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Yihong Tai,1,* Haonan Wang,1,* Yinghong Dai,2,* Liang Yu1,3 1Department of Exercise Physiology, School of Sport Science, Beijing Sport University, Beijing, 100084, People’s Republic of China; 2Xiangya School of Medicine, Central South University, Changsha, 410008, People’s Republic of China; 3Engineering Research Center of Strength and Conditioning Training Key Core Technology Integrated System and Equipment of Ministry of Education, Beijing Sport University, Beijing, 100084, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Yu, Engineering Research Center of Strength and Conditioning Training Key Core Technology Integrated System and Equipment of Ministry of Education, Beijing Sport University, Beijing, 100084, People’s Republic of China, Tel/Fax +86 1062967640, Email yuliang@bsu.edu.cnBackground: Sleep disorders and low grip strength often co-occur clinically and are geriatric symptoms that cause significant socioeconomic burden. Previous observational studies have found an association between sleep behaviors and grip strength, but the causal relationship remains unclear.Purpose: With the Mendelian randomization (MR) approach, the study aimed to determine the causal association between sleep traits (sleep duration, insomnia, daytime napping, sleep-wake disorders, chronotype) and low grip strength.Methods: The study used genetic variants from the genome-wide association study (GWAS) archived in UK Biobank and FinnGen. We assessed the potential causal relationship between sleep behaviors and grip strength using inverse variance weighting (IVW), weighted median (WM), and MR-Egger. Additionally, we performed sensitivity analyses using Cochran’s Q test, MR Egger Intercept test, funnel plots, and leave-one-out method.Results: We found that sleep duration is causally negatively associated with low grip strength (OR = 0.618, 95% CI = 0.424– 0.900, P = 0.012). Sleep-wake disorders have a positive association with low grip strength (OR = 1.018, 95% CI = 1.002– 1.034, P = 0.029). Reversely, high low grip strength risk was causally associated with increased daytime napping (OR = 1.018, 95% CI = 1.004– 1.032, P = 0.011).Conclusion: The study revealed causal associations between sleep duration, sleep-wake disorders, and low grip strength. Understanding their relationship helps in early clinical intervention to improve the life quality of the elderly.Keywords: sleep, low grip strength, Mendelian randomization

Zhihan Jiang,1,* Yingying Dai,2,* Jing Chang,2 Pingchao Xiang,3 Zhenyu Liang,4 Yan Yin,5 Yongchun Shen,6 Ruiying Wang,7 Bianba Qiongda,8 Hongling Chu,9 Nan Li,9 Xiaoyan Gai,1,10 Ying Liang,1,10 Yongchang Sun1,10 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 2School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Peking University Shougang Hospital, Beijing, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, GuangZhou, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Tibet Autonomous Region People’s Hospital, Lhasa, People’s Republic of China; 9Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 10Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Liang; Yongchang Sun, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, People’s Republic of China, Tel +86 13810964766 ; +86 13910979132, Fax +86 108 226 6989, Email bysyliangying@126.com; suny@bjmu.edu.cnBackground: Tuberculosis and chronic obstructive pulmonary disease (COPD) are significant public health challenges, with pulmonary tuberculosis recognized as a pivotal risk factor for the development of COPD. Tuberculosis-associated COPD is increasingly recognized as a distinct phenotype of COPD that potentially exhibits unique clinical features. A thorough understanding of the precise definition, clinical manifestations, prognosis, and most effective pharmacological strategies for tuberculosis-associated COPD warrants further investigation.Methods: This prospective, observational cohort study aims to enroll over 135 patients with tuberculosis-associated COPD and 405 patients with non-tuberculosis-associated COPD, across seven tertiary hospitals in mainland China. The diagnosis of tuberculosis-associated COPD will be established based on the following criteria: (1) history of pulmonary tuberculosis with standard antituberculosis treatment; (2) suspected pulmonary tuberculosis with radiological evidence indicative of tuberculosis sequelae; (3) no definitive history of pulmonary tuberculosis but with positive interferon-gamma release assay results and radiological signs suggestive of tuberculosis. At baseline, demographic information, medical history, respiratory questionnaires, complete blood count, interferon-gamma release assays, medications, spirometry, and chest computed tomography (CT) scans will be recorded. Participants will be followed for one year, with evaluations at six-month intervals to track the longitudinal changes in symptoms, treatment, lung function, and frequencies of COPD exacerbations and hospitalizations. At the final outpatient visit, additional assessments will include chest CT scans and total medical costs incurred.Discussion: The findings of this study are expected to delineate the specific characteristics of tuberculosis-associated COPD and may propose potential treatment options for this particular phenotype, potentially leading to improved clinical management and patient outcomes.Keywords: chronic obstructive pulmonary disease, COPD, pulmonary tuberculosis, tuberculosis-associated COPD, protocol

Wei He, Yangmin Hu, Difei Yao, Junjun Xu, Yunjian Dai, Haibin Dai Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Haibin Dai, Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of China, Email haibindai@zju.edu.cnBackground: The role of hospital pharmacists has shifted from primarily ensuring drug supply to providing comprehensive pharmaceutical care. To accommodate this shift, new positions are needed. The traditional training model for hospital pharmacists is no longer sufficient for the evolving demands of pharmaceutical care and these new roles. This study aimed to describe the development of a position-oriented learning system explicitly tailored for hospital pharmacists and to assess its impact on workforce development and pharmacy service.Methods: The position-oriented learning system for hospital pharmacists, aimed at enhancing training and workforce development, was evaluated based on two critical criteria: the completion rate of learning modules and the subsequent improvement in pharmaceutical care at the hospital. The completion rate assessed the engagement and effectiveness of the training content. At the same time, the improvement in pharmaceutical care evaluated practical outcomes such as percentages of patients who received pharmaceutical care and percentages of inappropriate medication orders intercepted.Results: In 2021, 218 employees participated in the learning system. The pharmacy department has identified 22 pharmacists for various positions through this system. The quantity and quality of pharmaceutical care have improved significantly.Conclusion: The position-oriented diversified learning system achieves the perfect combination of department development direction and individual career planning of employees. The learning system can significantly improve the learning efficiency of pharmacists, enhance the quality of various pharmaceutical care, and promote the development of disciplines.Keywords: learning system, position-oriented, clinical pharmacist, informatics pharmacist

Weiyu Cai,1– 3,&ast; Le Chen,1– 3,&ast; Yanyuan Dai,1– 3 Baixin Chen,1– 3 Dandan Zheng,1– 3 Yun Li1– 3 1Department of Sleep Medicine, Shantou University Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 3Joint Laboratory of Biological Psychiatry Shantou University-University of Manitoba, Shantou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Li, Department of Sleep Medicine, Shantou University Mental Health Center, North Taishan Road, Wanji District, Shantou, Guangdong Province, 515041, People’s Republic of China, Email s_liyun@stu.edu.cnPurpose: Major depressive disorder (MDD) is associated with cognitive impairment through unclear mechanisms. We examined the relationship between sleep electroencephalogram (EEG) power and attention level in MDD.Patients and Methods: Forty-seven untreated patients with MDD and forty-seven age- and sex-matched controls were included. We examined relative EEG power during non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep by fast Fourier transform. The Attention Network Test (ANT) was performed to evaluate attention levels.Results: Compared to controls, patients with MDD had lower theta power during NREM (P = 0.018) and REM (P = 0.002) sleep, while higher beta power (P = 0.050) during NREM sleep and delta power (P = 0.018) during REM sleep. Regarding attention level, patients with MDD had lower levels of accuracy (P = 0.021), longer mean reaction time (P < 0.001), poorer manifestations of the alerting effect (P = 0.038) and worse executive control (P = 0.048). Moreover, decreased theta power during NREM sleep was correlated with worsened accuracy (β = 0.329, P = 0.040), decreased theta power during REM sleep was correlated with worsened alerting effect (β = 0.355, P = 0.020), and increased delta power during REM sleep was correlated with longer mean reaction time (β = 0.325, P = 0.022) in patients with MDD. No association between ANT performance and other frequency bands was observed in patients with MDD.Conclusion: Our findings suggest that patients with MDD manifest impaired selective attention function that is associated with decreased theta power during NREM/REM sleep and increased delta power during REM sleep.Keywords: major depressive disorder, sleep, EEG power, attention

Sandip Patil,1,2,&ast; Xinye Li,3,&ast; Pai Liu,1 Yan Dai,3 Xiyi Zhu,3 Junjun Li,3 Sixi Liu,1 Feiqiu Wen1,2 1Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Paediatric Research Institute, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Paediatrics, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feiqiu Wen, Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China, Tel +86-755-83009888, Email fwen62@163.comBackground: Syphilis, a prevalent sexually transmitted infection, poses severe risks, especially during pregnancy. This study aimed to elucidate the trends and impacts of syphilis in Guangxi, China, focusing on prevalence, clinical manifestations, and treatment outcomes in pregnant women and newborns. The objectives included understanding the demographic characteristics of affected pregnant women, analysing the clinical manifestations in newborns, and assessing the effectiveness of the treatment protocol.Methods: Conducted in adherence to ethical guidelines, a retrospective cohort study from January 2013 to December 2023 included 54,048 pregnant women tested for T. pallidum. Diagnosis involved a comprehensive approach, utilizing tests like the Toluidine Red Unheated Serum Test (TRUST) and the Treponema pallidum Particle Agglutination (TPPA) assay. Infant diagnosis and clinical manifestations were evaluated through a decade-long follow-up. Treatment protocols, including Benzathine penicillin, were implemented. Statistical analyses were conducted using SAS version 9.4.Results: Among 54,048 pregnant women, 0.10% were syphilis positive, correlating with a rise in hospitalizations. Newborns exhibited varied clinical manifestations, with neonatal pneumonia and jaundice being prevalent. The treatment protocol, especially with Benzathine penicillin, achieved a remarkable 100% cure success rate. The study noted a significant reduction in mother-to-child transmission. Syphilis in mothers and babies was diagnosed at different clinical stages, including primary, secondary, latent, and tertiary.Conclusion: This study underscores the escalating impact of syphilis on pregnant women and newborns in Guangxi, China. The findings highlight the necessity for robust preventive measures, early diagnosis, and effective treatment strategies. The observed 100% cure success rate with Benzathine penicillin emphasizes the importance of strict treatment protocols in mitigating the adverse effects of congenital syphilis and reducing its transmission.Keywords: congenital syphilis, mother-to-child transmission, diagnosis, antibiotic treatment

Youren Dai,1,&ast; Huiyun Wu,1,&ast; Jiahui Cao,1,&ast; Yang Li,2 Wenjun Cheng,1 Chengyan Luo1 1Department of Gynecology, First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Pathology, First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengyan Luo, Department of Gynecology, First Affiliated Hospital with Nanjing Medical University, 368 North Jiangdong Road, Nanjing, 210036, People’s Republic of China, Email betteryuan66@njmu.edu.cnPurpose: To investigate prognostic factors affecting cancer-specific survival (CSS) and to analyze the survival outcomes of patients with undifferentiated and dedifferentiated endometrial carcinoma (UDEC) who underwent various postoperative adjuvant therapies.Methods: The independent risk factors affecting CSS were studied using univariate and multivariate Cox regression analysis, and CSS in the presence of various postoperative treatments was evaluated using Kaplan-Meier method based on the cohort with pathologically confirmed UDEC from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, the study included 18 cases with UDEC in our center and explored their molecular characteristics and prognosis.Results: Between 2000 and 2019, a total of 443 patients were included from the SEER database. The median CSS duration was 14 months, with corresponding 3- and 5-year CSS rates of 45.9% and 44.0%, respectively. Factors such as pTNM stage, surgical resection of primary lesion, and chemoradiation independently influenced CSS. Postoperative chemotherapy alone improved CSS in patients with initial tumor spread beyond the uterus (pT3 and pT4), or lymph node (LN) invasion, or distant metastases. Additionally, postoperative radiotherapy enhanced CSS in patients who had undergone postoperative chemotherapy, those with primary tumors progressing to stage pT3, and those with LN involvement but without distant metastases. Of the 18 patients diagnosed at our center, with a median follow-up of 15.5 months, one experienced relapse and two succumbed to UDEC, who exhibited aberrant p53 expression in immunohistochemical staining.Conclusion: Postoperative chemotherapy and radiotherapy are beneficial for UDEC patients with tumors extending beyond the uterus or involving lymph nodes.Keywords: undifferentiated and dedifferentiated endometrial carcinoma, cancer-specific survival, prognostic factors, postoperative adjuvant therapy

