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Biao Song,1– 3,* Xiaohan Liu,1– 3,* Hongzhong Jin1– 3 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongzhong Jin, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China, Email jinhongzhong@263.netAbstract: Erythrodermic psoriasis (EP) is a severe and rare variant of psoriasis, accounting for less than 3% of cases. It is characterized by widespread scaling and erythema that affects more than 90% of the body surface area. Alopecia can manifest as a symptom associated with the disease, further exacerbating the impact on the patient’s quality of life. We present the case of a patient with severe EP and diffuse alopecia who did not respond to conventional therapies. The patient was subsequently treated with ixekizumab as per labeled usage, resulting in complete resolution of both psoriatic skin lesions (Psoriasis area and severity index/PASI 100) and alopecia (The Severity of Alopecia Tool/SALT 0).Keywords: erythrodermic psoriasis, alopecia, ixekizumab

Yuan Gao,1– 3,* Ce Zong,1,* Ying Yao,4 Haixu Zhao,5 Yuan Song,4 Ke Zhang,1 Hongxun Yang,1 Hongbing Liu,1 Yunchao Wang,1 Yusheng Li,1– 3 Jing Yang,1– 3 Bo Song,1– 3 Yuming Xu1– 3 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, People’s Republic of China; 3Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4School of Health and Nursing, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5School of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuming Xu, Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, Henan Province, People’s Republic of China, 450052, Tel/Fax +86 13903711125, Email xuyuming@zzu.edu.cnPurpose: We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients.Patients and Methods: Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients.Results: In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0– 53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043– 1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063– 1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06– 1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05– 1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age.Conclusion: Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.Keywords: cerebral small vessel disease, incident stroke, fibrinogen-to-albumin ratio, inflammation

Xiaohan Liu,1– 3,* Biao Song,1– 3,* Hongzhong Jin1– 3 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Beijing, People’s Republic of China; 3National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongzhong Jin, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of China, Email jinhongzhong@263.netAbstract: Atopic dermatitis (AD) may sometimes be comorbid with alopecia areata (AA). However, traditional treatments for AA show limited efficacy. New treatment options, such as dupilumab and Janus kinase inhibitors, have proven efficacy in addressing both AD and AA. This article highlights the challenging case of a 12-year-old boy experiencing severe refractory AD and comorbid AA treated with oral abrocitinib after dupilumab failure with 1-year follow-up. After 3 months of treatment, his skin manifestations improved and the hair completely regenerated. No adverse reactions were observed during the 1-year follow-up period. This case provides evidence of the efficacy and safety of using abrocitinib to treat pediatric patients with both AD and AA.Keywords: atopic dermatitis, alopecia areata, Janus kinase inhibitors, dupilumab

Kaixiong Liu,1– 3,* Luling Wu,4,5,* Gongping Chen,1– 3,* Dunhuan Zeng,1– 3 Qiwei Zhong,6 Li Luo,1,2 Bin Song,7 Xiuhong Ying,1,2 Fayu Ni,8 Lifang Yu,8 Liyu Xu,9 Xin Lin,9 Xiaoyan Chen,10 Xin Zou,11 Jianhong Xiao,7 Yuekai Hu5,12,13 1Department of Respiratory and Critical Care medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 3Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People’s Republic of China; 4Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Minnan Hospital, the First Affiliated Hospital of Fujian Medical University, Quau zhou, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Mindong Hospital Affiliated to Fujian Medical University, Ningde, People’s Republic of China; 8Department of Respiratory, Fuqing General Hospital Affiliated to Fujian Medical University, Fuzhou, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, Fuzhou First Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 10Department of Emergency Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, People’s Republic of China; 11Department of Respiratory and Critical Care Medicine, LongYan First Hospital Affiliated to Fujian Medical University, Longyan, People’s Republic of China; 12Department of Infectious Diseases, First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 13Department of Infectious Diseases, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuekai Hu; Jianhong Xiao, Email huyuekai@fudan.edu.cn; xjh1030@sina.comObjective: This study aimed to describe and compare the epidemiological, demographic, clinical, laboratory and radiological characteristics as well as the complications, treatments, and outcomes of these patients.Methods: We retrospectively investigated clinical data of patients with C. psittaci infection (psittacosis) in eight Grade IIIA hospitals of Fujian. Metagenomic next-generation sequencing (mNGS) was used identify C. psittaci in clinical samples of all included patients.Results: A total of 74 patients (39 severe/35 non-severe) was diagnosed with psittacosis, 25 (33.8%) of whom had history of poultry exposure. Common symptoms included high fever (98% [37/74]), fatigue (52.7% [39/74]), and dyspnea (51.4% [38/74]). Common manifestations in imaging included consolidation (89.2%), pleural effusion (77.0%), and air bronchogram (66.2%). Common complications included acute respiratory distress syndrome (55.4% [41/74]), type I respiratory failure (52.7% [39/74]), acute liver injury (41.9% [31/74]), and secondary infection (27.0% [20/74]). The in-hospital mortality rate was 8.11% (6/74).Conclusion: C. psittaci infection is represents an underestimated cause of CAP. For SCAP patients with poultry and bird contact history, specimens were encouraged to be sended for mNGS test in time. C. psittaci infection can lead to severe, multiple system involvement, and several complications. mNGS facilitate timely diagnosis of C. psittaci infection.Keywords: Chlamydia psittaci, metagenomic next-generation sequencing, community-acquired pneumonia, bronchoalveolar lavage fluid

Bijia Song, Xiuliang Li, Jiguang Yang, Wenjing Li, Lei Wan Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of ChinaCorrespondence: Lei Wan, Email wanleimz@sina.comIntroduction: Seeking effective multimodal analgesia and anesthetic regimen is the basis for the success of ERAS. Opioid-free anesthesia (OFA) is a multimodal anesthesia associating hypnotics, N-methyl-D-aspartate (NMDA) antagonists, local anesthetics, anti-inflammatory drugs and α-2 agonists. Although previous studies have confirmed that OFA is safe and feasible for VATS surgery, there is great heterogeneity in how to select and combine anti-harm drugs to replace opioids. We hypothesized that the reduced opioid use during and after surgery allowed by OFA compared with standard of care will be associated with a reduction of postoperative opioid-related adverse events and an improvement in the quality of rehabilitation of patients after partial VATS lung resection.Methods/Analysis: The TEDOFA Study is a prospective double-blind, randomized, controlled clinical trial with a concealed allocation of patients scheduled to undergo elective partial VATS pneumonectomy 1:1 to receive either a standard anesthesia protocol or an OFA. A total of 146 patients were recruited in the study. Primary endpoint was the 15-item recovery quality scale (QoR-15) at 24 hours after surgery.Ethics and Dissemination: This trial has been approved by the Institutional Review Board of Beijing Friendship Hospital of China Capital University. The TEDOFA trial study protocol was approved on 27 February 2023. The trial started recruiting patients after registered on the Chinese Clinical Trial Registry.Trial Registration Number: ChiCTR2300069210; Pre-results.Keywords: opioid-free anesthesia, thoracoscopic surgery, postoperative recovery, chronic pain

Liu J, Kang Y, Yin S, et al. Int J Nanomedicine. 2017;12:8085–8099. The authors have advised the control images for Figure 4A and B were the same to represent the one and the same control group. To alleviate any potential confusion this may have created, the authors have provided a corrected Figure 4. This correction does not change the scientific conclusions of the article in any way. Figure 4 Confocal microscopy investigation of the cellular distribution of lysosomes and zinc ions in SH-SY5Y cells after the two types of ZnO NP treatments.Abbreviation: NP, nanoparticle.Notes: After the SH-SY5Y cells were untreated (the Control group) or treated with the ZnOa NPs and ZnOb NPs (50 µg/mL) for 1 h, 3 h, or 5 h, the cells were loaded with FluoZin3 (green), LysoTracker (red) and Hoechst 33342 (blue). We observed almost no zinc ion fluorescence in the Control group, but significant zinc ions (green) were observed within 1 h after the ZnO NP treatment, and a slight increase in the zinc fluorescence (green) was observed in a time-dependent manner. Treatment with ZnOb NPs exhibited more potent fluorescence values than treatment with ZnOa NPs at 1 h. Moreover, significant overlaps (yellow) between cellular zinc ions and lysosomes were observed at all timepoints. Scale bar = 50µm. Magnification x600.

