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Wenwu Zhang,1,2,* Yuhan Xiao,3,* Xin Zhu,1 Yanxia Zhang,1 Qin Xiang,1 Shunhong Wu,1 Xiaoyu Song,1 Junxiu Zhao,3 Ruanfei Yuan,1 Qiguang Li,1 Bin Xiao,1 Linhai Li1 1Department of Laboratory Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingyuan, Guangdong, 511518, People’s Republic of China; 2Department of Laboratory Medicine, Suzhou Municipal Hospital, Affiliated to Nanjing Medical University, Suzhou, 21500, People’s Republic of China; 3School of Public Health, Dali University, Dali, 671000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linhai Li; Bin Xiao, Email mature303@126.com; xiaobin2518@163.comPurpose: Meiotic nuclear division 1 (MND1) is a meiosis-specific protein that promotes lung adenocarcinoma progression. However, its expression and biological function across cancers remain largely unexplored.Patients and Methods: The expression, prognostic significance, mutation status, and methylation profile of MND1 in various cancers were comprehensively analyzed using the TIMER, GTEX, Kaplan-Meier plotter, cBioPortal, and GSCA databases. Additionally, we constructed a PPI network, enrichment analysis and single-cell transcriptomic sequencing to elucidate the underlying mechanism of MND1. Furthermore, we investigated the association between MND1 expression and drug sensitivity using CellMiner. Moreover, we also explored the correlation between MND1 expression and immune infiltration. Finally, we validated the functional role of MND1 in breast cancer through IHC staining, CCK8, EdU, colony formation, and flow cytometry assays.Results: MND1 has been reported to be highly expressed in Pan-cancer, High MND1 expression was significantly associated with poor prognosis in cancers. Additionally, MND1 mutation frequency is high in most cancers, and its expression correlates with methylation. Furthermore, MND1 expression significantly correlates with immune checkpoint blockade (ICB) markers, including PD-L1, PD-1, and CTLA-4. The PPI network reveals interactions between MND1 and PSMC3IP, BRCA1, and BRCA2. Enrichment analysis and single-cell sequencing indicate that MND1 positively correlates with cell cycle. ROC curve reveals favorable diagnostic efficacy of MND1 in breast cancer. In vitro, MND1 overexpression promotes breast cancer cell proliferation and increases the expression of key cell cycle regulators (CDK4, CDK6, and cyclin D3), accelerating the G1/S phase transition and leading to abnormal breast cancer cell proliferation. The immunohistochemical analysis revealed a robust expression of MND1 in breast cancer tissues, exhibiting a significant positive correlation with PD-L1 and FOXP3.Conclusion: MND1 is an oncogene and may serve as a biomarker for cancer prognosis and immunotherapy. Targeting MND1 may be a potential tumor treatment strategy.Keywords: meiosis-specific protein, pan-cancer, prognosis biomarker, immune infiltration, cell cycle

Lele Huang,1,2,* Jiamin Li,2,* Baiyang Xiao,2,3 Yin Tang,2 Jinghui Huang,2 Ying Li,2 Fanfu Fang2,3 1School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 2Department of Rehabilitation Medicine, The First Affiliated Hospital of the Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Department of Traditional Chinese Medicine, Naval Medical University, Shanghai, 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fanfu Fang, Department of Rehabilitation Medicine, The First Affiliated Hospital of the Naval Medical University, 168 Changhai Road, Shanghai, 200433, People’s Republic of China, Tel +86 21-81867388, Email fangfanfu@126.comPurpose: Low back pain (LBP) is a prevalent musculoskeletal disorder, and manual therapy (MT) is frequently employed as a non-pharmacological treatment for LBP. This study aims to explore the research hotspots and trends in MT for LBP. MT has gained widespread acceptance in clinical practice due to its proven safety and effectiveness. The study aims to analyze the developments in the field of MT for LBP over the past 23 years, including leading countries, institutions, authoritative authors, journals, keywords, and references. It endeavors to provide a comprehensive summary of the existing research foundation and to analyze the current cutting-edge research trends.Methods: Relevant articles between 2000 and 2023 were retrieved from the Web of Science Core Collection (WOSCC) database. We used the software VOSviewer and CiteSpace to perform the analysis and summarize current research hotspots and emerging trends.Results: Through screening, we included 1643 papers from 2000 to 2023. In general, the number of articles published each year showed an upward trend. The United States had the highest number of publications and citations. Canadian Memorial Chiropractic College was the most published research institution. The University of Pittsburgh in the United States had the most collaboration with other research institutions. Long, Cynthia R. was the active author. Journal of Manipulative and Physiological Therapeutics was the most prolific journal with 234 publications.Conclusion: This study provides an overview of the current status and trends of clinical studies on MT for LBP in the past 23 years using the visualization software, which may help researchers identify potential collaborators and collaborating institutions, hot topics, and new perspectives in research frontiers, while providing new clinical practice ideas for the treatment of LBP.Keywords: CiteSpace, VOSviewer, bibliometric analysis, back pain, manual therapy