Qingchen Li,1– 3 Xinyi Liu,1,2 Jiasong Yang,1,2,4 Yumeng Dai,1,2 Wensheng Li1,2,4 1Shanghai Aier Eye Hospital, Aier Eye Hospital Group Co. Ltd, Shanghai, 201103, People’s Republic of China; 2Shanghai Aier Eye Institute, Shanghai, 201103, People’s Republic of China; 3Department of Ophthalmology, the Second Xiangya Hospital of Central South University, Changsha, Hunan Province, 410011, People’s Republic of China; 4Aier School of Ophthalmology, Central South University, Changsha, Hunan Province, 410015, People’s Republic of ChinaCorrespondence: Wensheng Li, Shanghai Aier Eye Hospital, Aier Eye Hospital Group Co. Ltd, No. 83 Wuzhong Road, Xuhui District, Shanghai, 201103, People’s Republic of China, Email drlws@qq.comPurpose: To compare Barrett TK Universal II and Barrett Universal II TCRP calculations in the power calculations for 3 presbyopia-correcting intraocular lenses (PC-IOL).Methods: This observational study involved 64 eyes from 64 patients who prepared to undergo extraction of crystalline lenses combined with PC-IOL (Symfony ZXR00, PanOptix TFNT00, or AT LISA tri 839MP) implantation. All eyes underwent ocular biometric measurements with IOLMaster 700 and Pentacam HR, and the interdevice agreement of measurements including total keratometry (TK, IOLMaster 700) and total corneal refractive power (TCRP, Pentacam HR) was evaluated. IOL power calculations were performed using TK-based Barrett TK Universal II and TCRP-based Barrett Universal II calculations, respectively.Results: Paired t-tests showed that the differences in white-to-white diameter, central corneal thickness, anterior chamber depth, and mean TK between IOLMaster 700 and Pentacam HR were slight but significant (all P< 0.05), and the differences in recommended IOL power for emmetropia between two Barrett calculations were also significant in 3 PC-IOLs (all P< 0.05). The ROC curve showed that the AUC was 0.917 (95% CI, 0.820– 0.971) for the absolute value of the difference between TK and TCRP in discriminating the difference of ≥ ± 0.5 D in predicted IOL power with best cutoff values of 0.4 D.Conclusion: The novel Barrett TK Universal II formula built in IOLMaster 700 is comparable to TCRP-based Barrett Universal II calculation for IOL power calculation of PC-IOLs, and the convenience of using the Barrett TK Universal II formula should be founded on measurement consistency between devices.Keywords: presbyopic corrections, intraocular lens power calculation, refractive prediction accuracy, swept-source optical biometer, scheimpflug tomography

Chenyu Zhang,1 Yi Dai,1 Junji Zhang,1 Xiaoyan Li,1 Shuangzheng Jia,2 Jinghua Shi,1,&ast; Jinhua Leng1,&ast; 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, People’s Republic of China; 2Department of Gynecologic Oncology, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinghua Shi; Jinhua Leng, Tel +86 151-0101-6294 ; +86 137-0129-8616, Email elisa_1984@163.com; lengjenny@vip.sina.comObjective: This study aimed to explore the distribution of nerve fibers in abdominal wall endometriosis (AWE) and discern their association with pain.Methods: A retrospective case–control study was conducted. The cases comprised 30 patients diagnosed with AWE, while the control group consisted of 17 patients who had undergone laparotomy without any history of endometriosis. We analyzed clinical characteristics and examined the innervation patterns in samples using stains for S-100, neuron-specific enolase (NSE), protein gene product 9.5 (PGP9.5), neurofilament (NF), and substance P (SP) antibodies.Results: There was a notable increase in the density of S-100, NSE and PGP9.5 immunoreactive nerve fibers and a higher proportion of SP positivity in AWE lesions compared to standard abdominal wall scars (p < 0.05). However, there were no significant differences in the density or proportion of NF-immunoreactive nerve fibers between the cases and the controls. Moreover, no statistically significant correlation was observed between the density of S-100, NSE, PGP9.5, NF, or SP-positive nerve fibers and pain scores.Conclusion: This study demonstrated an increased immunoreactive nerve fiber density located in AWE lesions compared to normal abdominal wall scars. Further high-quality studies are needed to investigate the mechanisms responsible for pain in women with endometriosis.Keywords: abdominal wall endometriosis, pain, nerve fibers, immunohistochemistry

Pinggui Chen,1 Yaoxuan Li,2 Yunyan Dai,1 Zhiming Wang,1 Yunpeng Zhou,1 Yi Wang,1 Gaopeng Li1 1Department of Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi, People’s Republic of China; 2Department of School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Gaopeng Li, Email malone2001@163.comAbstract: Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and the primary cause of death in cancer cases, with significant public health concern worldwide. Despite the overall decline in the incidence and mortality rates of HCC in recent years in recent years, the emergence of metabolic liver disease-related HCC is causing heightened concern, especially in countries like the United States, the United Kingdom, and P.R. China. The escalation of metabolic liver disease-related HCC is attributed to a combination of factors, including genetic predisposition, lifestyle choices, and changes in the living environment. However, the pathogenesis of metabolic liver disease-associated HCC remains imperfect. In this review, we encapsulate the latest advances and essential aspects of the pathogenesis of metabolic liver disease-associated HCC, including alcoholic liver disease (ALD), metabolic dysfunction–associated steatotic liver disease (MASLD), and inherited metabolic liver diseases.Keywords: hepatocellular carcinoma, metabolic liver disease, pathogenesis, alcoholic liver disease, metabolic dysfunction–associated steatotic liver disease

Sijin Wu,1 Zhongli Chen,1 Yuan Gao,1 Songren Shu,2 Feng Chen,1 Ying Wu,1 Yan Dai,1 Shu Zhang,1 Keping Chen1 1Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Keping Chen, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email chenkeping@263.netBackground: The diagnosis of cardiac syncope remains a challenge. This study sought to develop and validate a diagnostic model for the early identification of individuals likely to have a cardiac cause.Methods: 877 syncope patients with a determined cause were retrospectively enrolled at a tertiary heart center. They were randomly divided into the training set and validation set at a 7:3 ratio. We analyzed the demographic information, medical history, laboratory tests, electrocardiogram, and echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. Then a multivariable logistic regression analysis was performed to identify independent predictors and construct a diagnostic model. The receiver operating characteristic curves, area under the curve (AUC), calibration curves, and decision curve analysis were used to evaluate the predictive accuracy and clinical value of this nomogram.Results: Five independent predictors for cardiac syncope were selected: BMI (OR 1.088; 95% CI 1.022– 1.158; P =0.008), chest symptoms preceding syncope (OR 5.251; 95% CI 3.326– 8.288; P < 0.001), logarithmic NT-proBNP (OR 1.463; 95% CI 1.240– 1.727; P < 0.001), left ventricular ejection fraction (OR 0.940; 95% CI 0.908– 0.973; P < 0.001), and abnormal electrocardiogram (OR 6.171; 95% CI 3.966– 9.600; P < 0.001). Subsequently, a nomogram based on a multivariate logistic regression model was developed and validated, yielding AUC of 0.873 (95% CI 0.845– 0.902) and 0.856 (95% CI 0.809– 0.903), respectively. The calibration curves showcased the nomogram’s reasonable calibration, and the decision curve analysis demonstrated good clinical utility.Conclusion: A diagnostic tool providing individualized probability predictions for cardiac syncope was developed and validated, which may potentially serve as an effective tool to facilitate early identification of such patients.Keywords: cardiac syncope, syncope, diagnosis, nomogram, prediction model

Sihan Yan,1,2,&ast; Dan Du,1,2,&ast; Xu Liu,1,2 Yingying Dai,1,2 Min-Kyu Kim,1,2 Xinyu Zhou,3 Lian Wang,1,2 Lu Zhang,1,2 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Dermatology, Nanbu County People’s Hospital, Nanbu County, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian Jiang; Lu Zhang, Email jiangxian@scu.edu.cn; zhangluhx@scu.edu.cnObjective: Artificial intelligence chatbot, particularly ChatGPT (Chat Generative Pre-trained Transformer), is capable of analyzing human input and generating human-like responses, which shows its potential application in healthcare. People with rosacea often have questions about alleviating symptoms and daily skin-care, which is suitable for ChatGPT to response. This study aims to assess the reliability and clinical applicability of ChatGPT 3.5 in responding to patients’ common queries about rosacea and to evaluate the extent of ChatGPT’s coverage in dermatology resources.Methods: Based on a qualitative analysis of the literature on the queries from rosacea patients, we have extracted 20 questions of patients’ greatest concerns, covering four main categories: treatment, triggers and diet, skincare, and special manifestations of rosacea. Each question was inputted into ChatGPT separately for three rounds of question-and-answer conversations. The generated answers will be evaluated by three experienced dermatologists with postgraduate degrees and over five years of clinical experience in dermatology, to assess their reliability and applicability for clinical practice.Results: The analysis results indicate that the reviewers unanimously agreed that ChatGPT achieved a high reliability of 92.22% to 97.78% in responding to patients’ common queries about rosacea. Additionally, almost all answers were applicable for supporting rosacea patient education, with a clinical applicability ranging from 98.61% to 100.00%. The consistency of the expert ratings was excellent (all significance levels were less than 0.05), with a consistency coefficient of 0.404 for content reliability and 0.456 for clinical practicality, indicating significant consistency in the results and a high level of agreement among the expert ratings.Conclusion: ChatGPT 3.5 exhibits excellent reliability and clinical applicability in responding to patients’ common queries about rosacea. This artificial intelligence tool is applicable for supporting rosacea patient education.Keywords: artificial intelligence, ChatGPT, rosacea, patient education

Haonan Wang,1,2 Yinghong Dai,3 Xiaotian Li,2,4 Liang Yu1 1Department of Exercise Physiology, School of Sport Science, Beijing Sport University, Beijing, 100084, People’s Republic of China; 2Department of Physical Education and Research, Central South University, Changsha, 410083, People’s Republic of China; 3Xiangya School of Medicine, Central South University, Changsha, 410008, People’s Republic of China; 4School of Sport Training, Wuhan Sports University, Wuhan, Hubei, 430079, People’s Republic of ChinaCorrespondence: Xiaotian Li, Department of Physical Education and Research, Central South University, Changsha, 410083, People’s Republic of China, Tel +86 18975197870, Fax +86 731 88876141, Email xiaotianli@csu.edu.cn Liang Yu, Department of Exercise Physiology, School of Sport Science, Beijing Sport University, Beijing, 100084, People’s Republic of China, Tel/Fax +86 1062967640, Email yuliang@bsu.edu.cnIntroduction: Poor sleep negatively impacts cognitive and physical functioning and affects athletic and academic achievement. “Dual-career” athletes emphasize the pursuit of academic excellence along with athletic performance.Purpose: The study aimed to assess sleep characteristics and sleep quality in dual-career collegiate badminton athletes. Furthermore, the study explored associations between training and academic stress and sleep, providing a theoretical basis for better training and sleep programs for dual-career athletes.Participants and Methods: In this study, 15 dual-career collegiate badminton athletes were recruited, and 12 subjects (male n = 8, female n = 4, mean age 20.3 ± 1.7) completed the questionnaire. Repeated measurements were taken monthly in the spring semester from March to August 2021. The questionnaire assessed sleep quality and daytime sleepiness by the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Score (ESS). Moreover, we collected average training, study time per week, and monthly sports competitions and academic tests to quantify participants’ training and academic stress.Results: An average of 36.1% of dual-career athletes reported poor sleep and 25.0% had excessive daytime sleepiness. Overall, a significant positive correlation existed between PSQI scores and weekly study hours (r = 0.308, p = 0.009). Significant positive correlations were found between the four stressors and PSQI (August: r = 0.868, p < 0.001; July: r = 0.573, p = 0.026) or ESS scores (March: r = − 0.678, p = 0.015; August: r = 0.598, p = 0.040) for specific months. Hierarchical linear modeling (HLM) analysis identified that lower study and training hours predict better sleep quality.Conclusion: Dual-career collegiate badminton athletes had a higher prevalence of poor sleep and daytime sleepiness, and daytime sleepiness did not result in better sleep quality; study and training hours had the greatest effect on the sleep quality of dual-career collegiate badminton athletes.Keywords: training stress, academic stress, dual-career collegiate athletes, sleep quality, subjective evaluation

Haili Huang,1 Yi Dai,1 Xinghuai Sun,1– 3,&ast; Yuan Fang1,&ast; 1Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, People’s Republic of China; 2State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, People’s Republic of China; 3NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinghuai Sun; Yuan Fang, Email xhsun@shmu.edu.cn; fangyuandoc@163.comPurpose: This study aimed to investigate the outbreak of acute primary angle-closure (APAC) during the COVID-19 Omicron variant pandemic in Shanghai.Methods: This single-center retrospective observational study included all newly diagnosed patients with APAC in Eye, Ear, Nose, and Throat Hospital of Fudan University from December 15, 2022, to January 14, 2023 (pandemic group) during the COVID-19 pandemic of Omicron Variant, and from November 15, 2021, to February 14, 2022 (control group) when the infection rate of COVID-19 is very low in Shanghai. Demographic features, intraocular pressure, axial length, anterior chamber depth, lens thickness and pupil diameter were compared between the two groups.Results: A total of 223 patients (261 eyes) were included in the pandemic group and 75 patients (82 eyes) in the control group. The number of APAC patients and eyes in the pandemic group is 8.92-fold and 9.55-fold of the monthly average number in the control group. The onset dates of acute angle-closure were mainly between December 17 and December 31, 2022. In the pandemic group, 72.65% of patients with APAC had a recent COVID-19 infection. Among the COVID-19-positive patients, 72% suffered APAC attacks within 24h of the occurrence of COVID-19 symptoms and 92% within 3 days. The pandemic group showed a longer time from symptoms to treatment and larger pupil diameter than the control group (7.92 ± 6.14 vs 3.63 ± 2.93 days, p = 0.006; 4.53 ± 1.17 vs 3.78 ± 1.24 mm, p = 0.003, respectively).Conclusion: An outbreak of APAC attack was observed in our eye center during the COVID-19 Omicron variant pandemic in Shanghai. There may be a correlation between the onset of APAC and new COVID-19 Omicron variant infection, but the exact reason needs to be investigated further.Keywords: acute primary angle-closure, COVID-19 pandemic, omicron variant, Shanghai