Haichuan Guo,1,&ast; Bixuan Song,2,&ast; Ruijuan Zhou,3 Jiahao Yu,1 Pengzhao Chen,1 Bin Yang,1 Naihao Pan,1 Chengsi Li,1 Yanbin Zhu,1,4 Juan Wang1,4 1Department of Orthopedic Surgery, The 3rd Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Division of Medical Sciences, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3College of Education, Hebei Normal University, Shijiazhuang, Hebei, 050010, People’s Republic of China; 4Orthopedic Research Institute of Hebei Province, Key Laboratory of Biomechanics of Hebei Province, Shijiazhuang, Hebei, 050051, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Wang; Yanbin Zhu, Department of Orthopaedics, the 3rd Hospital, Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, 050051, People’s Republic of China, Tel +86-311-88602015, Email wangj_heb3y@163.com; zhuyanbin111@126.comBackground: As the worldwide population ages, the population receiving open wedge high tibial osteotomy (OWHTO) is growing, and surgical site infection (SSI) is a rare but fatal surgical complication. This study aimed to identify risk factors independently associated with SSI following OWHTO and develop a predictive nomogram.Methods: Clinical data of patients who received OWHTO and followed up for more than 12 months in our hospital were retrospectively reviewed. Multivariable logistic regression was performed to determine independent risk factors for SSI and to construct predictive nomograms. The study further illustrated the predictive performance of the model by using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).Results: A total of 1294 eligible patients were included in the study. Multivariate analysis revealed tobacco consumption (OR=3.44, p=0.010), osteotomy size ≥ 12 mm (OR=3.3, p=0.015), the use of allogeneic bone or artificial bone graft substitutes (allogeneic bone vs none, OR=4.08, p=0.037; artificial bone vs none, OR=5.16, p=0.047), Kellgren-Lawrence (K-L) grade IV (OR=2.5, p=0.046), systemic immune-inflammation index (SII) > 423.62 (OR=6.2, p< 0.001), high-sensitivity C-reactive protein (HCRP) > 2.6 mg/L (OR=2.42, p=0.044), and a higher level of fasting blood glucose (FBG) (OR=1.32, p=0.022) were the independent predictors of SSI. The cutoff score of the model was 148, with a sensitivity of 76.0% and specificity of 81.0%. The concordance index (C-index) and Brier score of the nomogram were 0.856 and 0.017, and the corrected values after 1000 bootstrapping validations were 0.820 and 0.018, respectively. Furthermore, the ROC curve, calibration curve, and DCA exhibited excellent predictive accuracy and clinical applicability of the model.Conclusion: This study developed a dynamic nomogram based on seven predictors, which allowed surgeons to individualize risk stratification of patients and intervene promptly to reduce SSI rates.Keywords: open wedge high tibial osteotomy, surgical site infection, risk factors, nomogram

Liujiazi Shao,1 Yang Liu,2 Junqiang Hao,1 Jiayi Li,1 Hongyu Wang,1 Fu-Shan Xue,1 Bijia Song,1 Lei Wan1 1Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 2Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of ChinaCorrespondence: Bijia Song, Email songbijia@163.comObjective: Our study aimed to demonstrate that the combination of sevoflurane inhalation with continuous intravenous anesthesia can effectively reduce the dosage of muscle relaxants, shorten extubation time under anesthesia while meeting the requirements of laparoscopic deep neuromuscular block (dNMB) in obese patients. Additionally, we sought to assess the potential reduction in postoperative residual muscle relaxants.Methods: Fifty-nine patients were randomly assigned. Anesthesia-related variables, such as anesthetics dosages, muscle relaxant effective time, clinical muscle relaxant time, muscle relaxant in vivo action time, muscle relaxant recovery time, body movement times, and extubation duration were recorded. Surgery-related variables (the Leiden-Surgical Rating Scale (L-SRS), duration of the procedure) were recorded. Pain was measured using the visual analog scale (VAS) score before leaving the PACU. The duration of the PACU stay and patients’ satisfaction levels in the PACU were also recorded.Results: Patients who inhaled sevoflurane during the operation required a lower dosage of muscle relaxant to achieve the same deep neuromuscular block (dNMB) effect. The time from stopping the rocuronium pump to T1 recovery of 90% was shorter, and the time for T1 to recover from 25% to 75% was faster among patients who inhaled sevoflurane during the operation. Furthermore, the sevoflurane combined with continuous intravenous anesthesia group exhibited a shorter extubation time for obese patients undergoing laparoscopic bariatric surgery, along with a reduced risk of experiencing hypoxemia and a shorter observation time in the PACU.Conclusion: Inhaling sevoflurane combined with continuous intravenous anesthesia during the operation effectively reduces the dosage of muscle relaxant required to achieve the same deep neuromuscular block (dNMB) effect. Additionally, this approach significantly shortens the extubation time for obese patients undergoing laparoscopic bariatric surgery and reduces the risk of experiencing hypoxemia, along with reducing the observation time in the PACU.Keywords: obese, laparoscopy bariatric surgery, rocuronium, sevoflurane, deep neuromuscular block

Baifen Song,1 Yanmei Huang,2 Jinzhu Ma,2 Liquan Yu,2 Yongzhong Yu,2 Chen Peng,1 Wenxue Wu1 1Key Laboratory of Animal Epidemiology and Zoonosis, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 2The College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of ChinaCorrespondence: Wenxue Wu, Key Laboratory of Animal Epidemiology and Zoonosis, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People’s Republic of China, Tel/Fax +86-010-62733048, Email wuwenxue@cau.edu.cnBackground: Virus infection can cause the changes of lncRNA expression levels to regulate the interaction between virus and host, but the relationship between BHV-1 infection and lncRNA has not been reported.Methods: In this study, in order to reveal the molecular mechanism of RNA in BoHV-1 infection, the Madin-Darby bovine kidney (MDBK) cells were infected with BoHV-1, transcriptome sequencing were performed by next-generation sequencing at 18 h or 24 h or 33 h of viral infection and then based on the competitive endogenous RNA (ceRNA) theory, lncRNA-miRNA-mRNA networks were constructed using these high-throughput sequencing data. The network analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation and exploration of ncRNA ceRNAs in BoHV-1 infection.Results: The results showed that 48 lncRNAs, 123 mRNAs and 20 miRNAs as differentially expressed genes, and the mitogen activated protein kinase (MAPK) pathway and calcium signaling pathway were significantly enriched in the ceRNA network. Some differentially expressed lncRNA genes were randomly selected for verification by RT-qPCR, and the results showed that their expression trend was consistent with the results of transcriptome sequencing data.Conclusion: This study revealed that BoHV-1 infection can affect the expression of RNAs in MDBK cells and the regulation of ceRNA network to carry out corresponding biological functions in the host, but further experimental studies are still necessary to prove the hub genes function in ceRNA network and the molecular mechanism in BoHV-1 infection.Keywords: BoHV-1, bioinformatics analysis, ceRNA network, next-generation sequencing

Minling Teng, Jian Suo, Haojie Zhong, Ningbo Kou, Bingwen Song, Guopeng Li School of Architecture and Fine Art, Dalian University of Technology, Dalian, 116000, People’s Republic of ChinaCorrespondence: Jian Suo, School of Architecture and Fine Art, Dalian University of Technology, Dalian, Liaoning Province, People’s Republic of China, Tel +86-138-4090-7234, Fax +86 411-84707504, Email suojian727@dlut.edu.cnBackground: With the expansion of comprehensive renovation projects in China’s old residential areas, residents’ actual sense of access and well-being has become a source of concern. As the population in old residential areas ages, the results of old renovation will have a significant impact on the older adults quality of life and subjective well-being.Purpose: To date, most relevant studies have focused on urban and community scales, with little discussion of the impact of neighborhood-level renewal outcomes on the well-being of older adults. As a result, the purpose of this research is to optimize the quality renewal elements of existing old residential areas based on the results of their renovation in order to create a more livable living environment for older adults in existing old residential areas.Methods: Based on a survey of old neighborhoods in Dalian, the study examines the mediating effect of psychological resilience between multi-quality renewal elements and the subjective well-being of the older adults, and it discusses the influence of multi-quality renewal elements on the subjective well-being of the older adults in different residential types.Results: According to the findings, multi-quality renewal elements of residence positively predicted the subjective well-being of the older adults; there was a significant mediating effect of psychological resilience between the renewal elements and subjective well-being of the older adults. The study confirms that multiple quality renewal elements can contribute to older people’s subjective well-being, and that psychological resilience plays an important role in the selection of multiple quality renewal elements and older people’s subjective well-being.Conclusion: The research provides guidance for the establishment of health-oriented approaches to environmental restoration in residential areas for the sustainable development of communities and cities.Graphical Abstract: Keywords: existing old residential areas, multi-quality renewal elements, older adults, subjective well-being, impact

Tingting Zheng,1,&ast; Wenjuan Hu,1,&ast; Hao Wang,1 Xiaoli Xie,2 Lang Tang,3 Weiyan Liu,4 Pu-Yeh Wu,5 Jingjing Xu,1,&ast; Bin Song1,&ast; 1Department of Radiology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Pathology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Ultrasound, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of General Surgery, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 5GE Healthcare, MR Research China, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Song; Jingjing Xu, Department of Radiology, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, 201199, People’s Republic of China, Email songbin@fudan.edu.cn; sb72778@189.cnPurpose: BRAF V600E mutation can compensate for the low detection rate by fine-needle aspiration (FNA) and is related to aggressiveness and lymph node metastasis. This study aimed to investigate the relationship between texture analysis features based on magnetic resonance imaging (MRI) and mutations.Methods: Retrospective analysis was performed on patients with postoperative pathology confirmed papillary thyroid carcinoma (PTC) from 2017 to 2021. One thousand one hundred and thirty-two texture features were extracted from T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) separately by outlining the tumor volume of interest (VOI). Univariate, minimum redundancy maximum relevance (mRMR), and multivariate analyses were used for feature selection to construct 3 models (T2WI, CE-T1WI, and combined model) to predict mutation. The reproducibility between observers was evaluated by intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) analysis was used to assess the performance of models. The diagnostic performance of the optimal cut-off value of models were calculated and validated by 10-fold cross-validation.Results: A total of 80 PTCs (22 BRAF V600E wild-type and 58 BRAF V600E mutant) were included in our study. Good interobserver agreement was found on texture features we selected (all ICCs > 0.75). The area under the ROC curves (AUCs) for the T2WI model, CE-T1WI model, and combined model were 0.83 (95% CI: 0.75– 0.91), 0.83 (95% CI: 0.73– 0.90), and 0.88 (95% CI: 0.81– 0.94), respectively. The accuracy, sensitivity, specificity, PPV, and NPV were 0.776, 0.679, 0.905, 0.905, and 0.679 for the T2WI model at a cut-off value of 0.674; 0.755, 0.750, 0.762, 0.808, and 0.696 for the CE-T1WI model at a cut-off value of 0.573; 0.816, 0.893, 0.714, 0.806, and 0.833 for the combined model at a cut-off value of 0.420.Conclusion: MRI-based texture analysis could be a potential method for predicting BRAF V600E mutation in PTC preoperatively.Keywords: magnetic resonance imaging, texture analysis, radiomics, papillary thyroid carcinoma, BRAF V600E

