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Quirui Nie,1 Hui Qian,2,3 Shenjian Chen,3 Wenwen Xiang,3 Yu Shen3,4 1Department of Gerontology, Nanchang First Hospital, Nanchang, People’s Republic of China; 2Department of Neurology, Fengxin County People’s Hospital, Fengxin, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Yu Shen, Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China, Email shenyu19950712@sina.comObjective: To compare the differences in risk factors and etiological classification between cerebral infarction in young patients and elderly patients, and explore the correlation between cerebral infarction in young patients and white matter lesions (WMLs).Methods: Sixty young patients with cerebral infarction and 142 elderly patients with cerebral infarction were included. The distributions of risk factors such as hypertension, diabetes, heart disease, smoking status, alcohol consumption status, migraine status, and WMLs in the two groups were carefully investigated and statistically analyzed.Results: According to the univariate analysis, the proportions of males, obese patients, patients with migraine, and patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) in the young group were significantly greater than those in the elderly group. Hypertension, heart disease, and hyperhomocysteinemia were significantly more common in the elderly group than in the young group. According to the TOAST classification, the incidence of stroke of undetermined etiology in the young group was greater than that in the elderly group, whereas the incidence of large-artery atherosclerosis (LAA) in the elderly group was greater than that in the young group. Binary logistic regression analysis revealed that male sex, migraine status, and obstructive sleep apnea-hypopnea syndrome were independently associated with cerebral infarction in young adults, whereas hypertension, heart disease, and hyperhomocysteinemia were independently related to cerebral infarction in elderly individuals. In addition, the incidence of WMLs in the migraine group of young cerebral infarction patients was significantly greater than that in the nonmigraine group.Conclusion: Compared with those in elderly patients with cerebral infarction, the risk factors for cerebral infarction in young patients are relatively controllable. Furthermore, more methods are needed to determine the etiology of unexplained cerebral infarction in young patients. WMLs are thought to have a relatively high incidence in young patients with cerebral infarction and are significantly associated with migraine.Keywords: cerebral infarction, white matter lesions, young people, risk factors, migraine

Wei Xiang, Zhen Guo, Yiming Zhang, Yuanzhi Xu Department of Stomatology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of ChinaCorrespondence: Yuanzhi Xu; Yiming Zhang, Email amyxyz01@Hotmail.com; 1701086@tongji.edu.cnBackground: Hypertrophic scars (HS) are dermal diseases characterized by excessive fibroblast proliferation and collagen deposition following burns or trauma. While Tenascin-C (TNC)’s role in promoting visceral fibrosis has been established, its impact on skin tissue fibrosis remains unclear. This study aims to investigate the effects of TNC on HS.Methods: RNA sequence and IHC techniques were used to examine the upregulation of TNC gene in human hypertrophic scar tissue compared to normal tissues. Knockdown of TNC in Human skin fibroblasts (HFF-1) cells was achieved, and expression of Col1 and Col3 was evaluated using qPCR. Sirius red collagen staining assessed impact on total collagen content and ECM deposition. Effects on cell proliferation and migration were investigated through cck-8 and cell scratch experiments. Lentivirus infection was used to knock out TNC, and resulting samples were injected into ear wound of rabbits. Effects of TNC knockout on ear scar formation were measured using digital morphology, ultrasound, SEI, H&E, and Masson trichrome methods.Results: Cell experiments: downregulation of TNC decreased Col1 and Col3 expression, leading to reduced collagen production and extracellular matrix deposition. It did not affect HFF-1 cell proliferation and migration. Animal experiments: TNC knockdown promoted wound healing and reduced collagen deposition in rabbit ears.Conclusion: This study suggests that knocking down TNC inhibits collagen formation and extracellular matrix deposition, thereby inhibiting hypertrophic scar formation. Therefore, TNC can be considered a potential biomarker for HS formation and may offer promising treatment strategies for clinical management of hypertrophic scars.Keywords: Tenascin-C, hypertrophic scars, rabbit ear scar model, HFF-1

