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Yunxia Zhu,1 Deng Zhang,1 Liang Wu,1 Xiaoliang Ouyang,2 Shengcai Zhu,1 Xiuping Wang,1 Zhen Xiao,3 Yanping Tan,4 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of China; 4Department of Dermatology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Tel/Fax +86 79186278821, Email chunminglincu@163.comPurpose: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant inherited pigmentary dermatosis. The gene responsible for DSH has been identified as adenosine deaminase acting on RNA1 (ADAR1). This study aimed to identify the causative variants in the ADAR1 gene in three Chinese families with DSH.Patients and Methods: Data and blood samples were collected from three Chinese families with DSH. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients. Bioinformatics tools were used to predict the pathogenicity of the variants.Results: Four heterozygous ADAR1 variants were identified, including two novel missense variants c.2369G>C (Arg790Pro), and 503C>T (Pro168Leu), and two previously reported variants: c.3232C>T(R1078C), and c.1472C>G (p.S491X). The novel c.503C>T variant was predicted as “deleterious” (score =− 2.704) by PROVEAN, and “probably damaging” (score = 1) by PolyPhen2. The other novel variant c.2369G>C was also predicted as “deleterious” (score =− 4.167) by PROVEAN, “probably damaging” (score = 1) by PolyPhen2, and “disease-causing” (p = 0.999) by Mutation Taster.Conclusion: Two novel ADAR1 variants were found in Chinese patients with DSH. This research has expanded the ADAR1 gene database for DSH, enhancing our comprehension of the underlying mechanisms.Keywords: dyschromatosis symmetrica hereditaria, adenosine deaminase acting on RNA1, mutation analysis, Chinese

Zixuan Zhang,1 Jing Bai,1 Siqi Zhang,1 Renzhen Wang,1 Shaobing Zhu,1 Tianyue Li,1 Miao Zhang2 1Graduate Schools, Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China; 2Acupuncture and Moxibustion 10 Departments, The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Miao Zhang, Acupuncture and Moxibustion 10 Departments, The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, 150001, People’s Republic of China, Tel +86-13845088833, Fax +86-13114600132, Email hljzmzjzy@163.comAbstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disease caused by multiple causes. The main pathological features of AD are β-amyloid (Aβ) deposition, hyperphosphorylation of Tau protein, and progressive neuronal loss. Pyroptosis is one of the main forms of neuronal death, which is mainly caused by the activation of Gasdermin protein by upstream signals and the release of its N-terminal domain on the cell membrane. Studies have shown that there is a close relationship between Alzheimer’s disease (AD) and pyroptosis. Therefore, this paper summarizes the relationship between pyroptosis and its molecular mechanism and AD, as well as the related research of traditional Chinese medicine in the treatment of AD by regulating pyroptosis, in order to provide a new direction for the study of AD pathogenesis based on pyroptosis pathway.Keywords: Alzheimer’s disease, cell pyroptosis, inflammasome, traditional Chinese medicine

Liang Wu,1 Yunxia Zhu,1 Shengcai Zhu,1 Deng Zhang,1 Xiuping Wang,1 Zhen Xiao,2 Yanping Tan,3 Xiaoliang Ouyang,4 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Dermatology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, People’s Republic of China; 4Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Xiaoliang Ouyang, Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email ouliangncu@163.com Chunming Li, Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email chunminglincu@163.comBackground: Acne vulgaris (AV), a chronic inflammatory pilosebaceous disorder, affects 80– 90% of teenagers. This study aimed to discover lipid profiles and biomarkers of the rabbit ear acne model, and investigate the mechanism of isotretinoin in treating acne at the lipid level.Methods: Untargeted lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was performed to identify skin lipid metabolites in blank control (groups C), model group (group M) and isotretinoin group (group T). Multivariate statistical analysis was used to process the lipidomics data.Results: A total of 43 lipid classes comprising 6989 lipid species were identified from the mass spectrometry data. The orthogonal partial least squares discriminant analysis (OPLS-DA) model demonstrated significant separation in skin lipidomic profiles between group M and group C. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 299 significantly different lipid metabolites were identified. These lipid metabolites consisted mainly of ceramides (Cer) (53.85%), phosphatidylethanolamines (PE) (9.03%), phosphatidylcholines (PC)(5.35%), and sphingomyelin (SM)(4.01%). Combining with AUC ≥ 0.9 as the elected criteria, Cer (d18;1_24:0), zymosterol (ZyE)(33:5), Cer (t43:1), ZyE (33:6), ZyE (24:7), and ZyE (35:6) have “high” accuracy. Isotretinoin treatment normalized 25 lipid metabolites in the acne model.Conclusion: Our findings provide new insights into the role of lipid metabolism in the pathogenesis of acne and the action mechanism of isotretinoin.Keywords: acne vulgaris, lipidomics, isotretinoin, skin, animal model

Chong Zhao,&ast; Shuaiqi Zhu,&ast; Yan Liang, Shuai Xu Department of Spinal Surgery, Peking University People’s Hospital, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Liang; Shuai Xu, Department of Spinal Surgery, Peking University People’s Hospital, Peking University, Beijing, People’s Republic of China, Tel +86-010-88324110 ; +86-18811792718, Email liangyan7503@163.com; xushuairmyy@pku.edu.cnPurpose: To characterize the asymmetrical loss of bone mass and identify the association between scoliosis and osteopenia in patients with adolescent idiopathic scoliosis (AIS).Methods: Demographic information, Cobb angle, and Hounsfield unit (HU) of the neutral vertebra (NV) and apical vertebra (apex) of the major curve were collected retrospectively in 54 AIS patients. For 84 control subjects, HU values were measured at T12 and L5. Propensity score matching was performed to balance the interference of age and BMI.Results: In the AIS group, the concave and convex lateral HU of the NV and the convex lateral HU of the apex were negatively correlated with the Cobb angle. The AIS patients had lower bilateral HU. The mean HU and the apex-convex HU were also lower in the AIS group, while the apex-concave HU was slightly higher. After matching, the apex-convex HU of the AIS group remained lower, while the apex-concave HU was higher.Conclusion: Patients with AIS exhibit osteopenia, particularly on the convex side. The severity of scoliosis was found to be directly proportional to the severity of bone loss and the degree of bilateral osteopenia asymmetry. Appropriate intervention for bone loss may be able to curb the progression of scoliosis.Keywords: adolescent idiopathic scoliosis, osteopenia, osteoporosis, Hounsfield unit, propensity score matching

Lu Xu,1,&ast; Jing Liu,2,&ast; Suli Li,1 Xingchen Lu,1 Wenjie Gu,1 Shunhua Zhu,1 Meng Wang,1 Xiaojin Wu,3 Qingli Huang1 1Public Experimental Research Center of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, People’s Republic of China; 2Department of Neurology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou No. 1 People’s Hospital, Xuzhou, Jiangsu Province, 221100, People’s Republic of China; 3Department of radiotherapy, the affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou No. 1 People’s Hospital, Xuzhou, Jiangsu Province, 221100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojin Wu; Qingli Huang, Email xiaojinwu@xzhmu.edu.cn; qlhuang@xzhmu.edu.cnPurpose: Developing novel multimodal nanomaterials-based anticancer agents to meet complex clinical demands is an urgent challenge. This study presents a novel uniform hollow S-doped NiCuFe Prussian blue analogue (NiCuFe-S) with satisfactory size and properties as anticancer agents for efficient cervical cancer therapy using a simple and environmentally friendly procedure.Methods: The formation mechanism and the reason for enhanced performance of NiCuFe-S were characterized and discussed by diverse spectroscopic and microscopic methods. Moreover, to demonstrate the anti-cancer ability of NiCuFe-S, in vitro and in vivo experiments were carried out.Results: Compared to the non-doped NiCuFe, the NiCuFe-S exhibited significantly enhanced photothermal and catalytic activity attributed to the electronic bandgap-narrowing effect and the increased electron circuit paths resulting from S doping. The hollow structure of NiCuFe-S facilitated the loading of small-molecule drugs, such as doxorubicin (DOX), transforming it into a multimodal nanoplatform for cervical cancer treatment. In vitro and in vivo experiments proved the potential of the NiCuFe-S nanotheranostic agent for chemodynamic therapy (CDT), photothermal therapy (PTT), and chemotherapy for cervical cancer.Conclusion: This research not only overcomes inherent limitations but also significantly broadens the applications of Prussian blue analogues in biomedicine.Keywords: nanomaterials, Prussian blue analogue, catalytic, photothermal therapy, anticancer

Weitang Sun,1 Jingbin Zhong,1 Buyun Gao,2 Jieling Feng,1 Zijie Ye,1 Yueling Lin,3 Kelan Zhang,3 Wenqi Su,3 Shibo Zhu,1 Yinghua Li,4 Wei Jia1 1Department of Pediatric Urology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 3Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Center Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Wei Jia, Email jiawei198044@hotmail.comPurpose: Hydroxyapatite-based nanoparticles have found diverse applications in drug delivery, gene carriers, diagnostics, bioimaging and tissue engineering, owing to their ability to easily enter the bloodstream and target specific sites. However, there is limited understanding of the potential adverse effects and molecular mechanisms of these nanoparticles with varying geometries upon their entry into the bloodstream. Here, we used two commercially available hydroxyapatite nanoparticles (HANPs) with different geometries (less than 100 nm in size each) to investigate this issue.Methods: First, the particle size, Zeta potential, and surface morphology of nano-hydroxyapatite were characterized. Subsequently, the effects of 2~2000 μM nano-hydroxyapatite on the proliferation, migration, cell cycle distribution, and apoptosis levels of umbilical vein endothelial cells were evaluated. Additionally, the impact of nanoparticles of various shapes on the differential expression of genes was investigated using transcriptome sequencing. Additionally, we investigated the in vivo biocompatibility of HANPs through gavage administration of nanohydroxyapatite in mice.Results: Our results demonstrate that while rod-shaped HANPs promote proliferation in Human Umbilical Vein Endothelial Cell (HUVEC) monolayers at 200 μM, sphere-shaped HANPs exhibit significant toxicity to these monolayers at the same concentration, inducing apoptosis/necrosis and S-phase cell cycle arrest through inflammation. Additionally, sphere-shaped HANPs enhance SULT1A3 levels relative to rod-shaped HANPs, facilitating chemical carcinogenesis-DNA adduct signaling pathways in HUVEC monolayers. In vivo experiments have shown that while HANPs can influence the number of blood cells and comprehensive metabolic indicators in blood, they do not exhibit significant toxicity.Conclusion: In conclusion, this study has demonstrated that the geometry and surface area of HANPs significantly affect VEC survival status and proliferation. These findings hold significant implications for the optimization of biomaterials in cell engineering applications.Keywords: hydroxyapatite nanoparticle, circulatory system, biocompatibility, survival, proliferation

