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Lu Xu,1,* Jing Liu,2,* 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*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

Xiujing Lu,* Xi Lan,* Xiaoqian Fu, Jing Li, Min Wu, Lu Xiao, Yachang Zeng Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yachang Zeng, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China, Email zengyachang@163.comPurpose: Preeclampsia (PE) is a serious complication of obstetrics and represents a significant challenge in terms of understanding its underlying mechanism. It has been shown that a number of disorders involve dysregulation of the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2). However, the relationship between PE and CITED2 is still mostly unclear. This work aimed to confirm the hub genes linked to PE and explore the roles of CITED2 in trophoblast using experimental and bioinformatic methods.Methods: To determine the hub genes, bioinformatics research was performed on two datasets from the Gene Expression Omnibus (GEO) public database. Immune infiltration analysis and enrichment analysis were also used to identify the related pathways and immune cells. PCR and WB were then used to validate the mRNA and protein levels of CITED2 in the PE samples. Finally, the expression of CITED2 was knocked down using siRNA to investigate the function of CITED2 in trophoblast development in vitro.Results: The study’s findings showed that the NOTCH signaling pathways, glycolysis, and hypoxia were the main areas of enrichment for the six PE-related genes that were tested. The results of immune infiltration suggest that activated NK cells and regulatory T cells may play an important role in this process. CITED2 was significantly upregulated in the PE placenta. In functional tests, the knockdown of CITED2 may enhance apoptosis while suppressing migration, invasion, and proliferation of cells.Conclusion: This study offers important proof that CITED2 influences trophoblast cell function and may one day be a therapeutic target for PE.Keywords: preeclampsia, CITED2, placenta, cell function, bioinformatics

Hong Ding,1 Xiaofan Lu,2 Huimin Wang,3 Wenming Chen,3 Bing Niu4 1Otolaryngology Department, The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 2Respiratory Department, The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 3Otolaryngology Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 4Stomatology Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Hong Ding; Bing Niu, Henan University of Chinese Medicine, The Second Clinical Medical College, 6 Dongfeng Road, Jinshui District, Zhengzhou City, Henan Province, 450002, People’s Republic of China, Email superding@hactcm.edu.cn; 13838061768@163.comPurpose: Accumulating evidence indicates that oxidative stress and inflammation are the pathological basis of allergic diseases. Inhibition of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome could ameliorate allergic rhinitis (AR). Here, we explored the effects and mechanisms that underlie NLRP3 inhibition on oxidative stress and inflammation in AR.Methods: Ovalbumin (OVA)-induced AR murine model was established using wild-type (WT) and NLRP3-deficient mice. HNEpCs were stimulated with interleukin (IL)-13 with MCC950 pretreatment or PTEN-induced putative kinase 1 (PINK1) siRNA. The indicators of oxidative stress, inflammation, apoptosis, and mitophagy were determined both in vivo and in vitro.Results: NLRP3 knockout (KO) reduced the frequency of nasal rubbing and sneezing, the infiltration of eosinophils, the number of mast cells, and the accumulation of goblet cells in AR mice after OVA stimulation. The NLRP3 KO AR mice exhibited the increased concentrations of OVA-specific immunoglobulin E (OVA-sIgE), IL-1β, IL-4, IL-13, IL-6, TNF-α, and the upregulated level of IFN-γ. NLRP3 KO significantly inhibited oxidative stress, and also markedly decreased apoptosis in the nasal mucosa of AR mice. Moreover, evaluated protein expressions of PINK1, enzyme 3 (E3) ubiquitin ligase PRKN (Parkin), and LC3 II, decreased expression of TOM20, as well as the increased colocalization of LC3 with mitochondria were observed in NLRP3 KO AR mice. In vitro, IL-13 exposure increased the levels of NLRP3 and IL-1β. Inhibition of NLRP3 using MCC950 enhanced PINK1/Parkin-mediated mitophagy but attenuated inflammation, oxidative stress, and apoptosis. However, PINK1 knockdown abrogated mitophagy and also reversed the protective effects of MCC950 on inflammation, oxidative stress, and apoptosis in HNEpCs stimulated with IL-13.Conclusion: Inhibition of NLRP3 inflammasome exerts the protective effects on AR by facilitating mitophagy regulated by PINK1/Parkin signaling pathway.Keywords: NLRP3, mitophagy, inflammation, oxidative stress, PINK1/Parkin

Bohai Du,1 Tianlan Li,1 Haoqi He,1 Xun Xu,2 Chunmei Zhang,1 Xianzhu Lu,1 Yuhan Wang,1 Jingyi Cao,1 Yinghan Lu,1 Yiwa Liu,1 Shanshan Hu,1 Juxiao Li,1 Li Li,1 Ming Shi1 1Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of China; 2Experimental Animal Center, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of ChinaCorrespondence: Li Li; Ming Shi, School of Public Health, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of China, Tel +86-15889530426 ; +86-769-22896568, Email lily2017@gdmu.edu.cn; shiming@gdmu.edu.cnIntroduction: Studies have shown that microplastics (MPs) and nanoplastics (NPs) could accumulate in the human body and pose a potential threat to human health. The purpose of this study is to evaluate the biodistribution and toxicity of MPs/NPs with different particle sizes comprehensively and thoroughly.Methods: The purpose of this study was to investigate the biodistribution and in vivo toxicity of polystyrene (PS) MPs/NPs with different sizes (50 nm, 100 nm, and 500 nm). The BALB/c mice were given 100 μL of PS50, PS100 and PS500 at the dosage of 1 mg/kg BW or 10 mg/kg BW, respectively, by gavage once a day. After 28 consecutive days of treatment, the biodistribution of differently sized PS MPs/NPs was determined through cryosection fluorescence microscopy and fluorescent microplate reader analysis, and the subsequent effects of differently sized PS MPs/NPs on histopathology, hematology and blood biochemistry were also evaluated.Results: The results showed that the three different sizes of PS MPs/NPs were distributed in the organs of mice, mainly in the liver, spleen, and intestine. At the same time, the smaller the particle size, the more they accumulate in the body and more easily penetrate the tissue. During the whole observation period, no abnormal behavior and weight change were observed. The results of H&E staining showed that no severe histopathological abnormalities were observed in the main organs in the low-dose exposure group, while. Exposure of three sizes of PS MPs/NPs could cause some changes in hematological parameters or biochemical parameters related to heart, liver, and kidney function; meanwhile, there were size- and dose-dependencies.Conclusion: The biological distribution and toxicity of plastic particles in mice were more obvious with the decrease of particle size and the increase of concentration of plastic particles. Compared with MPs, NPs were easier to enter the tissues and produce changes in liver, kidney, and heart functions. Therefore, more attention should be paid to the toxicity of NPs.Keywords: microplastics, nanoplastics, polystyrene, size, biodistribution, nanotoxicology

Ente Li,1,2,* Qingfeng Zhu,3,* Ziman Lv,1,2,* Songsong Xie,3 Chunju Zhang,4 Wei Li,5 Ligu Mi,1,2 Quan Liu,6 Yuanzhi Wang,1,2 Xiaobo Lu2 1Department of Basic Medicine, School of Medicine, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 2Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, the Xinjiang Production and Construction Corps, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 3The First Affiliated Hospital of Shihezi University Medical College, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 4Tumxuk Center for Disease Prevention and Control, Tumxuk City, Xinjiang Uygur Autonomous Region, 843806, People’s Republic of China; 5Department of Basic Medicine, School of Medicine, Tarim University, Alaer City, Xinjiang Uygur Autonomous Region, 843300, People’s Republic of China; 6Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Key Laboratory of Zoonotic Diseases, The First Hospital of Jilin University, Changchun City, Jilin Province, 30061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanzhi Wang; Xiaobo Lu, Email wangyuanzhi621@126.com; xjykdluxiaobo@126.comAbstract: Visceral leishmaniasis (VL), also known as kala-azar. It is characterized by prolonged intermittent fever, anemia, splenomegaly, hepatomegaly, and skin darkening. VL is primarily endemic in regions, such as Brazil, East Africa, and India. However, Northern Xinjiang, which is located in northwestern China, is considered a low-incidence area for VL, contributing to its status as a neglected infectious disease. In this report, we present a case of VL caused by Leishmania donovani that was diagnosed using metagenomic next-generation sequencing (mNGS). This case underscores the diagnostic value of mNGS, particularly in regions with low incidence of VL. Keywords: Visceral leishmaniasis, Leishmania donovani, metagenomic next-generation sequencing, northwestern China

Huiqian Guo,1,2,* Jing Luo,1,3,* Suming Chen,1 Ting Yu,4 Xiaofei Mu,4 Fangzhou Chen,4 Xiuhui Lu,4 Jiaqi He,4 Yali Zheng,4 Chunmei Bao,2 Peng Wang,4 Zhe Yin,4 Boan Li1– 3 1Department of Clinical Laboratory, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China; 2School of Medical Laboratory, Weifang Medical University, Weifang, 261053, People’s Republic of China; 3Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 4State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Boan Li, Department of Clinical Laboratory, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China, Email lba@263.net Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China, Email jerry9yin@163.comPurpose: To investigate the genetic diversity of IncG plasmids, we have proposed a typing scheme based on replicon repA and performed comparative genomic analysis of five IncG plasmids from China.Methods: p30860-KPC, p116965-KPC, pA1705-KPC, pA1706-KPC and pNY5520-KPC total in five IncG plasmids from clinical isolates of Pseudomonas and Enterobacteriaceae, respectively, were fully sequenced and were compared with the previously collected reference plasmid p10265-KPC.Results: Based on phylogeny, IncG-type plasmids are divided into IncG-I to IncG-VIII, the five plasmids belong to IncG-VIII. A detailed sequence comparison was then presented that the IncG plasmid involved accessory region I (Tn 5563a/b/c/d/e), accessory region II (ISpa19), and accessory region III (blaKPC-2-region). Expect for the pNY5520-KPC, the rest of the plasmids had the same backbone structure as the reference one. Within the plasmids, insertion sequences Tn 5563d and Tn 5563e were identified, a novel unknown insertion region was found in Tn 5563b/c/d/e. In addition, Tn 6376b and Tn 6376c were newly designated in the study.Conclusion: The data presented here including a typing scheme and detailed genetic comparison which provide an insight into the diversification and evolution history of IncG plasmids.Keywords: IncG plasmids, blaKPC-2, phylogenetic tree, multidrug resistance, mobile elements

