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Zirui Bian,1,* Tianzhe Bao,2,* Xuequan Sun,3,4 Ning Wang,1 Qian Mu,5 Ting Jiang,6 Zhongxiang Yu,6 Junhang Ding,2 Ting Wang,7 Qihui Zhou2 1Department of Bone, Huangdao District Central Hospital, Qingdao, People’s Republic of China; 2Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 3Weifang Eye Institute, Weifang Eye Hospital, Zhengda Guangming Eye Group, Weifang, People’s Republic of China; 4Zhengda Guangming International Eye Research Center, Qingdao Zhengda Guangming Eye Hospital, Qingdao University, Qingdao, People’s Republic of China; 5Department of Biomaterials, LongScience Biological (Qingdao) Co, LTD, Qingdao, People’s Republic of China; 6Heart Center, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao University, Qingdao, People’s Republic of China; 7Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qihui Zhou; Junhang Ding, Tel +86-17660670299, Email qihuizhou@uor.edu.cn; dingjunhang@uor.edu.cnIntroduction: The emergence and rapid spread of multidrug-resistant bacteria (MRB) caused by the excessive use of antibiotics and the development of biofilms have been a growing threat to global public health. Nanoparticles as substitutes for antibiotics were proven to possess substantial abilities for tackling MRB infections via new antimicrobial mechanisms. Particularly, carbon dots (CDs) with unique (bio)physicochemical characteristics have been receiving considerable attention in combating MRB by damaging the bacterial wall, binding to DNA or enzymes, inducing hyperthermia locally, or forming reactive oxygen species.Methods: Herein, how the physicochemical features of various CDs affect their antimicrobial capacity is investigated with the assistance of machine learning (ML) tools.Results: The synthetic conditions and intrinsic properties of CDs from 121 samples are initially gathered to form the raw dataset, with Minimum inhibitory concentration (MIC) being the output. Four classification algorithms (KNN, SVM, RF, and XGBoost) are trained and validated with the input data. It is found that the ensemble learning methods turn out to be the best on our data. Also, ϵ-poly(L-lysine) CDs (PL-CDs) were developed to validate the practical application ability of the well-trained ML models in a laboratory with two ensemble models managing the prediction.Discussion: Thus, our results demonstrate that ML-based high-throughput theoretical calculation could be used to predict and decode the relationship between CD properties and the anti-bacterial effect, accelerating the development of high-performance nanoparticles and potential clinical translation. Keywords: carbon dots, machine learning, antibacterial, minimum inhibitory concentration, classification algorithms

Gang Chen,1 Qing Mu,1 Zhao-Ji Meng2 1Department of Respiratory and Critical Care Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Immune Allergy, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Gang Chen, Department of Respiratory and Critical Care Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, 7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Email chengangvips@163.comBackground: Dysregulation and pyroptosis of T-helper (Th) cells and inflammatory cytokines have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immune response mechanisms as a consequence of tobacco smoke exposure are not fully understood. We hypothesized that cigarette smoke-induced inflammation could be modulated through the cytokine milieu and T-cell nicotinic acetylcholine receptors (nAChRs).Methods: The proportions of peripheral blood Th1 and Th2 cells from patients with COPD, smokers without airway obstruction and healthy nonsmokers were analyzed using flow cytometry. The levels of plasma proinflammatory cytokines and their potential association with pulmonary function were also measured. The influence of cigarette smoke extract (CSE) on the conditioned differentiation of T helper cell subsets was further examined in vitro.Results: Significantly higher Th1 cell and plasma IFN-γ and IL-18 levels but lower levels of Th2 cells were found in the peripheral blood from patients with COPD. The increased plasma levels of IFN-γ and IL-18 were negatively correlated with pulmonary function (FEV1% predicted value). Pyroptosis participates in COPD development probably through the activation of the NLRP3 inflammasome upon exposure to CSE. CSE does not directly induce the differentiation of T helper cells; however, under conditioned medium, CSE promotes Th1 development through α 7 nAChR modification, while it does not substantially interfere with Th2 differentiation.Conclusion: The differences in the cytokine milieu play a key role in the effects of CSE on the immune response in patients with COPD.Keywords: chronic obstructive pulmonary disease, COPD, cigarette smoke, T helper 1, Th1 cells, Th2, nicotinic acetylcholine receptors, nAChRs

