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Bingran Yu, Ning Zhang, Yun Feng, Yongfa Zhang, Ti Zhang, Lu Wang Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Lu Wang, Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, No. 270 Dongan Road, Shanghai, 200032, People’s Republic of China, Email wangluzl@fudan.edu.cnBackground: Most patients with hepatocellular carcinoma (HCC) are not candidates for liver resection. We investigated the clinicopathological characteristics and prognosis of patients with initially unresectable HCC who underwent hepatectomy after conversion therapy with hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies.Materials and Methods: Patients with initially unresectable HCC who received HAIC combined with TKIs and anti-PD-1 antibodies followed by hepatectomy between December 2020 and December 2022, were retrospectively analyzed. Patient characteristics, tumor characteristics, treatment efficacy, perioperative characteristics, pathological characteristics, and survival outcomes were summarized and analyzed.Results: 67 patients were enrolled in this study. Patients were treated with 3 sessions (range:2– 6 sessions) of combination therapy and were performed with hepatectomy in 4 months (range:1.4– 17.8 months) after the initiation of the combination therapy. The median size of tumor shrinkage was 4.7 cm (range:0.9– 11.7 cm). A pathological complete response (pCR) was achieved in 34.3% of the patients (n = 23). The median recurrence-free survival (RFS) was 19.3 months and the median overall survival (OS) was 28.7 months. Patients who achieved pCR had a better RFS (P = 0.004) and those without microscopic vascular invasion (MVI) had a better prognosis (RFS, P = 0.011; OS, P = 0.023). Multivariable logistic analysis revealed that the tumor number was associated with pCR.Conclusion: Hepatectomy after conversion therapy with HAIC, TKIs, and anti-PD-1 antibodies is a feasible treatment strategy for patients with unresectable HCC. This treatment strategy is associated with a promising prognosis.Keywords: hepatectomy, conversion therapy, hepatocellular carcinoma, pathological complete response

Bingran Yu, Ning Zhang, Yun Feng, Yongfa Zhang, Ti Zhang, Lu Wang Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Lu Wang, Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, No. 270 Dongan Road, Shanghai, 200032, People’s Republic of China, Email wangluzl@fudan.edu.cnBackground: The combination of tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies with hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolization (TACE) has shown encouraging anti-tumor effects in the treatment of hepatocellular carcinoma (HCC). We explored the efficacy and safety of TKIs and anti-PD-1 antibodies combined with HAIC or TACE in HCC.Methods: Data from 302 HCC patients receiving HAIC combined with TKIs and anti-PD-1 antibodies (HAIC-TP group) and 446 HCC patients receiving TACE combined with TKIs and anti-PD-1 antibodies (TACE-TP group) were retrospectively collected. Clinicopathological characteristics, tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared between two groups. Propensity score matching (PSM) analysis was performed to minimize bias.Results: The HAIC-TP group exhibited better objective response rate (RECIST: 33.1% versus 7.8%, P < 0.001; mRECIST: 51.4% versus 17.5%, P < 0.001), longer PFS (12.4 months versus 8.2 months, P < 0.001), and longer OS (not reached versus 13.8 months, P < 0.001) than TACE-TP group. Surgery was performed after combination therapy in 34 patients of the HAIC-TP group and in 7 patients of the TACE-TP group (P < 0.001). Similar results were also observed in the PSM analysis. Multivariate analysis indicated type of treatment, alpha-fetoprotein, ALBI grade, portal vein tumor thrombus, and extrahepatic status were risk factors for poor prognosis. Nausea, vomiting, diarrhea, and abdominal pain occurred more frequently in the HAIC-TP group, whereas liver dysfunction occurred more frequently in the TACE-TP group. All AEs were acceptable and manageable as a result of treatment interruption or dose modification.Conclusion: The combination of HAIC with TKIs and anti-PD-1 antibodies is an effective and safe therapeutic regimen over TACE-based combination therapy for patients with HCC. A prospective study with a large sample size is required to validate the efficacy and safety of the combination therapy.Keywords: hepatocellular carcinoma, hepatic arterial infusion chemotherapy, transarterial chemoembolization, combination therapy

Menglong Wang,1– 3,&ast; Wei Pan,1– 3,&ast; Cheng Wei,1– 3,&ast; Jianfang Liu,1– 3 Jishou Zhang,1– 3 Junping Yu,1– 3 Mengmeng Zhao,1– 3 Shuwan Xu,1– 3 Jing Ye,1– 3 Zhen Wang,1– 3 Di Ye,1– 3 Yongqi Feng,1– 3 Yao Xu,1– 3 Jun Wan1– 3 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People’s Republic of China; 3Hubei Key Laboratory of Cardiology, Wuhan, 430060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wan; Yao Xu, Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of China, Tel +86-27-88041911, Fax +86-27-88042293, Email wanjun@whu.edu.cn; whuxuyao@163.comBackground: Increased inflammation contributes to pressure overload-induced myocardial remodeling. 17(R)-Resolvin D1 (17(R)-RvD1), a potent lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and pro-resolving properties. However, the association between 17(R)-RvD1 and pressure overload-induced cardiac hypertrophy remains unclear.Methods: Transverse aortic constriction (TAC) surgery was performed to establish a cardiac hypertrophy model. C57BL/6J mice were randomly assigned to the Sham, TAC and TAC+17(R)-RvD1 groups. 17(R)-RvD1 was injected (2 μg/kg, i.p.) before TAC surgery and once every other day after surgery for 4 weeks. The same volume of saline was injected into the mice in both Sham group and TAC group. Then, cardiac function was evaluated and heart tissues were collected for biological analysis.Results: 17(R)-RvD1 treatment attenuated TAC-induced increase in left ventricular diameter and decrease in left ventricular contractility, mitigated increased cardiomyocyte cross-sectional area, and downregulated the expression of hypertrophic genes. Besides, 17(R)-RvD1 attenuated myocardial fibrosis, as indicated by the decreased LV collagen volume and expression of fibrotic genes. In addition, 17(R)-RvD1 ameliorated the inflammatory response in cardiac tissue, as illustrated by the decreased infiltration of CD68+ macrophages and reduced production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. 17(R)-RvD1 treatment significantly suppressed the activation of NLRP3 inflammasome after TAC surgery, which might be responsible for the attenuation of inflammation in cardiac tissue.Conclusion: 17(R)-RvD1 attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and the possible mechanism may be associated with the inhibition of NLRP3 inflammasome. 17(R)-RvD1 may serve as a potential drug for the treatment of cardiac hypertrophy.Keywords: inflammation resolution, resolvin D1, cardiac hypertrophy, NLRP3 inflammasome, transverse aortic constriction

Yuqin Feng,1,2 Si Qin,3 Huarun Li,3 Yemei Yang,1 Yushi Zheng,1 Hongsheng Liu,4 Wei Yin Yap,1,5 Xianyi Zhou,1 Ju Wen2,3 1Department of Dermatology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of China; 2The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 3Department of Dermatology, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China; 4Guangdong Huace Life Medicine Research Center, Guangzhou, 511450, People’s Republic of China; 5School of International Education of Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaCorrespondence: Xianyi Zhou; Ju Wen, Email zxy1962@163.com; wenju3139@163.comBackground: Hydrogel dressings have been used as a crucial method to keep the wound wet and hasten the healing process. Due to safety concerns regarding the gel components, low mechanical adhesiveness, and unsatisfactory anti-inflammatory capacity qualities for practical uses in vivo, leading to the clinical translation of wound dressings is still difficult.Methods: A type of composite hydrogel (acrylamide/polyethylene glycol diacrylate/tannic acid, ie, AM/PEGDA/TA) by double bond crosslinking, Schiff base, and hydrogen bond interaction is proposed. The mechanical characteristics, adhesiveness, and biocompatibility of the hydrogel system were all thoroughly examined. Additionally, a full-thickness cutaneous wound model was employed to assess the in vivo wound healing capacity of resulting hydrogel dressings.Results: Benefiting the mechanism of multiple crosslinking, the designed composite hydrogels showed significant mechanical strength, outstanding adhesive capability, and good cytocompatibility. Moreover, the hydrogel system also had excellent shape adaptability, and they can be perfectly integrated into the irregularly shaped wounds through a fast in situ forming approach. Additional in vivo tests supported the findings that the full-thickness wound treated with the composite hydrogels showed quicker epithelial tissue regeneration, fewer inflammatory cells, more collagen deposition, and greater levels of platelet endothelial cell adhesion molecule (CD31) expression.Conclusion: These above results might offer a practical and affordable product or method of skin wound therapy in a medical context.Keywords: hydrogel dressing, tannins, multiple-crosslinking, anti-inflammatory, full-thickness wound healing

Yinxia Zheng, Xianfeng Li, Yan Xia, Xiaoqin Li, Genglin Yang, Rui Shi, Ying Feng Urumqi Maternal and Child Health Hospital, Urumqi, Xinjiang, People’s Republic of ChinaCorrespondence: Ying Feng, Email 623245060@qq.comObjective: To Analysis of the mediation effects of adverse mental health outcomes in HIV-infected women of childbearing age from multiple perspectives including discrimination perception, social capital, and other factors.Methods: A cross-sectional survey was conducted among 553 people in Xinjiang region of China using Survey scale. AMOS was used to identify factors that influenced the “discrimination perception/mental resilience/social capital-depression-poor mental health outcomes” pathway.Results: A total of 44.85% and 42.13% of the study participants had anxiety and depression symptoms, as perceived discrimination increased, the higher the level of depression in HIV-infected women of childbearing age. Correlation coefficient among depression with poor mental health outcomes was also significant. Psychological resilience, social capital and depression have mediating effects on perceived discrimination and poor mental health outcomes, discrimination perception had an indirect effect on depression through social capital and an indirect effect on adverse mental health outcomes through depression and psychological resilience. The modified model has a good fitting effect.Conclusion: Discrimination perception was shown to affect adverse mental health outcomes by impacting mental resilience, depression, and social capital. The findings suggest the need for measures to reduce adverse mental health outcomes by decreasing discrimination perception, increasing social capital, and enhancing psychological resilience.Keywords: women of childbearing age, HIV-infected, psychological resilience, discrimination perception, mental health

Yanan Feng,1,2,&ast; Yongsheng Hao,3,&ast; Yuanyuan Wang,3 Weijian Song,1,4 Shanxin Zhang,1 Dong Ni,5 Fei Yan,3 Litao Sun1 1Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Department of Abdominal Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 3Center for Cell and Gene Circuit Design, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People’s Republic of China; 4Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 5Medical Ultrasound Image Computing (MUSIC) Laboratory, Shenzhen University, Shenzhen, 518055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Litao Sun; Fei Yan, Tel +86 13946037056, Email litaosun1971@sina.com; fei.yan@siat.ac.cnPurpose: Ultrasound molecular imaging (UMI) has proven promising to diagnose the onset and progression of diseases such as angiogenesis, inflammation, and thrombosis. However, microbubble-based acoustic probes are confined to intravascular targets due to their relatively large particle size, greatly reducing the application value of UMI, especially for extravascular targets. Extradomain B fibronectin (ED-B FN) is an important glycoprotein associated with tumor genesis and development and highly expressed in many types of tumors. Here, we developed a gas vesicles (GVs)-based nanoscale acoustic probe (ZD2-GVs) through conjugating ZD2 peptides which can specially target to ED-B FN to the biosynthetic GVs.Materials and Methods: ED-B FN expression was evaluated in normal liver and tumor tissues with immunofluorescence and Western blot. ZD2-GVs were prepared by conjugating ZD2 to the surface of GVs by amide reaction. The inverted microscope was used to analyze the targeted binding capacity of ZD2-GVs to MB49 cells (bladder cancer cell line). The contrast-enhanced imaging features of GVs, non-targeted control GVs (CTR-GVs), and targeted GVs (ZD2-GVs) were compared in three MB49 tumor mice. The penetration ability of ZD2-GVs in tumor tissues was assessed by fluorescence immunohistochemistry. The biosafety of GVs was evaluated by CCK8, blood biochemistry, and HE staining.Results: Strong ED-B FN expression was observed in tumor tissues while little expression in normal liver tissues. The resulting ZD2-GVs had only 267.73 ± 2.86 nm particle size and exhibited excellent binding capability to the MB49 tumor cells. The in vivo UMI experiments showed that ZD2-GVs produced stronger and longer retention in the BC tumors than that of the non-targeted CTR-GVs and GVs. Fluorescence immunohistochemistry confirmed that ZD2-GVs could penetrate the tumor vascular into the interstitial space of the tumors. Biosafety analysis revealed there was no significant cytotoxicity to these tested mice.Conclusion: Thus, ZD2-GVs can function as a potential UMI probe for the early diagnosis of bladder cancer.Graphical Abstract: Keywords: ultrasound contrast agents, gas vesicles, ultrasound molecular imaging, tumor diagnosis