Lei Zheng,1 Xiaofei Yu,1 Zehai Xia,1 Yehao Guo,2 Yifan Dai1 1Respiratory Department, The Affiliated Hospital of Hangzhou Normal University, Hangzhou City, Zhejiang Province, People’s Republic of China; 2Postgraduate Training Base Department, Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yifan Dai, Department of Respiratory and Critical Care Medicine, Hangzhou Normal University, No. 126, Wenzhou Street, Gongshu District, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86-571-13208000079, Email 181207576@qq.comPurpose: Vitamins and carotenoids are essential in preventing and treating chronic obstructive pulmonary disease (COPD). This study investigated the associations between serum vitamins, carotenoids, and COPD in adults aged ≥ 40 years in the United States.Methods: We selected 3487 participants aged ≥ 40 from the NHANES (2017– 2018) and used demographic analysis, sensitivity tests, and different weighted multivariate regression models to investigate the relationship between serum vitamins, carotenoids, and COPD.Results: Subjects in the highest tertile of serum vitamin C, vitamin E (α-tocopherol), α-carotene, trans-β-carotene, and cis-β-carotene had a 50%, 35%, 51%, 54%, and 51% lower risk of COPD than those in the lowest tertile (P for trend: P=0.0005, < 0.0001, 0.0054, 0.0066, and 0.0049). Unfortunately, no significant correlation was found for serum vitamin D levels.Conclusion: Our analysis of nationally representative data from 3487 participants showed that serum levels of vitamin C, vitamin E (α-tocopherol), α-carotene, and β-carotene were negatively associated with the incidence of COPD in adults over 40 years of age in the US The findings highlighted the importance of antioxidant vitamins and carotenoids in respiratory health, while the data showed no significant correlation between vitamin D (25-OHD) and the incidence of COPD.Keywords: chronic obstructive pulmonary disease, morbidity, serum vitamins, serum carotenoids, anti-oxidation

Yu Cao,1 Ying Han,2 Jiangping Wu,1 Jianping Sun,3 Yanchao Dai,3 Guifang Qiao,3 Kang Li,3 Ang Li,3 Yonghong Zhang,4 Yingmin Ma,5,&ast; Qingkun Song1,3,&ast; 1Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Center of Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Center of Biobank, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Hepatic Intervention, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingmin Ma, Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Youanmen Wai 8, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83997022, Email ma.yingmin@163.com Qingkun Song, Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Youanmen Wai 8, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83997022, Email songqingkun@ccmu.edu.cnBackground: For the distinct immune/inflammatory responses from Omicron variant infection, this study aimed to investigate the diagnostic efficacy of systemic inflammatory indicators and the clinical efficacy of corticosteroids on the in-hospital mortality among COVID-19 patients.Methods: Under a retrospective cohort study, 1081 COVID-19 patients were recruited from Beijing Youan Hospital, Capital Medical University between November 16, 2022 and January 30, 2023. We chose neutrophil-to-lymphocyte ratio (NLR), CRP-to-lymphocyte ratio (CLR), and CRP-to-albumin ratio (CAR) as the systemic inflammatory indicators. Receiver operating curve (ROC) and multivariate logistic regression analysis were used to determine the diagnostic efficacy of systemic inflammatory indicators and the association between systemic inflammatory indicators and in-hospital mortality.Results: Among 684 patients included in analysis, 96 died during hospitalization. NLR, CLR and CAR performed well (with an area under the curve (AUC) greater than 0.75) in discriminating in-hospital mortality among COVID-19 patients. The severe status of systemic inflammation, with optimal cut-off value derived from ROC analysis, significantly associated higher risk of in-hospital mortality (OR = 3.81 for NLR ≥ 6.131; OR = 3.76 for CLR ≥ 45.455; OR = 5.10 for CAR ≥ 1.436). Corticosteroids use within 72 hours of admission increased the in-hospital mortality 2.88-fold for COVID-19 patients. In the subgroup of patients with severe systemic inflammation, corticosteroids increased the risk of in-hospital mortality (OR = 2.11 for NLR, p = 0.055; OR = 2.94 for CLR, p = 0.005; OR = 2.31 for CAR, p = 0.036).Conclusion: Systemic inflammatory indicators had good diagnostic performance for in-hospital mortality. Patients with severe systemic inflammatory status should not receive corticosteroid treatment and further studies are warranted for confirmation.Keywords: COVID-19, systemic inflammatory indicators, in-hospital mortality, anti-inflammatory treatment

Linghang Zhou, Jin Tan, Yuzhe Dai, Keke Zhu, Yanbo Xiao, Dan Wu, Zongkang Wang, Yisi Tan, Yijie Qin Department of Stomatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of ChinaCorrespondence: Jin Tan, Department of Stomatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, 95 Shaoshan Middle Road, Changsha, Hunan, People’s Republic of China, Email 310176@hnucm.edu.cnPurpose: Arecoline is one of the main toxic components of arecoline to cause oral mucosal lesions or canceration, which seriously affects the survival and life quality of patients. This study analyzed the mechanism of Jiawei Danxuan Koukang (JDK) in alleviating arecoline induced oral mucosal lesions, to provide new insights for the treatment of oral submucosal fibrosis (OSF) or cancerosis.Methods: Metabolomics was applied to analyze the composition of JDK and serum metabolites. The active ingredients of JDK were analyzed by the combined ultra-high performance liquid chromatography and mass spectrometry. The target network of JDK, metabolites and OSF was analyzed by network pharmacology, and molecular docking. Oral mucosal lesions and fibrosis were analyzed by HE and Masson staining. Cell differentiation, proliferation and apoptosis were detected. The expressions of α-SMA, Collagen I, Vimentin, Snail, E-cadherin, AR and NOTCH1 were detected by Western blot.Results: Arecoline induced the gradual atrophy and thinning of rat oral mucosal, collagen accumulation, the increase expressions of fibrosis-related proteins and Th17/Treg ratio. JDK inhibited arecoline-induced oral mucosal lesions and inflammatory infiltration. Arecoline induced changes of serum metabolites in Aminoacyl-tRNA biosynthesis, Alanine, aspartate and glutamate metabolism and Arginine biosynthesis pathways, which were reversed by M-JDK. Quercetin and AR were the active ingredients and key targets of JDK, metabolites and OSF interaction. Arecoline promoted the expression of AR protein, and the proliferation of oral fibroblasts. Quercetin inhibited the effect of arecoline on oral fibroblasts, but was reversed by AR overexpression. Arecoline induced NOTCH1 expression in CAL27 and SCC-25 cells, and promoted cell proliferation, but was reversed by M-JDK or quercetin.Conclusion: JDK improved the arecoline-induced OSF and serum metabolite functional pathway. Quercetin targeted AR protein to improve arecoline-induced OSF. JDK and quercetin inhibited arecoline-induced NOTCH1 protein expression in CAL27 and SCC-25 cells to play an anti-oral cancer role.Graphical Abstract: Keywords: oral submucous fibrosis, Jiawei Danxuan Koukang, arecoline, pharmacology, metabolomics

Yunfei Zhang,1,2,&ast; Ruofan Sheng,1,2,&ast; Chun Yang,2 Yongming Dai,3 Mengsu Zeng1,2 1Shanghai Institute of Medical Imaging, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 3School of Biomedical Engineering, ShanghaiTech University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongming Dai, School of Biomedical Engineering, ShanghaiTech University, Shanghai, 200032, People’s Republic of China, Tel +86 13917166155, Email daiyongming5555@163.com Mengsu Zeng, Department of Radiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +86-021-64041990, Email zengmengsu111@163.comPurpose: To assess the effectiveness of tri-exponential Intra-Voxel Incoherent Motion (tri-IVIM) MRI in preoperatively identifying microvascular invasion (MVI) in hepatocellular carcinoma (HCC).Patients and Methods: In this prospective study, 67 patients with HCC were included. Metrics from bi-exponential IVIM (bi-IVIM) and tri-IVIM were calculated. Subgroup comparisons were analyzed using the independent Student’s t-test or Mann–Whitney U-test. Logistic regression was performed to explore clinical risk factors. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis.Results: MVI-positive HCCs exhibited significantly lower true diffusion coefficient (Dt) from bi-IVIM, as well as fast-diffusion coefficients (Df) and slow-diffusion coefficients (Ds) from tri-IVIM, compared to MVI-negative HCCs (p < 0.05). Tumor size and alpha-fetoprotein (AFP) were identified as risk factors. The combination of tri-IVIM-derived metrics (Ds and Df) yielded higher diagnostic accuracy (AUC = 0.808) compared to bi-IVIM (AUC = 0.741). A predictive model based on a nomogram was constructed using Ds, Df, tumor size, and AFP, resulting in the highest diagnostic accuracy (AUC = 0.859). Decision curve analysis indicated that the constructed model, provided the highest net benefit by accurately stratifying the risk of MVI, followed by tri-IVIM and bi-IVIM.Conclusion: Tri-IVIM can provide information on perfusion and diffusion for evaluating MVI in HCC. Additionally, tri-IVIM outperformed bi-IVIM in identifying MVI-positive HCC. By integrating clinical risk factors and metrics from tri-IVIM, a predictive nomogram exhibited the highest diagnostic accuracy, potentially aiding in the noninvasive and preoperative assessment of MVI.Keywords: tri-exponential intra-voxel incoherent motion, diffusion weighted imaging, hepatocellular carcinoma, microvascular invasion

Junzhuo Wang,1,&ast; Ying Tan,1,&ast; Yang Dai,2,3,&ast; Ke Hu,2 Xi Tan,1 Shaoli Jiang,4 Guannan Li,1 Xinlin Zhang,1 Lina Kang,1 Xiaojian Wang,4 Biao Xu1,2 1Department of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Geriatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 4Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao Xu, Department of Cardiology, the Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, Jiangsu, People’s Republic of China, Email xubiao62@nju.edu.cn Xiaojian Wang, Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, People’s Republic of China, Email ias_xjwang@njtech.edu.cnPurpose: Myocardial ischemia-reperfusion injury after myocardial infarction has always been a difficult problem in clinical practice. Endothelial cells and their secreted extracellular vesicles are closely related to inflammation, thrombosis formation, and other processes after injury. Meanwhile, low-molecular-weight gelators have shown great potential for nasal administration. This study aims to explore the therapeutic effects and significance of endothelial cell-derived extracellular vesicles combined with a hydrogel for nasal administration on myocardial ischemia-reperfusion injury.Methods: We chose a gel system composed of a derivative of glutamine amide and benzaldehyde as the extracellular vesicle delivery vehicle. This hydrogel was combined with extracellular vesicles extracted from mouse aortic endothelial cells and administered multiple times intranasally in a mouse model of ischemia-reperfusion injury to the heart. The delivery efficiency of the extracellular vesicle-hydrogel combination was evaluated by flow cytometry and immunofluorescence. Echocardiography, TTC Evan’s Blue and Masson’s staining were used to assess mouse cardiac function, infarct area, and cardiac fibrosis level. Flow cytometry, ELISA, and immunofluorescence staining were used to investigate changes in mouse inflammatory cells, cytokines, and vascular neogenesis.Results: The vesicles combined with the hydrogel have good absorption in the nasal cavity. The hydrogel combined with vesicles reduces the levels of pro-inflammatory Ly6C (high) monocytes/macrophages and neutrophils. It can also reduce the formation of microcirculation thrombi in the infarcted area, improve endothelial barrier function, and increase microvascular density in the injured area. As a result, the heart function of mice is improved and the infarct area is reduced.Conclusion: We first demonstrated that the combination of extracellular vesicles and hydrogel has a better absorption efficiency in the nasal cavity, which can improve myocardial ischemia-reperfusion injury by inhibiting inflammatory reactions and protecting endothelial function. Nasal administration of vesicles combined with hydrogel is a potential therapeutic direction.Graphical Abstract: Keywords: myocardial ischemia-reperfusion injury, extracellular vesicles, hydrogel, intranasal delivery, inflammation

