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Yingying Lin,1,&ast; Yanyan Li,2,&ast; Xinyu Cui,2 Na Zhu,2 Xin Li1 1Department of Center of Integrated Traditional Chinese and Western Medicine, Peking University Ditan Teaching Hospital, Beijing, People’s Republic of China; 2Department of Center of Integrated Traditional Chinese and Western Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Li, Department of Center of Integrated Traditional Chinese and Western Medicine, Peking University Ditan Teaching Hospital, No. 8, Jingshun East Street, Chaoyang District, Beijing, 100015, People’s Republic of China, Tel +86 13910908996, Email leaxin@ccmu.edu.cnPurpose: Hyaluronic acid (HA) is a novel inflammatory biomarker with a prognostic value for several infectious diseases. This study investigated the association of HA with severity and prognosis in hospitalized patients with community-acquired pneumonia (CAP).Patients and Methods: We analyzed the differences of HA levels in different groups. Logistic regression analysis was performed to identify independent risk factors for severe CAP (SCAP). The predictive value of HA for SCAP was assessed using receiver operating characteristic (ROC) curves. Kaplan-Meier survival analysis was used to compare 30-day mortality between the high and low HA groups.Results: Compared to healthy controls (49.2 ± 15.3 ng/mL), patients with CAP exhibited significantly elevated levels of HA (P < 0.001). In CAP patients, increased HA levels were more pronounced in those with SCAP (SCAP vs non-SCAP:135.6 ± 51 ng/mL vs 100.7 ± 47.8 ng/mL, P < 0.001). Compared to survivors (109.9 ± 48.7 ng/mL), HA levels in non-survivors were significantly higher (180.9 ± 67.8 ng/mL) (P < 0.001). HA was an independent predictor of SCAP [odds ratio (OR): 1.013, 95% confidence interval (CI): 1.003– 1.022, P = 0.011] with high diagnostic accuracy [areas under the curve (AUC): 0.709, 95% CI: 0.622– 0.797, P = 0.001]. Additionally, HA was independently associated with death risk in patients with CAP (OR: 1.022, 95% CI: 1.005– 1.039, P = 0.010). Kaplan-Meier survival curves indicated that CAP patients in the high HA group exhibit a higher 30-day mortality rate compared to those in the low HA group (8.6% vs 1.5%, P = 0.008). Post hoc analysis indicated that our study possessed 98.857% statistical power.Conclusion: In conclusion, High HA levels are associated with severity and mortality in patients with CAP, and HA could serve as a novel serum biomarker to predict the risk of CAP progression.Keywords: hyaluronic acid, community-acquired pneumonia, severity, prognosis, biomarker

Jimei Li,&ast; Yulin Xiong,&ast; Shengyan Li, Qiong Ye, Yan Han, Xiuxin Zhang, Tongxiu Zhao, Yuan Yang, Xiaoshan Cui, Yinglan Li General Medicine Department, Qinghai Provincial People’s Hospital, Xining, Qinghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinglan Li, General Medicine Department, Qinghai Provincial People’s Hospital, Gonghe Road 2, Xining, Qinghai, People’s Republic of China, Tel +8613997233103, Email qhlyl@126.comPurpose: This study aimed to establish the prevalence of pulmonary embolism (PE) in chronic obstructive pulmonary disease (COPD) patients with secondary polycythemia (SP) and explore the risk factors for PE in COPD patients with SP.Patients and Methods: We analyzed the prevalence of PE among COPD patients with SP who were hospitalized at Qinghai Provincial People’s Hospital between January 2015 and December 2020. From January 2021 to January 2024, we enrolled patients into three groups (COPD+SP+PE, COPD+SP, and control) and performed laboratory measurements, biomarkers, echocardiography, and pulmonary function tests. Patients in the COPD+SP group received clinical treatment, and biomarkers were measured again seven days after treatment.Results: The prevalence of PE in patients with COPD SP was 5.21%. We found that COPD+SP+PE group had significantly higher levels of erythrocyte distribution width (RDW), platelet volume distribution width (PDW), mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), monocyte to large platelet ratio (MLPR), 5-hydroxytryptamine (5-HT), activated protein C (APC), urokinase-type plasminogen activator (u-PA), thrombomodulin (TM), interleukin-38 (IL-38), tissue factor (TF), and fractalkine (FKN) in contrast to COPD+SP group. Biomarkers, such as FKN, β-thromboglobulin (β-TG), APC, u-PA, TM, TF, and IL-38, were risk factors for COPD patients with SP who are complicated by PE. Clinical treatment significantly reduced the levels of β-TG, IL-38, APC, endothelin-1 (ET-1), u-PA, FKN, TM, 5-HT, and neutrophil extracellular traps (NETs) in patients with COPD+SP.Conclusion: PE incidence was significantly higher in patients with COPD and SP. In COPD patients with SP, routine joint detection of blood and cardiac markers, blood gas analysis, and pulmonary function tests can help to identify patients with PE. APC, u-PA, TF, FKN, TM, and IL-38 are risk factors for PE in patients with COPD and SP, and clinical treatment can effectively reduce this risk.Keywords: chronic obstructive pulmonary diseases, secondary polycythemia, pulmonary embolism, biomarker, risk factors

Xudong Cui,1,&ast; Tiewei Li,2,&ast; Jingping Yang,3 Xiaojuan Li,2 Pengfei Xuan,3 Hongyan Wang3 1Respiratory and Critical Care Medicine Department, Inner Mongolia Baogang Hospital, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 2Department of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, People’s Republic of China; 3Respiratory and Critical Care Medicine Department, Inner Mongolia Baogang Hospital, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tiewei Li; Jingping Yang, Email litieweind@163.com; yangron@sina.comBackground: Previous studies have demonstrated that neutrophil extracellular traps (NETs) are crucial in infectious diseases. This study aims to evaluate the clinical value of NET-related biomarkers in identifying the risk of COVID-19 and diagnosing the disease.Methods: This study involved 32 patients who tested positive for COVID-19 via polymerase chain reaction (PCR) between April and August 2023. During the same period, 30 healthy volunteers were enrolled as a control group. The principal biomarkers related to NETs are citrullinated histone H3 (CitH3), double-stranded DNA (dsDNA), myeloperoxidase-DNA complex (MPO-DNA), and Nucleosome. Elevated levels in two or more of these biomarkers indicate raised NET concentrations. Multivariable logistic regression analysis was employed to assess whether NET-related biomarkers were the independent risk factor of COVID-19. The diagnostic value of NET-related biomarkers in COVID-19 was further evaluated using receiver operating characteristic (ROC) curve analysis. Statistical procedures were executed in SPSS software (version 24.0, USA).Results: Compared with the control group, patients infected with COVID-19 had higher levels of dsDNA and nucleosomes (P < 0.001). Correlation analysis revealed a positive correlation between dsDNA levels and neutrophil count (r = 0.309, P = 0.015) as well as between nucleosome levels and neutrophil count (r = 0.446, P < 0.001). Further analysis showed that dsDNA and nucleosomes were independent risk factors for COVID-19 infection. ROC curve analysis showed that dsDNA area under the curve (AUC) = 0.777, 95% confidence interval (CI), 0.661– 0.893, P < 0.001, and nucleosomes (AUC = 0.884, 95% CI, 0.778– 0.991, P < 0.001) had well diagnostic value in the diagnosing COVID-19 infection.Conclusion: NET-related biomarkers, dsDNA and nucleosomes, were independent risk factors of COVID-19 infection and potentially useful biomarkers in diagnosing COVID-19 infection in older patients.Keywords: neutrophil extracellular traps, COVID-19, pneumonia, dsDNA, nucleosomes, older patient

Yang Chao,1 Xiya Jin,1 Rui Guo,2 Hongyu Zhang,2 Xueling Cui,3 Yan Qi2 1Department of Gastroendoscopy, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, People’s Republic of China; 3Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yan Qi; Xueling Cui, Email qiyan@jlu.edu.cn; cxl@jlu.edu.cnBackground: Chronic atrophic gastritis (CAG) is a severe condition characterized by inflammation and loss of appropriate mucosal glands in the stomach. The underlying mechanisms of CAG development remain unclear. Exploring immune-related circular RNAs (circRNAs) could provide insights for potential diagnostic and therapeutic strategies.Methods: Samples from 40 patients with CAG and non-CAG (CNAG) underwent high-throughput sequencing, and EdgeR analysis identified differentially expressed circRNAs and mRNAs. Gene Ontology (GO) analysis elucidated biological functions, while Immune Cell Abundance Identifier (ImmuCellAI) estimated immune cell abundance. Flow cytometry analyzed immune cell infiltration. Weighted gene co-expression network analysis (WGCNA) identified hub genes related to the immune response in CAG. CircRNA-mRNA networks were constructed, and qRT-PCR validated findings.Results: A total of 163 differentially expressed immune-related genes (DEIRGs) were identified between CAG and CNAG. The upregulated immune-related mRNAs in CAG were significantly enriched in antimicrobial humoral response, viral entry into host cells, neutrophil activation, and leukocyte migration. Conversely, downregulated immune-related mRNAs were linked to regulation of natural killer cell-mediated cytotoxicity, positive regulation of adaptive immune response, antigen receptor-mediated signaling pathway, and B cell activation. Immune Cell Abundance Identifier (ImmuCellAI) and flow cytometry confirmed increased neutrophil infiltration in CAG compared to CNAG. WGCNA identified 56 hub immune-related genes. Additionally, circRNA expression profiles in CNAG and CAG were explored, with 19 upregulated and 23 downregulated circRNAs identified in CAG. The upregulated circRNAs were associated with biological processes like carnitine metabolic process and regulation of B cell receptor signaling pathway. A circRNA-mRNA co-expression network was constructed based on five circRNAs highly related to hub immune-related genes. Furthermore, the expression of eight immune-related mRNAs and five circRNAs were validated in CAG.Conclusion: This study is the first systematic analysis of circRNA profiles in CAG and provide important insights for potential immunotherapeutic strategies and early diagnostic biomarkers in CAG treatment.Keywords: chronic atrophic gastritis, circRNAs, immune-related genes, immune cell infiltration

Xin Wang,1,&ast; Xuerong Cui,2,&ast; Huaping Fan,3 Tianyang Hu4 1Department of Respiratory and Critical Care Medicine, Deyang People’s Hospital, Deyang, Sichuan, 618099, People’s Republic of China; 2Department of Respiratory Medicine, People’s Hospital of Shizhu Tujia Autonomous County, Chongqing, 409199, People’s Republic of China; 3Department of Cardiology, 63650 Military Hospital, Urumqi, Xinjiang, 841700, People’s Republic of China; 4Precision Medicine Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaping Fan, Email doctfhp@163.com; Tianyang Hu, Email hutianyang@stu.cqmu.edu.cnPurpose: The triglyceride-glucose (TyG) index is a surrogate biomarker of insulin resistance which has been widely used in intensive care unit (ICU) to predict prognosis. However, its role in critically ill acute exacerbation of COPD (AECOPD) patients remains largely unknown.Material and methods: A total of 645 AECOPD patients were induced in this retrospective cohort study, which extracted data from the eICU Collaborative Research Database (eICU-CRD). The TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). The primary endpoint includes in-hospital mortality and ICU mortality. The secondary endpoint was sepsis, acute kidney injury (AKI), and acute respiratory failure (ARF).Results: Multivariable Cox regression analysis revealed that the TyG index was independently associated with an increased risk of in-hospital mortality (hazard ratio, HR: 1.45, 95% CI: 1.04– 2.01, P = 0.028) and ICU mortality (HR: 2.13, 95% CI: 1.28– 3.54, P = 0.004). Moreover, the TyG index was independently associated with an increased risk of sepsis (odds ratio, OR: 1.54, 95% CI: 1.24– 1.93, P < 0.001), AKI (OR: 1.57, 95% CI: 1.26– 2.02, P < 0.001) and ARF (OR: 1.50, 95% CI: 1.20– 1.87, P < 0.001). Kaplan–Meier survival analysis revealed that higher TyG indexes were also related to increased in-hospital mortality and ICU mortality. In addition, the restricted cubic splines regression model demonstrated that the in-hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.897, P for non-linearity = 0.897, respectively).Conclusion: Elevated TyG index was independently associated with an increased risk of poor clinical outcomes in critically ill AECOPD patients. A prospective study to define TyG as a biomarker for prognosis prediction in critically ill AECOPD patients is warranted.Keywords: triglyceride-glucose index, AECOPD, mortality, eICU-CRD database

