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Xiaoli Yang, Yongzhuo Wu, Fuqiong Jiang, Danqi Deng Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650101, People’s Republic of ChinaCorrespondence: Danqi Deng, Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Avenue, Wuhua District, Kunming, Yunnan, Tel +8613888139863, Fax +86-871-65351214, Email danqid128@sina.comBackground: Pyoderma gangrenosum (PG) is a rare cause of skin ulcers in children, posing challenges in diagnosis and treatment. As the disease is often associated with conditions such as inflammatory bowel disease (IBD), rheumatoid arthritis, haematological disorders and other diseases, diagnosis and treatment often require cooperation with other medical departments. Accordingly, dissemination of information about the disease to doctors in departments other than dermatologists, especially paediatricians, can help in its early detection.Case Presentation: The 11-year-old pediatric patient in the case initially diagnosed with acute febrile neutrophilic dermatosis was eventually confirmed as pustular PG through histopathological examinations of skin and other relevant examinations. The medical condition is lessened after treatment with a combination of glucocorticoids and adalimumab.Conclusion: PG is relatively rare in clinical settings, particularly among pediatric patients exhibiting persistent high fever and signs of pustular pyoderma gangrenosum. This case underscores the importance of considering the potential diagnosis of pediatric pustular PG when confronted with a child presenting persistent high fever and pustules after trauma. Additionally, the proactive initiation of adalimumab emerges as a promising treatment option for pediatric IBD -associated pustular PG.Keywords: pustular pyoderma gangrenosum, acute febrile neutrophilic dermatosis, misdiagnosis, adalimumab

Pingping Zheng,1,* Yating Lu,2,* You Tang,1,* Fudong Xu,3 Lin Wang,2 Rui Qian,4 Cancan Hui,5 Qian Xu,2 Jianle He,1 Datong Deng2 1The General Practice Department, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China; 2The Endocrinology Department, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China; 3The Pathology Department, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Shoudu Medical University, Beijing, People’s Republic of China; 4The Neurology Department, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China; 5The Geriatric endocrinology Department, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Datong Deng, Tel +86 13855134251, Fax +86 055163633742, Email 13855134251@163.comBackground: To investigate the change in hypothalamic kisspeptin-1 (Kiss1) expression during the development of polycystic ovary syndrome (PCOS) and hypoglycemic drug intervention.Methods: Letrozole lavage was used to construct a polycystic ovary rat model. After successful modeling, we treated PCOS rats with metformin, pioglitazone, and acarbose, and we then observed changes in weight, estrus, glucose tolerance, insulin resistance, sex hormones, and hypothalamic kiss1 expression.Results: PCOS rats exhibited increased body weight, abnormal estrous cycle, impaired glucose tolerance, insulin resistance, increased testosterone level, increased luteinizing hormone level, and increased Kiss1 expression in the hypothalamus. However, intervention with metformin, pioglitazone, and acarbose improved the reproductive and metabolic disorders as well as reduced hypothalamic Kiss1 expression.Conclusion: The expression of hypothalamic Kiss1 may play an important role in the pathogenesis of PCOS. Metformin, pioglitazone, and acarbose may reduce the expression of hypothalamic Kiss1 by improving insulin resistance, thereby improving reproductive and metabolic disorders in PCOS rats.Keywords: polycystic ovary syndrome, PCOS, kisspeptin, metformin, pioglitazone, acarbose

Di Kong, Danqi Deng Department of Dermatology, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650101, People’s Republic of ChinaCorrespondence: Danqi Deng, Fax +86-871-65351214, Email danqid128@sina.comAbstract: We report a case of a patient initially diagnosed with keloid and eventually diagnosed by skin histopathology and immunohistochemistry with primary cutaneous ALK-negative anaplastic large cell lymphoma.Keywords: primary cutaneous ALK-negative anaplastic large cell lymphoma, keloid, misdiagnosis

