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Jia Li,1,2 Wenjing Guo,1,2 Jieru Wang,1,2 Xiaomeng Feng,1,2 Qingsong Lin,1,2,&ast; Yizhou Zheng,1,2 Fengkui Zhang,1,2 Yingchang Mi,1,2 Xiaofan Zhu,1,2 Erlie Jiang,1,2 Zhijian Xiao,1,2 Jianxiang Wang,1,2 Sizhou Feng1,2,&ast; 1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, People’s Republic of China; 2Tianjin Institutes of Health Science, Tianjin, 301600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sizhou Feng, Hematopoietic Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 288 Nanjing Road, Tianjin, 300020, People’s Republic of China, Tel +86-022-23909162, Fax +022-23909047, Email doctor_szhfeng@163.com; szfeng@ihcams.ac.cnObjective: This study aimed to assess the impact of colonization status on the outcomes of Acinetobacter spp. bloodstream infection (BSI) and investigate the homology and within-host evolution between colonizing and bloodstream carbapenem-resistant Acinetobacter spp. (CRA) to inform antibiotic therapeutic decisions.Methods: We analyzed clinical outcomes of 46 hematological patients with Acinetobacter spp. BSI and performed whole-genome sequencing on the remaining CRA isolates.Results: Among the patients, 39.1% (n=18) had prior Acinetobacter spp. colonization. Colonized patients had higher rates of polymicrobial BSI (50.0% vs 21.4%, P=0.044) and CRA BSI (72.2% vs 17.9%, P< 0.001), resulting in elevated inflammatory markers and increased 30-day mortality. Each of the eight pairs of the remaining respiratory colonizing and bloodstream CRA strains belonged to the same genomospecies. Each pair exhibited definitive agreement in at least 21 of the 22 most representative antibiotic susceptibility tests. The minimum spanning tree based on multilocus sequence typing (MLST) and phylogenetic trees based on MLST and single nucleotide polymorphism (SNP) all indicated that each pair shared the same minimum branch. Very few non-synonymous SNPs in genic regions were identified during the transition from respiratory colonization to bloodstream infection, with minimal changes in virulence genes. Homology analysis suggested that CRA BSI originated from colonizing isolates in the respiratory tract.Conclusion: Strict infection control measures are needed to manage Acinetobacter spp. colonisation in hematological patients. Appropriate empirical therapy can be administered for suspected CRA BSI based on the antimicrobial minimum inhibitory concentration of CRA colonising the respiratory tract.Keywords: Acinetobacter, colonization, bloodstream infections, homology, therapy, carbapenem-resistant

Xin Liu,1– 3,&ast; Zhen Wang,1,&ast; Chaoran Zhang,1 Jingwen Xu,4 Ziheng Shen,4 Lixin Peng,1 Yanyan Mi,2,3 Haibo Xu1– 3 1School of Management, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2Center for Mental Health Education and Research, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 3Research Center for Psychological Crisis Prevention and Intervention of College Students in Jiangsu Province, Xuzhou medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 4The Second Clinical Medical School, Xuzhou medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haibo Xu; Yanyan Mi, Email xhb@xzhmu.edu.cn; miyanyan@126.comPurpose: Current interpersonal sensitivity among college students is easily linked to mood disorders such as anxiety, depression and other mood disorders. This study aims to examine the mediating role of psychological capital and its dimensions in the relationship between interpersonal sensitivity and depressive symptoms among undergraduates.Methods: The cross-sectional survey was conducted by using cluster stratified random sampling method across six Chinese universities between November and December 2022. The questionnaire consists of the Interpersonal Sensitivity sub-scale, the Patient Health Questionnaire, the Psychological Capital Questionnaire and the Socio-Demographic Feature Questionnaire.Results: A total of 2580 respondents participated in the survey, with the majority being females (69.73%) and an average age of 19.22± 1.28 years. Descriptive and correlation analyses were performed using SPSS v24.0, while direct and indirect effects were analyzed using PROCESS v3.4 macro. The findings revealed that interpersonal sensitivity had a significant direct effect on depression symptoms among undergraduates (β =0.416, 95% Boot CI [0.380, 0.453], p < 0.001) Additionally, psychological capital and its components were found to be negatively correlated with depression (p < 0.001). Further analysis demonstrated that hope, optimism, and resilience significantly mediated the association between interpersonal sensitivity and depressive symptoms (indirect effect: hope = 0.056, optimism = 0.074, resilience = 0.099; p < 0.001 for all).Conclusion: These results suggest that psychological capital, including its dimensions of hope, optimism, and resilience plays a crucial role in mitigating the negative effects of interpersonal sensitivity on depressive symptoms among undergraduates.Keywords: depressive symptoms, interpersonal sensitivity, psychological capital, Chinese undergraduates, multiple mediation

