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Haoyi Wang,* Zhen Ni,* Yinghao Chang Department of Infectious Disease, The General Hospital of Western Theater Command, Chengdu, 610083 People’s Republic of China*These authors contributed equally to this workCorrespondence: Yinghao Chang, Department of Infectious Disease, The General Hospital of Western Theater Command, Chengdu, 610083, People’s Republic of China, Email cyh19920913@126.comAbstract: Japanese spotted fever (JSF) is a neglected and potentially fatal infectious disease. Delays in diagnosis and treatment of JSF are important causes of poor prognosis. We report a case of JSF in a 75-year-old farmer who, following autumn field work in Sichuan, China, presented with an atypical triad of clinical symptoms: high fever, petechial rash, and notably no eschar. Without appropriate diagnosis and treatment, she developed septic shock and acute respiratory distress syndrome. The diagnosis of JSF was confirmed by the identification of Rickettsia japonica by metagenomic next-generation sequencing (mNGS) of the blood. After one week of treatment with doxycycline, the patient’s clinical symptoms subsided without any complaints of discomfort.Keywords: atypical triad of clinical symptoms of Japanese spotted fever, Rickettsia japonica, mNGS

Ling Jin,1,2,&ast; Kai Fan,1,2,&ast; Chunyan Yao,1,&ast; Yongjun Chang,1 Yang Wang,1 Jiawei Lu,1 Shaoqing Yu1,2 1Department of Otolaryngology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 2Department of Allergy,Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoqing Yu, Department of Otolaryngology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo District, Shanghai, 200065, People’s Republic of China, Tel/Fax +8602166111042, Email yu_shaoqing@163.comPurpose: The treatment of chronic rhinosinusitis (CRS) is often a difficult and long-term behavior, so it is necessary to seek a local treatment method that can be used for a long time, and is safe and effective. Nasal saline irrigation after functional endoscopic sinus surgery (FESS) is currently recognized as a local treatment method, but it has no anti-inflammatory, anti-damage, and healing-promoting functions. To investigate the efficacy and safety of hydrogen-rich saline (HRS) for nasal irrigation after CRS surgery.Patients and Methods: A total of 61 patients after CRS completed the study. Subjects were randomly assigned to rinse the nasal cavity with HRS or normal saline (NS) after CRS. Participants were followed up once a week for 12 times, and were evaluated with visual analogue score (VAS), 22-item Sinonasal Outcomes Test (SNOT-22), and Lund-Kennedy endoscopy scores (LKES). The primary outcome was the VAS score of patients.Results: After 12 weeks of follow-up, the VAS scores of both groups decreased, and the HRS group (0.52± 0.85) was lower than the NS group (1.47± 1.55), P=0.005. The total number of cases with complete control (clinical cure) in the short-term efficacy evaluation was more in the HRS group (20/31) than in the NS group (11/30), P=0.03< 0.05. No obvious adverse reactions occurred in the two groups during the follow-up.Conclusion: This study found that HRS was more effective than NS alone in nasal irrigation after CRS surgery, and could shorten the time of nasal mucosal healing and epithelialization, with a higher rate of recent complete control.Keywords: physiological saline, hydrogen -rich saline, nasal irrigation, chronic rhinosinusitis, endoscopic sinus surgery

Abstract While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric posterior fossa brain tumors, and evaluate its performance on a diverse, realistic, multi-center cohort. Pediatric brain tumors were targeted due to the scarcity of such datasets, even in tertiary care hospitals. Our platform orchestrates federated training for joint tumor classification and segmentation across 19 international sites. FL-PedBrain exhibits less than a 1.5% decrease in classification and a 3% reduction in segmentation performance compared to centralized data training. FL boosts segmentation performance by 20 to 30% on three external, out-of-network sites. Finally, we explore the sources of data heterogeneity and examine FL robustness in real-world scenarios with data imbalances.

Jiaxu Lu,1,2,&ast; Jiaxian Chen,2,&ast; Junhong Ye,2 Zhen Shi,2 Xiang Gao,1 Peicong Chen,2 Yanzhou Chang,2 Hao Lin,2 Peng Li1 1Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China; 2Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Lin, Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China, Email linhao@gdmu.edu.cn Peng Li, Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China, Email 13763086273@163.comIntroduction: Osteosarcoma is a prevalent and highly malignant primary bone tumor. However, current clinical therapeutic drugs for osteosarcoma are not suitable for long-term use due to significant side effects. Therefore, there is an urgent need to develop new drugs with fewer side effects. Dipsacus asperoides C. Y. Cheng et T. M. Ai, a traditional Chinese medicine, is commonly used for its anti-inflammatory, anti-pain, bone fracture healing, and anti-tumor effects. In this study, we investigated the effects of exosome-like nanoparticles derived from Dipsacus asperoides (DAELNs) on osteosarcoma cells in vitro and in vivo.Methods: DAELNs were isolated and purified from Dipsacus asperoides and their physical and chemical properties were characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The cellular uptake of DAELNs in osteosarcoma cells was analyzed by PKH26 staining. The proliferation, invasion, migration, and apoptosis of osteosarcoma cells were assessed using CCK8 assay, EdU assay, colony-formation assay, transwell assay, wound healing assay, and mitochondrial membrane potential measurement, respectively. The regulatory mechanism of DAELNs inhibiting the progression of osteosarcoma via activating P38/JNK signaling pathway was investigated using Western blotting and immunohistochemistry. Moreover, the therapeutic effects of DAELNs were evaluated using in vivo small animal imaging assay, HE staining, and immunohistochemistry.Results: Our results showed that DAELNs inhibited the proliferation, invasion, migration, and fostered the apoptosis of osteosarcoma cells in vitro and suppressed the tumor growth of osteosarcoma cells in a xenograft nude mouse model. Furthermore, the bio-distribution of DiD-labeled DAELNs showed preferential targeting of osteosarcoma tumors and excellent biosafety in histological analysis of the liver and kidney. Mechanistically, DAELNs activated the P38/JNK signaling pathway-induced apoptosis.Conclusion: Taken together, DAELNs are novel, natural, and osteosarcoma-targeted agents that can serve as safe and effective therapeutic approaches for the treatment of osteosarcoma.Keywords: osteosarcoma, Dipsacus asperoides-derived exosomes-like nanoparticles, P38/JNK signaling pathway

Ling Liu,1,&ast; Lei Wang,2,&ast; Hanni Zhou,3,4 Junli Yang,3 Wenju Wang,1 Xiaobo Luo,1 Yue Chang3,4,&ast; 1School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 2Primary Health Department of Guizhou Provincial Health Commission, Guiyang, Guizhou Province, People’s Republic of China; 3School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 4Center of Medicine Economics and Management Research, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Chang; Hanni Zhou, School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China, Email 4567401@qq.com; 340370813@qq.comPurpose: The purpose of this study is to assess the effect of glucocorticoid prescription feedback intervention in complex primary care institutions for regulating its inappropriate use.Design, Setting and Interventions: A six-month cluster randomized cross-over controlled trial was conducted in primary care institutions. A total of 347 physicians from 69 participating institutions were randomly allocated to either group A or group B. Both groups were given feedback interventions or serve as control. The feedback intervention comprised two components: a real-time pop-up warning of inappropriate glucocorticoid prescriptions based on the Hospital Information System and a high-proportion prescription feedback intervention warning system.Outcome Measures: The primary outcome measure was the 10-day inappropriate glucocorticoid prescription rate, while the 10-day glucocorticoid prescription rate served as secondary outcome measure.Results: At baseline, the 10-day inappropriate glucocorticoid prescription rates were 66.63% and 66.57% in group A and group B, respectively, showing no significant difference (p = 0.140). Following the intervention, group A exhibited a significant reduction in 10-day inappropriate glucocorticoid prescription rate at the crossing point by 13.69% (p < 0.001). In contrast, group B, which served as the control group, experienced an increase of 5.93% (p = 0.037) at the same crossover point. After the crossover point, there was a decrease in 10-day inappropriate glucocorticoid prescription rate for both groups. Group B as the intervention group demonstrated a reduction of 28.22% compared to the crossing point (p < 0.001), whereas group A showed a decrease of 12.20% (p = 0.339). The characteristics of physicians did not significantly influence the inappropriate glucocorticoid prescription rate.Conclusion: The real-time pop-up warning of inappropriate glucocorticoid prescriptions based on the Hospital Information System and high-proportion prescription feedback intervention warning system can effectively regulate the inappropriate glucocorticoid prescribing behavior of physicians.Trial Registration: ISRCTN11747547.Keywords: glucocorticoids, feedback intervention, primary care institutions, cluster randomized cross-over controlled trial

Yiwen Zhang,1 Wei Wang,2,&ast; Lili Xu,1 Zhexun Lian,3 Jiale Huang,4 Yaowei Chang,5 Junjie Guo,3 Yangang Wang,1,&ast; Kexiu Song,6 Hongwei Ji7,8,&ast; 1Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Hematology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 3Department of Cardiology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Department of Cardiology, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 6Department of International Medicine, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 7Tsinghua Medicine, Tsinghua University, Beijing, People’s Republic of China; 8Department of Internal Medicine, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangang Wang, Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email wangyg@qdu.edu.cn Hongwei Ji, Tsinghua Medicine, Tsinghua University, Beijing, People’s Republic of China, Email hongweijicn@gmail.com

Xiaoyi Li,1,&ast; Zhen Zeng,2,&ast; Xingying Fan,1,3 Wenju Wang,4 Xiaobo Luo,4 Junli Yang,1 Yue Chang1,3,&ast; 1School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 2Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, People’s Republic of China; 3Center of Medicine Economics and Management Research, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 4School of Public Health, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Chang; Xingying Fan, School of Medicine and Health Management, Guizhou Medical University, Gui’an New District, Guiyang, Guizhou Province, People’s Republic of China, Email 4567401@qq.com; 741284752@qq.comPurpose: The purpose of this study was to investigate the prescribing patterns and usage trends of systemic glucocorticoids in primary care institutions located in Southwest China from 2018 to 2021.Materials and Methods: A retrospective cross-sectional analysis of systemic glucocorticoids prescriptions was conducted in 32 primary care institutions located in Southwest China between 2018 and 2021. Prescriptions of systemic glucocorticoids were classified as appropriate or inappropriate use. Inappropriate use was further classified into (1) inappropriate indications and (2) inappropriate selection of glucocorticoids. Generalized estimation equations were employed to investigate the factors associated with inappropriate utilization of systemic glucocorticoids. The seasonal autoregressive integrated moving average (SARIMA) model was employed to predict the rate of inappropriate glucocorticoids prescriptions.Results: A total of 203,846 (92.89%) prescriptions were included, both the number of systemic glucocorticoids prescriptions and inappropriate prescriptions increased in winter. Diseases of the respiratory system (68.90%) were the most frequent targets of systemic glucocorticoids use. Of all prescriptions, 73.18% exhibited inappropriate indications, while 0.05% demonstrated inappropriate selection. The utilization of systemic glucocorticoids was deemed inappropriate for diseases of the respiratory system (94.19%), followed by diseases of the digestive system (87.75%). Physicians, who were female or younger than 33 years old, possess lower levels of education and professional titles and exhibit a higher likelihood of inappropriately prescribing systemic glucocorticoids. The phenomenon of inappropriate glucocorticoids use was commoner among male patients aged 65 years and older. After conducting model verification, it was determined that the SARIMA model could be used to predict the monthly rate of inappropriate systemic glucocorticoids prescriptions in primary care institutions in southwest China.Conclusion: The inappropriate use of systemic glucocorticoids remains a significant concern in primary care institutions. In this regard, continuing education and professional knowledge training of physicians should be strengthened in the future.Keywords: systemic glucocorticoids, primary care institutions, prescription patterns, inappropriate use, usage trends