Xiao-Bing Li, Hao Feng, Yi Dai, Wei Liu Department of Neurology, Beijing Haidian Hospital, Beijing, 100730, People’s Republic of ChinaCorrespondence: Wei Liu; Yi Dai, Department of Neurology, Beijing Haidian Hospital, No. 29 Zhongguancun Street, Haidian District, Beijing, 100730, People’s Republic of China, Tel +86– 10– 82693198 ; +86– 10– 82693192, Email liuweillma@126.com; daiyiddm8@126.comBackground: In Weber syndrome, one side of the cerebral peduncle of the midbrain is infarcted due to the occlusion of the interpeduncular branch of the posterior cerebral artery and the posterior choroidal artery, resulting in ipsilateral oculomotor nerve palsy and contralateral hemiparesis. However, Weber syndrome induced by simple anterior choroidal artery lesions has rarely been reported.Case Description: Computed tomographic angiography revealed occlusion of the left internal carotid artery in a 57-year-old male patient who was admitted to the Beijing Haidian Hospital with cerebral infarction. Thrombectomy to clear the occlusion of the left internal carotid artery and the middle cerebral artery was successfully performed in the emergency department. However, postoperative digital subtraction angiography indicated occlusion of the middle and distal segments of the left anterior choroidal artery. After recovery from anesthesia, the patient had left blepharoptosis, inability to abduct the left eye, limitation of the upward and downward gaze, left mydriasis, absence of response to light, and right hemiplegia. Complete head magnetic resonance imaging suggested left cerebral peduncle and basal ganglia infarction. Therefore, the diagnosis was that the patient had left Weber syndrome caused by a left anterior choroidal arterial embolism.Conclusion: When the anterior choroidal artery is the dominant supplier of blood to the medial region of the ipsilateral cerebral peduncle, the occlusion of this artery may lead to ipsilateral Weber syndrome.Keywords: cerebral infarction, mechanical thrombectomy, anterior choroidal artery, oculomotor nerve palsy, Weber syndrome

Mingfei Guo,1,2 Jiarong Gao,3 Lei Jiang,4 Yaji Dai4 1Department of Scientific Research, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Anhui Public Health Clinical Center, Hefei, Anhui, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 4Department of Pharmacy, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Yaji Dai, Department of Pharmacy, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, People’s Republic of China, Email dyj920914@163.comBackground: Diabetic nephropathy (DN), as a chronic inflammatory complication of diabetes, is characterized by hyperglycemia, albuminuria and edema, which ultimately becomes the leading cause of end-stage renal disease (ESRD). Astragalus polysaccharide (APS), extracted from the Astragalus membranaceus, was widely used in the treatment of diabetes mellitus. However, the functional roles of APS ameliorate inflammatory responses in DN, which remain poorly understood. Therefore, the purpose of this study was to explore the molecular mechanism of APS on DN in vivo and vitro models.Methods: We explored the beneficial effects of APS in streptozotocin (STZ)-induced DN rat model and high glucose (HG)-treated glomerular podocyte model. The fasting blood glucose (FBG) and ratio of kidney weight to body weight were measured after 4 weeks of APS treatment. The renal injury parameters containing serum creatinine (Scr), blood urea nitrogen (BUN) and 24 h urinary protein were evaluated. The renal pathological examination was observed by hematoxylin-eosin (HE) staining. The levels of IL-1β, IL-6 and MCP-1 were evaluated by ELISA assay. The proliferation of podocytes was determined using CCK-8 assay and flow cytometry. qRT-PCR and Western blot analysis were performed to determine the amounts of TLR4/NF-κB-related gene expression.Results: Our results indicated that APS effectively decreased the levels of FBG, BUN, Scr and renal pathological damage when compared with STZ-induced DN model group. Additionally, APS significantly ameliorated renal injury by reducing inflammatory cytokines IL-1β, IL-6, MCP-1 expression and inhibiting the TLR4/NF-κB pathway activity in DN rats. Consistent with the results in vitro, the HG-induced inflammatory response and proliferation of glomerular podocytes were also alleviated through APS administration.Conclusion: We found that APS ameliorated DN renal injury, and the mechanisms perhaps related to relieving inflammatory responses and attenuating the TLR4/NF-κB signaling pathway.Keywords: diabetic nephropathy, Astragalus polysaccharide, podocytes, TLR4/NF-κB, inflammatory response

Yunbo Chen,1,2 Yuanyuan Dai,3 Yizheng Zhou,4 Ying Huang,5 Yan Jin,6 Yan Geng,7 Bing Ji,8 Rong Xu,9 Wencheng Zhu,10 Shuyan Hu,11 Zhuo Li,12 Jinhua Liang,13 Yonghong Xiao1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People’s Republic of China; 3Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 4Clinical Laboratory, Jingzhou Central Hospital, Jingzhou, People’s Republic of China; 5Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 6Clinical Laboratory, Shandong Provincial Hospital, Jinan, People’s Republic of China; 7Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 8Clinical Laboratory, Affiliated Hospital of Binzhou Medical College, Binzhou, People’s Republic of China; 9Clinical Laboratory, People’s Hospital of Yichun City, Yichun, People’s Republic of China; 10Clinical Laboratory, Lu’an Civil Hospital, Lu’an, People’s Republic of China; 11Clinical Laboratory, People’s Hospital of Qingyang, Qingyang, People’s Republic of China; 12Clinical Laboratory, The First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 13Clinical Laboratory, The Affiliated Hongqi Hospital of Mudanjiang Medicine College, Mudanjiang, People’s Republic of ChinaCorrespondence: Yonghong Xiao, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel/Fax +86 571 87236421, Email xiao-yonghong@163.comPurpose: Blood cultures (BCs) are essential laboratory tests for diagnosing blood stream infections. BC diagnostic improvement depends on several factors during the preanalytical phase outside of innovative technologies. In order to evaluate the impact of an educational program on BC quality improvement, a total of 11 hospitals across China were included from June 1st 2020 to January 31st 2021.Methods: Each hospital recruited 3 to 4 wards to participate. The project was divided into three different periods, pre-implementation (baseline), implementation (educational activities administered to the medical staff) and post-implementation (experimental group). The educational program was led by hospital microbiologists and included professional presentations, morning meetings, academic salons, seminars, posters and procedural feedback.Results: The total number of valid BC case report forms was 6299, including 2739 sets during the pre-implementation period and 3560 sets during the post-implementation period. Compared with the pre-implementation period, some indicators, such as the proportion of patients who had 2 sets or more, volume of blood cultured, and BC sets per 1000 patient days, were improved in the post-implementation period (61.2% vs 49.8%, 18.56 vs 16.09 sets, and 8.0 vs 9.0mL). While BC positivity and contamination rates did not change following the educational intervention (10.44% vs 11.97%, 1.86% vs 1.94%, respectively), the proportion of coagulase negative staphylococci-positive samples decreased in BSI patients (6.87% vs 4.28%).Conclusion: Therefore, medical staff education can improve BC quality, especially increasing volume of blood cultured as the most important variable to determine BC positivity, which may lead to improved BSI diagnosis.Keywords: blood culture, bloodstream infection, medical education, medical staff, quality improvement

Li Lin,1,&ast; Qingyong Chen,1,&ast; Yue Dai,2 Yufeng Xia1 1Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China; 2Department of Traditional Chinese Medicine and Pharmacology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufeng Xia, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People’s Republic of China, Tel +862583271400, Fax +862585301528, Email yfxiacpu@126.comPurpose: Madecassic acid (MCA) is a natural triterpenoid isolated from centellae herba that has diverse biological effects, such as anti-inflammatory, antioxidant, and anticancer activities. However, the efficacy of MCA is limited by low oral bioavailability caused by its extremely poor aqueous solubility. This study aimed to develop a self-nanoemulsifying drug delivery system (SNEDDS) for MCA to improve its oral absorption.Methods: The utilized oil phases, surfactants, and co-surfactants for SNEDDS were selected based on the solubility of MCA and emulsification efficiency. The optimized formulation was characterized for pharmaceutical properties and its pharmacokinetic behavior was examined in rats. Besides, the intestinal absorption property of MCA was investigated using in situ single-pass intestinal perfusion and intestinal lymphatic transport.Results: The optimized nanoemulsion formula consists of Capryol 90:Labrasol:Kolliphor ELP:Transcutol HP in a weight ratio of 1:2.7:2.7:3.6 (w/w/w/w). MCA-loaded SNEDDS presented a small droplet size (21.52 ± 0.23 nm), with a zeta potential value of − 3.05 ± 0.3 mV. Compared with pure MCA, SNEDDS had a higher effective permeability coefficient and showed 8.47-fold and 4.01-fold of maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC), respectively. Cycloheximide was pretreated before the experiment to evaluate the degree of lymphatic uptake. The results showed that cycloheximide greatly influenced the absorption of SNEDDS, resulting in 82.26% and 76.98% reduction in Cmax and AUC, respectively.Conclusion: This study reports the MCA-loaded SNEDDS with distinctly enhanced in vitro and in vivo performance compared with pure MCA and concludes that the SNEDDS formulation could be a viable and effective strategy for improving the dissolution rate and bioavailability of poor aqueous-soluble ingredients.Keywords: madecassic acid, self-nanoemulsifying drug delivery system, pharmacokinetics, intestinal lymphatic transport

Yudi Jin,1,2 Ailin Lan,1 Yuran Dai,1 Linshan Jiang,1 Shengchun Liu1 1Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Pathology, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer (iCQBC), Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of ChinaCorrespondence: Shengchun Liu, Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email liushengchun1968@163.comBackground: Recent studies have investigated the features of breast cancer (BC) with low human epidermal growth factor receptor 2 (HER2) expression or HER2-0 expression. However, the results were inconsistent. In this study, we investigated the differences in the pathological complete response (pCR) rate and disease-free survival (DFS) between HER2-low and HER2-0 BC patients and between subgroups.Methods: HER2-negative BC patients who received neoadjuvant chemotherapy between January 2013 and December 2019 in our hospital were retrospectively reviewed. First, the pCR rate and DFS were compared between HER2-low and HER2-0 patients and among different hormone receptor (HR) and HER2 statuses. Subsequently, DFS was compared between different HER2 status populations with or without pCR. Finally, a Cox regression model was used to identify the prognostic factors.Results: Overall, 693 patients were selected: 561 were HER2-low, and 132 were HER2-0. Between the two groups, there were significant differences in N stage (P = 0.008) and HR status (P = 0.007). No significant difference in the pCR rate (12.12% vs 14.39%, P = 0.468) or DFS was observed, independent of HR status. HR+/HER2-low patients had a significantly worse pCR rate (P < 0.001) and longer DFS (P < 0.001) than HR-/HER2-low or HER2-0 patients. In addition, a longer DFS was found in HER2-low patients versus HER2-0 patients among those who did not achieve pCR. Cox regression showed that N stage and HR status were prognostic factors in the overall and HER2-low populations, while no prognostic factor was found in the HER2-0 group.Conclusion: This study suggested that HER2 status is not associated with the pCR rate or DFS. Longer DFS was found only among patients who did not achieve pCR in the HER2-low versus HER2-0 population. We speculated that the interaction of HR and HER2 might have played a crucial role in this process.Keywords: HER2-low, HER2-0, hormone receptor, pCR, DFS

Zhou Liu,1,* Xiubing Hang,1,* Tao Yan,1 Wenwen Chu,1 Zhen Gong,1 Yanyan Liu,2– 4 Yuanyuan Dai,5 Min Yang,6 Jiabin Li,2– 4 Qiang Zhou1 1Department of Laboratory Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, People’s Republic of China; 4Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 5Department of Laboratory Medicine, Anhui Provincial Hospital, Hefei, Anhui, People’s Republic of China; 6Department of Intensive Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Yang, Department of Intensive Care, The Second Affiliated Hospital of Anhui Medical University, Furong Road No. 678, Hefei, Anhui, 230032, People’s Republic of China, Email yangmin@ahmu.edu.cn Qiang Zhou, Department of Laboratory Medicine, The Second Affiliated Hospital of Anhui Medical University, Furong Road No. 678, Hefei, People’s Republic of China, Email Zhouqiang_ahmu@126.comPurpose: To establish and evaluate a simple disk stacking plus micro-elution (DSE) method that can be routinely performed to rapidly detect the synergistic effect between aztreonam (ATM) and ceftazidime/avibactam (CZA) against metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE).Methods: The DSE method was established, and a total of 32 MBL-producing CRE isolates collected from multiple centers were tested for ATM-CZA synergy. The results obtained after 8 h of incubation were compared with those obtained by a reference checkerboard assay (CBA) after 18~24 h. Reproducibility experiments were completed on three separate days.Results: The reproducibility study showed that the results of the DSE method were precise. Compared with CBA, the DSE method exhibited excellent performance, with 92.8% sensitivity, 100.0% specificity 93.8% categorical agreement, 0.0% very major error, 0.0% major error, and 6.2% minor error over three days of testing.Conclusion: The DSE method is a simple, rapid and practical method for ATM-CZA combination testing. Further evaluation should be completed to improve its clinical application.Keywords: aztreonam, ceftazidime/avibactam, metallo-β-lactamases, Enterobacterales, antimicrobial combinations, clinical method

