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Dafei Wei1 &ast;, Qi Wang2 &ast;, Shasha Liu,2 Xiaowu Tan,2 Lin Chen,2 Rongfang Tu,2 Qing Liu,2 Yuanhang Jia,2 Sha Liu2 1Department of Pediatrics, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sha Liu, Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China, Email 2018020001@usc.edu.cnObjective: To explore the clinical effects of different forced expiratory volume in 1s (FEV1) reference equations on chronic obstructive pulmonary disease (COPD) airflow limitation (AFL) classification.Methods: We conducted a COPD screening program for residents over 40 years old from 2019 to 2021. All residents received the COPD screening questionnaire (COPD-SQ) and spirometry. Postbronchodilator FEV1/FVC (forced vital capacity) < 0.7 was used as the diagnostic criterion of COPD and two reference equations of FEV1 predicted values were used for AFL severity classification: the European Respiratory Society Global Lung Function Initiative reference equation in 2012 (GLI-2012) and the Guangzhou Institute of Respiratory Health reference equation in 2017 (GIRH-2017). Clinical characteristics of patients in GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease) 1– 4 grades classified by the two reference equations were compared.Results: Among 3524 participants, 659 subjects obtained a COPD-SQ score of 16 or more and 743 participants were found to have AFL. The COPD-SQ showed high sensitivity (59%) and specificity (91%) in primary COPD screening. Great differences in COPD severity classification were found when applying the two equations (p < 0.001). Compared with GIRH-2017, patients with AFL classified by GLI-2012 equations were significantly severer. The relationship between symptom scores, acute exacerbation (AE) history distributions and COPD severities classified by the two equations showed a consistent trend of positive but weak correlation. Group A, B, C and D existed in all GOLD 1 to 3 COPD patients, but in GOLD 4, only Groups B and D existed. However, no clear significant differences were found in symptoms, AE risk assessments, risk factors exposure and even the combined ABCD grouping under the two equations.Conclusion: There were significant differences in COPD AFL severity classification with GLI-2012 and GIRH-2017 FEV1 reference equations. But these severity estimation differences did not affect symptoms, AE risk assessments and ABCD grouping of patients at all GOLD grades.Keywords: COPD, airflow limitation, FEV1%pred, symptoms assessment, acute exacerbation

Qingyu Wang,1,2 Xing Qu,3 Shannon H Houser,4 Yan Zhang,5 Meirong Tian,3 Qiong Zhang,6,7 Wei Zhang3 1West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, People’s Republic of China; 2HEOA Group, Institute for Healthy Cities and West China Research Center for Rural Health Development, Sichuan University, Chengdu, People’s Republic of China; 3Institute of Hospital Management, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Health Services Administration, the University of Alabama at Birmingham, Birmingham, AL, USA; 5Department of Maternity and Child Health Management, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, People’s Republic of China; 6Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 7State Key Laboratory of Oral Diseases & National Clinical Research, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xing Qu, Institute of Hospital Management, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, People’s Republic of China, +86 13880713452, Email qvxing@163.comBackground: Limited information is known about dental implementation by pediatric primary care physicians (PCPs) at the primary care level in China. This study aimed to explore the current status of primary oral care implementation and related influencing factors.Methods: A cross-sectional survey was conducted among PCPs in Sichuan Province, China. Multivariable logistic regression was used to analyse factors associated with CRA and dental referral for high caries-risk children.Results: A total of 504 out of 524 questionnaires remained for analysis. In all, 93.8% of PCPs reported that they usually or sometimes performed dental screening for children, 31.3% performed CRA, and 49.0% referred high caries-risk children to dentists. More CRA activities were associated with PCPs who encountered a greater number of children with caries during systematic care (adjusted OR: 2.37, 95% CI:[1.08,5.18], had dental knowledge training by pediatric dentists (aOR: 2.26, 95% CI:[1.36, 3.75], and learned pediatric dental knowledge on their own (aOR: 2.87, 95% CI: [1.51, 5.45]). In addition to the above associators, a higher rate of dental referrals for high caries-risk children was associated with having a dental department in the same work institute (aOR: 1.72, 95% CI: [1.09, 2.70] and having more confidence in their dental knowledge (aOR: 1.29, 95% CI: [1.04, 1.61]).Conclusion: Paediatric PCPs commonly implement dental screening but perform fewer CRAs and dental referrals for high caries-risk children during systematic health management in western China. To increase CRA activities and dental referral by paediatric PCPs, health policymakers could encourage interdisciplinary cooperation between dental professionals and paediatric PCPs.Keywords: caries risk assessment, dental referral, paediatric physicians, primary care, China

Shuai Wang,1 Peng Wang,1 Jun Liu,1 Chunxia Yang,1 Qiangyi Wang,2 Mingze Su,3 Ming Wei,1 Li Gu1 1Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Ming Wei; Li Gu, Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86-10-85231513, Email weiming@bjmu.edu.cn; guli2013227@foxmail.comPurpose: The biofilm formation of Candida albicans is an important virulence factor as it can increase tolerance to conventional antifungal drugs and the host immune system. The study aimed to assess the effect of essential fatty acids (EFAs) against biofilm formation and mature biofilms of C. albicans strains, which were isolated from vulvovaginal candidiasis and candidemia.Methods: The biofilm formation ability of C. albicans and antifungal activities of fluconazole were determined. Additionally, the effects of six EFAs [α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LOA), γ-linolenic acid (GLA), and arachidonic acid (AA)] against C. albicans under planktonic and biofilm conditions were evaluated.Results: 94.1% of C. albicans exhibited biofilm formation capacity, and 98.5% of C. albicans were susceptible to fluconazole. The biofilms of C. albicans were highly resistant to fluconazole with minimum biofilm eradication concentration values ≥ 64 μg/mL. The EFAs attenuated biofilm formation in a dose-dependent manner, and GLA displayed a remarkable inhibitory activity against biofilm formation of C. albicans. In addition, EPA, DHA, and GLA at 0.1 mM could inhibit the biofilm formation of C. albicans without affecting the planktonic growth rate. Notably, EPA and AA at 1 mM had both inhibitory and eradication activities on C. albicans biofilms.Conclusion: This is the first study to directly compare different EFAs for their capacity to affect C. albicans biofilm formation as well as biofilm eradication. These results suggest EPA and AA could serve as potential new antifungal agents for the treatment of clinical infections caused by C. albicans biofilms.Keywords: Candida albicans, polyunsaturated fatty acids, biofilm, inhibition, eradication

Qian Wang,1 Chen Yong,1 Min Wang,1 Lei Cui,1 Si-Ming Yuan1,2 1Department of Plastic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, People’s Republic of China; 2Department of Plastic Surgery, Jinling Hospital, Nanjing School of Clinical Medicine, Southern Medical University, Nanjing, 210002, People’s Republic of ChinaCorrespondence: Si-Ming Yuan, Department of Plastic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, People’s Republic of China, Email yuansm@163.comObjective: Refractory port-wine stain (PWS) usually contains hypertrophic, nodular lesions or severe scars due to improper treatment, making surgical treatment a necessity. This study aims to introduce our experiences in surgical management of refractory PWSs in the scalp and face.Methods: From January of 2013 to September of 2018, 25 patients with refractory PWSs in the scalp and face received surgeries in our department. Clinical manifestation of the disease, the surgical procedures and postoperative complications were reviewed. A Visual Analog Scale (VAS) was applied to evaluate the outcomes.Results: In this study, surgical procedures included serial resection (4 cases), complete resection followed by local flap transplantation (6 cases) or skin grafting (7 cases), and two-staged surgeries using expanded flaps (5 cases) or expanded prefabricated flap (3 cases). All the skin grafts and flaps survived well. Follow-up evaluation with VAS showed that most patients were satisfied with the surgery.Conclusion: The surgical procedures should depend on the site, area and type of the lesions and patients’ personal requirement. Individualized surgical treatment of refractory PWSs achieved satisfactory results in re-establishing symmetric facial contour and improving the overall appearance.Keywords: port-wine stain, surgery strategy, scalp and face

Yingze Li,&ast; Guojian Fang,&ast; Wei Cao,&ast; Jiali Yuan,&ast; Shuai Song, Hong Peng, Yuepeng Wang, Qunshan Wang Department of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qunshan Wang; Yuepeng Wang, Department of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, People’s Republic of China, Email wangqunshan@xinhuamed.com.cn; wangyuepeng@xinhuamed.com.cnBackground: In most cell types, replicative senescence (RS) is supposed to be a principle causative factor for aging. Atrial fibrosis, pathologically characterized by proliferation of atrial fibroblasts (AFs) and excessive accumulation of extracellular matrix proteins, is the most common substrate of atrial fibrillation (Afib) in the elderly. However, whether AFs’ RS develops in the aged and fibrotic left atrium (LA) and, if yes, what is the key regulator for the pathogenesis of AFs’ RS remain largely unknown.Methods: We obtained the left atrial tissues from young (6– 8 weeks old) and aged (24 months old) C57BL/6 male mice. Screening and validation of differential genes were performed using comparative analysis of RNA-seq results. Replicative senescence was examined in primary AFs after cell passage. Further gain-of-function and loss-of-function experiments were performed to explore the regulation of the AFs’ RS progression.Results: In the present study, we demonstrated that there was a considerable extent of AFs’ RS in the aged and fibrotic LA. Transcriptome screening showed that Ezh2 (Enhancer of zeste homolog 2) was significantly downregulated in the LA tissue of aged mice. Ezh2 is a histone methyltransferase that catalyzes H3K27me3 and mediates transcriptional silencing. We confirmed that Ezh2 was downregulated in the isolated pure senescent AFs. Knockdown of Ezh2 by siRNA or inhibition of Ezh2ʹs methyltransferase activities by GSK-126 and GSK-343 accelerated RS in the early passage of AFs, while its overexpression deaccelerated RS in the late passage of AFs. Mechanistically, Ezh2 suppressed CDKN2a (p16, p19) and Timp4 gene transcription by forming canonical H3K27me3 modifications in their promoter regions. Furthermore, the functional balance between Timp4 and MMP8 in AFs could be collapsed by changes in Ezh2 expression.Conclusion: These results thus indicate that Ezh2 is a key regulator of AFs’ RS and this work may provide a basis for future treatments for atrial fibrosis in the elderly.Graphical Abstract: Keywords: aging, replicative senescence, atrial fibrosis, Ezh2, H3K27me3

Nana Luo,1,2 Qiuyue Wang,1 Min Lei,1 Zhiyong Li,1 Tianhao Li,2 Pingsheng Hao2 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Tianhao Li; Pingsheng Hao, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, Sichuan Province, People’s Republic of China, Tel +86-13880986337 ; +86-13881965024, Fax +86-28-87732407, Email litianhao_doctor@163.com; hpswl@126.comCase Report: We present the case of a 51-year-old male who experienced temporary desquamation and recurrent burning sensation in primary skin lesions after the injection of dupilumab. The scaling lasted for 1 week and subsided, while the burning became aggravated with each injection of dupilumab, which gradually subsides after 8 weeks, and there was no recurrence since then.Conclusion: Dupilumab is an emerging and efficacious biologics medication for AD. The burning sensation and scaling we report may be the adverse events of dupilumab. Rare adverse reactions to biologics deserve the attention of physicians.Keywords: dupilumab, atopic dermatitis, burning, scaling, adverse event

Qiuyue Wang,1,2 Nana Luo,1,2 Min Lei,1,2 Lingyuan Zhong,1,2 Chunxiao Li,2,* Pingsheng Hao2,* 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxiao Li; Pingsheng Hao, Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610075, Sichuan, People’s Republic of China, Tel +86-18981937829 ; +86-13881965024, Fax +86-028-87732407, Email chunxiaolee@126.com; hpswl@126.comAbstract: Contact dermatitis and facial contact dermatitis caused by pesticides are not uncommon in China. However, clinically, due to the wide variety of pesticides, they mainly appear in the form of case reports. We reported a 70-year-old male patient developed facial irritant contact dermatitis (ICD) due to pyraclostrobin which was sprayed on his face. Initially, he felt facial burning and tingling, and localized erythematous-edematous and scaly rash appeared on his face as well as front hairline scalp. During the outpatient visit, the main symptoms were a facial burning sensation, itching, and tingling. The patient’s facial lesions improved after treatment. To better protect the skin of agricultural workers, preventive measures should be undertaken, such as personal protective equipment, gas masks, protective clothing and goggles, which are indispensable for manual pesticide spraying. Pyraclostrobin diluted according to the instructions is a potential source of ICD. Agricultural workers should undertake preventive measures during manual pesticide spraying. Safety education and publicity are particularly important. We need dermatologists to spread knowledge and agricultural workers to develop the right protective habits.Keywords: irritant contact dermatitis, pyraclostrobin, pesticide exposure, pesticides, farming, case report

