Search

Xiaolei Han,1,2,* Yongxiang Wang,2,3,* Ziying Jiang,1 Yuanjing Li,4 Yi Dong,1 Lin Cong,1– 3 Tingting Hou,1– 3 Yajun Liang,4,5 Erika J Laukka,4 Yifeng Du,1– 3 Chengxuan Qiu1,4 1Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Neurological Diseases, Jinan, Shandong Province, People’s Republic of China; 4Aging Research Center and Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden; 5Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden*These authors contributed equally to this workCorrespondence: Yifeng Du, Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, No. 324 Jingwuweiqi Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +86-531-68776354, Fax +86-531-68773274, Email du-yifeng@hotmail.comPurpose: We explore the associations of individual and composite cardiovascular health metrics with all-cause dementia, Alzheimer’s disease, and vascular dementia among rural-dwelling older adults and the potential age variations in their associations.Patients and Methods: This community-based cross-sectional study included 4980 older adults (age ≥ 65 years; 57.23% women) from the baseline examination of MIND-China. In March–September 2018, data were collected via face-to-face interviews, clinical examinations, and laboratory test. We defined six cardiovascular health metrics according to the modified American Heart Association’s recommendations. We diagnosed dementia and its subtypes following the international criteria. Data were analyzed using logistic regression models.Results: Of all the participants, 250 were diagnosed with dementia, including 165 with Alzheimer’s disease and 75 with vascular dementia. Ideal composite global cardiovascular health metrics (vs poor composite metrics) were associated with a multi-adjusted odds ratio (95% confidence interval) of 0.62 (0.42– 0.93) for dementia, 0.88 (0.52– 1.48) for Alzheimer’s disease, and 0.31 (0.16– 0.60) for vascular dementia. Moreover, ideal biological cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.52 (0.28– 0.95) for dementia and 0.21 (0.06– 0.77) for vascular dementia in young–old adults (65– 74 years), whereas ideal behavioral cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.48 (0.26– 0.89) for dementia and 0.16 (0.06– 0.43) for vascular dementia in old–old adults (≥ 75 years).Conclusion: Our results suggest that ideal cardiovascular health metrics are cross-sectionally associated with a low likelihood of dementia and vascular dementia among rural-dwelling older Chinese adults. The associations vary with age, components of cardiovascular health metrics, and dementia subtypes.Keywords: cardiovascular health, dementia, Alzheimer’s disease, vascular dementia, population-based study

Guangtai Shen, 1 Xiaoqiang Yu, 1 Tianyang Sun, 1 Tian Hou, 1 Heping He, 1 Tubuxin Bai, 1 Zhipeng Zhang, 1 Xiaoli Ding, 1 Qingping Li, 2 Ying Liang, 3 Yuhua Ma 4 1Department of Breast and Thyroid Surgery, Inner Mongolia Xing’an League People’s Hospital, Ulanhot, Inner Mongolia, 137400, People’s Republic of China; 2Department of Operating Room, Inner Mongolia Xing’an League People’s Hospital, Ulanhot, Inner Mongolia, 137400, People’s Republic of China; 3Department of Pathology, Inner Mongolia Xing’an League People’s Hospital, Ulanhot, Inner Mongolia, 137400, People’s Republic of China; 4Department of Anesthesiology, Inner Mongolia Xing’an League People’s Hospital, Ulanhot, Inner Mongolia, 137400, People’s Republic of ChinaCorrespondence: Xiaoqiang YuDepartment of Breast and Thyroid Surgery, Inner Mongolia Xing’an League People’s Hospital, Ulanhot, Inner Mongolia, 137400, People’s Republic of ChinaTel/Fax +86 0482-8413761Email yuxq66_dr@163.comObjective: To verify the volume similarity between unilateral mammary gland and autologous omentum in adult females.Methods: A total of 63 patients diagnosed with stage 0–II breast cancer and partial non-lactating multi-fistula mastitis in the breast surgery department of Inner Mongolia Xing’an League People’s Hospital from 2007 to 2020 were enrolled in the study, including 52 cases of stage 0–II breast cancer and 11 cases of non-lactating multi-fistula mastitis. The volume of the resected mammary gland and the omentum were measured by a “soft tissue measuring cylinder” and recorded. The appearance of the reconstructed breast was compared with that of the healthy side. The correlation between unilateral mammary gland volume and autologous omentum volume was analyzed by linear regression.Results: Valid data were obtained for 60 cases. Affected breast size, curve, texture, nipple, and inframammary fold after omentum breast reconstruction were similar and symmetrical to those of the unaffected side. Postoperative complications occurred in most patients; the majority of these (76.67%) involved numbness of the nipple, and other complications were few. Patient satisfaction with postoperative appearance, feel, and movement of the breast, as well as total treatment costs, was over 75.0%. Linear regression analysis indicates a linear relationship between subcutaneous gland volume (x) and autologous omentum volume (y): y = 0.9847x - 1.2132, R 2 = 0.9742.Conclusion: Only when the dissociated pedicled omentum is completely obtained under laparoscopy can the whole subcutaneous residual cavity of the mammary gland be filled to the same volume. This study verifies that the volume of the unilateral mammary gland is similar to that of the autologous omentum in adult females.Keywords: unilateral mammary gland, omentum, volume, similarity, laparoscope, breast reconstruction

