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Mingtang Zeng,1,* Maozhu Liu,2,* Xuelin Tao,1,* Xi Yin,1 Chao Shen,1 Xueyan Wang1 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueyan Wang, Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email wxy1226@126.comAbstract: Inflammation involves complex immune responses where cytokines such as TNF-α, IL-1, and IL-6 promote vasodilation and increased vascular permeability to facilitate immune cell migration to inflammation sites. Persistent inflammation is linked to diseases like cancer, arthritis, and neurodegenerative disorders. Although oral anti-inflammatory drugs are favored for their non-invasiveness and cost-effectiveness, their efficacy is often compromised due to gastrointestinal degradation and limited bioavailability. Recent advancements highlight the potential of extracellular vesicles (EVs) as nanocarriers that enhance drug delivery by encapsulating therapeutic agents, ensuring targeted release and reduced toxicity. These EVs, derived from dietary sources and cell cultures, exhibit excellent biocompatibility and stability, presenting a novel approach in anti-inflammatory therapies. This review discusses the classification and advantages of orally administered EVs (O-EVs), their mechanism of action, and their emerging role in treating inflammatory conditions, positioning them as promising vectors in the development of innovative anti-inflammatory drug delivery systems.Keywords: extracellular vesicles, anti-inflammatory, drug delivery systems, food, oral administration

Qichang Gao,1 Yiming Ma,1 Tuo Shao,1 Xiaoxuan Tao,2 Xiansheng Yang,1 Song Li,1 Jiaao Gu,1 Zhange Yu1 1Department of Spinal Surgery, The 1st Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Department of Radiotherapy, The 3st Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of ChinaCorrespondence: Zhange Yu, Email yuzhange1967@163.comBackground: Progress in research on expression profiles in osteoarthritis (OA) has been limited to individual tissues within the joint, such as the synovium, cartilage, or meniscus. This study aimed to comprehensively analyze the common gene expression characteristics of various structures in OA and construct a diagnostic model.Methods: Three datasets were selected: synovium, meniscus, and knee joint cartilage. Modular clustering and differential analysis of genes were used for further functional analyses and the construction of protein networks. Signature genes with the highest diagnostic potential were identified and verified using external gene datasets. The expression of these genes was validated in clinical samples by Real-time (RT)-qPCR and immunohistochemistry (IHC) staining. This study investigated the status of immune cells in OA by examining their infiltration.Results: The merged OA dataset included 438 DEGs clustered into seven modules using WGCNA. The intersection of these DEGs with WGCNA modules identified 190 genes. Using Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest algorithms, nine signature genes were identified (CDADC1, PPFIBP1, ENO2, NOM1, SLC25A14, METTL2A, LINC01089, L3HYPDH, NPHP3), each demonstrating substantial diagnostic potential (areas under the curve from 0.701 to 0.925). Furthermore, dysregulation of various immune cells has also been observed.Conclusion: CDADC1, PPFIBP1, ENO2, NOM1, SLC25A14, METTL2A, LINC01089, L3HYPDH, NPHP3 demonstrated significant diagnostic efficacy in OA and are involved in immune cell infiltration.Keywords: osteoarthritis, machine learning, immune cells infiltration, diagnostic model

Yinfeng Wang, Xiaogen Tao, Peng Jin Department of Intensive Care Unit, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of ChinaCorrespondence: Xiaogen Tao; Peng Jin, Department of Intensive Care Unit, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, People’s Republic of China, Email taoxgg@ustc.edu.cn; jinpeng1986@ustc.edu.cnBackground: This study examines the clinical outcomes and prognostic factors of COVID-19 in renal transplant recipients. Given their immunosuppressed status, these patients are at higher risk of severe complications from COVID-19. The study aims to provide healthcare professionals with critical insights for diagnosing and managing this vulnerable population.Patients and methods: This retrospective cohort study included adult renal transplant recipients diagnosed with COVID-19. Data on demographics, medical history, laboratory results, and patient outcomes were analyzed to identify clinical characteristics and prognostic factors.Results: This study included 115 renal transplant recipients with COVID-19, predominantly male, with a mortality rate of 10.4% (12 deaths). The overall vaccination rate was 20%. Univariate analysis showed significant differences between survivors and non-survivors in initial serum creatinine levels, and percentages of neutrophils, monocytes, and lymphocytes, along with CRP levels on day 3. Additionally, CRP levels, hemoglobin, and platelet counts on day 7 also differed significantly. Multivariate analysis identified CRP levels on days 3 and 7, day 7 hemoglobin and platelet counts, and concurrent bacterial infections as independent risk factors for mortality.Conclusion: Elevated CRP levels, renal impairment, and bacterial co-infections play a significant role in the outcomes of COVID-19 in kidney transplant recipients. This study highlights the importance of monitoring these factors for early identification and management of high-risk patients.Keywords: COVID-19, renal transplant recipients, clinical outcomes, prognostic factors, immunosuppression

Meihua He,1– 5,* Mingqiang Liu,1– 5,* Xiaohua Tao1– 5,* 1Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi Provincial Clinical Research Center For Skin Diseases, Nanchang, Jiangxi, People’s Republic of China; 3Candidate Branch of National Clinical Research Center for Skin Diseases, Nanchang, Jiangxi, People’s Republic of China; 4Dermatology Institute of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China; 5The Affiliated Dermatology Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohua Tao, Department of Dermatology, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, 330001, People’s Republic of China, Tel +86 15979086756, Fax +86-0791-85207512, Email taoxiaohua@126.comPurpose: Verruciform xanthoma (VX) is a rare, chronic, and benign lesion affecting the skin and mucous membranes. We reported a case of VX in the vulva of a female child.Patients and Methods: A 12-year-old female had vulvar lesions for over 10 years without any discomfort. Physical examination revealed red lobulated patches on the left labia majora with a few scales attached to the surface. Histopathological examination indicated excessive and incomplete keratinization, hypertrophic spinous layer hyperplasia, neutrophil infiltration in the epidermis, and foam-like tissue could be seen in the dermal papilla. Lymphocyte-dominated inflammatory cell infiltration was scattered around the blood vessels. Immunohistochemical results showed positive CD68.Results: The final diagnosis confirmed the presence of VX.Conclusion: Surgical intervention proved successful in achieving favorable outcomes for the patient.Plain Language Summary: Verruciform xanthoma (VX) is a rare and non-cancerous skin condition that usually appears in the mouth but can occur on the genitals. In this case, a 12-year-old girl had red, warty lesions on her left labia majora for over 10 years. The cause of VX is not well understood but may be linked to inflammation, trauma, or immune disorders rather than lipid metabolism. The girl’s condition was confirmed through a biopsy, and she underwent surgical removal with no recurrence after a year. VX in the genital area is known as Vegas xanthomas. Though VX can look like other skin issues, a detailed examination of tissue samples is crucial for an accurate diagnosis. Treatment options include surgery, laser therapy, or topical creams. While VX is generally benign, seeking medical attention is important to rule out other concerns.Keywords: verruciform xanthoma, labia, child, diagnose, treatment