Shuo Yuan,&ast; Xuanyu Lu,&ast; Lei Zang, Yuqi Mei, Ning Fan, Peng Du Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zang, Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, 5 JingYuan Road, Shijingshan District, Beijing, 100043, People’s Republic of China, Email zanglei@ccmu.edu.cnPurpose: Percutaneous transforaminal endoscopic discectomy (PTED) was used as a minimally invasive treatment option for lumbar disc herniation (LDH). However, studies focusing on the clinical outcomes of PTED for elderly patients with adjacent segment disease (ASD) were limited. This study aims to compare the clinical outcomes of PTED between ASD and LDH in elderly patients.Patients and Methods: This retrospective study enrolled 39 patients with ASD and 39 patients with LDH. Both groups had undergone PTED in Beijing Chaoyang Hospital from July 4, 2016 to July 30, 2021. Visual analog scale for back pain (VAS-BP) and leg pain (VAS-LP) and Oswestry disability index (ODI) were used to value the clinical outcomes of patients preoperatively, immediately postoperatively, 12, and 24 months postoperatively, and at final follow-up. Patients’ satisfaction was evaluated based on the MacNab criteria.Results: All operations were completed. The excellent or good clinical outcomes at final follow-up was demonstrated by 87.15% (34/39) and 89.74% (35/39) in ASD and non-ASD patients, respectively. Clinical improvement was observed immediately postoperatively in both groups and sustained stability during the postoperative follow-up. The ASD group demonstrated significantly longer hospital stays (p = 0.02) and operative time (p < 0.01) than the non-ASD group.Conclusion: PTED is an effective and minimally invasive treatment option for revision surgery of ASD, especially for elderly patients. However, the long-term prognosis of PTED treating ASD still needs further exploration.Keywords: adjacent segment degeneration, percutaneous transforaminal endoscopic discectomy, clinical outcomes, geriatric patients, minimally invasive

Huina Gao,1,* Yijun Song,2,* Kun Liu,1,* Xinyuan Lu,3 Jiacheng Shen,2 Sulan Wei,2 Hongni Jiang,1,2 Nuo Xu2 1Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nuo Xu, Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Email xu.nuo@zs-hospital.sh.cn; Hongni Jiang, Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, 668 Jinhu Road, Xiamen, 361015, People’s Republic of China, Email jiang.hongni@zs-hospital.sh.cnPurpose: Cigarette smoking is the most recognized risk factor of chronic obstructive pulmonary disease (COPD) in China. However, there are no studies analyzing the impact of different smoking behaviors on pulmonary function and pulmonary hypertension (PH) among Chinese male patients with COPD.Patients and Methods: Chinese male smokers with COPD performed pulmonary function tests. Clinical characteristics, smoking behavior features, spirometry and echocardiographic results were compared between the two groups stratified by initial smoking age (18 years old) or complicated PH.Results: The early-smoking group had more respiratory symptoms, more severe smoking behavior, worse pulmonary function with lower FEV1%pre (38.5% vs 70.2%) and FEV1/FVC% (47.5% vs 63.8%), and higher systolic pulmonary artery pressure (sPAP: 38.6 vs 33.9 mmHg) than the late-smoking group. Initiating smoking before adulthood was an independently contributing factor of ventilatory dysfunction and Global Initiative for Obstructive Lung Disease (GOLD) stage escalation. It also had a significant interaction with long smoking duration (≥ 30 years), characterized by markedly decreased lung volumes (VC%pre: 64.0% vs 84.5%), impaired diffusing capacity (DLCO%pre: 58.0% vs 76.8%) and severe emphysema (RV/TLC%pre: 145.2% vs 130.2%). COPD patients complicated with PH exhibited worse ventilatory function (FEV1%pre: 43.2% vs 56.2%), impaired diffusion capacity (DLCO%pre: 56.7% vs 77.1%) and decreased lung volume (VC%pre: 67.67% vs 75.38%). Both severe smoking behaviors and impaired pulmonary function had close correlations with sPAP.Conclusion: The early-smoking group exhibited predominantly ventilation dysfunction and had complex interactions with long smoking duration to further affect lung volume and diffusion capacity. Different smoking behaviors influenced variations of pulmonary dysfunction and comorbid PH in patients with COPD.Keywords: chronic obstructive pulmonary disease, pulmonary function, smoking behavior, initial smoking age, pulmonary hypertension

Shanshan Liu,1,2 Xiaomeng Ge,3 Xizhan Xu,4 Kang Zhang,1 Xinxin Lu1 1Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Infection Management, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People’s Hospital of Lianyungang, Jiangsu, People’s Republic of China; 3Microbial Resources and Big Data Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xinxin Lu, Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, No. 1, Dongjiaomin Lane, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-13911682566, Fax +8610-65125617, Email luxinxin2009@126.comPurpose: The clinical manifestations of pyogenic liver abscess (PLA) vary between patients with and without diabetes mellitus (DM). However, the relationship between PLA and the gut microbiome remains unknown. This study analyzed the composition of gut microbiota in PLA patients with and without DM and healthy controls (HCs) with the goal of identifying potential reasons for the observed variations in clinical manifestations.Patients and Methods: Using 16S ribosomal RNA(16S rRNA) gene sequencing, we analyzed the compositions of gut microbiota in 32 PLA patients with DM, 32 PLA patients without DM, and 29 matched HCs.Results: In PLA patients with DM, the D-dimer level, fibrinogen degradation products, and thrombin time were significantly higher compared to the PLA patients without DM (P < 0.05). The abundance and diversity of intestinal flora were reduced in both groups of PLA patients compared with the HCs (P < 0.05). Specifically, the PLA patients with DM showed significant decreases in the relative abundances of Bacteroides, Blautia, Prevotella9, and Faecalibacterium, whereas Enterococcus and Escherichia-Shigella were relatively more abundant (P < 0.05). Compared to PLA patients without DM, those with DM had lower relative abundances of Lactobacillus and Klebsiella (P < 0.05) and showed different bacterial flora, including Anaerosporobacter and Megamonas.Conclusion: PLA patients with DM exhibited more severe clinical manifestations of PLA compared to patients without DM. It is important to monitor blood coagulation in PLA patients with DM to prevent the development of thrombotic diseases. Additionally, PLA patients with DM exhibit distinct differences in the composition and diversity of their intestinal flora compared to both PLA patients without DM and HCs.Keywords: Gut microbiota, Pyogenic liver abscess, type 2 diabetes mellitus, 16S rRNA sequencing

Jufei Wu,1,&ast; Jishi Wu,2,&ast; Yan Zhou,3 Xiaohua Lu,4 Wane Zhao,4 Fengmei Xu1 1Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Department of General Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Interventional Radiology & Vascular Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 4Department of Endocrinology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zhou, Department of Interventional Radiology & Vascular Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China, Email 992054881@qq.com Xiaohua Lu, Department of Endocrinology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China, Email yhlu@163.comPurpose: To develop a prediction model for hypoglycemia in type 2 diabetes mellitus (T2DM) patients treated with an insulin pump during enteral nutrition.Methods: This retrospective study included T2DM patients treated with an insulin pump during enteral nutrition at the First Affiliated Hospital of Jinan University, Guangzhou Red Cross Hospital, Foshan First People’s Hospital, and Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2016 and December 2023. The patients were randomized 3:1 to the training and validation sets. The risk factors for hypoglycemia were analyzed. A prediction model was developed.Results: This study included 122 patients, and 57 patients had at least one hypoglycemic event during their hospitalization (46.72%). The multivariable logistic regression analysis showed that the time to reach the glycemic targets (odds ratio (OR)=1.408, 95% confidence interval (CI)=1.084– 1.825, P=0.006), average glycemia (OR=0.387, 95% CI=0.233– 0.643, P=0.010), coronary heart disease (OR=0.089, 95% CI=0.016– 0.497, P< 0.001), and the administration of hormone therapy (OR=6.807, 95% CI=1.128– 41.081, P=0.037) were independently associated with hypoglycemia. A nomogram was built. The receiver operating characteristics analysis showed that the area under the curve of the model was 0.872 (95% CI=0.0.803– 0.940) for the training set and 0.839 (95% CI=0.688– 0.991) in the validation set.Conclusion: A nomogram was successfully built to predict hypoglycemia in T2DM patients treated with an insulin pump during enteral nutrition, based on the time to reach the glycemic targets, average glycemia, coronary heart disease, and the administration of hormone therapy.Keywords: T2DM, hypoglycemia, enteral nutrition, insulin pump therapy, nomograms