Dandan Zhu,1,2,* Jierong Chen,2,* Tieying Hou1,2 1School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, People’s Republic of China; 2Department of Laboratory Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tieying HouDepartment of Laboratory Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People’s Republic of ChinaEmail houtieying@gdph.org.cnBackground: Previous studies reported that dysregulation of RNA-binding proteins (RBPs) is significantly associated with the development of cancer. However, there are few studies to date on the role of RBPs in colon adenocarcinoma (COAD).Methods: RNA sequencing and clinical data for COAD patients were downloaded from The Cancer Genome Atlas (TCGA) database to identify differentially expressed (DE) RBPs between COAD tissue and normal colon tissue, and then the expression and prognostic significance of these RBPs were investigated in detail by systematic bioinformatics analysis. qRT-PCR was used to validate the expressions of prognosis-related RBP-encoding genes.Results: Seven RBPs (RPL10L, ERI1, POP1, CAPRIN2, TDRD7, SNIP1 and PPARGC1A) were identified as hub genes associated with prognosis by a series of regression analyses, and were then used to construct a prognostic model. Further analysis based on this model indicated that the overall survival (OS) of the high-risk groups was lower than that of the low-risk groups. In this prognostic model, the area under the ROC curve (AUC) was 0.694, 0.709 and 0.665 for the TCGA cohort at 1, 3 and 5 years, respectively, while the AUC was 0.671, 0.633 and 0.601 for the GEO combined cohort at 1, 3 and 5 years, respectively, indicating the good predictive ability of the model. We also built a nomogram based on the 7 RBPs in the TCGA cohort, and the model showed good discriminatory ability for COAD.Conclusion: We screened seven prognosis-related genes in COAD patients based on RBP-related genes, validated the expressions of the seven prognosis-related RBP-encoding genes by qRT-PCR and constructed a prognosis-related nomogram for patients with COAD.Keywords: colon adenocarcinoma, RNA binding proteins, overall survival, prognostic model, bioinformatics, qRT-PCR

Yanhong Jia,1– 3,* Rui Liu,1,* Shi Tang,1,2,4 Dongming Zhang,5 Yongxiang Wang,1,2,4 Lin Cong,1,2,4 Tingting Hou,1,2,4 Juan Ren,1 Yifeng Du1,2,4 1Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Department of Neurology, Baotou Central Hospital, Baotou, Inner Mongolia, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Neurological Diseases, Jinan, Shandong, People’s Republic of China; 5Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yifeng DuDepartment of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, No. 324 Jingwuweiqi Road, Jinan, Shandong, 250021, People’s Republic of ChinaTel/ Fax +86 531 68776354Email duyifeng@email.sdu.edu.cnPurpose: To examine the associations of impaired fasting glucose (IFG) and glycaemic control of diabetes with dementia, global cognitive function and physical function among rural-dwelling Chinese older adults.Patients and Methods: This population-based cross-sectional study included 4583 participants (age ≥ 65 years, 57.3% women) living in Yanlou Town, Yanggu County, western Shandong Province, China. In 2018, data were collected through interviews, clinical examinations, neuropsychological tests, and laboratory tests. Diabetes status was defined by self-reported physician-diagnosed diabetes, current use of antidiabetic agents, and fasting blood glucose tests. Global cognitive function was assessed using the Mini-Mental State Examination. Dementia was diagnosed following DSM-IV criteria, and Alzheimer’s disease (AD) was diagnosed following the National Institute on Aging-Alzheimer’s Association criteria. Physical function was assessed by the Short Physical Performance Battery. Data were analysed using multiple logistic and general linear regression models.Results: IFG was found in 267 participants, and diabetes was diagnosed in 658 participants (257 with well-controlled diabetes, 401 with poorly controlled diabetes). Dementia was diagnosed in 166 participants (116 with AD), and physical functional impairment was found in 1973 participants. The multi-adjusted odds ratio (OR) of dementia associated with poorly controlled diabetes (vs without IFG or diabetes) was 2.41 (95% CI 1.52– 3.84), and the OR of AD associated with poorly controlled diabetes was 2.32 (1.34– 4.04). In addition, the adjusted OR of physical functional impairment was 1.40 (1.06– 1.85) for well-controlled diabetes and 1.69 (1.35– 2.12) for poorly controlled diabetes. However, IFG was not associated with cognitive or physical function.Conclusion: The glycaemic control status of diabetes patients was associated with cognitive impairment and physical functional impairment.Keywords: impaired fasting glucose, Alzheimer’s disease, cognitive function, physical functional impairment