Juan Li,1 Yuanyuan Zhai,1 Bowen Xiao,2 Xiaoying Xia,3 Jingyao Wang,1 Yanan Zhao,1 Li Ye,1 Yan Li1 1Shanghai Institute of Early Childhood Education, Shanghai Normal University, Shanghai, People’s Republic of China; 2Psychology Department, Carleton University, Ottawa, Ontario, Canada; 3School of Early Childhood Education, Shanghai Normal University Tianhua College, Shanghai, People’s Republic of ChinaCorrespondence: Yan Li, Shanghai Institute of Early Childhood Education, Shanghai Normal University, 100 Guilin Road, Xuhui District, Shanghai, People’s Republic of China, Email liyan@shnu.edu.cnIntroduction: Maternal distress increased during the COVID-19 pandemic, significantly impacting children’s media use. The purpose of this study was to explore the influence mechanism of maternal COVID-19 distress on preschoolers’ problematic media us through a moderated mediation model; specifically, we examined the possible mediating roles of parenting stress and negative instrumental use of media in parenting and the moderating role of supportive co-parenting.Methods: An online survey was conducted in a sample of 1357 children (Mage = 4.01, SD = 1.06; 47.4% boys) and their parents from six public kindergartens in Shanghai, China. The mothers provided information by completing measures on their levels of distress related to COVID-19, parenting stress levels, digital parenting practices, and perception of supportive co-parenting from their partners. Additionally, both parents rated their children’s problematic media use.Results: (1) maternal COVID-19 distress was significantly and positively related to children’s problematic media use; (2) this relationship was sequentially mediated by parenting stress and parents’ negative instrumental use of media in parenting; and (3) supportive co-parenting moderated the serial mediation path by reducing the effect of maternal COVID-19 distress on parenting stress.Conclusion: The findings provide some support and guidance for preventing children’s problematic media use and enhancing parental adaptation during the COVID-19 pandemic or in potentially adverse situations.Keywords: maternal COVID-19 distress, children’s problematic media use, parenting stress, negative instrumental use of media in parenting, supportive co-parenting

Bing Xiao,1 Lu-Lu Sun,2 Jing Yuan,3 Wan-Ling Xiao,1 Ying Liu,4 Man-Yuan Cai,5 Qiao-Huo Liao2 1Department of Outpatient, the Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 2Department of Pediatric, the Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 3Department of Infectious Diseases, the Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 4GI Medicine Department, the Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 5Science and Education Department, the Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of ChinaCorrespondence: Lu-Lu Sun, Department of Pediatric, the Third People’s Hospital of Shenzhen, No. 29 of Bulan Road, Longgang District, Shenzhen, 518000, People’s Republic of China, Tel +86 13510332310, Email sunlulu9x@126.comObjective: To explore a mask fitness test based on self-efficacy and diversified training in the assessment system for nosocomial infection training.Methods: From March 15 to April 5, 2022, 442 staff members (272 male and 170 female) of the Third People’s Hospital of Shenzhen who planned to enter the quarantine ward for secondary protection skill training assessment were selected. They comprised 56 doctors, 31 medical technicians, 72 nurses, and 283 property logistics staff. During the mask fitness test, a diversified training model based on self-efficacy was adopted to observe the passing status, the identification and selection of mask models, the method of mask-wearing, the fit between the mask and the face, and the changes in self-efficacy.Results: In the assessment system for nosocomial infection training, the passing rate of the mask fitness test was correlated with the identification and selection of mask models, the method of wearing masks, the fit between the mask and the face, and the diversified training, and the differences were statistically significant (P < 0.05). The difference in the self-efficacy in the test takers between those before and after the mask fitness test was statistically significant (P < 0.05).Conclusion: In the assessment system for nosocomial infection training, the mask fitness test based on self-efficacy and diversified training might improve the passing rate, the rate of correct mask model identification and selection, the rate of correct mask-wearing, and the degree of facial fit, thus to enhance the awareness of protection and improve self-efficacy.Keywords: self-efficacy, mask fitness test, training mode