Jiamin Li,1 Chen Zhu,1 Ying Liu,1 Baoyun Song,2 Jingfen Jin,3 Yilan Liu,4 Xianxiu Wen,5 Shouzhen Cheng,6 Xinjuan Wu1 1Department of Nursing, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Nursing, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People’s Republic of China; 4Department of Nursing, Wuhan Union Hospital, Jianghan District, Wuhan, People’s Republic of China; 5Department of Nursing, Sichuan Academy of Medical Sciences and Sichuan People’s Hospital, Chengdu, People’s Republic of China; 6Department of Nursing, Sun Yat-sen University First Affiliated Hospital, Guangzhou, People’s Republic of ChinaCorrespondence: Xinjuan Wu, Email wuxinjuan@sina.comBackground: Pressure injury is a common problem in intensive care units. Critical care nurses play an important role in multidisciplinary teams performing pressure injury treatment. Identifying the clinical status of pressure injury treatment may contribute to improving care quality.Aim: To identify the knowledge, attitudes, and practices regarding pressure injury treatment in critical care nurses.Design: A cross-sectional survey.Methods: Secondary data were extracted from a multicenter clinical trial. Knowledge and attitudes toward pressure injury treatment were assessed through a self-administered eight-item questionnaire. The observed practices were recorded using a case report form. The report was in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement.Results: A total of 950 critical care nurses in 15 hospitals from six provinces/municipalities of China were investigated. The mean knowledge score was 2.89 ± 1.16 (95% confidence interval: 2.82– 2.97) out of a possible total of 5 points. The correct rates of selecting wound dressings and pain management were 34.4% and 45.6%, respectively. The mean attitude score was 9.07 ± 1.09 (95% confidence interval: 9.00– 9.13) out of a possible total of 12 points. A total of 2092 patient days of pressure injury treatment practices were observed and recorded. Repositioning was the most commonly employed treatment measure (98.8%). Foam dressing was the common dressing for stage I (53.6%), stage II (47.5%), and more severe pressure injury (67.9%), including stage III, IV, unstageable, and suspected deep tissue injury.Conclusion: Critical care nurses exhibited a generally low level of knowledge and moderate attitudes regarding pressure injury treatment. Practices of pressure injury treatment were generally acceptable.Keywords: pressure injury, treatment, knowledge, attitude, practice, evidence implementation

Bingxin Song,1 Shishi Zhou,2 Chenghui Li,2 Hongjuan Zheng,2 Xia Zhang,2 Xiayun Jin,2 Jianfei Fu,2 Huixian Hu1 1Department of Medical Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of China; 2Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of ChinaCorrespondence: Jianfei Fu, Department of Medical Oncology, Zhejiang University Jinhua Hospital, 351 Mingyue Road, Jinhua, 321000, Zhejiang Province, People’s Republic of China, Fax +86-579-82552856, Email 11218276@zju.edu.cn Huixian Hu, Department of Medical Hematology, Zhejiang University Jinhua Hospital, 351 Mingyue Road, Jinhua, Zhejiang Province, 321000, People’s Republic of China, Fax +86-579-82136611, Email huhuixian@zju.edu.cnObjective: Chemotherapy-induced thrombocytopenia (CIT) can lead to chemotherapy dose delay or reduction, and even serious bleeding. This study aimed to develop a CIT-predicting model based on the laboratory indices of cancer patients undergoing chemotherapy.Material and Methods: From Jun 1, 2017 to Dec 30, 2021, a total of 2043 patients who had received 7676 cycles of chemotherapy were retrospectively enrolled. A logistic regression analysis was performed to identify predictive factors, on the basis of which a nomogram model for predicting CIT was established. A bootstrapping technique was applied for internal validation. A generalized additive mixed model (GAMM) was constructed to analyze the trends in the changes of aspartate aminotransferase (AST), ratio of AST to alanine transaminase (ALT) (AST/ALT ratio), and platelet (PLT) count in patients with solid tumors. P values ≤ 0.05 were considered statistically significant.Results: The patient-based incidence of CIT was 20.51% and the cycle-based incidence was 10.01%. The multivariate analysis showed that AST level, AST/ALT ratio, and total bilirubin (Tbil), white blood cell (WBC), platelet (PLT), hemoglobin (Hb) levels were significantly associated with the risk of CIT. The GAMM analysis showed that PLT level was inversely associated with AST/ALT ratio and AST level, more significantly with AST/ALT ratio. And both exhibited statistically predictive abilities for CIT. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.793, a sensitivity of 0.543 and a specificity of 0.930.Conclusion: The AST/ALT ratio was inversely associated with the CIT risk in cancer patients. The GAMM model based on laboratory indices presented a high accuracy in predicting the risk of CIT, and a potential to be translated into clinical management.Keywords: chemotherapy-induced thrombocytopenia, solid tumors, AST/ALT-ratio, prediction model

Wenxian Sun,1 Luyang Zhang,1 Weishi Liu,1 Mengke Tian,1 Xin Wang,1 Jing Liang,1 Yuying Wang,1 Lan Ding,1 Lulu Pei,1 Jie Lu,2 Yuming Xu,1 Bo Song1 1Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Department of Epidemiology and Health Statistics College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Bo SongDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, 1st Jianshe Eastern Road, Zhengzhou, 450052, Henan Province, People’s Republic of ChinaTel +86-13603983297Fax +86-371-66975140Email fccsongb@zzu.edu.cnBackground: Stroke and myocardial infarction (MI) are associated with each other, as demonstrated in observational studies. However, it is unclear whether this relationship is causal, and the purpose of this study was to explore the bidirectional causality between stroke and MI.Methods: Causality between stroke and MI was assessed using two-sample Mendelian randomization (MR). All genetic instruments related to stroke (40,585 cases; 406,111 controls) and MI (43,676 cases; 128,199 controls) were derived from large published genome-wide association study. The MR analysis was calculated with inverse-variance weighting, MR-Egger, weighted mode, weighted median, and simple mode methods, and sensitivity analyses are used to detect the heterogeneity or pleiotropy.Results: Genetically predicted large-artery stroke (LAS) was causally related to higher odds of MI (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.06– 1.20, p = 1.0× 10− 4), and the causal effect of LAS on MI was significantly weakened (OR = 1.09, 95% CI: 1.02– 1.17, p = 0.017) after excluding the multipotent single-nucleotide polymorphisms (SNPs). MI phenotypes were genetically correlated with all ischemic strokes (OR = 1.15, 95% CI: 1.03– 1.28, p = 0.013) and LAS (OR = 1.39, 95% CI: 1.14– 1.71, p = 0.001); but a causal effect of MI on all ischemic strokes (OR = 1.00, 95% CI: 0.95– 1.28, p = 0.219) and LAS (OR = 1.26, 95% CI: 0.93– 1.69, p = 0.130) was not observed after excluding the multipotent SNPs.Conclusion: This MR analysis provides evidence to support the causal effect of LAS subtype on MI, and some factors act as confiding factors whereas others may act as mediators.Keywords: causal inference, single-nucleotide polymorphism, genome-wide association study, epidemiologic methods, large-artery stroke

Bijia Song, Junchao Zhu Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Junchao ZhuDepartment of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaEmail zhujunchao1@hotmail.comAbstract: Perioperative sleep disturbances are commonly observed before, during, and after surgery and can be caused by several factors, such as preoperative negative moods, general anesthetics, surgery trauma, and pain. Over the past decade, the fast-acting antidepressant effects of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine represent one of the most attractive discoveries in the field of psychiatry, such as antidepressant and anxiolytic effects. It is also widely used as a short-acting anesthetic and analgesic. Recent research has revealed new possible applications for ketamine, such as for perioperative sleep disorders and circadian rhythm disorders. Here, we summarize the risk factors for perioperative sleep disturbances, outcomes of perioperative sleep disturbances, and mechanism of action of ketamine in improving perioperative sleep quality.Keywords: perioperative sleep disturbances, ketamine, antidepressant, anxiolytic, anti-inflammation

Tingting Zheng,1 Wenjuan Hu,1 Hao Wang,1 Xiaoli Xie,2 Lang Tang,3 Weiyan Liu,4 Pu-Yeh Wu,5 Jingjing Xu,1 Bin Song1 1Department of Radiology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Pathology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Ultrasound, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of General Surgery, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 5GE Healthcare, MR Research China, Beijing, People’s Republic of ChinaCorrespondence: Bin Song; Jingjing Xu, Department of Radiology, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, 201199, People’s Republic of China, Email songbin@fudan.edu.cn; sb72778@189.cn