Xigetu He,1,* Bailing Wang,1,* Xiujuan Jia,1 Yanfei Li,2 Hongxia Yan,1 Qiri Mu,1 Shana Chen3 1Department of Dermatology, International Mongolian Hospital of Inner Mongolia, Hohhot, 010020, People’s Republic of China; 2Department of Dermatology, The First Hospital of Hohhot, Hohhot, 010010, People’s Republic of China; 3Department of Hematology, International Mongolian Hospital of Inner Mongolia, Hohhot, 010020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiri Mu, Department of Dermatology, International Mongolian Hospital of Inner Mongolia, China, 83 University East Street, Hohhot, Inner Mongolia, People’s Republic of China, Email muqiri28@163.com Shana Chen, Department of Hematology, International Mongolian Hospital of Inner Mongolia, 83 University East Street, Hohhot, Inner Mongolia, People’s Republic of China, Email csnxyk@163.comAbstract: Facial flushing is one of the common conditions in dermatology, which affects the aesthetic of patients to a great extent, and even leads to psychological and economic burdens. The most common causes of facial flushing are often inflammatory skin diseases such as rosacea, contact dermatitis, and others, but the facial flushing as a sign can also be the cutaneous manifestation of systemic disease. Telangiectasia macularis eruptiva perstans (TMEP) is a rare disease associated with mast cells. Here, we describe an unusual clinical finding with persistent facial flushing in a patient with TMEP.Keywords: facial flushing, telangiectasia macularis eruptiva perstans, cutaneous mastocytosis, dermoscopy, mast cells

Tegexibaiyin Wang,1,* Fen Liu,2,* Xiujuan Jia,3 Jing Tan,3 Baopeng Qi,4 Jingxue Guo,4 Qiri Mu,3 Hong Zhang5 1Laboratory of Pharmacy, International Mongolian Hospital of Inner Mongolia, Hohhot, 010065, People’s Republic of China; 2Department of Intensive Care Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, People’s Republic of China; 3Department of Dermatology, International Mongolian Hospital of Inner Mongolia, Hohhot, 010020, People’s Republic of China; 4Inner Mongolia Medical University, Hohhot, 010010, People’s Republic of China; 5Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiri Mu, Department of Dermatology, International Mongolian Hospital of Inner Mongolia, 83 University East Street, Hohhot, Inner Mongolia, 010020, People’s Republic of China, Email muqiri28@163.com Hong Zhang, Department of Pediatrics, Qilu Hospital, Shandong University, 107 Wenhua West Road, Jinan, 250012, People’s Republic of China, Email zhanghong681011@163.comBackground: The biomarker to predict the depression in patients with rosacea was absent.Objective: We aimed to explore the potential association between BDNF and depression in patients with rosacea, and also to determine whether serum BDNF level is a potential biomarker for identifying depression in patients with rosacea.Methods: The patients with rosacea, rosacea with depression and healthy control were included, clinical evaluation (DLQI, RSSs, BDI-II) and serum BDNF levels detection were performed on subjects, the comparisons and correlation analysis of the obtained data were performed.Results: In clinical evaluation, whether DLQI or RSSs, rosacea with depression group was significantly higher compared to rosacea group. Besides, we found the serum BDNF levels were lower in patients with rosacea and rosacea with depression compared to healthy controls, also in the rosacea with depression group, serum BDNF levels were lower than in rosacea patients. Whatever in rosacea or rosacea with depression group, the statistical significance of serum BDNF levels between the different subtypes like the ETR and PPR was not found. In further correlation analysis, we found no correlation between serum BDNF and RSSs in patients with rosacea whatever the subtype of ETR or PPR. Interestingly, we found a negative correlation between serum BDNF levels and BDI-II in rosacea with depression group, the decreased serum BDNF levels were associated with the increased BDI-II, also the ROC confirmed it can evaluate the depression in patients with rosacea.Conclusion: Serum BDNF level is a potential biomarker for identifying depression in patients with rosacea.Keywords: rosacea, biomarker, brain-derived neurotrophic factor, depression

