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Lan Hong,1,* Huihui Xu,2,* Jiaqi Zheng,2 Xiujian Lin,2 Lijun Wang,2 Chengjia Zhao,3 Xiaolian Tu,4 Jingjing Zhang,5 Ke Zhao,1,6 Guohua Zhang6,7,* 1Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, 323000, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3School of Education, Renmin University of China, Beijing, 100872, People’s Republic of China; 4School of Renji, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 5School of Nursing, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 6Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 7Institute Of Aging, Key Laboratory Of Alzheimer’s Disease Of Zhejiang Province, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guohua Zhang, Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China, Email zghcnu@wmu.edu.cn Ke Zhao, Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, 323000, People’s Republic of China, Email cocozk1986@163.comBackground: Bedtime procrastination (BP) has become an important factor affecting individual well-being. This study aimed to assess the stability and changes in BP and examine risk and protective factors.Methods: The study recruited 1423 respondents. Latent profile analysis was used to identify subgroups of BP and latent transition analysis to determine transition probabilities for each subgroup. Logistic regression examined associations between identified classes and related factors.Results: Three subgroups of BP were identified. In terms of stability and changes, the moderate bedtime procrastination group showed the highest stability (66%), followed by the severe bedtime procrastination group (62.4%), and the mild bedtime procrastination group had a 52% probability of switching to moderate bedtime procrastination. In terms of influencing factors, more problematic phone use (PSU) (OR: 1.08; 95% CI = 1.05– 1.12), more depression (OR: 1.17; 95% CI = 1.06– 1.29) and anxiety (OR: 1.16; 95% CI = 1.05– 1.28) are all factors that aggravate the transition from mild to moderate sleep procrastination. Similarly, PSU (OR: 1.15; 95% CI = 1.12– 1.19), anxiety (OR: 1.10; 95% CI = 1.06– 1.14), and depression (OR: 1.10; 95% CI = 1.06– 1.14) increased the risk of severe bedtime procrastination. Self-control emerged as a protective factor against BP.Conclusion: This study identified three subgroups of BP at two time points and the rule of transition for each subgroup. Our findings indicate that BP were relatively stable, with some changes over time. The results also highlight the important function that PSU, depression, anxiety, and self-control can play in preventing and intervening in BP.Keywords: bedtime procrastination, latent profile analysis, latent transition analysis, problematic smartphone use, depression, anxiety, self-control

Yin-Ting Yang,1,2,* Xi-Ya Jiang,1,2,* Hong-Liang Xu,3,* Guo Chen,1,2,* Sen-Lin Wang,4 He-Ping Zhang,3 Lin Hong,1,2 Qin-Qin Jin,1,2 Hui Yao,1,2 Wei-Yu Zhang,1,2 Yu-Ting Zhu,1,2 Jie Mei,1,2 Lu Tian,1,2 Jie Ying,1,2 Jing-Jing Hu,5 Shu-Guang Zhou1,2 1Department of Gynecology and Obstetrics, Maternity and Child Healthcare Hospital Affiliated to Anhui Medical University, Anhui Province Maternity and Child Healthcare Hospital, Hefei, Anhui, 230001, People’s Republic of China; 2Department of Gynecology and Obstetrics, The Fifth Clinical College of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Pathology, Anhui Province Maternity and Child Healthcare Hospital, Hefei, Anhui, 230001, People’s Republic of China; 4Department of Medical Genetics Center, Anhui Province Maternity and Child Healthcare Hospital, Hefei, Anhui, 230001, People’s Republic of China; 5Department of Gynecology and Obstetrics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu-Guang Zhou, Department of Gynecology, Anhui Medical University Affiliated Maternity and Child Healthcare Hospital, The Fifth Clinical College of Anhui Medical University, Anhui Province Maternity and Child Healthcare Hospital, No. 15, Yi-Min Street, Lu-Yang District, Hefei, Anhui, 230001, People’s Republic of China, Email zhoushuguang@ahmu.edu.cn Jing-Jing Hu, Department of Gynecology and Obstetrics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email janejj55@126.comBackground: Endometriosis, a common gynecological condition, can cause symptoms such as dysmenorrhea, infertility, and abnormal bleeding, which can negatively affect a woman’s quality of life. In the current study, the pathophysiological mechanisms of endometriosis are unknown, but this study suggests that endometriosis is associated with dysregulation of the autoimmune system. This study identify hub genes involved in the prevalence, identification and diagnostic value of endometriosis and autoimmune diseases, and explore the central genes and immune infiltrates, the diagnosis of endometriosis provides a new sight of thinking about diagnosis and treatment.Methods and Results: The relevant datasets for endometriosis GSE141549, GSE7305 and autoimmune disease-related genes (AIDGs) were downloaded from online database. Using the “limma” package and WGCNA to screen out the autoimmune disease related genes and endometriosis related genes, the autoimmune disease gene-related differential genes (AID-DEGs) progressive GO, KEGG enrichment analysis, and then using the protein interaction network and Cytoscape software to select hub genes (CXCL12, PECAM1, NGF, CTGF, WNT5A), using the “pROC” package to analyze the hub genes for the diagnostic value of endometriosis. The difference in the importance of hub genes for the diagnosis of endometriosis was analyzed by machine learning random forest, and the combined diagnostic value of hub genes was analyzed by using the Support Vector Machine (SVM) algorithm. The eutopic (EU) and ectopic endometrium (EC) immune microenvironment of endometriosis was evaluated using CIBERSORT, the correlation of hub genes to the immune microenvironment was analyzed.Conclusion: The hub genes associated with AIDGs are differentially expressed in EC and EU of endometriosis and possess important value for the diagnosis of endometriosis. The hub genes have a very important impact on the immune microenvironment of endometriosis, which is important for exploring the connection between endometriosis and autoimmune diseases and provides a new insight for the subsequent study of immunotherapy and diagnosis of endometriosis.Keywords: EMT, hub genes, diagnosis, immunotherapy, immune microenvironment

Jie Liu,1,&ast; Ke Zhao,2,&ast; Wei Kang,1,&ast; Siyu Tong,1 Yao Xu,1 Wei Jin,1 Mengxuan Qiao,1 Yuan Li,1 Lan Hong,3 Keqing Yao,4,5 Tiansheng Zheng6 1School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, People’s Republic of China; 3The Third Hospital of Quzhou, Quzhou, People’s Republic of China; 4Shenzhen Mental Health Center, Shenzhen, Guangdong, People’s Republic of China; 5Shenzhen Kangning Hospital, Shenzhen, Guangdong, People’s Republic of China; 6The Affiliated Kangning Hospital of Wenzhou Medical University Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqing Yao, Shenzhen Mental Health Center, Shenzhen Kangning Hospital, Shenzhen, Guangdong, People’s Republic of China, Tel +86-755-82927264, Email KQKangning@gmail.com Tiansheng Zheng, The Affiliated Kangning Hospital of Wenzhou Medical University Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, People’s Republic of China, Email sky.tsh@163.comIntroduction: Non-suicidal self-injury (NSSI) is becoming an increasingly prevalent phenomenon among adolescents, endangering their health. The aims of this study were to 1) explore the associations between borderline personality features, alexithymia and NSSI and 2) examine if alexithymia mediates the relationships between borderline personality features and both the severity of NSSI and the various functions that maintain NSSI in adolescents.Methods: This cross-sectional study recruited 1779 outpatient and inpatient aged 12– 18 years from psychiatric hospitals. All adolescents completed a structured four-part questionnaire including demographic items, the Chinese version of the Functional Assessment of Self-Mutilation, the Borderline Personality Features Scale for Children and the Toronto Alexithymia Scale.Results: The structural equation modelling results indicated that alexithymia partially mediated the associations between borderline personality features and both the severity of NSSI and the emotion regulation function of NSSI (B = 0.058 and 0.099, both p < 0.001), after controlling for age and sex.Discussion: These findings suggest that alexithymia may play a role in the mechanism and treatment of NSSI among adolescents with borderline personality features. Further longitudinal studies are essential to validate these findings.Keywords: self-harm, health, emotion regulation, structural equation modelling

