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Yuxuan Yao,1– 3 Hong Zhao,4 Hua Lu,5 Xiaoli Liu,6 Hui Liu,7 Zhanli Fu,8 Chunyue Li,1 Fude Zhou,1– 3 Wanyin Hou,1– 3 Sufang Shi1– 3 1Department of Nephrology, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, People’s Republic of China; 2Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People’s Republic of China; 3Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, People’s Republic of China; 5Department of Nephrology, Xingtai People’s Hospital, Xingtai, Hebei, People’s Republic of China; 6Department of Pathology, Xingtai People’s Hospital, Xingtai, Hebei, People’s Republic of China; 7Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 8Department of Nuclear Medicine, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wanyin Hou; Hong Zhao, Peking University First Hospital, Xicheng District, Beijing, People’s Republic of China, Tel +86 10-83575685, Email helenwanyin@bjmu.edu.cn; zhaohong_pufh@bjmu.edu.cnAbstract: Q fever, an infectious zoonotic disease caused by Coxiella burnetii, remains prevalent in China. Systemic infections can result in renal or hepatic complications; however, it is rare for both the kidneys and liver to be simultaneously affected. We present a case of a patient who exhibited fever, rapid deterioration in renal function, thrombocytopenia, and severe ascites. Renal biopsy revealed crescentic glomerulonephritis, while liver biopsy demonstrated non-cirrhotic portal hypertension. Metagenomic next-generation sequencing (mNGS) identified the presence of Coxiella burnetii in both venous blood and liver tissue samples. Notably, the patient’s renal insufficiency and ascites showed a positive response to treatment for chronic Q fever. These findings provide valuable insights into the limited understanding of kidney and liver diseases associated with Q fever. Advanced diagnostic technologies, including mNGS and positron emission tomography/computed tomography (PET/CT), have been employed to identify Coxiella burnetii infection.Keywords: Coxiella burnetii, acute kidney injury, non-cirrhotic portal hypertension, biopsies

Yanling Liao,1,&ast; Siyu Xie,2,&ast; Yifen Zhuo,3,&ast; Sisi Chen,1 Yuxin Luo,1 Ying Wei,4 Yusheng Yao1 1Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 2Department of Anesthesiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, People’s Republic of China; 3Department of Anesthesiology, Xiamen Haicang Hospital, Xiamen, People’s Republic of China; 4Department of Anesthesiology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Wei, Department of Anesthesiology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, 350025, People’s Republic of China, Email whm444@fjmu.edu.cn Yusheng Yao, Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, 134 Dongjie Street, Fuzhou, 350001, People’s Republic of China, Email fjslyys@126.comPurpose: Emergence delirium and postoperative negative behavioral changes (PNBC) are common complications in pediatric anesthesia. This study evaluated whether intranasal premedication combining dexmedetomidine and esketamine more effectively reduces these complications compared to either drug alone in children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia.Patients and Methods: This randomized, double-blind trial involved 198 children aged 2− 5 years undergoing tonsillectomy and/or adenoidectomy. Participants received intranasal premedication with either dexmedetomidine (2 μg/kg), esketamine (1 mg/kg), or their combination (dexmedetomidine 1 μg/kg plus esketamine 0.5 mg/kg). The primary outcome was the incidence of emergence delirium, defined as a Pediatric Anesthesia Emergence Delirium (PAED) scale score ≥ 10. Secondary outcomes included the incidence of PNBC, sedation depth, easiness of separation from parents, acceptance of the mask for induction, emergence time, postoperative pain score, parental satisfaction, and adverse events.Results: The combination premedication significantly reduced emergence delirium incidence (9.4%) compared to esketamine alone (38.1%; relative risk [RR] 0.25, 95% confidence interval [CI] 0.11– 0.57, p < 0.001), but not compared to dexmedetomidine alone (17.2%; RR 0.55, 95% CI 0.21– 1.39, p = 0.193). PNBC incidence at day 7 was lower with the combination (28.1%) versus dexmedetomidine (48.4%; RR 0.58, 95% CI 0.36– 0.93, p = 0.018), but not significantly different from esketamine alone (20.6%; RR 1.38, 95% CI 0.74– 2.58, p = 0.326). The combination also provided significantly superior sedation, improved ease of separation from parents, better acceptance of the mask for induction, shorter emergence time, and higher parental satisfaction than both monotherapies.Conclusion: In children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia, intranasal dexmedetomidine-esketamine premedication more effectively reduces emergence delirium compared to esketamine alone and PNBC compared to dexmedetomidine alone. This combination also improves sedation, shortens emergence times, and enhances parental satisfaction compared to monotherapy without significant adverse effects.Trial Registration: The Chinese Clinical Trial Registry, ChiCTR2300076709. Keywords: adenoidectomy, dexmedetomidine, emergence delirium, esketamine, intranasal administration, pediatric anesthesia, postoperative complications, tonsillectomy

Yongcheng Yao,1,2 Jie Tang,3 Zhenzhen Li,1 Shuyan Chen,1 Haixia Du,1 Lingeng Lu4 1School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, Henan, People’s Republic of China; 2WorldPop, School of Geography and Environmental Science, University of Southampton, Southampton, UK; 3Library, Zhengzhou University of Technology, Zhengzhou, Henan, People’s Republic of China; 4Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, New Haven, CT, USACorrespondence: Yongcheng Yao, School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, Henan, 450044, People’s Republic of China, Email 806306944@qq.comObjective: COVID-19-related lockdown can lead to mental health problem, which displays heterogeneous between individuals. The aim of this study was to explore the association between mental health, social support and psychological capital state of professional staff with different personalities during the COVID-19 pandemic in China.Methods: A cross-section study was conducted via online survey using the questionnaires of General Health Questionnaire (GHQ-12), Multidimensional Scale of Perceived Social Support (MSPSS), Psychological Capital Questionnaire (PCQ), Eysenck Personality Questionnaire-Revision Short Scale of China (EPQ-RSC). A total of 626 employees were included. Multiple regression analysis was performed to investigate the association of psychological capital, perceived social support, EPQ-N and EPQ-E and their interactions in general mental health.Results: About 2.7% of professionals had mental health. The married had a higher mental health score than the single (P

Bingquan Zhu,1,&ast; Junfei Zhu,2,3,&ast; Lingyan Sheng,2 Yake Yao,2 Hua Zhou2 1Children’s Health Care Department, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Taizhou Central Hospital, Taizhou, 324110, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Zhou; Yake Yao, Email zhouhua1@zju.edu.cn; dryyk@zju.edu.cnBackground: Aspergillus-specific IgG antibody test is considered to be the most reliable method for diagnosing chronic pulmonary aspergillosis (CPA), while its diagnostic roles in different kinds of CPA are still uncertain and it is a challenge of having a threshold to interpret the IgG levels.Purpose: This study aimed to evaluate the diagnostic value of the Dynamiker quantitative Aspergillus fumigatus-specific IgG antibody in different types of CPA with the aim of providing a reference for clinical work.Methods: This prospective study collected the clinical data of patients with suspected CPA admitted to the hospital from January 2020 to December 2022 and divided them into two groups: CPA and non-CPA. The study analyzed clinical characteristics and Aspergillus-specific IgG antibody test’s diagnostic value, and a receiver operating characteristic (ROC) curve was used to evaluate diagnostic efficacy.Results: We enrolled 54 CPA patients and 132 non-CPA patients. The average admission age of the CPA group was 61.0 (43.8, 70.0) years, and the sex ratio was 32/22 (male/female). The level of Aspergillus fumigatus-specific IgG antibody in the CPA group was significantly higher than the non-CPA group (95.2 (31.3, 213.3) vs 47.5 (34.0, 80.3) AU/mL, p = 0.001). The area under the ROC curve was 0.653 (95% confidence interval [CI]: 0.580– 0.721, p = 0.003). The cutoff with the best diagnostic efficacy was 87 AU/mL, and the sensitivity and specificity were 57.4% and 77.3%, respectively. There was no significant difference in the level of specific IgG antibody among the five CPA types (p = 0.543); however, it was relatively higher in chronic cavitary pulmonary aspergillosis (CCPA).Conclusion: Aspergillus-specific IgG antibody is valuable diagnostic marker for CPA, while its value in differential diagnosis among different types of CPA is limited.Keywords: Aspergillus, chronic pulmonary aspergillosis, IgG, subtypes, diagnosis

Tianqing Cao,1,&ast; Fei Liu,2,&ast; Yan Yao,2 Danghong Sun,2 Rong Wang,3 Junxia Cao,3 Jie Meng,2 Ling Zhang,4 Weiming Li1 1Shanghai Tenth People’s Hospital, Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Cardiology, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, People’s Republic of China; 3Department of Pulmonology, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, People’s Republic of China; 4Department of Nursing, Changshu No.2 People’s Hospital/Affiliated Changshu Hospital of Nantong University, Changshu, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiming Li; Ling Zhang, Email 18917683469@189.cn; nancy120312@163.comObjective: Current scoring systems for short-term prognosis in patients with acute myocardial infarction (AMI) lack coverage of risk factors and have limitations in risk stratification. The aim of this study was to develop a novel assessment system based on laboratory indicators and frailty quantification to better infer short-term prognosis and risk indication in patients with AMI.Methods: A total of 365 patients with MI from January 2022 to June 2023 in Northern Jiangsu Province Hospital were included. The primary endpoint was all-cause mortality and major adverse cardiac events (MACE) during follow-up. A novel scoring model ranging from 0 to 12 was constructed, and the predictive ability of this scoring system was evaluated using the area under the receiver operating characteristic curve (AUC).Results: During follow-up, 68 patients experienced MACE. Five scoring indicators were selected through multivariate logistic regression analysis, resulting in a composite score with an AUC of 0.925, demonstrating good prognostic accuracy.Conclusion: The novel prognostic assessment system, which integrates age, Stress Hyperglycemia Ratio (SHR), Neutrophil to Lymphocyte Ratio (NLR), lactate, and frailty score, exhibits good predictive value for short-term MACE in patients with acute myocardial infarction and may enable more accurate risk classification for future use in MI patient risk management.Keywords: myocardial infarction, frailty index, major adverse cardiac events, prognosis, cohort study

Xueya Chen,1,&ast; Zhiling Yan,2,&ast; Weipeng Liu,1 Lili Guo,1 Jinmei Xu,2 Li Shi,3 Yufeng Yao1 1Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People’s Republic of China; 2Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Shi, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, 650118, People’s Republic of China, Email shili.imb@gmail.com Yufeng Yao, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, 650118, People’s Republic of China, Email leoyyf@gmail.com; yufeng_yao@imbcams.com.cnPurpose: Cervical cancer (CC) poses a significant threat to women’s health worldwide, and multiple signaling pathways have been confirmed to be involved in its development. The AMPK signaling pathway plays a central role in maintaining energy homeostasis, and its dysregulation is closely associated with the occurrence of CC. Changes in microRNA (miRNA) expression levels might be related to the AMPK signaling pathway. Single nucleotide polymorphisms (SNPs) can affect the function of miRNA and result in the development of CC. To investigate the association between the SNPs of AMPK pathway-associated miRNAs and CC in a Han Chinese population, we selected eight miRNA genes located in the AMPK pathway and analyzed nine SNP loci within these genes to explore whether they are associated with genetic susceptibility to cervical intraepithelial neoplasia (CIN) and CC.Methods: A total of 2,220 subjects were included in this study, including 928 healthy controls, 421 CIN patients, and 871 CC patients. Nine candidate SNPs (rs895819 in miR-27a, rs10061133 in miR-449b, rs41291179 in miR-216a, rs76481776 in miR-182, rs10406069 in miR-5196, rs12803915 and rs550894 in miR-612, rs66683138 in miR-3622b, and rs2620381 in miR-627) were genotyped using the TaqMan method.Results: The results showed significant differences in the allele distribution of rs41291179 and rs12803915 between the control group and the CIN group, as well as between the control group and the CC group (all P values < 0.005). The A allele of rs41291179 and the G allele of rs12803915 were associated with decreased risk of CIN (OR = 0.05, 95% CI: 0.01– 0.39; OR = 0.61, 95% CI: 0.49– 0.76) and CC (OR = 0.08, 95% CI: 0.01– 0.66; OR = 0.71, 95% CI: 0.59– 0.86), respectively.Conclusion: Our results suggest that polymorphisms in miRNA genes of the AMPK signaling pathway are associated with the development of CC.Keywords: genotyping, SNP, gene enrichment, genetic susceptibility

