leng,2 Wenxiu Sun,2 Siqi Ma,2 Jingbo Wei,2 Jiangong Hu,3 Xiaolan Zhang1 1Department of Gastroenterology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Histology and Embryology, Hebei United University School of Basic Medicine, Tangshan, Hebei, People’s Republic of China; 3Department of Pathology, the Second Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China Abstract: Inflammation is known to contribute to carcinogenesis in human colorectal cancer. Proinflammatory cytokine interleukin-17 (IL-17 or IL-17A) has been shown to play a critical role in colon carcinogenesis in mouse models. However, few studies have investigated IL-17A in human colon tissues. In the present study, we assessed IL-17-driven inflammatory responses in 17 cases of human colon adenocarcinomas, 16 cases of human normal colon tissues adjacent to the resected colon adenocarcinomas, ten cases of human ulcerative colitis tissues from biopsies, and eight cases of human colon polyps diagnosed as benign adenomas. We found that human colon adenocarcinomas contained the highest levels of IL-17A cytokine, which was significantly higher than the IL-17A levels in the adenomas, ulcerative colitis, and normal colon tissues (P

Pu Wang,1,* Yazhuo Qu,2,* Chuan Li,3 Li Yin,2 Caifei Shen,1 Wei Chen,3 Shiming Yang,4 Xiuwu Bian,2 Dianchun Fang11Institute of Gastroenterology, 2Institute of Pathology, 3Department of Radiology, Southwest Hospital, The Third Military Medical University, Chongqing, People’s Republic of China; 4Department of Gastroenterology, Xinqiao Hospital, The Third Military Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workPurpose: Nano dense-silica (dSiO2) has many advantages such as adjustable core–shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems.Methods: Superparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 as core–shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/­emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@dSiO2 core–shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW–SPION@dSiO2–YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW–SPION@dSiO2–YY146 to target tumor CD146.Results: 800ZW–SPION@dSiO2–YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20–30 nm with 15 nm SPION core and ~10 nm SiO2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSiO2 dispersed in water was measured to be 110.57 mM-1·s-1. Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW–SPION@dSiO2–YY146 more than the control group 800ZW–SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW–SPION@dSiO2–YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection.Conclusion: This is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW–SPION@dSiO2–YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery.Keywords: SPION, nanotechnology, EMT, SPION@dSiO2, xenograft, gastric cancer