Cong Shi,1,&ast; Shengping Gong,2,&ast; An Wu,3 Tingting Niu,1 Ningning Wu,1 Yi Zhang,1 Guifang Ouyang,3 Qitian Mu1 1Laboratory of Stem Cell Transplantation, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China; 2Cancer Radiotherapy and Chemotherapy Center, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China; 3Hematology Department, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guifang Ouyang; Qitian Mu, Email nbhematology@163.com; muqitian@163.comBackground: Myelodysplastic syndrome (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that fibrinogen (FIB) is associated with disease risk in several cancer types. Coagulation and fibrinolysis problems are widespread in MDS patients. Therefore, FIB might be one of these indicators. We thus examined the role of FIB levels in the prognosis of MDS.Methods: A cohort of 198 MDS patients were retrospectively analyzed to explore the prognostic value of the plasma FIB levels at diagnosis. Patients were divided into the high FIB group and low FIB group. The prognostic significance of FIB was determined by univariate and multivariate Cox hazard models.Results: In our cohort, the FIB levels in 198 MDS patients were higher than those in 100 healthy donors (3.9 g/L vs 2.9 g/L, P < 0.0001). MDS patients with high FIB levels had significantly shorter overall survival (OS; P = 0.001) and decreased leukemia-free survival (LFS; P = 0.036). Multivariate cox proportional hazards regression analysis indicated that, in addition to older age, gender, lower HB, poorer karyotype for OS, lower NE, and higher bone marrow blast percentage for OS and LFS, elevated FIB level was also an independent adverse prognostic factor for OS (P = 0.045) but not for LFS (P = 0.188).Conclusion: Elevated FIB levels may be associated with mortality risk among MDS patients and could predict disease progress and patient prognosis. Thus, assessment of FIB levels may promote the determination of the prognosis of MDS patients.Keywords: myelodysplastic syndrome, IPSS-R, prognostic, overall survival, fibrinogen

Rina Wu,1,&ast; Mengying Leng,2,&ast; Qila Sa,1 Qiri Mu,1 Haiguang Zhao2 1Department of Dermatology, International Mongolian Hospital of Inner Mongolia, Hohhot, 010020, People’s Republic of China; 2Department of Plastic Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, 266035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiri Mu, Department of Dermatology, International Mongolian Hospital of Inner Mongolia, 83 University East Street, Hohhot, 010020, Inner Mongolia, People’s Republic of China, Email muqiri28@163.comAbstract: With the rapid development of minimally invasive cosmetic procedures, the group receiving minimally invasive cosmetic procedures is gradually on the rise. The adverse reactions or complications of minimally invasive cosmetic procedures also show an upward trend, but clinicians especially the cosmetic dermatologist should be identified and pay attention to the prevention and treatment in such reactions associated with minimally invasive cosmetic procedures in clinical practice. Platelet-rich plasma (PRP), which as a novel treatment option for acne scars, has shown good cosmetic results. Here, we report a case with eczema herpeticum following skin microneedling plus PRP therapy in a patient with atrophic acne scars.Keywords: microneedling, cosmetic, infection, complication, PRP

Caifen Zheng,1 Yongping Zhang,2 Yingchun Zhao,3 Yuanfang Duan,1 Qianghua Mu,1 Xinying Wang1 1Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 2Blood Purifying Center, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 3Department of Cardiovascular Medicine, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of ChinaCorrespondence: Yingchun ZhaoDepartment of Cardiovascular Medicine, The First People’s Hospital of Lianyungang, No. 6 East Zhenhua Road, Haizhou, Lianyungang, Jiangsu, 222061, People’s Republic of ChinaTel +86-0518-85767023Email zyc6469@126.comBackground: Circular RNAs (circRNAs) have been identified to play roles in the respiratory diseases. Here, this study aimed to elucidate the function of circRNA oxysterol binding protein like 2 (circOSBPL2) in the development of smoke-related chronic obstructive pulmonary diseases (COPD).Methods: The expression of circ-OSBPL2, microRNA (miR)-193a-5p, and bromodomain-containing protein 4 (BRD4) was detected using qRT-PCR and Western blot assays. Cigarette smoke extract (CSE)-induced human bronchial epithelial cells (HBECs) was applied to mimic smoke-related COPD in vitro. Flow cytometric analysis of cell apoptosis and ELISA analysis of interleukins (IL)-6, IL-8, tumor necrosis factor-α (TNF-α) levels were performed. The malondialdehyde (MDA) and superoxide dismutase (SOD) production levels were analyzed according to the kit instructions. The binding interaction between miR-193a-5p and circ-OSBPL2 or BRD4 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assays.Results: Circ-OSBPL2 was highly expressed in lung tissues of smokers without or with COPD, particularly in smokers with COPD. Also, the expression of circ-OSBPL2 was dose and time-dependently elevated in CSE-induced HBECs. Circ-OSBPL2 down-regulation in HBECs attenuated CSE-evoked cell proliferation arrest, and cell apoptosis, inflammation and oxidative stress promotion. Mechanistically, circ-OSBPL2 served as a sponge for miR-193a-5p, and miR-193a-5p inhibition reversed the effects of circ-OSBPL2 knockdown on CSE-mediated HBECs. Besides that, miR-193a-5p directly targeted BRD4, and miR-193a-5p re-expression in HBECs abolished CSE-induced HBEC injury, which was reverted by BRD4 up-regulation. Additionally, we also found circ-OSBPL2 could indirectly regulate BRD4 via miR-193a-5p.Conclusion: Circ-OSBPL2 contributed to the apoptosis, inflammation, and oxidative stress of HBECs in smoke-related COPD by miR-193a-5p/BRD4 axis, suggesting a novel insight on the pathogenesis of COPD and a potential therapeutic strategy for future clinic intervention in COPD.Keywords: circ-OSBPL2, miR-193a-5p, BRD4, COPD

