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Taomei Li, Lu Tan, Fei Lei, Xiangdong Tang Sleep Medicine Center, Mental Health Center, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xiangdong Tang, Sleep Medicine Center, Mental Health Center, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 28 Dian Xin Nan Jie, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85422733, Fax +86-28-85422632, Email 2372564613@qq.comBackground: White blood cell (WBC) and its subset counts are standard, inexpensive, direct markers of inflammation. Obstructive sleep apnea (OSA) is implicated in changes in inflammation markers, and sex differences are evident in both OSA and inflammation. It is unknown whether sex modulates the relationship between OSA severity and leukocyte measures.Methods: 1222 patients (914 males, 308 females) underwent overnight laboratorial polysomnography and measurement of WBC and its subset (lymphocyte, neutrophil, monocyte) counts. Patients were divided into primary snoring and mild, moderate, and severe OSA groups, and differences in leukocyte parameters were analyzed separately by sex in multivariable analyses.Results: In multiple regression models, higher apnea-hypopnea index (AHI) was independently associated with neutrophil counts only in men, and with higher total WBC, lymphocyte and monocyte counts both in women and men. Further ordinal logistic regression analysis revealed a significant association between AHI and total WBC (OR 1.87, 95% CI 1.09– 3.23) and neutrophil (OR 1.77, 95% CI 1.02– 3.07) counts in men only. Correlation analysis also revealed more robust relationships between leukocyte measures and cardiometabolic risk markers in men than in women.Conclusion: This study provides novel data suggesting a significant association between neutrophil count and OSA severity only in men but not women. Similarly, the relationship between leukocyte parameters and cardiometabolic risk markers were more pronounced in men than women. Our findings suggest a sex-specific impact of OSA on leukocyte measures and on their relationship with indices of cardiometabolic risk.Keywords: obstructive sleep apnea, leukocyte measures, neutrophil, sex differences, cardiometabolic risk factors

Lei Tan,1,2,* Han She,1,2,* Yi Wang,1,2,* Yuanlin Du,1 Jun Zhang,1 Yunxia Du,1 Yinyu Wu,1 Wei Chen,1 Bingqiang Huang,1 Duanyang Long,1 Xiaoyong Peng,2 Qinghui Li,2 Qingxiang Mao,1 Tao Li,2 Yi Hu1 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Li; Yi Hu, Email lt200132@163.com; huyi921@sina.comBackground: Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer’s (AR) and Lactate Ringer’s solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear.Methods: The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury.Results: TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats’ survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity.Conclusion: The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis.Keywords: myocardial injury, hemorrhagic shock, mitochondria, ferroptosis

Jie Cheng,1,* Ya Liu,2,* Guangli Zhang,3 Liping Tan,1 Zhengxiu Luo3 1Department of Emergency, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Big Data Engineering Center, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Department of Pediatrics, Chongqing Youyoubaobei Women and Children’s Hospital, Chongqing, 401147, People’s Republic of China; 3Department of Respiratory Medicine, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Big Data Engineering Center, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengxiu Luo, Email luozhengxiu816@hospital.cqmu.edu.cnObjective: Mycoplasma pneumoniae (MP) is highly resistant to macrolides in China. However, macrolides still exhibit clinical effectiveness in some macrolide-resistant patients. We tend to explore azithromycin effectiveness in Mycoplasma pneumoniae pneumonia (MPP) children with A2063/2064G mutation.Methods: This retrospective observational cohort study was conducted at the Children’s Hospital of the Chongqing Medical University. Children with macrolide-resistant mutations (A2063/2064G) diagnosed as MPP were retrospectively enrolled. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to evaluate and identify independent risk factors for treatment failure (progress to refractory Mycoplasma pneumoniae pneumonia [RMPP]) in macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) children with the A2063/2064G mutation.Results: One hundred fifty-five children were retrospectively enrolled. More than 20% (36/155, 23.23%) of patients experienced defervescence within 3 days of azithromycin treatment. RMPP was diagnosed in 54 patients (54/155, 34.84%) and the incidence of RMPP during hospitalization was 22.72 per 1000 person-days. Logistic regression analysis showed that lactate dehydrogenase (LDH) ≥ 399 (U/L) was an independent risk factor for RMPP (odds ratio [OR] 4.66, 95% confidence interval [CI] 1.31– 17.10, P=0.017). During the year followed, RMPP patients had a significantly higher incidence of bronchiolitis obliterans and bronchiectasis than non-RMPP patients (16.67% vs 1.98%, P=0.001; 9.26% vs 0.00%, P=0.005, respectively).Conclusion: Azithromycin was effective in children with MPP with the A2063/2064G mutation. For MUMPP children with A2063/2064G mutation, children with LDH ≥ 399 (U/L) had significant higher risk for progression to RMPP, and should consider to be treated with alternative antibiotics (eg tetracyclines, and fluoroquinolones).Keywords: azithromycin effectiveness, A2063/2064G mutation, mycoplasma pneumoniae pneumonia, children

Zhaowei Huang,1,2,* Changming Chen,3,* Linlin Tan,4 Yi Ling,3 Wukai Ma,3 Jinan Zhang1,2 1Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 3Department of Rheumatology & Immunology, The Second Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, Guizhou, People’s Republic of China; 4Department of Internal Medicine, Jinshazhou Hospital Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinan Zhang, Email zhangjinan@hotmail.comBackground: Rheumatoid arthritis (RA) is a common autoimmune disease with the main symptoms being joint swelling and pain. In severe cases, joint deformity or even complete loss of function occurs. Technetium methylene diphosphonate (99Tc-MDP) is widely used for RA treatment in China, but there are no studies on the effects of 99Tc-MDP on intestinal flora.Objective: To explore the effects of 99Tc-MDP treatment on the composition and function of the intestinal flora and to provide new information on the mechanism of 99Tc-MDP in RA treatment.Methods: Stool samples from RA patients before and after 99Tc-MDP treatment were collected to form two groups (Before and After). Total genomic DNA of the samples was extracted for 16S rRNA gene sequencing. The altered composition of the intestinal flora, the key target bacteria regulated by 99Tc-MDP, and the pathways of action of 99 Tc-MDP were analyzed by bioinformatics.Results: A total of 64 fresh stool samples were collected from 32 RA patients. Compared to the Before group, the After group showed increased Bacteroidetes abundance and decreased Firmicutes abundance. At the genus level, Prevotella increased whereas Escherichia decreased. Both α and β diversity analyses showed that 99Tc-MDP treatment did not affect gut microbial diversity in RA patients. LEfSe analyses and random forest analyses showed Bacteroidetes, Prevotella, Enterococcus, Escherichia and Ruminococcaceae were the main 99Tc-MDP regulating bacteria. Functional enrichment analysis revealed that the functional differences in gut flora of the two groups centered on Metabolism and Genetic Information Processing.Conclusion: This study revealed differences in the composition of the gut microbiota in RA patients before and after 99Tc-MDP treatment. The therapeutic effect of 99Tc MDP is mainly achieved through Bacteroidetes, Prevotella, and Enterococcus. Regulating metabolism and genetic information processing of gut flora may be the mechanism of 99Tc-MDP in treating RA.Keywords: rheumatoid arthritis, 99Tc-MDP, gut microbiota, 16S rRNA, bioinformatics

Lingfang Tan,1 Xuefeng Yang,2 Jianxin Zhang,3 Kebing Zhou1,2 1The Nanhua Affiliated Hospital, Department of Respiratory Physicians, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 2The Nanhua Affiliated Hospital, Department of General Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 3The Nanhua Affiliated Hospital, Department of Cardiothoracic Surgeon, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of ChinaCorrespondence: Kebing Zhou, Tel +86-17397392536, Email zhoukebing9999@163.comBackground: Airway remodeling is a significant pathological characteristic of chronic obstructive pulmonary disease (COPD). In recent years, hypoxia-inducible factor 1-α (HIF-1α), a member of the hypoxia-inducible factor protein family, has gained attention. However, the potential correlation between HIF-1α and COPD airway remodeling remains unclear.Objective: This study explored the expression patterns of HIF-1α in patients with COPD and its association with airway remodelling. This investigation aims to furnish novel insights for the clinical identification of prospective therapeutic targets for ameliorating COPD-related airway remodelling.Patients and Methods: A total of 88 subjects were included, consisting of 28 controls and 60 COPD patients. Various staining methods were employed to observe the pathological changes in airway tissues. Immunohistochemistry was utilized to detect the expression of HIF-1α and MMP9 (matrix metalloproteinase 9) in airway tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration in serum of HIF-1α and MMP9. Computed tomography (CT) airway parameters were measured in all participants to assess airway remodeling. The relationship between serum HIF-1α and MMP9 concentrations and airway parameters was analyzed.Results: Staining of airway structures in COPD patients revealed significant pathological changes associated with airway remodelling, including mixed cilia and subepithelial fibrosis. The expression of HIF-1α and MMP9 was significantly higher in both human airway tissue and serum compared to controls. Chest CT scans exhibited typical imaging features of airway remodeling and increased airway parameters.Conclusion: The findings suggest a correlation between increased HIF-1α expression and COPD airway remodelling. This study provides novel evidence that HIF-1α may be a potential biomarker for airway remodelling in COPD patients.Keywords: hypoxia-inducible factor 1-α, chronic obstructive pulmonary disease, matrix metalloproteinase 9, airway remodelling

Liang Tan,1,&ast; Feilong Wang,1,&ast; Yi Huang,2 Chuhua Fu,3 Haijun Zhang,4 Jianfei Feng,5 Yincai Xu,6 Xinzhen Ye,7 Rongrui Tang,8 Yinglian Chen,9 Liansheng Mou,10 Ronghao Li,11 Jingyu Chen,1 Jishu Xian1 1Department of Neurosurgery, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Neurosurgery, The Ninth People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 3Department of Neurosurgery, Xiangyang No.1 People’s Hospital, University of Medicine, Xiangyang, Hubei, People’s Republic of China; 4Department of Neurosurgery, Kaifeng Central Hospital, Kaifeng, Henan, People’s Republic of China; 5Department of Encephalopathy, Beibei Traditional Chinese Medical Hospital, Chongqing, People’s Republic of China; 6Department of Neurosurgery, Zheng Coal General Hospital, Zhengzhou, Henan Province, People’s Republic of China; 7Department of Neurosurgery, Songshan General Hospital, Chongqing, People’s Republic of China; 8Department of Neurosurgery, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 9Zhuhai Brainlightning Research Institute, Zhuhai City, Guangdong, People’s Republic of China; 10Department of Neurosurgery, Liangping District People’s Hospital, Chongqing, People’s Republic of China; 11Department of Basic Medicine, Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyu Chen; Jishu Xian, Email Cjy1_2001@Hotmail.com; 1370321419@qq.comPurpose: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs.Materials and Methods: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes.Results: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p> 0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1– 12) vs 4(1– 8), p< 0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p< 0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death.Conclusion: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients.Trial Registration: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.Keywords: SARS-CoV-2, intensive care unit, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury

Jie Cheng,1 Ya Liu,2 Shaojun Li,1 Kaibin Pu,1 Lin Yang,1 Liping Tan1 1Department of Emergency, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Department of Pediatrics, Chongqing Youyoubaobei Women and Children’s Hospital, Chongqing, 401147, People’s Republic of ChinaCorrespondence: Liping Tan, Tel +86-23-63630194, Email tanlp0825@hotmail.comObjective: Third-generation cephalosporin-resistant (3GC-R) bloodstream infection (BSI) is associated with poor prognosis. We investigated the incidence of and risk factors for 3GC-R Escherichia coli (E. coli) BSI in children.Methods: Patients with E. coli BSIs who were hospitalized at the Children’s Hospital of Chongqing Medical University were retrospectively enrolled. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors for 3GC-R BSI.Results: Two hundred fifty-two children with E. coli BSIs were enrolled. The mortality rate was 11.51% (29/252). The infection rate of 3GC-R E. coli was 48.81% (123/252), and the incidence of E. coli BSI during hospitalization was 18.58 per 1000 person-days. Approximately half (47.22%, 119/252) of the children were infected with extended-spectrum beta-lactamases (ESBLs) produced by E. coli. More than one-third (37.30%, 94/252) of the children were unnecessarily administrated carbapenems. According to our logistic regression analysis, a history of carbapenem administration, an elevated Pediatric Sequential Organ Failure Assessment (pSOFA) score ≥ 2, and antimicrobial agent administration before blood culture were independently associated with 3GC-R BSI (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.08– 3.94, P=0.029; OR 2.00, 95% CI 1.10– 3.71, P=0.025, OR 1.86, 95% CI 1.02– 3.42, P=0.044, respectively).Conclusion: In this study, the incidence of 3GC-R E. coli BSI among children was retrospectively evaluated. Patients with a history of carbapenem administration, an elevated pSOFA score ≥ 2 and who were administrated antimicrobial agents before blood culture had an increased risk of 3GC-R E. coli BSI.Keywords: third-generation cephalosporin-resistant, inappropriate use of carbapenems, Escherichia coli, bloodstream infection, children