Yan Teng, Mingyang Ren, Xianhong Yang, Wei Lu, Xiaohua Tao Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of ChinaCorrespondence: Xiaohua Tao, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China, Tel +86-13505811700, Email taoxiaohua@hmc.edu.cnBackground: Mucous membrane pemphigoid (MMP), a rare autoimmune vesiculous and erosive disorder, may affect multiple mucous membranes, with the oral cavity being the most commonly affected site. Its treatment depends on the site(s) of mucosal involvement and disease severity.Patients and Methods: A 62-year-old female patient with MMP that predominantly involved the oral cavity strongly rejected systemic corticosteroid or immunosuppressive agents and was successfully treated with abrocitinib, a highly selective JAK-1 inhibitor with a good safety profile.Results: The case demonstrated good efficacy and safety profile of abrocitinib for the treatment of MMP with predominant oral involvement.Conclusion: Abrocitinib is a promising agent for the treatment of MMP with oral involvement.Keywords: abrocitinib, mucous membrane pemphigoid, JAK inhibitor

Abstract Phenotypic degeneration in Cordyceps militaris poses a significant concern for producers, yet the mechanisms underlying this phenomenon remain elusive. To address this concern, we isolated two strains that differ in their abilities to form fruiting bodies. Our observations revealed that the degenerated strain lost the capacity to develop fruiting bodies, exhibited limited radial expansion, increased spore density, and elevated intracellular glycerol levels. Transcriptome reanalysis uncovered dysregulation of genes involved in the MAPK signaling pathway in the degenerate strain. Our RT-qPCR results demonstrated reduced expression of sexual development genes, along with upregulation of genes involved in asexual sporulation, glycerol synthesis, and MAPK regulation, when compared to the wild-type strain. Additionally, we discovered that osmotic stress reduced radial growth but increased conidia sporulation and glycerol accumulation in all strains. Furthermore, hyperosmotic stress inhibited fruiting body formation in all neutralized strains. These findings indicate dysregulation of the MAPK signaling pathway, the possibility of the activation of the high-osmolarity glycerol and spore formation modules, as well as the downregulation of the pheromone response and filamentous growth cascades in the degenerate strain. Overall, our study sheds light on the mechanisms underlying Cordyceps militaris degeneration and identifies potential targets for improving cultivation practices.

Gongxin Yang,1,* Jikai Xia,2,* Xiaoqing Dai,1,* Hongbo Zhao,1 Weiqing Gao,1 Weilong Ding,1 Xiaofeng Tao,1 Ling Zhu1 1Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, People’s Republic of China; 2Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, 264100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaofeng Tao; Ling Zhu, Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, People’s Republic of China, Email cjr.taoxiaofeng@vip.163.com; zhuling011@126.comIntroduction: Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy.Methods: Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO).Results: The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T1-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T1-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells.Conclusion: Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis. Keywords: multi-crystalline manganese oxide, MRI contrast agent, tumor targeting, tumor selectivity, accurate diagnosis

Zhipeng Wang,1,* You Yin,2,* Yuhui Mu,1,3,* Lili Cui,1 Xinhua Song,1 Jianhua Zhuang,2 Shouhong Gao,1 Xia Tao,1 Wansheng Chen1 1Department of Pharmacy, Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai, 200003, People’s Republic of China; 2Department of Neurology, Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai, 200003, People’s Republic of China; 3College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, 650500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianhua Zhuang, Department of Neurology, Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), No. 415, Fengyang Road, Shanghai, 200003, People’s Republic of China, Email jianhuazh11@126.com Xia Tao, Department of Pharmacy, Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), No. 415, Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel/Fax +86– 21– 81886191, Email taoxia@smmu.edu.cnObjective: This study aims to explore the mechanism underlying the induction of phlebitis by aescinate and create an early-warning model of phlebitis based on metabolomics.Methods: Patients with cerebral infarction enrolled had been treated with aescinate. Plasma samples were collected either before administration of aescinate, upon the occurrence of phlebitis, or at the end of treatment. Non-targeted metabolomics and targeted amino acid metabolomics were carried out to analyze metabolic profiles and quantify the metabolites.Results: Untargeted metabolomics revealed six differential metabolites in baseline samples versus post-treatment samples and four differential metabolites in baseline samples from patients with or without phlebitis. Pathways of these differential metabolites were mainly enriched in amino acid metabolism. Ten differential amino acids with a VIP value of > 1 were identified in the baseline samples, enabling us to distinguish between patients with or without phlebitis. A logistic regression model was constructed (AUC 0.825) for early warning of phlebitis of grade 2 or higher.Conclusion: The occurrence of aescinate-induced phlebitis, which can be predicted early during onset, may be associated with perturbations of the endogenous metabolic profile, especially the metabolism of amino acids. Keywords: aescinate, diagnostic model, mechanism, metabolomics, phlebitis