Xingyue Gao,1 Sihao Shen,1 Wenzhong Xiang,2 Xiuzu Song2 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou Third People’s Hospital, Hangzhou, People’s Republic of China; 2Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Wenzhong Xiang, Department of Dermatology, Hangzhou Third People’s Hospital, Westlake Ave 38, Hangzhou, 310002, People’s Republic of China, Email xiangwenzhong@126.comPurpose: Coronavirus disease (COVID-19) may trigger the reactivation of the latent varicella-zoster virus and may be a risk factor for herpes zoster (HZ). However, the causal relationship between COVID-19 and varicella-zoster infections remains controversial. This study aimed to estimate the causal inferences between COVID-19 and HZ.Methods: This study used a two-sample Mendelian randomization (MR) design. The inverse variance-weighted method was used as the primary method and sensitivity analyses were conducted, including the MR-Egger regression, weighted median and weighted mode. We searched at https://gwas.mrcieu.ac.uk/ using the keywords “COVID-19” for exposure data and “zoster” for outcome datasets.Results: We got 26 COVID-19 datasets and five zoster datasets. We used 26 COVID-19 datasets as exposure data corresponding to each zoster dataset for the MR analysis. There were nine datasets of COVID-19 where the number of SNPs was fewer than three in the MR analysis of the risk of HZ, varicella zoster virus (VZV) glycoprotein E and I antibody levels, anti-VZV IgG seropositivity, and post-zoster neuralgia. In addition, there were 10 datasets of COVID-19 where the number of SNPs was less than three in the MR analysis of anti-VZV IgG levels. The results of the MR analysis showed that all p-values were greater than 0.05. Sensitivity analysis revealed no evidence of horizontal pleiotropy in most two sample MR analyses.Conclusion: Our results indicate that there is no causal relationship between COVID-19 and varicella-zoster infection, HZ progression, and postherpetic neuralgia.Keywords: COVID-19, herpes zoster, varicella-zoster virus, chronic pain

Huiyi Yao,1 Wenzhong Xiang2 1Department of Dermatology, Zhejiang Chinese Medical University, Hangzhou Third People’s Hospital, Hangzhou, People’s Republic of China; 2Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou Third People’s Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, People’s Republic of ChinaCorrespondence: Wenzhong Xiang, Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou Third People’s Hospital Affiliated to Zhejiang Chinese Medical University, Westlake Ave 38, Hangzhou, 310009, People’s Republic of China, Tel +86 13588004268, Email xiangwenzhong@126.comAbstract: Becker’s nevus (BN) is a kind of epidermal cutaneous hamartoma. A noticeable hyperpigmented patch with a big, unilateral, hyperpigmented macule and irregularly shaped borders is the manner in which BN often presents. In this case, a 16-year-old boy has asymptomatic dark brown colored follicular macule on the left side of the cheek shortly after birth. The lesions were initially inconspicuous but gradually became darker as time passed. The macules on some of them grew hair. This case of BN with apparent hypertrichosis on one side of the cheek, which made it challenging to make a differential diagnosis with whiskers. The primary point of differentiation is that the lesions of BN only appear unilaterally. On the other hand, the face has whiskers on both sides. Additionally, BN will show hyperpigmentation whereas whiskers do not. In conclusion, for its unusual clinical presentation, we believe that reporting this case may help dermatologists avoid misdiagnosing similar cases.Keywords: Becker’s nevus, misdiagnosed, whiskers, hypertrichosis

Weiwei Xiang,1,&ast; Yifan Wu,2,&ast; Hongyan Li,1,&ast; Desheng Zhu,1 Xiaoying Yao,1 Jie Ding,1 Ze Wang,1 Yangtai Guan1 1Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangtai Guan, Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Shanghai, People’s Republic of China, Email yangtaiguan@sina.comBackground: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system. However, few biomarkers have been found to predict the outcome of immunotherapy. We investigated the relationship between the serum albumin (S-Alb) and response to immunotherapy in acute NMOSD patients.Methods: A total of 107 consecutive Chinese patients with acute NMOSD diagnosed between January 2013 and January 2022 were included in our prospective observational study. S-Alb was measured by the use of bromocresol green and immunoturbidimetric methods on admission. The immunotherapy response was assessed by the percentage change in the expanded disability status scale (EDSS) score from admission to discharge after treatment. We evaluated the association between S-Alb and immunotherapy response through multivariate logistic regression analysis.Results: S-Alb levels were significantly lower in patients who were resistant to immunotherapy than in those who were responsive to treatment (p< 0.001). S-Alb levels were positively related to a favorable response to immunotherapy (r=0.386, p< 0.001). The odds ratio (95% CI) for the association between S-Alb level and response to immunotherapy was 1.27 (95% CI=1.08, 1.50; p=0.004) after adjusting for potential factors. ROC analysis showed that patients with S-Alb levels lower than 40.85 g/L were likely to be resistant to immunotherapy.Conclusion: Our study indicated that a higher S-Alb was an independent indicator of response to immunotherapy in acute NMOSD patients.Keywords: immune diseases, NMOSD, immunotherapy, albumin, multivariate analysis