Weiguo Wang, Qiuxaing Zhong, Ke Cheng, Lili Tan, Xincheng Huang Department of Clinical Laboratory, The First Hospital of Nanchang, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Xincheng Huang, Email Hxc1817281@163.comPurpose: This study aimed to investigate the molecular characteristics, antimicrobial resistance, and biofilm-forming ability of Staphylococcus aureus isolates from invasive infections.Methods: A total of 92 non-repetitive S. aureus isolates from invasive infections were analyzed by Multi-locus Sequence Typing (MLST), spa typing, and chromosomal cassette mec (SCCmec) typing. Antibiotic susceptibility testing was performed using the disk diffusion and agar dilution methods. Biofilm-forming ability was assessed using crystal violet assay. The presence and expression of biofilm-associated genes were examined using PCR and RT-qPCR.Results: Among the 55 Methicillin-resistant S. aureus (MRSA) and 41 Methicillin-sensitive S. aureus (MSSA) isolates, ST59 (43.6%) predominated in MRSA, while ST7 (39.0%) was most common in MSSA. As expected, MRSA exhibited higher antibiotic resistance rates compared to MSSA isolates. Biofilm formation assays revealed that the majority of isolates (88.5%) produced biofilms, with 26.0% classified as strong producers (OD570 ≥ 1.0) and 62.5% as weak producers (0.2 ≤ OD570< 1.0). MSSA exhibited a higher biofilm-forming ability than MRSA (P < 0.01), with variations across clones. Notably, ST7 isolates displayed greater biofilm-forming ability than other sequence types (ST59, ST5, and ST239). RT-qPCR results revealed that ST7 isolates exhibited higher expression levels of icaA compared to other sequence types.Conclusion: This study revealed significant molecular heterogeneity among invasive S. aureus isolates, with ST59 and ST7 as dominant clones. The strong biofilm-forming capacity of ST7 merits concern given its rising prevalence regionally. Continuous surveillance of emerging successful lineages is critical to help guide infection control strategies against invasive S. aureus infections.Keywords: Staphylococcus aureus, invasive infection, biofilm, ST7

Qianfei Liu,1,&ast; Liping Tan,2 Jianbo He,2 Ruiling Ning,2 Aiping Zeng,2,&ast; Yilin Chen1,&ast; 1Department of Pulmonary and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hu Bei, People’s Republic of China; 2Department of Respiratory Oncology, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aiping Zeng, No. 71 Hedi Road, Nanning City, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email zengaipingone@163.com Yilin Chen, No. 158 Wuyang Avenue, Enshi City, Hu Bei, 445000, People’s Republic of China, Email chenyl891128@163.comPurpose: This study examined the association between plasma D-dimer levels and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients treated with osimertinib.Methods: In this multicenter study, 88 patients with advanced non-small cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) mutations and receiving osimertinib were enrolled. The target independent and dependent variables were the D-dimer levels before osimertinib treatment and OS time, respectively. The t-test or chi-square test was utilized to analyze the variances among various groups. The predictive significance of D-dimer for overall survival (OS) was assessed using Kaplan-Meier survival analysis and the Cox proportional hazard regression model.Results: The selected patients had an average age of 58.01± 10.72 years, with females comprising 54.55%. Based on their D-dimer levels, the patients were categorized into three groups: low-level (< 0.6 mg/L), middle-level (0.6 ~ 2 mg/L), and high-level (≥ 2 mg/L). After accounting for possible confounding variables, the Cox proportional hazard model showed that increased D-dimer levels were linked to a greater likelihood of death (HR 2.28, 95% CI = 1.09 ~ 4.76, p = 0.029). Importantly, there was a significant trend indicating that as D-dimer levels rose, the risk of mortality also increased (p for trend, HR 1.15, 95% CI = 1.03 ~ 1.28, p = 0.012). Consistently comparable outcomes were noted in the majority of subcategories. Patients with low-middle and high D dimer levels had a median OS of 28.6 and 17 months, respectively (p =0.014).Conclusion: In conclusion, elevated levels of D-dimer in the bloodstream were found to have a significant negative correlation with the overall survival (OS) of patients with EGFR-positive non-small cell lung cancer (NSCLC) who underwent treatment with osimertinib.Keywords: D-dimer, EGFR, NSCLC, osimertinib, prognosis

Yinyi Chen,1 Chunlan Xiao,2 Yubin Liao,2 Liming Tan1 1Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, Hunan, People’s Republic of ChinaCorrespondence: Liming Tan, Email ndefy84029@ncu.edu.cnObjective: The purpose of the research was to explore the possible risk factors for the development of hypocomplementemia (HC) in rheumatoid arthritis (RA) patients by analyzing their clinical and laboratory features.Methods: This retrospective research contained 501 RA patients, divided into RA patients with HC (n=78) and RA patients without HC (n=423). Demographic characteristics and laboratory test results of RA patients were collected and analyzed, such as age, sex, anti-mutated citrullinated vimentin antibody (Anti-MCV), serum complements (C3, C4), immunoglobulins (IgA, IgG, IgM), hemoglobin (Hb), platelets (PLT) and erythrocyte sedimentation rate (ESR), etc. Spearman correlation was served as assessing the correlations of the levels of serum C3 and C4 with each index. Receiver operating characteristic (ROC) curves were served as assessing the diagnostic efficacy of each index for RA patients with HC. Furthermore, risk factors for the occurrence of HC in RA patients were analyzed by employing binary logistic regression of single and multiple factors.Results: Compared RA patients with HC to without HC, the former were older and had a longer disease duration with increased levels of Anti-MCV, IgM and DAS28 and lower levels of Hb, PLT and ESR; Spearman correlation analysis verified the level of serum Anti-MCV was a negative correlation with C3 (r=− 0.156); the area under the ROC curve (AUC) of PLT in diagnosing RA patients with HC was the largest at 0.65 (95% CI: 0.60– 0.69); binary logistic regression analysis indicated that advanced age (> 66 years), long disease duration (> 62 months), high DAS28 value (> 6.13), the levels of Anti-MCV> 107.68IU/mL, IgM> 1.54g/L, ESR≤ 69.00mm/h, Hb≤ 99.00g/L and PLT≤ 305.00× 109/L were probable risk factors for the occurrence of HC in RA patients.Conclusion: Age and disease duration, DAS28, Anti-MCV, IgM, ESR, Hb, and PLT are closely related to the development of HC in RA patients. Timely monitoring of these indicators can help to evaluate disease activity of RA patients and further improve their prognosis.Keywords: rheumatoid arthritis, hypocomplementemia, risk factors, disease activity

Bo Li,1 Weiqing Wu,1 Aijun Liu,1 Lifeng Feng,1 Bin Li,1 Yong Mei,1 Li Tan,1 Chaoyang Zhang,2 Yangtao Tian1 1Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China; 2Department of Ultrasound Medicine, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of ChinaCorrespondence: Yangtao Tian, Department of Pancreatic Surgery, Shangluo Center Hospital, 37 Shangyang, Shangzhou, Shangluo, Shaanxi, 726000, People’s Republic of China, Email 928763821@qq.comBackground: Severe acute pancreatitis (SAP) can progress to lung and kidney dysfunction, and blood clotting within 48 hours of its onset, and is associated with a high mortality rate. The aim of this study was to establish a reliable diagnostic prediction model for the early stage of severe pancreatitis.Methods: The clinical data of patients diagnosed with acute pancreatitis from October 2017 to June 2022 at the Shangluo Central Hospital were collected. The risk factors were screened by least absolute shrinkage and selection operator (LASSO) regression analysis. A novel nomogram model was then established by multivariable logistic regression analysis.Results: The data of 436 patients with acute pancreatitis, 45 (10.3%) patients had progressed to SAP. Through univariate and LASSO regression analyses, the neutrophils (P < 0.001), albumin (P < 0.001), blood glucose (P < 0.001), serum calcium (P < 0.001), serum creatinine (P < 0.001), blood urea nitrogen (P < 0.001) and procalcitonin (P = 0.005) were identified as independent predictive factors for SAP. The nomogram built on the basis of these factors predicted SAP with sensitivity of 0.733, specificity of 0.9, positive predictive value of 0.458 and negative predictive value of 0.967. Furthermore, the concordance index of the nomogram reached 0.889 (95% CI, 0.837– 0.941), and the area under the curve (AUC) in receiver operating characteristic curve (ROC) analysis was significantly higher than that of the APACHEII and ABISAP scoring systems. The established model was validated by plotting the clinical decision curve analysis (DCA) and clinical impact curve (CIC).Conclusion: We established a nomogram to predict the progression of early acute pancreatitis to SAP with high discrimination and accuracy.Keywords: acute pancreatitis, prediction model, risk factor, nomogram, decision curve analysis

Xiufen Wang,1– 3 Ying Wang,1,2 Li Luo,3 Liuting Tan,4 Wenzhi Cai,1 Ling Chen,1 Wei Ren1 1Department of Nursing, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, People’s Republic of China; 2School of Nursing, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of the Third Pulmonary Disease, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 4Department of Endocrine, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Wei Ren; Ling Chen, Department of Nursing, Shenzhen Hospital, Southern Medical University, 1333 Xinhu Road, Baoan District, Shenzhen, Guangdong Province, 518101, People’s Republic of China, Tel +86-755-23360006, Fax +86-755-23323777, Email renwei196911@163.com; dangdang601@smu.edu.cnIntroduction: Diabetic neurogenic bladder is one of the common complications in patients with diabetic neuropathy. However, studies reporting the prevalence and associated factors of urinary tract infections (UTIs) in patients with diabetic neuropathy are rare. Therefore, the present study aimed to explore the prevalence and influencing factors of UTI in patients with diabetic neuropathy.Methods: A hospital-based cross-sectional study that recruited patients with diabetic neuropathy was conducted from January 2019 to December 2021. Collected data included patient demographic information (age, sex, education level, body mass index), clinical data (duration of diabetes, method of administration), and laboratory tests. Multivariable logistic regression models were used to identify the factors associated with UTI risk. The strength of association was expressed as the odds ratio (OR) and 95% confidence interval (95% CI).Results: A total of 579 patients were recruited (male, 68.2%; overall average age, 57.89 years). Using multivariate analysis with adjustment for confounding factors, female sex (odds ratio [OR]: 4.12; 95% CI: 2.24– 7.60; P < 0.001), hypodermic insulin injection (OR: 2.10; 95% CI: 1.02– 4.35; P = 0.045), chronic kidney disease (OR: 3.12; 95% CI: 1.11– 8.80; P = 0.032), history of UTI (OR = 45.92; 95% CI: 8.62– 244.76; P < 0.001), positive urinary nitrite (OR: 32.87; 95% CI: 7.37– 146.70; P < 0.001), and high residual urine volume (OR: 2.19, 95% CI: 1.17– 4.10; P = 0.014) were independent risk factors for UTI in patients with diabetic neuropathy. Compared with the patients aged < 45 years, UTI prevalence increased 2.91-fold in patients aged 45– 54 years (OR: 3.91; 95% CI: 1.02– 15.03; P = 0.047) and 3.87-fold in those aged ≥ 65 years (OR: 4.87; 95% CI: 1.23– 19.25; P = 0.024).Conclusion: The main findings of this study showed that older age, female sex, hypodermic insulin injection, CKD, history of UTI, and positive urinary nitrite were independent risk factors for UTI in patients with diabetic neuropathy. To minimize the occurrence and resulting disease burden of UTI, knowledge regarding UTI risk factors in patients with diabetic neuropathy is critical to designate interventions.Keywords: epidemiology, prevalence, urinary tract infection, diabetic neuropathy, risk factors

