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Jingjing Li,1 Yu Zhang,2 Rui Wu,1 Guodong Ma,1 Li Sheng,1 Yun Feng,1 Yang Han,1 Lina Zhang,1 Janfeng Guo,1 Rongbo Li1 1Department of Infectious Diseases, Hohhot First Hospital, Hohhot, Inner Mongolia Autonomous Region, 010000, People’s Republic of China; 2Department of Dermatology and Venereology, Hohhot, Inner Mongolia Autonomous Region People’s Hospital, 010000, People’s Republic of ChinaCorrespondence: Jingjing Li, Department of Infectious Diseases, Hohhot First Hospital, No. 148, South Second Ring Road, Zhaojun Road, Yuquan District, Hohhot, Inner Mongolia Autonomous Region, 010000, Tel +86-18047422188, Email 1151664990@qq.comPurpose: To explore the value of different inflammatory markers in predicting the severity of coronavirus disease 2019 (COVID-19) in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 116 patients with COVID-19 in patients with T2DM were collected from December 2022 to March 2023 and were divided into a mild case group (77 cases) and a severe case group (39 cases). The ratio of neutrophil to lymphocyte (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil to lymphocyte × platelet ratio (NLPR), lymphocyte ratio to monocyte (LMR), systemic inflammatory response index (SIRI), systemic inflammatory index (SII), systemic inflammatory composite index (AISI), procalcitonin (PCT), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were compared between the two groups. The screening effect of each variable on the progression of the disease was analyzed using receiver operating characteristic (ROC) curves.Results: NLR, PLR, NLPR, MLR, SIRI, SII, AISI, LDH, CRP and PCT in severe case group were higher than those in mild case group (P< 0.05), and LMR was lower than those in mild case group (P< 0.05). ROC curve analysis further demonstrated the diagnostic performance of these biomarkers, with PCT having the largest area under the ROC curve (AUCROC) of 0.83.Conclusion: NLR, PLR, NLPR, SIRI, SII, LDH, CRP and PCT demonstrate greater reliability in diagnostic value and clinical utility for predicting the severity of COVID-19 in patients with T2DM.Keywords: COVID-19, T2DM, inflammatory index, LDH, CRP, PCT

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

Yue Xu,1,&ast; Shuhong Zhang,1,&ast; Ping Wang,1,&ast; Yuanyuan Chen,1 Yazhan Mao,2 Xina Yuan,3 Yinyi Li,4 Mingming Li,1 Li Sheng,1 Xiaoqian Li,1 Na Gao1 1Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Respiratory, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 3College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 4Department of Outpatient, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na Gao; Xiaoqian Li, Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China, Tel +86 18515165409, Email gaona301s@163.com; 41705763@qq.comObjective: This study aims to explore the correlates of frailty in hospitalized elderly hypertensive patients and its impact on clinical prognosis, and to construct a predictive model for the occurrence of frailty in this population.Methods: A cross-sectional and prospective observational cohort study was conducted, involving 312 elderly hypertensive patients diagnosed at the institution from January to June 2022. Frailty was diagnosed using the Fried Frailty Phenotype (FP), while the Charlson Comorbidities Index (CCI) assessed the presence of chronic conditions. Data analysis was performed using SPSS 22.0. Binary logistic regression analysis was conducted with frailty as the dependent variable to identify risk factors. Patients were followed for one year to monitor readmission rates and all-cause mortality.Results: Multivariate logistic regression identified CCI grade (P=0.030), gender (OR=21.618, 95% CI: 4.062– 115.061, P < 0.001), age (OR=1.147, 95% CI: 1.086– 1.211, P < 0.001), bedridden state (OR=11.620, 95% CI: 3.282– 41.140, P < 0.001), arrhythmia (OR=14.414, 95% CI: 4.558– 45.585, P < 0.001), heart failure (OR=5.439, 95% CI: 1.029– 28.740, P < 0.05), along with several biochemical markers, as independent predictors of frailty. A predictive model was developed, demonstrating a robust discriminative ability with an area under the receiver operating characteristic curve (AUC) of 0.915. Statistically significant differences in readmission rates and all-cause mortality were observed among the frail, pre-frail, and non-frail groups (P< 0.001), with the frail group exhibiting the highest incidence of these adverse outcomes. Notably, frailty emerged as a significant predictor of readmission (P< 0.05) but not of all-cause mortality in this cohort.Conclusion: This study establishes a robust frailty prediction model for elderly hypertensive patients, highlighting the influence of CCI grade, gender, age, and other clinical and biochemical factors on frailty. The model offers a valuable tool for healthcare providers to identify at-risk elderly individuals, facilitating targeted intervention strategies for cardiovascular disease management.Keywords: frailty, hypertension, older people, observational study, prediction model

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

Zanzan Wang,&ast; Yurong Bao,&ast; Zhijuan Xu, Yongcheng Sun, Xiao Yan, Lixia Sheng, Guifang Ouyang Department of Hematology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guifang Ouyang, Department of Hematology, The First Affiliated Hospital of Ningbo University, No. 59 Liuting Street, Haishu District, Ningbo, Zhejiang, 315000, People’s Republic of China, Tel/Fax +86 57487085166, Email nbougf@163.comPurpose: This study aimed to examine the predictive ability of inflammatory and nutritional markers and further establish a novel inflammatory nutritional prognostic scoring (INPS) system.Patients and Methods: We collected clinicopathological and baseline laboratory data of 352 patients with DLBCL between April 2010 and January 2023 at the First affiliated hospital of Ningbo University. Eligible patients were randomly divided into training and validation cohorts (n = 281 and 71, respectively) in an 8:2 ratio. We used the least absolute shrinkage and selection operator (LASSO) Cox regression model to determine the most important factors among the eight inflammatory-nutritional variables. The impact of INPS on OS was evaluated using the Kaplan–Meier curve and the Log rank test. A prognostic nomogram was developed based on the multivariate Cox regression method. Then, we used the concordance index (C-index), calibration plot, and time-dependent receiver operating characteristic (ROC) analysis to evaluate the prognostic performance and predictive accuracy of the nomogram.Results: Seven inflammatory-nutritional biomarkers, including neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), body mass index (BMI), monocyte-lymphocyte ratio (MLR), prealbumin, C reactive protein, and D-dimer were selected using the LASSO Cox analysis to construct INPS, In the multivariate analysis, IPI-High-intermediate group, IPI-High group, high INPS were independently associated with OS, respectively. The prognostic nomogram for overall survival consisting of the above two indicators showed excellent discrimination. The C-index for the nomogram was 0.94 and 0.95 in the training and validation cohorts. The time-dependent ROC curves showed that the predictive accuracy of the nomogram for OS was better than that of the NCCN-IPI system.Conclusion: The INPS based on seven inflammatory-nutritional indexes was a reliable and convenient predictor of outcomes in DLBCL patients.Keywords: diffuse large B cell lymphoma, LASSO Cox analysis, inflammatory-nutritional biomarker, prognostic nomograms, overall survival