Yunzhen Shi,1,&ast; Wanru Guo,2,&ast; Wenjuan Hu,2 Xiaomeng Li,2 Yanwan Shangguan,2 Xuewen Feng,2 Ming Hu,2 Jiafeng Xia,2 Shuting Wang,2 Jingnan Li,1 Li Hong,1 Bin Lu,1 Kaijin Xu2 1Department of Infectious Diseases, Dongyang People’s Hospital, Dongyang, People’s Republic of China; 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaijin Xu, Email zdyxyxkj@zju.edu.cnAbstract: Tuberculous aortitis (TA) is a rare disease with a high mortality rate. Aortic pseudoaneurysm is the most common vascular pattern of TA, and isolated arterial wall thickening and arterial stenosis can also be seen in TA. We report two cases of disseminated tuberculosis involving the aorta with clinical improvement after treatment. One patient who had an aortic ulcer and intermural hematoma received anti-tuberculosis along with steroids therapy. The other patient, who developed a tubercular abdominal aortic pseudoaneurysm during anti-tuberculosis therapy, successfully received endovascular stent implantation. Clinicians should be aware that TA should be considered in patients with aortitis and active tuberculosis.Keywords: tuberculosis aortitis, aortic pseudoaneurysm, anti-tuberculosis therapy, steroids, endovascular stent implantation

Dan Guo,1,&ast; Lemin Hong,1,&ast; Hao Ji,2,&ast; Yuwen Jiang,1 Ling Lu,1 Xinfeng Wang,1 Hongming Huang1 1Department of Hematology, The Affiliated Hospital of Nantong University, Jiangsu, People’s Republic of China; 2Department of Urology, Tumor Hospital Affiliated to Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinfeng Wang; Hongming Huang, Department of Hematology, The Affiliated Hospital of Nantong University, No. 20, Xisi Street, Nantong, 226001, Jiangsu, People’s Republic of China, Email wxf5204079@126.com; hhmmmc@163.comIntroduction: Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a rare and aggressive form of mature B-cell lymphoma commonly found in elder males, but its genetic features are poorly understood. In this study, we had performed target-sequencing of 360 lymphoma-related genes on 76 PT-DLBCL patients with a median age of 65 (33– 89). Our data provide a comprehensive understanding of the landscape of mutations in a small subset of PT-DLBCL.Methods: A total of 76 PT-DLBCL patients were sequenced, and their clinical data and follow-up data were collected. The relationship between mutated genes, clinical data and prognosis and survival of PT-DLBCL patients was retrospectively analyzed by statistical software.Results: We observed a median of 15 protein-altering variants per patient in our data and was identified recurrent oncogenic mutations of 360 lymphoma-related genes involved in PT-DLBCL, including PIM1 (74%), MYD88 (50%), KMT2D (38%), KMT2C (34%), BTG2 (34%), TBL1XR1 (34%) and ETV6 (24%). Compared with classic DLBCL, PT-DLBCL showed an increased mutation frequency of PIM1, MYD88, BTG2, while NOTCH1 appeared exclusive mutated with PIM1, MSH3 and ETV6. Cox risk model regression analysis showed that age ≥ 60 years, IPI 3– 5 points, BTG2 gene mutation and extranodal organ invasion suggested poor prognosis. Finally, we constructed an OS predict model of PT-DLBCL patients using above factors with a high accuracy.Conclusion: In conclusion, our results revealed genomic characterization of PT-DLBCL, and the mutation of BTG2 was an independent factor predicting a poor prognosis.Keywords: primary testicular diffuse large B-cell lymphoma, genetic mutation, BTG2, prognosis, survival

Xiaofeng Fu,1 Luwei Hong,2 Haiying Gong,3 Guangjuan Kan,4 Pengfei Zhang,1 Ting-Ting Cui,5 Gonglin Fan,6 Xing Si,7 Jiang Zhu1 1Department of Ultrasound, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 2Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 3Department of Ultrasound, Yiwu Traditional Chinese Medicine Hospital, Jinhua, Zhejiang, 321000, People’s Republic of China; 4Department of Ultrasound, The Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 5Department of Ultrasound, Taizhou Traditional Chinese Medicine Hospital, Taizhou, Zhejiang, 318000, People’s Republic of China; 6Department of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 7Hangzhou Normal University, Hangzhou, Zhejiang, 310000, People’s Republic of ChinaCorrespondence: Jiang Zhu, Department of Ultrasound, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 31000, People’s Republic of China, Tel +86 13757122629, Email zhujiang1046@zju.edu.cnBackground: Glioma is a common type of tumor in the central nervous system characterized by high morbidity and mortality. Autophagy plays vital roles in the development and progression of glioma, and is involved in both normal physiological and various pathophysiological progresses.Patients and Methods: A total of 531 autophagy-related genes (ARGs) were obtained and 1738 glioma patients were collected from three public databases. We performed least absolute shrinkage and selection operator regression to identify the optimal prognosis-related genes and constructed an autophagy-related risk signature. The performance of the signature was validated by receiver operating characteristic analysis, survival analysis, clinic correlation analysis, and Cox regression. A nomogram model was established by using multivariate Cox regression analysis. Schoenfeld’s global and individual test were used to estimate time-varying covariance for the assumption of the Cox proportional hazard regression analysis. The R programming language was used as the main data analysis and visualizing tool.Results: An overall survival-related risk signature consisting of 15 ARGs was constructed and significantly stratified glioma patients into high- and low-risk groups (P < 0.0001). The area under the ROC curve of 1-, 3-, 5-year survival was 0.890, 0.923, and 0.889, respectively. Univariate and multivariate Cox analyses indicated that the risk signature was a satisfactory independent prognostic factor. Moreover, a nomogram model integrating risk signature with clinical information for predicting survival rates of patients with glioma was constructed (C-index=0.861± 0.024).Conclusion: This study constructed a novel and reliable ARG-related risk signature, which was verified as a satisfactory prognostic marker. The nomogram model could provide a reference for individually predicting the prognosis for each patient with glioma and promoting the selection of optimal treatment.Keywords: glioma, autophagy, risk signature, prognosis, nomogram

Min Zhou,&ast; Bingshu Li,&ast; Jianfeng Liu, Li Hong Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li HongDepartment of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan, 430060, People’s Republic of ChinaTel/Fax +86 27-88041911Email drhongli7777@gmail.comPurpose: Pyroptosis is a form of lytic programmed cell death that is associated with the pathogenesis of many tumors. However, the potential roles of pyroptosis-related genes (PRGs) in the tumor microenvironment (TME) remain unclear.Materials and Methods: We systematically described the genetic and transcriptional alterations in PRGs in gynecological cancers. An unsupervised clustering method was used to investigate the molecular subtypes of ovarian cancer (OV) and systematically analyze the TME cell infiltration characteristics. A prognostic signature and nomogram were established to quantify the pyroptosis patterns of individual tumors. We also analyzed the expression levels of eight PRGs in the OV tissues.Results: Two distinct molecular subtypes of OV were identified, and these two distinct molecular subtypes could predict clinicopathological features, prognosis, TME stromal activity, immune infiltrating cells, and immune checkpoints. A prognostic signature was established, and its predictive capability was validated. Low risk score, characterized by activation of immunity, upregulation of programmed death-ligand 1 expression, lower tumor immune dysfunction and exclusion scores, lower tumor mutation burden, and favorable prognosis. These findings suggested that low-risk patients with OV may be more sensitive to immunotherapy. In addition, this signature could effectively predict the response to chemotherapy in patients with OV. Furthermore, a prognostic nomogram was generated, which exhibited superior predictive accuracy.Conclusion: This study highlights the crucial role of PRGs in the TME and may help develop immunotherapies and promote individualized therapeutic strategies for patients with OV.Keywords: pyroptosis, gynecological cancer, tumor microenvironment, immunotherapy, overall survival

