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Cutaneous neurofibromas (cNFs) are benign tumors of the skin that affect >95% of adults with neurofibromatosis type 1. Despite their benign histology, cNFs can significantly impact QOL due to disfigurement, pain, and pruritus. There are no approved therapies for cNFs. Existing treatments are limited to surgery or laser-based treatments that have had mixed success and cannot be readily applied to a large number of tumors. We review cNF treatment options that are currently available and under investigation, discuss the regulatory considerations specific to cNFs, and propose strategies to improve cNF clinical trial design and standardize clinical trial endpoints.

Jing Wang,1,* Yanxiang Sang,2,* Weijian Chen,3 Liang Cheng,2 Wenxiang Du,2 Hongjie Zhang,2 Benyan Zheng,2 Lei Song,2 Yuan Hu,2 Xiaopeng Ma1 1Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China; 2State Key Laboratory of Fire Science, University of Science and Technology of China, Hefei, Anhui, 230006, People’s Republic of China; 3Technology Center, China Tobacco Anhui Industrial Co, Ltd, Hefei, Anhui, 230088, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan Hu; Xiaopeng Ma, Email yuanhu@ustc.edu.cn; XiaopengMa@fsyy.ustc.edu.cnIntroduction: As an effective alternative choice to traditional mono-therapy, multifunctional nanoplatforms hold great promise for cancer therapy. Based on the strategies of Fenton-like reactions and reactive oxygen species (ROS)-mediated therapy, black phosphorus (BP) nanoplatform BP@Cu2O@L-Arg (BCL) co-assembly of cuprous oxide (Cu2O) and L-Arginine (L-Arg) nanoparticles was developed and evaluated for synergistic cascade breast cancer therapy.Methods: Cu2O particles were generated in situ on the surface of the BP nanosheets, followed by L-Arg incorporation through electrostatic interactions. In vitro ROS/nitric oxide (NO) generation and glutathione (GSH) depletion were evaluated. In vitro and in vivo anti-cancer activity were also assessed. Finally, immune response of BCL under ultrasound was investigated.Results: Cu2O was incorporated into BP to exhaust the overexpressed intracellular GSH in cancer cells via the Fenton reaction, thereby decreasing ROS consumption. Apart from being used as biocompatible carriers, BP nanoparticles served as sonosensitizers to produce excessive ROS under ultrasound irradiation. The enhanced ROS accumulation accelerated the oxidation of L-Arg, which further promoted NO generation for gas therapy. In vitro experiments revealed the outstanding therapeutic killing effects of BCL under ultrasound via mechanisms involving GSH deletion and excessive ROS and NO generation. In vivo studies have illustrated that the nanocomplex modified the immune response by promoting macrophage and CD8+ cell infiltration and inhibiting MDSC infiltration.Discussion: BCL nanoparticles exhibited multifunctional characteristics for GSH depletion-induced ROS/NO generation, making a new multitherapy strategy for cascade breast cancer therapy.Keywords: black phosphorus, combination cancer therapy, sonodynamic therapy, chemodynamic therapy, nitric oxide gas therapy