ADP-ribosylation plays a significant role in various biological processes including genomic stability maintenance, transcriptional regulation, energy metabolism, and cell death. Using macrodomain pull-down assay with microglia lysates and MALDI-TOF-MS analysis, we identified vimentin as a major protein highly ADP-ribosylated by the poly(ADP-ribose) polymerases-1 (PARP-1) in response to LPS. ABT-888, a potent inhibitor of PARP-1/2 blocks the disassembly and ADP-ribosylation of vimentin. PARP-1 is a highly abundant nuclear protein. Its nuclear functions in repairing DNA damages induced by various stress signals, such as inflammatory stresses, have been well studied. In contrast, limited studies have been done on the cytoplasmic role(s) of PARP-1. Our study focuses on the cytoplasmic role of PARP-1 during microglia activation. Using immunofluorescence microscopy and Western blotting, we showed that a significant amount of PARP-1 is present in the cytosol of microglia cells stimulated and activated by LPS. Live cell imaging showed the translocation of nuclear PARP-1-EGFP to the cytoplasm in vesicular structures upon LPS stimulation. ABT-888 and U0126 can block this translocation. Immunofluorescence staining with various organelle marker antibodies revealed that PARP-1 vesicles show colocalization with Lamin A/C, suggesting they might be derived from the nuclear envelope through nuclear envelope budding. In conclusion, we demonstrated that PARP-1 is translocated from the nucleus to cytoplasm via vesicles upon LPS stimulation and that cytoplasmic PARP-1 causes ADP-ribosylation and disassembly of vimentin filaments during microglia activation induced by LPS.

Jiali Liu,1,&ast; Yuanqiang Zhu,1,&ast; Yingjuan Chang,1,&ast; Ziliang Xu,1 Chen Wang,1 Pengpeng Zhang,1 Shuangxin Li,1 Wenxuan Yang,1 Rui An,1,2 Didi Wen,1 Jian Xu,1,2 Minwen Zheng1 1Department of Radiology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Interventional Surgery Center, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minwen Zheng, Department of Radiology, Xijing Hospital, Air Force Medical University, 127&num; Changle West Road, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel +86-29-84775421, Fax +86-29-84773732, Email zhengmw2007@163.com Jian Xu, Department of Interventional Surgery Center, Xijing Hospital, Air Force Medical University, 127&num; Changle West Road, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel +86-29-84775299, Fax +86-29-84775299, Email xujian771939@163.comPurpose: While prior research has highlighted a significant association between sleep characteristics and angina pectoris (AP) incidence, the link between sleep efficiency (SE) and angina remains unexplored. This study seeks to elucidate the relationship between AP and objectively quantified SE.Patients and Methods: We examined a cohort of 2990 participants (1320 males and 1670 females; mean age 63.69 ± 13.2 years) from the Sleep Heart Health Study. The main exposure variable was SE, as determined by baseline home polysomnography, while the primary outcome was the first incidence of angina pectoris (AP) during the period between the baseline polysomnography and the end of follow-up. A multivariate Cox regression model was utilized, controlling for factors such as age, gender, BMI, smoking and alcohol consumption habits, diabetes, hypertension, sleep duration, triglycerides, cholesterol, high-density lipoprotein, apnea-hypopnea index, nocturnal oxygen saturation, to analyze the relationship between SE and AP.Results: During an average follow-up of 11 years, 284 patients developed AP. The unadjusted Kaplan-Meier analysis identified the 2nd quartile of SE as having the lowest AP risk. The multivariate Cox proportional hazards model demonstrated a higher risk of AP in quartile 1 (HR, 1.679; 95% CI, 1.109– 2.542; P < 0.014) and quartile 3 (HR, 1.503; 95% CI, 1.037– 2.179; P < 0.031), compared to quartile 2 of SE. Upon stratified analysis, this relationship was particularly pronounced in hypertensive individuals.Conclusion: Our results highlight the critical role of optimal sleep efficiency in mitigating the risk of angina pectoris, especially among hypertensive individuals.Keywords: sleep efficiency, angina pectoris, polysomnography, cardiovascular risk, sleep heart health study, hypertension

Yanan Wang, Yuqiong Chai, Jieqiong Wang, Mingya Gao, Weiwei Zang, Yujie Chang Department of Genetics and Prenatal Diagnosis, Luoyang Maternal and Child Health Hospital, Luoyang, 471000, People’s Republic of ChinaCorrespondence: Yanan Wang, Department of Genetics and Prenatal Diagnosis, Luoyang Maternal and Child Health Hospital, No. 206 of Tongqu Street, Luolong District, Luoyang, 471000, People’s Republic of China, Tel +86-15896572343, Email Wangyanan_2023@yeah.netPurpose: The application value of ultrasound soft indicators in prenatal diagnosis was evaluated by copy number variation sequencing (CNV-seq).Methods: The authors conducted a retrospective analysis of 422 pregnant women who underwent CNV-seq testing at Luoyang Maternal and Child Health Hospital between January 2020 and November 2021. The women had presented with abnormal ultrasound soft markers; those identified as high-risk through non-invasive prenatal screening were excluded.Results: A total of 43 abnormal cases were detected in 422 pregnant women, including 24 aneuploidy (including chimerism) and 19 pathogenic or likely pathogenic copy number variations (CNVs). Based on the characteristics of ultrasound soft indicators, pregnant women were divided into five groups: isolated nuchal translucency (NT) group, combined NT group, isolated soft indicators group, combined soft indicators group and combined non-NT group. The abnormality detection rates in the five groups were 12.38% (13/105), 36.11% (13/36), 3.74% (4/103), 3.08% (2/63) and 10.09% (11/109), respectively. Statistical tests showed that the detection rate in the NT thickening combined with other abnormalities group was significantly higher than the other four groups, while there was no statistical difference in the detection rate among the other four groups.Conclusion: When NT thickening is combined with other abnormalities, it is more likely to indicate chromosome abnormalities or CNVs, so it should be regarded seriously upon finding, and pregnant women should be referred for prenatal diagnosis according to the examination results. In addition, NT thickening is an important indicator for prenatal diagnosis and should be considered regardless of whether it occurs independently. The authors recommend CNV-seq for prenatal diagnosis to prevent missing small fragments of CNVs during traditional karyotyping.Keywords: ultrasound soft indicators, isolated type, combined type, amniotic fluid, CNV-seq

Changlan Li,1,&ast; Zhezhe Cui,2 Du Wei,3,4,&ast; Quan Zhang,5,&ast; Junli Yang,3 Wenju Wang,1 Xiaobo Luo,1 Yue Chang3,4 1School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 2Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, Guangxi Province, People’s Republic of China; 3School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 4Center of Medicine Economics and Management Research, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 5Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Chang, School of Medicine and Health Management, Guizhou Medical University, Guizhou Medical University, University Town, GUI ‘an New District, Guiyang, Guizhou Province, People’s Republic of China, Tel/Fax +86-0851-88308118, Email 4567401@qq.com Zhezhe Cui, Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, 18 Jinzhou Road, Nanning, Guangxi Province, People’s Republic of China, Tel/Fax +86-0771-2518785, Email czz6997@163.comPurpose: To explore the prescription patterns and usage trends of antibiotics within primary care institutions located in underdeveloped regions of China from 2017 to 2022.Methods: A retrospective analysis of antibiotic prescriptions was conducted from 25 primary care institutions in Guizhou Province during the period of 2017– 2022. Antibiotic prescriptions were categorized into appropriate and inappropriate use. Appropriate use is further categorized into preferred medication, and antibiotics can be used or substituted. Inappropriate use is further categorized into unnecessary use, incorrect spectrum of antibiotics and combined use of antibiotics. Factors associated with inappropriate use were investigated using generalized estimation equations. Holt-Winters and SARIMA models were employed to predict the number of inappropriate antibiotic prescriptions as the alternative model.Results: A total of 941,924 prescriptions were included, revealing a decreasing trend in both the number and inappropriate rates of antibiotic prescriptions from 2017 to 2022. Diseases of the respiratory system (70.66%) was the most frequent target of antibiotic use, with acute upper respiratory infections of multiple and unspecified sites representing 52.04% of these cases. The most commonly used antibiotics were penicillins (64.44%). Among all prescriptions, inappropriate antibiotic prescriptions reached 66.19%. Physicians aged over 35, holding the title of associate chief physician and possessing more than 11 years of experience were more likely to prescribe antibiotics inappropriately. The phenomenon of inappropriate antibiotic use was commoner among children aged five or younger. By comparing model parameters, it was determined that the SARIMA model outperforms the Holt-Winters model in predicting the number of inappropriate antibiotic prescriptions among primary care institutions.Conclusion: The number and inappropriate rates of antibiotic prescriptions in southwest China exhibited a downward trend from 2017 to 2022, but inappropriate prescription remains a serious problem in primary care institutions. Therefore, future efforts should focus on strengthening physician education, training, and clinical practice. Additionally, physicians’ awareness of common misconceptions about inappropriate antibiotic use must be improved, and the prescribing behavior of physicians who fulfill patients’ expectations by prescribing antibiotics needs to be modified.Keywords: antibiotics, primary care institution, trends, prescription patterns, inappropriate medication

Blair McNamara, Yifan Chang, Ashley Goreshnik, Alessandro D Santin Department of Obstetrics, Gynecology, and Reproductive Sciences Yale University School of Medicine, New Haven, CT, 06520, USACorrespondence: Alessandro D Santin, Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT, 06520, USA, Tel +1 203-737-4450, Fax +1 203-737-4339, Email alessandro.santin@yale.eduAbstract: Antibody drug conjugates (ADCs) are a new class of targeted anti-cancer therapies that combine a monoclonal tumor surface receptor-targeting antibody with a highly cytotoxic molecule payload. They enable delivery of cytotoxic therapy more directly to tumor cells and minimize delivery to healthy tissues. This review summarizes the existing literature about ADC therapies approved for use in gynecologic malignancies, relevant preclinical studies, as well as ongoing clinical trials.Keywords: antibody-drug conjugate, gynecologic malignancy, chemotherapy, cervical cancer, ovarian cancer, endometrial cancer