Ziyi Zhang,1 Dingdan Zhang,1 Qing Lin,2 Xiang Cui1 1Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China; 2Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, 21287, USACorrespondence: Qing Lin, Department of Anesthesiology & Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, 21287, USA, Tel +1-4432072315, Email qlin2@jhmi.edu Xiang Cui, Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China, Tel + 86-10-64089422, Email drcuixiang@163.comAbstract: Recent studies have highlighted the immunomodulatory effects of acupuncture on sepsis and proposed novel non-pharmacological or bioelectronic approaches to managing inflammatory illnesses. Establishing rules for selectively activating sympathetic or vagal nerve-mediated anti-inflammatory pathways using acupuncture has valuable clinical applications. Over the years, studies have revealed the segmental modulatory role of acupuncture in regulating visceral function by targeting the autonomic nervous system (ANS). In this review, we aim to summarize recent findings on acupuncture in treating sepsis, focusing on the underlying ANS mechanism, as well as the rules of acupoint specificity, intensity, frequency, and other parameters utilized in these studies. Mechanistically, the immunomodulatory properties of the sympathetic nervous system have been highlighted. Furthermore, we explore the immunotherapeutic benefits of acupuncture in treating sepsis. A better understanding of the immunoregulatory mechanism of sympathetic nervous system may offer novel approaches for the development of therapeutics to treat or prevent a variety of inflammatory diseases.Keywords: inflammation, peripheral nerve stimulation, sympathetic nervous system, sympathoadrenal axis, macrophage, bioelectronic medicine

Xiaomei Cui,1,2 Ting Zhang,2 Tao Xie,2 Fang-xi Guo,2 Yu-ying Zhang,2 Yuan-jia Deng,2 Qi Wang,1,2 Yi-xing Guo,1,2 Ming-hua Dong,1,2 Xiao-ting Luo1,3 1Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 2School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of General Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Xiao-ting Luo, Golden Campus of Gannan Medical University, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Tel +86 13677975578, Email xtluo76@163.comAbstract: Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut–brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations. Keywords: blood pressure, metabolites, gut-brain, treatment

Xin Yang,1 Xiaoguang Cui,1 Xiao Yang,2 Bincheng Ren,1 Xiaojing Cheng,1 Xinrui Zhao,1 Shanshan Liu,1 Tian Tian,1 Hui Zhao,1 Li Qu,1 Xueyi Li1 1Department of Rheumatology, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of China; 2Scientific Research Center and Precision Medical Institute, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of ChinaCorrespondence: Xueyi Li, Department of Rheumatology, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of China, Tel +86 13992891987, Fax +86 02987679832, Email li-xueyi@139.comPurpose: This study aimed to assess liver involvement and investigate its correlation with rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 positive) DM patients.Patients and Methods: This retrospective study included 159 patients diagnosed with anti-MDA5 positive DM or anti-synthetase syndrome (ASyS). Clinical features and laboratory findings were compared between patients with anti-MDA5 positive DM and patients with ASyS. In the anti-MDA5 positive DM cohort, clinical features and laboratory findings between patients with liver involvement and without liver involvement were further compared. The effects of liver involvement on the overall survival (OS) and development of RP-ILD were also analyzed using Kaplan–Meier method and Cox regression analysis.Results: Levels of serum aspartate aminotransferase (AST), alanine transaminase (ALT), γ-glutamyl transferase (γGT) and alkaline phosphatase (ALP) were all significantly higher in patients with anti-MDA5 positive DM than those in patients with ASyS. In our cohort of anti-MDA5 positive DM patents, 31 patients (34.4%) were complicated with liver involvement. Survival analysis revealed that serum ferritin > 1030.0 ng/mL (p< 0.001), ALT > 103.0 U/l (p< 0.001), AST > 49.0 U/l (p< 0.001), γGT > 82.0 U/l (p< 0.001), ALP > 133.0 U/l (p< 0.001), lactate dehydrogenase (LDH)> 474.0 U/l (p< 0.001), plasma albumin (ALB) < 35.7 g/l (p< 0.001) and direct bilirubin (DBIL) > 2.80 μmol/l (p=0.002) predicted poor prognosis. The incidence of RP-ILD increased remarkably in patients with liver involvement compared to patients without liver involvement (58.1% vs 22.0%, p=0.001). Multivariate analysis revealed that elevated serum ALT level was an independent risk factor for mortality (HR 6.0, 95% CI 2.3, 16.2, p< 0.001) and RP-ILD (HR 5.9, 95% CI 2.2, 15.9, p< 0.001) in anti-MDA5 positive DM patents.Conclusion: Liver involvement is common in patients with anti-MDA5 positive DM. Elevated serum ALT level was an independent risk factor for RP-ILD and mortality in patients with anti-MDA5 positive DM.Keywords: anti-melanoma differentiation-associated gene 5 antibody, liver involvement, ferritin, macrophage, interstitial lung disease, dermatomyositis

Kang Liu, Xiaochun Liu, Tao Cao, Xianmei Cui, Pengyu Sun, Liang Zhang, Xiaoqin Wu Department of Obstetrics and Gynecology, Shanxi Bethune Hospital & Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, 030032, People’s Republic of ChinaCorrespondence: Xiaoqin Wu, Department of Obstetrics and Gynecology, Shanxi Bethune Hospital & Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital affiliated to Shanxi Medical University, Taiyuan, 030032, People’s Republic of China, Email liukang1212@sxmu.edu.cnObjective: This study explores the causal relationship between endometriosis and pelvic inflammatory diseases (PID).Methods: The study utilized genome-wide association study (GWAS) datasets for endometriosis (“finn-b-N14_ENDOMETRIOSIS“) and PID (”finn-b-N14_OTHFEMPELINF”). Subsequently, two-sample Mendelian randomization (MR) analyses were conducted using inverse variance weighting (IVW), Egger regression (MR-Egger), and weighted median (WM) methods. Heterogeneity was evaluated using Cochran’s Q test, and in case of detected outliers, they were removed for re-evaluation of MR causality.Results: From the endometriosis GWAS dataset, 33 single nucleotide polymorphisms (SNPs) were selected as instrumental variables. All three methods, IVW (OR = 1.39, P < 1× 10− 8), MR-Egger (OR = 1.41, P = 0.003), and WM (OR = 1.37, P = 1.16× 10− 5) confirmed a causal relationship between endometriosis and PID. The association between endometriosis and pelvic inflammation remained unaffected by the exclusion of individual SNPs. Lastly, Cochran’s Q test and funnel plots showed no evidence of SNP asymmetry.Conclusion: The results of the MR analysis support a potential causal relationship between endometriosis and an increased risk of PID.Keywords: endometriosis, pelvic inflammatory diseases, genome-wide association study, Mendelian randomization

Chang Su,1– 3 Zeyu Wang,4 Zhen Qin,1– 3 Yan Lv,1– 3 Yachen Hou,1– 3 Ge Zhang,1– 3 Mengdie Cheng,1– 3 Xinyue Cui,1– 3 Zhiyu Liu,1– 3 Pengchong Du,1– 3 Tianding Liu,1– 3 Peiyu Yuan,1– 3 Junnan Tang,1– 3 Jinying Zhang1– 3 1Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, People’s Republic of China; 3Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Junnan Tang; Jinying Zhang, Department of Cardiology, First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 15890696166 ; +86 13503830283, Email fcctangjn@zzu.edu.cn; jyzhang@zzu.edu.cnBackground: The triglyceride-glucose (TYG) index is a novel and reliable marker reflecting insulin resistance. Its predictive ability for cardiovascular disease onset and prognosis has been confirmed. However, for advanced chronic heart failure (acHF) patients, the prognostic value of TYG is challenged due to the often accompanying renal dysfunction (RD). Therefore, this study focuses on patients with aHF accompanied by RD to investigate the predictive value of the TYG index for their prognosis.Methods and Results: 717 acHF with RD patients were included. The acHF diagnosis was based on the 2021 ESC criteria for acHF. RD was defined as the eGFR < 90 mL/(min/1.73 m2). Patients were divided into two groups based on their TYG index values. The primary endpoint was major adverse cardiovascular events (MACEs), and the secondary endpoints is all-cause mortality (ACM). The follow-up duration was 21.58 (17.98– 25.39) months. The optimal cutoff values for predicting MACEs and ACM were determined using ROC curves. Hazard factors for MACEs and ACM were revealed through univariate and multivariate COX regression analyses. According to the univariate COX regression analysis, high TyG index was identified as a risk factor for MACEs (hazard ratio = 5.198; 95% confidence interval [CI], 3.702– 7.298; P < 0.001) and ACM (hazard ratio = 4.461; 95% CI, 2.962– 6.718; P < 0.001). The multivariate COX regression analysis showed that patients in the high TyG group experienced 440.2% MACEs risk increase (95% CI, 3.771– 7.739; P < 0.001) and 406.2% ACM risk increase (95% CI, 3.268– 7.839; P < 0.001). Kaplan-Meier survival analysis revealed that patients with high TyG index levels had an elevated risk of experiencing MACEs and ACM within 30 months.Conclusion: This study found that patients with high TYG index had an increased risk of MACEs and ACM, and the TYG index can serve as an independent predictor for prognosis.Keywords: TyG index, advanced chronic heart failure, renal dysfunction, prognosis factor

Mingxing Guo,1,&ast; Chen Pan,1,&ast; Ying Zhao,1 Wanyi Xu,1 Ye Xu,1 Dandan Li,1 Yichen Zhu,2 Xiangli Cui1 1Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangli Cui, Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China, Email xianglicui@ccmu.edu.cn Yichen Zhu, Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China, Email yczhu@ccmu.edu.cnBackground: The risk of transplant recipient infection is unknown when the preservation solution culture is positive.Methods: We developed a prediction model to evaluate the infection in kidney transplant recipients within microbial contaminated preservation solution. Univariate logistic regression was utilized to identify risk factors for infection. Both stepwise selection with Akaike information criterion (AIC) was used to identify variables for multivariate logistic regression. Selected variables were incorporated in the nomograms to predict the probability of infection for kidney transplant recipients with microbial contaminated preservation solution.Results: Age, preoperative creatinine, ESKAPE, PCT, hemofiltration, and sirolimus had a strongest association with infection risk, and a nomogram was established with an AUC value of 0.72 (95% confidence interval, 0.64– 0.80) and Brier index 0.20 (95% confidence interval, 0.18– 0.23). Finally, we found that when the infection probability was between 20% and 80%, the model oriented antibiotic strategy should have higher net benefits than the default strategy using decision curve analysis.Conclusion: Our study developed and validated a risk prediction model for evaluating the infection of microbial contaminated preservation solutions in kidney transplant recipients and demonstrated good net benefits when the total infection probability was between 20% and 80%.Keywords: risk prediction model, kidney transplant, nomogram, risk factors