Zhixin Liu,1,2,&ast; Huanyu Zhang,1 Nan Wang,1,&ast; Yajie Feng,1,&ast; Junping Liu,1 Lin Wu,1 Zhaoyue Liu,1 Xinru Liu,1 Libo Liang,1 Jie Liu,3 Qunhong Wu,1 Chaojie Liu4 1Department of Social Medicine, School of Health Management, Harbin Medical University, Harbin, People’s Republic of China; 2Department of Health Policy and Management, School of Public Health, Peking University, Beijing, People’s Republic of China; 3Intensive Care Unit, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Public Health, School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia&ast;These authors contributed equally to this workCorrespondence: Libo Liang; Jie Liu, Email llbhit@163.com; liujie21814@126.comBackground: This study aimed to test the mediating role of anxiety and insomnia in the association between fear of infection and fatigue.Methods: A cross-sectional questionnaire survey was conducted on the nurses deployed to Heihe. A serial multiple mediation model was established to determine the role of anxiety and insomnia in the association between fear of infection and fatigue.Findings: Over half (53.0%) of the study participants reported experiencing fear of infection despite stringent personal protection measures. The scores of anxiety (11.87± 5.19), insomnia (16.33± 5.95), and fatigue (45.94± 12.93) were moderately correlated, with a Pearson correlation coefficient ranging from 0.501 to 0.579. Anxiety, either alone or in combination with insomnia, mediated the association between fear of infection and fatigue.Conclusion: The findings suggest that anxiety and insomnia play a mediating role in the relationship between fear of infection and fatigue. These results emphasize the importance of implementing targeted mental health interventions and work arrangements to address the well-being of healthcare professionals.Keywords: fear of infection, anxiety, insomnia, fatigue, COVID-19

Xiaoyu Zhang,1 Yahui Feng,2 Dongmei Li,3 Jingjian Han,4 Dongmei Shi2,5 1School of Clinical Medicine, Weifang Medical University, Weifang, People’s Republic of China; 2Laboratory of Medical Mycology, Jining No. 1 People’s Hospital, Jining, People’s Republic of China; 3Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, USA; 4Department of Medical Cosmetology, Jining No. 1 People’s Hospital, Jining, People’s Republic of China; 5Department of Dermatology, Jining No. 1 People’s Hospital, Jining, People’s Republic of ChinaCorrespondence: Dongmei Shi, Laboratory of Medical Mycology & Department of Dermatology, Jining No. 1 People’s Hospital, No. 6 Jiankang Road, Jining, Shandong Province, 272067, People’s Republic of China, Tel +8618678769757, Email shidongmei28@163.com Jingjian Han, Department of Medical Cosmetology, Jining No. 1 People’s Hospital, No. 6 Jiankang Road, Jining, Shandong Province, 272067, People’s Republic of China, Email hjj_1983@163.comAbstract: Mycobacterium abscessus (M. abscessus) is a fast-growing, non-tuberculous mycobacterium (NTM) that can cause human infections varying from superficial infection to pulmonary or even systemic infections. The latter is more commonly appeared in immunocompromised patients. The skin infection caused by M. abscessus often appears after trauma or surgical procedure. It is often manifested by subcutaneous nodules, papules, erythema, tender erythematous or violaceous plaques, cellulitis, abscesses, ulcerations, and draining sinuses. Herein, we present a non-typical cutaneous manifestation of M. abscessus infection in a 46-year-old woman who presented with alopecia on the scalp with no itching or pain. The pathogen was isolated and identified as M. abscessus by morphology and DNA sequencing. To our best knowledge, there was no report that this organism could cause skin lesions mimicking patchy alopecia. After 3 months of antibacterial treatment, the cutaneous lesion disappeared, and new growth of hair occurred in this patient.Keywords: Mycobacterium abscessus, alopecia, non-tuberculous mycobacteria

Wan He,1,&ast; Changbu Wu,2,3,&ast; Guanping Chen,2– 4 Guili Zhang,2,3 Zihan Zhao,2,3 Shu’an Wen,2,3 Yuan Zhou,2,3 Xue Deng,2,3 Yu Feng,2,3 Lan-Lan Zhong,2,3 Guo-Bao Tian,2– 4 Min Dai1 1School of Laboratory Medicine, Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 2Department of Immunology and Microbiology, Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, People’s Republic of China; 4Department of Immunology, School of Medicine, Sun Yat-Sen University, Shenzhen, 518107, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Dai, School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan Province, People’s Republic of China, Tel +86 28-62739128, Email daimin1015@163.com Guo-Bao Tian, Department of Immunology and Microbiology, Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China, Tel/Fax +86 20 87335387, Email tiangb@mail.sysu.edu.cnBackground: The emergence and spread of hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is a potential epidemiological threat that needs to be monitored. However, the transmission and pathogenic characteristics of hv-CRKP in China remain unclear. We investigated the epidemiological characteristics of gut colonized hv-CRKP in a hospital in Guangdong Province, China.Methods: A total of 46 gut colonized hv-CRKP isolates were collected from Sun Yat-Sen Memorial Hospital (Guangzhou, China) from August 31st to December 31st, 2021. Minimum inhibitory concentrations (MICs) were obtained for 15 antibiotics for 46 hv-CRKP isolates. BALB/C mice infection model and mucoviscosity assay was used to evaluate the virulence of the isolates. The characteristics of genome, phylogenetic relationship and the structure of the plasmid of 46 gut colonized hv-CRKP isolates were compared with pathogenic isolates from GeneBank based on whole-genome data.Results: The hv-CRKP isolation rate of all gut colonized carbapenem-resistant Klebsiella pneumoniae was 17% (46/270), and the intestinal colonization rate of hv-CRKP was irrelevant to the sex, age, department of hospitalization, and history of antibiotic use of the host. The gut colonized hv-CRKP showed pandrug resistance and hypervirulence. The gut colonized hv-CRKP and pathogenic hv-CRKP prevalent in China were mainly ST11 hv-CRKP and had two major epidemic clades. The similarities in genomic characteristics between gut colonized hv-CRKP and pathogenic hv-CRKP were consistent. The gut colonized hv-CRKP carried an incomplete structure pK2044 virulence plasmid from hypervirulent K. pneumoniae NTUH-K2044 by analyzing the virulence plasmid structure.Conclusion: Our results suggest that the gut colonized ST11 hv-CRKP may serve as a reservoir for the clinical pathogenic ST11 HV-CRKP. It is necessary to further strengthen the monitoring of gut colonized hv-CRKP and research the potential mechanism of infection caused by gut colonized hv-CRKP.Keywords: K. pneumoniae, intestinal colonization, hypervirulent, genomic characterization, carbapenemase

Jianlin Wang,&ast; Zhaoyang Wen,&ast; Yumei Xu, Xin Ning, Deping Wang, Jimin Cao, Yanlin Feng Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanlin Feng; Jimin Cao, Email feng@sxmu.edu.cn; caojimin@sxmu.edu.cnBackground: Wound healing is a continuous and complex process that comprises multiple phases including hemostasis, inflammation, multiplication (proliferation) and remodeling. Although a variety of nanomaterials have been developed to control infection and accelerate wound healing, most of them can only promote one phase but not multiple phases, resulting in lower efficient healing. Although various formulations such as nitric oxide releasing wound dressings were developed for dual action, the nanostructure synthesis and the encapsulation process were complex.Materials and Methods: Here, we report on the design of graphene-barium titanate nanosystem to procedural promote the wound healing process. The antibacterial effect was assessed in Gram-negative Escherichia coli bacteria (E. coli) and Gram-positive Staphylococcus aureus bacteria (S. aureus), the cell proliferation and migration experiment was investigated in mouse embryonic fibroblast (NIH-3T3) cells, and the wound healing effect was analyzed in female BALB/c mice with infected skin wound on the back.Results: Results showed that graphene-barium titanate nanosystem could generate abundant ROS to kill both E. coli and S. aureus. The growth curves, bacterial viability, colony number formation and scanning electron microscopy (SEM) images of E. coli and S. aureus all confirmed the antibacterial effect. Cell Counting Kit-8 (CCK-8) assay displayed that GBT possesses great biocompatibility. EdU assay showed that GBT plus white light irradiation significantly promoted the proliferation and migration of NIH-3T3 cells. Scratch assay found that GBT could achieve a fast scratch closure compared to the control. In vivo wound healing effect indicates that GBT can accelerate wound repair procedure.Conclusion: GBT nanocomposite is capable of programmatically accelerating wound healing through multiple stages, including production of a large amount of ROS after white light exposure to effectively kill E. coli and S. aureus to prevent wound infection and as a scaffold to accelerate fibroblast proliferation and migration to the wound to accelerate wound healing.Keywords: graphene-barium titanate nanosystem, wound healing, reactive oxygen species, antibacterial, proliferation

Yajing You,1,&ast; Tao Yang,2,&ast; Shuhang Wei,1 Zongxin Liu,1 Chenxi Liu,1 Zijian Shen,3 Yinuo Yang,1 Yuemin Feng,1 Ping Yao,2 Qiang Zhu1,2 1Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China; 3Department of Radiology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Zhu, Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Email zhuqiang@sdu.edu.cn Ping Yao, Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Email pingyaozh@sina.comPurpose: Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality.Patients and Methods: A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes.Results: Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p< 0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p< 0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits.Conclusion: Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.Keywords: steatosis, diabetes, obesity, HBe Ag

Haicheng Wang,1,&ast; Renbin Wang,2,&ast; Jingwen Yang,3– 5 Yuan Feng,6 Shuyu Xu,6 Qing-Guo Pei7 1Department of Pathology, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, People’s Republic of China; 2Department of Gastroenterology, The People’s Hospital of Zhongjiang, Zhongjiang, Sichuan Province, 618100, People’s Republic of China; 3Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China; 4National Center of Stomatology & National Clinical Research Center for Oral Diseases, Beijing, 100081, People’s Republic of China; 5National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, People’s Republic of China; 6Department of Oral Implantology, School of & Hospital Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, People’s Republic of China; 7Department of Stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuyu Xu, Department of Oral Implantology, School of & Hospital Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, 399 Yanchang Road, Shanghai, 200072, People’s Republic of China, Tel +86-21-66313725/(8610) ; +8618616308949, Email shuyu_xu0809@163.com Qing-Guo Pei, Department of Stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Tel +86-21-37798330/(8610) ; +8613764521025, Email dentistpei@126.comBackground: To analyze the fibroblasts subtypes in the gingival tissues of healthy controls, gingivitis and periodontitis patients, as well as the effects of interaction between subtypes on alveolar bone destruction.Methods: Gingival tissues were divided into three groups according to clinical and radiographic examination, and the immunostaining of EDA+FN was assessed. Fibroblasts from gingiva developed colony formation units (CFUs) and induced Trap+MNCs. The expression of osteoclastogenesis-related genes was assessed by real-time PCR. Variances in the gene profiles of CFUs were identified by principal component analysis, and cluster analysis divided CFUs into subtypes. The induction of Trap+MNCs and gene expression were compared among individual or cocultured subtypes. The fibroblast subtypes exerted critical effect on Trap+MNCs formation were selected and edited by CRISPR/Cas to investigate the influence on osteoclastogenesis in the periodontitis in mice.Results: Most periodontitis samples exhibited intensive EDA+FN staining (P < 0.05), and these fibroblasts also induced most Trap+MNCs among three groups; consistently, fibroblasts from periodontitis highly expressed genes facilitating osteoclastogenesis. According to gene profiles and osteoclastogenic induction, four clusters of CFUs were identified. The proportion of clusters was significantly different (P < 0.05) among three groups, and their interaction influenced osteoclastogenic induction. Although Cluster 4 induced less osteoclasts, it enhanced the effects of Clusters 1 and 3 on Trap+MNCs formation (P < 0.05). EDA knockout in Cluster 4 abrogated this promotion (P < 0.05), and decreased osteoclasts and alveolar bone destruction in experimental periodontitis (P < 0.05).Conclusion: Heterogeneous fibroblast subtypes affect the switch or development of periodontitis. A subtype (Cluster 4) played important role during alveolar bone destruction, by regulating other subtypes via EDA+FN paracrine.Keywords: periodontitis, heterogeneity, fibroblast subtype, osteoclastogenesis, alveolar bone destruction

Yukun Feng,1,2,&ast; Na Ni,3,&ast; Wei Liu,4 Xinli Chi5,6 1Shenzhen Audencia Financial Technology Institute, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 2Faculty of Business Administration, University of Macau, Macau, People’s Republic of China; 3Faculty of Business, Lingnan University, Hong Kong, People’s Republic of China; 4School of Management, Xiamen University, Xiamen, 361005, People’s Republic of China; 5School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 6The Shenzhen Humanities & Social Sciences Key Research Bases of the Center for Mental Health, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Chi, School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Tel +86 755 26976348, Email xinlichi@126.comPurpose: Past studies have indicated that air pollution is a major environmental factor that negatively affects prosocial behavior in adolescents. However, the mechanism underlying this negative relationship has not been fully explored. This study postulated that this impact may occur through individual resilience, a major psychological capital for adolescents. In addition, we studied interpersonal relations, namely, adolescents’ perceived family and teacher support, which may moderate the proposed relationship.Methods: This study combined the three-year tracking survey data of 11-to-15 old adolescents (N=1301; approximately 48% female) in China with objective data from the air quality index (AQI) to measure the level of air pollution.Results: Findings from ordinary least squares analysis indicated that air pollution negatively influences adolescents’ prosocial behavior, and their resilience mediates this negative relationship. In addition, the results showed that the negative effect of air pollution on adolescent resilience is attenuated by higher family income, whereas it is accentuated by the absence of teacher support.Conclusion: Our study provides insight into how the negative effect of air pollution on adolescents’ prosocial behavior is mediated by their psychological resilience, and highlights the moderating role of adolescents’ interpersonal relations in the association between air pollution and their psychological resilience. Our research also provides practical advice on how families, teachers, and psychologists can mitigate this negative impact.Keywords: psychological resilience, environment, interpersonal relations, prosocial behavior, adolescents, China