Maomin Jiang,1,&ast; Yisong Yao,2,&ast; Xiaoqian Xia,3,&ast; Yang Kong,4 Nan Zhang5 1School of Public Affairs, Xiamen University, Xiamen, Fujiang, People’s Republic of China; 2School of The Fourth Clinical Medical College, Qingdao University, Yantai, Shangdong, People’s Republic of China; 3Department of Public Health, Environments & Society, London School of Hygiene & Tropical Medicine, London, UK; 4School of Health Management, Binzhou Medical University, Yantai, Shangdong, People’s Republic of China; 5Physical Education Department, Shandong Technology and Business University, Yantai, Shangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nan Zhang, Email zhangnansd@126.comBackground: This study aims to investigate the relationship between older adults’ perceived community services for the elderly (PCSE), life satisfaction (LS), and self-rated health (SRH).Methods: Data from four rounds of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008 to 2018 were used. A total of 2454 older adults were obtained. Unconditional Least Squares (ULS) was used to measure PCSE, LS, and SRH growth trajectories without covariates. Finally, a mediating latent growth model was constructed using Mplus 8.3 to examine the mediating role of LS in the relationship between PCSE and SRH after adjusting for some demographic characteristics.Results: The results from the ULS method indicate that the intercepts and slopes for PCSE and LS are significantly negatively correlated (β1 = − 0.629, β2 = − 0.579, p < 0.001). Additionally, there is a significant positive correlation between the intercept and slope of health levels (β = 0.774, p < 0.001). Using a parallel growth model, significant regression coefficients were found between the intercept of PCSE and the intercepts of SRH and LS (β1 = − 0.335, β2 = 0.378, p < 0.01). Similarly, the regression coefficients between the slope of PCSE and the slopes of SRH and LS were also significant (β1 = − 0.532, β2 = 0.344, p < 0.01). Furthermore, the regression coefficient between the intercept of LS and the intercept of SRH was significant (β = 0.415, p < 0.001). The regression coefficient between the slope of LS and the slope of SRH was also found to be significant (β = 0.729, p < 0.001).Conclusion: It is essential to ensure adequate supply and accessibility of community services for older adults. LS especially is, and should be a promising target for assessing the quality of life and utilization of PCSE supply.Keywords: perceived community services for elderly, life satisfaction, Self-rated health, Latent growth model, older adults

Yufeng Yao,1,2 Qiyuan Song,3 Jingnan Zhang,2,4 Yingying Wen,2,4 Xiaoyan Dou2 1Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 2Department of Ophthalmology, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Ophthalmology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 4Shenzhen University Medical College, No.1066 Xueyuan Road, Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Xiaoyan Dou, Email douxy08@163.comAbstract: The retina’s similar structure and function to the brain make it a unique visual “window” for studying cerebral disorders. Ophthalmic artery occlusion (OAO) or retinal artery occlusion (RAO) is a severe ophthalmic emergency that significantly affects visual acuity. Studies have demonstrated that patients with OAO or RAO face a notably higher risk of future acute ischemic stroke (AIS). However, ophthalmologists often overlook multidisciplinary approach involving the neurologist, to evaluate the risk of AIS and devise clinical treatment strategies for patients with OAO or RAO. Unlike the successful use of thrombolysis in AIS, the application of thrombolysis for OAO or RAO remains limited and controversial due to insufficient reliable evidence. In this review, we aim to summarize the anatomical and functional connections between the retina and the brain, and the clinical connection between OAO or RAO and AIS, compare and review recent advances in the effectiveness and safety of intravenous and intra-arterial thrombolysis therapy in patients with OAO or RAO, and discuss future research directions for OAO or RAO. Our goal is to advance the development of multidisciplinary diagnosis and treatment strategies for the disease, as well as to establish expedited pathways or thrombolysis guidelines for vascular intervention.Keywords: retina, brain, ophthalmic artery occlusion, retinal artery occlusion, stroke, thrombolysis

Zi Wang,1 Xiaoyu Li,1 Qing Xu,1 Yao Yao,1 Xiaoye Li,1 Hongmei Yan,2 Qianzhou Lv1 1Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Qianzhou Lv, Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Email lv.qianzhou@zs-hospital.sh.cn Hongmei Yan, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Email yan.hongmei@zs-hospital.sh.cnBackground: The influence of genetic variants on the glucose-lowering effects of dapagliflozin remains unclear. This study aims to investigate the impact of polymorphisms in solute carrier family 5 member 2 (SLC5A2), uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9), solute carrier family 2 member 2 (SLC2A2) and member 4 (SLC2A4) on the anti-hyperglycemic effect of dapagliflozin in patients with type-2 diabetes mellitus (T2DM).Methods: A total of 141 patients with T2DM were included in this prospective cohort study. Twenty-nine single nucleotide polymorphisms (SNPs) were selected and genotyped using the Sequenom MassArray platform or Sanger sequencing. Glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels were compared before and after the treatment with dapagliflozin.Results: Among the 29 SNPs selected, 27 were successfully analyzed. After three months of dapagliflozin treatment, FBG levels were significantly reduced (8.00 mmol/L (5.45– 10.71) mmol/L vs 6.40 mmol/L (5.45– 9.20) mmol/L, p = 0.003) in patients with T2DM. However, there was no significant change in HbA1c levels (8.10% (6.88– 10.00)% vs 8.10% (6.83– 10.00)%, p = 0.452). Analysis of covariance showed that patients with the minor allele homozygote or heterozygote of rs12471030 (CT/TT), rs12988520 (AC/CC) or rs2602381 (TC/CC) had higher FBG levels compared to those with the major allele homozygote (p = 0.014, p = 0.024, and p = 0.044, respectively). After adjusting for baseline FBG level, age, gender, body mass index, use of insulin and use of metformin, three SNPs—rs12471030, rs12988520 and rs2602381—were associated with the anti-hyperglycemic effect of dapagliflozin. However, using a stringent significance threshold (p < 0.002 with Bonferroni correction), none of these selected SNPs were significantly associated with FBG and HbA1c levels after dapagliflozin treatment.Conclusion: After adjusting for confounding variables, polymorphisms in SLC5A2, UGT1A9, SLC2A2 and SLC2A4 genes were not associated with the anti-hyperglycemic effect of dapagliflozin in the Chinese population.Clinical Trial Registration Number: ChiCTR2200059645.Keywords: dapagliflozin, fasting blood glucose, glycated hemoglobin, polymorphisms, UGT1A9

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

Yufeng Yao,1,2 Zhenli Lin,3 Baikang Ye,1 Tingxi Long,1,4 Suting Li,1,4 Huixian Liang,1,4 Tianyi Luo,1,4 Xiaoyan Dou1 1Department of Ophthalmology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of China; 2Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 3Department of Ophthalmology, Shenzhen University General Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 4Shenzhen University Medical College, Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Xiaoyan Dou, Department of Ophthalmology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, No. 3002 Sungang West Road, Futian District, Shenzhen, Guangdong Province, 518035, People’s Republic of China, Tel/Fax +86 13600169183, Email douxy08@163.comPurpose: Previous studies simply linearized the relationship between low density lipoprotein (LDL) and diabetic macular edema’s (DME) probability, ignoring the possibility of a nonlinear relationship between them. We aimed to investigate the nonlinear relationship between LDL and DME probability in patients with type 2 diabetes mellitus (T2DM).Patients and methods: The study recruited 431 T2DM patients who attended Guangdong Provincial People’s Hospital from December 2017 to November 2018. A multivariate logistic regression model was conducted to evaluate the association between LDL and DME probability. The nonlinear relationship was identified by generalized additive model. Subgroup analyses were performed to assess the consistency of the association in different subgroups.Results: LDL was positively associated with DME probability (OR=1.60, 95% CI: 1.10~2.34, P=0.0145) after adjusting for covariates. A nonlinear relationship between LDL and DME probability was discovered, with an inflection point for LDL around 4.85 mmol/L (95% CI: 4.18~4.93, P=0.037). The effect sizes and the confidence intervals on the left and right sides of inflection point were 2.17 (1.31 to 3.58) and 0.26 (0.04 to 1.77), respectively. Subgroup analyses revealed other variables had no effect on the association between them.Conclusion: Our finding suggested LDL was positively correlated with DME probability in T2DM patients. And the relationship between LDL and DME probability was nonlinear. Our findings need to be confirmed by further causal researches.Keywords: low density lipoprotein, diabetic macular edema, nonlinearity, association

Lingyan Sheng,1,&ast; Wenhong Jiang,1,2,&ast; Yake Yao,1 Jianying Zhou,1 Hua Zhou1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Jiangshan People Hospital, Quzhou, 324110, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Zhou, Email zhouhua1@zju.edu.cnBackground: The role of Aspergillus-specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also limited.Purpose: This study aims to evaluate the quantitative test value of Aspergillus fumigatus-specific IgG antibody in non-neutropenic IPA, which could provide additional evidence for related clinical diagnosis.Methods: This prospective study collected clinical data of suspected IPA patients from January, 2020 to December, 2022, and patients were divided into two groups, IPA and non-IPA. The study analyzed clinical characteristics and diagnostic value of Aspergillus-specific IgG antibody test, using the receiver operating characteristic (ROC) curve to evaluate diagnostic efficacy.Results: The study enrolled 59 IPA cases and 68 non-IPA cases, the average admission age of IPA group was 63.2± 9.6 (33– 79), and the gender ratio (male:female) of IPA group was 42:17. The proportion of patients with history of smoking and COPD were higher in IPA group (59.3% vs 39.7%, P=0.027; 33.9% vs 14.7%, P =0.011, respectively). The level of Aspergillus fumigatus-specific IgG antibody in IPA group was significantly higher than non-IPA group (202.1± 167.0 vs 62.6± 58.0, P< 0.001). The area under the ROC curve was 0.799 (95%CI: 0.718, 0.865 P< 0.001), and the cut-off with best diagnostic efficacy was 91 AU/mL.Conclusion: Immunological test plays an important role in the diagnosis of pulmonary aspergillosis, and Aspergillus-specific IgG antibody test has the good diagnostic value in non-neutropenic IPA.Keywords: Aspergillus, invasive pulmonary aspergillosis, IgG, non-neutropenic, diagnosis

Zi-Guo Sun,1,2 Shi-Cheng Xu,2 Qin Yang,3 Yun Yao,2 Qi-Long Mao,2 Cheng-Feng He,2 Chang-Jiang Guan,2 Yan Du,2 Li Ma,2 Xie-Shan Huang,2 Xiao-Long Hou,2 Hong-Mei Yang,2 Xia Peng,2 Jun-Jie Jian4 1Department of Intensive Care and Emergency Center, Bazhong Hospital of Integrated Chinese and Western Medicine, Bazhong, Sichuan, 636600, People’s Republic of China; 2Department of Critical Care Medicine, Bazhong Central Hospital, Bazhong, Sichuan, 636600, People’s Republic of China; 3School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, 610000, People’s Republic of China; 4Department of Health Management, Bazhong Center for Health Education and Health Management, Bazhong, Sichuan, 636600, People’s Republic of ChinaCorrespondence: Xia Peng; Jun-Jie Jian, Email bzyszkzx@126.com; 2906194909@qq.comBackground: Fat overload syndrome is a rare and severe adverse reaction triggered by the infusion of a single source of lipid emulsion, resulting in elevated blood triacylglycerol (TG) levels. The majority of literature reports focus on cases of fat overload syndrome in patients with mild symptoms. This case is significant because it demonstrates the diagnostic and therapeutic experience and provide valuable insights for the management for severe fat overload syndrome.Case Presentation: We present a case report of a female patient who developed fat overload syndrome following prolonged and excessive infusion of lipid emulsion after colon resection surgery. In the setting of compromised immune function and malnutrition, the patient’s pulmonary infection and respiratory distress symptoms have further exacerbated. Hence, in addition to severe pancreatitis, the patient has also contracted severe pneumonia. Upon admission, tracheal intubation, plasma exchange and blood perfusion were performed. Subsequently, comprehensive treatment was provided, including anti-infection, antispasmodic, acid suppression, enzyme inhibition, as well as targeted supportive measures to stabilize electrolytes and nutritional status. After treatment, there was a progressive reduction in blood lipid levels. After assessing the relevant risks, it was deemed necessary to perform an emergency computed tomography (CT)-guided percutaneous drainage tube placement procedure targeting the necrotic area of the pancreas while the patient was still intubated. Finally, the patient was discharged from the hospital.Conclusion: The case highlights the association between fat overload syndrome and pancreatitis as well as the use of lipid emulsions and suggests the treatment strategies for severe fat overload syndrome.Keywords: lipid overload syndrome, plasma exchange, blood perfusion, pancreatitis, pneumonia

Ting Wang,1,2,&ast; Lin Wang,1,&ast; Yunliang Yao,2,&ast; Nan Liu,1 Aiqin Peng,1 Min Ling,2 Fei Ye,1 JiaoJiao Sun1 1Affliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou Mental Health Center, Yangzhou, Jiangsu, People’s Republic of China; 2School of Medicine & Nursing, Huzhou University, Huzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Ye; Jiaojiao Sun, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou mental health center, Yangzhou, Jiangsu, 225000, People’s Republic of China, Tel +8613645251172 ; +8615150805127, Email 850906053@qq.com; sun15150805127@163.comBackground: The global incidence of acute events in psychiatric patients is intensifying, and models to successfully predict acute events have attracted much attention.Objective: To explore the influence factors of acute incident severe mental disorders (SMDs) and the application of Rstudio statistical software, and build and verify a nomogram prediction model.Methods: SMDs were taken as research objects. The questionnaire survey method was adopted to collect data. Patients with acute event independent factors were screened. R software multivariable Logistic regression model was constructed and a nomogram was drawn.Results: A total of 342 patients with SMDs were hospitalized, and the number of patients who encountered acute events was 64, which accounted for 18.70% of all patients. Statistical significances were found in many aspects (all P ˂ 0.05). Such aspects included Medication adherence, disease diagnosis, marital status, caregivers, social support and the hospitalization environment (odds ratio (OR) = 4.08, 11.62, 12.06, 10.52, 0.04 and 0.61, respectively) were independent risk factors for the acute events of patients with SMDs. The prediction model was modeled, and the AUC was 0.77 and 0.80. The calibration curve shows that the model has good calibration. The clinical decision curve shows that the model has a good clinical effect.Conclusion: The constructed risk prediction model shows good prediction effectiveness in the acute events of patients with SMDs, which is helpful for the early detection of clinical mental health staff at high risk of acute events.Keywords: SMDs, acute event, influencing factors, predictive model and nomogram

