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Zemin Ou, Yun You, Hong Yi, Xiaoqian Liu, Yan Tong, Dewen Liu, Jinyu Wang Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Dewen Liu; Jinyu Wang, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 10700, People’s Republic of China, Email dwliu@icmm.ac.cn; wangjinyu@icmm.ac.cnIntroduction: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment.Methods: We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model.Results: The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH.Conclusion: The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.Keywords: nanomedicine, brain delivery, angiopep-2, echinacoside, Parkinson’s disease, liposomes

Shuxiu Xiao,1,* Lili Lu,1,* Zhiyuan Lin,2,* Xinming Ye,3 Sheng Su,3 Chenlu Zhang,4 Yang You,4 Wei Li,4 Xiaowu Huang,3 Weizhong Wu,5 Yuhong Zhou1,4 1Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Liver Surgery and Transplantation, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 5Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuhong Zhou; Weizhong Wu, Email zhou.yuhong@zs-hospital.sh.cn; wu.weizhong@zs-hospital.sh.cnBackground: Layilin (LAYN) represents a valuable prognostic biomarker across various tumor types, while also serving as an innovative indicator of dysfunctional or exhausted CD8+ T cells and exhibiting correlation with immune context. However, the immune function and prognostic significance of LAYN in hepatocellular carcinoma (HCC) remain unexplored. Therefore, our objective is to investigate the role of LAYN in CD8+ T cell exhaustion, clinical prognosis, and the tumor microenvironment within HCC.Methods: TIMER or GEPIA databases were used to analyze LAYN expression level and its correlation with immune infiltration in HCC. Bioinformatics analysis was conducted on TCGA and scRNA-seq cohorts. The evaluation of LAYN expression level in fresh specimens was performed through IF, IHC, and ELISA assays. Flow cytometry and mRNA-seq were employed to investigate co-expressed genes of LAYN, the LAYN+CD8+ T cell exhaustion signature and immune function. Cell proliferation ability and killing activity were assessed using CCK8 and CFSE/PI.Results: The expression level of LAYN in HCC tumors was significantly higher compared to peri-tumors. Patients with high levels of LAYN exhibited poorer OS. GO or KEGG analysis confirmed that LAYN was involved in immune response and was positively associated with CD8+ T cell immune infiltration levels. Furthermore, LAYN negatively regulated the immune function of CD8+ T cells, leading to dysfunctional phenotypes characterized by elevated levels of CD39, TIM3 and reduced levels of perforin, TNF-α, Ki-67. CFSE/PI assays demonstrated that LAYN+CD8+ T cells displayed decreased cytotoxic activity. Additionally, there was a positive correlation between LAYN and CD146 levels, which are involved in adhesion and localization processes of CD8+ T cells. Interestingly, blocking LAYN partially restored the exhaustion properties of CD8+ T cells.Conclusion: LAYN exhibits a strong correlation with immune infiltration in the TME and represents a novel biomarker for predicting clinical prognosis in HCC. Moreover, targeting LAYN may hold promise as an effective strategy for HCC immunotherapy. Keywords: hepatocellular carcinoma, layilin, CD8+ T cell exhaustion, prognosis

Zihui Yuan,* Chao Du,* Yun You,* Jian Wang Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Wang, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +11-86-15902735929, Email jianwang1030@126.comPurpose: Iliac limb occlusion (ILO) is a serious complication of endovascular abdominal aneurysm repair (EVAR). This study aimed to identify predictive factors for ILO derived from aortoiliac morphology, endovascular procedure-related parameters, and aneurysmal remodeling characteristics.Patients and Methods: Patient demographics, pre-EVAR anatomical characteristics of the aneurysm, endovascular procedure details, and post-EVAR aneurysmal remodeling outcomes were analyzed and compared using univariate analysis. Statistically significant factors were subsequently subjected to Cox regression and Kaplan–Meier analyses.Results: Between January 2013 and April 2022, 66 patients were included in this study. Fourteen patients presented with ILO and were compared with 52 control patients with patent endograft limb over at least 1-year of follow-up. The tortuosity indices of the common iliac artery (CIA) and endograft iliac limb to vessel oversizing were significantly larger in the ILO group than in the patent endograft limb group. The CIA index of tortuosity ≥ 1.08, and endograft iliac limb to vessel oversizing ≥ 18.8% were independent predictors for ILO. During the follow-up of all patients, the proximal aortic neck and CIA diameters increased, aneurysm sac diameter decreased, and aortic neck and aortic length increased. The aortoiliac length increased over time in patients with patent endograft limb but not in patients with ILO. A change in the lowest renal artery-left iliac bifurcation distance ≦0.07 mm increased the risk of ILO.Conclusion: ILO is predisposed to occur when the CIA index of tortuosity ≥ 1.08 and endograft iliac limb to vessel oversizing ≥ 18.8% are present. Significant aortoiliac remodeling, including proximal aortic neck dilatation, neck straightening, aneurysmal sac regression, iliac artery enlargement, and aortic lengthening, occurs after EVAR. Aortoiliac elongation was observed in patients with patent endograft limb, but not in patients with ILO. ILO was associated with a change in the lowest renal artery–left iliac bifurcation from the postoperative measurements ≦ 0.07 mm.Keywords: abdominal aortic aneurysm, endovascular abdominal aneurysm repair, iliac limb occlusion, aortoiliac anatomy, aneurysmal remodeling, oversizing, aortoiliac tortuosity