Lianghua Guo,1 Bin Song,1 Jianhong Xiao,1 Hui Lin,1 Junhua Chen,1 Xianghua Su2 1Department of Respiratory Medicine, Mindong Hospital of Fujian Medical University, Fuan City, 355000, People’s Republic of China; 2Department of Neurosurgery, Mindong Hospital of Fujian Medical University, Fuan City, 355000, People’s Republic of ChinaCorrespondence: Xianghua SuDepartment of Respiratory Medicine, Mindong Hospital of Fujian Medical University, No. 89 Heshan Road, Fuan City, 355000, Fujian Province, People’s Republic of ChinaEmail Suxianghua505@126.comBackground: Survival in non-small cell lung cancer (NSCLC) remains poor. Early detection of NSCLC is of great significance to provide a chance to improve survival.Aim: We constructed predictive models to evaluate the predictive value of four tumor biomarkers by including serum human epididymis protein 4 (HE4), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), and cytokeratin 19 fragment (CY21-1) on detecting NSCLC in a Chinese elderly population.Methods: A total of 363 patients with NSCLC and 433 subjects without cancer (healthy control group) were admitted to the respiratory department in our hospital. We assessed serum levels of these four tumor biomarkers in the two groups and then the predictive value of predictive models was evaluated.Results: Serum median values of HE4 (143.3 pmol/L), CEA (4.60 ng/mL), SCCA (1.52 ng/mL), and CY21-1 (5.36 ng/mL) in patients with NSCLC were significantly higher than the healthy control group, respectively (all P< 0.05). A multivariate logistic regression model showed that HE4 (OR=2.10, 95% CI=1.22– 4.42, P=0.013), CEA (OR=2.30, 95% CI=1.44– 4.53, P=0.004), SCCA (OR=2.20, 95% CI=1.29– 4.55, P=0.011), and CY21-1 (OR=2.60, 95% CI=1.56– 6.25, P< 0.001) were significantly and independently associated with increased risk of NSCLC on admission after confounding factors were corrected. Importantly, the ROC curve suggested HE4 had a good value on predicting NSCLC in the Chinese elderly population. Additionally, the predictive model (CEA+SCCA+CY21-1+HE4) had better idea capability to detecting the existence of NSCLC (AUC=0.954, 95% CI=0.927– 0.999, P< 0.001).Conclusion: Our study showed that several lung cancer-related biomarkers were used to build prediction models, which has good value for early prediction of NSCLC.Keywords: NSCLC, HE4, CEA, SCCA, CY21-1, Chinese elderly population, predictive value

Shengyi Long,1,&ast; Fang Peng,1,&ast; Baohui Song,1,&ast; Liang Wang,2 Jun Chen,2 Bingbing Shang1 1The Second Hospital of Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China; 2Laboratory Animal Center, Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Chen Email chenjun@dmu.edu.cnBingbing Shang Email shangbingbing@dmu.edu.cnBackground: Hepatocellular carcinoma (HCC) is one of the most serious malignancies. The main features of HCC are vascular invasion and drug resistance. Ferroptosis is a novel cell program that is involved in several diseases, such as cancer. Heat shock protein beta 1 (HSPB1) is a major component of heat shock proteins. A recent study showed that HSPB1 could be a new therapeutic target for colorectal cancer with 5-fluorouracil-acquired resistance. However, the functional role of HSPB1 in HCC remains unclear.Aim: The aim of this study is to clarify HSPB1 expression in HCC and its potential therapeutic and prognostic value.Methods: We collected data on HSPB1 expression levels in HCC and normal liver tissues from The Cancer Genome Atlas and Gene Expression Omnibus databases. We then validated it using immunohistochemistry (IHC). Receiver operating characteristic and Kaplan–Meier survival curves were used to investigate the role of HSPB1 in the prognosis analysis of HCC. Further, we used the online Search Tool for the Retrieval of Interacting Genes/Proteins website, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes to conduct enrichment analysis and identify the predictive signaling pathways. Meanwhile, we used the TIMER and GSVA package of R (v3.6.3) to analyze the association between HSPB1 and immunocyte infiltration.Results: Compared to normal tissues, there was differential expression of HSPB1 in pan-cancers. HSPB1 expression was higher in HCC tissues than in normal tissues (p< 0.05). There was an evident significant difference between HSPB1 mRNA levels and histologic grade, vascular invasion, and alpha-fetoprotein level (all p values< 0.05). Univariate analysis indicated that HCC patients with high HSPB1 levels had shorter overall survival rates than those with low HSPB1 levels (p< 0.05). MAPK14, HSPA8, MAPKAPK3, MAPKAPK5, and MAPKAPK2 are essential proteins that interact with HSPB1. There was a significant correlation between HSPB1 expression levels and immune cell infiltration, including CD4+ T cells (r=0.203, p< 0.05).Conclusion: High HSPB1 expression is closely associated with a worse prognosis in HCC patients, and HSPB1 may be a target of immunotherapy in HCC.Keywords: hepatocellular carcinoma, ferroptosis, HSPB1, immune cells infiltration, bioinformatics analysis

Shiyi Li,1,* Bijia Song,2,* Yang Li,1 Junchao Zhu1 1Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Anesthesiology, Beijing 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 ChinaTel +86 18940257257Email zhujunchao1@hotmail.comObjective: Decreased postoperative sleep quality remains a serious problem in surgical settings at present. The purpose of our study was to compare the effect of propofol vs sevoflurane on early postoperative sleep quality and complications of patients receiving laparoscopic surgery after general anesthesia.Methods: Seventy-four patients undergoing selective laparoscopic surgery under general anesthesia were randomly assigned to the propofol group or sevoflurane group. The wireless portable sleep monitor (WPSM) is used to collect sleep quality on the night before surgery (sleep preop 1), the first night after surgery (sleep POD 1), and the third night after surgery (sleep POD 3). Record the subjective sleep quality and dreaming state during the operation. The perioperative hemodynamics, postoperative sleep and complications were also evaluated.Results: Compared with Sleep preop 1, patients showed lower sleep efficiency, Stable sleep and Unstable sleep during Sleep POD 1 and Sleep POD 3. In addition, compared with the propofol group, the proportion of REM sleep in the sevoflurane group was much higher during Sleep POD 1 and Sleep POD 3, and the incidence of dreaming was also higher in the sevoflurane group. Patients in the propofol group had better pain relief at 2, 4, and 6 hours after surgery. And the incidence of postoperative nausea and vomiting and dizziness in the sevoflurane group was significantly higher than that in the propofol group.Conclusion: The degree of postoperative sleep efficiency was better on Sleep POD1 and Sleep POD3; the incidence of postoperative nausea and vomiting, and dizziness was lower; and postoperative pain was slighter when the operation was performed under propofol anesthesia compared with patients in the sevoflurane group. Propofol should be considered a better choice during the operation to promote the patient’s postoperative sleep quality, relieve postoperative pain and improve the incidence of postoperative dizziness and nausea and vomiting.Keywords: postoperative sleep quality, general anesthesia, propofol, sevoflurane

Jian Zhao,1,2,* Wei Zhang,1,2,* Jun Zhang,1 Yun-Tian Chen,1 Wen-Jie Ma,3 Si-Yun Liu,4 Fu-Yu Li,3,* Bin Song1,* 1Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 2Department of Radiology, Armed Police Force Hospital of Sichuan, Leshan 614000, Sichuan, People’s Republic of China; 3Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 4GE Healthcare (China), Beijing 100176, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Song Email songlab_radiology@163.comPurpose: In current clinical practice, early recurrence (ER) is not commonly discussed in perihilar cholangiocarcinoma (pCCA), and its risk factors for this disease have not been well clarified. We carried out this study to analyze the risk factors contributing to ER and explored the prognostic factors after curative resection for pCCA.Patients and Methods: A total of 335 consecutive pCCA patients were retrospectively analyzed. Risk factors contributing to ER were evaluated using univariate and multivariate logistic regression analyses. Prognostic factors of the ER group were determined by univariate and multivariate Cox regression models. The overall survival (OS) rate was calculated using the Kaplan–Meier method. The Log rank test was used for OS comparison.Results: Of the 335 cases, 258 patients (77.0%) developed tumor recurrence, 136 patients (40.6%) developed ER, and 122 patients (36.4%) developed late recurrence (LR) postoperatively. The median OS of the ER and LR groups was 15 months and 36 months, respectively (P< 0.001). The multivariate analysis revealed that poor pathological differentiation (P=0.006; moderate vs well, odds ratio [OR]=2.162, 95% confidence interval [CI] 0.753– 6.208, P=0.152; poor vs well, OR=4.839, 95% CI 1.544– 15.170, P=0.007), perineural invasion (OR=4.797, 95% CI 1.586– 14.510, P=0.005), and high levels of preoperative carbohydrate antigen 19– 9 (CA19-9) (OR=2.205, 95% CI 1.208– 4.026, P=0.010) were independent risk factors of developing ER after resection. Adjuvant chemotherapy (HR=0.383, 95% CI 0.154– 0.953, P=0.039) remained as the independent protective factor of OS in patients with ER.Conclusion: It is recommended that patients with poorly differentiated tumors, presence of perineural invasion, and high levels of preoperative CA19-9 receive closer follow-up and adjuvant chemotherapy following surgery.Keywords: perihilar cholangiocarcinoma, adjuvant chemotherapy, overall survival, curative-intent resection, early recurrence