Lin Sheng,1– 4,&ast; Yumeng Wei,1,3,&ast; Chao Pi,1,3,&ast; Ju Cheng,3,4 Zhilian Su,1– 4 Yuanyuan Wang,1,5 Tao Chen,1– 4 Jie Wen,1– 4 Yuxun Wei,1– 4 Jingwen Ma,1– 4 Jia Tang,1– 4 Huiyang Liu,1– 4 Zerong Liu,6,7 Hongping Shen,8 Ying Zuo,9 Wenwu Zheng,10 Ling Zhao2– 4 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, People’s Republic of China; 2Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Clinical Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Central Nervous System Drug Key Laboratory of Sichuan Province, Sichuan Credit Pharmaceutical CO., Ltd. Luxian County, Luzhou City, People’s Republic of China; 7Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, People’s Republic of China; 8Clinical Trial Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 9Department of Comprehensive Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 10Department of cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenwu Zheng, Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 830 3165311, Email zhengwenwu888@163.com Ling Zhao, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 830 3160093, Email zhaoling@swmu.edu.cnPurpose: The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect.Methods: The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted.Results: The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC(0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the Cmax was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration.Conclusion: TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.Keywords: turmeric extract, curcuminoids, nanoemulsion, stability, antidepressant effect, 5-hydroxytryptamine

Yingjing Pan,1,&ast; Tianci Lin,1,&ast; Longquan Shao,2 Yulin Zhang,2 Qiao Han,3 Liyuan Sheng,4 Rui Guo,5 Ting Sun,1 Yanli Zhang2 1Foshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, 528225, People’s Republic of China; 2Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 3Stomatology Hospital of Guangzhou Medical University, Guangzhou, 510182, People’s Republic of China; 4Shenzhen Institute, Peking University, Shenzhen, 518057, People’s Republic of China; 5Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Sun, Foshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, 528225, People’s Republic of China, Email sun_ting1985@qq.com Yanli Zhang, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, People’s Republic of China, Email 541292702@qq.comPurpose: Puerarin is the main isoflavone extracted from Radix Puerariae lobata (Willd.) and exerts a strong protective effect on endothelial cells. This isoflavone also exerts proven angiogenic effects; however, the potential underlying mechanism has not been fully explored. Here in this work, we aimed to determine the proangiogenesis effect of a puerarin-attached lignin nanoparticle-incorporated hydrogel and explore the underlying mechanism.Materials and Methods: Puerarin-attached lignin nanoparticles were fabricated and mixed with the GelMA hydrogel. After the hydrogel was characterized, the angiogenic effect was evaluated in a mouse hind-limb ischemia model. To further explore the mechanism of angiogenesis, human endothelial cell line EA.hy926 was exposure to different concentrations of puerarin. Wound healing assays and tube formation assays were used to investigate the effects of puerarin on cell migration and angiogenesis. qPCR and Western blotting were performed to determine the changes in the levels of angiogenesis indicators, autophagy indicators and PPARβ/δ. 3-MA was used to assess the role of autophagy in the puerarin-mediated angiogenesis effect in vivo and in vitro.Results: The hydrogel significantly improved blood flow restoration in mice with hind-limb ischemia. This effect was mainly due to puerarin-mediated increases in the angiogenic capacity of endothelial cells and the promotion of autophagy activation. A potential underlying mechanism might be that puerarin-mediated activation of autophagy could induce an increase in PPARβ/δ expression.Conclusion: The puerarin-attached lignin nanoparticle-incorporated hydrogel effectively alleviated blood perfusion in mice with hind-limb ischemia. Puerarin has a prominent proangiogenic effect. The potential mechanisms might be that puerarin-mediated autophagy activation and increase in PPARβ/δ.Graphical Abstract: Keywords: puerarin, angiogenesis, autophagy, PPARβ/δ, vascular endothelial cell

Yajiao Liu,1,&ast; Li Sheng,1,&ast; Haiying Hua,1,2 Jingfen Zhou,1,2 Ying Zhao,2 Bei Wang3 1Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, 214000, People’s Republic of China; 2Department of Hematology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, 214000, People’s Republic of China; 3Institute of Integration of Traditional Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiying Hua, Hematology Department, Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Binhu District, Wuxi, Jiangsu Province, 214000, People’s Republic of China, Tel +86 15301516125, Email huahy007@163.comPurpose: We aimed to create a novel prognostic score, the inflammation-based prognosis score (IBPS). In addition, we attempted to establish and validate a nomogram to predict the overall survival (OS) of patients with DLBCL.Patients and Methods: We retrospectively investigated the data of 213 patients with DLBCL diagnosed and treated in the Affiliated Hospital of Jiangnan University and used these data to develop nomograms. At the same time, 89 patients diagnosed and treated in Wuxi People’s Hospital Affiliated with Nanjing Medical University from January 2015 to June 2021 were collected as an external validation cohort. We developed IBPS through the least absolute shrinkage and selection operator (LASSO) Cox regression. The univariate and multivariate Cox regression method was used to develop the nomogram. We used the concordance index (C-index), calibration chart, time-dependent receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and the Kaplan–Meier curve were used to assess the nomogram.Results: The systemic immune inflammation index (SII), prognostic nutrition index (PNI), and modified Glasgow prognostic score (mGPS) were used to construct IBPS. The Eastern Cooperative Oncology Group performance status (ECOG PS), IBPS, response to treatment, and whether accept surgery were used to construct the nomogram to predict the OS of DLBCL patients. The C-index in the training and validation cohorts were 0.844 and 0.828, respectively. According to the time-dependent ROC curve and DCA, the nomogram has good predictive accuracy and clinical net benefit. The Kaplan–Meier curve showed that according to the nomogram score, patients in the training and validation cohorts could be classified into three risk groups.Conclusion: In patients with DLBCL, baseline IBPS was a reliable predictor of OS. The survival probability of DLBCL patients can be precisely predicted using the prognosis nomogram based on IBPS.Keywords: diffuse large B-cell lymphoma, inflammatory indicators, overall survival, prediction model

Qin Zhang,1,&ast; Wenyi Wu,1,&ast; Lulu Sheng,1 Xuan Xi,1 Yuanke Zhou,1 Yi Wen,2 Qin Liu1 1School of Public Health, Research Center for Medicine and Social Development, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Liu, School of Public Health, Chongqing Medical University, No. 1 YixueyuanRoad, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-18623598789, Email liuqin@cqmu.edu.cnPurpose: To help firstborn children in families expecting a second child navigate the role transition more smoothly, we investigated the emotional and behavioral changes of firstborn children during the transition to siblinghood (TTS) and the factors that contribute to these changes.Patients and Methods: From March to December 2019, a total of 97 firstborn children (Mage=3.00± 0.97, and female = 51) were included in the study through a questionnaire survey of their mothers, and two follow-up visits were conducted in Chongqing, China. Individual in-depth interviews were conducted with 14 mothers.Results: Both quantitative and qualitative results suggest that emotional and behavioral problems of firstborn children tend to increase during TTS, particularly in issues such as anxiety/depression, somatic complaints, withdrawal, sleep problems, attention problems, and aggressive behavior, as well as internalization problems, externalization problems and total problems in the quantitative study (P< 0.05). A poor father-child relationship may increase emotional and behavioral problems in firstborn children (P=0.05). Further qualitative analysis found that younger age and outgoing personality of the firstborn child may improve the emotional and behavioral problems.Conclusion: The firstborn children did have more emotional and behavioral problems during TTS. But these problems can be regulated by family factors and their own characteristics.Keywords: emotion and behavior, transition to siblinghood, firstborn children, preschool, mixed method