Xinmiao Hu,1– 3,* Qian Wu,1,2,* Qunfeng Lu,4,5,* Jiangao Zhang,6 Xiaowei Yang,7 Wenjian Chen,3 Ping Wang,3 Qinglin Yu,3 Jingan Dong,3 Yan Sang8 1School of Medicine, Tong University, Shanghai, People’s Republic of China; 2Department of Nursing, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China; 3Department of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Nursing, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 5School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 6Nantong Visionland Eye Hospital, Jiangsu, People’s Republic of China; 7School of Medicine, Nantong University, Jiangsu, People’s Republic of China; 8Department of Nursing, Department of Computer Technology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Sang, Department of Computer Technology, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong, Jiangsu, 226001, People’s Republic of China, Tel +86 13862915051, Email sangyan_cn@126.comPurpose: To identify the difficulties and burdens related to the experience of caring for children.Methods: A phenomenological approach was used in this qualitative study. Semi-structured and adolescents with idiopathic nephrotic syndrome (INS) in mainland China. Interviews lasting 35– 90 minutes were conducted with 13 parental caregivers of youth with INS. The Colaizzi’s analysis was used in data analysis.Results: The mean age of parental caregivers was 40.3 ± 6.1 years, and the average caregiving year of 3.2 ± 3.3 years. Most INS patients were male (69.2%), had a mean age of 7.6 ± 4.2 years. Based on the analysis of the data, five major themes emerged. These were: persistent emotional burden; neglected physical burden; overwhelming financial burden; absence of social support system and burden related to loss of normal life.Conclusion: Health professionals must develop strategies to provide stage-by-stage, targeted health education and psychological support services to parental caregivers of INS youth in China. The government must subsidize routine medications and frequent hospitalizations to minimize the financial burden on parental caregivers of INS youth. Moreover, anti-discrimination policies must be established to protect caregivers from explicit discrimination in public places.Keywords: caregiver, burden, idiopathic nephrotic syndrome, youth

Yi Liang,1,2 Xiaohong Li,1 Fang Wang,2 Zongting Yan,2 Yuhuan Sang,2 Yuan Yuan,2 Yun Qin,1 Xuefei Zhang,1 Mei Ju2 1Health Management Center, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Nursing College, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of ChinaCorrespondence: Mei Ju; Xiaohong Li, Email 593576753@qq.com; 1848922774@qq.comBackground: Thyroid nodules (TNs) are among the most common thyroid lesions, and rates of these nodules have risen over the past three decades. As the majority of TN patients remain asymptomatic when these nodules are in the early stages of development, malignant nodules may continue to develop into thyroid cancer when not detected. As such, early screening and diagnosis-based strategies represent the most promising means of preventing or treating TNs and associated cancers. The present study was thus developed to explore TN prevalence among individuals in Luzhou, China.Methods: Here, thyroid ultrasonography and metabolic-related indicators from 45,023 adults undergoing routine physical examinations in the Health Management Center of a large Grade A hospital in Luzhou over the last three years were retrospectively reviewed in an effort to identify factors associated with TN risk and the detection of these nodules through univariate and multivariate logistic regression analyses.Results: In total, 13,437 TNs were detected in these 45,023 healthy adults for an overall 29.8% detection rate. This TN detection rate rose with age, and multivariate logistic regression analyses revealed that independent risk factors associated with TNs included greater age (≥ 31 years old), female (OR = 2.283, 95% CI: 2.177– 2.393), central obesity (OR = 1.115, 95% CI: 1.051– 1.183), impaired fasting glucose (OR = 1.203, 95% CI: 1.063– 1.360), overweight status (OR = 1.085, 95% CI: 1.026– 1.147), and obesity (OR = 1.156, 95% CI: 1.054– 1.268), while low BMI was a protective factor associated with lower rates of TN incidence (OR = 0.789, 95% CI: 0.706– 0.882). When results were stratified by gender, impaired fasting glucose was not an independent predictor of TN risk among males, while high LDL levels were an independent predictor of TNs among females, and other risk factors were not significantly changed.Conclusion: TN detection rates were high among adults in Southwestern China. Female, elderly individuals, individuals exhibiting central obesity, and those with high levels of fasting plasma glucose are more likely to develop TN.Keywords: thyroid nodules, detection rate, influence factors