Tao Xie,1 Rong Huang,1 Daishuo Deng,1 Peipei Tang,2 Yufeng Fu,2 Yulong Zheng,1 Yufeng Wan1 1Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China; 2Institute of Medicinal Biotechnology, Jiangsu College of Nursing, Huai’an, Jiangsu, People’s Republic of ChinaCorrespondence: Yulong Zheng; Yufeng Wan, Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China, Tel +86 137 7670 7363 ; +86 158 0523 0282, Fax +86 517 8087 1636 ; +86 517 8087 1616, Email ha183@163.com; ggwanyufeng@163.comPurpose: Corticosteroid insensitivity has become a major barrier in the treatment of chronic obstructive pulmonary disease (COPD). It is known that oxidative stress reduces the expression and activity of histone deacetylase (HDAC)-2 by activating phosphoinositide-3-kinase-δ(PI3Kδ)/Akt pathway, which is a common mechanism. The aim of this study was to investigate whether cryptotanshinone (CPT) can improve corticosteroid sensitivity and to investigate the molecular mechanisms by which this occurs.Patients and Methods: Corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) collected from COPD patients, or in human monocytic U937 monocytic cells exposed to cigarette smoke extract (CSE), was quantified as the dexamethasone concentration required to achieve 30% inhibition of tumor necrosis factor-α (TNFα)–induced interleukin 8 (IL-8) production in the presence or absence of cryptotanshinone. PI3K/Akt activity (measured as the relative ratio of phosphorylated Akt at Ser-473 to total Akt) and HDAC2 expression levels were determined by western blotting. HDAC activity was evaluated by a Fluo-Lys HDAC activity assay kit in U937 monocytic cells.Results: Both PBMCs in patients with COPD and U937 cells exposed to CSE were found to be insensitive to dexamethasone, accompanied by increased phosphorylated Akt (pAkt) and decreased HDAC2 protein expression. The pretreatment of cryptotanshinone restored their sensitivity to dexamethasone, and simultaneously downregulated the level of phosphorylated Akt and upregulated the level of HDAC2 protein. Pretreatment with cryptotanshinone or IC87114 reversed the decrease in HDAC activity in CSE-stimulated U937 cells.Conclusion: Cryptotanshinone restores corticosteroid sensitivity induced by oxidative stress via inhibition of PI3Kδ and is a potential treatment for corticosteroid-insensitive diseases such as COPD.Keywords: corticosteroid insensitivity, chronic obstructive pulmonary disease, phosphoinositide-3-kinase-δ, histone deacetylase 2, cryptotanshinone

Dongmei Deng,1,* Mu Niu,1,* Jie Yang,1 Lijun Deng2 1Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, People’s Republic of China; 2Department of Dermatovenereology, Wuzhong People’s Hospital, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Yang, Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, People’s Republic of China, Email 13337564169@163.com Lijun Deng, Department of Dermatovenereology, Wuzhong People’s Hospital, Suzhou, 215128, People’s Republic of China, Email 474974283@qq.comAbstract: As scrotal simple lymphangioma is a rare benign proliferation of lymphatic vessels in the scrotum, a few reports were documented. A 68-year-old man gradually developed vesicles on the scrotum for ten years and easily ruptured due to friction. Physical examination showed diffuse millet-sized vesicles on the scrotum with milky white fluids and chyle-like exudates. Histopathological examination revealed proliferating and dilated lymphatic vessels with various sizes of lumens in the dermis. An immunohistochemical study showed positive staining for D2-40 and CD31. Therefore, the patient was diagnosed with scrotal lymphangioma and received carbon dioxide laser therapy. After the treatment, the vesicles markedly decreased, and no apparent exudates were observed. During one year of the follow-up, no relapse, scars, or other complications occurred.Keywords: lymphangioma, scrotum, carbon dioxide laser