Qingzhu Zhang,1,2 Yinhui Yao,3 Yufeng Chen,1 Dong Ren,1 Pengcheng Wang1 1Orthopedic Trauma Service Center, Third Hospital of Hebei Medical University, Major Laboratory of Orthopedic Biomechanics in Hebei Province, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Orthopedics, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, People’s Republic of China; 3Department of Pharmacy, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, People’s Republic of ChinaCorrespondence: Pengcheng Wang, Orthopedic Trauma Service Center, Third Hospital of Hebei Medical University, Major Laboratory of Orthopedic Biomechanics in Hebei Province, Shijiazhuang, Hebei Province, People’s Republic of China, Email zhengzainingmeng@163.comAim: A high percentage of the elderly suffer from knee osteoarthritis (KOA), which imposes a certain economic burden on them and on society as a whole. The purpose of this study is to examine the risk of KOA and to develop a KOA nomogram model that can timely intervene in this disease to decrease patient psychological burdens.Methods: Data was collected from patients with KOA and without KOA at our hospital from February 2021 to February 2023. Initially, a comparison was conducted between the variables, identifying statistical differences between the two groups. Subsequently, the risk of KOA was evaluated using the Least Absolute Shrinkage and Selection Operator method and multivariate logistic regression to determine the most effective predictive index and develop a prediction model. The examination of the disease risk prediction model in KOA includes the corresponding nomogram, which encompasses various potential predictors. The assessment of disease risk entails the application of various metrics, including the consistency index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, the calibration chart, the GiViTi calibration band, and the model for predicting KOA. Furthermore, the potential clinical significance of the model is explored through decision curve analysis (DCA) and clinical influence curve analysis.Results: The study included a total of 582 patients, consisting of 392 patients with KOA and 190 patients without KOA. The nomogram utilized age, haematocrit, platelet count, apolipoprotein a1, potassium, magnesium, hydroxybutyrate dehydrogenase, creatine kinase, and estimated glomerular filtration rate as predictors. The C index, AUC, calibration plot, Giviti calibration band, DCA and clinical influence KOA indicated the ability of nomogram model to differentiate KOA.Conclusion: Using nomogram based on disease risk, high-risk KOA can be identified directly without imaging.Keywords: decision support, knee osteoarthritis, nomogram, predictors, risk factors

Tongtong Zhang,1,&ast; Xincheng Liao,2,&ast; Yuzhi Chen,3,&ast; Xinru Shu,3 Deshan Liu,4 Yusheng Yao3,5 1Department of Anesthesiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Anesthesiology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 3Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 4Department of Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 5Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deshan Liu; Yusheng Yao, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, 134, Dongjie Street, Fuzhou, 350001, People’s Republic of China, Email liudeshan198491@163.com; fjslyys@126.comPurpose: Intravenous regional anesthesia (IVRA) using lidocaine provides effective localized analgesia but its duration is limited. The mechanism by which dexmedetomidine enhances lidocaine IVRA is unclear but may involve modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.Materials and Methods: Lidocaine IVRA with varying dexmedetomidine concentrations was performed in the tails of Sprague-Dawley rats. Tail-flick and tail-clamping tests assessed IVRA analgesia and anesthesia efficacy and duration. Contributions of α2 adrenergic receptors and HCN channels were evaluated by incorporating an α adrenergic receptor antagonist, the HCN channel inhibitor ZD7288, and the HCN channel agonist forskolin. Furthermore, whole-cell patch clamp electrophysiology quantified the effects of dexmedetomidine on HCN channels mediating hyperpolarization-activated cation current (Ih) in isolated dorsal root ganglion neurons.Results: Dexmedetomidine dose-dependently extended lidocaine IVRA duration and analgesia, unaffected by α2 receptor blockade. The HCN channel inhibitor ZD7288 also prolonged lidocaine IVRA effects, while the HCN channel activator forskolin shortened effects. In dorsal root ganglion neurons, dexmedetomidine concentration-dependently inhibited Ih amplitude and shifted the voltage-dependence of HCN channel activation.Conclusion: Dexmedetomidine prolongs lidocaine IVRA duration by directly inhibiting HCN channel activity, independent of α2 adrenergic receptor activation. This HCN channel inhibition represents a novel mechanism underlying the anesthetic and analgesic adjuvant effects of dexmedetomidine in IVRA.Keywords: dexmedetomidine, hyperpolarization-activated cyclic nucleotide-gated channel, intravenous regional anesthesia, lidocaine

Diguo Zhai,1,2 Qingwei Chen,1,2 Ying Yao,3 Taotao Ru,1,2 Guofu Zhou1,2 1Guangdong Provincial Key Laboratory of Optical Information Materials and Technology, Institute of Electronic Paper Displays, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou, 510006, People’s Republic of China; 2National Center for International Research on Green Optoelectronics, South China Normal University, Guangzhou, 510006, People’s Republic of China; 3Anhui Provincial Library, Hefei, 230000, People’s Republic of ChinaCorrespondence: Taotao Ru; Qingwei Chen, Lab of Light and Physio-Psychological Health-National Center for International Research on Green Optoelectronics-South China Academy of Advanced Optoelectronics-South China Normal University, No. 55, West Zhongshan Road, Tianhe District, Guangzhou, 510631, People’s Republic of China, Tel +86 15603063417 ; +86 15521094813, Email taotao.ru@m.scnu.edu.cn; qingwei.chen@m.scnu.edu.cnPurpose: To explore whether sleep electroencephalogram (EEG) microarousals of different standard durations predict daytime mood and attention performance in healthy individuals after mild sleep restriction.Participants and Methods: Sixteen (nine female) healthy college students were recruited to examine the correlations between nocturnal EEG microarousals of different standard durations (≥ 3 s, ≥ 5 s, ≥ 7 s, ≥ 9 s) under mild sleep restriction (1.5 h) and the following morning’s subjective alertness, mood, sustained attention, and selective attention task performance.Results: Results revealed that mild sleep restriction significantly reduced subjective alertness and positive mood, while having no significant effect on negative mood, sustained attention and selective attention performance. The number of microarousals (≥ 5 s) was negatively associated with positive mood at 6:30. The number of microarousals was significantly and positively correlated with the response time difference value of disengagement component of the selective attention task at around 7:30 (≥ 5 s and ≥ 7 s) and 9:00 (≥ 5 s). The number of microarousals (≥ 7 s) was significantly and positively correlated with the inaccuracy difference value of orientation component of the selective attention task at around 9:00.Conclusion: The number of EEG microarousals during sleep in healthy adults with mild sleep restriction was significantly and negatively related to their daytime positive affect while positively associated with the deterioration of disengagement and orientation of selective attention performance, but this link is dependent on the standard duration of microarousals, test time and the type of task.Keywords: microarousal, alertness, sustained attention, selective attention, sleep restriction

Yan Zhang,1,&ast; Qiongyao Yang,2– 4,&ast; Qianru Ma,5,&ast; Yuanxiong Wu,5,&ast; Yue Wang,2– 4 Chuanchuan Chen,2– 4 Yitan Yao,2– 4 Ziqiao Feng,2,3 Xiaoping Yuan,2,3 Shengya Shi,2,3 Kai Zhang2,3 1Department of Pneumology, Second People’s Hospital of Anhui Province, Hefei, People’s Republic of China; 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Anhui Psychiatric Center, Anhui Medical University, Hefei, People’s Republic of China; 4School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Psychiatry, Third People’s Hospital of Fuyang, Fuyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Zhang, Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, People’s Republic of China, Tel/Fax +86-551-82324114, Email zhangkai@ahmu.edu.cnPurpose: Masks are designed to reduce the spread of airborne pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although wearing a mask has some adverse effects. The primary objective of this study was to explore the effects of surgical masks and N95 respirators on patients diagnosed with anxiety.Methods: Subjects diagnosed with first-episode anxiety disorders were recruited from outpatient departments between February and July, 2023. A self-administered questionnaire was administered at baseline and at follow-up. The questionnaire addressed demographic information, Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D) and Insomnia Severity Index (ISI). Subjects were divided into three groups (n=30 each): control (no mask); surgical mask; and N95 respirator. The Kruskal–Wallis test and repeated measures analysis of variance were used to examine associations between face mask use and emotion.Results: Ninety subjects completed the study, of whom 51 (56.67%) were male and 39 (43.33%) were female. Time and group effects were observed in HAM-A score among the 3 groups. After 4 weeks, mean (± SD) HAM-A score decreased from 32.63± 13.37 to 28.07± 9.33 in the control group, increased from 33.67± 12.47 to 36.80± 10.32 in the surgical mask group, and from 32.33± 14.73 to 41.13± 8.29 in the N95 respirator group, with no sex differences among the 3 groups. HAM-A score was significantly higher in the mask groups than that in the control group at follow-up. Only N95 respirator group exhibited significant time effects on HAM-D and ISI scores, with a decreasing trend in HAM-D score and an opposite trend in ISI score.Conclusion: Prolonged mask use may exacerbate anxiety, especially among those wearing N95 respirator masks. In a post-pandemic environment, governments should improve public health beliefs regarding coronavirus disease 2019 and promote the safety of face mask use, thus reducing the physiological and psychological effects of improper mask use.Keywords: anxiety, COVID-19, health beliefs, mask, N95

Lei Feng,1,&ast; Ning Zhang,1,&ast; Lan Luo,1,&ast; Jie Liu,1,&ast; Yong Yao,1,&ast; Ming-Sheng Gao,1,&ast; Jin Pan,1,&ast; Cai He2 1The Division of Gastroenterology and Hepatology, Suining Central Hospital, Suining City, Sichuan Province, People’s Republic of China; 2The Division of Gastroenterology and Hepatology, Yibin Second People’s Hospital, Yibin City, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Feng, The Division of Gastroenterology and Hepatology, Suining Central Hospital, Suining City, Sichuan Province, People’s Republic of China, Tel +8618008258982, Email fenglei822@163.comBackground: Several studies suggest that Proteasome 26S Subunit, ATPase (PSMC) family genes are of great importance in tumor progression and spreading, but the study for systematic evaluation of the function of PSMC genes in hepatocellular carcinoma (HCC) is currently lacking.Methods: The functions of PSMC genes in HCC were analyzed using multiple online databases, including the TCGA database, GEO database, HPA database, cBioPortal database, DAVID, and KEGG pathway. Experiments were later conducted to verify PSMC expression.Results: High levels of PSMC gene expression were detected in HCC tissues and PSMCs exhibited potentially powerful abilities in diagnosing HCC patients. All PSMC proteins are expressed to varying degrees in HCC tissues and high expression of the PSMC genes lead to poor prognosis in patients with HCC. Moreover, DNA methylation involves the regulation of the expression of PSMC2 and PSMC5 in HCC, and the levels of methylation of PSMC2 or PSMC5 correlate positively with patient overall survival in HCC patients. The copy number alteration and mutation of PSMC genes were observed and related to the expression of PSMCs in HCC. Functional enrichment analysis showed that many highly co-expressed genes of PSMCs had a potential role in tumor progression and metastasis, which merited further in-depth study. Functional network analysis also suggests that the primary biological function of PSMC genes is the regulation of protein homeostasis and energy metabolism in HCC. Moreover, the expression levels of PSMCs are related to immune cell infiltrates and immunomodulatory factors in HCC.Conclusion: Our study indicates that PSMC genes are the potential target for precision immunotherapy and novel prognostic biomarkers for HCC.Keywords: Proteasome 26s Subunit, ATPase, PSMC, hepatocellular carcinoma, prognostic biomarkers, therapeutic targets

Yuting Kang,1,&ast; Qiujie Li,2,&ast; Yao Yao,3 Chao Xu,2 Zhuoran Qiu,2 Wei Jia,1,3 Gang Li,1,3 Pengtao Wang1 1Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3Center of Medical Laboratory, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Li; Pengtao Wang, General Hospital of Ningxia Medical University, Technology Building 601, 804 Shengli Road, Yinchuan, People’s Republic of China, Tel +86-0951-6744462 ; +86-0951-6743330, Email gone.lee@163.com; wangpengtao2021@163.comPurpose: The objective of this study was to determine the clinical distribution, in vitro antifungal susceptibility and underlying resistance mechanisms of Aspergillus fumigatus (A. fumigatus) isolates from the General Hospital of Ningxia Medical University between November 2021 and May 2023.Methods: Antifungal susceptibility testing was performed using the Sensititre YeastOne YO10, and isolates with high minimal inhibitory concentrations (MICs) were further confirmed using the standard broth microdilution assays established by the Clinical and Laboratory Standards Institute (CLSI) M38-third edition. Whole-Genome Resequencing and RT-qPCR in azole-resistant A. fumigatus strains were performed to investigate the underlying resistance mechanisms.Results: Overall, a total of 276 A. fumigatus isolates were identified from various clinical departments, showing an increasing trend in the number of isolates over the past 3 years. Two azole-resistant A. fumigatus strains (0.72%) were observed, one of which showed overexpression of cyp51A, cyp51B, cdr1B, MDR1/2, artR, srbA, erg24A, and erg4B, but no cyp51A mutation. However, the other strain harbored two alterations in the cyp51A sequences (L98H/S297T). Therefore, we first described two azole-resistant clinical A. fumigatus strains in Ningxia, China, and reported one azole-resistant strain that has the L98H/S297T mutations in the cyp51A gene without any tandem repeat (TR) sequences in the promoter region.Conclusions: This study emphasizes the importance of enhancing attention and surveillance of azole-resistant A. fumigatus, particularly those with non-TR point mutations of cyp51A or non-cyp51A mutations, in order to gain a better understanding of their prevalence and spread in the region.Keywords: Aspergillus fumigatus, azole resistance, cyp51A mutation, tandem repeat sequences