Yuzhen Wang,1 Hong Li,2 Fakun Dong,3 Fang Yan,3 Min Cheng,4 Wanzhong Li,3 Qi Chang,3 Tianzi Song,3 Aoying Liu,3 Bo Song3 1Medical Imaging Specialty, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Basic Medical School, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 3School of Pharmacy, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 4Clinical Medical College, Weifang Medical University, Weifang, Shandong, People’s Republic of ChinaCorrespondence: Bo SongWeifang Medical University, Baotong Street, No. 7166, Weifang, Shandong 261053, People’s Republic of ChinaTel/Fax +86-536-8462490Email songsbob@163.comPurpose: Many exopolysaccharides (EPS) have significant emulsifying activity. Some EPS produced by the marine bacterial strain FYS have stronger emulsifying activity in the form of nanoparticles, suggesting that they could potentially form Pickering emulsions. We prepared novel EPS/CT Pickering nanoemulsions (ECPN) with EPS as emulsifiers and assessed their ability to ameliorate the poor permeability of calcipotriol (CT) in skin affected by psoriasis vulgaris.Methods: A strain of marine bacterium FYS was identified. Molecular weight, monosaccharide composition and microstructure of EPS were determined by gel permeation chromatography, high-performance liquid chromatography and scanning electron microscopy. EPS nanoparticles were prepared by adjusting the pH, and the emulsifying activity was studied at different pH. ECPN were prepared by ultrasound and optimized by the response surface method. The size distribution, microstructure, stability and in vitro drug release of ECPN were studied. The therapeutic effect of ECPN on psoriasis vulgaris was explored by animal experiments and characterizing histomorphology in vivo.Results: A phylogenetic tree revealed that FYS was a Bacillus halodurans strain. EPS produced by the strain were heteropolysaccharides with a three-dimensional network composed of glucose, galactose, glucuronic acid, rhamnose, galacturonic acid and mannose (32.0:34.3:9.7:7.4:10.3:6.3). The EPS can form nanoparticles at pH = 4– 6 with enhanced emulsifying ability. Transmission electron microscopy revealed that EPS nanoparticles adhered to the surface of oil droplets to stabilize the emulsions via a Pickering emulsification mechanism. The prepared ECPN have high stability with a sustained-release effect. Finally, animal experiments showed that ECPN effectively shortened the treatment course of psoriasis vulgaris.Conclusion: EPS is highly possible to have the potential Pickering emulsification mechanism. The stability of the nanoemulsion was high. ECPN also showed potential for use in the treatment of psoriasis vulgaris. This study provides new insight into the medical applications of EPS and the treatment of psoriasis.Keywords: Bacillus halotolerans, exopolysaccharides, response surface method, psoriasis

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

Man Luo,1,* Bijia Song,1,2,* 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 Zhu Department of AnesthesiologyShengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaEmail zhujunchao1@hotmail.comAbstract: General anesthesia produces a state of drug-induced unconsciousness that is controlled by the extent and duration of administered agents. Whether inhalation or intravenous in formulation, such agents may interfere with normal sleep–wake cycles, impairing postoperative sleep quality and creating complications. Electroacupuncture is a new approach widely applied in clinical practice during recent years. This particular technology helps regulate neurotransmitter concentrations in the brain, lowering norepinephrine and dopamine levels to improve sleep quality. It also alleviates surgical pain that degrades postoperative sleep quality after general anesthesia by downregulating immune activity (SP, NK-1, and COX-1) and upregulating serotonin receptor (5-HT1AR, 5-HT2AR) and endocannabinoid expression levels. However, large-scale, multicenter studies are still needed to determine the optimal duration, frequency, and timing of electroacupuncture for such use.Keywords: general anesthesia, sleep quality, acupoints, electroacupuncture

Enrui Chen,1,* Shangcong Han,1,* Bo Song,2 Lisa Xu,1 Haicheng Yuan,2 Mingtao Liang,3 Yong Sun1 1Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, People’s Republic of China; 2Department of Neurology, Qingdao Central Hospital, Qingdao, People’s Republic of China; 3Department of Pharmaceutics, School of Biomedical Science and Pharmacy, University of Newcastle, Newcastle, NSW, Australia*These authors contributed equally to this workCorrespondence: Yong SunDepartment of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, People’s Republic of ChinaTel +86-532-82991203Email sunyong@qdu.edu.cnBackground: Hyaluronic acid (HA) is a major component of extracellular matrix (ECM) and its over expression in tumor tissues contributes to the increase of interstitial fluid pressure (IFP) and hinders the penetration of nanoparticles into solid tumors.Materials and Methods: We here reported a tumoral microenvironment responsive multistage drug delivery system (NPs-EPI/HAase) which was formed layer by layer via electrostatic interaction with epirubicin (EPI)-loaded PEG-b-poly(2-(diisopropylamino)ethyl methacrylate)-b-poly(2-guanidinoethylmethacrylate) (mPEG-PDPA-PG, PEDG) micelles (NPs-EPI) and hyaluronidase (HAase). In this paper, we focused on the hyaluronidase-combined nanoparticles (NPs-EPI/HAase) for tumor penetration in tumor spheroid and solid tumor models in vitro and in vivo.Results: Our results showed that NPs-EPI/HAase effectively degrade the HA in ECM and facilitate deep penetration of NPs-EPI into solid tumor. Moreover, NPs-EPI mainly employed clathrin-mediated and macropinocytosis-mediated endocytic pathways for cellular uptake and were subsequently directed to the lysosomes for further drug release triggered by proton sponge effect. Compared with NPs-EPI, the HAase coating group showed an enhanced tumoral drug delivery efficacy and inhibition of tumor growth.Conclusion: Overall, our studies demonstrated that coating nanoparticles with HAase can provide a simple but efficient strategy for nano-drug carriers to enhance solid tumor penetration and chemotherapeutic efficacy.Keywords: hyaluronidase, nanoparticles, tumor penetration, ECM

Bijia Song, Yang Li, Xiufei Teng, Xiuyan Li, Yanchao Yang, Junchao Zhu Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Junchao ZhuDepartment of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaEmail zhujunchao1@hotmail.comObjective: Postoperative sleep disorders can cause serious adverse effects on postoperative outcomes. The purpose of our study was to compare the effects of the timing of surgery under general anesthesia on intraoperative anesthetic drug requirements, postoperative sleep quality and pain in patients.Materials and Methods: Eighty-four patients who underwent selective laparoscopic abdominal surgeries under general anesthesia were randomly assigned to the Day Group (8:00– 12:00) or the Night Group (18:00– 22:00). The portable sleep monitor (PSM) was used to determine sleep quality on the night before surgery (Sleep-preop), the first night after surgery (Sleep POD 1), and the third night after surgery (Sleep POD 3). The visual analog scale (VAS) was used to evaluate postoperative pain scores and the Athens Insomnia Scale (AIS) was used for assessing insomnia symptoms. The total dose of general anesthetics required and adverse effects after surgery were also assessed.Results: Compared to Sleep-preop, patients presented with a lower sleep efficiency and a higher AIS score during Sleep POD 1 and Sleep POD 3. Furthermore, the Night Group had a significantly lower proportion of rapid eye movement sleep, stable sleep, and unstable sleep than did the Day Group at Sleep POD 1 and Sleep POD 3. The dosage of propofol and remifentanil required in the Day Group was significantly higher than that in the Night Group. Furthermore, patients in the Day Group had better pain relief, with a lower VAS score at 1, 6, 12, and 24 hours after surgery. The incidences of postoperative nausea and vomiting and dizziness were significantly higher in the Night Group than those in the Day Group.Conclusion: Morning operations required a higher dose of anesthetic drugs than did evening operations, which may be related to the circadian rhythm. The degree of postoperative sleep disorders was greater when the operation was performed in the evening than in the morning, which was also associated with increased pain perception and increased incidence of postoperative adverse effects. Thus, our results suggest that patients with hyperalgesia and sleep disorders may benefit from operations performed in the morning.Keywords: morning operation, evening operation, sleep quality, general anesthesia, circadian rhythm

Abhijit H Phakatkar,1 Emre Firlar,1– 3 Laura Alzate1,†, Boao Song,2 Surya Narayanan,1 Ramin Rojaee,2 Tara Foroozan,2 Ramasubramonian Deivanayagam,2 David James Banner,1 Reza Shahbazian-Yassar,2 Tolou Shokuhfar1 1Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA; 2Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, IL 60607, USA; 3Institute for Quantitative Biomedicine, Rutgers University, Piscataway, NJ 08854, USA†Laura Alzate passed away on October 20, 2019Correspondence: Tolou ShokuhfarDepartment of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USATel +1 312 413 9872Email tolou@uic.eduReza Shahbazian-YassarDepartment of Mechanical and Industrial Engineering, University of Illinois at Chicago, IL 60607, USATel +1 312 996 3440Email rsyassar@uic.eduPurpose: Recently, two-dimensional (2D) nanomaterials are gaining tremendous attention as novel antibacterial platforms to combat against continuously evolving antimicrobial resistance levels. Among the family of 2D nanomaterials, black phosphorus (BP) nanosheets have demonstrated promising potential for biomedical applications. However, there is a need to gain nanoscale insights of the antibacterial activity of BP nanosheets which lies at the center of technical challenges.Methods: Ultra-large BP nanosheets were synthesized by liquid-exfoliation method in the eco-friendly deoxygenated water. Synthesized BP nanosheets were characterized by TEM, AFM, and Raman spectroscopy techniques and their chemical stability was evaluated by EDS and EELS elemental analysis. The antibacterial activity of BP nanosheets was evaluated at nanoscale by the ultramicrotome TEM technique. Further, HAADF-STEM image and EDS elemental line map of the damaged bacterium were utilized to analyze the presence of diagnostic ions. Supportive SEM and ATR-FTIR studies were carried out to confirm the bacterial cell wall damage. In vitro colony counting method was utilized to evaluate the antibacterial performance of ultra-large BP nanosheets.Results: Elemental EELS and EDS analysis of BP nanosheets stored in deoxygenated water confirmed the absence of oxygen peak. TEM studies indicate the various events of bacterial cell damage with the lost cellular metabolism and structural integrity. Colony counting test results show that as-synthesized BP nanosheets (100 μg/mL) can kill ∼ 95% bacteria within 12 hours.Conclusion: TEM studies demonstrate the various events of E. coli membrane damage and the loss of structural integrity. These events include the BP nanosheets interaction with the bacterial cell wall, cytoplasmic leakage, detachment of cytoplasm from the cell membrane, reduced density of lipid bilayer and agglomerated DNA structure. The EDS elemental line mapping of the damaged bacterium confirms the disrupted cell membrane permeability and the lost cellular metabolism. SEM micrographs and ATR-FTIR supportive results confirm the bacterial cell wall damage.Keywords: phosphorene, transmission electron microscopy, black phosphorus nanosheet, two-dimensional materials, antibacterial