Chunyu Yuan,1,* Dongmei Deng,2,* Jianqiu Yang,1 Simeng Liu,3 Qihong Qian,4 Min Chen,1 Shengru Zhou,1 Yujiang Li,5 Min Li1,4 1Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou Ctiy, Jiangsu, People’s Republic of China; 2Health Management Center, The Fifth People’s Hospital of Hainan Province, Haikou Ctiy, Hainan, People’s Republic of China; 3Department of Dermatology, Aerospace Center Hospital, Beijing Ctiy, People’s Republic of China; 4Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou Ctiy, Jiangsu, People’s Republic of China; 5Department of Dermatology, Sanmenxia Central Hospital, Sanmenxia Ctiy, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yujiang Li, Department of Dermatology, Sanmenxia Central Hospital, Middle Road of Yaoshan, Hubin District, Sanmenxia, Henan, 472000, People’s Republic of China, Tel +86-13525857005, Email 294161298@qq.com Min Li, Department of Dermatology, the First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Gusu District, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-18936140383, Email lmpfdoctor@163.comPurpose: Dyskeratosis congenita (DC) is an inherited telomere biology disorder characterized clinically by mucocutaneous triad of reticulate hyperpigmentation, nail changes and oral leukoplakia. Bone marrow failure, pulmonary fibrosis and malignancies are the mainly life-threatening causes. There are X-linked recessive, autosomal dominant and autosomal recessive patterns of DC. DKC1 is the most common pathogenic mutation gene responsible for X-linked DC, and it encodes a protein, dyskerin, which is a component of telomerase holoenzyme complex essential for telomere maintenance. Patients with DC have very short telomeres, but the precise pathogenic mechanism remains unclear. This study aimed to identify the causative mutations in the DKC1 gene in three Chinese families with the X-linked form of DC.Patients and Methods: Three Chinese families with DC were included in this study. Whole exome sequencing and Sanger sequencing were performed to clarify the mutation of DKC1 gene. Measurement of relative telomere length through qPCR. Predictions of protein structure and function were performed using bioinformatics tools, including I-TASSER, Polyphen-2 and SIFT.Results: There were four males with DC and a female carrier in three Chinese pedigrees. The novel mutation c.92A>C (p. Q31P) and the missense mutation c.1058C>T (p. A353V) in DKC1 were identified. Both mutations locally changed the structure of dyskerin. Variant Q31P and A353V were predicted to have “deleterious” and “natural” effects on the function of dyskerin, respectively.Conclusion: The novel variant and missense variant detected in the DKC1 gene improve our understanding of DC and broaden the mutation spectrum of the DKC1 gene.Keywords: dyskeratosis congenita, mucocutaneous triad, DKC1 gene, mutation

Xinran Gu, Guangyi Xu, Chen Qian, Saichao Chang, Dandan Deng School of Business Administration, South China University of Technology, Guangzhou, People’s Republic of ChinaCorrespondence: Chen Qian, School of Business Administration, South China University of Technology, Tianhe District, Guangzhou, People’s Republic of China, Email 201710105492@mail.scut.edu.cnPurpose: Prior work suggests that responsibility is negatively associated with employee procrastination behavior. Based on the conservation of resources (COR) theory, we suggest this view is oversimplified and propose that procrastination can be induced when employees have congruent job and family responsibilities via the mediating effect of emotional exhaustion.Methods: This is a quantitative study of the configurational approach. Survey data were collected from 323 employees at two stages in southern Chinese internet enterprises in September 2020. A randomized cluster sample was used and an anonymous self-assessment questionnaire was distributed to all selected respondents (employees). Samples involved different departments, and the procrastination phenomenon is more significant among them. SPSS20.2 and MPLUS 8.3 software and Response Surface Analysis Strategy were used to test the hypotheses.Results: The data analysis results indicated that: a) employee procrastination behavior is higher when employees’ job responsibility and family responsibility are congruent than the incongruent configurations. b) Procrastination is lower when job-family dyads are congruent at high levels of responsibility compared the low levels. c) Procrastination decreases as employees’ job and family responsibilities become more discrepant (ie, incongruent); employees with low job-high family responsibilities procrastinate more than those with high job-low family responsibilities. d) Additionally, employee-experienced emotional exhaustion mediates the relationship in four configurations between job-family responsibilities congruence and procrastination behavior.Conclusion: Drawing on the conservation of resources theory, we proposed a model clarifying how varying combinations of job and family responsibilities affect employee procrastination behavior. The results showed that there are significant differences in the impact of different job-family responsibility combinations on employee procrastination behavior. Employee procrastination behavior is higher when employees’ job-family responsibility are congruent than the incongruent configurations. Additionally, employee-experienced emotional exhaustion mediates the relationship in four configurations between job-family responsibilities congruence and procrastination behavior.Keywords: job-family responsibilities congruence, emotional exhaustion, employee procrastination behavior, conservation of resources theory, configurational approach