Du Wei,1,&ast; Yue Chang,1,2,&ast; Qi Chen,3,&ast; Qin Wang,4 Hanni Zhou,1,2 Shengyan Wu,1,2 Xiaomin Xian,5 Zhezhe Cui6 1School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Center of Medicine Economics and Management Research, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Pharmacy Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 4Department of Health Education, Tongren Centre for Disease Control and Prevention, Tongren, Guizhou, People’s Republic of China; 5School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 6Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Guangxi Key Discipline platform of Tuberculosis Control, Guangxi Centre for Disease Control and Prevention, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhezhe Cui, Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Guangxi key discipline platform of tuberculosis control, Guangxi Centre for Disease Control and Prevention, Nanning, Guangxi, People’s Republic of China, Tel/Fax +86-0771-2518785, Email czz6997@163.com Yue Chang, School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China, Tel/Fax +86-0851-88308118, Email changyue@gmc.edu.cnPurpose: To establish a concise and easy-to-understand reference manual for outpatient primary care providers, promoting correct diagnosis of digestive system diseases and rational antimicrobial use.Methods: The establishment of the manual encompassed two processes: the development of a draft manual and the validation of the manual. The development process was based on a literature review and expert discussion. The manual comprises portions for disease diagnosis and rationality of antimicrobial use. The validation process employed a two-round Delphi technique, collecting consensus through paper-based or mail-based communications. The response of the Delphi group was assessed by the level of authority and commitment of the panelists and the degree of agreement among them. Furthermore, the manual was preliminarily applied among primary care physicians.Results: A total of 29 panelists completed the Delphi working process. They were authoritative in their professional fields with authority coefficients of 0.813 and 0.818 for the two portions of the manual, respectively. The level of commitment of the panelists was measured by response rates, which were 100.00% and 96.67% for Round 1 and 2. After two rounds, a consensus was achieved with the consensus rates for the two portions of the manual being greater than 65% and 70%, respectively. Kendall W-tests had P-values < 0.001 in both rounds. This reference manual provides 200 diagnostic indicators for 29 common digestive diseases and recommendations for the rational use of antimicrobial agents for 13 categories of digestive diseases. The primary care physicians who used the reference manual reported high satisfaction and frequent usage.Conclusion: Based on a collective consensus of professionals, a reference manual has been established, to provide a concise and easy-to-understand guide specifically for physicians and pharmacists in outpatient primary care. It could facilitate rapid learning to improve the accuracy of diagnosis and treatment for digestive disorders.Keywords: primary health care, digestive system, diagnosis, antimicrobial agents, rational drug use, Delphi technique

Xin Yao,1 Qingyu Wang,1 Changge Han,1 Jiaojiao Nie,1 Yaotian Chang,1 Lipeng Xu,1 Bingya Wu,1 Jingtian Yan,1 Zhiyuan Chen,1 Wei Kong,1,2 Yuhua Shi,1 Yaming Shan1,2 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, 130012, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, 130012, People’s Republic of ChinaCorrespondence: Yaming Shan, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, Jilin, 130012, People’s Republic of China, Tel +86 133 2446 4361, Email shanym@jlu.edu.cnIntroduction: Broadly neutralizing antibodies (bNAbs) have the ability to neutralize a considerable breadth of genetically diverse human immunodeficiency virus (HIV) strains. Passive immunization can potentially provide protection against HIV infection in animal models. However, the direct antibody infusion effect is limited due to the short half-life and deficient immunogenicity of the antibody. As an alternative strategy, we propose the use of nano viral vectors, specifically the adeno-associated virus (AAV), to continuously and systematically produce bNAbs against HIV.Methods: Plasmids expressing bNAbs PG9, PG16, 10E8, and NIH45-46 antibodies were constructed, targeting three different epitopes of HIV. Additionally, the bNAbs gene mediated by rAAV8 was administered to generate long-term expression with a single injection. We established both single and combined immunization groups. The neutralizing activity of antibodies expressed in mice sera was subsequently evaluated.Results: The expression of bNAbs in BALB/c mice can last for > 24 weeks after a single intramuscular injection of rAAV8. Further studies show that neutralization of the HIV pseudovirus by sera from co-immunized mice with rAAV8 expressing 10E8 and PG16 was enhanced compared with mice immunized with 10E8 or PG16 alone.Conclusion: The prolonged expression of neutralizing antibodies can be maintained over long periods in BALB/c mice. This combined immunization is a promising candidate strategy for HIV treatment.Graphical Abstract: Keywords: AAV delivery, HIV therapy, passive immunotherapy, combined immunotherapy

Xuanxia Wu,1,&ast; Mingming Zhou,2,&ast; Juan Bu,1 Yuwen Chang,2 Yeledan Mahan,1 Huanhuan Lu,2 Yanmin Zhang,3 Xiaoling Zhang,1 Zhaoxia Wang,1 Ling Zhou1 1Medical Research and Transformation Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Health Management Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 3Scientific Research and Education Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhou, Medical Research and Transformation Center, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86-13609959575, Email zlrmyy@sina.comPurpose: In this study, the aim was to investigate the prevalence and risk factors of hyperuricemia (HUA) in the urban health checkup population in Urumqi, Xinjiang, and thus provide clues for the prevention of HUA.Methods: People who attended medical examinations from May 2021 to June 2022 at a hospital in Urumqi, Xinjiang, were selected for evaluation based on their general information, physical examination results, and laboratory test results. The chi-square test was used to determine whether there was a difference in the prevalence of HUA among participants with different characteristics. Using logistic regression analyses, risk factors for HUA were identified.Results: There were 8722 participants diagnosed with HUA, with an overall prevalence of 26.96%. The prevalence in men was 37.72%, significantly higher than in women (13.29%). Participants were characterized by a multiethnic composition, with Han (28.61%), Hui (27.88%) and Manchu (38.46%) being the three ethnicities with the highest prevalence. According to logistic regression analyses, HUA was associated with age, ethnicity, residence, marital status, body mass index (BMI), diastolic blood pressure (DBP), fasting blood glucose (FPG), triglyceride glucose (TyG) index, abdominal obesity, and dyslipidemia differently in males and females.Conclusion: The prevalence of HUA was high in the urban health checkup population in Urumqi, Xinjiang, particularly among men and youth. The early intervention for HUA should be enhanced to reduce the risk of cardiovascular disease and other related conditions.Keywords: hyperuricemia, ethnicity, prevalence, risk factors, epidemiology

Lianjun Lin,1,&ast; Ruixue Zhang,1,&ast; Zhi Zhang,2,3 Yujun Chang,2,3 Rongnan Lin,2,3 Haiwei Dou,4 He Wang,5 Yuchuan Wang,6 Bo Zheng7 1Geriatric Department, Peking University First Hospital, Beijing, People’s Republic of China; 2National Engineering Research Center for Beijing Biochip Technology, Beijing, People’s Republic of China; 3CapitalBio Corporation, Beijing, People’s Republic of China; 4Beijing Friendship Hospital, Capital Medical University, Beijing Tropical Medicine Research Institute, Beijing, People’s Republic of China; 5Department of Imaging, Peking University First Hospital, Beijing, People’s Republic of China; 6Department of Cardiology, Beijing Shijitan Hospital, Beijing, People’s Republic of China; 7Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi Zhang, National Engineering Research Center for Beijing Biochip Technology, Changping District, Beijing, 102206, People’s Republic of China, Email zhizhang@capitalbio.com Lianjun Lin, Geriatric Department, Peking University First Hospital, Xishiku Avenue 8, Xicheng District, Beijing, 100034, People’s Republic of China, Email 06474@pkufh.comBackground: Mycoplasma pneumoniae is an important infectious pathogen of lower respiratory tract infection in children and adolescents. Macrolide resistant M. pneumoniae (MRMP) has become increasingly prevalent, and identifying pathogen resistance genes is crucial for treatment.Case Presentation: We report a patient with severe refractory M. pneumoniae pneumonia (MPP). The failure of initial clinical treatment prompted the re-analysis of metagenomic next-generation sequencing (mNGS) data for macrolide-resistant gene. Macrolide-resistance 23S ribosomal RNA gene was confirmed with read depth of 64 X for the A2063G mutation, which can decrease the affinity of macrolide with M. pneumoniae ribosome resulting in macrolide resistance. Furthermore, antimicrobial susceptibility testing demonstrated that M. pneumoniae was resistant to macrolide. PCR confirmatory test about M. pneumoniae resistance A2063G mutation, clinical treatment course and prognosis with altered treatment strategy, and M. pneumoniae antimicrobial susceptibility confirmed that the severe refractory MPP was due to macrolide resistant M. pneumoniae.Conclusion: As a new molecular level detection, mNGS is an effective method for detecting M. pneumoniae resistance genes. Early recognition of macrolide resistance and suitable antibiotics strategy is of vital importance for the prognosis of severe refractory MPP.Keywords: Mycoplasma pneumoniae, pneumonia, macrolide-resistant gene, metagenomic next-generation sequencing, A2063G mutation

Xin Tan, Wenjie Liu, Ying Chang, Wanmin Wu, Lichun Yang, Jiewei Liu Cataract Department, Shanxi Eye Hospital, Taiyuan, Shanxi Province, People’s Republic of ChinaCorrespondence: Jiewei Liu, Cataract Department, Shanxi Eye Hospital, Taiyuan, Shanxi Province, People’s Republic of China, Tel +86-13834648535, Email Jieweiliu1967@sina.comPurpose: The safety and stability of implantable collamer lens (ICL) implantation are closely related to the vault. We aimed to assess clinical data from patients with similar anterior segment anatomy who received ICL of the same model placed in the same position and analyze common range and factors affecting the vault inter-eye difference.Patients and Methods: A prospective study was performed, including 162 eyes of 81 patients with a bilateral ICL (V4c) implantation. Subjects were evaluated before the surgery and 1 day, 1 week, and 1 month postoperatively, and they were divided into 4 groups based on the ICL size. Bivariate correlation and multiple linear regression (stepwise) analyzed associations between vault inter-eye differences and horizontal sulcus-to-sulcus diameter, anterior chamber depth, lens thickness, ICL size, spherical equivalent, and vault.Results: One month after surgery, mean vault inter-eye differences were 74.59 ± 55.59 μm. Nearly 70% of patients presented with vault inter-eye differences lower than 100 μm. The second eye vault variance of 69% was attributed to the first eye vault. Vault inter-eye differences were positively correlated with ICL spherical equivalent (regression equation: vault inter-eye differences (μm) = 139.415 + 6.295 × ICL spherical equivalent). Vaults after ICL implantation were similar in fellow eyes, with some considerable differences. The 95% confidence interval of the vault inter-eye difference was − 34.4 ~ 183.6 μm.Conclusion: In eyes with similar anterior segment anatomy, there is a 95% probability that the vault will vary from − 34.4 μm to − 183.6 μm when a similar ICL is implanted. These results can help surgeons to select an appropriate ICL size to achieve an ideal vault. The smaller the spherical equivalent, the larger the difference between the two vaults, which provides a reference for size in moderate myopia. ICL spherical equivalent affects and predicts vault inter-eye differences after ICL implantation.Keywords: implantable collamer lens, vault, inter-eye differences