Wenting Tu,1,&ast; Taohu Zhou,1,2,&ast; Xiuxiu Zhou,1,&ast; Yanqing Ma,3 Shaofeng Duan,4 Yun Wang,1 Xiang Wang,1 Tian Liu,1 HanXiao Zhang,5 Yan Feng,1 Wenjun Huang,2 Xinang Jiang,1 Yi Xiao,1 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China; 2School of Medical Imaging, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 3Department of Radiology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People’s Republic of China; 4GE Healthcare, Precision Health Institution, Shanghai, 210000, People’s Republic of China; 5School of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu, 221018, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiyuan Liu; Li Fan, Department of Radiology, Second Affiliated Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86 21 81886012 ; +86 21 81886018, Fax +86 21 63587668, Email cjr.liushiyuan@vip.163.com; fanli0930@163.comPurpose: This study aimed to screen out computed tomography (CT) morphological features and clinical characteristics of patients with lung cancer to identify chronic obstructive pulmonary disease (COPD). Further, we aimed to develop and validate different diagnostic nomograms for predicting whether lung cancer is comorbid with COPD.Patients and Methods: This retrospective study examined data from 498 patients with lung cancer (280 with COPD, 218 without COPD; 349 in training cohort, 149 in validation cohort) from two centers. Five clinical characteristics and 20 CT morphological features were evaluated. Differences in all variables were assessed between COPD and non-COPD groups. Models were developed using multivariable logistic regression to identify COPD, including clinical, imaging, and combined nomograms. Receiver operating characteristic curves were used to evaluate and compare the performance of nomograms.Results: Age, sex, interface, bronchus cutoff sign, spine-like process, and spiculation sign were independent predictors of COPD in patients with lung cancer. In the training and validation cohorts, the clinical nomogram showed good performance to predict COPD in lung cancer patients (areas under the curves [AUCs] of 0.807 [95% CI, 0.761– 0.854] and 0.753 [95% CI, 0.674– 0.832]); while the imaging nomogram showed slightly better performance (AUCs of 0.814 [95% CI, 0.770– 0.858] and 0.780 [95% CI, 0.705– 0.856]). For the combined nomogram generated with clinical and imaging features, the performance was further improved (AUC=0.863 [95% CI, 0.824– 0.903], 0.811 [95% CI, 0.742– 0.880] in the training and validation cohort). At 60% risk threshold, there were more true negative predictions (48 vs 44) and higher accuracy (73.15% vs 71.14%) for the combined nomogram compared with the clinical nomogram in the validation cohort.Conclusion: The combined nomogram developed with clinical and imaging features outperformed clinical and imaging nomograms; this provides a convenient method to detect COPD in patients with lung cancer using one-stop CT scanning.Keywords: chronic obstructive pulmonary disease, lung cancer, computed tomography, chest imaging, nomogram

Jia Tang, Tiantian Song, Ming Kuang, Yiping Feng, Guangrong Liu, Hongying Liu Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Hongying Liu, Hangzhou Kang Ming Information Technology Co., Ltd, 401 Building 4, Haichuang Park (across from Taobao City) 998 Wenyi West Road, Yuhang District, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Tel +86 021 64045531, Email hongyingliu@91jkys.comAbstract: The COVID-19 pandemic is a huge public health crisis in the 21st century. In addition to the acute symptoms, a considerable proportion of patients worldwide have suffered from post-COVID-19 syndrome, commonly known as Long COVID. The impact of Long COVID on individual and public health burden cannot be ignored. According to recent researches, Long COVID has been affecting multiple organ systems throughout the body, with respiratory, mental, nervous and digestive symptoms often seen in Chinese population. Clinical studies have proved that symptoms were alleviated by a variety of treatments, such as physical therapy, rehabilitation training, psychological support, behavioral cognitive therapy, stem cell therapy, etc. Based on the current clinical evidence, it is recommended to strengthen the scientific research on Long COVID and actively carry out early monitoring and intervention in the future, so as to effectively prevent the long-term disease burden and economic pressure.Keywords: Long COVID, post-COVID conditions, China, clinical characteristics, management strategies

Lanlan Zong,1,&ast; Yanling Wang,1,&ast; Shiyu Song,1 Huiqi Zhang,1 Shengcai Mu,1 Wenshang Liu,1 Yu Feng,1 Shumin Wang,1 Ziwei Tu,1 Qi Yuan,1 Luhui Li,2 Xiaohui Pu1 1School of Pharmacy and Henan Province Engineering Research Center of High Value Utilization to Natural Medical Resource in Yellow River Basin, Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 2Medical school, Henan Technical Institute, Kaifeng, Henan, 475004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Yuan; Xiaohui Pu, Tel/Fax +86-371-23880680, Email kaifengYQ2017@163.com; pgh425@163.comIntroduction: Hepatoma is the leading cause of death among liver diseases worldwide. Modern pharmacological studies suggest that some natural monomeric compounds have a significant effect on inhibiting tumor growth. However, poor stability and solubility, and side effects are the main factors limiting the clinical application of natural monomeric compounds.Methods: In this paper, drug-co-loaded nanoself-assemblies were selected as a delivery system to improve the chemical stability and solubility of Tanshinone II A and Glycyrrhetinic acid, and to produce a synergetic anti-hepatoma effect.Results: The study suggested that the drug co-loaded nanoself-assemblies showed high drug loading capacity, good physical and chemical stability, and controlled release. In vitro cell experiments verified that the drug-co-loaded nanoself-assemblies could increase the cellular uptake and cell inhibitory activity. In vivo studies verified that the drug co-loaded nanoself-assemblies could prolong the MRT0-∞, increase accumulation in tumor and liver tissues, and show strong synergistic anti-tumor effect and good bio-safety in H22 tumor-bearing mice.Conclusion: This work indicates that natural monomeric compounds co-loaded nanoself-assemblies would be a potential strategy for the treatment of hepatoma.Graphical Abstract: Keywords: nanoself-assemblies, drug combination, glycyrrhetinic acid, tanshinone IIA, liver cancer

Xiaoyu Huang,1,2 Ming Zhang,1,3 Lin Chang,1,2 Dali Zheng,2 Wei Lin,4 Yan Feng,1,2 Youguang Lu1,2 1Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Fujian Key Laboratory of Oral Diseases, School of Stomatology, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Conservative and Endodontic Dentistry, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 4College of Chemistry, Fuzhou University, Fuzhou, Fujian Province, People’s Republic of ChinaCorrespondence: Youguang Lu, Tel +86-591-83736429, Fax +86-591-83720599, Email fjlyg63@fjmu.edu.cn; Yan Feng, Tel/Fax +86-591-22862632, Email fengyan@fjmu.edu.cnObjective: The study aims to enhance the anti-caries performance of pit and fissure sealants through the synthesis of novel silver nanocomposites, and to evaluate their mechanical properties and biological safety in vitro and in vivo.Methods: The antibacterial properties of synthetic eggshell/Ag were detected by bacterial inhibition zone, minimum bacteriostatic concentration, fluorescence staining and scanning electron microscopy. The synthetic products were then combined with pit and fissure sealants to prepare specimens, and their effects on mechanical properties, antibacterial properties and cytotoxicity were evaluated. Furthermore, an oral mucosal contact model of golden hamsters was established according to the ISO10933 standard to evaluate local stimulation and systemic effects.Results: The novel nanocomposite eggshell/Ag was confirmed to exhibit strong broad-spectrum antibacterial activity, and that the eggshell/Ag-modified pit and fissure sealant had strong antibacterial properties against common dental caries bacterial biofilms, without any significant change in mechanical properties. The gradient dilution extract showed acceptable cytotoxicity, and in the golden hamster oral contact model, there were no visible abnormalities in local mucosal tissues, blood indices, or liver and kidney histopathology.Conclusions: These findings suggest that eggshell/Ag combined with pit and fissure sealants has strong antibacterial activity and excellent biosafety in vitro and in vivo, making it a promising candidate for clinical applications.Keywords: silver nanocomposites, antibacterial, pit and fissure sealants, biosafety

Pengcheng Ma,1 Yadi Li,2 Yusen Feng,1 Gang Wu,3 Bin Li,4 Haiyan Wu5 1Department of Radiology, Kunming Yan ‘an Hospital, Kunming, 650000, People’s Republic of China; 2Department of Ophthalmology, Affiliated Hospital of Yunnan University, Kunming, 650000, People’s Republic of China; 3Department of Neurology, Kunming Yan ‘an Hospital, Kunming, 650000, People’s Republic of China; 4Department of Neurosurgery, Kunming Yan ‘an Hospital, Kunming, 650000, People’s Republic of China; 5Department of Cardiovascular, Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650000, People’s Republic of ChinaCorrespondence: Gang Wu, Tel/Fax +86 0871 632111408, Email yngangwu1126@126.comPurpose: To evaluate the stability of unruptured intracranial aneurysm (UIA) with high-resolution magnetic resonance imaging of the vessel wall (HR-VWI).Materials and Methods: A total of 92 UIA patients were enrolled. After MRA, HR-VWI imaging, the reconstruction of volume rendering (VR) and maximum intensity projection (MIP) were performed to observe the location and size of aneurysms, AR value (ratio of aneurysm height to aneurysmal diameter), SR value (ratio of maximum tumor depth to proximal parent artery diameter), and signal intensity were measured.Results: There were 7 aneurysms with UIA located in the anterior cerebral artery, 31 aneurysms with UIA in the middle cerebral artery, 1 aneurysm with UIA in the posterior cerebral artery, 18 aneurysms with UIA in the anterior communication, 5 aneurysms with UIA in the posterior communication, 34 aneurysms with UIA in the intracranial segment of the internal carotid artery and 3 aneurysms with UIA in the vertebral artery. Among them, 8 patients had more than two multiple aneurysms. The lesion size was 2– 38mm (6.3 ± 5.09). There are 46 aneurysms with wall enhancement: the maximum SR value was 7.03 and the minimum 1.2, and the maximum AR value was 7.5 and the minimum 1.0. Fifty-five aneurysms showed no enhancement of the tumor wall. The maximum SR value was 4.55 and the minimum 0.58, and the maximum AR value was 4.0 and the minimum 0.6, respectively. Patients were divided into a stable group and an unstable group according to the aneurysm wall. The enhancement rate, SR value, and AR value in the stable aneurysm group were significantly lower than those in the unstable aneurysm group (P < 0.05).Conclusion: MRA and HR-VWI can objectively reflect the stability of aneurysms by judging the morphology, SR value, and signal enhancement of UIA, and can provide a certain basis for diagnosis and treatment, which has become routine examination.Keywords: high-resolution magnetic resonance imaging of the vessel wall, unruptured intracranial aneurysm, signal intensity, enhancement, diagnosis

Yumiao Feng,1,2,&ast; Miaomiao Wang,2,3,&ast; Haiqin Jiang,2 Ying Shi,2 Wenyue Zhang,2 Hongsheng Wang2 1Department of Dermatology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, People’s Republic of China; 2Department of Mycobacterium, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIS, Institute of Dermatology & Hospital of Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, People’s Republic of China; 3Department of Dermatology, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongsheng Wang, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 12 Jiangwangmiao Street, Nanjing, People’s Republic of China, Tel +86 025 8547 8953, Email whs33@vip.sina.comPurpose: Culture of Mycobacterium marinum is very time-consuming, taking several weeks to produce positive results. Seeking rapid and sensitive diagnostic methods for diagnosis can greatly improve patient treatment. Our study aimed to compare the rapid diagnostic abilities of polymerase chain reaction (PCR), nested PCR and loop mediated isothermal amplification (LAMP) of detecting M. marinum in skin samples from patients with M. marinum infection.Methods: A total of 6 M. marinum strains and 6 skin samples with definite diagnosis of M. marinum infection were included in the study. We optimized LAMP performance for detection of M. marinum genomic DNA and confirmed the specificity of the primers. Then, the sensitivity of the LAMP and nested PCR assays were assessed by M. marinum strains and clinical samples.Results: Nested PCR was 10-fold more sensitive than the LAMP assay by serial dilution of M. marinum DNA. PCR positive samples were all positive by LAMP detection of 6 clinical M. marinum strains. Out of 6 clinical skin specimens confirmed as M. marinum infection, 0 (0%), 3 (50%), 3 (50%), and 4 (66.6%) were positive by PCR, nested PCR, LAMP and culture. The LAMP shared the same sensitivity than nested PCR in M. marinum strains and clinical samples, but it was easy to perform and faster than nested PCR assay.Conclusion: Compared with conventional PCR, LAMP and nested PCR are more sensitive and have a higher detection rate of M. marinum in clinical skin specimens. The LAMP assay proved to be more suitable for rapid diagnosis of M. marinum infection in a shorter time, especially in resource-limited settings.Keywords: Mycobacterium marinum, diagnosis, PCR, nested PCR, LAMP