Hupo Bian,1 Shaoqi Zhu,2 Yonghua Zhang,3 Qiang Fei,4 Xiuhua Peng,1 Zanhui Jin,1 Tianxiang Zhou,5 Hongxing Zhao1,6 1Department of Radiology, The First Affiliated Hospital of Huzhou Normal University, Huzhou, Zhejiang, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Huzhou Normal University, Huzhou, Zhejiang, People’s Republic of China; 3Department of Radiology, The Wuxing District People’s Hospital, Huzhou, Zhejiang, People’s Republic of China; 4Department of Radiology, The Linghu People’s Hospital, Huzhou, Zhejiang, People’s Republic of China; 5Department of Urinary Surgery, The First Affiliated Hospital of Huzhou Normal University, Huzhou, Zhejiang, People’s Republic of China; 6Huzhou Key Laboratory of Precise Diagnosis and Treatment of Urinary Tumors, Huzhou, Zhejiang, 313000, People’s Republic of ChinaCorrespondence: Hongxing Zhao, Department of Radiology, The First Affiliated Hospital of Huzhou Normal University, No. 158, Plaza Back Road, Wuxing District, Huzhou City, Zhejiang Province, People’s Republic of China, Email zhx2113408@126.comObjective: A bibliometric analysis was conducted using VOSviewer and CiteSpace to examine studies published between 2009 and 2023 on the utilization of artificial intelligence (AI) in chronic obstructive pulmonary disease (COPD).Methods: On March 24, 2024, a computer search was conducted on the Web of Science (WOS) core collection dataset published between January 1, 2009, and December 30, 2023, to identify literature related to the application of artificial intelligence in chronic obstructive pulmonary disease (COPD). VOSviewer was utilized for visual analysis of countries, institutions, authors, co-cited authors, and keywords. CiteSpace was employed to analyze the intermediary centrality of institutions, references, keyword outbreaks, and co-cited literature. Relevant descriptive analysis tables were created using Excel2021 software.Results: This study included a total of 646 papers from WOS. The number of papers remained small and stable from 2009 to 2017 but started increasing significantly annually since 2018. The United States had the highest number of publications among countries/regions while Silverman Edwin K and Harvard Medical School were the most prolific authors and institutions respectively. Lynch DA, Kirby M. and Vestbo J. were among the top three most cited authors overall. Scientific Reports had the largest number of publications while Radiology ranked as one of the top ten influential journals. The Genetic Epidemiology of COPD (COPDGene) Study Design was frequently cited. Through keyword clustering analysis, all keywords were categorized into four groups: epidemiological study of COPD; AI-assisted imaging diagnosis; AI-assisted diagnosis; and AI-assisted treatment and prognosis prediction in the COPD research field. Currently, hot research topics include explainable artificial intelligence framework, chest CT imaging, and lung radiomics.Conclusion: At present, AI is predominantly employed in genetic biology, early diagnosis, risk staging, efficacy evaluation, and prediction modeling of COPD. This study’s results offer novel insights and directions for future research endeavors related to COPD.Keywords: chronic obstructive pulmonary disease, artificial intelligence, visual analysis, bibliometric analysis

Siqi Zhu,1– 3,&ast; Yajun Cui,2,3,&ast; Weidong Zhang,2,3 Yu Ji,2,3 Lingshuang Li,2,3 Shenglei Luo,4 Jing Cui,5,6 Minqi Li2,3 1School of Stomatology, Jinzhou Medical University, Jinzhou, People’s Republic of China; 2Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People’s Republic of China; 3Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, People’s Republic of China; 4Department of Oral and Maxillofacial Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 5Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital, Jinan, People’s Republic of China; 6Central Laboratory, Jinan Key Laboratory of oral tissue regeneration, Shandong Provincial Health Commission Key Laboratory of Oral Diseases and Tissue Regeneration, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Cui, Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital, Jinglv Road 101, Jinan, 250001, People’s Republic of China, Tel +86-0531-86261960, Email 2005cuijing@163.com Minqi Li, Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Wenhua West Road 44-1, Jinan, 250012, People’s Republic of China, Tel +86-0531-88382095, Email liminqi@sdu.edu.cnPurpose: Zoledronate (ZA) stands as a highly effective antiresorptive agent known to trigger medication-related osteonecrosis of the jaw (MRONJ). Its clinical dosages primarily encompass those used for oncologic and osteoporosis treatments. While inflammation is recognized as a potential disruptor of mucosal healing processes associated with ZA, prior research has overlooked the influence of varying ZA dosages on tissue adaptability. Therefore, a deeper understanding of the specific mechanisms by which inflammation exacerbates ZA-induced MRONJ, particularly when inflammation acts as a risk factor, remains crucial.Methods: Cell proliferation and migration of human oral keratinocytes (HOK) was analyzed after treatment with different doses of ZA and/or lipopolysaccharide (LPS) to assess their possible effect on mucosal healing of extraction wounds. Mouse periodontitis models were established using LPS, and histological changes in extraction wounds were observed after the administration of oncologic dose ZA. Hematoxylin and eosin (HE) staining and immunofluorescence were used to evaluate mucosal healing.Results: In vitro, LPS did not exacerbate the effects of osteoporosis therapeutic dose of ZA on the proliferation and migration of HOK cells, while aggravated these with the oncologic dose of ZA treatment by inducing mitochondrial dysfunction and oxidative stress via regulating SIRT1 expression. Furthermore, SIRT1 overexpression can alleviate this process. In vivo, local injection of LPS increased the nonunion of mucous membranes in MRONJ and decreased the expression of SIRT1, PGC-1α, and MnSOD.Conclusion: Inflammation aggravates oncologic dose of ZA-induced mitochondrial dysfunction and oxidative stress via a SIRT1-dependent pathway, enhancing the risk of impaired mucosal healing in MRONJ. Our study implies that inflammation becomes a critical risk factor for MRONJ development at higher ZA concentrations. Elucidating the mechanisms of inflammation as a risk factor for mucosal non-healing in MRONJ could inform the development of SIRT1-targeted therapies.Keywords: MRONJ, mucosal healing, inflammation, oxidative stress, mitochondrial dysfunction, SIRT1

Chenglin Ye,1,&ast; Sizhe Zhu,2,&ast; Jingping Yuan,1 Xiuxue Yuan3 1Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, People’s Republic of China; 3Medical College of Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingping Yuan; Xiuxue Yuan, Email yuanjingping@whu.edu.cn; exiuwust@gmail.comPurpose: Crohn’s disease (CD) represents a multifaceted inflammatory gastrointestinal condition, with a profound significance placed on unraveling its molecular pathways to enhance both diagnostic capabilities and therapeutic interventions. This study focused on identifying a robust macrophage-related signatures (MacroSig) for diagnosing CD, emphasizing the role of FPR1 in macrophage polarization and its implications in CD.Patients and Methods: Expression profiles from intestinal biopsies and macrophages of 1804 CD patients were retrieved from the Gene Expression Omnibus (GEO). Utilizing CIBERSORTx, differential expression analysis, and weighted correlation network analysis to to identify macrophage-related genes (MRGs). By unsupervised clustering, distinct clusters of CD were identified. Potential biomarkers were identified via using four machine learning algorithms, leading to the establishment of MacroSig which combines insights from 12 machine learning algorithms. Furthermore, the expression of FPR1 was verified in intestinal biopsies of CD patients and two murine experimental colitis models. Finally, we further explored the role of FPR1 in macrophage polarization through single-cell analysis as well as through the study of RAW264.7 cells and peritoneal macrophages.Results: Two distinct clusters with differential levels of macrophage infiltration and inflammation were identified. The MacroSig, which included FPR1 and LILRB2, exhibited high diagnostic accuracy and outperformed existing biomarkers and signatures. Clinical analysis demonstrated a strong correlation of FPR1 with disease activity, endoscopic inflammation status, and response to infliximab treatment. The expression levels of FPR1 were validated in our CD cohort by immunohistochemistry and confirmed in two colitis mouse models. Single-cell analysis indicated that FPR1 is predominantly expressed in macrophages and monocytes. In vitro studies demonstrated that FPR1 was upregulated in M1 macrophages, and its activation promoted M1 polarization.Conclusion: We developed a promising diagnostic signature for CD, and targeting FPR1 to modulate macrophage polarization may represent a novel therapeutic strategy.Keywords: Crohn’s disease, macrophage, diagnostic signature, FPR1, machine learning

Tong Zhang,1– 3,&ast; Han Wu,1,2,&ast; Chenling Qiu,1,2 Mingxin Wang,1,2 Haiting Wang,1,2 Shunhua Zhu,1,4 Yinhai Xu,2 Qingli Huang,1,4 Shibao Li1,2 1Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 3Chuzhou Center for Disease Control and Prevention, Chuzhou City, Anhui, 239000, People’s Republic of China; 4Public Experimental Research Center of Xuzhou Medical University, Xuzhou City, Jiangsu, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingli Huang; Shibao Li, Email qlhuang@xzhmu.edu.cn; sdjnshlb@xzhmu.edu.cnIntroduction: Insulin and C-peptide played crucial roles as clinical indicators for diabetes and certain liver diseases. However, there has been limited research on the simultaneous detection of insulin and C-peptide in trace serum. It is necessary to develop a novel method with high sensitivity and specificity for detecting insulin and C-peptide simultaneously.Methods: A core-shell-satellites hierarchical structured nanocomposite was fabricated as SERS biosensor using a simple wet-chemical method, employing 4-MBA and DTNB for recognition and antibodies for specific capture. Gold nanorods (Au NRs) were modified with Raman reporter molecules and silver nanoparticles (Ag NPs), creating SERS tags with high sensitivity for detecting insulin and C-peptide. Antibody-modified commercial carboxylated magnetic bead@antibody served as the capture probes. Target materials were captured by probes and combined with SERS tags, forming a “sandwich” composite structure for subsequent detection.Results: Under optimized conditions, the nanocomposite fabricated could be used to detect simultaneously for insulin and C-peptide with the detection limit of 4.29 × 10− 5 pM and 1.76 × 10− 10 nM in serum. The insulin concentration (4.29 × 10− 5– 4.29 pM) showed a strong linear correlation with the SERS intensity at 1075 cm− 1, with high recoveries (96.4– 105.3%) and low RSD (0.8%– 10.0%) in detecting human serum samples. Meanwhile, the C-peptide concentration (1.76 × 10− 10– 1.76 × 10− 3 nM) also showed a specific linear correlation with the SERS intensity at 1333 cm− 1, with recoveries 85.4%– 105.0% and RSD 1.7%– 10.8%.Conclusion: This breakthrough provided a novel, sensitive, convenient and stable approach for clinical diagnosis of diabetes and certain liver diseases. Overall, our findings presented a significant contribution to the field of biomedical research, opening up new possibilities for improved diagnosis and monitoring of diabetes and liver diseases.Keywords: surface-enhanced Raman scattering, SERS, nanocomposites, insulin, C-peptide

Lin Wang,1,2 Fulan Wang,1,2 Hong Qin,2 Li Hou,2 Shiqiong Zhu,3 Fang He,2 Chao Zeng2 1Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Gynecology Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 3Gynecology Department, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, 610031, People’s Republic of ChinaCorrespondence: Fulan Wang, Department of Nursing, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China, Tel +86-13012370558, Email WFL3076@163.comBackground: Bladder dysfunction is a common complication following radical hysterectomy, affecting patients’ QOL. Exploring interventions, particularly IC continuity care, is crucial for identifying strategies to enhance postoperative outcomes. This study aimed to assess the impact of continuous intermittent catheterization (IC) care on bladder function recovery and quality of life (QOL) in patients undergoing radical hysterectomy for cervical cancer.Methods: The primary outcome measured was the time to bladder function recovery, with secondary outcomes comprising EORTC QLQ-C30 assessments at 3 and 6 months post-surgery, as well as EORTC QLQ-CX24 evaluations. Meanwhile, urinary complications, readmissions, and outpatient follow-up were also compared.Results: Among the 128 participants, with 64 in each group, indwelling catheterization durations were similar. However, the IC continuity care group exhibited significantly shorter IC duration and bladder recovery time. This group demonstrated superior QOL, lower occurrence rates post-IC, reduced urethral injuries, and higher readmission and outpatient follow-up rates.Conclusion: This study underscores continuous IC care emerges as a beneficial intervention, facilitating accelerated bladder function recovery and improved QOL in patients following radical hysterectomy for cervical cancer.Keywords: intermittent urethral catheterization, cervical cancer, urinary bladder neurogenic dysfunction, continuity of patient care, rehabilitation