Changxiu Li,1,&ast; Jing Wang,2,&ast; Qiushi Wang,3,4 Beibei Liu,4 Heqin Dang,1 Jin Li,5 Dapeng Hou4 1Department of Pharmacy, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China; 2Department of Respiratory and Critical Care, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China; 3Simulation Teaching Center, Capital Medical University, Beijng, People’s Republic of China; 4Department of Intensive Care Unit, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China; 5Department of Laboratory, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dapeng Hou, Department of Intensive Care Unit, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China, Tel +86-18505386932, Email tyfyhdp@163.comPurpose: To analyze the effect of a quick Pitt bacteremia score (qpitt) on the prognosis of patients with bloodstream infection (BSI) secondary to urinary tract infection (UTI) and to further explore its use in aiding appropriate selection of initial antibiotic treatment.Methods: Medical records of patients with BSIs secondary to UTIs who were admitted to our hospital from January 2018 to December 2020 were retrospectively collected. To screen for independent risk factors, logistic analysis was conducted on statistically significant variables. The receiver operating characteristic (ROC) curve was drawn with prognosis and death as the state variables to evaluate the predictive value. Patients were grouped by qpitt 2-point cutoff, to explore the impact of initial antimicrobial treatment regimens on poor prognosis and death in different subgroups. Poor prognosis was defined as a hospital length of stay (HLOS) ≥ 14 days or death within 28 days from BSI onset (ie, 28-day death).Results: A total of 266 patients were included in this study. In BSIs secondary to UTIs, we observed a pathogenic composition of 77.44% Gram-negative bacteria, 19.55% Gram-positive bacteria, and 3.01% fungi. The qpitt had poor predictive value for poor prognosis [area under ROC (AUROC) = 0.653, p < 0.001], while it had a high predictive value for death (AUROC = 0.890, p < 0.001). For patients with a qpitt ≥ 2, the poor prognosis and death rates of patients who were initially treated with carbapenem antibiotics were lower (p < 0.01). In comparison, initial treatment with carbapenem antibiotics had no significant effect on prognosis and death rates in patients with qpitt < 2 (p > 0.1).Conclusion: The qpitt is highly predictive for death in patients with BSIs secondary to UTIs and can be used to inform first-line antibiotic treatment strategy.Keywords: bloodstream infection, urinary tract infection, a quick Pitt bacteremia score, antibiotics

Yuanjie Qiu, Yan Wang, Nirui Shen, Qingting Wang, Limin Chai, Jin Liu, Yuqian Chen, Manxiang Li Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Manxiang Li, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277, West Yanta Road, Xi’an, 710061, People’s Republic of China, Tel/Fax +86-029-85323850, Email manxiangli@hotmail.comPurpose: High levels of red blood cell distribution width (RDW) and hypoalbuminemia are markers of poor prognosis in chronic obstructive pulmonary disease (COPD) patients. However, few studies have shown that the red blood cell distribution width–albumin ratio (RAR) is related to the mortality of COPD. This study aimed to explore the relationship between RAR and hospital mortality in COPD patients admitted to the intensive care unit (ICU).Patients and Methods: Patients were retrospectively incorporated from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and divided into two groups by a cutoff value of RAR. Propensity score matching (PSM) was performed to adjust for the imbalance of covariates. Logistic regression models and subgroup analyses were carried out to investigate the relationship between RAR and hospital mortality. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of RAR and decision curve analysis (DCA) to assess the clinical utility.Results: In total, 1174 patients were finally identified from the MIMIC-IV database. The cutoff value for RAR was 5.315%/g/dL. After PSM at a 1:1 ratio, 638 patients were included in the matched cohort. In the original and matched cohorts, the high RAR group had higher hospital mortality and longer hospital stays. Logistic regression analysis suggested that RAR was an independent risk factor for hospital mortality. The areas under the ROC curve in the original and matched cohorts were 0.706 and 0.611, respectively, which were larger than applying RDW alone (the original cohort: 0.600, the matched cohort: 0.514). The DCA indicated that RAR had a clinical utility.Conclusion: A higher RAR (> 5.315%/g/dL) was associated with hospital mortality in COPD patients admitted to ICU. As an easily available peripheral blood marker, RAR can predict hospital mortality in critically ill patients with COPD independently.Graphical Abstract: Keywords: chronic obstructive pulmonary disease, red blood cell distribution width, albumin, hospital mortality, MIMIC-IV

Lin Cheng, Pu Yao, Hongping Wang, Qian Yuan, Xiaowen Wang, Wei Feng, Fengjun Sun, Qian Wang Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, 400038, People’s Republic of ChinaCorrespondence: Qian Wang; Fengjun Sun, Email xqwq411@126.com; fengj_sun@163.comObjective: In this study, the Lactobacillus plantarum HFY15 (LP-HFY15) strain isolated from naturally fermented yak yogurt was investigated. An animal model of lupus nephritis was established by pristane to verify the interventional effect of LP-HFY15 on mouse lupus nephritis by regulating the transforming growth factor-β 1 (TGF-β 1) signaling pathway.Materials and Methods: Indexes in mouse serum and tissues were detected by kits, pathological changes in mouse kidney were observed by hematoxylin-eosin (H&E) staining, and quantitative polymerase chain reaction (qPCR) was used to detect TGF-β 1-related expression in mouse kidney tissue, which further elucidated the mechanism of LP-HFY15.Results: LP-HFY15 decreased the elevation of urinary protein and the levels of interleukin-6 (IL-6), IL-12, tumor necrosis factor alpha (TNF-α), and interferon γ (IFN-γ) in serum and kidney tissue. LP-HFY15 also reduced serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and raised total protein (TP), and albumin (ALB) levels in mice with nephritis. In addition, LP-HFY15 inhibited the positive rate of double-stranded deoxyribonucleic acid (dsDNA) antibodies in mice with nephritis. The observation of H&E sections showed that LP-HFY15 alleviated the glomerulus morphological incompleteness and inflammatory infiltration caused by nephritis. Further results showed that LP-HFY15 downregulated the mRNA expression of TGF-β 1, vascular endothelial growth factor (VEGF), and nuclear factor kappa-B (NF-κB) in the kidneys of lupus nephritis mice, and the expression of inhibitor of NF-κB (IκB-α), copper/zinc superoxide dismutase (Cu/Zn-SOD), and manganese superoxide dismutase (Mn-SOD) was also upregulated.Conclusion: These results indicated that LP-HFY15 plays a significant role in experimental intervention for lupus nephritis. The effect of LP-HFY15 was positively correlated with its concentration, and the effect was similar to that of prednisone at 109 CFU/kg.Keywords: lactic acid bacteria, lupus nephritis, TGF-β 1, dsDNA, pristane

Lei Liu,1 Mengmeng Wang,1 Guocheng Li,2 Qi Wang1,3 1Graduate School of Bengbu Medical College, Bengbu Medical College, Bengbu City, People’s Republic of China; 2School of Finance & Mathematics, West Anhui University, Lu’an City, People’s Republic of China; 3Department of Endocrinology, Lu’an Hospital of Anhui Medical University, Lu’an City, People’s Republic of ChinaCorrespondence: Qi Wang, Department of Endocrinology, Lu’an Hospital of Anhui Medical University, No. 21, Wanxi West Road, Lu’an City, People’s Republic of China, Tel +86-13966299858, Email 249451948@qq.comPurpose: The common cause of blindness in people with type 2 diabetes (T2D) is diabetic retinopathy (DR). Early fundus examinations have been shown to prevent vision loss, but routine ophthalmic screenings for patients with diabetes present significant financial and material challenges to existing health-care systems. The purpose of this study is to build a DR prediction model based on the extreme learning machine (ELM) and to compare the performance with the DR prediction models based on support machine vector (SVM), K proximity (KNN), random forest (RF) and artificial neural network (ANN).Methods: From January 1, 2020 to November 31, 2021, data were collected from electronic inpatient medical records at Lu’an Hospital of Anhui Medical University in China. An extreme learning machine (ELM) algorithm was used to develop a prediction model based on demographic data and blood testing and urine test results. Several metrics were used to evaluate the model’s performance: (1) classification accuracy (ACC), (2) sensitivity, (3) specificity, (4) Precision,(5) Negative predictive value (NPV), (6) Training time and (7) area under the receiver operating characteristic (ROC) curve (AUC).Results: In terms of ACC, Sensitivity, Specificity, Precision, NPV and AUC, DR prediction model based on SVM and ELM is better than DR prediction model based on ANN, KNN and RF. The prediction model for diabetic retinopathy based on elm is the best among them in terms of ACC, Precision, Specificity, Training time and AUC, with 84.45%, 83.93%, 93.16%,1.24s, and 88.34%, respectively. The DR prediction model based on SVM is the best in terms of sensitivity and NPV, which are, respectively, 70.82% and 85.60%.Conclusion: According to the findings of this study, the model based on the extreme learning machine presents an outstanding performance in predicting diabetic retinopathy thus providing technological assistance for screening of diabetic retinopathy.Keywords: type 2, diabetic retinopathy, extreme learning machine, predictive model

Zhang S, Wang Q, Li D, et al. Cancer Manag Res. 2020;12:10389–10396. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors did not respond to our queries, nor did they provide original data for their study. As verifying the validity of the published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Qiu Wang, Xiuxian Huang, Wensheng Lu Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Wensheng Lu, Email Lwswxqz@163.com

Zheng S, Zhang M, Bai H, et al. Int J Nanomedicine. 2019;14:9513–9524. The authors have advised due to an error at the time of figure assembly, the image of Spleen at 1 day in Figure 8B on page 9522 is incorrect. The correct Figure 8 is shown below. Figure 8 In vivo toxicity test of Mn-MoS2 QDs: (A(a–l)) Mouse serum biochemistry analysis and blood routine analysis before (0d, control) and after injection of Mn-MoS2 QDs for 1, 7, 21d. (B) Histological images of the heart, lungs, liver, spleen and kidneys of mice 1, 7 and 21 days post-intravenous injection of Mn-MoS2 QDs and in control mice. The organs were sectioned and stained with hematoxylin and eosin (H&E) and observed under a light microscope, scale bar = 100 μm. The authors apologize for this error and advise it does not affect the results of the paper.

Jia-Qi Ning,1,2 Jian-Sheng Luo,1,2 Ling-Ling Ding,2 Yu-Hong Guo,3 Zhuo-Ya Chen,2 Qi Wang,2 Rui-Ling Zhou2 1Department of Anesthesiology, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 3Department of Emergency, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of ChinaCorrespondence: Ling-Ling Ding, Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China, Tel/Fax +86 1087906647, Email dignlilbc@outlook.com; dinglingling301@126.comObjective: This study aimed to evaluate the effect of electroacupuncture preconditioning on regional cerebral oxygen saturation (rSO2) levels in elderly patients with diabetes.Methods: Forty patients undergoing elective diabetic foot surgery were enrolled in this study. All patients were aged 65 years and above and weighed 45– 75 kg. All were characterized as class II or III according to the American Society of Anesthesiologists’ physical status classification system. Patients were divided randomly into an electroacupuncture group (group E) and a control group (group C); both groups comprised 20 patients. In group E, the DU20 (Baihui), DU24 (Shenting), and EX-HN1 (Sishencong) acupoints were selected for electroacupuncture 30 min prior to administering anesthesia, while in group C, patients underwent routine anesthesia without electroacupuncture. The patients in both groups were anesthetized using a sciatic nerve block. The number of cases with increased or decreased regional oxygen saturation (rSO2) compared with the baseline as well as rSO2 variability in the two groups were recorded and compared.Results: There was no significant difference in the preoperative rSO2 values between the two groups (54.4 ± 4.8 (L), 53.9 ± 5.2 (R) [group C] vs 54.1 ± 5.2 (L), 54.5 ± 4.6 (R)[group E]). Compared with group C, the rSO2 in group E increased (50.3 ± 3.9 [group C] vs 58.4 ± 3.2[group E]), and this difference was statistically significant (P < 0.001).Conclusion: Electroacupuncture stimulation can increase rSO2 levels in patients with diabetes.Clinical Registration Number: ChiCTR2100048783 (http://www.chictr.org.cn).Keywords: electroacupuncture, preconditioning, regional cerebral oxygen saturation, diabetes

Jian Xu,1,&ast; Yingli Ma,2,&ast; Haibing Mei,1 Qimin Wang1 1Department of Radiology, Ningbo Women & Children’s Hospital, Ningbo, People’s Republic of China; 2Department of Neurology, Ningbo Hospital of Traditional Chinese Medicine, Ningbo, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haibing Mei, Department of Radiology, Ningbo Women & Children’s Hospital, Ningbo, People’s Republic of China, Email meihbgg@163.comBackground: The status of pelvic lymph node (PLN) metastasis affects treatment and prognosis plans in patients with cervical cancer. However, it is hard to be diagnosed in clinical practice.Purpose: The present study aimed to evaluate the diagnostic value of multimodal magnetic resonance imaging (MRI) in discriminating between metastatic and non-metastatic pelvic lymph nodes (PLNs) in cervical cancer.Methods: This retrospective study analyzed MRIs of 209 PLNs in 25 women with pathologically proven cervical cancer. All PLNs had been assessed by pre-treatment multimodal MRIs, and their status was finally confirmed by histopathology. In conventional MRI, lymph node characteristics were compared between metastatic and non-metastatic PLNs. Signal intensity, time–intensity curve (TIC) patterns minimal and mean apparent diffusion coefficients (ADC) were compared between them in DWI. In DCE-MRI, quantitative (Ktrans, Kep and Ve) analyses were performed on DCE-MRI sequences, and their predictive values were analyzed by ROC curves.Results: Of 209 PLNs, 22 (10.53%) were metastases and 187 (89.47%) were non-metastases at histopathologic examination. Considering a comparison of lymph node characteristics, the short axis size, the long axis size, and the boundary differed significantly between the two groups (P< 0.05).The differences in ADCmin, TIC types, Ktrans and Ve between metastatic and non-metastatic PLNs were significant as well (P< 0.05). The good diagnostic performance of multimodal MRI was shown in discriminating between metastatic and non-metastatic PLNs, with the sensitivity of 85.0% (17/20), specificity of 97.3% (184/189), and accuracy of 96.2% (201/209). ROC analyses showed that the diagnostic accuracy of ADCmin, Ktrans and Ve for discriminating between metastatic and non-metastatic PLNs in cervical cancer was 83.7%, 91.4%, and 92.4% with the cut-off values of 0.72 × 10− 3mm2/s, 0.52 min− 1, and 0.53 min− 1, respectively.Conclusion: Multimodal MRI showed good diagnostic performance in determining PLN status in cervical cancer.Keywords: multimodal magnetic resonance imaging, cervical cancer, lymphatic metastasis, apparent diffusion coefficient