Yan Zhang,1 Haolin Jiang,2 Wenkai Xiang,3 Jun Zhu,3 Xueqin Hou,3 Shu Liang,1 Dan Yuan,1 Chang Zhou,1 Ling Su1 1Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, People’s Republic of China; 2Department of Epidemiology and Statistics, Chengdu Medical College, Chengdu, People’s Republic of China; 3Center for AIDS/STD Control and Prevention, Guangyuan Center for Disease Control and Prevention, Guangyuan, People’s Republic of ChinaCorrespondence: Ling Su, Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, No. 6, Middle School Road, Wuhou District, Chengdu, Sichuan Province, 610000, People’s Republic of China, Tel +8618982092195, Email sl7512@163.comPurpose: Guangyuan was selected as the first pilot city of molecular transmission network in Sichuan Province to implement dynamic monitoring. This study aim to insight the characteristics of HIV-1 molecular epidemiology and explore the influencing factors of transmission dynamics. Furthermore, it predict the driving factors of network expansion by established a transmission risk prediction model.Patients and Methods: A longitudinal cohort study was conducted to obtain a total of 1434 plasma samples from newly diagnosed HIV-infected patients from 2010 to June 2022. Phylogenetic relationship and cluster analysis were performed using HIV-1 polymerase (pol) gene sequences to study the risk factors of clustering. We applied Logistic ML algorithms to establish a transmission risk prediction model, and model performance was checked using 10-fold cross-validation in the training set and receiver operating characteristic (ROC) curve analysis.Results: A total of 1360 pol sequences linked demographics obtained in this study cover approximately 94.8% of newly notified infections from 2010 to June 2022. The major epidemic genotypes were CRF07_BC, CRF01_AE, CRF08_BC and B subtypes, accounting for 93.82% of all. The differences of some clinical and demographic factors (eg, age, marital status) were statistically significant (P< 0.05). We identified 136 clusters containing 654 HIV-1 pol sequences and observed that some characteristics (eg, over 50 years, married) were more likely to associated to the clusters (P< 0.05). The predictive model showed excellent predictive ability to forecast cluster growth.Conclusion: The epidemic genotypes were relatively complex and diverse in Guangyuan. There was a potential transmission association caused widely spread in local area after the new strains entering. The transmission risk prediction model showed excellent predictive ability to forecast cluster growth which can predict the risk factors causing clusters expansion and provide a guidance for precise intervention strategies.Keywords: HIV-1, genotype, cluster analysis, transmission risk prediction model

Sihao Shen,1 Jiangfeng Feng,1 Xiuzu Song,2 Wenzhong Xiang2 1Department of Dermatology, Hangzhou Third People’s Hospital, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Wenzhong Xiang, Department of Dermatology, Hangzhou Third People’s Hospital; Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Westlake Ave 38, Hangzhou, 310009, People’s Republic of China, Tel +86 13588004268, Email xiangwenzhong@126.comAbstract: Periorificial dermatitis (PD) is an inflammatory disorder of the facial skin that mainly occurs around the mouth and manifests as erythema, papules, pustules, scales and other lesions. Special attention is needed in the clinical diagnosis of PD to distinguish it from acne, seborrheic dermatitis (SD), granulomatous rosacea (GR), sarcoidosis and childhood granulomatous periorificial dermatitis (CGPD). We used reflectance confocal microscopy (RCM) images of a patient with PD to assist in the diagnosis of PD. RCM of PD showed slight oedema of the spinous layer. Numerous dendritic cells, scattered hair follicular keratotic plugging and hair follicle dilatation were observed. The dilation and congestion of superficial dermis blood vessels, an increasing vascular density and accelerated blood flow, and a greater abundance of infiltrated inflammatory cells were also detected.Keywords: periorificial dermatitis, reflectance confocal microscopy, acne, seborrheic dermatitis, granulomatous rosacea, sarcoidosis, childhood granulomatous periorificial dermatitis

Xiaoshan Ye,1,&ast; Qionglin Zhou,2,&ast; Pengcheng Ren,1,3,4 Wei Xiang,1,3 Le Xiao1 1Hainan Women and Children’s Medical Center, School of Pediatrics, Hainan Medical University, Haikou, People’s Republic of China; 2International School of Public Health and One Health, Hainan Medical University, Haikou, People’s Republic of China; 3National Health Commission (NHC) Key Laboratory of Control of Tropical Diseases, Hainan Medical University, Haikou, People’s Republic of China; 4School of Basic Medicine and Life Science, Hainan Medical University, Haikou, People’s Republic of China&ast;These authors contributed equally to this workThese authors contributed equally to this workCorrespondence: Le Xiao; Wei Xiang, Hainan Women and Children’s Medical Center, Hainan Medical University, Haikou, People’s Republic of China, Email Le.Xiao@hainmc.edu.cn; 13907533529@163.comAbstract: Vitamin D deficiency/insufficiency is a public health issue around the world. According to epidemiological studies, low vitamin D levels have been associated with an increased risk of some neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Animal models reveal that vitamin D has a variety of impacts on the synapses and circuits in the brain. A lack of vitamin D affects the expression of synaptic proteins, as well as the synthesis and metabolism of various neurotransmitters. Depending on where vitamin D receptors (VDRs) are expressed, vitamin D may also regulate certain neuronal circuits through the endocannabinoid signaling, mTOR pathway and oxytocin signaling. While inconsistently, some data suggest that vitamin D supplementation may be able to reduce the core symptoms of ASD and ADHD. This review emphasizes vitamin D’s role in the synaptic and circuit mechanisms of neurodevelopmental disorders including ASD and ADHD. Future application of vitamin D in these disorders will depend on both basic research and clinical studies, in order to make the transition from the bench to the bedside.Keywords: vitamin D, neurodevelopmental disorders, autism spectrum disorder, ASD, attention-deficit hyperactivity disorder, ADHD, synapses, circuits