Guang Yang,1,2,&ast; Lishan Tan,1,&ast; Hua Yao,3 Zuying Xiong,1 Jun Wu,4,5 Xiaoyan Huang1 1Division of Renal Medicine, Peking University Shenzhen Hospital, Peking University, Shenzhen, 518000, People’s Republic of China; 2Department of Life Sciences, Yuncheng University, Yuncheng, 044006, People’s Republic of China; 3Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical College, Guilin, 541004, People’s Republic of China; 4Department of Burn and Plastic Surgery, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of China; 5Human Histology & Embryology Section, Department of Surgery, Dentistry, Pediatrics & Gynecology, University of Verona Medical School, Verona, Venetia, 37134, Italy&ast;These authors contributed equally to this workCorrespondence: Xiaoyan Huang; Jun Wu, Email huangxiaoyan@pku.org.cn; junwupro@126.comAbstract: Burns are a seriously underestimated form of trauma that not only damage the skin system but also cause various complications, such as acute kidney injury (AKI). Recent clinical studies have shown that the proportion of chronic kidney diseases (CKD) in burn patients after discharge is significantly higher than that in the general population, but the mechanism behind this is controversial. The traditional view is that CKD is associated with hypoperfusion, AKI, sepsis, and drugs administered in the early stages of burns. However, recent studies have shown that burns can cause long-term immune dysfunction, which is a high-risk factor for CKD. This suggests that burns affect the kidneys more than previously recognized. In other words, severe burns are not only an acute injury but also a chronic disease. Neglecting to study long-term kidney function in burn patients also results in a lack of preventive and therapeutic methods being developed. Furthermore, stem cells and their exosomes have shown excellent comprehensive therapeutic properties in the prevention and treatment of CKD, making them increasingly the focus of research attention. Their engineering strategy further improved the therapeutic performance. This review will focus on the research advances in burns on the development of CKD, illustrating the possible mechanism of burn-induced CKD and introducing potential biological treatment options and their engineering strategies.Keywords: inflammation, acute kidney injury, chronic kidney diseases, stem cells, exosomes, sepsis, cytokine storm

Huan Liu,1,2,&ast; Zhiping Yu,3,&ast; Yueguang Liu,4 Mingzhen Li,1,2 Cheng Chen,1,2 Zhiyu Zhu,4 Fang Liu,4 Liming Tan2,3 1Department of Precision Medicine Center, The Second People’s Hospital of Huaihua, Huaihua, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Treatment of Huaihua, Huaihua, People’s Republic of China; 3School of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Department of Clinicopathology Center, The Second People’s Hospital of Huaihua, Huaihua, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liming Tan, The Second People’s Hospital of Huaihua, Lulin Road, Huaihua, 418000, People’s Republic of China, Email tanliming1973@126.comPurpose: C-type lectin domain family 4 member M (CLEC4M) has been found to be involved in the occurrence and development of cancer, but its role in NSCLC remains to be fully explored. Our work aims to evaluate the diagnostic and prognostic value of CLEC4M in NSCLC and to investigate the underlying mechanisms of CLEC4M in the immune microenvironment of NSCLC.Methods: Integrating publicly accessible data and clinical tissue samples to verify the expression of CLEC4M in NSCLC. The diagnostic value of CLEC4M was determined by receiver operating characteristic (ROC) curve. Kaplan–Meier survival analysis, nomogram plot, univariate and multivariate Cox regression models were performed to evaluate the prognostic impact of CLEC4M on NSCLC patients. The correlation between CLEC4M and tumor immune infiltration was estimated using TIMER and UALCAN databases. Functional assessments including GO, KEGG pathway and GSEA analyses were implemented to illustrate the potential mechanisms of CLEC4M in NSCLC.Results: CLEC4M was significantly downregulated in NSCLC tissue, as confirmed by immunohistochemistry of clinical tissues. The high AUC value of ROC curves demonstrated the diagnostic accuracy of CLEC4M in NSCLC. Additionally, low CLEC4M expression was associated with poor survival in NSCLC patients. Furthermore, CLEC4M was found to be significantly associated with tumor immune infiltration, and CLEC4M may be involved in immune activation and proliferation inhibition through the functional assessment, suggesting that CLEC4M may be a therapeutic target for NSCLC patients.Conclusion: Our findings reveal CLEC4M is significantly downregulated in NSCLC tissues, and illustrate the diagnostic and prognostic value of CLEC4M in NSCLC, as well as its potential serve as an immune-related therapeutic target.Keywords: CLEC4M, non-small cell lung carcinoma, NSCLC, prognosis, diagnosis, tumor immune microenvironment

Wang W, Zhong Q, Cheng K, Tan L, Huang X. Infect Drug Resist. 2023;16:7671–7681. Page 7671, Abstract, Methods section, first line, the text “A total of 92 non-repetitive” should read “A total of 96 non-repetitive”. The authors apologize for this error.

Ning-Ke Guo,1,2,&ast; Han She,1,&ast; Lei Tan,1 Yuan-Qun Zhou,1 Chun-Qiong Tang,1 Xiao-Yong Peng,1 Chun-Hua Ma,1 Tao Li,1 Liang-Ming Liu1 1State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 2The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Li; Liang-Ming Liu, Email lt200132@163.com; lmliu62@tmmu.edu.cnBackground: Intestinal barrier dysfunction is an important complication of sepsis, while the treatment is limited. Recently, parthenolide (PTL) has attracted much attention as a strategy of sepsis, but whether nano parthenolide (Nano PTL) is therapeutic in sepsis-induced intestinal barrier dysfunction is obscured.Methods: In this study, cecal ligation and puncture (CLP)-induced sepsis rats and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IECs) were used to investigate the effect of PTL on intestinal barrier dysfunction. Meanwhile, we synthesized Nano PTL and compared the protective effect of Nano PTL with ordinary PTL on intestinal barrier function in septic rats and IECs. Network pharmacology and serotonin 2A (5-HTR2A) inhibitor were used to explore the mechanism of PTL on the intestinal barrier function of sepsis.Results: The encapsulation rate of Nano PTL was 95± 1.5%, the drug loading rate was 11± 0.5%, and the average uptake rate of intestinal epithelial cells was 94%. Ordinary PTL and Nano PTL improved the survival rate and survival time of septic rats, reduced the mean arterial pressure and the serum level of inflammatory cytokines, and protected the liver and kidney functions in vivo, and increased the value of transmembrane resistance (TEER) reduced the reactive oxygen species (ROS) and apoptosis in IECs in vitro through 5-HTR2A. Nano PTL had better effect than ordinary PTL.Conclusion: Ordinary PTL and Nano PTL can protect the intestinal barrier function of septic rats by inhibiting apoptosis and ROS through up-regulating 5-HTR2A, Nano PTL is better than ordinary PTL.Keywords: sepsis, nano PTL, intestinal permeability, 5-HTR2A, apoptosis

Bailong Hu,1,2,&ast; Mei Zhang,2,&ast; Zhen Wu,2,&ast; Xiaoyuan Zhang,2,&ast; Xiaohua Zou,1,2 Li Tan,1 Tao Song,1 Xingyu Li1 1Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 2College of Anesthesiology, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohua Zou, Email zouxiaohuazxh@163.comBackground: Remimazolam tosilate (RT) is a new ultrashort-acting γ-aminobutyric acid subtype A (GABAA) agonist, with the characteristics of rapid onset and offset, minimal cardiorespiratory depression. Currently, few studies have compared the effect of RT and etomidate on hemodynamics during anesthesia induction. Here, we aimed to compare the hemodynamic effects of different doses of RT and etomidate for anesthesia induction in patients undergoing cardiac surgeries.Methods: Patients were recruited from January to September 2022 in this single-center, prospective, randomized, double-blind trial. A total of 117 patients undergoing selective valve replacement surgery were randomly divided into low-dose RT (0.2 mg/kg) group (group LR), high-dose RT (0.3 mg/kg) group (group HR), or etomidate (1.5 mg/kg) group (group E), respectively. The primary outcome was hemodynamic fluctuations (mean arterial pressure fluctuation value [∆MAP]; heart rate fluctuation value [∆HR]) during anesthesia induction. Secondary outcomes included the incidence of adverse drug reactions (injection pain and myoclonus) and adverse cardiovascular events, vital signs at different time points and the cumulative doses of vasoactive drugs.Results: The hemodynamic fluctuations (∆MAP) in group LR and group E were significantly lower than that in group HR. In addition, the incidence of hypotension and the cumulative norepinephrine doses in group E and group LR were also significantly lower than that in group HR. Furthermore, the incidence of injection pain and myoclonus in group LR and group HR were less frequently recorded compared with group E. There were no significant differences in terms of ∆HR, tachycardia, hypertension, severe bradycardia, vital signs at different time points, lactic acid and blood glucose between both groups.Conclusion: Compared with etomidate, low-dose RT (0.2mg/kg) can not only provide stable hemodynamic parameters but also cause fewer adverse reactions when used for anesthesia induction in patients with cardiac disease.Keywords: remimazolam tosilate, etomidate, hemodynamics, cardiac surgery

Lingcan Tan,1 Hong Yu,1 Junyu Yan,2 Chunyuan Liu,3 Kun Xiao,4 Jin Yin,5 Yunxia Zuo,1 Tao Zhu,1 Xiaoqian Deng1 1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Anesthesiology, Karamay Hospital of Integrated Traditional Chinese and Western Medicine, Karamay, People’s Republic of China; 3Department of Anesthesiology, Chongqing Liangping District People’s Hospital, Chongqing, 405200, People’s Republic of China; 4School of Information and Software Engineering, University of Electronic Science and Technology of China, Chengdu, 610054, People’s Republic of China; 5West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Xiaoqian Deng, Department of Anesthesiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People’s Republic of China, Email d_xiaoqian@163.comPurpose: The National Remote Emergency System for Malignant Hyperthermia (MH-NRES) is an applet in China, designed to help anesthesiologists manage MH crisis. However, there is limited information about encountered difficulties in dealing with MH among Chinese anesthesiologists. The purpose of the study was to explore the current competency and encountered difficulties in the management of MH, as a key first step for assessing the potential user needs to develop the MH-NRES.Methods: The hospitals of different levels in different provinces across China were invited to participate in an online survey from November to December 2021. Anesthesiologists completed the online questionnaire containing four sections including demographic information, knowledge, competency, and continuing education about MH.Results: A total of 1357 valid questionnaires were completed from anesthesiologists, most respondents (66.7%, n = 905) correctly answered the MH trigger drugs included volatile anesthetics and succinylcholine. However, most respondents (77.0%, n = 1045) did not know that the recommended initial dose of domestic dantrolene. Up to 83.9% (n = 1138) stated that their hospitals did not store dantrolene for MH emergency. More than half of respondents thought that it would take more than one hour to obtain dantrolene in emergency. Less work experiences, lower levels of hospital and educations and professional titles were associated with lower competency scores in managing MH. Only 31.0% (n = 936) reported that their hospital had ever conducted MH continuing education curricula. Scenario simulation is the training method that most interests the participants (79.0%, n = 1072) but a whopping 46.9% (n = 637) never received simulation.Conclusion: The study indicated that difficulty in obtaining dantrolene, lack of competency in management of MH, difficulty in obtaining professional help, and poor teamwork were the main problems of most anesthesiologists in face of MH.Keywords: malignant hyperthermia, questionnaire, competency, dantrolene, education

Lingcan Tan,1,&ast; Yi Teng,1,&ast; Hong Yu,1 Chunyuan Liu,2 Kun Xiao,3 Jin Yin,4 Yunxia Zuo,1 Tao Zhu,1 Xiaoqian Deng1 1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Anesthesiology, Chongqing Liangping District People’s Hospital, Chongqing, 405200, People’s Republic of China; 3School of Information and Software Engineering, University of Electronic Science and Technology of China, Chengdu, 610054, People’s Republic of China; 4West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqian Deng, Department of Anesthesiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People’s Republic of China, Tel +86 885423592, Email d_xiaoqian@163.comPurpose: Malignant hyperthermia (MH) is a rare but fatal pharmacogenetic disorder, triggered by inhalational anesthetics or succinylcholine. Since the first nonprofit academic organization China Malignant Hyperthermia Emergency Assistance WeChat-based Group (CMHEA Group) was established in 2015, they have actively participated in the diagnosis and treatment of MH patients. Based on the CMHEA Group, the aim of the study was to retrospectively analyze the characteristics of suspected MH in China from 2015 to 2020.Methods: We conducted a retrospective analysis of the suspected MH patients from 2015 to 2020, for analyzing the current clinical diagnosis, treatment and prognosis of MH in China.Results: A total of 58 suspected MH cases occurred from 2015 to 2020, of these, 36 cases were collected with detailed data. The MH clinical grading score of 36 patients ranged from 33 to 73, with a median of 55. Abnormal hyperthermia and hypercarbia were the most common early signs of MH. Four patients were confirmed carrying six different potential MH-causative mutations. Of the total 58 cases, 14 patients (24.1%) received dantrolene and the whole mortality rate was 53.4%. Compared to the patients not receiving dantrolene treatment, the survival rate of patients receiving dantrolene treatment was significantly higher than that of patients not receiving dantrolene (78.6% vs 36.4%, p = 0.007).Conclusion: The current main diagnostic methods of suspected MH in China are still clinical diagnosis. Hence, it is critical to keep dantrolene for immediate accessibility with the introduction of domestic dantrolene to China. The WeChat group model has played an important but limited role in quick diagnosis and treatment of MH.Keywords: malignant hyperthermia, dantrolene, mortality, China