Understanding reaction kinetics can provide valuable information for the design and optimization of a reaction process. In this study, the reduction degree and carbonitriding ratio of TiO2 in the CH4-H2-N2 system were investigated to understand the kinetics of carbonitriding reduction. The experimental results revealed the following important findings. The reduction degree of TiO2 increased significantly within the temperature range of 1000°C to 1200°C. At the same time, the duration of complete carbonitride time decreased with increasing temperature. However, it was found that excessively high temperatures (1200°C) had a detrimental effect on the degree of reduction. Consequently, the optimal reduction temperature was set at 1100°C, in order to achieve a balance between reduction degree and reaction time. The process of carbonitride reduction of TiO2 in the CH4-H2-N2 system corresponded to the unreacted nuclear model, where the process was mainly controlled by chemical reactions. A calculated apparent activation energy of 99.35 kJ/mol was obtained for the carbonitriding reduction process. The identification of the optimal reduction temperature and the dominant role of chemical reactions provide valuable insights for the design and optimization of carbonitriding processes with titanium compounds.

Zhimei Zhao,1,* Xiang Han,1,* Yunhong You,1 Jiankang Zhang,2 Keke Nie,1 Youxin Ji1 1Department of Oncology, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Cancer Hospital, Qingdao City, People’s Republic of China; 2Department of Medicine, Qingdao Medical College, Qingdao University, Qingdao City, People’s Republic of China*These authors contributed equally to this workCorrespondence: Keke Nie; Youxin Ji, Department of Oncology, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Cancer Hospital, 127 Si Liu South Road, Shibei District, Qingdao City, 266042, People’s Republic of China, Tel + (86)532-6866-5078, Fax + (86)532-8486-3506, Email niekekeqd@163.com; mdji001@gmail.comBackground: We study the characteristics and outcomes in lung cancer patients with COVID-19 Omicron variant infection.Methods: Hospitalized lung cancer patients with advanced-stage disease and laboratory-confirmed COVID-19 Omicron infection were included. Pneumonitis involving at least 25% of lung parenchyma on CT scans, accompanied by symptoms and oxygen saturation below 93%, were criteria for enrollment. Pneumonitis severity was graded using CTCAE v5.0. Treatment included Paxlovid, prednisolone, anticoagulation, and ventilation. Initial data, radiographic findings, and outcomes were compared. Logistic regression was employed to determine risk factors for in-hospital mortality.Results: Fifteen patients (median age: 65 years; 80.0% males) were included. 73.3% improved and were discharged, 20.0% died, and 6.7% remained intubated. Initial symptoms included cough (100.0%), fever (73.3%), and shortness of breath (53.3%). Symptoms resolved in discharged patients. Median fever duration was 3.5 days, and respiratory symptom recovery took 26 days. Three patients died due to respiratory failure from Omicron pneumonia. Lower oxygen saturation, reduced lymphocyte/neutrophil ratio on day 7, and diffuse bilateral lung lesions were poor prognostic factors.Conclusion: This study underscores the importance of prompt intervention and early diagnosis for lung cancer patients infected with the COVID-19 Omicron variant. Lower oxygen saturation, decreased lymphocyte/neutrophil ratio on day 7, and diffuse lung lesions on CT scans were associated with worse outcomes. Clinicians should prioritize timely and comprehensive management to improve survival rates in this population.Keywords: COVID-19 omicronvariant, lung cancer, oxygen saturation, lymphocyte and neutrophils ratio, chest CT scan