Miaomei Yu,1 Lili Pan,1 Chen Sang,2 Qinfeng Mu,1 Lu Zheng,1 Guanghua Luo,1 Ning Xu31Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of China; 2Department of Cardiothoracic Surgery, the Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of China; 3Section of Clinical Chemistry and Pharmacology, Institute of Laboratory Medicine, Lunds University, Lund S‑22185, SwedenObjective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality-to-incidence ratios. Apolipoprotein M (ApoM), a member of the apolipoprotein family, is mainly synthesized in the liver, whereas its role in HCC has not been elucidated. Here, we examined the effect of ApoM on the biological behavior of HCC cells and the possible mechanisms.Methods: We used CRISPR/Cas9 technology to knock out ApoM in SMMC7721 cells. Differentially expressed genes before and after ApoM knockout (KO) were analyzed by GeneChip microarrays and confirmed by qRT-PCR. Cell assays of proliferation, apoptosis, migration and invasion were performed in SMMC7721 cells, and the expression of epithelial–mesenchymal transition (EMT) markers was performed by western blot. And we performed functional recovery experiments by overexpressing vitamin D receptor (VDR) in SMMC7721.Results: The ApoM-KO SMMC7721 cell line was successfully constructed using the CRISPR/Cas9 technology. Our results showed that silencing ApoM suppressed apoptosis and promoted proliferation, migration, invasion and EMT of SMMC7721 cells. The microarray data revealed that a total of 1,868 differentially expressed genes were identified, including VDR. The qRT-PCR and western blot verification results demonstrated that knocking out ApoM could significantly reduce the expression of VDR. The functional recovery experiments indicated that VDR overexpression could offset the inhibition of cell apoptosis and the promotion of cell proliferation, migration, invasion and EMT caused by knocking out ApoM in SMMC7721 cells.Conclusion: ApoM could function as a tumor suppressor to inhibit the growth and metastasis of SMMC7721 cells via VDR signaling in HCC.Keywords: apolipoprotein M, CRISPR/Cas9, hepatocellular carcinoma cells, GeneChip microarrays, vitamin D receptor

OBJECTIVE: The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+ T-cells are seen in severe and critically ill patients with COVID-19. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to discuss the prognostic significance of peripheral interleukin-6 (IL-6) and CD4+ and CD8+ T cells in COVID-19. PATIENTS AND METHODS: Eighty-four COVID-19 patients were retrospectively analyzed and classified into three groups, including the moderate group (15 cases), the serious group (45 cases), and the critical group (24 cases). The levels of peripheral IL-6, CD4+, and CD8+ T cells and CD4+/CD8+ were determined for each group. It was assessed whether these indicators were correlated to the prognosis and death risks of COVID-19 patients. RESULTS: The three groups of COVID-19 patients differed significantly in the levels of peripheral IL-6 and CD4+ and CD8+ cells. The IL-6 levels in the critical, moderate, and serious groups were increased successively, but the changed levels of CD4+ and CD8+ T cells were just opposite to that of IL-6 (p<0.05). The peripheral IL-6 level increased dramatically in the death group, while the levels of CD4+ and CD8+ T cells decreased significantly (p<0.05). The peripheral IL-6 level was significantly correlated with the level of CD8+ T cells and CD4+/CD8+ ratio in the critical group (p<0.05). The logistic regression analysis indicated a dramatic increase in the peripheral IL-6 level in the death group (p=0.025). CONCLUSIONS: The aggressiveness and survival of COVID-19 were highly correlated with the increases in IL-6 and CD4+/CD8+ T cells. The fatalities of COVID-19 individuals remained at increased incidence due to elevated peripheral IL-6 levels. [ABSTRACT FROM AUTHOR]