He Sui,1,&ast; Yu Gong,2,&ast; Lin Liu,1 Zhongwen Lv,1 Yunfei Zhang,3 Yongming Dai,3 Zhanhao Mo1 1Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Medical Imaging Department, Linyi People’s Hospital, Linyi, People’s Republic of China; 3MR Collaboration, Central Research Institute, United Imaging Healthcare, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanhao Mo, Department of Radiology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Erdao Dist., Changchun, People’s Republic of China, Email mozhanhao@jlu.edu.cnPurpose: To evaluate and compare the image quality and diagnostic accuracy of Artificial Intelligence-assisted Compressed Sensing (ACS) sequences for lumbar disease, as an acceleration method for MRI combining parallel imaging, half-Fourier, compressed sensing and neural network and routine 2D sequences for lumbar spine.Methods: We collected data from 82 healthy subjects and 213 patients who used 2D ACS accelerated sequences to examine the lumbar spine while 95 healthy subjects and 234 patients used routine 2D sequences. Acquisitions included axial T2WI, sagittal T2WI, T1WI, and T2-fs sequences. All obtained images of these subjects were analyzed in the light of calculating image quality factors such as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for selected regions of interest. The lumbar image quality, artifacts and visibility of lesion structure were assessed by two radiologists independently. Differences between the evaluation values above were tested for statistical significance by the Wilcoxon signed-ranks test. Inter-observer agreements of image quality between two radiologists were measured using Cohen’s kappa correlation coefficient.Results: The ACS accelerated sequences not only reduced the scanning time by 18.9%, but also retained basically the same image quality as the routine 2D sequences in both healthy subjects and patients. Artifacts are less produced on ACS accelerated sequences compared with routine 2D sequences (p < 0.05). Apart from this, there were no significant differences in quantitative SNR, CNR measurements and qualitative scores within reviewing radiologists for each group (p > 0.05). Moreover, inter-observer agreement between two radiologists in scoring image quality was substantial consistently for ACS accelerated sequences and routine sequences (kappa = 0.622– 0.986).Conclusion: Compared with routine 2D sequences, ACS accelerated sequences allow for faster lumbar spine imaging with similar imaging quality and present reliable diagnostic accuracy, which can potentially improve workflow and patient comfort in musculoskeletal examinations.Keywords: accelerated MRI, lumbar imaging, AI-assisted compressed sensing

Dan Long,1 Ting Yang,1 Jie Chen,1 Ying Dai,1 Li Chen,1 Feiyong Jia,2 Lijie Wu,3 Yan Hao,4 Ling Li,5 Jie Zhang,6 Xiaoyan Ke,7 Mingji Yi,8 Qi Hong,9 Jinjin Chen,10 Shuanfeng Fang,11 Yichao Wang,12 Qi Wang,13 Chunhua Jin,14 Tingyu Li1 1Chongqing Key Laboratory of Child Nutrition and Health, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center of Child Health and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Developmental and Behavioral Pediatrics, The First Hospital of Jilin University, Changchun, People’s Republic of China; 3Research Center for Child Development and Behavior, Harbin Medical University, Harbin, People’s Republic of China; 4Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Department of Children Rehabilitation, Hainan Women and Children’s Medical Center, Haikou, People’s Republic of China; 6Children Health Care Center, Xi’an Children’s Hospital, Xi’an, People’s Republic of China; 7The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 8Department of Child Health Care, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 9Maternal and Child Health Hospital of Baoan, Shenzhen, People’s Republic of China; 10Department of Child Health Care, Shanghai Children’s Hospital, Shanghai, People’s Republic of China; 11Department of Child Health Care, Children’s Hospital Affiliated of Zhengzhou University, Zhengzhou, People’s Republic of China; 12National Health Commission Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Hospital, Changsha, People’s Republic of China; 13Deyang Maternal and Child Health Hospital, Deyang, People’s Republic of China; 14Department of Children Health Care, Capital Institute of Pediatrics, Beijing, People’s Republic of ChinaCorrespondence: Tingyu Li, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China, Tel +86 23 63630913, Fax +86 23 63622754, Email tyli@vip.sina.comPurpose: The present study investigated the age of diagnosis, treatment and demographic factors of Chinese children with autism spectrum disorders (ASD), to provide a scientific basis for the early detection, diagnosis, and intervention of ASD.Patients and Methods: A total of 1500 ASD children aged 2– 7 years old from 13 cities in China were administered questionnaires to examine their diagnosis, treatment, and basic family information. The Childhood Autism Rating Scale (CARS) was used to measure the symptoms and severity of ASD children, and the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was utilized to measure neurodevelopmental levels of ASD children.Results: We found that for children with ASD, the median (p25, p75) age for the initial detection of social behavioral developmental delay was 24 (18, 30) months, while the age for the initial diagnosis was 29 (24, 36) months and the age for the beginning of intervention was 33 (27, 42) months. Multiple linear regression (MLR) analysis suggested that in children with ASD whose parents were divorced, separated, or widowed, or whose mothers were engaged in physical work, the initial detection of social behavioral developmental delay happened later. For the children with ASD who lived in urban areas, had higher levels of ASD symptom severity or whose parents were not divorced or separated, the age for the initial diagnosis was earlier. For the children with ASD who lived in urban areas or whose mothers had received higher level of education, the earlier age for the beginning of intervention was observed, while for those with ASD whose mothers were engaged in physical work, the age for the beginning of training was later.Conclusion: It is recommended to actively carry out health education of ASD and strengthen the support for ASD families to enhance their rehabilitation level.Keywords: autism spectrum disorders, children, age, influencing factors, multicenter

Lin Sun,1,2,&ast; Nan Meng,1,&ast; Zecheng Wang,1 Jiaxin Hong,1 Yuqi Dai,1 Zhenyu Wang,1 Jing Wang,1,2 Xinan Jiao1,2 1Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, People’s Republic of China; 2Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wang; Xinan Jiao, Email wj1231@yzu.edu.cn; jiao@yzu.edu.cnPurpose: Limited data are available on the prevalence and antimicrobial resistance of extended spectrum β-lactamase- (ESBL) and AmpC β-lactamase-producing Escherichia coli in stray dogs. We aimed to investigate the genomic characteristics of ESBL/AmpC-producing E. coli isolated from stray dogs sheltered in Yangzhou, China.Methods: We collected 156 samples including 115 fecal swabs, 35 kennel floor swabs, two breeder hand and shoe sole swabs, and four feed samples. The isolates were tested for resistance by antimicrobial susceptibility testing and further analyzed for cefotaxime-resistant E. coli isolates by whole genome sequencing.Results: We identified 80 cefotaxime-resistant E. coli isolates (51.3%), 59 isolates (73.8%) from feces and 21 (26.2%) from the environment. Whole-genome sequencing analysis showed that blaCTX-M-15 (n=30) and blaCTX-M-55 (n=29) were the most prevalent genotypes. Two isolates only carried the AmpC β-lactamase gene blaCMY-2; one isolate had a combination of AmpC β-lactamase gene blaDHA-1 and ESBL β-lactamase gene blaCTX-M-14. Other important resistance genes such as blaOXA-10, blaTEM-1B, blaTEM-135, blaTEM-106, tet(A), qnrS1, qnrB4, and oqxAB were also detected. The serotype combination was highly abundant, with O10:H25 predominating (n=12). Most cefotaxime-resistant E. coli isolates belonged to phylogroup A (62.5%, n=50), followed by phylogroup B1 (26.3%, n=21). Thirty different sequence types (STs) and 27 distinct plasmid replicons were identified, among which ST2325 (n=12) and IncFII (n=38) was the most frequent ST and plasmid, respectively. ESBL/AmpC-producing isolates were divided into four major clades; clade IV was the primary lineage containing 37 isolates from feces and 13 from the environment. Three high-risk E. coli clone ST23 strains and one ST10 strain belonged to clades III and IV, respectively.Conclusion: Our study provides a comprehensive overview of resistance profiles and genomic characteristics in ESBL/AmpC-producing E. coli and highlights the possible role of stray dogs as an antibiotic resistance gene reservoir.Keywords: Escherichia coli, ESBL/AmpC, stray dogs, antimicrobial resistance, whole genome sequencing

Yue Dai,1,2,&ast; Xuan Sha,1,&ast; Xiaoxi Song,1 Xiuli Zhang,1,2 Mengyuan Xing,1 Siwen Liu,1 Kai Xu,1,2 Jingjing Li1,2 1School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Xu; Jingjing Li, Email xkpaper@163.com; qingchao0124@163.comPurpose: Early diagnosis and treatment of atherosclerosis (AS) vulnerable plaque has important clinical significance for the prognosis of patients. In this work, the integrated diagnosis and treatment nanoparticles based on Gd-doped Prussian blue (GPB) were constructed for the fluorescence/MR dual-mode imaging and anti-ROS treatment of vulnerable AS plaques in vitro and in vivo.Methods: To fabricate the theranostic NPs, GPB was modified with water-soluble polymer polyethyleneimine (PEI), fluorescence molecule rhodamine (Rd), and targeted molecule dextran sulfate (DS) step by step via electrostatic adsorption to construct GPRD NPs. The fluorescence/MR imaging ability and various nano-enzymes activity of GPRD NPs were detected, and the biocompatibility and safety of GPRD were also evaluated. Subsequently, RAW264.7 cells and ApoE -/- model mice were used to evaluate the effect of GPRD NPs on the targeted dual-mode imaging and anti-ROS treatment of vulnerable plaque in vitro and in vivo.Results: The experimental results showed that our fabricated GPRD NPs not only displayed excellent MR/fluorescence dual-modality imaging of vulnerable plaque in vivo but also effectively utilized the nano-enzyme activity of GPB to inhibit the AS progress by ROS scavenging and the following reduction of inflammation, apoptosis, and foam cells’ formation, providing a new avenue for the diagnosis and treatment of AS vulnerable plaque.Conclusion: The fabricated multimodal imaging nanoparticles with ROS-scavenging ability provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.Graphical Abstract: Keywords: vulnerable plaques, ROS scavengers, nano-enzyme, MRI, fluorescence imaging

Yujie Huang,1 You Zhai,1 Meijia Wu,1 Chengdong Chang,2 Jindan Luo,3 Dongsheng Hong,1 Qingwei Zhao,1 Yao Dai,4 Jian Liu1 1Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Radiation Oncology, College of Medicine, University of Florida, Gainesville, FL, USACorrespondence: Jian Liu, Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel +86-571-87236560, Fax +86-571-87236531, Email lindaliu87@zju.edu.cn Yao Dai, Department of Radiation Oncology, College of Medicine, University of Florida, Gainesville, FL, USA, Tel +1-352-273-8237, Fax +1-352-273-8252, Email yaodai1111@hotmail.comPurpose: Mammalian Target of rapamycin (mTOR) plays a central role in regulating cell growth, proliferation, and cell cycle. The key component of mTORC2 is highly expressed in docetaxel-resistant prostate cells. However, the underlying molecular effects on prostate cells remain unclear.Methods: A docetaxel-resistant human prostate cell line (PC-3/DTX) was constructed to investigate the role of mTORC2 in docetaxel resistance. The lentivirus was transfected into cells to knock down the expression of Rictor, and cell viability was measured by Cell Counting Kit 8 (CCK-8). Flow cytometry was used to analyze the cell cycle, and the changes in related signal cascades were assessed by immunohistochemistry (IHC) staining and Western blot.Results: Docetaxel showed the lowest IC50 (50% inhibitory concentration) in PC-3/DTX cells with sh-RNA. Decreased Rictor expression resulted in a larger proportion of arrested cells in the G0/G1 phase in PC-3/DTX cells. The IC50 values of the AZD8055 group were lower than in the Rapamycin group when treated with docetaxel again. Furthermore, a larger proportion of PC-3/DTX cells were arrested in the G0/G1 phase in the AZD8055 group compared to the Rapamycin group. The IHC results of the prostate cancer tissues from a CRPC patient revealed the over expression of Rictor only, while Raptor expression was unaffected.Conclusion: We investigated the role of mTORC2 signaling on the acquired docetaxel -resistant PC-3 cells to identify potential methods for clinical treatment. MTORC2 expression is essential for docetaxel drug resistance of PC-3 cells. The mTORC1/2 inhibitor AZD8055 caused more significant disruption of mTORC2 kinase activity than the mTORC1 inhibitor Rapamycin, which lead to decreased docetaxel-mediated resistance. Therefore, reversing docetaxel resistance, may become a therapeutic option in the treatment of mCRPC patients.Keywords: prostate cancer cell, docetaxel, drug resistance, mTORC2, reverse