Tingting Wu,&ast; Dandan Xie,&ast; Xiaotong Zhao, Murong Xu, Li Luo, Datong Deng, Mingwei Chen Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwei ChenDepartment of Endocrinology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230032, People’s Republic of ChinaEmail chmw1@163.comObjective: To explore the correlation between the expression of miR-34c in peripheral blood of patients with type 2 diabetes mellitus (T2DM) and the onset of diabetic foot ulcer (DFU) and diabetic foot osteomyelitis (DFO).Methods: Sixty newly diagnosed patients with T2DM without DFU (T2DM group), 112 T2DM patients with DFU (DFU group) and 60 controls with normal glucose tolerance (NC group). The DFU group patients were subdivided into DFO (n=64) and NDFO (n=48) groups. Quantitative real-time PCR (qRT-PCR) method was used to determine miR-34c expression levels in the peripheral blood of subjects to analyze the clinical characteristics of DFU and DFO risk factors.Results: MiR-34c expression level in the T2DM group was marked higher than the NC group [2.99 (1.45– 6.22) vs 1.01 (0.89– 1.52)] (P < 0.05). However, the expression level of miR-34c in the DFU group was significantly higher than the T2DM group [9.65 (6.15– 18.63) vs 2.99 (1.45– 6.22)] (P < 0.01). Compared with the NDFO group, the expression level of miR-34c in the DFO group was also obviously increased [13.46 (8.89– 19.11) vs 6.02 (5.93– 14.72)] (P < 0.01). The expression level of miR-34c in DFU patients was positively correlated with the amputation rate of foot ulcers (P=0.030) and was negatively correlated with the healing rate of foot ulcers after eight weeks (P=0.025). Multifactorial logistic regression analysis showed that increased expression of miR-34c was an independent risk factor for DFU and DFO (ORDFU=3.47, ORDFO=4.25, P < 0.01). Meanwhile, the ROC curve analysis indicated that the AUC of miR-34c for the diagnosis of DFU and DFO was 0.803 and 0.904, the optimum sensitivity being was 100% and 98.7%, the optimum specificity was 98.4% and 98.4%, respectively.Conclusion: The increased expression of miR-34c in peripheral blood of T2DM patients is closely related to the occurrence, development and prognosis of DFU and DFO.Keywords: type 2 diabetes, diabetic foot, diabetic foot osteomyelitis, miRNAs