Qixun Wang,1,&ast; Jinping Liu,1,&ast; Iokfai Cheang,2,&ast; Jinghang Li,3 Tingzhen Chen,4 Yanxiu Li,4 Bo Yu1 1Department of Cardiovascular Surgery, The First People’s Hospital of Lianyungang, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, 222000, Jiangsu, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of China; 3Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of China; 4Department of Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Yu, Department of Cardiovascular Surgery, The First People’s Hospital of Lianyungang, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, 222000, Jiangsu, People’s Republic of China, Email okpopo@163.com Yanxiu Li, Department of Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of China, Email liyanx2008@126.comBackground: E2F transcription factors (E2Fs), code a family of pivotal transcription factors, have been identified as key regulators in tumor tumorigenesis. However, the function of E2F family in human lung adenocarcinoma (LUAD) have not been fully elucidated.Methods: Herein, The Cancer Genome Atlas (TCGA) databases, Kaplan-Meier plotter, cBioPortal and TIMER were used to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of E2Fs in LUAD patients.Results: The expression levels of E2Fs (E2F1-8) were all significantly upregulated in LUAD tissues compared with normal lung tissues. All eight E2Fs had low rates of gene mutation in LUAD patients from cBioPortal databases. Survival analysis revealed that E2F2 (P=0.038; HR 1.36; 95% CI 1.02– 1.81), E2F7 (P< 0.001; HR 1.78; 95% CI 1.33– 2.39) and E2F8 (P=0.03; HR 1.37; 95% CI 1.02– 1.82) were significantly associated with poor prognosis. Multivariate cox regression analysis found that only E2F7 (P< 0.001; HR 2.72; 95% CI 1.75– 4.25) was an independent prognostic predictor in LUAD after adjusting common clinical parameters. The receiver operating characteristic (ROC) analysis also found that E2F7 had high diagnostic value for LUAD (AUC=0.901). Further analysis found that E2F7 was significantly associated with LUAD immune cell infiltration of B cell, T cell, neutrophil, and myeloid dendritic cell. E2F7 also have positive correlations with immune checkpoint genes including SIGLEC15, CD274, HAVCR2, PDCD1LG2, CTLA4, TIGIT, LAG3 and PDCD1 in LUAD.Conclusion: Our findings showed various association of E2F7 in LUAD diagnostic and prognostic aspects, which suggested its potential in becoming a novel biomarker.Keywords: lung adenocarcinoma, E2F transcription factors, TCGA, prognosis, immune cell infiltration

Xiujiao Wang,1,&ast; Dongju Feng,2,&ast; Yao Ke,1 Lei Gu,1 Chengyin Lv,1 Miaojia Zhang,1 Qiang Wang,1 Yanyan Wang1 1Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Wang; Yanyan Wang, Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +86-13913889877 ; +86-13813892892, Fax +86-25-68306893, Email jerrytortoise@163.com; yongchy@sina.comPurpose: Neuropsychiatric systemic lupus erythematosus (NPSLE) is the main cause of disability and death in systemic lupus erythematosus (SLE). It can cause cognitive impairment and organic brain syndrome. Brain-reactive antibodies, such as anti-DNA/anti-N-methyl-D-aspartate receptor (NMDAR) antibodies (DNRAbs), anti-microtubule-associated protein 2 (anti-MAP2) antibodies, and anti-glial fibrillary acidic protein (anti-GFAP) antibodies are thought to participate in the progression of NPSLE and thus considered potential diagnostic biomarkers, but whether they can be used for evaluating therapeutic efficacy in NPSLE is unknown.Patients and methods: Overall, 17 NPSLE patients and 10 non-SLE controls were included in this study. All the patients were treated with glucocorticoid (GC) pulse therapy. Serum and cerebrospinal fluid (CSF) concentrations of DNRAbs and anti-MAP2 and anti-GFAP antibodies were measured using enzyme-linked immunosorbent assay. The differences between the CSF concentrations of these antibodies in NPSLE patients before and after GC pulse therapy were analyzed.Results: CSF concentrations of DNRAbs and anti-MAP2 and anti-GFAP antibodies were significantly higher in NPSLE patients compared to the non-SLE controls. Among the patients, CSF concentration of DNRAbs was significantly higher in the patients with acute confusional state (ACS) than in those with non-ACS diffuse NPSLE or focal NPSLE. Additionally, CSF concentration of DNRAbs was significantly correlated with QIgG (r=0.4884, P=0.0467) and IgG index (r=0.5319, P=0.0280) in NPSLE patients. Moreover, CSF concentrations of DNRAbs, anti-MAP2, and anti-GFAP antibodies and QIgG were significantly decreased after GC pulse therapy in NPSLE patients.Conclusion: These results indicate that CSF DNRAbs and anti-MAP2 and anti-GFAP antibodies are potential biomarkers for evaluating therapeutic efficacy in NPSLE.Keywords: autoantibodies, neuropsychiatric systemic lupus erythematosus, efficacy evaluation, CSF biomarkers

Carmel L Mercado,1,2 Colin P Froines,3 Eric D Gaier,4– 7 Qinyun Wang,8 Maanasa Indaram,8 Michael J Wan,9 Ankoor S Shah,4– 6 Euna B Koo10 1Department of Ophthalmology, University of Washington, Seattle, WA, USA; 2Department of Ophthalmology, Seattle Children’s Hospital, Seattle, WA, USA; 3School of Medicine, University of Washington, Seattle, WA, USA; 4Department of Ophthalmology, Boston Children’s Hospital, Boston, MA, USA; 5Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA; 6Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; 7Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA; 8Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA; 9Department of Ophthalmology and Vision Sciences, SickKids, Toronto, ON, Canada; 10Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USACorrespondence: Euna B Koo, Department of Ophthalmology, Stanford University School of Medicine, 2452 Watson Ct, Palo Alto, CA, 94303, USA, Tel +1 650-723-6995, Email eunakoo@stanford.eduPurpose: The objective of this study was to identify the prevalence of CMV ocular disease in children and to identify associated risk factors for ocular involvement.Design: Retrospective multicenter, cross-sectional study.Methods: Setting: Hospitalized patients screened for CMV viremia by PCR between 2005 and 2018 at four pediatric referral centers. Participants: Seven-hundred and ninety-three children showed CMV viremia (> 135 copies/mL by polymerase chain reaction; PCR). Main Outcomes and Measures: (1) Occurrence of ophthalmologic examination. (2) Presence of CMV ocular disease, defined as retinitis, vasculitis, hemorrhage, optic nerve atrophy, or anterior uveitis in the setting of CMV viremia without other identifiable causes.Results: A total of 296/793 (37%) underwent ophthalmologic examination following CMV viremia. A total of23/296 patients (8%) had ocular symptoms prompting evaluation while the rest had eye exams for baseline screening unrelated to CMV viremia. Of these, 13 cases (4% of those with an eye exam) with ocular disease were identified (three congenital CMV, five severe combined immunodeficiency disorder (SCID) status post-stem cell transplantation, three hematologic malignancy status post-stem cell transplantation for two of them, one Evans syndrome status post-stem cell transplantation, and one medulloblastoma status post-bone marrow transplantation). No patients with solid organ transplantation developed CMV ocular disease in our cohort.Conclusion: CMV ocular disease was a rare occurrence in this cohort without an identifiable pattern across sub-groups. Excluding the three congenital CMV cases, nine out of ten patients with CMV ocular disease were status post-stem cell transplantation. We provide integrated screening guidelines based on the best available evidence for this rare condition.Keywords: cytomegalovirus, retinitis, CMV, screening guidelines, pediatrics

Dan Li,1,2 Qiang Wang,3 Chengyou Jia,1 Zhongwei Lv,1 Jianshe Yang1,3 1Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 3Basic Medical School, Gansu Medical College, Pingliang, 744000, People’s Republic of ChinaCorrespondence: Jianshe Yang, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China, Tel/Fax +86-21-66302721, Email yangjs@impcas.ac.cnAbstract: The coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a multi-organ and multi-system disease with high morbidity and mortality in severe cases due to respiratory failure and severe cardiovascular events. However, the various manifestations of neurological and psychiatric (N/P) systems of COVID-19 should not be neglected. Some clinical studies have reported a high risk of N/P disorders in COVID-19 and post-COVID-19 patients and that their outcomes were positively associated with the disease severity. These clinical manifestations could attribute to direct SARS-CoV-2 invasion into the central nervous system (CNS), which is often complicated by systemic hypoxia, the dysfunctional activity of the renin–angiotensin system and other relevant pathological changes. These changes may remain long term and may even lead to persistent post-COVID consequences on the CNS, such as memory, attention and focus issues, persistent headaches, lingering loss of smell and taste, enduring muscle aches and chronic fatigue. Mild confusion and coma are serious adverse outcomes of neuropathological manifestations in COVID-19 patients, which could be diversiform and vary at different stages of the clinical course. Although lab investigations and neuro-imaging findings may help quantify the disease’s risk, progress and prognosis, large-scale and persistent multicenter clinical cohort studies are needed to evaluate the impact of COVID-19 on the N/P systems. However, we used “Boolean Operators” to search for relevant research articles, reviews and clinical trials from PubMed and the ClinicalTrials dataset for “COVID-19 sequelae of N/P systems during post-COVID periods” with the time frame from December 2019 to April 2022, only found 42 in 254,716 COVID-19-related articles and 2 of 7931 clinical trials involved N/P sequelae during post-COVID periods. Due to the increasing number of infected cases and the incessant mutation characteristics of this virus, diagnostic and therapeutic guidelines for N/P manifestations should be further refined.Keywords: COVID-19, neurological, post-COVID, psychiatric, SARS-CoV-2, sequelae

Lichuan Zeng,1,&ast; Qu Wang,2,&ast; Haodong Liao,1,&ast; Fengchun Ren,1 Yudong Zhang,1 Jian Du,3 Huaqiang Liao,1 Mingguo Xie,1 Wenbin Wu3 1Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Ultrasound, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingguo Xie, Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, People’s Republic of China, Email 767030837@qq.com Wenbin Wu, Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, People’s Republic of China, Email wwb1201@vip.sina.comPurpose: We aimed to investigate the prevalence of fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) and the clinical–radiological correlation in transient ischemic attack (TIA) patients.Materials and Methods: We performed a retrospective analysis of TIA patients who had undergone magnetic resonance imaging (MRI) within 24 h of symptom onset. Two independent neuroradiologists investigated the presence of FVHs, large-artery severe stenosis or occlusion (LASO) in magnetic resonance angiograms, and the nature of factors associated with FVH.Results: A total of 207 patients were enrolled in this study. FVHs were detected in 42 (20.3%) patients, in whom atrial fibrillation (AF) was confirmed in 25 (59.5%) cases and LASO was confirmed in 30 (71.4%) cases. The corresponding figures were 33 (20.0%) and 10 (6.1%), respectively, for the 165 FVH-negative patients. Logistic regression analysis showed that time from symptom onset to MRI (odds ratio [OR] = 0.82, 95% CI 0.76– 0.97, p = 0.042), previous stroke (OR = 2.95, 95% CI 1.58– 6.74, p = 0.002), AF (OR = 5.83, 95% CI 2.24– 9.46, p < 0.001), and LASO (OR = 4.28, 95% CI 2.96– 10.28, p < 0.001) were independently associated with FVH. Overall, the sensitivity and specificity of FVH for predicting LASO were 0.75 and 0.93, respectively, and the positive predictive value, negative predictive value, and accuracy were 0.71, 0.94, and 0.89, respectively. The area under the receiver operating characteristic curve was 0.839. FVH-positive TIA patients with LASO had less AF (14 [46.7%] versus 11 [91.7%], p = 0.019) and longer times from symptom onset to MRI (6.8 ± 2.8 h versus 4.8 ± 1.3 h, p = 0.004) than those without LASO.Conclusion: The presence of FVH could be an important marker in TIA patients. Many factors, including LASO, AF, and time from symptom onset to MRI, are associated with the detection of FVH.Keywords: FLAIR vascular hyperintensity, hyperintense vessel, transient ischemic attack, magnetic resonance imaging