Yuxun Wei,1– 4,&ast; Yumeng Wei,1– 4,&ast; Lin Sheng,1– 4 Jingwen Ma,1– 4 Zhilian Su,1– 4 Jie Wen,1– 4 Lanmei Li,5 Qiang Jia,2,6 Huiyang Liu,1– 4 Hui Si,2,4 Linjin Xiong,1– 4 Jinglin Chen,1– 4 Ju Cheng,3,4 Ying Zuo,2,7 Hongru Yang,8 Ling Zhao2– 4 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, People’s Republic of China; 2Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University; Luzhou, Sichuan, People’s Republic of China; 3Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Nanchong Key Laboratory of Individualized Drug Therapy, Department of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 6Ethics Committee Office, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of Comprehensive Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhao, Key Laboratory of Medical Electrophysiology, Ministry of Education, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Tel/Fax +86 830 3160093, Email zhaoling-998@163.com Hongru Yang, Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Tel/Fax +86 830 8585668, Email yanghongru801@126.comPurpose: The present study aimed to construct a co-loading platform encapsulating curcumin and paclitaxel at ratios of 2:1– 80:1 (w/w) designated “CU-PTX-LNP” and explored the synergistic effects of CU-PTX at different composite proportions on liver cancer cells using the combination index (CI) method.Methods: The CU lipid nanoplatform (CU-LNP) formulation was optimized via single-factor and orthogonal experiments. Various concentrations of PTX were added to the optimal formulation of CU-LNP to generate CU-PTX-LNP and the nanoplatform characterized via differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD), zeta potential, polydispersity index (PDI), and size analyses. The cumulative release, stability, and cytotoxicity of CU-PTX-LNP in LO2, HepG2, and SMMC-7221 cells were assessed in vitro, followed by safety investigation and pharmacokinetic studies in vivo. The anti-tumor activity of CU-PTX-LNP was also evaluated using nude mice.Results: CU-PTX-LNP formulations containing CU:PTX at a range of proportions (2:1– 80:1; w/w) appeared as uniformly dispersed nanosized spherical particles with high entrapment efficiency (EE> 90%), sustained release and long-lasting stability. Data from in vitro cytotoxicity assays showed a decrease in the IC50 value of PTX of CU-PTX-LNP (by 5.47– 332.7 times in HepG2 and 4.29– 143.21 times in SMMC-7221 cells) compared to free PTX. In vivo, CU-PTX-LNP displayed excellent biosafety, significant anti-tumor benefits and enhanced pharmacokinetic behavior with longer mean residence time (MRT(0-t); CU: 4.31-fold, PTX: 4.61-fold) and half-life (t1/2z; CU: 1.83-fold, PTX: 2.28-fold) relative to free drugs.Conclusion: The newly designed CU-PTX-LNP platform may serve as a viable technological support system for the successful production of CU-PTX composite preparations.Keywords: curcumin, paclitaxel, lipid nano platform, synergistic effect

Juan Wu,1,2 Hongrong Xu,1 Hui Li,1 Lei Ma,3 Juan Chen,3 Fei Yuan,1 Lei Sheng,1 Chao Liu,1 Weili Chen,1 Xuening Li1 1Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Pharmacy, Shanghai Children’s Medical Center, School of Medicine, Shanghai JiaoTong University, Shanghai, People’s Republic of China; 3Haihe Biopharma Co., Ltd, Shanghai, People’s Republic of ChinaCorrespondence: Xuening Li, Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan University, 180 Fenglin Road, Shanghai, People’s Republic of China, 200032, Tel +86 21 3158 7860, Fax +86 21 3158 7866, Email li.xuening@zs-hospital.sh.cnObjective: This study aimed to investigate the effect of food on the pharmacokinetics and safety profiles of SCC244, a novel oral c-Met inhibitor in healthy Chinese male subjects.Methods: It was a randomized, open-label, and 3-period crossover design, single-dose phase I clinical trial. A total of 18 healthy male subjects were enrolled. These subjects received a single oral 300 mg dose of SCC244 with a 14-day washout between each period. Blood samples were collected at the designated time points and determined using a validated liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters were calculated by noncompartmental methods. Tolerability was assessed by physical examination, vital sign measurements, 12-lead ECG, clinical laboratory tests, and adverse events (AEs) monitoring throughout the study.Results: Eighteen eligible subjects were enrolled in the study. The ratios (90% CI) of Cmax values for SCC244 in high-fat and low-fat meal states to that observed in fasted state were 194.8% (174.3– 217.7%) and 194.6% (174.1– 217.5%), respectively. The ratios of AUC0-t and AUC0-inf in the high-fat meal state versus the fasted state were 237.4% (208.7– 270.0%) and 235.9% (207.5– 268.3%), respectively. The ratios of AUC0-t and AUC0-inf in the low-fat meal state versus the fasted state were 219.2% (192.7– 249.3%) and 218.3% (192.0– 248.3%), respectively. Median Tmax values and mean t1/2 were similar in all groups. The most common AEs were headache, blood fibrinogen decreased, head discomfort, dizziness, and protein urine presence. All AEs were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 (except 1 case of grade 2) and have resolved by the end of the study.Conclusion: The bioavailability of the tablet formulation of SCC244 was significantly increased when administered with high- and low-fat meals. However, the meals did not affect the median Tmax and t1/2. Safety under different fed conditions was comparable to fasted conditions in this study.Keywords: SCC244, c-Met inhibitor, food effect, pharmacokinetics, safety

Fengzhen Yang, Lipeng Wang, Qi Zhao, Jinying Wu, Lihua Jiang, Li Sheng, Leyan Zhang, Zhaoping Xue, Maoli Yi Department of Laboratory Medicine, Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital, Yantai, People’s Republic of ChinaCorrespondence: Maoli Yi, Department of Laboratory Medicine, Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital, 20# Yuhuangding East Road, Zhifu District, Yantai, Shandong Province, 264000, People’s Republic of China, Tel +86-0535-6691999-81505, Email yimaoli76@163.comPurpose: To investigate the epidemiological features of Klebsiella pneumoniae infection of the hepatobiliary system of patients in Yantai, China.Methods: This retrospective study was conducted from January to December 2019 in Yantai Yuhuangding Hospital. Patients for whom K. pneumoniae was isolated from the hepatobiliary system were considered for inclusion. The clinical features and genetic analyses were conducted to explore the epidemiological characteristics.Results: A total of 88 cases were enrolled, including 69 cases of hypervirulent K. pneumoniae (hvKP) and 19 cases of classical K. pneumoniae (cKP). Community-acquired infections, fever, liver abscess, and C-reactive protein (CRP) and procalcitonin (PCT) levels were significantly higher, while biliary tract disease was lower in the hvKP group compared with the cKP group. Among the 69 hvKP infections, 61 developed a liver abscess. Community-acquired infections, fever, and CRP and PCT levels were higher, whereas biliary tract disease and malignancy were lower in the liver abscess group compared with the non-liver abscess group. All strains were susceptible to the majority of antibiotics tested. All hvKP strains possessed the blaSHV, oqxA, oqxB and fosA resistance genes. K1 and K2 accounted for 78% of hvKP strains. K1 strains belonged to sequence types ST23 and ST700, whereas K2 strains belonged to ST65, ST86 and ST5212. K1 isolates possessed the most virulence determinants, followed by K2 and non-K1/K2 isolates. K2 isolates lacked the allS gene, which was rare in non K1/K2 isolates, but present in most K1 isolates. The mceG gene was only detected in K1 isolates. AllS and virulence determinants were significantly more prevalent in the liver abscess group than in the non-liver abscess group.Conclusion: The prevalence of hvKP among K. pneumoniae infections of the hepatobiliary system is high in Yantai, China. Greater vigilance of hvKP infection is required in clinical and microbiological laboratories.Keywords: liver abscess, Klebsiella pneumoniae, genome sequencing, virulence determinant, serotype

