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Juan Li,1,* Ting Zhou,1,* Pei Wang,1,* Ruian Yin,1 Shengqi Zhang,1 Yile Cao,1 Lijuan Zong,1 Ming Xiao,2 Yongjie Zhang,3 Wentao Liu,4 Lingxiao Deng,5 Fei Huang,6 Jianfei Sun,7,* Hongxing Wang1,* 1Department of Rehabilitation Medicine, Zhongda Hospital Southeast University, Nanjing, 210024, People’s Republic of China; 2Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 3Department of Human Anatomy, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 4Department of Pharmacology, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 5Department of Neurological Surgery, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indianapolis, IN, 46202-2266, USA; 6Institute of Neurobiology, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 7State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianfei Sun, State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China, Email sunzaghi@seu.edu.cn Hongxing Wang, Department of Rehabilitation Medicine, Southeast University Zhongda Hospital, Nanjing, 210024, People’s Republic of China, Email 101012648@seu.edu.cnBackground: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms.Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs’ projections and evaluate neurotransmitters’ expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn.Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters’ expression in anterior horn of lumbar spinal cord.Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters’ expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit. Keywords: gigantocellular reticular nucleus, locomotion, magnetic stimulation, spinal cord injury, superparamagnetic iron oxide nanoparticles, treadmill training

Biao Hou,1– 3,* Bo Li,4,* Wanjun Deng,3,* Bo Li,1,2 Bibo Ren,5 Chao Hu,3 Guowei Zhang,1,2 Fen Yang,6 Meimei Xiao,3 Songlin Xie,3 Denghui Xie1,2 1Department of Joint Surgery and Sports Medicine, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Academy of Orthopedics, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Hand and Foot Microsurgery, The affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5College of Biomass Science and Engineering, Sichuan University, Chengdu, People’s Republic of China; 6Department of Infectious Diseases, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Denghui Xie; Songlin Xie, Email smuspine@163.com; xiesonglin0929@163.comPurpose: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme’s size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes’ potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.Keywords: copper nanozyme, aggregate induced emission, photodynamic antibacterial therapy, antimicrobial resistance, diabetic wound healing

Mengbo Xiao,1 Ying Di,1 Yu An,1 Yunfeng Cui2 1Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Yunfeng Cui, Department of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, 6 Changjiang Road, Nankai District, Tianjin, 300100, People’s Republic of China, Tel +86-150-2263-3356, Email nkyycyf@163.comAbstract: This report presents a unique case of acute necrotizing pancreatitis(ANP) concomitant with paroxysmal nocturnal hemoglobinuria(PNH), a combination that has not been documented in existing literature. The impact of PNH on ANP and its treatment remains uncertain due to the lack of consensus. The case described herein involves a patient who exhibited both ANP and PNH, subsequently experiencing splanchnic vein thrombosis (SVT), resulting in substantial intra-abdominal and gastrointestinal hemorrhaging. We attempted to analyze the role of PNH in the formation of SVT in ANP and propose some new insights and hypotheses for the treatment of such patients.Keywords: acute necrotizing pancreatitis, paroxysmal nocturnal hemoglobinuria, splanchnic vein thrombosis

Jie Wu,1 Yingzhuo Ma,1 Jun Wang,1 Mingzhao Xiao2 1Department of Nursing, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Mingzhao Xiao, Department of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email xmz.2004@163.com Jun Wang, Department of Nursing, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email smile@stu.cqmu.edu.cnPurpose: ChatGPT has a wide range of applications in the medical field. Therefore, this review aims to define the key issues and provide a comprehensive view of the literature based on the application of ChatGPT in medicine.Methods: This scope follows Arksey and O’Malley’s five-stage framework. A comprehensive literature search of publications (30 November 2022 to 16 August 2023) was conducted. Six databases were searched and relevant references were systematically catalogued. Attention was focused on the general characteristics of the articles, their fields of application, and the advantages and disadvantages of using ChatGPT. Descriptive statistics and narrative synthesis methods were used for data analysis.Results: Of the 3426 studies, 247 met the criteria for inclusion in this review. The majority of articles (31.17%) were from the United States. Editorials (43.32%) ranked first, followed by experimental studys (11.74%). The potential applications of ChatGPT in medicine are varied, with the largest number of studies (45.75%) exploring clinical practice, including assisting with clinical decision support and providing disease information and medical advice. This was followed by medical education (27.13%) and scientific research (16.19%). Particularly noteworthy in the discipline statistics were radiology, surgery and dentistry at the top of the list. However, ChatGPT in medicine also faces issues of data privacy, inaccuracy and plagiarism.Conclusion: The application of ChatGPT in medicine focuses on different disciplines and general application scenarios. ChatGPT has a paradoxical nature: it offers significant advantages, but at the same time raises great concerns about its application in healthcare settings. Therefore, it is imperative to develop theoretical frameworks that not only address its widespread use in healthcare but also facilitate a comprehensive assessment. In addition, these frameworks should contribute to the development of strict and effective guidelines and regulatory measures.Keywords: ChatGPT, large language model, medicine, nursing, scoping review, bibliometric analysis

Mei Xiao,1 Guangwen Luo,1 Zhaowei Zhang,1 Yanfen Liu,2 Rui Gong,3 Jianghuan Ke1 1Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 2Department of Endocrinology and Metabolism, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of ChinaCorrespondence: Guangwen Luo, Department of pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China, Tel +86-0579-82552760, Email lgw2018@126.comPurpose: To investigate the correlation between thyroid-related hormones and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).Patients and Methods: Patients with T2DM admitted to our hospital between January 2023 and June 2023 were retrospectively analyzed. The patients were divided into DR and non-diabetic retinopathy (NDR) groups according to whether DR occurred. Thyroid function-related hormones (TSH, FT3, and FT4), blood glucose indices (FBG and HbA1c), and blood lipid indices (HDL-C, LDL-C, TC, and TG) of the two groups were analyzed by univariate and multivariate logistic regression to explore the risk factors for DR. Pearson correlation analysis and multiple stepwise regression analysis were used to investigate the correlation of TSH or FT3 with FBG, HbA1c, and TG in DR patients.Results: Of the 286 patients with T2DM included in this study, 101 (35.31%) developed DR and 185 (64.69%) did not. High TG, FBG, HbA1c, and TSH and low FT3 levels were independent risk factors for DR in T2DM patients. TSH positively correlated with TG, whereas FT3 negatively correlated with TG and HbA1c in T2DM patients with DR.Conclusion: Higher TSH and lower FT3 in T2DM patients with normal thyroid function may affect glucose and lipid metabolism, thereby increasing the risk of DR.Keywords: type 2 diabetes mellitus, diabetic retinopathy, thyroid-stimulating hormone, free triiodothyronine, glucose and lipid metabolism

Xin He,1,2 Dongyue Yang,1,2 Lingyao Lai,1,2 Jing Lang,1,2 Kebo Wei,1,2 Min Xiao1 1Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaCorrespondence: Min Xiao, Email xiaomin@cdutcm.edu.cnAbstract: Alopecia Areata is a hair disorder influenced by factors such as genetics, immune system, and environmental triggers. The pathogenesis of this condition is still unclear, leading to unsatisfactory current treatments and causing a large number of patients to suffer from it. Janus kinase inhibitors are a new class of drugs that have emerged in recent years and are expected to be promising therapeutic tools for alopecia areata. We report five patients with varying backgrounds and severity of alopecia areata. All of them had received conventional therapy without success. Five patients took Upadacitinib at a dose of 15 mg once daily, and all of them achieved satisfactory efficacy. No adverse events were observed during the treatment of 5 patients.Keywords: upadacitinib, alopecia areata, JAK inhibitors, JAK-STAT

Xing Wang,1,2,* Xiaojing Yang,1,3,* Yiming Zhang,1 Afei Guo,1 Suju Luo,1 Meng Xiao,1 Lu Xue,1 Guohui Zhang,2 Huiping Wang1 1Department of Dermatovenereology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Dermatovenereology, Baotou Central Hospital, Baotou City, Inner Mongolia, People’s Republic of China; 3Department of Dermatovenereology, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huiping Wang; Guohui Zhang, Email huiping1208@163.com; 1259314465@qq.comIntroduction: Skin cutaneous melanoma is becoming more dangerous since it has a poor prognosis and is resistant to treatment. Previous research has shown that lncRNAs and fatty acid metabolism are essential for numerous biological activities. There are no studies on the relationship between fatty acid metabolism-Related lncRNAs and skin cutaneous melanoma.Methods and Results: In order to better understand the prognosis and survival of SKCM patients, we investigated the significance of lncRNAs related to fatty acid metabolism. In this work, we looked at the fatty acid metabolism genes and lncRNAs expression patterns. On the basis of lncRNAs associated with fatty acid metabolism, a nomogram and a prognosis prediction model were created. Based on the profile of lncRNAs associated with fatty acid metabolism, functional and pharmacological sensitivity investigations were also carried out. We also looked at the connection between immunotherapy and the immune response. The findings demonstrated that a risk score model based on 11 essential lncRNAs for fatty acid metabolism may discriminate between the clinical condition of SKCM and more accurately predict prognosis and survival. We conducted quantitative reverse transcription polymerase-chain reaction (RT-PCR) to verify the model.Conclusion: These important lncRNAs further showed a strong association with the tumor immune system, and these important lncRNAs also showed a connection between SKCM and chemotherapeutic treatment sensitivity. Our research strives to provide fresh viewpoints and innovative approaches to the treatment and administration of SKCM.Keywords: skin cutaneous melanoma, lncRNA, fatty acid metabolism, bioinformatics, tumor immune

Jun Wang,1,* Hongmei Chen,2,* Lin Yang,2 Xiuli Yu,3 Dandan Zhang,3 Qinghua Zhao,1 Mingzhao Xiao4 1Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Qinggang Senior Care Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingzhao Xiao, Department of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, People’s Republic of China, Tel +8613608399433, Fax +86-23-89012206, Email mingzhaoxiao@cqmu.edu.cnAbstract: This paper aims to describe a randomized controlled trial protocol evaluating the effectiveness, cost, and process of a stress process model-based program in dementia caregiving (DeCare-SPM) for family caregivers. Family caregivers of individuals with dementia will be recruited from memory clinics and community settings and randomly assigned to either DeCare-SPM or usual care. DeCare-SPM comprises three face-to-face sessions (ie, problem-based coping, emotion-based coping, meaning-based coping), and a fourth session (ie, social support) including weekly telephone-based consultation for four weeks and then monthly face-to-face boosters. Outcomes will be measured at baseline (T0), and at one (T1), three (T2), and six months (T3). The primary outcome is positive aspects of caregiving and secondary outcomes are caregiving (ie, sense of competence, caregiver burden, social support, anxiety, depression, and quality of life), dementia-related (ie, care dependency, neuropsychiatric symptoms, and quality of life), and stress-related biomarkers of blood and saliva. In addition, process and economic evaluations will be performed. Mixed-effects models will be used to assess intervention effects. Content analysis will be performed on the qualitative data. This paper described the protocol for comprehensive evaluation of the effectiveness, cost, and process of the theory-driven DeCare-SPM to inform how and why interventions work. It highlights the need to reduce challenges and enhance the positive aspects of dementia care. The DeCare-SPM will provide evidence-based insights into how to support and empower family caregivers in their important roles, thereby, leading to improved dementia care.Keywords: Alzheimer’s disease, stress coping, informal caregivers, community, psychosocial