Yun Li &ast;, Junfeng Lin &ast;, Zihui Wang &ast;, Zhufeng Wang, Lunfang Tan, Shuyi Liu, Jinhai Huang, Yi Gao, Jinping Zheng National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Gao; Jinping Zheng, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Yuexiu District, Guangzhou, 510120, People’s Republic of China, Tel +86 20 83062869, Fax +86 20 83062729, Email misstall2@163.com; jpzhenggy@163.comBackground: In the 2021 ERS/ATS interpretive strategies for routine lung function tests, a positive bronchodilator response (BDR) was updated as a change of > 10% relative to the predicted value in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC). We aimed to explore the differences between the 2005 and 2021 ERS/ATS criteria applied to patients with asthma as well as chronic obstructive pulmonary disease (COPD).Methods: BDR test data about asthma patients aged 6– 80 years and COPD patients aged 18– 80 years were derived from the National Respiratory Medicine Center, First Affiliated Hospital of Guangzhou Medical University, from January 2017 to March 2022. BDR results defined by the 2005 and 2021 ERS/ATS criteria were named 2005-BDR and 2021-BDR, respectively. We compared differences between 2005-BDR and 2021-BDR and analyzed the trend in the proportion of positive BDR (BDR+) with the level of airflow obstruction.Results: A total of 4457 patients with asthma and 7764 patients with COPD were included in the analysis. The percentages of 2005-BDR+ and 2021-BDR+ were 63.32% and 52.84% for asthma, 30.92% and 22.94% for COPD, respectively. Of patients with 2005-BDR+, 81.86% for asthma and 70.18% for COPD showed 2021-BDR+ results, and these patients had higher FEV1%pred, FVC%pred (all P< 0.05). Whichever BDR criterion was adopted, the proportion of BDR+ had an upward linear trend with the increased degree of airflow obstruction in COPD, but exhibited an approximate inverted U-shaped curve in asthma. In COPD, the proportion of BDRFEV1 was negatively associated with the degree of airflow obstruction, while BDRFVC was positively associated (all P< 0.05).Conclusion: Compared with 2005-BDR+, the proportion of 2021-BDR+ reduced markedly in patients with asthma and COPD, but their trends with the degree of airflow obstruction did not change. Patients with consistent BDR+ had higher initial FEV1%pred and FVC%pred.Keywords: pulmonary function test, bronchodilator responsiveness testing, asthma, chronic obstructive pulmonary disease, European Respiratory Society, ERS, American Thoracic Society, ATS

Dongting Zhang,1,&ast; Fengmei Tian,2,&ast; Wenjun Gao,2 Yvfeng Huang,3 Hui Huang,2 Liping Tan2 1Department of Nursing, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Nursing, the Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3School of Nursing, Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Huang; Liping Tan, Department of Nursing, the Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Suzhou, 215004, People’s Republic of China, Tel +86-15312187852 ; +86-13962514643, Email 15312187852@163.com; tlping67@126.comPurpose: To examine the reliability and validity of the Chinese short version of the Activities-specific Balance Confidence scale (ABC-6), and its predictive value for prospective falls in community-dwelling older adults.Patients and Methods: A total of 391 community older adults completed the prospective study. Internal consistency reliability, test-retest reliability, structural validity and discriminant validity were analyzed. To determine the accuracy of ABC-6 total score in predicting falls, a receiver operating characteristic curve analysis was performed, and comparisons with the Activities-specific Balance Confidence scale (ABC-16) and Berg Balance Scale (BBS) were made.Results: Excellent internal consistency (Cronbach’s α = 0.938) and test-retest reliability (ICC=0.964, 95% CI: 0.947– 0.977) were found for the ABC-6. Exploratory factor analysis suggested that ABC-6 had a one-factor structure (explained variance, 68.30%). The optimal cutoff value, sensitivity and specificity of ABC-6 to distinguish fallers from non-fallers was ≤ 60.00%, 70.83% and 84.26%, respectively, and there was no significant difference in the predictive value among the ABC-6, ABC-16, and BBS.Conclusion: The Chinese version of the ABC-6 scale was a valid and reliable tool for measuring self-perceived balance confidence in community-dwelling older adults, and can be used as an effective assessment tool to predict future falls.Keywords: activities-specific balance confidence scale, Chinese version, older adults, falls, predictive

Lu Tan,1 Taomei Li,1 Lian Luo,1 Xiaofang Xue,2,3 Fei Lei,1 Rong Ren,1 Ye Zhang,1 Jiaming He,2,3 Konrad E Bloch,4 Xiangdong Tang1,5– 7 1Sleep Medicine Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Emergency, Diqing Tibetan Autonomous Prefectural People’s Hospital, Shangri-La, People’s Republic of China; 3Department of Intensive Care Unit, Diqing Tibetan Autonomous Prefectural People’s Hospital, Shangri-La, People’s Republic of China; 4Department of Respiratory Medicine, Sleep Disorders Center, University Hospital of Zurich, Zurich, Switzerland; 5Mental Health Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 7State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xiangdong Tang, Sleep Medicine Center, Mental Health Center, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 28 Dian Xin Nan Jie, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85422733, Fax +86-28-85422632, Email 2372564613@qq.comPurpose: Obstructive sleep apnea (OSA) is common both at low and high altitude. Since adaptations to high altitude and respiratory control may differ among Tibetans and Hans, we compared characteristics of sleep-disordered breathing in the two ethnic groups at high altitude.Materials and Methods: This was a prospective observational study including 86 Tibetan and Han long-term (> 5 years) high altitude residents with chief complaints of snoring and/or witnessed apnea underwent clinical evaluation and polysomnography at 3200 meters in Shangri-La, China.Results: In 42 Tibetans, 38 men, median (quartiles) age was 50.0 (41.0; 56.0)y, total apnea/hypopnea index (AHI) 53.9 (32.0; 77.5)/h, obstructive AHI 51.0 (28.0; 72.2)/h and central AHI 1.5 (0.2; 3.1)/h. In 44 Hans, 32 men, median (quartiles) age was 47.0 (43.5; 51.0)y, total AHI 22.2 (12.8; 39.2)/h, obstructive AHI 17.7 (12.0; 33.0)/h and central AHI 2.4 (0.5; 3.4)/h (p < 0.001 total and obstructive AHI vs Tibetans). In Tibetans, mean nocturnal oxygen saturation was lower [median 85.0 (83.0; 88.0)% vs 88.5 (87.0; 90.0)%] and obstructive apnea and hypopnea duration was longer [22.0 (19.6; 24.8) sec vs 18.3 (16.7; 20.6) sec] than in Hans (all p < 0.001). In regression analysis, Tibetan ethnicity, neck circumference and high-altitude living duration were the predictors of total AHI. We also found that with every 10/h increase in total AHI, there were an approximately 0.9 beat/min and 0.8 beat/min increase in mean heart rate during rapid eye movement (REM) and non-REM sleep and 1.9 mmHg and 2.0 mmHg increase in evening and morning systolic blood pressure.Conclusion: Our data suggest that Tibetans presented more severe obstructive sleep apnea, hypoxemia and longer apnea duration compared to Hans at 3200 meters, which was correlated with higher heart rate and blood pressure suggesting a greater cardiovascular risk.Keywords: obstructive sleep apnea, high altitude, Tibetan, long-term Han resident

Bowen Wu,1 Li Tan,2 Weihua Wang,3 Xingzhong Feng,4 Dan Yan1,5,6 1Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Center of Pharmaceutical Technology, Tsinghua University, Beijing, People’s Republic of China; 4Tsinghua University Yuquan Hospital, Beijing, People’s Republic of China; 5Beijing Institute of Clinical Pharmacy, Beijing, People’s Republic of China; 6Beijing Key Laboratory for Evaluation of Rational Drug Use, Beijing, People’s Republic of ChinaCorrespondence: Xingzhong Feng, Tsinghua University Yuquan Hospital, No. 5 Shijingshan Road, Shijingshan District, Beijing, People’s Republic of China, Email fengxz9797@sina.com Dan Yan, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong’an Road, Xicheng District, Beijing, People’s Republic of China, Email pharmsci@126.comBackground: Imidazole Propionate (ImP) is a new marker of Type 2 diabetes mellitus (T2DM), which can induce impaired glucose metabolism and weaken the efficacy of metformin. An extensive exploration into literature suggests that ImP may be associated with stool consistency.Purpose: Through an in-depth study of the relationship between stool consistency, bile acids, fecal microbiota and ImP, we intend to explore the mechanism driving the ImP content difference in T2DM.Patients Under Study and Methods: This is a single-center, prospective, cross-sectional study. Plasma ImP and stool consistency were analyzed among 96 diabetic subjects and 45 healthy subjects. All subjects were divided into the stool consistency normal (N) group and the stool consistency abnormal group, of which the abnormal group was sub-divided into the hard stool (H) group and the soft stool (S) group. After identifying the correlation between ImP and stool consistency, we analyzed the influence of bile acids and fecal microbiota on ImP in diabetic subjects.Results: For T2DM patients, the ImP level of the abnormal stool consistency group was significantly higher than that of the normal stool consistency group (P < 0.001). Results were verified in 45 healthy subjects (P = 0.002). ImP was significantly associated with taurocholic acid (TCA) (P = 0.003) in feces, taurodeoxycholate (TDCA) (P = 0.003), glycochenodeoxycholate (GCDCA) (P = 0.021), and glycocholic acid (GCA) (P = 0.031) in plasma. The Shannon index of Group N was significantly higher than that of Group H (P = 0.041) and Group S (P = 0.003).Conclusion: ImP was higher in diabetic patients with abnormal stool consistency than in those with normal stool consistency, which was related to the proportion of bile acids and fecal microbial structure. These findings may improve our understanding of ImP and contribute to the treatment of T2DM by improving stool consistency.Keywords: ImP, T2DM, stool consistency, bile acids

Feng Su,1,&ast; Yong Fang,1,&ast; Jinjie Yu,1 Tian Jiang,1 Siyun Lin,1 Shaoyuan Zhang,1 Lu Lv,2 Tao Long,2 Huiwen Pan,2 Junqing Qi,2 Qiang Zhou,3 Weifeng Tang,4 Guowen Ding,2 Liming Wang,5 Lijie Tan,1 Jun Yin1 1Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Jiangsu, People’s Republic of China; 3Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan, People’s Republic of China; 4Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Jiangsu, People’s Republic of China; 5Department of Respiratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Yin; Lijie Tan, Zhongshan Hospital of Fudan University, 180 Fenglin road, Xuhui District, Shanghai, 200032, People’s Republic of China, Email jun_yin@fudan.edu.cn; tan.lijie@zs-hospital.sh.cnBackground: The σ 1A subunit of the adaptor protein 1 (AP1S1) participates in various intracellular transport pathways, especially the maintenance of copper homeostasis, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case-control study, we investigated the genetic susceptibility to ESCC in relation to SNPs of AP1S1 among Chinese population.Methods: A database containing a total of 1303 controls and 1043 ESCC patients were retrospectively studied. The AP1S1 SNPs were analyzed based on ligation detection reaction (LDR) method. Then, the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P< 0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step.Results: AP1S1 rs77387752 C>T genotype TT was an independent risk factor for ESCC, while rs4729666 C>T genotype TC and rs35208462 C>T genotype TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers.Conclusion: AP1S1 rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. AP1S1 SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers.Keywords: AP1S1, single nucleotide polymorphism, SNP, esophageal squamous cell carcinoma, ESCC