Nan Liu, Bo Chen, Luchuan Li, Qingdong Zeng, Lei Sheng, Bin Zhang, Weili Liang, Bin Lv Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Bin LvDepartment of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaEmail lvbin@sdu.edu.cnBackground: Recurrent laryngeal nerve injury (RLNI) still occurs in total endoscopic thyroidectomy (TET) by using intraoperative neuromonitoring (IONM). As the region where most injuries occur, more attention should be paid to RLNI near the nerve entry point (NEP) in TET.Materials and Methods: This cohort study collected retrospectively data from 415 patients who underwent TET between February 2012 and December 2019. The functions of the recurrent laryngeal nerve (RLN) in TET were recorded by IONM. The patients with RLNI near the NEP were followed up by laryngoscopies. The demographic and clinical characteristics, the mechanisms of RLNI, and the outcomes of RLNI were recorded and analyzed.Results: There were a total of 444 at-risk nerves in 405 patients were analyzed. The incidence of RLNI near the NEP was 7.9%. RLNs with extralaryngeal branches were more likely to be injured near the NEP (P = 0.037). The incidences of different types of RLNI, in order of frequency, were 68.8% for thermal injury (n = 22), 28.1% for traction/compression injury (n = 9), and 3.1% for transverse injury (n = 1). A total of 93.8% (n = 30) of RLNI patients had complete recovery of vocal cord activity function.Conclusion: The extralaryngeal branch was a risk factor for RLNI near the NEP in TET. Thermal injury caused by an ultrasonic scalpel was the most common cause of RLNI near the NEP. Most RLNIs near the NEP would eventually recover.Keywords: thyroid surgery, total endoscopic thyroidectomy, recurrent laryngeal nerve injury, intraoperative neuromonitoring, recovery time

Nan Liu, Bo Chen, Luchuan Li, Qingdong Zeng, Lei Sheng, Bin Zhang, Bin Lv Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People’s Republic of ChinaCorrespondence: Bin LvDepartment of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People’s Republic of ChinaEmail lvbin@sdu.edu.cnPurpose: Papillary thyroid carcinoma (PTC) has a high incidence of lymph node metastasis (LNM). Our aim was to determine whether tumor location is a useful feature to predict bilateral central lymph node metastasis (CLNM) in unilateral 1– 4 cm PTC.Patients and Methods: Data on unilateral 1– 4 cm PTC patients from 2016 to 2019 were collected retrospectively. The clinical and pathological characteristics of the tumors and lymph nodes were analyzed statistically.Results: The mean patient age was 49.1± 12.3 (23– 73) years, and the majority were women (n=1334, 75.4%). A total of 1767 patients were analyzed, and 256 (14.5%) had bilateral CLNM. Tumor location was an independent risk factor in predicting bilateral CLNM (p< 0.001). The odds of bilateral CLNM were the highest in the near isthmus (OR 6.452, 95% CI: 3.658– 11.379, p< 0.001). In a multivariate regression model adjusting for other risk factors, near-isthmus tumors had the highest risk of bilateral CLNM (OR 7.319, 95% CI: 3.844– 13.933, p< 0.001), followed by lower lobe tumors (OR 2.338, 95% CI: 1.315– 4.155, p=0.004) and middle lobe tumors (OR 1.845, 95% CI: 1.035– 3.291, p=0.038), compared to upper lobe tumors.Conclusion: Tumor location is an independent risk factor in predicting the risk of bilateral CLNM. Near-isthmus tumors carry the highest risk of bilateral CLNM.Keywords: papillary thyroid carcinoma, location, predictive factor, lymph node metastasis

Liguang Zhou,1 Gang Chen,2 Lei Sheng,3 Nan Liu,3 Bin Zhang,3 Qingdong Zeng,3 Bo Chen3 1Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of General Surgery, Shandong Guoxin Healthcare Group Xinwen Center Hospital, Taian, People’s Republic of China; 3Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of ChinaCorrespondence: Bo ChenDepartment of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, People’s Republic of ChinaTel + 86-531-82165383Email chenbo_780721@hotmail.comPurpose: To analyze the effect of Hashimoto’s thyroiditis (HT) concurrent with papillary thyroid cancer (PTC) on cervical lymph node metastasis (LNM).Methods: Two thousand nine hundred twenty-six patients who underwent thyroidectomy and lymph node dissection between January 2015 and December 2018 were enrolled in this study. Patient demographics and clinicopathologic features were analyzed.Results: Of the total enrolled patients, 598 (20.4%) had concurrent HT. There were 1482 PTC cases with N0, 1033 cases with N1a, and 411 cases with N1b. Patients with HT had lower frequency of extrathyroidal extension (ETE), lymphatic vascular (LV) invasion, high pathological T stage (III+IV) and central LNM rate. Stratifying central LNM by non-ETE or without intrathyroidal spreading, it was further found that central LNM rate in patients with HT was lower than that of patients without HT. However, there was no significant difference in the central LNM rate in patients with PTC stratified by ETE or intrathyroidal spreading. HT with PTC played a weak protective role in N1a, reducing the risk of N1a by 16.4%. Conversely, HT is a risk factor for N1b, increasing the risk by 1.336 times compared to patients without HT. TgAb is an independent risk factor for N1b, which appears related to the promotion of N1b by HT.Conclusion: In PTC, HT has a protective effect on central LNM and a risk effect on lateral LNM, although the difference was not significant. This weak protective effect on N1a is more obvious in PTC with less aggressive clinicopathologic characteristics. The risk effect of HT on N1b may be associated with TgAb.Keywords: Hashimoto’s thyroiditis, papillary thyroid cancer, lymph node metastasis, influence factor, extrathyroidal extension, intrathyroidal spreading

Lei Sheng,1,* Wei Cao,2,* Pingping Lin,3 Weili Chen,1 Hongrong Xu,1 Chunjiu Zhong,4 Fei Yuan,1 Hanjing Chen,1 Hui Li,1 Chao Liu,1 Mengjie Yang,1 Xuening Li1 1Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Shanghai Rixin Biotechnology Co., Ltd, Shanghai, 200237, People’s Republic of China; 3Phase I Clinical Research Center, The Affiliated Hospital of Qingdao University, Shandong, 266071, People’s Republic of China; 4Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuening LiDepartment of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, People’s Republic of ChinaTel +86 21 3158 7860Fax +86 21 6443 7963Email li.xuening@zs-hospital.sh.cnPurpose: Safety, tolerability and pharmacokinetics of single and multiple ascending doses (SADs/MADs) of benfotiamine were assessed after oral administration in two randomized, double-blind, placebo-controlled, phase I trials.Methods: Healthy subjects were sequentially enrolled into one of five SAD (150– 1200 mg) or three MAD (150, 300 or 600 mg) cohorts. In SAD study, each cohort of 12 subjects (n = 10, active; n = 2, placebo) were administrated once-daily doses. In MAD study, each cohort of 16 subjects (n = 12, active; n = 4, placebo) were administrated once-daily on day 1 and twice-daily on day 4– 9, followed by a single morning dose on day 10.Results: In the SAD study, the median time to reach maximum concentration (Tmax) arrived 1.0 to 2.0 h for thiamine (TM), 3.5 to 8.0 h for thiamine monophosphate (TMP), and 8.0 to 24.0 h for thiamine diphosphate (TDP) after administration of benfotiamine. The area under concentration-time curve from 0 to last measurable concentration (AUC0-t) or maximum observed concentration (Cmax) of TM, TMP, and TDP was less or more dose proportional over the single dose studied except Cmax of TM. Food consumption did not increase the level of TM and TDP at baseline. TM exhibited a relatively long elimination half-life (t1/2) in all doses studied, resulting in accumulation ratio (Rac) of 1.96 to 2.11 and accumulation ratio based on Cmax (Rac, Cmax) of 1.60 to 1.88 following 7 days of multiple dosing. Comparable accumulation results were also obtained for TDP after multiple dosing. The incidence and severity of adverse events (AEs) were similar between benfotiamine and placebo. The commonly reported drug-related AEs were increased ALT and urinary WBC.Conclusion: Both SAD and MAD studies of benfotiamine in healthy subjects were safe and well tolerated. TM and TDP exhibited moderate accumulation on repeated administration of benfotiamine.Keywords: Alzheimer’s disease, benfotiamine, thiamine, thiamine diphosphate, pharmacokinetics