Meng Liu,1,&ast; Xinyi Liu,1,&ast; Yuqian Wang,1 Ziyang Wang,1 Huihui Tuo,1 Yiguo Feng,2 Yan Zheng1 1Department of Dermatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Dermatology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiguo Feng, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email fengyiguo70@163.com Yan Zheng, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email zenyan66@126.comBackground: Epidermal cysts are common benign epithelial tumors. They are known to result from penetrating-type injuries or infection of human papillomavirus. The differential diagnosis commonly includes multiplex steatocystoma, lipoma, and neurofibroma. Pathological examination is essential for diagnosis, and surgical excision is the recommended treatment.Objective: We report a case in a man who presented with a cystic lesion on the scalp over 22 years to provide clinical evidence for mechanism of epidermal cysts. We conducted epidemiological analysis of 3949 patients with epidermal cysts to clarify the epidemiological characteristics and clinical features of epidermal cysts.Patients and Methods: A total of 3949 individuals with confirmed epidermal cysts were collected for analysis. Data were expressed as mean ± SEM and analyzed using Student’s t-test.Results: Our data showed that the mean age of diagnosis of males was statistically earlier than that of females (P< 0.001), but no significant difference in sex predilection was observed (P=0.55). The high incidence age of males and females was in the young and middle stage. Lesion locations were a bit different among age groups, but the face was the most common site of epidermal cyst at all age stages.Conclusion: Our case offers clinical evidence to the theory which refers trauma as one of the main causes of epidermal cysts in hair-bearing area. According to analysis of large number of samples, we can further support the idea that epidermal cyst has equal sex predilection and mainly occurs on the young and middle-aged adults. It is usually solitary and most likely to be found on face and trunk.Keywords: epidermal cysts, etiology, epidemiological analysis, treatment

Abstract Background Parkinsonism after ventriculoperitoneal shunt in patients with hydrocephalus is a rare and profound complication that is often misdiagnosed, causing treatment to be delayed. To date, the characteristics of this disease have not been well described and summarized. Here, we report a rare case of parkinsonism after ventriculoperitoneal shunt; symptoms were aggravated by antipsychotic drugs but showed a good response to Madopar. Such cases have rarely been reported previously. Case presentation A 44-year-old man presented with parkinsonism, bilateral pyramidal tract signs, and oculomotor impairment four years after a successful ventriculoperitoneal shunt for idiopathic aqueduct stenosis resulting in obstructive hydrocephalus. Brain magnetic resonance imaging and computed tomography showed fluctuations in the lateral ventricle and the third ventricle without any intervention. The patient’s condition was aggravated by antipsychotic drugs but showed a good response to Madopar. Conclusion This observation suggests that parkinsonism in this patient was caused by reversible dysfunction of the presynaptic nigrostriatal dopaminergic pathway due to fluctuations in the lateral ventricle, representing the first hit to the dopaminergic signalling pathway, and antipsychotic drugs had an antagonistic effect on dopamine D2 receptors, representing the second hit. In addition, we summarize the pathophysiological mechanisms, clinical manifestations, treatments, and prognoses of this complication in 38 patients who met the inclusion criteria in 24 previous studies to increase neurologists’ understanding of the disease.

Jiongdi Lu,1,2,&ast; Zhi Zheng,3,&ast; Yixuan Ding,1,2 Yuanxu Qu,1,2 Wentong Mei,1,2 Zhen Fang,1,2 Chang Qu,1,2,&ast; Yulu Feng,4 Yulin Guo,1,2 Chongchong Gao,1,2 Feng Cao,1,2 Fei Li1,2 1Clinical Center of Acute Pancreatitis, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Chui Yang Liu Hospital Affiliated Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Clinical Center of Acute Pancreatitis, Department of General Surgery, Department of Surgery, Xuanwu Hospital of Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-10-83198731, Fax +86-10-83198868, Email feili36@ccmu.edu.cn Feng Cao, Clinical Center of Acute Pancreatitis, Department of General Surgery, Xuanwu Hospital of Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Email f.cao@xwhosp.orgObjective: To clarify the incidence of colonic complications in patients with NP and their impact on prognosis.Methods: The clinical data of NP patients admitted to the Department of General Surgery of Xuanwu Hospital, Capital Medical University from January 2014 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of colonic complications, and the clinical prognosis of the two groups was analyzed after matching using a 1:1 propensity score, The primary study endpoint was patient mortality during hospitalization. Data are reported as median (range) or percentage of patients (%).Results: A total of 306 patients with NP were included in this study, and the incidence of colonic complications was 12.4%, including 15 cases of colonic obstruction, 17 cases of colonic fistula, and 9 cases of colonic hemorrhage. Before matching, patients in the colonic group had severe admissions and poor clinical outcomes (P< 0.05). After matching, the baseline data and clinical characteristics at admission were comparable between the two groups of patients. In terms of clinical outcomes, although the mortality was similar in the two groups (P> 0.05), but patients in the colonic group were more likely to have multiorgan failure, length of nutrition support, number of minimally invasive interventions, number of extra-pancreatic infections, length of ICU stay and total length of stay were significantly higher than those of patients in the group without colonic complications (P< 0.05). During long-term follow-up, patients in the colonic group were more likely to develop recurrent pancreatitis.Conclusion: About 12.4% of NP patients developed colonic complications, and after PSM it was found that colonic complications only led to a longer hospital stay and an increased number of clinical interventions in NP patients and did not increase the mortality.Keywords: necrotizing pancreatitis, colon involvement, propensity score match

Yanzheng Zou,1,* Ming Yue,2,* Linna Jia,1 Yidi Wang,1 Hongbo Chen,3 Yifan Wang,3 Meiling Zhang,3 Yue Feng,4 Rongbin Yu,1 Sheng Yang,5 Peng Huang1 1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Infectious Disease, Jurong Hospital Affiliated to Jiangsu University, Jurong, People’s Republic of China; 4Faculty of Life Science and Technology, Kunming University of Science and Technology, Yunnan, People’s Republic of China; 5Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Huang, Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China, Email huangpeng@njmu.edu.cn Sheng Yang, Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China, Email yangsheng@njmu.edu.cnPurpose: It is unclear whether and how the long-term risk of hepatocellular carcinoma (HCC) will change in hepatitis C virus (HCV) infected patients who have reached sustained virologic response (SVR) with direct-acting antivirals (DAA). In this study, we assessed the long-term risk of HCC up to 10 years after SVR using fibrosis 4 score (FIB-4) and its dynamic changes.Patients and Methods: A total of 701 DAA-treated patients who achieved SVR between January 2012 to October 2020 were enrolled in the study. The FIB-4 score of each patient was measured at the date of SVR and each follow-up visit annually. Patients were followed until December 31, 2021, with the longest follow-up time being 9.82 years.Results: Following SVR, 27 cases of HCC were observed. The annual incidence rate of HCC remained stable with no obvious downward trend. Patients with a FIB-4 > 3.25 at baseline or anytime during follow-up were at a higher risk of developing HCC than those whose FIB-4 remained below 3.25. Patients with cirrhosis and patients with no cirrhosis but a FIB-4 > 3.25 were at higher risk of developing HCC than patients with no cirrhosis and a FIB-4 ≦3.25.Conclusion: FIB-4 > 3.25 measured at SVR or any time post-SVR was associated with HCC risks. The repeated measurement of FIB-4 revealed a better predictive ability of HCC risks than the simple measurement of FIB-4 at baseline. The additional stratification of patients by combining FIB-4 and cirrhosis leads to more accurately identifying high-risk patients. Surveillance of HCC is recommended for virologically cured patients with a FIB-4 > 3.25 at SVR or anytime afterward and patients diagnosed with cirrhosis.Keywords: chronic hepatitis C, sustained virologic response, direct-acting antivirals, serum biomarker, hepatocellular carcinoma

Jufang Wang,1 Yating Feng,2 Yan Zhang,3 Jing Liu,2 Le Gong,2 Xiaohong Zhang,1 Hui Liao4 1Department of Ultrasonic Diagnosis, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, People’s Republic of China; 2School of Pharmacy, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, People’s Republic of China; 4Department of Pharmacy, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, People’s Republic of ChinaCorrespondence: Xiaohong Zhang, Department of Ultrasonic Diagnosis, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, People’s Republic of China, Email doctorzhangxh@126.com Hui Liao, Department of Pharmacy, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), No. 29 Shuangtasi Street, Taiyuan, Shanxi Province, People’s Republic of China, Email huiliao@263.netPurpose: Diabetic nephropathy (DN) is a serious microvascular complication in those with type 2 diabetes mellitus (T2DM). Evidence confirms that serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the T2DM stage are proposed as prognostic markers for DN development, but it is unclear how they affect renal podocyte-associated nephrin and WT-1 expression. In the presence of podocyte injury, glomerular vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) and hemodynamic parameters are dysregulated. The current research aimed to clarify the relationship of TNF-α and IL-1β with podocyte injury by altering VEGF/eNOS expression and hemodynamic parameters.Methods: A high-fat diet/streptozotocin-induced DN rat model was established. Serum TNF-α and IL-1β levels were tracked in the pre-T2DM, T2DM and DN stages. In the DN stage, the mRNA and protein expression levels of renal TNF-α, IL-1β, VEGF, eNOS, nephrin and WT-1 were studied. Renal hemodynamic parameters, including peak systolic velocity, end-diastolic flow velocity and mean velocity were measured with a color Doppler ultrasound technique.Results: Compared to those in the normal control (CTL) group, serum TNF-α and IL-1β levels increased significantly in the pre-T2DM stage (obesity, insulin resistance and hyperlipidemia), T2DM stage (hyperglycemia) and DN stage (abnormal renal functions) (all: P < 0.05) in the DN group. Serum TNF-α and IL-1β levels in the T2DM stage were significantly higher than those in the pre-T2DM stage (two: P < 0.05). Compared to the CTL group, renal nephrin, WT-1, TNF-α, IL-1β, eNOS and VEGF expression and hemodynamic parameters in the DN stage all showed significant differences separately (all: P < 0.05).Conclusion: Increased serum and renal TNF-α and IL-1β levels played important roles in reducing renal nephrin and WT-1 expression levels, which may be related to the fact that the former affected renal VEGF/eNOS expression and blood flow parameters in the DN rats.Keywords: TNF-α, IL-1β, podocyte injury, vascular endothelial growth factor, endothelial nitric oxide synthase, hemodynamic parameters

Teng Zhang,1,2,&ast; Juan Huang,1,3,&ast; Yanru Li,1,&ast; Dubo Zhong,4 Songmei Wang,1 Fang Xu,1 Xuehui Zhang,1 Yuemei Feng,1 Jianzhong Yin1,2 1School of Public Health, Kunming Medical University, Kunming, People’s Republic of China; 2Baoshan College of Traditional Chinese Medicine, Baoshan, People’s Republic of China; 3Ultrasonography Department, First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Yunnan Yunce Quality Inspection Limited Company, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianzhong Yin, Baoshan College of Traditional Chinese Medicine, Longyang District, Baoshan, Yunnan Province, 678000, People’s Republic of China, Tel +86 13987645337, Email yinjianzhong2005@sina.com Yuemei Feng, School of Public Health, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, People’s Republic of China, Tel +86 13678754163, Email fengyuemei2013@163.comBackground: Dietary fatty acids (DFAs) and plasma fatty acids (PFAs) are linked to obesity. However, whether this association exists among ethnic minorities remains lacking. The present cross-sectional study was designed to investigate the correlation between DFAs, PFAs and obesity in four ethnic minority groups to Southwest China.Methods: A total of 166 obese people, and 166 normal-BMI subjects matched based on their age-, sex-, and ethnicity- were recruited from four different ethnic minority groups. DFAs were obtained through food frequency questionnaires. PFAs were assayed by GC/MS method. Binary and multiple regression analyses were performed to evaluate the correlation among DFAs, PFAs and obesity. Canonical correlation analysis (CCA) was conducted to assess the relationship between DFAs and PFAs.Results: FAs were found to be highest in the Naxi people and lowest in the Hani people. Multiple logistic regression analysis revealed that plasma C16:0 (OR = 1.310; 95% CI, 1.028– 1.669) in the Hani people; plasma C20:3 n-6 (OR = 6.250; 95% CI, 1.224– 31.927) and dietary C20:1 (OR = 9.231; 95% CI, 1.253– 68.016) in the Wa people; plasma C18:0 (OR = 0.788; 95% CI, 0.681– 0.912) in the Naxi people were seen to be independent predictive factors for obesity. CCA showed that DFAs were positively correlated with PFAs in the Naxi (r: 0.676; P < 0.05) and Bulang people (r: 0.897; P < 0.05), but there was no correlation in the Hani and Wa people.Conclusion: In this study, PFAs but not DFAs were independently associated with obesity, and different among the four ethnic minorities.Keywords: dietary fatty acids, plasma fatty acids, obesity, minorities, canonical correlation analysis