Shenglan Zhu,1 Junlin Ren,2 Ling Feng,1 Yi Jiang1 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Computer Science, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of ChinaCorrespondence: Yi Jiang; Ling Feng, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, Hubei, 430030, People’s Republic of China, Email einsmeer@foxmail.com; fltj007@163.comIntroduction: Previous studies have shown that pregnant women with systemic lupus erythematosus (SLE) tend to have a higher risk of adverse pregnancy outcomes, but the potential causal role remained unclear. In this study, we aimed to investigate the causal relationship between SLE and some common pregnancy complications and outcomes using two-sample Mendelian randomization (MR).Methods: The genetic tools were derived from genome-wide association studies of SLE and pregnancy complications and outcomes. MR analysis was performed using inverse variance weighting as primary method. Sensitivity analyses were performed to evaluate the robustness of the results. A retrospective analysis was conducted on 200 pregnant women with SLE and a control group of pregnant women delivering at Tongji Hospital.Results: In the results, we found that genetic susceptibility to SLE was associated with a higher risk of gestational diabetes mellitus (OR = 1.028, 95% CI: 1.006– 1.050), premature delivery (OR = 1.039, 95% CI: 1.013– 1.066), polyhydramnios (OR = 1.075, 95% CI: 1.004– 1.151) and premature rupture of membranes (OR = 1.030, 95% CI: 1.001– 1.060). Some of the retrospective analysis results align with the findings from the MR analysis, indicating that pregnant women with SLE have a higher risk of developing gestational diabetes mellitus and preterm birth. Additionally, although MR analysis did not reveal a causal relationship between SLE and preeclampsia/eclampsia, retrospective analysis discovered that SLE pregnant women are more susceptible to developing preeclampsia/eclampsia (OR = 2.935, 95% CI: 1.118– 7.620).Conclusion: Our study findings suggest a potential causal relationship between SLE and increased risks of gestational diabetes and preterm delivery. Clinical data indicate that pregnant women with SLE are more prone to developing preeclampsia/eclampsia. Clinicians need to be vigilant about the occurrence of these conditions when managing pregnant women with SLE.Keywords: systemic lupus erythematosus, pregnancy complications, Mendelian randomization, gestational diabetes mellitus, preeclampsia, retrospective analysis

Wei Li,1,2 Jun Wang,1,2 Chao Tang,1,2 Xuan Lv,1,2 Suijun Zhu1,2 1Department of Neurosurgery, First People’s Hospital of Linping District, Hangzhou, People’s Republic of China; 2Department of Neurosurgery, Linping Campus, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Suijun Zhu, Department of Neurosurgery, First People’s Hospital of Linping District, Hangzhou, People’s Republic of China, Email chaolinaweiminfu@126.comBackground: Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 1 (NLRP1) participates in neuroinflammation. This study aimed to identify serum NLRP as a potential prognostic biomarker of acute intracerebral hemorrhage (ICH).Methods: This prospective cohort study enrolled 145 patients with supratentorial ICH and 51 healthy controls. Serum NLRP1 levels were quantified on admission of all 145 patients, on days 1, 3, 5, 7, and 10 after stroke in 51 of 145 patients and at entry into the study of controls. Poststroke 6-month modified Rankin Scale (mRS) scores of 3– 6 signified a poor prognosis.Results: Compared to controls, patients had prominently increased serum NLRP1 levels until day 10 after ICH, with the highest levels at days 1 and 3. Serum NLRP1 levels were independently correlated with National Institutes of Health Stroke Scale (NIHSS) scores, hematoma volume and six-month mRS scores, and independently predicted six-month bad prognosis. A linear relationship was observed between serum NLRP1 levels and the risk of poor prognosis in a restricted cubic spline. Under the receiver operating characteristic (ROC) curve, serum NLRP levels efficiently discriminated poor prognosis. Serum NLRP1, NIHSS, and hematoma volume were merged into a prognosis prediction model, which was portrayed using a nomogram. Good performance of the model was verified using calibration curve, decision curve, and ROC curve.Conclusion: Serum NLRP1 levels are elevated during the early period following ICH and are independently related to hemorrhagic severity and poor prognosis, suggesting that serum NLRP1 may represent a promising prognostic biomarker of ICH.Keywords: intracerebral hemorrhage, NLRP1, prognosis, severity, biomarkers

Xin Fang,1 Yalong Yin,2 Haimei Lun,3 Yaoli Liu,1 Shangyong Zhu1 1Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Traditional Chinese Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Ultrasound, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Shangyong Zhu, Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email zhushangyong2022@sina.cnPurpose: Few studies have assessed the effects of sphingosine kinase 1/sphingosine-1-phosphate (SPHK1/S1P) on microangiogenesis at rat myofascial trigger points (MTrPs) using contrast-enhanced ultrasonography (CEUS). This study aimed to address these deficiencies. Here, we investigated the effects of SPHK1/S1P on MTrP microangiogenesis and the value of CEUS in evaluating these effects.Methods: Forty Sprague‒Dawley rats were subdivided into two groups: control and MTrP groups. MTrPs were established by 8 weeks of the strike procedure combined with eccentric motion and 4 weeks of recovery. All rats were euthanized after having undergone CEUS with an overdose of pentobarbital sodium. MTrP and control tissue samples were removed for haematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) imaging. The tissue was dehydrated, cleared, and embedded before sectioning. The sections were then incubated overnight at 4°C, and immunohistochemistry was carried out with primary antibodies including rabbit anti-CD31, rabbit anti-SPHK1and rabbit anti-S1PR1.Results: MTrP rats exhibited spontaneous electrical activity (SEA) and a local twitch response (LTR) during electromyography (EMG) examination. The CEUS time-intensity curves (TICs) showed that the perfusion intensity in the MTrPs and surrounding tissue area was increased, with faster perfusion than in normal sites, while the TICs in the control group slowly increased and then slowly decreased. The correlation coefficient between the microvessel density (MVD) and sphingosine 1-phosphate receptor 1 (S1PR1) was 0.716 (p < 0.01). Spearman correlation analysis revealed that Spearman’s rho (ρ) values between the MVD and peak intensity (PI), between the MVD and area under the curve (AUC), and between the MVD and SPHK1 were > 0.5 (p < 0.05), > 0.7 (p < 0.01), and > 0.7 (p < 0.01), respectively.Conclusion: CEUS is valuable for detecting microangiogenesis within MTrPs, and SPHK1/S1P plays an important role in promoting MTrP tissue microangiogenesis.Keywords: ultrasound, myofascial pain syndrome, diagnosis, angiogenesis

Zhan Shi,1,&ast; Sihui Zhu,2,&ast; Yuncheng Jin,1 Liang Qi,1 Mingzhen Zhou,1 Ziyan Zhou,1 Juan Zhang,1 Baorui Liu,1 Jie Shen1 1Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu Province, 210008, People’s Republic of China; 2The Comprehensive Cancer Centre of Nanjing International Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Shen; Baorui Liu, Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu Province, 210008, People’s Republic of China, Fax +86-025-83106666, Email shenjie2008nju@163.com; baoruiliu@nju.edu.cnBackground: Stereotactic body radiotherapy (SBRT) has emerged as an alternative approach for patients with hepatocellular carcinoma (HCC), and we aim to find potential prognostic biomarkers for HCC patients who received SBRT.Methods: In this study, we retrospectively analyzed HCC patients who underwent SBRT in our institution from January 2018 to December 2022. The inflammatory parameters, along with baseline patients’ characteristics were collected to elucidate the potential relationship with survival benefits and liver toxicities.Results: Overall, 35 patients were enrolled in our study. For the efficacy population (25 patients who underwent SBRT for primary liver lesions), the objective response rate (ORR) and disease control rate (DCR) were 60% and 100%, respectively. The median progression-free survival (PFS) was 9.9 months [95% confidence interval (CI) 5.6– 14.1 months], and the median overall survival (OS) was 18.5 months (95% CI 14.2– 22.8 months). We further confirmed that higher baseline lymphocyte-C-reactive protein ratio (LCR) (≥ 2361.11) was positively related to both longer PFS (12.0 vs 4.3 months, P = 0.002) and OS (21.9 vs 11.4 months, P = 0.022). Moreover, patients with diabetes and higher alpha-fetoprotein (AFP) (≥ 400 ng/mL) were also found to be associated with worse OS. The most common hepatotoxicity was elevated gamma-glutamyl transferase (GGT) (84.0%).Conclusion: In conclusion, for patients with inoperable HCC, SBRT resulted in satisfactory local control, survival benefits, and acceptable liver toxicity. Pre-radiotherapy LCR might be an independent and readily available predictor for survival, which facilitates us to find the most appropriate treatment options.Keywords: hepatocellular carcinoma, stereotactic body radiotherapy, lymphocyte-C-reactive protein ratio, survival, liver toxicity

Guanghua Yang,1,&ast; Jiaxi Pu,1,&ast; Sibo Zhu,2 Yong Shi,3 Yi Yang,3 Jiangnan Mao,3 Yongkang Sun,1 Bin Zhao1 1Department of General Surgery, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, People’s Republic of China; 2School of Life Sciences, Fudan University, Shanghai, 200438, People’s Republic of China; 3Cinoasia Institute, Shanghai, 200438, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Zhao, Department of General Surgery, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, No. 358, Datong Road, Gaoqiao, Pudong New Area, Shanghai, 200137, People’s Republic of China, Tel +86 13918468421, Email zhaobin0727@sina.com Yongkang Sun, Department of Ultrasound, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, No. 358, Datong Road, Gaoqiao, Pudong New Area, Shanghai, 200137, People’s Republic of China, Tel +86 13601659860, Email elangwang@126.comBackground: Thyroidectomy is commonly performed for benign or malignant thyroid tumors, often resulting in hypothyroidism. Levothyroxine (LT4) supplementation is crucial to maintain hormone levels within the normal range and suppress TSH for cancer control. However, determining the optimal dosage remains challenging, leading to uncertain outcomes and potential side effects.Methods: We analyzed clinical examination data from 510 total thyroidectomy patients, including demographic information, blood tests, and thyroid function. Using R, we applied data preprocessing techniques and identified 274 samples with 98 variables. Principal Component Analysis, correlation analysis, and regression analysis were conducted to identify factors associated with optimal LT4 dosage.Results: The analysis revealed that only eight variables significantly influenced the final satisfactory dosage of LT4 in tablets: Benign0/Malignant1 (benign or malignant), BQB (electrophoretic albumin ratio), TP (total protein), FDP (fibrin degradation products), TRAB_1 (thyroid-stimulating hormone receptor antibody), PT (prothrombin time), MONO&num; (monocyte count), and HCV0C (hepatitis C antibody). The resulting predictive model was: .Conclusion: Parameters such as benign/malignant status, TRAB_1, and BQB ratio during medication can serve as observational indicators for postoperative LT4 dosage. The calculated linear model can predict the LT4 dosage for patients after thyroidectomy, leading to improved treatment effectiveness and conserving medical resources.Keywords: thyroid, levothyroxine, dosage, model, prediction