Xinyang Fu,1,&ast; Zhiqiang Lin,1,&ast; Sumei Chen,2 Limian Hong,1 Xueping Yu,2 Shuifa Wu1 1Department of Pharmacy, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 2Department of Infectious Disease, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuifa WuDepartment of Pharmacy, Quanzhou First Hospital Affiliated to Fujian Medical University, No. 250 East Street, Licheng District, Quanzhou, Fujian, 362000, People’s Republic of ChinaEmail shfw0116@126.comXueping YuDepartment of Infectious Disease, Quanzhou First Hospital Affiliated to Fujian Medical University, No. 250 East Street, Licheng District, Quanzhou, Fujian, 362000, People’s Republic of ChinaEmail xpyu15@fudan.edu.cnAbstract: The pharmacokinetic/pharmacodynamic (PK/PD) parameter for evaluating the efficacy of vancomycin is now recommended to target an AUC/MIC (area under the curve, AUC; minimum inhibitory concentration, MIC) ratio of 400 to 600, and trough concentration should not be used as a substitute. We report a case of intracranial infection caused by methicillin-resistant Staphylococcus epidermidis (MRSE), which was sensitive to vancomycin (MIC=2μg/mL) and linezolid (MIC=4μg/mL). The trough concentration of vancomycin in serum was 18.3 μg/mL, and the vancomycin concentration in CSF was 5.0 μg/mL, all within normal range. However, the AUC/MIC ratio was calculated to be 125 mg·h·L− 1, unable to reach target AUC/MIC. Vancomycin was replaced with linezolid after 36 days of treatment due to poor outcome, and the patient was eventually cured. Further, 23 cases of intracranial methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative Staphylococcus (MRCoNS) infections were reported, of which 1 case with MRSA had a vancomycin MIC of 1 μg/mL, while the remaining 22 cases had vancomycin MICs > 1 μg/mL. The linezolid-containing regimen was used after drug susceptibility results or if the initial treatment failed, leading to recovery in 19 patients, microbial clearance in 3 patients, and treatment failure in 1 case. In conclusion, vancomycin dosing should be based on AUC-guided dosing and monitoring. When the vancomycin MIC of MRSA/MRCoNS is > 1 μg/mL, the target AUC/MIC may not be achieved. In such cases, linezolid can effectively be considered as a good alternative to vancomycin.Keywords: AUC/MIC, trough concentration, intracranial infection, vancomycin, linezolid

Jiang Yang,* Bingshu Li,* Jin Liu, Wanlin Zeng, Li Hong Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li HongDepartment of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, 430060, People’s Republic of ChinaEmail drhongli77@gmail.comObjective: To introduce a modified hysteroscopic-laparoscopic operation for cesarean scar pregnancy (CSP) of stable type III.Patients and Methods: We retrospectively studied the case notes of 31 patients with stable type III cesarean scar pregnancy who underwent hysteroscopic-laparoscopic surgery in our hospital. Thirteen patients received the modified hysteroscopic-laparoscopic surgery (modified surgery group), and eighteen patients received traditional hysteroscopic-laparoscopic surgery (traditional surgery group).Results: There was no significant difference in patients’ age, gestational age, number of previous cesarean sections, the serum human chorionic gonadotropin (hCG) level before surgery, gestational sac diameter, myometrium thickness between the two groups. In the modified hysteroscopic-laparoscopic surgery, the mean surgical time was 50.45± 24.45 mins, the mean length of stay in hospital was 4.50± 0.50 days, which was significantly shorter than the traditional surgery group (84.75± 33.28 mins and 5.50± 0.75 days, respectively). And the intraoperative hemorrhage in the modified group was also less than that in the traditional group (40.50± 12.25 mL vs 75.33± 25.45mL). Whereas the time for hCG normalization, postoperative vaginal bleeding and menstrual recovery had no significant difference between the modified surgery group and the traditional surgery group. There was no recurrence of CSP in both groups.Conclusion: The modified hysteroscopic-laparoscopic surgery had shorter operation time, less blood loss, and sooner recovery time after surgery compared to traditional hysteroscopic-laparoscopic surgery, which could be more beneficial to our patients and should be applied in clinics generally.Keywords: cesarean scar pregnancy, hysteroscopic-laparoscopic surgery, modified surgery, traditional surgery

ABSTRACT Serological surveillance studies of infectious diseases provide population-level estimates of infection and antibody prevalence, generating crucial insight into population-level immunity, risk factors leading to infection, and effectiveness of public health measures. These studies traditionally rely on detection of pathogen-specific antibodies in samples derived from venipuncture, an expensive and logistically challenging aspect of serological surveillance. During the COVID-19 pandemic, guidelines implemented to prevent the spread of SARS-CoV-2 infection made collection of venous blood logistically difficult at a time when SARS-CoV-2 serosurveillance was urgently needed. Dried blood spots (DBS) have generated interest as an alternative to venous blood for SARS-CoV-2 serological applications due to their stability, low cost, and ease of collection; DBS samples can be self-generated via fingerprick by community members and mailed at ambient temperatures. Here, we detail the development of four DBS-based SARS-CoV-2 serological methods and demonstrate their implementation in a large serological survey of community members from 12 cities in the East Bay region of the San Francisco metropolitan area using at-home DBS collection. We find that DBS perform similarly to plasma/serum in enzyme-linked immunosorbent assays and commercial SARS-CoV-2 serological assays. In addition, we show that DBS samples can reliably detect antibody responses months postinfection and track antibody kinetics after vaccination. Implementation of DBS enabled collection of valuable serological data from our study population to investigate changes in seroprevalence over an 8-month period. Our work makes a strong argument for the implementation of DBS in serological studies, not just for SARS-CoV-2, but any situation where phlebotomy is inaccessible. IMPORTANCE Estimation of community-level antibody responses to SARS-CoV-2 from infection or vaccination is critical to inform public health responses. Traditional studies of antibodies rely on collection of blood via venipuncture, an invasive procedure not amenable to pandemic-related social-distancing measures. Dried blood spots (DBS) are an alternative to venipuncture, since they can be self-collected by study participants at home and do not require refrigeration for shipment or storage. However, DBS-based assays to measure antibody levels to SARS-CoV-2 have not been widely utilized. Here, we show that DBS are comparable to blood as a sampling method for antibody responses to SARS-CoV-2 infection and vaccination over time measured using four distinct serological assays. The DBS format enabled antibody surveillance in a longitudinal cohort where study participants self-collected samples, ensuring the participants’ safety during an ongoing pandemic. Our work demonstrates that DBS are an excellent sampling method for measuring antibody responses whenever venipuncture is impractical.

Yuzi Zhao,1 Jie Pi,1 Lihua Liu,2 Wenjie Yan,1 Shufang Ma,3 Li Hong1 1Department of Gynaecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Huanggang Huangzhou Maternity and Child Health Care Hospital, Huanggang, People’s Republic of China; 3Reproductive Medicine Center, Wuhan Kangjian Women and Infants Hospital, Wuhan, People’s Republic of ChinaCorrespondence: Li HongRenmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, Hubei 430060, People’s Republic of ChinaTel +86-13476814853Email orange826@163.comBackground: This study aimed to identify the hub genes associated with prognosis of patients with ovarian cancer by using integrated bioinformatics analysis and experimental validation.Methods: Four microarray datasets (GSE12470, GSE14407, GSE18521 and GSE46169) were analyzed by the GEO2R tool to screen common differentially expressed genes (DEGs). Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, the (KEGG) pathway and Reactome pathway enrichment analysis, protein–protein interaction (PPI) construction, and the identification of hub genes were performed. Furthermore, we performed the survival and expression analysis of the hub genes. In vitro functional assays were performed to assess the effects of hub genes on ovarian cancer cell proliferation, caspase-3/7 activity and invasion.Results: A total of 89 common DEGs were identified among these four datasets. The KEGG and Reactome pathway results showed that the DEGs were mainly associated with cell cycle, mitotic and p53 signaling pathway. A total of 20 hub genes were identified from the PPI network by using sub-module analysis. The survival analysis revealed that high expression of six hub genes (AURKA, BUB1B, CENPF, KIF11, KIF23 and TOP2A) were significantly correlated with shorter overall survival and progression-free survival of patients with ovarian cancer. Furthermore, the expression of the six hub genes were validated by the GEPIA database and Human Protein Atlas, and functional studies revealed that knockdown of KIF11 and KIF23 suppressed the SKOV3 cell proliferation, increased caspase-3/7 activity and attenuated invasive potentials of SKOV3 cells. In addition, knockdown of KIF11 and KIF23 up-regulated E-cadherin mRNA expression but down-regulated N-cadherin and vimentin mRNA expression in SKOV3 cells.Conclusion: Our results showed that six hub genes were up-regulated in ovarian cancer tissues and may predict poor prognosis of patients with ovarian cancer. KIF11 and KIF23 may play oncogenic roles in ovarian cancer cell progression via promoting ovarian cancer cell proliferation and invasion.Keywords: ovarian cancer, bioinformatics, cell cycle, hub genes, survival, prognosis