Suzhen Chen,1,2 Zhi Xu,1,2 Yinghui Li,1,2 Tianyu Wang,1,2 Yingying Yue,1,2 Zhenghua Hou,1,2 Linlin You,1,2 Na Lu,1,2 Yingying Yin,1,2 Xiaoyun Liu,1,2 Liangliang Tan,1,2 Houcheng Ji,3 Yaoran Shi,1,2 Xiaoyun Xin,1,2 Wenhao Jiang,1,2 Yonggui Yuan1,2 1Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Psychosomatics, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Psychiatry, The Second People’s Hospital of Jiangning District, Nanjing, People’s Republic of ChinaCorrespondence: Yonggui Yuan, Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Gulou District, Nanjing, 210009, People’s Republic of China, Tel +86-25-83285124, Email yygylh2000@sina.comPurpose: Shumian capsule (SMC) is a patent Chinese herbal medicine that can soothe the liver and relieves depression, quiet the spirit. Here, we aimed to investigate the efficacy of SMC for treating insomnia using both scales and polysomnography (PSG).Patients and Methods: A randomized, double-blind, placebo-controlled trial was performed. Twenty-six insomnia patients randomly received SMC (n = 11) or placebo (n = 15) for four weeks. Pittsburgh Sleep Quality Inventory (PSQI), Insomnia Severity Index (ISI), 9-items Patient Health Questionnaire (PHQ-9), 7-items Generalized Anxiety Disorder (GAD-7), 17-item Hamilton Depression Rating Scale (HAMD-17), and Hamilton Anxiety Rating Scale (HAMA) were applied at the baseline and the 2nd, 4th week after treatment. Treatment Emergent Symptom Scale was used to assess adverse reactions. We used PSG to record and analyze sleep features at baseline and after four weeks.Results: PSQI, ISI, PHQ-9, HAMD-17, and HAMA scores decreased significantly after SMC treatment. Also, the total sleep time, rapid-eye-movement (REM) sleep latency, stage 2 sleep, deep sleep, REM sleep, and sleep efficiency improved significantly after SMC treatment. In the placebo group, the only significant change was the decrease of PHQ-9 at week-2. Furthermore, both SMC and placebo reported no adverse events.Conclusion: SMC could safely improve sleep quality with depression and anxiety remission in insomnia patients.Keywords: Chinese herbal medicine, shumian capsule, insomnia, polysomnography, clinical trial, randomized and double-blind method

Han She,1,2,&ast; Yi Hu,1,&ast; Yuanqun Zhou,2 Lei Tan,1 Yu Zhu,2 Chunhua Ma,2 Yue Wu,2 Wei Chen,1 Li Wang,2 Zisen Zhang,2 Li Wang,1 Liangming Liu,2 Tao Li2 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangming Liu; Tao Li Email liangmingliu@yahoo.com; Lt200132@163.comIntroduction: Vascular leakage plays a vital role in sepsis-induced multi-organ dysfunction. Currently, no specific measures are available for vascular leakage. Ferroptosis, as a recently recognized form of cell death, plays a crucial role in cell dysfunction. It is still unknown whether ferroptosis participates in the occurrence of organ dysfunction following sepsis. Our previous study showed that dexmedetomidine (Dex) could alleviate sepsis-induced organ dysfunction. However, whether the mechanism is related to ferroptosis is not clear.Methods: The publicly available datasets of septic patients were reanalyzed, and septic models in vivo and vitro by cecal ligation and puncture and lipopolysaccharide-stimulated vascular endothelial cells (VECs) were applied. The occurrence of ferroptosis in septic patients and rats was observed, and the protective effects of Dex on ferroptosis, and related mechanisms on regulating metabolic reprogramming and mitochondrial fission were further studied.Results: The transcriptomics data of patients from the GEO database showed that ferroptosis was closely related to sepsis. Sepsis induced significant ferroptosis in VECs by metabolomics analysis. The level of lipid peroxidation was increased in VECs, and the mitochondrial cristae was decreased after sepsis. Metabolomics analysis showed that Dex activated the pentose phosphate pathway and increased glutathione in VECs via up-regulation of G6PD expression. Dex could antagonize sepsis-induced the decrease in the level of Nrf2. The Nrf2 inhibitor reversed the protective effect of Dex on ferroptosis. Further study showed that Dex significantly alleviated sepsis-induced mitochondrial over-division, improved mitochondrial function, and decreased ROS, further inhibiting the ferroptosis of VECs. Dex alleviated the permeability of vessels by reducing ferroptosis and enhanced the intercellular junction of VECs.Conclusion: Dex protects vascular leakage following sepsis by inhibiting ferroptosis. The mechanism is mainly related to metabolic reprogramming via Nrf2 up-regulation and inhibition of mitochondrial fission.Keywords: dexmedetomidine, sepsis, ferroptosis, metabolic reprogramming, mitochondrial fission

Liao Tan,1,2 Qian Xu,3 Ruizheng Shi2 1Department of Cardiology, The Third Xiangya Hospital, Central South University Changsha, Hunan, People’s Republic of China; 2Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Ruizheng ShiDepartment of Cardiovascular Medicine, Xiangya Hospital, Central South University, 88 Xiangya Road, Changsha, 410013, People’s Republic of ChinaEmail xyshiruizheng@csu.edu.cnBackground: This study aims to construct and validate an early-stage nomogram for predicting hospital mortality of ICU patients with acute myocardial infarction (AMI), to help clinicians determine the appropriate intervention.Methods: The primary cohort of 2704 patients diagnosed with acute myocardial infarction in admission records from eICU-Collaborative Research Database (eICU-CRD) v2.0. Univariate logistic regression analysis and multivariate logistic regression analysis were enrolled for the construction of the predictive nomogram. Demographic factors, history of clinical cardiovascular disease, vital signs, the use of vasopressors, urine output, and serum variables in the first 24 hours were included in this analysis. The nomogram was evaluated by performance traits including Harrell’s concordance index (C-index) and area under the receiver operating characteristic (AUC) analysis, calibration curve, and decision curve analysis (DCA). The nomogram was validated in a different cohort containing 1026 subjects collected from MIMIC-III Database v1.4. Finally, in order to compare the performance with other classic prediction models, AUC analysis, calibration curve, DCA and accuracy analysis (net reclassification improvement (NRI)) were conducted for three ICU scores in validated cohort.Results: The nomogram revealed 14 predictors of the first 24 hours derived from univariate and multivariable analyses, including age, history of peripheral vascular disease, atrial fibrillation, cardiogenic shock and cardiac arrest, the use of norepinephrine, urine output, white blood cell (WBC), hemoglobin (Hb), red blood cell (RBC), red cell distribution width (RDW), glucose, bicarbonate and magnesium. The C-index of this nomogram was 0.834 (95% CI 0.812 to 0.856). Then, the result of AUC analysis, the DCA and calibration curve indicated that our nomogram was feasible for clinical prediction. The predictive ability and clinical use of the nomogram were verified in the validated cohort. The AUC analysis of ICU scores showed that the AUC of these score systems was ranged from 0.811 to 0.860 (the AUC of nomogram: 0.885). Moreover, our nomogram also showed a better performance in calibration curve and DCA NRI.Conclusion: The study presents a prediction nomogram incorporating 14 variables that could help identify AMI patients admitted in ICU who might have a high risk of hospital mortality in the first hospitalized 24 hours. This nomogram showed a better performance than normal ICU score systems.Keywords: prediction, acute myocardial infarction, ICU, nomogram, hospital mortality

Liao Tan,1,2 Qian Xu,3 Chan Li,2 Xuliang Chen,3 Hui Bai3 1Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Hui BaiDepartment of Cardiovascular Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410013, People’s Republic of ChinaEmail 2211200403@qq.comObjective: Serum bicarbonate (HCO3−) level is strongly related to multiple cardiovascular complications. Currently, there is no study evaluating the prognostic ability of serum HCO3− level in intensive care unit (ICU) patients with acute aortic dissection (AAD). Hence, this study was to assess the relationship between admission serum HCO3− level and clinical outcomes in patients with AAD.Design, Settings and Participants: Clinical data were extracted from the MIMIC-III database. Cox proportional hazards models and Kaplan–Meier (KM) survival curve were used to evaluate the association between serum HCO3− levels and short- and long-term mortality in ICU patients with AAD. The subgroup analysis and the receiver operating characteristic (ROC) curve analysis and further KM survival curve based on best cut-off value were applied to assessment of the performance of HCO3− in predicting the mortality in each period (30 days, 90 days, 1 year and 5 years).Main Results: Firstly, 336 eligible patients were trisected to low-HCO3− level group (< 22 mmol/L), mid-HCO3− level group (22– 24 mmol/L) and high-HCO3− level group (> 24 mmol/L). Then, in multivariate analysis, the serum HCO3− of low levels (< 22 mmol/L) was a significant risk predictor of all-cause mortality in 30 days, 90 days, 1 year and 5 years. Subgroup analyses indicated that there is no interaction in most strata. Finally, areas under ROC curve ranged from 0.60 to 0.69.Conclusion: The low HCO3− serum level measured at ICU admission significantly predicts short-term and long-term mortality in AAD patients.Keywords: serum bicarbonate, intensive care unit, acute aortic dissection, all-cause mortality

Tongtong Zhou,1,2,&ast; Li Tan,1,&ast; Yang Gui,1 Jing Zhang,1 Xueqi Chen,1 Menghua Dai,3 Mengsu Xiao,1 Qing Zhang,1 Xiaoyan Chang,4 Qun Xu,5 Chunmei Bai,6 Yuejuan Cheng,6 Qiang Xu,3 Xue Wang,7 Hua Meng,1 Wanying Jia,1 Ke Lv,1 Yuxin Jiang1 1Department of Ultrasound, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Ultrasound, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 7Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Lv; Yuxin JiangDepartment of Ultrasound, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaTel/Fax +86 10-69155493; +86 10-69155491Email lvke@163.com; yuxinjiangxh@163.comObjective: Investigate the CEUS enhancement patterns of PDAC and analyse correlations between the CEUS enhancement pattern and both the degree of tumour tissue differentiation and overall survival (OS).Methods: The study included 56 patients with locally advanced PDAC, performed conventional ultrasound and CEUS, and analysed characteristics of the CEUS enhancement patterns. In addition, clinical data, such as serum level of CA19-9, TNM stage were collected, and patients’ survival times were followed up. TICs of dynamic CEUS images were acquired using image processing software to obtain the peak, TP, sharpness, and AUC. Correlations of the CEUS enhancement patterns of PDAC with the degree of differentiation of tumour tissue and OS were quantitatively analysed, as were the correlations of the TIC parameters and CEUS enhancement patterns with OS.Results: Enhancement in the arterial phase included iso-enhancement (30.3%) and hypo-enhancement (69.6%), and was not significantly correlated with sex, age at disease onset, or lesion size. Also was not significantly correlated with tumour tissue differentiation. Clear survival times were obtained for 50 patients during follow-up, and the median survival time was significantly longer for the patients with iso-enhancement than hypo-enhancement. Among the TIC parameters, peaktumour, sharpnesstumour, AEsharpness, and REsharpness differed significantly between the group with iso-enhancement and hypo-enhancement (p < 0.05).Conclusion: The CEUS enhancement patterns of PDAC in the arterial phase include iso-enhancement and hypo-enhancement. Enhancement pattern was not significantly correlated with the degree of differentiation of tumour tissue, but patient survival time differed significantly between the two enhancement patterns, with longer survival for patients with iso-enhancement.Keywords: contrast-enhanced ultrasound, pancreatic ductal adenocarcinoma, survival time, enhancement pattern, time-intensity curve

Xiaohang Li,1 Xu Li,1 Simei Chen,1 Yang Wu,1 Yuhan Liu,1 Tingting Hu,1 Jiayi Huang,1 Jianlin Yu,1 Zihuan Pei,1 Tingting Zeng,2 Liming Tan1 1Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, Jiangxi, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Liming TanDepartment of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Jiangxi Province Key Laboratory of Laboratory Medicine, No. 1 Minde Road, Donghu District, Nanchang, Jiangxi, People’s Republic of ChinaTel +86 791-86300410Email ndefy84029@ncu.edu.cnPurpose: To explore the clinical significance of tumor necrosis factor receptor-associated protein (TRAP1), mitotic arrest deficient 2 (mad2) and anti-nuclear mitotic spindle apparatus antibody (MSA) in the diagnosis of small cell lung cancer (SCLC).Patients and Methods: Serum concentrations of TRAP1 and MSA were determined by enzyme-linked immunosorbent assay (ELISA), including SCLC group (Num.=86), non-small cell lung cancer (NSCLC) group (Num.=105), pulmonary nodules (PN) group (Num.=94), and 60 healthy subjects as control group (Num.=60). Whereas fluorescence quantitative PCR (qt-PCR) method was used to detect the expression of mad2.Results: The expression of TRAP1 was low in SCLC and NSCLC compared with the other two groups, and was the lowest in SCLC, which was negatively correlated with the occurrence of the disease (P< 0.05); the sensitivity and specificity of TRAP1 for SCLC were 75.29%, 93.33%, and the area under SCLC curve was 0.903; compared with the other three groups, the level of MSA was the highest in the SCLC, and the results were significantly different (P< 0.05), while the area under the SCLC curve was 0.856, and the sensitivity and specificity were 62.78% and 95.24%, respectively. Mad2 is overexpressed in SCLC, but not in PN. The area under the SCLC curve is 0.835, and the sensitivity and specificity are 56.98% and 92.38%; TRAP1 levels are negatively correlated with SCLC tumor stage, the level of TRAP1 was significantly lower in stage III–IV than in stage I–II (P< 0.05); combined analysis of TRAP1 and MAD2 and MSA showed that the sensitivity and specificity for SCLS were 95.35% and 99.05%, respectively.Conclusion: TRAP1 is of great value in the early diagnosis of SCLC as well as differential diagnosis with NSCLC. TRAP1 combined with MAD2 and MSA improved the sensitivity and specificity and provided a new idea for the clinical diagnosis of SCLC.Keywords: TRAP1, diagnosis, small cell lung cancer, clinical stage, metastasis