Yanjun Gao,1,2 Yingge Li,1,2 Zheming Liu,1,2 Yi Dong,1,2 Siqi Yang,1,2 Bin Wu,1,3 Mengxia Xiao,1,4 Chen Chen,5 Yingmei Wen,1,2 Lei Chen,1 Haijuan Jiang,6 Yi Yao1,2 1Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Hubei Provincial Research Center for Precision Medicine of Cancer, Wuhan, 430200, People’s Republic of China; 3Department of Oncology, Huang-Gang Central Hospital, Huanggang, 438000, People’s Republic of China; 4Department of Oncology, Yichun People’s Hospital, Yichun, 336000, People’s Republic of China; 5Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 6Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Yi Yao, Email yaoyi2018@whu.edu.cnBackground: Activator of heat shock protein 90 (HSP90) ATPase Activity 1 (AHSA1) regulates proliferation, apoptosis, migration, and invasion of osteosarcoma and hepatocellular carcinoma (HCC). However, the novel mechanism of AHSA1 in the tumor biology of hepatocellular carcinoma (HCC) remains unclear.Methods: We analyzed AHSA1 expression in 85 pairs of clinical samples of HCC and the Cancer Genome Atlas database. The role of AHSA1 in HCC was proved by cell proliferation, colony formation, migration, cell cycle analysis in vitro, xenograft models and tumor metastasis assay in vivo, and bioinformatics.Results: High AHSA1 expression was demonstrated in HCC and associated with invasive depth, clinical stage, and poor overall survival of patients. Univariate Cox analysis confirmed that AHSA1 was an independent prognostic factor for patients with HCC. Meanwhile, AHSA1 upregulation promoted cell proliferation, colony formation, and cell migration in vitro and tumor cell proliferation and metastasis of HCC cells in vivo. AHSA1 upregulation increased the cell cycle transition from G1 to S phase by increasing the expression of cyclinD1, cyclinD3, and cyclin-dependent kinase 6(CD). Transforming growth factor beta 1 (TGF-β 1)-induced protein kinase B (Akt) signaling regulated the expression of downstream targets, including cyclinD1. AHSA1 expression was closely correlated with the expression of TGF-β, Akt, cyclinD1, cyclinD3, and CDK6 using the Gene Expression Profiling Interactive Analysis database. AHSA1 upregulation participated in HCC progression by regulating TGF-β/Akt-cyclinD1/CDK6 signaling.Conclusion: AHSA1 might serve as a biomarker for predicting the clinical outcome of patients with HCC. It is vital in tumor metastasis and disease progression of HCC and may facilitate the development of clinical intervention strategies against HCC.Keywords: AHSA1, AKT/cyclinD1/CDK6 signaling, cell cycle, hepatocellular carcinoma, TGF-&#x03B2

Xi Chen, Xiaoyan Qian, Min Xiao, Pin Zhang Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Pin Zhang, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, Tel +861087788200, Email zppumc@163.comPurpose: The study aimed to compare the survival outcomes and efficacy of platinum in early breast cancer patients with BRCA1 and BRCA2 mutations.Methods: Patients diagnosed with stage I–III breast cancer and carrying germline pathogenic/likely pathogenic BRCA mutations in three medical institutions in China from April 2016 to January 2021 were retrospectively analyzed. Data on clinical and pathological characteristics, treatment information, pathogenic variants of BRCA, and survival outcomes were collected for all eligible patients.Outcomes: One hundred and sixty-nine patients with BRCA mutations were enrolled, including BRCA1 mutation (53.3%, n = 90) and BRCA2 mutation (46.7%, n = 79). The median age was 39 years, and most patients (68.1%, n = 115) were stage I–II. Patients with BRCA1 mutations were characterized by histological grade III (55.6%) and higher Ki-67 index (Ki-67 ≥ 30%, 78.9%) compared with patients with BRCA2 mutations (27.8%, 58.2%). BRCA1 mutation patients accounted for a significantly higher proportion of triple negative breast cancer than BRCA2 mutation patients (71.1% vs 19.0%, P < 0.0001). A total of 142 (84.0%) patients received neo/adjuvant chemotherapy, including anthracycline and/or taxane-based regimens (55.6%) or platinum-based regimens (27.2%). Median follow-up was 33.2 months. Three-year DFS (disease-free survival) and DRFS (distant recurrence-free survival) had no significant differences between patients with BRCA1 and BRCA2 mutations (82.0% vs 85.4%, P = 0.35; 94.3% vs 94.6%, P = 0.39). The 3-year DFS rate in BRCA1 mutation cohort of patients received platinum regimen was significantly higher than patients received non-platinum regimen (96.0% vs 75.2%, P = 0.01). No differences between DFS and DRFS were observed in patients with BRCA2 mutation received platinum regimen and non-platinum regimen.Conclusion: Similar survival outcomes were observed in early breast cancer patients with BRCA1 and BRCA2 mutation, though they had different biological characteristics. Patients with BRCA1 mutations are more benefit from platinum-regimen. The value of platinum-regimen for early breast cancer patients with BRCA1 and BRCA2 needs to be verified further.Plain Language Summary: BRCA pathogenic mutation has been the principal genetic cause of breast cancer. Since the majority of studies have focused on the clinical manifestation and survival of patients with BRCA mutations and the wild type, few studies gave a concern about the survival outcome of breast cancer patients with BRCA1 and BRCA2 mutation. We aimed to compare the survival outcomes and efficacy of platinum between early breast cancer patients with BRCA1 and BRCA2. Our results showed that patients with BRCA1 and BRCA2 mutations had different biological characteristics, but similar survival outcomes in the early stages. Patients with BRCA1 mutations are more sensitive to platinum therapy in neoadjuvant settings.Keywords: breast cancer, BRCA mutation, survival outcome, chemotherapy, platinum

Shengsheng Yao,1,&ast; Bo Zhang,2,&ast; Xiang Fei,3 Mingming Xiao,4 Li Lu,5 Daming Liu,6 Siyuan Zhang,7 Jianchun Cui3 1China Medical University - Department of Thyroid and Breast Surgery, Liaoning Provincial People’s Hospital, Shenyang, Liaoning Province, 110015, People’s Republic of China; 2Department of Science and Education, The 10th Division of Xinjiang Production and Construction Corps, Beitun General Hospital, Beitun City, Xinjiang Province, 831300, People’s Republic of China; 3Department of Thyroid and Breast Surgery, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 4Department of Pathology, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 5Department of Endocrinology, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 6Department of Ultrasound, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 7Department of Thyroid and Breast Surgery, The 10th Division of Xinjiang Production and Construction Corps, Beitun General Hospital, Beitun City, Xinjiang Province, 831300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianchun Cui, Department of Thyroid and Breast Surgery, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), No. 33 of Wenyi Road, Shenhe District, Shenyang, Liaoning Province, 110015, People’s Republic of China, Tel +86 24 24016014, Fax +86 24 24016014, Email cjc7162003@aliyun.comAbstract: The prevalence of antibody-negative chronic autoimmune thyroiditis (SN-CAT) is increasing. The early diagnosis of SN-CAT can effectively prevent its further development. Thyroid ultrasound can diagnose autoimmune thyroiditis and predict hypothyroidism. Primary hypothyroidism with a hypoechoic pattern suggested by thyroid ultrasound and negative thyroid serum antibodies is the main basis for the diagnosis of SN-CAT. However, for early SN-CAT, only hypoechoic thyroid changes and serological antibodies are currently available. This study explored how to achieve an accurate and early diagnosis of SN-CAT and prevent the development of SN-CAT combined with hypothyroidism. The diagnosis of a hypoechoic thyroid by artificial intelligence is expected to be a breakthrough in the accurate diagnosis of SN-CAT.Keywords: antibody negative, autoimmune thyroiditis, hypothyroidism, hypoechoic thyroid, artificial intelligence, Hashimoto’s disease

Dandan Xie,1– 3,&ast; Kai Li,1,&ast; Ruxue Feng,4,&ast; Man Xiao,5 Zhifeng Sheng,2 Yiqiang Xie1 1College of Traditional Chinese Medicine, Hainan Medical University, Haikou, Hainan, People’s Republic of China; 2National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Metabolism and Endocrinology, Health Management Center, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Clinical Nutrition, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People’s Republic of China; 4Department of Stomatology, Geriatric Hospital of Hainan, Haikou, Hainan, People’s Republic of China; 5Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiqiang Xie, College of Traditional Chinese Medicine, Hainan Medical University, No. 3, Xueyuan Road, Haikou, Hainan, 571199, People’s Republic of China, Tel +86 13036001921, Email xieyiqiang@hainmc.edu.cn Zhifeng Sheng, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Metabolism and Endocrinology, Health Management Center, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Tel +86 13574806523, Email shengzhifeng@csu.edu.cnAbstract: Ferroptosis, an emerging form of regulated programmed cell death, has garnered significant attention in the past decade. It is characterized by the accumulation of lipid peroxides and subsequent damage to cellular membranes, which is dependent on iron. Ferroptosis has been implicated in the pathogenesis of various diseases, including tumors and diabetes mellitus. Traditional Chinese medicine (TCM) has unique advantages in preventing and treating type 2 diabetes mellitus (T2DM) due to its anti-inflammatory, antioxidant, immunomodulatory, and intestinal flora-regulating functions. Recent studies have determined that TCM may exert therapeutic effects on T2DM and its complications by modulating the ferroptosis-related pathways. Therefore, a comprehensive and systematic understanding of the role of ferroptosis in the pathogenesis and TCM treatment of T2DM is of great significance for developing therapeutic drugs for T2DM and enriching the spectrum of effective T2DM treatment with TCM. In this review, we review the concept, mechanism, and regulatory pathways of ferroptosis and the ferroptosis mechanism of action involved in the development of T2DM. Also, we develop a search strategy, establish strict inclusion and exclusion criteria, and summarize and analyze the application of the ferroptosis mechanism in TCM studies related to T2DM and its complications. Finally, we discuss the shortcomings of current studies and propose a future research focus.Keywords: ferroptosis, traditional Chinese medicine, type 2 diabetes mellitus, complications