Hongyu Qiao,1 Zhongxiang Ding,2 Youcai Zhu,1 Yuguo Wei,3 Baochen Xiao,1 Yongzhen Zhao,1 Qi Feng2 1Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China; 2Department of Radiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3GE Healthcare Life Sciences, Hangzhou, People’s Republic of ChinaCorrespondence: Qi Feng, Tel +86-13588764520, Email fengqi0707@126.comBackground: The role of TP53 mutations in the diagnosis and treatment of lung cancer has attracted increasing attention from experts worldwide. This study aimed to explore the expression of TP53 gene in lung cancer and its correlation with radiomics quantitative features.Methods: A total of 93 cases of lung cancer confirmed by pathology were selected, including 44 cases with TP53 mutations and 49 cases with TP53 wild-type. ITK-SNAP software was used to segment the pulmonary nodules, AK software was used to extract radiomic features, and a model was established to predict the type of TP53 gene mutation in lung cancer lesions.Results: A total of 852 features were extracted, and 10 features remained after feature selection. The accuracy, areas under the curve, specificity, sensitivity, positive predictive value, and negative predictive value of the logistic regression model were 0.80, 0.86, 0.89, 0.74, 0.90, and 0.71, respectively.Conclusion: TP53 gene mutations are correlated with radiomic features in lung cancer, which may have application value for TP53 therapy in the future.Keywords: radiomics, TP53, lung cancer, mutation

Bo Wang,1,&ast; Song Gong,2,&ast; Lizhi Han,2 Wenkai Shao,2 Zilin Li,2 Jiawei Xu,2 Xiao Lv,2 Baojun Xiao,2 Yong Feng2 1Department of Rehabilitation, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baojun Xiao; Yong Feng, Email drxiao999@sohu.com; fengyong@hust.edu.cnBackground: Histone deacetylase 9 (HDAC9) is a member of the HDAC gene family that plays essential roles in the organization of transcriptional regulation by catalyzing deacetylation of histone proteins. However, the effects of HDAC9 on osteonecrosis of femoral head (ONFH) have not been investigated. The present study aimed to reveal whether histone deacetylase 9 (HDAC9) regulated osteogenic differentiation.Methods: A lentiviral knockdown HDAC9 model was established in hBMSCs. Osteoblast-specific gene expression, such as Runx2, OCN was examined by qRT-PCR and Western blot, respectively. Though transcriptome sequencing and enrichment analysis, related signal pathways caused by down-regulation of HDAC9 were screened. The effect of HDAC9 on MAPK signaling pathway was determined by Western blot. Eventually, tert-Butylhydroquinone (tBHQ) was used to examine the effect of MAPK activation on osteogenesis in HDAC9 knockdown hBMSCs.Results: A lentiviral knockdown HDAC9 model was successfully established in hBMSCs. HDAC9 knockdown significantly inhibited osteoblast-specific gene expression, such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and mineral deposition in vitro. Moreover, a total of 950 DEGs were identified in HDAC9-knockdown hBMSCs. We discovered that the MAPK signaling pathway might be related to this process by pathway enrichment analysis. HDAC9 knockdown significantly reduced the expression level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). Finally, the decreased osteogenesis due to HDAC9 knockdown was partly rescued by a MAPK signaling pathway activator.Conclusion: Taken together, these results suggest that HDAC9 knockdown inhibits osteogenic differentiation of hBMSCs, partially through the MAPK signaling pathway. HDAC9 may serve as a potential target for the treatment of ONFH.Keywords: HDAC9, hBMSCs, osteogenesis, MAPK signaling pathway