Ruiteng Song,1 Fang Yan,1 Min Cheng,2 Fakun Dong,1 Yongqi Lin,1 Yuzhen Wang,3 Bo Song1 1School of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China; 2Clinical Medical College, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China; 3Medical Imaging Specialty, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of ChinaCorrespondence: Yuzhen Wang; Bo SongWeifang Medical University, Baotong Street, No. 7166, Weifang, Shandong 261053, People’s Republic of ChinaTel +86-536-8462490Email wangyz@wfmc.edu.cn; songsbob@163.comPurpose: As one of the classic anti-Canidia albicans (CA) and vulvovaginal candidiasis (VVC) drugs, nystatin (NYS) is limited by poor water solubility and easy aggregation. Traditional NYS vaginal delivery formulations do not fully adapt to the specific environment of the vaginal cavity. The use of exopolysaccharides (EPS) has great application potential in emulsifiers, but its use has not been reported in nanoemulsions. In this work, an EPS/NYS nanoemulsion (ENNE) was developed to improve the activities of NYS against CA and VVCMethods: The ENNE was prepared by ultrasonic method using EPS as an emulsifier, liquid paraffin oil as an oil phase, PEG400 as a co-emulsifier, and NYS as the loaded drug. ENNE preparation was optimized by response surface method. After optimization, in vitro and in vivo analysis of the anti-CA activity; animal experiments; staining with propidium iodide (PI), periodic acid-schiff (PAS), and hematoxylin-eosin (H&E); and cytokine experiments were performed to investigate the therapeutic ability against VVC.Results: The optimal formulation and preparation parameters of ENNE were determined as follows: EPS content of 1.5%, PEG400 content of 3.2%, NYS content of 700 μg/mL, paraffin oil content of 5.0%, ultrasonic time of 15 min, and ultrasonic amplitude of 35%. The ENNE showed an encapsulated structure with an average particle size of 131.1 ± 4.32 nm. ENNE exhibited high storage and pH stability, as well as slow release. The minimum inhibitory concentration (MIC) of ENNE against CA was only 0.125 μg/mL and the inhibition zone was 19.0 ± 0.5 mm, for greatly improved anti-CA effect. The prepared ENNE destroyed the membrane of CA cells, and exhibited good anti-CA effect in vivo and therapeutic ability against VVC.Conclusion: The results of this study will promote the application of EPS in nanotechnology, which should lead to new and effective local drug formulations for treating VVC.Keywords: Canidia albicans, ultrasonic, response surface method, antifungal

Qi Li,1 Jia Xu,1 Zheng He,2 Xue Wen,1 Fengmei Wang,1 Peng Zhang,1 Jun Li,1 Bei Song,1 Qingyong Wang,1 Ronghai Li,1 Hai Huang3 1Department of Clinical Laboratory of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China; 2Department of Clinical Laboratory, The PLA General Hospital, Beijing 100853, People’s Republic of China; 3Department of Urology, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, People’s Republic of ChinaCorrespondence: Hai HuangDepartment of Urology, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, People’s Republic of ChinaEmail huanghai257@126.comBackground: Matrine (MAT) exhibits higher efficacy of chemotherapy when it is combined with other chemotherapeutic drugs; however, the therapeutic efficacy of matrine in combination with docetaxel (DOC) for prostate cancer, or even androgen-independent prostate cancer, remains poorly understood and the underlying molecular mechanisms have not yet been clearly defined. In the present study, we investigated whether matrine combined with docetaxel can strengthen anti-cancer effect.Methods: In this study, 7 groups were established, including (1) blank control group (cells). (2) 0.1 g/L MAT group, (3) 0.5 g/L MAT group, (4) 0.1 g/L MAT+ 50 μg/L DOC group, (5) 0.5 g/L MAT+ 50 μg/L DOC group, (6) 0.1 g/L MAT+ 100 μg/L DOC group, and (7) 0.5 g/L MAT+ 100 μg/L DOC group. MTS assay was performed to detect the anti-proliferative effects of each group on DU145 and PC-3 cells. At the same time, Transwell assay was performed to detect anti-migrative and anti-invasive effects of each group on DU145 and PC-3 cells. Biochemical colorimetric method and enzyme-linked immunosorbent assay were performed to detect the levels of LDH, IL-1β and IL-18 of each group on DU145 and PC-3 cells. Flow cytometry (FCM) assay was used to do the apoptosis analysis on DU145 and PC-3 cells of each group. At last, Western blot analysis was performed to investigate the expression levels of caspase1 in cells of each group. Statistical analyses were performed with SPSS 17.0 (SPSS Inc, USA) software, and one-way ANOVA and Fisher’s exact test was taken.Results: MTS assay showed that matrine combined with docetaxel could inhibit both DU145 and PC-3 cells’ proliferation in a dose- and time-dependent manner. Transwell assay showed that matrine combined with docetaxel could inhibit both DU145 and PC-3 cells’ migration and invasion in a dose- and time-dependent manner. The levels of LDH, IL-1β and IL-18 of matrine combined with docetaxel-treated DU145 and PC-3 cells were significantly increased, compared with the untreated control cells. Flow cytometry, as well as Annexin-V/PI staining, showed a significant and dose-dependent increase in the number of early, as well as late-stage apoptotic cells in both DU145 and PC-3 cells compared with the untreated control cells. Western blot analysis showed that matrine combined with docetaxel treatment led to the expression of caspase1 in both DU145 and PC-3 cells.Conclusion: It may be more effective to use matrine in combination with docetaxel to treat androgen-resistant prostate cancer because matrine can help to affect proliferation, migration, invasion, apoptosis, metabolism, and have anti-inflammation effect on the tumor cells.Keywords: matrine, docetaxel, androgen-independent prostate cancer, DU145, PC-3

Wen-jing Zhang, Bing Song, Tao Yang Department of General Surgery, Tianjin First Central Hospital, Tianjin 300192, People’s Republic of ChinaCorrespondence: Bing Song Email song2002bing@163.comIntroduction: The objective of this study was to assess the clinical significance of determining the levels of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and TIMP-2 in the peripheral blood of patients with differentiated thyroid carcinoma (DTC).Methods: Forty-nine patients with benign thyroid lesions and 57 patients with DTC were examined using the enzyme-linked immunosorbent assay method preoperatively and 1 month after operation.Results: The levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the peripheral blood of patients with DTC were significantly higher than those measured in patients with benign thyroid disease (P0.05). However, after operation, these levels in the peripheral blood of patients with DTC were significantly lower (P

Jun-zi Wu,1,* Yuqing Yang,1,* Shude Li,2 Anhua Shi,1 Bo Song,1 Shiwei Niu,3 WenHui Chen,1 Zheng Yao1 1Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, School of Basic Medical, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, College of Basic Medicine, Kunming Medical University, Kunming, Yunnan 650500, People’s Republic of China; 3Department of Biotechnology, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People’s Republic of China*These authors contributed equally to this workCorrespondence: WenHui Chen; Zheng YaoYunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, School of Basic Medical, Yunnan University of Chinese Medicine, No. 1076, Yuhua Road, Chenggong District, Kunming, Yunnan 650500, People’s Republic of ChinaTel/fax +86 871 8855 7524Email cwh6581908@126.com; yaozhmail@126.comBackground: Compared with random copolymers, block copolymerization is easier to prepare for nanoparticles with core-shell structure, and they will have better glucose sensitivity and higher insulin loading.Purpose: In our study, insulin-loaded poly (3-acrylamidophenylboronic acid-block-N-vinyl caprolactam) p(AAPBA-b-NVCL) nanoparticles were successfully prepared and were glucose-sensitive, which could effectively lower the blood sugar levels within 72 hrs.Methods: The polymer of p(AAPBA-b-NVCL) was produced by reversible addition-fragmentation chain transfer polymerization based on different ratios of 3-acrylamidophenylboronic acid (AAPBA) and N-vinylcaprolactam (NVCL), and its structure was discussed by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance . Next, the polymer was manufactured into the nanoparticles, and the characteristics of nanoparticles were detected by dynamic light scattering, lower critical solution temperature, and transmission electron microscopy. After that, the cell and animal toxicity of nanoparticles were also investigated.Results: The results demonstrated that p(AAPBA-b-NVCL) was successfully synthesized, and can be easily self-assembled to form nanoparticles. The new nanoparticles included monodisperse submicron particles, with the size of the nanoparticle ranged between 150 and 300nm and are glucose- and temperature-sensitive. Meanwhile, insulin can be easily loaded by p(AAPBA-b-NVCL) nanoparticles and an effective sustained release of insulin was observed when the nanoparticles were placed in physiological saline. Besides, MTT assay revealed that cell viability was more than 80%, and mice demonstrated no negative impact on blood biochemistry and heart, liver, spleen, lung, and kidney after intraperitoneal injection of 10 mg/kg/d of nanoparticles. This suggested that the nanoparticles were low-toxic to both cells and animals. Moreover, they could lower the blood sugar level within 72h.Conclusion: Our research suggested that these p(AAPBA-b-NVCL) nanoparticles might have the potential to be applied in a delivery system for insulin or other hypoglycemic proteins.Keywords: N-vinylcaprolactam, NVCL, 3-acrylamidophenylboronic acid, AAPBA, nanoparticles, glucose-sensitive, temperature-sensitive