Qi Zhou,1 Lili Yu,2 Chunping Yin,1 Qi Zhang,3 Yanlei Tai,1 Lian Zhu,4 Jiangtao Dong,5 Qiujun Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of China; 3Department of Anesthesiology, Hebei Children’s Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Orthopaedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 5Department of Joint Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Qiujun Wang, Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Email wangqiujunsy@163.comPurpose: The aim of this study was to investigate whether transauricular vagus nerve stimulation (taVNS) could reduce the incidence of rebound pain in patients undergoing anterior cruciate ligament reconstruction (ACLR) under general anesthesia combined with preoperative femoral nerve block.Methods: In total, 78 patients were enrolled in this prospective, randomized, double-blind, and sham-controlled study. Patients were randomly assigned to 2 groups (n=39): Group taVNS received taVNS (1h /1time, 6times) within the first 12 h after surgery; Group SS received sham stimulation (SS) in the same manner. Pain scores at 0, 4, 8, 12, 24, 48 h after surgery were assessed with Numeric Pain Rating Scale (NRS). The incidence, duration and onset of rebound pain were recorded. In addition, additional analgesic requirements and side effects in the first 48 h postoperatively, as well as sleep disturbance on the night of surgery, were examined.Results: The incidence and duration of rebound pain were lower in the taVNS group than in the SS group (P=0.025 and P=0.015, respectively). Pain scores at 8 h and 12 h postoperatively were significantly lower in the taVNS group compared with the SS group (P< 0.05). The number of times to press the patient-controlled analgesia (PCA) pump and the number of patients requiring additional analgesic were significantly lower in the taVNS group than in the SS group until 12 h after surgery (P=0.021 and P=0.004, respectively). The number of patients with sleep disturbance in the taVNS group was lower than that in the SS group (P=0.030).Conclusion: The taVNS exerts beneficial effect on rebound pain after femoral nerve block in patients undergoing ACLR, which reduces the incidence and duration of rebound pain, the need for postoperative additional analgesic, and the number of complications.Keywords: rebound pain, transauricular vagus nerve stimulation, femoral nerve block, anterior cruciate ligament reconstruction

Qiuyue Wang,1,2,&ast; Nana Luo,1,2,&ast; Min Lei,1,2 Xian Chen,3 Chunxiao Li,2 Pingsheng Hao2 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunxiao Li; Pingsheng Hao, Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu 610075, Sichuan, People’s Republic of China, Tel +86-18981937829 ; +86-13881965024, Fax +86-028-87732407, Email chunxiaolee@126.com; hpswl@126.comAbstract: Grover’s disease (GD), also known as Transient acantholytic dermatosis, has no typical clinical rash features. It usually occurs in elderly white men but very rarely in China. This is a disease of acantholysis and dyskeratosis, which is usually considered to be spontaneous remission. The skin lesions of the disease are diverse, and the main symptom is severe itching. We have reported a case of GD in a 14-year-old Chinese Tibetan male whose clinical manifestations were pruritic red papule, generalized red papules, papulo vesicles and blisters ranging from millet rice to soybean size. Skin lesions change rapidly and variously. In order to confirm the diagnosis, we have done skin biopsies, immunofluorescence, dermoscopy, microscopy and other examinations. Pathological skin biopsy showed acantholysis. Intraepidermal blisters and the presence of blisters on the basal cells as well as under the stratum corneum can be observed on the same pathological section. Type IV collagen immunohistochemistry showed blisters in the epidermis. The diagnosis of GD depended on the exclusion of other diseases. After we performed whole exon sequencing (WES) on DNA from the patient’s blood, pathogenic gene mutations were not found. Pustular psoriasis, Subcorneal pustular dermatosis, Herpesvirus infections, Dermatitis herpetiformis, Pemphigus vulgaris, Norwegian scabies, Darier’s disease, and Hailey-Hailey disease were all excluded. We successfully treated adolescent GD with minocycline combined with methotrexate. The patient was followed up for 19 months without recurrence.Keywords: Grover’s disease, Chinese, minocycline, methotrexate, adolescent, case report

Jinqiang Wang,1 Hongtao Luo,2 Qi Wang,1 Xiaohui Zhu3 1Department of Emergency, Air Force Characteristic Medical Center, Beijing, 100142, People’s Republic of China; 2Department of Orthopaedics, Air Force Characteristic Medical Center, Beijing, 100142, People’s Republic of China; 3Department of Neurosurgery, Emergency Management Department Emergency General Hospital, Beijing, 100028, People’s Republic of ChinaCorrespondence: Hongtao Luo, Department of Orthopaedics, Air Force characteristic Medical Center, Beijing, 100142, People’s Republic of China, Tel +86 13701210368, Email luohongtaolht@126.comObjective: This study aimed to investigate the surgical outcomes in elderly (age ≥ 65) patients with hip fractures combined with hemiplegia and compare them with the surgical outcomes in elderly patients with hip fractures but no hemiplegia.Methods: A total of 761 elderly patients with hip fractures who were treated between January 2013 and December 2019 were enrolled in this study using a retrospective study design. The patients were divided into two groups: a hemiplegia group (77 cases, 10.1%) and a non-hemiplegia group (684 cases, 89.9%). Length of hospital stay, postoperative complications, 30-day and one-year mortalities, and one-year functional status were compared between the two groups.Results: The average length of hospital stay in the hemiplegia group (13.51 ± 10.17 days) was longer than in the non-hemiplegia group (12.60 ± 7.83 days), but the difference was not statistically significant (P = 0.354). The incidence of postoperative complications in patients with hemiplegia (28.6%, 22/77) was higher than in patients without hemiplegia (15.4%, 105/684), and the difference was statistically significant (P = 0.003). The 30-day and one-year mortalities in the hemiplegia group were higher than in the non-hemiplegia group (30 days after surgery: 10.4%, 8/77 vs 4.5%, 31/684; one year after surgery: 29.9%, 23/77 vs 15.2%, 104/684), and the difference was statistically significant (30 days after surgery: P = 0.027; one year after surgery: P = 0.001). One year after surgery, the average activity of daily living score was 56.02 ± 9.63 in the hemiplegia group and 76.89 ± 8.40 in the non-hemiplegia group, and the difference was statistically significant (P = 0.000).Conclusion: Hemiplegia can increase the incidence of postoperative complications and 30-day and one-year mortalities in patients with hip fractures.Keywords: hip fracture, hemiplegia, curative effect, elderly patients, comorbidity, recovery, complications

Lu Yang,1,&ast; Li Sun,1 Yalan Cao,1 Qi Wang,1,2 Anni Song,1 Ru Zhu,1 Wenqi Liu,1 Shengjun Lu1,&ast; 1Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Histology and Embryology, School of Basic Medicine, Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengjun Lu; Wenqi Liu, Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 15307159688 ; +86 13886014791, Fax +86-27-83692608, Email Lushengjun@hust.edu.cn; liu_wq2002cn@hotmail.comPurpose: In schistosomiasis-associated hepatic fibrosis, the role of murine UL16-binding protein-like transcript 1 (MULT1), the strongest ligand of natural killer group 2-member D receptor (NKG2D), remains unclear. Here, Schistosoma japonicum-infected mice administered with MULT1-encoding DNA were used to test MULT1 as a potential therapy for schistosomiasis-associated hepatic fibrosis and explore relevant mechanisms.Materials and Methods: A recombinant plasmid encoding MULT1 (p-rMULT1) was constructed and administered to Schistosoma japonicum-infected BALB/c mice via hydrodynamic tail vein injection. Egg granulomas in liver, hepatic fibrosis biomarkers and levels of cytokines were investigated. Comparisons of CD4+ T, CD8+ T, NK and NKT proportions as well as their phenotype were performed not only between Schistosoma infected, p-rMULT1 treated group and Schistosoma infected, backbone plasmid pEGFP-N1 treated group but also between infected, nontreated group and health control group.Results: Reduced area of granuloma formation and fibrosis around single eggs, downregulated expression of collagen I, α-smooth muscle actin, TGF-β and IL-10, and upregulated expression of IFN-γ, were observed in the livers of p-rMULT1 treated mice. p-rMULT1 treatment improved Schistosoma infection impacted immune microenvironment by modulating proportion of CD4+ T CD8+ T, natural killer (NK) and NKT cells, enhancing expression of NKG2D, in lymphocytes, and augmenting IFN-γ secretion by CD4+ T, CD8+ T, NK and NKT cells, as well as partially reversing some other phenotype changes of lymphocytes.Conclusion: To the best of our knowledge, we provided the first in vivo evidence that MULT1 is a favorable anti-fibrosis factor in the context of schistosomiasis. The inhibitory effect of MULT1 overexpression on schistosomiasis associated with hepatic fibrosis may result from augmenting the proportion and function of NKG2D-expressing immune cells, and from enhancing NK- and T-cell activation, as well as regulating the helper T (Th)1/Th2 balance.Keywords: schistosomiasis, NKG2D, liver fibrosis, IFN-γ, natural killer cells, T lymphocytes

Hongyu Liu,1 Yisheng Huang,1 Mingshu Huang,1 Zhijie Huang,1 Qin Wang,1 Ling Qing,1 Li Li,1 Shuaimei Xu,2 Bo Jia1 1Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Shuaimei Xu; Bo Jia, Email xushuaimei@126.com; dentist-jia@163.comAbstract: Oral cancer is one of the most common cancers in the world, with more than 300,000 cases diagnosed each year, of which oral squamous cell carcinoma accounts for more than 90%, with a 5-year survival rate of only 40– 60%, and poor prognosis. Exploring new strategies for the early diagnosis and treatment of oral cancer is key to improving the survival rate. Exosomes are nanoscale lipid bilayer membrane vesicles that are secreted by almost all cell types. During the development of oral cancer, exosomes can transport their contents (DNA, RNA, proteins, etc) to target cells and promote or inhibit the proliferation, invasion, and metastasis of oral cancer cells by influencing the host immune response, drug-resistant metastasis, and tumour angiogenesis. Therefore, exosomes have great potential and advantages as biomarkers for oral cancer diagnosis, and as drug delivery vehicles or targets for oral cancer therapy. In this review, we first describe the biogenesis, biological functions, and isolation methods of exosomes, followed by their relationship with oral cancer. Here, we focused on the potential of exosomes as oral cancer biomarkers, drug carriers, and therapeutic targets. Finally, we provide an insightful discussion of the opportunities and challenges of exosome application in oral cancer diagnosis and treatment, intending to offer new ideas for the clinical management of oral cancer.Keywords: exosomes, oral cancer, biomarkers, drug delivery vehicles, therapeutic target

Jinjian Li,1,&ast; Kun Yang,2,&ast; Xinghui Pan,1 Hui Peng,1 Chenting Hou,1 Jie Xiao,1 Qing Wang1 1Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao, 266500, People’s Republic of China; 2Medical Research Center, Affiliated Hospital of Qingdao University, Qingdao, 266500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wang, Ophthalmology, Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266500, People’s Republic of China, Tel +86 17853290636, Fax +86 532 82911747, Email wangqing6836@sina.comPurpose: The biological role and mechanism of long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) in dry eye remain to be illustrated. Pyroptosis is a noticeable form of inflammatory activation, which is characteristic of gasdermin D (GSDMD)-driven cell death. The present study was designed to explore the role of MIAT in pyroptosis and apoptosis induced by hyperosmolarity stress (HS) in human corneal epithelial cells (HCECs).Methods: HCECs were cultured in 70– 120 mM hyperosmotic medium for 24 h to create a dry eye model in vitro. The level of the pyroptosis marker GSDMD was measured, and the cell inflammatory response was evaluated by detecting IL-1β and IL-18 levels. Exogenous caspase-1 inhibitor Ac-YVAD-CHO was used. The pyroptosis in HCECs was examined by caspase-1 activity, immunofluorescent staining, and Western blotting. Flow cytometry was performed to test the apoptosis rate of HCECs. Cell migration and proliferation were detected. The expression of the lncRNA MIAT in HCECs was detected by quantitative real-time PCR. MIAT was knocked down by small interfering RNA (siRNA) transfection. The effects of caspase-1 inhibition on pyroptosis, apoptosis, migration, and proliferation were observed.Results: HS promoted pyroptosis in HCECs by elevating caspase-1, GSDMD, and the active cleavage of GSDMD (N-terminal domain, N-GSDMD), and increased the release of IL-1β, IL-18, LDH and the rate of apoptosis, with reduced cell migration. These changes were prevented by the inhibition of caspase-1. The expression of MIAT was significantly increased in HCECs exposed to a hyperosmotic medium. Silencing MIAT increased the expression of GSDMD, caspase-1, and inflammatory chemokines IL-1β and IL-18, and promoted apoptosis while inhibiting migration and proliferation in HCECs.Conclusion: The lncRNA MIAT is involved in HS-induced pyroptosis and apoptosis and the inflammatory response of HCECs and provides a new understanding of the pathogenesis of dry eye.Keywords: myocardial infarction-associated transcript, dry eye, pyroptosis, apoptosis