Jiongdi Lu,1,2 Yixuan Ding,1,2 Yuanxu Qu,1,2 Wentong Mei,1,2 Yulin Guo,1,2 Zhen Fang,1,2 Chang Qu,1,2 Chongchong Gao,1,2 Feng Cao,1,2,&ast; Fei Li,1,2,&ast; Yulu Feng3 1Clinical Center of Acute Pancreatitis, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pediatric, Chui Yang Liu Hospital Affiliated Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li; Feng Cao, Clinical Center of Acute Pancreatitis, Capital Medical University, Department of General Surgery, Department of Surgery, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-10-83198731, Fax +86-10-83198868, Email feili36@ccmu.edu.cn; f.cao@xwhosp.orgObjective: The incidence of acute pancreatitis (AP) is increasing. Twenty percent of AP patients with developing necrotizing pancreatitis (NP), while ~40– 70% of NP patients develop potentially fatal infectious complications. When patients are suspected or confirmed infected pancreatic necrosis (IPN), antibiotics should be administered timeously to control the infection, but long-term use of antibiotics can lead to multidrug-resistant bacteria (MDRB) infection and eventually to increased mortality. Our study aimed to determine the incidence of MDRB infection and evaluate the risk factors for MDRB infection in IPN patients.Methods: Clinical data of IPN patients admitted to the general surgery department of Xuanwu Hospital of Capital Medical University between January 1, 2014, and December 31, 2021, were retrospectively analyzed.Results: IPN patients (n = 267) were assigned to MDRB infection (n = 124) and non-MDRB infection (n = 143) groups. On admission, patients in the MDRB group had a higher modified computer tomography severity index (CTSI) score (P < 0.05), pancreatic necrosis degree, and PCT level (P < 0.05) than those in the non-MDRB group, and the prognosis of patients in MDRB group was poor. The most common gram-negative bacteria were Acinetobacter baumannii (n = 117), the most common gram-positive bacteria were Enterococcus faecium (n = 98), and the most common fungal infection was Candida albicans (n = 47). Multivariable analysis showed that complications of EPI (OR: 4.116, 95% CI: 1.381– 12.271, P = 0.011), procalcitonin (PCT) level at admission (OR: 2.728, 95% CI: 1.502– 4.954, P = 0.001), and degree of pancreatic necrosis (OR: 2.741, 95% CI: 1.109– 6.775, P = 0.029) were independent risk factors for MDRB infection in IPN patients.Conclusion: We identified common infectious strains and risk factors for MDRB infection in IPN patients.Keywords: infected pancreatic necrosis, extra-pancreatic infection, multidrug-resistant bacteria, risk factor analysis

Hongxia Lin,1,2,&ast; Yulian Gao,1,2,&ast; Yanli Qiu,3,&ast; Haixing Zhu,1,2 Shengxiong Zhang,1,2 Hanssa Dwarka Summah,4 Guochao Shi,1,2 Tingting Cheng,5,&ast; Zhitao Yang,6 Yun Feng1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 20025, People’s Republic of China; 3Department of Anesthesia, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 4Poudre D’Or Chest Hospital, Rivière du Rempart, Mauritius; 5Department of Respiratory and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 20025, People’s Republic of China; 6Department of Emergency, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhitao Yang; Yun Feng, Email yangzhitao@hotmail.fr; fy01057@163.comIntroduction: Elderly patients with immunosuppressive status may have increased risk of mortality. At present, few studies have explored the clinical characteristics of the elderly immunosuppressed population with bloodstream infection. Our objectives were to evaluate the prognostic factors in immunosuppressed elderly patients with bloodstream infection.Methods: Three hundred and seventy-six elderly patients who were diagnosed with bloodstream infection in immunosuppressive status while receiving treatment in our hospital were selected from 2015 to 2019. The demographic data, underlying diseases, comorbidity, inducement, complications, pathogen sources, etiologies and the antibiotic therapy were analyzed between 90-day survival groups and 90-day mortality groups. The prognostic factors of 90-day mortality were evaluated by univariate logistic regression analysis and multivariate logistic regression analysis.Results: The clinical characteristics of 376 immunosuppressed elderly people diagnosed with bloodstream infection were analyzed, and among those people about 111 were 90-day mortality. By univariate logistic regression analysis and multivariate logistic regression analysis, we found ICU admission (OR: 2.052, 95%CI: 1.088– 3.871, p=0.026), the decrease in BMI (OR: 0.307, 95%CI: 0.130– 0.723, p=0.007), coronary heart disease (OR: 2.028, 95%CI: 1.078– 3.816, p=0.028), biliary infection (OR: 4.406, 95%CI: 1.794– 10.821, p=0.001) and the use of tigecycline (OR: 2.480, 95%CI: 1.195– 5.147, p=0.015) were significantly different between the 90-day survival and 90-day mortality groups.Conclusion: ICU admission, coronary heart disease, biliary infection, and the use of tigecycline were the independent prognostic risk factors of 90-day mortality in immunosuppressed elderly people, and the decrease in BMI was the protective factor, which would have the benefit of discriminating the prognostic factors in immunosuppressed elderly people with bloodstream infection.Keywords: bloodstream infection, elderly people, mortality, immunosuppressive states, prognosis

Yanan Feng,1,&ast; Wenxiu Sun,2,&ast; Fengcui Sun,1 Guoliang Yin,1 Pengpeng Liang,1 Suwen Chen,1 Xiangyi Liu,1 Tongfei Jiang,3 Fengxia Zhang4 1Shandong University of Traditional Chinese Medicine, Jinan, 250000, People’s Republic of China; 2Department of Nursing, Taishan Vocational College of Nursing, Taian, People’s Republic of China; 3Capital Medical University, Beijing, 100069, People’s Republic of China; 4Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengxia Zhang, Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China, Tel +86-131-5317-5246, Email fxzhang0987@163.comAbstract: Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disorders from non-alcoholic fatty liver (NAFL) to the more severe non-alcoholic steatohepatitis (NASH), is the leading etiology of chronic liver disease and its global prevalence is increasing. Hepatic steatosis, a condition marked by an abnormal buildup of triglycerides in the liver, is the precursor to NAFLD. Differentiated cluster 36 (CD36), a scavenger receptor class B protein, is a membrane receptor that recognizes multiple lipid and non-lipid ligands. It is generally agreed that CD36 contributes significantly to hepatic steatosis by taking part in fatty acid uptake as well as triglyceride storage and secretion. While there has not been any conclusive research on how CD36 inhibitors prevent NAFLD from progressing and no clinically approved CD36 inhibitors are currently available for use in NAFLD, CD36 remains a target worthy of further investigation in NAFLD. In recent years, the potential role of natural products acting through CD36 in treating non-alcoholic fatty liver disease has attracted much attention. This paper offers an overview of the pathogenesis of CD36 in NAFLD and summarizes some of the natural compounds or extracts that are currently being investigated for modulating NAFLD via CD36 or the CD36 pathway, providing an alternative approach to the development of CD36-related drugs in NAFLD.Keywords: NAFLD, CD36, natural inhibitors, FFA, TG

Changshui Wang,1,&ast; Shuzhen Zhao,2,&ast; Yuan Xu,3 Wenxue Sun,4 Yuanyuan Feng,2 Deshuai Liang,5 Yun Guan3 1Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272000, People’s Republic of China; 2Children’s Rehabilitation Center, Jining Maternal and Child Health Family Planning Service Center, Jining, 272000, People’s Republic of China; 3Department of Hematology, Jining NO. 1 People’s Hospital, Jining, 272000, People’s Republic of China; 4Institute of Clinical Pharmacy and Pharmacology, Jining NO. 1 People’s Hospital, Jining Medical University, Jining, 272000, People’s Republic of China; 5Department of pharmacy, Jining NO. 1 People’s Hospital, Jining, 272000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Guan; Deshuai Liang, Jining NO. 1 People’s Hospital, 6 Jiankang Road, Jining, Shandong, 272000, People’s Republic of China, Tel/Fax +86-0537 2087092, Email gyuanun1989@163.com; 13468322037@163.comPurpose: We designed this study to investigate the potential correlations between gut microbiota compositions and hepatic metabolomic disorders in mice with methotrexate (MTX)-induced hepatoxicity.Methods: We used MTX to induce hepatoxicity in healthy Kunming mice, and we determined plasma ALT and AST levels and assessed the liver tissue histopathology. We applied an integrated gas chromatography-mass spectrometry (GC-MS) and 16S ribosomal RNA (rRNA) gene sequencing approach to evaluate the effects of MTX on the gut microbiota and hepatic metabolic profiles of mice. We uncovered correlations between the gut microbiota and hepatic metabolomic profiles by calculating the Spearman correlation coefficient.Results: MTX caused ALT and AST level elevations and hepatoxicity in our mouse model. MTX disrupted amino acid metabolic pathways (including biosyntheses of valine, leucine, and isoleucine; and arginine; and, metabolism of alanine, aspartate, and glutamate; histidine; beta-alanine; and glycine, serine, and threonine); biosyntheses of aminoacyl-tRNA; and pantothenate, and CoA; and, metabolic pathways of energy, glutathione, and porphyrin; and chlorophyll. In addition, MTX increased the abundances of Staphylococcus, Enterococcus, Collinsella, Streptococcus, and Aerococcus, but decreased the amounts of Lactobacillus, Ruminococcus, norank_f_Muribaculaceae, unclassified_f_Lachnospiraceae, norank_f_Lachnospiraceae, A2, Eubacterium_xylanophilum_group, Phascolarctobacterium, Bifidobacterium, and Faecalibaculum. Our correlation analyses showed that different flora abundance changes including those of Phascolarctobacterium, Faecalibaculum, norank_f_Muribaculaceae, Streptococcus, Enterococcus, Staphylococcus, and Collinsella were associated with liver injury.Conclusion: We present evidence supporting the notion that MTX causes hepatoxicity by altering the gut microbiota and hepatic metabolite profiles, our findings provide new venues for the management of MTX-induced hepatoxicity.Keywords: gas chromatography-mass spectrometry, 16S ribosomal RNA, methotrexate, hepatoxicity

Yulian Gao,1,&ast; Hongxia Lin,1,&ast; Yumin Xu,2,&ast; Yijin Yao,1,&ast; Dake Shi,1 Junjie Li,1 Haixing Zhu,1 Hanssa Dwarka Summah,3 Lei Ni,1 Yun Feng1 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Hospital Infection Management, Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Respiratory, Poudre D’Or Chest Hospital, Rivière du Rempart, Mauritius&ast;These authors contributed equally to this workCorrespondence: Yun Feng; Lei Ni, Email fy01057@163.com; nilei625@139.comPurpose: Carbapenem-resistant Gram-negative bacteria bloodstream infection (CRGNB-BSI) has gradually become a major threat worldwide due to its treatment difficulty and high mortality. This study aimed to determine the risk factors for CRGNB-BSI in immunosuppressed patients.Patients and Methods: A total of 427 immunosuppressed patients with CRGNB-BSI were retrospectively investigated from 2015 to 2021. Both univariate and multivariate logistic regression analyses were applied to evaluate independent risk factors for CRGNB-BSI.Results: The most common etiology was Klebsiella Pneumoniae (50.59%; 216/427), while the Acinetobacillus baumannii infection was associated with the highest mortality (58.25%) among all etiologies. The 60-day mortality of immunosuppressed patients with CRGNB-BSI was 52.48% (224/427). Procalcitonin (PCT) > 0.5 μg/L (OR = 2.32, 95% CI: 1.28– 4.19, P = 0.005) and age > 55 years (OR = 2.06, 95% CI: 1.17– 3.64, P = 0.012) were found to be predictors of 60-day mortality of CRGNB-BSI, and tigecycline regimen (OR = 3.20, 95% CI: 1.81– 5.67, P < 0.001) was associated with higher mortality. Multivariate analysis also revealed that patients who developed acute kidney injury (AKI) (OR = 2.19, 95% CI: 1.11– 4.30, P = 0.023), gastrointestinal bleeding (OR = 3.18, 95% CI: 1.10– 9.16, P = 0.032), multiple organ dysfunction syndrome (MODS) (OR = 12.11, 95% CI: 2.61– 56.19, P = 0.001), and septic shock (OR = 3.24, 95% CI: 1.77– 5.94, P < 0.001) showed worse outcomes. The risk factors were also significantly associated with mortality in the different subgroups.Conclusion: This study demonstrated that PCT > 0.5 μg/L, age > 55 years, and the tigecycline regimen were significantly associated with higher 60-day mortality among immunosuppressed patients with CRGNB- BSI. Patients developing MODS, septic shock, or AKI had worse clinical outcomes.&#x2003Keywords: bloodstream infection, carbapenem-resistant, immunosuppressed patients, subgroups, prognosis

Yuanyuan Xu,1,2 Yu Zhao,2 Shanji Liu,2 Sidi Lv,3 Ling Chen,4 Wanzhen Wang,1 Yueying Feng,1 Fen Fu,1 Hengyi Xu2 1The Second Affiliated Hospital of Nanchang University, Nanchang, 330000, People’s Republic of China; 2State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, People’s Republic of China; 3Second Clinical Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 4The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341001, People’s Republic of ChinaCorrespondence: Fen Fu, The Second Affiliated Hospital of Nanchang University, No. 1 Mingde Rode, Nanchang, 330000, People’s Republic of China, Tel +86-791-8631-1753, Email fu_fen@163.com Hengyi Xu, State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang, 330047, People’s Republic of China, Tel +86-791-8830-4447-ext-9520, Fax +86-791-8830-4400, Email HengyiXu@ncu.edu.cnIntroduction: Zinc oxide nanoparticles (ZnO NPs) participate in all aspects of our lives, but with their wide application, more and more disadvantages are exposed. The goal of this study was to investigate the toxicity of ZnO NPs in female mice ovaries and explore its potential mechanism.Methods: In this study, adult female mice were orally exposed to 0, 100, 200, and 400 mg/kg ZnO NPs for 7 days. We explored the underlying mechanisms via the intraperitoneal injection of N-acetyl-cysteine (NAC), an inhibitor of oxidative stress, and salubrinal (Sal), an inhibitor of endoplasmic reticulum (ER) stress.Results: The results indicated that serum estradiol and progesterone levels declined greatly with increasing ZnO NPs dosage. Hematoxylin and eosin (HE) staining revealed increased atretic follicles and exfoliated follicular granulosa cells. Moreover, at the transcriptional level, antioxidant-related genes such as Keap1 and Nrf2, and ER stress-related genes PERK, eIF2α, and ATF4 were markedly upregulated. In addition, the expression of Caspase12, Caspase9, and Caspase3, which are genes related to apoptosis, was also upregulated in all ZnO NPs treatment groups. Serum malondialdehyde (MDA) content was remarkably up-regulated, whereas superoxide dismutase (SOD) activity was down-regulated. The 400 mg/kg ZnO NPs treatment group suffered the most substantial harm. However, ovarian damage was repaired when NAC and Sal were added to this group.Conclusion: ZnO NPs had toxic effects on the ovary of female mice, which were due to oxidative stress, ER stress, and the eventual activation of apoptosis.Graphical Abstract: Keywords: zinc oxide nanoparticles, ovary, oxidative stress, endoplasmic reticulum stress, apoptosis