Bijia Song, Yang Li, Xiufei Teng, Xiuyan Li, Yanchao Yang, Junchao Zhu Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Junchao ZhuDepartment of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaEmail zhujunchao1@hotmail.comObjectives: The aim of our study was to compare the effect of using dexmedetomidine (DEX) during the daytime operation or the nighttime operation under general anesthesia on postoperative sleep quality and pain of patients.Methods: Seventy-five patients scheduled for elective laparoscopic abdominal surgeries under general anesthesia were randomly assigned to receive operation in the Day Group (8:00–12:00) and the Night Group (18:00–22:00). The Portable Sleep Monitor (PSM) was performed on the following 3 nights: the night before surgery (Sleep 1), the first night after surgery (Sleep 2), and the third night after surgery (Sleep 3). Postoperative pain scores using visual analogue scoring scale, subjective sleep quality using the Athens Insomnia Scale, total dose of general anesthetics and PCA pump press numbers were also recorded.Results: Intraoperative administration of DEX for patients in the Day Group could improve sleep quality with a higher sleep efficiency and a lower AIS subjective sleep quality than patients in the Night Group at Sleep 2 (P < 0.001 and P = 0.001, respectively) and Sleep 3 (P < 0.001, respectively). There were marked lower rapid eye movement (REM) sleep and Stable sleep in the Night Group than that in the Day Group at Sleep 2 (P < 0.001 and P = 0.032, respectively) and Sleep 3 (P < 0.001, respectively). Patients in the Day Group have better pain relief and less PCA pump press numbers than patients in the Night Group.Conclusion: Using dexmedetomidine during the daytime operation can better improve postoperative sleep quality and pain than nighttime operation in patients undergoing laparoscopic abdominal surgeries.Keywords: dexmedetomidine, sleep quality, general anesthesia, postoperative pain

Lu Zhao,1 Ruihao Wang,1,2 Hui Fang,1 Bo Song,1 Dongyi Liang,3 Yuming Xu11Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Neurology, University of Erlangen-Nuremberg, D-91054 Erlangen, Germany; 3Department of NICU, Zhengzhou Central Hospital, Zhengzhou, Henan, People’s Republic of ChinaBackground: The clinical manifestations of the transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome are variable, and involuntary movements have not been reported. The etiology and treatment of the syndrome are not entirely clarified.Case: A 25-year-old female presented with recurrent transient headache, involuntary movements (left upper extremity chorea) and paralysis. Lumbar punctures showed intracranial hypertension and cerebrospinal fluid pleocytosis. Symptoms and intracranial hypertension were relieved after administration of steroids.Discussion/conclusion: Chorea may also present in the HaNDL syndrome. Steroids might relieve the symptoms of the HaNDL syndrome, which indicates the possible treatment strategy for HaNDL and supports the infectious or postinfectious autoimmune etiology hypothesis.Keywords: syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL), involuntary movement, steroids, intracranial hypertension

Emre Firlar,1,2 Meagan Ouy,1 Leigha Covnot,1 Yuan Xing,3 Daniel Lee,1,4 Alessandro Chan,1,4 Yi He,3 Boao Song,2 Solomon Afelik,4 Yong Wang,3 Reza Shahbazian-Yassar,2 Jose Oberholzer,1,3 Tolou Shokuhfar1 1Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA; 2University of Illinois at Chicago, Department of Mechanical and Industrial Engineering, Chicago, IL, USA; 3University of Virginia, Department of Surgery, Charlottesville, VA, USA; 4University of Illinois at Chicago, Department of Surgery, Chicago, IL, USA Background: Islet cell transplantation is one of the key treatments for type 1 diabetes. Understanding the mechanisms of insulin fusion and exocytosis are of utmost importance for the improvement of the current islet cell transplantation and treatment of diabetes. These phenomena have not been fully evaluated due either to the lack of proper dynamic imaging, or the lack of proper cell preservation during imaging at nanoscales. Methods: By maintaining the native environment of pancreatic β-cells between two graphene monolayer sheets, we were able to monitor the subcellular events using in situ graphene liquid cell (GLC)-transmission electron microscopy (TEM) with both high temporal and high spatial resolution. Results: For the first time, the nucleation and growth of insulin particles until the later stages of fusion were imaged at nanometer scales. The release of insulin from plasma membrane involves the degradation of plasma membrane and drastic reductions in the shorter axis of the insulin particles. Sequential exocytosis results indicated the nucleation, growth and attachment of the new insulin particles to the already anchored ones, which is thermodynamically favorable due to the reduction in total surface, further reducing the Gibbs free energy. The retraction of the already anchored insulin toward the cell is also monitored for the first time live at nanoscale resolution. Conclusion: Investigation of insulin granule dynamics in β-cells can be investigated via GLC-TEM. Our findings with this technology open new realms for the development of novel drugs on pathological pancreatic β-cells, because this approach facilitates observing the effects of the stimuli on the live cells and insulin granules. Keywords: transmission electron microscopy, graphene liquid cell, insulin secretion, exocytosis

Li Y, Song B, Li Z, et al. Nat Sci Sleep. 2021;13:821–828. On page 823, Results, The Comparison of Demographic Characteristics of the Two Groups section, line 3, the text “duration of the operation (min) (P = 0.062)” should read “duration of surgery (min) (P = 0.517)”. Table 1 on page 824, the Duration of surgery (min) row is incorrect. The correct Table 1 is shown in Download Article. Read the original article

Ruolan Wang,1 Bin Song,2 Junrong Wu,1 Yanli Zhang,1 Aijie Chen,1 Longquan Shao1,3 1Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; 2Guizhou Provincial People’s Hospital, Guiyang 550002, China; 3Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou 510515, China Abstract: With the vigorous development of nanometer-sized materials, nanoproducts are becoming widely used in all aspects of life. In medicine, nanoparticles (NPs) can be used as nanoscopic drug carriers and for nanoimaging technologies. Thus, substantial attention has been paid to the potential risks of NPs. Previous studies have shown that numerous types of NPs are able to pass certain biological barriers and exert toxic effects on crucial organs, such as the brain, liver, and kidney. Only recently, attention has been directed toward the reproductive toxicity of nanomaterials. NPs can pass through the blood–testis barrier, placental barrier, and epithelial barrier, which protect reproductive tissues, and then accumulate in reproductive organs. NP accumulation damages organs (testis, epididymis, ovary, and uterus) by destroying Sertoli cells, Leydig cells, and germ cells, causing reproductive organ dysfunction that adversely affects sperm quality, quantity, morphology, and motility or reduces the number of mature oocytes and disrupts primary and secondary follicular development. In addition, NPs can disrupt the levels of secreted hormones, causing changes in sexual behavior. However, the current review primarily examines toxicological phenomena. The molecular mechanisms involved in NP toxicity to the reproductive system are not fully understood, but possible mechanisms include oxidative stress, apoptosis, inflammation, and genotoxicity. Previous studies have shown that NPs can increase inflammation, oxidative stress, and apoptosis and induce ROS, causing damage at the molecular and genetic levels which results in cytotoxicity. This review provides an understanding of the applications and toxicological effects of NPs on the reproductive system. Keywords: nanoparticles, toxic, reproductive, sperm, ovary, ROS

Ji Li, Yuting Han, Yue Lu, Baohui Song, Ming Zhao, Haiyang Hu, Dawei Chen Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China Background: Polyamidoamine (PAMAM) dendrimers modified by polyethylene glycol (PEG) have frequently been investigated as a delivery carrier for gene therapy. However, modification of PAMAM with PEG using covalent linkage significantly reduces the cellular uptake rate and the transfection efficiency. How to conquer these barriers becomes a burning question in gene delivery. Materials and methods: The present study constructed an effective disulfide bond-mediated cleavable RGD modified gene delivery system to overcome the aforementioned limitations. The disulfide bond was introduced between PAMAM dendrimers and PEG chains to realize the cleavage of PEG from the carrier system, whereas the arginine-glycine-aspartate (RGD) peptide was expected to promote the cellular uptake rate. A high mobility group Box 1 (HMGB1) protein containing nuclear localization signal (NLS) was simultaneously introduced to further promote gene expression efficiency. A pDNA/HMGB1/PAMAM-SS-PEG-RGD (DHP) nanocomplex was prepared via electrostatic interaction and characterized. Results: The results showed that DHP generated small particles and was able to condense and protect pDNA against degradation. In addition, the RGD peptide could significantly promote the cellular uptake of a nanocomplex. Intracellular trafficking and in vitro expression study indicated that the DHP nanocomplex escaped from lysosomes and the disulfide bonds between PAMAM and PEG cleaved due to the high concentration of GSH in the cytoplasm, pDNA consequently became exclusively located in the nucleus under the guidance of HMGB1, thereby promoting the red fluorescence protein (RFP) expression. Importantly, an in vivo antitumor activity study demonstrated that the DHP nanocomplex had higher antitumor activity than any other reference preparation. Conclusion: All these results confirm that DHP could be a new strategy for improving the transfection and expression efficiency in gene delivery. Keywords: PAMAM dendrimers, disulfide bond, RGD, HMGB1, gene delivery

Jia Liu,1 Yiyuan Kang,1 Suhan Yin,1 Bin Song,2 Limin Wei,3 Liangjiao Chen,4 Longquan Shao1 1Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 2Department of Stomatology, Guizhou Provincial People’s Hospital, Guiyang, 3Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 4Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China Abstract: Due to the widespread applications of zinc oxide nanoparticles (ZnO NPs), the potential exposure of workers, consumers, and scientists to these particles has increased. This potential for exposure has attracted extensive attention in the science community. Many studies have examined the toxicological profile of ZnO NPs in the immune system, digestive system, however, information regarding the toxicity of ZnO NPs in the nervous system is scarce. In this study, we detected the cytotoxicity of two types of ZnO NPs of various sizes – ZnOa NPs and ZnOb NPs – and we characterized the shedding ability of zinc ions within culture medium and the cytoplasm. We found that reactive oxygen species played a crucial role in ZnO NP-induced cytotoxicity, likely because zinc ions were leached from ZnO NPs. Apoptosis and cytoskeleton changes were also toxic responses induced by the ZnO NPs, and ZnOb NPs induced more significant toxic responses than ZnOa NPs in SHSY5Y cells. In conclusion, ZnO NPs induced toxic responses in SHSY5Y cells in a size-dependent manner, which can probably be attributed to their ion-shedding ability. Keywords: zinc oxide, nanoparticles, SHSY5Y cells, reactive oxygen species, apoptosis, cell cytoskeleton