Xi Luo,1,&ast; Sudan Wu,2,&ast; Meng Xiao,1 Huan Gu,1 Huan Zhang,1 Jianping Chen,3 Yang Liu,4 Chen Zhang,1 Jinming Zhang1 1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Blood Purification Center, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Lika Shing Faculty of Medicine, School of Chinese Medicine, the University of Hong KOng, Hong Kong, People’s Republic of China; 4Department of Vascular Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Liu, Hospital of Chengdu University of Traditional Chinese Medicine, No. 37, Shierqiao Road, Jinniu District, Chengdu, Sichuan, People’s Republic of China, Email zjobliu@163.com Jinming Zhang, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, No.1166, Liutai Avenue, Wenjiang District, Chengdu, Sichuan, People’s Republic of China, Email cdutcmzjm@126.comAbstract: Zein is a type of prolamine protein that is derived from corn, and it has been recognized by the US FDA as one of the safest biological materials available. Zein possesses valuable characteristics that have made it a popular choice for the preparation of drug carriers, which can be administered through various routes to improve the therapeutic effect of antitumor drugs. Additionally, zein contains free hydroxyl and amino groups that offer numerous modification sites, enabling it to be hybridized with other materials to create functionalized drug delivery systems. However, despite its potential, the clinical translation of drug-loaded zein-based carriers remains challenging due to insufficient basic research and relatively strong hydrophobicity. In this paper, we aim to systematically introduce the main interactions between loaded drugs and zein, administration routes, and the functionalization of zein-based antitumor drug delivery systems, in order to demonstrate its development potential and promote their further application. We also provide perspectives and future directions for this promising area of research.Graphical Abstract: Keywords: zein, nanomedicine, drug delivery, antitumor

Jun Luo,1 Qing Liu,2 Zhujizhaba Gama,3 Deji Gesang,3 Ying Zhu,2 Lining Yang,2 Dingqun Bai,2 Qinghua Zhao,4 Mingzhao Xiao1 1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Rehabilitation Medicine, Tibet Autonomous Region People’s Hospital, Tibet, People’s Republic of China; 4Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Mingzhao Xiao, 1st Youyi Road, Chongqing, 400016, People’s Republic of China, Tel +86 13608399433, Email xmz.2004@163.comPurpose: To investigate the current situation of assistive device (AD) usage among seniors in Tibet, China, and explore its influencing factors.Methods: A mixed-methods design was used. Cognition, attitude, behavior, and preference toward ADs were assessed by a self-designed questionnaire. Additionally, participants responded to the open-ended questions. Anderson’s behavior model analyzed the impacts of the prerequisite factors, enabling factors, and demand factors influencing the utilization of ADs by Tibetan seniors.Results: Of the 211 Tibetan seniors, 149 (70.6%) Tibetan seniors expressed the willingness to utilize ADs. Binary Logistic regression analysis showed that one prerequisite factor: age; one enabling factor: care situation, and one demand factor: dysfunctional condition were factors influencing the utilization of ADs. Qualitative comments described: psychological, physical environment, and social support factors were the main influencing factors.Conclusion: This study presents the current situation to utilize ADs by Tibetan seniors on the Qinghai-Tibet Plateau, incorporates Anderson’s behavioral model for quantitative analysis, and combines qualitative research to explore the facilitating and hindering factors, to provide reference and basis for the development of ADs for seniors and policy formulation. The sample size of this study is relatively small and limited to ethnic groups, and we plan to increase the sample size and include more ethnic groups in the future study.Keywords: assistive devices, seniors, Qinghai-Tibet Plateau, mixed-methods research

Huanhuan Huang,1 Huimei Yin,2 Wenxin Xu,1 Qi Wang,3 Mingzhao Xiao,4 Qinghua Zhao1 1Department of Nursing, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Medical Informatics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Urology, Urologist, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Qinghua Zhao, Department of Nursing, the First Affiliated Hospital of Chongqing Medical University, 1st Youyi Road, Chongqing, 400016, People’s Republic of China, Tel +86 023 89012206, Email qh20063@163.comPurpose: To design and develop a blood collection management workstation with high usability to reduce the risk of preanalytical errors and improve patient safety.Methods: A five-phase mobile application development lifecycle model (MADLC) and experience-based co-design (EBCD) were used for design and development. Subsequently, the blood collection management workstation was evaluated using the Chinese System Usability Scale (SUS) in a general ward setting from January to June 2021.Results: It was used on 2593 in-patients who underwent phlebotomy with 12,378 tubes being labeled. The rate of errors and meantime for blood sampling were decreased compared with the same period in the previous year. A total of 14 nurses agreed to participate in the evaluation, and the overall raw SUS score was 69.26 ± 10.39, which indicated above average results.Conclusion: The blood collection management workstation has shown the potential to decrease errors and improve working efficiency in a clinical setting. The study also identified some weaknesses, which will be amended in the future.Keywords: patient safety, identification, pre-analytical phase, phlebotomy, technology

Haizhe Jin,1 Meng Xiao,2 Zibo Gong,3 Yinan Zhao4 1Department of Industrial Engineering, School of Business Administration, Northeastern University, Shenyang, People’s Republic of China; 2School of Business Administration, Northeastern University, Shenyang, People’s Republic of China; 3Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 4Department of Neurology, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Zibo Gong, Department of Radiology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, People’s Republic of China, Email gongzibomed@163.com Yinan Zhao, Department of Neurology, The First Hospital of China Medical University, Shenyang, People’s Republic of China, Email zhaoyinan1616@yahoo.co.jpBackground: COVID-19 has brought greater workload pressures to the medical field, such as medical staff being required to wear personal protective equipment (PPE). While PPE can protect the safety of staff during the pandemic, it can also accelerate the accumulation of fatigue among operators.Objective: This study explores the influence of different protection states on the mental fatigue of nurses.Methods: In this study, 10 participants (5 males and 5 females) were randomly selected among applicants to monitor mental fatigue during the nurses’ daily work in four different PPE states (low temperature and low protection; low temperature and high protection; high temperature and low protection; high temperature and high protection). The NASA subjective mental fatigue scale was used for subjective evaluation. Reaction time, attention concentration, attention distribution, memory, and main task completion time were used for objective evaluation.Results: The results demonstrated a significant difference in the effects of different protection states on mental fatigue. The state of high temperature and high protection had the greatest influence on mental fatigue, the state of low temperature and low protection had the least, and states of high (low) temperature and low (high) protection had intermediate effects on mental fatigue. Furthermore, the correlation between the subjective and objective fatigue indices was analyzed using a multiple regression model.Conclusion: This study clarified the influence of different protection states on the mental fatigue of nurses, and verified that nurses require more time and energy to complete the same work as before under high protection states. It provides a basis for evaluating the mental fatigue of nurses in the unique period of the COVID-19 pandemic and specific ideas for optimizing the nursing process.Keywords: COVID-19, personal protective equipment, mental fatigue, experimental research, nurse

Min Xiao,1,&ast; Di Wang,2,&ast; Guo-Ling Lin,1 Xin Lin,3 Li-Yan Tao,4 Qi-Yong Li1,5 1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China; 2Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Division of Hepatobiliary and Pancreatic Surgery, Department of Nursing, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China; 5Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi-Yong Li, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou, 310000, People’s Republic of China, Email liqiyong@zju.edu.cnPurpose: To explore the feasibility and safety of using the left lateral decubitus position (LLDP) to perform laparoscopic liver resection (LLR) for the treatment of hepatic lesions in segment VI and/or VII.Patients and Methods: Clinical data concerning 50 patients underwent LLR including 25 patients in the LLDP and the other 25 patients in the routine operative position (ROP) at Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College (Hangzhou, China) and Shulan (Quzhou) Hospital between March 2019 and May 2022 were retrospectively analyzed. All of the patients underwent LLR while in the LLDP or the ROP for the treatment of hepatic lesions located in segment VI and/or VII.Results: The preoperative clinical and laboratory parameters were comparable between the two groups (P > 0.05). All patients completed the surgery successfully. There were two patients required conversion to open resection in the ROP comparing with zero in the LLDP. The mean operative time was 256.9 ± 132.7 minutes in LLDP and 255.7 ± 92.1 minutes in ROP, while the median perioperative blood loss was 100 mL (range: 50– 300 mL) in LLDP and 200 mL (range: 50– 425 mL), respectively. The postoperative pathological examination showed that margin-negative resection was achieved all of the cases. The important postoperative parameters all returned to normal within five days after the LLR. The mean postoperative hospital stay (15.6 vs 19.3 days; p < 0.05) and the extraction of the drainage tube time (7.8 vs 10.4 days; p < 0.05) were shorter for patients in LLDP.Conclusion: The LLDP represents a safe and feasible position for performing LLR in selected patients with lesions in segment VI and/or VII. LLR in the LLDP is helpful in terms of the exposure of the surgical field and the recovery of the patient.Keywords: laparoscopic, liver resection, left lateral decubitus position

Wei Bu,1,&ast; Liping Xing,2,&ast; Meixia Xiao,1,&ast; Pan Chang,1 Yaqian Du,1 Hongying Xie3 1Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 3Nursing Department, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongying Xie, Nursing Department, The First Affiliated Hospital of Gannan Medical University, 23 Youth Road, Zhanggong District, Ganzhou, Jiangxi, 341000, People’s Republic of China, Tel +86-797-8266016, Fax +86-797-8269500, Email xiehongying_20216@163.comObjective: To investigate the willingness of Ganzhou residents to participate in “Internet + Nursing services” and analyse the relevant influencing factors.Methods: From May to June 2021, 426 Ganzhou residents were surveyed using an Internet + Nursing services questionnaire and the relevant influencing factors were analysed. The questionnaire comprised two parts: demographic characteristic section and a questionnaire on residents’ willingness to participate in Internet + Nursing services including for dimensions (awareness, participation, trust and need), a 5-point Likert scale was used.Results: A total of 397 valid questionnaires were recovered, and the total willingness of Ganzhou residents to participate in the service was derived as 11.59 ± 2.14. The results of multiple linear regression analyses showed that the presence of family members with a chronic disease or mobility difficulties, and an awareness and trust of Internet + Nursing services were influencing factors of residents’ participation willingness (P < 0.05).Conclusion: The participation willingness of Ganzhou residents in Internet + Nursing services is modestly low, and the reasons for participation varied. It is suggested that the government and pilot hospitals strengthen the publicity surrounding these services, improve safety measures, strengthen team training, and develop products suitable for the elderly to increase residents’ participation willingness.Keywords: internet + nursing services, willingness to participate, residents, trust, awareness