Jin Li,1,* Junqiang Bao,2,* Chao Gao,2 Zibin Wei,2 Liguo Tan,3 Ping Liu,2 Zhiwei Wang,2 Shujuan Tian2 1Department of Neurosurgery, The Affiliated Hospital of the Nco School, The Army Medical University, Shijiazhuang, 050041, Hebei, People’s Republic of China; 2Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, 050030, Hebei, People’s Republic of China; 3Department of Field Internal Medicine, The NCO School of The Army Medical University, Shijiazhuang, 050031 Hebei, China*These authors contributed equally to this workCorrespondence: Zhiwei Wang; Shujuan TianDepartment of neurology, The First Hospital of Hebei Medical University, No. 89 Donggang Road, Shijiazhuang, 050030, Hebei, People’s Republic of ChinaEmail wzw0412@163.com; 2581810783@qq.comBackground: Previous studies have reported that patients with stroke have a high incidence of cognitive decline. The aim was to elucidate the association between serum E-selectin levels and cognitive function in stroke patients.Materials and Methods: Serum levels of E-selectin were measured in 322 patients with stroke at baseline. Cox proportional hazard analysis was used to evaluate the predictive value of serum E-selectin for predicting cognitive decline (end point) in patients with stroke.Results: Multivariate linear regression analysis revealed that serum E-selectin levels were independently associated with MOCA score after adjusting for age, gender, BMI, current smoker, current drinker, admission systolic and diastolic BP, CVD history and laboratory measurements in patients with stroke at baseline (Sβ= − 0.156; 95% CI, - 0.170– - 0.074; P< 0.001). The multivariate Cox proportional hazard analysis revealed that serum E-selectin (HR=2.481, 95% CI 1.533– 4.327, P-trend < 0.001) was an independent prognostic factor for cognitive decline in these patients with stroke during the follow-up period.Conclusion: Our results showed that increased serum E-selectin levels were significantly and independently associated with cognitive decline and had independent predictive value for cognitive decline in patients with stroke. Serum E-selectin might enable early recognition of cognitive decline among stroke patients.Keywords: E-selectin, stroke cognitive decline, prognostic value

Langzi Tan, Yayu Chen, Wenyue Wu, Chaorong Liu, Yujiao Fu, Jialinzi He, Min Zhang, Ge Wang, Kangrun Wang, Hongyu Long, Wenbiao Xiao, Bo Xiao, Lili Long Department of Neurology, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Lili LongDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaTel +86 0731 84328888Fax +86 0731 84327332Email longlili1982@126.comPurpose: Patients with temporal lobe epilepsy (TLE) are at high risk of cognitive impairment. In addition to persistent seizures and antiepileptic drugs (AEDs), genetic factors also play an important role in the progression of cognitive deficits in TLE patients. Defining a cognitive endophenotype for TLE can provide information on the risk of cognitive impairment in patients. This study investigated the cognitive endophenotype of TLE by comparing neuropsychological function between patients with TLE, their unaffected siblings, and healthy control subjects.Patients and Methods: A total of 46 patients with TLE, 26 siblings, and 33 control subjects were recruited. Cognitive function (ie, general cognition, short- and long-term memory, attention, visuospatial and executive functions, and working memory) was assessed with a battery of neuropsychological tests. Differences between groups were evaluated by analysis of covariance, with age and years of education as covariates. The Kruskal–Wallis test was used to evaluate data that did not satisfy the homogeneity of variance assumption. Pairwise comparisons were adjusted by Bonferroni correction, with a significance threshold of P< 0.05.Results: Patients with TLE showed deficits in the information test (P< 0.001), arithmetic test (P=0.003), digit symbol substitution test (P=0.001), block design test (BDT; P=0.005), and backward digit span test (P=0.001) and took a longer time to complete the Hayling test Part A (P=0.011) compared to controls. Left TLE patients tended to have worse executive function test scores than right TLE patients. The siblings of TLE patients showed deficits in the BDT (P=0.006, Bonferroni-corrected) relative to controls.Conclusion: Patients with TLE exhibit cognitive impairment. Executive function is worse in patients with left TLE than in those with right TLE. Siblings show impaired visuospatial function relative to controls. Thus, cognitive deficits in TLE patients have a genetic component and are independent of seizures or AED use.Keywords: temporal lobe epilepsy, cognitive impairment, endophenotype

Understanding how and why species abundance distributions (SADs) vary with sampling scale has been a long-standing issue in ecology. By fitting various SAD models with observations collected in three large forest field plots, the objective of this study is to explore how the shape of SADs and the predictive ability of SAD models vary with sampling scales. Based on a large dataset collected in the Changbaishan, Jiaohe and Liangshui forests in northeastern China, observed SADs were compared with SADs estimated using five different models (log-normal, broken stick, Zipf, niche preemption and neutral model) at four sampling scales (10 × 10 m, 30 × 30 m, 60 × 60 m and 90 × 90 m). The results show that the studied SADs are scale dependent. Niche-based models provided a better fit at small sample sizes, the predictive ability decreasing with increasing sampling scale. The neutral model performed better at large sample sizes, the predictive ability increasing with increasing sampling scale. We identify the models that provided the best fit to observed species abundance distributions across spatial scales, and conclude that there is not one best SAD model for all spatial scales. Future studies should consider the scale effects on the species abundance distribution.

Feiwen Liu,1 Shaozhang Zhou,1,2 Liping Tan,2 Huiqin Jiang,1 Yucong Huang1 1Oncology Medical College, Guangxi Medical University, Nanning City 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, Nanning City 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Shaozhang Zhou; Liping TanDepartment of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, No. 71 Heti Road, Nanning City 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel +86-13977183708; +86-18776404799Fax +86-771-5300613Email zhoushaozhang@gxmu.edu.cn; 988tan@163.comPurpose: Neutrophil-to-lymphocyte ratio (NLR) has been suggested as an independent risk factor for progression-free survival (PFS) and overall survival (OS) in small cell lung cancer (SCLC). However, it is still unknown whether there is a linear relationship between the NLR and the risk of death in SCLC. The objective of this study is to provide further results.Patients and Methods: A retrospective cohort study was performed among a total of 251 participants with SCLC. Smooth curve fitting and piecewise Cox regression model were used to determine the linear relationship between NLR and mortality risk. A multivariable Cox regression model was used to estimate the effects of NLR on OS. Interaction and stratified analyses were conducted according to covariates.Results: The analysis indicated no significant nonlinear relationship or threshold effect between NLR and hazard of death. Multivariate analysis revealed that every unit increase in NLR was associated with a 10% increase in mortality risk. High NLR (> 3.5) at baseline was associated with poor OS (hazard ratio [HR]=1.97, P=0.009). The difference in median OS duration between the high and low NLR groups was statistically significant (9.1 months vs 14.6 months, P=0.0067). Furthermore, interaction analysis identified the chemotherapy regimen to play an interactive role in the association between NLR and hazard of death.Conclusion: NLR was identified as an independent risk factor for OS in SCLC and the linear correlation was observed between them. Administration of etoposide plus cisplatin (EP) regimen in patients with low NLR resulted in better long-term outcome than that of etoposide plus carboplatin (EC) regimen, while administration of the EC regimen conferred longer OS than that of the EP regimen in patients with high NLR.Keywords: neutrophil-to-lymphocyte ratio, NLR, overall survival, small cell lung cancer, SCLC, etoposide plus carboplatin/cisplatin, mortality risk

Reika Miyokawa,1 Celeste Kivler,1 Samuel Louie,1 Dorottya Godor,2 Laren Tan,3 Nicholas Kenyon1,4 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA; 2Northwick Park Hospital London North West University Healthcare NHS Trust Watford Road, London HA1 3UJ, UK; 3Division of Pulmonary & Critical Care Medicine, Department of Internal Medicine, School of Medicine Loma Linda University, Loma Linda, CA 92354, USA; 4VA Northern California Health Care System, Mather, CA 95655, USACorrespondence: Nicholas KenyonDivision of Pulmonary, Critical Care and Sleep Medicine University of California Davis, 4150 V Street, Suite 3400, Sacramento, CA 95816, USATel +1 916-734-3564Email njkenyon@ucdavis.eduAbstract: The increasing use of advanced biologic therapies for patients with severe asthma is transforming the standard of care, clinic workflow, and the clinic business model. Expanded patient access to at-home injection treatment possibilities with some biologics has the potential to improve patient adherence and outcomes. Simultaneously, transition to the home setting can address the escalating costs that limit access for certain patients and healthcare facilities. Such moves come with recognized risks. Garnering input from physicians and other healthcare specialists as well as scrutinizing best practice position statements are vital to implementing truly patient-safe and cost-effective strategies in medicine. Mepolizumab is the first anti-IL-5 inhibitor to receive FDA approval in late 2015. We focus on this injectable medication and discuss the specific indications and contraindications for transitioning patients to at-home injection with mepolizumab. In doing so, we review our recent real-world experiences in the University of California, Davis and Loma Linda University severe asthma clinics, which can provide the foundation for building a comprehensive clinic and home-based biologics asthma program. In addition, we offer insight into the barriers to implementing a successful program and strategies for overcoming them.Keywords: asthma, mepolizumab, home administration, best practice

Xuandi Lai,1 Xinran Geng,2 Lishan Tan,1 Jianqiang Hu,2 Shubin Wang1 1Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, People’s Republic of China; 2Nanobiological Medicine Center, Key Laboratory of Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, People’s Republic of ChinaCorrespondence: Jianqiang HuNanobiological Medicine Center, Key Laboratory of Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, No. 381, Wushan Road, Tianhe District, Guangzhou 510640, People’s Republic of ChinaTel +86-186 6571 1833Email jqhusc@scut.edu.cnShubin WangDepartment of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center, No. 1120, Lianhua Road, Futian District, Shenzhen 518036, People’s Republic of ChinaTel +86-755-83923333Fax +86-755-83061340Email wangshubin2013@163.comBackground: Stimuli-responsive gold nano-assemblies have attracted attention as drug delivery systems in the biomedical field. However, there are challenges achieving targeted delivery and controllable drug release for specific diseases.Materials and Methods: In this study, a glutathione (GSH)-modified fluorescent gold nanoparticle termed AuLA-GSH was prepared and a Co2+-induced self-assembly drug delivery platform termed AuLA-GSH-Co was constructed. Both the pH-responsive character and drug loading behavior of AuLA-GSH-Co were studied in vitro. Kidney-targeting capability was investigated in vitro and in vivo. Finally, the anti-fibrosis efficiency of AuLA-GSH-Co in a mouse model of unilateral ureteral obstruction (UUO) was explored.Results: AuLA-GSH-Co was sensitive to pH changes and released Co2+ in acidic conditions, allowing it to have controllable drug release abilities. AuLA-GSH-Co was found to improve cellular uptake of Co2+ ions compared to CoCl2 in vitro. AuLA-GSH exhibited specific renal targeting and prolonged renal retention time with low non-specific accumulation in vivo. Moreover, the anti-fibrosis efficiency of AuLA-GSH-Co was higher compared to CoCl2 in a mouse model of unilateral ureteral obstruction (UUO).Conclusion: AuLA-GSH-Co could greatly enhance drug delivery efficiency with renal targeting capability and obviously relieve renal fibrosis, providing a promising strategy for renal fibrosis therapy.Keywords: gold nanoparticles, self-assembly, pH sensitivity, drug delivery, renal fibrosis