Qionglin Zhou,1,&ast; Xiaoshan Ye,1,&ast; Chongxia Wei,2,&ast; Yufan Wu,1 Pengcheng Ren,1 Xuewei Lin,2 Ling Li,2 Wei Xiang,1,2 Le Xiao1,2 1Hainan Medical University, Haikou, People’s Republic of China; 2Hainan Women and Children’s Medical Center, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Le Xiao; Wei Xiang, Hainan Woman and Children’s Medical Center, Haikou, People’s Republic of China, Email Le.Xiao@hainmc.edu.cn; 13907533529@163.comPurpose: Although many studies have reported the cognitive profiles in attention-deficit/hyperactivity disorder (ADHD), the interactions between ADHD symptoms and the patients’ cognitive profiles have not been carefully examined through the network analysis. Here, in this study, we systematically analyzed the ADHD patents’ symptoms and cognitive profiles, and identified a set of interactions between ADHD symptoms and cognitive domains using the network approach.Patients and Methods: A total of 146 children with ADHD, 6 to 15 years of age, were included in the study. All participants were assessed by the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) test. The patients’ ADHD symptoms were evaluated by the Vanderbilt ADHD parent and teacher rating scales. GraphPad Prism 9.1.1 software was used for descriptive statistics and R 4.2.2 was used for network model construction.Results: The ADHD children in our sample showed lower scores for full scale intelligence quotient (FSIQ), verbal comprehension index (VCI), processing speed index (PSI) and working memory index (WMI). Among all the ADHD core symptoms and comorbid symptoms, the academic ability, inattention symptoms and mood disorder showed direct interaction with the cognitive domains of WISC-IV. In addition, oppositional defiant of the ADHD comorbid symptoms, and perceptual reasoning of the cognitive domains exhibited the highest strength centrality in the ADHD-Cognition network based on parent ratings. Classroom behaviors of the ADHD functional impairment, and verbal comprehension of the cognitive domains exhibited the highest strength centrality in the network based on teacher ratings.Conclusion: We highlighted the importance of considering the interactions between the ADHD symptoms and cognitive properties when designing the intervention plans for the ADHD children.Keywords: attention-deficit/hyperactivity disorder, Wechsler Intelligence Scale for Children-Fourth Edition, network analysis

Shina Qiao, Xiaoming Zhang, Weilan Xiang, Linyan Yao, Xuemei Xian Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Shina Qiao, Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel +86 13575764508, Email qiaoshina08@zju.edu.cnBackground: Compared to Western countries, palliative and hospice care services are used less often in Asian countries. While both types have been implemented in mainland China in recent years, their utilization rates have not increased satisfactorily. Moreover, few hospitals in mainland China implement hospice care using the hospice shared care model.Objective: This study investigated a case in which the hospice shared care model was implemented for one patient with advanced colon cancer who had received treatment at a general tertiary hospital in mainland China.Methods: Critical points of care included pain symptom management, nutritional support, application of the SHARE model for disease notification, family meetings to assist medical decision-making, relaxation therapy to relieve depressive symptoms, provisions to address end-of-life wishes, and support for primary caregivers.Results: The patient’s basic pain was controlled (Numeric Rating Scale, NRS2-3), and the score of the Depression Screening Scale (PHQ-9) decreased from 15 to 10 after intervention during hospitalization. In the end, the patient died comfortably and peacefully at home.Conclusion: The hospice shared care team helped the patient with her physical and psychological pain, met her end-of-life wishes, and provided support for the families.Keywords: advanced colon cancer, palliative care, symptom management, hospice share care, case report

Hu Zhou,1,2,&ast; Yuan Yuan,1– 3,&ast; Haorun Wang,1,2 Wei Xiang,1,2 shenjie Li,1,2 Haowen Zheng,1,2 Yuqi Wen,1,2 Yang Ming,1,2 Ligang Chen,1,2,4,5 Jie Zhou1,2,4,5 1Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People’s Republic of China; 3Department of Operation and Anaesthesia, Yibin First People’s Hospital, Yibin, Sichuan, People’s Republic of China; 4Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, People’s Republic of China; 5Neurological Diseases and Brain Function Laboratory, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Zhou Email zj000718@yeah.netAbstract: The gut microbiota plays a crucial role in many physiological processes in the human body. Dysbiosis can disrupt the intestinal barrier and alter metabolism and immune responses, leading to the development of diseases. Over the past few decades, evidence has accumulated linking changes in the composition of the gut microbiota to dozens of seemingly unrelated conditions, including cancer. Overall, the gut microbiota mainly affects the occurrence and development of cancer by damaging host DNA, forming and maintaining a pro-inflammatory environment, and affecting host immune responses. In addition, the gut microbiota can also affect the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Scientists attempt to improve the efficacy and decrease the toxicity of these treatment modalities by fine-tuning the gut microbiota. The aim of this review is to assist researchers and clinicians in developing new strategies for the detection and treatment of tumors by providing the latest information on the intestinal microbiome and cancer, as well as exploring potential application prospects and mechanisms of action.Keywords: intestinal flora, carcinogenesis, mechanism, therapy, fecal bacteria transplantation