Yi Yao,1,&ast; Juan Li,2,&ast; Wenwu Sun,1,&ast; Chaoping Ma,2,&ast; Ning Ning,1 Jiaoyan Li,1 Tongtian Ni,1 Menglu Gui,1 Ying Chen,1 Bing Zhao,1 Jiyuan Zhang,2 Jiyue Zhu,3 Chengjin Gao,2 Huiqiu Sheng,1 Enqiang Mao1 1Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 2Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqiu Sheng, Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China, Tel +86-15801971839, Email shenghq803@163.com Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Tel +86-18221088783, Email gaochengjin@xinhuamed.com.cnPurpose: Both nonthyroidal illness syndrome (NTIS) and disseminated intravascular coagulation (DIC) are commonly occurred in sepsis. The objective of this study is to evaluate the association between NTIS and DIC, as well as their impacts on the mortality in adults with sepsis.Patients and methods: A total of 1219 septic patients in two Chinese academic centers from October 2012 and October 2022 were enrolled in analysis. We conduct logistic regression models to analyze the independent risk factors for DIC. Modified Poisson regression models are used to estimate the relative risk (RR) of NTIS on the 28 days mortality in septic patients with DIC. Correlation analysis between thyroid function parameters and coagulation parameters is performed with Pearson coefficient be reported.Results: DIC is diagnosed on 388 (31.8%) of all the 1219 enrolled septic patients within 72 hours after admission. In multivariate logistic regression models, NTIS (OR 3.19; CI 2.31– 4.46; p< 0.001) is a statistically significant independent risk factor for DIC after adjustment for potential confounders. Twenty-eight days mortality is significantly higher in DIC patients complicated with NTIS compared with the other DIC patients (23.2% vs 14.0%, p=0.024). This result is also robust in different modified Poisson regression models (Model 1: RR 1.46; CI 1.25– 1.70; p< 0.001; Model 2: RR 1.35; CI 1.14– 1.60; p< 0.001; Model 3: RR 1.18; CI 1.02– 1.37; p=0.026). Correlation analysis reveals that the thyroid function parameters of FT3, FT4 and TSH only have weak correlations with coagulation parameters of platelet count, fibrinogen, FDP, D-dimers, PT, APTT and INR in sepsis.Conclusion: NTIS is an independent risk factor for DIC in adults with sepsis. DIC patients complicated with NTIS have significantly higher severity and higher rate of mortality.Keywords: sepsis, low T3 syndrome, nonthyroidal illness syndrome, thyroid function, disseminated intravascular coagulation

Yinzheng Li,1 Shulin Ma,1 Zheng Wang,1 Mengxia Shi,1 Rui Zeng,1– 4,&ast; Ying Yao1,5,&ast; 1Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, People’s Republic of China; 3NHC Key Laboratory of Organ Transplantation, Wuhan, 430030, People’s Republic of China; 4Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, 430030, People’s Republic of China; 5Department of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Yao; Rui Zeng, Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 13720379867 ; +86 15002726366, Email yaoyingkk@126.com; zengrui@tjh.tjmu.edu.cnPurpose: The distal nephron of kidney plays a pivotal role in advancing acute kidney injury (AKI). Understanding the role of distal nephrons in AKI and identifying markers of injured distal nephrons are critical to comprehending the mechanism of renal injury and identifying novel therapeutic targets.Methods: We analyzed single-cell RNA sequencing (scRNA-seq) data from mice with AKI induced by ischemia-reperfusion (IR), unilateral ureteral obstruction (UUO), cisplatin (CP), sodium oxalate (SO) and lipopolysaccharide (LPS). Additionally, we analyzed renal transcriptomics samples for AKI. Subsequently, we validated the effectiveness of targeting the biomarker Gclc in vitro and in vivo through metabolomics and immunofluorescence.Results: The LOH-Inj and DCT-Inj subtypes were identified through scRNA-seq. Compared to normal distal nephrons, the injured distal nephrons exhibited higher levels of ferroptosis, pro-inflammation, and fibrosis. The expression of ferroptosis-related gene Gclc were high in various AKI models. Furthermore, Gclc was exclusively expressed in the distal nephron and upregulated in the injury subtype. To confirm our findings, we suppressed GCLC expression in the kidneys, resulting to aggravated IR-induced AKI. Inhibition of Gclc promoted damage to primarily renal tubular epithelial cells by promoting inflammatory infiltration, inhibiting glutathione metabolism and exacerbating oxidative stress.Conclusion: Our research findings suggest that Gclc is a potential marker for injured distal nephron.Keywords: Gclc, distal nephron, acute kidney injury, single-cell sequencing

Fang Yang,1,&ast; Cong Li,2,&ast; Yuling Qiu,1 Xinjie Chen,3 Kelin Zheng,4 Donglin Kang,5 Yin Zhang,2 Baorui Liu,1 Yongzhong Yao,2 Li Xie1 1The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China; 2Department of Breast Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3The Comprehensive Cancer Center, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China; 4Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Xie, The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China, Email xieli@njglyy.com Yongzhong Yao, Department of Breast Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China, Tel/Fax +86-025-83106666, Email yyz1006@hotmail.comPurpose: The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has delayed medical consultations, especially for patients receiving intravenous anti-cancer therapy. We aim to investigate alterations in immune function among breast cancer patients who experience delayed intravenous therapy due to SARS-CoV-2 infection.Patients and Methods: We performed an observational investigation of breast cancer patients in Nanjing Drum Tower Hospital from December 27, 2022, to January 20, 2023. Patients who recovered from SARS-CoV-2 infection were eligible for enrollment. Peripheral blood samples were taken prior to the restart of intravenous anti-cancer therapy to examine hematologic parameters.Results: A total of 131 patients were included in the final analysis. Cough (74.0%), fever (62.6%), and expectoration (46.6%) were identified as the most presenting symptoms of SARS-CoV-2 infection in breast cancer. The average nucleic acid conversion time and delayed treatment time was 13.4 days and 13.9 days, respectively. The patients > 60 years old experienced prolonged nucleic acid conversion time (P = 0.017) and delayed treatment time (P = 0.028) compared to those

Weilu Cheng,1,* Lili Zhang,1,* Biwei Chen,1 Xin Tian,1 Yaqi Yao,1 Zezhou Zhang,1 Shaozong Chen2,3 1Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Institute of Acupuncture and Moxibustion and Massage, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 3Shaozong Chen, Cross-Regional Acupuncture Data Open Application Laboratory in the Yellow River Basin, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaozong Chen, Cross-regional Acupuncture Data Open Application Laboratory in the Yellow River Basin, Jinan, 250355, People’s Republic of China, Email ccsz1963@163.comObjective: This study aims to explore formula patterns and application rules for SP6 as the main acupoint in prescriptions, utilizing association rules.Methods: We conducted an extensive search in databases including China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (CDDB), China Science and Technology Journal Database (CSTJ), PubMed and Web of Science databases for literature published between January 2013 and June 2023, focusing on acupuncture prescriptions with SP6 as the main acupoint for various diseases. Inclusion and exclusion criteria were applied for literature screening. Relevant data was extracted, creating a database. Acupoints in conjunction with SP6 were analyzed using SPSS Modeler 18.0 and Cytoscape 3.7.2 software for acupoints appearing ≥ 15 times. Gephi software constructed a complex network model. The frequency of acupuncture points was analyzed to summarize the composition rules and clinical application rules of acupuncture points.Results: A total of 902 articles met inclusion criteria, yielding 672 prescriptions with SP6 as the main acupoint, paired with 197 different acupoints including ST36, CV4, and LI4. Neurological, obstetric, and gynecologic, as well as urological diseases, were predominantly treated. Among them, the predominant diseases include insomnia, primary dysmenorrhea, sequelae of stroke, and others, totaling 42 types.Conclusion: SP6-based prescriptions exhibit diverse applications, effectively treating insomnia, post-stroke sequelae, and primary dysmenorrhea. Commonly paired acupoints belong to Conception Vessel, Stomach meridian of foot-yangming, and Governor Vessel, and there are certain rules in their composition.Keywords: Sanyinjiao, SP6, acupuncture prescriptions, acupoint combinations regularity, application regularity

Yanjun Gao,1,2 Yingge Li,1,2 Zheming Liu,1,2 Yi Dong,1,2 Siqi Yang,1,2 Bin Wu,1,3 Mengxia Xiao,1,4 Chen Chen,5 Yingmei Wen,1,2 Lei Chen,1 Haijuan Jiang,6 Yi Yao1,2 1Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Hubei Provincial Research Center for Precision Medicine of Cancer, Wuhan, 430200, People’s Republic of China; 3Department of Oncology, Huang-Gang Central Hospital, Huanggang, 438000, People’s Republic of China; 4Department of Oncology, Yichun People’s Hospital, Yichun, 336000, People’s Republic of China; 5Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 6Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Yi Yao, Email yaoyi2018@whu.edu.cnBackground: Activator of heat shock protein 90 (HSP90) ATPase Activity 1 (AHSA1) regulates proliferation, apoptosis, migration, and invasion of osteosarcoma and hepatocellular carcinoma (HCC). However, the novel mechanism of AHSA1 in the tumor biology of hepatocellular carcinoma (HCC) remains unclear.Methods: We analyzed AHSA1 expression in 85 pairs of clinical samples of HCC and the Cancer Genome Atlas database. The role of AHSA1 in HCC was proved by cell proliferation, colony formation, migration, cell cycle analysis in vitro, xenograft models and tumor metastasis assay in vivo, and bioinformatics.Results: High AHSA1 expression was demonstrated in HCC and associated with invasive depth, clinical stage, and poor overall survival of patients. Univariate Cox analysis confirmed that AHSA1 was an independent prognostic factor for patients with HCC. Meanwhile, AHSA1 upregulation promoted cell proliferation, colony formation, and cell migration in vitro and tumor cell proliferation and metastasis of HCC cells in vivo. AHSA1 upregulation increased the cell cycle transition from G1 to S phase by increasing the expression of cyclinD1, cyclinD3, and cyclin-dependent kinase 6(CD). Transforming growth factor beta 1 (TGF-β 1)-induced protein kinase B (Akt) signaling regulated the expression of downstream targets, including cyclinD1. AHSA1 expression was closely correlated with the expression of TGF-β, Akt, cyclinD1, cyclinD3, and CDK6 using the Gene Expression Profiling Interactive Analysis database. AHSA1 upregulation participated in HCC progression by regulating TGF-β/Akt-cyclinD1/CDK6 signaling.Conclusion: AHSA1 might serve as a biomarker for predicting the clinical outcome of patients with HCC. It is vital in tumor metastasis and disease progression of HCC and may facilitate the development of clinical intervention strategies against HCC.Keywords: AHSA1, AKT/cyclinD1/CDK6 signaling, cell cycle, hepatocellular carcinoma, TGF-&#x03B2

Yao Yao,1,&ast; Liu Yang,1,&ast; Zhe Zhang,1,&ast; Binbin Wang,1 Baisui Feng,1 Zhanju Liu1,2 1Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, People’s Republic of China; 2Department of Gastroenterology, the Shanghai Tenth People’s Hospital of Tongji University, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanju Liu; Baisui Feng, Tel +86-18917683431 ; +86-18756585626, Email fbsktz@163.com; fengbs@zzu.edu.cnBackground: Anti-TNF medications are the first-line treatment for Crohn’s Disease (CD), despite the fact that a significant portion of the population continues to be ineffectively treated. This research aims to discover accurate intervention targets for the follow-up of anti-TNF non-responders using bioinformatics technology.Methods: GSE16879, GSE111761, and GSE52746 retrieved from the GEO database. Unbiased differentially expressed genes (DEGs) were discovered utilizing the limma and RobustRankAggreg (RRA) tools. Then, we used weighted gene co-expression network analysis (WGCNA) to identify the module most strongly associated with non responders and subjected this module to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis with overlapping genes of the DEGs. GSEA analysis applied to check the results of GO and KEGG. Using the Cytoscape program, the protein-protein interaction (PPI) network was constructed. The software’s MCODE addon and CytoHubba addon was used to find the most important modules and the hub genes. Subsequently, we employed reverse transcription-polymerase chain reaction (RT-PCR) to confirm hub gene expression from mucosal biopsy specimens.Results: There were a total of 142 genes co-upregulated and 65 genes co-downregulated. According to the WGCNA analysis, 42 genes were duplicated inside the light cyan module. GO and KEGG enrichment analyses of overlapped genes in nonresponders demonstrated an increase in the expression of genes associated with inflammation and immune response, consistent with GSEA results. The PPI network was constructed using 41 protein nodes and 177 edges. After validation, 8 of the top 10 genes were verified to be differentially expressed.Conclusion: Our investigation is the first to integrate three CD databases after the anti-TNF medication treatment. We identified IL1B, CCL4, CXCL1, CXCL10, CCL3, CSF3, TREM1, and IL1RN as potential therapeutic targets for patients whose anti-TNF treatment failed.Keywords: Crohn’s disease, weighted gene co-expression network analysis, robust rank aggreg, therapeutic targets