Ying Zhou,1 Zhixian Luo,1 Mengying Yu,1 Chenyi Zhan,1 Haoli Xu,1 Ru Lin,1 Shuying Bian,1 Yunjun Yang,2,3 Zhenghao Jiang,4 Xinyi Tao,4 Zusen Ye,5 Meihao Wang,1 Dongqin Zhu2 1Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Nuclear, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Key Laboratory of Novel Nuclide Technologies on Precision Diagnosis and Treatment & Clinical Transformation of Wenzhou, Wenzhou, People’s Republic of China; 4The First School of Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Dongqin Zhu, Department of Nuclear, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China, Tel +86 0577 55579667, Email zhudongqin96@163.comObjective: Post-stroke hyperglycemia as a common phenomenon is associated with unfavorable outcomes. Focusing on admission hyperglycemia, other markers of dysglycemia were overlooked. This study aimed to explore the contribution of acute phase blood glucose levels in combination with other radiological signs to the prognostication of functional outcomes in patients with spontaneous intracerebral hemorrhage (sICH).Methods: Consecutive patients with sICH with at least five random plasma glucose measurements and complete radiological data during hospitalization were included. We calculated the average, maximum, minimum, standard deviation, and coefficient of variation of blood glucose levels for each patient. Radiological data, including island, black hole, blend, and satellite signs were collected. Functional outcomes were evaluated using the Barthel index. Unfavorable outcomes were defined as a Barthel index score ≤ 60. Univariate and multivariate analyses were performed to identify independent predictors of unfavorable outcomes.Results: Two hundred and thirty-eight patients (mean age 58.5, 163 men and 75 women) were included, and 71 had a history of diabetes. Unfavorable outcomes occurred in 107 patients (45.0%) at 3 months. Multivariate logistic regression analysis demonstrated that maximum blood glucose levels (odds ratio, 1.256; 95% confidence interval, 1.124‒1.404; p < 0.001) and island sign (odds ratio, 2.701; 95% confidence interval, 1.322‒5.521; p = 0.006) were independent predictors of unfavorable outcomes in the nondiabetic group. Meanwhile, patients without diabetes who experienced hematoma expansion had higher average (p = 0.036) and maximum blood glucose levels (p = 0.014).Interpretation: Maximum blood glucose levels and island sign were independently associated with unfavorable outcomes in patients without diabetes, whereas no glycemic variability indices were associated with unfavorable outcomes. Glucose levels influenced hematoma expansion and functional outcomes, particularly in patients without diabetes with sICH. Thus, clinical management of blood glucose levels should be strengthened for patients with sICH with or without a history of diabetes.Keywords: spontaneous intracerebral hemorrhage, glycemic variability, functional outcomes, island sign, diabetes

Mingyang Ren,1 Xianhong Yang,2 Yan Teng,2 Wei Lu,2 Yang Ding,2 Xiaohua Tao2 1Department of Graduate School, Bengbu Medical College, Bengbu, People’s Republic of China; 2Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, People’s Republic of ChinaCorrespondence: Xiaohua Tao, Email txhtxh@sina.comAbstract: Granulomatous rosacea (GR) is a rare inflammatory skin disease characterized by persistent, hard, yellow, brown, red, or flesh-colored papules, plaques, or nodules on the face. Limited data are available on patients treated for GR, with only case reports and case series published. Herein, we describe the case of a 53-year-old woman who presented to the hospital with persistent red to brown and pink patches on both cheeks accompanied by a burning sensation for one month. Histopathological examination of a cutaneous biopsy revealed granulomatous inflammation in focal areas. Both acid-fast and Periodic acid-Schiff staining were negative. The patient was diagnosed with GR based on her clinical presentation and laboratory test results. She was treated with abrocitinib, a JAK-1 inhibitor, for 20 weeks. This resulted in substantial improvement in her rash and the associated burning sensation. Subsequent follow-up visits indicated no adverse effects or relapses. Additionally, a literature review was conducted to compare with the current case, which concluded that abrocitinib is a viable treatment option for GR, exhibiting a relatively high safety profile with minimal side effects.Keywords: JAK inhibitor, granulomatous rosacea, abrocitinib, efficacy

Bingyan Ren,1,&ast; Hanbin Ye,2,&ast; Wenyuan Shan,3 Xuelei Tao,4 Zi Ye2 1Department of Emergency, the Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, Nantong, People’s Republic of China; 2Department of Neurosurgery, the Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, Nantong, People’s Republic of China; 3Department of Neurosurgery, the Fourth Affiliated Hospital of Nantong University, Nantong Fourth People’s Hospital, Nantong, People’s Republic of China; 4Department of Neurosurgery, Nantong Second People’s Hospital, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zi Ye, Department of Neurosurgery, the Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, No. 6 of North of Haierxiang Road, Hepingqiao District, Nantong, 216000, People’s Republic of China, Email yezileafff@126.com Xuelei Tao, Department of Neurosurgery, Nantong Second People’s Hospital, No. 43 of Xinglong Road, Nantong, 100730, People’s Republic of China, Email xueleitaonshxzh@126.comObjective: To examine the impact of hyperbaric oxygen intervention on oxidative stress and nerve growth factor in patients with craniocerebral injury.Methods: Using the random number table method, 40 patients with craniocerebral injury who were treated at the First People’s Hospital of Nantong were randomly assigned to either the control group or the hyperbaric oxygen group, with 20 patients in each group. The control group received routine intervention for clinical traumatic brain injury, while the hyperbaric oxygen group received additional hyperbaric oxygen intervention during the 7 to 30 days of routine intervention. Indicators of oxidative stress and nerve growth factor levels were compared between the two groups at the time of admission and 30 days after therapy.Results: The serum levels of superoxide dismutase, endothelium-derived relaxing factor—nitric oxide, and nerve growth factor in the hyperbaric oxygen group increased more significantly than in the control group. The serum malondialdehyde concentration was also significantly reduced in the hyperbaric oxygen group.Conclusion: Hyperbaric oxygen intervention can successfully lower systemic oxidative stress response and increase the expression level of nerve growth factor in patients with craniocerebral injury.Keywords: craniocerebral injury, hyperbaric oxygen, nerve growth factor, oxidative stress

Yan Teng,1,&ast; Mingyang Ren,2,&ast; Yang Ding,1 Xianhong Yang,1 Yibin Fan,1 Xiaohua Tao1 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Graduate School of Clinical Medicine, Bengbu Medical School, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohua Tao; Yibin Fan, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang provincial people’s hospital, People’s Hospital of Hangzhou Medical College, Tel +86-13505811700 ; +86-18806538451, Email taoxiaohua@hmc.edu.cn; fanyibin@hmc.edu.cnAbstract: Perioral dermatitis (POD) is a chronic inflammatory skin disease that primarily affects females between the ages of 16 and 45. Conventional therapies face the challenge of limited efficacy and a high recurrence rate. In this report, we present the case of a 26-year-old male patient with POD who was successfully treated using the Janus kinase (JAK) inhibitor, abrocitinib. This treatment exhibited both good efficacy and safety. Abrocitinib, as a JAK inhibitor, holds promise as a potential therapy for cases of POD that might be resistant to conventional therapies.Keywords: JAK inhibitors, abrocitinib, perioral dermatitis