Lingling Ou,1,2 Shaoqiang Lin,2 Bin Song,1 Jia Liu,1 Renfa Lai,2 Longquan Shao1 1Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Stomatology, the First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China Abstract: Graphene-based materials (GBMs) are widely used in many fields, including biomedicine. To date, much attention had been paid to the potential unexpected toxic effects of GBMs. Here, we review the recent literature regarding the impact of GBMs on programmed cell death (PCD). Apoptosis, autophagy, and programmed necrosis are three major PCDs. Mechanistic studies demonstrated that the mitochondrial pathways and MAPKs (JNK, ERK, and p38)- and TGF-β-related signaling pathways are implicated in GBMs-induced apoptosis. Autophagy, unlike apoptosis and necroptosis which are already clear cell death types, plays a vital pro-survival role in cell homeostasis, so its role in cell death should be carefully considered. However, GBMs always induce unrestrained autophagy accelerating cell death. GBMs trigger autophagy through inducing autophagosome accumulation and lysosome impairment. Mitochondrial dysfunction, ER stress, TLRs signaling pathways, and p38 MAPK and NF-κB pathways participate in GBMs-induced autophagy. Programmed necrosis can be activated by RIP kinases, PARP, and TLR-4 signaling in macrophages after GBMs exposure. Though apoptosis, autophagy, and necroptosis are distinguished by some characteristics, their numerous signaling pathways comprise an interconnected network and correlate with each other, such as the TLRs, p53 signaling pathways, and the Beclin-1 and Bcl-2 interaction. A better understanding of the mechanisms of PCD induced by GBMs may allow for a thorough study of the toxicology of GBMs and a more precise determination of the consequences of human exposure to GBMs. These determinations will also benefit safety assessments of the biomedical and therapeutic applications of GBMs. Keywords: graphene based materials, cell toxicity, programmed cell death, mechanisms

Chengrong Kang,1,2 Limin Wei,1 Bin Song,1 Liangjiao Chen,3 Jia Liu,1 Bin Deng,4 Xuan Pan,2 Longquan Shao1 1Department of Stomatology, Nanfang Hospital, Southern Medical University, 2Department of Stomatology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 3Department of Orthodontics, Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, 4Department of Stomatology, The General Hospital of People’s Liberation Army, Beijing, China Abstract: Porous tantalum (Ta) implants are highly corrosion resistant and biocompatible, and they possess significantly better initial stability than that of conventional titanium (Ti) implants. During loading wear, Ta nanoparticles (Ta-NPs) that were deposited on the surface of a porous Ta implant are inevitably released and come into direct contact with peri-implant osteoblasts. The wear debris may influence cell behavior and implant stabilization. However, the interaction of Ta-NPs with osteoblasts has not been clearly investigated. This study aimed to investigate the effect of Ta-NPs on cell proliferation and their underlying mechanism. The Cell Counting Kit-8 (CCK-8) assay was used to measure the cell viability of MC3T3-E1 mouse osteoblasts and showed that Ta-NP treatment could increase cell viability. Then, confocal microscopy, Western blotting, and transmission electron microscopy were used to confirm the autophagy induced by Ta-NPs, and evidence of autophagy induction was observed as positive LC3 puncta, high-LC3-II expression, and autophagic vesicle ultrastructures. The CCK-8 assay revealed that the cell viability was further increased and decreased by the application of an autophagy inducer and inhibitor, respectively. In addition, pre-treatment with autophagy inhibitor 3-methyladenine (3-MA) inhibited the Ta-NP-induced autophagy. These results indicate that the Ta-NPs can promote cell proliferation, that an autophagy inducer can further strengthen this effect and that an autophagy inhibitor can weaken this effect. In conclusion, autophagy was involved in Ta-NP-induced cell proliferation and had a promoting effect. Keywords: tantalum nanoparticles, osteoblast, autophagy, proliferation

Jia Wang,1,2 Shouren Fan,1,3 Jie Liu,2 Bao Song4 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, 2Department of Oncology, Shandong Cancer Hospital affiliated to Shandong University, 3Department of Intervention, Qihe People’s Hospital, 4Elementary Laboratory, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People’s Republic of China Abstract: Primary bone lymphoma is a rare and peculiar extranodal presentation of non-Hodgkin’s lymphoma, which threatens human health. It can be defined as a lymphoma that occurs in the bone, consisting of a single bone lesion with or without regional lymphadenopathies, and its underlying causes are largely unknown. In this case report, we describe a male who presented with left-sided distal forearm pain, swelling of 2 months duration, and progressive limited wrist motion for about 1 month. The patient had no significant medical history except diabetes. Magnetic Resonance Imaging demonstrated a sheet-like bone destruction area in the left-sided radius, localized discontinuous bone cortex, and adjacent soft tissue masses. Finally, a bone biopsy examined by histopathological and immunochemical methods confirmed a diagnosis of primary bone diffuse large B-cell lymphoma. Due to the rarity of this disease, the level of evidence supporting some diagnostic and therapeutic decisions remains low, and therefore, the details of the rare case may facilitate treatment of similar diseases and provide insight about this obscure lymphoproliferative malignancy. Also, related recent literature reports of primary bone lymphoma are reviewed. Keywords: DLBCL, diffuse large B-cell lymphoma, primary DLBCL bone lymphoma, radius, consolidation radiotherapy, rituximab

Yang Yang,1 Feng Xiao,1 Jin Wang,1 Bo Song,1 Xi-Hui Li,1 Jian Li,2 Zhi-Song He,3 Huan Zhang,4 Ling Yin5 1Department of Cardiac Surgery, 2Department of Thoracic Surgery, 3Department of Urology Surgery, 4Department of General Surgery, 5Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, People’s Republic of China Background: To investigate the possibility and feasibility of simultaneous cardiac and noncardiac surgery.Methods: From August 2000 to March 2015, 64 patients suffering from cardiac and noncardiac diseases have been treated by simultaneous surgeries.Results: Two patients died after operations in hospital; thus, the hospital mortality rate was 3.1%. One patient with coronary heart disease, acute myocardial infarction, and a recurrence of bladder cancer accepted emergency simultaneous coronary artery bypass grafting (CABG), bladder cystectomy, and ureterostomy. He died of acute cerebral infarction complicated with multiple organ failure on the 153rd day after operation. The other patient with chronic constrictive pericarditis and right lung cancer underwent pericardial stripping and right lung lower lobectomy, which resulted in multiple organ failure, and the patient died on the tenth day postoperatively. The remaining 62 patients recovered and were discharged. The total operative morbidity was 17.2%: postoperative hemorrhage (n, % [1, 1.6%]), pulmonary infection and hypoxemia (2, 3.1%), hemorrhage of upper digestive tract (1, 1.6%), incisional infection (3, 4.7%), subphrenic abscess (1, 1.6%), and postoperative acute renal failure and hemofiltration (3, 4.7%). Of the 62 patients discharged, 61 patients were followed up. Eleven patients died with 10 months to 10 years during the follow-up. The mean survival time is 116.2±12.4 months. The cumulative survival rate is 50.8%.Conclusion: Simultaneous surgeries in patients suffering from both cardiac and noncardiac benign or malignant diseases are safe and possible with satisfactory short-term and long-term survival. Keywords: cardiac surgery, noncardiac surgery, coronary artery bypass grafting (CABG), tumor resection, simultaneous surgery

Haipeng Wang,1,2 Zengjun Li,2 Yanlai Sun,2 Zhongfa Xu,2 Jianjun Han,2 Bao Song,3 Wentao Song,1,2 Chen Qin,1,2 Lei Yin1,2 1Department of Surgery, Shandong Academy of Medical Sciences, University of Jinan, Jinan, Shandong, People’s Republic of China; 2Department of General Surgery, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, University of Jinan, Jinan, Shandong, People’s Republic of China; 3Cancer Research Center, Shandong Provincial Key Laboratory of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, University of Jinan, Jinan, Shandong, People’s Republic of China Objective: To implement a meta-analysis to investigate the relationship between high-mobility group box 1 (HMGB1) overexpression in the tissue and serum of ovarian cancer patients, and to evaluate its prognostic significance.Methods: Searches were made of China National Knowledge Infrastructure, EMBASE, WanFang, PubMed, MEDLINE, and Web of Science databases up to August 2015, with no language or style restrictions. Reference lists of related studies were also carefully reviewed to identify additional articles.Results: The literature search identified a total of 12 relevant studies on HMGB1 expression for inclusion in the meta-analysis: seven in ovarian tumor tissue, four in ovarian tumor patient serum, and one in both tissue and serum. HMGB1 protein levels in ovarian cancer tissues were notably higher than those in normal ovarian tissues with no evidence of heterogeneity between studies (RD=0.64, 95% confidence interval (CI): 0.57–0.70, Z=18.70, P

Rui Fang,1,2 Shupei Qiao,1 Yi Liu,1 Qingyuan Meng,3 Xiongbiao Chen,2,4 Bing Song,5 Xiaolu Hou,6 Weiming Tian1 1Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin, People’s Republic of China; 2Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, SK, Canada; 3State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Department of Mechanical Engineering, University of Saskatchewan, Saskatoon, SK, Canada; 5College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK; 6Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Abstract: Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization. Keywords: myocardial infarction, gelatin nanoparticle, cardiomyocyte proliferation, injectable hydrogel