Ying Cao,1,* Yibei Dai,1,* Lingyu Zhang,1 Danhua Wang,1 Wen Hu,2 Qiao Yu,3 Xuchu Wang,1 Pan Yu,1 Weiwei Liu,1 Ying Ping,1 Tao Sun,1 Yiwen Sang,1 Zhenping Liu,4 Yan Chen,3 Zhihua Tao1 1Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People’s Republic of China; 2National Clinical Research Center for Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, People’s Republic of China; 3Center for Inflammatory Bowel Diseases, Department of Gastroenterology, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People’s Republic of China; 4Department of Laboratory Medicine, the First People’s Hospital of Yuhang District, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Chen; Zhihua Tao Tel +86 571 8778 3752Fax +86 571 8689 8730Email chenyan72_72@zju.edu.cn; zrtzh@zju.edu.cnBackground: Fecal biomarkers have emerged as one of the most useful tools for clinical management of inflammatory bowel disease (IBD). Oncostatin M (OSM), like fecal calprotectin (FC), is highly expressed in the inflamed intestinal mucosa which may have potential usefulness. We aimed to evaluate the additional utility of these two fecal biomarkers for IBD diagnosis, activity, and prediction of infliximab response over FC alone.Methods: In group 1, 236 IBD patients (145 Crohn’s disease, 91 ulcerative colitis), 50 disease controls, and 32 healthy controls were recruited for IBD diagnosis and activity. In group 2, baseline stool samples were collected from 62 patients to predict infliximab response at week 28 and 52. The performance of fecal biomarkers for IBD management was assessed by the area under the receiver operating characteristic curve (AUC).Results: Fecal OSM and FC levels were increased in IBD patients and were positively correlated with clinical and endoscopic activity. Their combination showed a better ability for disease diagnosis (AUC = 0.93) and slightly improved the capability to identify mucosal healing (AUC = 0.923). Baseline OSM and FC levels were elevated in non-responders at week 28 and 52. The AUCs of OSM, FC, and their combination to predict therapeutic response were 0.763, 0.834, and 0.859 at week 28, 0.638, 0.661, and 0.704 at week 52, respectively. Combined use of fecal and blood biomarkers improved predictive accuracy with an AUC of 0.919 at week 28 and 0.887 at week 52.Conclusion: In addition to FC, OSM is a novel fecal biomarker, and their combination is more beneficial for disease diagnosis and prediction of infliximab response but not for disease activity in IBD patients. Further larger-scale studies are required to confirm our findings.Keywords: inflammatory bowel disease, fecal biomarkers, oncostatin M, calprotectin, diagnosis, activity, infliximab response

Abstract Background Cerebral venous thrombosis can be a fatal complication of the postpartum period. Pregnancy is known to be a risk factor for thromboembolism in itself. Case presentation A normal spontaneous vaginal delivery was planned for a 20-year-old primigravida patient with patient-controlled epidural analgesia. Next morning, the patient complained of an occipital headache. An epidural blood patch was performed for diagnostic and therapeutic purpose with 10 ml of autologous blood. That night, she had an episode of seizures. Endotracheal intubation was done to secure the airway. She was transferred to an intensive care unit. Brain CT angiography and MRI showed superior sagittal sinus thrombosis with acute infarct and mild subarachnoid haemorrhage. For cerebral venous thrombosis treatment, heparin was injected and for intracranial pressure control, a hypertonic solution was injected. Despite this medical treatment, intracranial pressure continued to rise. The next day, her mental state changed to stupor. Emergency decompressive craniectomy was performed. Her mental state improved rapidly after surgery. A week later, she was transferred to a general ward. Her health recovered and she was discharged. Conclusions We experienced postpartum cerebral venous thrombosis misdiagnosed as postdural puncture headache. We hope that this case report would be helpful in situation which a postpartum young woman complains severe headache in spite of management for headache including autologous epidural blood patch.

Abstract Introduction This prospective multicenter study aimed at investigating the safety and metabolic advantages of steroid withdrawal (SW) therapy in kidney transplant recipients with tacrolimus–mycophenolate mofetil‐based immunosuppression. Methods We analyzed 179 recipients who received kidney transplantation from March 2016 and September 2018. In 179 recipients, 114 patients maintained an immunosuppressive regimen including steroids (steroid continuation [SC] group). The remaining 65 patients were determined to withdraw steroid therapy after 6 months posttransplant (SW group). Metabolic parameters and graft functions of the two groups were evaluated. Results The estimated glomerular filtration rates at 12 months posttransplant were 67.29 ± 20.29 ml/min/1.73 m2 in SC group and 73.72 ± 17.57 ml/min/1.73 m2 in SW group (p