Aiyuan Zhou, 1,* Qing Song, 1,* Yating Peng, 1 Dingding Deng, 2 Xin Liao, 3 Peng Huang, 4 Wenlong Liu, 5 Zhi Xiang, 6 Qimi Liu, 7 Mingyan Jiang, 8 Xiaoying Huang, 9 Xudong Xiang, 10 Hong Peng, 1 Ping Chen 1 1Department of Respiratory and Critical Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Respiratory Medicine, The First Attached Hospital of Shaoyang University, Shaoyang, Hunan, 422001, People’s Republic of China; 3Department of Respiratory Medicine, Affiliated Shaoyang Central Hospital of University of South China, Shaoyang, Hunan, 422001, People’s Republic of China; 4Department of Respiratory Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, 412000, People’s Republic of China; 5Department of Respiratory Medicine, Yueyang Second People’s Hospital, Designated Hospital of Junshan District, Yueyang, Hunan, 414005, People’s Republic of China; 6Department of Respiratory Medicine, The First People’s Hospital of Huaihua Affiliated to University of South China, Huaihua, Hunan, 418000, People’s Republic of China; 7Department of Respiratory Medicine, The Second People’s Hospital of Guilin, Guilin, Guangxi, 541001, People’s Republic of China; 8Department of Respiratory and Critical Medicine, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of China; 9Department of Respiratory and Critical Medicine, Loudi Central Hospital, Loudi, Hunan, 411100, People’s Republic of China; 10Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Chen; Hong PengDepartment of Respiratory and Critical Care Medicine, Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan, 410011, People’s Republic of ChinaEmail pingchen0731@csu.edu.cn; penghong66@csu.edu.cnBackground: Oxygen therapy (OT) is the most widely used supportive regime in patients with hypoxemic acute respiratory failure (ARF) due to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. The aim of this study was to identify the effect of noninvasive ventilation support on coronavirus disease 2019 (COVID-19) patients and risk factors for invasive mechanical ventilation (IMV).Methods: We retrospectively analyzed confirmed COVID-19 subjects from nine hospitals outside Wuhan. All hospitalized patients who tested positive for COVID-19 by real-time polymerase chain reaction between January 1st and March 31st, 2020, were recruited. The patients were divided into four groups based on the most advanced OT regime, including no OT, nasal oxygen therapy, high-flow nasal oxygen therapy (HFNOT) or noninvasive ventilation (NIV), and IMV. Multiple logistic regression models were performed to determine risk factors for IMV.Results: Of the 683 recruited subjects, 315 (46.1%) subjects did not need OT, 300 (43.9%) received nasal oxygen therapy, 51 (7.5%) received HFNOT or NIV, while 17 (2.5%) subjects had to be intubated. The lactate in the OT group was higher than in the no OT group (2.7 vs 1.6, P = 0.02). In addition, HFNOT or NIV patients had a higher respiratory rate, but a lower PaO2 (P < 0.001). HFNOT and NIV had an obvious beneficial effect on ARF with 75% of COVID-19 patients recovering from respiratory failure. Patients with IMV were older (P < 0.001), had a higher rate of hypertension (P < 0.001) and more secondary bacterial infections (P < 0.001) compared to those without intubation. The multivariate model showed that secondary bacterial infection (OR = 6.87, P = 0.009) was independently associated with IMV failure among COVID-19 patients.Conclusion: We identified that HFNOT and NIV had an obvious beneficial effect on ARF among COVID-19 patients. We also demonstrated that secondary bacterial infection was an independent risk factor for NIV failure in patients infected by SARS-COV2.Keywords: COVID-19, SARS-CoV-2, oxygen therapy, invasive mechanical ventilation

Aiyuan Zhou,1,2 Zijing Zhou,1,2 Dingding Deng,3 Yiyang Zhao,1,2 Jiaxi Duan,1,2 Wei Cheng,1,2 Cong Liu,1,2 Ping Chen1,2 1Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, People’s Republic of China; 3Department of Respiratory Medicine, The First Affiliated People’s Hospital, Shaoyang College, Shaoyang, Hunan 422000, People’s Republic of ChinaCorrespondence: Ping ChenDepartment of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaEmail pingchen0731@csu.edu.cnBackground: Fractional exhaled nitric oxide (FENO) has been shown to be a marker of airway inflammation in various pulmonary diseases, including chronic obstructive pulmonary disease (COPD). In this study, we assessed the FENO level in patients with acute exacerbations of COPD (AECOPD) and analyzed the predictive value of the FENO level for treatment response.Methods: Demographic data were collected at admission. FENO, lung function, blood gases, COPD Assessment Test (CAT), and modified Medical Research Council (mMRC) scores were measured at admission and on day 7. At the second visit, the patients were asked to report their health status; scores ranged from 1 to 5, representing “much better”, “slightly better”, “no change”, “slightly worse”, and “much worse”, respectively. The treatment response was evaluated based on the patient’s reported health status (responders were those who reported much better and slightly better) and lung function (responders were those who presented an increase in FEV1 over 200 mL).Results: A total of 182 patients were recruited into the analysis. The FENO level positively correlated with an increase in FEV1 and FEV1% (r = 0.291, p < 0.001 and r = 0.205, p = 0.005, respectively), but negatively correlated with a decrease in the COPD Assessment Test (CAT) score (r = − 0.197, p = 0.008) and patient-reported health status (rho = − 0.408, p< 0.001). An inverse correlation was observed between FENO concentrations at admission and the length of hospital stay. The cut-off point for differentiating responders, identified by health status, was 18 ppb, with the sensitivity being 89.7% and specificity 88.9%.Conclusion: FENO levels, determined at hospital admission, are potential to predict the overall treatment response in AECOPD patients, including remission in subjective patient-reported health statuses and, also, improvements in lung function.Registry Number: ChiCTR-ROC-16,009,087 (http://www.chictr.org.cn/).Keywords: COPD, exacerbation, FENO, lung function, treatment response