Tieying Hou,1,2 Long Ye,2 Shulin Wu1 1Ph.D. Program of Immunology, Shantou University Medical College, Shantou, Guangdong Province, 515041, People’s Republic of China; 2Laboratory Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510000, People’s Republic of ChinaCorrespondence: Shulin WuPh.D. Program of Immunology, Shantou University Medical College, No. 22 Xinling Road, Shantou, Guangdong Province, 515041, People’s Republic of ChinaTel +86-754-88550917Fax +86-754-88550917Email shulinwu66@126.comIntroduction: Breast cancer is one of the most common cancers in the world. Long noncoding RNA 00504 (LINC00504) was reported to be a functional gene in some tumours but not breast. Accordingly, the purpose of this article is to study the function of LINC00504 in breast cancer.Methods: qPCR assay was used to detect the expression of LINC00504 in tissue and cell lines. The online database and chromatin immunoprecipitation assay (ChIP) were employed to confirm the transcription factor of LINC00504. Cell function assays including cell proliferation, migration and invasion were designed to detect the function of LINC00504 in vitro and in vivo. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm the relationship between LINC00504 and miR‐140-5p. And Western blot assay was employed for testing the key protein.Results: We found that LINC00504 is upregulated in breast cancer. In addition, we found that the transcription factor regulatory factor X5 (RFX5) can strongly bind to the LINC00504 promoter region and subsequently increase its transcriptional activity. We also found that the manipulation of RFX5 expression can significantly affect LINC00504 expression, which suggested that RFX5 can transcriptionally activate LINC00504 in breast cancer (BC). Knockdown of LINC00504 inhibits cell proliferation, migration and invasion in vitro and in vivo. We further found that LINCOO504 inhibits miR‐140-5p, which decreases the levels of VEGFA. The further results showed that miR-140-5p was one of the target gene of LINC00504. The WB assay demonstrated that the E-cadherin was increased and Vimentin was decreased when knocking down of LINC00504 and they can be rescued while adding the inhibitors of miR-140-5p.Discussion: Our results demonstrated the mechanism by which the LINC00504–miR‐140-5p–VEGFA axis participates in breast cancer cell proliferation and invasion and may lead to new lncRNA-based diagnostic or therapeutic strategies for breast cancer.Keywords: breast cancer, LINC00504, proliferation, invasion, miR-140-5p