Weili Liang,1 Lei Sheng,1 Liguang Zhou,2 Changyuan Ding,1 Zhongyang Yao,1 Chao Gao,1 Qingdong Zeng,1 Bo Chen1 1Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Bo ChenDepartment of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, People’s Republic of ChinaTel +86 18560085112Email chenbo_780721@hotmail.comPurpose: Papillary thyroid carcinoma (PTC) in children and adolescents is prone to lateral lymph node metastasis (LNM), which is a high-risk factor for recurrence. However, few studies focused on identifying risk factors and establishing prediction models for lateral LNM of PTC in children and adolescents.Patients and Methods: We retrospectively reviewed consecutive cases of children and adolescents with PTC undergoing thyroidectomy and cervical lymph node dissection between January 2009 and December 2019. The demographics and clinicopathologic features were collected and analyzed.Results: A total of 102 children and adolescents with PTC were enrolled in our study; 51 of whom had lateral LNM (50%). After adjusting for other risk factors, the independent risk factors for lateral LNM were multifocality (odds ratio [OR]: 6.04; 95% confidence interval [CI]: 1.653– 22.092; p=0.007), tumor size (OR: 1.752; 95% CI: 1.043– 2.945; p=0.034), and the number of central LNM (OR: 1.23; 95% CI: 1.028– 1.472; p=0.023). The formula of the combined predictor is: Multifocality + 0.31 × Tumor size + 0.115 × Number of central LNM. The area under the receiver operating characteristic curve of multifocality, tumor size, number of central LNM, and the combined predictor was 0.706, 0.762, 0.748, and 0.855, respectively. When the value of the combined predictor was ≥ 2.2744, lateral LNM could be predicted. The sensitivity and specificity of the predicted value were 82.4% and 74.5%, respectively.Conclusion: The independent risk factors for lateral LNM in children and adolescents with PTC were multifocality, tumor size, and the number of central LNM. The prediction model can better predict the presence of lateral LNM.Keywords: papillary thyroid cancer, lymph node metastasis, risk factor, prediction model, pediatric surgery

Nan Liu,1 Yupeng Yang,2 Bo Chen,1 Luchuan Li,1 Qingdong Zeng,1 Lei Sheng,1 Bin Zhang,1 Weili Liang,1 Bin Lv1 1Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, People’s Republic of China; 2Department of Thyroid Surgery, Jinan Zhangqiu District Hospital of TCM, Jinan 250200, Shandong, People’s Republic of ChinaCorrespondence: Bin LvDepartment of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, People’s Republic of ChinaEmail lvbin@sdu.edu.cnPurpose: Papillary thyroid carcinomas (PTCs) frequently metastasize to the central neck compartment. Therapeutic central compartment neck dissection (CCND) is a well-established treatment for PTC nodal metastases; however, the extent to which therapeutic CCND should be performed remains controversial. In this study, we investigated the predictive risk factors for contralateral paratracheal lymph node metastasis (LNM) in unilateral cT1N1a or cT2N1a PTC.Patients and Methods: In this case–control study, which was conducted at a single center, demographic and pathological data from unilateral cT1N1a or cT2N1a PTC patients were collected from January 2017 to March 2019. All patients were treated with total thyroidectomy and bilateral CCND.Results: Two hundred thirty-seven patients met the inclusion criteria. Forty-nine patients (20.7%) were diagnosed with positive lymph nodes in the contralateral paratracheal region. Male sex (p=0.003), T2 disease (21– 40 mm) (p< 0.001), inferior pole tumor (p=0.011), near isthmus tumor (p< 0.001), aggressive pathology (p< 0.001), intraglandular dissemination (p=0.009), pretracheal LNM (p< 0.001), > 5 metastatic lymph nodes (p< 0.001) and extranodal invasion (p=0.003) were significantly associated with contralateral paratracheal LNM in univariate analysis. Multivariate analysis showed that male sex (p=0.005, OR=17.545), T2 disease (p=0.003, OR=34.317), inferior pole tumor (p=0.022, OR=8.289), near isthmus tumor (p=0.001, OR=40.229), aggressive pathology (p=0.027, OR=48.063), pretracheal LNM (p=0.002, OR=14.235) and > 5 metastatic lymph nodes (p=0.025, OR=23.426) were independent risk factors for contralateral paratracheal LNM.Conclusion: Male sex, T2 disease, a tumor located near the isthmus or inferior pole, aggressive pathology, pretracheal LNM and > 5 metastatic lymph nodes were predictive factors for contralateral paratracheal LNM in unilateral cT1N1a or cT2N1a PTC. These data may be useful to identify targets for surveillance or develop therapeutic interventions for patients with CCND.Keywords: papillary thyroid carcinoma, central compartment neck dissection, predictive factor, lymph node metastasis

Yiping Zhu,1 Kai Li,2 Jieling Zhang,2 Lu Wang,1 Lili Sheng,1 Liang Yan2 1Department of Oncology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China; 2Provincial Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, Anhui, People’s Republic of ChinaCorrespondence: Lili Sheng; Liang Yan Email 13605535185@163.com; yane2002@126.comIntroduction: Although the survival rate of colorectal cancer (CRC) patients can be improved by surgery, radiotherapy, and chemotherapy, the resistance to 5-fluorouracil (5-Fu) affects the effect of chemotherapy and the prognosis of patients. An increasing number of studies showed that 5-Fu resistance was the main reason for the failure of colorectal cancer treatment. The poor prognosis of colorectal cancer greatly harms people’s health. This study aimed to clarify the correlation between cyclin-dependent kinase 1 (CDK1) and 5-Fu-induced tumor resistance.Materials and Methods: Cell proliferation and invasion experiments showed that down-regulation of CDK1 inhibited fluorouracil-resistant CRC cell proliferation. The expression level of CDK1 was detected in 5-Fu-resistant CRC cells in vitro. Tumor growth was inhibited by down-regulation of CDK1 in tumor xenograft mouse models.Results: We found that CDK1 was highly expressed in tumor tissues, especially in fluorouracil-resistant tissues. We also confirmed that the differential expression of 5-Fu in tumor tissues was related to tumor site, lymph node metastasis and stage. CDK1 promoted migration, invasion and inhibited apoptosis in 5-Fu-resistant CRC cells. Down-regulation of CDK1 inhibited fluorouracil-resistant CRC cell proliferation and tumorigenesis in vivo.Conclusion: High expression of CDK1 may lead to poor clinical prognosis, and inhibition of CDK1 enhances 5-Fu sensitivity in CRC. Our research suggested that CDK1 may be used to predict 5-Fu efficacy and as a therapeutic target for CRC.Keywords: CDK1, colorectal cancer, 5-Fu, drug resistance