Congyang Xue,1 Xiaopei Lu,2 Guangda Sun,1 Nan Wang,1 Gansheng He,1 Wenqiang Xu,1 Zhipeng Xi,1 Lin Xie1 1Department of Spine Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Traditional Chinese Medicine Surgery, Nanjing Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Lin Xie, Department of Spine Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100th. Shizi Street, Nanjing, Jiangsu Province, 210028, People’s Republic of China, Email xielin@njucm.edu.cnPurpose: To explore the validity of the thoracic spine Hounsfield Unit (HU) measured by chest computed tomography (CT) for opportunistic screening of diabetic osteoporosis. The current study attempted to establish a diagnostic threshold for thoracic spine HU in a type 2 diabetes mellitus (T2DM) population with osteoporosis.Patients and Methods: The current study retrospectively included 334 patients with T2DM. They underwent chest CT and Dual-energy X-ray (DXA) between August 2021 and January 2022 in our hospital. HU values were measured on the resulting chest CT images at thoracic spine 11 and 12 to construct regions of interest. All patients were grouped according to the lowest T-value of DXA examination: osteoporosis, osteopenia and normal bone density. HU values were compared with T-values in each group of patients, and receiver operating characteristics curves were plotted to calculate diagnostic thresholds as well as sensitivity and specificity.Results: There was a strong correlation between the HU values of chest CT and the T-values of DXA (p < 0.01). The sensitivity for osteoporosis was 88.7% for T11 attenuation≤ 98 HU and the specificity for osteoporosis was 87.5% for T12 attenuation ≤ 117HU; the specificity for normal BMD was 85.4% for T11 attenuation ≥ 147 HU and 82% for T12 attenuation ≥ 146 HU.Conclusion: Chest CT can be used to screen patients with T2DM for opportunistic osteoporosis and help determine if they need DXA screening. The current study suggests that when the HU threshold of T11 ≤ 98/T12 ≤ 117, patients may need further osteoporosis screening.Keywords: osteoporosis, T2DM, HU, thoracic vertebra, chest CT

Jiaqi He,1,&ast; Xiuhui Lu,2,&ast; Chenchen Yuan,1 Yali Zheng,2 Fangzhou Chen,2 Jing Luo,2 Kejiao Ma,2 Fan Yang,2 Peng Wang,2 Dongsheng Zhou,2 Li Wang,1 Zhe Yin2 1Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang, Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China, Email wangli851217@163.com Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China, Email jerry9yin@163.comPurpose: Pseudomonas aeruginosa is a common causative bacteria in nosocomial infections. This study aims to describe the structure and evolutionary characteristics of mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) from P. aeruginosa and to conduct bioinformatics and comparative genomic analysis to provide a deeper understanding of the genetic characteristics and diversity of MGEs in P. aeruginosa.Methods: Fifteen clinical isolates of P. aeruginosa from China were collected and sequenced in this study, and 15 novel MGEs were identified. Together with four MGEs from GenBank, a total of 19 MGEs were used to perform detailed modular structure dissection and sequence comparison. Then, the biological experiments were carried out to verify the biological characteristics of these isolates and MEGs.Results: The novel MGEs identified in this study displayed diversification in modular structures, which showed complex mosaic natures. The seven types of 19 MGEs included in this study were divided into three groups: i) novel MGEs (firstly identified in this study): four IncpSE5381-aadB plasmids and three Tn 7495-related integrative and mobilizable elements (IMEs); ii) newly defined MGEs (firstly designated in this study, but with previously determined sequences): four Tn 7665-related IMEs; iii) novel transposons with reference prototypes identified in this study: two Tn 6417-related integrative and conjugative elements (ICEs), two IS-based transposition units, two Tn 501-related unit transposons, two Tn 1403-related unit transposons. At least 36 ARGs involved in resistance to 11 different classes of antimicrobials and heavy metals were identified. Additionally, three novel blaOXA variants were identified. Antimicrobial susceptibility testing showed that these variants were resistant to some β-lactamase antibiotics and blaOXA-1204 was additionally resistant to cephalosporins.Conclusion: The continuous evolution of ARG-carrying MGEs during transmission, leading to the emergence of novel MGEs or ARGs, which facilitates the spread of antibiotic resistance in P. aeruginosa and enhances the diversity of transmission modes of bacterial resistance.Keywords: Pseudomonas aeruginosa, genome sequencing, mobile genetic elements, antimicrobial resistance, OXA

Jingxuan Wu,1,2,&ast; Wenzhu Zhang,1,2,&ast; Hong Zhang,1,2,&ast; Xingjia Lu,1,2,&ast; Biqing Luan,1,2,&ast; Qizhi Yang,1,2,&ast; Liang Chen,1,&ast; Wenlin Chen,3,&ast; Fei Ge1,&ast; 1Department of Breast Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China; 2No. 1 School of Clinical Medicine, Kunming Medical University, Kunming, 650000, People’s Republic of China; 3Third Department of Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Ge, Department of Breast Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China, Email ajqnadjd@hotmail.com Wenlin Chen, Third Department of Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China, Email chenwenlin1@hotmail.comAbstract: Breast cancer is one of the most common malignant tumors affecting women worldwide. Breast cancer is a complex disease characterized by abnormal growth of cells in the breast tissue. Metastasis, the spread of cancer cells from the primary tumor site to distant organs, is a major challenge in the management of breast cancer. Although metastasis to distant sites is a well-known feature of breast cancer, scalp involvement is relatively rare. The occurrence of scalp metastasis signifies an advanced stage of the disease. The 51-year-old female discovered a firm, painless mass in her right breast that had been there for two years. It had been pricking for a month, and the biopsy revealed that the mass was invasive carcinoma of the right breast. Imaging tests suggested that the tumor was malignant. Adjuvant endocrine therapy and postoperative adjuvant chemotherapy were administered following a modified radical resection for breast cancer. Eleven months later, radiation treatment and replace endocrine therapy was used. 32 months following surgery, a scalp tumor was discovered; a pathology biopsy verified the origin of the breast cancer; three months later, bone, brain, and visceral metastases were discovered. After that, she received oral capecitabine treatment and was admitted into the hospital for advanced rescue treatment. She is currently in the disease stability state, her disease is effectively managed, and no new metastatic lesions have been discovered.Keywords: breast cancer, scalp metastasis, chemotherapy, radiotherapy, endocrine therapy, case report

Xixia Chen,1 Sang Lin,2 Qiwen Jin,1 Lu Zhang,3 Wei Jiang,3 Xin Lu,3 Guochun Wang,1,3 Yongpeng Ge3 1Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Rheumatology, Key Myositis Laboratories, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yongpeng Ge, Department of Rheumatology, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13716106183, Email gyp2016@163.comObjective: To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM).Methods: A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared.Results: Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with Aspergillus fumigatus being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (P> 0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels (P all< 0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, P=0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with Pneumocystis jirovecii (P all< 0.05).Conclusion: IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors.Keywords: invasive pulmonary aspergillosis, opportunistic infection, anti-MDA5+ dermatomyositis, prevalence, risk factors, prognosis

XiaoLang Miao,1 Yanxia Han,1 Zhenyun Wu,1 Xiaoliang Jin,1 Mei’e Niu,1 Qian Zhao,1 Xiangmin Lu2 1Department of Respiratory Medicine, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2School of Nursing, Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Mei’e Niu, Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, 899th, Pinghai Road, Suzhou, 215006, People’s Republic of China, Tel +86 13812671786, Email meniu_123@163.comPurpose: To translate a disease-specific anxiety questionnaire on chronic obstructive pulmonary disease (COPD) and test its reliability and validity in China.Patients and Methods: The German version of the revised COPD Anxiety Questionnaire (CAF-R) was initially validated using step-by-step translation, back-translation, and cross-cultural adaptation. The reliability and validity of the Chinese version of the CAF-R (CAF-R-CN) were tested among 448 patients with COPD (mean age =71.42± 9.33 years, 17.2% female) from four medical institutions in Suzhou, Jiangsu Province, using convenience sampling, from April 2022 to June 2023.Results: The CAF-R-CN included six dimensions with a total of 25 items. The item-level content validity index was 0.860– 1.000; the scale-level content validity index was 0.920. The structural validity χ2/df was 2.326, the root mean square error of approximation was 0.077, the comparative fit index was 0.924, and the Tucker–Lewis index was 0.912. The six-dimensional internal consistency index Cronbach’s α coefficient was 0.696– 0.910, and the test–retest reliability was 0.949. An optimal cut-off score of 50.5 was selected with a sensitivity of 0.786 and specificity of 0.870.Conclusion: The CAF-R-CN had satisfactory reliability and validity and can be used to identify and assess anxiety in COPD patients with a Chinese cultural background.Keywords: fear, scale, specificity, chronic respiratory disease, Chinese translation, assessment

Shixuan Liu,&ast; Lin Liu,&ast; Xinyue Lu, Tingfeng Yao Department of Rehabilitation, School of Sport Health, Nanjing Sport Institute, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Liu, Department of Rehabilitation, School of Sport Health, Nanjing Sport Institute, Nanjing, People’s Republic of China, Email liulinst1989@126.comPurpose: Myofascial trigger points (MTrPs) are the main cause of myofascial pain syndrome (MPS), and patients with MPS also have symptoms of sympathetic abnormalities. Consequently, this study aimed to investigate the potential relationship between MTrPs and sympathetic nerves.Materials and Methods: Twenty-four seven-week-old male rats were randomly divided into four groups (six rats every group). Groups I and II were kept in normal condition (n=12), and groups III and IV underwent MTrPs modelling (n=12). After successful MTrPs modelling, differences in sympathetic outcomes between the MTrPs groups (III and IV) and non-MTrPs groups (I and II) were observed. Sympathetic blockade was then applied to groups III and I (n=12). Data were collected on peak inversion spontaneous potentials (PISPs) and the H-reflex-evoked electromyography during spontaneous discharge at the MTrPs before and after sympathetic blockade.Results: Systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate were significantly higher in the MTrPs group than in the non-MTrPs group (P< 0.05). Compared with group I, group III had the PISPs potential lower wave amplitude, shorter duration and amplitude-to-duration ratio, and lower H latency and latency difference H-M (P< 0.05). Compared with group IV, group III had the PISPs potential lower wave amplitude, duration, amplitude-to-duration ratio, M-wave latency, H maximum wave amplitude, and maximal wave amplitude ratio H/M (P< 0.05). The changes before and after sympathetic blockade in the MTrPs group were significant, and the amplitude, duration, and amplitude-to-duration ratio of the PISPs potentials were lower after the blockade (P< 0.05).Conclusion: MTrPs and sympathetic nerves interact with each other forming a specific relationship. MTrPs sensitize sympathetic nerves, and sympathetic nerve abnormalities affect local muscle myoelectric hyperactivity, leading to MTrPs. This finding is instructive for the clinical management of sympathetic disorders.Keywords: myofascial trigger point, sympathetic blockade, electromyography, H-reflex, myofascial pain syndrome