Ruoyun Yin,1 Yuan Yang,2 Yujiao Chang,3 Lei Tang,1 Qian Hu,1 Jian Yang,1 Chong Cheng,1 Lei Xiao,1 Fan Zhang1 1School of Public Health and Management, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Cardiovascular Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Infection, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Fan Zhang, School of Public Health, Research Center for Medicine and Social Development, Chongqing Medical University, No. 61 Daxuecheng Middle Road, Shapingba District, Chongqing, 401331, People’s Republic of China, Email zhangfan@cqmu.edu.cnBackground: Drinking in summer vacation, as an important part of college students’ drinking behavior, has rarely been studied. At present, there is no research to explore the association between alcohol expectancy and college students’ drinking behavior during the summer vacation.Methods: A total of 487 college students were selected from three universities in Chongqing from July 30, 2017, to August 30, 2017, by cluster sampling. The electronic questionnaires were distributed to complete the anonymous survey related to drinking. The questionnaire on drinking mainly included baseline characteristics, influencing factors related to drinking, drinking behavior in the last year and summer vacation, and alcohol expectancy. Independent sample t-test and one-way ANOVA were used for multi-factor analysis. Multi-level logistic regression analysis and ordered logistic regression analysis were used for multivariate analysis.Results: The past drinking rate in the study group was 86.24%. In the past year, the drinking rate and binge drinking rate of college students were 63.24% and 23.20%. In summer drinking, these two indicators were 29.57% and 8.42%, respectively. About 92.50% of the moderate and heavy drinking groups among college students had drinking behavior during the summer vacation. The average negative expectancy among college students was 3.26 ± 0.87 while the average positive expectancy was 2.63 ± 0.66. In drinking last year, positive expectancy was a risk factor for occasional and light drinking compared with those of non-drinkers (P< 0.05). In summer vacation drinking, compared with those of non-drinkers, negative expectancy was a protective factor for occasional drinking (OR: 1.847, 95% CI: 1.293– 2.638), negative expectancy and positive expectancy were both influencing factors for light drinking (P< 0.05).Conclusion: The drinking rate in the study group was at a high level in the past. The association between alcohol expectancy and drinking behavior among college students would be different according to the period and amount of drinking.Keywords: drinking behavior, drinking pattern, alcohol expectancy, college students, summer vacation

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

Lei Zhu,1,2 Chuanqing Yu,2 Yueyue Chang,2 Shiyu Sun,2 Zhongwu Sun1 1Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of ChinaCorrespondence: Zhongwu Sun, Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China, Email sunzhwu@126.comPurpose: Cystatins are associated with neuronal degeneration and nervous system healing. Cystatin C (Cys C) has recently been linked to brain injury and immunological inflammation. This study aimed to determine the relationship between serum Cys C levels and depression following intracranial hemorrhage (ICH).Patients and Methods: Between September 2020 and December 2022, 337 patients with ICH were sequentially recruited and followed up for three months. The post-stroke depression (PSD) and non-PSD groups were separated based on the 17-item Hamilton Depression Rating Scale (HAMD). The PSD diagnosis was established based on the DSM-IV criteria. Cys-C levels were documented within twenty-four hours of admission.Results: Three months after ICH, 93 (27.6%) of 337 enrolled patients were diagnosed with depression. The Cys C levels were significantly higher in depressed patients than in nondepressed patients after ICH (1.32 vs 1.01; p< 0.001). After adjusting for potential confounding variables, depression after ICH was associated with the highest quartile of Cys C levels (odds ratio (OR) = 3.195, 95% CI: 1.562– 6.536; p=0.001). The receiver operating characteristic curve (ROC) curve predicted that the ideal cut-off for CysC levels as a predictor of depression after ICH would be 0.730, resulting in 84.5% sensitivity and 88.4% specificity, with an area under curve (AUC) of 0.880 (95% CI: 0.843– 0.917; p< 0.0001).Conclusion: Increased CysC concentrations were independently related to depression three months after ICH, highlighting that CysC levels at admission may be a potential biomarker for predicting the onset of depression following ICH.Keywords: cystatin C, depression, intracerebral hemorrhage, post-stroke depression

Yulan Chang,1 Shujie Guo,2 Binbin Yuan,3 Huiling Chen,4 Ruxin Jiang5 1Department of Nursing, Henan Vocational College of Nursing, Anyang, Henan, 455001, People’s Republic of China; 2Department of Outpatient, Henan Provincial People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 3Department of Cardiovascular Surgery, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 4Department of Structural Heart Disease, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 5Department of Anesthesia and Perioperative Medicine, Henan Provincial People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of ChinaCorrespondence: Shujie Guo, Department of Outpatient, Henan Provincial People’s Hospital, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86 18538298287, Email guosj2022@yeah.netPurpose: The purpose of this study is to understand the risk perception, risk emotions and humanistic care needs of nursing staff during the Novel Coronavirus 2019 (Covid-19) pandemic.Methods: A cross-sectional survey was conducted on the perceived risk, risk emotions and humanistic care needs of 35,068 nurses in 18 cities of the Henan Province, China.We collected a total of 35,188 questionnaires, of which 35,068 were effectively returned, with an effective return rate of 99.7%. The collected data were summarized and statistically analyzed using Excel 97 2003 and IBM SPSS software.Results: Nurses’ risk perceptions and emotions vary during the covid-19 pandemic. In order to provide nurses with targeted psychological intervention to prevent nurses from suffering from unhealthy mental states.The results show that the total score of the nurses’ risk perceptions of Covid-19 was 3.66 ± 0.39, the highest score of nurses’ risk perception part is 5 points, and ≥ 3 points represent high risk and 88.3% of nurses believed that the Covid-19 risk was high. There were significant differences in the nurses’ total perceived risk scores for Covid-19 based on gender, age, prior contact with patients with suspected or confirmed Covid-19 and previous participation in other similar public health emergencies (P < 0.050). Of the nurses included in the study, 44.8% had some level of fear relating to Covid-19 and 35.7% were able to remain calm and objective. There were significant differences in the total scores for risk emotions relating to Covid-19 based on gender, age and prior contact with patients with suspected or confirmed Covid-19 (P < 0.050). Of the nurses included in the study, 84.8% were willing to receive humanistic care and 77.6% of these expected to be provided with humanistic care by institutions in the healthcare sector.Conclusion: Nurses with different basic data have different risk cognition and risk emotions. Different psychological needs should be considered, and targeted multi-sectoral psychological intervention services should be provided to help prevent nurses from developing unhealthy psychological states.Keywords: Covid-19, public health emergencies, risk perception, risk emotion, humanistic care

Min Tan,1,2 Mei Li,1,2 Hui’e Li,1,2 Jin Li,1,2 You Chang,1,2 Guanfei Zhang,1,2 Yiping Zhong1,2 1Department of Psychology, Hunan Normal University, Changsha, People’s Republic of China; 2Cognition and Human Behavior Key Laboratory of Hunan Province, Changsha, People’s Republic of ChinaCorrespondence: Yiping Zhong, Department of Psychology, School of Education Science, Hunan Normal University, No. 36 Lushan Road, Changsha, Hunan, People’s Republic of China, Tel/Fax +86 731-88872112, Email ypzhong@hunnu.edu.cnBackground: Previous studies have examined the negative effects of materialism, which refers to the importance of possessing material wealth and image, on the pro-environmental behavior. Recently, a study found that highly materialistic individuals showed more pro-environmental behaviors involving self-benefit (vs other-benefit) appeals. However, previous studies ignored the role of public accountability.Purpose: This study aimed to explore the relationship between advertising appeals and the pro-environmental behavior of materialistic individuals in public (vs private) situations.Methods: This study used the material values scale to measure the materialistic extent and employed different advertising pictures. Meanwhile, Study 1(N=593) used the public cue, and Study 2 (N=622) used the eye cue to manipulate public accountability. Environmental donation was an indicator of the pro-environmental behavior.Results: Studies 1 and 2 found that the pro-environmental behavior of participants low in materialism was significantly higher than that of participants high in materialism involving other-benefit appeals, while this difference was not significant for pro-environmental behavior involving self-benefit appeals in the private situation. Participants with low and high materialism were not significantly different in the pro-environmental behavior involving self-benefit and other-benefit appeals in the public situation.Conclusion: The relationship between materialism and pro-environmental behavior involving self-benefit and other-benefit appeals can be moderated by the public accountability. In the private context, self-benefit appeals led materialistic people to engage in more pro-environmental behavior, while in the public context, the effectiveness of self-benefit and other-benefit appeals on the pro-environmental behavior of materialistic individuals was similar.Keywords: materialism, pro-environmental behavior, advertising appeals, public situation, private situation, social exchange theory

Lili Yu,1,2 Qi Zhou,1 Wei Li,1 Qin Zhang,3 Xiuling Cui,2 Yulin Chang,2 Qiujun Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, People’s Republic of China; 3Surgical Department of Thyroid and Mammary Tumors, Cangzhou Central Hospital, Cangzhou, People’s Republic of ChinaCorrespondence: Qiujun Wang, Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang City, Hebei, People’s Republic of China, Tel/Fax +86-311-8860-2072, Email wangqiujunsy@163.comPurpose: To evaluate the effect of esketamine combined with ultrasound-guided pectoral nerve block type II (Pecs II block) on the quality of early postoperative recovery in patients undergoing a modified radical mastectomy (MRM) for breast cancer.Patients and Methods: A total of 136 female patients undergoing an elective MRM for unilateral breast cancer (UBC) for the first time were randomly divided into the control group (group C, n=68) and the experimental group (PE group, n=68). In group C, sufentanil was used for anesthesia induction and patient-controlled intravenous analgesia (PCIA). Esketamine was used for anesthesia induction and PCIA in the PE group. Ultrasound-guided Pecs II block was performed after anesthesia induction in the two groups. All other anesthetics were administered in the same way. The primary outcome was the 40-item Quality of Recovery (QoR-40) score at discharge. The secondary outcomes were postoperative Observer’s Assessment of Alertness/Sedation Scale (OAA/S) scores, time of anesthesia recovery, Numeric Rating Scale (NRS) scores, serum inflammatory cytokines interleukin-10 (IL-10), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), Hospital Anxiety and Depression Scale (HADS) scores, length of postoperative Postanesthesia Care Unit (PACU) stay, length of postoperative hospital stay and patient satisfaction score.Results: Compared with group C, the PE group had higher QoR-40 scores at discharge (P< 0.05), decreased IL-6 levels at 24 h after surgery (P< 0.05), lower anxiety and depression scores (P< 0.05) and higher patient satisfaction scores at discharge (P< 0.05). No significant difference was found in the NRS score postoperatively between the two groups (P> 0.05). There was no significant difference in the postoperative OAA/S score, time of anesthesia recovery, length of postoperative PACU and hospital stays between the two groups (P> 0.05).Conclusion: Esketamine combined with Pecs II block can be used for anesthesia in MRM for breast cancer, thus, improving patient quality of early postoperative recovery.Keywords: esketamine, ultrasound-guided nerve block, thoracic nerves, mastectomy, modified radical, anesthesia, recovery