BackgroundYoung adults and other working-age adults with cancer are at risk for cancer-related financial toxicity (FT), including material hardships, depletion of coping resources, and psychological burden. This study compares FT domains in young adults (18-39 years old) (YAs), other working-age adults (40-64 years old), and older adults (≥65 years old) receiving cancer care.MethodsA total of 311 adults were surveyed using the multi-domain Economic Strain and Resilience in Cancer instrument measuring FT (0-10 score indicating least to greatest FT; score ≥5 severe FT). Participants were receiving ambulatory care from March-September 2019. Associations of age with overall FT and material hardship, coping resource depletion, and psychological burden FT domains were tested using Kruskal-Wallis and χ2 tests and multivariable generalized linear models with gamma distribution.ResultsYAs (median age, 31.5 years) comprised 9.6% of the sample; other working-age adults comprised 56.9%. Overall, material, coping, and psychological FT scores were worse in younger age adults versus older adults (P

The pursuit of knowledge in particle physics requires constant learning. Asnew tools become available, new theories are developed, and physicists searchfor new answers with ever-evolving methods. However, it is the case that formaleducational systems serve as the primary training grounds for particlephysicists. Graduate school (and undergraduate school to a lesser extent) iswhere researchers learn most of the technical skills required for research,develop scientific problem-solving abilities, learn how to establish themselvesin their field, and begin developing their career. It is unfortunate, then,that the skills gained by physicists during their formal education are oftenmismatched with the skills actually required for a successful career inphysics. We performed a survey of the U.S. particle physics community todetermine the missing elements of graduate and undergraduate education and togauge how to bridge these gaps. In this contributed paper, part of the 2021-22Snowmass Community Planning Exercise, we report the results of this survey. Wealso recommend several specific community actions to improve the quality ofparticle physics education; the "community" here refers to physics departments,national labs, professional societies, funding agencies, and individualphysicists.

Yajing You,1,&ast; Tao Yang,2,&ast; Shuhang Wei,1 Zongxin Liu,1 Chenxi Liu,1 Zijian Shen,3 Yinuo Yang,1 Yuemin Feng,1 Ping Yao,2 Qiang Zhu1,2 1Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China; 3Department of Radiology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Zhu, Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Email zhuqiang@sdu.edu.cn Ping Yao, Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Email pingyaozh@sina.comPurpose: Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality.Patients and Methods: A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes.Results: Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p< 0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p< 0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits.Conclusion: Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.Keywords: steatosis, diabetes, obesity, HBe Ag

Xiaoyi Chen,1,2 Jingyu Zhao,3 Yanxue You,1,2 Zelin Li,2 Shuchun Chen2 1Graduate School, Hebei North University, Zhangjiakou, 075000, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China; 3Graduate School, North China University of Science and Technology, Tangshan, 063210, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email chenshuchunwork88@163.comPurpose: Type 2 diabetic retinopathy is a long-term chronic inflammatory disease. The aim of this study was to investigate the relationship between fibrinogen to albumin ratio (FAR) and retinopathy in type 2 diabetic patients.Methods: This was a retrospective study that included 500 patients with type 2 diabetes mellitus (T2DM), and were divided into non-diabetic retinopathy group (NDR, n=297) and diabetic retinopathy group (DR, n=203) according to fundus examination findings, and the DR group was further divided into non-proliferative retinopathy group (NPDR, n=182) and proliferative retinopathy group (PDR, n=21). Baseline data of patients were collected, and the fibrinogen to albumin ratio (FAR) and neutrophil to lymphocyte ratio (NLR) were calculated to analyze the correlation between FAR and NLR and type 2 diabetic retinopathy.Results: The FAR and NLR were significantly higher in the DR group compared with the NDR group (both P < 0.001). Spearman correlation analysis showed that FAR was positively correlated with NLR and DR (P < 0.05). As the FAR quartile increased, the prevalence of DR increased (14.8%, 16.7%, 25.1%, and 43.30%, respectively; P < 0.05). Multifactorial logistic regression analysis showed that FAR, diabetic course, systolic blood pressure (SBP) and diabetic peripheral neuropathy (DPN) were risk factors for the development of DR in patients with T2DM. The area under the ROC curve for FAR to predict DR progression was 0.708, with an optimal critical value of 7.04, and the area under the ROC curve for diabetes duration and SBP to predict DR was 0.705 and 0.588, respectively.Conclusion: Our findings show for the first time that FAR is an independent risk factor for assessing DR in patients with type 2 diabetes.Keywords: fibrinogen to albumin ratio, type 2 diabetes mellitus, diabetic retinopathy, inflammation, influencing factors