Qi Wang,1,2 Tao Xie,2 Ting Zhang,2 Yuanjia Deng,2 Yuying Zhang,2 Qingfeng Wu,1,2 Minghua Dong,1,2 Xiaoting Luo1– 3 1Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 2School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of General Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Xiaoting Luo, Tel +86 13677975578, Fax +86 0797-8169600, Email xtluo76@163.comPurpose: The main purpose of this study was to examine the effect of the cumulative exposure of blood lipid parameters on type 2 diabetes mellitus (T2DM). Another purpose was to explore whether the cumulative burden of blood lipid parameters plays a certain role in the pathogenesis of diet affecting T2DM.Patients and Methods: A total of 63 cases of diabetes occurred from 2017 to 2020, with an incidence density of 3.71 person-years. The dietary intake of the residents was obtained by using a dietary frequency questionnaire (FFQ). Cumulative lipid parameter burden was calculated according to the number of years (2016– 2020) multiplied by total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG). A Cox proportional hazard model was used to estimate the effect of cumulative lipid burden on T2DM. A mediating analysis of accelerated failure time (AFT) was used to investigate the mediating effects of certain foods, the cumulative lipid parameter burden and T2DM.Results: A higher cumulative TG load corresponded to a higher risk of T2DM onset (Ptrend=0.021). After adjusting for covariates, the highest quartile cumulative TG burden had a 3.462 times higher risk of T2DM than that in the lowest quartile (HR=3.462, 95% CI: 1.297– 9.243). Moreover, a higher cumulative HDL load corresponded to a lower risk of T2DM onset (Ptrend =0.006). After adjusting for covariates, the risk of T2DM was 0.314-fold lower in the highest quartile of cumulative HDL burden than that in the lowest quartile (HR=0.314, 95% CI: 0.131– 0.753). Cumulative TG burden partially mediated the association between red meat and T2DM.Conclusion: The increase in cumulative HDL burden and the decrease in cumulative HDL burden are related to the incidence of T2DM. Cumulative TG burden was shown to play a partial mediating role in the pathogenesis of red meat and diabetes.Keywords: type 2 diabetes mellitus, cumulative lipid parameter burden, diet, cohort study

Qianning Wang, Xinping Zhang, Feiyang Zheng, Lu Wang, Tiantian Yu School of Medicine and Health Management, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Xinping Zhang, School of Medicine and Health Management, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China, Tel +133 4995 0095, Email xpzhang602@hust.edu.cnPurpose: Antimicrobial resistance (AR) is a global public health problem, improving clinicians’ intention to submit microbiological pathogenic test (submission intention) can effectively increase the value for rational use antibiotics to curb AR. However, there are few studies on the factors influencing improvement of the submission intention, especially from the perspective of hospital management. This study will fill the gap and provide evidence that can continuously support improvement of antibiotics prescribing rationally.Patients and Methods: A cross-sectional survey of clinicians was conducted in all public hospitals in Hubei, China. Dependent variables were submission intention of non-restricted-use, restricted-use and special-use antibiotics which were measured submission, not sure submission, no submission. Independent variables were frequency of training and publicity on submission, and hospital with or without submission performance assessment, guideline, information decision system and laboratory items, including bacterial culture item, fungal culture item and so on. Clinicians’ demographics were applied as control variables. Multinomial logistic regression was performed to model independent variables influencing submission intention.Results: For non-restricted-use antibiotics, guideline (OR = 0.263; 95% CI = [0.188, 0.369]) (OR = 0.526; 95% CI = [0.375, 0.738]) and bacterial culture item (OR = 0.141; 95% CI = [0.074, 0.268]) (OR = 0.520; 95% CI = [0.292, 0.927]) are key factors that positively affect clinicians’ intention on submission and not sure submission; For restricted-use and special-use antibiotics, training frequency and bacterial culture item (OR = 0.155; 95% CI = [0.076, 0.315]) (OR = 0.092; 95% CI = [0.036, 0.232]) (OR = 0.106; 95% CI = [0.046, 0.248]) (OR = 0.027; 95% CI = [0.006, 0.117]) are key factors that positively affect clinicians’ intention on submission and not sure submission.Conclusion: This study found that bacterial culture item, guideline, and training frequency are key factors that affect clinicians’ intention on submission and not sure submission, but various factors exist different effects level on different types of antibiotics. Consequently, a focus should be placed on the construction and implementation of management factors, as well as reformation of antimicrobial stewardship in hospitals according to the types of antibiotics.Keywords: pathogenic microbial specimen, submission intention, hospital management, antimicrobial stewardship, effects assessment

Fang Wei,1 Qiuyue Wang,1 Hang Liu,1 Xuejing Yang,1 Wenyu Cao,1 Weiman Zhao,1 Yingying Li,1 Lijie Zheng,1 Tao Ma,1,2 Qingqing Wang1– 3 1School of Pharmacy, Bengbu Medical College, Bengbu, Anhui Province, 233030, People’s Republic of China; 2Engineering Research Center for Biochemical Pharmaceuticals of Anhui Province, Bengbu Medical College, Bengbu, Anhui Province, 233030, People’s Republic of China; 3Bengbu BBCA Medical Science Co., Ltd., Bengbu, Anhui Province, 233030, People’s Republic of ChinaCorrespondence: Qingqing Wang; Tao Ma, School of Pharmacy, Bengbu Medical College, Bengbu, Anhui Province, 233030, People’s Republic of China, Tel +86 15605528300 ; +86 13855266592, Email qingqingwang@bbmc.edu.cn; matao1992@foxmail.comIntroduction: Methotrexate (MTX) is the first-line drug for the treatment of rheumatoid arthritis (RA) in several countries. However, MTX has an extremely low solubility in water, and the side effects caused by its delivery mode restrict its curative effect. In this study, we designed a dissolving microneedles array (DMNA) containing MTX nanocrystals (MTX-NCs) (MTX-NC@DMNA) to improve the treatment of RA. DMNA-based drug delivery combines the advantages of patient compliance with the use of transdermal drug delivery systems and high-efficiency injection administration; thus, it can mitigate the side effects that result from current administration routes. Carrier-free and surfactant-free MTX-NCs were prepared to overcome bioavailability limitations and poor drug loading problems.Methods: The MTX-NCs prepared by reverse solvent precipitation method was encapsulated in the DMNA. The morphology, mechanical properties, safety, stability and in vivo dissolution were evaluated, and its pharmacodynamic characteristics were assessed in a rat model of RA.Results: The particle size of the MTX-NCs was 148.1 ± 10.1 nm. The MTX-NC@DMNA were found to be rigid enough to penetrate the skin and deliver the drug successfully. The results indicated effective skin recovery after removal of the DMNA. It was found that the MTX-NC@DMNA significantly reduced foot swelling in the rats and regulated the balance in the levels of related cytokines. It also reduced pathological damage to the synovium, joint, and cartilage, and effectively alleviated organ injury in the rats.Conclusion: Transdermal administration of MTX-NC@DMNA may be an effective approach for treating RA.Graphical Abstract: Keywords: nanocrystals, inflammation, dissolving microneedles array, transdermal, rheumatoid arthritis

Qingling Wang,1,2,&ast; Mingyu Zhu,2,&ast; Hu Li,3 Peizhan Chen,4 Mingjie Wang,2 Leilei Gu,2 Xinxin Zhang,5 Li Chen2 1The Affiliated Hospital of Kunming University of Science and Technology, Kunming, People’s Republic of China; 2Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 4Central Laboratory, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 5Department of Infectious Disease, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Chen, Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China, Email drchenli@163.comPurpose: Elevated serum ferritin (SF), also defined as hyperferritinemia, is commonly seen in patients with nonalcoholic fatty liver disease (NAFLD). However, the clinical significance of SF in NAFLD remains controversial. The aim of this study was to characterize the NAFLD patients with elevated SF and to explore the association of hyperferritinemia with the severity of NAFLD proved by liver biopsy in the Chinese population.Patients and Methods: A total of 136 NAFLD patients proved by liver biopsy were enrolled. The demographic, anthropometric, clinical historic, laboratory, and histological characteristics were compared between elevated and normal SF groups. The independent factors for elevated SF were determined using multivariate logistic regression analysis.Results: The median age and body mass index were 41.00 (33.00– 57.75) years and 28.28 (26.28– 31.34) kg/m2, respectively. Hyperferritinemia was detected in 57 (41.9%) patients. Patients in the elevated SF group presented with more severe lipo- and glucometabolic disorder, and higher aminotransferases compared to those in the normal SF group (p < 0.05). In terms of histopathology, elevated SF was associated with worse steatosis and a higher proportion of positive iron staining (p < 0.05). Multivariate logistic regression analysis identified homeostasis model assessment of insulin resistance (OR: 1.170, 95% CI: 1.036– 1.322, p = 0.012), alanine aminotransferase (OR: 1.012, 95% CI: 1.005– 1.019, p < 0.001), and positive Perl’s staining (OR: 4.880, 95% CI: 2.072– 11.494, p < 0.001) as independent risk factors of hyperferritinemia.Conclusion: NAFLD patients with hyperferritinemia were characterized as more severe metabolic dysfunction and liver injury. More attention should be paid to the metabolism state of NAFLD patients with elevated SF. Hyperferritinemia was correlated to hepatic steatosis in Chinese NAFLD patients.Keywords: nonalcoholic fatty liver disease, hyperferritinemia, histopathology, metabolic dysregulation, steatosis

Yu Cui,&ast; Yao Lu,&ast; Qiang Huang, Congming Zhang, Liang Sun, Cheng Ren, Qian Wang, Teng Ma, Zhong Li, Kun Zhang, Zhimeng Wang, Hanzhong Xue Department of Orthopedics and Trauma, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi, 710000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhimeng Wang; Hanzhong Xue, Department of Orthopedics and Trauma, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi, 710000, People’s Republic of China, Email enshuo99@126.com; 13759963709@163.comIntroduction: Research on preoperative blood management in older patients with delayed surgery for intertrochanteric fracture is scarce, especially regarding hematopoiesis and hemostasis. We assessed the effectiveness of optimized blood management programs in older patients undergoing delayed surgery for intertrochanteric fractures.Methods: This retrospective study included 456 patients who underwent delayed surgery for intertrochanteric fractures. According to the optimized blood management plan, the patients were divided into four groups: group A was the control group; group B received 1 g of tranexamic acid (TXA) intravenously at admission; group C underwent sequential TXA treatment after admission until 1 day before surgery (1 g/day); and group D received iron supplements (200 mg/day) in addition to the treatment administered to group C, with or without recombinant human erythropoietin (rHuEPO; 40,000 IU). The primary outcomes were preoperative hidden blood loss (HBL), preoperative allogeneic blood transfusion (ABT) rate, hemoglobin (Hb) change, and actual Hb drop.Results: The Hb reduction, calculated HBL, and hospitalization duration in groups C and D were significantly lower than those in groups A and B. The preoperative ABT rates in groups C and D were significantly lower than those in groups A and B, with no significant difference between groups C and D.Discussion: The results of this study suggested that iron supplementation (with or without rHuEPO) combined with the sequential IV TXA scheme did not show a better clinical effect than the sequential IV TXA scheme in the management of patients undergoing delayed surgery for intertrochanteric fractures. Therefore, further evaluation is needed before recommending iron supplements and rHuEPO in older patients.Keywords: blood management, iron supplements, surgical delay, intertrochanteric fractures, tranexamic acid

Qiuning Wang,1,&ast; Weiying Chen,2,&ast; Xuefeng Yang,3 Ying Song,4 Xiaowei Sun,5 Guizhou Tao,6 Hong Wang,7 Nan Zhao,7 Yue Huang,1 Erqing Chai,8 Futian Tang9 1Department of Pharmacology, Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 2Department of Drug Quality Analysis, Jiuquan Drug Inspection and Testing Center, Jiuquan, Gansu Province, People’s Republic of China; 3Department of Physiology, Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 4Cardiovascular Laboratory, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 5Department of Neurosurgery, China Resources Liaojian Group, General Hospital of Fuxin Mining Group (10th Clinical College of China Medical University), Fuxin, Liaoning Province, People’s Republic of China; 6Internal Medicine-Cardiovascular Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 7Allergy and Clinical Immunology Center, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 8Neurointerventional Department, Emergency General Hospital, Beijing, People’s Republic of China; 9Department of Cardiovascular Disease and Key Laboratory of Digestive System Tumor of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Futian Tang, Department of Cardiovascular Disease and Key Laboratory of Digestive System Tumor of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People’s Republic of China, Email tangft@163.com Erqing Chai, Neurointerventional Department, Emergency General Hospital, Beijing, People’s Republic of China, Email happybirds998@126.comIntroduction: Astragaloside IV (AS-IV) is one of the main active components isolated from the traditional Chinese medicinal herb, Astragalus membranaceus. The present study was designed to investigate whether the regulation of microRNA-1 (miR-1)-mediated inflammation and autophagy contributes to the protective effect of AS-IV against cardiac dysfunction in rats treated with lipopolysaccharides (LPS).Methods: Animal model of cardiac dysfunction in rats or cellular model of injured H9c2 heart cell line was established by using LPS. Echocardiography, electron microscopy, enzyme-linked immunosorbent assay, immunofluorescence, quantitative RT-PCR, and Western blotting were used to determine the cardiac function and expression of inflammation- and autophagy-related proteins at both the mRNA and protein levels.Results: LPS caused cardiac dysfunction in rats or injury in H9c2 cells and induced inflammation and autophagy. Compared with LPS treatment, AS-IV treatment attenuated cardiac dysfunction or cell injury, accompanied by inhibition of inflammation and autophagy. However, the miR-1 mimics partly abolished the effects of AS-IV. In addition, the effect of the miR-1 inhibitor was similar to that of AS-IV in the LPS model. Further analyses showed that AS-IV treatment decreased the mRNA expression of miR-1 in the heart tissue of rats and H9c2 cells treated with LPS.Conclusion: These results suggest that AS-IV attenuated cardiac dysfunction caused by LPS by inhibiting miR-1-mediated inflammation and autophagy, thereby providing a novel mechanism for the protection against cardiac diseases.Keywords: lipopolysaccharides, astragaloside IV, cardiac dysfunction, inflammation, autophagy, miRNA-1