Shuxing Zhu, Yaqing Liu, Xiuli Wang, Liang Wang, Jinru Li, Xiaoming Xue, Zhao Li, Jiaxin Liu, Xin Liu, Shuang Zhao Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaCorrespondence: Shuang Zhao, Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel +86 13613210924, Email zhaoshuang810924@163.comBackground: Postoperative delirium (POD) is of great concern as a complication of surgery in older adult patients. Sedation strategies influence the development of POD. This study compared how sedation strategies administered during spinal anesthesia influenced POD in patients aged ≥ 65 years undergoing elective surgery for hip fracture repair.Patients and Methods: A randomized clinical trial was conducted from 1 August 2021 to 30 June 2022 at a single academic medical center. Two hundred and twenty-six patients were randomly divided into four groups: lighter sedation with propofol (LP), heavier sedation with propofol (HP), lighter sedation with dexmedetomidine (LD), and heavier sedation with dexmedetomidine (HD). The incidence of delirium was the primary outcome and was assessed daily by the blinded Confusion Assessment Method.Results: There was a significant association between dexmedetomidine (LD+HD group) and a lower incidence of delirium (11.9% [13/109] vs the propofol group (23.6% [26/110]; Risk ratio, 0.51; 95% CI, 0.274 to 0.929; p=0.024). In the propofol group, heavier sedation had a higher rate of POD (32.7% [18/55] vs the lighter sedation group (14.5% [8/55]; Risk ratio, 2.25; 95% CI, 1.069 to 4.736; p=0.025).Conclusion: Dexmedetomidine was associated with a lower incidence of delirium than that with propofol among older patients with hip fractures. In patients that received propofol, heavier sedation was associated with high incidence of POD.Keywords: aged, anesthetics, hip surgery, propofol, spinal anesthesia

Hong Li,1,2 Juan Su,3 Mingfang Zhu,4 Yaqi Zhu,1,2 Shilin Zhu1 1Department of Nursing, The Second Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2School of Nursing, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 3Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Department of Dermatology, The Second Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Shilin Zhu, Email zhushilin@hnucm.edu.cn

Chuanchuan Sun,1 Heng Shi,1 Xinhai Zhao,2 Yu-Ling Chang,2 Xianghong Wang,3 Shiping Zhu,2 Shengyun Sun1 1Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Endocrinology and Metabolism, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, People’s Republic of ChinaCorrespondence: Shengyun Sun, Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510630, People’s Republic of China, Email shengyunsun2020@163.comAbstract: The activation of the cGAS-STING pathway is associated with many sterile inflammatory and inflammatory conditions, including acute kidney injury. As a cytoplasmic DNA sensor, sensitization of the cGAS-STING pathway can ignite the innate immune response in vivo and trigger a series of biological effects. In recent years, there is increasing evidence showing that the cGAS-STING pathway plays a vital role in acute kidney injury, a non-inflammatory disease induced by activation of innate immune cells, and closely related to intracellular reactive oxygen species, mitochondrial DNA, and the cGAS-STING pathway. This review provides a prospect of the cGAS-STING pathway and its relationship to acute kidney injury.Keywords: mitochondrial DNA, innate immunity, reactive oxygen species, mitochondrial dysfunction, acute kidney injury

Jiayu Shao, Hangdong Dai, Liwei Xu, Shuilong Zhu, Jufang Zhu, Hangyu Fu, Minxia Ge, Xianhong He Department of Clinical Laboratory, the Third People’s Hospital of Xiaoshan, Hangzhou, People’s Republic of ChinaCorrespondence: Xianhong He; Minxia Ge, Department of Clinical Laboratory, the Third People’s Hospital of Xiaoshan, 76 Zhishan North Road, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 15088760041 ; +86 18057155059, Email miriam1023@163.com; cqmxszj@163.comPurpose: The isolation rate of extended spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing, posing a challenge to clinical anti-infective therapy. This study aims to provide new insight into the genomic characteristics and antimicrobial resistance mechanisms of extended spectrum β-lactamase producing E. coli isolates recovered from a district hospital in China.Methods: A total of 36 ESBL-producing E. coli isolates were collected from body fluid samples from a Chinese district hospital. All isolates were subjected to whole genome sequencing to identify their antimicrobial resistance genes, virulence genes, serotypes, sequence types, and phylogenetic relationships by BacWGSTdb 2.0 webserver.Results: Among these isolates, all were resistant to cefazolin, cefotaxime, ceftriaxone, ampicillin, 24 (66.7%) were resistant to aztreonam, 16 (44.4%) were resistant to cefepime, and 15 were resistant (41.7%) to ceftazidime. The blaCTX-M gene was detected in all ESBL-producing E. coli isolates. Two isolates carrying two different types of blaCTX-M genes simultaneously. The carbapenem resistance gene blaKPC-2 was detected in one (2.8%) isolate. A total of 17 sequence types (STs) were found, with ST131 accounting for the majority (n =13; 36.1%). The most common serotype was O16:H5 associated with seven ST131 strains, followed by O25:H4/ST131 (n = 5) and O75:H5/ST1193 (n = 5). Evaluation of clonal relatedness revealed that all blaCTX-M gene-carrying E. coli had a difference of SNPs range from 7 to 79,198, which could be divided into four clusters. Only 7 SNPs could be found between EC266 and EC622, indicating that they are variants of the same clonal lineage.Conclusion: This study investigated the genomic characteristics of ESBL-producing E. coli isolates recovered from a district hospital in China. Continuous surveillance of ESBL-producing E. coli infections is imperative to create efficient strategies for controlling the transmission of these multi-drug resistant bacteria in clinical and community settings.Keywords: Escherichia coli, ESBLs, antimicrobial resistance, whole genome sequencing

Xianhong He, Liwei Xu, Hangdong Dai, Minxia Ge, Jufang Zhu, Hangyu Fu, Shuilong Zhu, Jiayu Shao Department of Clinical Laboratory, The Third People’s Hospital of Xiaoshan, Hangzhou, People’s Republic of ChinaCorrespondence: Jiayu Shao; Shuilong Zhu, Department of Clinical Laboratory, The Third People’s Hospital of Xiaoshan, 76 Zhishan North Road, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 18505812918 ; +86 18057155360, Email 583744598@qq.com; zslong1976@163.comBackground: The transmission of carbapenem-resistant Enterobacterales pose a significant threat to global public health, which weakens the effectiveness of most antimicrobial agents. The aim of this study is to present the genomic characteristics of a multidrug-resistant Escherichia coli, which contains both blaKPC-2 and blaCTX-M-15 genes, discovered from a respiratory infection in China.Methods: The antimicrobial susceptibility of E. coli isolate 488 was measured by using the broth microdilution method. The Oxford Nanopore MinION and Illumina NovaSeq 6000 platforms were applied to determine the whole-genome sequence of this isolate. De novo assembly of short Illumina reads and long MinION reads were performed by Unicycler. In silico multilocus sequence typing (MLST), antimicrobial resistance genes and plasmid replicon types were determined using the genome sequencing data. Additionally, a pairwise core genome single nucleotide polymorphism (cgSNP) comparison between E. coli 488 and all ST648 E. coli strains retrieved from NCBI GenBank database were conducted using the BacWGSTdb 2.0 server.Results: E. coli 488 was resistant to aztreonam, levofloxacin, cefepime, fosfomycin, amikacin, imipenem, cefotaxime, and meropenem. The complete genome sequence of E. coli 488 (belong to ST648) is made up of eleven contigs totaling 5,573,915 bp, including one chromosome and ten plasmids. Eight antimicrobial resistance genes were identified, including blaKPC-2 located in a 46,161 bp IncI1-type plasmid and the blaCTX-M-15 gene situated in the chromosome. Other two E. coli S617-2 and R616-1 isolates, recovered from China in 2018, are the closest relatives of E. coli 488, with only 52 SNPs difference. The genome also contains at least 57 genomic islands and several IS elements.Conclusion: Our study reveals the first ST648 E. coli isolate containing both blaKPC-2 and blaCTX-M-15 in China. These results could provide valuable insights into the genetic characteristics, antimicrobial resistance mechanisms, and transmission dynamics of carbapenem-resistant Enterobacterales in clinical settings.Keywords: blaKPC-2, blaCTX-M-15, whole genome sequencing, multidrug-resistant, Escherichia coli

Yang Wang,1,&ast; Zheng Wang,1,&ast; Xiao Wu,1,&ast; Song Zhu,2,&ast; Qiru Guo,1 Zhong Jin,1 Zixian Chen,3 Delai Zhang,2 Wangming Hu,1 Huan Xu,1 Liangqin Shi,1 Lan Yang,1 Yong Wang1 1College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Wang, College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Tel +86 18280350393, Email yongwang1008@hotmail.com; wangyong@cdutcm.edu.cnPurpose: Dysfunction of endothelium is associated with multiple pathological vascular diseases. However, how to regulate reendothelialization after vascular injury is not well defined. This study aims to determine whether and how Paeonol controls reendothelialization following artery injury.Methods: The endothelium of murine carotid artery was denuded by catheter guide wires injury. H&E staining and IF staining were performed to determine whether Paeonol is critical for reendothelialization. BRDU Incorporation Assay, Boyden Chamber Migration Assay, Tube Formation Assay, and Spheroid Sprouting Assay were used to investigate whether Paeonol is involved in regulating proliferation and migration of endothelial cells. The underlying mechanism of how Paeonol regulates reendothelialization was determined by Molecular docking simulation and CO-IP Assay.Results: Paeonol treatment significantly inhibits neointima formation in carotid artery ligation model by promoting proliferation and migration of endothelial cells. Mechanistically, Paeonol enhances c-Myc expression, consequently interacts with VEGFR2 results in activating VEGF signaling pathway, and eventually promotes reendothelialization after vascular injury.Conclusion: Our data demonstrated that Paeonol plays a critical role in regulating vascular reendothelialization, which may be therapeutically used for treatment of pathological vascular diseases.Graphical Abstract: Keywords: Paeonol, c-Myc, VEGFR2, vascular injury, reendothelialization