Yanxu Zhong,1,2 Huan Lu,3 Xiaodan Lu,4 Zhini He,4 Yuyan Jiang,1 Jie Chen,1 Tippawan Liabsuetrakul2 1Food Safety Monitoring and Evaluation Department, Guangxi Zhuang Autonomous Region Centre for Disease Control and Prevention, Nanning, Guangxi Region, 530000, People’s Republic of China; 2Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; 3Infectious Diseases Department, the Fourth People’s Hospital of Nanning, Nanning, Guangxi Region, 530000, People’s Republic of China; 4Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of ChinaCorrespondence: Tippawan Liabsuetrakul, Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand, Tel +66 74 451165, Fax +66 74 281166, Email tippawan.l@psu.ac.thBackground: Cooking oil and dietary foods are easily contaminated by aflatoxins (AFs) in Guangxi, China where low birth weight and preterm birth were prevalent. However, there are no data on AF exposure in pregnant women or their impact on newborn birth outcomes. This study aims to measure the levels and correlations of AFs in cooking oil, estimated dietary intake (EDI) of AFs in dietary foods, and serum AFB1 albumin adducts (AFB1-alb) with newborn birthweight and gestational age at birth.Methods: A prospective study was conducted among 126 pregnant women in Guangxi, China. All recruited women were interviewed for demographic data and behavior and obstetric information and then followed up until giving birth. AF measurements were obtained from cooking oil, dietary foods, maternal serum, and cord blood and the correlations of AF levels with newborn birthweight and gestational age at birth were tested using correlation analysis.Results: The median EDI of AFs in cooking oil was 2.61 ng/kg.bw/day and in dietary foods 2.95 ng/kg.bw/day. High positive correlations among EDI of aflatoxin B1 (AFB1) from cooking oil and dietary foods were found (r > 0.7). Low positive correlations of AFB1-alb in maternal serum and cord blood and both EDI of AFB1 in both cooking oil and dietary foods were shown (r &ap;0.3). Significant correlations between AF levels in both cooking oil and dietary foods with birth weight were found, but very low negative correlations (r = - 0.244 ~ − 0.285). AFB1 levels in foods, maternal serum and cord blood levels were high in pregnant women with newborn low birth weight and preterm birth.Conclusion: The EDIs of AFB1 from both cooking oil and dietary foods were significantly correlated with AFB1-alb in maternal serum and cord blood. Negative correlations of AFs from cooking oils and foods with newborn birth weight should be paid more attention.Keywords: aflatoxins, EDI, birthweight, gestational age at birth, AFB1 albumin adducts

Xin Liu,1,&ast; Fangchao Zhao,2,&ast; Xiaodan Wang,2,&ast; Zheng Ma,2 Hongjiang Yan,2 Xuchao Lu,2 Shujun Li,2 Haiyong Zhu,2,&ast; Shaolin Gao2 1Second Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaolin Gao, Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei, People’s Republic of China, Tel/Fax +86-311-66003588, Email gaoshaolinHB2H@163.comBackground: Long non-coding RNAs (lncRNAs) were demonstrated to be key to cancer progression and highly associated with the tumor immune microenvironment. Oxidative stress and immune may modulate the biological behaviors of tumors. Therefore, biomarkers that combined oxidative stress, immune, and lncRNA can be a promising candidate bioindicator in clinical therapy of cancers.Methods: Immune-related genes (IRGs) and oxidative stress-related genes (ORGs) were identified based on a detailed review of published literatures. The transcriptome data and clinical information of lung adenocarcinoma (LUAD) patients were obtained from TCGA database. Lasso and Cox regression analyses were conducted to develop a prognostic model. Additionally, the link between immune checkpoints, immune cells, and the prognostic model was investigated, and predict the sensitivity of immunotherapy.Results: 2498 IRGs and 809 ORGs were extracted from previous studies, and 190 immune- and oxidative stress-related genes (IOGs) were acquired by overlapping the above genes. 658 immune- and oxidative stress-related lncRNAs (IOLs) were screened by Pearson correlation analysis. A total of 25 prognosis-related IOLs were screened by univariate regression analysis. Finally, LASSO Cox regression analysis was adopted for determining a 12-IOLs prognostic risk signature. The signature performance was confirmed in the training cohort and the testing cohort, and cases were classified into low- and high-risk groups by the risk score calculated from the signature. Patients in the high-risk group had poor prognoses and immunosuppression, while the risk score was significantly associated with tumor-infiltrating immune cells, immune checkpoint expression, and immunotherapy responses. In vitro experiments further confirmed the expression of key signature gene.Conclusion: Our new IOLs-related prognostic signature can be reliable prognostic tools and therapeutic targets for LUAD patients.Keywords: immune, oxidative stress, lung adenocarcinoma, prognostic model

Yang Li,1,&ast; Yuling Sun,1,&ast; Ji Wu,1,&ast; Zhongya Gao,1 Youcai Qiu,1 Lin Han,2 Xuhua Lu1 1Department of Orthopaedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Orthopaedics, Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuhua Lu, Department of Orthopaedics, Shanghai Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86-21-81885793, Email xuhualu415@163.com Lin Han, Department of Orthopaedics, Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China, Email hanlin1018@163.comBackground and Aim: Cervical hyperextension injury is very frequent with anterior longitudinal ligament (ALL) injury, and the ligament damage has a remarkable effect on whether and what type of operation should be performed. This study aims to establish a new scoring system for the accurate diagnosis of ALL damage.Methods: The imaging data of the consecutive patients was measured and scored by four radiologists. Intraoperative exploration was performed by three surgeons. The crude and adjusted odds ratios (cOR and aOR) and receiver operating characteristic curve (ROC) were constructed to assess the diagnostic accuracy of the scoring system.Results: A total of 255 patients with cervical spine trauma were included in this study. There was no statistical difference in the relationship between demographics and ALL injuries (P > 0.05). Thickness of prevertebral soft tissue (aOR = 11.922, P = 0.004), intervertebral disk angle (aOR = 13.21, P = 0.002), avulsion fracture of the anterior edge of the vertebral body (aOR = 13.844, P = 0.029), ALL disrupted in T1-weighted sequence (aOR = 18.349, P < 0.001), and high signal area in T2-weighted sequence (aOR = 20.898, P = 0.002) had significantly higher diagnostic accuracy. The scoring system’s sensitivity and specificity were 94.0% and 88.1%, respectively, and the accuracy was 90.8%.Conclusion: The study established a new scoring system for ALL injuries based on the analysis of a series of clinical data and statistics. A total of five scoring items, a total score of 7 points, and an ALL injury may be diagnosed when the score is not less than 3 points. This scoring system enables an efficient and accurate diagnosis of all injuries.Keywords: cervical hyperextension injury, anterior longitudinal ligament injury, cervical spine trauma, scoring system

Jieliang Liu,1,&ast; Junguo Jin,1,&ast; Bingyan Yu,2 Shanghong Zhang,2 Xiaoqi Lu,1 Guoqiang Chen,2 Yi Yang,2 Haojian Dong1,3 1Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Nyingchi People’s Hospital, Nyingchi, Tibet, 860000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haojian Dong, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People’s Republic of China, Email donghaojian@gdph.org.cn Yi Yang, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China, Email 13825084233@163.comBackground: Discordance between the anatomy and physiology of the coronary has important implications for managing patients with stable coronary disease, but its significance in ST-elevation myocardial infarction has not been fully elucidated.Methods: The retrospective study involved patients diagnosed with ST-elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI), along with quantitative coronary angiography (QCA) and quantitative flow ratio (QFR) assessments. Patients were stratified into four groups regarding the severity of the culprit vessel, both visually and functionally: concordantly negative (QCA-diameter stenosis [DS] ≤ 50% and QFR > 0.80), mismatch (QCA-DS > 50% and QFR > 0.80), reverse mismatch (QCA-DS ≤ 50% and QFR ≤ 0.80), and concordantly positive (QCA-DS > 50% and QFR ≤ 0.80). Multivariable logistic regression analyses were conducted to identify the clinical factors linked to visual-functional mismatches. Kaplan‒Meier analysis was conducted to estimate the 18-month adverse cardiovascular events (MACE)-free survival between the four groups.Results: The study involved 310 patients, with 68 presenting visual-functional mismatch, and 51 exhibiting reverse mismatch. The mismatch was associated with higher angiography-derived microcirculatory resistance (AMR) (adjusted odds ratio [aOR]=1.016, 95% CI: 1.010– 1.022, P< 0.001). Reverse mismatch was associated with larger area stenosis (aOR=1.044, 95% CI: 1.004– 1.086, P=0.032), lower coronary flow velocity (aOR=0.690, 95% CI: 0.567– 0.970, P< 0.001) and lower AMR (aOR=0.947, 95% CI: 0.924– 0.970, P< 0.001). Additionally, the mismatch group showed the worst 18-month MACE-free survival among the four groups (Log rank test p = 0.013).Conclusion: AMR plays a significant role in the occurrence of visual-functional mismatches between QCA-DS and QFR, and the mismatch group showed the worst prognosis.Keywords: ST-elevation myocardial infarction, quantitative coronary angiography, quantitative flow ratio, angiography-derived microcirculatory resistance