Zhoujing Zhao, Huaizhi Ge, Wei Xiang, Guanghui Bai Department of Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of ChinaCorrespondence: Guanghui BaiDepartment of Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of ChinaTel/Fax +86 577 88002750Email zzhoujing1869@163.comPurpose: To explore the application of magnetic resonance imaging (MRI) T2 mapping technique in clinical practice through morphological and quantitative analysis of T2 mapping sequences in adolescents with temporomandibular disorders (TMDs) and control groups comprising healthy participants.Patients and Methods: A total of 45 and 63 patients, who had articular disc displacement with and without reduction, respectively, were assigned to the experimental groups, and 57 participants with normal articular discs of the temporomandibular joint were considered as the control group. All participants in the three groups underwent MRI. T2 mapping was performed in the oblique sagittal plane. The regions of interest (ROIs) for the T2 relaxation time maps of the disc were selected manually. The performance of morphological and structural changes and quantitative parameters in MRI T2 mapping image artifacts were statistically compared.Results: In the control group, the mean T2 value was 39.284 ± 5.634 ms, in the group of disc displacement with reduction, the mean T2 value was 33.634 ± 4.235 ms, and in the group of disc displacement without reduction, the mean T2 value was 30.982 ± 3.205 ms. The T2 mapping values of the experimental groups, together with different morphological structures, were significantly lower than were those of the control group.Conclusion: MRI T2 mapping enables a more accurate evaluation of TMD severity. Sequentially, it helps provide a more reliable medical imaging basis for classifying diagnosis and evaluation in clinical practice.Keywords: temporomandibular joint disorders, articular disc of temporomandibular joint, adolescents, magnetic resonance imaging

Yihao Wang,1 Fangcheng Zhang,1 Nanxiang Xiong,2 Hao Xu,3 Songshan Chai,1 Haofei Wang,1 Jiajing Wang,1 Hongyang Zhao,1 Xiaobing Jiang,1 Peng Fu,1 Wei Xiang1 1Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, 430071, People’s Republic of China; 3Department of Neurosurgery, General Hospital of the Yangtze River Shipping, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Peng Fu; Wei XiangDepartment of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaTel +86 15902706600; +86 13667291375Fax +86 27 85350819Email pfu@hust.edu.cn; xiangwei20@hotmail.comAbstract: The blood-brain barrier (BBB) is an essential structure of the central nervous system (CNS), and its existence makes the local internal environment of the CNS a relatively independent structure distinct from other internal environments of the human body to ensure normal physiological and high stability of activities of the CNS. Changes in BBB structure and function are fundamental to the pathophysiology of many diseases. The occurrence and development of glioma are often accompanied by a series of changes in the structure and function of the internal environment, the most significant of which is remodelling of the BBB. The remodelling of the BBB usually leads to changes in the permeability of local microvessels, which provide certain favourable conditions for the occurrence and development of glioma. Meanwhile, the newly generated abnormal blood vessels and the remaining intact regions of the BBB also hinder the effects of drug treatments. Changes in permeability and structural function often lead to the creation of abnormally functioning vascular regions, which pose further treatment challenges. At present, therapeutic methods for glioma have not achieved satisfactory effects in clinical practice, and emerging therapeutic methods have not yet been widely used in clinical practice. In this review, we summarize the knowledge of remodelling of the BBB in the glioma environment, the type of changes that occur, and current BBB treatment methods and prospects for the treatment of glioma.Keywords: blood-brain barrier, glioma, blood-brain barrier-associated therapy, remodelling, structural and functional changes