Jinjie Yu,1,* Yunpeng Dong,1,* Weifeng Tang,2 Huiwen Pan,2 Lu Lv,2 Tao Long,2 Qiang Zhou,2 Junqing Qi,2 Jianchao Liu,2 Guowen Ding,2 Jun Yin,1 Lijie Tan1 1Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Yin; Lijie TanDepartment of Thoracic Surgery, Zhongshan Hospital of Fudan University, No. 180, Fenglin Road, Xuhui District, Shanghai, People’s Republic of ChinaTel +86 13917483128; +86 13681972151Email yin.jun2@zs-hospital.sh.cn; tan.lijie@zs-hospital.sh.cnBackground: The TGF-β signal pathways play a key role in the development and promotion of squamous cell carcinoma (SCC). The pathway is mediated by the SMAD family proteins that include SMAD3 and SMAD6. Our study aimed to evaluate the relationship between single nucleotide polymorphism (SNP) of SMAD3/SMAD6 and susceptibility to esophageal squamous cell carcinoma (ESCC) in the Chinese population.Patients and Methods: This was a hospital-based case–control study compromised of 1043 ESCC patients and 1315 non-cancer patients. Seven SMAD3/SMAD6 (rs8028147, rs3743343, rs3743342, rs8025774, rs8031440, rs803167, and rs34643453) SNPs were selected and used to evaluate their correlation with ESCC susceptibility. Genetic model tests, stratified analyses, linkage disequilibrium analyses, and haplotype analyses were performed in our study.Results: Participants with SMAD3 rs3743342 C>T, rs8025774 C>T, rs8031440 G>A or rs8031627 G>A had a significantly higher risk of ESCC. This was more evident in males, older patients (> 63 years), smokers, and non-alcohol drinking participants. Linkage disequilibrium analyses further revealed that there were strong correlations between SMAD3 rs3743342 C>T, rs8025774 C>T, rs8031440 G>A, and rs8031627 G>A. In the same line, haplotype analyses revealed that SMAD3 ACCCGGSMAD6A and SMAD3AGCCGGSMAD6A were associated with less susceptibility to ESCC while SMAD3ATTTAASMAD6A was associated with a higher risk of ESCC.Conclusion: SNPs of SMAD3 were related to higher susceptibility to ESCC. As such, they may contribute to the development of viable strategies for early diagnosis and treatment of ESCC. However, more detailed association mechanisms between SMAD3/SMAD6 SNPs and ESCC need further experiments to prove.Keywords: SMAD, single nucleotide polymorphism, esophageal squamous cell carcinoma

Ileen Gilbert,1 Keiko Wada,2 Chakkarin Burudpakdee,2 Chirag Ghai,2 Laren Tan3 1AstraZeneca, Wilmington, DE, USA; 2IQVIA, Falls Church, VA, USA; 3Loma Linda University Health, Department of Medicine, Division of Pulmonary, Critical Care, Hyperbaric, Allergy and Sleep Medicine, Loma Linda, CA, USACorrespondence: Ileen Gilbert Email ileen.gilbert@astrazeneca.comPurpose: Budesonide/formoterol pressurized metered-dose inhaler (pMDI) was removed from a Medicare Part D formulary, and patients switched to fluticasone-based dry powder inhaler (DPI) therapies. This study describes the experience, satisfaction, and disease control among patients with asthma or chronic obstructive pulmonary disease (COPD) who switched due to removal from the formulary.Patients and Methods: A patient survey was conducted among adults with asthma or COPD who used budesonide/formoterol pMDI for ≥ 3 months prior to the formulary block and the new medication for ≥ 3 weeks after switching, recruited by providers in a research panel. Survey comprised both validated instruments (PASAPQ, OEQ, ACQ-6, and CAT) and stand-alone questions. Patient characteristics, switch experience, device and treatment satisfaction, onset of effect, and disease control were compared between disease (asthma and COPD) and medication (once and twice daily) cohorts. Minimal significance for group differences: P≤ 0.05.Results: Among 100 patients, 93% received communication from their doctor or nurse about the switch and 73% received training on using the new inhaler. Patients used their new treatment for an average of 7 months prior to completing the survey. Patient satisfaction with the new therapy was high (PASAPQ; mean overall satisfaction: 6.2 for asthma; 6.0 for COPD; P=0.338). However, asthma was not well controlled (ACQ-6) in 62% of patients with asthma, and 56% of patients with COPD reported high/very high impact of their illness on their lives (CAT). Sixty-eight percent and 70% of patients with asthma and COPD, respectively, required reliever medication (≥ 3 puffs) most days during the week prior to the survey. There were no significant differences in disease control (ACQ-6, CAT) between once-daily and twice-daily treatments (P> 0.05 for both asthma and COPD).Conclusion: Even when reporting satisfaction with their new medication, objective measures showed substantial morbidity, regardless of DPI device or dosing regimen.Keywords: asthma, pulmonary disease, chronic obstructive, Medicare Part D, dry powder inhalers, metered dose inhalers, surveys, questionnaires

Liwei Tan,1,* Jiaojiao Zou,1,* Yunhui Zhang,2 Qing Yang,3 Huijing Shi1 1Department of Maternal, Child and Adolescent Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Department of Environmental Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3Department of Child Care, The Maternal and Child Healthcare Institute of Songjiang District, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huijing Shi; Qing Yang Tel +86-21-54237022; +86 021-37621588Fax +86 21-54237022Email hjshi@fudan.edu.cn; yqzjj888@126.comPurpose: To explore the association between maternal physical activity (PA) and sleep quality during pregnancy, and the necessary PA level at different gestational stages to attain improved sleep quality.Methods: A total of 2443 participants were recruited from the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC) study, who had completed questionnaires including the Pittsburgh Sleep Quality Index (PSQI) and the International Physical Activity Questionnaire (IPAQ) at gestational weeks (GW) of 12– 16 and 32– 36. PSQI scores and their seven components at the two GW were compared, as were PSQI scores at 12– 16 and 32– 36 GW and the increment in PSQI relative to PA. Regression analysis was conducted to assess the effect of PA and its change on the total PSQI score at different GW.Results: The mean PSQI scores increased significantly during pregnancy, from 6.30 ± 3.01 at 12– 16 GW to 7.23 ± 3.47 at 32– 36 GW. Compared with women in low PA level, moderate levels of PA at both 12– 16 GW and 32– 36 GW were significantly reduced PSQI scores of 0.42 (95% CI:-0.68,-0.16) and 0.32 (95% CI:-0.63,-0.01), respectively. At 32– 36 GW, high PA level also significantly decreased PSQI score, with a greater decline than moderate PA level. (AOR=− 0.87,95% CI:-1.57,-0.18). PA increment from 12– 16 to 32– 36 weeks of pregnancy created a significant decline of 0.54 in PSQI scores.Conclusion: The study revealed sleep quality was worse at the third trimester and moderate PA level had the potential for improvement of sleep quality both in the first and the third trimester. High PA level was also beneficial to improve sleep quality of pregnant women in the third trimester.Keywords: gestational weeks, pregnancy, sleep quality, physical activity

Yongcang Zhang,1,2,* Lan Liu,2,3,* Cuiting Liang,2 Lingyu Zhou,2 Lixia Tan,2 Yonghua Zong,4 Lili Wu,5 Tonghua Liu4,5 1Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 2Medical College, Tibet University, Lhasa 850000, People’s Republic of China; 3West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 4Tibet Traditional Medicine University, Lhasa 850000, People’s Republic of China; 5Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lili WuKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of ChinaEmail qingniao_566@163.comTonghua LiuTibet Traditional Medicine University, Lhasa 850000, People’s Republic of ChinaKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China Email thliu@vip.163.comBackground: The unique geographical environment at high altitudes may cause a series of diseases, such as acute altitude reaction, cerebral edema, and pulmonary edema. Gymnadenia conopsea (L.) R. Br. has been reported to have an effect on high-altitude hypoxia. However, the molecular mechanism, especially the expression of long noncoding RNAs (lncRNAs), is not yet clear.Methods: The expression profiles of lncRNAs in high-altitude hypoxia-induced brain injury mice treated with Gymnadenia conopsea (L.) R. Br. by using a microarray method.Results: A total of 226 differentially expressed lncRNAs, 126 significantly dysregulated mRNAs and 23 differentially expressed circRNAs were detected (> 2.0-fold, p< 0.05). The expression of selected lncRNAs, mRNAs and circRNAs was validated by qRT-PCR. KEGG analysis showed that the mRNAs coexpressed with lncRNAs were involved in inflammation and hypoxia pathways, including the HIF-1, PI3K-Akt, and NF-kappa B signaling pathways. The lncRNA-TF network analysis results indicated that the lncRNAs were regulated mostly by HMGA2, SRY, GATA4, SOX5, and ZBTB16.Conclusion: This study is the first to report the expression profiles of lncRNAs, mRNAs and circRNAs in mice with high-altitude hypoxia-induced brain injury treated with Gymnadenia conopsea (L.) R. Br. and may improve the understanding of the molecular mechanism of Gymnadenia conopsea (L.) R. Br. in treating high altitude hypoxia-induced brain injury.Keywords: expression profile, noncoding RNAs, high-altitude hypoxia, Gymnadenia conopsea (L.) R. Br

Bailong Hu,1,* Haiyan Zhou,2,* Xiaohua Zou,1 Jing Shi,1 Xingyu Li,1 Li Tan1 1Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang,People’s Republic of China; 2Department of Clinical Research Centre, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bailong Hu Email 375896605@qq.comObjective: To compare the efficacy of dexmedetomidine and midazolam in the prevention of postoperative nausea and vomiting (PONV) caused by hemabate in postpartum hemorrhage during cesarean delivery.Methods: One hundred and five parturients with American Society of Anesthesiology (ASA) physical status I and II, aged 20– 40 years, undergoing elective cesarean delivery under epidural anesthesia were randomly allocated into dexmedetomidine group (group D, n=35), midazolam group (group M, n=35) and control group (group C, n=35). Patients received an intrauterine injection of 250 μg hemabate and continuous intravenous infusion of 5 units oxytocin immediately following the delivery of the infant. At the same time, patients in group D received 1μg/kg intravenous dexmedetomidine, group M received 0.02 mg/kg intravenous midazolam and group C received 20 mL intravenous saline. Parameters such as the PONV, other adverse reactions (chest distress, flush, etc.) caused by hemabate, patient satisfaction, the sedation (OAA/S) scores, and the hemodynamic parameters were recorded in both groups.Results: The PONV incidence in group D and group M was significantly lower compared with group C (6%, 17%, and 71% for group D, group M, and group C, respectively, P< 0.05). The sedation (OAA/S) scores in group D and group M was significantly higher compared with group C (1.62± 0.28, 1.75± 0.31, and 1.00± 0.00 for group D, group M, and group C, respectively, P< 0.05). The patient satisfaction in group D and group M was significantly higher compared with group C (94%, 69%, and 46% for group D, group M, and group C, respectively, P< 0.05). Furthermore, there were more patients satisfied with group D than group M (94% vs.69%, P< 0.05).Conclusion: Intravenous dexmedetomidine (1 μg/kg) and midazolam (0.02 mg/kg) were equally effective in preventing PONV introduced by hemabate and dexmedetomidine is superior to midazolam in patient satisfaction.Keywords: dexmedetomidine, midazolam, PONV, hemabate, cesarean delivery