Li-Jen Cheng,1 Benfa Gong,2 Christopher H Young,3 Prabhuram Krishnan,1 Ying Wang,2 Hui Wei,2 Chunlin Zhou,2 Shuning Wei,2 Yan Li,2 Qiuyun Fang,2 Jia Zhong,4 Eric Q Wu,5 Yingchang Mi,2 Jianxiang Wang2 1Medical Affairs, Astellas Pharma Singapore Pte. Ltd., Singapore; 2Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People’s Republic of China; 3Advanced Informatics & Analytics, Astellas Pharma US Inc., Northbrook, IL, USA; 4Analysis Group, Inc., Beijing, People’s Republic of China; 5Analysis Group, Inc., Boston, MA, USACorrespondence: Jianxiang Wang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, People’s Republic of China, Tel +86 13821389157, Email wangjx@ihcams.ac.cnIntroduction: For acute myeloid leukemia (AML), prognosis is particularly poor in patients harboring FMS-like tyrosine kinase 3 (FLT3) gene mutations, though routine screening for these mutations at diagnosis has been shown to be insufficient. The understanding of the impact of FLT3 mutations on treatment decisions is limited.Methods: In this retrospective, observational study, we investigated the key epidemiological characteristics, treatment patterns and responses among adult patients with newly diagnosed (ND) AML in China, who initiated treatment from January 1, 2015, to December 31, 2019, or progressed to relapsed/refractory (R/R) AML by December 31, 2020.Results: Of the 853 ND AML patients included, 63.4% were screened for FLT3 status, and 20.1% tested positive (FLT3MUT) at initial diagnosis. Of 289 patients who progressed to R/R AML during the study period, 24.9% were screened at the diagnosis of R/R AML, and 19.4% tested positive; 20.5% of screened patients changed FLT3 status at first diagnosis of R/R AML. Initial treatment regimens or treatment responses did not seem to differ in patients with ND AML by FLT3 mutation status. In patients with R/R AML, there was an apparent difference in second-line treatment choices by FLT3 mutation status; however, the number of FLT3-mutated patients were limited to demonstrate any meaningful distinction. FLT3-mutated R/R AML was associated with shorter relapse time.Conclusion: Study findings showed that there was a lack of routine testing for FLT3 mutations at first diagnosis of R/R AML, and initial treatment decisions did not differ by FLT3 mutation status. Given the clinical burden of FLT3MUT, likelihood of FLT3 status changes, and emerging FLT3 inhibitors, further routine FLT3 screening is needed to optimize treatment of R/R AML. Keywords: acute myeloid leukemia, epidemiology, real-world, retrospective study

Junwei Zheng,1,2 Yan Mi,3 Jinghan Liang,1 Huili Li,1 Peiqi Shao,1 Hong Wen,1 Yun Wang1 1Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, People’s Republic of China; 3Department of Anesthesiology, Tumour Hospital, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Yun Wang; Hong Wen, Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China, Tel +86-10-85231330, Fax +86-10-65077808, Email wangyun129@ccmu.edu.cn; wendoctorhong@sina.comPurpose: Total hip arthroplasty (THA) is often associated with moderate to severe pain. The present study compared the efficacy of circum-psoas block (CPB) with supra-inguinal fascia iliaca block (SIFIB) for postoperative analgesia in patients undergoing THA.Patients and Methods: In this randomized trial, sixty-four patients undergoing THA were allocated randomly to the CPB group or SIFIB group with 40 mL of 0.3% ropivacaine. The primary outcome was dynamic pain score at 6 h postoperatively. Secondary outcomes included dynamic pain scores at 12, 24 and 48 h; static pain scores; sensory and motor block; opioid consumption; time to first opioid request; length of hospital stay; patient satisfaction; and adverse events.Results: CPB patients showed significantly lower dynamic pain scores at 6 (3.11 ± 0.66 vs 4.47 ± 0.74, respectively; P = 0.000), 12 (2.52 ± 0.73 vs 3.53 ± 0.85, respectively; P = 0.000) and 24 h (2.30 ± 0.57 vs 2.87 ± 0.71, respectively; P = 0.001) after surgery, as well as lower static pain scores at 6 and 12h (P = 0.001 and P = 0.033 respectively) than SIFIB patients. Lower opioid consumption was observed in the CPB group at 24 and 48 h (P = 0.000, both) than in the SIFIB group. Patients in the CPB group reported improved quadriceps strength at 6 and 12 h (P = 0.000, both), as well as better muscle strength of hip flexion at 6, 12 and 24 h (P = 0.000, P = 0.000 and P = 0.025 respectively). Compared with SIFIB, CPB was associated with increased sensory block coverage at 6, 12 and 24 h (P = 0.000, P = 0.000, and P =0.022, respectively).Conclusion: CPB has a greater potential to alleviate postoperative pain and improve recovery in THA patients than SIFIB.Keywords: total hip arthroplasty, lumbar plexus, sacral plexus, regional anesthesia

In this work, we use an extreme-ultraviolet (XUV) free-electron laser (FEL) to resonantly excite the I: 4d5/2-σ∗ transition of a gas-phase di-iodomethane (CH2I2) target. This site-specific excitation generates a 4d core hole located at an iodine site, which leaves the molecule in a well-defined excited state. We subsequently measure the time-dependent absorption change of the molecule with the FEL probe spectrum centered on the same I: 4d resonance. Using ab initio calculations of absorption spectra of a transient isomerization pathway observed in earlier studies, our time-resolved measurements allow us to assign the timescales of the previously reported direct and indirect dissociation pathways. The presented method is thus sensitive to excited-state molecular geometries in a time-resolved manner, following a core-resonant site-specific trigger.