Hongyi Zhou,1,&ast; Xueping Cui,2,&ast; Leilei Zhu,1 Zhuoqun Xu,1 Zhuo Wang,3 Jianfeng Shao4 1Department of Urology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, 214023, People’s Republic of China; 2Department of Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui, Zhejiang Province, 323000, People’s Republic of China; 3Department of Geriatrics, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, 214023, People’s Republic of China; 4Department of Urology, Wuxi No. 2 People’s Hospital (Jiangnan University Medical Center), Wuxi, Jiangsu Province, 214023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Shao; Zhuo Wang, Email jianfenguro@163.com; wangzhuoausten@163.comBackground: Circular RNA PVT1 (circPVT1) is aberrantly expressed in several cancers, but its functional role and clinical relevance in bladder urothelial carcinoma (BLCA) remain unknown. This study aimed to identify the expression level of circPVT1 in BLCA and investigated its functional relevance with BLCA progression both in vitro and in vivo.Methods: GEPIA, UALCAN, and OncoLnc were referred to presented data. Quantitative real-time PCR (qPCR) was used for the measurement of transnational expression of genes in BLCA specimens and cell lines. Immunohistochemistry (IHC) and fluorescence in situ hybridization analysis (FISH) assays were performed to detect HER2 amplification, Pearson’s correlation analysis to analyze the correlation between circPVT1 expression and clinical characteristics, Cox regression and K-M survival analyses to analyze prognostic factors. A nomogram was constructed for predicting prognosis. The proliferation of cells was measured by CCK-8 and colony formation assay, and the proliferation in vivo was evaluated using nude mouse models. qPCR was used to detect the expression of proliferation-related genes.Results: circPVT1 was but mRNA PVT1 was not significantly overexpressed in BLCA. A high circPVT1 expression was associated with a better survival and negative HER2, but not with age, gender, and T stage. circPVT1 was an independent prognostic factor for the overall survival of BLCA patients. Knocking down circPVT1 promoted BLCA proliferation in vitro and in vivo. Knocking down circPVT1 upregulated ERBB2, MKI67, and PCNA expression and downregulated TP53 expression, but exerted no influence on CCND1 and CCNB1 expression.Conclusion: circPVT1 is a tumor suppressor and novel prognostic biomarker for BLCA.Keywords: circPVT1, bladder cancer, biomarker, proliferation, HER2 amplification, BLCA

Ye Ren,1,&ast; Xiaochuan Cui,2,&ast; Xiaowen Zhu,1 Hua Guo,2 Qunyan Zhou,3 Peng Yuan,4 Haiyan Cheng,1 Wenjun Wu1 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Sleep Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Nutrition Department, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 4Department of Rehabilitation, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Wu, Department of Endocrinology, Wuxi People’s Hospital, No. 299, Qingyang Road, Wuxi, 214023, People’s Republic of China, Tel +86-15358008856, Email wuwenjung@163.comPurpose: The present study aimed to evaluate the efficiency of traditional anthropometric and body composition parameters in predicting apnea hypopnea index (AHI) change after weight loss.Patients and Methods: Chinese adults with overweight and obesity were included into this study containing two parts. A cross-sectional study was conducted in 137 individuals using the baseline data from two weight loss intervention trials. The second part was the weight-loss intervention study conducted in 60 overweight and obese patients with obstructive sleep apnea (OSA). All participants underwent physical examination, bioelectrical impedance analysis and overnight polysomnography. Multivariate linear regression models were used to identify the most accurate parameters to predict AHI and the mediation analysis to evaluate the mediators between weight loss and AHI reduction.Results: Waist circumference (WC), body mass index and fat mass were positively associated with AHI after adjusting multiple collinearities in the cross-sectional study. After weight-loss intervention, body weight decreased from 94.6 ± 15.3 to 88.0 ± 13.9 kg, and AHI decreased from 41.9 (13.0,66.9) to 20.7 (8.7,51.2) events/h. Among these parameters, only percentage changes in WC and AHI across the intervention were positively intercorrelated after controlling for covariates (adjusted r = 0.271, P = 0.041). The mediation analysis supported WC as a mediator between weight loss and AHI reduction (standardized indirect effect [95% CI] = 4.272[0.936,7.999]).Conclusion: Both general and abdominal obesity are of high prognostic value for OSA. WC as an easily accessible parameter mediates the effects of weight loss in decreasing OSA severity.Plain Language Summary: Current Knowledge: Obesity is a well-recognized risk factor for the development of obstructive sleep apnea (OSA), whereas weight loss has been written into the treatment guidelines for overweight and obese patients with OSA. However, the anthropometric parameters more related to OSA have not been fully clarified, and an easily acquired index is needed to predict the effect of weight loss on apnea hypopnea index (AHI) improvement.Study Impact: This study found that both general obesity and abdominal obesity were positively associated with AHI, and waist circumference mediated the effect of weight loss in improving AHI. These results provide an easily acquired index to monitor the effect of weight loss on OSA.Keywords: obesity, obstructive sleep apnea, weight loss, waist circumference, body composition

Yuxia Zhang,1 Xiaobing Lu,1 Xianping Wang,1 Xueqing Wu,1 Xuan Jing,2 Xiangrong Cui1 1Reproductive Medicine Center, the Affiliated Children’s Hospital of Shanxi Medical University, Children’s Hospital of Shanxi, Shanxi Maternal and Child Health Hospital, Taiyuan, 030001, People’s Republic of China; 2Clinical Laboratory, Shanxi Provincial People’s Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, 030001, People’s Republic of ChinaCorrespondence: Xiangrong Cui; Xuan Jing, Email cuixiangrong094030@163.com; jx05070103@163.comBackground: Unilateral twin ectopic pregnancy is extremely rare in natural pregnancy, with an incidence rate of only 1 in 200,000– 2,500,000, represents a major health risk for reproductive-aged women, leading to even life-threatening complications. There is a lack of data on the prevalence of this rare disease after in-vitro fertilization-embryo transfer (IVF-ET) cycles.Case Report: We present a case of a 51-year-old woman with rare unilateral twin ectopic pregnancy after frozen embryo transfer treated with bilateral salpingectomy, followed by a review of the literature.Conclusion: Twin ectopic pregnancy is a very rare type of pregnancy that requires a high index of suspicion to diagnose and treat early to prevent complications and maternal death.Keywords: twin ectopic, pregnancy, unilateral, rare condition, assisted reproductive technology

Hongwei Wang,1 Fangying Tian,2 Xueyu Wang,3 Ming Zhao,1 Ruiqin Gao,1 Xinyu Cui1 1Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Infection Management Department of the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Infectious Diseases, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Fangying Tian, Department of Hospital Infection Management, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan, Shanxi, People’s Republic of China, Tel/Fax +86-0351-3365612, Email tfy8048@163.comBackground: Healthcare-associated infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are now a global public health problem, increasing the burden of disease and public healthcare expenditures in various countries. The aim of this study was to analyse the risk factors for CRKP infections and to develop nomogram models to help clinicians predict CRKP infections at an early stage to facilitate diagnosis and treatment.Methods: The clinical data of patients with Klebsiella pneumoniae (KP) infections in our hospital from January 2018 to January 2023 were collected. 174 patients with CRKP infections and 219 patients with CSKP infections were selected for case-control study. 27 predictors related to CRKP infections were determined. The least absolute shrinkage and selection operator (Lasso) regression was used to screen the characteristic variables, Multivariate logistic regression analysis was performed on the selected variables and a nomogram model was established. The discrimination and calibration of the nomogram model were evaluated by receiver operator curves (ROC) and calibration curves.Results: Six predictive factors of ICU stay, fever time, central venous catheterization time, catheter indwelling time, carbapenem use and tetracycline use screened by lasso regression were included in the logistic regression model, and the nomogram was drawn to visualize the results. The area under ROC curve of training set and validation set was 0.894 (95% CI: 0.857, 0.931) and 0.872 (95% CI: 0.805, 0.939); The results of decision curve analysis also show that the model has good prediction accuracy.Conclusion: This study established a nomogram to predict CRKP infection based on lasso-logistic regression model, which has certain guiding significance for early diagnosis of CRKP infections.Keywords: carbapenem resistance, Klebsiella pneumoniae, risk factors, nomogram model

Xiaozhen Cui,1 Zhi Cheng,2 Han Li,2 Xiaobao Zhang,2 Hengfei Luan,2 Zhibin Zhao,2 Pin Zhu2 1Department of Anesthesiology, Graduate Training Base of Lianyungang First People’s Hospital of Jinzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Pin Zhu, The First People’s Hospital of Lianyungang, No. 6 East Zhenhua Road, Lianyungang, Jiangsu, People’s Republic of China, Email zhupin198348@163.comBackground: Remimazolam is a novel benzodiazepine narcotic. When used for gastrointestinal endoscopy or bronchoscopy, it provides adequate sedation and rapid recovery. However, studies on the optimal initial loading dose of remimazolam remain inadequate. Therefore, we conducted a randomized controlled clinical trial to investigate the efficacy and safety of different doses of remimazolam applied in upper gastrointestinal endoscopy.Methods: A total of 218 patients scheduled for upper gastrointestinal endoscopy were included in our trial and divided into experimental and control groups: the experimental groups were the remimazolam groups (R1 of 0.2 mg/kg, R2 of 0.3 mg/kg, and R3 of 0.4 mg/kg), and the control group was the propofol group. Following a single injection of trial drugs during the induction period, operational requirements were evaluated based on MOAA/S scores. When the sedation was successfully achieved, safety was evaluated based on the incidence of various intraoperative and postoperative adverse events.Results: The success rates of intraoperative sedation were 82% in group R1, 98% in group R2, 96% in group R3, and 100% in group P. The incidence of hypotension was lower in the remimazolam groups than in the propofol group (16%), 4% in group R1, 6% in group R2, and 6% in group R3. The incidence of postoperative vertigo was significantly higher, and sedation recovery time was prolonged in high-concentration remimazolam group.Conclusion: Satisfactory efficacy can be obtained with higher concentrations of remimazolam tosilate in patients undergoing upper gastrointestinal endoscopy with ASA grade I or II. However, as the dose is progressively increased, the incidence of adverse reactions by remimazolam tosilate are also significantly increased, such as vertigo and prolonged sedation recovery time.Trial Registration: The trial was registered prior to enrollment at the Chinese Clinical Trial Registry (ChiCTR 2000032067).Keywords: remimazolam, sedation, hypotension, hypoxemia, upper gastrointestinal endoscopy

Xiang Cui,1 Ziyi Zhang,1,2 Hanqing Xi,1 Kun Liu,1 Bing Zhu,1 Xinyan Gao1 1Department of Physiology, Institute of Acupuncture and Moxibustion, Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China; 2College of Acupuncture and Tuina, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, People’s Republic of ChinaCorrespondence: Xiang Cui; Xinyan Gao, Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China, Tel +86-10-64089422 ; +86-10-64089420, Email drcuixiang@163.com; xinyangao2001@msn.comAbstract: A series of studies have demonstrated acupoint sensitization, in which acupoints can be activated in combination with sensory hypersensitivity and functional plasticity during visceral disorders. However, the mechanisms of acupoint sensitization remain unclear. Neuroanatomy evidence showed nociceptors innervated in acupoints contribute to the mechanism of acupoint sensitization. Increasing studies suggested sympathetic nerve plays a key role in modulating sensory transmission by sprouting or coupling with sensory neuron/nociceptor in the peripheral, forming the functional structure of the sympathetic-sensory coupling. Notably, the sensory inputs of the disease-induced sensitized acupoint contribute to the homeostatic regulation and also involve in delivering therapeutic information under acupuncture, hence, the role of sprouted sympathetic in acupoint function should be given attention. We herein reviewed the current knowledge of sympathetic and its sprouting in pain modulation, then discussed and highlighted the potential value of sympathetic-sensory coupling in acupoint functional plasticity.Keywords: referred pain, hyperalgesia, acupuncture, nociceptor, Somato-sympathetic-viscera reflex

Xuran Cui,1– 3 Xiaolong Xu,1– 3 Yahui Hu,1,3 Rui Li,1,3 Qingquan Liu1– 3 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 2Beijing Institute of Chinese Medicine, Beijing, 100010, People’s Republic of China; 3Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, 100010, People’s Republic of ChinaCorrespondence: Qingquan Liu, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Gallery Backstreet No.23, Dongcheng District, Beijing, 100010, People’s Republic of China, Tel +8613910055687, Email liuqingquan_2003@126.comBackground: Qiguiyin decoction (QGYD) was a traditional Chinese medicine (TCM) used to treat Pseudomonas aeruginosa infection in China. This study investigated the therapeutic effect and the potential mechanism of QGYD on carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection.Materials and Methods: Pulmonary infections were induced in mice by CRPA. The therapeutic effect of QGYD was evaluated by lung index and pulmonary pathology. The potential effects of QGYD on intestinal flora were detected by gut microbiome. The overall metabolism regulation of QGYD in blood was investigated by metabonomics. Next, the correlation between intestinal flora and metabolites was analyzed to illustrate the relationship between the regulatory effects of QGYD on metabolites and the beneficial effects of intestinal flora.Results: QGYD has significant therapeutic effect on CRPA infection. QGYD profoundly inhibited the excessive accumulation of Deferribacteres and Mucispirillum at phylum and genus levels, respectively. Eleven potential metabolites that were abnormally expressed by CRPA infection and significantly reversed by QGYD were identified. Ten of the eleven metabolites significantly regulated by QGYD were related to Deferribacteres. Deferribacteres showed significant positive correlation with DL-lactic acid, phenylalanine and other metabolites and significant negative correlation with vitamin k1. At the genus level, Mucispirillum was closely related to metabolites significantly regulated by QGYD. Mucispirillum was positively correlated with metabolites such as Dl-lactate and negatively correlated with vitamin k1.Conclusion: QGYD can improve CRPA infection and has the effect of regulating intestinal flora and metabolism. It was a promising drug against infection.Keywords: infection, drug-resistant bacteria, traditional Chinese medicine, Qiguiyin Decoction, pharmacodynamic mechanism