Dingding Deng, 1,* Aiyuan Zhou, 2–4,* Ping Chen, 2–4 Qingcui Shuang 1 1Department of Respiratory Medicine, First Affiliated People’s Hospital of Shaoyang College, Shaoyang, Hunan 422001, People’s Republic of China; 2Department of Respiratory and Critical Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 3Respiratory Disease Research Unit, Central South University, Changsha, Hunan 410011, People’s Republic of China; 4Respiratory Disease Diagnosis and Treatment Center, Central South University, Changsha, Hunan 410011, People’s Republic of China *These authors contributed equally to this workCorrespondence: Qingcui ShuangDepartment of Respiratory Medicine, First Affiliated People’s Hospital of Shaoyang College, West Side of Dongfeng Pedestrian Street, Shuangqing District, Shaoyang, Hunan 422001, People’s Republic of ChinaTel +86 136 0739 8125Fax +86 0739 523 4441Email shuangqingcui@sina.comPurpose: Depression is reported in association with chronic obstructive pulmonary disease (COPD). However, to date, no multidimensional indices have taken depression into consideration to predict COPD patients’ prognosis. This study aimed to determine whether a new multidimensional index named CODEXS, based on comorbidities, airflow obstruction, dyspnea, previous exacerbation and depression assessed by Self-Rating Depression Scale (SDS), could predict 1-year exacerbations.Methods: This was a prospective study, patients with stable COPD were used to develop CODEXS at the first visit, and followed up in the 3rd, 6th, and 12th months. After the last visit, patients were divided into frequent and infrequent exacerbators. Another cohort of COPD patients was used for validation. The SDS scoring system in the multidimensional indices ranged from 0 to 4 based on the modified SDS value, representing no depression (25– 39 [0], 40– 49 [1]), mild depression (50– 59), moderate depression (60– 69), and severe depression (≥ 70). Comorbidity, dyspnea, airflow obstruction, and severe exacerbations were calculated according to CODEX thresholds.Results: Two sets of 105 and 107 patients were recruited in the development and validation cohorts, respectively. Depression was demonstrated as an independent risk factor for frequent exacerbators (odds ratio (OR)=  1.14, 95% confidence interval (CI) =  1.06– 1.23, P

Bing Zhong, Di Deng, Jin-Tao Du, Fei Chen, Ya-Feng Liu, Shi-Xi Liu Department of Otorhinolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Shi-Xi LiuDepartment of Otorhinolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu 610041, Sichuan Province, People’s Republic of ChinaTel +86 18980601411Fax +86 2885423627Email lsxent@163.comObjective: This study explored the effectiveness of a new inflammatory prognostic system, using preoperative neutrophil to lymphocyte ratio (NLR) to predict the postoperative survival rate of patients with sinonasal squamous cell carcinoma (SSCC).Methods: Patients diagnosed with SSCC who undergone surgically treated without neoadjuvant therapy were included in the study between May 2008 and October 2017. Preoperative NLR is defined as: preoperative neutrophil/postoperative lymphocyte ratio. The prognostic value was uncovered by univariate and multivariate Cox hazards analysis.Results: A total of 147 patients were included in this study. Through the multivariate analysis, pathological T stage (hazard ratio [HR] 1.719, confidence interval [CI] 1.277–3.642, p