Xuchen Huang,1,2 Sainan Li,1,2 Wei Gao,1,2 Jiajie Shi,1,2 Meng Cheng,1,2 Yunzhe Mi,1,2 Yueping Liu,3 Meixiang Sang,4 Ziyi Li,4 Cuizhi Geng1,2 1Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Key Laboratory in Hebei Province for Molecular Medicine of Breast Cancer, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Research Center and Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Cuizhi Geng, Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Tel/Fax +86-311-66696313, Email gengcuizhisci@163.comPurpose: Our aim was to verify whether KIF20A has the potential to serve as a prognostic marker for female patients with estrogen receptor (ER)-positive breast cancer (BC) and treated with tamoxifen (TAM).Patients and Methods: Online tools were used to investigate the potential correlation between KIF20A gene expression and survival of patients with ER-positive BC and TAM treatment. Furthermore, immunohistochemistry (IHC) was conducted to assess the expression levels of KIF20A in patients included from our center. The prognostic value of KIF20A for disease-free survival (DFS) and overall survival (OS) was further evaluated using Cox regression analysis.Results: According to the results obtained from online tools, it was found that patients with low KIF20A expression exhibited significantly better survival outcomes in terms of relapse-free survival (RFS), distant metastasis-free survival (DMFS), and OS compared to those with high KIF20A expression (P < 0.001, P < 0.001, and P = 0.008, respectively). Additionally, significantly lower gene expression of KIF20A was found in patients who responded to TAM than in those who did not respond to TAM (P < 0.001). We further included 203 patients with adjuvant TAM therapy, and IHC for KIF20A was performed on sections from paraffin-embedded blocks. Patients with low KIF20A expression had significantly better DFS and OS (P = 0.001 and 0.002, respectively, log rank test), and the expression of KIF20A was identified as an independent factor for predicting both DFS and OS (P = 0.001 and 0.008, respectively).Conclusion: KIF20A expression is an independent prognostic factor for survival in patients with ER-positive BC who received adjuvant TAM therapy. In clinical practice, IHC evaluation of KIF20A expression in surgical samples before administering tamoxifen may assist in predicting the treatment outcomes of these patients.Keywords: KIF20A, breast carcinoma, biomarker, tamoxifen, survival, prognosis

Fei Tian,1,&ast; Zuyang Xi,1,&ast; Ling Ai,2 Xiaojing Zhou,1 Zhaohui Zhang,1,&ast; Jinglan Liu,1 Yuanyuan Mi,3 Shengmin Gui,1 Chaxiang Li,1 Min Liu1 1The First College of Clinical Medical Science, China Three Gorges University, Teaching and Research Section of Clinical Nursing, Yichang, People’s Republic of China; 2Nursing Department, China Xingshan County People’s Hospital, Xingshan, People’s Republic of China; 3Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Tian, The First College of Clinical Medical Science, China Three Gorges University, Teaching and Research Section of Clinical Nursing, Yichang, 433000, People’s Republic of China, Tel +86 13687271927, Email 980347043@qq.comObjective: To investigate the willingness of nurses in Yichang to participate in “Internet plus nursing services” and analyze the influencing factors in order to provide reference for the implementation of “Internet plus nursing services”.Methods: Using the “Internet plus Nursing Service” questionnaire, a cross-sectional survey was conducted among 1447 nurses in Yichang by convenience sampling from July to September in 2022, and the related influencing factors were analyzed. The questionnaire was composed of two parts: the demographic characteristics and the questionnaire of nurses’ willingness to participate in “Internet plus nursing service”, including 4 dimensions: awareness, promoting factors, concern factors and training needs. Likert 5-point scoring method was used for scoring. Binary logistic regression was used to screen the variables, and the ROC curve and Nomogram risk prediction model were drawn.Results: A total of 1233 valid questionnaires were collected. It shows that 76.07% of nurses in Yichang are willing to participate in “Internet plus nursing services”. Among them, education background, specialist nurses, awareness, promotion factors, concerns and training needs are the independent influencing factors (all P < 0.05). The area under the ROC curve (AUC) of the prediction model is 0.802, and the consistency index (c-index) of nomogram is 0.800. The average absolute error of internal calibration is 0.014, and the model has good accuracy and discrimination.Conclusion: Nurses in Yichang have a high willingness to participate in “Internet plus nursing services”, a low awareness of the program and a high demand for relevant professional training. It is suggested that the government and hospitals should strengthen the publicity of “Internet plus nursing services”, improve relevant laws and regulations and strengthen the construction of specialist nurses’ team, so as to provide a good practice environment for nurses’ door-to-door service.Keywords: internet plus nursing services, willingness, influencing factors

Xiaoning Zhang,1,2,&ast; Xin Liu,1,2,&ast; Yanyan Mi,2 Wei Wang,2,3 Haibo Xu1,2 1School of Management, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Center for Mental Health Education and Research, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haibo Xu, Email xhb@xzhmu.edu.cnPurpose: The COVID-19 pandemic has greatly affected people’s mental health. The direct and indirect pathways between social support and suicidal ideation in the period are still unclear. This study explores the pathways from social support to suicidal ideation through resilience and depressive symptoms among undergraduates during the COVID-19 campus lockdown.Methods: During two weeks of the COVID-19 campus lockdown, a total of 12,945 undergraduates at a university in eastern China completed the questionnaire including sociodemographic characteristics, suicidal ideation, social support, resilience, and depressive symptoms. A structural equation modeling (SEM) approach was used to analyze the direct and indirect pathways from social support to suicidal ideation via the mediators of resilience and depressive symptoms.Results: Of the 12,917 undergraduates included in this study, 7.4% (n = 955) reported they sometimes had suicidal ideation, 0.8% (n = 109) reported they often had suicidal ideation, 0.9% (n = 122) reported they always had suicidal ideation, and 13.2% (n = 1704) reported they had depressive symptoms. Social support exerted significant direct (β = − 0.058), indirect (β = − 0.225), and total (β = − 0.283) effects on suicidal ideation; 20.5% of the total effect was direct, and 79.5% was indirect. Social support predicted suicidal ideation through resilience (β = − 0.038), and depressive symptoms (β = − 0.087), explaining 13.4%, and 30.7% of the total effect, respectively. Social support predicted suicidal ideation through the sequential mediation of resilience and depressive symptoms (β = − 0.099), explaining 35.0% of the total effect.Conclusion: This is the first study to provide the evidence of pathways from social support to suicidal ideation through resilience and depressive symptoms during the COVID-19 campus lockdown among undergraduates in China. Both direct and indirect pathways from social support to suicidal ideation were identified as intervention targets to reduce suicidal ideation.Keywords: depressive symptoms, resilience, social support, suicidal ideation, COVID-19, campus lockdown