Hanbi Wang,1 Zhiyuan Zhang,2 Jie Chen,1 Han Dong,3 Ying Zou,4 Wei Wang,5 Qingmei Zheng,6 Ying Feng,7 Zhangyun Tan,8 Xiaoqin Zeng,9 Yinqing Zhao,8 Yanfang Wang,1 Aijun Sun1 1Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of International Medical Service, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, People’s Republic of China; 4Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, People’s Republic of China; 5Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 6Department of Gynecology, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 7Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 8Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, People’s Republic of China; 9Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnObjective: To explore the needs of obstetricians and gynecologists with different working years for the contents and forms of CME.Methods: The online questionnaire was distributed on the largest academic training platform for obstetrics and gynecology in China from April 2020 to May 2020. The survey contents mainly included the training forms and training contents of CME, as well as the mastery of diseases by doctors with different working years.Results: 4458 questionnaires were returned, of which 3954 questionnaires were included in the study. There was a significant (p < 0.001) positive correlation between the mastery of 19 diseases by obstetricians and gynecologists with different working years. After adjusting for specialist departments, hospital grades, nature of units and ages, it was found that there was no statistically significant difference between the groups in gynecological endocrine-related diseases, such as precocious puberty/delayed puberty, and there was also no statistically significant difference between the groups of shorter working years in infertility, menopausal syndrome, hyperprolactinemia and premature ovarian failure.Conclusion: The most popular training content for obstetricians and gynecologists with different working years is common gynecological endocrine diseases, of which abnormal uterine bleeding, menopausal syndrome, polycystic ovarian syndrome and cervical lesions are the most selected diseases, and the most popular form of training is online.Keywords: continuing medical education, working years, internet, obstetrics and gynecology

Tianyu Liu,1,&ast; Zhiyong Cheng,2,&ast; Shiya Zou,3,&ast; Chao Xu,4 Shoudong Pan,3 Huabei Zeng,2 Yidong Shan,2 Yi Feng,1 Hong Zhang1 1Department of Anesthesiology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Anesthesiology, Suqian Maternity Hospital, Suqian, Jangsu, People’s Republic of China; 3Department of Anesthesiology, Capital Institute of Pediatrics Affiliated Children’s Hospital, Beijing, People’s Republic of China; 4Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Feng; Hong Zhang, Department of Anesthesiology, Peking University People’s Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, People’s Republic of China, Tel +86-13601083503 ; +86-13311281808, Email doctor_yifeng@sina.com; zhangh_18@sina.comPurpose: Many previous trials have compared the effects of different vasoactive drugs on cesarean section patients, but their infusion rate is based on experience rather than high-quality evidence. It is difficult to judge whether the effect of vasoactive drug comes from the better choice or a more appropriate at rates of vasoactive drugs. The effect of vasoactive drugs at the rates of the 90% effective dose needs to be verified and compared.Patients and Methods: Women undergoing elective caesarean delivery under combined spinal-epidural anaesthesia were randomized to receive phenylephrine or norepinephrine or metaraminol infusion at the rate that was assumed to be the 90% effective dose. Anesthetic management was standardized and included fluid loading with 10 mL/kg of Ringer. The primary outcome was the umbilical artery pH.Results: 78 patients were included. The umbilical artery pH was not significantly different among the three groups (phenylephrine group: 7.33 ± 0.03 vs norepinephrine group: 7.33 ± 0.04 vs metaraminol group: 7.33 ± 0.04, P = 0.99). There were no significant differences in the incidence of hypotension, hypertension, bradycardia, and nausea and vomiting among the three groups. The SBP of the phenylephrine group was significantly higher than that of the metaraminol group (adjustive P value = 0.005).Conclusion: Phenylephrine (0.54 μg/kg/min) or metaraminol (2 μg/kg/min) or norepinephrine (0.08 μg/kg/min) administered to healthy patients with elective cesarean section after spinal anesthesia has no significant effect on the acid-base balance of the fetus.Keywords: cesarean section, vasoactive drugs, foetal acid-base balance, randomized controlled trial

Kaifang Wang,1,2 Xin Ning,1 Chuanyue Qin,1 Jianlin Wang,1 Wenjie Yan,1 Xin Zhou,1 Deping Wang,1 Jimin Cao,1 Yanlin Feng1 1Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Cardiology, First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Jimin Cao; Yanlin Feng, Email caojimin@sxmu.edu.cn; feng@sxmu.edu.cnIntroduction: The wide application of copper oxide nanoparticles (CuO NPs) in industry, agriculture, environmental remediation, and biomedicine has increased the risk of human exposure to CuO NPs. Recent studies suggested that CuO NPs have genotoxic and cytotoxic effects on various cells. However, little is known about the toxicity of CuO NPs on major peripheral organs after respiratory exposure.Materials and Methods: We investigated the toxicities of CuO NPs on human bronchial epithelial (BEAS-2B) and human cardiomyocytes (AC16) cells in vitro, and on the lungs, liver, kidneys, and heart of spontaneously hypertensive rats (SHRs) at 24 and 72 h after intrabronchial instillation in vivo.Results: CuO NPs induced concentration-dependent toxicities in both BEAS-2B and AC16 cells mainly through hierarchical oxidative stress mechanisms, involving generation of reactive oxygen species (ROS), upregulation of heme oxygenase-1 (HO-1), mitochondrial dysfunction, and secretion of proinflammatory and profibrogenic cytokines. Respiratory exposure to CuO NPs induced acute multiple organ injuries in SHRs manifesting through inflammation and fibrosis. However, cardiac injury was relatively less severe than injuries in the lungs, liver, and kidneys. Upregulation of serum C-reaction protein (CRP), tumor necrosis factor α (TNF-α), intercellular adhesion molecule 1 (ICAM-1), endothelin-1 (ET-1), angiotensin converting enzyme (ACE), and von Willebrand factor (vWF) after exposure to CuO NPs indicated systematic inflammation, endothelial injury, and potential prothrombosis.Conclusion: Respiratory exposure to CuO NPs induced acute injuries in main peripheral organs, including the lungs, liver, kidneys, and heart. Individuals with existing cardiovascular diseases were susceptible to exposure to CuO NPs. This study provides a warning about the extensive toxic effects of CuO NPs, especially in the susceptible population.Keywords: CuO nanoparticle, nanotoxicology, hierarchical oxidative stress response, intratracheal instillation, spontaneously hypertensive rat

Wang N, Feng Y, Xie J, Han H, Dong Q, Wang W. Cancer Manag Res. 2020;12:13285-13300. At the author’s request, we, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 5 and 7 with images from other unrelated articles. Specifically, The image for Figure 5G, HL-60, ZNF667-AS1 si+miR-206 inh, has been duplicated with the image for Figure 5d, H460, miR-520a control, from Xie Y, Xue C, Guo S, Yang L. MicroRNA-520a Suppresses Pathogenesis and Progression of Non-Small-Cell Lung Cancer through Targeting the RRM2/Wnt Axis. Analytical Cellular Pathology. 2021;2021: Article ID 9652420. https://doi.org/10.1155/2021/9652420. The image for Figure 7H, HL-60, miR-206 inh+NC, has been duplicated with the image for Figure 4H, HSC-1, TIMP3 si, from Yin S, Lin X. MicroRNA-21 Contributes to Cutaneous Squamous Cell Carcinoma Progression via Mediating TIMP3/PI3K/AKT Signaling Axis. Int J Gen Med. 2021;14:27-39. https://doi.org/10.2147/IJGM.S275016. In addition, Figure 5G, HL-60, ZNF667-AS1 si+miR-206 inh and Figure 7H, HL-60, miR-206 inh+NC, have been duplicated. When approached for an explanation, the authors were cooperative and provided some data for their study. However, the author’s explanation and the provided data did not sufficiently explain how the duplication of these images occurred and was unable to alleviate the journal’s concerns regarding the validity of the findings. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Editor and Publisher agreed with this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Zhao F, Feng Y, Zhang X, Liu X, Li A. Cancer Manag Res. 2020;12:12769–12778. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Since publication, concerns have been raised about the integrity of the data in the article. This includes the duplication of tumor images for Figure 5A with images for Figure 5A from Gao Z-Y, Yu F, Jia H-X, Ye Z, Yao S-J. ASPM predicts poor prognosis and regulates cell proliferation in bladder cancer. Kaohsiung J Med Sci. 2020;36:1021–1029. https://doi.org/10.1002/kjm2.12284. When approached for an explanation, the authors were cooperative but were unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were informed of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Yanfei Feng,1,&ast; Zitong Yang,2,&ast; Xin Xu2 1The Second Affiliated College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Xu, Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79th Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel +86 19858164566, Fax +86 571 87236114, Email drxuxin@zju.edu.cnAbstract: Mesenchymal-epithelial transition factor (c-Met) belongs to the tyrosine kinase receptor family and is overexpressed in various human cancers. Its ligand is hepatocyte growth factor (HGF), and the HGF/c-Met signaling pathway is involved in a wide range of cellular processes, including cell proliferation, migration, and metastasis. Emerging studies have indicated that c-Met expression is strongly associated with bladder cancer (BCa) development and prognosis. Therefore, c-Met is a potential therapeutic target for BCa treatment. Recently, the aberrant expression of noncoding RNAs was found to play a significant role in tumour progression. There is a close connection between c-Met and noncoding RNA. Herein, we summarized the biological function and prognostic value of c-Met in BCa, as well as its potential role as a drug target. The relation of c-Met and ncRNA was also described in the paper.Keywords: c-Met, HGF, noncoding RNA, bladder cancer, review

Yong Feng, Na Li, Yi Ren Department of Thoracic Surgery, Shenyang Chest Hospital, the Tenth People’s Hospital of Shenyang, Shenyang, People’s Republic of ChinaCorrespondence: Yi Ren, Shenyang Chest Hospital, the Tenth People’s Hospital of Shenyang, 11 Beihai Street, Shenyang, 110044, People’s Republic of China, Tel +8615942068710, Email yi498857876@163.comBackground: Glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) is a key enzyme in the biosynthetic pathway of uridine diphosphate-N-acetylglucosamine and is upregulated in multiple malignancies. However, its function in cancer biology remains unclear.Methods: Using TCGA dataset, this study analysed GNPNAT1 expression in non-small cell lung cancer (NSCLC) and assessed the correlation between GNPNAT1 and NSCLC patient prognosis. MTT and transwell assays were performed to determine the effect of GNPNAT1 on the growth and metastatic ability of lung cancer cells. GNPNAT1 expression was detected using immunohistochemistry in 78 NSCLC patients, and we analysed the correlation among clinicopathological parameters, overall survival (OS) and GNPNAT1 levels. Transcription factors that potentially regulate GNPNAT1 were explored using database analysis. RNF2 expression was verified using immunohistochemistry in NSCLC tissues.Results: The results indicated that GNPNAT1 was upregulated in NSCLC, and patients with high GNPNAT1 levels had a poor prognosis. GNPNAT1 overexpression promoted the proliferative and metastatic ability of lung cancer cells, whereas GNPNAT1 knockdown showed the opposite effect. GNPNAT1 expression was upregulated in NSCLC tissues compared to matched normal tissues as assessed by immunohistochemistry. Moreover, GNPNAT1 levels were positively correlated with histological type and pathological stage. The negative correlation between GNPNAT1 levels and OS was confirmed in 78 NSCLC patients. Aberrant RNF2 partly contributed to the upregulation of GNPNAT1 expression in NSCLC.Conclusion: These findings suggested that GNPNAT1 was upregulated and played an important role in NSCLC. GNPNAT1 is expected to represent an effective prognostic biomarker for NSCLC patients.Keywords: non-small cell lung cancer, glucosamine-phosphate N-acetyltransferase 1, overall survival, proliferation, metastasis