Shan Jiang,1,2 Zhaolei Cui,3 Jianfeng Zheng,1 Qiaoling Wu,1 Haijuan Yu,1 Yiqing You,3 Chaoqiang Zheng,3 Yang Sun1 1Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, People’s Republic of China; 2College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China; 3Laboratory of Biochemistry and Molecular Biology Research, Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, People’s Republic of ChinaCorrespondence: Yang Sun, Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No. 420 Fuma Road, Fuzhou, Fujian, 350014, People’s Republic of China, Email sunyang@fjzlhospital.comBackground: Immunogenic cell death (ICD) can reshape the immune microenvironment of tumors. Driven by stressful pressure, by directly destroying tumor cells and activating the body’s adaptive immunity, ICD acts as a modulator of cell death, enabling the body to generate an anti-tumor immune response that produces a more effective therapeutic effect, while tumor cells are driven to kill. Hence, this research aimed to find and evaluate ICD-related genetic signatures as cervical cancer (CC) prognostic factors.Methods: Data of CC patients from the Tumor Genome Atlas (TCGA) were used as the basis to obtain immunogenic cell-death-related prognostic genes (IPGs) in patients with CC, using the least absolute shrinkage and selection operator and Cox regression screening, and the IPGs scoring system was constructed to classify patients into high- and low-risk groups, with the Gene Expression Omnibus (GEO) dataset as the validation group. Finally, the difference analysis of single-sample gene set enrichment analysis, tumor microenvironment (TME), immune cells, tumor mutational burden, and chemotherapeutic drug sensitivity between the high-risk and low-risk groups was investigated.Results: A prognostic model with four IPGs (PDIA3, CASP8, IL1, and LY96) was developed, and it was found that the group of CC patients with a higher risk score of IPGs expression had a lower survival rate. Single and multifactor Cox regression analysis also showed that this risk score was a reliable predictor of overall survival. In comparison to the low-risk group, the high-risk group had lower TME scores and immune cell infiltration, and gene set variation analysis showed that immune-related pathways were more enriched in the high-risk group.Conclusion: A risk model constructed from four IPGs can independently predict the prognosis of CC patients and recommend more appropriate immunotherapy strategies for patients.Keywords: ICD, cervical cancer, immunity, prognosis, immunotherapy response

ObjectivePatients with Lynch syndrome (LS) are at markedly increased risk for colorectal cancer. It is being increasingly recognised that the immune system plays an essential role in LS tumour development, thus making an ideal target for cancer prevention. Our objective was to evaluate the safety, assess the activity and discover novel molecular pathways involved in the activity of naproxen as primary and secondary chemoprevention in patients with LS.DesignWe conducted a Phase Ib, placebo-controlled, randomised clinical trial of two dose levels of naproxen sodium (440 and 220 mg) administered daily for 6 months to 80 participants with LS, and a co-clinical trial using a genetically engineered mouse model of LS and patient-derived organoids (PDOs).ResultsOverall, the total number of adverse events was not different across treatment arms with excellent tolerance of the intervention. The level of prostaglandin E2 in the colorectal mucosa was significantly decreased after treatment with naproxen when compared with placebo. Naproxen activated different resident immune cell types without any increase in lymphoid cellularity, and changed the expression patterns of the intestinal crypt towards epithelial differentiation and stem cell regulation. Naproxen demonstrated robust chemopreventive activity in a mouse co-clinical trial and gene expression profiles induced by naproxen in humans showed perfect discrimination of mice specimens with LS and PDOs treated with naproxen and control.ConclusionsNaproxen is a promising strategy for immune interception in LS. We have discovered naproxen-induced gene expression profiles for their potential use as predictive biomarkers of drug activity.Trial registration numbergov Identifier: NCT02052908.

An increasing number of studies are describing potential uses of circulating tumour DNA (ctDNA) in the care of patients with colorectal cancer. Owing to this rapidly developing area of research, the Colon and Rectal-Anal Task Forces of the United States National Cancer Institute convened a panel of multidisciplinary experts to summarize current data on the utility of ctDNA in the management of colorectal cancer and to provide guidance in promoting the efficient development and integration of this technology into clinical care. The panel focused on four key areas in which ctDNA has the potential to change clinical practice, including the detection of minimal residual disease, the management of patients with rectal cancer, monitoring responses to therapy, and tracking clonal dynamics in response to targeted therapies and other systemic treatments. The panel also provides general guidelines with relevance for ctDNA-related research efforts, irrespective of indication.