Chunmei Xie,1,* Qing Li,1,* Linhai Li,2,3,* Xiaohua Peng,4,5,* Zhijian Ling,1 Bin Xiao,3 Jingjing Feng,4,6 Zhenhong Chen,7 De Chang,2,8 Lixin Xie,2 Charles S Dela Cruz,4 Lokesh Sharma4 1Department of Blood Transfusion, Guangzhou 8th People’s Hospital, Guangzhou Medical University, Guangzhou, 510440, People’s Republic of China; 2College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing, 100083, People’s Republic of China; 3Department of Laboratory Medicine, General Hospital of Southern Theatre Command of PLA, Guangzhou, 510010, People’s Republic of China; 4Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA; 5Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, Secondary Medical Center, Chinese PLA General Hospital, Beijing, 100083, People’s Republic of China; 8 Department of Pulmonary and Critical Care Medicine, Third Medical Center, Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lixin Xie; De Chang Email 2464277169@qq.com; changde5501@foxmail.comBackground: Disease severity in COVID-19 ranges from asymptomatic infection to severe disease and death, especially in older subjects. The risk for severe infection and death has been reported to be 2X in those between 30 and 40 years, 3X in those between 40 and 50 years, and 4X in those between 50 and 65 years, compared to the reference group of 18– 29 years.Objective: To investigate the early changes in host immune responses that are altered with age and the difference in the early host inflammatory response that dictates a symptomatic versus asymptomatic course of COVID-19.Patients and Methods: COVID-19 subjects were identified by screening at the airport upon arrival from a foreign destination to China. Patients were either asymptomatic or had a mild disease when the first oro-pharyngeal (OP) swab samples were collected. Patients were quarantined and blood and throat swabs were collected during the course of the disease, allowing identification of the earliest host response to COVID-19. These patients were followed until their OP sample turned COVID-19 negative.Results: Data were obtained from 126 PCR-confirmed COVID-19 patients. The blood samples were obtained within 48 days of qPCR confirmation of viral infection. Older subjects (> 30 years) had significantly elevated levels of anti-inflammatory cytokine IL-10, a significant decrease in the percentage of CD8+ T cells, and expansion in NKT cell fraction. This was associated with significantly elevated viral load and a delayed humoral response in older subjects. Compared to symptomatic subjects, asymptomatic patients had an early increase in pro-inflammatory cytokine IL-2, while a decrease in both T regulatory cells and anti-inflammatory cytokine IL-10. Further, asymptomatic disease was associated with early humoral response and faster viral clearance.Conclusion: Early inflammatory response potentially plays a critical role for host-defense in COVID-19. The impaired early inflammatory response was associated with older age while a robust early inflammation was associated with asymptomatic disease.Keywords: COVID-19, SARS-CoV-2, early inflammation, asymptomatic patient, elder patient