Tian Liu,1,&ast; Shangcong Han,2,&ast; Yu Yao,1 Guiming Zhang1 1Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guiming Zhang, Department of Urology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, People’s Republic of China, Email zhangguiming9@126.comAbstract: In recent years, the abnormal glucose metabolism of tumor cells has attracted increasing attention. Abnormal glucose metabolism is closely related to the occurrence and development of tumors. Monocarboxylate transporters (MCTs) transport the sugar metabolites lactic acid and pyruvate, which affect glucose metabolism and tumor progression in a variety of ways. Thus, research has recently focused on MCTs and their potential functions in cancer. The MCT superfamily consists of 14 members. MCT1 and MCT4 play a crucial role in the maintenance of intracellular pH in tumor cells by transporting monocarboxylic acids (such as lactate, pyruvate and butyrate). MCT1 and MCT4 are highly expressed in a variety of tumor cells and are involved the proliferation, invasion and migration of tumor cells, which are closely related to the prognosis of cancer. Because of their important functions in tumor cells, MCT1 and MCT4 have become potential targets for cancer treatment. In this review, we focus on the structure, function and regulation of MCT1 and MCT4 and discuss the developed inhibitors of MCT1 and MCT4 to provide more comprehensive information that might aid in the development of strategies targeting MCTs in cancer.Keywords: monocarboxylate transporter, tumor, tumor microenvironment, function, regulation

Qiuling Tong,1,2 Yu Yao,3 Yanhuo Xia,4 Zhibo Chen,2 Gangze Ji,2 Liuzhu Chen,2 Rujun Jin,2 Wanli Dong1 1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Neurology, Ningbo First Hospital, Ningbo, People’s Republic of China; 4Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Wanli Dong, Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +8651265223637, Fax +8657755579318, Email wanlidong23@163.comObjective: To investigate the influence of patent foramen ovale (PFO) on the clinical features of migraine without aura (MoA).Methods: We consecutively enrolled 390 MoA patients and compared the frequency of headache, episode duration, and the Visual Analogue Scale (VAS), Headache Impact Test 6 (HIT-6), and European Health Interview Survey-Quality of Life 8-item index (EUROHIS-QOL8) scores of patients with and without PFO, those with the mild right-to-left shunt (RLS) and moderate to large RLS, and those with permanent RLS and latent RLS using a nonparametric Mann–Whitney U-test. In addition, we analyzed the clinical features of migraine in 39 MoA patients before and after PFO closure treatment using the paired Wilcoxon test.Results: The prevalence of PFO in the 390 MoA patients was 44.4%. Patients with PFO had significantly higher frequency of headaches, VAS scores, HIT-6 scores, and incidence of white matter lesions than those without PFO (all p< 0.05). Patients with moderate to large RLS had significantly higher VAS scores than those with mild RLS (p = 0.002). Additionally, 39 MoA patients underwent PFO closure, which remarkably decreased their frequency of headache, episode duration, VAS scores, and HIT-6 scores, and increased their EUROHIS-QOL8 scores.Conclusion: The migraine features in MoA patients could be influenced by PFO, especially in patients with moderate to large shunt, in whom PFO closure improved the symptoms.Keywords: migraine without aura, patent foramen ovale, clinical features, closure treatment

Wenwen Pang,1,&ast; Bowei Zhang,2,&ast; Leixin Jin,3 Yao Yao,3 Qiurong Han,3 Xiaoli Zheng1 1Department of Clinical Laboratory, Tianjin Union Medical Center, Nankai University, Tianjin, People’s Republic of China; 2School of Medicine, Nankai University, Tianjin, People’s Republic of China; 3School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoli Zheng, 190 Huayuan Road, Tianjin, People’s Republic of China, Tel +86 13612135765, Fax +022 87729595, Email zhengxiaoli0217@163.comPurpose: To explore whether machine learning models using serological markers can predict the relapse of Ulcerative colitis (UC).Patients and Methods: This clinical cohort study included 292 UC patients, and serological markers were obtained when patients were discharged from the hospital. Subsequently, four machine learning models including the random forest (RF) model, the logistic regression model, the decision tree, and the neural network were compared to predict the relapse of UC. A nomogram was constructed, and the performance of these models was evaluated by accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC).Results: Based on the patients’ characteristics and serological markers, we selected the relevant variables associated with relapse and developed a LR model. The novel model including gender, white blood cell count, percentage of leukomonocyte, percentage of monocyte, absolute value of neutrophilic granulocyte, and erythrocyte sedimentation rate was established for predicting the relapse. In addition, the average AUC of the four machine learning models was 0.828, of which the RF model was the best. The AUC of the test group was 0.889, the accuracy was 76.4%, the sensitivity was 78.5%, and the specificity was 76.4%. There were 45 variables in the RF models, and the relative weight coefficients of these variables were determined. Age has the greatest impact on classification results, followed by hemoglobin concentration, white blood cell count, and platelet distribution width.Conclusion: Machine learning models based on serological markers had high accuracy in predicting the relapse of UC. The model can be used to noninvasively predict patient outcomes and can be an effective tool for determining personalized treatment plans.Keywords: ulcerative colitis, relapse, serological markers, machine learning, random forest model

Dehai Wu,1,&ast; Guanqun Liao,2,&ast; Yuanfei Yao,3,&ast; Lining Huang,4 Bowen Dong,5 Yong Ma,6 Guangchao Yang6 1Department of Hepatic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Hepatobiliary Surgery, Foshan Hospital Affiliated to Southern Medical University, Foshan, People’s Republic of China; 3Key Laboratory of Tumor Immunology in Heilongjiang, Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 4Department of Hepatobiliary Surgery, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, People’s Republic of China; 5Department of Biochemistry & Molecular Biology, Harbin Medical University, Harbin, People’s Republic of China; 6Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Minimal Invasive Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangchao Yang; Yong Ma, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Minimal Invasive Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China, Tel +86 13796000181 ; +86 13836006500, Email guangchaoyang@hrbmu.edu.com; doctormy80@163.comBackground: The aim of this study is to explore the role of acetyl-CoA acyltransferase 2 (ACAA2) in the progression of hepatocellular carcinoma (HCC).Methods: Bulk RNA data and single-cell RNA data were acquired from The Cancer Genome Atlas and Gene Expression Omnibus. Both in vitro and in vivo studies were used to determine the effect of ACAA2 on the progression of HCC, and RNA sequencing analysis was performed to explore the mechanism.Results: We found downregulation of ACAA2 was involved in the malignant progression of HCC. The patient with low ACAA2 level had an immunosuppressive microenvironment in the HCC and predicted to have a poor prognosis. Decreased ACAA2 facilitated HCC proliferation and metastasis by activating the nuclear factor-κB (NFκB) signaling pathway. And increased CXCL1 induced by NFκB signaling pathway might be responsible for low level of ACAA2 related immunosuppressive microenvironment. Furthermore, the expression of ACAA2 was also detected in immune cells. The expression of ACAA2 in CD4+TCF7+T, CD4+FOXP3+T, CD8+GZMK+T, and CD8+KLRD1+T cells was inversely correlated with the composition of CD8+PDCD1+T cells in HCC. This effect might be due to the CCL5-CCRs and HLA-E-KLRCs ligand-receptor networks.Conclusion: In a conclusion, downregulated ACAA2 promoted the progression of hepatocellular carcinoma and might be participated in the formation of immunosuppressive microenvironment. ACAA2 could be served as a favorable indicator for the prognosis of HCC and an ideal biomarker for immunotherapy.Keywords: hepatocellular carcinoma, acetyl-CoA acyltransferase 2, immunotherapy, nuclear factor-κB signaling pathway, biomarker

Tianyou Chen,1,&ast; Chong Liu,1 Zide Zhang,2 Tuo Liang,2 Jichong Zhu,1 Chenxing Zhou,1 Shaofeng Wu,1 Yuanlin Yao,1,&ast; Chengqian Huang,1 Bin Zhang,1 Sitan Feng,1 Zequn Wang,1 Shengsheng Huang,1 Xuhua Sun,1 Liyi Chen,1 Xinli Zhan1 1Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Spine Ward, Liuzhou People’s Hospital, Liuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Zhan, Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email zhanxinli@stu.gxmu.edu.cnObjective: The objective of this study was to utilize machine learning techniques to analyze perioperative factors and identify blood glucose levels that can predict the occurrence of surgical site infection following posterior lumbar spinal surgery.Methods: A total of 4019 patients receiving lumbar internal fixation surgery from an institute were enrolled between June 2012 and February 2021. First, the filtered data were randomized into the test and verification groups. Second, in the test group, specific variables were screened using logistic regression analysis, Lasso regression analysis, support vector machine, and random forest. Specific variables obtained using the four methods were intersected, and a dynamic model was constructed. ROC and calibration curves were constructed to assess model performance. Finally, internal model performance was verified in the verification group using ROC and calibration curves.Results: The data from 4019 patients were collected. In total, 1327 eligible cases were selected. By combining logistic regression analysis with three machine learning algorithms, this study identified four predictors associated with SSI, namely Modic changes, sebum thickness, hemoglobin, and glucose. Using this information, a prediction model was developed and visually represented. Then, we constructed ROC and calibration curves using the test group; the area under the ROC curve was 0.988. Further, calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index of our model was 0.986 (95% CI 0.981– 0.994). Finally, we used the validation group to validate the model internally; the AUC was 0.987. Calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index was 0.982 (95% CI 0.974– 0.999).Conclusion: Logistic regression analysis and machine learning were employed to select four risk factors: Modic changes, sebum thickness, hemoglobin, and glucose. Then, a dynamic prediction model was constructed to help clinicians simplify the monitoring and prevention of SSI.Keywords: surgical site infection, lumbar spine surgery, machine learning, blood glucose, dynamic prediction model

Haoran Ding,&ast; Guoqi Zhu,&ast; Hao Lin, Jiapeng Chu, Deqiang Yuan, Yi’an Yao, Yanhua Gao, Fei Chen, Xuebo Liu Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Chen; Xuebo Liu, Email riverapt@126.com; lxb70@hotmail.comBackground: The risk of acute myocardial infarction (AMI) is elevated in patients with systemic lupus erythematosus (SLE), and it is of great clinical value to identify potential molecular mechanisms and diagnostic markers of AMI associated with SLE by analyzing public database data and transcriptome sequencing data.Methods: AMI and SLE-related sequencing datasets GSE62646, GSE60993, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database and divided into prediction and validation cohorts. To identify the key genes associated with AMI related to SLE, WGCNA and DEGs analysis were performed for the prediction and validation cohorts, respectively. The related signaling pathways were identified by GO/KEGG enrichment analysis. Peripheral blood mononuclear cells (PBMCs) from patients with AMI were collected for transcriptome sequencing to validate the expression of key genes in patients with AMI. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to screen diagnostic biomarkers. The diagnostic efficacy of biomarkers was validated by ROC analysis, and the CIBERSORTx platform was used to analyze the composition of immune cells in AMI and SLE.Results: A total of 108 genes closely related to AMI and SLE were identified in the prediction cohort, and GO/KEGG analysis showed significantly enriched signaling pathways. The results of differential analysis in validation cohort were consistent with them. By transcriptional sequencing of PBMCs from peripheral blood of AMI patients, combined with the results of prediction and validation cohort analysis, seven genes were finally screened out. LASSO analysis finally identifies DYSF, LRG1 and CSF3R as diagnostic biomarkers of SLE-related-AMI. CIBERSORTx analysis revealed that the biomarkers were highly correlated with neutrophils.Conclusion: Neutrophil degranulation and NETs formation play important roles in SLE-related AMI, and DYSF, LRG1 and CSF3R were identified as important diagnostic markers for the development and progression of SLE-related AMI.Keywords: myocardial infarction, systemic lupus erythematosus, WGCNA, DEGs, RNA-seq, neutrophil