Ning Xia,1 Dehua Deng,1,2 Yiru Wang,1 Chao Fang,3 Su-Juan Li1 1Henan Province of Key Laboratory of New Optoelectronic Functional Materials, College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang, Henan, People’s Republic of China; 2College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan, People’s Republic of China; 3School of Chemical Engineering, Xiamen University Malaysia, Sepang, Selangor, Malaysia Background: Prostate-specific antigen (PSA), a serine protease, is a biomarker for preoperative diagnosis and screening of prostate cancer and monitoring of its posttreatment. Methods: In this work, we reported a colorimetric method for clinical detection of PSA using gold nanoparticles (AuNPs) as the reporters. The method is based on ascorbic acid (AA)-induced in situ formation of AuNPs and Cu2+-catalyzed oxidation of AA. Specifically, HAuCl4 can be reduced into AuNPs by AA; Cu2+ ion can catalyze the oxidation of AA by O2 to inhibit the formation of AuNPs. In the presence of the PSA-specific peptide (DAHSSKLQLAPP)-modified gold-coated magnetic microbeads (MMBs; denoted as DAHSSKLQLAPP-MMBs), complexation of Cu2+ by the MMBs through the DAH–Cu2+ interaction depressed the catalyzed oxidation of AA and thus allowed for the formation of red AuNPs. However, once the peptide immobilized on the MMB surface was cleaved by PSA, the DAHSSKLQ segment would be released. The resultant LAPP fragment remaining on the MMB surface could not sequestrate Cu2+ to depress its catalytic activity toward AA oxidation. Consequently, no or less AuNPs were generated. Results: The linear range for PSA detection was found to be 0~0.8 ng/mL with a detection limit of 0.02 ng/mL. Because of the separation of cleavage step and measurement step, the interference of matrix components in biological samples was avoided. Conclusion: The high extinction coefficient of AuNPs facilitates the colorimetric analysis of PSA in serum samples. This work is helpful for designing of other protease biosensors by matching specific peptide substrates. Keywords: colorimetric assay, gold nanoparticles, prostate-specific antigen, ascorbic acid, Cu2+ ion

Bin Wang, Ling Tan, Dengpu Deng, Ting Lu, Changwei Zhou, Zhongkui Li, Zhenjie Tang, Zhongshi Wu, Hao Tang Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China Background: Cell therapy is a promising strategy for tissue regeneration. Key to this strategy is mobilization and recruitment of exogenous or autologous stem/progenitor cells by cytokines. However, there is no effective cytokine delivery system available for clinic application, in particular for myocardial regeneration. The aim of this study was to develop a novel cytokine delivery system that is stable in solution at physiological pH. Methods: Four groups of self-assembled chitosan oligosaccharide/heparin (CSO/H) nanoparticles were prepared with various volume ratios of chitosan oligosaccharide to heparin (5:2, 5:4, 4:15, 1:5) and characterized by laser diffraction, particle size analysis, and transmission electron microscopy. The encapsulation efficiency and loading content of two cytokines, ie, stromal cell-derived factor (SDF)-1α and vascular endothelial growth factor (VEGF) were quantified using an enzyme-linked immunosorbent assay. The biological activity of the loaded SDF-1α and VEGF was evaluated using the transwell migration assay and MTT assay. The dispersion profiles for the cytokine-loaded nanoparticles were quantified using fluorescence molecular tomography. Results: CSO/H nanoparticles were prepared successfully in solution with physiological pH. The particle sizes in the four treatment groups were in the range of 96.2–210.5 nm and the zeta potential ranged from -29.4 mV to 24.2 mV. The loading efficiency in the CSO/H nanoparticle groups with the first three ratios was more than 90%. SDF-1α loaded into CSO/H nanoparticles retained its migration activity and VEGF loaded into CSO/H nanoparticles continued to show proliferation activity. The in vivo dispersion test showed that the CSO/H nanoparticles enabled to VEGF to accumulate locally for a longer period of time. Conclusion: CSO/H nanoparticles have a high cytokine loading capacity and allow cytokines to maintain their bioactivity for longer, are stable in an environment with physiological pH, and may be a promising cytokine delivery system for tissue regeneration. Keywords: cytokine delivery system, nanoparticles, chitosan oligosaccharide, physiological pH, stromal cell-derived factor-1α, vascular endothelial growth factor