Ran Jing,1– 3 Ian Morrissey,4 Meng Xiao,1,3 Tian-Shu Sun,3,5 Ge Zhang,1,3 Wei Kang,1,3 Da-Wen Guo,6 Jalal A Aram,7 Jeffrey Wang,8 Eric A Utt,7 Yao Wang,1,3 Ying-Chun Xu1– 3 1Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People’s Republic of China; 4IHMA Europe Sarl, Monthey, Valias, Switzerland; 5Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Laboratory Medicine, the First Clinical Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 7Medical Affairs, Pfizer Inc, Groton, CT, USA; 8Clinical Development, Pfizer, Beijing, People’s Republic of ChinaCorrespondence: Ying-Chun Xu; Yao Wang, Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Number 1, Shuaifuyuan Road, Dongcheng District, Beijing, People’s Republic of China, Fax +86 10 69159766, Email xycpumch@139.com; yaoo_wang@163.comPurpose: Monitoring antifungal susceptibility patterns for new or established antifungals is imperative. Antifungal resistance is frequent in molds, frequently leading to invasive mold infections (IMIs) in immunocompromised patients with high morbidity and mortality. Limited availability of effective antifungals for treatment of IMIs in China is an enormous challenge. The purpose of this study was to monitor in vitro antifungal resistance profiles of mold isolates from China, with a particular focus on evaluating in vitro isavuconazole (ISA) activity against these isolates, contributing to the treatment guidance in clinics.Methods: We evaluated the in vitro activity of ISA and its comparators (voriconazole [VOR] and amphotericin B [AMB]) against 131 clinical isolates of Aspergillus spp. (n = 105) and Mucorales order (n = 26) collected between 2017 and 2020 from China.Results: ISA and VOR exhibited similar in vitro activity against Aspergillus spp., with minimum inhibitory concentration (MIC)50 of 1 μg/mL and MIC90 of 2 μg/mL, respectively. Overall, AMB was less active than azoles against Aspergillus spp. (MIC50: 4 μg/mL, MIC90: 8 μg/mL). Against the Mucorales order, ISA demonstrated MIC50 of 0.5 μg/mL and MIC90 of 1 μg/mL; however, one strain each of Mucor circinelloides and Syncephalastrum racemosum were resistant to ISA (MICs: > 8 μg/mL). VOR exhibited little or no activity (MIC50: 8 μg/mL, MIC90: > 8 μg/mL) against the Mucorales order, whereas AMB had MIC50 and MIC90 of 1 μg/mL.Conclusion: This was the first multicenter, in vitro study conducted in China and demonstrated the excellent activities of ISA against most species of the Mucorales order. MIC indicated an advantage over currently available azole antifungals, positioning ISA as a potential alternative to VOR for clinical management of IMIs. As with other antimicrobials, clinicians should employ stewardship and best practices in relation to potential resistance to new azole antifungals.Keywords: Mucorales order, Aspergillus species, antifungal susceptibility testing, isavuconazole, resistance

Yun Yuan,1 Fan Zhang,1 Jingfu Qiu,1 Liling Chen,2 Meng Xiao,1 Wenge Tang,2 Qinwen Luo,1 Xianbin Ding,2 Xiaojun Tang1 1School of Public Health and Management, Medical and Social Development Research Center, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Chongqing Municipal Center for Disease Control and Prevention, Chongqing, 400042, People’s Republic of ChinaCorrespondence: Xiaojun Tang, School of Public Health and Management, Medical and Social Development Research Center, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-13668023656, Email 100108@cqmu.edu.cn Xianbin Ding, Chongqing Municipal Center for Disease Control and Prevention, Chongqing, 400042, People’s Republic of China, Tel +86-13896096430, Email xianbinding@126.comPurpose: To examine the relationship between diabetes and snoring frequency and determine the effect of menopause and postmenopausal years on this relationship.Methods: We included 12,218 premenopausal and postmenopausal women from part of the baseline of the China Multi-Ethnic Cohort study (CMEC) in Chongqing province. Face-to-face questionnaires, physical examination, and biological samples were used to collect data. Logistic regression and subgroup analysis were used to explore the relationship between snoring and diabetes in women with various menopausal statuses.Results: The risk of diabetes increased with the snoring frequency, with adjusted odds ratios of 1.23 (95% CI:1.05– 1.43) and 1.47 (95% CI:1.25– 1.73) for sometimes snoring and frequent snoring, compared to non-snoring. In premenopausal and postmenopausal women, frequent snoring increased the odds of diabetes by 58% (95% CI: 7– 132%) and 43% (95% CI: 20– 72%), respectively, compared to non-snoring. Only in women who were ≥ 10 years postmenopausal had a statistical association between frequent snoring and diabetes, with a 54% (95% CI: 23– 92%) increased odds of diabetes, compared to women who did not snore.Conclusion: Snoring frequency is positively associated with diabetes. Women who snore frequently before and for at least ten years after menopause are at higher risk of developing diabetes. Frequent snorers and long-term postmenopausal women should monitor blood glucose levels to aid in the early detection and treatment of diabetes.Keywords: Chinese Han population, diabetes, menopause, snoring

Jun Wang,1 Weichu Liu,2 Houwei Wang,3 Qinghua Zhao,4 Mingzhao Xiao1 1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3School of Mathematics & Physics and Big Data, Chongqing University of Science and Technology, Chongqing, People’s Republic of China; 4Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Qinghua Zhao; Mingzhao Xiao, Email qh20063@163.com; xmz.2004@163.comBackground: Physical restraint (PR) is widespread use among older adults in long-term care (LTC) facilities, which has negative effects on older adults’ health and quality of care. Considering that research on PR use in Chinese LTC facilities is rare, assessment of nursing staff’s knowledge, attitude, and practice (KAP) is a prerequisite before minimized PR program and staff training project development.Purpose: This study aimed at determining the differentiation of levels and factors of KAP toward PR use between nurses and nursing assistants in LTC facilities.Methods: A cross-sectional study was conducted in six Chinese LTC facilities from November to December in 2019 and May to June in 2020. A total of 316 nursing staff, comprising 69 nurses and 247 nursing assistants were investigated using the Chinese version of the Staff Knowledge, Attitudes and Practices Questionnaire regarding PR. One-way analysis of variance, chi-squared test, Welch test, the Mann–Whitney U-test, and multiple linear regression were performed for data analysis.Results: Mean scores of overall knowledge, attitude, and practice were 5.90± 2.27, 31.97± 3.01, 30.89± 4.82, respectively. PR knowledge and practice of nurses were significantly higher than that of nursing assistants (all P< 0.001), whereas PR attitude with no significant difference (P=0.084). In-school training, in-job training, and knowledge on PR significantly affected PR practice of nurses and nursing assistants. Further, nursing assistants’ practice was also significantly predicted by education (β=0.131, P=0.019), age (β=− 0.140, P=0.034), monthly income (β=− 0.184, P=0.002), and attitude (β=0.130, P=0.030). In-job training (β=0.283, P< 0.001), age (β=− 0.164, P=0.021), and knowledge (β=0.292, P< 0.001) significantly affected nursing assistants’ attitude, while their knowledge was influenced by monthly income (β=0.153, P=0.019) and work years in LTC (β=0.343, P< 0.001).Conclusion: Specific knowledge deficits, negative fields of attitude, and practice were dissimilar between nurses and nursing assistants. The targeted and stratified PR education approaches were suggested to prompt their KAP.Keywords: physical restraint, long-term care, nursing, knowledge, attitudes, practice, nursing homes, nursing staff

Xiangyuan Qiu,1 Xinying Li,1 Yuanliang Yan,2 Yuan Cai,3 Qiuju Liang,2 Bi Peng,3 Zhijie Xu,3– 5 Muzhang Xiao,6 Fada Xia,1 Jinwu Peng3,4 1Department of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China; 2Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China; 3Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China; 4Department of Pathology, Xiangya Changde Hospital, Changde, 415000, Hunan, People’s Republic of China; 5National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China; 6Department of Burn and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of ChinaCorrespondence: Muzhang XiaoDepartment of Burn and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of ChinaEmail xmzsir@sina.comFada XiaDepartment of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of ChinaEmail xiafada@csu.edu.cnBackground: N6-methyladenosine (m6A) is most common internal RNA modification in eukaryotic cells. Existing evidence shows that m6A is closely related to pathogenesis and progression in breast cancer (BRCA). Therefore, it is critical to investigate the key role of m6A target genes in BRCA.Methods: M6A target genes in BRCA are acquired using RMVar online database. The differentially expressed genes (DEGs) from three microarray datasets (GSE5764, GSE22358, GSE9014) is processed by GEO2R. Oncomine, GEPIA, UALCAN and TNMplot were applied to validate the expression of DST. Survival analyses were performed via DRUGSURV and Kaplan–Meier Plotter database. Univariable survival and multivariate Cox analysis were completed to assess the prognostic value of DST and receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of DST. We also investigated the correlation between DST and cancer immune infiltration via using CIBERSORT, TIMER and TISIDB.Results: DST and COL11A1 were significantly expressed in both DEGs and m6A target genes set. COL11A1 show no significance on the patients’ survival. However, high expression of DST was related to the favorable prognosis. Multivariate analysis revealed that the DST dysregulation is an independent prognostic factor and ROC indicated that the great diagnostic value of DST with AUC of 0.948. Subsequently, immunological analyses showed that DST was significantly associated with various immune infiltration cells, including NK cells, T helper cells and Mast cells. Furthermore, DST was also related with multiple immune checkpoints and chemokines, including LAG3, LMTK3 CD24, CXCL12, KDR and CX3CR1. These results indicated the potential roles of DST in the development of BRCA via altering the immune response.Conclusion: DST can influence the development and progression of BRCA by altering the immune microenvironment.Keywords: breast cancer, DST, N6-methyladenosine, immune microenvironment, immune infiltration