Yao Cheng,1 Jianhua Liu,2 Qing Liao,1 Xuejiao Hu,1 Hongyan Lv,3 Peiyan Ding,3 Shaofa Nie,1 Li Tan4 1Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Infectious Diseases Prevention and Control, Yichang Centers for Diseases Prevention and Control, Yichang, People’s Republic of China; 3Department of Chronic Disease Prevention and Control, Jiang’an District Centers for Disease Preventive and Control, Wuhan, People’s Republic of China; 4Department of Hospital Infection Management, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Shaofa NieDepartment of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, People’s Republic of ChinaTel +86 130 0719 9772Email sf_nie@mails.tjmu.edu.cn Li TanTongji Hospital of Tongji Medical College 1095 Hangkong Road, Wuhan 430030, People’s Republic of ChinaTel +86 159 9745 1097Email tanlidyx@126.comObjective: Incidence and mortality rates of malignant tumors in China are higher than global averages, especially for gastrointestinal (GI) cancers. To advance understanding of the epidemiology of GI cancers and to seek clues for cancer control, this study compared the incidence, mortality, and survival for GI cancers among residents of Wuhan (central China) and Chinese Americans.Methods: A population-based study of cancer epidemiology was carried out on Wuhan residents and Chinese Americans. Data were collected from the Cancer Registry of Jiang’an District in Wuhan and the Surveillance, Epidemiology, and End Results (SEER) program. Joinpoint regression analyses were used to examine trends in the incidence and mortality of GI cancers in Wuhan. Furthermore, we estimated age-specific rates of incidence and mortality and survival rates of GI cancers in both populations.Results: Among male GI cancer patients, mortality rates exhibited a significant increasing trend during 2006–2016 in Wuhan, with an annual percentage change (APC) of 7.4% (95% CI 1.7%–13.3%). Among female patients, the incidence of GI cancers showed a declining trend (APC –2.3%, 95% CI –3.4% to –1.3%) during 2006–2013, then escalated with an APC of 6.2% (95% CI 2.3%–10.2%) during 2013–2016. Both male and female patients with esophageal cancer in Wuhan experienced better survival than Chinese Americans. However, survival rates for the other three GI cancers in Wuhan were relatively lower than Chinese Americans.Conclusion: Escalating trends were observed in incidence among women and mortality among men with GI cancers. In addition, the survival rates of GI cancer patients in Wuhan were lower than Chinese Americans. As such, additional efforts are needed to control GI cancers in Wuhan, central China.Keywords: mortality, incidence, population-based data, gastrointestinal cancer, China

Luyuan Tan,1,2,* Ya Sun,3,* Liling Zhu,1,2,* Xin Lei,4 Dongya Liang,5 Nanyan Rao,1,2 Fengxi Su,1,2 Kai Chen,1,2 Shunrong Li1,2 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Breast Surgery, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 4State Key Laboratory of Oncology in South China, Guangzhou, People’s Republic of China; 5Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shunrong Li; Kai ChenDepartment of Breast Surgery, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People’s Republic of ChinaTel +86 203 407 0091Email lishr@mail.sysu.edu.cn; Chenkai23@mail.sysu.edu.cnPurpose: Totally implantable venous access devices (TIVADs) are widely used in cancer patients. The main purpose of our study is to observe the incidence and identified risk factors of catheter-related thrombosis (CRT) in breast cancer patients with TIVAD.Patients and methods: We performed a retrospective cohort study of consecutive breast cancer patients who received the ultrasound-guided TIVAD implantation for the administration of chemotherapy from 2013 to 2016. The primary outcome was CRT (both symptomatic and asymptomatic detected by ultrasound). Univariable and multivariable logistic regression analyses were used to identify the risk factors for breast cancer TIVAD-related CRT.Results: A total of 209 breast cancer patients with a newly implanted TIVAD for chemotherapy were included in this study. The average time of port duration was 7 months. Of the enrolled 209 patients, 33 patients (15.8%) had CRT, 2 of the 33 cases were symptomatic (1 pulmonary embolism, 1 deep-venous thrombosis [DVT]), the other 31 cases were asymptomatic detected by routine ultrasound examination of the catheter-associated vein before TIVAD removal with all cycles of chemotherapy completed. In total, 19 (57.6%) of CRT patients underwent directly TIVAD removal without any further treatments, 14 patients received anticoagulation treatments for 3–30 days followed by TIVAD removal. No DVT event was observed within at least 1.5 years of follow-up. In the multiple-variable analysis, tumor size >2 cm (OR 2.735, 95% CI 1.042–7.177; P=0.032), positive HbsAg (OR 2.803 95% CI 1.027–7.856; P=0.047) and low-density lipoprotein (LDL) >3.6 mmol/L (OR 2.360, 95% CI 1.059–5.351; P=0.040) were the significant independent risk factors of breast cancer TIVAD-related CRT.Conclusion: CRT is a common complication in breast cancer patients with TIVAD for chemotherapy. Tumor size, HbsAg status and LDL level were independent predictors of breast cancer for TIVAD-related CRT. Removal of the port without anticoagulation treatments might be a feasible choice for asymptomatic TIVAD-related CRT.Keywords: deep-venous thrombosis, hepatitis B virus, breast cancer, totally implantable venous access devices

Shaojian Lin,* Langping Tan,* Dingyuan Luo,* Xinzhi Peng, Yue Zhu, Honghao Li Department of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Honghao LiDepartment of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 of Yanjiangxi Road, Guangzhou 510120, Guangdong, People’s Republic of ChinaEmail lihonghao63@163.comPurpose: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and its incidence has continuously increased in recent years. Therefore, it is essential to develop more useful therapeutic strategies.Methods: We collected 56 pairs of PTC tissues and adjacent normal tissues and determined the expression patterns of linc01278, miR-376c-3p and DNM3. In addition, we analyzed the relationship between linc01278 expression and pathological information of PTC patients. Furthermore, the effects of linc01278, miR-376c-3p and DNM3 overexpression on proliferation, clonality, apoptosis, migration and invasion of PTC cell lines TPC1 and BCPAP were evaluated. The dual luciferase reporter assay was used to confirm the direct interaction between miR-376c-3p and linc01278.Results: Linc01278 and DNM3 were remarkably down-regulated in PTC tissues and cell lines, whereas miR-376c-3p was significantly up-regulated. In addition, lower linc01278 expression was associated with increased tumor size, lymph node metastasis and higher clinical stage. Linc01278 inhibited cell proliferation of PTC cells by inducing apoptosis, and demonstrated attenuating effects on migration and invasion abilities of PTC cells by regulating the EMT process. More importantly, dual luciferase reporter experiments demonstrated the direct interaction between miR-376c-3p and linc01278, which revealed that DNM3 was a novel target of miR-376c-3p. The miR-376c-3p mimic significantly promoted the proliferation, migration and invasion of PTC cells, and inhibited cell apoptosis. Overexpression of DNM3 abolished the effects of the miR-376c-3p mimic on PTC cells. DNM3 expression was negatively correlated with miR-376c-3p expression, but was positively correlated with linc01278 expression.Conclusion: Overall, we found that linc01278 can act as a competing endogenous RNA (ceRNA) to sponge miR-376c-3p, thereby positively regulating DNM3 expression and ultimately acting as a tumor suppressor gene in PTC progression.Keywords: linc01278, papillary thyroid carcinoma, ceRNA, DNM3

Hong-Fa Xu,1,2,* Tie-Jun Huang,3,* Qin Yang,1 Liang Xu,1 Fen Lin,1 Yan-Hong Lang,1 Hao Hu,4 Li-Xia Peng,1 Dong-Fang Meng,1 Yu-Jie Xie,1 Li Tan,5 Chao-Nan Qian,1 Bi-Jun Huang11Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 2Zhuhai Precision Medical Center, Zhuhai People’s Hospital Affiliated to Jinan University, Zhuhai 519000, People’s Republic of China; 3Department of Nuclear Medicine, The Second People’s Hospital of Shenzhen, Shenzhen 518035, People’s Republic of China; 4Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510060, People’s Republic of China; 5Center of Hematology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, People’s Republic of China*These authors contributed equally to this work Background/Aims: The tumor-suppressive functions of interferon regulatory factor 6 (IRF6) in some tumors have been preliminarily established, but its pathogenesis and underlying molecular mechanisms in breast cancer, the most common malignancy in women, remains poorly understood.Methods: Pairs of typical breast cancer cell lines (high- and low-aggressive) in addition to 27 breast cancer tissue samples and 31 non-cancerous breast tissues were used to investigate the expression level of IRF6 and Lentivirus-mediated gain-of-function studies, short hairpin RNA-mediated loss-of-function studies in vivo and in vitro were used to validate the role of IRF6 in breast cancer. Next, we performed RNA-Seq analysis to identify the molecular mechanisms of IRF6 involved in breast cancer progression.Results: Our findings showed that IRF6 was downregulated in highly invasive breast cancer cell lines but upregulated in poorly aggressive ones. Functional assays revealed that elevated IRF6 expression could suppress cell proliferation and tumorigenicity, and enhanced cellular chemotherapeutic sensitivity. To identify the molecular mechanisms involved, we performed a genome-wide and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis in breast cancer cells using RNA sequencing of gene expression profiles following the overexpression of IRF6. Genome-wide and KEGG analyses showed that IRF6 might mediate the PI3K-regulatory subunit PIK3R2, which in turn modulated the PI3K/AKT pathway to control breast cancer pathogenesis.Conclusion: We provide the first evidence of the involvement of IRF6 in breast cancer pathogenesis, which was found to modulate the PI3K/AKT pathway via mediating PIK3R2; indicating that IRF6 can be targeted as a potential therapeutic treatment of breast cancer.Keywords: breast cancer, IRF6, proliferation, RNA sequencing, PIK3R2, PI3K/AKT

Zhikun Zhang,1 Rong Zhang,2 Peng Qin,3 Liwen Tan4 1Mental Health Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; 2Department of Psychiatry, Staff Hospital of Zhongyuan Oil Field Company, Puyang, Henan, China; 3Department of Psychiatry, Changde Rehabilitation Hospital, Changde, Hunan, China; 4Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China Purpose: This study aimed to investigate cognitive functioning, negative symptoms, and the relationships in schizophrenia (SP) pedigrees and to explore the effect of genetic loading on those endophenotypes.Patients and methods: Forty-four patients with SP, 81 first-degree non-psychotic relatives of patients from simplex and multiplex families, 14 matched control probands, and 29 first-degree relatives of the patients from communities were assessed by the vocabulary subtest (VS) of Wechsler Adult Intelligence Scale, memory span subtests of the Multiple Memory Assessment Scale (MMAS), Wisconsin Card Sorting Test (WCST), Continuous Performance Test (CPT), and Negative Scale of Positive and Negative Syndrome Scale.Results: Compared with controls, patients with SP and their relatives had worse performances in WCST and CPT, and more serious negative symptoms. Patients from multiple families performed poorly on most tests while patients from simplex families had impairments only on the parameters of CPT and WSCT as compared to control probands. Patients from multiple families differed significantly from the patients from simplex families in the digit span and word span of MMAS. After controlling for education, in comparison with relatives of control probands, relatives from multiple families showed impairments in VS, multiple domains of CPT, whereas relatives from simplex families had lower scores on the VS and more total cards and random errors in WSCT. The performances of most tests were linked to negative symptoms in patients with SP. For patients with SP, VS, correct numbers and categories in the WCST, and visual and acoustic errors in the CPT predicted 68.8% of the variability in negative symptoms.Conclusion: Our findings support that cognitive deficits and negative symptoms may be markers of hereditary susceptibility of SP and aggravate as the degree of genetic load increases. There are certain relationships between cognitive deficits and negative symptoms in patients with SP. Keywords: schizophrenia, first-degree relatives, cognitive function, negative symptoms, genetic load

Lunmei Tan,1 Sen Han,2 Shizhen Ding,2 Weiming Xiao,3,4 Yanbing Ding,3 Li Qian,2,4 Chenming Wang,1,5 Weijuan Gong1–5 1Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 2Department of Immunology, School of Medicine, 3Department of Gastroenterology, The Second Clinical Medical College, 4Department of Integrated Chinese and Western Medicine, School of Medicine, 5Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, People’s Republic of China Abstract: Nanoparticles can be loaded with exogenous DNA for the potential expression of cytokines with immune-stimulatory function. NKG2D identifies major histocompatibility complex class I chain-related protein in human and retinoic acid early induced transcript-1 in mouse, which acts as tumor-associated antigens. Biologic agents based on interleukin 21 (IL-21) have displayed antitumor activities through lymphocyte activation. The NKG2D–IL-21 fusion protein theoretically identifies tumor cells through NKG2D moiety and activates T cells through IL-21 moiety. In this study, double-gene fragments that encode the extracellular domains of NKG2D and IL-21 genes were connected and then inserted into the pcDNA3.1(–) plasmid. PcDNA3.1–dsNKG2D–IL-21 plasmid nanoparticles based on chitosan were generated. Tumor cells pretransfected with dsNKG2D–IL-21 gene nanoparticles can activate natural killer (NK) and CD8+ T cells in vitro. Serum IL-21 levels were enhanced in mice intramuscularly injected with the gene nanoparticles. DsNKG2D–IL-21 gene nanoparticles accumulated in tumor tissues after being intravenously injected for ~4–24 h. Treatment of dsNKG2D–IL-21 gene nanoparticles also retarded tumor growth and elongated the life span of tumor-bearing mice by activating NK and T cells in vivo. Thus, the dsNKG2D–IL-21 gene nanoparticles exerted efficient antitumor activities and would be potentially used for tumor therapy. Keywords: NKG2D, IL-21, fusion gene, cancer, chitosan nanoparticle