Yaolin Wang,1– 3,&ast; Kai Zhao,4,5,&ast; Nanling Wu,1– 3 Tao Ji,1– 3 Gaowei Su,1– 3 Xiaojie Cui,1– 3 Yushan Dong,1– 3 Xiuxia Chen1– 3 1NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui, People’s Republic of China; 5Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuxia Chen, Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Tel +86 18052268332, Email cxxlxy@sina.comPurpose: This study was designed to investigate the effects of different doses of butorphanol on postoperative shivering and quality of recovery in elderly patients.Patients and Methods: A total of 147 elderly patients (aged 60 or older) scheduled for elective transurethral resection of the prostate were enrolled in the current study. Patients were randomly and evenly assigned into four groups: Group C (0.9% normal saline), Group B1 (butorphanol 0.01 mg/kg), Group B2 (butorphanol 0.02 mg/kg) and Group B3 (butorphanol 0.03 mg/kg). All drugs were diluted to 5mL and injected intravenously slowly 5 min before induction of anesthesia. The primary outcome measure was the incidence of postoperative shivering in the post-anesthesia care unit. Quality of Recovery-40 (QoR-40) scores were assessed on postoperative day (POD) 1, 2 and 3. Perioperative core and skin temperature, extubation time and adverse events were also recorded.Results: Patients among the four groups had comparable baseline characteristics. Compared with Group C, the incidence of shivering was significantly lower in Group B2 and B3 (P = 0.006 and P = 0.005, respectively). The QoR-40 scores on POD1 were significantly higher in all butorphanol groups than that in Group C (P < 0.0083). In Group B2 and B3, patients experienced lower pain intensity (P < 0.001). In addition, the incidence of catheter-related bladder discomfort (CRBD) was lower in all butorphanol groups than in Group C (P < 0.0083).Conclusion: Butorphanol 0.02 or 0.03 mg/kg could effectively prevent the occurrence of postoperative shivering in elderly patients scheduled for transurethral resection of the prostate, provided effective postoperative recovery and postoperative analgesia.Keywords: butorphanol, elderly patients, postoperative shivering, recovery quality, postoperative pain

Mingpeng Li,1,2,&ast; Xiaorui Cui,3,&ast; Yanbin Meng,4 Mengli Cheng,4 Jinsong He,3 Wei Yuan,3 Jing Ni,5 Jianping Liu6 1Department of Cardiovascular, Chenzhou No. 1 People’s Hospital, Chenzhou, People’s Republic of China; 2The First Affiliated Hospital of Xiangnan University, Chenzhou, People’s Republic of China; 3Department of Neurology, Affiliated Hospital of Xiangnan University, Chenzhou, People’s Republic of China; 4Xiangnan University, Chenzhou, People’s Republic of China; 5Hunan University of Science and Technology, Xiangtan, People’s Republic of China; 6Institute of Cardiovascular and Cerebrovascular Diseases, Xiangnan University, Chenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianping Liu, No. 25 Renmin West Road, Chenzhou, 423000, People’s Republic of China, Email xxgyjs@163.comBackground: Although the prevalence of hypertension has been well studied in middle age and elderly populations, few studies have systematically investigated the prevalence of hypertension and its association with cardiovascular and cerebrovascular risk factors in young populations.Objective: This study examined the prevalence of hypertension in college students and its correlation with cardiovascular and cerebrovascular risk factors, such as neck circumference and body mass index (BMI).Methods: This population-based study recruited a total of 1719 students (723 were junior, 502 were sophomore, and 494 were freshman), including 996 males (average age: 20.8 years) and 723 females (average age: 20.4 years). Hypertension was defined by the 2018 revised edition of the Chinese Guidelines for Prevention and Treatment of Hypertension. Blood and pulse pressure were measured using standard protocols. Circulating levels of lipids, glucose, glycosylated hemoglobin (GHb), leptin, and adiponectin were determined using standard methods. The Chi-squared (χ2) test was used for comparison of significant differences between groups. Linear and logistic regression analyses were used to explore risk factors that significantly influence hypertension.Findings: The prevalence of hypertension was 10.59% in the total cohort, and sophomores had a higher prevalence of hypertension than freshmen and juniors (χ2 = 19.372; P < 0.001). In addition, male students had a significantly higher prevalence of hypertension (10.24%) and abnormal pulse pressure (8.13%) than female students (1.4% and 0.83%) (χ2 = 327.424, P < 0.001 for high SBP and χ2 = 60.49, P < 0.001 for high DBP, respectively). Correlation analysis revealed that hypertension was significantly correlated with neck circumference and BMI (r = 0.509, P < 0.001; r = 0.474, P < 0.001), but not significantly correlated with the other parameters examined.Conclusion: The prevalence of hypertension in college students is closely correlated with two obesity indicators, neck circumference and BMI.Keywords: cardiovascular and cerebrovascular events, college students, correlation, hypertension, risk factors

Yanhong Yan,1 Jiao Geng,2 Xu Cui,1 Guiyu Lei,1 Lili Wu,1 Guyan Wang1 1Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomingxiang, Beijing, 100730, People’s Republic of China, Tel +86-13910985139, Fax +86-10-58268017, Email guyanwang2006@163.comPurpose: Thoracic paravertebral block (TPVB) may be highly beneficial for thoracoscopic lobectomy patients, but it may increase the risk of hypothermia. Apart from its anesthetic-reducing effects, this randomized controlled trial aimed to investigate the hypothermic effect of TPVB, and thus optimize its clinical use.Patients and methods: Adult patients were randomly allocated to two groups: TPVB + general anesthesia (GA) group or GA group. In the TPVB+GA group, the block was performed after GA induction by an experienced but unrelated anesthesiologist. Both the lower esophageal and axillary temperature were recorded at the beginning of surgery (T0) and every 15 min thereafter (T1-T8), and the end of surgery (Tp). The primary outcome was the lower esophageal temperature at Tp. The secondary outcomes included lower esophageal temperature from T0-T8 and axillary temperature from T0-Tp. The total propofol, analgesics, and norepinephrine consumption and the incidence of adverse events were also recorded.Results: Forty-eight patients were randomly allocated to the TPVB+GA (n=24) and GA (n=24) groups. The core temperature at the end of the surgery was lower in the TPVB+GA group than the GA group (35.90± 0.30°C vs 36.35± 0.33°C, P< 0.001), with a significant difference from 45 min after the surgery began until the end of the surgery (P< 0.05). In contrast, the peripheral temperature showed a significant difference at 60 min after the surgery began till the end (P< 0.05). TPVB+GA exhibited excellent analgesic and sedative-sparing effects compared to GA alone (P< 0.001), though it increased norepinephrine consumption due to hypotension (P< 0.001).Conclusion: Although thorough warming strategies were used, TPVB combined with GA remarkably reduced the body temperature, which is an easily neglected side effect. Further studies on the most effective precautions are needed to optimize the clinical use of TPVB.Keywords: core temperature, peripheral temperature, general anesthesia, warming strategy

Yuanbo Wang1,2 &ast;, Xia Li1,2 &ast;, Rui Jing,2 Wenshan Yang,1,2 Yichen Wang,1,2 Chaochen Wang,1,2 Lei Yao,1,2 Xiaoming Cui,3 Yuan Hu2 1Graduate School of PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Health Medicine, The Third Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoming Cui, Department of Health Medicine, The Third Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China, Email 18611206336@163.com Yuan Hu, Department of Pharmacy, Medical Supplies Center of PLA General Hospital, No. 28 FuXing Road, Beijing, 100853, People’s Republic of China, Email huyuan1980619@126.comPurpose: Tryptophan metabolism is involved in the etiology and exacerbation of depressive disorders. Kai-Xin-San (KXS), a traditional Chinese medicine formula, has been widely used to treat depression and modulate serotonin simultaneously, but how it regulates depressive-like behavior by shifting the balance of the tryptophan-serotonin metabolism and kynurenine pathway remains vague.Patients and Methods: Ten participants with mild to moderate depression treated with KXS (KXS preparation) were analyzed in this study. Depression rating scale score and the concentration of serum tryptophan, 5-hydroxytryptophan and kynurenine was measured at baseline and the endpoint of KXS treatment. To explore the specific regulatory mechanism of KXS in tryptophan metabolism, the chronic restraint stress (CRS) was used to induce depressive-like syndrome in rats and the hippocampus level of tryptophan, 5-hydroxytryptophan, kynurenine with downstream metabolites (kynurenic acid, quinolinic acid) and key enzymes (indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase, kynurenine aminotransferase) were analyzed by liquid chromatography–electros pray ionization tandem mass spectrometry, high performance liquid chromatography and enzyme-linked immunosorbent assay respectively.Results: KXS significantly decreased depression rating scale scores and increased the serum tryptophan and kynurenine concentration in depressive patients compared to baseline. Also, it alleviated the depressive behavior in CRS rats obviously. Comparing with CRS group, KXS increased tryptophan, 5-hydroxytryptophan, kynurenine level in rat hippocampus. Furthermore, in kynurenine pathway, KXS decreased the expression of indoleamine 2,3-dioxygenase, increased kynurenic acid by upregulating the expression of kynurenine aminotransferase while decreased quinolinic acid level in hippocampus, which suggested that KXS more favored improving serotonin pathway, and neuroprotective kynurenic acid branch in the tryptophan metabolism.Conclusion: This is the first tryptophan metabolomic study of patients with depression undergoing KXS treatment. Combining these clinical results with CRS induced rat model studies, it verified that KXS achieves an excellent antidepressant effect and balances tryptophan-kynurenine metabolic pathways by regulating some key metabolic products and enzymes.Keywords: depression, amino acids, TCM, KaiXinSan

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

Pan Li, Xinfeng Liu, Yanmei Lang, Xiaowei Cui, Yanxi Shi Respiratory Department, Children’s Hospital of Hebei Province, Shijiazhuang, 050031, People’s Republic of ChinaCorrespondence: Yanxi Shi, Respiratory Department, Children’s Hospital of Hebei Province, 133 Jianhua South Street, Shijiazhuang, 050031, People’s Republic of China, Email Daniel_2022@126.comIntroduction: Influenza B viruses are less common than influenza A viruses in most seasons and cause relatively milder forms of infection that are less studied. We witnessed a dominance of influenza B in Shijiazhuang, China, in the 2021– 2022 winter season. In this study, we comparatively investigated the severe and critical influenza B in pediatric patients.Methods: Children who were hospitalized from December 2021 to January 2022 and diagnosed with influenza B were included in this study. Those who tested positive for COVID-19 were excluded. Demographic data, clinical features, underlying medical conditions, laboratory testing results, and treatment outcomes were retrieved and analyzed retrospectively. Disease severity was classified as severe or critical according to Chinese expert consensus on diagnosis and treatment of influenza in children.Results: A significantly greater proportion of patients with critical influenza had extra-pulmonary complications and bacterial coinfections. Children with critical influenza B had substantially higher levels of procalcitonin and lactate dehydrogenase, a markedly higher neutrophil percentage and a significantly lower CD4+ lymphocyte percentage.Conclusion: Our findings suggest that, to effectively manage critical influenza B, therapeutic regimens should consist of organ-specific supportive care, antibiotic application if bacterial coinfection is present, and anti-inflammatory and immune-boosting treatments.Keywords: influenza B, critically ill children, extra-pulmonary complication, bacterial coinfection, treatment