Hong Xiao,1 Dan Xu,2 Rui Mao,3 Minqin Xiao,1 Yang Fang,4 Yin Liu1 1Department of Plastic Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3School of Stomatology, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 4Wushi Jiamei Beauty Hospital, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Yin LiuDepartment of Plastic Surgery, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Road, Kunming, Yunnan, 650103, People’s Republic of ChinaTel +86-136 5888 3652Email liuyinsky@163.comPurpose: Platelet-rich plasma (PRP) is a promising noninvasive technique for facial rejuvenation. This systematic literature review aims to appraise the nature and quality of published evidence evaluating the effectiveness and safety of PRP in facial rejuvenation.Patients and Methods: A systematic literature review was conducted with the search string “Platelet-rich plasma AND Facial rejuvenation” in PubMed and Embase. Clinical studies evaluating the outcomes after PRP-based facial rejuvenation either as monotherapy or in combination with other treatment modalities were included. Studies evaluating wound-healing properties of PRP were excluded. The outcomes included both patient-reported and physician-assessed outcomes. Nonstatistical synthesis of evidence was performed by qualitative assessment. The results are reported by the Synthesis Without Meta-analysis (SWiM) reporting standard.Results: A total of 36 studies that included a total of 3172 patients were considered for the evidence synthesis. The number of patients in the included studies ranging from 11 to 2005 with a median of 27.5 patients that reflects the challenges in clinically assessing the aesthetic outcomes after PRP-based facial rejuvenation. Among the 36 studies, 17 were observational studies and 18 were interventional studies with 1 being case report PRP was evaluated either alone or in combination with hyaluronic acid, lipofilling, micro-needling technique, and laser-based interventions. Among the studies, 1 study reported the enhanced platelet concentrate in a fibrin matrix to be relatively safe and effective with a maximum benefit observed at 12 weeks suggesting the platelet-rich fibrin matrix may provide desired aesthetic outcomes and it requires further studies to substantiate.Conclusion: The results suggest very limited clinical evidence, and further clinical studies are warranted to establish the effectiveness of PRP in facial rejuvenation. Furthermore, a consensus for end points used for establishing clinical utility in patients requiring facial rejuvenation is warranted.Keywords: fibrin, hyaluronic acid, platelet-rich plasma, rejuvenation, wound healing

Tongtong Zhou,1,2,&ast; Li Tan,1,&ast; Yang Gui,1 Jing Zhang,1 Xueqi Chen,1 Menghua Dai,3 Mengsu Xiao,1 Qing Zhang,1 Xiaoyan Chang,4 Qun Xu,5 Chunmei Bai,6 Yuejuan Cheng,6 Qiang Xu,3 Xue Wang,7 Hua Meng,1 Wanying Jia,1 Ke Lv,1 Yuxin Jiang1 1Department of Ultrasound, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Ultrasound, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 7Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Lv; Yuxin JiangDepartment of Ultrasound, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaTel/Fax +86 10-69155493; +86 10-69155491Email lvke@163.com; yuxinjiangxh@163.comObjective: Investigate the CEUS enhancement patterns of PDAC and analyse correlations between the CEUS enhancement pattern and both the degree of tumour tissue differentiation and overall survival (OS).Methods: The study included 56 patients with locally advanced PDAC, performed conventional ultrasound and CEUS, and analysed characteristics of the CEUS enhancement patterns. In addition, clinical data, such as serum level of CA19-9, TNM stage were collected, and patients’ survival times were followed up. TICs of dynamic CEUS images were acquired using image processing software to obtain the peak, TP, sharpness, and AUC. Correlations of the CEUS enhancement patterns of PDAC with the degree of differentiation of tumour tissue and OS were quantitatively analysed, as were the correlations of the TIC parameters and CEUS enhancement patterns with OS.Results: Enhancement in the arterial phase included iso-enhancement (30.3%) and hypo-enhancement (69.6%), and was not significantly correlated with sex, age at disease onset, or lesion size. Also was not significantly correlated with tumour tissue differentiation. Clear survival times were obtained for 50 patients during follow-up, and the median survival time was significantly longer for the patients with iso-enhancement than hypo-enhancement. Among the TIC parameters, peaktumour, sharpnesstumour, AEsharpness, and REsharpness differed significantly between the group with iso-enhancement and hypo-enhancement (p < 0.05).Conclusion: The CEUS enhancement patterns of PDAC in the arterial phase include iso-enhancement and hypo-enhancement. Enhancement pattern was not significantly correlated with the degree of differentiation of tumour tissue, but patient survival time differed significantly between the two enhancement patterns, with longer survival for patients with iso-enhancement.Keywords: contrast-enhanced ultrasound, pancreatic ductal adenocarcinoma, survival time, enhancement pattern, time-intensity curve

Yanru Pei,* Mingyue Shi,* Juanjuan Song, Xiaona Niu, Shengjie Wei, Liurui Dou, Mengyu Xiao, Dan Li, Fangfang Xu, Yanliang Bai, Kai Sun Department of Hematology, Zhengzhou University People’s Hospital and Henan Provincial People’s Hospital, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kai Sun; Yanliang BaiDepartment of Hematology, Zhengzhou University People’s Hospital and Henan Provincial People’s Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou, Henan, 450003, People’s Republic of ChinaTel +86-18237110038; +86-13783605211Email sunkai@cellscience.org; yanliangbai@126.comBackground: Hemorrhagic complications are the most common cause of early death in patients with APL and remain a major challenge in the management of APL. Early fatal bleeding events occur not only in high-risk but also in non-high-risk acute promyelocytic leukemia (APL) patients with normal or low WBC counts.Objectives and Methods: To demonstrate the role of the absolute number of circulating leukemic cells in early bleeding events in APL patients. Clinical and laboratory characteristics of 149 patients newly diagnosed with APL were obtained from medical records and retrospectively investigated.Results: In this study, circulating absolute leukemic cells were positively correlated with the WBC count (r=0.9813, p< 0.001) in all patients with APL, and importantly, they were strongly associated with significant bleeding events in non-high-risk patients. Multivariate logistic regression analysis showed that the absolute number of leukemia cells was an independent risk factor for significant bleeding events in APL patients. A cut-off value of 2.59× 109/L for circulating leukemic cells to predict significant bleeding events in APL patients was obtained by ROC curve analysis. We further confirmed that the significant bleeding rate of patients with non-high-risk APL was statistically increased when the absolute number of circulating leukemic cells was ≥ 2.59× 109/L.Conclusion: Circulating leukemic cell content has great clinical value for predicting early bleeding events in APL patients, especially in non-high-risk APL.Keywords: circulating leukemic cells, early fatal bleeding events, non-high-risk acute promyelocytic leukemia

Jun Wang,1 Weichu Liu,2 Qinghua Zhao,1 Mingzhao Xiao,3 Daomei Peng4 1Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4The First Social Welfare Home of Chongqing, Chongqing, People’s Republic of ChinaCorrespondence: Qinghua Zhao 1 Youyi Road, Chongqing, 400016, People’s Republic of ChinaTel +8618602308866Fax +023-89012206Email qh20063@163.comPurpose: Understanding the factors that affect nursing staffs’ intention and practice of physical restraint (PR) on older adults help develop restraint-reduction programs. This study aimed to identify the relationship between the Theory of Planned Behavior (TPB) constructs and nursing staffs’ practice to use PR in long-term care (LTC) facilities.Patients and Methods: A cross-sectional survey was conducted via convenience sampling among 316 nursing staff in six Chinese LTC facilities. PR-TPB questionnaire and the practice subscale of the Chinese version of the Staff Knowledge, Attitudes and Practices Questionnaire regarding PR were used to collect the data. Structural equation modeling (SEM) was used to examine the relationship between variables.Results: The SEM fit well with the data (χ2/df =1.639, RMSEA = 0.045, CFI= 0.955, GFI=0.945). Attitude (β=0.536, P< 0.001) and perceived behavioral control (PBC) (β=0.139, P< 0.05) predicted intention (R2=0.359). PBC was a significant predictor of practice, with R2 accounting for 0.151.Conclusion: TPB provided useful insight into better understanding nursing staffs’ PR practices, although it did not support all the TPB principles significantly. Prospective studies may be conducted to design and implement multi-component interventions based on TPB and explore the effectiveness of PR reduction in LTC facilities in-depth.Keywords: physical restraints, nursing home, aged, the theory of planned behavior, nursing, China

Chuan-Ling Wang, Yi Tang, Ming Li, Ming Xiao, Qing-Shu Li, Lian Yang, Xian Li, Ling Yin, Ya-Lan Wang Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Ya-Lan WangDepartment of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaTel +86 13628308360Fax +86 23 6848 5111Email wangyalan@cqmu.edu.cnBackground: Colorectal cancer remains a major public health problem with high morbidity and mortality rates. In the search for the mechanisms of colorectal cancer occurrence and development, increasing attention has been focused on epigenetics. The overall level of Mono-ADP-ribosylation, an epigenetic, has not been investigated now. The aim of our study was to analysis of the overall level of mono-ADP-ribosylation in colorectal cancer.Methods: Immunohistochemistry was used to investigate the level of mono-ADP-ribosylation in colorectal cancer and normal colorectal adjacent tissue from 64 CRC patients. The data of patient demographic, clinical and pathological characteristics were acquired and analyzed.Results: Mono-ADP-ribosylation was present in both colorectal adenocarcinoma and normal colorectal tissue. The overall level of mono-ADP-ribosylation in colorectal cancer was significantly higher than that in normal colorectal adjacent tissue. In the nucleus, the majority of samples in the high-level group were colorectal adenocarcinoma (55/64), but the opposite was true for normal colorectal tissues (7/32). In particular, increases in the level of mono-ADP-ribosylation in the cytoplasm of colorectal cancer cells was associated with a greater invasion depth of the tumor.Conclusion: The increased level of mono-ADP-ribosylation in colorectal cancer enhances tumor invasion, which suggests that mono-ADP-ribosylation is involved in the development of colorectal cancer and may become a new direction to solve the problem of colorectal cancer.Keywords: mono-ADP-ribosylation, colorectal cancer, immunohistochemistry

Yuan Fang,1,* Jingyi Cheng,1,* Li Zhu,1 Ming Xiao,2 Xinghuai Sun1,3– 5 1Department of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, People’s Republic of China; 2Department of Ophthalmology, Shanghai Bei Zhan Hospital, Shanghai 200070, People’s Republic of China; 3Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, People’s Republic of China; 4NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences (Fudan University), Shanghai 200031, People’s Republic of China; 5State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinghuai SunDepartment of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, People’s Republic of ChinaTel +86 21 64377134Email xhsun@shmu.edu.cnPurpose: To evaluate the effect of routine health examination (RHE) for screening primary open angle glaucoma (POAG) in Eastern China.Materials and Methods: We enrolled patients with newly diagnosed and untreated POAG admitted to the Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai, China. Patients who were screened on RHE and then diagnosed with POAG were classified into the RHE group. The rest were classified as the non-RHE group. Demographic and ocular characteristics, 24-hour intraocular pressure (IOP), and glaucoma grade classified as the mild, moderate and severe groups according to glaucomatous optic neuropathy evaluated based on the enhanced Glaucoma Staging System were compared between the two groups.Results: In total, 172 patients with POAG (74 cases in the RHE group and 98 cases in the non-RHE group) were enrolled. The average age of patients in the RHE and non-RHE groups was 47.53 ± 1.48 years and 51.47 ± 1.46 years, respectively (P = 0.064), while the average mean deviation (MD) was 5.98 ± 0.66 dB and 9.79 ± 0.80 dB (P = 0.001), respectively. The frequency of mild, moderate and severe grade glaucoma in the RHE group was 47.3%, 36.5%, and 16.2%, respectively, while that in the non-RHE group was 27.6%, 31.6%, and 40.8%, respectively (P = 0.001). The presumed visual field MD progression rate for Chinese patients with untreated POAG was 0.97 dB/year. Additionally, the 24-hour IOP curve in the two groups was similar, with the exception of the IOP at 10:00 PM and 2:00 AM, which was higher in the RHE group than that in the non-RHE group.Conclusion: Our study showed RHE was an important and practical method to screen for POAG in Eastern China. RHE also assisted with an earlier diagnosis of POAG and may assist in preventing visual field loss.Keywords: primary open angle glaucoma, screening, routine health examination, visual field progression