Qingyun Yang,&ast; Jian Yang,&ast; Shuigen Sun, Jingyi Zhao, Shuang Liang, Yi Feng, Minchen Liu, Jiquan Zhang Engineering Research Center of Modern Preparation Technology of TCM of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Feng; Jiquan Zhang, Engineering Research Center of Modern Preparation Technology of TCM of Ministry of Education, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, People’s Republic of China, Tel +86-21-51322431 ; +86 13816062506, Email fyi@vip.sina.com; jqzhang@shutcm.edu.cnBackground: Rhodojaponin III (RJ-III) is a bioactive diterpenoid, which is mainly found in Rhododendron molle G. Don (Ericaceae), a potent analgesia in traditional Chinese medicine with several years of clinical applications in the country. However, its clinical use is limited by its acute toxicity and poor pharmacokinetic profiles. To reduce such limitations, the current study incorporated RJ-III into the colloidal drug delivery system of hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-modified solid lipid nanoparticles (SLNs) to improve its sustained release and antinociceptive effects in vivo for oral delivery.Results: The optimized RJ-III@HACC-SLNs were close to spherical, approximately 134 nm in size, and with a positive zeta potential. In vitro experiments showed that RJ-III@HACC-SLNs were stable in the simulated gastric fluid and had a prolonged release in PBS (pH = 6.8). Pharmacokinetic results showed that after intragastric administration in mice, the relative bioavailability of RJ-III@HACC-SLNs was 87.9%. Further, it was evident that the peak time, half-time, and mean retention time of RJ-III@HACC-SLNs were improved than RJ-III after the administration. In addition, pharmacodynamic studies revealed that RJ-III@HACC-SLNs markedly reduced the acetic acid, hot, and formalin-induced nociceptive responses in mice (P < 0.001), and notably increased the analgesic time (P < 0.01). Moreover, RJ-III@HACC-SLNs not only showed good biocompatibility with Caco-2 cells in vitro but its LD50 value was also increased by 1.8-fold as compared with that of RJ-III in vivo.Conclusion: These results demonstrated that RJ-III@HACC-SLNs improved the pharmacokinetic characteristics of the RJ-III, thereby exhibiting toxicity-attenuating potential and antinociceptive enhancing properties. Consequently, HACC-SLNs loaded with RJ-III could become a promising oral formulation for pain management that deserves further investigation in the future.Graphical Abstract: Keywords: rhodojaponin III, multimodal antinociceptive, oral administration, solid lipid nanoparticles, hydroxypropyl trimethyl ammonium chloride chitosan, pharmacokinetic

Zhiqiang Nie,1,2,&ast; Hongbin Xu,2,&ast; Chen Chen,3,&ast; Yong Gan,2 Guo Chen,1 Chao Wang,2 Wei Yue,4 Feng Yan,5 Yingqing Feng,1 Zuxun Lu2 1Department of Cardiology, Hypertension Research Laboratory, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Respiratory, Pediatric Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Department of Neurology, Tianjin Huanhu Hospital, Tianjin, People’s Republic of China; 5Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuxun Lu, School of Public Health, Tongji Medical College, No. 13 Hangkong Road, Wuhan, 430030, People’s Republic of China, Email zuxunlu@yahoo.com Yingqing Feng, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Two Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Email 651792209@qq.comBackground: There is an association between atrial fibrillation (AF) and overall mortality as well as mobility. It is not known, however, what the preventable burden of AF in China is. This study aims to identify what proportion of the burden of AF may be avoided by modifiable risk factors.Methods: As part of the China National Stroke Screening and Prevention Project, 726,451 adults aged ≥ 40 years were enrolled in a representative cross-sectional study. The following seven factors have been categorized as modifiable risk factors for AF: body mass index, smoking, alcohol consumption, physical inactivity, hypertension, diabetes mellitus, and dyslipidemia. In order to calculate population-attributable risks (PARs), odds ratios (ORs) were calculated for selected risk factors.Results: The crude ORs increased with age (ORs ranged from 1.92 to 4.02). A total of 18,736 cases of prevalent AF have been identified. The overall prevalence of AF was 2.6%. The crude ORs increased with age (ORs range 1.92– 4.03). The adjusted ORs and the corresponding confidence intervals (CIs) for these seven modifiable factors were 1.16 (95% confidence interval [CI]: 1.12– 1.19), 1.56 (95% CI: 1.49– 1.62), 2.15 (95% CI: 2.02– 2.28), 2.07 (95% CI: 2.01– 2.14), 2.71 (95% CI: 2.62– 2.79), 2.10 (95% CI: 2.02– 2.19), 2.52 (95% CI: 2.44– 2.60), and 3.32 (95% CI: 3.18– 3.48), respectively. Accordingly, 59.3% of all cases of AF could be explained by having these modifiable risk factors, among which hypertension accounted for the greatest share.Conclusion: In China, hypertension is the leading preventable cause of AF, and more than half of these cases can be prevented through improving those modifiable risk factors.Keywords: atrial fibrillation, risk factors, population attributable risk, odds ratio, hypertension

Bo Wang,1,&ast; Song Gong,2,&ast; Lizhi Han,2 Wenkai Shao,2 Zilin Li,2 Jiawei Xu,2 Xiao Lv,2 Baojun Xiao,2 Yong Feng2 1Department of Rehabilitation, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baojun Xiao; Yong Feng, Email drxiao999@sohu.com; fengyong@hust.edu.cnBackground: Histone deacetylase 9 (HDAC9) is a member of the HDAC gene family that plays essential roles in the organization of transcriptional regulation by catalyzing deacetylation of histone proteins. However, the effects of HDAC9 on osteonecrosis of femoral head (ONFH) have not been investigated. The present study aimed to reveal whether histone deacetylase 9 (HDAC9) regulated osteogenic differentiation.Methods: A lentiviral knockdown HDAC9 model was established in hBMSCs. Osteoblast-specific gene expression, such as Runx2, OCN was examined by qRT-PCR and Western blot, respectively. Though transcriptome sequencing and enrichment analysis, related signal pathways caused by down-regulation of HDAC9 were screened. The effect of HDAC9 on MAPK signaling pathway was determined by Western blot. Eventually, tert-Butylhydroquinone (tBHQ) was used to examine the effect of MAPK activation on osteogenesis in HDAC9 knockdown hBMSCs.Results: A lentiviral knockdown HDAC9 model was successfully established in hBMSCs. HDAC9 knockdown significantly inhibited osteoblast-specific gene expression, such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and mineral deposition in vitro. Moreover, a total of 950 DEGs were identified in HDAC9-knockdown hBMSCs. We discovered that the MAPK signaling pathway might be related to this process by pathway enrichment analysis. HDAC9 knockdown significantly reduced the expression level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). Finally, the decreased osteogenesis due to HDAC9 knockdown was partly rescued by a MAPK signaling pathway activator.Conclusion: Taken together, these results suggest that HDAC9 knockdown inhibits osteogenic differentiation of hBMSCs, partially through the MAPK signaling pathway. HDAC9 may serve as a potential target for the treatment of ONFH.Keywords: HDAC9, hBMSCs, osteogenesis, MAPK signaling pathway

Fangfang Zhang,1,2 Yahui Feng,1 Sisi Wang,3 Dongmei Li,4 Dongmei Shi3,5 1College of Clinical Medicine, Jining Medical University, Jining, 272000, People’s Republic of China; 2Department of Dermatology, Jining Dermatosis Prevention and Treatment Hospital, Jining, 272000, People’s Republic of China; 3Laboratory of Medical Mycology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of China; 4Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, 20057, USA; 5Department of Dermatology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of ChinaCorrespondence: Dongmei Shi, Laboratory of Medical Mycology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of China, Tel +86 537-6051008, Email shidongmei28@163.comAbstract: Impetigo, commonly caused by bacteria, is characterized by lesions of pustules, bullae or golden yellow crusts; it is seldom caused by fungi. Here, we report one case of a 17-year-old female patient with a 1-month history of erythematous pustules on her left cheek. She was clinically diagnosed with “impetigo”, but did not respond to 1 week of treatment with topical mupirocin cream (antibacterial agent). We then saw that a fungal colony grew on the culture, which was identified as T. mentagrophytes based on the morphological and molecular characteristics. The patient was then diagnosed with tinea faciei and was topically treated with 0.2% ketoconazole cream twice per day for 7 days. Through a literature review, we found another 18 cases of impetigo-like tinea faciei with similar clinical manifestations and pathogenic characteristics. Among these, the most common causative agent was T. mentagrophytes complex, which frequently occurs in children and adolescents and exhibits no gender preferences. Systemic and topical antifungals such as terbinafine or itraconazole are effective for impetigo-like tinea faciei caused by T. mentagrophytes complex. However, prolonged course of impetigo in more than 50% cases highlights the importance of mycological examination when dealing with apparent antibiotic-resistant impetigo cases in clinical settings.Keywords: tinea faciei, impetigo, Trichophyton mentagrophytes

Jiake Xu,1 Shaochun Li,2 Ye Feng,1 Jie Zhang,1 Youduo Peng,2 Xiaohong Wang,2 Hongwei Wang2 1Department of Gastroenterology, Kunshan Second People’s Hospital, Kunshan, People’s Republic of China; 2Department of General Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hongwei Wang, Tel +86 15021133649, Email 15021133649@163.comPurpose: The fibrinogen/albumin ratio (FAR) is increasingly considered as a potential biomarker for predicting prognosis in various malignant tumors, whereas the value of the FAR in predicting the recurrence-free survival (RFS) in patients with combined hepatocellular cholangiocarcinoma (cHCC-CCA) after surgery has not been studied.Patients and Methods: A total of 104 patients with surgical-pathologically proved cHCC-CCA were retrospectively analyzed. The best cut-off value of the FAR was calculated via receiver operating characteristic (ROC) curve analysis, and the cohort was then divided into two groups as high-FAR (H-FAR) group and low-FAR (L-FAR) group. The correlation between the preoperative FAR and clinicopathological characteristics was analyzed. Uni- and multi-variable analyses for RFS were evaluated using a Cox proportional hazards model to verify the predictive value of FAR on the RFS of cHCC-CCA. Additionally, a novel clinical nomogram based on FAR was developed to preoperatively predict the RFS of HCC-CCA. The C-index and calibration were conducted to evaluate the performance of the developed nomogram.Results: According to the cut-off value of the FAR, the patients were grouped into the H-FARI (> 0.075) and L-FARI (≤ 0.075) groups. FAR was significantly correlated with several clinical-pathological features, including age, cirrhosis, AFP, CA19-9, BCLC staging, NLR, and PLR. In the multi-variate analysis, FAR, cirrhosis and tumor size were independent prognostic predictors for poor RFS in cHCC-CCA patients after surgery. Moreover, the clinical nomogram based on FAR was constructed, showing well-predictive accuracy.Conclusion: The preoperative FAR is a convenient and feasible serum biomarker for predicting the RFS of cHCC-CCA after surgery. Such developed FAR-based nomogram integrating tumor size and cirrhosis could be served as a feasible and convenient tool to assist the decision-making of clinical strategy.Keywords: combined hepatocellular cholangiocarcinoma, fibrinogen-to-albumin ratio, surgery, prognosis

Shanshan Hou,1,2 Xiaokang Wang,3 Fang Wang,4 Zhongliang Li,5 Hui Wang,6 Jiahui Li,7 Jing Wang,8 Haiying He,9 Liping Deng,10 Yushu Feng,11 Xiufang Fan,12 Wen Li,13 Qinghua Lu,14 Yanying Ma,15 Guoying Zhao,16 Simmy Reddy,17 Yanqiu Wu,2,&ast; Yonghui Yu1,3,&ast; 1Department of Neonatology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, People’s Republic of China; 2Department of Pediatric, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, People’s Republic of China; 3Department of Neonatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 4Department of Neonatology, Liaocheng People’s Hospital, Liaocheng, 252000, People’s Republic of China; 5Department of Neonatology, W.F. Maternal and Child Health Hospital, Weifang, 261011, People’s Republic of China; 6Department of Neonatology, Hebei PetroChina Central Hospital, Langfang, 065000, People’s Republic of China; 7Department of Neonatology, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, People’s Republic of China; 8Department of Neonatology, Women and Children’s Healthcare Hospital of Linyi, Linyi, 276000, People’s Republic of China; 9Department of Neonatology, Baogang Third Hospital of Hongci Group, Baotou, 014010, People’s Republic of China; 10Department of Neonatology, Heze Municipal Hospital, Heze, 274031, People’s Republic of China; 11Department of Neonatology, Linyi People’s Hospital, Linyi, 276000, People’s Republic of China; 12Department of Neonatology, Jinan Maternity and Child Health Care Hospital, Jinan, 250001, People’s Republic of China; 13Department of Neonatology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 14Department of Neonatology, Shandong Maternal and Child Health Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, People’s Republic of China; 15Department of Neonatology, Jinan Second Maternal and Child Health Care Hospital, Jinan, 271100, People’s Republic of China; 16Department of Neonatology, Binzhou Medical University Hospital, Binzhou, 256603, People’s Republic of China; 17Cheeloo College of Medicine, Shandong University, Jinan, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghui Yu, Department of Neonatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 234, Jingwu, Road, Huai Yin District, Jinan, Shandong, 250021, People’s Republic of China, Tel +86-0531-66953201, Email alice20402@126.com; yuyonghui6888@126.com Yanqiu Wu, Department of Pediatric, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuhuangding East Road, Zhi fu District, Yantai, 264000, People’s Republic of China, Tel +86-0535-6691999, Email yqwu76@126.comPurpose: Significant antibiotic overuse due to prolonged antibiotic duration has not draw enough attention in developing countries with high antibiotic consumption. We aimed to describe the current status of prolonged early antibiotic duration in very-low-birth-weight (VLBW) infants in a large regional multicenter cohort in China.Patients and Methods: Institution-based prospective cohort study was conducted in all VLBW infants admitted to 16 Grade A tertiary hospitals between January 1, 2019 and December 31, 2020. Early antibiotic use was defined as antibiotic initiation within the first 3 days of life. Prolonged early antibiotic course was defined as early antibiotic initiation for more than 7 days in infants with early-onset sepsis (EOS) or more than 3 days in infants with unlikely EOS. Antibiotic use was described as days of therapy (DOT) per 1000 patient days (PD).Results: Among 1684 eligible VLBW infants, 1544 (91.7%) infants were prescribed with prolonged early antibiotic course, including 618 infants with EOS and 926 infants with unlikely EOS. The median duration of early antibiotic course was 13 (IQR 8;20) days, with 78.0% of courses > 7 days and 43.6% of courses > 14 days. Total early antibiotic use was 408.3DOT/1000Pd, of which prolonged antibiotic courses accounted for 98.2% of all antibiotic use days. More than three antibiotics used, escalation antibiotic therapy, antibiotics for special use and the use of third generation cephalosporins and carbapenems were significantly common in prolonged courses compared to short courses in both infants with EOS and unlikely EOS group (P< 0.05).Conclusion: A large proportion of VLBW infants had excessively prolonged early antibiotic durations in the regional multicenter in China. Timely discontinuation of antibiotics in VLBW infants according to standardized guidelines and limit on the use of third-generation cephalosporins and carbapenems may be key drivers in reducing the antibiotic overuse in developing countries like ours.Keywords: very-low-birth-weight infants, early antibiotic use, prolonged antibiotic course, days of therapy