Jun-Yan Wang, Fan Zhang, Lei Hong, Su-Ju Wei Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People’s Republic of ChinaCorrespondence: Su-Ju WeiDepartment of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People’s Republic of ChinaTel +86 311-86095672Email wei11071@126.comBackground: Non-small-cell lung carcinoma (NSCLC) is the most common type of lung cancer. Circular RNA_0000429 (circ_0000429) is an identified circular RNA (circRNA) that is correlated with cancer progression. However, the role of circ_0000429 in NSCLC remains unknown. In the present study, we aimed to investigate the function of circ_0000429 in NSCLC and the underlying mechanism.Methods: The expression patterns of circ_0000429 were determined using qRT-PCR in NSCLC samples and cell lines. The subcellular distribution of circ_0000429 in NSCLC cells was analyzed by fluorescence in situ hybridization (FISH). Cell proliferation was examined utilizing the CCK-8 assay. Cell migration and invasion were evaluated using the transwell assay. We used the bioinformatics software TargetScan and miRanda to predict circRNA–miRNA and miRNA–mRNA interactions.Results: Our results showed that circ_0000429 expressions were significantly upregulated in NSCLC tissues and cell lines. Knockdown of circ_0000429 significantly inhibited the cell proliferation, migration, and invasion of NSCLC cells in vitro. Furthermore, we demonstrated that circ_0000429 acted as a sponge to absorb microRNA-1197 (miR-1197) and promoted MADD expression.Conclusion: Collectively, our results demonstrated that circ_0000429 exhibited a carcinogenic role by sponging miR-1197 and regulating CMADD expression in NSCLC. These findings provided evidence for understanding the role of circ_0000429 in NSCLC tumorigenesis.Keywords: circRNA_0000429, miRNA-1197, MADD, NSCLC

Jiang Yang,* Jin Liu,* Suting Li, Li Hong Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Hong Email drhongli77@gmail.comAbstract: COVID-19 has the characteristics of rapid onset, strong infectivity, and fast course change, which has caused a worldwide pandemic. Now, our hospital and department have implemented a series of efficacious stratagems to control the spread of the COVID-19. However, the daily-increasing cases are continuously at an extraordinary level, which mean the requirement and mission to prevent and control the pandemic are enormous and urgent. However, because of the urgency of the disease and the timeliness of treatment, gynecological tumor patients cannot be administered in the hospital until the pandemic situation could be controlled entirely. Consequently, this review proposes the following suggestions and our experience about preventing and controlling of COVID-19 and the treatment for patients with gynecological tumors in gynecology departments.Keywords: COVID-19, prevention and control strategies, treatment, strategy

Objective The present study aimed to evaluate the performance of odor abatement by using two different ventilation-biofilter systems with recycled stablized swine wastewater. Methods The performance of odor removal efficiency was evaluated using two different ventilation-biofilter-recycled wastewater arrangements. A recirculating air-flow ventilation system connected to a vertical biofilter (M1) and a plug-flow ventilation system connected to a horizontal biofilter (M2) were installed. Water dripping over the surface of the biofilter was recycled at a flow rate of 0.83 L/h in summer and 0.58 L/h in winter to reduce odorous compounds and particulate matter (PM). The experiments were performed for 64 days with M1 and M2 to investigate how these two ventilation-biofilter systems influenced the reduction of odor compounds in the model houses. Odorous compounds, NH3 and volatile organic compounds (VOCs) were analyzed, and microclimatic variables such as temperature, humidity, and PM were monitored. Results Ammonia concentration inside M1 was about 41% higher on average than that in M2. PM and total suspended particles (TSPs) inside M1 were about 62.2% and 69.9%, respectively, higher than those in M2. TSPs in the model house were positively correlated with the concentration of NH3 and VOCs. Conclusion M2 emitted lower concentration of odorous compounds than M1. Moreover, M2 could maintain the optimum temperature condition for a swine house during the cooler season. The plug-flow ventilation–horizontal biofilter system could be used for pig houses to minimize air pollution produced by swine farming activities and maintain optimum microclimate conditions for pigs.

Lei Wang,1,* Rong Fan,1,* Chen Zhang,1 Liwen Hong,1 Tianyu Zhang,1 Ying Chen,2 Kai Liu,2 Zhengting Wang,1 Jie Zhong1 1Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2CareLinker Co., Ltd., Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengting Wang; Jie ZhongDepartment of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijiner Road, Shanghai 200025, People’s Republic of ChinaTel +86-21-64370045 ext. 600901Email Dake_wang@126.com; jimmyzj64@hotmail.comObjective: Medication adherence is crucial in the management of Crohn’s disease (CD), and yet the adherence remains low. This study aimed to develop machine learning models that can help predict CD patients of nonadherence to azathioprine (AZA), and thus assist caregivers to streamline the intervention process.Methods: This single-centered, cross-sectional study recruited 446 CD patients who have been prescribed AZA between Sep 2005 and Sep 2018. Questionnaires of medication adherence, anxiety and depression, beliefs of medication necessity and concerns, and medication knowledge were provided to patients, while other data were extracted from the electronic medical records. Two machine learning models of back-propagation neural network (BPNN) and support vector machine (SVM) were developed and compared with logistic regression (LR), and assessed by accuracy, recall, precision, F1 score and the area under the receiver operating characteristic curve (AUC).Results: The average classification accuracy and AUC of the three models were 81.6% and 0.896 for LR, 85.9% and 0.912 for BPNN, and 87.7% and 0.930 for SVM, respectively. Multivariate analysis identified four risk factors associated with AZA nonadherence: medication concern belief (OR=3.130, p< 0.001), education (OR=2.199, p< 0.001), anxiety (OR=1.549, p< 0.001) and depression (OR=1.190, p< 0.001), while medication necessity belief (OR=0.004, p< 0.001) and medication knowledge (OR=0.805, p=0.013) were protective factors.Conclusion: We developed three machine learning models and proposed an SVM model with promising accuracy in the prediction of AZA nonadherence in Chinese CD patients. The study also reconfirmed that education, psychologic distress, and medication beliefs and knowledge are correlated to AZA nonadherence.Keywords: Crohn’s disease, azathioprine, medication adherence, maintenance therapy, machine learning, support vector machine, back-propagation neural network