Lei Lyu, Wei Xiang, Jin-Yan Zhu, Tao Huang, Jing-Dong Yuan, Chuan-Hua ZhangDepartment of Urology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People’s Republic of ChinaBackground: Long noncoding RNAs (lncRNAs) play important roles in competing endogenous RNA (ceRNA) networks involved in the development and progression of various cancers, including muscle-invasive bladder cancer (MIBC).Purpose: This study aims to construct the lncRNA-associated ceRNA network and identify lncRNA signatures correlated with the clinical features of MIBC tissue samples from The Cancer Genome Atlas (TGCA) database.Methods: The differential expression profiles of MIBC associated lncRNAs, miRNAs and mRNAs were obtained from TCGA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the principal functions of significantly dysregulated mRNAs. The dysregulated lncRNA-associated ceRNA network of MIBC was constructed based on the bioinformatics data, and the correlations between lncRNA expression and clinical features were analyzed using a weighted gene coexpression network analysis (WGCNA). Six cancer specific lncRNAs from the ceRNA network were randomly selected to detect their expression in 32 paired MIBC tissue samples and 5 bladder cancer cell lines using quantitative real-time polymerase chain reaction (qRT-PCR).Results: The ceRNA network was constructed with 30 lncRNAs, 13 miRNAs and 32 mRNAs. Seventeen lncRNAs in the ceRNA network correlated with certain clinical features, and only 1 lncRNA (MIR137HG) correlated with the overall survival (OS) of patients with MIBC (log-rank test P

Wei Xiang,1 Ya Qing Sun,2 Hui Chin Teoh3 1Medical Affairs, Boehringer Ingelheim (China) Investment Co. Ltd, Shanghai, People’s Republic of China; 2Biostatistics and Data Sciences, Boehringer Ingelheim (China) Investment Co. Ltd, Shanghai, People’s Republic of China; 3Clinical Operations, Boehringer Ingelheim (China) Investment Co. Ltd, Shanghai, People’s Republic of China Background: Nocturnal symptoms are common in Parkinson’s disease (PD), which greatly affect the quality of life but are often overlooked in clinical settings. Treatment strategies that provide sustained dopaminergic stimulation may have sleep benefits. Objective: To investigate the treatment effects of pramipexole (PPX) sustained release (SR) versus PPX immediate release (IR) on nocturnal symptoms in advanced PD patients with sleep disturbances. Materials and methods: In this study, the PPX clinical trial (NCT00466167) was retrospectively analyzed for PD Sleep Scale (PDSS) total and domain scores in patients with advanced idiopathic PD receiving either PPX SR or PPX IR, who experienced motor fluctuations while on stable levodopa with a baseline PDSS total score of

Lei Lyu,1,* Lu-qi Huang,2,* Tao Huang,1 Wei Xiang,1 Jing-dong Yuan,1 Chuan-hua Zhang1 1Department of Urology, Wuhan No 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Neurology, Wuhan No 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Background: Gambogic acid (GA) is the main active ingredient of resin gamboges and possesses anti-cancer activity toward various human cancer cells. However, clinical application of GA has been limited by its poor aqueous solubility and dose-limiting toxicities. Cell-penetrating peptides (CPPs) are widely used to deliver anti-cancer drugs into cancer cells and to enhance the water solubility of drugs.Purpose: The object of this study was to synthesize peptide-drug conjugates in which the cell-penetrating peptide TAT (trans-activator of transcription) was conjugated to GA and evaluated the anti-cancer activity of this GA-CPP conjugate (GA-TAT) in EJ bladder cancer cells.Methods: GA is built onto the TAT, and the GA-TAT conjugates are cleaved from the solid support and purified via HPLC. The equilibrium solubility of GA-TAT was measured using the shake-flask method. The effects of GA-TAT on EJ cell viability and proliferation were determined by MTT assay, Edu assay and colony formation assay, respectively. After treated with 1.0 μM GA-TAT for 24 h, the apoptosis rate of EJ cells were detected by Acridine orange/ethidium bromide (AO/EB) assay and flow cytometry assay. The proteins of caspase-3 (processing), caspase-9 (processing), Bcl-2 and Bax were analyzed by Western blotting, and the intracellular reactive oxygen species (ROS) production was evaluated by a reactive oxygen species assay.Results: In contrast to free GA, the solubility of GA-TAT in water was significantly improved. Meanwhile, GA-TAT significantly increased EJ cellular uptake, toxicity and apoptosis. Mechanistic analysis revealed that GA-TAT enhanced the anti-cancer effect of GA against EJ cells through ROS-mediated apoptosis. The results were demonstrated that GA-TAT increased the ROS level in EJ cells, and N-acetyl-l-cysteine (NAC; a well-known ROS scavenger) inhibited GA-TAT-induced ROS generation and apoptosis. Additionally, GA-TAT activated caspase-3 and caspase-9 and down-regulated the Bcl-2/Bax ratio, but these effects were largely rescued by NAC.Conclusion: GA-TAT has outstanding potential for promoting tumor apoptosis and exhibits promise for use in bladder cancer therapy. Keywords: gambogic acid, cell-penetrating peptides, apoptosis, bladder cancer