Huining Zhou,1,* Zhengyi Wu,1,* Hui Wang,1 Wenya Yu,1 Jiaoling Huang,1 Liang Zhou,1 Dehua Yu,2 Tianchun Hou,1 Yipeng Lv,1 Chen Chen,3 Li Luo,4 Jianwei Shi,1,5 Zhaoxin Wang1,6 1School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of General Practice, Yangpu Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Jing‘an District Jiangning Road Community Health Service Center, Shanghai, People’s Republic of China; 4School of Public Health, Fudan University, Shanghai, People’s Republic of China; 5Shanghai General Practice and Community Health Development Research Center, Shanghai, People’s Republic of China; 6General Practice Center, Nanhai Hospital, Southern Medical University, Foshan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianwei Shi; Zhaoxin WangSchool of Public Health, Shanghai Jiaotong University School of Medicine, 227 South Chongqing Road, Shanghai 200025, People’s Republic of ChinaTel +86 188 1820 9852; +86 139 1853 7473Email shijianwei_amy@126.com; supercell002@sina.comPurpose: The purpose of this study was to use the hospital information system to analyze the cancer profile and compare demographics, hospitalization, status of surgery and treatment cost of various cancer categories based on the electronic health record (EHR) of outpatient children with tumors in Shanghai, China.Patients and Methods: Information was collected from 3834 inpatients aged 0– 18 who were diagnosed with malignant tumors in all 17 hospitals with pediatric wards in the Pudong New District of Shanghai from 2011 to 2016. All patients were classified according to the International Classification of Childhood Cancer-3 (ICCC-3). The chi-squared test was used to compare demographics, hospitalization information, status of surgery and treatment cost according to inpatients’ cancer category.Results: In both the malignant non-solid tumor and solid tumor groups, males and those aged 0– 4 years were the dominant groups. Lymphocytic leukemia was the most common cancer in all inpatients (n=994, 25.93%), and the acute myeloid leukemia had the longest length of stay of inpatients (median=26.00 days). In both the non-solid and solid tumor groups, patients who received only one type of surgery had an advantage. The highest proportion of patients who had undergone surgery was found in non-Hodgkin lymphoma patients. In terms of total cost, surgical cost and medicine cost, the expenditure of central nervous system tumor patients was the highest. Astrocytoma had the highest total cost.Conclusion: Leukemia is common in children with cancer in Pudong and should be given attention. Because the highest financial burden falls on patients with central nervous system tumors and acute myeloid leukemias, the government should take immediate and targeted measures for these cancers in particular.Keywords: malignant tumors, disease burden, demographics, hospitalization information, epidemiology

Shun Jiang,1 Sisi Wang,1 Qianqian Wang,2 Chao Deng,1 Yuhua Feng,1 Fang Ma,1 Jin’an Ma,1 Xianling Liu,1 Chunhong Hu,1 Tao Hou1 1Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China; 2Department of Oncology, The Affiliated ZhuZhou Hospital of XiangYa Medical College, Central South University, ZhuZhou, 412007, Hunan, People’s Republic of ChinaCorrespondence: Tao HouDepartment of Oncology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaTel +86-13786122515Email houtao@csu.edu.cnBackground: Systemic inflammation response index (SIRI) has been reported to be an effective blood-based biomarker for predicting prognosis in various kinds of cancer patients. However, the prognostic role of SIRI in advanced lung adenocarcinoma patient remains unclear.Methods: The aim of the present study is to evaluate the prognostic role of SIRI in EGFR-mutant advanced lung adenocarcinoma patients treated with first-generation EGFR-TKIs. A total of 245 patients who received gefitinib, erlotinib, or icotinib at the Second Xiangya Hospital were retrospectively evaluated. SIRI was defined as neutrophil count×monocyte/lymphocyte count. The optimal cut-off value was determined according to receiver operation characteristic curve analysis. Characteristics of patients were compared via chi-square test or Fisher’s exact test. Survivals were estimated by the Kaplan–Meier method and compared by the Log rank test. Multivariate analysis was estimated using the Cox proportional hazards model.Results: It is showed that high SIRI was associated with male patient, smoker, worse ECOG PS, 19-DEL mutation. Kaplan–Meier survival analysis showed that ECOG PS, brain metastasis, SIRI were significantly correlated with progression-free survival (PFS), and gender, ECOG PS, brain metastasis, NLR and SIRI were significantly correlated with overall survival (OS). Multivariate analysis showed that SIRI and ECOG PS independently predict PFS and OS.Conclusion: Our findings indicate that SIRI is an effective and convenient marker for predicting prognosis in advanced EGFR-mutant lung adenocarcinoma patients treated with first-generation TKI.Keywords: lung adenocarcinoma, EGFR-TKI, SIRI, prognosis