Jun Chang,1,2 Ling Hong,2 Yaozhong Liu,3 Yiwen Pan,2 Hao Yang,2 Wenrui Ye,3 Keli Xu,4 Zhijian Li,1 Shubing Zhang1,2,5,6 1Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of China; 3Xiangya Medical School, Central South University, Changsha, Hunan 410013, People’s Republic of China; 4Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA; 5Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, Hunan 410013, People’s Republic of China; 6Breast Cancer Research Center, School of Life Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of ChinaCorrespondence: Zhijian LiDepartment of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, People’s Republic of ChinaTel +8613787314214Email lizhijian@csu.edu.cnShubing ZhangDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of ChinaTel +861397589680Email shubingzhang@csu.edu.cnPurpose: Molecular targeting is a powerful approach for aggressive claudin-low breast cancer (CLBC). Overexpression of PI3K catalytic subunit gamma (PIK3CG) in human CLBC is offering a promising opportunity for targeted therapies. We utilized a specific inhibitor of PIK3CG combined with paclitaxel (PTX) to treat CLBC cells in vitro and in vivo.Patients and Methods: The tumor cells growth and apoptosis in vitro were analyzed by CCK8, plate clone formation assay, tumorsphere assay, Hoechst staining and flow cytometry. The invasion and metastasis ability of tumor cells in vitro were investigated by wound healing and transwell experiments. Critical gene expression levels were checked by qRT-PCR and Western blot. Xenograft models with CLBC cell lines in SCID mice were established to investigate the effect of combined drugs in vivo.Results: We identified that PIK3CG was a potential therapeutic target for CLBC patients. Targeting PIK3CG potentiated CLBC cells growth inhibition in 2D and 3D cultures by PTX. Inhibition of PIK3CG activation could enhance CLBC cells apoptosis and migration suppression induced by PTX. Manipulating autophagy was a validated approach for the use of PIK3CG inhibitor. Using CLBC xenograft mice model, we found that CLBC tumors in vivo could be well treated by combined drugs of PIK3CG inhibitor and PTX.Conclusion: We demonstrated that PIK3CG was a potential target for the therapy of CLBC and inhibition of PIK3CG activation could reinforce the therapeutic effect of this aggressive disease by PTX. The combined use of PIK3CG inhibitor and PTX might be a potential regimen for treating this subtype of breast cancer.Keywords: PIK3CG, paclitaxel, claudin-low breast cancer, combined drugs, targeted therapy

The separation of computing units and memory in the computer architecture mandates energy-intensive data transfers creating the von Neumann bottleneck. This bottleneck is exposed at the application level by the steady growth of IoT and data-centric deep learning algorithms demanding extraordinary throughput. On the hardware level, analog Processing-in-Memory (PiM) schemes are used to build platforms that eliminate the compute-memory gap to overcome the von Neumann bottleneck. PiM can be efficiently implemented with ferroelectric transistors (FeFET), an emerging non-volatile memory technology. However, PiM and FeFET are heavily impacted by process variation, especially in sub 14 nm technology nodes, reducing the reliability and thus inducing errors. Brain-inspired Hyperdimensional Computing (HDC) is robust against such errors. Further, it is able to learn from very little data cutting energy-intensive transfers. Hence, HDC, in combination with PiM, tackles the von Neumann bottleneck at both levels. Nevertheless, the analog nature of PiM schemes necessitates the conversion of results to digital, which is often not considered. Yet, the conversion introduces large overheads and diminishes the PiM efficiency. In this paper, we propose an all-in-memory scheme performing computation and conversion at once, utilizing programmable FeFET synapses to build the comparator used for the conversion. Our experimental setup is first calibrated against Intel 14 nm FinFET technology for both transistor electrical characteristics and variability. Then, a physics-based model of ferroelectric is included to realize the Fe-FinFETs. Using this setup, we analyze the circuit’s susceptibility to process variation, derive a comprehensive error probability model, and inject it into the inference algorithm of HDC. The robustness of HDC against noise and errors is able to withstand the high error probabilities with a loss of merely 0.3% inference accuracy.

Comprehensive data on transmission mitigation behaviors and both SARS-CoV-2 infection and serostatus are needed from large, community-based cohorts to identify COVID-19 risk factors and the impact of public health measures. We conducted a longitudinal, population-based study in the East Bay Area of Northern California. From July 2020-March 2021, approximately 5,500 adults were recruited and followed over three data collection rounds to investigate the association between geographic and demographic characteristics and transmission mitigation behavior with SARS-CoV-2 prevalence. We estimated the populated-adjusted prevalence of antibodies from SARS-CoV-2 infection and COVID-19 vaccination, and self-reported COVID-19 test positivity. Population-adjusted SARS-CoV-2 seroprevalence was low, increasing from 1.03% (95% CI: 0.50-1.96) in Round 1 (July-September 2020), to 1.37% (95% CI: 0.75-2.39) in Round 2 (October-December 2020), to 2.18% (95% CI: 1.48-3.17) in Round 3 (February-March 2021). Population-adjusted seroprevalence of COVID-19 vaccination was 21.64% (95% CI: 19.20-24.34) in Round 3, with White individuals having 4.35% (95% CI: 0.35-8.32) higher COVID-19 vaccine seroprevalence than individuals identifying as African American or Black, American Indian or Alaskan Native, Asian, Hispanic, two or more races, or other. No evidence for an association between transmission mitigation behavior and seroprevalence was observed. Despite >99% of participants reporting wearing masks individuals identifying as African American or Black, American Indian or Alaskan Native, Asian, Hispanic, two or more races, or other, as well as those in lower-income households, and lower-educated individuals had the highest SARS-CoV-2 seroprevalence and lowest vaccination seroprevalence. Results demonstrate that more effective policies are needed to address these disparities and inequities.

Lei Hong,1 Haijuan Wang,2 Junyan Wang,1 Suju Wei,1 Fan Zhang,1 Jing Han,1 Yan Liu,1 Minting Ma,1 Chengyuan Liu,1 Yu Xu,1 Da Jiang1 1Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People’s Republic of China; 2Examination and Training Center Health and Family Planning Commission of Hebei, Shijiazhuang, Hebei 050051, People’s Republic of ChinaCorrespondence: Da JiangDepartment of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People’s Republic of ChinaTel +86 311 8609 5672Email yzc1244@163.comBackground: The tumor suppressor role of lncRNA PTCSC3 has been reported in papillary thyroid carcinoma, our study aimed to investigate its involvement in gastric cancer.Methods: Tumor tissues and adjacent healthy tissues were collected from gastric cancer patients. Expression of PTCSC3 and lncRNA Linc-pint in these tissues was analyzed by RT-qPCR. The interaction between PTCSC3 and Linc-pint was analyzed by overexpression experiments. Cell proliferation and stemness were analyzed by CCK-8 assay and cell stemness assay, respectively.Results: PTCSC3 and lncRNA Linc-pint were both downregulated in tumor tissues than in adjacent healthy tissues of gastric cancer patients. Low levels of PTCSC3 and Linc-pint were closely correlated with poor survival. PTCSC3 and Linc-pint overexpression inhibited tumor growth and cancer cell stemness, while Linc-pint knockdown played an opposite role an attenuated the effects of PTCSC3 overexpression. Expression levels of PTCSC3 and Linc-pint were significantly correlated in tumor tissues but not in adjacent healthy tissues. Overexpression of PTCSC3 and Linc-pint upregulated the expression of each other.Conclusion: PTCSC3 inhibits tumor growth and cancer cell stemness in gastric cancer by interacting with lncRNA Linc-pint.Keywords: gastric cancer, lncRNA PTCSC3, lncRNA Linc-pint, growth, stemness

Huan Lin,1,* Jiahuai Wen,1,* Lixia Hong,2,* Ying Chen,1 Yannan Wu,1 Shaowen Zhong1 1Department of Breast Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of General Surgery, The Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaowen ZhongDepartment of Breast Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510060, People’s Republic of ChinaTel +86-20-81887233Email zhongshaowentcd@sina.comBackground: Breast cancer is the most common cancer in women worldwide, and reproductive factors and family history of malignancy are considered as high risk factors. The present study aimed to evaluate the synergistic effect of reproductive factors and family history on breast cancer.Method: A total of 1215 breast cancer patients and 1215 control participants from two medical centers were enrolled, and reproductive factor history and family cancer history information was collected. Multivariate logistic regression analyses were performed to estimate the adjusted odds ratio (OR), and synergy index (SI) was used to assess the combined effect of potential factors.Results: Compared to the controls, a negative association between full-term pregnancy/breastfeeding and breast cancer was observed regardless of the status of family cancer history (OR: 0.675, 95% CI: 0.560–0.814 and OR: 0.631, 95% CI: 0.503–0.789 respectively) after adjustment of other confounders, while the risk effect of abortion was unproven. The synergistic effect of history of full-term pregnancy and family history of malignancy was indicated in the combined analyses with SI as 9.429 (95% CI:1.248–71.245).Conclusion: Full-term pregnancy/breastfeeding were protective factors against breast cancer and synergistic additive effect was demonstrated between no full-term pregnancy/breastfeeding and a family history of malignancy on the risk of breast cancer.Keywords: breast cancer, full-term pregnancy, breastfeeding, family cancer history

BET-bromodomain inhibitors could be used to treat medulloblastoma tumors with Myc amplifications. Here, the authors show that both the response and resistance to BET inhibitors in mice is mediated by bHLH/homeobox transcription factors.