Hui Xue,1,2 Wenping Xiang,2 Yichuan Yu,3 Guorong Liu,2 Yi Chong,2 Jiying Zhou1 1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 2Department of Neurology, Baotou Central Hospital, Inner Mongolia, Baotou, China; 3Department of Emergency, Yongchuan Hospital of Chongqing Medical University, Chongqing, China Background: Vestibular paroxysmia (VP) is a rare episodic peripheral vestibular disorder. This study was conducted to compare the efficacy and acceptability of carbamazepine (CBZ) plus betahistine mesilate tablets (BMT) (CBZ+BMT) and oxcarbazepine (OXC) plus BMT (OXC+BMT) in treating VP, and investigated whether the synergistic effect could be increased along with the increased dose of BMT.Methods: VP patients were recruited and randomly assigned to receive CBZ+BMT or OXC+BMT. The doses of CBZ and OXC were set to 200 and 300 mg/time, twice daily, respectively. The doses of BMT were set to 12 and 18 mg/time, twice daily. Half of the patients in each group received BMT 12 mg/time and the other half received BMT 18 mg/time. The treatment was continued for 12 weeks. The vertigo frequency, vertigo score, vertigo duration, response rate, and drug-related side effects were analyzed.Results: In total, 92 patients in the CBZ+BMT group and 93 patients in the OXC+BMT group completed this trial. After 12 weeks of treatment, the two groups had similar average vertigo frequency, average vertigo score, average vertigo duration, and response rate. But the incidence of side effects was significantly higher in the CBZ+BMT group than in the OXC+BMT group (p=0.04). Subgroup analysis found that patients receiving BMT (18 mg) had greater reductions in average vertigo frequency, average vertigo duration, and average vertigo score, and higher response rates than patients receiving BMT (12 mg).Conclusion: These results demonstrated that OXC+BMT may be suitable as an alternative method in VP patients with CBZ hypersensitivity, and the synergistic effect could be increased along with the increased dose of BMT. Keywords: vestibular paroxysmia, betahistine mesilate tablets, carbamazepine, oxcarbazepine

Fei-Min Yang,1 Zhi-Hong Ye,2 Lei-Wen Tang,3 Wei-Lan Xiang,3 Lin-Juan Yan,4 Min-Li Xiang5 1Department of General Surgery, 2Department of Nursing, 3Department of Nursing Education, 4Department of Surgical Oncology, 5Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China Objective: To examine factors that are associated with the apprehension levels of oncology nurses toward hospice care. Factors examined in this study included demographics, nursing experience, education levels, title and post, personal experiences, and attitudes toward end-of-life care. Methods: Questionnaires were provided to nurses (n=201) from three first-tier hospitals in China. A quantitative scale, Professional End-of-life Care Attitude Scale (PEAS), was used to assess personal and professional apprehension levels toward hospice care. The PEAS was translated to Chinese with terms adapted to the cultural environment in China. Statistical analyses were performed to examine the relationships between the apprehension levels and various factors. Results: The total PEAS scores exhibited internal consistency and reliability, with a Cronbach α=0.897 and Pearson’s r=0.9030. Of the 201 nurses, 184 provided a valid response (91.5%). Education level was significantly correlated with personal (P

Wenping Xiang,1 Hui Xue,2 Baojun Wang,2 Yuechun Li,2 Jun Zhang,2 Changchun Jiang,2 Furu Liang,2 Jiangxia Pang,2 Lehua Yu1 1Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Neurology, Baotou Central Hospital, Baotou, Inner Mongolia, People’s Republic of China Background: Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) commonly occurs after recovering from acute CO poisoning. This study was performed to assess the efficacy of the combined application of dexamethasone and hyperbaric oxygen (HBO) therapy in patients with DEACMP.Patients and methods: A total of 120 patients with DEACMP were recruited and randomly assigned into the experimental group (receiving dexamethasone 5 mg/day or 10 mg/day plus HBO therapy) and control group (HBO therapy as monotherapy). Meanwhile, the conventional treatments were provided for all the patients. We used the Mini-Mental State Examination (MMSE) scale to assess the cognitive function, the National Institutes of Health Stroke Scale (NIHSS) to assess the neurological function and the remission rate (RR) to assess the clinical efficacy. Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) was also measured.Results: After 4 weeks of treatment, compared to the control group, the experimental group had a significantly higher remission rate (P=0.032), a significantly higher average MMSE score (P=0.037) and a significantly lower average NIHSS score (P=0.002). Meanwhile, there was a trend toward better improvement with dexamethasone 10 mg/day, and the level of MBP in the CSF of patients was significantly lower in the experimental group than in the control group (P