Xuning Lu,1,2 Guoju Li,1 Qin Wu,1 Wei Ni,1 Silin Pan,1 Quansheng Xing1 1Heart Center, Qingdao Women and Children’s Hospital, Shandong University, Qingdao, Shandong Province, People’s Republic of China; 2Heart Center, Dalian Municipal Women and Children’s Medical Center (Group), Dalian, Liaoning Province, People’s Republic of ChinaCorrespondence: Quansheng Xing, Heart Center, Qingdao Women and Children’s Hospital, Shandong University, 217 Liaoyang West Road, Qingdao, Shandong Province, 266034, People’s Republic of China, Tel +86 136 0642 6893, Fax +86 532 8285 7650, Email xqs_qdfnet@126.comObjective: The outcomes of fetuses with isolated congenital heart disease (CHD) diagnosed prenatally have not been investigated in a population-based study in China. This population-based study aimed to evaluate the rate of voluntary termination of pregnancy after the prenatal diagnosis of isolated CHD in Qingdao, China.Methods: This was a population-based retrospective study in which data were collected from all pregnant women in Qingdao (eastern China) from August 2018 to July 2020; fetal data, maternal data and data on pregnancy outcomes were extracted from medical records regarding prenatal diagnosis of CHD. The inclusion criteria were as follows: pregnant women or their husbands who had a household registration in Qingdao and who underwent regular prenatal screening in Qingdao. The exclusion criterion was the failure to sign an informed consent form. Counseling for all parents of fetuses with CHD was provided by a multidisciplinary team of experienced pediatric cardiologists, obstetricians, geneticists, etc. According to the type and severity of CHD, the pregnancy termination rate was analyzed.Results: Among the 126,843 pregnant women, 1299 fetuses with a prenatal diagnosis of CHD were included in the study. Among the included fetuses, 1075 were diagnosed with isolated CHD, and the overall pregnancy termination rate was 22.8%. Termination rates varied according to the complexity of CHD (low complexity vs moderate complexity, P=0.000; low complexity vs high complexity, P=0.000; moderate complexity vs high complexity, P=0.000), with rates of 6.0% for low complexity, 54.2% for moderate complexity, and 99.1% for high complexity. The decision to terminate the pregnancy in cases of isolated CHD was unrelated to maternal age (P=0.091) but was related to gestational age (p=0.000).Conclusion: In Qingdao, 99.1% of parents whose fetuses were diagnosed with isolated high-complexity CHD chose to voluntarily terminate the pregnancy. The pregnancy termination rate increased with increasing complexity of prenatally diagnosed CHD.Plain Language Summary: In our study population, with the popularity of prenatal diagnosis, complex congenital heart disease will disappear, because 99.1% of parents whose fetuses were diagnosed with isolated high-complexity congenital heart disease chose voluntary pregnancy termination.Keywords: congenital heart defect, fetal echocardiography, prenatal diagnosis, termination of pregnancy

Boyi Yu,1– 4 Xuanyi Lu,5 Xianglong Feng,1– 4 Ting Zhao,1– 4 Jiaxin Li,1– 4 Yudie Lu,5 Fei Ye,1– 4 Xiongxiong Liu,1– 4 Xiaogang Zheng,1– 4 Zheyu Shen,5 Xiaodong Jin,1– 4 Weiqiang Chen,1– 4 Qiang Li1– 4 1Biomedical Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, People’s Republic of China; 2Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, People’s Republic of China; 3Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, Gansu Province, People’s Republic of China; 4College of Life Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 5School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Xiaodong Jin; Weiqiang Chen, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou, Gansu Province, 730000, People’s Republic of China, Tel +86-931-4969316, Fax +86-931-8272100, Email jinxd@impcas.ac.cn; chenwq7315@impcas.ac.cnIntroduction: Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo.Methods: 1.0 T small animal MR imaging (MRI) system was employed to trace GONs in vivo, while 225 kVp X-ray irradiation equipment was utilized for investigating the radiosensitization of GONs in 4T1 breast cancer cells in vitro and in vivo. Western blot, quantitative real-time PCR (RT-qPCR), immunohistochemistry, immunofluorescence, clonal survival assay, flow cytometry and reactive oxygen species assay were used to explore the biological mechanism of GON sensitization.Results: GONs exhibited exceptional utility as contrast agents for both in vivo and in vitro MRI imaging. Interestingly, a single dose of 8.0 Gy X-rays together with GONs failed to confer superior therapeutic effects in tumor-bearing mice, while only 3.0 Gy × 3 fractions X-rays combined with GONs exhibited effective tumor growth inhibition. Moreover, fractionated X-ray irradiation with GONs demonstrated a superior capacity to activate the cGAS-STING pathway.Discussion: Fractionated X-ray irradiation in the presence of GONs has demonstrated the most significant activation of the anti-tumor immune response by boosting the cGAS-STING pathway. Keywords: gadolinium oxide nanoparticles, magnetic resonance imaging, radiosensitization, cGAS-STING pathway, 4T1 breast cancer cells

Na Chen,1,2 Xiaojuan Wang,1,2 Yinyan Li,1,2 Ping Yang,1,2 Mingzhu Huang,1,2 Xiaoyang Lu1,2 1Department of Pharmaceutical, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiaoyang Lu; Mingzhu Huang, Email luxiaoyang@zju.edu.cn; hmzj2002@zju.edu.cnAbstract: Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral preparation approved for invasive mucormycosis. In recent years, population pharmacokinetic studies of ISA have been reported continuously. This paper aims to summarize the characteristics of population pharmacokinetic models of ISA in adults, and provide theoretical basis for individualized administration of ISA. We systematically searched PubMed, Embase, CNKI, Wanfang, VIP and other databases to collect population pharmacokinetic models published from the establishment of the database to March 2023. A total of 6 studies were included in this review, including healthy men and women, invasive fungal infections with malignant tumors or neutropenia, solid organ transplantation. The dose of ISA was 40– 400mg for single-dose. The multiple-dose of ISA was 200mg every 8 hours for the first 48 hours and then 200mg once daily. All studies used a two-compartment model, first-order elimination. For oral formulations, except for one study that used first-order absorption, the others used Weibull absorption. Body mass index (BMI) was the most common covariable, followed by total body weight, lean body mass, race, sex, population type (healthy volunteers/patients), and creatinine clearance. These studies included several covariates, and the clearance rate (CL) was similar among populations. In the future, external validation and population pharmacokinetic studies in special populations such as patients with severe liver disease and ECMO support are needed.Keywords: isavuconazonium sulfate, isavuconazole, population pharmacokinetics, covariates

Zequn Zhuang,1,&ast; Peng Zhou,1,&ast; Jing Wang,2 Xiaojing Lu,1 Yigang Chen1– 3 1Department of General Surgery, the Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 2Jiangnan University Medical Center, Wuxi, People’s Republic of China; 3Wuxi Clinical College, Nantong University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yigang Chen, Department of General Surgery, the Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China, Email 9862023226@jiangnan.edu.cnAbstract: Presently, obesity has emerged as a significant global public health concern due to its escalating prevalence and incidence rates. The gut microbiota, being a crucial environmental factor, has emerged as a key player in the etiology of obesity. Nevertheless, the intricate and specific interactions between obesity and gut microbiota, along with the underlying mechanisms, remain incompletely understood. This review comprehensively summarizes the gut microbiota characteristics in obesity, the mechanisms by which it induces obesity, and explores targeted therapies centered on gut microbiota restoration.Keywords: gut microbiota, obesity, dysbiosis, metabolism

Qiaona Jiang,1,&ast; Xiaofei Zhang,1,&ast; Xiaohui Lu,2 Yanzhe Li,3 Chenghao Lu,1 Jinghui Chi,1 Yanyan Ma,1 Xiaomei Shi,1 Lili Wang,1 Shen Li3 1Department of Psychiatry, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Psychiatry, Qingdao Mental Health Center, Qingdao, People’s Republic of China; 3Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Wang, Department of Psychiatry, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, No. 13, Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel +00-86-022-88188796, Email tjadyywll@163.com Shen Li, Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, No. 13, Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel +00-86-022-88188875, Email lishen@tmu.edu.cnObjective: Tardive dyskinesia (TD) is a severe rhythmic movement disorder caused by long-term antipsychotic medication in chronic patients with schizophrenia (SCZ). We aimed to investigate the association between polymorphisms in oxidative stress-related genes (GSTM1, SOD2, NOS1, and NOS3) and adenosine receptor gene (ADORA2A), as well as their interactions, with the occurrence and severity of TD, and cognitive impairments in a Chinese Han population of SCZ patients.Methods: Two hundred and sixteen SCZ patients were recruited and divided into TD group (n=157) and non-TD group (n=59). DNA extraction was performed by a high-salt method, followed by SNP genotyping using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The severity of TD, psychopathology and cognitive functioning were assessed using the Abnormal Involuntary Movement Scale (AIMS), the Positive and Negative Syndrome Scale (PANSS) and the Repeated Battery for Assessment of Neuropsychological Status (RBANS), respectively.Results: The combination of GSTM1-rs738491, NOS1-rs738409 and ADORA2A-rs229883 was identified as the best three-point model to predict TD occurrence (p=0.01). Additionally, GSTM-rs738491 CC or NOS3-rs1800779 AG genotypes may be protective factors for psychiatric symptoms in TD patients. TD patients carrying the NOS1-rs738409 AG or ADORA2A-rs229883 TT genotypes exhibited poorer cognitive performance.Conclusion: Our findings suggest that the interaction of oxidative stress-related genes and adenosine receptor gene may play a role in the susceptibility and severity of TD in Chinese Han SCZ patient. Furthermore, these genes may also affect the psychiatric symptoms and cognitive function of TD patients.Keywords: tardive dyskinesia, schizophrenia, oxidative stress, adenosine receptor, polymorphisms, cognitive impairments