Jin Zhang,1,* Donghui Zhao,1,* Qingjun Li,2 Xiuluan Du,1 Yanxiang Liu,1 Xin Dai,1 Lianqing Hong3 1Department of Pathology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, P.R. China; 2Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, P.R. China; 3Department of Pathology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Chinese Medicine, Nanjing, P.R. China *These authors contributed equally to this work Background: Gastric cancer (GC) is a common malignant tumor of the digestive system. In addition, GC metastasis is an extremely complicated process. A previous study has found that lysine-specific demethylase 1 (LSD1) is abnormal expression in a variety of cancers and its overexpression correlates with aggressive disease and poor outcome. Methods: qRT-PCR and Western blot assays were used to assess the expression of LSD1 in GC tissue samples and cell lines. Colony formation assay, CCK-8 assay, scratch-wound assay and transwell invasion, were performed to determine the effect of LSD1 on cell proliferation and migration as well as invasion in GC. Results: Our results show that LSD1 was up-regulated in GC tumor tissues and cell lines, and high expression level of LSD1 was found to be positively correlated with tumor size, lymph node metastasis and pathological grade. Moreover, LSD1 promoted cell proliferation, migration and invasion of GC. In addition, LSD1 regulated E-cadherin expression through demethylating H3K4me2, thereby promoting EMT in GC. Conclusion: Our work indicated that LSD1 may be used as a potential target of gastric cancer. Keywords: LSD1, EMT, E-cadherin, H3K4me2, gastric cancer

Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenias alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.

Wanli Yang,1,* Jiaojiao Ma,1,* Wei Zhou,1,* Zichao Li,2 Xin Zhou,2 Bo Cao,2 Yujie Zhang,1 Jinqiang Liu,1 Zhiping Yang,1 Hongwei Zhang,3 Qingchuan Zhao,3 Liu Hong,1 Daiming Fan1 1State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Military Medical University, Xi’an, China; 2The First Brigade of Student, Air Force Military Medical University, Xi’an, China; 3Department of Digestive Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, China *These authors contributed equally to this work Background: Colon cancer is one of the leading malignant neoplasms worldwide. Until now, the concrete mechanisms of colonic cancerogenesis are largely unknown; identification of driven genes and pathways is, therefore, of great importance for monitoring and conquering this disease. This study aims to explore the potential biomarkers and therapeutic targets for colon cancer treatment. Methods: The gene expression profile of GSE44076 from Gene Expression Omnibus database, including 98 primary colon cancers and 98 normal distant colon mucosa, was deeply analyzed. GEO2R tool was used to screen the differentially expressed genes (DEGs) between colon cancer tissues and normal samples. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed for screening DEGs using Database for Annotation, Visualization and Integrated Discovery database and Panther database. Moreover, Search Tool for the Retrieval of Interacting Genes, Cytoscape software, and Molecular Complex Detection plug-in were used to visualize the protein–protein interaction of these DEGs. Results: A total of 497 DEGs were obtained, including 129 upregulated genes mainly enriched in Hippo signaling pathway, Wnt signaling pathway, and cytokine–cytokine receptor interaction and 368 downregulated genes enriched in retinol metabolism, steroid hormone biosynthesis, drug metabolism, and chemical carcinogenesis. Using Molecular Complex Detection software, three important modules were selected from the protein–protein interaction network. Moreover, 20 hub genes with high degree of connectivity were selected, including COL1A1, CXCL5, GNG4, TIMP1, and so on. The Kaplan–Meier analysis for overall survival and correlation analysis were applied among the hub genes. Conclusion: Taken together, DEGs, especially the hub genes such as COL1A1, might be the driven genes in colon cancer progression. More importantly, they might be the novel biomarkers for diagnosis and guiding therapeutic strategies of colon cancer. Keywords: colon cancer, protein–protein interaction, bioinformatics analysis, diagnosis, prognosis

Abstract Background Connexin 43 (Cx43) plays a central role in the inflammatory response and wound healing. Targeting Cx43 expression reduces inflammation in a variety of injuries. The expression pattern of Cx43 has not been described for many inflammatory skin diseases. Objectives To describe the expression patterns of Cx43 in eczema, psoriasis, Steven‐Johnson syndrome/toxic epidermal necrolysis. Methods Archival skin biopsies from patients with eczema, psoriasis, and Steven‐Johnson syndrome/toxic epidermal necrosis were identified and examined, with sister sections stained for Cx43 and imaged by confocal microscopy. All samples were compared to age and site‐matched normal skin controls. Results Epidermal Cx43 is reduced in acute eczema, absent in regions of spongiosis, and is highly elevated in subacute and chronic eczema. In plaque psoriasis, Cx43 is overexpressed in areas with psoriasiform hyperplasia with a fish‐scale‐like appearance but is lost in regions surrounding neutrophil microabscesses. Cx43 staining is strong in the neutrophils within these microabscesses. In SJS/TEN, Cx43 expression is elevated in areas bordering normal tissue but is rapidly lost in areas of keratinocyte necrosis. Conclusions Dynamic changes in Cx43 levels are seen in inflammatory skin diseases and may represent future potential therapeutic targets.

Maochen Zhang,* Tianyu Zhang,* Liwen Hong, Chen Zhang, Jie Zhou, Rong Fan, Lei Wang, Zhengting Wang, Bin Xu, Jie Zhong Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Patients with newly diagnosed Crohn’s disease (CD) are associated with impaired physical and psychological well-being. These psychological characteristics are dynamic with the course of disease and could be influenced by medical treatment. Infliximab is effective and widely used in moderate-to-severe CD patients. The aim of this study was to evaluate the improvement of psychological status after infliximab treatment in patients with newly diagnosed CD.Methods: Newly diagnosed moderate-to-severe CD patients were prospectively enrolled in our study. Infliximab 5 mg/kg was administered at weeks 0, 2, 6, 14, 22, and 30. Outcomes including disease severity, illness perceptions, coping strategies, anxiety, depression, and quality of life (QoL) were measured at baseline, week 14, and week 30.Results: Eighty-two patients completed our study. The rates of clinical remission at weeks 14 and 30 were 59/82 (72.0%) and 58/82 (70.7%), respectively. Patients who achieved clinical remission at weeks 14 and 30 significantly improved in illness perceptions (P

Maochen Zhang,* Tianyu Zhang,* Liwen Hong, Qiangqiang Wu, Yun Lin, Mengfan Xie, Rong Fan, Zhengting Wang, Jie Zhou, Jie Zhong Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Computed tomography enterography (CTE) and double-balloon enteroscopy (DBE) are widely used in diagnosis of small bowel diseases. Both of these examinations bring discomfort to patients. The aim of this study was to compare patients’ tolerance and preference between CTE and DBE. Methods: From August 1, 2014 to December 31, 2016, patients with suspected or known small bowel diseases who underwent both CTE and DBE were prospectively enrolled in our study. They were asked to fill out a questionnaire evaluating discomfort of the procedure after each examination. Results: One hundred and seven patients completed our study. Abdominal distension, painfulness, tenesmus, general discomfort, prolonged duration, difficulty in completing the test, and discomfort after the examination were significantly lower with CTE than with DBE (P