NV Reddy,1 Huizhen Li,1 Tianyu Hou,1 MS Bethu,2 Zhiqing Ren,1 Zhijun Zhang1 1School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi Province, People’s Republic of China; 2Pharmacology and Toxicology Division, Indian Institute of Chemical Engineering and Technology, Hyderabad, Telangana State, IndiaCorrespondence: Zhijun ZhangSchool of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi Province 030051, People’s Republic of ChinaEmail sxzzj@163.comPurpose: The present study investigates the phytosynthesis of silver nanoparticles (AgNPs) using Perilla frutescens leaf extract, which acts as a reducing agent for the conversion of silver ions (Ag+) into AgNPs. P. frutescens leaf synthesized AgNPs (PF@AgNPs) were evaluated for biomedical properties including antibacterial, antioxidant and anticancer activities.Materials and Methods: PF@AgNPs were synthesized using P. frutescens leaf extract and silver nitrate solution. The morphology and physical properties of PF@AgNPs were studied by spectroscopic techniques including, UV-Vis, FTIR, TEM, XRD, DLS, and TGA. Antibacterial activity of PF@AgNPs was evaluated by disk diffusion assay. Antioxidant activity of PF@AgNPs was checked by 2.2-diphenyl-1-picrylhydrazyl (DPPH), and 2.2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging assays. Anticancer activity of PF@AgNPs was checked by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Cytotoxic effects of PF@AgNPs on most susceptible cancer cell lines were observed by phase contrast microscopy.Results: PF@AgNPs showed surface plasmon resonance peak at 461 nm. XRD pattern showed that the PF@AgNPs were face-centered cubic crystals with a mean size of 25.71 nm. TEM analysis revealed the different shapes (spherical, rhombic, triangle, and rod) of PF@AgNPs. Zeta potential value (− 25.83 mV) indicated that PF@AgNPs were long-term stable and not agglomerated. A low polydispersity index value (0.389) indicated the monodispersity of PF@AgNPs. TGA revealed the high thermal stability of PF@AgNPs. PF@AgNPs exhibited maximum inhibition against Escherichia coli, followed by Bacillus subtilis and Staphylococcus aureus. PF@AgNPs showed maximum inhibition of 68.02 and 62.93% against DPPH and ABTS-free radicals, respectively. PF@AgNPs showed significant anticancer activity against human colon cancer (COLO205) and prostate adenocarcinoma (LNCaP). PF@AgNPs exhibited apoptotic effects on LNCaP cells including cell shrinkage, membrane blebbing, chromatin condensation, fragmentation of nuclei, and formation of apoptotic bodies.Conclusion: The present study reports the successful synthesis of PF@AgNPs using P. frutescens leaf extract. The synthesized PF@AgNPs are FCC crystals, monodispersed, long-term stable, and non-agglomerated. The observed antibacterial, antioxidant, and anticancer activities demonstrate the potential biomedical applications of PF@AgNPs.Keywords: Perilla frutescens, silver nanoparticles, antibacterial activity, antioxidant activity, anticancer activity, LNCaP

Xiuping Pang,1,* Shuang Liang,1,* Tianqi Wang,1 Shuangjiang Yu,2 Rui Yang,1 Teng Hou,1 Yongjun Liu,1 Chaoliang He,2 Na Zhang1 1Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong Province 250012, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaoliang He; Na Zhang Email clhe@ciac.ac.cn; zhangnancy9@sdu.edu.cnPurpose: Combined chemotherapeutic drug and protein drug has been a widely employed strategy for tumor treatment. To realize both tumor accumulation and deep tumor penetration for drugs with different pharmacokinetics, we propose a structure-transformable, thermo-pH dual responsive co-delivery system to co-load granzyme B/docetaxel (GrB/DTX).Methods: Thermo-sensitive hydrogels based on diblock copolymers (mPEG-b-PELG) were synthesized through ring opening polymerization. GrB/DTX mini micelles (GDM) was developed by co-loading these two drugs in pH-sensitive mini micelles, and the GDM-incorporated thermo-sensitive hydrogel (GDMH) was constructed. The thermo-induced gelation behavior of diblock copolymers and the physiochemical properties of GDMH were characterized. GDMH degradation and deep tumor penetration of released mini micelles were confirmed. The pH-sensitive disassembly and lysosomal escape abilities of released mini micelles were evaluated. In vitro cytotoxicity was studied using MTT assays and the in vivo antitumor efficacy study was evaluated in B16-bearing C57BL/6 mice.Results: GDMH was gelatinized at body temperature and can be degraded by proteinase to release mini micelles. The mini micelles incorporated in GDMH can achieve deep tumor penetration and escape from lysosomes to release GrB and DTX. MTT results showed that maximum synergistic antitumor efficacy of GrB and DTX was observed at mass ratio of 1:100. Our in vivo antitumor efficacy study showed that GDMH inhibited tumor growth in the subcutaneous tumor model and in the post-surgical recurrence model.Conclusion: The smart-designed transformable GDMH can facilitate tumor accumulation, deep tumor penetration, and rapid drug release to achieve synergistic chemo-protein therapy.Keywords: structure-transformable, thermo-pH dual responsive, hydrogel, chemo-protein combination therapy