Man Li,1,&ast; Xingyu Wang,2,&ast; Mojun Chen,1 Yuan Chang,1 Linfeng Li,1 Shan Zhong1 1Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shan Zhong, Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China, Tel +86-13810056088, Fax +86-10-63139108, Email zhongshan@ccmu.edu.cnBackground: Bickerstaff brainstem encephalitis (BBE) is a rare demyelinating disease of the central nervous system (CNS) that is caused by a direct viral infection or secondary autoimmune responses. BBE secondary to Herpes zoster has rarely been reported.Case Presentation: A 68-year-old man developed a painful vesicular rash and drooping eyelid on the left side of his face for 20 days. Physical examination revealed left-sided blepharoptosis and crusted erythema on the left front side of his face, left upper eyelid, and left nasal tip. Neurological examination showed impaired sensation over the left side of his face and cheek. His left pupil was dilated (4mm compared to 2mm on the right side), and the Pupillary light reflection (PLR) was absent, with an ocular movement disorder (limited adduction) and diplopia. Brain imaging did not reveal abnormalities. Cerebrospinal fluid (CSF) examination showed leukocytosis and increased protein levels. He was treated with intravenous acyclovir for 7 days, but developed disturbance of consciousness and right limb weakness. Neurological examination revealed right lower limb hypoesthesia. The Heel-Knee-Shin test was positive on the left side, and Babinski’s sign was present on the right side. He was diagnosed with Bickerstaff brainstem encephalitis caused by herpes zoster. After 2 days of intravenous acyclovir combined with intravenous immune globulin (IVIG), the patient developed acute kidney injury (AKI). Then, his treatment was changed to systemic steroids. At the 3-month follow-up, his pupils were bilaterally equal and reactive to light, and there was a significant improvement in ocular motility and ptosis. At the 6-month follow-up, his diplopia had completely resolved.Conclusion: BBE associated with herpes zoster is very rare and can be overlooked. Dermatologists should be aware of the expanding spectrum of neurological complications caused by varicella zoster virus (VZV) infections to aid early diagnosis and treatment.Keywords: herpes zoster, Bickerstaff brainstem encephalitis, acute kidney injury, treatment

A 5-day old neonate presented with several episodes of seizure-like activity associated with hypoxia. The episodes were responsive to anti-epileptic medications and the infant was given empiric antibiotics and antiviral coverage. Cerebrospinal fluid polymerase chain reaction (PCR), culture, and gram stain were negative for viral or bacterial etiology. However, a nasopharyngeal PCR of the infant was positive for SARS-COV-2. While head computed tomography (CT) was negative, magnetic resonance imaging (MRI) showed evidence of white matter injury in the subcortical and periventricular regions and corpus callosum. With supportive therapies, the infant made a full neurologic recovery and was discharged following a 5-day admission. This case highlights the growing evidence of SARS-COV-2 associated leukoencephalopathy in neonates, and physicians should consider this diagnosis in neonates with similar presentation.

Lei Dong,1,&ast; Nana Li,1,&ast; Xixi Wei,2 Yongling Wang,2 Liansheng Chang,3 Hongwei Wu,4 Liujiang Song,5 Kang Guo,6 Yuqiao Chang,1 Yaling Yin,2 Min Pan,7 Yuanyuan Shen,8 Feng Wang1 1Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 2Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 3Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 4Department of Chemistry, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 5Department of Ophthalmology, Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27517, USA; 6Department of Oncology, The Third affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 7Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, 518034, People’s Republic of China; 8National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Wang, Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453002, People’s Republic of China, Email wfeng100@126.com Min Pan, Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, No. 6001 Beihuan Avenue, Shenzhen, 518034, People’s Republic of China, Email min.pan@siat.ac.cnBackground: The blood–brain barrier (BBB) inhibits the delivery of macromolecular chemotherapeutic drugs to brain tumors, leading to low utilization rates and toxic side effects to surrounding tissues and organs. Ultrasonic targeted microbubble destruction (UTMD) technology can open the BBB, leading to a new type of drug delivery system with particular utility in glioma.Purpose: We have developed a new type of drug-loaded microbubble complex based on poly(lactic-co-glycolic acid) (PLGA) that targets gambogic acid (GA) to the area of brain tumors through UTMD.Methods: GA/PLGA nanoparticles were prepared by the double emulsification method, and cationic microbubbles (CMBs) were prepared by a thin film hydration method. The GA/PLGA-CMB microbubble complex was assembled through electrostatic attractions and was characterized chemically. The anti-glioblastoma effect of GA/PLGA-CMB combined with focused ultrasound (FUS) was evaluated by biochemical and imaging assays in cultured cells and model mice.Results: GA/PLGA-CMB combined with FUS demonstrated a significant inhibitory effect on glioblastoma cell lines U87 and U251 as compared with controls (P< 0.05). Tumor access and imaging analyses demonstrated that administration of GA/PLGA-CMBs combined with FUS can open the BBB and target the treatment of glioblastoma in a mouse model, as compared with control groups (P< 0.05).Conclusion: The combination of PLGA-CMB with FUS provides an effective and biocompatible drug delivery system, and its application to the delivery of GA in a mouse glioblastoma model was successful.Keywords: microbubbles, cavitation effect, glioblastoma, focused ultrasound

Yulan Chang,1 Shujie Guo,2 Haixin Zhang,3 Binbin Yuan,4 Jun Xu5 1Department of Nursing, Henan Vocational College of Nursing, Anyang, 455001, People’s Republic of China; 2Outpatient Department, Henan Provincial People’s Hospital, Zhengzhou, 450003, People’s Republic of China; 3Department of Nursing, Henan Provincial People’s Hospital, Zhengzhou, 450003, People’s Republic of China; 4Department of Cardiovascular Surgery, Fuwai Huazhong Cardiovascular Hospital, Zhengzhou, 450003, People’s Republic of China; 5Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou, 450003, People’s Republic of ChinaCorrespondence: Shujie Guo, Outpatient Department, Henan Provincial People’s Hospital, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86-18538298287, Email shujie_guo116@21cn.comBackground: Novel coronavirus 2019 (COVID-19) infections are highly contagious and have spread worldwide. Healthcare workers must understand the laws and regulations related to major public health emergencies to work effectively within this environment. Through investigation and analysis, a review was conducted to help gain a better understanding of a Level-1 response to public health events and the relevant laws and regulations applicable to medical staff. Based on the results, this study formulated measures for working in the current COVID-19 healthcare context.Methods: A total of 42,490 medical personnel in 18 cities in Henan Province (China) were reviewed and analysed using the convenience sampling method. A questionnaire was employed to address two areas of cognitive status quo (25 items), ie, “general information” and “major public events and rules of the law”.Results: More than 90% of medical staff had a good understanding related to knowledge about prevention and control in the pandemic context, as well as their due diligence and legal responsibility for controlling the pandemic and preventing others from being infected. However, 3.47– 32.61% of medical staff still had a minimal understanding of a Level-1 response to public health events and its relevant laws and regulations.Conclusion: The response to public health events required strengthening at all levels through promotion and education, by implementing an optimised treatment system and establishing an improved legal mechanism for the treatment of major conditions, such as hierarchical, stratified and triaged infectious diseases.Keywords: coronavirus disease 2019, major public health events, laws and regulations, cognitive behaviour

Chen Wang,1,&ast; Peng Fang,2,&ast; Ya Li,1,&ast; Lin Wu,2,&ast; Tian Hu,3 Qi Yang,4 Aiping Han,5 Yingjuan Chang,1 Xing Tang,1 Xiuhua Lv,1 Ziliang Xu,1 Yongqiang Xu,1 Leilei Li,1 Minwen Zheng,1 Yuanqiang Zhu1 1Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Department of Military Medical Psychology, Air Force Medical University, Xi’an, People’s Republic of China; 3Department of Radiology, Yan’an University Affiliated Hospital, Yan’an, People’s Republic of China; 4Department of Radiology, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, People’s Republic of China; 5Imaging Diagnosis and Treatment Center, Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanqiang Zhu, Department of Radiology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi’an, 710032, People’s Republic of China, Tel/Fax +86-29-84775415, Email Zhu_YQ_fmmu@163.com Minwen Zheng, Department of Radiology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi’an, 710032, People’s Republic of China, Tel/Fax +86-29-84771938, Email zhengmw2007@163.comBackground: Large individual differences exist in sleep deprivation (SD) induced sustained attention deterioration. Several brain imaging studies have suggested that the activities within frontal-parietal network, cortico-thalamic connections, and inter-hemispheric connectivity might underlie the neural correlates of vulnerability/resistance to SD. However, those traditional approaches are based on average estimates of differences at the group level. Currently, a neuroimaging marker that can reliably predict this vulnerability at the individual level is lacking.Methods: Efficient transfer of information relies on the integrity of white matter (WM) tracts in the human brain, we therefore applied machine learning approach to investigate whether the WM diffusion metrics can predict vulnerability to SD. Forty-nine participants completed the psychomotor vigilance task (PVT) both after resting wakefulness (RW) and after 24 h of sleep deprivation (SD). The number of PVT lapse (reaction time > 500 ms) was calculated for both RW condition and SD condition and participants were categorized as vulnerable (24 participants) or resistant (25 participants) to SD according to the change in the number of PVT lapses between the two conditions. Diffusion tensor imaging were acquired to extract four multitype WM features at a regional level: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) learning approach using leave-one-out cross-validation (LOOCV) was performed to assess the discriminative power of WM features in SD-vulnerable and SD-resistant participants.Results: LSVM analysis achieved a correct classification rate of 83.67% (sensitivity: 87.50%; specificity: 80.00%; and area under the receiver operating characteristic curve: 0.85) for differentiating SD-vulnerable from SD-resistant participants. WM fiber tracts that contributed most to the classification model were primarily commissural pathways (superior longitudinal fasciculus), projection pathways (posterior corona radiata, anterior limb of internal capsule) and association pathways (body and genu of corpus callosum). Furthermore, we found a significantly negative correlation between changes in PVT lapses and the LSVM decision value.Conclusion: These findings suggest that WM fibers connecting (1) regions within frontal-parietal attention network, (2) the thalamus to the prefrontal cortex, and (3) the left and right hemispheres contributed the most to classification accuracy.Keywords: sleep deprivation, vulnerability, diffusion tensor imaging, machine learning, psychomotor vigilance task

Meng-Huan Tsai,1 Chun-Chieh Chen,1– 3 Chih-Hsiang Chang,1– 3 Yuhan Chang,1– 3 Pang-Hsin Hsieh,1– 3 Chih-Chien Hu1– 3 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan; 2Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan; 3College of Medicine, Chang Gung University, Taoyuan, 33305, TaiwanCorrespondence: Chih-Chien Hu, Bone and Joint Research Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200, ext. 2420, Email chihchienhu@hotmail.comBackground: Revision total hip arthroplasty (RTHA) for loosening the femoral stem is a technical challenge. Distally fixed, full-porous-coated long stems are widely accepted as the standard selection for these revisions. However, the success of primary stems in RTHA is not well known.Methods: This study enrolled 24 patients with aseptic loosening of the femoral stem who underwent RTHA using primary stems. Another 72 patients with aseptic loosening who underwent RTHA using full-porous-coated long stems were matched in terms of operation date, proximal femoral bone stock (Paprosky classification), sex, and age. The primary and secondary outcomes of failure were the need for revision for any reason and the radiographic change in the stem respectively.Results: In the primary stem group, one patient had a periprosthetic fracture and received a second RTHA 2 years after the previous one. The primary outcome’s 5-and 10-year survival rates were both 95.8%. For the matched comparison group, one patient had an immediate periprosthetic fracture of the femoral shaft requiring further open reduction internal fixation surgery. Another patient had a full-porous-coated long stem breakage 6 years postoperatively, which required a second RTHA. The primary outcome’s 5-and 10-year survival rates were 98.6% and 97.2%, respectively.Conclusion: Primary stems can achieve non-inferior clinical success compared to a full-porous-coated long stem for aseptic stem loosening RTHA in patients with adequate proximal femoral bone stock.Keywords: revision total hip arthroplasty, aseptic loosening, primary stem, full-porous-coated long stem