Lijuan Sheng,1 Lihong Yin,1 Dezhen Peng,1 Liping Zhao2 1Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Department of Nursing, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaCorrespondence: Liping ZhaoDepartment of Nursing, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaTel/ Fax +86 731-8529-4072Email zhaolp0818@csu.edu.cnBackground: Best evidence regarding enteral nutrition from continuous nasal feeding in stroke patients is limited. The aim of this study was to explore the best evidence of continuous nasal feeding in stroke patients and translate the evidence into clinical practice.Methods: This study utilized the standard procedures of the Joanna Briggs Institute (JBI) evidence-based nursing centers’ clinical evidence-practice application system. The baseline assessment of stroke patients in the neurology ward was conducted. A pre- and post-implementation audit approach was used in this study and adopted the Getting Research into Practice program. We analyzed the compliance of nurses with best practice and its impact on patients’ gastrointestinal function and complications, aspiration, aspiration pneumonia, nurses’ daily workload of nasal feeding, and the length of hospitalization before and after implementing the evidence-based strategies.Results: After application of the evidence-based strategies, nurses’ compliance with best practice was improved. The incidence of patients’ gastrointestinal complications including vomit (χ 2 = 5.195, P=0.023), palirrhea (χ 2 = 4.216, P=0.039), diarrhea (χ 2 = 4.514, P=0.042), constipation (χ 2 = 5.535, P=0.035) and gastric retention (χ 2 = 4.541, P=0.042) decreased significantly after the application of the best evidence. The working time of nurses undergoing nasal feeding decreased from 23.71 ± 3.22 min to 7.73 ± 1.14 min (P =0.000) and the length of patient’s hospitalization decreased from 35.63 ± 4.45 days to 35.00 ± 3.70 days (P=0.534). The rate of aspiration, aspiration pneumonia did not show a significant difference after implementation of the evidence-based strategies.Conclusion: The results revealed that the evidence-based practice of continuous nasal feeding in stroke patients is an effective method to improve nursing quality and reduce gastrointestinal complications, which was worthy of clinical application.Keywords: stroke, nasal feeding, evidence-based nursing, best evidence, complications

Ling Chen,1 Li Guo,2 Ziwen Sun,3 Guochun Yang,4 Jing Guo,5 Kai Chen,6 Ruixue Xiao,7 Xigui Yang,1 Lijun Sheng1 1Department of Oncology, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Clinical Laboratory, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Department of Scientific Research and Education, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Department of Emergency Medicine, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 5Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 6The Department of Cardiovascular and Thoracic Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 7Department of Pathology, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Lijun Sheng Email shenglijun328@126.comObjective: Monoamine oxidase A (MAO-A) is a mitochondrial protein involved in tumourigenesis in different types of cancer. However, the biological function of MAO-A in gastric cancer development remains unknown.Methods: We examined MAO-A expression in gastric cancer tissues and in gastric cancer cell lines by immunohistochemistry and Western blot analyses. CCK8, FACS and bromodeoxyuridine incorporation assays were performed to assess the effects of MAO-A on gastric cancer cell proliferation. The role of MAO-A in mitochondrial function was determined through MitoSOX Red staining, ATP generation and glycolysis assays.Results: In the present study, we observed that MAO-A was significantly upregulated in gastric cancer tissues and in AGS and MGC803 cells. The observed MAO-A inhibition indicated decreased cell cycle progression and proliferation. Silencing MAO-A expression was associated with suppressed migration and invasion of gastric cancer cells in vitro. Moreover, alleviated mitochondrial damage in these cells was demonstrated by decreased levels of mitochondrial reactive oxygen species and increased ATP generation. MAO-A knockdown also regulated the expression of the glycolysis rate-limiting enzymes hexokinase 2 and pyruvate dehydrogenase. Finally, we observed that the glycolysis-mediated effect was weakened in AGS and MGC803 cells when MAO-A was blocked.Conclusion: The findings of the present study indicate that MAO-A is responsible for mitochondrial dysfunction and aerobic glycolysis, which in turn leads to the proliferation and metastasis of human gastric tumour cells.Keywords: monoamine oxidase A, mitochondrial dysfunction, gastric cancer, glycolysis

Wanren Peng,1,* Fenglin Zhang,2,* Zishu Wang,3,* Dongliang Li,4,* Yifu He,5,* Zhongliang Ning,6 Lili Sheng,7 Jidong Wang,8 Xiaoyang Xia,9 Changjun Yu,10 Zian Wang,3 Yong Zhao,11 Hui Liang,12 Bing Hu,13 Cuiling Sun,14 Daoqin Wang,15 Yunsheng Cheng,16 Ming Pan,17 Liming Xia,18 Xinglai Guo,19 Yanshun Zhang,20 Zhiqiang Hu,21 Xinzhong Li,22 Lin Lu,23 Jun Zhang,24 Hong Qian,8 Hua Xie,25 Guoping Sun1,* 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People’s Republic of China; 2Department of Oncology, People’s Hospital of Maanshan City, Maanshan, Anhui 243000, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, People’s Republic of China; 4Department of Gastrointestinal Surgery, People’s Hospital of Lu’an City, Lu’an, Anhui 237005, People’s Republic of China; 5Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei, Anhui 230022, People’s Republic of China; 6Department of Gastrointestinal Surgery, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei, Anhui 230022, People’s Republic of China; 7Department of Oncology, Yijishan Hospital of WanNan Medical College, Wuhu, Anhui 340202, People’s Republic of China; 8Department of Oncology, The Navy Anqing Hospital, Anqing, Anhui 246003, People’s Republic of China; 9Department of Oncology, The First People’s Hospital of Chuzhou City, Chuzhou, Anhui 239000, People’s Republic of China; 10Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People’s Republic of China; 11Department of Oncology, People’s Hospital of Lu’an City, Lu’an, Anhui 237005, People’s Republic of China; 12Department of Oncology, Lu’an Hospital of Traditional Chinese Medicine, Lu’an, Anhui 237006, People’s Republic of China; 13Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230022, People’s Republic of China; 14Department of Oncology, People’s Hospital of Fuyang City, Fuyang, Anhui 236047, People’s Republic of China; 15Department of Gastrointestinal Surgery, Wanbei Coal-Electricity Group General Hospital, Suzhou, Anhui 234000, People’s Republic of China; 16Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, People’s Republic of China; 17Department of Oncology, People’s Hospital of Chizhou City, Chizhou, Anhui 247000, People’s Republic of China; 18Department of Oncology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, People’s Republic of China; 19Department of Oncology, Fuyang Cancer Hospital, Fuyang, Anhui 236033, People’s Republic of China; 20Department of Oncology, Huainan First People’s Hospital, Huainan, Anhui 232000, People’s Republic of China; 21Department of Oncology, Huaibei Miners General Hospital, Huaibei, Anhui 235000, People’s Republic of China; 22Department of Oncology, People’s Hospital of Huaibei, Huaibei, Anhui 235000, People’s Republic of China; 23Department of Oncology, The 901 Hospital of the Joint Logistic Support Force of the People’s Liberation Army of China, Hefei, Anhui 230033, People’s Republic of China; 24Department of Oncology, The Second People’s Hospital of Wuhu, Wuhu, Anhui 241001, People’s Republic of China; 25Department of Oncology, The People’s Hospital of Xuancheng City, Xuancheng, Anhui 242000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoping Sun Email sungp@ahmu.edu.cnBackground: In China, gastric cancer (GC) ranks second in incidence and mortality. Over 80% of patients with GC were diagnosed at an advanced stage with poor clinical outcome. Chemotherapy was the mainstream treatment with limited benefit. Apatinib, an inhibitor of targeting vascular endothelial growth factor receptor 2 (VEGFR2), has been approved for third-line treatment of advanced gastric cancer. However, the data of apatinib treatment in the real-world setting are limited. In this real-world study, we aimed to understand the current treatment pattern of apatinib, investigate the effectiveness and safety of apatinib in real-world settings, and explore the potential factors associated with the clinical outcomes.Methods: This was a prospective, multicenter observational study in a real-world setting. Patients aged ≥ 18 years with histologic diagnosis of advanced GC were eligible for enrollment. The eligible patients received either apatinib monotherapy or apatinib plus chemotherapy by physician’s discretion. Apatinib treatment could be used as first-line, second-line, or third-line and above therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), ORR, DCR, and safety profile.Results: A total of 737 patients with advanced gastric cancer treated with apatinib were included in the FAS population. A total of 54.9% patients used apatinib monotherapy and 45.1% patients used apatinib combination therapy. A total of 44.1% patients received apatinib in first-line treatment, 28.2% in second-line, and 27.7% in third-line and above. In first-line treatment, the objective response rate (ORR) was 9.09% and 16.42% in apatinib monotherapy and combination therapy groups, and disease control rate (DCR) was 78.41% and 89.29%, respectively. Patients who received combination therapy achieved significantly longer median progression-free survival (mPFS; 6.18 vs 3.52 months, p< 0.01) and median overall survival (mOS; 8.72 vs 5.92 months, p< 0.01) compared with monotherapy. In second-line and third-line therapy, combination therapy showed a better trend in tumor response and survival outcomes compared with monotherapy. For all patients, apatinib combined with paclitaxel were associated with longer mPFS compared with other combinations (8.88 vs 6.62 months). Multivariate analysis showed that combination with paclitaxel (p=0.02) and experience of apatinib-related specific AEs (p< 0.01) were independent predictors for PFS and OS. The safety profile was tolerable and no unexpected adverse events were reported.Conclusion: In a real-world setting, apatinib showed a favorable effectiveness and safety profile in patients with advanced gastric cancer. Apatinib combination therapy, especially combined with paclitaxel, might lead to better survival benefit in first-line treatment. Combination with paclitaxel and the occurrence of apatinib-specific AEs were independent factors associated with better survival outcomes.Trial Registration: NCT03333967.Keywords: apatinib, combination therapy, real-world, advanced gastric cancer