Yan Teng,1,&ast; Huiting Zhong,2,&ast; Xianhong Yang,1 Xiaohua Tao,1,&ast; Yibin Fan1,&ast; 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Department of Dermatology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yibin Fan; Xiaohua Tao, Center for plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Tel +86-18806538451 ; +86-13505811700, Email fanyibin@hmc.edu.cn; taoxiaohua@hmc.edu.cnAbstract: Atopic dermatitis (AD) in the elderly has recently emerged as a distinct subgroup of AD, garnering widespread concern due to its increasing global incidence rate. Epidermal barrier dysfunction, inflammatory response, and chronic pruritus interact with each other, contributing to the pathogenesis and pathophysiology of AD in the elderly. Although fundamental medications are essential for managing AD in the elderly, older adults often struggle with regular usage of moisturizing emollients, topical medications, and avoidance of environmental triggers, leading to recurrent or even exacerbated disease progression. Therefore, a systematic medication approach is necessary to control pruritus and skin lesions. Traditional systemic treatments may not adequately meet the treatment needs of moderate and severe AD in the elderly and may even pose certain safety risks. Biologics and Janus kinase (JAK) inhibitors, exhibiting excellent clinical efficacy, have made significant breakthroughs in AD treatment. Existing evidence suggests that dupilumab, a human monoclonal IgG4 antibody, has been confirmed as an effective and safe first-line systematic treatment for moderate to severe AD in the elderly, with no notable differences between adults and the elderly. However, the limited inclusion of elderly patients in related clinical studies hinders the generalizability of these findings. As older patients face a higher risk of adverse events with JAK inhibitors, JAK inhibitors are recommended when no other suitable treatment options are available. Obtaining population-specific data is crucial for making evidence-based treatment choices when managing AD in older adults with JAK inhibitors.Keywords: atopic dermatitis in the elderly, treatments, biologics, JAK inhibitors

Xianhong Yang,1 Yunlin Ren,1,2 Huachu Liu,1,3 Yan Ten,1 Yang Ding,1 Shasha Fan,1 Xiaohua Tao,1 Wei Lu1 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, 310014, People’s Republic of China; 2Department of Dermatology and Venereology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Dermatology and Venereology, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Zhong Shan Hospital), Hangzhou, 310009, People’s Republic of ChinaCorrespondence: Xiaohua Tao; Wei Lu, Email txhtxh@sina.com; miniluwei@163.comAbstract: We report a case of 32-year-old patient who presented with painless erythematous plaque gradually ulcerated for 9 years. He had a history of pulmonary tuberculosis 12 years ago and was cured by the treatment of 2HRZE/4HR. The laboratory examination of t-spot and PPD skin test was positive. Histopathology examinations of left cervical lymph node as well as skin revealed granulomatous inflammation with caseous necrosis. A diagnosis of scrofuloderma was made. Negative sputum culture and chest CT scan results excluded pulmonary tuberculosis. The patient was treated with a standard antituberculosis therapy and recovered well after 5 months’ follow-up. Scrofuloderma is a rare manifestation of mycobacterial infection. Early diagnosis and treatment are very important.Keywords: case report, cutaneous tuberculosis, scrofuloderma, caseous necrosis

Yan Teng,1 Yibin Fan,1 Danying Shang,1 Xiaohua Tao,1,&ast; Dongsheng Sun2,&ast; 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Geriatric Medicine Center, Department of Geriatric Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Sun, Geriatric Medicine Center, Department of Geriatric Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Email sunds@163.com Xiaohua Tao, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China, Email taoxiaohua@hmc.edu.cnAbstract: Drug-induced alopecia areata is a rare adverse event wherein medications such as antimicrobials, anticonvulsants, and biologics, trigger the premature transition of actively growing hairs into the telogen phase. Herein, a unique case of alopecia universalis observed during a clinical trial involving sacubitril/alisartan, a novel angiotensin receptor-neprilysin inhibitor (ARNI) has been reported. This case contributes to the range of cutaneous reactions that might be observed in association with ARNI therapy.Keywords: alopecia universalis, sacubitril/alisartan, angiotensin receptor-neprilysin inhibitor

Yan Teng,1,&ast; Hui Tang,2,&ast; Yong Yu,1 Yibin Fan,1 Xiaohua Tao,1 Danfeng Xu1 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Danfeng Xu; Xiaohua Tao, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, 158 Shangtang Road, Gongshu District, Hangzhou, 310014, People’s Republic of China, Tel +86-13567122384 ; +86-13505811700, Email 3100102508@zju.edu.cn; taoxiaohua@hmc.edu.cnBackground: There is limited literature on AD with a predominant involvement of nipple among the adult male group. SARS-CoV-2 infection might have been an exacerbating factor of AD by initiating the “cytokine storm”. Conventional treatment suffers from a dilemma of poor efficacy and a high recurrence. The JAK inhibitors have been clinically applied to treat the AD with a good outcome.Patients and Methods: We present a case of a 28-year-old male AD patient with a predominant nipple involvement successfully treated with JAK inhibitor abrocitinib, with no adverse affects.Results: The case shows a good clinical efficacy of JAK inhibitor abrocitinib in the treatment of AD with a predominant nipple involvement during the COVID-19 pandemic with a rapid and long-term symptomatic relief.Conclusion: JAK inhibitor abrocitinib might become a promising agent for the treatment with AD with a predominant uncommon region like nipple that might be resistant to conventional therapies during the COVID-19 pandemic.Keywords: atopic dermatitis, nipple and areola, JAK inhibitors, abrocitinib, COVID-19