© 2015 Elsevier Ltd.Background: The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditiona

High-grade gliomas (HGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis in both adult and pediatric patients. Clinical response is compounded by resistance to standard frontline antineoplastic agents, an absence of novel therapeutics, and poor in vitro models to evaluate these. We screened a range of recently identified anticancer compounds in conventional adult, pediatric, and new biopsy-derived HGG models. These in vitro lines showed a range of sensitivity to standard chemotherapeutics, with varying expression levels of the prognostic markers hypoxia-induced factor (HIF) 1α and p53. Our evaluation of lead DIVERSet library compounds identified that JAG-6A, a compound that was significantly more potent than temozolomide or etoposide, was effective against HGG models in two-dimensional and three-dimensional systems; mediated this response by the potent inhibition of topoisomerase Iiα; remained effective under normoxic and hypoxic conditions; and displayed limited toxicity to non-neoplastic astrocytes. These data suggest that JAG-6A could be an alternative topoisomerase IIα inhibitor and used for the treatment of HGG.

Abstract Background Upstream open reading frames (uORFs) initiate translation within mRNA 5′ leaders, and have the potential to alter main coding sequence (CDS) translation on transcripts in which they reside. Ribosome profiling (RP) studies suggest that translating ribosomes are pervasive within 5′ leaders across model systems. However, the significance of this observation remains unclear. To explore a role for uORF usage in a model of neuronal differentiation, we performed RP on undifferentiated and differentiated human neuroblastoma cells. Results Using a spectral coherence algorithm (SPECtre), we identify 4954 consistently translated uORFs across 31% of all neuroblastoma transcripts. These uORFs predominantly utilize non-AUG initiation codons and exhibit translational efficiencies (TE) comparable to annotated coding regions. On a population basis, the global impact of both AUG and non-AUG initiated uORFs on basal CDS translation were small, even when analysis is limited to conserved and consistently translated uORFs. However, uORFs did alter the translation of a subset of genes, including the Diamond-Blackfan Anemia associated ribosomal gene RPS24. With retinoic acid induced differentiation, we observed an overall positive correlation in translational shifts between uORF/CDS pairs. However, CDSs downstream of uORFs show smaller shifts in TE with differentiation relative to CDSs without a predicted uORF, suggesting that uORF translation buffers cell state dependent fluctuations in CDS translation. Conclusion This work provides insights into the dynamic relationships and potential regulatory functions of uORF/CDS pairs in a model of neuronal differentiation.

Despite the recent interest in organic electrochemical transistors (OECTs) as chemical and biological sensors, little is known about the role that device architecture and materials parameters play in determining sensor performance. We use numerical modeling to establish design rules in two regimes of operation: We find that for operation as an ion-to-electron converter, the response of OECTs is maximized through the use of a gate electrode that is much larger than the channel or through the use of a nonpolarizable gate electrode. Improving the conductivity of the polymer and using a channel geometry that maximizes channel width and thickness, and minimizes channel length helps increase the response. For operation as an electrochemical sensor, the sensitivity is maximized in OECTs with gate electrodes that are smaller than their channels. The sensitivity can be improved by increasing the charge carrier mobility and the capacitance per unit area of the conducting polymer, and also its ability to be penetrated by ions from the electrolyte. A channel geometry that maximizes channel width and minimizes channel length also improves sensitivity. © 2010 Wiley Periodicals, Inc.