The unique eco-environment of the Qinghai–Tibet Plateau breeds abundant microbial resources. In this research, Bacillus amyloliquefaciens GL18, isolated from the rhizosphere of Kobresia myosuroides from an alpine meadow, and the antagonistic activity, bacteriostatic hydrolase activity, and low temperature, salt, and drought resistance of it were determined and analysed. The seedlings of Avena sativa were root-irrigated using bacteria suspensions (cell concentration 1 × 107 cfu/mL) of GL18, and the growth-promoting effect of GL18 on it was determined under cold, salt and drought stress, respectively. The whole genome of GL18 was sequenced, and its functional genes were analysed. GL18 presented significant antagonistic activity to Fusarium graminearum, Fusarium acuminatum, Fusarium oxysporum and Aspergillus niger (inhibition zone diameter > 17 mm). Transparent zones formed on four hydrolase detection media, indicating that GL18 secreted cellulase, protease, pectinase and β-1,3-glucanase. GL18 tolerated conditions of 10 °C, 11% NaCl and 15% PEG-6000, presenting cold, salt and drought resistance. GL18 improved the cold, salt and drought tolerance of A. sativa and it showed significant growth effects under different stress. The total length of the GL18 genome was 3,915,550 bp, and the number of coding DNA sequence was 3726. Compared with the clusters of orthologous groups of proteins, gene ontology and kyoto encyclopedia of genes and genomes databases, 3088, 2869 and 2357 functional genes were annotated, respectively. GL18 contained gene clusters related to antibacterial substances, functional genes related to the synthesis of plant growth-promoting substances, and encoding genes related to stress resistance. This study identified an excellent Bacillus strain and provided a theoretical basis for improving stress resistance and promoting the growth of herbages under abiotic stress. [ABSTRACT FROM AUTHOR]

Shuyu Li,1,2 Qingzhen Zhao,1 Yuzhi Zhen,1 Lizhuo Li,1 Yiqing Mi,1 Tongxin Li,1 Kunshen Liu,1 Chao Liu1 1The First Cardiology Division, First Affiliated Hospital of Hebei Medical University, Shijiazhuang, 050022, People’s Republic of China; 2The Second Cardiology Division, North China University of Science and Technology Affiliated Hospital, Tangshan, 063000, People’s Republic of ChinaCorrespondence: Chao LiuThe First Cardiology Division, First Affiliated Hospital of Hebei Medical University, Hebei Medical University, No. 89 of Donggang Road, Yuhua District, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaTel +86 311 8591 7032Fax +86 311 8591 7290Email dr.liuchao@gmail.comBackground: Positive inotropic and renal protective actions of glucocorticoids have been observed clinically. Therefore, glucocorticoids may be used in patients with heart failure and low blood pressure (HF-LBP).Methods: The medical records of 144 consecutive patients with HF-LBP who received glucocorticoids as an adjunctive treatment to facilitate the up-titration of β-blocker and angiotensin-converting enzyme inhibitor were reviewed.Results: After four weeks of treatment, the metoprolol and captopril (or equivalent) dosages were progressively and consistently increased from 25 (interquartile range [IQR] = 12.5– 75 mg/day) to 100 mg/day (IQR = 50– 178.8 mg/day) and from 0 (IQR = 0– 25 mg/day) to 12.5 mg/day (IQR = 0– 50 mg/day), respectively. There was a remarkable beneficial hemodynamic response to the glucocorticoid treatment signified by an increase in blood pressure and decrease in heart rate. The average heart rate decreased by 6 beat per minute (bpm) (0.5– 16 bpm), and the mean arterial blood pressure increased from 74.06 ± 7.81 to 78.85 ± 7.91 mmHg. We also observed an improvement in renal function and an increased diuretic response following glucocorticoid treatment. As a result, the left ventricular ejection fraction increased from 28.92 ± 8.06% to 33.86 ± 8.76%, and the diuretic response increased from 776.7 mL/40 mg furosemide (IQR = 133.8– 2000 mL) to 4000 mL/40 mg furosemide on day 28 (IQR = 2200– 5925 mL).Conclusion: The use of glucocorticoid treatment to maintain hemodynamic and renal functional targets when titrating guideline-directed medical treatment in patients with HF-LBP may be safe, effective, and feasible.Keywords: cardiac output, β-blocker, angiotensin-converting enzyme inhibitor, diuretic response, left ventricular ejection, renal function

ObjectiveThe Sjögren's International Collaborative Clinical Alliance (SICCA) is an international data registry and biorepository derived from a multisite observational study of participants in whom genotyping was performed on the Omni2.5M platform and who had undergone deep phenotyping using common protocol-directed methods. The aim of this study was to examine the genetic etiology of Sjögren's syndrome (SS) across ancestry and disease subsets.MethodsWe performed genome-wide association study analyses using SICCA subjects and external controls obtained from dbGaP data sets, one using all participants (1,405 cases, 1,622 SICCA controls, and 3,125 external controls), one using European participants (585, 966, and 580, respectively), and one using Asian participants (460, 224, and 901, respectively) with ancestry adjustments via principal components analyses. We also investigated whether subphenotype distributions differ by ethnicity, and whether this contributes to the heterogeneity of genetic associations.ResultsWe observed significant associations in established regions of the major histocompatibility complex (MHC), IRF5, and STAT4 (P = 3 × 10-42 , P = 3 × 10-14 , and P = 9 × 10-10 , respectively), and several novel suggestive regions (those with 2 or more associations at P