Yan Xie,1 Wenni Zhou,1 Xiang Tao,2 Hui Lv,3 Zhongping Cheng1 1Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 2Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200090, People’s Republic of China; 3SG+ Bio-Testing Inc, Shanghai, 200093, People’s Republic of ChinaCorrespondence: Zhongping Cheng; Hui Lv, Email mdcheng18@tongji.edu.cn; lvhui@sgplus.cnObjective: Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common pregnancy complications that share some common risk factors. GDM patients are also at high risk for PE. There are no sensitive markers for prediction, especially for the occurrence of PE in GDM patients. This study investigated plasma proteins for the prediction of PE in GDM patients.Methods: A total of 10 PE, 10 GDM, and 5 PE complicated with GDM cases, as well as 10 pregnant controls without obvious complications, were included in the nested cohort. The proteomics in the plasma collected at 12– 20 weeks of gestational age (GA) were analyzed by liquid chromatography‒mass spectrometry/mass spectrometry. Some potential markers, such as soluble transferrin receptor (sTfR), ceruloplasmin (CP), apolipoprotein E (ApoE) and inositol 1,4,5-trisphosphate receptor 1 (ITPR1), were validated using enzyme-linked immunosorbent assays.Results: Functional analysis of the plasma showed that proteasome activation, pancreatic secretion, and fatty acid degradation were activated in the GDM group, and renin secretion-, lysosome-, and proteasome pathways involving iron transport and lipid metabolism were enriched in the PE group, distinguishing PE complicating GDM.Conclusion: Through proteomics analysis of plasma in early pregnancy, PE complicating GDM may have a unique mechanism from that of PE alone. Plasma sTfR, CP and ApoE levels have potential clinical applications in early screening.Keywords: gestational diabetes mellitus, preeclampsia, preeclampsia complicating gestational diabetes mellitus, proteomics, plasma biomarkers

Fengjun Xia,1,2,&ast; Xiaoyan Tao,2,3,&ast; Haichen Wang,1,2 Jian Shui,4 Changhang Min,1,2 Yubing Xia,1,2 Jun Li,1,2 Mengli Tang,1,2 ZhaoJun Liu,1,2 Yongmei Hu,1,2 Huidan Luo,1,2 Mingxiang Zou1,2 1National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 3Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China; 4Department of Clinical Laboratory, Changsha Central Hospital, Changsha, 410008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingxiang Zou, National Clinical Research Center for Geriatric Disorders, Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China, Tel/Fax +86-7384327440, Email zoumingxiang@csu.edu.cnPurpose: As an under-explored biomaterial, bacterial biofilms have a wide range of applications in the green synthesis of nanomaterials. The biofilm supernatant of Pseudomonas aeruginosa PA75 was used to synthesize novel silver nanoparticles (AgNPs). BF75-AgNPs were found to possess several biological properties.Methods: In this study, we biosynthesized BF75-AgNPs using biofilm supernatant as the reducing agent, stabilizer, and dispersant and investigated their biopotential in terms of antibacterial, antibiofilm, and antitumor activities.Results: The synthesized BF75-AgNPs demonstrated a typical face-centered cubic crystal structure; they were well dispersed; and they were spherical with a size of 13.899 ± 4.036 nm. The average zeta potential of the BF75-AgNPs was − 31.0 ± 8.1 mV. The BF75-AgNPs exhibited strong antibacterial activities against the methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase Escherichia coli (ESBL-EC), extensively drug-resistant Klebsiella pneumoniae (XDR-KP), and carbapenem-resistant Pseudomonas aeruginosa (CR-PA). Moreover, the BF75-AgNPs had a strong bactericidal effect on XDR-KP at 1/2 × MIC, and the expression level of reactive oxygen species (ROS) in bacteria was significantly increased. A synergistic effect was observed when the BF75-AgNPs and colistin were used for the co-treatment of two colistin-resistant XDR-KP strains, with fractional inhibitory concentration index (FICI) values of 0.281 and 0.187, respectively. Furthermore, the BF75-AgNPs demonstrated a strong biofilm inhibition activity and mature biofilm bactericidal activity against XDR-KP. The BF75-AgNPs also exhibited a strong antitumor activity against melanoma cells and low cytotoxicity against normal epidermal cells. In addition, the BF75-AgNPs increased the proportion of apoptotic cells in two melanoma cell lines, and the proportion of late apoptotic cells increased with BF75-AgNP concentration.Conclusion: This study suggests that BF75-AgNPs synthesized from biofilm supernatant have broad prospects for antibacterial, antibiofilm, and antitumor applications.Graphical Abstract: Keywords: multidrug resistant, green synthesis, colistin, metallic silver, melanoma

Yan Teng,1 Danfeng Xu,1 Xianhong Yang,1 Hui Tang,2 Xiaohua Tao,1 Yibin Fan,1,&ast; Yang Ding1,&ast; 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Ding; Yibin Fan, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China, Tel +86-13732261339 ; +86-13505811700, Email dingyang@hmc.edu.cn; taoxiaohua@hmc.edu.cnAbstract: Unlike apoptosis, pyroptosis, necroptosis, and ferroptosis are recently identified modes of programmed cell death (PCD) with unique molecular pathways. Increasing evidence has indicated that these PCD modes play a crucial role in the pathogenesis of various non-malignant dermatoses (a group of cutaneous disorders), including infective dermatoses, immune-related dermatoses, allergic dermatoses, benign proliferative dermatoses, etc. Moreover, their molecular mechanisms have been suggested as potential therapeutic targets for the prevention and treatment of these dermatoses. In this article, we aim to review and summarize the molecular mechanisms of pyroptosis, necroptosis, and ferroptosis and their roles in the pathogenesis of some non-malignant dermatoses.Keywords: pyroptosis, necroptosis, ferroptosis, molecular mechanisms, non-malignant dermatoses