Rui Wang,1,&ast; Yijing Yao,1,2,&ast; Yihui Gao,1 Mengyao Liu,1 Qian Yu,3 Xuejiao Song,4 Xiao Han,5 Dechao Niu,6 Lixin Jiang1,2 1Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, People’s Republic of China; 2Shanghai Institute of Ultrasound in Medicine, Shanghai, 200233, People’s Republic of China; 3Department of Ultrasonography, Shanghai Jiao Tong University Affiliated No. 6 Hospital, Shanghai, 200233, People’s Republic of China; 4School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, 211800, People’s Republic of China; 5Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 6Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixin Jiang; Dechao Niu, Email jinger_28@sina.com; dcniu@ecust.edu.cnBackground: Pancreatic cancer is regarded as one of the most lethal types of tumor in the world, and optional way to treat the tumor are urgently needed. Cancer stem cells (CSCs) play a key role in the occurrence and development of pancreatic tumors. CD133 is a specific antigen for targeting the pancreatic CSCs subpopulation. Previous studies have shown that CSC-targeted therapy is effective in inhibiting tumorigenesis and transmission. However, CD133 targeted therapy combined with HIFU for pancreatic cancer is absent.Purpose: To improve therapeutic efficiency and minimize side effects, we carry a potent combination of CSCs antibody with synergist by an effective and visualized delivery nanocarrier to pancreatic cancer.Materials and Methods: Multifunctional CD133-targeted nanovesicles (CD133-grafted Cy5.5/PFOB@P-HVs) with encapsulated perfluorooctyl bromide (PFOB) in a 3-mercaptopropyltrimethoxysilane (MPTMS) shell modified with poly ethylene glycol (PEG) and superficially modified with CD133 and Cy 5.5 were constructed following the prescribed order. The nanovesicles were characterized for the biological and chemical characteristics feature. We explored the specific targeting capacity in vitro and the therapeutic effect in vivo.Results: The in vitro targeting experiment and in vivo FL and ultrasonic experiments showed the aggregation of CD133-grafted Cy5.5/PFOB@P-HVs around CSCs. In vivo FL imaging experiments demonstrated that the nanovesicles assemble for the highest concentration in the tumor at 24 h after administration. Under HIFU irradiation, the synergistic efficacy of the combination of the CD133-targeting carrier and HIFU for tumor treatment was obvious.Conclusion: CD133-grafted Cy5.5/PFOB@P-HVs combined with HIFU irradiation could enhance the tumor treatment effect not only by improving the delivery of nanovesicles but also by enhancing the HIFU thermal and mechanical effects in the tumor microenvironment, which is a highly effective targeted therapy for treating pancreatic cancer.Keywords: multifunctional nanovesicles, cancer stem cells, high-intensity focused ultrasound, in vivo fluorescent imaging, ultrasonic imaging

Weikun Qu,1,2,&ast; Yalu Yao,1,&ast; Yaqian Liu,1,&ast; HyonSu Jo,1,3 Qianran Zhang,1,&ast; Haidong Zhao1,&ast; 1Department of Oncology & Department of Breast Surgery, The Second Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of China; 2OPO Office, The Second Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of China; 3Department of General Surgery, the Hospital of Pyongyang Medical University, Pyongyang, 999093, Democratic People’s Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Haidong Zhao; Qianran Zhang, Department of Breast Surgery, Second Affiliated Hospital of Dalian Medical University, 467, Zhongshan Road, Shahekou District, Dalian, Liaoning, 116023, People’s Republic of China, Tel +86 13354288881 ; +86 13278089966, Email z.hddl@hotmail.com; 382026591@qq.comPurpose: The expression and function of CES2 in breast cancer (BRCA) has not been fully elucidated. The purpose of this study was to investigate its clinical significance in BRCA.Patients and Methods: Bioinformatics analysis tools and databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, SURVIVAL packages, STRING database, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set variation analysis (GSVA), and Tumor Immunity Estimation Resource (TIMER), were utilized to measure the expression level and clarify the clinical significance of CES2 in BRCA. In addition, we verified the expression level of CES2 in BRCA at the cellular and tissue levels by Western blot, immunohistochemistry (IHC) and real-time fluorescence quantitative PCR assays. Furthermore, DDAB is the first reported near-infrared fluorescent probe that can be used to monitor CES2 in vivo. We applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time and verified its physicochemical properties and labeling sorting ability by CCK-8, cytofluorimetric imaging, flow cytometry fluorescence detection, and isolated human tumor tissue imaging assays.Results: The expression of CES2 was higher in normal tissues than that in BRCA tissues. Patients with lower CES2 expression in the BRCA T4 stage had a poorer prognosis. Finally, we applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time, which was demonstrated to have good cellular imaging performance with low biological toxicity in BRCA cells and ex vivo human breast tumor tissue models.Conclusion: CES2 can be considered a potential biomarker to predict the prognosis of breast cancer at stage T4 and might contribute to the development of immunological treatment strategies. Meanwhile, CES2 is able to distinguish between breast normal and tumor tissues, the CES2-targeting NIR fluorescent probe DDAB may have potential for surgical applications in BRCA.Keywords: carboxylesterase 2, breast cancer, fluorescent probe, bioinformatics, molecular markers

Zhirong Yan,1,&ast; Huifen Lin,2,&ast; Ying Yang,3 Jialin Yang,3 Xueshan Li,2 Yusheng Yao3,4 1Department of Anesthesiology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Anesthesiology, Affiliated Sanming First Hospital of Fujian Medical University, Sanming, People’s Republic of China; 3Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 4Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yusheng Yao, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, No.134 Dongjie Street, Fuzhou, People’s Republic of China, Tel +86-13559939629, Fax +86-591-88217841, Email fjslyys@126.comPurpose: This study aimed to examine the effectiveness of ultrasound-guided thoracic paravertebral block on postoperative quality of recovery in patients undergoing percutaneous nephrolithotomy.Patients and Methods: In this randomized, double-blind, placebo-controlled trial, we enrolled patients scheduled for unilateral percutaneous nephrolithotomy. Patients were randomly allocated to receive thoracic paravertebral block either with 20 mL of 0.5% ropivacaine (PVB group) or an equal volume of saline (control group). The primary outcome was the quality of patient recovery at 24 h postoperatively, assessed using the 15-item Quality of Recovery scale. The secondary outcomes included the area under the curve of pain scores over time, time to first rescue analgesia, and postoperative 24 h morphine consumption.Results: We analyzed the data of 70 recruited participants. The median Quality of Recovery-15 score at 24 h postoperatively was 127 (interquartile range, 117– 133) in the PVB group, which was significantly higher than 114 (interquartile range, 109– 122) in the control group, with a median difference of 10 points (95% confidence interval, 5– 14; P< 0.001). The area under the curve of pain scores over time was lower in patients receiving thoracic PVB than in those receiving saline block (P< 0.001). The median time to first rescue analgesia in the PVB group (10.8 h, interquartile range 7.1– 22.8 h) was longer than that in the control group (1.9 h, interquartile range 0.5– 4.3 h) (P< 0.001). Similarly, the median postoperative 24-hour morphine consumption was nearly half as low in the PVB group as in the control group (P< 0.001). The occurrence of postoperative nausea and vomiting, and pruritus were significantly higher in the control group (P=0.016 and P=0.023, respectively).Conclusion: Preoperative ultrasound-guided single injection of thoracic paravertebral block with ropivacaine improved the postoperative quality of recovery and analgesia in patients undergoing percutaneous nephrolithotomy.Keywords: pain management, quality of recovery, regional anesthesia, ultrasonography

Tianchang Lu,1,&ast; Minyi Wang,1,2,&ast; Nannan Liu,1 Shuqiong Zhang,3 Lei Shi,1 Ling Bao,3 Feng Luo,3 Li Shi,1 Shuyuan Liu,1 Yufeng Yao4 1Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China; 2School of Life Science, Yunnan University, Kunming, 650500, People’s Republic of China; 3Department of Clinical Laboratory, The Third People’s Hospital of Kunming, Kunming, 650041, People’s Republic of China; 4Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Kunming, 650118, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuyuan Liu, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China, Tel +86 871 68334483, Email shuyuanliuoo@gmail.com Yufeng Yao, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Kunming, 650118, People’s Republic of China, Tel +86 871 68335632, Email leoyyf@gmail.comPurpose: Tuberculosis (TB) is known to result from a complex interaction between the host immune response and Mycobacterium infection. The transporter associated with antigen processing (TAP) plays an important role in the processing and presentation pathways for the Mycobacterium tuberculosis (M. tb) antigen. To investigate the possible association of the TAP1 and TAP2 genes with TB.Patients and Methods: A total of 449 TB patients and 435 control subjects were included in this study, and single nucleotide polymorphisms (SNPs) in the TAP gene, as well as TAP1 and TAP2 alleles, were genotyped.Results: TAP gene association analysis of TB diseases showed that rs41551515-T in the TAP1 gene was significantly associated with susceptibility to TB (P=7.96E-04, OR=4.124, 95% CI: 1.683– 10.102), especially pulmonary TB (PTB, P=6.84E-04, OR=4.350, 95% CI: 1.727– 10.945), and the combination of rs1057141-T-rs1135216-C in the TAP1 gene significantly increased the risk of TB susceptibility (P=5.51E-05, OR=10.899, 95% CI: 2.555– 46.493). Five novel TAP1 alleles were detected in Yunnan Han people, and the allele frequency of TAP1&ast;unknown_3 (rs41555220-rs41549617-rs1057141-rs1135216-rs1057149-rs41551515: C-A-T-C-C-T) was notably increased in all TB patients, including in the PTB and EPTB subgroups, and was significantly associated with the risk of susceptibility to TB. However, no association between the TAP2 gene and TB was found in this study.Conclusion: Host genetic variants of rs41551515-T and the combination rs1057141-T-rs1135216-C, as well as TAP1&ast;unknown_3 may play a critical role in susceptibility to TB disease.Keywords: tuberculosis, association, TAP gene, polymorphism, novel allele

Fan Y, Li Z, Wu L, et al. Drug Des Devel Ther. 2021;15:1509–1519. At the author’s request, we, the Editors and Publisher of Drug Design, Development and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 2 and 3 with images from other unrelated articles. Specifically, Images for Figure 2D, have been duplicated with images for Figure 6d from Cheng S, Xia B, Li H, et al. RETRACTED ARTICLE: Long non-coding RNA SATB2-AS1 inhibits microRNA-155-3p to suppress breast cancer cell growth by promoting breast cancer metastasis suppressor 1-like. Cancer Cell Int. 2020;20:321. https://doi.org/10.1186/s12935-020-01411-8; Figure 2B from Wei Y, Liao Y, Deng Y, Zu Y, Zhao B, Li F. MicroRNA-503 Inhibits Non-Small Cell Lung Cancer Progression By Targeting PDK1/PI3K/AKT Pathway. Onco Targets Ther. 2019;12:9005–9016. https://doi.org/10.2147/OTT.S213059; Figure 3B from Qiao Z, Tang J, Wu W, et al. Acteoside inhibits inflammatory response via JAK/STAT signaling pathway in osteoarthritic rats. BMC Complement Altern Med. 2019;19:264. https://doi.org/10.1186/s12906-019-2673-7; Figure 6c from Zhong Q, Huang J, Wei J, et al. Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma. Cancer Cell Int. 2019;19:252. https://doi.org/10.1186/s12935-019-0959-y and Figure 2B from Ma F, Xie Y, Lei Y, et al. The microRNA-130a-5p/RUNX2/STK32A network modulates tumor invasive and metastatic potential in non-small cell lung cancer. BMC Cancer. 2020;20:580. https://doi.org/10.1186/s12885-020-07056-0. Images for Figure 3A and 3B, have been duplicated with images for Figure 2C and Figure 6C from Tantai J, Zhang Y, Zhao H. Heterophyllin B inhibits the adhesion and invasion of ECA‑109 human esophageal carcinoma cells by targeting PI3K/AKT/β‑catenin signaling. Molecular Medicine Reports. 2016;13:1097–1104. https://doi.org/10.3892/mmr.2015.4659 and Figure 5B from Xu G, Lu X, Huang T, Fan J. ARHGAP24 inhibits cell cycle progression, induces apoptosis and suppresses invasion in renal cell carcinoma. Oncotarget. 2016;7:51829–51839. https://www.oncotarget.com/article/10386/text/. The authors were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Editor and Publisher agreed with this decision. 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’.

Tommy Tsang Cheung,1,&ast; Tu H Mai,2,&ast; Yen Lin Chia,2 Desmond YH Yap,1 Chi-Ho Lee,1 Cecil Chi-Keung Chen,2 Ying Huang,3 Yuwen Jin,3 James Johnston,4 Viktoria Werkström,5 Yuhui Yao,6 Xiaoyun Ge,7 Wenying Zheng8 1Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, People’s Republic of China; 2Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, South San Francisco, CA, USA; 3Clinical Pharmacology, R&D China, AstraZeneca, Shanghai, People’s Republic of China; 4Late-stage Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK; 5Late-Stage Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; 6Respiratory & Immunology, R&D China, AstraZeneca, Shanghai, People’s Republic of China; 7Clinical Safety, R&D China, AstraZeneca, Shanghai, People’s Republic of China; 8Biometrics, R&D China, AstraZeneca, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yen Lin Chia, Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, 701 Gateway Blvd, South San Francisco, CA, 9408, USA, Tel +1 425 5272574, Email yenlin@gmail.comPurpose: Biological therapies targeting eosinophils have been shown to be effective in treating patients with severe eosinophilic asthma. Benralizumab (Fasenra®, AstraZeneca) is a humanized monoclonal antibody binding to the alpha subunit of the interleukin-5 receptor, which rapidly depletes eosinophils via antibody-dependent cellular cytotoxicity. The aim of this Phase 1 study was to assess the safety, tolerability, and pharmacokinetics of benralizumab in healthy Chinese individuals.Materials and Methods: In this randomized, single-blind study (NCT03928262), healthy Chinese adult participants aged 18 to 45 years, weighing 50 to 100 kg, were randomized 1:1:1 to receive a single subcutaneous (SC) injection of benralizumab 10 mg, 30 mg, or 100 mg in the upper arms on Day 1. Safety was monitored throughout the study (up to Day 85), and blood samples were taken to determine serum benralizumab concentrations and for detection of anti-drug antibody. A non-compartmental analysis was conducted to estimate the pharmacokinetic parameters.Results: Thirty-six healthy participants were enrolled, 12 in each dose group (mean [SD] age 26 [6] years). Following a single SC injection of benralizumab, 13 adverse events were reported by 10 participants (28%), with one mild injection-site reaction assessed as related. The mean serum benralizumab concentrations increased in a dose proportional manner, followed by exponential decreases. The mean terminal half-lives were 15.1 days for the 10 mg dose, 14.4 days for the 30 mg dose, and 15.4 days for the 100 mg dose. All doses resulted in near-complete depletion of eosinophils on Day 2, which was maintained throughout the study to Day 85.Conclusion: A single SC injection of benralizumab was well tolerated by healthy Chinese participants, with no new or unexpected safety findings. The pharmacokinetics of benralizumab in Chinese participants was dose-proportional and consistent with those of non-Chinese participants observed in previous studies.Clinical Trial Registration: NCT03928262 (https://clinicaltrials.gov/ct2/show/NCT03928262)Keywords: benralizumab, pharmacokinetics, healthy Chinese