Kai Yue,1,2 Chao Yang,1 Yu You,1,2 Xueying Wang,3 Xinxin Zhang1 1School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, People’s Republic of China; 2Shunde Graduate School of University of Science and Technology Beijing, Shunde, Guangdong Province, 528399, People’s Republic of China; 3School of Chemistry and Chemical Engineering, University of Jinan, Jinan, Shandong Province, 250022, People’s Republic of ChinaCorrespondence: Kai Yue, Email yuekai@ustb.edu.cnBackground: A good understanding of the adhesion behaviors of the nanocarriers in microvessels in chemo-hyperthermia synergistic therapy is conducive to nanocarrier design for targeted drug delivery.Methods: In this study, we constructed an artificial blood vessel system using gelatins with a complete endothelial monolayer formed on the inner vessel wall. The numbers of adhered NPs under different conditions were measured, as well as the interaction forces between the arginine–glycine–aspartic acid (RGD) ligands and endothelial cells.Results: The experimental results on the adhesion of ligand–coated nanoparticles (NPs) with different sizes and morphologies in the blood vessel verified that the gelatin-based artificial vessel possessed good cytocompatibility and mechanical properties, which are suitable for the investigation on NP adhesion characteristics in microvessels. When the temperature deviated from 37 °C, an increase or decrease in temperature resulted in a decrease in the number of adhered NPs, but the margination probability of NP adhesion increased at high temperatures due to the enhanced Brownian movement and flow disturbance. It is found that the effect of cooling was less than that of heating according to the observed changes in cell morphology and a decrease in cell activity under the static and perfusion culture conditions within the temperature range of 25 °C– 43 °C. Furthermore, the measurement results of change in the RGD ligand-cell interaction with temperature showed good agreement with those in the number of adhered NPs.Conclusion: The Findings suggest that designing ligands that can bind to the receptor and are least susceptible to temperature variation can be an effective means to enhance drug retention.Keywords: artificial vessel, drug delivery, nanoparticle, temperature variation, particle–wall adhesion

Meihua Mei,1– 4,&ast; Danping Liu,1– 4,&ast; Xiuxin Tang,1– 4,&ast; Ying You,1– 4 Baogang Peng,5 Xiaoshun He,1– 3 Junqi Huang1– 4 1Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Organ Donation & Transplant Immunology, Guangzhou, 510080, People’s Republic of China; 3Guangdong Provincial International Cooperation Base of Science & Technology (Organ Transplantation), Guangzhou, 510080, People’s Republic of China; 4Department of Laboratory Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 5Hepatobiliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junqi Huang, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhong Shan Er Lu, Guangzhou, 510080, People’s Republic of China, Tel +86 (20) 28823388 ext. 8670, Email huangjq@mail.sysu.edu.cnPurpose: To clarify the underlying regulatory mechanisms of progression from liver cirrhosis to hepatocellular carcinoma (HCC), we analyzed the microbiomics, metabolomics, and proteomics in plasma and tissues from patients with HCC or decompensated liver cirrhosis (DC).Patients and Methods: Tissues and plasma from 44 HCC patients and 28 patients with DC were collected for metabolomic analysis. 16S rRNA sequencing was performed in nine HCC tissues (HCCT), four distal noncancerous tissues (HCCN), and 11 DC tissues (DCT). Five HCC tissues had liver cirrhosis (HCCT-LC). Five hepatocellular carcinoma tissues without liver cirrhosis (HCCT-NLC) and five DCT were selected for proteomic sequencing. After combining proteomic and metabolomic analysis, we constructed a mouse model of chronic liver injury using carbon tetrachloride (CCl4) and treated them with vitamin B6 (VB6).Results: 16s rRNA sequence results showed that HCC tissues had higher alpha diversity. The highest LDA scores were detected for Elizabethkingia in HCCT, Subsaxibacter in DCT, and Stenotrophomon in HCCN. Metabolomics results demonstrated some metabolites, including capric acid, L-threonate, choline, alpha-D-Glucose, D-ribose, betaine, 2E-eicosenoic acid, linoleic acid, L-palmitoylcarnitine, taurodeoxycholic acid, L-pyroglutamic acid, androsterone sulfate, and phthalic acid mono-2-ethylhexyl ester (MEHP), had better diagnostic efficacy than AFP (AUC: 0.852; 95% CI: 0.749, 0.954). In a combined analysis of metabolomics and proteomics, we found that HCCT-LC had more obvious disorders of VB6 metabolism and pentose and glucuronate interconversions than DCT, and kynurenine metabolism disorder was more significant in HCCT-LC than in HCCT-NLC. In the CCl4-induced chronic liver injury model, after VB6 supplementation, inflammatory cell infiltration, hepatocyte edema, and degeneration were significantly improved.Conclusion: We found significant differences in the flora distribution between HCCT and DC; MEHP was a new diagnostic biomarker of HCC, and VB6 ameliorated the inflammatory cell infiltration, hepatocyte edema, and degeneration in chronic liver injury.Keywords: hepatocellular carcinoma, cirrhosis, proteomics, metabolomics, microbiomics, vitamin B6