Zhao Zhou,1,2,&ast; Xiaohan Cui,1,2,&ast; Peng Gao,2 Xudong Zhang,2 Chunfu Zhu,2 Beicheng Sun1 1Department of Hepatobiliary Surgery of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2The Affiliated Changzhou NO.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunfu Zhu, The Affiliated Changzhou NO.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China, Email zcfmlm@njmu.edu.cn Beicheng Sun, Department of Hepatobiliary Surgery of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China, Email sunbc@nju.edu.cnObjective: Recently, emerging studies have validated that circular RNAs participate in multiple biological progresses in various human malignant tumors, including hepatocellular carcinoma (HCC). However, until now, the elucidated mechanism of circular RNAs is only the tip of the iceberg. In this study, we firstly identify a novel circular RNA circRASSF5 (the only circular RNA derived from the RASSF5 gene), and attempt to investigate its biological function and underlying mechanism in HCC.Methods: qRT-PCR, Western blotting and IHC were applied to detect the expression of related genes. CCK-8 assay, EdU staining, wound healing and transwell assays were used to investigate HCC proliferation, migration and invasion abilities. Animal model studies were included to investigate the function of circRASSF5 in HCC tumorigenesis and metastasis. RNA pull-down assay, luciferase reporter assay and FISH (fluorescence in situ hybridization) assay were performed to explore the potential biological mechanism underlying circRASSF5 function in HCC.Results: CircRASSF5 is obviously downregulated in both HCC tissues and cell lines. Low level of circRASSF5 is negatively associated with larger tumor size, severe vascular invasion, more portal vein tumor embolus and unfavorable prognosis. Loss-of-function assay reveals that circRASSF5 remarkably impedes the growth and metastasis of HCC cells in vitro and in vivo. Mechanistically, circRASSF5 directly interacts with miR-331-3p as a sponge, and then enhances the expression of PH domain and leucine-rich repeat protein phosphatase (PHLPP), thus restraining the progression of HCC cells.Conclusion: Altogether, we validate that circRASSF5 is a tumor suppressor in HCC, which competitively sponges with miR-331-3p and then enhances the tumor inhibitory effect of PHLPP, indicating the potential application value of circRASSF5 for HCC diagnosis and clinical treatment.Keywords: circRASSF5, miR-331-3p, PHLPP, HCC

Zhili Zhang,1,&ast; Xin Zhang,1,2,&ast; Xue Chen,1,2 Xiao Cui,1 Miaotian Cai,1 Liu Yang,1 Yulin Zhang1,2 1Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulin Zhang, Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China, Tel +86 10-83997143, Fax +86 10-63293371, Email yulinzhang@ccmu.edu.cnPurpose: Brucellosis is an ongoing zoonotic disease in China, but there are few data in Beijing. This study was designed to illustrate clinical characteristics of patients with brucellosis in Beijing, China and explore the risk factors for focal brucellosis.Patients and Methods: Data of patients with brucellosis were retrospectively collected from the patients’ electronic medical records in Beijing Youan Hospital during 2010 to 2021, including epidemiological, demographic and clinical features. Risk factors for focal brucellosis were identified by multivariable logistic regression models.Results: A total of 197 patients were included in the study, with 165 (83.8%) cases in acute phase and 32 (16.2%) cases in chronic phase. Patients in acute phase were more likely to have splenomegaly (24.2% vs 3.1%, p=0.007) than those in chronic phase, but had less arthralgia (62.4% vs 81.3%, p=0.040). The median level of alanine aminotransferase (36.9 vs 20.7, p=0.001) was higher in patients at acute stage than those at chronic stage. Of all the patients, 76 (38.6%) were reported with focal complications, including 16 (8.1%) peripheral arthritis, 36 (18.3%) spondylitis, 17 (8.6%) epididymoorchitis, 8 (4.1%) meningitis and 3 (1.3%) endocarditis. Additionally, male (OR 2.76, 95% CI 1.15– 6.64, p = 0.023), arthralgia (OR 6.23, 95% CI 2.36– 16.43, p < 0.001) and higher level of platelets (OR 1.01, 95% CI 1.00– 1.01, p < 0.001) were the independent risk factors for focal brucellosis.Conclusion: The control of human brucellosis still cannot be ignored due to the re-emerging cases in Beijing, which are more likely to present splenomegaly and abnormal liver function in acute phase. Moreover, male, arthralgia and high level of platelets were the independent risk factors for focal brucellosis.Keywords: brucellosis, clinical characteristics, epidemiology, focal complications, risk factors

Runjie Sun,1 Jiang Liu,2 Manya Yu,1 Mengting Xia,3 Yanyu Zhang,1 Xiaoqi Sun,1 Yunsheng Xu,4 Xing Cui4 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 2Department of Foreign Affairs Office, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 3First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 4Second School of Clinical Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250001, People’s Republic of ChinaCorrespondence: Yunsheng Xu; Xing Cui, Second School of Clinical Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 1 Jingba Road, Jinan, 250001, People’s Republic of China, Email xys65@126.com; cdz45@foxmail.comBackground: Bortezomib-induced peripheral neuropathy (BiPN) is a common complication of multiple myeloma (MM) treatment that seriously affects the quality of life of patients. The purpose of the present study was to explore the therapeutic effect of paeoniflorin on BiPN and its possible mechanism.Methods: ELISA was used to measure the level of interleukin-6 (IL6) in the plasma of MM patients, and bioinformatics analysis was used to predict the mechanism underlying the effect of paeoniflorin on peripheral neuropathy. Cell and animal models of BiPN were constructed to evaluate mitochondrial function by measuring cell viability and mitochondrial quality and labeling mitochondria with MitoTracker Green. Nerve injury in mice with BiPN was assessed by behavioral tests, evaluation of motor nerve conduction velocity, hematoxylin-eosin (HE) staining, electron microscopy and analysis of the levels of reactive oxygen species (ROS). Western blotting and immunohistochemistry (IHC) were used to assess the expression of autophagy-related proteins.Results: In MM patients, IL6 levels were positively correlated with the degree of PN. The results of bioinformatics analysis suggested that paeoniflorin ameliorated PN by altering inflammation levels and mitochondrial autophagy. Paeoniflorin increased PC12 cell viability and mitochondrial autophagy levels, alleviated mitochondrial damage, and reduced IL6 levels. In addition, paeoniflorin effectively improved the behavior of mice with BiPN, relieved sciatic nerve injury in mice, increased the expression of LC3II/I, beclin-1, and Parkin in sciatic nerve cells, and increased the expression of LC3B and Parkin in the nerve tissue.Conclusion: The present study confirmed that paeoniflorin significantly ameliorated peripheral neuropathy (PN) caused by bortezomib, possibly by reducing IL6 levels to regulate PARKIN-mediated mitochondrial autophagy and mitochondrial damage.Keywords: multiple myeloma, paeoniflorin, peripheral neuropathy, mitochondria, autophagy

Feihong Liu, Chunhua Xi, Xu Cui, Guyan Wang Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China, Tel +86-13910985139, Email Guyanwang2006@163.comBackground: Flexible laryngeal mask airways (FLMAs) ventilation have been widely used as airway devices during general anesthesia, especially in otologic surgery. However, the current literature reports that the clinical success and failure rates for FLMA usage are quite different, and there remains a paucity of data regarding factors associated with FLMA failure and complications related to FLMA usage.Purpose: To evaluate the success and failure rates of FLMA usage in otologic surgery, the factors associated with FLMA failure and complications related to FLMA usage.Patients and Methods: All patients who underwent otologic surgery, including middle ear and mastoid procedures, under general anesthesia at a large tertiary general hospital from 2015 to 2019 were reviewed. The primary outcome was the FLMA failure rate, defined as any airway event requiring device removal and tracheal intubation, including primary and secondary failure. The secondary outcomes were specific clinical factors, including patient sex, age, weight, American Society of Anesthesiologists (ASA) classification, body mass index (BMI) and duration of surgery, which were analyzed as related risk factors.Results: Among 5557 patients with planned FLMA use, the final success rate was 98.5%. Sixty-seven percent of the failures occurred during initial introduction of the FLMA, 8% occurred after head and neck rotation, and 25% occurred during the procedures. Two independent clinical factors associated with FLMA failure were male sex and age. Respiratory complications were observed in 0.61% of patients, and the rate of severe nerve and tissue damage associated with FLMA use was 0.05.Conclusion: This study demonstrates a high success rate of 98.5% for FLMA use in adults undergoing otologic surgery with rare adverse airway events and injuries complications. Two independent risk factors require attention and thorough and accurate management is necessary for every clinician.Keywords: otologic surgery, flexible laryngeal mask airway, safety, efficacy, airway complications

Zhongbiao Nie,1 Xianmei Cui,2 Ran Zhang,3 Zhihong Li,1 Bin Lu,4 Suxian Li,1 Tao Cao,2 Ping Zhuang4 1Pharmaceutical Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030012, People’s Republic of China; 2Obstetrics Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030012, People’s Republic of China; 3Nephrology Department, Affiliated Hospital of Shanxi University of Traditional Chinese Medicine, Taiyuan, 030036, People’s Republic of China; 4Anesthesiology Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030012, People’s Republic of ChinaCorrespondence: Ping Zhuang, Anesthesiology Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030012, People’s Republic of China, Tel +86-13700503507, Email 13700503507@163.comPurpose: To investigate the effectiveness of sufentanil patient-controlled intravenous analgesia pump (PCIA) and background infusion in patients of post-cesarean analgesia.Patients and Methods: This trial compared two groups of women undergoing cesarean section and receiving PCIA: no background infusion group (n=30), 6-min lockout time, and background infusion group (n=30), 2 mL/h infusion, 10-min lockout time. Both groups with 2 μg/kg sufentanil was diluted to 100 mL with normal saline. VAS scores at rest at 36 h was the primary endpoint. The secondary endpoints were the VAS scores at rest at 6, 12, and 24 h, the total amount of sufentanil consumed, the Ramsay sedation score (RSS) assessed at the same time points, postpartum bleeding within 24 h, the injection/attempt (I/A) ratio, BP and HR, PONV, side effects of sufentanil.Results: Compared with the no background infusion group, the background infusion group showed lower VAS pain scores at 6, 12, and 24 h (P< 0.01), but no differences at 36 h (95% CI = − 0.5– 0.8. P> 0.05). Attempts, injections, and total sufentanil consumption were significantly different between the two groups (P< 0.001), but without difference in I/A. Bleeding was less in the background infusion group at 1 h (P=0.03). The minimal respiration rates were not significantly different between groups.Conclusion: Background infusion increased the total consumption of sufentanil within 36 h after cesarean section. Although it did not reduce uterine contraction pain and wound pain at 36 h, it significantly reduced the pain at 6, 12, and 24 h after cesarean section. It improved patient satisfaction and reduced the amount of bleeding after 1 h. Importantly, it did not increase the incidence of hypertension, PONV and respiratory depression.Keywords: background infusion, patient-controlled intravenous analgesia, PCIA, sufentanil