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

Kai Chen,* Boen Xiao,* Zhe Zhou, Weihui Peng, Wei Liu Department of Biliopancreatic Surgery and Metabolic Surgery, Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Liu Email liuweixy@csu.edu.cnBackground: Roux-en-Y gastric bypass (RYGB) has been proved to be more effective than other bariatric procedures in the long term on body-weight loss and remission of diabetes. However, the mechanism remains poorly understood. Long-term changes in energy metabolism after RYGB have rarely been reported.Objective: To investigate the long-term effects of RYGB on energy metabolism on a diet-induced obesity (DIO) mouse model.Methods: DIO mice fed a high-fat diet were assigned to two groups: RYGB (n=8) and sham (n=7), followed by high-fat diet feeding until 12 weeks after surgery. Body weight and food intake were recorded weekly. Measurement of body composition and energy metabolism by metabolic chamber were conducted at weeks 4, 8, and 12 after surgery. Fecal energy measurement, intraperitoneal glucose-tolerance tests, and insulin-tolerance tests were conducted at postoperative week 12.Results: Food intake was reduced in the RYGB group within the first 3 weeks after surgery and increased to the same as the sham group from postoperative week 4. At 12 weeks after surgery, body weight had reduced by 36%± 3.2% in the RYGB group compared to a 16%± 2% body-weight gain in the sham group, while fat mass had reduced significantly in the RYGB group compared to the sham group (9.2%± 1.5% versus 30.1%± 0.7%). Energy expenditure was significantly higher at postoperative week 8 in the RYGB group than the sham group. In comparison with the sham group, the respiratory exchange ratio was unchanged, decreased, and increased in the RYGB group at postoperative weeks 4, 8, and 12, respectively. Fecal energy measurement showed that feces from mice in the RYGB group contained higher energy levels than the sham group. Glucose metabolism had significantly improved in the RYGB group, in contrast to the sham group, demonstrated by intraperitoneal glucose tolerance tests (AUC 1,502± 104 versus 2,277± 198, respectively) and insulin tolerance tests (AUC 524± 50 versus 838± 63, respectively).Conclusion: Increased energy expenditure and energy loss through feces contribute to long-term body-weight control after RYGB. Enhanced glucose utilization might play a role in long-term improvement in glucose metabolism.Keywords: Roux-en-Y gastric bypass, mouse model, glucose metabolism, energy expenditure, respiratory exchange ratio

Haoyue Zhu, Mengqi Zhang, Yujiao Fu, Hongyu Long, Wenbiao Xiao, Li Feng, Bo Xiao, Luo Zhou Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of ChinaCorrespondence: Luo ZhouDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of ChinaTel +86 731 8432 8888Fax +86 731 8432 7332Email zhouluo33@163.comBackground and Purpose: Epilepsy is a common chronic neurological disorder. About one third of epilepsy patients will suffer from drug resistance after rational selection of antiepileptic drug treatment. The formation of drug-resistant epilepsy has quite a few causes of which genetic factors are considered to be the most important. Previous studies have suggested that the aquaporin 4(AQP4) and inward rectifier potassium ion channel Kir4.1 (encoded by gene KCNJ10) may act in concert to adjust water homeostasis and concentration of potassium ions in extracellular spaces of the central nervous system. Therefore, these two molecules would play a major role in the regulation of the excitability of neurons. In order to explore the potential mechanism of genetic factors related to AQP4 and Kir4.1, we conducted a study to analyze the effects of the AQP4 and KCNJ10 genes’ single nucleotide polymorphisms (SNPs) on epileptic drug resistance and seizure susceptibility in a group of Chinese Han patients with focal epilepsy.Materials and Methods: In total, 510 patients with focal-onset seizures and 206 healthy controls were recruited. Among the patients, 222 were drug resistant and 288 were responsive. The selection of tag SNPs was based on the Hapmap database and Haploview software. Genotyping of three loci of the AQP4 gene (rs1058424, rs3763043 and rs35931) and nine loci of the KCNJ10 gene (rs12122979, rs1186685, rs6690889, rs2486253, rs1186675, rs12402969, rs12729701, rs1890532 and rs3795339) was conducted on the Sequenom MassARRAY iPLEX platform.Results: The distribution of genotype and allele frequencies of selected SNP loci of AQP4 and KCNJ10 genes showed no significant difference between the drug-resistant and drug-responsive groups (p>0.05), and no significant difference between all the idiopathic focal epilepsy patients and healthy controls either.Conclusion: AQP4 and KCNJ10 genetic polymorphisms may not be associated with drug resistance or seizure susceptibility of focal epilepsy in the Chinese Han population.Keywords: AQP4, KCNJ10, focal epilepsy, polymorphism, Chinese Han population