Ning Wang,1,* Yanqi Peng,1,* Lu Wang,1 Lin Song,2 Bo Sun,2 Junxiang Wei,3 Ting Wang,4 Yang Mi,3 Wei Cui1 1Department of Endocrinology and Second Department of Geriatrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, People’s Republic of China; 3The Second Department of Obstetrics, Northwest Women and Children’s Hospital, Xi’an, People’s Republic of China; 4Department of Respiratory Medicine, Xi’an No.4 Hospital, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang MiThe Second Department of Obstetrics, Northwest Women and Children’s Hospital, 1616 Yanxiang Road, Xi’an, Shaanxi, 710065, People’s Republic of ChinaTel +86-13700222172Email miyangmm@163.comWei CuiDepartment of Endocrinology and Second Department of Geriatrics, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shaanxi, 710061, People’s Republic of ChinaTel +86-13609281695Email doctorweiweixjtu@126.comPurpose: To study the risk factors of gestational diabetes mellitus (GDM) heterogeneity, and to evaluate the correlation between the risk factors and obesity.Methods: We performed a case–control study of 452 women with GDM and 516 women with normal glucose tolerance (NGT) at the first and second trimester. We defined GDM women as GDM-resistance subtype, GDM-dysfunction subtype, and GDM-mixed subtype, according to their simultaneous insulin-release test with predominant insulin-sensitivity defect, insulin-secretion defect, or both defects.Results: We found that higher maternal age, family history of diabetes, the elevated level of fasting blood glucose in the first trimester (≥ 5.1 mmol/L) were risk factors of all GDM subtypes. Pre-pregnancy overweight/obesity and the increased gestational weight gain (GWG) in the first-trimester are risk factors of the GDM-resistance subtype. Indicators including younger age at first menstruation, the elevated levels of alanine aminotransferase (ALT), total bile acid (TBA), triglyceride (TG), and the decreased level of high-density lipoprotein cholesterol (HDL-C) are risk factors of the GDM-resistance subtype. However, the associations between those risk factors and GDM-resistance subtype attenuated after adjusted by pre-pregnancy body mass index (pre-BMI) and gestational weight gain (GWG) in the first trimester. Nonalcoholic fatty liver disease (NAFLD) and the improved level of TG are independent risk factors for the GDM-resistance subtype and the GDM-mixed subtype, respectively.Conclusion: Women with GDM exhibited heterogeneity based on glycemic physiology and their risk factors are not all the same. Some obesity-related risk factors are specific to the GDM-resistance subtype, which are mediated by pre-pregnancy overweight/obesity and the elevated GWG the first-trimester.Keywords: pregnancy, pre-pregnancy BMI, gestational weight gain, obesity, insulin resistance, insulin secretion

Yanjun Mi,1,* Yongwen Li,2,* Zhuo He,3,* Donghan Chen,2 Qingqi Hong,2 Jun You2 1Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian Province, 361003, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian Province, 361003, People’s Republic of China; 3Department of Gastropancreatoduodenal Surgery, Hunan Cancer Hospital, Changsha, Hunan Province, 410013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun YouDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, No. 55 Zhenhai Road, Si Ming District, Xiamen, Fujian Province, 361003, People’s Republic of ChinaTel +86 13906051681Email youjun1681@163.comBackground: Linc-ROR is a long non-coding RNA, that is found aberrantly expressed in various human cancers. We aim here to unveil the role of Linc-ROR in gastric cancer (GC) progression.Methods: qPCR was used to determine gene expression. Cell viability was measured by CCK-8 assay. Transwell assays were performed to evaluate the GC cells’ migratory and invasive abilities. Xenograft mouse model was conducted to measure tumor growth.Results: We found that Linc-ROR were overexpressed in GC tissues compared to the adjacent tissues. High Linc-ROR predicts poor prognosis of GC patients. The prediction of bioinformatics online revealed that Linc-ROR could bind to miR-212-3p. Further, dual-luciferase reporter assay confirmed a direct interaction between Linc-ROR and miR-212-3p. Overexpression of miR-212-3p facilitated GC cells’ migration and invasion, while the silencing of miR-212-3p attenuated GC cell migratory and invasive abilities. Moreover, Linc-ROR knockdown significantly suppressed the proliferation, migration, and invasion of GC cells, whereas miR-212-3p antagomir partially reversed Linc-ROR knockdown-induced phenotypes. Fibroblast growth factor 7 (FGF7), a downstream molecule of miR-212-3p, was overexpressed in GC cells. The recovery of FGF7 expression partially reversed the phenotypes caused by Linc-ROR silencing. Mechanistically, silencing of Linc-ROR contributed to the downregulation of CDK4, CDK6, Cyclin D1, N-Cadherin, Vimentin, MMP-9, MMP-2, but caused the upregulation of P21, P27, E-Cadherin, CK-19 in MGC-803 cells; however, FGF7 treatment could reverse the results induced by Linc-ROR silencing. Results in vivo further suggested that Linc-ROR knockdown repressed GC tumor growth, where the expression of miR-212-3p was up-regulated and FGF7 expression was downregulated in tumor tissues of mice.Conclusion: These findings indicated that Linc-ROR/miR-212-3p/FGF7 axis played an important role in gastric cancer progression. Linc-ROR expression level was associated with the prognosis of GC patients.Keywords: Linc-ROR, miR-212-3p, FGF7, gastric cancer