Mengxia Shi,1 Bin Hu,1 Yu Hong,1 Meng Wang,1,&ast; Ying Yao1,2,&ast; 1Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Yao, Department of Nephrology and Department of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, People’s Republic of China, Tel +86-13720379867, Email yaoyingkk@126.com Meng Wang, Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, People’s Republic of China, Tel +86-15927407065, Email nishuihan2003@163.comPurpose: Deep sea water (DSW) is a natural resource rich in minerals, which participates in biological processes such as energy metabolism, regulates serum glucose and lipids levels, and has a certain protective effect on endocrine and metabolism-related diseases. Studies have shown that the improvement of glucose tolerance in diabetic mice by DSW may be associated with the protective effect on the structure and function of pancreatic islets, and the specific mechanism is still unclear. Other studies have shown that long-term exposure to high concentrations of fatty acids can lead to apoptosis and dysfunction of pancreatic β-cell, increasing the risk of type 2 diabetes mellitus (T2DM). Down-regulation of plasma fatty acid levels may reduce pancreatic β-cell dysfunction, thereby improving glucose homeostasis. Understanding the specific mechanism of DSW regulating blood glucose is of great significance for its clinical application.Methods: In the present study we used db/db mice as a T2DM model and treated mice with deep ocean mineral concentration (DOMC, a commercial product of DSW) for 4 and 12 weeks. Basic information, serum biochemical indicators, and pathological tissues were gathered for exploration.Results: The db/db mice treated with 4 weeks’ DOMC (db/db+DOMC) showed decreased plasma cholesterol and triglyceride levels. Tests implied that in adipose tissues, the db/db+DOMC group’s lipolysis process was inhibited, and the β-fatty acid oxidation process was promoted. Besides, DOMC reduced lipogenesis and encouraged β-oxidation in the liver, as a result, improved fatty liver in db/db mice. Further measurements showed DOMC improved glucose homeostasis slightly in db/db animals after a 12-week treatment by preventing pancreatic β-cell apoptosis.Conclusion: DOMC inhibited pancreatic β-cell apoptosis and regulated glucose homeostasis in db/db mice by lowering the lipid levels via regulation of fatty acid β-oxidation, lipolysis, and lipogenesis processes.Keywords: deep sea water, type 2 diabetes mellitus, lipid metabolism, glucose homeostasis, pancreatic β-cell apoptosis

Yabo Yao, Tianhao Li, Yuanen Huang, Hongbin Cheng Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Hongbin Cheng, Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39, Shi-er-qiao Road, Jinniu District, Chengdu, People’s Republic of China, Email chenghongbin@cdutcm.edu.cnAbstract: A 78-year-old female patient with right ear agenesis presented with a skin manifestation of approximately 7 cm × 8 cm deep-invasive ulcer with well-defined borders and a small amount of yellow purulent discharge visible at the base, surrounded by pearl-like margins in a dyke-like elevation, covered with a small amount of necrotic tissue and black crust. The disease lasted for more than 20 years and was diagnosed as giant basal cell carcinoma complicated by primary cutaneous aspergillosis after two histopathological examinations of the skin lesions. There are similarities in the clinical manifestations of these two diseases, which need to be differentiated, and the simultaneous complications are infrequent. It has not been reported.Keywords: giant basal cell carcinoma, primary, cutaneous aspergillosis

Long Feng,1,&ast; Di Wu,2,&ast; Ping Ping,3,&ast; Jieqiong Lin,4,&ast; Yali Zhao,5 Yao Yao,6,7 Pei Zhang,8 Shihui Fu2,9 1Department of Anesthesiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 2Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 3General Station for Drug and Instrument Supervision and Control, Joint Logistic Support Force of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 4Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 5Central Laboratory, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 6Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham, NC, USA; 7Center for Healthy Aging and Development Studies, National School of Development, Peking University, Beijing, People’s Republic of China; 8School of Life Science, Beijing Institute of Technology, Beijing, People’s Republic of China; 9Department of Geriatric Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shihui Fu, Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China, Email xiaoxiao0915@126.com Yali Zhao, Central Laboratory, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China, Email zhaoyl301@163.comPurpose: Age related cognitive function (ARCF) is of increasing concern in an aging population. Few studies have examined the relationships between ARCF and antibody expression or blood pressure, particularly in older populations. Large sample sizes are needed to elucidate these relationships to inform better strategies for identification and prevention of cognitive decline. The present study was designed to investigate these relationships in Chinese oldest-old and centenarian adults.Patients and Methods: A household survey was performed that included 436 centenarians and 520 oldest-old adults (80– 99 years) residing in 16 cities and counties of Hainan province, China. ARCF was assessed using the mini-mental state examination.Results: The median age of participants in this study was 92 years, with a range of 80 to 116 years. Females accounted for 68.5% (655) of the participant pool. Multivariate linear regression analysis showed that age [Exp(B): − 0.220, 95% confidence interval (CI): − 0.270–-0.169], female gender [Exp(B): − 3.459, 95% CI:-4.458–-2.460], Han ethnicity [Exp(B): − 1.732, 95% CI: − 2.693–-0.772], serum creatinine [Exp(B): − 0.019, 95% CI: − 0.037–-0.001], immunoglobulin light chain KAP [Exp(B): − 0.008, 95% CI: − 0.015– 0.000], and anti-ribonucleoprotein antibody [Exp(B): − 6.393, 95% CI: − 10.898–-1.887] were negatively associated with ARCF (P < 0.05). Coronary artery disease [Exp(B): 1.957, 95% CI: 0.170– 3.744] and diastolic pressure [Exp(B): 0.041, 95% CI: 0.002– 0.079] were positively associated with ARCF (P < 0.05).Conclusion: ARCF was positively associated with diastolic pressure and negatively associated with antibody expression in Chinese oldest-old and centenarian adults.Keywords: age related cognitive function, antibody expression, centenarian, diastolic pressure, oldest-old

Yulian Gao,1,&ast; Hongxia Lin,1,&ast; Yumin Xu,2,&ast; Yijin Yao,1,&ast; Dake Shi,1 Junjie Li,1 Haixing Zhu,1 Hanssa Dwarka Summah,3 Lei Ni,1 Yun Feng1 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Hospital Infection Management, Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Respiratory, Poudre D’Or Chest Hospital, Rivière du Rempart, Mauritius&ast;These authors contributed equally to this workCorrespondence: Yun Feng; Lei Ni, Email fy01057@163.com; nilei625@139.comPurpose: Carbapenem-resistant Gram-negative bacteria bloodstream infection (CRGNB-BSI) has gradually become a major threat worldwide due to its treatment difficulty and high mortality. This study aimed to determine the risk factors for CRGNB-BSI in immunosuppressed patients.Patients and Methods: A total of 427 immunosuppressed patients with CRGNB-BSI were retrospectively investigated from 2015 to 2021. Both univariate and multivariate logistic regression analyses were applied to evaluate independent risk factors for CRGNB-BSI.Results: The most common etiology was Klebsiella Pneumoniae (50.59%; 216/427), while the Acinetobacillus baumannii infection was associated with the highest mortality (58.25%) among all etiologies. The 60-day mortality of immunosuppressed patients with CRGNB-BSI was 52.48% (224/427). Procalcitonin (PCT) > 0.5 μg/L (OR = 2.32, 95% CI: 1.28– 4.19, P = 0.005) and age > 55 years (OR = 2.06, 95% CI: 1.17– 3.64, P = 0.012) were found to be predictors of 60-day mortality of CRGNB-BSI, and tigecycline regimen (OR = 3.20, 95% CI: 1.81– 5.67, P < 0.001) was associated with higher mortality. Multivariate analysis also revealed that patients who developed acute kidney injury (AKI) (OR = 2.19, 95% CI: 1.11– 4.30, P = 0.023), gastrointestinal bleeding (OR = 3.18, 95% CI: 1.10– 9.16, P = 0.032), multiple organ dysfunction syndrome (MODS) (OR = 12.11, 95% CI: 2.61– 56.19, P = 0.001), and septic shock (OR = 3.24, 95% CI: 1.77– 5.94, P < 0.001) showed worse outcomes. The risk factors were also significantly associated with mortality in the different subgroups.Conclusion: This study demonstrated that PCT > 0.5 μg/L, age > 55 years, and the tigecycline regimen were significantly associated with higher 60-day mortality among immunosuppressed patients with CRGNB- BSI. Patients developing MODS, septic shock, or AKI had worse clinical outcomes.&#x2003Keywords: bloodstream infection, carbapenem-resistant, immunosuppressed patients, subgroups, prognosis

Tian Wang,1,&ast; Feng Lin,2,&ast; Yujing Huang,2 Guowei Qian,2 Wenxi Yu,2 Haiyan Hu,2 Tong Ji,3 Lina Tang,2 Yang Yao2 1The Eighth People’s Hospital of Shanghai, Shanghai, People’s Republic of China; 2Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 3Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Yao; Lina Tang, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, No. 600 Yishan Road, Xuhui Distinct, Shanghai, 200233, People’s Republic of China, Tel +86 2164369181 ; +86 2164701361, Email yangyao_6@hotmail.com; Tina_8042@hotmail.comPurpose: The options for the second-line treatment of metastatic osteosarcoma are still limited. Anlotinib is a multi-kinase inhibitor which has shown promising efficacy and good tolerability in various cancer types. This retrospective study was conducted to evaluate the efficacy and safety of anlotinib combined with gemcitabine/docetaxel (GD) in patients with metastatic osteosarcoma who have failed first-line chemotherapy.Patients and Methods: The data of patients who received anlotinib combined with GD or GD were collected. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate and safety.Results: From July 2013 to November 2020, a total of 32 patients were enrolled, 13 received anlotinib combined with GD and 19 received GD. Median PFS was 9.0 months (95% CI 6.7– 39.1) in the combination group and 5.0 months (95% CI 1.2– 6.7) in the chemotherapy group. ORR were 38.4% and 15.8%, DCR were 69.2% and 38.1% in the combination and chemotherapy group, respectively. The most common adverse events included fatigue (78.9% in the combination group vs 69.2% in the chemotherapy group), hypertension (46.2% vs 10.5%), diarrhea (38.5% vs 21.1%), hypothyroidism (38.5% vs 15.8%), neutropenia (23.1% vs 36.8%) and AST elevation (30.8% vs 21.1%). The most common grade 3 or worse adverse events included hand-foot reaction (7.7% vs 5.3%), hypothyroidism (15.4% vs 0), neutropenia (0 vs 10.5%).Conclusion: The combination of anlotinib and GD showed favorable efficacy with manageable toxicities compared with GD in the second-line treatment for metastatic osteosarcoma. This combination therapy deserves further investigations in patients with osteosarcoma.Keywords: anlotinib, refractory metastatic osteosarcoma, combination therapy

Xue Yang,1,&ast; Chuantao Lin,2,&ast; Sisi Chen,3 Yuezhou Huang,3 Qiong Cheng,1 Yusheng Yao3 1Department of Neurology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Anesthesiology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiong Cheng, Email chengqiong13@126.comPurpose: To identify the effectiveness of remimazolam at the end of tonsillectomy and adenoidectomy for preventing emergence delirium in children under sevoflurane anesthesia.Patients and Methods: One hundred and four patients aged 3– 7 years scheduled for tonsillectomy and adenoidectomy under sevoflurane anesthesia were recruited. Patients were randomly assigned to receive either remimazolam 0.2 mg kg– 1 (intervention, n=52) or 0.9% normal saline (control, n=52) at the end of the procedure. The primary outcome was the incidence of emergence delirium, defined as a Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10. Secondary outcomes were peak PAED score, emergence time, postoperative pain intensity, length of postanesthesia care unit (PACU) stay, parental satisfaction, and postoperative behavior changes three days postoperatively.Results: Emergence delirium occurred in 6 of 51 (12%) patients receiving remimazolam versus 22 of 50 (44%) patients receiving saline (risk difference 32% [95% confidence interval, 16% to 49%], relative risk 0.27 [95% confidence interval, 0.12 to 0.60]; P< 0.001). The peak PAED scores (median [interquartile range]) were lower in the remimazolam group than in the saline group (7 [6– 8] versus 9 [8– 11], P< 0.001). Likewise, parental satisfaction was improved in the remimazolam group compared with the saline group (9 [8– 10] versus 8 [7– 8], P< 0.001). There was no difference between groups concerning postoperative pain scores, length of PACU stay, or postoperative behavior changes.Conclusion: In children undergoing tonsillectomy and adenoidectomy, administration of remimazolam 0.2 mg kg– 1 at the end of the surgery, compared with 0.9% saline, resulted in a significantly lower likelihood of emergence delirium after sevoflurane anesthesia.Keywords: remimazolam, general anesthesia, pediatric anesthesia, emergence delirium