Jiamin Wen,1 Jitian Weng,2 Wei Lu,3 Xiaohua Tao,3 Hao Cheng,4,&ast; Yi Tang3,&ast; 1Department of Dermatology, People’s Hospital of Tiantai County, Zhejiang University, Taizhou, People’s Republic of China; 2School of Public Health, Hangzhou Normal University, Zhejiang University, Hangzhou, People’s Republic of China; 3Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Zhejiang University Hangzhou 310014 People’s Republic of China; 4Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Tang, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Zhejiang University, 158 Shangtang Road, Xiacheng District, Hangzhou, 310014, People’s Republic of China, Tel +86-13968076453, Fax +86-0571-85335800, Email tangyi@hmc.edu.cn Hao Cheng, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, 310016, People’s Republic of China, Tel +86-13588706943, Fax +86-571-86006975, Email chenghao1@zju.edu.cnPurpose: To investigate the expression of Plasmacytoid Dendritic Cells (pDCs) and TLR7/9-MyD88-IRAKs pathway in chronic eczema lesions.Patients and Methods: Lesional tissues and the surrounding healthy tissues were collected from 25 individuals with chronic eczema, and immunohistochemistry was used to detect and comparatively analyze the expression profile of CD123, CD2AP, toll-like receptor 7 (TLR7), toll-like receptor 9 (TLR9) along with interleukin-1 receptor-associated kinase 1 (IRAK1) and interferon regulatory factor 7 (IRF7) in signaling pathways.Results: The positive rates of CD2AP + pDC and CD123 + pDC in lesional tissues were significantly elevated compared to the surrounding healthy tissues (P < 0.05). They were distributed in both the epidermal and dermal layers of the lesional tissue, but the majority were in the dermal layer. The TLR7, TLR9, IRAK1 and IRF7 were more expressed in dermal layers of the lesional tissue with higher positive rates of expression compared to the surrounding healthy tissues (P < 0.05). IRAK1 and IRF7 were expressed in a small amount in the epidermal layer with higher positive rates of expression than in the surrounding healthy tissues (P < 0.05), while the positive rates of TLR7 and TLR9 expression in the epidermal layer were not statistically different from those in the surrounding healthy tissues (P > 0.05).Conclusion: PDC and TLR7/9-MyD88-IRAKs pathways are actively expressed in chronic eczema lesions and may be involved in pathogenesis and disease progression.Keywords: eczema, plasmacytoid dendritic cells, toll-like receptor 7, toll-like receptor 9, immunohistochemistry

Yan Teng,1 Sujing Li,2 Hui Tang,2 Xiaohua Tao,1 Yibin Fan,1,&ast; Youming Huang1,&ast; 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youming Huang; Yibin Fan, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Tel +86-18368023136 ; +86-18806538451, Email huangyouming@hmc.edu.cn; fanyibin@hmc.edu.cnAbstract: Skin infections are common diseases for which patients seek inpatient and outpatient medical care. Globally, an increasing number of people are affected by skin infections that could lead to physical and psychological damage. Skin infections always have a broad spectrum of clinical presentations that require physicians to make an aggressive and accurate diagnosis for prescribing the proper symptomatic antimicrobials. In most instances, the treatment for skin infections mainly includes oral or topical anti-infective drugs. However, some of the classical anti-infective drugs have limitations, such as poor water solubility, low bioavailability, and poor targeting efficiency, which can lead to poor efficacy, adverse effects, and drug resistance. Therefore, research priorities should focus on the development of more effective drug delivery systems with new materials. Hydrogels are a highly multifunctional class of medical materials with potential applications in dermatology. Several hydrogel dressings with anti-infective functions have been formulated and demonstrated to improve the efficacy and tolerance of oral or topical classical anti-infective drugs to a certain degree. In this study, the medical applications of hydrogels for the treatment of various skin infections are systematically reviewed to provide an important theoretical reference for future research studies on the treatment options for skin infections.Keywords: hydrogel, dermatology, skin infections, anti-infective agent, drug delivery systems

Yan Teng, Youming Huang, Xu Danfeng, Xiaohua Tao,* Yibin Fan* Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yibin Fan; Xiaohua Tao, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Tel +86-18806538451 ; Tel +86-13505811700, Email fanyibin@hmc.edu.cn; txhtxh@sina.comAbstract: Solar ultraviolet radiation (UVR) is the primary pathogenetic factor in skin photoaging. It can disrupt cellular homeostasis by damaging DNA, inducing an inflammatory cascade, immunosuppression, and extracellular matrix (ECM) remodeling, resulting in a variety of dermatologic conditions. The skin microbiome plays an important role in the homeostasis and maintenance of healthy skin. Emerging evidence has indicated that highly diverse gut microbiome may also have an impact on the skin health, referred to as the gut-skin axis (GSA). Oral and topical probiotics through modulating the skin microbiome and gut-skin microbial interactions could serve as potential management to prevent and treat the skin photoaging by multiple pathways including reducing oxidative stress, inhibiting ECM remodeling, inhibiting the inflammatory cascade reaction, and maintaining immune homeostasis. In this review, the effects of oral and topical probiotics in skin photoaging and related mechanisms are both described systematically and comprehensively.Keywords: probiotics, skin photoaging, skin microbiome, gut-skin axis, ultraviolet radiation, reactive oxygen species, extracellular matrix

Qixian Sun,1 Xinrong Tao,1– 4 Bing Li,1 Hangbing Cao,1 Haoming Chen,1 Yuanjie Zou,1 Huihui Tao,1– 4 Min Mu,1– 4 Wenyang Wang,1 Keyi Xu1– 4 1Center for Medical Research, Medical School, Anhui University of Science and Technology, Huainan, People’s Republic of China; 2Key Laboratory of Industrial Dust Control and Occupational Health, Ministry of Education, Anhui University of Science and Technology, Huainan, People’s Republic of China; 3Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety, Anhui Higher Education Institutes, Anhui University of Science and Technology, Huainan, People’s Republic of China; 4Engineering Laboratory of Occupational Safety and Health, Anhui Province, Anhui University of Science and Technology, Huainan, People’s Republic of ChinaCorrespondence: Xinrong Tao, Medical School, Anhui University of Science and Technology, Huainan, People’s Republic of China, Email xrtao1116@hotmail.comBackground: Silicosis is a severe pulmonary disease caused by inhaling dust containing crystalline silica. The progression of silicosis to pulmonary fibrosis is usually unavoidable. Recent studies have revealed positivity for the overexpression of C-X-C chemokine receptor type 4 (CXCR4) in pulmonary fibrosis and shown that the CXCR4 inhibitor AMD3100 attenuated pulmonary fibrosis after bleomycin challenge and paraquat exposure. However, it is unclear whether AMD3100 reduces crystalline silica-induced pulmonary fibrosis.Methods: C57BL/6 male mice were instilled intranasally with a single dose of crystalline silica (12 mg/60 μL) to establish an acute silicosis mouse model. Twelve hours later, the mice were injected intraperitoneally with 5 mg/kg AMD3100 or control solution. Then, the mice were weighed daily and sacrificed on day 7, 14, or 28 to collect lung tissue and peripheral blood. Western blotting was also applied to determine the level of CXCR4, while different histological techniques were used to assess pulmonary inflammation and fibrosis. In addition, the level of B cells in peripheral blood was measured by flow cytometry.Results: CXCR4 and its ligand CXCL12 were upregulated in the lung tissues of crystalline silica-exposed mice. Blocking CXCR4 with AMD3100 suppressed the upregulation of CXCR4/CXCL12, reduced the severity of lung injury, and prevented weight loss. It also inhibited neutrophil infiltration at inflammatory sites and neutrophil extracellular trap formation, as well as reduced B-lymphocyte aggregates in the lung. Additionally, it decreased the recruitment of circulating fibrocytes (CD45+collagen I+CXCR4+) to the lung and the deposition of collagen I and α-smooth muscle actin in lung tissue. AMD3100 also increased the level of B cells in peripheral blood, preventing circulating B cells from migrating to the injured lungs.Conclusion: Blocking CXCR4 with AMD3100 delays pulmonary inflammation and fibrosis in a silicosis mouse model, suggesting the potential of AMD3100 as a drug for treating silicosis.Keywords: CXCR4, silicosis, pulmonary fibrosis, inflammation, AMD3100, mice