Meng-Nan Xu,1,&ast; Qian Wang,1,&ast; Min Wang,1 Yuan Xu,1 Si-Ming Yuan1,2 1Department of Plastic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210002, People’s Republic of China; 2Department of Plastic Surgery, Jinling Hospital, Nanjing School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu, 210002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Si-Ming Yuan, Department of Plastic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210002, People’s Republic of China, Email yuansm@163.comBackground: Port wine stain (PWS) is a congenital skin lesion involving capillary malformations. Most PWS lesions will gradually become hypertrophic and appear nodular in contour. Current research shows that rapamycin, an mTOR inhibitor, is probably a promising adjunctive therapy for PWS, which suggests that the mTOR signaling pathway may play an important role in its pathological process.Methods: From January 2013 to January 2019, 13 samples were obtained during the surgical excision. Each sample was divided into 3 parts according to the type of lesion, namely, the flat, hypertrophic and nodular lesions. Pathologic structures of each type were observed under the microscope after HE staining. The expression of mTORC1, p70S6, p-p70S6, eIF4EBP1 and p-eIF4EBP1 was examined by immunohistochemical staining and western blotting. The location of the expression of mTORC1, p-p70S6 and p-elF4EBP1 was further detected by immunofluorescence staining.Results: Large amounts of dilated and malformed vessels were observed in all types of PWS lesions. Abundant hyperplastic hair follicles/glands were shown in the hypertrophic or nodular lesions. Phosphorylation level of p70S6 and elF4EBP1 in PWS was significantly higher than those in normal skin and increased accordingly in the progression of PWS. Activated molecules in mTOR signaling pathway were mostly located in the endothelium of malformed vessels. They were also located in the hyperplastic hair follicles/glands of hypertrophic and nodular lesions.Conclusion: The mTOR signaling pathway was increasingly activated during the progression of PWS. Enhanced activation of mTOR signaling pathway may contribute to the hypertrophy and nodularity of PWS. The results provide preliminary evidence for treating PWS and related syndromes by inhibiting mTOR signaling pathway.Keywords: port wine stain, mTOR signaling pathway

Yan Su,1 Yikun Guo,2 Zhuoyou Chen,2 Min Zhang,2 Jianfang Liu,2 Qian Wang,2 Tian Yao2 1Department of Radiology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Neurology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Yikun Guo, Department of Neurology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, 68# Middle Gehu Road, Changzhou, 213164, Jiangsu Province, People’s Republic of China, Tel +86-519-81087079, Fax +86-519-81087711, Email guoyikun000@163.comPurpose: This study was to explore the role of pre-existing small vessel disease (SVD) on the 3-month outcomes of acute cardioembolic stroke (CES) patients.Patients and Methods: Data of 189 consecutive acute CES patients at a single center were retrospectively enrolled. SVD imaging markers of lacunes, white matter hyperintensities (WMH) and enlarged perivascular spaces (EPVS) were evaluated and their total burden score (0– 3 points) was calculated. Patients were divided into the good functional outcome group (modified Rankin scale, mRS ≤ 2) and the poor functional outcome group (mRS ≥ 3) at 3 months after stroke onset. The effect of each single SVD marker and its total burden score on the outcome was identified using binary logistic regression.Results: Overall, 100 (52.9%), 52 (27.1%), 28 (14.8%) and 9 (4.8%) patients had 0, 1, 2 and 3 SVD imaging markers. Patients with a total SVD burden score of 2 and 3 were significantly older and had higher baseline National Institutes of Health Stroke Scale (NIHSS) score than those with a score of 0 and 1 (P< 0.01). Forty-seven (24.9%) patients had a poor outcome. Patients in the poor outcome group had significantly higher baseline NIHSS score, increased incidence of stroke associated pneumonia, and heavier burden of lacunes, WMH and EPVS, and thus had elevated total SVD burden score than those in good outcome group (P< 0.05). After adjusting for potential confounders, the WMH (odds ratio [OR] = 2.6777, 95% confidence interval [CI] = 1.052– 6.812, P = 0.039) and the total SVD burden score (OR = 1.717, 95% CI = 1.072– 2.749, P = 0.024) were, respectively, independent risk factors for a poor outcome.Conclusion: The pre-existing SVD may be associated with the 3-month prognosis of CES.Keywords: cardioembolic stroke, small vessel disease, imaging marker, total burden score, prognosis

Shuai Fu,&ast; Quan Wang,&ast; Weidong Chen, Hong Liu, Hongbo Li Department of Nephrology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbo Li, Department of Nephrology, Wuhan No. 1 Hospital, No.215 Zhongshan Avenue, Wuhan, Hubei, 430022, People’s Republic of China, Tel +86-27-85332343, Email 53926553@qq.comBackground: The aim of this study was to construct and external validate a nomogram for predicting cardiogenic shock acute kidney injury (CS-AKI) in patients in intensive care unit (ICU).Methods: All patients diagnosed with CS from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the eICU Collaborative Research Database (eICU-CRD) were included in this study. Least absolute shrinkage and selection operator (LASSO) regression and recursive feature elimination for support vector machine (SVM-RFE) were used to determine the overlapping clinical features associated with CS-AKI. The predictive nomogram was established based on the significant clinical parameters and externally verified in this study.Results: LASSO regression and SVM-RFE demonstrated that Charlson Comorbidity Index (CCI), usage of mechanical ventilation, SOFA score, white blood cell, albumin, eGFR, anion gap, and positive fluid balance were closely associated with CS-AKI in the training cohort. The predictive nomogram based on the eight parameters showed good predictive performance as calculated by C-index were 0.823 (95% confidence index, 95% CI 0.798– 0.849), 0.819 (95% CI 0.769– 0.849), and 0.733 (95% CI 0.704– 0.763) in the training set, in the internal validation set and in the external validation sets, respectively. Moreover, the nomogram exhibited not only encouraging calibration ability but also great clinical utility in the training set and in the validation sets.Conclusion: CCI, usage of mechanical ventilation, SOFA score, white blood cell, albumin, eGFR, anion gap, and positive fluid balance were closely associated with CS-AKI. The predictive nomogram for CS-AKI manifested well-predictive ability for the identification of ICU patients with CS-AKI.Keywords: cardiogenic shock, acute kidney injury, Medical Information Mart for Intensive Care, eICU Collaborative Research Database, intensive care unit, nomogram

Zixi Song,&ast; Jiahong Zou,&ast; Mengya Wang, Zhenwei Chen, Qingchao Wang Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingchao Wang, Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, College of Fisheries, Huazhong Agricultural University, Shizishan Street 1st, Hongshan District, Wuhan, Hubei, People’s Republic of China, Tel +86-138 71499065, Fax +86-27 87282113, Email qcwang@mail.hzau.edu.cnAbstract: Pyroptosis is a form of programmed cell death, which is executed by gasdermin family proteins. Under the stimulation of pathogen- and/or damage-associated molecular patterns, pattern recognition receptors (PRRs) such as Nod like receptors could recruit apoptosis-associated speck-like protein containing a CARD (ASC) and pro-caspases to form inflammasomes and then activate caspases through various pathways. The activated caspases then cleave gasdermin family proteins, and N-terminal (NT) domains of gasdermins were released to form oligomeric pores, resulting in the increased membrane permeability, cell swelling, and final pyroptosis. During this process, caspases also promote the maturation and release of inflammatory cytokines such as IL-1β and IL-18, thus pyroptosis is also named inflammatory cell death. Unlike numerous gasdermin family proteins in mammals, only gasdermin E (GSDME) has been identified in fish. GSDME in fish can be cleaved by caspase-a/-b to release its NT domain and induce pyroptosis. Studies indicated that pyroptosis in fish mainly depends on NLR family pyrin domain-containing 3 (NLRP3) inflammasome. ASC and different caspase proteins also were identified in different fish species. The influences of pathogenic microorganism infection and environmental pollutants on fish pyroptosis were studied in recent years. Considering that fish living environment is affected by multiple factors such as water salinity, temperature, oxygen supply, and highly fluctuating food supply, the in-depth research about fish pyroptosis will contribute to revealing the mechanism of pyroptosis during evolution.Graphical Abstract: Keywords: pyroptosis, fish, gasdermin E, caspases

Ping Zheng,1 Kexing Zhang,2 Xifang Lv,1 Chuanhe Liu,3 Qiang Wang,1 Xuetao Bai1 1China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Immunization Program, Xinwu District Center for Disease Control and Prevention, Wuxi, People’s Republic of China; 3Children’s Hospital, Capital Institute of Pediatrics, Beijing, People’s Republic of ChinaCorrespondence: Qiang Wang; Xuetao Bai, China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86 10 50930251, Email wangqiang@nieh.chinacdc.cn; xuetaobai@163.comPurpose: This study aimed to investigate the characteristics of gut bacteria and the derived metabolites among allergic asthmatic children, non-allergic asthmatic children and healthy children without asthma.Methods: Fecal samples were collected from 57 participants, including 20 healthy children, 27 allergic asthmatic children, and 10 non-allergic asthmatic children. 16S rRNA gene sequencing was conducted for analyzing gut bacterial compositions and untargeted metabolomics was used to analyze the alterations of gut microbe-derived metabolites. The associations between gut bacterial compositions and metabolites were analyzed by the method of Spearman correlation.Results: The results showed that the compositions and metabolites of gut microbiome were altered both in allergic and non-allergic asthmatics compared with healthy controls. Chao1 (p = 0.025) index reflected a higher bacterial richness and Simpson (p = 0.024) index showed a lower diversity in asthma group. PERMANOVA analysis showed significant differences among the three groups based on unweighted UniFrac distance (p = 0.001). Both allergic and non-allergic asthmatics showed a higher relative abundance of Proteobacteria and a lower relative abundance of genera from Clostridia. More bacteria were altered in non-allergic asthmatics compared with allergic asthmatics. Metabolomics analysis identified that 42 metabolites were significantly associated with allergic asthma, and 58 metabolites were significantly associated with non-allergic asthma (multiple linear regression, p < 0.05). Histamine was 4 folds up-regulated only in the non-allergic asthma group. The relative abundance of Candidatus Accumulib was significantly correlated with the upregulation of histamine. The relative abundance of genera from Clostridia was significantly correlated with the downregulation of lipid and tryptophan metabolism.Conclusion: The altered gut microbes was associated with the mechanism of asthma attack through metabolites in allergic and non-allergic asthma group, respectively. The result suggested that gut microbiome had an impact on the development of both allergic and non-allergic asthma. The distinct gut microbiome and microbiome-derived metabolites in non-allergic asthma children suggested that gut microbiome might play a critical role in modulation of asthma phenotype.Keywords: gut microbiome, untargeted metabolomics, allergic childhood asthma, non-allergic childhood asthma, 16S rRNA gene sequencing

Leifang Zhang,1 Deyi Kong,1 Junxia Huang,1 Qiongfen Wang,2 Lilin Shao1 1Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, 316022, People’s Republic of China; 2Zhoushan Institute of Calibration and Testing for Quality and Technical Supervision, Zhoushan, 316012, Zhejiang, People’s Republic of ChinaCorrespondence: Leifang Zhang, Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, 1 Haida South Road, Changzhi Island, Zhoushan, 316022, Zhejiang, People’s Republic of China, Tel +86 18 8570 63534, Fax +86 58 0 254 781, Email zhanglf@zjou.edu.cnBackground: Seawater drowning-induced acute lung injury (ALI) is a severe clinical condition characterized by increased alveolar-capillary permeability, excessive inflammatory response, and refractory hypoxemia. C-phycocyanin (C-PC), a biliprotein found in blue-green algae such as spirulina platensis, is widely used in the food and dietary nutritional supplement fields due to its beneficial pharmacological effects. Previous studies have revealed that C-PC has anti-inflammatory, antioxidant, and anti-apoptotic activities.Purpose: Therefore, this study investigated the protective effect and underlying mechanisms of C-PC on lipopolysaccharide (LPS) and seawater (SW) induced ALI (SW and LPS-induced ALI).Methods: An SW and LPS mouse model of ALI mice was established through intratracheal administration of 5mg/kg LPS and 25% SW. Different doses of C-PC (100, 200 and 400 mg/kg) were administered by intraperitoneal injection for seven days. In addition, gap junction communication in RAW264.7 and MLE-12 cells was determined following stimulation with 25% SW and 10 μg/ml LPS after treatment with C-PC (120 μg/ml). Moreover, the arterial partial pressure of oxygen, lung wet/dry weight ratios, total protein content and MPO levels in the bronchoalveolar lavage fluid (BALF), and the histopathologic and ultrastructure staining of the lung tissues were determined. The oxidative stress index, levels of the pro-inflammatory mediators, epithelial cell viability and apoptosis, and the regulatory effect of C-PC on the NF-κB/NLRP3 axis were investigated.Results: The results showed that C-PC significantly alleviated pathological damages, suppressed oxidative stress, inflammation and apoptosis, and enhanced the viability of epithelial cells in the lung tissues. Furthermore, C-PC was shown to inhibit activation of the NF-κB/NLRP3 pathway and the formation of the NLRP3 inflammasome complex.Conclusions: In conclusion, C-PC shows promising therapeutic value in SW and LPS-induced ALI/ARDS, providing new insight into ALI/ARDS treatment.Keywords: C-phycocyanin, acute lung injury, inflammation, NF-κB/NLRP3, apoptosis