Tiewei Li,1,&ast; Xiaojuan Li,1,&ast; Xinrui Liu,1 Zhiwei Zhu,1 Min Zhang,1 Zhe Xu,1 Yulei Wei,1 Yichuang Feng,1 Xiaoliang Qiao,2 Junmei Yang,1 Geng Dong1 1Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, People’s Republic of China; 2Center of Laboratory Medicine, Women & Infants Hospital of Zhengzhou, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junmei Yang; Geng Dong, Email yangjunmei7683@163.com; donggeng90@126.comPurpose: Previous studies have demonstrated that procalcitonin and albumin have a close correlation with sepsis. However, the role of procalcitonin (PCT) to albumin (ALB) ratio (PAR) in sepsis was still unclear, especially in neonates. Thus, this study aimed to investigate the association between PAR and neonatal sepsis.Patients and Methods: A total of 1,196 neonates with suspected sepsis were included in this study. Neonates were divided into control group and sepsis group, according to whether they were diagnosed with sepsis. Neonates with sepsis were further divided into mild sepsis and severe sepsis group according to the severity of sepsis. PAR was calculated as serum PCT (ng/mL)/ALB (mg/mL). All statistical analyses were performed using the statistical package SPSS 24.0, as appropriate.Results: Compared with the control group, neonates with sepsis had a higher PAR. PAR also showed a significant gradual increase in the control, mild sepsis, and severe sepsis groups (P< 0.001). Correlation analysis showed that there was a strong positive correlation between PAR and hsCRP, neonatal sequential organ failure assessment score (nSOFA), and prolonged length of hospital stay (P< 0.001). On multiple logistic regression, higher PAR was independently associated with the presence and severity of neonatal sepsis. According to the receiver operating characteristic curve analysis, a PAR ≥ 0.065 had 64% sensitivity and 72% specificity in predicting the presence of neonatal sepsis (area under curve (AUC)=0.72, 95% CI=0.69– 0.75, P< 0.001) and a PAR≥ 0.070 had 69% sensitivity and 63% specificity in predicting the presence of severe sepsis (AUC=0.71, 95% CI=0.68– 0.74, P< 0.001).Conclusion: PAR is significantly higher in neonates with sepsis and correlated with the severity of the disease. Increased PAR is an independent predictor useful for identifying the presence and severity of neonatal sepsis.Keywords: procalcitonin-to-albumin ratio, neonatal sepsis, severe sepsis, predictor

Zhou Li, Yanqi Feng, Piao Li, Shennan Wang, Xinyue Liu, Shu Xia Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Shu Xia, Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People’s Republic of China, Tel +86 15827110062, Fax +86 27-83662834, Email xiashutj@hotmail.comPurpose: Tumor mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) have been well recognized as molecular determinants of immunotherapy responsiveness. In this study, we aimed to construct a TMB prognostic model and explore biomarkers that have predictive potential for prognosis and therapeutic effect in lung adenocarcinoma (LUAD).Patients and Methods: The TCGA, GEO and Immport databases were used to analyze the mutation profiles and immune infiltration of LUAD. TMB scores were calculated and differential analysis was conducted to identify TMB-related genes. Then, Cox regression model and survival analysis were applied to identify the prognostic genes and construct a TMB prognostic model. The expression and prognostic value of CD1B were further verified by immunohistochemistry (IHC) in 92 patient tissue samples. GSEA was performed to analyze the signaling pathways associated with CD1B expression.Results: High-TMB samples exhibited higher infiltration of CD8+ T cells, CD4+ memory T cells, and M1 macrophages. A total of 397 TMB-related differentially expressed genes were identified, of which 47 were immune-related genes. Cox regression analyses determined 3 hub TMB-related immune genes (CD1B, SCGB3A1, and VEGFD) with prognostic effects, and a TMB prognostic model was constructed. The model demonstrated robust predictive ability in both the training (TCGA) and testing (GEO) datasets. Notably, CD1B was identified as an independent prognostic factor. IHC of clinical samples showed that low expression of CD1B was related to poor overall survival and advanced pathological stages. In addition, there was a strong positive correlation between CD1B and most immune checkpoint molecules, including PD-L1. CD1B expression was associated with immune cell infiltration and immune activation in LUAD.Conclusion: Our study constructed a TMB prognostic model that effectively predicted the prognosis of LUAD patients. CD1B expression is correlated with better prognosis and promotes antitumor immunity in LUAD, which may serve as a potential prognostic biomarker and immune-related therapeutic target for LUAD.Keywords: lung adenocarcinoma, tumor mutation burden, CD1B, prognosis, immune infiltrates

Ronghua Mu,1,2,&ast; Xiaoyan Qin,2,&ast; Zixuan Guo,1,2,&ast; Zhuoni Meng,1,2 Fuzhen Liu,2 Zeyu Zhuang,1,2 Wei Zheng,1,2 Xin Li,2 Peng Yang,2 Yuling Feng,2 Yanchun Jiang,3 Xiqi Zhu2 1Graduate School of Guilin Medical University, Guilin, 541004, People’s Republic of China; 2Department of Radiology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, 541004, People’s Republic of China; 3Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, 541004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiqi Zhu, Tel +86 13737399757, Email xiqi.zhu@163.comPurpose: To study the variation tendency of cerebral small vessel disease (CSVD) imaging markers and total burden with aging and to research the relationship between aging, CSVD markers and cognitive function.Methods: Participants in local urban communities were recruited for neuropsychological and magnetic resonance imaging assessments. Montreal Cognitive Assessment (MoCA), Mini-mental State Examination (MMSE), Number Connection Test A (NCT-A) and Digital Symbol Test (DST) were adopted as neuropsychological scale. Age was stratified at 5-year intervals, and the variation tendency of imaging markers and variables of neuropsychological scales in different age groups was studied. We further studied the relationship between aging, image markers and neuropsychological scales by multi-linear regression.Results: Finally, a total of 401 stroke-free participants (age, 54.83± 7.74y; 45.9% were male) were included in the present analysis. With the increase of age, the incidence of imaging markers of CSVD were increased with aging except cerebral microbleeds. The performance results of NCT-A and DST were significant difference in 6 age groups (P < 0.001). In addition, linear decline of the neuropsychological function reflected by NCT-A and DST variables was observed. Linear regression found that age was an independent factor affecting the neuropsychological function reflected by NCT-A and DST variables, and the standard correction coefficients among different age groups increased gradually with age. In addition, brain atrophy is an independent factor affecting neuropsychological variables (odds ratio: − 2.929, 95% CI: [− 5.094 to − 0.765]). There was no correlation between the number of neuroimaging markers and neuropsychological variables after full adjustment.Conclusion: There are many CVSD markers even in younger people, the incidence rate and CVSD marker numbers increase with age. Aging and CSVD may eventually affect cognitive function through brain atrophy.Keywords: cerebral small vessel disease, aging, imaging marker, neuropsychological scales, community-based study

Zhou X, Feng Y, Liu S, et al. Cancer Manag Res. 2021;13:2379–2388. We, the Editors and Publisher of Cancer Management and Research, have retracted the published article. Concerns were raised following the authors request to make changes to Figures 1 and 2 after finding some images had been duplicated. It was also found that tumor images in Figure 6 had been duplicated with images from another article. Specifically, The images for Figure 1A and 1B, have been duplicated with the images for Figure 2C and 2E, respectively. Several of the tumor images shown in Figure 6A, appear to have been duplicated with images from Figure 4B from Zhang J, Cai R, Zhang Y, Wang X. Involvement of a novel circularRNA, hsa_circ_0000520, attenuates tumorigenesis of cervical cancer cell through competitively binding with miR-146b-3p. J Cell Mol Med. 2020;24:8480–8490. https://doi.org/10.1111/jcmm.15414. When approached for an explanation, the authors did not respond to our queries, nor did they provide original data for their study. As verifying the validity of the published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Dan Zhou,1 Mengqi Yan,1 Songtao Tang,2 Yingqing Feng1 1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2Department of Internal Medicine, Community Health Center of Liaobu Community, Dongguan, People’s Republic of ChinaCorrespondence: Yingqing Feng, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Two Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Email 1250780250@qq.comBackground: Diabetes is most commonly associated with aortic stiffness, but the importance of nondiabetic glucometabolic status for aortic stiffness (AS) in hypertension patients is unclear.Methods: We included 1065 hypertension patients without diabetes in a cohort study. Carotid–femoral pulse wave velocity (cfPWV) > 10 m/s can broadly be defined as AS. Pearson correlation analysis and multiple regression analysis are used to reveal the relationship between elevated fasting blood glucose (FBG) and AS.Results: The 1065 hypertension patients (mean age 60 years) included 48% male, 22% smokers, 94.3% with anti-hypertensive drugs, 17.9% with AS, 80% with abdominal obesity, 42% with elevated triglycerides (TG), and 27% with elevated FBG. The mean values for office systolic blood pressure (SBP)/diastolic blood pressure (DBP) and central SBP/DBP were 130/85mmHg and 132/86mmHg. Mean cfPWV was 8.7m/s. Multiple regression analysis revealed that age, office SBP, and elevated FBG were independently related to AS in the whole hypertension. Elevated FBG had 1.6-fold risk of AS in hypertension patients compared with below the cutoff. In subgroup analysis, elevated FBG increased 2.68-fold risk for AS in those without metabolic syndrome (MS), not in MS. The area under curve (AUC) of office SBP was higher than central SBP for AS in receiver operating characteristic (ROC) analysis.Conclusion: We found that elevated FBG was an independent risk factor for AS in hypertension patients without MS, although there was a high proportion of abdominal obesity. Office SBP was better than central SBP to assess AS in community hypertension.Keywords: aortic stiffness, hypertension, elevated plasma blood glucose, carotid–femoral pulse wave velocity

Yuheng Jia1 &ast;, Gaden Luosang2,3 &ast;, Yiming Li,1 Jianyong Wang,2 Pengyu Li,4 Tianyuan Xiong,1 Yijian Li,1 Yanbiao Liao,1 Zhengang Zhao,1 Yong Peng,1 Yuan Feng,1 Weili Jiang,2 Wenjian Li,2 Xinpei Zhang,2 Zhang Yi,2 Mao Chen1 1Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Machine Intelligence Laboratory, College of Computer Science, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Information Science and Technology, Tibet University, Lhasa City, People’s Republic of China; 4West China Medical School, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao ChenDepartment of Cardiology, West China Hospital, Sichuan University, No. 37 Guoxue Street, Chengdu, 610041, People’s Republic of ChinaTel +86-18980602046Fax +86-28-85423169Email hmaochen@vip.sina.comZhang YiMachine Intelligence Laboratory, College of Computer Science, Sichuan University, Chengdu, 610065, People’s Republic of ChinaTel +86-13882217717Fax +86-28-85466062Email zhangyi@scu.edu.cnPurpose: Late major bleeding is one of the main complications after transcatheter aortic valve replacement (TAVR). We aimed to develop a risk prediction model based on deep learning to predict major or life-threatening bleeding complications (MLBCs) after TAVR.Patients and Methods: This was a retrospective study including TAVR patients from West China Hospital of Sichuan University Transcatheter Aortic Valve Replacement Registry (ChiCTR2000033419) between April 17, 2012 and May 27, 2020. A deep learning-based model named BLeNet was developed with 56 features covering baseline, procedural, and post-procedural characteristics. The model was validated with the bootstrap method and evaluated using Harrell’s concordance index (c-index), receiver operating characteristics (ROC) curve, calibration curve, and Kaplan–Meier estimate. Captum interpretation library was applied to identify feature importance. The BLeNet model was compared with the traditional Cox proportional hazard (Cox-PH) model and the random survival forest model in the metrics mentioned above.Results: The BLeNet model outperformed the Cox-PH and random survival forest models significantly in discrimination [optimism-corrected c-index of BLeNet vs Cox-PH vs random survival forest: 0.81 (95% CI: 0.79– 0.92) vs 0.72 (95% CI: 0.63– 0.77) vs 0.70 (95% CI: 0.61– 0.74)] and calibration (integrated calibration index of BLeNet vs Cox-PH vs random survival forest: 0.007 vs 0.015 vs 0.019). In Kaplan–Meier analysis, BLeNet model had great performance in stratifying high- and low-bleeding risk patients (p < 0.0001).Conclusion: Deep learning is a feasible way to build prediction models concerning TAVR prognosis. A dedicated bleeding risk prediction model was developed for TAVR patients to facilitate well-informed clinical decisions.Keywords: deep learning, transcatheter aortic valve replacement, major or life-threatening bleeding complications, prediction model