Liu Liu1 &ast;, Xiao Li2,3 &ast;, Pei Xue,4 Min Wu,4 Si Zeng,1 Yuee Dai,1 Junying Zhou4,5 1Department of Anesthesiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Psychology, Sleep Research Clinic and Laboratory, the University of Hong Kong, Hong Kong Special Administrative Regions, People’s Republic of China; 3State Key Laboratory of Brain and Cognitive Sciences, the University of Hong Kong, Hong Kong Special Administrative Regions, People’s Republic of China; 4Sleep Medicine Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5Department of Neurology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junying Zhou, Sleep Medicine Center, West China Hospital, Sichuan University, 28 Dian Xin Nan Jie, Chengdu, Sichuan Province, People’s Republic of China, Email zhoujy2016@scu.edu.cnObjective: This study aimed to determine the prevalence of chronic pain and its risk factors in patients with obstructive sleep apnea (OSA).Methods: A total of 145 patients diagnosed with OSA were consecutively recruited from the Sleep Medicine Center in West China Hospital. All patients were divided into two groups including OSA with and without chronic pain. They were assessed the subjective sleep (Pittsburgh Sleep Quality Index, Insomnia Severity Index), objective sleep (polysomnography), mood symptoms (Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale), and pain characteristics (Short-Form McGill Pain Questionnaire). Demographic, clinical, subjective and objective sleep parameters were compared between OSA patients with and without chronic pain. Binary logistic regression models and linear regression models were used to examine the risk factors of chronic pain in OSA.Results: Fifty-five (37.9%) patients with OSA were diagnosed with chronic pain. There were more severe subjective sleep disruption and symptoms of anxiety and depression in patients with chronic pain compared to those without chronic pain. After controlling for potential confounders, poor subjective sleep quality and severe insomnia and mood disorders (all ps < 0.05), but not objective sleep fragmentation or nocturnal hypoxemia (all ps > 0.05) were associated with the increased risk of pain and pain intensity, respectively.Conclusion: More than one-third of patients with OSA had chronic pain. Subjective sleep disruption and mood disorders are the risk factors of chronic pain in OSA. Our findings suggest that subjective sleep quality should be valued highly in the relationship between OSA and pain.Keywords: obstructive sleep apnea, subjective sleep disruption, insomnia, anxiety, depression, chronic pain

Bing Wu, Jun Yang, Yonghong Dai, Le Xiong Department of Critical Care Medicine, Jiangjin Central Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Le Xiong, Department of Critical Care Medicine, Jiangjin Central Hospital, No. 725, Jiangzhou Road, Dingshan Street, Jiangjin District, Chongqing, 402260, People’s Republic of China, Tel +86-2347521342, Email xiongle2022@126.comPurpose: To evaluate the predictive value of combination of Bedside Index for Severity in AP (BISAP) score and miR-155 for the severity of acute pancreatitis (AP).Patients and Methods: A total of 1046 AP patients were divided into control group and case group according to the severity of AP [mild and moderately severe AP vs severe AP (SAP)]. Demographic data, comorbidities, clinical characteristics and laboratory data were collected. Multivariate analysis was conducted for the variables with two-sided P< 0.10 in univariate analysis to identify independent associated factors for progression to SAP in AP patients. The predictive values were evaluated using receiver operating characteristic (ROC) curve, and the area under curve (AUC) was compared using Z test.Results: A total of 117 (11.2%) patients were evaluated as SAP. Univariate analysis showed that there were significant differences in age, hypertension, ICU admission, hospital stay, Leukocytes, CRP, BUN, BISAP score and miR-155 between case group and control group (P< 0.05), and the P value of Fibrinogen was < 0.10. Multivariate analysis showed that the BISAP score, BUN, Leukocytes, age and CRP were independent risk factors for progression to SAP among AP patients after adjusting for hypertension, ICU admission, hospital stay and Fibrinogen, while miR-155 was a protective factor. The ROC curves demonstrated the AUCs of BISAP score, miR-155 and their combination were 0.842 (SE: 0.017, 95% CI: 0.809– 0.874), 0.751 (SE: 0.022, 95% CI: 0.708– 0.793) and 0.945 (SE: 0.007, 95% CI: 0.931– 0.959), respectively. Z test showed that the AUC of combination prediction was significantly higher than that of individual predictions (0.945 vs 0.842, Z=5.602, P< 0.001; 0.945 vs 0.751, Z=8.403, P< 0.001). The sensitivity, specificity and negative predictive value (NPV) of combination prediction were 95.7%, 93.6% and 99.4%, respectively.Conclusion: The combination of the BISAP score and miR-155 should be utilized to elevate the predictive value for the severity of AP in clinic.Keywords: severe acute pancreatitis, Bedside Index for Severity in AP score, miR-155, prediction

Yeshen Zhang,1,2,&ast; Zhengrong Xu,3,&ast; Wenfei He,4,&ast; Zehuo Lin,1,2 Yaoxin Liu,1,2 Yining Dai,1,2 Wei Chen,5 Weikun Chen,1,2 Wenlong He,1,2 Chongyang Duan,6 Pengcheng He,1,2 Yuanhui Liu,1,2 Ning Tan1,2 1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3Department of Cardiology, People’s Hospital of Baoan Shenzhen, Guangzhou, People’s Republic of China; 4Department of Cardiology, Guangdong Provincial People’s Hospital’s Nanhai Hospital, the Second People’s Hospital of Nanhai District Foshan City, Foshan, People’s Republic of China; 5Department of Cardiology, Fujian Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fujian Institute of Cardiovascular Disease, Fuzhou, People’s Republic of China; 6Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Tan; Yuanhui Liu, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Tel +86-20-83819161, Fax +86-20-83824369, Email gdtanning@126.com; liuyuanhui@gdph.org.cnBackground: The serum uric acid/albumin ratio (sUAR), a novel inflammatory marker, effectively predicts acute kidney injury (AKI) and cardiovascular outcomes. However, whether the sUAR predicts post-contrast acute kidney injury (PC-AKI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) remains uncertain. In this study, we evaluated the association between the sUAR and PC-AKI in patients with STEMI undergoing PCI.Methods: We consecutively recruited patients with STEMI who underwent PCI and stratified them into three groups according to the terciles of the sUAR. The primary outcome was the incidence of PC-AKI. The association between the sUAR and PC-AKI was assessed by multivariate logistic regression analysis.Results: A total of 2861 patients with STEMI were included in this study. The incidence of PC-AKI increased stepwise with increasing sUAR tercile (2.6% vs 4.0% vs 11.6%, p < 0.001), and the incidence of in-hospital major adverse clinical events (MACEs) was highest among patients in the Q3 group. Multivariate logistic regression analysis revealed that the sUAR was also an independent predictor of PC-AKI (continuous sUAR, per 1-unit increase, odds ratio [OR] [95% confidence interval (CI)]: 1.06 [1.02– 1.10], p = 0.005; tercile of sUAR, OR [95% CI] for Q2 and Q3: 1.18 [0.69– 2.01] and 1.85 [1.12– 3.06], respectively, with Q1 as a reference) but not in-hospital MACEs. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of the sUAR for predicting PC-AKI was 0.708 (95% CI: 0.666– 0.751), and ROC analysis also showed that the sUAR was superior to uric acid and albumin alone in predicting PC-AKI.Conclusion: Increasing sUAR was significantly associated with a higher risk of PC-AKI but not in-hospital MACEs in patients with STEMI who underwent PCI, suggesting that sUAR had a predictive value for PC-AKI after PCI in patients with STEMI. Further studies are required to confirm this finding.Keywords: serum uric acid/albumin ratio, post-contrast acute kidney injury, ST-segment elevation myocardial infarction

Yuanfei Bao,1,&ast; Yao Zhang,2,&ast; Chaopin Du,1 Yan Ji,1 Yiwei Dai,1 Wei Jiang3 1Department of Neurology, Affiliated Nantong Hospital 3 of Nantong University, Nantong, 226000, People’s Republic of China; 2Department of Neurology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210002, People’s Republic of China; 3Department of Neurology, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, 214000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Jiang, Department of Neurology, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, No. 68 Zhongshan Road, Wuxi, 214000, People’s Republic of China, Tel/Fax +86 0510-68562222, Email jianghaot1986@163.comBackground and Purpose: This study aimed to investigate the relationship between malnutrition and early neurological deterioration (END) in elderly patients with acute ischemic stroke in China.Methods: We used the registry data in the Third Affiliated Hospital of Nantong University and Nanjing Brain Hospital from June 2019 to January 2021. Malnutrition risk was evaluated by controlling nutritional status score (CONUT), geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI) score, respectively. END was defined as an increment of at least two points in the total NIHSS score within three days after admission. We evaluated the relationship between malnutrition and END with multivariable logistic regression models and reclassification indexes.Results: A total of 732 elderly patients with first-ever acute ischemic stroke were included in the study. 243 patients developed END. 5.7%, 21.4%, 4.6% patients were classified as moderate to severe malnutrition by CONUT, GNRI and PNI, respectively. Malnutrition was associated with the risk of END for CONUT (odds ratio [OR], 1.210; 95% confidence interval [CI] 1.092– 1.341; P < 0.001), for GNRI (OR, 0.943; 95% CI, 0.919– 0.967; P < 0.001), and for PNI (OR, 0.936; 95% CI, 0.908– 0.965; P < 0.001) in multivariable logistic regression models using the back-ward selection method. The discriminative ability was 0.763 (95% CI, 0.727– 0.798) for CONUT, 0.769 (95% CI, 0.733– 0.805) for GNRI and 0.769 (95% CI, 0.733– 0.805) for PNI after adjusting for confounders. Besides, adding malnutrition indexes into models made the prediction of END more accurate.Conclusion: Malnutrition was associated with END in elderly Chinese patients with acute ischemic stroke.Keywords: malnutrition, ischemic stroke, elderly, early neurological deterioration

Qiwen Dai,1 Yanhong Dai,1 Chunyu Zhang,1 Zhiming Meng,2 Zeyu Chen,1 Senlin Hu3 1School of Economics and Management, Guangxi Normal University, Guilin, People’s Republic of China; 2School of Innovation and Entrepreneurship, Guangxi Normal University, Guilin, People’s Republic of China; 3School of Urban Development Research, East China Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Chunyu Zhang, School of Economics and Management, Guangxi Normal University, Guilin, Guangxi, 541004, People’s Republic of China, Email 468160345@qq.comPurpose: Drawing on the motivation theory, this study investigated the effect and consequences of personal motivation and innovative climate on innovative behavior among university students in mainland China. The study also examined whether the effect of personal motivation and innovative climate on Chinese university students’ innovative behavior is heterogeneous between disciplines and place of residence.Methods: A quantitative study was conducted to test the hypotheses. Data were collected from 245 undergraduate students at Chinese universities with paper-based questionnaires. Self-report scales were used to measure levels of personal motivation, innovative climate, and innovative behaviors. A confirmatory factor analysis was used to test the scale and questionnaire’s reliability and validity. The logistic model was applied to analyze the data and test the hypotheses.Results: Personal motivation and innovative climate have significant effects on Chinese university students’ innovative behavior. The effect of personal motivation and innovative climate on students’ innovative behavior is heterogeneous between disciplines and place of residence. Further, extrinsic motivation serves as a positive incentive. Mentor support, good academic climate, and knowledge sharing affect students’ innovative behavior positively. However, insufficient guaranteed resources has a significant negative influence. The data demonstrated no statistically significant difference between intrinsic motivation and students’ innovative behavior.Conclusion: This study contributes to the empirical literature on mechanisms that influence innovative behavior by testing the relation between personal motivation, innovative climate, and innovative behavior on the part of Chinese university students. In addition, these findings also provide evidence for ways to improve university students’ innovative consciousness and innovative ability, as well as universities’ management practice of innovative education.Keywords: innovative behavior, personal motivation, innovative climate, university students

Xipei Wu, Yongzhao Dai, Ke Nie School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Ke Nie, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Email nicknk@hotmail.com; knie@gdpu.edu.cnAbstract: Tumor-associated anorexia, mainly including cancerous anorexia and chemotherapy-induced anorexia, severely reduces the life quality of cancer patients but lacks of effective control until now. Liujunzi decoction (LJZD), a classical tonifying formula in traditional Chinese medicine, has promising effect in preventing and treating many kinds of anorexia. A growing number of evidence showed that LJZD is able to improve tumor-associated anorexia. Up to March 2022, a total of 58 articles studying LJZD or Rikkunshito (the name of LJZD in Japanese herbal medicine) in the treatment of tumor-associated anorexia are searched out in PubMed. This paper summarizes the effect of LJZD in ameliorating tumor-associated anorexia, in order to provide a theoretical basis for the clinical application of LJZD in treating tumor-associated anorexia, laying foundation for further research.Keywords: Liujunzi decoction, tumor-associated anorexia, review