Fusang Wang,1,2,* Xiaohan Zheng,1,2,* Juan Zhang,3,* Fuping Jiang,4 Nihong Chen,5 Mengyi Xu,5 Yuezhang Wu,2 Jianjun Zou,2,5 Xiaoli Cui,3 Junshan Zhou6 1School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Department of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Neurology, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Geriatrics, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 5Department of Clinical Pharmacology, Nanjing First Hospital, China Pharmaceutical University, Nanjing, People’s Republic of China; 6Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianjun Zou; Xiaoli Cui, Email zoujianjun100@126.com; 849110554@qq.comBackground and Purpose: Predicting poor outcome for stroke patients with chronic kidney disease (CKD) in clinical practice is difficult. There are no tools available to use for predicting poor outcome in these patients. We aimed to construct and validate a dynamic nomogram to identify CKD–stroke patients at high risk of a 3-month poor outcome.Patients and Methods: We used data for 502 CKD patients who had an acute ischemic stroke, from Nanjing First Hospital, between September 2014 and September 2020, to train the nomogram. An additional 108 patients enrolled from October 2020 to May 2021 were used for temporal external validation. The performance of the nomogram was evaluated by the area under the receiver operating characteristics curve (AUC) and a calibration plot. The clinical utility of the nomogram was measured by decision curve analysis (DCA) and the clinical impact curve (CIC).Results: The median age of the cohort was 79 (70– 84) years. Age, urea, premorbid modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS) on admission, hemiplegia, mechanical thrombectomy, early neurological deterioration, and respiratory infection were used as predictors of 3-month poor outcome to develop the nomogram. In the training set, the AUC of the dynamic nomogram was 0.873 and the calibration plot showed good predictive ability, and both DCA and CIC indicated the excellent clinical usefulness and applicability of the nomogram. In the external validation set, the AUC was 0.875 and the calibration plot also showed good agreement.Conclusion: This is the first dynamic nomogram constructed for CKD–stroke patients to precisely and expediently identify patients with a high risk of 3-month poor outcome. The outstanding performance and great clinical predictive utility demonstrated the ability of the dynamic nomogram to help clinicians to deploy preventive interventions.Keywords: dynamic nomogram, stroke, chronic kidney disease, poor outcome, predict

Zhengzheng Gao,1 Jianmin Zhang,1 Xiaolu Nie,2 Xiaohuan Cui1 1Department of Anesthesiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2Center for Clinical Epidemiology and Evidence-based Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of ChinaCorrespondence: Jianmin Zhang, Department of Anesthesiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 South Lishi Road, Xicheng District, Beijing, 100045, People’s Republic of China, Tel +86 10-59616415, Email sunbrighangel@sina.comBackground: Emergence agitation (EA) has a negative effect on the recovery from general anesthesia in children. This study aimed to evaluate the effectiveness of intravenous ibuprofen in reducing the incidence of EA in children.Methods: This randomized, double-blind, placebo-controlled, single-center study analyzed data from patients aged 3– 9 years undergoing tonsillectomy under general anesthesia with propofol and remifentanil. These patients were randomly assigned to receive either the ibuprofen or the placebo intraoperatively. The primary endpoint was a between-group difference in the incidence of EA at 15 min following extubation. EA was defined as Pediatric Anesthesia Emergence Delirium score ≥ 10. The secondary endpoint included the associated factors of EA.Results: Eighty-nine patients were included in the study. Ibuprofen decreased the incidence of EA at 15 min following extubation (8.9% in the treatment group vs 34.1% in the control group; odds ratio [OR], 0.261; 95% confidence interval [CI], 0.094– 0.724; P=0.004). Compared with the control group, there was a significant reduction in the number of rescue fentanyl doses (P=0.045), and fewer patients experienced moderate to severe pain at 15 min following extubation in the treatment group (P=0.048). Upon logistic regression analysis, high modified Pediatric Anesthesia Behavior and pain scores following surgery were considered the risk factors related to EA (OR, 8.07; 95% CI, 1.12– 58.07, P=0.038 and OR, 2.78; 95% CI, 1.60– 4.82, P< 0.001, respectively). Ibuprofen administration was the protective factor related to EA (OR, 0.05; 95% CI, 0.01– 0.67, P=0.023).Conclusion: Intraoperative ibuprofen infusion can significantly reduce the incidence of EA following general anesthesia with propofol and remifentanil in children.Trial Registration: The study was registered with the Chinese Clinical Trial Registry on 7 April 2021 (number: ChiCTR2100045128; https://www.chictr.org.cn/edit.aspx?pid=124595&htm=4).Keywords: emergence agitation, children, ibuprofen, general anesthesia, protective factor

Kai Zhao,1,&ast; Yushan Dong,1,&ast; Gaowei Su,1 Yaolin Wang,1 Tao Ji,1 Nanling Wu,1 Xiaojie Cui,1 Wenzhan Li,1 Yanming Yang,1 Xiuxia Chen1,2 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuxia Chen, Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Tel +86 18052268332, Fax +0516-8346-9496, Email cxxlxy@sina.comPurpose: Lidocaine has been gradually used in general anesthesia. This study was designed to investigate the effect of systemic lidocaine on postoperative quality of recovery (QoR) in patients undergoing supratentorial tumor resection, and to explore its brain-injury alleviation effect in neurosurgical anesthesia.Patients and Methods: Sixty adult patients undergoing elective supratentorial tumor resection. Patients were randomly assigned either to receive lidocaine (Group L: 1.5 mg/kg bolus completed 10 min before anesthesia induction followed by an infusion at 2.0 mg/kg/h) or to receive normal saline (Group C: received volume-matched normal saline at the same infusion rate). Primary outcome measures were Quality of Recovery-40 (QoR-40) scores on postoperative day (POD) 1 and 2. Plasma concentrations of S100B protein (S100B), neuron specific enolase (NSE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before anesthesia induction and at the end of surgery were assessed. Visual Analogue Scale (VAS) scores were assessed at 1, 2, 6, 12, 24 and 48 h after surgery. Perioperative parameters and adverse events were also recorded.Results: Patients between two groups had comparable baseline characteristics. Global QoR-40 scores on POD 1 and POD 2 were significantly higher (P < 0.001) in group L (165.5± 3.8 vs 173.7± 4.7) than those in group C (155.6± 4.0 vs 163.2± 4.5); and scores of physical comfort, emotional state, and pain in group L were superior to those in group C (P < 0.05). In group L, patients possessed lower plasma concentration of pro-inflammatory factors (IL-6, TNF-α) and brain injury-related factors (S100B, NSE) (P < 0.05), consumed less remifentanil and propofol, and experienced lower pain intensity. Multiple linear regression analysis demonstrated age and pain were correlated with postperative recovery quality.Conclusion: Systemic lidocaine improved early recovery quality after supratentorial tumor resection with general anesthesia, and had certain brain-injury alleviation effects. These benefits may be attributed to the inflammation-alleviating and analgesic properties of lidocaine.Keywords: lidocaine, brain neoplasm, supratentorial tumor resection, recovery quality, brain protection, postoperative pain

Yan Chen,1,2 Xinyu Cui,2 Jiahuan Zhuoma,2 Fang Zhu,2 Li Luo,3 Juan Xie,2 Yongzhong Cheng2 1Institute of Hospital Management, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2The Commission for Discipline Inspection, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 3Industrial Engineering and Engineering Management Department, College of Business of Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Li Luo; Juan Xie, Industrial Engineering and Engineering Management Department, Business School of Sichuan University, Chengdu, People’s Republic of China, Email luolicc@scu.edu.cn; 857538446@qq.comPurpose: To examine how employees perceive corruption risks in their hospital and to provide recommendations for good governance in that hospital.Methods: The “Questionnaire of Corruption Risk Perception Index in Public Hospitals” was designed and a questionnaire survey was conducted online from April 17 to 30, 2020 in West China Hospital of Sichuan University, to explore employees’ assessment of corruption risk. Employees were asked to evaluate the likelihood and impact of corruption risk to form a corruption risk perception index (CRPI). Related factors were examined in multifactor analysis.Results: A total of 5525 employees participated in the survey. Among all 15 kinds of risks, unreasonable personnel changes (CRPI=8.24), no collective discussion about important issues (CRPI=7.95), and violating the individual moral character (CRPI=7.85) were the top 3 ones that participants rated highest, while illegal procurement (CRPI=7.38), violating teaching ethics (CRPI=7.12) and medical ethics (CRPI=6.93) were rated lowest. Corruption risks were mainly concentrated in internal management, treatment regulation, professional conduct, and external cooperation. The OR value that the CRPI of leaders was 0.768 times that of ordinary employees (95% CI: 0.623– 0.945, χ 2=6.189, P=0.013). Fluke ideas were the most selected personal reason for corruption. Suggestions for strengthening the education of corruption risk were mentioned most.Conclusion: The results indicate the emphasis and direction of hospital management. First, WCH needs to pay attention to the construction and dynamic improvement of the hospital’s internal management regulations and external cooperation management regulations, and increase the transparency of decision-making and implementation. Second, it is necessary to restrict the discretion of leaders at all levels and strengthen supervision. In addition, WCH needs to carry out education from the perspectives of power awareness and corruption cost, and to strive to build a clean, honest culture.Keywords: corruption risk perception index, corruption risk, anti-corruption, public hospital

Xingming Liu, Guoxin Guan, Xinye Cui, Yaqing Liu, Yinghan Liu, Fuwen Luo Department of General Surgery, The Second Affiliated Hospital, Dalian Medical University, Dalian, 116023, People’s Republic of ChinaCorrespondence: Fuwen Luo Email dyeylfw@163.comObjective: Systemic immune-inflammation index (SII) is a new systemic inflammatory prognostic indicator associated with outcomes in patients with different tumors. Studies have shown an association between SII and many chronic/acute inflammatory diseases. This study aimed at exploring whether SII can be used as an effective parameter for predicting the severity of acute pancreatitis (AP).Methods: A total of 101 acute pancreatitis patients were enrolled in this study (mild acute pancreatitis (MAP): n = 73 and severe acute pancreatitis (SAP): n = 28). Patient demographics and SII were analyzed using the chi-square test, Student’s t-test, and Mann–Whitney U-test. A receiver operating characteristic curve was generated to test the potential of using neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and SII to predict AP’s severity. Logistic regression analysis was performed to determine major risk factors.Results: Patients with SII value ≥ 2207.53 had a higher probability of having SAP (sensitivity = 92.9%, specificity = 87.7%, and AUC = 0.920), and SII was a significantly better predictive value than PLR and NLR. Logistic regression analysis results showed SII could differentiate MAP from SAP as a major risk factor.Conclusion: This study has shown that SII is a potential indicator for predicting the severity of acute pancreatitis. The findings suggested that SII is more sensitive and specific than NLR and PLR in predicting the severity of acute pancreatitis.Keywords: acute pancreatitis, severity, systemic immune inflammation index

Xiangyi Cui,1 Yuhong Lü,1,2 Changwu Yue1,2 1Key Laboratory of Microbial Drugs Innovation and Transformation of Yan’an, School of Basic Medicine, Yan’an University, Yan’an, 716000, Shaanxi, People’s Republic of China; 2Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources, Yan’an University, Yan’an, 716000, Shaanxi, People’s Republic of ChinaCorrespondence: Yuhong Lü; Changwu YueYan’an University, No. 580 Shengdi Road, Baota District, Yan’an, 716000, Shaanxi, People’s Republic of ChinaTel/Fax +86 911-2332-067Email yuhonglyu@126.com; changwuyue@126.comAbstract: Bacterial resistance has become increasingly serious because of the widespread use and abuse of antibiotics. In particular, the emergence of multidrug-resistant bacteria has posed a serious threat to human public health and attracted the attention of the World Health Organization (WHO) and the governments of various countries. Therefore, the establishment of measures against bacterial resistance and the discovery of new antibacterial drugs are increasingly urgent to better contain the emergence of bacterial resistance and provide a reference for the development of new antibacterial drugs. In this review, we discuss some antibiotic drugs that have been approved for clinical use and a partial summary of the meaningful research results of anti-drug resistant bacterial drugs in different fields, including the antibiotic drugs approved by the FDA from 2015 to 2020, the potential drugs against drug-resistant bacteria, the new molecules synthesized by chemical modification, combination therapy, drug repurposing, immunotherapy and other therapies.Keywords: multidrug-resistant bacteria, antimicrobial resistance, novel antibiotics, antibiotics, antibiotic discovery