Yuxia Zhang,1 Xiaobing Lu,1 Xianping Wang,1 Xueqing Wu,1 Xuan Jing,2 Xiangrong Cui1 1Reproductive Medicine Center, the Affiliated Children’s Hospital of Shanxi Medical University, Children’s Hospital of Shanxi, Shanxi Maternal and Child Health Hospital, Taiyuan, 030001, People’s Republic of China; 2Clinical Laboratory, Shanxi Provincial People’s Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, 030001, People’s Republic of ChinaCorrespondence: Xiangrong Cui; Xuan Jing, Email cuixiangrong094030@163.com; jx05070103@163.comBackground: Unilateral twin ectopic pregnancy is extremely rare in natural pregnancy, with an incidence rate of only 1 in 200,000– 2,500,000, represents a major health risk for reproductive-aged women, leading to even life-threatening complications. There is a lack of data on the prevalence of this rare disease after in-vitro fertilization-embryo transfer (IVF-ET) cycles.Case Report: We present a case of a 51-year-old woman with rare unilateral twin ectopic pregnancy after frozen embryo transfer treated with bilateral salpingectomy, followed by a review of the literature.Conclusion: Twin ectopic pregnancy is a very rare type of pregnancy that requires a high index of suspicion to diagnose and treat early to prevent complications and maternal death.Keywords: twin ectopic, pregnancy, unilateral, rare condition, assisted reproductive technology

Cuiying Mo,1,&ast; Xufen Huang,2,&ast; Xiaohua Lu,3 Yan Zhou,4 Yingyi Su,1 Huanhua Zhang1 1Department of Endocrinology, The First People’s Hospital of Foshan, Foshan, People’s Republic of China; 2Department of Pediatrics, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Endocrinology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 4Department of Interventional Radiology & Vascular Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohua Lu, Department of Endocrinology, The First Affiliated Hospital of Jinan University, No. 613, Huangpu Avenue West, Tianhe District, Guangzhou, 510630, People’s Republic of China, Tel +8618028089803, Email yhlu@163.com Yan Zhou, Department of Interventional Radiology & Vascular Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China, Email 992054881@qq.comPurpose: To investigate the knowledge, attitude, and practice (KAP) on insulin pump among non-endocrinology nurses in Southern China.Methods: This multicenter cross-sectional study enrolled non-endocrinology nurses in Southern China between November 2020 and December 2020. A structured questionnaire about insulin pumps was designed and used to collect data.Results: A total of 1118 nurses from 29 hospitals participated in the study. The majority of them were female (98.48%), and 513 worked in the department of internal medicine (45.89%), followed by surgery (235, 21.00%), pediatrics (147, 13.14%), gynecology (127, 11.35%), and oncology (96, 8.71%). None of the nurses answered all questions correctly in the knowledge section. The score of knowledge was 50.12 ± 3.42 (total score range, 0 to 85). The attitude score of nurses in the department of gynecology was 47.76 ± 5.11 (total score range, 10 to 50), followed by nurses in the department of internal medicine (47.43 ± 4.65), pediatrics (46.71 ± 4.96), surgery (46.77 ± 5.78) and oncology (46.25 ± 5.87). The practice score of nurses in the internal medicine department was 79.16 ± 9.03 (total score range, 17 to 85), followed by nurses in the department of gynecology (78.76 ± 10.76), surgery (78.14 ± 10.09), oncology (76.89 ± 12.70) and pediatrics (73.35 ± 19.04).Conclusion: There was limited knowledge regarding insulin pumps among nurses, although they had a positive attitude and attached importance to the management of insulin pumps. In clinical practice, their implementation of insulin pump management norms was acceptable.Keywords: nurse, insulin pumps, knowledge, attitude, practice

Xiaofang Lu, Shengsheng Zhang Center of Digestive, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Shengsheng Zhang, Center of Digestive, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China, Tel/Fax +86-10-87906634, Email zhangshengsheng@bjzhongyi.comPurpose: Diarrhea-predominant irritable bowel syndrome (D-IBS) is a frequent functional gastrointestinal disease that affects health and quality of life owing to its high incidence and recurrence rate. Tongxie-Yaofang (TXYF) is a traditional Chinese medicine prescribed for D-IBS. However, the therapeutic mechanism of TXYF has not been fully elucidated. This study aimed to investigate the effects of TXYF on visceral hypersensitivity in stress-induced D-IBS rats and the underlying mechanisms.Methods: Electromyographic (EMG) activity of the external oblique muscles and the abdominal withdrawal reflex (AWR) score captured by Barostat were used to quantify the effect of TXYF on visceral sensitivity. Transmission electron microscopy (TEM) was used to observe the ultrastructure of the enteric nervous system (ENS). For molecular detection, the colonic expression of enteric glial cell’s (EGC’s) activation markers, glial fibrillary acidic protein (GFAP) and calcium-binding protein S100β, NGF, TrkA, synaptic plasticity-related factors, synaptophysin (SYN) and postsynaptic density-95 (PSD-95), glutamate, glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR), and N-methyl-D-aspartate receptor (NMDAR) were detected by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time PCR. An ex vivo experiment was conducted to measure the EGC-induced NGF release.Results: TXYF decreased the EMG activity and AWR scores in rats with D-IBS. Under TEM, TXYF improved the dense and irregular nerve arrangement, narrowed the synaptic cleft, and decreased the number of synaptic vesicles in D-IBS rats. In addition, TXYF decreased the expression of GFAP, S100β, SYN, and PSD-95; down-regulated the levels of NGF, TrkA, and glutamate; and reduced the mRNA expression of AMPAR1, NMDAR1, and NMDAR2B. In an ex vivo experiment, TXYF decreased NGF release in D-IBS rats, and this trend disappeared under EGC inhibition.Conclusion: TXYF alleviated visceral hypersensitivity in D-IBS rats possibly by improving synaptic plasticity through inhibiting the activity of EGCs and the NGF/TrkA signaling pathway in the colon.Keywords: diarrhea-predominant irritable bowel syndrome, Tongxie-Yaofang, visceral hypersensitivity, synaptic plasticity, enteric glial cell

Dongsheng Hong,1,2 Duo Lv,1 Jiaying Wu,1 Xin Li,1 Qingwei Zhao,1 Xiaoyang Lu,1 Lu Li2 1Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Social Medicine of school of Public Health, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Xiaoyang Lu, Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Email luxiaoyang@zju.edu.cn Lu Li, Department of Social Medicine of school of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, People’s Republic of China, Email lilu@zju.edu.cnBackground: DIP is a new medical insurance payment system developed in China which was implemented in Guangzhou in January 2018, but few studies have focused on its intervention effect on the drug burden of elderly hypertensive patients.Methods: Nine medical institutions in Guangzhou, China, were selected, among which, daily full medical orders of elderly hypertensive inpatients from 2016 to 2020 were randomly collected. To assess the impact of DIP policy intervention on patient drug burden, we took the data after policy implementation in January 2018, as the intervention data, and applied a segmented regression model with interrupted time series to analyze the trend and changes in average daily drug costs per month and medication structure, stratified by age, sex, and inpatient department.Results: A total of 34,276 elderly hypertensive patients’ daily full medical orders were obtained. The immediate level change of drug costs after intervention was − 23.884 RMB/month (P = 0.652), and the trend change was statistically significant (− 15.642 RMB/month, P = 0.002). The relative cumulative effect at the end of the study was − 78.860% (95% CI: − 86.087% to − 69.076%), and the intervention effect was more significant in surgical and male patients. The analysis of drug structure changes showed that after the implementation of the DIP policy intervention, the proportion of anti-infective drugs, anti-tumor drugs, and biological products all showed a significant downward trend (P < 0.05), while nutritional drugs showed a significant upward trend (P = 0.011), but no immediate horizontal change in slope was observed.Conclusion: The typical practice in China showed that DIP policy intervention can improve the drug burden of elderly hypertensive hospitalized patients and has a stable long-term effect, and the intervention effect is not consistent across different clinical department and populations with different characteristics, and it would also cause changes in the medication structure.Keywords: diagnosis-intervention packet policy, daily drug cost, interrupted time series analysis, elderly hypertension, medication structure