Li Zhang,1,&ast; Jing Xu,1,&ast; Xiaoling Qi,1 Zheying Tao,1 Zhitao Yang,2 Wei Chen,3 Xiaoli Wang,1 Tingting Pan,1 Yunqi Dai,1 Rui Tian,1 Yang Chen,1 Bin Tang,1 Zhaojun Liu,1 Ruoming Tan,1 Hongping Qu,1 Yue Yu,1 Jialin Liu1 1Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Emergency Department, Ruijin Hospital affiliate to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Ruijin Hospital Affiliate to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jialin Liu; Yue Yu, Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200020, People’s Republic of China, Email ljl11243@rjh.com.cn; yy12356@rjh.com.cnBackground: Since the outbreak of coronavirus disease (COVID-19) in December 2019 in Wuhan, it has spread rapidly worldwide. We aimed to establish and validate a nomogram that predicts the probability of coronavirus-associated acute respiratory distress syndrome (CARDS).Methods: In this single-centre, retrospective study, 261 patients with COVID-19 were recruited using positive reverse transcription–polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 in Tongji Hospital at Huazhong University of Science and Technology (Wuhan, China). These patients were randomly distributed into the training cohort (75%) and the validation cohort (25%). The factors included in the nomogram were determined using univariate and multivariate logistic regression analyses based on the training cohort. The area under the receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in the training and validation cohorts.Results: Independent predictive factors, including fasting plasma glucose, platelet, D-dimer, and cTnI, were determined using the nomogram. In the training cohort, the AUC and concordance index were 0.93. Similarly, in the validation cohort, the nomogram still showed great distinction (AUC: 0.92) and better calibration. The calibration plot also showed a high degree of agreement between the predicted and actual probabilities of CARDS. In addition, the DCA proved that the nomogram was clinically beneficial.Conclusion: Based on the results of laboratory tests, we established a predictive model for acute respiratory distress syndrome in patients with COVID-19. This model shows good performance and can be used clinically to identify CARDS early.Trial Registration: Ethics committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (No.:(2020) Linlun-34th).Keywords: COVID-19, CARDS, nomogram, risk factor, prediction

Yuan Cheng,1,2,&ast; Fushun Kou,1,2,&ast; Xiaosi Zhang,1,2 Yi Dai,3 Lei Shi,2 Chune Xie,2 Xiaohong Li,2 Junxiang Li2 1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Pharmacotherapy and Oriental Medicine, School of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan&ast;These authors contributed equally to this workCorrespondence: Junxiang Li; Xiaohong Li, Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6, 1st Section Fangxingyuan, Fangzhuang, Fengtai District, Beijing, 100078, People’s Republic of China, Email junxiangli1226@126.com; lxhktxz@163.comPurpose: Proton pump inhibitors, as the first-line drugs for treating gastroesophageal reflux disease (GERD), are unable to completely relieve patients’ symptoms and patients are prone to recurrence after prolonged drug withdrawal. Thus, it is crucial to find herbal medicines as a complementary and alternative treatment. Hewei Jiangni granule (HWJNG) is a classical Chinese medicinal formula with clinical therapeutic effects on GERD, but its pharmacological mechanism of action remains unclear. This study aimed to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy.Methods: A network pharmacology approach was applied to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. The active ingredients of HWJNG, as well as therapeutic targets of GERD were acquired from specialized databases. The “herb-ingredient-gene-target” network for HWJNG in GERD treatment was built. The protein–protein interaction (PPI) network was constructed to screen the core coincident targets. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The core targets and signaling pathways associated with the anti-neurogenic inflammatory effect were partially verified via experiments in vivo at molecular level.Results: In total, 179 chemical ingredients in HWJNG and 298 intersection targets between GERD and HWJNG were selected from databases. A large proportion of core targets and top signaling pathways were involved in neurogenic inflammation. HWJNG significantly alleviated pathological injuries of esophagus and reversed dilated intracellular spaces. Additionally, HWJNG markedly inhibited the excessive release of inflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factor receptor (TNF-a), as well as regulated stimulation sensors including transient receptor potential vanilloid type 1 (TRPV1) and its related neuroinflammatory mediators in GERD mice.Conclusion: HWJNG is a promising therapeutic strategy for GERD treatment via regulation of multiple targets and pathways, its effects in alleviating neurogenic inflammation are especially acknowledged.Keywords: Hewei Jiangni granule, gastroesophageal reflux disease, network pharmacology, neurogenic inflammation

Jiangyan Wei,1,&ast; Lu Liu,1,&ast; Zhijuan Li,1 Tianli Lyu,1 Luopeng Zhao,2 Xiaobai Xu,1 Yine Song,1 Yidan Dai,1 Bin Li1 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, People’s Republic of China; 2Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Li, Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, 23 Meishuguan Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Tel +86-18910781852, Fax +86-87906055, Email libin@bjzhongyi.comPurpose: Macrophage polarization contributes to the mechanisms of treating knee osteoarthritis (KOA). In previous studies, fire needling acupuncture has been shown to affect KOA favorably. However, the mechanism of fire needling acupuncture on macrophage polarization is not well-defined. Thus, this study was conducted to determine that fire needling acupuncture exerts a therapeutic role in KOA by modulating macrophage polarization.Methods: Thirty mice were allocated at random into three groups of ten. The groups were labeled as “control”, “model”, and “fire needling acupuncture”. Each group consisted of ten mice. From the second day of intra-articular injection MIA, the right “xiyan” (EX-LE5), “dubi” (ST35), “liangqiu” (ST34), and “xuehai” (SP10) acupoints were manipulated once every other day for two weeks in the fire needling acupuncture group. Mechanical withdrawal threshold and weight distribution were evaluated for behavioral testing in each group. The synovial morphology was monitored by HE staining. Pathological morphology was observed by HE staining, Saf-O staining, and toluidine blue staining. The polarization of macrophages in synovial tissue was detected using immunofluorescence (F4/80, CD86, and CD206).Results: Fire needling acupuncture increased the percentage weight-bearing difference and the mechanical withdrawal threshold, and improved synovial inflammation and cartilage damage in MIA-induced KOA mice. F4/80 and CD86 expression were downregulated by fire needling acupuncture, but CD206 was increased.Conclusion: Fire needling acupuncture decreases pain behaviors in KOA mice and improves synovial membrane injury and pathological cartilage damage. The macrophage polarization is involved in the mechanism of fire needling acupuncture’s amelioration of articular cartilage damage.Keywords: fire needling acupuncture, knee osteoarthritis, synovial membrane, cartilage, macrophage polarization

Yanmei Dai,1 Huijie Jiang,1 Shi-Ting Feng,2 Yuwei Xia,3 Jinping Li,1 Sheng Zhao,1 Dandan Wang,1 Xu Zeng,1 Yusi Chen,1 Yanjie Xin,1 Dongmin Liu1 1Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150086, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510030, People’s Republic of China; 3Huiying Medical Technology Co., Ltd, Beijing City, 100192, People’s Republic of ChinaCorrespondence: Huijie Jiang; Shi-Ting Feng, Tel +86 86605576, Email jianghuijie@hrbmu.edu.cn; fengsht@mail.sysu.edu.cnPurpose: This study aims to develop a new model to more comprehensively and accurately predict the survival of patients with HCC after initial TACE.Patients and Methods: The whole cohort (n = 102) was randomly divided into a training cohort and a validation cohort in the ratio of 8:2. The optimal radiomics signatures were screened using the least absolute shrinkage and selection operator algorithm (LASSO) regression for constructing the radscore to predict overall survival (OS). The C-index (95% confidence interval, CI), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the models. The independent risk factors (hazard ratio, HR) for predicting OS were stratified by Kaplan–Meier (K-M) analysis and the Log rank test.Results: The median OS was 439 days (95% CI: 215.795– 662.205) in whole cohort, and in the training cohort and validation cohort, the median OS was 552 days (95% CI: 171.172– 932.828), 395 days (95% CI: 309.415– 480.585), respectively (P = 0.889). After multivariate cox regression, the combined radscore-clinical model was consisted of radscore (HR: 2.065, 95% CI: 1.285– 3.316; P = 0.0029) and post-response (HR: 1.880, 95% CI: 1.310– 2.697; P = 0.0007), both of which were independent risk factors for the OS. In the validation cohort, the efficacy of both the radscore (C-index: 0.769, 95% CI: 0.496– 1.000) and combined model (C-index: 0.770, 95% CI: 0.581– 0.806) were higher than that of the clinical model (C-index: 0.655, 95% CI: 0.508– 0.802). The calibration curve of the combined model for predicting OS presented good consistency between observations and predictions in both the training cohort and validation cohort.Conclusion: Noninvasive imaging has a good prediction performance of survival after initial TACE in patients with HCC. The combined model consisting of post-response and radscore may be able to better predict outcome.Keywords: computed tomography, hepatocellular carcinoma, overall survival, radiomics, transarterial chemoembolization

Wei Zhang,1,&ast; Yuyang Zhang,1,&ast; Jingjing Gao,1 Dangwei Peng,1 Yao Zhang,1 Xu Wu,1 Guodong Liu,1 Yutian Dai,2 Hui Jiang,3 Xiansheng Zhang1 1Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Urology, Gulou Hospital of Nanjing University, Nanjing, Jiangsu Province, People’s Republic of China; 3Department of Reproductive Medicine Center, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiansheng Zhang; Hui Jiang, Email xiansheng-zhang@163.com; jianghui55@163.comPurpose: To determine the role of poor sleep quality as a risk factor for acquired premature ejaculation (APE) after considering the various risk factors, such as ages, lower urinary tract symptoms (LUTS), anxiety, depression, and erectile dysfunction.Methods: This study presents a multivariate analysis to identify risk factors for PE, including the covariate of age, International Prostate Symptom Score (IPSS), General Anxiety Disorder-7 (GAD-7) score, Patient Health Questionnaire-9 (PHQ-9) score, International Index of Erectile Function (IIEF) score, and Pittsburgh Sleep Quality Index (PSQI). Acquired PE was defined as self-reported intravaginal ejaculation latency time ≤ 3 minutes, and poor sleep quality was diagnosed using the Pittsburgh Sleep Quality Index tool.Results: A total of 349 men were enrolled in the study after completing the questionnaires and the medical history survey. Among 349 men, 203 individuals (58.17%) suffered from acquired PE. The IIEF-5 score, IPSS, GAD-7 score, PHQ-9 score, and PSQI score of the population with PE were significantly different from the non-PE group. Further multivariate analysis showed that erectile dysfunction, depression, severe prostatitis-like symptoms, and poor sleep quality were high-risk factors of APE. Additionally, our study showed that premature ejaculation diagnostic tool (PEDT) score was associated with IPSS/GAD-7/PHQ-9/PSQI scores positively and associated with IIEF-5 scores negatively. The stratified analysis of sleep quality showed that APE patients with different sleep qualities have different prevalence rates of anxiety, depression, prostatitis-like symptoms, and erectile function.Conclusion: In general, sleep quality may be a potential risk factor for patients with acquired premature ejaculation. Our research revealed the impact of sleep quality on premature ejaculation and provided new viewpoints for further understanding and perfecting the pathogenesis of premature ejaculation.Keywords: sleep quality, acquired premature ejaculation, multivariate analysis

He Sui,1,&ast; Jin Li,2,3,&ast; Lin Liu,1 Zhongwen Lv,1 Yunfei Zhang,4 Yongming Dai,4 Zhanhao Mo1 1China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Jilin Province People’s Hospital, Changchun, People’s Republic of China; 3The Department of Trauma Surgery, Shanghai Oriental Hospital, Shanghai, People’s Republic of China; 4Central Research Institute, United Imaging Healthcare, Shanghai, 201800, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanhao Mo, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Erdao District, Changchun, People’s Republic of China, Email mozhanhao@jlu.edu.cnPurpose: The three-dimensional (3D) sequence of magnetic resonance imaging (MRI) plays a critical role in the imaging of musculoskeletal joints; however, its long acquisition time limits its clinical application. In such conditions, compressed sensing (CS) is introduced to accelerate MRI in clinical practice. We aimed to investigate the feasibility of an isotropic 3D variable-flip-angle fast spin echo (FSE) sequence with CS technique (CS-MATRIX) compared to conventional 2D sequences in knee imaging.Methods: Images from different sequences of both the accelerated CS-MATRIX and the corresponding conventional acquisitions were prospectively analyzed and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the structures within the knees were measured for quantitative analysis. The subjective image quality and diagnostic agreement were compared between CS-MATRIX and conventional 2D sequences. Quantitative and subjective image quality scores were statistically analyzed with the paired t-test and Wilcoxon signed-rank test, respectively. Diagnostic agreements of knee substructure were assessed using Cohen’s weighted kappa statistic.Results: For quantitative analysis, images from the CS-MATRIX sequence showed a significantly higher SNR than T2-fs 2D sequences for visualizing cartilage, menisci, and ligaments, as well as a higher SNR than proton density (pd) 2D sequences for visualizing menisci and ligaments. There was no significant difference between CS-MATRIX and 2D T2-fs sequences in subjective image quality assessment. The diagnostic agreement was rated as moderate to very good between CS-MATRIX and 2D sequences.Conclusion: This study demonstrates the feasibility and clinical potential of the CS-MATRIX sequence technique for detecting knee lesions The CS-MATRIX sequence allows for faster knee imaging than conventional 2D sequences, yielding similar image quality to 2D sequences.Keywords: knee MRI, compressed sensing, 3D variable-flip-angle fast spin echo