Yong Li,1,2,&ast; Senbo Zhu,2,&ast; Junchao Luo,2 Yu Tong,2 Yixuan Zheng,1 Lichen Ji,2 Zeju He,2 Qiangan Jing,1 Jiaqing Huang,2 Yinjun Zhang,1 Qing Bi2 1College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Laboratory Medicine Center, Department of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinjun Zhang, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-13735494556, Email zhangyj@zjut.edu.cn Qing Bi, Laboratory Medicine Center, Department of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-13588302991, Email bqzjsrmyy@163.comIntroduction: Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration. OA usually manifests as joint pain, limited mobility, and joint effusion. Currently, the primary OA treatment is non-steroidal anti-inflammatory drugs (NSAIDs). Although they can alleviate the disease’s clinical symptoms and signs, the drugs have some side effects. Selenium nanoparticles (SeNPs) may be an alternative to relieve OA symptoms.Materials and Results: We confirmed the anti-inflammatory effect of selenium nanoparticles (SeNPs) in vitro and in vivo experiments for OA disease in this study. In vitro experiments, we found that SeNPs could significantly reduce the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the major inflammatory factors, and had significant anti-inflammatory and anti-arthritic effects. SeNPs can inhibit reactive oxygen species (ROS) production and increased glutathione peroxidase (GPx) activity in interleukin-1beta (IL-1β)-stimulated cells. Additionally, SeNPs down-regulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) expressions, while up-regulated type II collagen (COL-2) and aggrecan (ACAN) expressions stimulated by IL-1β. The findings also indicated that SeNPs may exert their effects through suppressing the NF-κB p65 and p38/MAPK pathways. In vivo experiments, the prevention of OA development brought on by SeNPs was demonstrated using a DMM model.Discussion: Our results suggest that SeNPs may be a potential anti-inflammatory agent for treating OA.Keywords: osteoarthritis, NF-κB p65 signaling pathway, p38/MAPK signaling pathway, selenium nanoparticles

Yuhao Zeng,1,&ast; Sha Zhu,1,&ast; Zilin Wang,1 Junru Chen,1 Jindong Dai,1 Zhenhua Liu,1 Guangxi Sun,1 Jiayu Liang,1 Xingming Zhang,1 Zhipeng Wang,1 Jinge Zhao,1 Yuchao Ni,1 Jiyu Yang,1 Minghao Wang,1 Qiang Wei,1 Xiang Li,1 Ni Chen,2 Zhiping Li,3 Xin Wang,3 Yali Shen,3 Jin Yao,4 Rui Huang,5 Jiyan Liu,6 Diming Cai,7 Hao Zeng,1 Pengfei Shen1 1Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Department of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 7Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengfei Shen; Hao Zeng, Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Email cdhx510@163.com; kucaizeng@163.comPurpose: Multidisciplinary team (MDT) discussion is a widely used model to manage patients diagnosed with cancer. However, there has been no direct evidence to prove its effect on the prognosis of metastatic renal cell carcinoma (mRCC) patients, so this study explored the impact of MDT discussion on mRCC patient survival.Methods: The clinical data of 269 mRCC patients were retrospectively collected from 2012 to 2021. The cases were grouped into the MDT and non-MDT groups, then subgroup analysis was performed according to different histology types, as well as exploring the role of MDT in patients who have undergone multiple-line therapy. Overall survival (OS) and progression free survival (PFS) were set as the study endpoint.Results: Approximately half (48.0%, 129/269) of the patients were in the MDT group, with univariable survival analyses showing these patients had remarkably longer median OS (MDT group: 73.7 months; non-MDT group: 33.2 months, hazard ratio (HR): 0.423 (0.288, 0.622), p< 0.001) and longer median PFS (MDT group: 16.9 months, non-MDT group: 12.7 months, HR: 0.722 (0.542, 0.962), p=0.026). Furthermore, MDT management resulted in longer survival for both ccRCC and non-ccRCC subgroups. Patients in the MDT group were more likely to receive multi-line therapy (MDT group: 79/129, 61.2% vs non-MDT group: 56/140, 40.0%, p< 0.001), and within this patient group, MDT management still resulted in longer OS (MDT group: 94.0 months; non-MDT group: 43.5 months, p=0.009).Conclusion: MDT is associated with prolonged overall survival in mRCC independent of histology, ensuring that patients receive better management and precise treatment.Keywords: mRCC, MDT, overall survival, prognosis, ccRCC, non-ccRCC, multi-line treatment

Yuehong Ren,1,&ast; Linghui Nie,2,&ast; Chunhua Luo,3,&ast; Shiping Zhu,4 Xingwang Zhang1 1Department of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China; 2ASD Medical Rehabilitation Center, the Second People’s Hospital of Guangdong Province, Guangzhou, People’s Republic of China; 3Newborn Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of China; 4Department of Chinese Traditional Medicine, the First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingwang Zhang, Department of Pharmaceutics, College of Pharmacy, Jinan University, No. 855 East Xingye Avenue, Guangzhou, 511443, People’s Republic of China, Email zhangxw@jnu.edu.cn Shiping Zhu, Department of Chinese Traditional Medicine, the First Affiliated Hospital of Jinan University, 613 West Huangpu Avenue, Guangzhou, 513630, People’s Republic of China, Email zhushiping@jnu.edu.cnAbstract: Intestinal flora has become a therapeutic target for the intervention of colonic diseases (CDs) with better understanding of the interplay between microbiota and CDs. Depending on unique properties and prominent ability of regulating the intestinal flora, prebiotics can not only achieve a colon-specific drug delivery but also maintain the intestinal homeostasis, thus playing a positive role in the intervention of CDs. Currently, different studies on prebiotic-based nanoparticles have been contrived for colonic drug delivery and have shown great potential in curing various CDs, such as colitis and colorectal cancer. Nevertheless, there is a lack of systematic survey on the use of prebiotic nanoparticles for the treatment of CDs. This review aims to generalize the state-of-the-art of prebiotic nanomedicines specific for CDs. The species and function of intestinal flora and various kinds of prebiotics available as well as their regulating effects on intestinal flora were expounded. A variety of prebiotic nanoparticles pertinent to colon-targeted drug delivery systems were illustrated with particular emphasis on their curative activities on CDs. The efficacy and safety of prebiotic-based colonic drug delivery systems (p-CDDs) were also analyzed. In conclusion, the synergy between prebiotic nanoparticles and their cargos may hold promise for the treatment and intervention of CDs.Keywords: colonic diseases, prebiotics, nanoparticles, therapeutic intervention, drug delivery

Xu Jiang,1,&ast; Yang Pan,1,&ast; Sha Zhu,1 Yaxi Wang,1 Ruxin Gu,1 Yinyin Jiang,1 Bo Shen,1 Jun Zhu,1 Shulan Xu,1 Jun Yan,1 Jingde Dong,1 Wenbin Zhang,2 Chaoyong Xiao,3 Li Zhang1 1Department of Geriatrics, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Radiology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Zhang, Department of Geriatrics, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China, Email jx13773958367@163.comObjective: Patients with rapid eye movement (REM) sleep behavior disorder (RBD) in Parkinson’s disease (PD-RBD) tend to have poor cognitive performance and faster cognitive deterioration, and the potential mechanism is still ambiguous. Therefore, this study aimed to detect the alterations in local brain function in PD-RBD.Methods: Fifty patients, including 23 patients with PD-RBD and 27 patients with PD without RBD (PD-nRBD), and 26 healthy controls were enrolled. All subjects were subjected to one-night polysomnography and underwent resting-state functional magnetic resonance imaging (rs-fMRI). The fMRI images of the three groups were analyzed by regional homogeneity (ReHo) to observe the local neural activity. Correlations between altered ReHo values and chin electromyographic (EMG) density scores and cognitive scores in the PD subgroups were assessed.Results: Compared with the patients with PD-nRBD, the patients with PD-RBD had higher ReHo values in the frontal cortex (the right superior frontal gyrus, the right middle frontal gyrus and the left medial superior frontal gyrus), the right caudate nucleus and the right anterior cingulate gyrus, and compared with the HCs, the patients with PD-RBD had lower ReHo values in the bilateral cuneus, the bilateral precuneus, the left inferior temporal gyrus and the left inferior occipital gyrus. For the patients with PD-RBD, the phasic chin EMG density scores were positively correlated with the ReHo values in the left medial superior frontal gyrus, and the tonic chin EMG density scores were positively correlated with the ReHo values in the right anterior cingulate gyrus.Conclusion: This study indicates that increased ReHo in the frontal cortex, the caudate nucleus and the anterior cingulate gyrus may be linked with the abnormal motor behaviors during REM sleep and that decreased ReHo in the posterior regions may be related to the visuospatial–executive function in patients with PD-RBD.Keywords: Parkinson’s disease, rapid eye movement sleep behavior disorder, resting-state fMRI, regional homogeneity

Zhongjian Pu,1,&ast; Yujia Wei,2,3,&ast; Yuanpeng Sun,1 Yajun Wang,1 Shilin Zhu1 1Department of Oncology, Haian Hospital of Traditional Chinese Medicine, Haian, 216600, People’s Republic of China; 2School of Medicine, Yangzhou University, Yangzhou, 225009, People’s Republic of China; 3Department of General Practice, Suzhou Wuzhong Hospital of Traditional Chinese Medicine, Suzhou, 215101, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yajun Wang; Shilin Zhu, Department of Oncology, Haian Hospital of Traditional Chinese Medicine, Haian, 216600, People’s Republic of China, Email wangyajunhaian@21cn.com; zhushilinhaian@tom.comAbstract: Non-small cell lung cancer (NSCLC) is a global burden leading to millions of deaths worldwide every year. Nanomedicine refers to the use of materials at the nanoscale for drug delivery and subsequent therapeutic approaches in cancer. Carbon nanotubes (CNTs) are widely used as nanocarriers for therapeutic molecules such as plasmids, siRNAs, antisense agents, aptamers and molecules related to the immunotherapy for several cancers. They are usually functionalized and loaded with standard drug molecules to improve their therapeutic efficiency. Functionalization and drug loading possibly decrease the genotoxic and carcinogenic potential of CNTs. In addition, the targeted cytotoxic properties of the drug improve and undesired toxicity decreases after drug loading and/or conjugation with proteins, including antibodies. For intended drug delivery, a lysosomal pH of 5.5 is more suitable and effective for the slow and extended release of cytotoxic drugs than a physiological of pH 7.4. Remarkably, CNTs possess intrinsic antitumor properties and are usually internalized by endocytosis. After being internalized, several mechanisms are involved in the therapeutic and carcinogenic effects of CNTs. They are generally safe for therapy, and their toxicity profile remains dependent on their physicochemical properties. Moreover, the dose, route, duration of exposure, surface properties and degradative potential determine the toxicity outcomes of CNTs locally or systemically. In summary, the use of CNTs in drug delivery and NSCLC therapy, as well as their genotoxic and carcinogenic potential and the possible mechanisms, has been discussed in this review. The therapeutic index is generally high for NSCLC cells treated with drug-loaded CNTs; therefore, they are effective carriers in implementing targeted therapy for NSCLC.Keywords: NSCLC, CNTs, drug delivery, antitumor, carcinogenic

Zhan Su,&ast; Jie Zhang,&ast; Peijie Tan, Songsong Zhu,&ast; Nan Jiang&ast; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral & Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Songsong Zhu; Nan Jiang, Email zss_1977@163.com; dent_jn@163.comIntroduction: Polyetheretherketone (PEEK) has good biosafety and chemical stability for bone repair. However, PEEK is biologically inert and cannot promote bone apposition. This study investigated whether graphene-modified PEEK (G-PEEK) could improve cell adhesion and osteogenic differentiation.Methods: G-PEEK was prepared by melted blending and was characterized. In vitro, the biocompatibility of G-PPEK and the ability to promote cell adhesion and osteogenic differentiation in rabbit bone marrow mesenchymal stem cells (rBMSCs) were examined using live and dead cell double staining, the cell counting kit-8 (CCK-8) assay, immunofluorescence and quantitative real-time PCR (qRT‒PCR). An in vivo rabbit extra-articular graft-to-bone healing model was established. At 4 and 12 weeks after surgery, CT analysis and histological evaluation were performed.Results: In vitro, G-PEEK significantly improved the adhesion and proliferation of rBMSCs, with good biocompatibility. In vivo, G-PEEK promoted new bone formation at the site of the bone defect.Conclusion: G-PEEK showed excellent osteogenesis performance, which promises new applications in implant materials.Keywords: polyetheretherketone, graphene, nanocomposites, cell adhesion, osteogenic differentiation