Ying Wang,1 Sheng-Gang Sun,2 Sui-Qiang Zhu,3 Chun-Feng Liu,4 Yi-Ming Liu,5 Qing Di,6 Hui-Fang Shang,7 Yan Ren,8 Wei Xiang,9 Sheng-Di Chen1 1Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of Neurology, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 3Department of Neurology, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 4Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, 5Department of Neurology, Qilu Hospital Affiliated to Shandong University, Jinan, 6Department of Neurology, Nanjing Brain Hospital, Nanjing, 7Department of Neurology, West China Hospital Affiliated to Sichuan University, Chengdu, 8Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, 9Medical Department, Boehringer Ingelheim (China) Investment Co., Ltd., Shanghai, People’s Republic of China Background: Pramipexole (PPX), a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson’s disease (PD). A critical dose level above which a better benefit-to-harm ratio exists has not been examined.Methods: Chinese PD patients (n=464) were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II) and Motor Examination (III) of the Unified Parkinson’s Disease Rating Scale (UPDRS II+III) was used as a covariate for final score adjustment.Results: Sustained-release (SR) and immediate-release (IR) PPX showed similar efficacy based on score changes at 18 weeks, with comparable tolerability. Approximately two-third of patients received PPX at ≥1.5 mg/d, and one fourth of patients had ≥20% tremor contribution to UPDRS II+III. After treatment, patients receiving PPX ≥1.5 mg/d showed better improvement in UPDRS II+III scores (P=0.0025), with similar trends with the IR and SR formulations. Patients with ≥20% tremor contribution showed better improvement in UPDRS II+III scores (P=0.0017). No differences were seen based on PD stage or combined levodopa dose. The overall proportions of adverse events (AEs) were similar. More patients discontinued because of intolerable side effects, and more investigator-defined drug-related AEs were recorded in the

Wei Xiang, Jingwei Zhang, Meilin Liu, Fang Liu, Xueru Feng, Yuchuan Wang Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China Objective: Non-valvular atrial fibrillation (NVAF) is one common arrhythmia in the elderly. However, use of antithrombotic therapy in this population is not well known in the People’s Republic of China. This study aimed at investigating antithrombotic therapy status in elderly patients with NVAF in our hospital.Methods: A cross-sectional study of consecutive geriatric patients aged ≥60 years with NVAF who discharged from our hospital between January 2012 and December 2013 were collected. CHA2DS2-VASc score (cardiac failure or dysfunction, hypertension, age ≥75 [doubled], diabetes, stroke or transient ischemic attack [doubled], vascular disease, age 65–74, and sex category [female]) was used to analyze antithrombotic indication.Results: We consecutively collected data of 1,000 discharged elderly patients (≥60 years) with NVAF (mean age 75.3±8.0 years, 75 years or older 54.7%, female 42.7%). The proportion of paroxysmal atrial fibrillation and non-paroxysmal atrial fibrillation (persistent or permanent) patients were 39.4% and 60.6%, respectively. Among 1,000 patients, 29.1% received oral anticoagulant therapy (OAT), including warfarin (27.8%) and novel oral anticoagulants (1.3%), 39.5% of patients received antiplatelet therapy, and 31.4% received neither therapy. Based on CHA2DS2-VASc score for stroke risk stratification, 68.9% patients with score ≥1 and 70.2% patients with score ≥2 received antithrombotic therapy, while the rates of OAT were 29.1% and 29.5%, respectively. Among patients with high stroke risk, those with paroxysmal atrial fibrillation were less likely to receive OAT compared with the patients with non-paroxysmal atrial fibrillation (19.5% vs 35.7%, P

Baoyue Ding1,2, Xin Wu1, Wei Fan1,3, Zhaoyong Wu4, Jing Gao5, Wei Zhang1, Lulu Ma5, Wang Xiang1, Quangang Zhu1, Jiyong Liu1, Xueying Ding5, Shen Gao11Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 2Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, 3The 425th Hospital of PLA, Department of Pharmacy, Sanya, 4Department of Pharmaceutics, Jiaxing Maternal and Childcare Hospital, Jiaxing, 5Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China The first three authors contributed equally to this work. Background: The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specifc immunotherapy. Methods: The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. Results: Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifcally target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. Conclusion: The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma.Keywords: malignant melanoma, DR5 monoclonal antibodies, dacarbazine, apoptosis, chemoimmunotherapy, active targeting nanoparticles

The Majorana Collaboration is building the Majorana Demonstrator, a 60 kg array of high purity germanium detectors housed in an ultra-low background shield at the Sanford Underground Laboratory in Lead, SD. The Majorana Demonstrator will search for neutrinoless double-beta decay of 76Ge while demonstrating the feasibility of a tonne-scale experiment. It may also carry out a dark matter search in the 110 GeV/c2 mass range. We have found that customized Broad Energy Germanium (BEGe) detectors produced by Canberra have several desirable features for a neutrinoless double-beta decay experiment, including low electronic noise, excellent pulse shape analysis capabilities, and simple fabrication. We have deployed a customized BEGe, the Majorana Low-Background BEGe at Kimballton (MALBEK), in a low-background cryostat and shield at the Kimballton Underground Research Facility in Virginia. This paper will focus on the detector characteristics and measurements that can be performed with such a radiation detector in a low-background environment. © 2010 Elsevier B.V.