Wei Wang,1,2,&ast; Zaoxiu Hu,3,&ast; Mingsheng Ma,4 Haoyuan Yin,4 Yunchao Huang,1 Guangqiang Zhao,1 Xin Cui,1 Qinling Sun,1 Yantao Yang,1 Yichen Yang,1 Biying Wang,1 Lianhua Ye1 1Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Thoracic Surgery, Taihe Hospital (Hubei University of Medicine), Shiyan, People’s Republic of China; 3Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Department of Thoracic Surgery, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianhua YeDepartment of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, No. 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province, People’s Republic of ChinaEmail lhye1204@aliyun.comPurpose: Currently, there is no uniform standard to guide postoperative adjuvant chemotherapy for patients with multifocal non-small cell lung cancers (NSCLCs) ≤ 3 cm. Therefore, there is an urgent need to explore prognostic molecular markers to identify high-risk patients with multifocal NSCLCs ≤ 3 cm. We aimed to explore the potential value of metastasis-associated protein 1(MTA1) expression in risk stratification of patients with multifocal NSCLCs ≤ 3 cm.Methods: We retrospectively analyzed the clinical data and postoperative survival data of patients with multifocal NSCLCs ≤ 3 cm. Paraffin-embedded tissue sections were used for immunohistochemistry. Semiquantitative immunoreactivity scoring (IRS) system was used to evaluate the nuclear expression of MTA1. SPSS software (version 23.0) was used to analyze the data.Results: The IRS of MTA1 nuclear expression in 259 lesions of 119 patients ranged from 2.2 to 11.7 (median: 5.6). Our results showed that MTA1 expression was highest in high-risk pathological subtypes of lung adenocarcinoma. MTA1 expression in multiple primary lung cancers (MPLCs) was lower than that in intrapulmonary metastases (IPMs). The median follow-up duration was 25.97 months. The disease-free survival (DFS) of patients with MPLCs was significantly better than that of patients with IPMs, and the DFS of patients with high MTA1 expression was significantly worse than that of patients with low MTA1 expression. Multivariate Cox analysis showed that high MTA1 expression (hazard ratio: 7.937, 95% confidence interval: 2.433– 25.64, p =0.001) was a statistically significant predictor of worse DFS in patients with multifocal NSCLCs ≤ 3 cm.Conclusion: MTA1 expression can stratify the risk in patients with multifocal NSCLCs ≤ 3 cm. Patients with MTA1 immunohistochemical score > 5.6 are at a high risk of postoperative recurrence, and these patients may benefit from postoperative adjuvant chemotherapy.Keywords: multifocal, non-small cell lung cancer, MTA1, multiple primary lung cancers, intrapulmonary metastases, risk of postoperative recurrence

Xiumin Cui,1,2 Xinli Chi3 1College of Education for the Future, Beijing Normal University, Zhuhai, 519087, People’s Republic of China; 2The Affiliated Kindergarten of Meilian Primary School, Shenzhen, 518035, People’s Republic of China; 3School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of ChinaCorrespondence: Xinli ChiSchool of Psychology, Shenzhen University, 1688 Nanhai Avenue, Nanshan District, Shenzhen, Guangdong Province, People’s Republic of ChinaEmail xinlichi@126.comIntroduction: Lockdowns and online homeschooling during the COVID-19 coronavirus pandemic have significantly increased Internet use and adolescents’ risk of developing or reinforcing related addictive behaviors. While various theoretical propositions have suggested that social support, resilience, and post-traumatic stress disorder (PTSD) symptoms can predict Internet addiction, no study has yet examined the combined influence of these factors on Internet addiction. This study therefore aimed to investigate the mediating roles of resilience and PTSD symptoms in the relationship between perceived social support and the Internet addiction of Chinese adolescents in the context of COVID-19.Methods: This study included 2544 adolescents living in the south China city of Qinzhou. The participants completed a self-report questionnaire one week before their return to classes after homeschooling. To examine whether resilience and PTSD symptoms mediated the relationship between social support and Internet addiction, we performed serial mediation analysis using the Model 6 PROCESS macro developed by Hayes (2013).Results: Social support was negatively and directly associated with Internet addiction and indirectly via resilience, PTSD symptoms, and by the multiple mediation of resilience to PTSD symptoms.Discussion: The results of this study suggest that, to address Internet addiction, it may be more effective to focus not on addictive behaviors themselves but on individuals’ existing mental health. It is important to provide adequate social support to improve the resilience of adolescents, thereby reducing PTSD symptoms and Internet addiction.Keywords: social support, resilience, PTSD symptoms, Internet addiction, COVID-19 pandemic, adolescents

Hirotaka Kanzaki,1 Avradip Chatterjee,1 Hanieh Hossein Nejad Ariani,1 Xinfeng Zhang,2 Stacey Chung,2 Nan Deng,3,4 V Krishnan Ramanujan,4 Xiaojiang Cui,1,2,4 Mark I Greene,5 Ramachandran Murali1 1Department of Biomedical Sciences, Research Division of Immunology; 2Department of Surgery; 3Biostatistics and Bioinformatics Research Center; 4Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; 5Department of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USACorrespondence: Ramachandran Murali Email ramachandran.murali@csmc.eduIntroduction: Constitutive activation of NF-κB has been implicated as being contributive to cancer cell growth, drug resistance, and tumor recurrence in many cancers including breast cancer. Activation of NF-κB leads to nuclear translocation of RelA, a critical component of the NF-κB transcription factor complex, which subsequently binds to specific DNA sites and activates a multitude of genes involved in diverse cell functions. Studies show that triple-negative breast cancer (TNBC) cells possess constitutively active NF-κB and concomitantly have higher levels of nuclear localization of RelA than cytoplasmic RelA. This feature is considered to be associated with the response to chemotherapy. However, currently, there is no specific inhibitor to block nuclear translocation of RelA.Methods: A structure-based approach was used to develop a small-molecule inhibitor of RelA nuclear translocation. The interaction between this molecule and RelA was verified biophysically through isothermal titration calorimetry and microscale thermophoresis. TNBC cell lines MDA-MB-231 and MDA-MB-468 and a human TNBC xenograft model were used to verify in vitro and in vivo efficacy of the small molecule, respectively.Results: We found that the small molecule, CRL1101, bound specifically to RelA as indicated by the biophysical assays. Further, CRL1101 blocked RelA nuclear translocation in breast cancer cells in vitro, and markedly reduced breast tumor growth in a triple-negative breast cancer xenograft model.Conclusion: Our study demonstrates that CRL1101 may lead to new NF-κB-targeted therapeutics for TNBC. Further, blocking of nuclear translocation of shuttling transcription factors may be a useful general strategy in cancer drug development.Keywords: transcription factors, breast cancer, computer aided drug design, nuclear transport, drug-target

Xiaopeng Cui,1,2,* Wen-Qiang Xin,1,* Bangyue Wang,1 Yan Zhao,1 Changkai Hou,1 Shifei Cai,1 Chao Peng,1 Zhen Wang,1 Jian Li,1 Linchun Huan,3 Lei Chen,2 Xinyu Yang1 1Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Neurosurgery, Tianjin Fifth Central Hospital, Tianjin, People’s Republic of China; 3Department of Neurosurgery, Linyi People’s Hospital, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinyu YangDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Medical University, 154 Anshan Road, Peace Zone, Tianjin, 300041, People’s Republic of ChinaEmail yangxinyu@tmu.edu.cnLei ChenDepartment of Neurosurgery, Tianjin Fifth Central Hospital, 41 Zhejiang Road, Binhai New Area, Tianjin, 300450, People’s Republic of ChinaEmail chenlei1130@163.comObjective: Several studies have reported that single-nucleotide polymorphisms (SNPs) of the CDKN2A/CDKN2B gene on chromosome 9p21.3 are associated with increased risk of intracranial aneurysm (IA). However, the association between IAs and SNPs of CDKN2A/CDKN2B in Chinese Han people is yet to be evaluated. This study examined the association of the SNPs rs10811661 and rs4977574 with IA in the Chinese Han population.Methods: A total of 595 IA patients and 600 sex- and age-matched controls were enrolled in the study. Peripheral blood was collected and stored at – 80°C until use. CDKN2A/CDKN2B was identified using polymerase chain reaction–ligase detection reaction. SNP genotyping was performed for rs10811661 and rs4977574 using a MassArray system. Associations between these two SNPs and IAs was tested with χ2 or Fisher’s exact tests and multivariate logistic regression.Results: rs10811661 and rs4977574 were significantly associated with IA. The frequency of rs10811661-T in IA was higher than in controls (OR 1.26, 95% CI 1.07– 1.49; P< 0.01). There was no significant difference in frequency of haplotype between control subjects and IA patients.Conclusion: rs10811661 and rs4977574 on 9p21.3 were strongly associated with genetic susceptibility to IA in the Chinese Han population, which emphasizes a need for further investigation.Keywords: intracranial aneurysm, CDKN2A/CDKN2B gene, Chinese Han population, SNP

Kai Liu,1,* Xinjuan Yu,2,* Xuefen Cui,2 Yi Su,2 Lixin Sun,3 Jiulong Yang,4 Wei Han2 1Department of Rehabilitation, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 2Department of Respiratory and Critical Medicine, Respiratory Disease Key Laboratory of Qingdao, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 3Department of Anesthesia, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 4Hospital Office, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei HanDepartment of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, 266071, People’s Republic of ChinaTel +86 532 85937579Email hanw@qdu.edu.cnJiulong YangHospital Office, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, 266071, People’s Republic of ChinaTel +86 532 88905509Email qdyxkp@163.comBackground: The proprioceptive neuromuscular facilitation (PNF) stretching could improve the contractile capacity of respiratory muscles, but the effect on pulmonary function, when it is combined with aerobic training, remains unknown.Objective: To evaluate the effect of PNF combined with aerobic training on respiratory symptoms, pulmonary function and neck/shoulder mobility in patients with COPD.Design: Randomized controlled trial.Participants: Fifty-five COPD patients were randomly divided into PNF group (n=28) and control group (n=27).Intervention: On the basis of conventional treatment, the control group performed 30 min aerobic training on a treadmill, while the PNF group added 10-minute PNF stretching 3 times every training day. Both groups did their training in 5 days per week for 6 weeks.Measures: Measures were taken before and after 6 weeks of training. COPD Assessment Test (CAT), dyspnea Visual Analog Scale (VAS), forced vital capacity (FVC), forced expiratory volume in first second (FEV1), inspiratory capacity (IC), inspiratory reserve volume (IRV), 6-minute walk test (6MWT), the range of motion (ROM) of head protraction, shoulder flexion, and the non-dominant pectoralis minor muscle (PmM) length were measured.Results: All the indicators of both groups were significantly improved after 6 weeks of intervention except for FVC, FEV1 and PmM length. Compared to the control group, the PNF group showed significant improvement in the CAT score, dyspnea VAS score, IC, IRV, 6MWT, as well as head protraction ROM and shoulder flexion ROM. Furthermore, IC was positively correlated with the head protraction ROM and PmM length (r=0.415, 0.579, P=0.028, 0.001); IRV was positively correlated with the shoulder flexion ROM (r=0.405, P=0.032) in the PNF group.Conclusion: PNF stretching combined with aerobic training reduces dyspnea and improves some pulmonary function measures, which is associated with neck/shoulder mobility, in COPD patients.Keywords: chronic obstructive pulmonary disease, proprioceptive neuromuscular facilitation stretching, aerobic training, pulmonary function

Yang Yang,1,* Xiao Cui,1,* Huaying Wei,1 Caiping Guo,1 Yulin Zhang2 1Department of Infectious Diseases, Beijing You an Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing, 100069, People’s Republic of China; 2Department of Respiratory and Infectious Diseases, Beijing You an Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing, 100069, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yulin ZhangDepartment of Respiratory and Infectious Diseases, Beijing You an Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing, 100069, People’s Republic of ChinaTel +86 10-83997143Fax +86 10-63293371Email yulinzhang@ccmu.edu.cnAbstract: Severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) is an emerging pathogen, which is similar to previous SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) occurrences. However, we only get few understandings about the pathogenesis of SARS-CoV-2, which need to further be studied. The discovery of an agent that has a treatment efficacy against SARS-CoV-2 is very urgent. In this review, we briefly discuss the virology of this pathogen and focus on the available understanding of the pathogenesis and treatments of this pathogen including the uses of nucleoside analogues, protease inhibitors, interferons, and other small-molecule drugs, on the basis previous comprehensions of SARS and MERS. These reviewed concepts may be beneficial in providing new insights and potential treatments for COVID-19.Keywords: COVID-19, SARS, MERS, virology, pathogenesis, treatment