Ziyi Xu,1,&ast; Xuezhi Hao,1,&ast; Qi Wang,2 Jing Wang,2 Ke Yang,3 Shouzheng Wang,1 Fei Teng,1 Junling Li,1 Puyuan Xing1 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2Department of Medical Oncology, Beijing Chaoyang Sanhuan Hospital, Beijing, 100021, People’s Republic of China; 3Department of Medical Oncology, Cancer Hospital of Huanxing, Beijing, 100021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junling Li; Puyuan Xing, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email lijunling@cicams.ac.cn; xingpuyuan@cicams.ac.cnObjective: Osimertinib is the standard targeted strategy for lung adenocarcinoma patients harboring epidermal growth factor receptor (EGFR)-activating mutation who have achieved acquired mutation T790M beyond progression of first-line EGFR-tyrosine kinase inhibitor (TKI). In a real world setting, the efficacy for osimertinib as a subsequent treatment beyond first-generation EGFR-TKI progression under complex circumstances such as different T790M mutation status is still worth exploring.Methods: Records of 84 lung adenocarcinoma patients with an EGFR sensitive mutation who received first-generation EGFR-TKI as first-line therapy and sequenced by osimertinib after progression were retrospectively reviewed in this study. The assessment of efficacy of subsequent osimertinib treatment was evaluated by progression free survival (PFS), objective response rate (ORR), complete response (CR), partial response (PR), disease control rate (DCR) and stable disease (SD) rates. Relationship between PFS and clinicopathological characteristics was analyzed using univariate analysis.Results: Until the median follow-up time of 23.7 months (IQR 10.8– 29.0 months), the median PFS (mPFS) of subsequent osimertinib was 17.0 months (HR 1.744, 95% CI, 13.547– 20.382). Among 60 patients who had at least one measurable lesion, 35.0% of patients (21/60) had PR to osimertinib, and 63.3% patients (38/60) had SD during osimertinib treatment. The ORR was 35.0%, and the DCR was 98.3%. Patients with acquired T790M mutation which was detected by NGS or ddPCR assay had an mPFS of 17.0 months (HR = 1.032, 95% CI, 14.941– 18.987), while the remaining 17 patients who had negative or unknown T790M mutation status had an mPFS of 23.5 months (HR = 9.404, 95% CI, 5.068– 41.932). No significant difference was observed in those with and without T790M mutation (P = 0.704).Conclusion: Osimertinib may serve as an alternative subsequent choice after progression of first-generation EGFR-TKI in EGFR-mutated lung adenocarcinoma and may represent a potential treatment option for selected T790M-negative patients.Keywords: osimertinib, progression, subsequent therapy, lung adenocarcinoma, T790M mutation

Xianjin Zhou,1– 3 Sha Tian,3 Xian Zhou,3 Huimin Shi,3 Yi Li,3 Jianjiang Xiao,3 Kun Chen,4 Bobin Chen,5 Gezhi Xu,1,2 Qingping Wang3 1Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, People’s Republic of China; 3Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Department of Hematology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Qingping Wang, Department of Ophthalmology, Huashan Hospital, Fudan University, No. 12 Middle Urumqi Road, Shanghai, 200040, People’s Republic of China, Email wangqingping71@163.com Gezhi Xu, Department of Ophthalmology, Eye & ENT Hospital, Fudan University, No. 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email drxugezhi@163.comPurpose: To describe the characteristic manifestations of vitreoretinal lymphoma (VRL) with optical coherence tomography (OCT) and monitor their outcomes after treatmEnt.Patients and Methods: Patients with primary central nervous system lymphoma (PCNSL) and intraocular involvement were assigned to the VRL group. OCT manifestations were analyzed and changes in abnormalities were recorded after intravitreal methotrexate injections. OCT manifestations of PCNSL patients without intraocular involvement were analyzed as well (non-VRL group).Results: There were 48 eyes with high-quality OCT records in the VRL group, of which 19 had abnormal manifestations. The most frequent abnormality was outer retina (OR) fuzzy borders (14 of 19, 73.7%). Other abnormalities included: focal subretinal deposits (8 of 19, 42.1%), hyperreflective subretinal dots (2 of 19, 10.5%), pigment epithelium detachment (PED) (5 of 19, 26.3%), preretinal deposits (5 of 19, 26.3%), epiretinal membrane (3 of 19, 15.8%), cystoid macular edema (3 of 19, 15.8%), subretinal fluid (3 of 19, 15.8%), outer retina atrophy (2 of 19, 10.5%), unilateral optic papilledema (2 of 19, 10.5%), retinal thickening (1 of 19, 5.3%), and subretinal fibrosis (1 of 19, 5.3%). Nine eyes with retinal abnormalities were receiving regular intravitreal methotrexate. The retinal structure of seven eyes (only outer retina involved) returned to almost normal on OCT images. The remaining two eyes (with severe retinal vasculitis) showed little improvement after treatment.Conclusion: OCT is helpful for the diagnosis of PCNSL with intraocular involvement and long-term follow-up of the disease.Summary Statement: The characteristic manifestations of vitreoretinal lymphoma (VRL) with optical coherence tomography (OCT) were described and their outcomes after treatment were monitored. These findings suggested that OCT is helpful for the diagnosis of PCNSL with intraocular involvement and long-term follow-up of the disease.Keywords: intravitreal injection, methotrexate, optical coherence tomography, primary central nervous system lymphoma, vitreoretinal lymphoma

Li-li Hu,1 Qing Wang,2,3 Yan-hu Wang,1 Ling-xi Gu,1 Tian-gui Yu1 1Department of Public Health, Shandong Mental Health Center, Jinan, People’s Republic of China; 2Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Institute for Medical Dataology, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Tian-gui Yu, Department of Public Health, Shandong Mental Health Center, Jinan, People’s Republic of China, Tel +86-531-86336798, Email sdyutg@163.comPurpose: To describe the mortality rate and cause of death among Han Chinese schizophrenia patients and to explore the risk factors affecting survival.Methods: We performed a retrospective analysis of death among patients with schizophrenia from Jan 1, 2012, to Dec 31, 2019, using the Severe Mental Disorders Information System of Shandong Province (henceforth referred to as the SMDI system) in Shandong, China. The cohort included 72,102 patients, and 11,766 patients died during follow-up. The data in this cohort study were derived from the SMDI system. We calculated the crude mortality rate and standardized mortality rate (SMR, standardized according to the sex and age composition of the population in Shandong Province) for patients with schizophrenia. Cox regression analysis was used to analyze the risk factors affecting patient survival, and the statistical index was the hazard ratio (HR).Results: The mean age of the cohort patients was 47.21± 14.05 years; 51.79% were males, and 48.21% were females. Among them, 68.98% (49,735) had only a primary education level, 85.36% (61,549) were farmers, 64.37% (46,413) were married, and 94.01% (67,775) received community management. A total of 16.32% of the cohort died. The SMR in patients with schizophrenia was 4.9, and it was higher for males than females (4.99 versus 4.82). Among the 6 registered causes of death, physical illness had the highest SMR (5.15), followed by other causes of death (4.86), mental illness-related complications (4.57), homicide (4.31), accidents (4.13), and suicide (3.87). Higher levels of education, employment (in-service status), marriage, and urban residence were protective factors for survival among patients with schizophrenia.Conclusion: In China, the SMR of schizophrenia is relatively high, and physical diseases are the main cause of death. We suggest that a variety of measures should be taken early to treat somatic diseases and reduce SMR in patients with schizophrenia.Keywords: schizophrenia, cause of death, mortality, physical illness

Fan Lai,1,&ast; Xin Li,1,&ast; Qi Wang,1,&ast; Yingjuan Luo,1 Xin Wang,1 Xiuhua Huang,1 Jiajia Zhang,1 Jieru Peng,1 Qin Wang,1 Li Fan,1 Wen Li,1 Junrong Huo,1 Tianjiao Liu,1 Yalan Li,2 Yonghong Lin,1 Xiao Yang1 1Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2The Fourth People’s Hospital of Chengdu, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao Yang; Yonghong Lin, Chengdu Women’s and Children’s Central Hospital, 1617 Riyue Avenue, Qingyang District, Chengdu, 611731, Sichuan, People’s Republic of China, Tel +86 13882288881 ; +86 13808031895, Email yangxiaocwcch@aliyun.com; linyonghongcwcch@aliyun.comPurpose: Fever is one of the most typical clinical symptoms of coronavirus disease 2019 (COVID-19), and non-contact infrared thermometers (NCITs) are commonly used to screen for fever. However, there is a lack of authoritative data to define a “fever” when an NCIT is used and previous studies have shown that NCIT readings fluctuate widely depending on ambient temperatures and the body surface site screened. The aim of this study was to establish cut-off points for normal temperatures of different body sites (neck, forehead, temples, and wrist) and investigate the accuracy of NCITs at various ambient temperatures to improve the standardization and accuracy of fever screening.Patients and Methods: A prospective investigation was conducted among 904 participants in the outpatient and emergency departments of Chengdu Women’s and Children’s Central Hospital. Body temperature was measured using NCITs and mercury axillary thermometers. A receiver operating characteristic curve was used to determine the accuracy of body temperature detection at the four body surface sites. Data on participant characteristics were also collected.Results: Among the four surface sites, the neck temperature detection group had the highest accuracy. When the neck temperature was 37.35°C as the optimum fever diagnostic threshold, the sensitivity was 0.866. The optimum fever diagnostic thresholds for forehead, temporal, and wrist temperature were 36.65°C, 36.65°C, and 36.75°C, respectively. Moreover, triple neck temperature detection had the highest sensitivity, up to 0.998, whereas the sensitivity of triple wrist temperature detections was 0.949. Notably, the accuracy of NCITs significantly reduced when the temperature was lower than 18°C.Conclusion: Neck temperature had the highest accuracy among the four NCIT temperature measurement sites, with an optimum fever diagnostic threshold of 37.35°C. Considering the findings reported in our study, we recommend triple neck temperature detection with NCITs as the fever screening standard for COVID-19.Keywords: COVID-19, epidemiology, fever, infrared rays, mass screening

Changlan Peng,1 Chunxiao Li,2 Yingying Zhou,1 Qiuyue Wang,1 Ping Xie,1 Tianhao Li,2,&ast; Pingsheng Hao2,&ast; 1Department of Dermatology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianhao Li; Pingsheng Hao, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, Sichuan Province, People’s Republic of China, Tel +86-13880986337 ; +86-13881965024, Fax +86-28-87732407, Email litianhao_doctor@163.com; hpswl@126.comPurpose: Despite recent advances in the treatment of prurigo nodularis, conventional treatment suffers from a dilemma of poor efficacy. The clinical use of Janus kinase (JAK) inhibitors in the treatment of Prurigo nodularis has rarely been explored.Patients and Methods: We present a case of prurigo nodularis successfully treated with, JAK inhibitor tofacitinib with no adverse effects.Results: This case report of successful treatment shows a good clinical efficacy of using JAK inhibitor tofacitinib in the treatment of prurigo nodularis. Cytokines may be an important cause of prurigo nodularis.Conclusion: JAK inhibitor tofacitinib may be a new option for the treatment of prurigo nodularis, especially for patients who have failed conventional treatment.Keywords: prurigo nodularis, JAK inhibitors, tofacitinib