Chunze Zhang,1,2,* Tingting Yin,3,* Ran Tao,4,* Bo Xiao,5,* Jing Chen,4 Zixuan Li,5 Xueyuan Miao,3 Qing Peng,3 Liu Sun,3 Weihua Zhang,1 Junxu Ren,4 Zhao Zhang,1 Ying Zhang,1 Xichuan Li,6 Wei Zhang51Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, People’s Republic of China; 2State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, People’s Republic of China; 3Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4Department of Histology and Embryology, School of Basic Medical Sciences, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China; 5School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People’s Republic of China; 6Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, People’s Republic of China *These authors contributed equally to this work Purpose: Y-box binding protein 1 (YBX1) is a multifunctional protein linked to tumor progression and its elevated expression is an indicator of poor prognosis in various cancers. This meta-analysis aimed to investigate the prognostic value and clinical significance of YBX1 in malignant cancer.Methods: Relevant articles published through September 12, 2018 were identified from a comprehensive electronic and manual search in PubMed, Web of Science and Embase databases. The combined odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to estimate the relationship among clinicopathological characteristics, overall survival and disease-free-survival of patients with solid tumor and YBX1 expression.Results: The study included 27 studies and 5,996 patients. Our analysis revealed significant association between increased YBX1 expression and tumor differentiation status, tumor size and lymph node metastasis; moreover, the pooled HR values demonstrated that high nuclear YBX1 expression was significantly associated with worse overall survival (HR=2.14; 95% CI: 1.72–2.67, P

Yansong Liu,1 Xin Wang,2 Zhonghua Zhang,3 Bin Xiao,4 Baoming An,5 Jun Zhang6 1Breast Department, Shandong Cancer Hospital, Affiliated to Shandong University, Shandong, China; 2Breast Department, Yinan Country People’s Hospital, Shandong, China; 3Breast Department, Dongping Country People’s Hospital, Shandong, China; 4Breast Department, Shanxian Hygeia Hospital, Shandong, China; 5Breast Department, Wulian Country People’s Hospital, Shandong, China; 6Breast Department, Zhangqiu Hospital of Chinese Medicine, Shandong, China Background: Rab9 is a small GTPase that localizes to the trans-Golgi Network (TGN) and late endosomes and is involved in the recycling of mannose-6-phosphate receptors (MPRs). Materials and methods: To determine new treatment strategies for breast cancer and to elucidate the mechanism underlying the phenomenon, we investigated the effects of Rab9 in the human breast cancer cell lines MCF7 and MDA-MB-231.Results: We observed that knockdown of Rab9 inhibited the survival and proliferation of MCF7 and MDA-MB-231 cells, whereas Rab9 overexpression facilitated cell survival and proliferation by inducing or suppressing apoptosis. These results were further confirmed by the Bax/Bcl-2 ratio in affected MCF7 and MDA-MB-231 cells, which demonstrated whether the mitochondrial apoptotic pathway was triggered. Furthermore, the AKT/PI3K pathway is implicated in cell growth and survival and Rab9 changed the expression and phosphorylation of PI3K signaling pathway members. XBP1 is a key regulator of Rab9 and further confirmed that Rab9 play important roles in breast cancer tumorigenesis.Conclusion: These data suggest that Rab9 is a good candidate for a novel therapeutic strategy for the treatment of breast cancer. Keywords: transcription factor, proliferation, MCF7, MDA-MB-231

Bingkun Xiao,1 Weilan Wang,2 Dezhi Zhang3 1Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China; 2Department of Pharmacy, Chinese PLA General Hospital, Beijing, China; 3Department of Pharmacy, The 264th Hospital of PLA, Taiyuan, Shanxi, China Aim: Bevacizumab and ramucirumab are antiangiogenic monoclonal antibodies, which target vascular endothelial growth factor-A and vascular endothelial growth factor receptor-2, respectively, used in various cancers. Bleeding events have been described with these two agents. We conducted an up-to-date meta-analysis to determine the relative risk (RR) associated with the use of antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab. Methods: This meta-analysis of randomized controlled trials was performed after searching PubMed, American Society for Clinical Oncology Abstracts, European Society for Medical Oncology Abstracts, and the proceedings of major conferences for relevant clinical trials. RR and 95% CIs were calculated by random-effects or fixed-effects models for all-grade and high-grade bleeding events related to the angiogenesis inhibitors.Results: Eighty-five randomized controlled trials were selected for the meta-analysis, covering 46,630 patients. The results showed that antiangiogenic monoclonal antibodies significantly increased the risk of all-grade (RR: 2.38, 95% CI: 2.09–2.71, p