Li-Na Guo,1,2 Shu-Ying Yu,1– 3 Meng Xiao,1,2 Chun-Xia Yang,4 Chun-Mei Bao,5 Yan-Hua Yu,6 Li-Yan Ye,7 Yang Yang,1,2 Ge Zhang,1,2 Jie Liu,8 Guo-Wei Liang,9 Rong Min,10 Yu Zhu,11 Hong Lei,12 Yu-Lei Liu,13 Lin-Juan Liu,14 Yun-Jian Hu,15 Po-Ren Hsueh,16 Ying-Chun Xu1,2 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences; 2Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447); 3Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences; 4Department of Infectious Diseases & Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University; 5Clinical Laboratory Medical Center, The Fifth Medical Center of Chinese PLA General Hospital; 6Department of Clinical Laboratory, You’an Hospital, Capital Medical University; 7Center for Clinical Laboratory Medicine, Chinese PLA General Hospital; 8Department of Clinical Laboratory, Seventh Medical Center, PLA General Hospital; 9Department of Clinical Laboratory, Aerospace Center Hospital; 10Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University; 11Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; 12Department of Clinical Laboratory, The 8th Medical Center of Chinese PLA General Hospital; 13Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University; 14Department of Clinical Laboratory, Peking University Cancer Hospital and Institute; 15Department of Clinical Laboratory, Beijing Hospital, Beijing, People’s Republic of China; 16Departments of Laboratory Medicine & Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanCorrespondence Ying-Chun XuDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan Wangfujing, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel/ Fax +86 106 915 9766Email xycpumch@139.comPo-Ren HsuehDepartments of Laboratory Medicine & Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanTel +886-2-23224262 ext. 65355Fax +886-2-23955072Email hsporen@ntu.edu.twObjective: Invasive candidiasis (IC), a life-threatening fungal infection prevalent among hospitalized patients, has highly variable regional epidemiology. We conducted a multicenter surveillance study to investigate recent trends in species distribution and antifungal susceptibility patterns among IC-associated Candida spp. in Beijing, China, from 2016 to 2017.Materials and Methods: A total of 1496 non-duplicate Candida isolates, recovered from blood and other sterile body fluids of IC patients, were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry combined with ribosomal DNA internal transcribed spacer (ITS) region sequencing. Broth microdilution-based susceptibility testing using six antifungal agents was also conducted.Results: Candida albicans was the most frequently isolated species (49.9%), followed by Candida tropicalis (15.5%), Candida glabrata (14.7%) and Candida parapsilosis (14.2%). No significant differences in species distribution were observed when compared with a 2012– 2013 dataset. Overall, the rates of susceptibility to fluconazole and voriconazole were high among C. albicans (98% and 97.2%, respectively) and C. parapsilosis species complex (91.1% and 92%, respectively) isolates but low among C. tropicalis (81.5% and 81.1%, respectively) isolates. In addition, the rate of azole resistance among C. tropicalis isolates increased significantly (1.8-fold, P< 0.05) compared with that observed in 2012– 2013, while micafungin resistance rates were < 5% for all tested Candida species.Conclusion: Our results suggest that species distribution has remained stable among IC-associated Candida isolates in Beijing. Resistance to micafungin was rare, but increased azole resistance among C. tropicalis isolates was noted. Our study provides information on local epidemiology that will be important for the selection of empirical antifungal agents and contributes to global assessments of antifungal resistance.Keywords: invasive fungal infections, Candida, species distribution, antifungal resistance, surveillance, Beijing

Jing Ye,1,* Bing Liao,2,* Xiaohua Jiang,1 Zhihuai Dong,1 Sunhong Hu,1 Yuehui Liu,2 Mang Xiao1 1Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuehui Liu; Mang Xiao Email liuyuehuiclark@21cn.com; joelxm@zju.edu.cnBackground: Peripheral blood inflammation factor neutrophil-lymphocyte ratio (NLR), platelet count (PLT) and nutritional factor serum albumin (ALB) have been proposed as prognostic markers of head and neck squamous carcinoma cancer (HNSCC) in recent years. In the current study, nomogram predict models based on pre-treatment hematological parameters and a modified risk-stratified score system have been built.Methods: A total of 197 patients with oropharyngeal, hypopharyngeal and laryngeal cancers receiving multimodality treatment between 2012 and 2014 were included. The pre-treatment ALB, neutrophil, lymphocyte and platelet count (PLT) were detected. Cancer-specific survival and locoregional recurrence (LRC) by 5 years’ follow-up in the cases were obtained. To integrate clinical characteristics, we propose a modified risk-stratified score system. Kaplan–Meier method, proportional hazards COX model, logistic models were used to establish nomograms within external validation.Results: Five-year LRC was decreased (p=0.004) for 140 patients with pre-treatment NLR < 2.77. Five-year LRC and 5-year cancer-specific survival were decreased (p=0.031, p=0.021) with pre-treatment PLT ≥ 248× 109/L. Comparison of univariate parametric models demonstrated that pre-treatment NLR evaluation and PLT> 248× 109/L were better among tested models. On Bayesian information criteria (BIC) analysis, the optimal prognostic model was then used to develop nomograms predicting 3- and 5-year LRC. The external validation of this predictive model was confirmed in 57 patients from another hospital.Conclusion: Pre-treatment NLR elevation and PLT> 248× 109/L are promising predictors of prognosis in patients with operable HNSCC. Nomograms based on the pre-treatment hematological markers and modified risk-stratified score system provide distinct risk stratifications. There results provided the feasibility of anti-inflammatory and antiplatelet treatments for HNSCC patients.Keywords: head and neck squamous cell carcinoma, neutrophil-lymphocyte ratio, platelet count, albumin, nomogram

Hepatocellular carcinoma (HCC) is the most common type of primary liver malignancy with poor prognosis worldwide. Emerging evidences demonstrated critical roles of lipid de novo synthesis in HCC progression, yet its regulatory mechanisms are not fully understood. Herein, we found that tuftelin 1 (TUFT1), an acidic phosphorylated glycoprotein with secretory capacity, was significantly upregulated in HCC and had an excellent correlation with patient survival and malignancy features. Through database mining and experimental validation, we found that TUFT1 was associated with fatty acid metabolism and promoted lipid accumulation in HCC cells. Further, we found that TUFT1 can interact with CREB1, a transcription factor for hepatic lipid metabolism, and regulate its activity and the transcriptions of key enzymes for lipogenesis. TUFT1 promoted HCC cell proliferation significantly, which was partially reversed by treatment of an inhibitor of CREB1, KG-501. Moreover, TUFT1 promoted the capacity of HCC cell invasion in vitro, which was likely mediated by its association with zyxin, a zinc-binding phosphoprotein responsible for the formation of fully mature focal adhesions on extracellular matrix. We found that TUFT1 can interact with ZYX and inhibit its expression and recruitments to focal complexes in HCC cells. Collectively, our study uncovered new regulatory mechanisms of TUFT1-mediated lipogenesis, cell proliferation, and invasion.

Xiaosheng Fan,1,2 Ming Xiao,1 Qinghai Zhang,1 Na Li,1 Peili Bu1 1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Department of Cardiology, Laiwu People’s Hospital, Laiwu, Shandong 271100, People’s Republic of ChinaCorrespondence: Peili BuThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Jinan 250012, People’s Republic of ChinaEmail bupeili@outlook.comObjective: Apoptosis plays an essential role in cell development and aging, which is associated with a series of diseases, such as neurodegeneration. MircoRNAs exert important roles in the regulation of gene expression. As a stress-responsive deacetylase in mitochondria, sirtuin-3 (sirt3) is a key regulator for mitochondrial function and apoptosis. Also, miR-195 has been demonstrated to be involved in cell cycle and apoptosis. Therefore, this study aimed to investigate the effects of miR-195-sirt3 axis on angiotensin II (ANG II)-induced hippocampal apoptosis and behavioral influence.Materials and methods: ANG II infusion was used to establish the hypertensive model in HT22 cells and 129S6/SvEvTac mice, respectively. TUNEL assay was used to evaluate the apoptosis level. Mitochondrial membrane potential (MMP) was measured to evaluate the mitochondrial property. Immunohistochemistry, RT-PCR, Western blotting, and luciferase reporter assay were conducted to determine the underlying molecular mechanism.Results: The results revealed that ANG II treatment promoted apoptosis in the hippocampal cells and tissues, along with increased sirt3 and decreased miR-195 expression. Silencing sirt3 by genetic engineering or siRNA reversed ANG II-induced hippocampal apoptosis. Sirt3 was identified as a direct target gene of miR-195. Forced expression of miR-195 could play counteractive roles in hippocampal apoptosis induced by ANG II. Furthermore, the behavioral assay demonstrated that ANG II-induced hippocampal apoptosis impaired the performance in the spatial navigation task, but not in the spatial memory task.Conclusion: The results suggested that miR-195-sirt3 axis plays an important role in the ANG II-induced hippocampal apoptosis via altering mitochondria-apoptosis proteins and mitochondria permeability and that hippocampal apoptosis is associated with impaired learning capability in hypertensive mice. This study provides insights into the molecular architecture of apoptosis-related neurodegenerative diseases.Keywords: Sirt3, miR-195, hippocampus, apoptosis, hypertension, mitochondria, learning