Yiping He,1,2,* Xiaoji Ma,1,2,* Ke Chen,2,3,* Fangqi Liu,1,2 Sanjun Cai,1,2 Han Han-Zhang,4 Ting Hou,4 Jianxing Xiang,4 Junjie Peng1,2 1Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of Endoscopy, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 4Burning Rock Biotech, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junjie PengDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong’An Road, Shanghai 200032, People’s Republic of ChinaTel +86 21 64175590Email pengjj67@hotmail.comBackground: The surgical resection of colorectal cancer with liver metastases (CLM) has proven to be the most important modality for long-term survival, while effective biomarkers for outcome prediction or postoperative surveillance are still lacking. Currently, circulating biomarkers obtained from a liquid biopsy are widely used to assess the treatment response, disease recurrence and progression. In this study, we analyzed the value of the liquid biopsy, which includes circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA), in patients with CLM.Methods: Capture-based targeted deep sequencing was performed on matched pre-surgery, post-surgery and liver metastatic tissues of 20 CRC patients who underwent the resection of liver metastases between May and September 2017 using a panel consisting of 41 genes. Mutation landscapes obtained from pre-surgery plasma samples and metastatic tissue samples were compared.Results: Collectively, we identified 47 mutations from 17 pre-surgery plasma samples (85%), and the remaining 3 patients had no mutation detected from the panel. We revealed a high by-variant concordance rate of 82.14% between pre-surgery plasma samples and liver metastatic tissue samples. We further analyzed the correlation between ctDNA, cfDNA, CEA and tumor burden and revealed a positive correlation between ctDNA and tumor burden (R=0.69, p=0.002). As of the date for data cutoff, 8/20 patients experienced relapse. Our study also demonstrated that pre-surgery ctDNA (p< 0.001), cfDNA (p=0.001) and CEA (p=0.012) levels had predictive value for relapse. Patients with low pre-surgery ctDNA (p< 0.001), cfDNA (p=0.001) or CEA (p=0.012) levels were more likely to experience prolonged progression-free survival.Conclusion: Our data demonstrate that the genomic profile obtained from ctDNA is comparable with the genomic profile obtained from metastatic liver tumors. Furthermore, our study also show that pre-surgery ctDNA levels are positively correlated with tumor burden. In addition, pre-surgery ctDNA, cfDNA and CEA levels have predictive value for relapse.Keywords: colorectal liver metastases, CLM, circulating tumor DNA, ctDNA, tumor burden, prognosis

Ying Zhang,1 Shanshan Wu,2 Xinlei Zhuang,1 Gaoqi Weng,1 Jiansheng Fan,1 Xiaoyue Yang,1 Yingchun Xu,1 Liqiang Pan,1 Tingjun Hou,1,3 Zhan Zhou,1 Shuqing Chen1 1Institute of Drug Metabolism and Pharmaceutical Analysis and Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People’s Republic of China; 2Precision Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, People’s Republic of China; 3State Key Laboratory of Computer Aided Design and Computer Graphics (CAD&CG), Zhejiang University, Hangzhou 310058, People’s Republic of ChinaCorrespondence: Zhan Zhou; Shuqing ChenInstitute of Drug Metabolism and Pharmaceutical Analysis and Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People’s Republic of ChinaTel +86-0571-8820-8410Email zhanzhou@zju.edu.cn; chenshuqing@zju.edu.cnBackground: The aberrant expression of HER2 is highly associated with tumour occurrence and metastasis, therefore HER2 is extensively targeted for tumour immunotherapy. For example, trastuzumab and pertuzumab are FDA-approved monoclonal antibodies that target HER2-positive tumour cells. Despite their advances in clinical applications, emerging resistance to these two HER2-targeting antibodies has hindered their further application. Somatic mutations in HER2 receptor have been identified as one of the major reasons for resistance to anti-HER2 antibodies.Methods: We analysed the frequency of somatic mutations in various tumour types based on TCGA and COSMIC databases. Then, the effect of the most frequent mutation (S310F) on the interaction between pertuzumab and HER2 was analysed by molecular modelling analysis. The effect of the S310F mutation was further evaluated through multiple in vitro binding experiments and antitumour activity assays.Results: We found through bioinformatics analysis that S310F, an activating mutation in the HER2 extracellular domain, was the most frequent mutation in HER2. The S310F mutation was shown to confer resistance of HER2-positive tumour cells to pertuzumab treatment. With molecular modelling analysis, we confirmed the possibility that the S310F mutation might disrupt the interaction between pertuzumab and HER2 as a result of a significant change in the critical residue S310. Further functional analyses revealed that the S310F mutation completely abolished pertuzumab binding to HER2 receptor and inhibited pertuzumab antitumour efficacy.Conclusion: We demonstrated the loss-of-function mechanism underlying pertuzumab resistance in HER2-positive tumour cells bearing the S310F mutation.Keywords: HER2, mutation, pertuzumab, drug resistance, tumour cells