Every choice we make in health professions education has a cost, whether it be financial or otherwise; by choosing one action (e.g., integrating more simulation, studying more for a summative examination) we lose the opportunity to take an alternative action (e.g., freeing up time for other teaching, leisure time). Economics significantly shapes the way we behave and think as educators and learners and so there is increasing interest in using economic ways of thinking and approaches to examine and understand how choices are made, the influence of constraints and boundaries in educational decision making, and how costs are felt. Thus, in this article, we provide a brief historical overview of modern economics, to illustrate how the core concepts of economics--scarcity (and desirability), rationality, and optimization--developed over time. We explain the important concept of bounded rationality, which explains how individual, meso-factors and contextual factors influence decision making. We then consider the opportunities that these concepts afford for health professions education and research. We conclude by proposing that embracing economic thinking opens up new questions and new ways of approaching old questions which can add knowledge about how choice is enacted in contemporary health professions education.

Otters (subfamily Lutrinae) are semi-aquatic predators in the family Mustelidae. Modern otters have a worldwide distribution but their fossil record is poor, often consisting of fragmentary jaws and teeth. Multiple lineages have developed bunodont dentitions with enlargements of molars, usually for cracking molluscs or other hard foods. Some lineages have evolved badger-like teeth and, as a result, were often confused with melines (Old World badger clade). Siamogale thailandica Ginsburg, Invagat, & Tassy, 1983 from the middle Miocene basin of Mae Moh in northern Thailand is one such species, whose fragmentary dental remains have thus far impeded our understanding. A new species of fossil otter, Siamogale melilutra sp. nov., represented by a nearly complete cranium, mandible and partial skeletons of at least three individuals, was recovered from the latest Miocene (∼6.2 Ma) lignite beds of the Shuitangba Site in north-eastern Yunnan Province, south-western China. Computed tomography (CT) restoration of the crushed skull reveals a combination of otter-like and badger-like cranial and dental characteristics. The new species belongs to the Lutrinae because of its possession of a large infraorbital canal and ventral expansion of the mastoid process, among other traits. A distally expanded M1, however, gives a badger-like appearance. In overall morphology the Shuitangba otter is closest to Siamogale thailandica. A previously described jaw (‘Lutra’ aonychoides) from the early Pliocene of the Yushe Basin in north China is also here referred to S. melilutra. No previous attempt has been made to provide a global phylogenetic framework for otters. We present the first combined morphological and molecular (nuclear and mitochondrial DNAs) character matrices of five extant (Pteronura, Lontra, Enhydra, Aonyx, Lutra) and eight extinct genera (Tyrrhenolutra, Paralutra, Paludolutra, Enhydritherium, Siamogale, Vishnuonyx, Sivaonyx, Enhydriodon) to better understand the evolution of bunodont otters. Parsimony and Bayesian analyses consistently recover an eastern Asian clade that includes forms from Shuitangba, Yushe and Mae Moh, all of which are referred to Siamogale. http://zoobank.org/urn:lsid:zoobank.org:pub:5C637018-0772-4C78-AA4B-783B71085D9D.

Training neural networks has become a big bottleneck. For example, training ImageNet dataset on one NVIDIA K20 GPU needs 21 days. To speed up the training process, the current deep learning systems heavily rely on the hardware accelerators. However, these accelerators have limited on-chip memory compared with CPUs. We use both self-host Intel Knights Landing (KNL) clusters and multi-GPU clusters as our target platforms. From the algorithm aspect, we focus on Elastic Averaging SGD (EASGD) to design algorithms for HPC clusters. We redesign four efficient algorithms for HPC systems to improve EASGD's poor scaling on clusters. Async EASGD, Async MEASGD, and Hogwild EASGD are faster than existing counterpart methods (Async SGD, Async MSGD, and Hogwild SGD) in all comparisons. Sync EASGD achieves 5.3X speedup over original EASGD on the same platform. We achieve 91.5% weak scaling efficiency on 4253 KNL cores, which is higher than the state-of-the-art implementation.