Lei Zhu,1 Chuanqing Yu,1 Shuping Zhou,2 Min Xue,1 Jie Chen,3 Meijun Wu,4 Shuyang Dong,1 Guanmin Huang,5 Yueyue Chang,1 Mei Zhang1 1Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, 232007, People’s Republic of China; 2Department of Gastroenterology, First Affiliated Hospital of Anhui University of Science and Technology,First People’s Hospital of Huainan, Huainan, 232007, People’s Republic of China; 3Department of Neurosurgery, General Hospital of Huainan Oriental Hospital Group, Huainan, 232007, People’s Republic of China; 4Department of Comprehensive Health Care, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, People’s Republic of China; 5Department of Neurosurgery, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, 232007, People’s Republic of ChinaCorrespondence: Chuanqing Yu; Mei ZhangDepartment of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, 203 Huaibin Road, Huainan, 232007, Anhui Province, People’s Republic of ChinaTel +86-18949669880; +86-18949669978Email yuchuanqin1967@126.com; hnzhangmei2008@126.comObjective: The proteoglycan versican (VCAN) plays an important role in extracellular matrix (ECM) assembly, and diminished maintenance of the ECM has been increasingly regarded as an important factor in the development of intracranial aneurysms (IAs). Previous studies have revealed that single-nucleotide polymorphisms (SNPs) of the VCAN gene are associated with susceptibility to IAs in European or Japanese populations. However, the association between IA susceptibility and VCAN SNPs in the Eastern Chinese population remains unclear. This study aimed to investigate the associations of the SNPs rs251124, rs2287926, and rs173686 with IA susceptibility in the Eastern Chinese population.Methods: A total of 162 patients with IA and 182 controls were enrolled in this study. The study was conducted between January 2017 and December 2020. SNP genotyping for rs251124, rs2287926, and rs173686 was performed using Kompetitive Allele Specific PCR (KASP) after DNA extraction. The SNP data were analysed with CFX Manager Software version 3.1 (Bio-Rad).Results: rs251124 and rs173686 were significantly associated with susceptibility to IA. The frequency of rs251124-TT in IA was higher than in controls (OR =1.26, 95% CI: 1.07– 1.49; P< 0.01), and its risk mainly came from the T allele. Furthermore, logistic regression analysis showed that the T/T genotype and T allele of rs251124 were independent risk factors for IA (OR=1.726, 95% CI: 1.136– 2.263; P=0.011). Moreover, the G/G genotype and G allele of rs173686 were associated with increased IA susceptibility (OR=2.52, 95% CI: 1.261– 5.037; P=0.009).Conclusion: The SNPs rs251124 and rs173686 were strongly associated with genetic susceptibility to IA in the Eastern Chinese population; however, no such association was found in the SNP rs2287926 of VCAN. Our findings suggest that the VCAN gene is an IA susceptible gene that should be further studied as a screening marker for IAs.Keywords: intracranial aneurysm, susceptibility, VCAN gene, Eastern Chinese population, SNP

Feng-Hsiang Chiu,1,2 Yi Chang,3 Wen-Wei Liao,3 Yu-Ling Yeh,3 Chia-Mo Lin,4– 6 Ofer Jacobowitz,7 Ying-Shuo Hsu8,9 1Department of Otolaryngology, Head and Neck Surgery, Tri-service General Hospital, Taipei, Taiwan; 2National Defense Medical Center, Taipei City, Taiwan; 3Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 4Division of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 5Department of Chemistry, Fu-Jen Catholic University, New Taipei City, Taiwan; 6Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan; 7ENT & Allergy Associates, New York, NY, USA; 8Department of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 9School of Medicine, Fu Jen Catholic University, New Taipei City, TaiwanCorrespondence: Ofer JacobowitzENT & Allergy Associates, New York, NY, USATel +1 646 868-4300Email ojacobowitz@entandallergy.comYing-Shuo HsuDepartment of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanTel +1-886-2-28332211 ext.2551Email sulisky@gmail.comIntroduction: The findings of drug-induced sleep endoscopy (DISE) are not always correlated with the outcome of upper airway surgery for obstructive sleep apnea (OSA), and whether multilevel surgery is truly required in treating multilevel obstruction identified in preoperative DISE remains an issue. We attempted to compare DISE findings before and after palatopharyngoplasty in patients with OSA because changes in DISE may be beneficial to better understand polysomnographic and anatomical outcomes.Methods: This was a prospective cohort study for 34 patients with moderate to severe OSA who underwent palatopharyngoplasty at a tertiary care center from 2016 to 2018. We recorded the patients’ demographic characteristics, procedures, and surgical outcomes and compared the preoperative and postoperative DISE staging patterns.Results: The apnea-hypopnea index (AHI) values of 34 adults improved significantly after surgery (40.6 ± 23.3 versus 25.6 ± 20.6, P < 0.001). The majority of patients, 26/34, had preoperative complete concentric collapse at the velum, and for most (20/26, 77%) there was a change of the collapse pattern into anteroposterior collapse postoperatively. Patients with postoperative velar collapse had higher follow-up AHI values than those who without (27.8 ± 21.9 versus 15.2 ± 7.7, P = 0.023). Patients with preoperative complete tongue base collapse had higher follow-up AHI values than did those with no or partial collapse (40.6 ± 21.0 versus 21.0 ± 18.6, P = 0.017). Patients with postoperative complete tongue base collapse also had higher follow-up AHI values than the others (42.7 ± 22.1 versus 18.5 ± 15.4, P = 0.001).Conclusion: Palatopharyngoplasty could change the collapse pattern at the velum in most patients. Preoperative and postoperative complete tongue base collapse and postoperative velar collapse identified in TCI-DISE were associated with relatively poor outcomes.Keywords: obstructive sleep apnea, drug-induced sleep endoscopy, palatopharyngoplasty, postoperative, complete concentric collapse, tongue base collapse

Pathogenic CACNA1A gene variants are associated with a spectrum of disorders including migraine with or without hemiplegia, ataxia, epilepsy, and developmental disability. We present a case of a pathogenic variant (c.4046G>A, p.R1349Q) in the CACNA1A gene associated with a clinical phenotype of global developmental delay, left hemiparesis, epilepsy, and stroke-like episodes. Longitudinal neuroimaging demonstrates hemispheric encephalomalacia with mismatched perfusion and angiographic imaging, in addition to progressive cerebellar atrophy.

Wenjuan Feng,* Siqiang Niu,* Yanbin Chang, Xiaojiong Jia, Shifeng Huang, Ping Yang Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shifeng Huang; Ping YangDepartment of Clinical Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Friendship Road, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86-18623027077; +86-13637993035Fax +86-23-89012513; +86-23-89012513Email sfhuang@hospital.cqmu.edu.cn; 201903@cqmu.edu.cnPurpose: Carbapenemase-producing Enterobacteriaceae (CPE) infection constitutes a public health threat. Timely and efficient diagnosis is of paramount importance for prompt and effective therapy. In order to quickly and comprehensively detect the five major families of carbapenemases (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48-like), colorimetric loop-mediated isothermal amplification (LAMP) was employed.Materials and Methods: Five sets of LAMP primers were designed, each of which can, respectively, amplify all the carbapenemase subtypes described in this work. Twenty whole genome sequencing-verified-“standard strains”, including 1 blaNDM-1, 1 blaNDM-5, 1 blaNDM-6, 1 blaNDM-7, 2 blaIMP-4, 1 blaIMP-8, 2 blaKPC-2, 1 blaKPC-3, 1 blaKPC-4, 1 blaKPC-5, 1 blaKPC-6, 1 blaKPC-7, 1 blaOXA-48 and 1 blaOXA-181 carrier, and 1 blaVIM and blaOXA-244, 1 blaKPC-2 and blaIMP-4, 1 blaKPC-2 and blaVIM-1 and 1 blaKPC-2 and blaNDM-1-co-carriers, were used to establish a 25-microliter visual LAMP reaction system (kept at 65°C for 30 minutes in water bath). Color change from bright pink to yellow indicated positive amplification. In addition, 126 pre-verified clinical carbapenem-resistant Enterobacteriaceae (CRE) isolates, including 65 CPE (23 blaNDM, 2 blaOXA-48-like, 1 blaKPC and blaVIM, 2 blaIMP, and 37 blaKPC carriers) and 61 non-CPE, were also detected.Results: With the lowest detection limit of 10 colony forming units (CFU) per reaction for LAMP and 103 CFU per reaction for PCR, the LAMP system demonstrated dramatically higher sensitivity while retaining the same specificity. Furthermore, we demonstrated concordant results between the two methods for the 126 clinical isolates.Conclusion: Therefore, LAMP could be used for rapid identification of the five major carbapenemase gene families in routine clinical laboratories.Keywords: carbapenemase-producing Enterobacteriaceae, loop-mediated isothermal amplification, blaNDM, blaKPC, blaVIM, blaIMP, blaOXA-48-like

Hui Jia,1,* Yuele Chang,1,* Long Zhao,1 Yunxia Li,1 Lei Chen,1 Qian Zhang,1 Xianzhi Lou,2 Chenwei Li,2 Shuyue Xia1 1Department of Respiratory and Critical Care Medicine, Shenyang Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110000, People’s Republic of China; 2Department of Infectious Disease, Shenyang Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuyue XiaDepartment of Respiratory and Critical Care Medicine, Shenyang Central Hospital Affiliated to Shenyang Medical College, No. 5 Of Nanqi West Road, Tiexi District, Shenyang, 110000, People’s Republic of ChinaTel +8613309880832Email xiashuyuelk@163.comIntroduction: Novel coronavirus pneumonia (COVID-19) is an acute respiratory infectious disease, which has the characteristic of human-to-human transmission and is extremely contagious. Correctly standardizing the process of early screening of infection or suspected cases in the fever clinic has become a key part of the fight against the pandemic.Methods: A retrospective analysis of patients in the fever clinic of Shenyang Medical College Affiliated Central Hospital from January 23 to March 1, 2020, was conducted in the present study.Results: It was found that 16 suspected cases of COVID-19 in the fever clinic were diagnosed with respiratory infections, accounting for 0.59%.Conclusion: In case of a negative result in the second nucleic acid test, strategic triage and typing might be more conducive for the following nucleic acid tests for suspected cases in order to prevent the spread of the epidemic caused by missed diagnosis.Keywords: COVID-19, infection control, epidemic prevention and control, work process, fever clinic