Hui Xu,1,* Shu-Ying Yu,2–4,* Meng-Lan Zhou,2–4 Ya-Ting Ning,2–4 Meng Xiao,2,4 Xiao-Gai Li,1 Meng Chen,2,5 Fanrong Kong,6 Sharon Chen,6 Liang Ming,1 Ying-Chun Xu2,3 1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University and Key Laboratory of Clinical Laboratory of Henan Province, Henan 450003, People’s Republic of China; 2Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 3Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 4Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, People’s Republic of China; 5Department of Clinical Laboratory, Beijing Pinggu Hospital of Traditional Chinese Medicine, Beijing 101200, People’s Republic of China; 6Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR – New South Wales Health Pathology, The University of Sydney, Westmead Hospital, Westmead, NSW, Australia*These authors contributed equally to this workCorrespondence: Liang MingDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, 1E Jianshe Road, Zhengzhou, Henan 450052, People’s Republic of ChinaTel +86 371 6691 3118Email mingliang3072@163.com Ying-Chun XuDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel/Fax +86 10 6915 9766Email xycpumch@139.comIntroduction: As participants of the national China Hospital Invasive Fungal Surveillance Net program, we sought to describe the epidemiology and antifungal susceptibility patterns of yeast isolates obtained from patients with invasive fungal infection at the First Affiliated Hospital of Zhengzhou University, China.Methods: A total of 434 yeast isolates recovered from blood and other sterile body fluids were identified to species by matrix-assisted laser desorption ionization –time of flight mass spectrometry with or without supplementation by DNA sequencing. Antifungal susceptibilities were determined by Sensititre YeastOneTM YO10 methodology.Results: Candida albicans was the most common causative species (33.9% of isolates) but significantly decreased in frequency from 37.2% to 27.7% from 2012 to 2014. C. tropicalis was the next most common pathogen (25.1%), followed by C. parapsilosis complex (17.3%), C. glabrata (9%), and C. pelliculosa (6.7%), with other species comprising 8% of isolates. Caspofungin, micafungin, and anidulafungin exhibited potent in vitro activities against the majority of Candida isolates. Azoles demonstrated in vitro activities against C. albicans with a susceptibility rate of >95% and against C. parapsilosis complex, >95% isolates were susceptible. Among C. tropicalis and C. glabrata isolates, resistance rates to fluconazole and voriconazole were 11.9%, 9.1% and 7.7%, 28.2%, respectively. Of note, C. pelliculosa had a high incidence rate in newborns and high rates of resistance to fluconazole and voriconazole of 55.2% and 41.4%, respectively.Conclusion: The present study provided valuable local surveillance data on the epidemiology and antifungal susceptibilities of invasive yeast species, which is essential for guiding antifungal treatment protocol development.Keywords: invasive yeast infection, epidemiology, antifungal susceptibility

Jing Ye, Xiaohua Jiang, Zhihuai Dong, Sunhong Hu, Mang Xiao Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Mang XiaoDepartment of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, East Qingchun Road Nr.3, Hangzhou, Zhejiang 310016, People’s Republic of ChinaEmail joelxm@zju.edu.cnIntroduction: RSL3-induced ferroptosis is a cell death pathway dependent upon intracellular iron and is characterized by accumulation of lipid hydroperoxides. Glutaminolysis, a glutamine-fueled intracellular metabolic pathway, is an essential pathway of ferroptosis in cancer cells. Recent findings showed low-concentration paclitaxel (PTX) could inhibit cell death by upregulating p53 expression; downregulating glutaminolysis-related genes.Methods: The therapeutic effect of RSL3 plus low-concentration PTX combination therapy was investigated in HPSCC cells harboring mutant p53 (mtp53). Relative cell viability, ferroptosis-specific lipid peroxidation and relevant protein expression were evaluated.Results: We demonstrated that neither PTX nor RSL3 in low concentration caused significant cell death; however, the combination therapy is shown to induce ferroptosis and significant cell death in mtp53 HPSCC. We discovered that low-concentration PTX enhanced the RSL3-induced ferroptosis by upregulating mtp53 expression. Furthermore, mtp53-mediated transcriptional regulation of SLC7A11 could be the key determinant.Discussion: Although gain-of-function of p53 variants remains to be characterized, our findings provide new insight into the synergistical cell death by regulating ferroptosis and p53.Keywords: HPSCC, ferroptosis, low-concentration paclitaxel, RSL3, synthetic cell death, mtp53, SLC7A11, GOF p53 variants

Menglan Zhou,1–3 Shuying Yu,1–3 Timothy Kudinha,4 Meng Xiao,1,3 He Wang,1,3 Yingchun Xu,1,3 Hongmei Zhao51Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 4Central West Pathology Laboratory, Charles Sturt University, Orange, New South Wales, Australia; 5Department of Clinical Laboratory, The People’s Hospital of Liaoning Province, Liaoning 110016, People’s Republic of ChinaBackground: Kodamaea ohmeri has been a rare fungal pathogen in the past decades but is now becoming more common in various invasive fungal diseases, with high mortality. There are limited data on the occurrence and distribution of K. ohmeri.Methods: Sixty-two K. ohmeri isolates collected from 24 hospitals in China over a 7-year period were studied. Performance of three phenotypic methods in the identification of this organism was assessed against a gold standard, 26S rDNA sequencing. Original identification results submitted by the participating local hospitals were reviewed. The Sensititre YeastOne YO10 (SYY) was evaluated in determining the in vitro antifungal susceptibilities using standard broth microdilution method (BMD) as a reference, and essential agreement (EA) was calculated.Results: Accurate species identification was achieved in 82.3% and 96.8% of the cases by Vitek 2 Compact and Vitek mass spectrometry (MS), respectively. For Bruker MS, 12.9% and 96.8% of the isolates were correctly identified to species level using the direct transfer and protein extraction methods, respectively. Only 29 (46.8%) isolates were initially correctly identified as K. ohmeri by the local hospitals. The highest misidentification rate (100%, 16/16) was observed in CHROMagar. According to BMD, the highest MIC90 was seen in fluconazole (8 μg/mL), followed by 1 μg/mL for micafungin, caspofungin, 5-fluorocytosine, and amphotericin B, 0.5 μg/mL for itraconazole, 0.25 μg/mL for posaconazole and voriconazole. Significant differences in EAs for different drugs were observed, ranging from 95.2% for amphotericin B to 22.6% for itraconazole between SYY and BMD.Conclusion: Our study emphasizes the need for accurate identification of clinical K. ohmeri isolates and the importance of validating antifungal susceptibility by standard BMD.Keywords: Kodamaea ohmeri, identification, antifungal susceptibility profiles, invasive fungal disease, surveillance

Shu-Ying Yu,1–3 Li Zhang,1,3 Sharon Chen,4 Fanrong Kong,4 Meng Xiao,1,3 He Wang,1,3 Xin Hou,1–3 Meng-Lan Zhou,1–3 Ge Zhang,1,3 Jing-Jia Zhang,1,3 Si-Meng Duan,1,3 Wei Kang,1,3 Ying-Chun Xu1,31Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, People’s Republic of China; 4Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR –New South Wales Health Pathology, The University of Sydney, Westmead, New South Wales, AustraliaIntroduction: We studied the species distribution and antifungal susceptibilities of Candida isolates causing refractory or recurrent oropharyngeal candidiasis (OPC) in a multicenter study in China (2013–2016).Methods: Species identification was performed using the Bruker Biotyper (Bruker Daltonics, Germany) matrix-assisted laser desorption/ionization time of flight mass spectrometry system supplemented by internal transcribed spacer sequencing as required. Antifungal susceptibilities were determined by the Clinical and Laboratory Standards Institute document (CLSI) M27-A3 broth microdilution methodology.Results: A total of 558 non-duplicate Candida isolates comprising 10 species were obtained from 535 patients. Candida albicans was the most common species (89.6%), followed by C. glabrata (5.2%), C. tropicalis (2.9%), and C. parapsilosis (0.7%). Azoles were active against C. albicans with susceptibility rates of 96% and 95.8% for fluconazole and voriconazole, respectively. MIC50 values of C. albicans to fluconazole, voriconazole, itraconazole, and miconazole were 1, 0.03, 0.25 and 0.12 μg/mL, respectively, higher than those in previous studies of which OPC patients (corresponding MIC50 values of 0.25 , 0.015 , 0.06 , and 0.03 μg/mL). Except for itraconazole, the MIC50 and MIC90 values of 58 non-C. albicans to other azoles were two to threefold higher than C. albicans. Miconazole, amphotericin B, nystatin, and 5-flucytosine had good in vitro antifungal activity for all isolates.Conclusion: The study provides valuable data on the species distribution and antifungal susceptibility of oropharyngeal Candida isolates from geographically diverse areas of China. C. albicans remains the most common species but with increasing rates of azoles resistance.Keywords: oral candidiasis, Candida, identification, antifungal susceptibility

Qingtao Hou,1,* Yang Guan,1,* Weihua Yu,2 Xintong Liu,1 Lihua Wu,2 Mingzhao Xiao,3 Yang Lü1 1Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Anatomy, Institute of Neuroscience, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to investigate the relationship between obesity and cognitive impairment in the Chinese elderly.Patients and methods: Patients aged 60 years or above were enrolled from the Department of Geriatrics of The First Affiliated Hospital of Chongqing Medical University from March 2013 to May 2017. Mini-Mental State Examination scale was used to assess the cognitive function. Body mass index (BMI) and waist–hip ratio were used to classify obesity. Student’s t-test, Mann–Whitney U-test, or chi-squared test was used to compare the data between participants with normal cognition and participants with cognitive impairment as appropriate. Univariate logistic regression models and multivariate logistic regression models were performed to explore the relationship between BMI or abdominal obesity and cognitive impairment.Results: A total of 1,100 patients including 568 men and 532 women aged 60–98 years (median age 79 years) were enrolled. After adjusting for age, gender, smoking, drinking, education level, hypercholesterolemia, hypertension, and diabetes, overweight was significantly associated with a decreased risk of cognitive impairment (OR=0.458, 95% CI=0.298–0.703, P

Xiaohua Jiang,* Jing Ye,* Zhihuai Dong, Sunhong Hu, Mang Xiao Department of Otolaryngology Head and Neck Surgery, Sir Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China *These authors contributed equally to this work Abstract: Head and neck squamous cell carcinoma (HNSCC) is highly variable by tumor site, histologic type, molecular characteristics, and clinical outcome. During recent years, emerging targeted therapies have been focused on driver genes. HNSCC involves several genetic alterations, such as co-occurrence, multiple feedback loops, and cross-talk communications. These different kinds of genetic alterations interact with each other and mediate targeted therapy response. In the current review, it is emphasized that future treatment strategy in HNSCC will not solely be based on “synthetic lethality” approaches directed against overactivated genes. More importantly, biologic, genetic, and epigenetic alterations of HNSCC will be taken into consideration to guide the therapy. The emerging genetic alterations in HNSCC and its effect on targeted therapy response are discussed in detail. Hopefully, novel combination regimens for the treatment of HNSCC can be developed. Keywords: head and neck malignancy, gene mutations, deletions, amplifications, genetic interactions, target therapy