Jingchao Wei,1 Xiaohang Wu,2 Yuxiang Li,2 Xiaowu Tao,2 Bo Wang,2 Guangming Yin2 1Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of ChinaCorrespondence: Guangming Yin, Email yingm75@126.comBackground: Prostate cancer is a common malignancy in men. Radical prostatectomy is one of the primary treatment modalities for patients with prostate cancer. However, early identification of biochemical recurrence is a major challenge for post-radical prostatectomy surveillance. There is a lack of reliable predictors of biochemical recurrence. The purpose of this study was to explore potential biochemical recurrence indicators for prostate cancer.Materials and Methods: We analyzed transcriptomic data of cases with biochemical recurrence in The Cancer Genome Atlas (TCGA). Then, we performed integrative bioinformatics analyses to establish a biochemical recurrence predictor model of prostate cancer.Results: There were 146 differentially expressed genes (DEGs) between prostate cancer and normal prostate, including 12 upregulated and 134 downregulated genes. Comprehensive pathway enrichment analyses revealed that these DEGs were associated with multiple cellular metabolic pathways. Subsequently, according to the random assignment principle, 208 patients were assigned to the training cohort and 205 patients to the validation cohort. Univariate Cox regression analysis showed that 7 genes were significantly associated with the biochemical recurrence of prostate cancer. A model consisting of 5 genes was constructed using LASSO regression and multivariate Cox regression to predict biochemical recurrence of prostate cancer. Expression of PAH and AOC1 decreased with an increasing incidence of prostate cancer, whereas expression of DDC, LINC01436 and ORM1 increased with increasing incidence of prostate cancer. Kaplan–Meier curves and receiver operator characteristic (ROC) curves indicated that the 5-gene model had reliable utility in identifying the risk of biochemical recurrence of prostate cancer.Conclusion: This study provides a model for predicting prostate cancer recurrence after surgery, which may be an optional indicator for postoperative follow-up.Keywords: prostate cancer, biochemical recurrence, predictor, signature, follow-up

Accurate climate projections require an understanding of the effects of warming on ecological communities and the underlying mechanisms that drive them1–3. However, little is known about the effects of climate warming on the succession of microbial communities4,5. Here we examined the temporal succession of soil microbes in a long-term climate change experiment at a tall-grass prairie ecosystem. Experimental warming was found to significantly alter the community structure of bacteria and fungi. By determining the time-decay relationships and the paired differences of microbial communities under warming and ambient conditions, experimental warming was shown to lead to increasingly divergent succession of the soil microbial communities, with possibly higher impacts on fungi than bacteria. Variation partition- and null model-based analyses indicate that stochastic processes played larger roles than deterministic ones in explaining microbial community taxonomic and phylogenetic compositions. However, in warmed soils, the relative importance of stochastic processes decreased over time, indicating a potential deterministic environmental filtering elicited by warming. Although successional trajectories of microbial communities are difficult to predict under future climate change scenarios, their composition and structure are projected to be less variable due to warming-driven selection.

Luna Sun,1,2,&ast; Bin Yi,3,&ast; Xiao Pan,4,&ast; Lili Wu,1,2,&ast; Zhilei Shang,1,2,&ast; Yanpu Jia,1,2 Xiandong Tao,3 Feng Zhao,5 Weifen Xie,6 Zhuoer Sun,1,2 Yonghai Bai,4 Weizhi Liu1,2 1Lab for Post-Traumatic Stress Disorder, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2The Emotion & Cognition Lab, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Eastern Hepatobiliary Surgery Hospital, Shanghai; Department II of Infectious Disease, Huoshenshan Hospital, Wuhan, 430100, People’s Republic of China; 4Department of Medical Psychology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China; 5Hongkou District of Changhai Hospital, Naval Medical University, Shanghai, 200081, People’s Republic of China; 6Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhi LiuLab for Post-Traumatic Stress Disorder, Faculty of Psychology and Mental Health, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, People’s Republic of ChinaTel/Fax +86-21-81871671Email 13024141970@163.comYonghai BaiDepartment of Medical Psychology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of ChinaTel/Fax +86-21-81885057Email baiyonghai179@126.comBackground: The outbreak of COVID-19 has developed into a pandemic. Data are required that specifically address the psychological consequences in COVID-19 confirmed patients. This study mainly aimed to examine posttraumatic stress disorder (PTSD) symptoms and sleep quality among COVID-19 confirmed patients during hospitalization.Methods: An observational study was conducted in two designated hospitals in Wuhan, China. Data were collected from 190 patients hospitalized with laboratory-confirmed COVID-19 infection between February 10, 2020 and March 13, 2020.Results: The mean age of the 190 confirmed patients was 55.7 years (SD = 13.7), of which 96 (50.5%) were female and 88 (46.3%) had family members or acquaintances infected with COVID-19. Lymphocytopenia was presented in 62 (32.6%) patients and 25 (13.2%) patients showed oxygen desaturation. The prevalence of high PTSD symptoms was 22.6% among the 190 patients. The median time from symptom onset to first medical visit and hospitalization was 2 days (IQR, 1– 5) and 16 days (IQR, 10– 27), respectively. Patients’ PTSD symptoms were positively related to the time from symptom onset to first medical visit (r = 0.156, p < 0.05) and hospitalization (r = 0.181, p < 0.01). There were significant correlations between sleep quality and PTSD symptoms (r = 0.312– 0.547, p < 0.01).Conclusion: The prevalence of high PTSD symptoms was 22.6% among hospitalized COVID-19 patients. Early diagnosis and treatment of COVID-19 symptoms are beneficial to infected patients both physically and psychologically. With the recovery of physical symptoms, psychological intervention is desired to promote the trauma recovery in COVID-19 patients.Keywords: COVID-19, patients, psychological, PTSD, sleep quality