Dawei Deng,* Yang Li,* Jianpeng Xue, Jie Wang, Guanhua Ai, Xin Li, Yueqing GuDepartment of Biomedical Engineering, China Pharmaceutical University, Nanjing, People’s Republic of China*These authors contributed equally to this workAbstract: Messenger RNA (mRNA), a single-strand ribonucleic acid with functional gene information is usually abnormally expressed in cancer cells and has become a promising biomarker for the study of tumor progress. Hairpin DNA-coated gold nanoparticle (hDAuNP) beacon containing a bare gold nanoparticle (AuNP) as fluorescence quencher and thiol-terminated fluorescently labeled stem–loop–stem oligonucleotide sequences attached by Au–S bond is currently a new nanoscale biodiagnostic platform capable of mRNA detection, in which the design of the loop region sequence is crucial for hybridizing with the target mRNA. Hence, in this study, to improve the sensitivity and selectivity of hDAuNP beacon simultaneously, the loop region of hairpin DNA was screened by bioinformatics strategy. Here, signal transducer and activator of transcription 5b (STAT5b) mRNA was selected and used as a practical example. The results from the combined characterizations using optical techniques, flow cytometry assay, and cell microscopic imaging showed that after optimization, the as-prepared hDAuNP beacon had higher selectivity and sensitivity for the detection of STAT5b mRNA in living cells, as compared with our previous beacon. Thus, the bioinformatics method may be a promising new strategy for assisting in the designing of the hDAuNP beacon, extending its application in the detection of mRNA expression and the resultant mRNA-based biological processes and disease pathogenesis.Keywords: molecular beacon, bioinformatics, gold nanoparticle, STAT5b mRNA, visual detection

An unexploited property of graphene-based heterojunctions is the tunable doping of the junction via electrostatic gating. This unique property may be key in advancing electronic transport across interfaces with semiconductors. Here, we engineer transport in semiconducting TMDs by constructing a lateral heterostructure with epitaxial graphene and tuning its intrinsic doping to form a p–n junction between the graphene and the semiconducting TMDs. Graphene grown on SiC (epitaxial graphene) is intrinsically doped via substrate polarization without the introduction of an external dopant, thus enabling a platform for pristine heterostructures with a target band alignment. We demonstrate an electrostatically tunable graphene/MoS2p–n junction with >20× reduction and >10× increased tunability in contact resistance (Rc) compared with metal/TMD junctions, attributed to band alignment engineering and the tunable density of states in graphene. This unique concept provides improved control over transport across 2D p–n junctions.

Identifying how different wave modes interaction with each other is an important topic in space physics. Using measurements from the Magnetospheric Multiscale (MMS) mission, we report an event in the Earth's magnetosheath where ultra‐low‐frequency (ULF) waves, whistler waves, and quasi‐electrostatic whistler harmonics were observed simultaneously. Specifically, our analyses show that the parallel components of ULF waves modulate the electron butterfly distributions which provide the free energy to the excitation of the observed whistler waves. Meanwhile, quasi‐electrostatic waves sharing frequencies that are nearly integral multiples of the frequency of the observed whistlers are identified as nonlinear harmonics of whistler waves. The close correlations between the whistler waves and the electric field harmonics, as well as the high bicoherence indexes within the frequency ranges of the whistlers and harmonics, suggest the significant nonlinear couplings between the whistler waves and quasi‐electrostatic whistler harmonics. Our work provides new insights to the interactions between waves at different frequency bands. Key Points: Ultra‐low‐frequency (ULF) waves, whistler waves, and quasi‐electrostatic whistler harmonics are observed simultaneously in the magnetosheath plasmaULF waves modulate the electron butterfly shaped distributions which provide free energy for the excitation of the observed whistler wavesQuasi‐electrostatic waves are identified as the whistler harmonics, and may be generated by the wave‐wave nonlinear coupling [ABSTRACT FROM AUTHOR]

An 8-week growth trial was conducted to study carbohydrate utilization by white sturgeon fed diets containing glucose or hydrolyzed potato starch (HPS). Four diets supplemented with 15% or 30% of glucose or HPS and a control diet with no added carbohydrate were each fed to triplicate groups of fish. The diets were processed by a 3-min 80 degrees C microwave moist heating, followed by 1-h 70 degrees C drying. Feeding rates varied from 1.7% to 3.2% body weight day(-1) so that all treatment groups were fed the same amount of dietary protein and lipid. The HPS groups showed the highest (P