Yuanjun Cheng,1,* Donglai Chen,2,* Li Shi,1 Wentao Yang,1 Yonghua Sang,1 Shanzhou Duan,1 Yongbing Chen1 1Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China; 2Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China *These authors contributed equally to this work Abstract: Esophageal bronchogenic cysts are extremely rare. Here we report a case of massive upper digestive tract hematoma and bronchogenic cyst mimicking aortic dissection that was safely removed without esophagectomy. A 30-year-old man was referred to our hospital for the treatment of a mediastinal cystic tumor located in the submucosa of the distal esophagus. His chief complaints were dysphagia > 1 week and severe persistent upper abdominal pain mimicking aortic dissection with constant vomiting for 1 day after gastroscopy examination. The serum level of carbohydrate antigen (CA)199 was > 1,000 U/mL and CA125 was 4,816 U/mL. Hemoglobin levels decreased from 122 g/L to 85 g/L in 5 days. Imaging examinations detected a huge hematoma of the gastric wall. Preoperative diagnosis was difficult. Although the pain indicated a possible aortic dissection, the abnormal levels of tumor biomarkers suggested malignancy. The patient underwent left thoracotomy. The cyst showed an exophytic lesion connected to the esophageal wall at the level of the gastroesophageal junction. Muddy brown contents were obtained by aspiration of the mass intraoperatively. Because enucleation could not be performed, esophageal myotomy in the distal esophagus and partial resection of the cyst were selected. Histopathological examination indicated a bronchogenic cyst of the esophagus. At a follow-up visit 3 months later, the patient had no signs of disease recurrence or any complaints. Postoperative tumor biomarkers returned to normal range. The present report summarizes the clinical details of the case and reviews the literature in order to improve the accuracy of diagnosis. Keywords: esophagus, bronchogenic cyst, thoracotomy, tumor biomarkers, hematoma

Objectives: To investigate differences in the incidence of enteropathy or intestinal malabsorption in patients taking angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), and beta blockers (BBs) at a single center in Korea. Methods: In this retrospective study, we utilized data from the Yangsan electronic medical records to identify 129,169 patients. These individuals were prescribed olmesartan, other ARBs, ACEI, CCB, and BBs between November 2008 and February 2021. Results: Of the 44,775 patients, 51 (0.11%) were observed to have enteropathy or intestinal malabsorption. Compared with the ACEI group, the adjusted odds ratios (ORs) for enteropathy and intestinal malabsorption were OR=1.313 (95% confidence interval [CI]: [0.188-6.798], p=0.893) for olmesartan, OR=0.915 (95% CI: [0.525-1.595], p=0.754) for the other ARBs, OR=0.928 (95% CI: [0.200-4.307]; p=0.924) for the CCB, and OR=0.663 (95% CI: [0.151-2.906]; p=0.586) for the BBs group. These findings were adjusted for factors such as age, gender, duration of antihypertensive medication, and comorbidities. Conclusion: In a retrospective cohort study of patients on antihypertensive medications, no significant difference was found in the incidence of enteropathy or intestinal malabsorption when ACEI was compared to olmesartan, other ARBs, CCB, and BBs. [ABSTRACT FROM AUTHOR]

Qin Feng,1,* Fei Gai,2,* Yaxiong Sang,2 Jie Zhang,3 Ping Wang,1 Yue Wang,1 Bing Liu,2 Dongmei Lin,1 Yang Yu,2 Jian Fang3 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, 2Oncology Business Division, Beijing Novogene Bioinformatics Technology Co., Ltd, 3Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Oncology II, Peking University Cancer Hospital & Institute, Beijing, China *These authors contributed equally to this work Background: The AURA3 clinical trial has shown that advanced non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations in circulating tumor DNA (ctDNA) could benefit from osimertinib.Purpose: The aim of this study was to assess the usefulness of QuantStudio™ 3D Digital PCR System platform for the detection of plasma EGFR T790M mutations in NSCLC patients, and compare the performances of 3D Digital PCR and ARMS-PCR.Patients and methods: A total of 119 Chinese patients were enrolled in this study. Mutant allele frequency of plasma EGFR T790M was detected by 3D Digital PCR, then 25 selected samples were verified by ARMS-PCR and four of them were verified by next generation sequencing (NGS).Results: In total, 52.94% (69/119) had EGFR T790M mutations detected by 3D Digital PCR. In 69 positive samples, the median mutant allele frequency (AF) was 1.09% and three cases presented low concentration (AF