Maochen Zhang,1,* Liwen Hong,1,* Tianyu Zhang,1 Yun Lin,1 Sichang Zheng,1 Xiaolin Zhou,1 Rong Fan,1 Zhengting Wang,1 Chenli Zhang,2 Jie Zhong1 1Department of Gastroenterology, 2Exclusive Medical Center, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Disease severity, illness perceptions, coping strategies, stress, psychological well-being, and quality of life were reported to have close relationships. According to the Common Sense Model, illness perceptions and coping strategies could mediate the relationship between illness stimuli and illness outcomes such as psychological health and quality of life. Stress was also associated with the individual’s disease severity, anxiety, depression, and quality of life. Objectives: The study aimed to explore the influencing factors of illness outcomes, and to what extent illness perceptions, coping strategies, and stress mediate the relationship between disease severity and anxiety, and depression and quality of life. Methods: Our study included 159 patients with Crohn’s disease who were attending a tertiary hospital outpatient clinic or who were hospitalized. Disease severity was measured with the Crohn’s Disease Activity Index. Illness perceptions were measured with the Brief Illness Perceptions Questionnaire. Coping strategies were measured with the Carver Brief Coping Questionnaire. Stress was measured with the Perceived Stress Questionnaire. Anxiety and depression were measured with the Hospital Anxiety and Depression Scale. Quality of life was measured with the Inflammatory Bowel Disease Questionnaire. Results: Disease severity, illness perceptions, maladaptive coping, stress, anxiety, depression and quality of life were significantly correlated with each other among patients with Crohn’s disease. Using structural equation modeling to describe the inner relationship of the aforementioned variables, an excellent-fitted model was drawn. (χ2[10]=13.83, P=0.18, χ2/N=1.38, standardized root mean square residual [SRMR] 0.97, comparative fit index [CFI] >0.99). Disease severity had a direct influence on illness perceptions. Illness perceptions had a direct influence on stress. Both illness perceptions and stress had direct influences on anxiety, depression, and quality of life, while maladaptive coping did not directly influence anxiety, depression, or quality of life. Stress had a direct influence on maladaptive coping. Quality of life was also directly influenced by disease severity and anxiety.Conclusion: Interrelationships between disease stimuli, disease perceptions and management and disease outcomes could be found in patients with Crohn’s disease. Illness perceptions and stress mediated an individual’s disease severity and anxiety, depression and quality of life, while coping strategy was not an applicable mediator. Keywords: Crohn’s disease, disease severity, illness perceptions, coping strategies, stress, psychological well-being, quality of life

Yun-Chun Zhao,1 Li Zhang,2 Shi-Sen Feng,3 Lu Hong,3 Hai-Li Zheng,3 Li-Li Chen,4 Xiao-Ling Zheng,1 Yi-Qing Ye,1 Meng-Dan Zhao,1 Wen-Xi Wang,3 Cai-Hong Zheng1 1Pharmacy Department, Women’s Hospital, 2Pharmacy Department, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Pharmaceutic Preparation, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 4Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Abstract: A novel cationic cholesterol derivative-based small interfering RNA (siRNA) interference strategy was suggested to inhibit Notch1 activation in SKOV3 cells for the gene therapy of ovarian cancer. The cationic cholesterol derivative, N-(cholesterylhemisuccinoyl-amino-3-propyl)-N, N-dimethylamine (DMAPA-chems) liposome, was incubated with siRNA at different nitrogen-to-phosphate ratios to form stabilized, near-spherical siRNA/DMAPA-chems nanoparticles with sizes of 100–200 nm and zeta potentials of 40–50 mV. The siRNA/DMAPA-chems nanoparticles protected siRNA from nuclease degradation in 25% fetal bovine serum. The nanoparticles exhibited high cell uptake and Notch1 gene knockdown efficiency in SKOV3 cells at an nitrogen-to-phosphate ratio of 100 and an siRNA concentration of 50 nM. They also inhibited the growth and promoted the apoptosis of SKOV3 cells. These results may provide the potential for using cationic cholesterol derivatives as efficient nonviral siRNA carriers for the suppression of Notch1 activation in ovarian cancer cells. Keywords: siRNA, cationic cholesterol derivative, Notch1, ovarian cancer cells

A total of 152 pig farms were randomly selected from the five provinces in South Korea. During the experiment, the average temperature and relative humidity was 24.7°C and 74% in summer and 2.4°C and 53% in winter, respectively. The correlation between floor space allowance (FSA) and productivity index was analyzed, including non-productive sow days (NPD), number of weaners (NOW), survival rate (SR), appearance rate of A-grade pork (ARA), and days at a slaughter weight of 110 kg (d-SW) at different growth stages. The objectives of the present study were i) to determine the effect of FSA on the pig productivity index and ii) to suggest the minimum FSA for pigs based on scientific baseline data. For the pregnant sow, NPD could be decreased if pregnant sows were raised with a medium level (M) of FSA (3.10 to 3.67 m2/head) while also keeping the pig house clean which improves hygiene, and operating the ventilation system properly. For the farrowing sows, the NOW tended to decrease as the FSA increased. Similarly, a high level of FSA (H) is significantly negative with weaner SR of farrowing sows (p-value = 0.017), indicating this FSA tends to depress SR. Therefore, a FSA of 2.30 to 6.40 m2/head (very low) could be appropriate for weaners because a limited space can provide a sense of security and protection from external interruptions. The opposite trend was observed that an increase in floor space (>1.12 m2/head) leads to increase the SR of growing pigs. For the fattening pigs, H level of FSA was negatively correlated with SR, but M level of FSA was positively correlated with SR, indicating that SR tended to increase with the FSA of 1.10 to 1.27 m2/head. In contrast, ARA of male fattening pigs showed opposite results. H level of FSA (1.27 to 1.47 m2/head) was suggested to increase productivity because ARA was most affected by H level of space allowance with positive correlation (R2 = 0.523). The relationship between the FSA and d-SW of fattening pigs was hard to identify because of the low R2 value. However, the farms that provided a relatively large floor space (1.27 to 1.54 m2/head) during the winter period showed d-SW was significantly and negatively affected by FSA.

The effects of Flavomycin, Bacillus licheniformis and Enramycin on broiler performance, nutrient digestibility, gut morphology and the intestinal microflora were studied in a 42-d experiment. A total of 288, one-day-old, male, Arbor Acres broilers were randomly assigned to 1 of 4 dietary treatments with 12 pens per treatment and 6 birds per pen. The treatments were comprised of a control diet without supplementation, a diet supplemented with 5 ppm Flavomycin, a diet supplemented with the combination of 5 ppm Flavomycin and 1.35×109 CFU/kg Bacillus licheniformis, as well as a diet supplemented with 5 ppm Enramycin. The average daily gain (ADG) and feed conversion ratio (FCR) of birds fed the diet with Flavomycin combined with Bacillus licheniformis and the Enramycin diet were improved (P

The temporal distribution patterns of bacterial communities, as an important group in mountain soil, are affected by various environmental factors. To improve knowledge regarding the successional seasonal dynamics of the mountain soil bacterial communities, the rhizospheric soil of a 30-year-old natural secondary Pinus tabulaeformis forest, located in the high-altitude (1900 m a.s.l.) of the temperate Qinling Mountains, was sampled and studied during four different seasons. The bacterial community composition and structure in the rhizospheric soil were studied using an Illumina MiSeq Sequencing platform. Furthermore, the edaphic properties and soil enzymatic activities (urease, phosphatase, and catalase) were measured in order to identify the main impact factors on the soil bacterial community. According to the results, all of the edaphic properties and soil enzymatic activities were significantly affected by the seasonal changes, except for the C/N ratio. Although the biomasses of soil bacterial communities increased during the summer and autumn (warm seasons), their Shannon diversity and Pielou’s evenness were decreased. Proteobacteria, Acidobacteria, Actinobacteria, Planctomycetes, and Bacteroidetes were the predominant bacterial groups in all of the soil samples, and the genera of Ktedonobacter, Sphingobium as well as an unclassified member of the Ktedonobacteria were the keystone taxa. The composition and structure of soil bacterial communities were strongly impacted by the edaphic properties, especially the temperature, moisture, ammoniacal nitrogen, available phosphorus and total phosphorus which were the crucial factors to drive the temporal distribution of the soil bacterial community and diversity. In conclusion, the soil temperature, moisture and the nutrients N and P were the crucial edaphic factors for shaping the rhizospheric soil bacterial communities as season and climate change in a P. tabulaeformis forest of Qinling Mountains.