Bo Xiao, Shuai Wang, Jianbo Liu, Tiantian Meng, Yuqiong He, Xuerong Luo Mental Health Institute of the Second Xiangya Hospital, Central South University, National Clinical Research Center on Mental Health Disorders, National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, People’s Republic of China Objective: The localized dysfunction of specialized brain regions in schizophrenia patients and their unaffected relatives has been identified in a large-scale brain network; however, evidence is inconsistent. We aimed to identify abnormalities in the localized connectivity in schizophrenia patients and their relatives by conducting a meta-analysis of regional homogeneity (ReHo) studies.Methods: Fourteen studies on resting-state functional magnetic resonance imaging, with 316 schizophrenia patients, 342 healthy controls, and 66 unaffected relatives, were included in the meta-analysis. This analysis was performed using anisotropic effect-size-based signed differential mapping software.Results: Schizophrenia patients showed increased ReHo in right superior frontal gyrus and right superior temporal gyrus, as well as decreased ReHo in left fusiform gyrus, left superior temporal gyrus, left postcentral gyrus, and right precentral gyrus. Unaffected relatives showed decreased ReHo in right insula and right superior temporal gyrus. These results remained widely unchanged in both sensitivity and subgroup analyses.Conclusion: Schizophrenia patients and their unaffected relatives had extensive abnormal localized connectivity in cerebrum, especially in superior temporal gyrus, which were the potential diagnostic markers and expounded the pathophysiological hypothesis for the disorder. Keywords: schizophrenia, localized connectivity, regional homogeneity, resting-state fMRI, meta-analysis, effect-size-based signed differential mapping

Lili Long,1 Yanmin Song,1 Linlin Zhang,2 Chongyu Hu,3 Jian Gong,2 Lin Xu,1 Hongyu Long,1 Luo Zhou,1 Yunci Zhang,2 Yong Zhang,2 Bo Xiao1 1Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 2The People’s Hospital of Fuyang, Anhui Province, People’s Republic of China; 3Department of Neurology, Hunan Provincial People’s Hospital, People’s Republic of China Background: Benign adult familial myoclonic epilepsy (BAFME) is a rare form of epilepsy syndrome. The pathogenesis of BAFME remains unclear, though it seems to involve dysfunction of the cerebellum. Objectives: The purpose of this study was to use proton magnetic resonance spectroscopy (1H-MRS) to investigate whether neurochemical changes underlie abnormal brain function in BAFME. Methods: Twelve BAFME patients from one family and 12 age- and sex-matched healthy controls were enrolled in this study. The ratios of NAA/Cr, NAA/Cho, Cho/Cr, and NAA/(Cr+Cho) were analyzed. Results: The BAFME patients exhibited a decreased N-acetylaspartate (NAA)/choline (Cho) ratio in the cerebellar cortex, whereas there were no significant differences in the NAA/creatine (Cr), Cho/Cr, and NAA/(Cr+Cho) ratios compared with healthy controls. There were no significant differences in 1H-MRS values in the frontal cortex or thalamus between the BAFME patients and controls. No correlation was detected between the NAA/Cho ratio in the cerebellar cortex and disease duration, myoclonus severity, or tremor severity. Conclusion: Our results indicate clear cerebellar dysfunction in BAFME. 1H-MRS is a useful tool for the diagnosis of BAFME in combination with family history and electrophysiological examination. Keywords: benign adult familial myoclonic epilepsy (BAFME), proton magnetic resonance spectroscopy (1H-MRS), cerebellum, cortical tremor, myoclonus