Mengwen Liu,1 Quan Wang,2 Haican Liu,3 Chunjie Yin,1 Xiaokaiti Mijiti,2 Aiketaguli Anwaierjiang,1 Kanglin Wan,3 Miao Xu,2 Machao Li,3 Siqin Nong,4 Guilian Li,3 Hui Xiao1 1School of Public Health, Xinjiang Medical University, Urumqi, 830011, People’s Republic of China; 2The Eighth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830001, People’s Republic of China; 3State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 4College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, People’s Republic of ChinaCorrespondence: Guilian Li; Hui Xiao, Email liguilian@icdc.cn; xh20108262@sina.comPurpose: Polymorphisms in MBL2 may contribute to the susceptibility to tuberculosis. The aim of the present study was to determine the associations of the polymorphisms of five loci (rs1800450, rs1800451, rs7096206, rs7095891, and rs11003125) in the MBL2 gene with susceptibility to tuberculosis and specific lineages of Mycobacterium tuberculosis causing tuberculosis in the Uyghur population of Xinjiang, China.Methods: From January 2019 to January 2020, we enrolled 170 Uyghur tuberculosis patients as the case group and 147 Uyghur staff with no clinical symptoms as the control group from four designated tuberculosis hospitals in southern Xinjiang, China. The polymorphisms of five loci in MBL2 of human were detected by sequencing. Whole-genome sequencing was applied in 68 M. tuberculosis isolates from the case group and the data were used to perform genealogy analysis.Results: The distributions of allele and genotype frequencies of five loci in MBL2 varied little between the case and control groups and varied little among the groups, including those infected with different lineages of M. tuberculosis and the control (except those of rs11003125), the P values were all > 0.05. The distribution of alleles of rs11003125 was statistically different between patients infected with lineages 3 and 4 M. tuberculosis (χ2=7.037, P=0.008). The C allele and CC genotype of rs11003125 were found to be protective factors against lineage 4 infection when compared to lineage 3 (ORs were 0.190 and 0.158, respectively; 95% confidence intervals were 0.053∼ 0.690 and 0.025∼ 0.999, respectively).Conclusion: Our results suggested that human’s susceptibility to tuberculosis is affected both by the host genetic polymorphisms and the lineage of the M. tuberculosis that people were exposed to. However, due to the limitation of the sample size in the present study, larger sample size and more rigorous design should be guaranteed in future studies.Keywords: mannose-binding lectin 2 gene, polymorphism, tuberculosis, Mycobacterium tuberculosis, lineage

Xi-Yuan Jiang,1,2 Qing Wang,1 Ying Zhang,3 Yong Chen,1 Long-Fei Wu4 1Center of Osteoporosis, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, Jiangsu, 215300, People’s Republic of China; 2School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 3Department of Clinical Laboratory, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, Jiangsu, 215300, People’s Republic of China; 4School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of ChinaCorrespondence: Xi-Yuan JiangCenter of Osteoporosis, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, Jiangsu, 215300, People’s Republic of China, Tel/Fax +86-512-57928140, Email 397365264@qq.comBackground: Chemerin has been suggested to be a risk factor for osteoporosis; however, its relationship with osteoporotic fracture is poorly understood. Herein, we intend to explore the association between serum chemerin and osteoporotic fracture.Methods: A total of 111 elderly women patients diagnosed with osteoporotic fracture were selected as the observation group, and 40 healthy subjects were enrolled as controls. Dual-energy X-ray absorptiometry, enzyme-linked immunosorbent assay, electrochemiluminescence immunoassay, and biochemical analysis were separately performed to determine body bone mineral density (BMD), chemerin levels, bone turnover markers, and other parameters. Pearson’s correlation analysis was conducted to examine a relationship between chemerin and laboratory parameters. Moreover, the levels of chemokine-like receptor 1 (CMKLR), C-C motif chemokine receptor-like 2 (CCRL2), collagen type I alpha (COLA1), and runt-related transcription factor-2 (RUNX2) were confirmed by quantitative polymerase chain reaction, and the effect of chemerin on osteogenic differentiation of hFOB1.19 cells was indicated by tartrate-resistant acid phosphatase and alkaline phosphatase double staining.Results: A higher level of chemerin was generally detected in patients with osteoporotic fracture compared with those without (P< 0.05). Compared with controls, lower BMD levels and higher β-CTx and P1NP levels were detected in patients with osteoporotic fracture (all P< 0.05). Interestingly, chemerin level was negatively correlated to BMD, but positively related to P1NP and β-CTx. Risk of osteoporotic fracture was 2.75-fold higher in subjects with each standard deviation increment of chemerin. Compared with controls, there were no significant differences in CMKLR1 and CCRL2 mRNA after incubation with osteogenic differentiation medium (all P> 0.05), whereas there was a remarkable decrease of COLA1 and RUNX2 after incubation with chemerin for nine days (all P< 0.05). Furthermore, prolonged incubation with chemerin enhanced osteoclast differentiation and maturation, consequently contributing to an increased risk of fracture.Conclusion: Chemerin is a strong and independent risk factor for osteoporosis-related fracture among elderly Chinese women.Keywords: chemerin, osteoporotic fracture, risk factor, elderly women

Qing Wang,1,&ast; Song Zhang,2,&ast; Qiaodong Xu,1 Jiahong Liang,1 Peidong Zhang,1 Wenlong Huang,1 Zhihuan Lin,1 Shaodong Zheng,1 Songgang Gu,1 Jiang Yan1 1Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong, People’s Republic of China; 2Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiang Yan; Songgang Gu, Email jyan@stu.edu.cn; gusonggang@163.comPurpose: Polymerase δ (POLD) proteins is a pivotal B-family DNA polymerase in the process of genome replication and repair and are comprised of POLD1-4. The predictive value of POLDs in hepatocellular carcinoma (HCC) has not been evaluated until now.Patients and Methods: A total of 369 hepatocellular carcinoma samples and 50 adjacent normal samples were enrolled from the TCGA-LIHC database, and the GSE10186 database was also used. Transcription, methylation and genetic alteration status of HCC patients were evaluated by GEPIA, Kaplan–Meier plotter, cBioPortal, MethHC, MethSurv. SurvExpress was employed to generate the overall prognosis prediction signature of POLDs. POLDs coexpressed genes were explored and enriched in potential pathways. K-M curves were generated to compare the different survival results in different groups, while ROC curves were used to validate the efficiency of the POLD signature.Results: All four POLD subunits were highly expressed in HCC tumor tissues. POLD1-3 and increased mRNA levels were also positively associated with advanced tumor stage and OS prognosis. Methylation in the promoter of POLDs affects mRNA expression and OS, especially for some specific CpG sites. Meanwhile, POLDs could preferably predict the prognosis for patients who suffered from a high gene mutation burden. We evaluated the combined prognostic predictive value of four POLD subunits in both the TCGA-LIHC and GSE10186 databases and recognized the statistically significant HR of the high-risk group, along with the reliable predictive value. The coexpressed gene sets and annotation results showed that the POLD coexpressed genes were mostly associated with DNA repair and cell cycle regulation pathways.Conclusion: POLD is an essential predictive factor for the prognosis of HCC. The united signature could precisely identify unfavorable clinical outcome of HCC.Keywords: DNA polymerase δ subunits, hepatocellular carcinoma, DNA repair, prognosis

Qian Wang,1,2 Huanhuan Zhu,1 Ruiming Dai,1 Tiantian Zhang1 1School of Public Health, Fudan University, Shanghai, 200032, People’s Republic of China; 2Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Tiantian Zhang, School of Public Health, Fudan University, 130 Dong’an Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Email Tiantianzhang18@fudan.edu.cnAim: The effect of sleep duration on cognitive function has been reported. However, the studies about the combined effects of total sleep duration and midday napping on cognition in elders were limited and inconclusive. We aimed to investigate the associations between total sleep duration, midday napping and cognitive function among middle-aged and older Chinese adults.Methods: Based on the 3rd wave of the China Health and Retirement Longitudinal Study (CHARLS) in 2015, a total of 9218 participants aged ≥ 45 years with completed cognition measurements were included. Cognitive functions were assessed by a combined global cognition score of episodic memory and mental status. Information about sleep-related variables, demographic characteristics, and health status were collected by validated questionnaires. Multivariate linear regression models were performed to evaluate the associations between total sleep duration, midday napping, and cognitive function. Stratified analyses were used to explore the potential effect modifier.Results: Overall, the global cognition score was 10.38 ± 4.30 among the participants (mean age: 61.5 ± 8.7 years). For sleep duration, both short sleep and long sleep duration were significantly associated with the increased risk of cognitive impairment after controlling for demographics and other confounders. Compared with sleeping for 7h per day, the adjusted β-coefficient and 95% CI of the risk of cognitive impairment was − 0.967 (95% CIs: − 1.191, − 0.742) for ≤ 5h, − 0.257 (− 0.498, − 0.016) for 6h, − 0.424 (− 0.650, − 0.198) for 8h and − 0.664 (− 0.876, − 0.452) for ≥ 9h. The combined effect analysis indicated that subjects with extended or without naps had a significantly higher risk of cognitive impairment in the ≤ 5h sleep time group (ref: 7h) and in extended nappers or without naps group (ref: short nappers). Subjects with extended naps or without naps might increase the risk of cognitive impairment, especially those having ≤ 5h total sleep time. Stratified analysis showed that participants aged ≥ 60 years without social activity increased the risk of cognitive decline.Conclusion: An inverted U-shaped association was observed between total sleep duration and cognitive function in Chinese elders, especially in those aged ≥ 60 years or without social activity. Short midday naps could mitigate the deleterious effects of poor sleep quality and shorter sleep duration on cognitive function. The findings could help us identify the vulnerable population and decrease the burden of cognitive impairment.Keywords: cognitive function, sleep, midday napping, epidemiology, China

Xiaowu Ma,1,2,&ast; Hongkai Zhuang,1,2,&ast; Qingbin Wang,1,2 Lei Yang,1,2 Zhiqin Xie,1,2 Ziyu Zhang,1,2 Wenliang Tan,1,2 Chenwei Tang,1,2 Yajin Chen,1,2 Changzhen Shang1,2 1Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yajin Chen; Changzhen Shang, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Tel +86-2034070701, Email cyj0509@126.com; shangcz_sysu@163.comBackground: Solute carrier family 39 member 1 (SLC39A1) has been identified as a zinc ion transport protein that possesses oncogenic properties in various types of cancers. However, its potential function in hepatocellular carcinoma (HCC) remains unknown. This study aimed to investigate the expression profile and potential mechanisms of SLC39A1 in HCC.Methods: SLC39A1 expression was analyzed using multiple databases. The clinical significance and associated biological pathways of SLC39A1 were investigated using bioinformatics analysis. Potential correlations between SLC39A1 expression and tumor immunity in HCC were also evaluated using single-sample gene set enrichment analysis (GSEA). Sixty paired HCC samples were used to verify the expression pattern of SLC39A1. In vitro studies were performed to investigate the oncogenic effects of SLC39A1 in HCC. Western blot analysis was conducted to further investigate the possible involved signaling pathways.Results: The overexpression of SLC39A1 in HCC was determined by bioinformatics analysis and was confirmed in tissues from our center. SLC39A1 overexpression was also significantly correlated with worse prognosis, advanced TNM stage, and histological grade. GSEA analysis demonstrated that SLC39A1 overexpression was involved in various tumor-related pathways, such as the cell cycle and Wnt signaling pathway. SLC39A1 knockdown repressed the proliferation, invasion, and migration abilities of HCC cells. Furthermore, SLC39A1 knockdown decreased the expression of the tumor progression-related proteins (eg, cyclin D1 and MMP2) and Wnt signaling pathway-related proteins (eg, Wnt3A and β-catenin). In addition, SLC39A1 overexpression may be associated with impaired tumor immunity in HCC, as evidenced by the increased infiltration of Th2 cells and reduced infiltration of cytotoxic cells.Conclusion: These findings preliminarily suggested the crucial effect of SLC39A1 overexpression on HCC tumor progression and immunosuppression, suggesting its potential as a novel prognostic and therapeutic target in HCC.Keywords: SLC39A1, hepatocellular carcinoma, prognosis, Wnt signaling pathway, immune infiltration

Heng Chen,1,&ast; Xingang Sun,1,&ast; Chengui Zhuo,2 Jianqiang Zhao,3 Aohan Zu,1 Qiqi Wang,1 Liangrong Zheng1 1Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Cardiology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, People’s Republic of China; 3Department of Cardiology, The Fourth Affiliated Hospital, College of Medicine, Zhejiang University, Yiwu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangrong Zheng; Qiqi Wang, Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Email 1191066@zju.edu.cn; 1508036@zju.edu.cnPurpose: Cardiac troponin I (cTnI) is a well-established biomarker for stroke prediction, especially in patients with heart diseases. However, the causal effect of circulating cTnI on stroke remains unclear.Methods: We employed Mendelian Randomization (MR) analysis to determine the associations between genetically predicted circulating cTnI levels and stroke and its subtypes. Summary-level data for exposure and outcomes were generated from different genome-wide association studies. Single-nucleotide polymorphisms (SNPs) associated with circulating cTnI at genome-wide significance level (P < 5 × 10− 8) were employed as instrumental variables (IVs). We used fixed-effect inverse-variance weighted (IVW) as the main method for pooling MR estimates. Sensitivity analyses and multivariable MR analyses were carried out to assess the robustness of the results.Results: Using the fixed-effects IVW method, we found that genetically elevated plasma cTnI levels may have a causal effect on the risk of cardioembolic stroke (CES) (odds ratio (OR), 1.58; 95% confidence interval (CI), 1.17– 2.13; P = 0.003). Additional analyses including multiplicative random-effects (mre) IVW, weighted median, MR-Egger and MR-PRESSO yielded similar results, but with broader CIs that span 1.0. The total effect of cTnI on CES was attenuated by adjusting for the effect of atrial fibrillation (OR,1.26; 95% CI, 0.76– 2.11; P = 0.371) and smoking (OR,1.53; 95% CI, 0.87– 2.66; P = 0.137). In addition, we found no causal effect of cTnI on the risk of any stroke and other stroke subtypes, including any ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, and intracerebral hemorrhage. These results were consistent across sensitivity analyses.Conclusion: This study provides little evidence that increased serum cTnI levels lead to a higher risk of stroke.Keywords: Mendelian randomization, cardiac troponin I, stroke, causation, genome-wide association studies