Maoli Yi,* Lipeng Wang,* Weihao Xu, Li Sheng, Lihua Jiang, Fengzhen Yang, Qingmei Cao, Jinying Wu Department of Laboratory Medicine, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinying WuDepartment Of Laboratory Medicine, Yantai Yuhuangding Hospital, 20# Yuhuangding East Road, Zhifu District, Yantai, Shandong Province 264000, People’s Republic of ChinaTel +86-0535-6691999-81505Email ymlytyhd@163.comPurpose: This study aimed to investigate the species distributions and drug sensitivities among 19 strains of Nocardia isolated from Yantai, China, from 2017 to 2019.Patients and methods: Definitive species identification was performed by sequencing a fragment of the 16S rRNA gene (1480 bp) and by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The susceptibilities of the isolates to 15 commonly-used antibiotics were tested using the microbroth dilution method.Results: Among the 19 Nocardia isolates, five species were confirmed. Seventeen of the 19 Nocardia spp. strains were identified consistently by the two methods, while two isolates of N. cyriacigeorgica were misidentified as N. otitidiscaviarum by MALDI-TOF MS. N. farcinica was the most common species (8/19), followed by N. cyriacigeorgica (6/19), N. otitidiscaviarum (2/19), N. brasiliensis (2/19), and N. nova (1/19). All isolates were susceptible to trimethoprim-sulfamethoxazole and amikacin, followed by linezolid and tigecycline (94.7% susceptibility rates). The sensitivity and minimum inhibitory concentration patterns for ciprofloxacin, moxifloxacin, clarithromycin, and tobramycin were significantly correlated with the species.Conclusion: These results regarding the distribution and antibiotic resistance features of Nocardia species further our understanding of the diversity of Nocardia species circulating in Yantai, China, and thus support the use of more accurate empirical treatments.Keywords: antibiotic susceptibility, Nocardia, nocardiosis, species distribution

In this work, the damage mechanism and characteristics of the 2219-C10S aluminum alloy under the combined action of an exfoliation corrosion solution and shear stress were investigated. Simple shear specimens of the material (based on ASTM B831-14) were subjected to environmental exposure experiments under simple shear stress conditions. During testing, a small band-shaped zone of simple shear stress formed in the middle of the exposed region on the specimen surface. After the specified exposure duration in the corrosive medium, the corrosion micromorphology, crack nucleation location, and crack propagation direction were analyzed. The results demonstrated that under the combined action of the corrosion solution and shear stress, tiny pits appeared on the surface of the specimen after a certain exposure duration; the shear stress promoted slip dissolution of the material at the edge of the pit via the shear slip mechanism, resulting in the formation of microcracks from the edge of the pit along the shear stress direction. The microcracks still propagated along the grain boundary in the direction roughly parallel to the shear stress. The shear stress level had no clear effect on the average corrosion depth, but it had a substantial impact on the maximum corrosion depth. With increasing shear stress, the maximum corrosion depth markedly increased along with the risk for corrosion-induced specimen failure. On doubling the exposure duration, both the average corrosion depth and the maximum corrosion depth increased, but the growth rate for the average corrosion depth decreased and it increased for the maximum corrosion depth.

Abstract The gut microbiota plays multiple critical roles in maintaining the health of the host, especially in ruminants. However, our understanding of the establishment of gut microbiota from birth to adulthood is still limited. To address this, the bacterial ecology of the rumen, abomasum, duodenum, and rectum in Holstein cows ranging in age from 1 week to 5 years old was investigated using 16S rRNA gene sequencing in this study. A major change in the composition, diversity, and abundance of bacteria was observed with increased age (p 0.94) were applied. Importantly, the Gompertz model parameter differed between the gut segments, with the highest microbiota growth rate found in the rectum, followed by the rumen, abomasum, and duodenum. Compared to older animals, greater microbiota similarities were found in the adjacent gut segments of younger animals (p

Disruption of normal barrier function is a fundamental factor in the pathogenesis of inflammatory bowel disease, and intestinal stem cell (ISC) transplantation may be an optional treatment for patients. However, it is complicated and inefficient to isolate ISCs from the intestine, which hampers its wide application in clinic. We developed a two-step protocol in which mesenchymal stem cells (MSCs) were first induced into Sox17- or Foxa2-positive definitive endoderm cells by activin A treatment and then into Lgr5-positive ISC-like cells by miR-17 and FGF2 treatment. Furthermore, these Lgr5-positive cells could differentiate into enterocyte-like cells following induction with EGF. The results from an in vivo experiment showed that the MSC-derived Lgr5-positive cells were able to protect against dextran sulfate sodium-induced colitis. Taken together, our work might provide a new source of autologous ISCs. Keywords: mesenchymal stem cells, differentiation, intestinal stem cells