A well-managed chemical nitrogen (N) fertilization practice combined with treated swine slurry (TSS) is necessary to improve sustainability and N use efficiency in rice farming. However, little is known about the fate of N derived from chemical N fertilizer with and without TSS in paddy soil-plant systems. The objectives of this study were (1) to estimate the contribution of applied N fertilizer to N turnover in rice paddy soil with different N fertilization practices that were manipulated by the quantity of treated swine slurry and chemical N fertilizer (i.e., HTSS+LAS, a high amount of TSS with a low amount of ammonium sulfate; LTSS+HAS, a low amount of TSS with a high amount of ammonium sulfate; AS, ammonium sulfate with phosphorus and potassium; C, the control) and (2) to compare the rice response to applied N derived from each N fertilization practice. Rice biomass yield, 15N recovery in both rice grain and stems, soil total N (TN), soil inorganic N, and soil 15N recovery were analyzed. Similar amounts of 15N uptake by rice in the TSS+AS plots were obtained, indicating that the effects of the different quantities of TSS on chemical fertilizer N recovery in rice during the experimental period were not significant. The soil 15N recoveries of HTSS+LAS, LTSS+HAS, and AS in each soil layer were not significantly different. For the HTSS+LAS, LTSS+HAS and AS applications, total 15N recoveries were 42%, 43% and 54%, respectively. Because the effects of reducing the use of chemical N fertilizer were attributed to enhancing soil quality and cost-effectiveness, HTSS+LAS could be an appropriate N fertilization practice for improving the long-term sustainability of paddy soil-plant systems. However, N losses, especially through the coupled nitrification-denitrification process, can diminish the benefits that HTSS+LAS offers.

This research aims at the identification of time varying axle load of moving vehicles though the determinations of influence lines of bridge bending moment.With the approach of this research, based on the theorem of modal superposition, the modal acceleration of the bridge subjected to moving loads is determined by the responding acceleration data of the sections. At any given time, the dynamic moment at a section is considered as a static moment due to the distributed inertia force and moving loads on the bridge. By using the bending moment influence line of the bridge, the relationship between the moments and the moving load is established. A method for identifying the moving loads though the bending moment influence lines is thus developed.With the application of the matrix singularity, there is no need to solve for dynamic equations and ill-conditioned matrix, and thus the proposed method is highly effcient for engineering applications.

Sialic acids are a family of acidic monosaccharides often found on the termini of cell surface proteins or lipid glycoconjugates of higher animals. Herein we describe the enzymatic synthesis of the two isotopically labeled sialic acid derivatives d3-X-Gal-α-2,3-Neu5Ac and d3-X-Gal-α-2,3-Neu5Gc. Using deuterium oxide as the reaction solvent, deuterium atoms could be successfully introduced during the enzymatic epimerization and aldol addition reactions when the sialosides were generated. NMR and mass spectrometric analyses confirmed that the resulting sialosides were indeed tri-deuterated. These compounds may be of interest as internal standards in liquid chromatography/mass spectrometric assays for biochemical or clinical studies of sialic acids. This was further exemplified by the use of this tri-deuterated sialosides as internal standards for the quantification of sialic acids in meat and egg samples.

Considering geometry nonlinear of the bridge, the differential equations of vehicle-bridge coupled interaction system are established. Using numerical method, the numerical solution of the coupling nonlinear differential equation are obtained. As an example, single vehicle pass through the bridge is studied. The result shows nonlinear items has little effects to the response in this case. In the other example, the train is modeled as serious spring-mass system pass through bridge. In this case, the subharmonic resonance are studied. The result shows when the bridge is excited period force, nonlinear affect can not be ignored.

ObjectiveWe undertook this study to estimate changes in cell-specific DNA methylation (DNAm) associated with methotrexate (MTX) response using whole blood samples collected from rheumatoid arthritis (RA) patients before and after initiation of MTX treatment.MethodsPatients included in this study were from the Rheumatoid Arthritis Medication Study (n = 66) and the University of California San Francisco Rheumatoid Arthritis study (n = 11). All patients met the American College of Rheumatology RA classification criteria. Blood samples were collected at baseline and following treatment. Disease Activity Scores in 28 joints using the C-reactive protein level were collected at baseline and after 3-6 months of treatment with MTX. Methylation profiles were generated using the Illumina Infinium HumanMethylation450 and MethylationEPIC v1.0 BeadChip arrays using DNA from whole blood. MTX response was defined using the EULAR response criteria (responders showed good/moderate response; nonresponders showed no response). Differentially methylated positions were identified using the Limma software package and Tensor Composition Analysis, which is a method for identifying cell-specific differential DNAm at the CpG level from tissue-level ("bulk") data. Differentially methylated regions were identified using Comb-p software.ResultsWe found evidence of differential global methylation between treatment response groups. Further, we found patterns of cell-specific differential global methylation associated with MTX response. After correction for multiple testing, 1 differentially methylated position was associated with differential DNAm between responders and nonresponders at baseline in CD4+ T cells, CD8+ T cells, and natural killer cells. Thirty-nine cell-specific differentially methylated regions associated with MTX treatment response were identified. There were no significant findings in analyses of whole blood samples.ConclusionWe identified cell-specific changes in DNAm that were associated with MTX treatment response in RA patients. Future studies of DNAm and MTX treatment response should include measurements of DNAm from sorted cells.

This study was aimed to determine changes of the characteristics of raw pig slurry as liquid organic fertilizer at various storage times. A completely randomized design was used in this research. The treatments were storage times, i.e.: 0, 15, 30, 45, and 60 days. Variables observed were loss of the slurry, degree of acidity (pH), electrical conductivity (EC), total solid (TS), volatile solid (VS), total chemical oxygen demand (tCOD), soluble chemical oxygen demand (sCOD), total nitrogen (TN), ammonia-nitrogen (NH3-N), nitrate–nitrogen (NO3-N), total phosphate (TP), and dissolve reactive phosphate (DRP). The results showed that storage time significantly affected all the observed variables, except the concentration of NO3-N and total phosphate content. The pH, TS, VS, DRP, and losses of slurry lost during storage times increased, while EC, TN, NH3-N, tCOD, and sCOD decreased. Physico-chemical properties of slurry during storage times changed, as a result of organic matter breakdown.

BackgroundRare genetic variants are emerging as important contributors to the heritability of multiple sclerosis (MS). Whether rare variants also contribute to pediatric-onset multiple sclerosis (POMS) is unknown.ObjectiveTo test whether genes harboring rare variants associated with adult-onset MS risk (PRF1, PRKRA, NLRP8, and HDAC7) and 52 major histocompatibility complex (MHC) genes are associated with POMS.MethodsWe analyzed DNA samples from 330 POMS cases and 306 controls from the US Network of Pediatric MS Centers and Kaiser Permanente Northern California for which Illumina ExomeChip genotypes were available. Using the gene-based method "SKAT-O," we tested the association between candidate genes and POMS risk.ResultsAfter correction for multiple comparisons, one adult-onset MS gene (PRF1, p = 2.70 × 10-3) and two MHC genes (BRD2, p = 5.89 × 10-5 and AGER, p = 7.96 × 10-5) were significantly associated with POMS. Results suggest these are independent of HLA-DRB1*1501.ConclusionFindings support a role for rare coding variants in POMS susceptibility. In particular, rare minor alleles within PRF1 were more common among individuals with POMS compared to controls while the opposite was true for rare variants within significant MHC genes, BRD2 and AGER. These genes would not have been identified by common variant studies, emphasizing the merits of investigating rare genetic variation in complex diseases.