Hui Jiang1,2 *,* Kefeng Cao3 *,* Chang Fan,1,2 Xiaoya Cui,1,2 Yanzhen Ma,1,2 Jian Liu1 1Experimental Center of Clinical Research, First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 2School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 3Departments of Laboratory Medicine, Traditional Chinese Medical Hospital of Taihe County, Fuyang, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian LiuFirst Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Hefei, Anhui, People’s Republic of ChinaTel +86 181 5607 8363Email liujian_arthritis@126.comIntroduction: N6-methyladenosine (m6A) is the most frequent internal modification in eukaryotic mRNAs and is closely related to the occurrence and development of many diseases, especially tumors. However, the relationship between m6A methylation and rheumatoid arthritis (RA) is still a mystery.Methods: Two high-throughput sequencing methods, namely, m6A modified RNA immunoprecipitation sequence (m6A-seq) and RNA sequence (RNA-seq) were performed to identify the differentially expressed m6A methylation in human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A after stimulation with TNF-α. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to obtain enriched GO terms and significant KEGG pathways. Then, four candidate genes, Wilms tumor 1-associating protein (WTAP), receptor-interacting serine/threonine protein kinase 2 (RIPK2), Janus kinase 3 (JAK3) and tumor necrosis factor receptor SF10A (TNFRSF10A) were selected to further validate the m6A methylation, mRNA and protein expression levels in MH7A cells and synovial tissues of adjuvant arthritis (AA) rats by RT-qPCR and Western blot.Results: Using m6A-seq, we identified a total of 206 genes with differentially expressed m6A methylation, of which 118 were significantly upregulated and 88 genes were significantly downregulated. Likewise, 1207 differentially mRNA expressed mRNAs were obtained by RNA-seq, of which 793 were upregulated and 414 downregulated. Further joint analysis showed that the m6A methylation and mRNA expression levels of 88 genes changed significantly, of which 30 genes displayed increased m6A methylation and decreased mRNA expression, 57 genes displayed decreased m6A methylation and increased mRNA expression increased, and 1 gene displayed increased m6A methylation and increased mRNA expression. GO and KEGG analyses indicated that these unique genes were mainly enriched in inflammation-related pathways, cell proliferation and apoptosis. In addition, the validations of WTAP, RIPK2, JAK3 and TNFRSF10A were in accordance with the m6A and RNA sequencing results.Conclusion: This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and RA related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent.Keywords: m6A methylation, m6A-seq, RNA-seq, rheumatoid arthritis, MH7A cells

Zhengzhong Gu,1 Xiaohan Cui,2 Pengda Sun,1 Xudong Wang1 1Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Xudong WangDepartment of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, No. 218, Ziqiang Street, Changchun 130041 Jilin Province, People’s Republic of ChinaTel +86 13514406378Email wangxudong1971@126.comAbstract: Tumor necrosis factor-alpha (TNF-α)-induced protein 8 (TNFAIP8/TIPE) family, including TNFAIP8 (TIPE), TNFAIP8 like-protein 1 (TNFAIP8L1/TIPE1), TNFAIP8 like-protein 2 (TNFAIP8L2/TIPE2), and TNFAIP8 like-protein 3 (TNFAIP8L3/TIPE3), plays a vital role in regulating inflammatory responses, immune homeostasis, and cancer development. Over the last decade, studies have shown that TIPE2 protein is differentially expressed in diverse cells and tissues. The dysregulation of TIPE2 protein can lead to dysregulation of inflammatory responses and immune homeostasis, and change the basic characteristics of cancers. In consideration of the immeasurable values of TIPE2 in diagnosis, treatment, and prognosis of various human diseases, this review will focus on the expression pattern, structure, and regulatory roles of TIPE2 in inflammation, immunity, and cancers.Keywords: TIPE2, inflammation, immune homeostasis, tumor, tumorigenesis, metastasis

Xiaofeng Cui, Huaiyu Zhang, Tong Chen, Wei Yu, Kexin Shen Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaCorrespondence: Wei Yu; Kexin ShenDepartment of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Street, Changchun, Jilin 130033, People’s Republic of ChinaTel/Fax +86-0431-84996792Email yu_wei@jlu.edu.cn; shenkexin1314@jlu.edu.cnBackground: The correlation between long non-coding RNAs (lncRNAs) and gastric cancer (GC) has been indicated. As a newly found lncRNA, small nucleolar RNA host gene 22 (SNHG22) functions as an oncogene in ovarian carcinoma and breast cancer. However, its action has not been explored in GC. Herein, the purpose of the current research was to examine the influence of SNHG22 on GC development.Methods: RT-qPCR was used to identify SNHG22 and microRNA-361-3p (miR-361-3p) in GC tissues and cells. Functional assays were implemented to measure changes on biological activities of GC cells under different transfections. Besides, after human umbilical vein endothelial cells (HUVECs) were co-cultured with supernatant of transfected GC cells, angiogenesis was assessed by tube formation assay in vitro. HMGA1 and β-catenin expression were determined. Finally, mechanistic assays, including RNA pull-down assay and dual-luciferase reporter assay, were employed to assess relationships among SNHG22, miR-361-3p, and HMGA1.Results: SNHG22 and HMGA1 were highly expressed but miR-361-3p was poorly expressed in GC tissues. Mechanistically, SNHG22 bound to miR-361-3p, and miR-361-3p targeted HMGA1 to disrupt the Wnt/β-catenin pathway. Following SNHG22 or HMGA1 silencing or miR-361-3p upregulation, we observed a decline of proliferation, migration, and invasion of GC cells and HUVEC angiogenesis but acceleration of GC cell apoptosis and cell cycle arrest.Conclusion: Collectively, SNHG22 silencing possessed tumor-suppressing potentials in GC development via Wnt/β-catenin pathway by binding to miR-361-3p and downregulating HMGA1, highlighting a new promising road for GC treatment development.Keywords: gastric cancer, long noncoding RNA SNHG22, microRNA-361-3p, HMGA1, Wnt/β-catenin pathway

Yang Dong,* Dongfei Wang,* Jialan Lv, Zhicheng Pan, Rui Xu, Jie Ding, Xiao Cui, Xudong Xie, Xiaogang Guo Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaogang GuoDepartment of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, No. 79 Qing Chun Road, Hangzhou 310006, People’s Republic of ChinaTel + 86-13867441856Email gxg22222@zju.edu.cnPurpose: We aimed to study the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk model’s prognostic value and relationship with left ventricular remodeling in dilated cardiomyopathy.Patients and Methods: Dilated cardiomyopathy patients were prospectively recruited and underwent clinical assessments. MAGGIC risk score was calculated. Patients were followed up for adverse events and echocardiography. Primary endpoints were all-cause mortality and first rehospitalization due to heart failure. Secondary endpoint was left ventricular remodeling defined as a decline in left ventricular ejection fraction > 10% or an increase in left ventricular end-diastolic diameter > 10%. Survival status was examined using Cox regression analysis. The model’s ability to discriminate adverse events and left ventricular remodeling was calculated using a receiver operating characteristics curve.Results: In total, 114 patients were included (median follow-up time = 31 months). The risk score was independently related to adverse events (2-year all-cause mortality: hazard ratio [HR] = 1.122; 95% confidence interval [CI], 1.043– 1.208; 1-year first rehospitalization due to heart failure: HR = 1.094; 95% CI, 1.032– 1.158; 2-year first rehospitalization due to heart failure: HR = 1.088; 95% CI, 1.033– 1.147, all P < 0.05). One-year change in left ventricular end-diastolic diameter was correlated with the risk score (r = 0.305, P = 0.002). The model demonstrated modest ability in discriminating adverse events and left ventricular remodeling (all areas under the curve were 0.6– 0.7).Conclusion: The MAGGIC risk score was related to adverse events and left ventricular remodeling in dilated cardiomyopathy.Keywords: dilated cardiomyopathy, left ventricular remodeling, prognosis, risk model

Yanyu Zhang,1 Ning Huang,2 Jie Xu,3 Wei Zheng,3 Xing Cui3 1Department of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Clinical Laboratory Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of ChinaCorrespondence: Xing CuiDepartment of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250014, People’s Republic of ChinaTel/Fax +86 68616042Email cdz45@foxmail.comPurpose: Homoharringtonine (HHT) has been used as an antileukemia agent in the clinic which processes a high-potential therapeutic efficacy against multiple myeloma (MM). In this study, we investigated the antimyeloma mechanism of HHT.Methods: Three MM cell lines and a xenograft model were applied. Mitochondrial function was evaluated by detecting MitoTracker Green, the mtDNA copy number, mitochondrial protein and enzyme activity, the mitochondrial membrane potential and mitochondrial morphology. Mitophagy levels were assessed by monitoring autophagosomes, performing a colocalization analysis and determining the levels of related proteins. An shRNA was applied to knockdown Parkin.Results: Based on the results of the in vitro experiments, HHT exerted a promising antiproliferative effect on the MM.1S, RPMI 8226 and H929 cell lines by increasing mitophagy. In addition, HHT markedly inhibited myeloma tumor growth and prolonged survival by promoting mitophagy in vivo. Furthermore, HHT treatment contributed to notable mitochondrial dysfunction and Parkin-dependent mitophagy, as evidenced by the destruction of mitochondria, the decrease in the mtDNA copy number, decrease in the Bcl-2/Bax ratio, and decrease in the levels of mitochondrial proteins and the optimal expression of Parkin and NDP52. However, the addition of rapamycin did not produce significant synergistic effect with HHT, indicating that HHT reached the threshold level to induce mitophagy. The colocalization analysis and assessment of mitochondrial function examination further confirmed that HHT triggered mitophagy and mitochondrial dysfunction. Moreover, the antiproliferative effect of HHT was reversed by an shRNA targeting Parkin, highlighting the indispensable role of Parkin-dependent mitophagy in the antimyeloma effect of HHT.Conclusion: HHT exerts an antimyeloma effect by inducing excess mitophagy, providing new mechanistic insights into a therapeutic strategy for MM.Keywords: homoharringtonine, multiple myeloma, mitophagy, Parkin, mitochondrial dysfunction

Le-jing Lian,1 Bin Lin,2 Xiao Cui,1 Jie He,1 Zhe Wang,1 Xiao-dong Lin,1 Wei-jian Ye,1 Rui-jie Chen,1 Wei Sun1 1Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, People’s Republic of China; 2Department of Clinical Pharmacy, Changxing People’s Hospital, Changxing 313100, People’s Republic of ChinaCorrespondence: Wei Sun; Rui-jie Chen Tel +8613968803162; +8613806890233Email 33sunwei@163.com; crj@wzhealth.comPurpose: Precise and timely detection of methotrexate (MTX) concentration played a key role in high-dose MTX individualization therapy in acute lymphoblastic leukemia (ALL) children to avoid serious adverse effects or nonresponse. This report described a sensibility and validation of ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for therapeutic drug monitoring (TDM) of methotrexate concentration in children’s plasma.Methods: One-step protein precipitation of samples was accomplished by adding 200 μL of acetonitrile to 100 μL of plasma sample. The separation of plasma samples was carried out on a ZORBAX Eclipse Plus C18 Rapid Resolution HD column with gradient elution using a mobile phase constituted of acetonitrile and 1% formic acid. The detection was executed by electrospray ionization (ESI) of triple quadrupole tandem mass spectrometer (TQMS) in the multiple reaction monitoring (MRM) mode with the transitions m/z 455.2 → 307.9 for methotrexate and m/z 458.2 → 311.2 for IS, separately. Linear concentration range of the calibration curve was 44– 11,000 nmol/L and 44 nmol/L was the lower limit of quantification.Results: The methotrexate elution time was at 1.577 min, and the overall running time was only 3.3 min. The intra- and interday precision for all the analysis results was within 11.24%, and mean recoveries rate of methotrexate exceeded 87.98%.Conclusion: The described and fully validated UHPLC-MS/MS method was successfully applied in clinical TDM after infusion of high-dose methotrexate 1– 5 g/m2 to 41 childpatients.Keywords: high-dose methotrexate, UHPLC-MS/MS, therapeutic drug monitoring, children, acute lymphoblastic leukemia