Yi Jiang,1 Lijie Wei,1 Huiting Zhang,1 Yuting Chen,1 Peng Gao,1 Jingyi Zhang,1 Xuan Zhou,1 Shenglan Zhu,1 Yuanyuan Du,1 Chenyun Fang,1 Jiaqi Li,2 Ling Feng,1 Mengzhou He,1 Shaoshuai Wang,1 Jun Yu1 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 33006, People’s Republic of ChinaCorrespondence: Jun Yu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei Province, People’s Republic of China, Email yjtj2010@163.comIntroduction: Gestational diabetes mellitus (GDM) is one of the common metabolic disorders of pregnancy and results in poor pregnancy outcomes for both mother and fetus. MiR-17-5p is considered as the strongest predictor of metabolic syndrome status, but the relationship between GDM and miR-17-5p remains unclear. TXNIP, which leads to activation of NLRP3, is considered as a potential target of miR-17-5p, and the miR-17-5p/TXNIP/NLRP3 axis has been shown to play a major role in the occurrence and development of many metabolic diseases but has not been validated in GDM.Methods: MiR-17-5p was detected by RT-qPCR. The expression of TXNIP and NLRP3 in placenta was detected by immunofluorescence, RT-qPCR and Western blot. To explore the effect of miR-17-5p on TXNIP and NLRP3 and glucose uptake of HTR8/SVneo cells, miR-17-5p mimic and miR-17-5p inhibitor were transfected to achieve overexpression and inhibition. The interaction between miR-17-5p and TXNIP was confirmed by dual-luciferase reporter assay. Besides, glucose consumption of trophoblast cells was detected by glucose assay kit.Results: MiR-17-5p expression was down-regulated, while the expression of TXNIP and NLRP3 was up-regulated in GDM placental tissues. MiR-17-5p targeted TXNIP and inhibited its expression. MiR-17-5p also regulated NLRP3 expression and glucose uptake of HTR8/SVneo cells, which could be reversed by overexpression of TXNIP, suggesting that miR-17-5p improved glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis. The results were consistent with the above findings in high-glucose treated HTR8/SVneo cells.Conclusion: Our results suggested that miR-17-5p ameliorates the glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis, which may provide a new idea for offspring health of GDM patients.Keywords: diabetes, gestational, microRNAs, pregnancy, inflammation

Yuehong Ren,1,&ast; Linghui Nie,2,&ast; Shiping Zhu,3 Xingwang Zhang1 1Department of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China; 2ASD Medical Rehabilitation Center, the Second People’s Hospital of Guangdong Province, Guangzhou, People’s Republic of China; 3Department of Chinese Traditional Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiping Zhu, Department of Chinese Traditional Medicine, The First Affiliated Hospital of Jinan University, 613 West Huangpu Avenue, Guangzhou, 513630, People’s Republic of China, Email zhushiping@jnu.edu.cn Xingwang Zhang, Department of Pharmaceutics, College of Pharmacy, Jinan University, No. 855 East Xingye Avenue, Guangzhou, 511443, People’s Republic of China, Email zhangxw@jnu.edu.cnAbstract: Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for effective treatment. Nanovesicles as pleiotropic oral vehicles can solubilize, encapsulate, stabilize an active ingredient and promote the payload absorption via various mechanisms. Vesicular systems with nanoscale size, such as liposomes, niosomes and polymersomes, provide a versatile platform for oral delivery of drugs with distinct nature. The amphiphilicity of vesicles in structure allows hydrophilic and lipophilic molecule(s) either or both to be loaded, being encapsulated in the aqueous cavity or the inner core, respectively. Depending on high oral transport efficiency based on their structural flexibility, gastrointestinal stability, biocompatibility, and/or intestinal epithelial affinity, nanovesicles can markedly augment the oral bioavailability of various poorly absorbed drugs. Vesicular drug delivery systems (VDDSs) demonstrate a lot of preferences and are becoming more prominent of late years in biomedical applications. Equally, these systems can potentiate a drug’s therapeutic index by ameliorating the oral absorption. This review devotes to comment on various VDDSs with special emphasis on the peroral drug delivery. The classification of nanovesicles, preparative processes, intestinal transport mechanisms, in vivo fate, and design rationale were expounded. Knowledge on vesicles-mediated oral drug delivery for bioavailability enhancement has been properly provided. It can be concluded that VDDSs with many merits will step into an energetic arena in oral drug delivery.Keywords: vesicles, oral drug delivery, bioavailability, liposomes, niosomes, exosomes

Sha Zhu, Yaxi Wang, Yinyin Jiang, Ruxin Gu, Min Zhong, Xu Jiang, Bo Shen, Jun Zhu, Jun Yan, Yang Pan, Li Zhang Department of Geriatric Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Li Zhang, Department of Geriatric Neurology, The Affiliated Brain Hospital of Nanjing Medical University, No. 264 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Email neuro_zhangli@163.comBackground: Transcranial ultrasound (TCS) can be used to reveal structural changes in the substantia nigra (SN) and is a potential tool for the early diagnosis of Parkinson’s disease (PD). This study aimed to explore the relationship between substantia nigra hyperechogenicity (SNH) and the clinical features of PD patients.Methods: A total of 96 PD patients were included in our study. All patients were detected by TCS and divided into two groups: PD patients with SNH (PDSN+) and those with normal SN echogenicity (PDSN-). The Unified Parkinson’s Disease Rating Scale (UPDRS) and the Hoehn & Yahr stage were used to assess the extent of disease-related disability of the PD patients. Non-motor symptoms were evaluated by using several scales. The instrumented stand and walk test was performed on all subjects, and gait data were gathered using a JiBuEn gait analysis system.Results: Seventy-five PD patients were successfully assessed by TCS. We found that SNH was associated with a higher UPDRS II scores (p = 0.028). In addition, compared with PDSN- group, the PDSN+ group exhibited more severe gait impairment, including increased variability in stride length (p = 0.042), decreased heel strike angle (p = 0.017), decreased range of motion of hip joints (p = 0.031), and a more asymmetrical walking pattern (p = 0.028).Conclusion: Our study demonstrated that SNH significantly correlated with activities of daily living and gait impairment in Chinese patients with PD, suggesting the formation of SNH might be a dynamic biomarker reflecting disease severity.Keywords: Parkinson’s disease, transcranial sonography, substantia nigra hyperechogenicity, non-motor symptoms, gait analysis

Bei Gu,1 Shiyang Zhu,2 Xuesong Ding,2 Yan Deng,2 Xiao Ma,2 Jingwen Gan,2 Yanfang Wang,2 Aijun Sun2 1Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, the Ninth Clinical Medical College of Peking University, Beijing, People’s Republic of China; 2National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Aijun Sun, Tel +86 18600045466, Email saj@pumch.cnBackground: Primary dysmenorrhea (PD) is one of the most common complaints in women of childbearing age. Therefore, this trial aimed to assess the efficacy and safety of low-power visible-light-activated photodynamic therapy (PDT) in the treatment of primary dysmenorrhea (PD), and to further investigate their possible mechanisms of action.Methods: This study was conducted by using a multicenter, randomized, open, parallel control design. Qualified subjects are randomly assigned to two groups: Group A (low-power visible-light-activated PDT group), Group B (placebo group) and are treated with corresponding protocols for three consecutive menstrual cycles. Baseline data are collected during the trial period. Changes in the scores of VAS scales and the fluctuation of pain factors (PGE2, PGF2α) are recorded before and after the treatment for each group. A comparison of effectiveness in pain control and symptom control is made among the two groups.Results: After treatment, for the PDT group, the scores of VAS scales decline compared with the scores before treatment. The level of pain factors including PGE2 and PGF2α also drops significantly (P < 0.05). There are no serious adverse events during the study.Conclusion: Low-power visible-light-activated PDT is a new type of treatment for primary dysmenorrhea which is safe, effective and does not affect normal pregnancy preparation. It may exert its therapeutic effect by adjusting downward the level of PGE2, PGF2α in the body. These factors can be used not only to study the treatment mechanism for primary dysmenorrhea, but also to serve as quantitative indicators for objective assessment of whether dysmenorrhea is relieved.Keywords: primary dysmenorrhea, low-power visible-light-activated photodynamic therapeutic device, prostaglandins E2, prostaglandins F2alpha

This work briefly introduces our recent studies on reactions induced by proton drip-line nuclei, 8B and 17F, at energies around the Coulomb barrier. Using detector arrays with large solid-angle coverage, the complete kinematics measurements were performed for systems of 8B+120Sn and 17F+58Ni. For the 8B+120Sn, the coincident measurement of the breakup fragments was achieved for the first time for a proton-halo nuclear system. The correlations between the breakup fragments reveal that the prompt breakup occurring on the outgoing trajectory dominates the breakup dynamics of 8B. For 17F+58Ni, the complete reaction channel information, such as quasi-elastic scattering, breakup and total fusion, was derived for the first time. An enhancement of the fusion cross section of 17F+58Ni was observed at the energy below the Coulomb barrier. Theoretical calculations indicate that this phenomenon is mainly due to the couplings to the continuum states. Moreover, different direct reaction dynamics were found in 8B and 17F systems, suggesting the influence of proton-halo structure on the reaction dynamics.

Numerous studies have demonstrated that the phenomenological optical potential of tightly bound nuclear systems presents a threshold anomaly phenomenon in the near-Coulomb barrier energy region, where the relationship between the real and imaginary potentials can be well described by the dispersion relation. However, for some weakly bound nuclear systems, the phenomenological optical potential seems to manifest differently, and the dispersion relation struggles to describe the behavior between real and imaginary potentials. Recently, we measured the angular distributions of the transfer reaction 207Pb(7Li,6Li)208Pb in both near and deep barrier energy regions, as well as the elastic scattering angular distributions of the entrance channel 7Li+207Pb. Optical potentials of the 6Li+208Pb system were extracted.The current results indicate that the optical potentials exhibit an abnormal threshold anomaly, and the dispersion relation is not applicable. Possible explanations are discussed, yet further investigations into the underlying physics are required.

Reactions of weakly bound stable and unstable nuclei have been extensively investigated for several decades. Unique structural effects and breakup mechanisms of weakly bound nuclei have consistently been focal points in the research of nuclear physics, especially at energies around the Coulomb barrier. This paper will review the recent experimental researches performed by the Nuclear Reaction Group at the China Institute of Atomic Energy on weakly bound nuclear reactions in the near-barrier energy region. A anomalous threshold phenomenon in the optical potentials of the 6He + 208Bi system has been observed. Results indicate that the dispersion relation cannot describe the relation between the real part and imaginary part of the optical potential. Moreover, breakup mechanisms of stable weakly bound nuclei 6,7Li as well as proton-rich nuclei 17F and 8B have been studied. The similarities and differences in breakup mechanisms and their effects are discussed.