Zihao Liu, Ying Liang, Honghua Wang, Zhenhe Lu, Jinsheng Chen, Qiaodong Huang, Lei Sheng, Yinghong Ma, Huiying Du, Qingjuan GongDepartment of Pain Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Abstract: Neuropathic pain is a common and refractory chronic pain that affects millions of people worldwide. Its underlying mechanisms are still unclear, but they may involve long noncoding RNAs (lncRNAs), which play crucial roles in a variety of biological functions, including nociception. We used microarrays to investigate the possible interactions between lncRNAs and neuropathic pain and identified 22,213 lncRNAs and 19,528 mRNAs in the spinal cord in a mouse model of spared nerve injury (SNI)-induced neuropathic pain. The abundance levels of 183 lncRNAs and 102 mRNAs were significantly modulated by both SNI and administration of minocycline. A quantitative real-time polymerase chain reaction analysis validated expression changes in three lncRNAs (NR_015491, ENSMUST00000174263, and ENSMUST00000146263). Class distribution analysis of differentially expressed lncRNAs revealed intergenic lncRNAs as the largest category. Functional analysis indicated that SNI-induced gene regulations might be involved in the activities of cytokines (IL17A and IL17F) and chemokines (CCL2, CCL5, and CCL7), whereas minocycline might exert a pain-alleviating effect on mice through actin binding, thereby regulating nociception by controlling the cytoskeleton. Thus, lncRNAs might be responsible for SNI-induced neuropathic pain and the attenuation caused by minocycline. Our study could implicate lncRNAs as potential targets for future treatment of neuropathic pain. Keywords: LncRNA, neuropathic pain, spinal cord, minocycline

Fashui Hong,1–4 Yingjun Zhou,1–4 Xiaoyang Zhao,5 Lei Sheng,5 Ling Wang6 1Jiangsu Collaborative Innovation Center of Regional Modern Agriculture and Environmental Protection, 2Jiangsu Key Laboratory for Food Safety and Nutritional Function, 3Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, 4School of Life Sciences, Huaiyin Normal University, Huaian, 5Medical College of Soochow University, Suzhou, 6Library of Soochow University, Suzhou, Jiangsu, China Abstract: Although nanoscale titanium dioxide (nano-TiO2) has been extensively used in industrial food applications and daily products for pregnant women, infants, and children, its potential toxicity on fetal development has been rarely studied. The main objective of this investigation was to establish the effects of maternal exposure of nano-TiO2 on developing embryos. Female imprinting control region mice were orally administered nano-TiO2 from gestational day 0 to 17. Our findings showed that Ti concentrations in maternal serum, placenta, and fetus were increased in nano-TiO2-exposed mice when compared to controls, which resulted in reductions in the contents of calcium and zinc in maternal serum, placenta, and fetus, maternal weight gain, placental weight, fetal weight, number of live fetuses, and fetal crown–rump length as well as cauda length, and caused an increase in the number of both dead fetuses and resorptions. Furthermore, maternal nano-TiO2 exposure inhibited development of the fetal skeleton, suggesting a significant absence of cartilage, reduced or absent ossification, and an increase in the number of fetuses with dysplasia, including exencephaly, spina bifida, coiled tail, scoliosis, rib absence, and sternum absence. These findings indicated that nano-TiO2 can cross the blood–fetal barrier and placental barrier, thereby delaying the development of fetal mice and inducing skeletal malformation. These factors may be associated with reductions in both calcium and zinc in maternal serum and the fetus, and both the placenta and embryos may be major targets of developmental toxicity following maternal exposure to nano-TiO2 during the prenatal period. Therefore, the application of nano-TiO2 should be carried out with caution. Keywords: nanosized titanium dioxide, maternal exposure, embryonic toxicity, skeleton developmental suppression

Hongrong Xu,1,* Lei Sheng,1,* Weili Chen,1 Fei Yuan,1 Mengjie Yang,1 Hui Li,1 Xuening Li,1 John Choi,2 Guiyu Zhao,2 Tianxin Hu,2 Yongguo Li,2 Yi Zhang,2 Li Chen2 1Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, Shanghai, 2Department of Clinical Research & Development, Hua Medicine, Shanghai, People’s Republic of China *These authors have contributed equally to this work Background: HMS5552, a novel fourth-generation glucokinase (GK) activator, has demonstrated promising effects on glycemic control in preclinical models of type 2 diabetes. This single ascending dose study was conducted to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of HMS5552 during its first-in-human exposure.Methods: Sixty healthy subjects were enrolled. In each of six dose-cohorts (5, 10, 15, 25, 35, and 50 mg), ten subjects were randomized with eight subjects receiving the same cohort-dose of HMS5552 and two receiving placebo. Plasma HMS5552 exposure, glucose, and insulin were measured repeatedly during fasting and after a standardized meal. Assessment included safety, PK, and PD endpoints.Results: HMS5552 showed dose-proportional increases in area under the curve 0 to the last quantifiable concentration (AUC0–t) and maximum plasma concentration (Cmax). Slopes estimated by linear regression for AUC0–t and Cmax were ~1.0 (0.932 and 0.933, respectively). Geometric mean elimination half-life ranged from 4.48 to 7.51 hours and apparent clearance ranged from 11.5 to 13.1 L/h across all doses. No significant sex effect was observed in PK parameters. HMS5552 also demonstrated dose-related PD responses in terms of maximum glucose change from baseline (%) and mean glucose area under effect curve 0–4 hours change from baseline (%) (P

A self-pumping enzymatic biofuel cell (self-pumping EBC) with a new cathodic catalyst which was modified by coating the mixture of carbon nanotubes/caffeic acid (CNTs/CA) on a carbon cloth (CC) to form a CNTs/CA/CC cathode electrode was fabricated. By using UV spectrophotometer, the absorbance of CA, CNTs, and the CNTs/CA composite was observed. To evaluate how the CNTs/CA/CC cathodic electrode improves the electrochemical performance of the self-pumping EBC, the measurement of the redox reaction current peak by cyclic voltammetry (CV) was implemented. In accordance with CV measurement, the utilization of the modified CNTs/CA/CC cathodic electrode exhibited a higher oxygen reduction current peak at 319.1μA under the saturated oxygen. The anode and cathode flow rates were 0.416μls−1 and 0.844 μls−1 which contribute to obtaining the capillary driven liquid efficiency as 30% for the former and 59% for the latter. Moreover, the self-pumping EBC performance tests showed that the maximum power density (MPD) of the self-pumping EBC with the modified cathodic electrode achieved 0.592 mWcm−2 which improved 10% in the performance compared with the bare CC electrode, 0.534 mWcm−2.

Gut microbiota plays multiple important roles in intestinal and physiological homeostasis, and using fecal microbiota transplantation (FMT) to reprogram gut microbiota has demonstrated promise for redressing intestinal and physiological disorders. This study tested the alterations in reprogramming efficiency caused by different gut preparation procedures and explored the associated underlying mechanisms. We prepared the guts of mice for FMT by administering one of the three most-clinically used pretreatments [antibiotics, bowel cleansing (BC) solution, or no pretreatment], and we found that preparing the gut with antibiotics induced a more efficient modification of the gut bacterial community than was induced by either of the other two pretreatment types. The increased efficiency of antibiotic treatment appeared to occur via increasing the xenomicrobiota colonization. Further analysis demonstrated that antibiotic treatment of mice induced intestinal microbiota disruption, mostly by expelling antibiotic-sensitive bacteria, while the indigenous microbiota was maintained after treatment with a BC solution or in the absence of pretreatment. The amount of antibiotic-resistant bacteria increased shortly after antibiotics usage but subsequently decreased after FMT administration. Together, these results suggest that FMT relied on the available niches in the intestinal mucosa and that preparing the gut with antibiotics facilitated xenomicrobiota colonization in the intestinal mucosa, which thus enhanced the overall gut microbiota reprogramming efficiency.