Shanshan Li,1,* Zhaoqin Wang,2,* Huangan Wu,3,* Hongyu Yue,1 Ping Yin,1 Wei Zhang,4 Lixing Lao,5 Yiqun Mi,1 Shifen Xu1 1Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, People’s Republic of China; 2Department of Aeronautics and Astronautics, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai 200433, People’s Republic of China; 3Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, People’s Republic of China; 4Department of Biostatistics, School of Public Health, Fudan University, Shanghai 200032, People’s Republic of China; 5Virginia University of Integrative Medicine, Fairfax, VA 22031, USA*These authors contributed equally to this workCorrespondence: Shifen Xu; Yiqun MiShanghai Municipal Hospital of Traditional Chinese Medicine, 274 Middle Zhijiang Road, Shanghai 200071, People’s Republic of ChinaTel +86 13761931393; Tel +8618930177567Email xu_teacher2006@126.com; miyiqun@126.comObjective: To evaluate the short- and long-term effects of acupuncture on perimenopausal insomnia (PMI) and quality of life.Patients and Methods: We designed a semi-standardized, patient-blinded, randomized placebo-controlled trial. A total of 84 patients were recruited, all of whom met the criteria for diagnosis of PMI. Either acupuncture therapy or a noninvasive placebo acupuncture therapy designed to treat insomnia was implemented 18 times over the course of 8 weeks (3 times per week for 4 weeks, twice per week for 2 weeks, once per week for 2 weeks). The primary outcome was the change in Pittsburgh Sleep Quality Index (PSQI) scores from baseline to the end of treatment, week 8. Secondary outcomes included climacteric symptoms and quality of life measured by the Menopause Quality of Life (Men-QoL), Insomnia Severity Index (ISI), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), sleep parameters recorded in the actigraphy and adverse events. The PSQI and Men-QoL were assessed at weeks 0, 4, 8, 12 and 20. Other assessments were performed at week 0 and week 8.Results: The participants were randomly assigned to either acupuncture (n=42) or sham acupuncture (n=42) groups. The mean difference from baseline of PSQI score at the end of treatment between real acupuncture and sham acupuncture group was − 2.38 (95% CI, − 3.46 to − 1.30; P< 0.001). The acupuncture group was associated with significantly lower scores than the sham acupuncture group at week 12 and during the 20-week follow-up visits (all P < 0.001). Acupuncture was also associated with significantly higher quality of life in vasomotor and other physical dimensions (all P < 0.001). At the end of treatment, researchers found a significantly higher total sleep time (TST), sleep efficiency (SE) and lower number of average awakenings (AA) (P =0.007 0.023 and 0.011, respectively) in the acupuncture group than in the sham acupuncture group. No severe adverse events were reported.Conclusion: The findings suggest that acupuncture may be a safe and effective treatment for PMI and improving quality of sleep in patients with menopause and could have a long-lasting effect.Trial Registration: Chinese Clinical Trial Registry (ChiCTR); Trial ID: ChiCTR1800018645. URL: http://www.chictr.org.cn/showproj.aspx?proj=31482.Keywords: acupuncture, perimenopausal insomnia, randomized controlled trial

Yanhong Wang,1,* Yang Mi,2,* Jihua Tian,1,* Xi Qiao,3 Xiaole Su,3 Jing Kang,1 Zhijing Wu,1 Guiqing Wang,1 Xiaoshuang Zhou,4 Yun Zhou,4 Rongshan Li4 1Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Urology, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan, Shanxi, People’s Republic of China; 3Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4Department of Nephrology, The Affiliated People’s Hospital of Shanxi Medical University, Shanxi Provincial People’s Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun ZhouDepartment of Nephrology, The Affiliated People’s Hospital of Shanxi Medical University, Shanxi Provincial People’s Hospital, No. 29 Shuang Ta East Street, Taiyuan, Shanxi 030012, People’s Republic of ChinaEmail zhouyun_sx@163.comRongshan LiDepartment of Nephrology, The Affiliated People’s Hospital of Shanxi Medical University, Shanxi Provincial People’s Hospital, No. 29 Shuang Ta East Street, Taiyuan 030012, People’s Republic of ChinaEmail rongshanli13@163.comBackground: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and increases the risk of subsequently developing chronic kidney disease. Angiogenesis has been shown to play an important role in reducing renal injury after ischemia reperfusion. In this study, we investigated whether IMD could reduce renal IRI by promoting angiogenesis.Methods: The kidneys of Wistar rats were subjected to 45 min of warm ischemia followed by 24 h of reperfusion. IMD was overexpressed in vivo using the vector pcDNA3.1-IMD transfected by an ultrasound-mediated system. The renal injury after ischemia reperfusion was assessed by detection of the serum creatinine concentration and histologic examinations of renal tissues stained by PAS and H&E. Real-time PCR and Western blotting were used to determine the mRNA and protein levels, respectively. Histological examinations were used to assess the expression of CD31, MMP2, MMP9, ET-1, VEGF and VEGFR2 in tissues.Results: Renal function and renal histological damage were significantly ameliorated in IMD-transfected rats after ischemia reperfusion. Compared to the IRI, IMD significantly promoted angiogenesis. IMD also upregulated the protein and mRNA expression levels of VEGF and VEGFR2 and downregulated the expression level of MMP2, MMP9 and ET-1.Conclusion: IMD could protect the kidney after renal ischemia-reperfusion injury by promoting angiogenesis and reducing the destruction of the perivascular matrix.Keywords: intermedin, ischemia-reperfusion injury, kidney, angiogenesis, VEGF, VEGFR2, MMP2, MMP9, ET-1