Huajie Yang,1,&ast; Xiang Huang,2,&ast; Chunyu Yang,3 Sufen Zhu,4 Xiaoyi Chen,5 Man Zhang,2 Xiao Yu,3 Harry HX Wang3,6,7 1School of Health Technology, Guangdong Open University (Guangdong Polytechnic Institute), Guangzhou, People’s Republic of China; 2Department of Public Health, Sanxiang Community Health Service Centre of Zhongshan, Zhongshan, People’s Republic of China; 3School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK; 5School of Nursing, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 6Department of General Practice, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 7JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region&ast;These authors contributed equally to this workCorrespondence: Harry HX Wang, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China, Tel +86 20 87330672, Email wanghx27@mail.sysu.edu.cn; haoxiangwang@cuhk.edu.hk Huajie Yang, School of Health Technology, Guangdong Open University (Guangdong Polytechnic Institute), Guangzhou, 510091, People’s Republic of China, Tel +86 760 89911522, Email hjyang@gdpi.edu.cnIntroduction: Time-to-treatment window is critical for managing acute ischaemic stroke. The community healthcare practitioners (CHPs) who deliver frontline care in the health system play an important role in stroke prevention and treatment.Methods: A multi-stage sampling design was adopted in Guangdong province, China. A total of 997 CHPs who participated in the survey were divided into two groups (the awareness group vs the unawareness group) according to their knowledge on the time window for stroke management. Logistic regression analysis was performed to explore factors associated with the awareness of “time window”.Results: Overall, less than half (49.1%) of CHPs were aware of the time window for stroke management. The proportion of CHPs who were able to recognise stroke symptoms were higher in the awareness group (42.7%) than that in the unawareness group (38.8%). Most CHPs (82.9%) in the awareness group had the knowledge about the effectiveness of intravenous thrombolysis in treating acute cerebral infarction, whereas this was perceived by only less than half (43.6%) of CHPs in the unawareness group. Factors associated with the knowledge of time window for stroke management included participation in cerebrovascular disease management training (adjusted odds ratio [aOR]=4.203, 95% CI: 1.707– 10.348, p=0.002), awareness of the time frame for CT initiation (aOR=5.214, 95% CI: 1.803– 15.078, p=0.002) and for urokinase thrombolysis administration (aOR=11.927, 95% CI: 4.393– 32.382, p< 0.001), accurate perceptions about the target for blood pressure lowering (aOR=4.181, 95% CI: 1.713– 10.207, p=0.002) and blood glucose control (aOR=2.446, 95% CI: 1.019– 5.869, p=0.045), and the familiarity with prehospital stroke management principles (aOR=3.593, 95% CI: 1.383– 9.332, p=0.009).Conclusion: The CHPs need to enhance their ability to address the acute ischaemic stroke onset promptly to provide effective treatment within the beneficial “time window”. This may help improve the stroke chain of survival with better multidisciplinary decision support systems that enable optimal stroke care delivery.Keywords: time window, stroke, cross-sectional study, primary care

Xiaoxin Zhao,1 Shuyi Zhu,1 Yang Cao,2 Peipei Cheng,1 Yuxiong Lin,1 Zhixin Sun,1 Wenqing Jiang,1 Yasong Du1 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Suzhou Guangji Hospital, Suzhou, People’s Republic of ChinaCorrespondence: Yasong Du, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, No. 600 Wanping Nan Road, Shanghai, 200030, People’s Republic of China, Tel +86 18816935313, Email yasongdu2020@126.comBackground: Previous studies have indicated abnormal gray matter volume (GMV) in individuals with autism spectrum disorder (ASD); however, there is little consistency across the findings within these studies, partly due to small sample size and great heterogeneity among participants between studies. Additionally, few studies have explored the correlation between clinical symptoms and GMV abnormalities in individuals with ASD. Here, the current study examined GMV alterations in whole brain and their correlations with clinical symptoms in a relatively large and homogeneous sample of participants with ASD matched typically developing (TD) controls.Methods: Forty-eight adolescents with high-functioning ASD and 29 group-matched TD controls underwent structural magnetic resonance images. Voxel-based morphometry was applied to investigate regional GMV alterations. The participants with ASD were examined for the severity of clinical symptoms with Autism Behavior Checklist (ABC). The relationship between GMV abnormalities and clinical symptoms was explored in ASD group using voxel-wise correlation analysis within brain regions that showed significant GMV alterations in individuals with ASD compared with TD controls.Results: We found increased GMV in multiple brain regions, including the inferior frontal gyrus, medial frontal gyrus, superior frontal gyrus, superior temporal gyrus, occipital pole, anterior cingulate, cerebellum anterior lobe, cerebellum posterior lobe, and midbrain, as well as decreased GMV in cerebellum posterior lobe in individuals with ASD. The correlation analysis showed the GMV in the left fusiform was negatively associated with the scores of sensory factor, and the GMV in the right cerebellum anterior lobe was positively associated with the scores of social self-help factor.Conclusion: Our results indicated that widespread GMV abnormalities of brain regions occurred in individuals with ASD, suggesting a potential neural basis for the pathogenesis and symptomatology of ASD.Keywords: autism spectrum disorder, symptoms severity, Autism Behavior Checklist, structural magnetic resonance imaging, gray matter volume

Yan Lan, Chensheng Pan, Xiuli Qiu, Jinfeng Miao, Wenzhe Sun, Guo Li, Xin Zhao, Zhou Zhu, Suiqiang Zhu Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Zhou Zhu; Suiqiang Zhu, Tel +86-18171081029 ; +86-13035101141, Email zhouzhu@hust.edu.cn; zhusuiqiang@163.comPurpose: Previous studies have shown that persistent post-stroke depression (PSD) was associated with unfavorable prognosis. The aim of this multicenter prospective study was to investigate the predictors associated with persistent PSD, develop a nomogram and validate its clinical usefulness by decision curve analysis (DCA).Patients and Methods: A total of 875 acute ischemic stroke patients from four hospitals were consecutively recruited and completed 1-year follow-ups. Sociodemographic indicators, vascular risk factors, clinical information, serum biochemical indicators and cytokines were collected on admission. The functional outcome was assessed at 1 year after stroke. Persistent depression was defined as having a presentation of depression at each follow-up points and the depressive symptoms occurring persistently since the diagnosis of depression.Results: There were 513 patients who experienced PSD during the 1-year follow-up, the cumulative incidence of PSD within 1 year was 58.6%. Persistent PSD was recorded in 289 patients, of which 59 (20.4%) result in unfavorable outcomes. The risk factors of persistent PSD in 1 year after stroke were the Hamilton Depression Scale-17 items (HAMD-17) score at admission, serum direct bilirubin and free serum thyroxine (FT4) level and activated partial thromboplastin time (APTT). Nomogram conducted based on these factors has a C-index (± standard deviation) of 0.655 ± 0.039, and the DCA demonstrated that the nomogram had a favorable clinical utility.Conclusion: We found that persistent depression after stroke in the first-year time course after stroke was associated with HAMD-17 score at admission, lower serum direct bilirubin and FT4 level, and APTT. A nomogram was developed with advisable clinical usefulness in our study.Keywords: persistent post-stroke depression, nomogram, decision curve analysis

Yanyan Wang,1 He Wang,2 Wenzhe Sun,1 Jinfeng Miao,1 Wenwen Liang,1 Xiuli Qiu,1 Yan Lan,1 Chensheng Pan,1 Guo Li,1 Xin Zhao,1 Zhou Zhu,1 Suiqiang Zhu1 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Medical Affairs, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaCorrespondence: Zhou Zhu; Suiqiang Zhu, Tel +86 18171081029 ; +86 13035101141, Fax +86 27-83663337, Email zhouzhu@hust.edu.cn; zhusuiqiang@163.comBackground: Post-stroke depression (PSD) is the most common neuropsychiatric complication after stroke, seriously affecting the quality of survivors’ life. As one of the important causes of PSD, neuroendocrine mechanism has been widely studied in recent years. The main objective of this study was to investigate the relationship between adrenocorticotropic hormone (ACTH) on admission and PSD at 3 months.Methods: This is a hospital-based prospective cohort study, which was conducted at three independent hospitals (Tongji Hospital, Wuhan First Hospital and Wuhan Central Hospital) between August 2018 and June 2019. A total of 768 ischemic stroke patients were finally eligible for analysis and categorized into equal tertiles according to the distribution of ACTH and the number of patients. The χ2-test, Mann–Whitney U-test and Kruskal–Wallis test were used to check for statistical significance. And restricted cubic spline (RCS) regression model was used to explore the non-linear relationship between continuous ACTH levels and PSD at 3 months.Results: The optimal cut-off points of ACTH were as follows: (T1) 0.32– 20.55 pg/mL, (T2) 20.56– 39.79 pg/mL, (T3) 39.80– 143.40 pg/mL. A total of 305 patients (39.7%) were diagnosed as PSD at 3 months follow-up. Significant differences were found between the PSD and non-PSD groups in ACTH concentration (P = 0.001). After adjustment for all conventional confounders, the odds ratios of PSD were 1.735 (95% CI = 1.176– 2.560, P = 0.005) for the highest tertile of ACTH and 1.496 (95% CI = 1.019– 2.194, P = 0.040) for the middle tertile of ACTH, as compared with the lowest tertile. In multiple-adjusted RCS regression, continuous ACTH showed saturation effect relation with PSD risk after 31.02 pg/mL (P for nonlinear = 0.0143).Conclusion: Higher ACTH level on admission is a significant and independent biomarker to predict the development of PSD at 3 months follow-up. Besides, saturation effect was revealed even if the underlying mechanism is unclear. For stroke patients, doctors should pay attention to the baseline ACTH for screening high-risk PSD in clinical practice.Keywords: neuroendocrinology, HPA axis, adrenocorticotropic hormone, post-stroke depression, restricted cubic spline, saturation effect

Tianjun Yang,1,2,&ast; Qing Mei,1,2,&ast; Xiaowei Fang,1,2 Shoujun Zhu,1,2 Yinzhong Wang,1,2 Wanli Li,1,2 Aijun Pan1,2 1Department of Intensive Care Unit, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui Province, 230001, People’s Republic of China; 2Department of Intensive Care Unit, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui Province, 230001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aijun Pan; Qing Mei, Department of Intensive Care Unit, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, No. 17, Lu Jiang Road, Hefei, Anhui Province, 230001, People’s Republic of China, Fax +86-551-62283114, Email aijunpan@fsyy.ustc.edu.cn; qingmei@fsyy.ustc.edu.cnBackground: Metagenomics next-generation sequencing (mNGS) is more efficient in identifying pathogens responsible for pneumonia. However, whether these patients ultimately benefit from this improvement remains unknown.Methods: In this retrospective, nested, case–control study, patients with severe hospital-acquired pneumonia (HAP) who had undergone mNGS of bronchoalveolar lavage fluid while in our intensive care unit from March 2017 to December 2020 (n = 33) were matched in a ratio of 1 to 2 (n = 66) by sex, age, comorbidities, immune status, Acute Physiology and Chronic Health Evaluation II score, severity of pulmonary infection, and use of extracorporeal life support with patients who had undergone conventional microbiological testing only. The primary outcome was 90-day mortality; secondary outcomes being length of intensive care unit stay, duration of mechanical ventilation support, 7-day and 28-day mortality, and efficacy of treatment of pulmonary infection.Results: In the CMT group, 17 patients (25.8%) had negative results, whereas only one (3.0%) had negative results in the mNGS group (P < 0.001). After receipt of microbiology results, antibiotics were altered in 23/33 patients (70.0%) in the mNGS group, but in only 29/66 (43.9%) in the CMT group (P = 0.016). Pulmonary infection-related findings improved in 20/33 patients (60.6%) in the mNGS group in the subsequent 7 days, but in only 25/66 (37.9%) in the CMT group (P = 0.032). However, the 28-day (33.3% vs 31.2%, P = 1.0) and 90-day (48.5% vs 45.5%, P = 0.78) mortality rates did not differ significantly between the two groups. These findings were supported by Cox-regression and Kaplan–Meier survival curve analyses.Conclusion: mNGS is helpful in the treatment of severe HAP but does not improve medium or long-term survival rates, especially in patients with severe comorbidities.Keywords: next generation sequencing, severe hospital-acquired pneumonia, bronchoalveolar lavage fluid, mortality, pathogenic microbes