Yali Zhang,1,2,* Chengguang Zhao,1,2,* Wenfei He,2,* Zhe Wang,2 Qilu Fang,2 Bing Xiao,2 Zhiguo Liu,2 Guang Liang,2 Shulin Yang1 1School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, People's Republic of China; 2Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China *These authors contributed equally to this work Abstract: Sepsis is a systemic inflammatory response syndrome and is mainly caused by lipopolysaccharides (LPS) – a component of the cell walls of gram-negative bacteria, via toll-like receptor 4–mitogen-activated protein kinases/nuclear factor-kappa B-dependent proinflammatory signaling pathway. Here, we synthesized 26 asymmetric monocarbonyl analogs of curcumin and evaluated their anti-inflammatory activity by inhibiting the LPS-induced secretion of tumor necrosis factor-α and interleukin-6 in mouse RAW264.7 macrophages. Five active compounds (3a, 3c, 3d, 3j, and 3l) exhibited dose-dependent inhibition against the release of tumor necrosis factor-α and interleukin-6, and they also showed much higher chemical stability than curcumin in vitro. The anti-inflammatory activity of analogs 3a and 3c may be associated with their inhibition of the phosphorylation of extracellular signal-regulated kinase and the activation of nuclear factor-kappa B. In addition, 3c exhibited significant protection against LPS-induced septic death in vivo. These results indicate that asymmetrical monocarbonyl curcumin analogs may be utilized as candidates for the treatment of acute inflammatory diseases. Keywords: sepsis, inflammatory cytokines, anti-inflammation, quantitative structure–activity relationship

High-throughput genomic mutation screening for primary tumors has characteristically been expensive, labor-intensive, and inadequate to detect low levels of mutation in a background of wild-type signal. We present a new, combined PCR and colorimetric approach that is inexpensive, simple, and can detect the presence of 1% mutation in a background of wild-type. We compared manual dideoxy sequencing of p53 for eight lung cancer samples to a novel assay combining a primer extension step and an enzymatic colorimetric step in a 96-well plate with covalently attached oligonucleotide sequences. For every sample, we were able to detect the presence or absence of the specific mutation with a statistically significant difference between the sample optical density (OD) and the background OD, with a sensitivity and specificity of 100%. This assay is straightforward, accurate, inexpensive, and allows for rapid, high-throughput analysis of samples, making it ideal for genomic mutation or polymorphism screening studies in both clinical and research settings.

The porous carbon blacks rationally designed by a facile yet efficient NH3 thermal etching route have been investigated as anode materials in an ether-based electrolyte for sodium-ion batteries. The as-synthesized CBN35 carbon black with a 35% weight loss after NH3 thermal etching exhibited a large specific charge capacity of 352 mAh g−1 at 50 mA g−1 and a superior rate capability of 101 mAh g−1 at 16000 mA g−1, due to its highest microporosity, an appropriate surface area, a desirable microstructure, and a promising hybrid intercalation mechanism. Impressively, even cycled at 1600 mA g−1 over 3200 cycles, an outstanding reversible capacity of 103 mAh g−1 with a negligible 0.0162% capacity loss per cycle can still be achieved. Based on the multimodal characterizations including the structural probes of phase evolution for carbon materials, the electrochemical techniques, and the surface-sensitive XAS measurements, the exceptional electrochemical properties should stem from several merits of modified carbon black system. While the particular microporous structure provides relatively more accessible sodium storage sites, a novel hybrid intercalation mechanism in ether-based electrolyte would incorporate the sodium ion insertion into the disordered structure with the solvated sodium ion species co-intercalation into the graphitic phase. In addition to the diffusion-controlled redox reactions, the noticeable surface-induced pseudocapacitive reactions also significantly contribute to the charge storage upon sodiation and guarantee the rapid migrations of sodium ions/solvated compounds. This system further features a controlled emergence of a robust but thin solid electrolyte interphase layer, which could suppress the side reactions of active electrode with reactive electrolyte, maintain the fragile porous structure upon cycling, and facilitate the migrations of sodium ions and solvated sodium ion compounds.