Abstract 3D bioprinting is a promising approach for the repair of cartilage tissue after damage due to injury or disease; however, the design of 3D printed scaffolds has been limited by the availability of bioinks with requisite printability, cytocompatibility, and bioactivity. To address this, we developed an approach termed in situ crosslinking that permits the printing of non-viscous, photocrosslinkable bioinks via the direct-curing of the bioink with light through a photopermeable capillary prior to deposition. Using a norbornene-modified hyaluronic acid (NorHA) macromer as a representative bioink and our understanding of thiol-ene curing kinetics with visible light, we varied the printing parameters (e.g., capillary length, flow rate, light intensity) to identify printing conditions that were optimal for the ink. The printing process was cytocompatible, with high cell viability and homogenous distribution of mesenchymal stromal cells (MSCs) observed throughout printed constructs. Over 56 days of culture in chondrogenic media, printed constructs increased in compressive moduli, biochemical content (i.e., sulfated glycosaminoglycans, collagen), and histological staining of matrix associated with cartilage tissue. This generalizable printing approach may be used towards the repair of focal defects in articular cartilage or broadly towards widespread biomedical applications across a range of photocrosslinkable bioinks that can now be printed.

ObjectiveTo determine whether the Sjögren's syndrome B (SSB)-positive/Sjögren's syndrome A (SSA)-negative antibody profile is associated with key phenotypic features of SS.MethodsAmong registrants in the Sjögren's International Collaborative Clinical Alliance (SICCA) with possible or established SS, we compared anti-SSA/anti-SSB reactivity profiles against concurrent phenotypic features. We fitted logistic regression models to explore the association between anti-SSA/anti-SSB reactivity profile and each key SS phenotypic feature, controlling for potential confounders.ResultsAmong 3297 participants, 2061 (63%) had negative anti-SSA/anti-SSB, 1162 (35%) had anti-SSA with or without anti-SSB, and 74 (2%) anti-SSB alone. Key SS phenotypic features were more prevalent and had measures indicative of greater disease activity in those participants with anti-SSA, either alone or with anti-SSB, than in those with anti-SSB alone or negative SSA/SSB serology. These between-group differences were highly significant and not explained by confounding by age, race/ethnicity or gender. Participants with anti-SSB alone were comparable to those with negative SSA/SSB serology in their association with these key phenotypic features. Among SICCA participants classified with SS on the basis of the American-European Consensus Group or American College of Rheumatology criteria, only 2% required the anti-SSB-alone test result to meet these criteria.ConclusionsThe presence of anti-SSB, without anti-SSA antibodies, had no significant association with SS phenotypic features, relative to seronegative participants. The solitary presence of anti-SSB antibodies does not provide any more support than negative serology for the diagnosis of SS. This serological profile should thus be interpreted cautiously in clinical practice and potentially eliminated from future classification criteria.

In the context of the economic globalization, there is an increased disruption risk in the supply chain network due to the outsourcing, complexity and uncertainty. At the same time, the disruption may propagate across the entire supply chain network because of the interdependence. With the resource constraints, appropriate recovery strategies which can minimize the impact of disruption propagation and effectively improve the supply chain network resilience have attracted a great deal of attention. In this paper, we first construct the disruption propagation model considering the recovery strategy based on the characteristics of the competitiveness, time delay and underload cascading failure in the supply chain network. This model uses the memetic algorithm to determine the set of recovery nodes among all disruption nodes, which can minimize the impact of disruption propagation. And then, the simulation analysis is conducted on the synthetic network and the real-world supply chain network. We compare the proposed recovery strategy with other strategies (according to the genetic algorithm, according to the descending order of the load of failure node, according to the ascending order of the load of failure node, according to the descending order of the node degree, according to the ascending order of the node degree) and provide decision-making reference against supply chain disruptions. [ABSTRACT FROM AUTHOR]

Yanan Dong,1–3 Rongzhan Fu,1–3 Jing Yang,1–3 Pei Ma,1–3 Lihua Liang,2 Yu Mi,1–3 Daidi Fan1–31Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi’an, Shaanxi 710069, People’s Republic of China; 2Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi’an, Shaanxi 710069, People’s Republic of China; 3Biotech & Biomed Research Institute, Northwest University, Xi’an, Shaanxi 710069, People’s Republic of ChinaCorrespondence: Yu Mi; Daidi FanShaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi’an, Shaanxi 710069, People’s Republic of ChinaEmail mi_yu@nwu.edu.cn; fandaidi@nwu.edu.cnBackground and purpose: Ginsenoside Rg5 (Rg5), a triterpene saponin, extracted from the natural herbal plant ginseng, is one of the most potent anticancer drugs against various carcinoma cells. However, the therapeutic potential of Rg5 is limited by its low solubility in water, poor bioavailability, and nontargeted delivery. Therefore, we prepared folic acid (FA)-modified bovine serum albumin (BSA) nanoparticles (FA-Rg5-BSA NPs) to improve the therapeutic efficacy and tumor targetability of Rg5.Methods: Various aspects of the FA-Rg5-BSA NPs were characterized, including size, polydispersity, zeta potential, morphology, entrapment efficiency (EE), drug loading (DL), in vitro drug release, thermal stability, in vitro cytotoxicity, cell apoptosis, cellular uptake, in vivo antitumor effects and in vivo biodistribution imaging.Results: The FA-Rg5-BSA NPs showed a particle size of 201.4 nm with a polydispersity index of 0.081, uniform spherical shape, and drug loading of 12.64±4.02%. The aqueous solution of FA-Rg5-BSA NPs had favorable stability for 8 weeks at 4°C. The FA-Rg5-BSA NPs dissolved under acidic conditions. Moreover, the Rg5-BSA NPs and FA-Rg5-BSA NPs had advanced anticancer activity compared with Rg5 in MCF-7 cells, while poor cytotoxicity was observed in L929 cells. The FA-Rg5-BSA NPs facilitated cellular uptake and induced apoptosis in MCF-7 cells. In addition, in an MCF-7 xenograft mouse model, the in vivo antitumor evaluation revealed that FA-Rg5-BSA NPs were more effective in inhibiting tumor growth than Rg5 and Rg5-BSA NPs. The in vivo real-time bioimaging study showed that the FA-Rg5-BSA NPs exhibited superior tumor accumulation ability.Conclusion: The results suggested that FA-Rg5-BSA NPs could serve as a promising system to improve the antitumor effect of Rg5.Keywords: ginsenoside Rg5, drug delivery, nanoparticles, antitumor activity, human MCF-7 breast cancer cells