Xiangzhi Jing,1 Hongling Meng,2 Yuping Li,2 Lingeng Lu,3 Yongcheng Yao2 1School of Medicine, Xinyang Vocational and Technical College, Xinyang, People’s Republic of China; 2School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, People’s Republic of China; 3Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, New Haven, CT, USACorrespondence: Yongcheng Yao, Zhengzhou Normal University, Zhengzhou, Henan, 450044, People’s Republic of China, Email 806306944@qq.comBackground: COVID-19 lockdown can lead to mental health problem, and the problem is heterogeneous across individuals. In this study, we aimed to explore the association between the self-reported health status, emotional coping style, emotional intelligence and positive psychological state of college students during the COVID-19 pandemic in China.Methods: The questionnaires of Self-rated Health Measurement Scale (SRHMS), Emotional Intelligence Scale (EIS), Psychological Capital Questionnaire (PCQ), Simplified Coping Style Questionnaire (SCSQ) were used for online survey. The study included 367 undergraduates.Results: Undergraduate sex, sibling and birth of place were associated with either psychological capital scores or emotional intelligence. Online time per day had significantly negative associations with self-rated health and psychological capital scores. Multivariate analysis showed that the interaction between emotional intelligence, psychological capital and coping styles was statistically significant (β = − 0.112, p = 0.045) in health status with psychological capital ranking the top (β = 0.428). Mediation analysis showed that psychological capital and coping style modified the effect of emotional intelligence on health status.Conclusion: Psychological capital and coping style modified the effect of emotional intelligence on health status in college students during the COVID-19 pandemic. In this pandemic emergency, a comprehensive intervention, such as positive coping styles with optimistic emotional perception and understanding as well as social support, is an important measure against the pandemic-induced mental health problem in college students in China.Keywords: college students, coping style, emotional intelligence, health status, psychological capital

Yao Yao,1,&ast; Chunlai Shao,2,&ast; Xiaoye Li,1 Zi Wang,1 Chengchun Zuo,1 Yan Yan,3 Qianzhou Lv1 1Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Yan; Qianzhou Lv, Zhongshan Hospital, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +86 13916088938, Fax +86 021-64041990, Email yan.yan@zs-hospital.sh.cn; 13916088938@163.comPurpose: The Global Registry of Acute Coronary Events (GRACE) score has proven value in predicting short-term prognosis in non-ST-elevation myocardial infarction (NSTEMI), but it has only moderate discrimination for long-term outcomes. The purpose of this study is to develop and test a multi-biomarker score for better risk stratification and indication of 2-year risk in patients with NSTEMI.Patients and Methods: A total of 6076 consecutive patients with NSTEMI (66 [59– 73] years, 73.1% males) admitted at Zhongshan Hospital, Fudan University were collected in this observational, prospective study between 2012 and 2018 with a 24-month follow-up. The primary endpoint was all-cause death and non-fatal major adverse cardiac events (MACE). A biomarker score ranged from 0 to 12 was constructed. The predictive power of the biomarker score was evaluated alone or combined with the GRACE score by C-statistic, net reclassification index (NRI) and integrated discrimination index (IDI).Results: During a 2-year follow-up, all-cause death occurred in 159 patients (2.6%), and non-fatal MACEs were presented in 709 patients (11.7%). When added to the GRACE score, the biomarker score demonstrated better prognostic accuracy, patient reclassification and risk discrimination for both mortality and non-fatal MACEs at 2 years by improving the C-statistic from 0.714 (0.671– 0.756) and 0.623 (0.600– 0.646) to 0.851 (0.820– 0.882) and 0.721 (0.702– 0.741) with NRI > 25% (P< 0.001) and IDI > 0.30 (P< 0.001).Conclusion: The single use of biomarker score could markedly enhance the prognostic value of concurrent risk stratification tools for 2-year mortality and non-fatal MACEs in NSTEMI. The GRACE score with incorporation of the biomarker score led to more accurate risk reclassification and warrants more consideration in further NSTEMI management.Keywords: risk stratification, prognosis, net reclassification improvement, integrated discrimination improvement

Wei Yang,1– 3 Xue He,1,2 Yuying Yao,2 Hongyan Lu,2 Yuliang Wang,2 Zhanhao Zhang,2 Yuhe Wang,1,2,4 Li Wang,1,2 Yongjun He,1,2 Dongya Yuan,1,2 Tianbo Jin1,2 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 2School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 3Department of Emergency, The Affiliated Hospital of Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 4Department of Clinical Laboratory, The Affiliated Hospital of Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Tianbo Jin, Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6 East Wenhui Road, Xianyang, Shaanxi, 712082, People’s Republic of China, Tel/Fax +86-29-88895902, Email tianbo__jin@163.comBackground: Hematological characteristics have positive reference value as clinical indicators in the evaluation of various diseases. The purpose of this study was to determine the gene loci associated with 20 hematological phenotypes in the Han population from northwest China.Methods: A genome-wide association study (GWAS) was conducted on hematological indicators of 1005 Han people from northwest China. Genotyping was performed with a GeneTitan multichannel instrument and Axiom Analysis Suite 6.0. Using the 1000 Genomes Project (phase 3) as a reference, haplotype imputation was performed with IMPUTE2. SNVs (single nucleotide variants) significantly associated with hematological phenotypes were identified. The top SNV (p < 5E-7) was then selected for replication detection.Results: Ninety genetic variations identified in the GWAS were significantly associated with hematological indicators. Among them, only rs35289401 (CCDC157) was significantly associated (genome-wide) with red blood cell distribution width (RDW) (p = 4.21E-08). The fourteen top SNVs were selected for replication verification and were significantly associated with hematological phenotypes. However, only HBS1 L-MYB rs1331309 was significantly associated with the mean hemoglobin content (p = 6.42E-07). We also found that the mean corpuscular hemoglobin (MCH) level in the rs1331309 GG/GT genotype was significantly higher than that in the TT genotype (p = 0.023).Conclusion: The GWAS identified a total of 90 genetic variants significantly associated with hematological phenotypic indicators. In particular, rs1331309 (HBS1 L-MYB) is expected to be a biomarker for monitoring the dynamics of MCH levels. This study provides a reference for related studies on the genetic structure of hematological characteristics. It provides a valuable reference for the clinical diagnosis or prediction of a variety of diseases.Keywords: hematological, GWAS, hematological phenotype, MCH, Han population from northwest China

Aihong Peng,1 Funa Lu,1 Jianxiao Xing,1 Yu Dou,1 Yuanjun Yao,1 Juan Li,1 Junqin Li,1 Ruixia Hou,1 Kaiming Zhang,2 Guohua Yin1 1Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, People’s Republic of ChinaCorrespondence: Guohua Yin, Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, No. 5, Dong San Dao Xiang, Jiefang Road, Taiyuan, People’s Republic of China, Tel +86-0351-5656080, Email yinguohua1999@sina.comPurpose: Our recent studies found a splice region mutation in C3 accompanied by a significantly increased C3 in psoriatic peripheral blood. Mesenchymal stem cells (MSCs) are a key immunological suppression cell. We further investigate the regulation of MSCs on C3 in psoriasis.Patients and Methods: We analyzed the C3 and its upstream S100A9, S100A8 and downstream MCP1 in psoriatic and control skin, and in normal human epidermal keratinocytes (NHEKs) co-cultured with psoriatic versus control dermal-derived mesenchymal stem cells (DMSCs) by mRNA, iTRAQ (isobaric tags for relative and absolute quantitative) and simple Western analysis.Results: The mRNA and Simple Western analysis showed that the expression of C3, S100A8 and S100A9 are upregulated in psoriatic lesion (C3: mRNA, 9.23-fold, p = 0.0092; protein, 3.56-fold, p = 0.0244. S100A8: mRNA, 28.35-fold, p = 0.0015; protein, 4.68-fold, p = 0.0215. S100A9: mRNA, 79.45-fold, p = 0.0066; protein, 12.42-fold, p > 0.05). Moreover, the iTRAQ showed that C3 and S100A9 were significantly increased in NHEKs after co-cultured with psoriatic DMSCs compared to that of control DMSCs (C3: 3.40-fold, p = 0, FDR = 0; S100A9: 2.30-fold, p = 9.86E-241, FDR = 6.50E-239), verified by Simple Western. However, the expression of S100A8 and MCP1 was slightly different between the two groups.Conclusion: Our results suggest that psoriatic DMSCs contribute to the increased C3 expression in psoriatic lesion via upregulating S100A9, providing the theoretical basis for the role of C3 and DMSCs in the pathogenesis of psoriasis.Keywords: psoriasis, dermal mesenchymal stem cells, keratinocytes, C3, S100A9

Hao-Ran Zheng,1,2,&ast; Ai-Min Jiang,1,&ast; Huan Gao,1 Na Liu,1 Xiao-Qiang Zheng,1 Xiao Fu,1 Rui Zhang,1 Zhi-Ping Ruan,1 Tao Tian,1 Xuan Liang,1 Yu Yao1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Medical Oncology, Xi’an No.3 Hospital, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuan Liang; Yu Yao, Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel +86-29-85324600, Fax +86-29-85324086, Email liangxuan029@163.com; 13572101611@163.comPurpose: Anlotinib, an antiangiogenic multi-target tyrosine kinase inhibitor (TKI), has shown favorable anticancer efficacy and acceptable safety in treating extensive-stage small cell lung cancer (ES-SCLC) in some clinical studies. This research aimed to explore the real-world efficacy and safety of anlotinib in ES-SCLC.Methods: Pathologically confirmed ES-SCLC patients receiving anlotinib were enrolled for this retrospective study. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse reactions.Results: In total, 202 patients were included in this study. The median PFS of all patients was 4.8 months [95% confidence interval (CI): 3.9– 5.7], and the median OS was 7.6 months (95% CI 6.5– 8.7). Respectively, the overall ORR and DCR were 30.2% and 87.1%. The univariate and multivariate Cox regression analyses revealed that patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1, plus chemotherapy or immunotherapy, plus radiotherapy, and post-medication hypertension might have longer PFS and OS. The PFS and OS were significantly prolonged in combination group than that in monotherapy group [PFS 6.0 vs 3.6 months, hazards ratio (HR)=0.49, 95% CI 0.34– 0.70, P < 0.001; OS 9.2 vs 4.8 months, HR = 0.48, 95% CI 0.32– 0.72, P < 0.001]. The main treatment-related adverse reactions were generally tolerated. The incidence of adverse reactions in combination group was higher than that in monotherapy group (75.0% vs 52.6%, P = 0.001). The most common adverse reaction was hypertension, followed by hand-foot syndrome and fatigue, regardless of monotherapy or combination group.Conclusion: Anlotinib is effective and well tolerated in patients with ES-SCLC in the real-world. The clinical efficacy of anlotinib combined with chemotherapy or immunotherapy is better than that of monotherapy. Further investigations are needed for prospective studies with larger sample size.Keywords: anlotinib, small cell lung cancer, real-world, efficacy, safety

Wenzeng Xu, Yiqi Fu, Yake Yao, Jianying Zhou, Hua Zhou Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of ChinaCorrespondence: Hua Zhou; Jianying Zhou, Email zhouhua1@zju.edu.cn; zjyhz@zju.edu.cnBackground: The effect of nosocomial infections (NIs) in adult patients undergoing ECMO has been rarely reported in China. Moreover, the effect of NIs on ECMO patients’ mortality is still unclear and inconclusive according to literature data. In this study, we examined the prevalence, risk factors, causative organisms, and effects on outcomes of NIs in ECMO patients.Methods: A total of 79 nonsurgical patients (mean age 53.3± 15.2 year (yr); 66% male) who underwent ECMO between January 2011 and September 2020 were enrolled in this retrospective study. Patients’ demographic and clinical data and ECMO parameters were collected from all patients.Results: Among 79 patients who underwent ECMO for a total of 1253 ECMO days (mean time 15.9± 14.1 d), 42 developed NIs. We observed 30 ventilator-associated pneumonia (VAP), 19 bloodstream infections (BSIs), and 4 urinary tract infections, corresponding to 23.9/1000 ECMO days, 15.2/1000 ECMO days, and 3.2/1000 ECMO days, respectively. ECMO duration (22.0± 16.5 VS 8.9± 5.3 d, P < 0.001), invasive mechanical ventilation (IMV) duration (27.4± 20.5 VS 11.4± 10.1 d, P < 0001), and ICU length of stay (35.9± 22.9 VS 15.7± 9.2 d, P < 0.001) were longer in patients with NIs. The independent risk factors for NIs were ECMO duration (Odds Ratio [OR], 1.414; 95% Confidence Interval [CI], (1.051– 1.238); P = 0.002) and viral pneumonia (OR, 5.788; 95% CI, (1.551– 21.596); P = 0.009). Gram-negative bacteria were the most common causative organisms of NIs; Acinetobacter baumannii (A. baumannii), Klebsiella pneumoniae (K. pneumoniae), and Pseudomonas aeruginosa (P. aeruginosa) were the most common bacteria. BSI (OR, 8.106; 95% CI, (1.384– 47.474); P = 0.02) was an independent predictor for mortality.Conclusion: NIs are common complications in patients during ECMO treatment, especially VAP, followed by BSI. Also, BSI can negatively affect the survival rate.Keywords: extracorporeal membrane oxygenation, healthcare-associated infections, bloodstream infections, risk factors, mortality