Ying Cao,1,&ast; Yibei Dai,1,&ast; Lingyu Zhang,1 Danhua Wang,1 Wen Hu,2 Qiao Yu,3 Xuchu Wang,1 Pan Yu,1 Weiwei Liu,1 Ying Ping,1 Tao Sun,1 Yiwen Sang,1 Zhenping Liu,4 Yan Chen,3 Zhihua Tao1 1Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People’s Republic of China; 2National Clinical Research Center for Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, People’s Republic of China; 3Center for Inflammatory Bowel Diseases, Department of Gastroenterology, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People’s Republic of China; 4Department of Laboratory Medicine, the First People’s Hospital of Yuhang District, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Zhihua Tao Tel +86 571 8778 3752Fax +86 571 8689 8730Email chenyan72_72@zju.edu.cn; zrtzh@zju.edu.cnBackground: Fecal biomarkers have emerged as one of the most useful tools for clinical management of inflammatory bowel disease (IBD). Oncostatin M (OSM), like fecal calprotectin (FC), is highly expressed in the inflamed intestinal mucosa which may have potential usefulness. We aimed to evaluate the additional utility of these two fecal biomarkers for IBD diagnosis, activity, and prediction of infliximab response over FC alone.Methods: In group 1, 236 IBD patients (145 Crohn’s disease, 91 ulcerative colitis), 50 disease controls, and 32 healthy controls were recruited for IBD diagnosis and activity. In group 2, baseline stool samples were collected from 62 patients to predict infliximab response at week 28 and 52. The performance of fecal biomarkers for IBD management was assessed by the area under the receiver operating characteristic curve (AUC).Results: Fecal OSM and FC levels were increased in IBD patients and were positively correlated with clinical and endoscopic activity. Their combination showed a better ability for disease diagnosis (AUC = 0.93) and slightly improved the capability to identify mucosal healing (AUC = 0.923). Baseline OSM and FC levels were elevated in non-responders at week 28 and 52. The AUCs of OSM, FC, and their combination to predict therapeutic response were 0.763, 0.834, and 0.859 at week 28, 0.638, 0.661, and 0.704 at week 52, respectively. Combined use of fecal and blood biomarkers improved predictive accuracy with an AUC of 0.919 at week 28 and 0.887 at week 52.Conclusion: In addition to FC, OSM is a novel fecal biomarker, and their combination is more beneficial for disease diagnosis and prediction of infliximab response but not for disease activity in IBD patients. Further larger-scale studies are required to confirm our findings.Keywords: inflammatory bowel disease, fecal biomarkers, oncostatin M, calprotectin, diagnosis, activity, infliximab response

Danhua Guo,1 Deqin He,1 Qingmei Shen,1 Na Lin,1 Shuqiong He,1 Yifang Dai,1 Ying Li,1 Liangpu Xu,1 Xiaoqing Wu1,2 1Medical Genetic Diagnosis and Therapy Center of Fujian Provincial Maternity and Child Hospital, Affiliated Hospital of Fujian Medical University, Fujian Provincial Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou City, Fujian Province, People’s Republic of China; 2Department of Laboratory Medicine, Fujian Medical University, Fuzhou, 350002, Fujian, People’s Republic of ChinaCorrespondence: Liangpu Xu; Xiaoqing WuMedical Genetic Diagnosis and Therapy Center of Fujian Provincial Maternity and Child Hospital, Affiliated Hospital of Fujian Medical University, Fujian Provincial Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou City, Fujian Province, 350001, People’s Republic of ChinaEmail xiliangpu@fjmu.edu.cn; wuxiaoqing013@126.comObjective: This retrospective study aimed to systematically evaluate the genetic disorders, cytomegalovirus (CMV) infection, extra ultrasound findings and outcomes of fetuses with bilateral ventriculomegaly (BVM).Methods: Data from pregnancies with fetal BVM were obtained between 2014 and 2020. The cases were divided into groups of isolated bilateral ventriculomegaly (IBVM) and non-isolated bilateral ventriculomegaly (NIBVM) according to the presence of extra prenatal imaging. Subgroups of mild, moderate, and severe were determined according to lateral ventricle widths. The NIBVM group was further classified into pregnancies with soft markers, non-structural abnormalities, and structural abnormalities.Results: A total of 353 pregnancies were enrolled, including 153 cases of IBVM and 200 cases of NIBVM. Conventional karyotyping was performed on 192 samples, and 15 cases of numerical abnormalities and 3 cases of unbalanced structural abnormalities were identified. Chromosomal microarray analysis (CMA) was concurrently performed on 108 of them and revealed additional 5 cases (4.7%) of copy number variants with clinical significance. CMV DNA testing was performed on 154 of the 192 cases that underwent invasive prenatal diagnosis, and a positive result was found in 2 (1.3%) cases. In the IBVM group, the percentage of favorable prognosis in the mild, moderate and severe pregnancies were 94.4%, 79.2%, and 4.8%, respectively, and the termination of pregnancy (TOP) rates were 4.6%, 20.8%, and 85.7%, respectively. In both the mild and moderate NIBVM, the TOP rates progressively increased and the favorable prognosis survival rates progressively decreased relative to the soft markers, non-structural abnormalities, and structural abnormalities, respectively. Approximately 94.1% of severe NIBVM ended in termination.Conclusion: Genetic disorders and fetal infection are important etiology of BVM. CMA is highly recommended for genetic disorders’ evaluation. Pregnancies with severe BVM always ended in TOP, while in mild-to-moderate NIBVM, prenatal imaging by ultrasound and/or MRI plays important roles in the pregnancy outcomes.Keywords: bilateral ventriculomegaly, genetic disorders, cytomegalovirus infection, prenatal imaging

Li J, You J, Wu C, et al. Int J Nanomedicine. 2018;13:4607-4625. An error during the preparation of Figure S1 for publishing led to the inadvertent creation of a duplicate region in figure part S1B on page 4622. The journal wishes to apologise for this error. The correct version of Figure S1 is as follows. Figure S1 Transmission electron microscopy characterizations of Fe3O4 nanoparticles (NPs) (A) and Fe3O4@mSiO2 NPs (B). The insert in (A) is the distribution of Fe3O4 NP size.

Yuanyuan Dai,1 Wenjiao Chang,1 Xin Zhou,1 Wei Yu,2 Chen Huang,2 Yunbo Chen,2 Xiaoling Ma,1 Huaiwei Lu,1 Rujin Ji,2 Chaoqun Ying,2 Peipei Wang,2 Zhiying Liu,2 Qingfeng Yuan,1 Yonghong Xiao2 1Department of Laboratory, First Affiliated Hospital of University of Science and Technology of China, Hefei, People’s Republic of China; 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Yonghong Xiao Tel/Fax +865 718 723 6421Email xiao-yonghong@163.comPurpose: To evaluate the administration regimen of ceftazidime/avibactam (CZA) for bloodstream infections caused by Enterobacteriaceae and Pseudomonas aeruginosa.Methods: The minimal inhibitory concentrations (MICs) of CZA against Enterobacteriaceae and P. aeruginosa isolated from blood cultures at member hospitals in BRICS (Blood Bacterial Resistant Investigation Collaborative System) in 2019 were determined by broth micro-dilution methodology. A 10,000-patient Monte Carlo simulation (MCS) was used to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) for different CZA dosage regimens to evaluate their efficacies and optimize the best initial dosage regimen.Results: Altogether, 6487 Enterobacteriaceae and P. aeruginosa strains were isolated from the blood cultures. The overall CZA resistance rate was 2.31%, of which the Enterobacteriaceae and P. aeruginosa rates were 1.57% and 14.29%, respectively. The MCS showed that the greater the MIC value, the worse the therapeutic effect. When the CZA MIC was ≤ 8 mg/L, the standard dose (2.5g iv q8h) achieved 90% PTA in the subset of patients with creatinine clearance (CrCl) values from 51 to 120 mL/min. Although the high-dose regimen (3.75g iv q8h) achieved 90% PTA in patients with CrCl values from 121 to 190 mL/min, implementing the low-dose regimen (1.25g iv q8h) was also effective for patients in the 51– 89 mL/min CrCl range. Generally, the high-dose regimen (3.75g iv q8h) reached 90% CFR against all of the strains. Conversely, in patients with CrCl values of 121– 190 mL/min, the standard dose (2.5g iv q8h) failed to reach 90% CFR against some Enterobacteriaceae members and P. aeruginosa. When the dose was reduced to the low-dose regimen (1.25g iv q8h), no patients reached 90% CFR against some Enterobacteriaceae members and P. aeruginosa.Conclusion: CZA has good antibacterial activity against Enterobacteriaceae and P. aeruginosa in bloodstream infections. Clinicians could make individualized treatment regimens in accordance with the sensitivity of the strains and the level of renal function in their patients to best predict the drug-related clinical responses.Keywords: Gram-negative bacteria, extended-spectrum β-lactamase, dosage regimens, pharmacokinetics, pharmacodynamics, minimum inhibitory concentration

Yun Yan,1 Li Jiang,2 Jianjiang Fang,2 Yi Dai,3 Xingzi Chenyu,3 Jinhua Ding4 1Department of Ultrasound, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China; 2Department of General Practice, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China; 3Ningbo University School of Medicine, Ningbo, Zhejiang, 315000, People’s Republic of China; 4Department of Breast and Thyroid Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of ChinaCorrespondence: Jinhua DingDepartment of Breast and Thyroid Surgery, Ningbo Medical Center Lihuili Hospital, No. 1111, Jiangnan Road, Ningbo, Zhejiang, 315000, People’s Republic of ChinaTel +86 13957498690Email cookie800128@sina.comPurpose: Interpectoral lymph nodes (IPNs) are one of the lymphatic drainage pathways in breast cancer. However, the clinical significance of IPN dissection is controversial, and there is no international consensus regarding the management of IPN for resectable breast cancer. Our study aims to identify the independent predictors of IPN metastasis in invasive breast cancer (IBC) and provide some evidence for rational decision-making.Methods: Data from 214 IBC patients who were treated with modified radical mastectomy (MRM) plus IPN dissection or biopsy in Ningbo Medical Center Lihuili Hospital were retrospectively reviewed. Univariate analysis and multivariate logistic regression analysis were used to analyse the correlations between IPN occurrence or metastasis and clinicopathological characteristics.Results: The occurrence rate of IPN in overall population was 75.2%. Univariate analysis showed that tumour size, involvement of axillary lymph nodes (ALNs), histological grading, Ki67 index and molecular subtype were associated with the occurrence of IPN. However, involvement of ALN was the only independent predictor by multivariate logistic regression analysis. In 161 patients whose IPNs were detected, 46 (28.6%) patients had one or more metastatic IPNs. Univariate analysis showed that tumour size, involvement of ALN, oestrogen receptor status and molecular subtype were associated with IPN metastasis. However, involvement of ALN was the only predictor by multivariate logistic regression analysis. In total, 0%, 5.0%, 26.1% and 84.2% of pN0, pN1, pN2, and pN3 patients had metastatic IPNs, respectively.Conclusion: The relatively low rate of IPN metastasis in patients with pN0/N1 breast cancer suggests that IPN dissection can be safely spared in patients with low tumour burden in axillary lymph nodes (pN0/N1), when MRM even breast conservation surgery is performed.Keywords: breast cancer, interpectoral lymph node, axillary lymph node, metastasis

Lipeng Zhu,1 Yunlu Dai,1,2 Lizeng Gao,3 Qi Zhao1,2 1Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, People’s Republic of China; 2MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, People’s Republic of China; 3CAS Engineering Laboratory for Nanozyme, Institute of Biophysics, Chinese Academy of Science, Beijing, People’s Republic of ChinaCorrespondence: Qi ZhaoCancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, People’s Republic of ChinaEmail qizhao@um.edu.moPurpose: Reactive oxygen species (ROS) are a group of signaling biomolecules that play important roles in the cell cycle. When intracellular ROS homeostasis is disrupted, it can induce cellular necrosis and apoptosis. It is desirable to effectively cascade-amplifying ROS generation and weaken antioxidant defense for disrupting ROS homeostasis in tumor microenvironment (TME), which has been recognized as a novel and ideal antitumor strategy. Multifunctional nanozymes are highly promising agents for ROS-mediated therapy.Methods: This study constructed a novel theranostic nanoagent based on PEG@Cu2-xS@Ce6 nanozymes (PCCNs) through a facile one-step hydrothermal method. We systematically investigated the photodynamic therapy (PDT)/photothermal therapy (PTT) properties, catalytic therapy (CTT) and glutathione (GSH) depletion activities of PCCNs, antitumor efficacy induced by PCCNs in vitro and in vivo.Results: PCCNs generate singlet oxygen (1O2) with laser (660 nm) irradiation and use catalytic reactions to produce hydroxyl radical (•OH). Moreover, PCCNs show the high photothermal performance under NIR II 1064-nm laser irradiation, which can enhance CTT/PDT efficiencies to increase ROS generation. The properties of O2 evolution and GSH consumption of PCCNs achieve hypoxia-relieved PDT and destroy cellular antioxidant defense system respectively. The excellent antitumor efficacy in 4T1 tumor-bearing mice of PCCNs is achieved through disrupting ROS homeostasis-involved therapy under the guidance of photothermal/photoacoustic imaging.Conclusion: Our study provides a proof of concept of “all-in-one” nanozymes to eliminate tumors via disrupting ROS homeostasis.Keywords: ROS homeostasis, nanozyme, tumor microenvironment, catalytic therapy, photodynamic/photothermal therapy, photothermal/photoacoustic imaging