Guanglan Li,1,2 Jing Yu,1,2 Simin Jiang,1,2 Kefei Wu,1,2 Yiping Xu,1,2 Xiaohui Lu,1,2 Yating Wang,1,2 Jianxiong Lin,1,2 Xiao Yang,1,2 Zhibin Li,3 Haiping Mao1,2 1Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; 2NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China; 3Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361005, ChinaCorrespondence: Haiping Mao, Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China, Email maohp@mail.sysu.edu.cnPurpose: The prognosis of patients receiving peritoneal dialysis (PD) is associated with inflammation. Systemic immune-inflammation index (SII) is one of inflammatory markers, and the role in predicting clinical outcomes in PD patients is unclear. We aimed to investigate the relationship between the SII and all-cause and cardiovascular-specific mortalities in patients undergoing PD.Patients and Methods: A total of 1419 PD patients from the First Affiliated Hospital of Sun Yat-sen University between January 1, 2007 and December 31, 2019 were retrospectively included at baseline, and the patients were followed up until November 31, 2021. SII was calculated as platelet count×neutrophil count/lymphocyte count. Kaplan–Meier curves and Cox proportional hazards regression models were used to determine the relationship between SII levels and all-cause and cardiovascular-specific mortalities.Results: During follow-up (median period was 42 months), 321 patients died (171 died of cardiovascular disease). With adjustment for the potential confounding factors, each 1-SD increase in the SII was associated with 20.2% increase in all-cause mortality (hazard ratio [HR]: 1.202, 95% confidence interval [CI]: 1.088– 1.327, P< 0.001) and 28.0% increase in cardiovascular-specific mortality (HR: 1.280, 95% CI: 1.126– 1.456, P< 0.001). High SII (vs low SII) was significantly associated with increased risks of all-cause mortality (HR: 1.391, 95% CI: 1.066– 1.815, P-value: 0.015) and cardiovascular-specific mortality (HR: 1.637, 95% CI: 1.185– 2.261, P-value: 0.003). Subgroups analyses showed similar results for those younger than 65-year-old only.Conclusion: Elevated SII level was independently associated with increased risks of all-cause and cardiovascular-specific mortalities in PD patients, especially for those younger than 65-year-old.Keywords: all-cause mortality, cardiovascular mortality, peritoneal dialysis, systemic immune-inflammation index

Xiaoxiao Lu,1 Bruno Emond,2 Laura Morrison,2 Frederic Kinkead,2 Patrick Lefebvre,2 Marie-Hélène Lafeuille,2 Wasiulla Khan,1 Linda H Wu,1 Zaina P Qureshi,1 Ryan Jacobs3 1Real World Value and Evidence, Oncology, Janssen Scientific Affairs, LLC, Horsham, PA, USA; 2Health Economics and Outcomes Research, Analysis Group, Inc, Montréal, Québec, Canada; 3Hematology and Medical Oncology, Atrium Health Levine Cancer Institute, Charlotte, NC, USACorrespondence: Bruno Emond, Analysis Group, Inc, 1190 avenue des Canadiens-de-Montréal, Tour Deloitte, Suite 1500, Montréal, Quebec, H3B 0G7, Canada, Tel +1-514-394-4455, Fax +1-514-394-4461, Email Bruno.Emond@analysisgroup.comPurpose: Increased dosing frequency adversely affects treatment adherence and outcomes in chronic diseases; however, such data related to treatment adherence is lacking in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). This study compared adherence between patients treated with ibrutinib (once-daily) versus acalabrutinib (twice-daily) as first-line (1L) therapy for CLL/SLL.Patients and Methods: Specialty pharmacy electronic medical records were used to identify adults with CLL/SLL initiating 1L ibrutinib or acalabrutinib between 01/01/2018 and 11/30/2020. Adherence was measured by the proportion of days covered (PDC) and medication possession ratio (MPR) and was compared between cohorts using odds ratios (ORs) obtained from logistic regression models adjusted for baseline characteristics.Results: Between 01/01/2018 and 11/30/2020, 1374 and 140 patients initiated ibrutinib and acalabrutinib, respectively. Based on PDC/MPR ≥ 80%, patients treated with once-daily ibrutinib were more likely to be adherent than those treated with twice-daily acalabrutinib (OR ranges: PDC: 1.04– 1.76; MPR: 1.03– 1.58). At 6 months, patients on ibrutinib had a 58– 76% higher likelihood of staying adherent compared to patients on acalabrutinib (PDC: 75.9% for ibrutinib vs 63.6% for acalabrutinib, OR: 1.76, P= 0.008; MPR: 76.8% vs 66.9%, OR: 1.58, P= 0.036) with a similar trend noted for the entire line of treatment (LOT) (PDC: 53.0% vs 41.4%, OR: 1.53, P= 0.021; MPR: 58.7% vs 47.1%, OR: 1.50, P= 0.027).Conclusion: In this real-world analysis, CLL/SLL patients initiating 1L once-daily ibrutinib had > 50% higher treatment adherence than those initiating twice-daily acalabrutinib during their LOT. Given the importance of sustained adherence for disease control in CLL/SLL, dosing frequency may be an important consideration for patients and physicians.Graphical Abstract: Keywords: CLL/SLL, Bruton’s tyrosine kinase inhibitor, treatment compliance, proportion of days covered, medication possession ratio

Shaoxing Zhang,1 Yuxin Zhang,1 Ruijie Liu,1 Shuying Yuan,2 Yanwen Chen,1 Wenjie Li,1 Xinrong Lu,3 Yongliang Tong,3 Linlin Hou,4 Li Chen,3 Guiqin Sun1 1School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Clinical Laboratory Department, Jiaxing Maternity and Child Health Care Hospital, Jiaxing, Zhejiang, People’s Republic of China; 3Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China; 4College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Guiqin Sun, School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 13868118601, Fax +86 571-86633307, Email sunguiqin2001@163.com Li Chen, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, 131 Dongan Road, Xuhui District, Shanghai, People’s Republic of China, Tel +86 15821138980, Fax +86 21-54237381, Email lichen_bk@fudan.edu.cnPurpose: Elizabethkingia meningoseptica (EM) is a multi-drug-resistant bacterium of global concern for its role in nosocomial infection and is generally resistant to aminoglycoside antibiotics. In the whole genome of an EM strain (FMS-007), an aminoglycoside-6-adenyl transferase gene (ant(6)FMS-007) was predicted. This study aimed to characterize the biochemical function of ANT(6)FMS-007 and analyze the relationship between genotype and phenotype of ant(6) in clinical EM isolates, so as to provide evidence for clinical precision drug use. This study could establish a method for the verification of known or unknown functionally resistant genes.Methods: A total of 42 EM clinical isolates were collected from clinical departments during 2015– 2023. The phenotype of aminoglycoside antibiotics was analyzed by broth microdilution (BMD) and Kirby-Bauer (K-B) methods. The whole-length ant(6) from EM clinical isolates was analyzed by polymerase chain reaction (PCR) and sequencing. The biochemical function of predictive ANT(6)FMS-007 from the FMS-007 whole genome was identified by 3D plate experiment and mass spectrometry analysis. Candidate active sites were predicted by multi-species sequence alignment and molecular docking, and other important sites were identified in the comparison of ant(6) genotypes and phenotypes of EM clinical isolates. Drug susceptibility test was used to verify the function of these sites.Results: The predictive ANT(6)FMS-007 protein could inactivate STR by modifying STR with ATP to form STR-AMP. Four active sites (Asp-38, Asp-42, Lys-95, and Lys-213) of ANT(6)FMS-007 were identified. Thirty-one EM clinical isolates (74%) carried the ant(6) gene. Eight EM clinical isolates containing the ant(6) gene had MIC values (

Xun Lu,1– 3 Yue Yuan,4 Ning Cai,1– 3 Dean Rao,1– 3 Min Chen,4 Xiaoping Chen,1– 3 Bixiang Zhang,1– 3 Huifang Liang,1– 3 Lei Zhang3,5 1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Clinical Medical Research Center of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Division of Gastroenterology, Department of Internal Medicine at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province (Preparatory), Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Medical University; Shanxi Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, People’s Republic of ChinaCorrespondence: Lei Zhang, Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province (Preparatory), Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Medical University; Shanxi Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, 030032, People’s Republic of China, Email zhangl@tjh.tjmu.edu.cn Huifang Liang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People’s Republic of China, Email lianghuifang1997@126.comPurpose: Tripartite motif containing 55 (TRIM55) is a member of the TRIM family and functions as an E3 ubiquitin ligase. It acts as a cancer promoter or suppressor in the malignant processes of multiple cancers. However, its proliferative function in hepatocellular carcinoma (HCC) has been poorly studied, and its underlying molecular mechanism remains unclear. In the present study, we investigated the role of TRIM55 in HCC and its mechanism of promoting HCC proliferation.Materials and Methods: Protein expression levels of TRIM55 were measured in paired HCC and normal tissue samples using immunohistochemical (IHC) staining. The correlation between TRIM55 and clinical features was evaluated by statistical analysis. At the same time, overexpression and knockdown experiments, cycloheximide (CHX) interference experiments, ubiquitination, co-immunoprecipitation and immunofluorescence staining experiments, as well as animal experiments were used to evaluate the potential mechanism that TRIM55 promotes proliferation of hepatocellular carcinoma in vitro and in vivo.Results: TRIM55 expression in HCC specimens was higher compared with the corresponding non-tumor tissues. The overall survival and disease-free survival time of patients with high TRIM55 expression were shorter than those with low expression of TRIM55. Functionally, TRIM55 promoted the proliferation of HCC cells and accelerated the growth of HCC xenografts. Mechanistically, TRIM55 interacted with thyroid receptor interacting protein 6 (TRIP6) and regulate its stability by influencing the ubiquitination process, thereby affecting the Wnt signaling pathway.Conclusion: Our results indicate that TRIM55 promotes HCC proliferation by activating Wnt signaling pathways by stabilizing TRIP6. Therefore, targeting TRIM55 may be an effective therapeutic strategy to inhibit HCC growth.Keywords: TRIM55, TRIP6, hepatocellular carcinoma, proliferation