Ling Li,1,* Tong Zhang,1,* Chunru Li,2 Lu Xie,3 Ning Li,4 Tianling Hou,1 Yuqin Wang,2 Bing Wang1 1Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Zhejiang BioAsia Pharmaceutical Co., Ltd., Pinghu, Zhejiang, China; 3Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; 4Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China *These authors contributed equally to this work Background: Natural Cordyceps cicadae (C. cicadae) has been utilized extensively in traditional Chinese medicine to treat chronic renal diseases, heart palpitations, infantile convulsions, and dizziness. However, given its slow growth and immoderate exploitation, C. cicadae resources have been severely depleted. By contrast, Paecilomyces cicadae (P. cicadae), as the anamorph stage of C. cicadae, is easy to cultivate, and this kind of cultivated P. cicadae has good and controllable quality. Purpose: This study aimed to compare the therapeutic effects of C. cicadae and P. cicadae on adenine-induced chronic renal failure (CRF) rats. In accordance with the aforementioned studies, our work subsequently analyzed the intrinsic relationships between the efficacy and pharmacodynamic substances of C. cicadae and P. cicadae to conclude whether or not P. cicadae could be used as an alternative to C. cicadae in treating CRF. Methods: Rats were administered with C. cicadae (1.0 g/kg) or P. cicadae (1.0 g/kg) by gavage for 4 weeks. Furthermore, we applied Fourier transform infrared spectroscopy, gas chromatography–mass spectrometry, liquid chromatography–tandem mass spectrometry, and ultraviolet spectropho­tometry to comprehensively detect and analyze the chemical constituent differences from ten batches each of C. cicadae and P. cicadae. Results: This study revealed that both C. cicadae and P. cicadae exerted obvious therapeutic effects on CRF and were more consistent with their chemical compositions. Conclusion: P. cicadae can be used as an alternative to C. cicadae for treating CRF to cater to market demands. Keywords: Cordyceps cicadae, Paecilomyces cicadae, chronic renal failure, FTIR, GC-MS, LC-MS/MS, identification

A brief description of the impact of the recent HERA run I+II combination of inclusive deep inelastic scattering cross-section data on the CT14 global analysis of PDFs is given. The new CT14HERA2 PDFs at NLO and NNLO are illustrated. They employ the same parametrization used in the CT14 analysis, but with an additional shape parameter for describing the strange quark PDF. The HERA I+II data are reasonably well described by both CT14 and CT14HERA2 PDFs, and differences are smaller than the PDF uncertainties of the standard CT14 analysis. Both sets are acceptable when the error estimates are calculated in the CTEQ-TEA (CT) methodology and the standard CT14 PDFs are recommended to be continuously used for the analysis of LHC measurements.