Lin Lin,1,* Yanjun Mi,2,* Xun Li,3 Cuixin Peng,2 Zhaoshui Shangguan,1 Zhibin Li,4 Suhuan Liu1 1Central Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, China; 2Division of Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China; 3Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, China; 4Epidemiology Research Unit, The First Affiliated Hospital of Xiamen University, Xiamen, China *These authors contributed equally to this work Purpose: We aimed to explore the association of plasma TP53-induced glycolysis and apoptosis regulator (TIGAR) level with colorectal cancer (CRC) metastasis. Methods: A cross-sectional study of 126 CRC patients was conducted in Xiamen, China. Multivariable logistic regression was used to calculate adjusted OR and 95% CIs of plasma TIGAR concentration for CRC metastasis in different models with adjustment for potential confounders. Area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. Results: CRC patients with metastasis showed significantly decreased plasma TIGAR concentration compared to their controls (1.97±0.64 vs 2.49±0.69 ng/mL [log transformed], P=0.002). Higher plasma TIGAR was significantly associated with the decreased risk of CRC metastasis, and the adjusted OR (95% CI) was 0.134 (0.027–0.676, P=0.015) for per SD increase in plasma TIGAR concentration, and the trend test for increasing tertiles showed a negative trend of plasma TIGAR on risk of CRC metastasis (P for trend test: 0.005). Pearson correlation coefficients of plasma TIGAR with other cancer biomarkers (carbohydrate antigen 50 [CA50], carbohydrate antigen 199 [CA199], carbohydrate antigen 125 [CA125], carbohydrate antigen 724 [CA724], carcinoembryonic antigen [CEA], and ferritin [FER]) was low (P>0.05). AUC (95% CI) of ROC curve of plasma TIGAR for CRC metastasis was comparable to the values of cancer biomarkers (all P-values

Tools to investigate a wide range of 3D microenvironmental parameters are important for understanding and controlling cell fate. Here, the authors develop hydrogels with orthogonal biochemical gradients and use this screening system to identify microenvironments that induce mesenchymal stem cell chondrogenesis.

OBJECTIVE: This study delves into the role of N-terminal propeptide type III collagen (PIIINP) in the diagnosis and management of liver pathological changes associated with non-alcoholic steatohepatitis (NASH). PATIENTS AND METHODS: We collected baseline information, pathological data, and serum PIIINP levels of 168 patients diagnosed with non-alcoholic fatty liver disease (NAFLD) via ultrasound imaging in our hospital. Based on the non-alcoholic fatty liver disease activity score (NAS), patients with different NAFLD patterns were divided into a Definite NASH group and a Not/borderline group. Differences in PIIINP levels and pathological features between the two groups were compared and analyzed. The diagnostic value of PIIINP for NASH was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: Patients with NASH exhibited significantly higher values of homeostatic model assessment for insulin resistance (HOMA-IR), fibrosis biomarker fibrosis-4 (FIB-4), aminotransferase-to-platelet ratio index (APRI), and serum PIIINP levels than those classified as Not/borderline. A marked increase in the serum concentrations of PIIINP was observed with the severity of fatty degeneration, lobular inflammation, and hepatocellular ballooning. The AUC of PIIINP for diagnosing definite NASH was 0.766 (95% CI: 0.694, 0.839), APRI was 0.634 (95% CI: 0.549, 0.718), and FIB-4 was 0.621 (95% CI: 0.534, 0.708). The AUC of PIIINP for diagnosing definite NASH was significantly higher than that of APRI and FIB-4 (all p<0.05). Utilizing the predetermined threshold values for diagnostic parameters, the PIIINP measure demonstrated a sensitivity of 71.6% and a specificity of 73.6% in diagnosing definitive NASH when its value exceeded 7.72 ng/dL. This yielded a Youden index of 0.45. Similarly, when the APRI measure exceeded 0.21, it exhibited a sensitivity of 60.5% and a specificity of 63.2%, resulting in a Youden index of 0.24. Moreover, when the FIB-4 index surpassed 0.26, it showed a sensitivity of 46.9% and a specificity of 79.3%, culminating in a Youden index of 0.26. CONCLUSIONS: NASH patients in this study exhibited significantly elevated PIIINP serum levels, which were closely associated with hepatocyte pathological changes. PIIINP demonstrated superior competence in diagnosing NASH than APRI and FIB-4 and thus offers a viable alternative for the clinical diagnosis of NASH. [ABSTRACT FROM AUTHOR]