Chenyang Zhao,1,* Mengsu Xiao,1,* Yuxin Jiang,1 He Liu,1 Ming Wang,1 Hongyan Wang,1 Qiang Sun,2 Qingli Zhu1 1Department of Ultrasound, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing 100730, China; 2Department of Breast Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing 100730, China *These authors contributed equally to this work Objective: To investigate the feasibility of a CAD system S-detect on a database from a single Chinese medical center.Materials and methods: An experienced radiologist performed breast US examinations and made assessments of 266 consecutive breast lesions in 227 patients. S-detect classified the lesions automatically in a dichotomous form. An in-training resident who was blind to both the US diagnostic results and histological results reviewed the images afterward. The final histological results were considered as the diagnostic gold standard. The diagnostic performances and interrater agreements were analyzed.Results: A total of 266 focal breast lesions (161 benign lesions and 105 malignant lesions) were assessed in this study. S-detect had a lower sensitivity (87.07%) and a higher specificity (72.27%) compared with the experienced radiologist (sensitivity 98.1% and specificity 65.43%). The sensitivity and specificity of S-detect were better than that of the resident (sensitivity 82.86% and specificity 68.94%). The AUC value of S-detect (0.807) showed no significant difference with the experienced radiologist (0.817) and was higher than that of the resident (0.758). S-detect had moderate agreement with the experienced radiologist.Conclusion: In this single-center study, a high level of diagnostic performance of S-detect on 266 breast lesions of Chinese women was observed. S-detect had almost equal diagnostic capacity with an experienced radiologist and performed better than a novice reader. S-detect was also distinguished for its high specificity. These results supported the feasibility of S-detect in aiding the diagnosis of breast lesions on an independent database. Keywords: ultrasonography, breast neoplasms, image interpretation, computer-assisted, diagnostic imaging

BackgroundThe lack of understanding of molecular pathologies of the solitary functioning kidney makes improving and strengthening the continuity of care between pediatric and adult nephrological patients difficult. Copy number variations (CNVs) account for a molecular cause of solitary functioning kidney, but characterization of the pathogenic genes remains challenging.MethodsIn our prospective cohort study, 99 fetuses clinically diagnosed with a solitary functioning kidney were enrolled and evaluated using chromosomal microarray analysis (CMA). The genetic drivers for the pathogenic CNVs were analyzed. We characterized QPRT localization in fetal kidneys using immunohistochemistry and its expression in adult kidneys using quantitative RT-PCR. Further, QPRT was knocked down using siRNA in human embryonic kidney (HEK293T) cells, and the cell cycle and proliferation were tested.ResultsBesides one Triple X syndrome and one Down syndrome, we identified a total of 45 CNVs out of 34 subjects. Among the 14 pathogenic CNVs, CNV 16p11.2 reached the highest number of records with the phenotype of kidney anomalies in the Decipher database. Among the 26 genes within the 16p11.2 region, as a key enzyme for nicotinamide adenine dinucleotide (NAD+) biosynthesis, QPRT was distinctly localized in renal tubules but was barely observed in renal interstitial and glomeruli in fetal kidneys. The loss of QPRT prevented cells’ efficient transition into S phase, affected cell-cycle progression, and abrogated proliferation of human embryonic kidney cells.ConclusionOur data suggest that QPRT is a candidate gene associated with susceptibility for solitary functioning kidney. The CNVs discovered in our study exhibit great potential for future applications in genetic counseling and pregnancy management.

Current antiviral therapy can not cure chronic hepatitis B virus (HBV) infection or eliminate the risk of hepatocellular carcinoma. The licensed epidermal growth factor receptor (EGFR) inhibitors have found to inhibit hepatitis C virus replication via downregulation of signal transducers and activators of transcription 3 (STAT3) phosphorylation. Since STAT3 is also involved in HBV replication, we further studied the anti-HBV efficacy of the EGFR inhibitors in this study. HBV-transfected HepG2.2.15 cells and HBV-infected HepG2-NTCP cells were used as cell models, and HBV replication, the syntheses of viral antigens and the magnitude of the covalently closed circular DNA (cccDNA) reservoir were used as indictors to test the anti-HBV effects of EGFR inhibitors erlotinib and gefitinib. Erlotinib inhibited HBV replication with a half-maximal inhibitory concentration of 1.05 μM. It also reduced the syntheses of viral antigens at concentrations of 2.5 μM or higher. The underlying mechanism was possibly correlated with its inhibition on STAT3 phosphorylation via up-regulation of suppressor of cytokine signaling 3. Gefitinib also inhibited HBV replication and antigen syntheses. Compared with the commonest antiviral drug entecavir, these EGFR inhibitors additionally reduced hepatitis B e antigen and erlotinib also marginally affected the cccDNA reservoir in HBV-infected HepG2-NTCP cells. Interestingly, these promising anti-HBV effects were significantly enhanced by extension of treatment duration. In conclusion, EGFR inhibitors demonstrated a comprehensive anti-HBV potential, highlighting a new strategy to cure HBV infection and suggesting animal model-related studies or clinical try in the future.

Haihe Gao,1 Lisha Li,2 Mang Xiao,3 Yongwei Guo,4 Yi Shen,5,6 Lixin Cheng,5 Ming Tang5 1Department of Otolaryngology Head and Neck Surgery, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2Department of Nursing, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo 315041, People’s Republic of China; 3Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Ophthalmology, University of Cologne, 50937, Cologne, Germany; 5Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, People’s Republic of China; 6Department of Otolaryngology Head and Neck Surgery, School of Medicine, Ningbo University, Ningbo 315211, People’s Republic of China Purpose: DKK1 is an antagonist of the Wnt signaling pathway that has various roles in human physiology. Notably, aberrant DKK1 expression is observed in several cancers. In this retrospective study, we assessed the association between DKK1 expression levels and head and neck squamous cell carcinoma (HNSCC) and its prognostic value.Materials and methods: Using RNA-seq data from HNSCC tumors (N=520) and adjacent normal tissue (N=44) in The Cancer Genome Atlas, we evaluated DKK1 expression levels. Additionally, we evaluated the association of DKK1 expression levels and pathophysiological features of patients with HNSCC and the value of DKK1 expression for prediction of overall survival (OS). We also explored the correlation between DKK1 expression and methylation of its promoter in HNSCC.Results: DKK1 expression was significantly upregulated in HNSCC compared with normal tissues. Moreover, DKK1 expression was significantly associated with smoking, alcohol abuse, sex, human papillomavirus status, tumor site, tumor invasion, and pathologic stage in HNSCC patients. Kaplan–Meier curves showed that high DKK1 expression was correlated with inferior OS. In addition, univariate and multivariate analyses showed that elevated DKK1 expression was an independent prognostic factor for poor OS (HR: 1.85, 95% CI: 1.31–2.62, P

Meng Xiao,1,2 Sharon C–A Chen,3 Fanrong Kong,3 Xin Fan,2,4 Jing-Wei Cheng,1,2 Xin Hou,1,2 Meng-Lan Zhou,1,2 He Wang,1,2 Ying-Chun Xu1,2 On behalf of the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study Group 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; 2Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, China; 3Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, University of Sydney, Sydney, NSW, Australia; 4Department of Infectious Diseases and Clinical Microbiology, Beijing Chaoyang Hospital, Beijing, China Purpose: In this study, we report results from a 5-year surveillance for noncandidal yeast species causing invasive infections from 65 hospitals in China.Materials and methods: Species identification was carried out by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) supplemented by rDNA sequencing, and fluconazole and voriconazole susceptibilities of yeasts were determined by Clinical and Laboratory Standards Institute (CLSI) disk diffusion methods.Results: Overall, 884 noncandidal isolates belonging to 38 species were collected. Cryptococcus neoformans was the most common (75.6%), which also comprised 96.5% of the isolates from cerebrospinal fluid (CSF) and 62.6% from blood, followed by Trichosporon asahii (6.9%) and Rhodotorula mucilaginosa (5.1%). Fluconazole susceptibility and resistant rates were 74.1% and 9.7% for C. neoformans and 81.0% and 5.2% for T. asahii. Voriconazole exhibited good activity in comparison to these two species (99.5% and 98.3% of the isolates, were susceptible). However, 100% of the R. mucilaginosa isolates were resistant to both azoles. Other noncandidal yeast species showed reduced susceptibility to fluconazole (53.3%) but most were susceptible to voriconazole (94.3%). Over the 5 years, a decrease in the proportion of fluconazole-susceptible isolates was observed for C. neoformans (90%–67%, P

Yi Zhu,1,* Han Wu,2,* Ming Qi,3 Sheng Wang,4 Qin Zhang,1 Li Zhou,1 Shiyan Wang,5 Wei Wang,6 Ting Wu,6 Ming Xiao,7 Siyu Yang,8 Hong Chen,9 Ling Zhang,4 Kathryn Chu Zhang,10 Jinhui Ma,11,12 Tong Wang1 1Rehabilitation Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; 2Rehabilitation Department, Nanjing Drum Tower Hospital, The Affiliated Hospital of the Medical School at Nanjing University, Nanjing, Jiangsu, China; 3Radiology Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; 4Rehabilitation Department, Suzhou Science and Technology Town Hospital, Suzhou, Jiangsu, China; 5Rehabilitation Department, Zhejiang Province Hospital, Hangzhou, Zhejiang, China; 6Neurological Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; 7Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, China; 8Neurological Department, The Second Affiliated Hospital of Wan’nan Medical College, Wuhu, Anhui, China; 9Department of Physical Diagnosis, Nanjing Brain Hospital, Nanjing, Jiangsu, China; 10Dalla Lana School of Public Health, University of Toronto, ON, Canada; 11School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada; 12Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada *These authors contributed equally to this work Background: Mild cognitive impairment (MCI) is known as a transitional stage or phase between normal aging and dementia. In addition, it is associated with an increased risk of dementia. Research has shown that moderate-intensity exercise is associated with a decreased risk of cognitive impairment. Two recent studies demonstrated that dance interventions are associated with improved cognitive function in the elderly with MCI.Purpose: We evaluated the effect of a moderate-intensity aerobic dance routine on the cognitive function in patients with MCI.Patients and methods: This is a single-blind randomized controlled trial. Sixty MCI patients were randomized to receive either treatment (aerobic dance routine + usual care) or control (usual care only) for 3 months. All patients received usual care for an additional 3 months thereafter. The aerobic dance routine was a specially designed dance routine which involved cognitive effort for patients to memorize the complex movements. Wechsler memory scale-revised logical memory (WMS-R LM) and event-related evoked potentials (ERPs) P300 latency were used to assess patients’ cognitive function at baseline, 3 months, and 6 months.Results: Twenty-nine patients received exercise therapy and 31 patients received usual care. Patients in the treatment group showed a greater improvement in memory (difference in WMS-R LM changes over 3 months 4.6; 95% CI 2.2, 7.0; p