A brief description of the CT14 global analysis of quantum chromodynamics at next-to-next-to leading order (NNLO) from the CTEQ-TEAgroup is given. Predictions for standard candle processes at the LHC are illustrated together with the main features of the CT14 parton distribution functions

SnS has recently been shown to possess unique valleytronic capability with a large polarization degree, where non-degenerate valleys can be accessed using linearly polarized light, bestowed upon by the unique anisotropy and wavefunction symmetry. It is thus of utmost importance to demonstrate the extension of such effects for the IV-VI system in general, thereby elucidating the generality and tunability of such valleytronics. We show the highly tunable valleytronics via gradual compositional control of the tin(II) sulfo-selenide (SnSxSe1-x) alloy system with excellent retainment of symmetry-determined selection rules. We show the presence of both ΓY and ΓX valleys in all alloy compositions via selectivity in absorption and emission of linearly polarized light by optical reflection (R)/transmission (T) and photoluminescence measurements and tuned the bandgaps of the valleys within a range of 1.28 eV-1.05 eV and 1.48 eV-1.24 eV, respectively. This simultaneous tuning of non-degenerate valleys agrees well with theoretical calculations. We then fitted the bandgap values in compositional space, obtaining bowing parameters as a useful database. We further demonstrated the feasibility of using IV-VI valleytronics systems in general by elucidating the retainment of strong polarization degrees of as high as 91% across all compositions. The generalization of such purely symmetry-dependent valleytronics also opens up opportunities for the discovery of more multi-functional materials.

Fluoroethylene carbonate (FEC) has been proposed as an effective electrolyte additive that enhances the stability and elasticity of the solid electrolyte interphase (SEI) of emerging Si and Li metal anodes. However, uncertainties still remain on the exact mechanism through which FEC alters the electrolyte decomposition and SEI formation process. Herein, the influence of FEC on LiPF6/ethylene carbonate (EC) electrolytes for Si anodes is investigated through classical molecular dynamics, Fourier-transform infrared spectroscopy, and quantum chemical calculations. Albeit a minority species, FEC is found to significantly modify the solvation structure and reduction behavior of the electrolyte while being innocuous to transport properties. Even with limited 10% of FEC, the Li+ solvation structure exhibits a notably higher contact-ion pair ratio (14%) than the parent EC electrolyte (6%). Moreover, FEC itself, as a new fluorine-containing species, appears in 1/5 of the Li+ solvation shells. The Li+-coordinated FEC is found to reduce prior to EC and uncoordinated FEC which will passivate the anode surface at an early onset (ca. 0.3 V higher than EC) by forming LiF. The critical role of FEC in tailoring the Li+ solvation structure and as-formed protective SEI composition provides mechanistic insight that will aid in the rational design of novel electrolytes.

Applied Materials, Inc. has reported a novel and manufacturable microLED display architecture, featuring UV‐A microLEDs, 4‐subpixel layout, pixel isolation wells filled with inkjetted Cd‐free R/G/B quantum dots (QDs), and a blanket UV blocker on top. A 1.37" smart‐watch active‐matrix display prototype was assembled using such method. Our QDs, including blue QD and the matrix materials exhibit excellent stability under UV excitation, as verified by accelerated lifetime test under higher UV flux and elevated temperature. The emission properties of our R/G/B QDs was further optimized, paving a path to achieve 99% DCI‐P3 color space coverage. Our display demonstrates a highly uniform Lambertian emission pattern with minimal color shift at high viewing angles, attributing to all emissions originating from QD embedded in the same polymer matrix. Furthermore, we can eliminate the QD photon‐brightening effect and demonstrate display with high thermal stability up to 90⁰C. [ABSTRACT FROM AUTHOR]

A 1.37" smart‐watch size active‐matrix microLED display prototype was fabricated by Cd‐free R/G/B quantum dots pumped by UV microLEDs in an innovative 4‐sub‐pixel architecture. The temperature‐dependent emission properties from such quantum dot display have been studied based on the competing processes between LTPS TFT output current and UV microLED radiance. Our studies show that with proper thermal treatment, the photo brightening of QDs can be stabilized within 5%. This presents a promising route to develop microLED displays with brightness insensitive to operation temperature up to 90ºC. [ABSTRACT FROM AUTHOR]

This Report summarizes the proceedings of the 2015 Les Houches workshop onPhysics at TeV Colliders. Session 1 dealt with (I) new developments relevantfor high precision Standard Model calculations, (II) the new PDF4LHC partondistributions, (III) issues in the theoretical description of the production ofStandard Model Higgs bosons and how to relate experimental measurements, (IV) ahost of phenomenological studies essential for comparing LHC data from Run Iwith theoretical predictions and projections for future measurements in Run II,and (V) new developments in Monte Carlo event generators.