Min Zhang,1,&ast; Jia Yu,2,&ast; Hui Huang,1 Cunjian Zhou,1 Zhifang Zhai,1 Yi You,1 Zhiqiang Song1 1Department of Dermatology and Venereology, The First Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Dermatology, Distinct HealthCare, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqiang SongDepartment of Dermatology and Venereology, The First Affiliated Hospital, Army Medical University, No. 30 Gaotanyan Street, Chongqing, 400038, People’s Republic of ChinaTel +86-2368773025Email zycocozm2011@qq.comAbstract: Syphilis is a complex, systemic infectious disease caused by Treponema pallidum subspecies pallidum. Herein, we report a rare case of secondary syphilis with probable neurosyphilis that was misdiagnosed as pityriasis lichenoides et varioliformis acuta (PLEVA) in a 12-year-old human immunodeficiency virus (HIV) negative patient. A female patient presented to our hospital with a four-month history of relapsed systemic rash, accompanied by hair loss, arthralgia and fatigue. Based on physical examination and skin biopsy, she was initially diagnosed as PLEVA and treated both locally and systemically but failed to present a dermatologic improvement. The diagnosis of secondary syphilis with probable neurosyphilis was made based on serologic and cerebrospinal fluid tests. After neurosyphilis therapy, the clinical manifestations of the patient were significantly improved. Physicians should be alert for the possibility of syphilis when encountering cases with unusual clinical manifestations.Keywords: syphilis, neurosyphilis, pityriasis lichenoides et varioliformis acuta

Ding Wang,1,&ast; Xi Zhan,1,&ast; Rui Wu,2 Yan You,3 Weixian Chen,1 Liang Duan1 1Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Duan; Weixian ChenDepartment of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Yu Zhong District, Chongqing, People’s Republic of ChinaTel/Fax +86-023-63693193; +86-023-63693701Email duanliang@cqmu.edu.cn; chenweixian75@163.comPurpose: The diagnosis and management of liver cirrhosis remain challenging due to its diverse clinical manifestations and elusive severity evaluation. Pyroptosis, an identified inflammatory form of cell death, has recently been reported to participate in cirrhosis development. Nonetheless, the clinical significance of pyroptosis in liver cirrhosis remains largely unexplored.Patients and Methods: One hundred and fifty-one liver cirrhosis patients either alone or in combination with various complications and twenty-nine gender- and age-matched healthy controls (HCs) were enrolled in this study. Pyroptosis-related indicators gasdermin D (GSDMD), IL-1ß and IL-18 were measured by IHC in tissue section and by ELISA in serum, respectively, and correlations of their circulating levels with disease severity as well as their potential as biomarkers for monitoring cirrhosis progression were evaluated.Results: Increased levels of the circulating pyroptosis-related indicators GSDMD, IL-1ß and IL-18 were observed in liver cirrhosis patients, especially those with an etiology of viral infection. In addition, all three indicators were positively correlated with disease severity parameters, including Child-Pugh classification, APRI scores and compensated status. Furthermore, receiver operating characteristic (ROC) analysis showed that circulating IL-1ß exerted potential discriminating power for SBP occurrence in liver cirrhosis, but GSDMD possessed differentiating power for SBP in liver cirrhosis with ascites, which yielded area under the ROC curve (AUC) of 0.81 and 0.80, respectively.Conclusion: Liver cirrhosis patients exhibited increased levels of circulating GSDMD, IL-1ß and IL-18, all of which were positively correlated with disease severity. More importantly, the identified circulating IL-1ß and GSDMD exhibited potentials as novel biomarkers for liver cirrhosis patients presenting with SBP.Keywords: GSDMD, IL-1ß, IL-18, liver cirrhosis, severity, complication

Yongfei You,1 Panpan Wang,1 Xi Wan,2 Liping Xu,3 Yi Gong,4 Weihua Zhang1 1Department of Oncology, The First Hospital of Nanchang, Nanchang, Jiangxi, 330008, People’s Republic of China; 2Operating Room, The First Hospital of Nanchang, Nanchang, Jiangxi, 330008, People’s Republic of China; 3Department of Pathology, The First Hospital of Nanchang, Nanchang, Jiangxi, 330008, People’s Republic of China; 4Department of Imaging, The First Hospital of Nanchang, Nanchang, Jiangxi, 330008, People’s Republic of ChinaCorrespondence: Yongfei YouDepartment of Oncology, The First Hospital of Nanchang, Xiangshan North Road, Donghu District, Nanchang, Jiangxi, 330008, People’s Republic of ChinaTel +86 15070836919Email 59185325@qq.comAbstract: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with high rates of recurrence and metastasis. There are no standard treatment options available for patients with recurrence and metastases. The case of a 61-year-old male with SDC of the left parotid gland is presented in this study. The results revealed that the patient’s tumour had strong positive staining for androgen receptor (AR) expression, mutations in HRAS and PIK3CA but not in other related genes, and no gene amplification of HER-2. After the primary therapy of parotidectomy with neck dissection and postoperative radiation, bone metastases were found in the ribs, pelvis and spine. Androgen deprivation therapy (ADT) involving combined androgen blockade (CAB) was effective as the first-line therapy for the patient’s metastases and resulted in a progression-free survival (PFS) of over 7 months to date. In conclusion, androgen deprivation therapy is recommended for patients with recurrent or metastatic SDC positive for androgen receptor expression.Keywords: salivary duct carcinoma, androgen receptor, androgen deprivation therapy, case report