Ying Ben,1,2,* Juan Hao,1,* Zhihong Zhang,1,2 Yunzhao Xiong,1 Cuijuan Zhang,1,2 Yi Chang,1,2 Fan Yang,1,2 Hui Li,1,2 Tianya Zhang,1 Xiangting Wang,1,2 Qingyou Xu1,2 1Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China; 2Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingyou XuHebei University of Chinese Medicine, No. 326 Xinshinan Road, Qiaoxi District, Shijiazhuang, Hebei Province, 050090, People’s Republic of ChinaTel +86 13832368865Fax +86 311 89926000Email qingyouxu@sohu.comPurpose: To investigate the effect of astragaloside IV (AS-IV) on mitochondrial-dependent apoptosis in the dorsal root ganglion of diabetic peripheral neuropathy (DPN) rats through the SIRT1/p53 pathway.Methods: Diabetic rat model was induced by high-carbohydrate/high-fat diet and intraperitoneal injection of STZ. Diabetic rats were divided into three groups (n =16 per group): DPN group, AS-IV group (60mg/kg/d) and α-lipoic acid (ALA) group (60mg/kg/d). Weight and blood glucose levels were monitored every 4 weeks for 12 weeks. DPN was evaluated using the Von Frey Filaments Test and nerve conduction velocity. The dorsal root ganglia of rats were isolated and the pathological changes of mitochondria were observed by electron microscopy. The activity of mitochondrial electron transport chain complex, mitochondrial membrane potential, malonaldehyde (MDA) and glutathione (GSH) levels were measured. Neural apoptosis was detected using the Terminal Deoxynucleotidyl Nick-End Labeling (TUNEL) assay kit. The cleaved caspase-3, major proteins in the SIRT1/p53 pathway, including SIRT1, acetyl p53, Drp1, BAX, and BCL-2, were detected using immunohistochemistry and Western blot. Gene expression of major proteins in the SIRT1/p53 pathway was also detected.Results: After 12 weeks of treatment, AS-IV and ALA did not significantly affect body weight or fasting glucose levels, but reduced mechanical abnormal pain in DPN and improved nerve conduction velocity. AS-IV and ALA increased the level of GSH and decreased the level of MDA. Both AS-IV and ALA can reduce mitochondrial damage, improve mitochondrial electron transport chain complex activity and mitochondrial membrane potential, and reduce the percentages of positive cells with DNA fragmentation and the expression of cleaved caspase-3 protein. AS-IV and ALA up-regulated the expression of SIRT1 and down-regulated the expression of acetyl-p53, Drp1 and the ratio of BAX to BCL-2. Changes in gene expression were similar.Conclusion: AS-IV can reduce the occurrence of mitochondrial-dependent apoptosis by regulating the SIRT1/p53 pathway. It has a similar therapeutic effect as ALA and is therefore a promising drug for the potential treatment of DPN.Keywords: astragaloside IV, diabetic peripheral neuropathy, dorsal root ganglion, mitochondria, apoptosis, SIRT1/p53 pathway

Yanbin Chang,* Daiqin Zhang,* Siqiang Niu, Qian Chen, Qiuxia Lin, Xiaobing Zhang Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaobing ZhangDepartment of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel + 86-15123967161Fax + 86-23-89012742Email xhpg85@aliyun.comObjective: To assess the risk factors associated with infections and in-hospital mortality, antimicrobial susceptibility patterns and carbapenem resistance mechanisms in E. anophelis.Methods: This retrospective case–control study was conducted to reveal the risk factors associated with Elizabethkingia anophelis (E. anophelis) infection and in-hospital mortality in a university tertiary hospital in southwest China, using multivariable logistic-regression analyses. Complete 16S rRNA gene sequencing was used to reconfirm the identity of all isolates. We employed the broth microdilution method to investigate the antimicrobial susceptibility profiles. The presence of resistance genes was confirmed by polymerase chain reaction and DNA sequencing. Full-length resistance genes were cloned into the pET-28a vector for further functional studies.Results: Our multivariate analysis indicated that coronary artery disease, chronic obstructive pulmonary disease, surgery in the past 6 months, anemia and systemic steroid use were independent risk factors for the acquisition of E. anophelis. Additionally, anemia was the only independent risk factor associated with in-hospital mortality in patients with E. anophelis infections. E. anophelis isolates showed high in-vitro susceptibility towards minocycline (100%) and piperacillin/tazobactam (71.8%), but were resistant to colistin, fosfomycin, ceftazidime/avibactam and aztreonam/avibactam. The PCR revealed the presence of blaGOB and blaBlaB in 37 isolates, and blaCME β-lactamase genes in 36 isolates out of 39 E. anophelis isolates. Additionally, we showed that two metallo-β-lactamases (MBLs) BlaB and GOB, were responsible for carbapenem resistance and the serine-β-lactamase, CME, was functionally involved in resistance to cephalosporins and monobactams. Interestingly, the various putative efflux pumps in E. anophelis were not responsible for resistance.Conclusion: Our findings will help clinicians to identify high-risk patients and suggests that minocycline should be considered as a therapeutic option for E. anophelis infections. Additionally, carbapenem resistance in E. anophelis is mainly associated with the MBLs, BlaB and GOB, rather than various putative efflux pumps.Keywords: Elizabethkingia anophelis, risk factors, antimicrobial susceptibility patterns, carbapenem resistance

Ying Chu, Yi Chang, Wei Lu, Xiumei Sheng, Shengjun Wang, Huaxi Xu, Jie Ma Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, People’s Republic of ChinaCorrespondence: Jie MaDepartment of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, 301 XueFu Road, Zhenjiang, Jiangsu Province 212013, People’s Republic of ChinaTel +86-1377-555-5586Email jsdxmajie@163.comAbstract: Autophagy is a critical cellular process that generally protects cells and organisms from harsh environment, including limitations in adenosine triphosphate (ATP) availability or a lack of essential nutrients. Metabolic reprogramming, a hallmark of cancer, has recently gained interest in the area of cancer therapy. It is well known that cancer cells prefer to utilize glycolysis rather than oxidative phosphorylation (OXPHOS) as their major energy source to rapidly generate ATP even in aerobic environment called the Warburg effect. Both autophagy and glycolysis play essential roles in pathological processes of cancer. A mechanism of metabolic changes to drive tumor progression is its ability to regulate autophagy. This review will elucidate the role and the mechanism of glycolysis in regulating autophagy during tumor growth. Indeed, understanding how glycolysis can modulate cellular autophagy will enable more effective combinatorial therapeutic strategies.Keywords: glycolysis, autophagy, lung cancer, lactate, metabolism

Acquired third nerve palsies are infrequently seen in children, but are often associated with serious pathologies. This article presents a pediatric case of tumor-associated, isolated third nerve palsy, which took two years to diagnose. The patient initially presented with an isolated, dilated pupil and progressed over several months to a complete third nerve palsy. In this case, high-resolution neuroimaging eventually led to the diagnosis of a presumed schwannoma as the cause of her third nerve palsy. We review her case, the importance of high-resolution imaging, and management options.

Yulin Zhang,1 Yi Li,2 Ji Zeng,3 Yanzi Chang,4 Shouhua Han,5 Jiankang Zhao,1 Yanyan Fan,1 Zhujia Xiong,1 Xiaohui Zou,1 Chunlei Wang,1 Binbin Li,1 Haibo Li,1 Jiajing Han,1 Xinmeng Liu,1 Yudi Xia,1 Binghuai Lu,1 Bin Cao1,6,7 1Department of Pulmonary and Critical Care Medicine, Laboratory of Clinical Microbiology and Infectious Diseases, Center for Respiratory Diseases, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, People’s Republic of China; 2Department of Laboratory Medicine, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Laboratory Medicine, Wuhan Pu Ai Hospital of Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Laboratory Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, People’s Republic of China; 5Department of Laboratory Medicine, Weifang No.2 People’s Hospital, Weifang, People’s Republic of China; 6Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, People’s Republic of China; 7Tsinghua University-Peking University, Joint Center for Life Sciences, Beijing, People’s Republic of ChinaCorrespondence: Binghuai Lu; Bin CaoDepartment of Pulmonary and Critical Care Medicine, Laboratory of Clinical Microbiology and Infectious Diseases, Center for Respiratory Diseases, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, Chaoyang District, Beijing 100029, People’s Republic of ChinaTel/Fax +86-10-84206257Email zs25041@126.com; caobin_ben@163.comPurpose: Pseudomonas aeruginosa bacteremia presents a severe challenge to hospitalized patients. However, to date, the risk factors for mortality among inpatients with P. aeruginosa bacteremia in China remain unclear.Patients and Methods: This retrospective multicenter study was performed to analyze 215 patients with culture-confirmed P. aeruginosa bacteremia in five healthcare centers in China during the years 2012– 2019.Results: Of 215 patients with P. aeruginosa bacteremia, 61 (28.4%) died during the study period. Logistic multivariable analysis revealed that cardiovascular disease (OR=3.978, P=0.001), blood transfusion (OR=5.855, P< 0.001) and carbapenem-resistant P. aeruginosa (CRPA) phenotype (OR=4.485, P=0.038) constituted the independent risk factors of mortality. Furthermore, both CRPA and multidrug-resistant P. aeruginosa (MDRPA) phenotypes were found to be significantly associated with 5-day mortality (Log-rank, P< 0.05).Conclusion: This study revealed a high mortality rate amongst hospitalized patients with P. aeruginosa bacteremia, and those with cardiovascular diseases, CRPA and MDRPA phenotypes, should be highlighted and given appropriate management in China.Keywords: risk factors, mortality, Pseudomonas aeruginosa, bacteremia

Chih-Chien Hu,1– 4 Chih-Hsiang Chang,1– 3 Yuhan Chang,1– 3 Jang-Hsing Hsieh,5,6 Steve Wen-Neng Ueng1– 3 1Bone and Joint Research Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan 33305, Taiwan; 2Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Kweishan, Taoyuan 33305, Taiwan; 3College of Medicine, Chang Gung University, Kweishan, Taoyuan 33302, Taiwan; 4Department of Orthopedic Surgery, Xiamen Chang Gung Hospital, Xiamen, Fujian, People’s Republic of China; 5Department of Materials Engineering, Ming Chi University of Technology, Taishan, Taipei 24301, Taiwan; 6Center for Thin Film Technologies and Applications, Ming Chi University of Technology, Taishan, Taipei 24301, TaiwanCorrespondence: Steve Wen-Neng UengDepartment of Orthopedic Surgery, Chang Gung Memorial Hospital, No. 5, Fu-Hsin St, Kweishan, Taoyuan 33305, TaiwanTel +88633281200-2420Fax +886 33278113Email wenneng@adm.cgmh.org.twPurpose: In this study, a novel oxygenated nanocomposite thin film, TaON-Ag, was investigated in vitro and in vivo to evaluate its biocompatibility and antibacterial ability.Material and Methods: The antibacterial ability of TaON-Ag nanocomposite-coated titanium (Ti) was evaluated using the Kirby-Bauer disk diffusion susceptibility test. The effects of TaON-Ag nanocomposite-coated metal on osteogenesis were further evaluated in an in vitro osteogenic culture model with rat marrow-derived mesenchymal stem cells (rMSCs). Furthermore, titanium rods coated with TaON-Ag were implanted into a rat femur fracture model either with or without osteomyelitis to investigate the effects of TaON-Ag in osteogenesis.Results: The TaON-Ag-coated Ti exhibited an effective antibacterial effect against Staphylococcus aureus, coagulase-negative Staphylococcus, and the Gram-negative strains Escherichia coli and Pseudomonas aeruginosa. Using an osteogenic culture with rMSCs and a rat femoral fracture model, the TaON-Ag-coated Ti did not interfere with the ossification of rMSCs in vitro or during fracture healing in vivo. Field-emission scanning electron microscopy (FE-SEM) revealed that coating with TaON-Ag could inhibit pathogen adhesion and biofilm formation in both Staphylococcus aureus and Escherichia coli.Conclusion: Using the proposed novel oxygenation process, TaON-Ag nanocomposite-coated Ti yielded robust biocompatibility and antibacterial ability against common microorganisms in orthopedic infections, thereby demonstrating potential for use in clinical applications.Keywords: silver nanoparticles, ossification, antibacterial ability, biofilm