Sirong Zhu,1,&ast; Chao Sun,1,&ast; Longjiang Zhang,1 Xiaoan Du,1 Xiaodong Tan,1,2 Shuzhen Peng3 1School of Public Health, Wuhan University, Wuhan, Hubei, People’s Republic of China; 2School of Nursing, Wuchang University of Technology, Wuhan, Hubei, People’s Republic of China; 3The People’s Hospital of Huangpi, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodong Tan; Shuzhen Peng, Email 00300469@whu.edu.cn; 1718274898@qq.comPurpose: This study aimed to analyze the incidence trend and further explore the risk factors influencing the survival among patients of malignant skin cancer in America.Methods: Age-adjusted incidence rates, annual percentage change (APC) of different sex and ethnicity in 1973– 2015 and patient records were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate analysis and multivariate Cox regression were used to analyze risk factors influencing the survival in skin cancer patients. Survival curves and nomograms were constructed to evaluate the survival prediction by R.Results: The overall age-adjusted incidence of skin cancer increased in America from 1973 to 2005 (APC = 2.8%, 95% CI: 2.6– 2.9%, P < 0.05), particularly in white patients, 66-year-old people, and males. The 3- and 5-year overall survival (OS) rates were 51.4% and 33.8%, respectively. Independent predictors for short OS include age over 65, white ethnicity, other marital status and no surgery (P < 0.05). Stage was not an independent factor of survival (P > 0.05). The nomogram with a C-index of 0.72 (95% CI: 0.71– 0.73) matched an appropriate calibration curve.Conclusion: Incidence of skin cancer in America was on the rise during 1973– 2015 based on SEER database. Age, ethnicity, marital status and surgical history were related with survival of malignant skin cancer. Nomograms were effective tools for predicting the survival prognosis.Keywords: malignant skin cancer, primary site surgery, SEER, incidence, overall survival, nomogram

Xiaonan Zhou,1,2,&ast; Kai Zhu,1,2,&ast; Yiqiu Zhang,3– 5,&ast; Yang Ming,1,2 Dai Shi,3– 5 Hui Tan,3– 5 Bitao Xiang,1,2 Shichao Zhu,1,2 Dengfeng Cheng,3– 5 Hao Lai,1,2 Chunsheng Wang,1,2 Guobing Liu3– 5 1Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, People’s Republic of China; 3Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 4Institute of Nuclear Medicine, Fudan University, Shanghai, 200032, People’s Republic of China; 5Shanghai Institute of Medical Imaging, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guobing Liu, Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 in Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +8618317086732, Fax +86-21-62489191, Email liu.guobing@zs-hospital.sh.cn Chunsheng Wang, Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, No. 180 in Fenglin Road, Shanghai, 200032, People’s Republic of China, Email wangchunsheng@fudan.edu.cnPurpose: To investigate the feasibility of a pre-targeted imaging strategy based on the cycloaddition between 1,2,4,5-terazine (Tz) and trans-cyclooctene (TCO) for evaluating CD11b expression in inflammatory aortic aneurysm (AA) using single photon emission computed tomography/computed tomography (SPECT/CT).Methods: C57BL/6J mice were fed β-aminopropionitrile (1 g/kg/day) for 4 weeks to establish AA models. Anti-CD11b-TCO was synthesized and 99mTc-HYNIC-PEG11-Tz was designed for pre-targeted SPECT/CT. The affinity and specificity of the probe for the inflammatory cell line Raw-264.7 were investigated. Then, anti-CD11b-TCO pre-targeted and 99mTc-HYNIC-PEG11-Tz based SPECT/CT were performed to detect in vivo inflammation in AA. Finally, ex vivo aortic breast-specific gamma imaging (BSGI), Western blot assays, and immunohistochemical CD11b staining were performed to confirm the in vivo findings of SPECT/CT.Results: In the AA models, 65.22% (15/23) had aortic lesions, including 43.48% (10/23) AA lesions. The anti-CD11b-TCO presented with a high TCO coupling ratio (7.43), and the 99mTc-HYNIC-PEG11-Tz showed high radio-purity (> 95%), good in vitro stability and a rapid clearance rate. Additionally, anti-CD11b-TCO and 99mTc-HYNIC-PEG11-Tz presented high click rate (∼ 89%). The in vitro clicked compound, 99mTc-HYNIC-PEG11-Tz/TCO-anti-CD11b, showed high affinity and specificity for Raw-264.7 cells. 99mTc-HYNIC-PEG11-Tz/TCO-anti-CD11b pre-targeting SPECT/CT successfully demonstrated inflammatory AA with a high AA-to-background ratio in AA mice, compared to AA mice that were injected with 99mTc-HYNIC-Tz/TCO-IgG (8.13 versus 3.71, P < 0.001) and control mice injected with 99mTc-HYNIC-Tz/TCO-anti-CD11b (8.13 versus 3.66, P < 0.001). This result was confirmed by ex vivo BSGI performed immediately after SPECT/CT and immunohistochemical CD11b staining.Conclusion: SPECT/CT imaging using the anti-CD11b-TCO/Tz-PEG11-HYNIC-99mTc based pre-targeting imaging strategy allows for the detection of inflammation in progressive AA.Keywords: aortic aneurysm, inflammation, SPECT/CT, CD11b, macrophage

Guilan Cheng,1,&ast; Dingxi Wang,1,&ast; Ping Zhu,2 Ziqi Lin,2 Shichao Zhu,3 Juan Li,1 Linqian Li,1 Yipeng Zhang,4 Guixiang Li1 1Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Infection Control, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Information Centre, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guixiang Li, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37 Wainan Guoxue Alley, Chengdu, 610041, People’s Republic of China, Tel +86 18980601726, Email liguixiang@wchscu.cnBackground: There are few published reports describing the clinical characteristics of acute pancreatitis (AP) patients with multidrug-resistant organism (MDRO) infection.Methods: This was a retrospective analysis of AP patients with MDRO infection in West China Hospital between July 2015 and June 2020. Basic clinical data, disease progression states, and prognoses of the MDRO and non-MDRO infection groups were compared and analyzed. Logistic regression analysis was performed to explore the related risk factors for MDRO infection. The prognoses of different MDRO infection types were compared.Results: In total, 9812 AP patients were included, 2436 (24.83%) of whom had healthcare-associated infections (641 [26.31%] MDRO infections and 1795 [73.69%] non-MDRO infections). The main MDRO strain was carbapenem-resistant Acinetobacter baumannii (CRAB) (400/62.40%). The rate of discharge against doctor’s advice, mortality, hospitalization expenses, and hospitalization days was higher in the MDRO infection group than in the noninfection group. By logistic regression analysis, the independent risk factors associated with MDRO infection included male sex (OR 1.36, 95% CI 1.09∼ 1.70), severity (OR 1.40, 95% CI 1.10∼ 1.78), ICU referral (OR 2.48, 95% CI 1.79∼ 3.44), abdominal puncture (OR 2.78, 95% CI 1.93∼ 4.02), fiberoptic bronchoscopy (OR 1.95, CI 1.35∼ 2.81), and PICC/CVC placement (OR 1.48, CI 1.06∼ 2.06). Compared with biliary and hypertriglyceridemia (HTG) (OR 0.94, 95% CI 0.73∼ 1.23), alcohol (OR 0.30, 95% CI 0.19∼ 0.47) and other etiologies (OR 0.58, 95% CI 0.41∼ 0.81) conferred a lower risk of MDRO infection. The carbapenem-resistant Klebsiella pneumoniae (CRKP) infection rate was highest in the patients who died.Conclusion: The CRAB proportion was highest in AP patients with MDRO infection. MDRO infection is related to many factors, has a poor prognosis, and increases the patient burden. CRKP infection is directly related to poor prognosis.Keywords: acute pancreatitis, multidrug-resistant organisms, infection

Xian Sun,1 Yiting Huang,1 Sha Zhu,1 Jin Yan,2 Ke Gan,3 Zijing Xu,4 Shuaishuai Wang,4 Xiaoyu Kang,4 Junfeng Zhang,4 Wei Sun2 1The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Department of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 3Department of Rheumatology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 4School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of ChinaCorrespondence: Wei Sun, Department of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China, Tel +86-13505199810, Email yfy0074@njucm.edu.cn Junfeng Zhang, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Tel +86-13805186836, Email Zhangjunfeng419@njucm.edu.cnBackground: Chronic kidney disease (CKD) is considered a global public health problem with high morbidity and mortality. Yishen Qingli Heluo granule (YQHG) is representative traditional Chinese medicine (TCM) remedy for clinical treatment of CKD. This study aims to explore the mechanism of YQHG on CKD through network pharmacology and experimental validation.Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and wide-scale literature mining were applied to screen active compounds of YQHG. Multiple bioinformatic tools and online databases were applied by us to obtain relevant targets of YQHG and CKD. The intersection targets between YQHG and CKD were considered as candidate targets. The compound-target, herb-candidate target and protein–protein interaction networks were constructed and visualized for topological analyses. GO and KEGG enrichment analyses were conducted to determine the biological processes and signaling pathways. Molecular docking was used to verify the reliability of network pharmacology. Finally, pharmacological evaluation was performed to explore the mechanism of YQHG against CKD on a 5/6 nephrectomy model.Results: Seventy-nine candidate targets, ten core biological processes and one key signaling pathway (p53) were screened. PTGS2 was identified as a key target based on H-CT network. The molecular docking showed that Quercetin, Kaempferol, Luteolin were three key compounds with the best binding activity. In addition, IL6 and Quercetin could form a stable complex with high binding affinity (− 7.29 kcal/mol). In vivo experiment revealed that YQHG improved kidney function and fibrosis in 5/6 nephrectomized rats. Moreover, the decreased expression of PTGS2, IL6, and the increased expression of p53 were observed in kidney tissue. Notably, the gut microbiota of rats treated with YQHG was reshaped, which was characterized by a reduced ratio of Firmicutes/Bacteroidota.Conclusion: Our results predicted and verified the potential targets of YQHG on CKD from a holistic perspective, and provided valuable direction for the further research of YQHG.Keywords: Yishen Qingli Heluo granule, network pharmacology, chronic kidney disease, 5/6 nephrectomy, gut microbiota