Lin Fan,1,* Yiwen You,1,* Yao Fan,2 Chong Shen,3 Yong Xue4 1Department of Pharmacy, Huai’an Third People’s Hospital, Huai’an, People’s Republic of China; 2Division of Clinical Epidemiology, Affiliated Geriatric Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Medical Laboratory, Huai’an Third People’s Hospital, Huai’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong XueDepartment of Medical Laboratory, Huai’an Third People’s Hospital, Huai’an, People’s Republic of ChinaTel +86 13861583118Email xueyong3@126.comPurpose: Dyslipidemia frequently occurs in schizophrenia patients treated with antipsychotic drugs (APDs), especially atypical APDs. Apolipoprotein A1 (ApoA1) plays a key role in lipid metabolism. The aim of this study was to investigate whether ApoA1 gene polymorphisms are associated with APD-induced dyslipidemia in schizophrenia patients.Patients and Methods: A total of 1987 patients with schizophrenia were enrolled in this study. Serum lipid profiles were determined with a biochemistry analyzer. Genotyping for the rs5072 polymorphism of ApoA1 was performed with TaqMan assay. Logistic regression analysis was carried out to evaluate the relationship between ApoA1 gene polymorphisms and APD-induced dyslipidemia. The effects of drug classification (typical vs atypical APD) and drug regimen (monotherapy vs combination therapy) on serum lipid levels were also analyzed.Results: A significant association was found between rs5072 and triglyceride (TG) levels in the recessive model of the logistic regression analysis (adjusted odds ratio [OR]=1.50, 95% confidence interval [CI]: 1.03, 2.17; P< 0.05). TG level was significantly higher in patients treated with combination therapy (1.03 (0.71, 1.51) mmol/l) compared to monotherapy (0.93 (0.67, 1.43) mmol/l) and was also associated with sex. There were significant differences in TG levels among the three genotypes of ApoA1 rs5072 (GG, GA, and AA) in the whole study population and in patients treated with atypical APDs.Conclusion: The ApoA1 rs5072 variant is associated with dysregulated TG metabolism in schizophrenia patients treated with APDs, which may increase susceptibility to dyslipidemia.Keywords: apolipoprotein A1, gene polymorphism, dyslipidemia, schizophrenia, antipsychotic drug

Multidisciplinary management of rectal cancer has rapidly evolved over the last several years. This review describes recent data surrounding total neoadjuvant therapy, organ preservation, and management of lateral pelvic lymph nodes. It then presents our treatment algorithm for management of rectal cancer at The University of Texas MD Anderson Cancer Center in the context of this and other existing literature. As part of this discussion, the review describes how we tailor management based upon both patient and tumor‐related factors in an effort to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Aim: As multidisciplinary treatment strategies for colorectal cancer have improved, aggressive surgical resection has become commonplace. Multivisceral and extended resections offer curative‐intent resection with significant survival benefit. However, limited data exist regarding the feasibility and oncological efficacy of performing extended resection via a minimally invasive approach. The aim of this study was to determine the perioperative and long‐term outcomes following robotic extended resection for colorectal cancer. Method: We describe the population of patients undergoing robotic multivisceral resection for colorectal cancer at our single institution. We evaluated perioperative details and investigated short‐ and long‐term outcomes, using the Kaplan–Meier method to analyse overall and recurrence‐free survival. Results: Among the 86 patients most tumours were T3 (47%) or T4 (47%) lesions in the rectum (78%). Most resections involved the anterior compartment (72%): bladder (n = 13), seminal vesicle/vas deferens (n = 27), ureter (n = 6), prostate (n = 15) and uterus/vagina/adnexa (n = 27). Three cases required conversion to open surgery; 10 patients had grade 3 complications. The median hospital stay was 4 days. Resections were R0 (>1 mm) in 78 and R1 (0 to ≤1 mm) in 8, with none being R2. The average nodal yield was 26 and 48 (55.8%) were pN0. Three‐year overall survival was 88% and median progression‐free survival was 19.4 months. Local recurrence was 6.1% and distant recurrence was 26.1% at 3 years. Conclusion: Performance of multivisceral and extended resection on the robotic platform allows patients the benefit of minimally invasive surgery while achieving oncologically sound resection of colorectal cancer. [ABSTRACT FROM AUTHOR]