Bijia Song,1,2,* Yuanyuan Chang,1,* Yang Li,1 Junchao Zhu1 1Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Anesthesiology, Friendship Hospital of Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junchao ZhuDepartment of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaEmail zhujunchao1@hotmail.comObjective: Postoperative sleep disturbances have serious adverse effects on postoperative outcomes. Our paper aimed to observe the effect of using transcutaneous electrical acupoint stimulation (TEAS) on sleep quality and complications after surgery in patients undergoing selective video-assisted thoracoscopic surgery.Patients and Methods: Eighty-five patients were divided into the TEAS group or the control group randomly. Thirty minutes of TEAS treatment was performed on TEAS group at the following time points: the first night before surgery, at the end of surgery, and before sleeping on the second and third nights after surgery. The Portable Sleep Monitor (PSM) was performed to determine the sleep quality of the two nights before the operation (Sleep preop 2 and Sleep preop 1) and the first and third night after surgery (Sleep POD 1 and Sleep POD 3). The visual analog scale (VAS) was performed to evaluate pain scores after surgery and the Athens Insomnia Scale (AIS) was used for evaluating subjective sleep quality.Results: Participants in the TEAS group had a lower AIS score and higher sleep efficiency at each time point except Sleep preop 2. Participants in the TEAS group showed significantly higher proportion of each sleep stage during Sleep-preop 1, Sleep POD 1, and Sleep POD 3. Patients in the TEAS group had significantly lower VAS scores at 2, 4, and 6 h during the first 24 h after surgery. The incidence of nausea and vomiting and dizziness in the control group was statistically higher than in the TEAS group.Conclusion: Patients usually have sleep disturbances after video-assisted thoracoscopic surgery, such as decreased distribution of each sleep stage, lower sleep efficiency, and higher AIS score. Undergoing TEAS treatment perioperatively can improve sleep quality, and effectively promote the postoperative analgesic effect and alleviate postoperative complications.Keywords: acupoints, general anesthesia, pain, sleep quality, transcutaneous electrical acupoint stimulation

Hongru Li, Peng Xia, Su Pan, Zhiping Qi, Chuan Fu, Ziyuan Yu, Weijian Kong, Yuxin Chang, Kai Wang, Dankai Wu, Xiaoyu Yang Department of Orthopedic Surgery, The Second Hospital of Jilin University, Changchun 130041, People’s Republic of ChinaCorrespondence: Dankai Wu; Xiaoyu YangDepartment of Orthopedic Surgery, The Second Hospital of Jilin University, Changchun, TX 130041, People’s Republic of ChinaEmail wudankai@163.com; yangxiaoy@jlu.edu.cnAbstract: The ongoing biomedical nanotechnology has intrigued increasingly intense interests in cerium oxide nanoparticles, ceria nanoparticles or nano-ceria (CeO2-NPs). Their remarkable vacancy-oxygen defect (VO) facilitates the redox process and catalytic activity. The verification has illustrated that CeO2-NPs, a nanozyme based on inorganic nanoparticles, can achieve the anti-inflammatory effect, cancer resistance, and angiogenesis. Also, they can well complement other materials in tissue engineering (TE). Pertinent to the properties of CeO2-NPs and the pragmatic biosynthesis methods, this review will emphasize the recent application of CeO2-NPs to orthopedic biomedicine, in particular, the bone tissue engineering (BTE). The presentation, assessment, and outlook of the orthopedic potential and shortcomings of CeO2-NPs in this review expect to provide reference values for the future research and development of therapeutic agents based on CeO2-NPs.Keywords: CeO2-NPs, green synthesis, ROS, bone tissue engineering, coating, orthopedic implants

Miscanthus is a perennial grass with potential for lignocellulosic ethanol production. To ensure its utility for this purpose, breeding efforts should focus on increasing genetic diversity of the nothospecies Miscanthus × giganteus (M×g) beyond the single clone used in many programs. Germplasm from the corresponding parental species M. sinensis (Msi) and M. sacchariflorus (Msa) could theoretically be used as training sets for genomic prediction of M×g clones with optimal genomic estimated breeding values for biofuel traits. To this end, we first showed that subpopulation structure makes a substantial contribution to the genomic selection (GS) prediction accuracies within a 538-member diversity panel of predominately Msi individuals and a 598-member diversity panels of Msa individuals. We then assessed the ability of these two diversity panels to train GS models that predict breeding values in an interspecific diploid 216-member M×g F2 panel. Low and negative prediction accuracies were observed when various subsets of the two diversity panels were used to train these GS models. To overcome the drawback of having only one interspecific M×g F2 panel available, we also evaluated prediction accuracies for traits simulated in 50 simulated interspecific M×g F2 panels derived from different sets of Msi and diploid Msa parents. The results revealed that genetic architectures with common causal mutations across Msi and Msa yielded the highest prediction accuracies. Ultimately, these results suggest that the ideal training set should contain the same causal mutations segregating within interspecific M×g populations, and thus efforts should be undertaken to ensure that individuals in the training and validation sets are as closely related as possible.

Lara A Kahale,1 Assem M Khamis,2 Batoul Diab,1 Yaping Chang,3 Luciane Cruz Lopes,4 Arnav Agarwal,3,5 Ling Li,6 Reem A Mustafa,3,7 Serge Koujanian,8 Reem Waziry,9 Jason W Busse,3,10– 12 Abeer Dakik,1 Lotty Hooft,13 Gordon H Guyatt,3,14 Rob JPM Scholten,13 Elie A Akl1,3 1Clinical Research Institute, American University of Beirut, Beirut, Lebanon; 2Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Hull, UK; 3Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; 4Pharmaceutical Sciences Post Graduate Course, University of Sorocaba, UNISO, Sorocaba, Sao Paulo, Brazil; 5Department of Medicine, University of Toronto, Toronto, Ontario, Canada; 6Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 7Departments of Medicine and Biomedical & Health Informatics, University of Missouri-Kansas City, Kansas City, MO, USA; 8Department of Evaluative Clinical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; 9Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 10Department of Anesthesia, McMaster University, Hamilton, Canada; 11The Michael G. DeGroote National Pain Centre, McMaster University, Hamilton, Canada; 12Chronic Pain Centre of Excellence for Canadian Veterans, Hamilton, Canada; 13Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; 14Department of Medicine, McMaster University, Hamilton, CanadaCorrespondence: Elie A AklDepartment of Internal Medicine, American University of Beirut Medical Center, P.O. Box: 11-0236; Riad-El-Solh, Beirut 1107– 2020, LebanonTel +961 1 374374Email ea32@aub.edu.lbBackground: How systematic review authors address missing data among eligible primary studies remains uncertain.Objective: To assess whether systematic review authors are consistent in the way they handle missing data, both across trials included in the same meta-analysis, and with their reported methods.Methods: We first identified 100 eligible systematic reviews that included a statistically significant meta-analysis of a patient-important dichotomous efficacy outcome. Then, we successfully retrieved 638 of the 653 trials included in these systematic reviews’ meta-analyses. From each trial report, we extracted statistical data used in the analysis of the outcome of interest to compare with the data used in the meta-analysis. First, we used these comparisons to classify the “analytical method actually used” for handling missing data by the systematic review authors for each included trial. Second, we assessed whether systematic reviews explicitly reported their analytical method of handling missing data. Third, we calculated the proportion of systematic reviews that were consistent in their “analytical method actually used” across trials included in the same meta-analysis. Fourth, among systematic reviews that were consistent in the “analytical method actually used” across trials and explicitly reported on a method for handling missing data, we assessed whether the “analytical method actually used” and the reported methods were consistent.Results: We were unable to determine the “analytical method reviews actually used” for handling missing outcome data among 397 trials. Among the remaining 241, systematic review authors most commonly conducted “complete case analysis” (n=128, 53%) or assumed “none of the participants with missing data had the event of interest” (n=58, 24%). Only eight of 100 systematic reviews were consistent in their approach to handling missing data across included trials, but none of these reported methods for handling missing data. Among seven reviews that did explicitly report their analytical method of handling missing data, only one was consistent in their approach across included trials (using complete case analysis), and their approach was inconsistent with their reported methods (assumed all participants with missing data had the event).Conclusion: The majority of systematic review authors were inconsistent in their approach towards reporting and handling missing outcome data across eligible primary trials, and most did not explicitly report their methods to handle missing data. Systematic review authors should clearly identify missing outcome data among their eligible trials, specify an approach for handling missing data in their analyses, and apply their approach consistently across all primary trials.Keywords: missing data, assumption, randomized controlled trial, systematic review, meta-analysis

Xinran Ma,* Ling Li,* Lei Zhang, Xiaorui Fu, Xin Li, Xinhua Wang, Jingjing Wu, Zhenchang Sun, Xudong Zhang, Xiaoyan Feng, Yu Chang, Zhiyuan Zhou, Feifei Nan, Jieming Zhang, Zhaoming Li, Mingzhi Zhang Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingzhi ZhangDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Lymphoma Diagnosis and Treatment Centre of Henan Province, Zhengzhou 450002, Henan, People’s Republic of ChinaTel +86-13838565629Email mingzhi_zhang1@163.comPurpose: Treatment options for relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) represent an unmet medical need. Apatinib is a new oral tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptor-2 (VEGFR-2) to inhibit tumour angiogenesis. In the present study, we evaluated the efficacy and safety of apatinib for patients with RR DLBCL.Patients and Methods: In this phase II, open-label, single-arm, prospective study, we enrolled patients aged 14– 70 years with treatment failure of at least two chemotherapeutic regimens using Simon’s two-stage design. All patients were administered apatinib at an initial dose of 500 mg on a 4-week cycle at home and visited the outpatient clinic every two cycles to evaluate efficacy and to record adverse events. We considered objective response rate (ORR) as the primary end point, and progression-free survival (PFS), and overall survival (OS) plus duration of response (DoR) as the secondary end point. (This trial was registered at ClinicalTrials.gov, identifier: NCT03376958.).Results: From January 2017 to February 2019, we screened 35 patients and enrolled 32 eligible patients. At the cutoff point (April 2019), we noted 2 (6.3%) complete responses, 12 (37.5%) partial responses, and 9 (28.1%) stable diseases, attributing to an ORR of 43.8% and a disease control rate of 71.9%. The median PFS and OS were 6.9 (95% confidence interval [CI], 5.8– 7.9) and 7.9 months (95% CI, 7.0– 8.7), respectively. The median DoR was 5.0 months (95% CI, 3.5– 6.5) for patients who achieved PR. The most common grade 3– 4 adverse events (AE) were hypertension (12.6%), hand–foot syndrome (9.4%), and leucopenia (6.3%). No apatinib-related deaths were noted.Conclusion: Home administration of apatinib shows promising efficacy and manageable AEs in patients with RR DLBCL.Keywords: apatinib, relapsed or refractory diffuse large B-cell lymphoma, VEGFR-2, efficacy, safety

Kuo YH, Liu TJ, Chiu FH, et al. Nat Sci Sleep. 2021;13:2087–2099. The authors have advised that the funding statement on page 2098 is incorrect. The text “This study was supported by a grant from Shin Kong Wu- Ho-Su memorial Hospital (2018SKHADR018)” should read “This study was supported by a grant from Shin Kong Wu-Ho-Su memorial Hospital (2019SKHADR027)”. The authors apologize for this error. Read the original article