Jiuling Deng,1,&ast; Ying Ma,2,&ast; Yuqiong He,1,&ast; Hong Yang,2 Yanhong Chen,2 Liang Wang,1 Doudou Huang,1 Shi Qiu,1,&ast; Xia Tao,2 Wansheng Chen1 1Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wansheng ChenInstitute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaTel +64 021 81886182Email chenwansheng@shutcm.edu.cnXia TaoDepartment of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of ChinaTel +64 021 81886182Email taoxia2003@126.comPurpose: Isatis indigotica (Ii) is a cruciferous herb that is widely distributed in China, and its roots and leaves have been used in two renowned antipyretic detoxicate crude drugs in Chinese Pharmacopoeia, Radix (R) and Folium (F) Isatidis. However, the pharmacodynamic material basis and underlying mechanisms of the herbal efficacy remained to be elucidated.Methods: Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was adopted for the chemical profiling of R and F Isatidis. The active ingredients were screened out through the prediction of gastrointestinal absorption and druglikeness analysis using SwissADME. A herb-ingredient-target network was constructed through target prediction of the herbal active ingredients and anti-inflammation or anti-viral properties, followed by protein–protein interaction analysis. Then, the potential relevant signaling pathways were predicted by pathway enrichment. Finally, for verification, RAW 264.7 cell line was adopted to examine the anti-inflammatory and anti-viral activities of 6 representative ingredients in Ii.Results: Seventy-three compounds have been identified from Ii through UPLC-Q-TOF-MS. A total of 17 potential active ingredients were screened through pharmacokinetics and drug-likeness evaluation using SwissADME. It was shown that key targets might include TNF, AKT1, SRC, IL2, CASP9, and CASP3 in our herb-ingredient-target network, and isovitexin, a flavonoid, tended to participate in the inflammatory response, indoles were more likely to affect the cell proliferation processes, and lignans might have a broader affinity to key targets than the other active ingredients, such as regulating immune system (targeting IL-2) and PI3K-Akt signaling pathway. In vitro, indigo and secoisolariciresinol diglucoside markedly reduced TNF-α expression in Poly (I: C)-incubated cells. Isovitexin significantly inhibited TNF-α expression, and isatin treatment markedly reduced IL-1β expression in LPS-incubated cells.Conclusion: As the pharmacodynamics material basis of Ii, indoles, lignans, and flavonoids are believed to confer beneficial properties through various cellular aspects with multiple signaling pathways involved.Keywords: Isatis indigotica, UPLC-Q-TOF-MS, network analysis, bioassay analysis

Nonlinear wave-particle interaction during chorus wave generation was assumed to be in the adiabatic regime in previous studies, i.e., the particle phase-space trapping timescale (τtr) is considered to be much smaller than the nonlinear dynamics timescale τNL. In this work, we use particle-in-cell simulations to demonstrate that τtr∼τNL, i.e., the interaction regime during chorus generation is in the nonadiabatic regime. The timescale for nonlinear evolution of resonant particle phase-space structures is determined by making the time-averaged power exchange plot, which clearly demonstrates that particles with pitch angle near 80° make the most significant contribution to wave growth. The phase-space trapping timescale is also comparable to the amplitude modulation timescale of chorus, suggesting that chorus subpackets are formed because of the self-consistent evolution of resonant particle phase-space structures and spatiotemporal features of the fluctuation spectrum.

Menglei Zhang,1,2,* Fangyue Zhou,1,* Yuan He,3 Xiang Tao,4 Keqin Hua,1,2 Jingxin Ding1,2 1Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China; 2Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, People’s Republic of China; 3Public Health School of Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingxin DingDepartment of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, 128 Shen-Yang Road, Shanghai, 200011, People’s Republic of ChinaTel +86-13918206746Fax +86-21-63455090Email djxdd@sina.comPurpose: This study aimed to establish a predictive model for lymph node involvement (LNI) in patients with borderline ovarian tumor (BOT) using clinicopathological factors.Patients and Methods: We collected clinical data from consecutive patients who underwent lymphadenectomy for BOT between 2001 and 2018 and analyzed their clinicopathological features. Multivariate logistic regression was used to identify all independent risk factors associated with LNI; these were then incorporated into the prediction model.Results: In total, we included 248 patients with BOT who were undergoing lymphadenectomy. These were divided into a training cohort (n=174) and a validation cohort (n=74). When considering histopathological data, 16 and 5 patients were identified to have LNI in the training and validation cohorts, respectively. Overall, 13.5% (21/156) patients with serous BOT had LNI while 0% (0/92) patients with non-serous BOT had LNI. We identified several predictors of LNI: the largest tumor being ≥ 12.2cm in diameter, the presence of lesions on the ovarian surface, and the presence of pelvic or abdominal lesions. We created a prediction model and nomogram that incorporated these three risk factors for serous BOT. The model achieved good discriminatory abilities of 0.951 and 0.848 when predicting LNI in the training and validation cohorts, respectively. The LNI-predicting nomogram had an area under curve (AUC) of 0.951 and generated well-fitted calibration curves.Conclusion: Non-serous BOT may not require lymphadenectomy as part of surgical staging. The individual risk of LNI in patients with serous BOT can be accurately estimated using our prediction model and nomogram. The use of LNI criteria provides a practical way to support the clinician in making an optimal decision relating to surgical scope for patients with BOT.Keywords: lymph node involvement, borderline ovarian tumor, lymphadenectomy, prediction model, nomogram