Xujun Lu, Wenge Wang Department of Pediatrics, Air Force Medical Center, Air Force Medical University, PLA, Beijing, 100142 People’s Republic of ChinaCorrespondence: Wenge Wang, Department of Pediatrics, Air Force Medical Center, Air Force Medical University, PLA, Beijing, 100142, People’s Republic of China, Email 1264516006@qq.comAbstract: Erythrodermic psoriasis (EP) is a rare and severe type of psoriasis. Common systemic therapies for children with EP include treatment with glucocorticoids, cyclosporine, acitretin, and methotrexate. Although these drugs are effective, they may cause serious side effects to children. Secukinumab has recently demonstrated efficacy in treating plaque psoriasis, but its efficacy in EP children remains unknown. We report a case of a seven-year-old patient who transitioned from generalized pustular psoriasis (GPP) to EP after routine systemic drug treatment. The patient was then treated with secukinumab. The patient’s condition improved noticeably within 48 hours after the first injection. After the fifth injection, she almost completely cleared her skin lesions and achieved Psoriasis Area and Severity Index 90 (PASI 90) scores. During this period, she experienced only one respiratory infection. She completed all 11 doses of secukinumab by October 14, 2022, with no new rash (PASI 100) and no adverse drug reactions. Follow-up observation on March 15, 2023, showed no new rash (PASI 100) and no adverse reactions after medication withdrawal. This case suggests that it may also be effective in treating children with EP.Keywords: erythrodermic psoriasis, children, generalized pustular psoriasis, secukinumab, therapy

Youwei Wang,1,&ast; Yang Yang,2,&ast; Xiaowei Cao,3 Zhensheng Liu,4 Bing Chen,5 Qiu Du,1,&ast; Xiaoxia Lu6,&ast; 1Department of Neurosurgery, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China; 2Department of Clinical Laboratory, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China; 3Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China; 4Department of Interventional Radiology, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China; 5Department of neurosurgery, The Affiliated hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China; 6Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoxia Lu, Department of oncology, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China, Tel +86 514-82981199, Email luxiaoxia19870318@126.com Qiu Du, Department of neurosurgery, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China, Tel +86 514-82981199, Email 092102@yzu.edu.cnPurpose: Circulating tumor DNA (ctDNA) is more representative and accurate than biopsy and is also conducive to dynamic monitoring, facilitating accurate diagnosis and prognosis of glioma. Therefore, the present study aimed to establish and validate a novel amplified method for the detection of IDH1 R132H and BRAF V600E, which were associated with the genetic diagnosis of glioma.Patients and Methods: A dual-signal amplification method based on magnetic aggregation and catalytic hairpin assembly (CHA) was constructed for the simultaneous detection of ctDNAs. When target ctDNAs are present, the CHA reaction is initiated and leads to the assembly of Au-Ag nanoshuttles (Au-Ag NSs) onto magnetic beads (MBs). Further enrichment of MBs under an external magnetic field facilitated the dual-signal amplification of SERS.Results: The limit of detection (LOD) for IDH1 R132H and BRAF V600E in serum was as low as 6.01 aM and 5.48 aM. The reproducibility and selectivity of the proposed SERS analysis platform was satisfactory. Finally, the platform was applied to quantify IDH1 R132H and BRAF V600E in the serum of subcutaneous-tumor‑bearing nude mice, and the results obtained by SERS were consistent with those from quantitative real-time polymerase chain reaction (qRT-PCR).Conclusion: The present study showed that the dual-signal amplification method is a simple and ultrasensitive strategy for gliomas-associated ctDNAs detection, which is crucial for early diagnosis and dynamic monitoring.Keywords: circulating tumor DNA, Au-Ag nanoshuttles, magnetic beads, catalytic hairpin assembly, surface-enhanced Raman spectroscopy

Xingbing Lu,&ast; Huan Yang,&ast; Yanxi Wang, Yi Xie Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Xie, Email xieyi@scu.edu.cnIntroduction: To analyze the demographics and clinical features of 59 cases of Listeria monocytogenes, and determine the predisposing conditions for severe meningitis infections for reference.Materials and methods: A total of 59 cases isolated L. monocytogenes from 2009 to 2020 were enrolled. Electronic medical record data were used to determine the epidemiological and clinical characteristics of L. monocytogenes infection. Univariate and multifactorial logistic regression analyses were performed to predict risk factors for Listeria meningitis.Results: A total of 59 cases (median age of 52 years, 30 females and 29 males) were enrolled. Twenty-five patients (42.37%) developed a neuroinvasive infection. The indexes of interleukin-6 (IL-6), CD3+T, CD4+T, and CD8+T cells in the study group were higher than those in the control group (P< 0.05). In univariate analysis, the use of hormone drugs (odds ratio=3.21, P=0.000) and immunosuppressive agents (odds ratio=3.06, P=0.000) were relevant predictors of severe meningitis. 47 patients (79.66%) were treated with ampicillin (27.12%), carbapenems (18.64%), quinolones (11.86%), and β-lactamase inhibitors (11.86%) as the primary agents of antimicrobial therapy. Thirty-four patients (57.63%) showed clinical improvement, five patients (8.47%) had a poor prognosis, and two patients (3.39%) died.Conclusion: Infection with Listeria changed the levels of IL-6, CD3+T, CD4+T, and CD8+T cells, and these analyzing items were significantly different between L. monocytogenes and other bacterial infections. Long-term use of immunosuppressants and hormones may be risk factors for severe adult forms of Listeria-related infections. Sensitive antibiotics, such as penicillins and carbapenems, should be added or replaced in the early empiric treatment of L. monocytogenes.Keywords: Listeria monocytogenes, sepsis, meningitis, antimicrobials, clinical and laboratory characteristics

Xinfeng Lu,1,2,&ast; Haijun Guo,2,3,&ast; Xuyong Wei,2,3 Di Lu,2,3 Wenzhi Shu,2,4 Yisu Song,2,4 Nasha Qiu,1,2 Xiao Xu1– 4 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310000, People’s Republic of China; 2Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 4Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao Xu, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China, Email zjxu@zju.edu.cn Nasha Qiu, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, People’s Republic of China, Email qiunasha@163.comAbstract: With the improvement of the average life expectancy and increasing incidence of obesity, the burden of liver disease is increasing. Liver disease is a serious threat to human health. Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, liver transplantation still faces unavoidable difficulties. Mesenchymal stem cells (MSCs) can be used as an alternative therapy for liver disease, especially liver cirrhosis, liver failure, and liver transplantation complications. However, MSCs may have potential tumorigenic effects. Exosomes derived from MSCs (MSC-Exos), as the important intercellular communication mode of MSCs, contain various proteins, nucleic acids, and DNA. MSC-Exos can be used as a delivery system to treat liver diseases through immune regulation, apoptosis inhibition, regeneration promotion, drug delivery, and other ways. Good histocompatibility and material exchangeability make MSC-Exos a new treatment for liver diseases. This review summarizes the latest research on MSC-Exos as delivery vehicles in different liver diseases, including liver injury, liver failure, liver fibrosis, hepatocellular carcinoma (HCC), and ischemia and reperfusion injury. In addition, we discuss the advantages, disadvantages, and clinical application prospects of MSC-Exos-based delivery vectors in the treatment of liver diseases.Keywords: exosomes, mesenchymal stem cells, liver disease, nanocarriers

Yun Wang,1 Zhongfeng Huang,2 Huijuan Chen,3 Ye Yuan,2 Edward B McNeil,4 Xiaolong Lu,5 Aihua Zhang1 1Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Tuberculosis, Guiyang Public Health Clinical Center, Guiyang, Guizhou, People’s Republic of China; 3Department of Tuberculosis Prevention and Control, Guizhou Center for Disease Prevention and Control, Guiyang, Guizhou, People’s Republic of China; 4Department of Infectious Diseases, School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 5School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Aihua Zhang, Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China, Tel +86 851 88416187, Fax +86 851 88416187, Email 97349238@qq.comPurpose: We aimed to assess the household financial burden due to multidrug-resistant tuberculosis (MDR-TB) treatment and its predictors, examine its association with patient mobility, and test their impact on patient loss to follow-up (LTFU).Methods: A cross-sectional study combining follow-up data collection was conducted at the largest designated MDR-TB hospital in Guizhou. Data were collected from medical records and questionnaires. Household financial burden was measured by the incidence of 2 indicators: catastrophic total costs (CTC) and catastrophic health expenditure (CHE). Mobility was classified as mover or non-mover after the patient’s address was verified twice. A multivariate logistic regression model was used to identify associations between variables. Model I and Model II were separated by CHE and CTC.Results: Out of 180 households, the incidence of CHE and CTC was 51.7% and 80.6%, respectively. Families with low income and patients who were primary income earners were significantly associated with catastrophic costs. 42.8% of patients were movers. Patients from households with CHE (ORadj=2.2, 95% CI: 1.1– 4.1) or with CTC (ORadj=2.6, 95% CI: 1.1– 6.3) were more likely to move. Finding a job against financial difficulty (58.4%) was the top reason for movers. 20.0% of patients experienced LTFU. Patients from households with catastrophic payments (CHE: ORadj=4.1, 95% CI 1.6– 10.5 in Model I; CTC: ORadj=4.8, 95% CI 1.0– 22.9 in Model II), patients who were movers (ORadj=6.1, 95% CI 2.5– 14.8 in Model I; ORadj=7.4, 95% CI 3.0– 18.7 in Model II) and primary income earners (ORadj=2.5, 95% CI: 1.0– 5.9 in Model I; ORadj=2.7, 95% CI 1.1– 6.6 in Model II) had an increased risk of LTFU.Conclusion: There is a significant association between household financial burden due to MDR-TB treatment and patient mobility in Guizhou. They impact patients’ treatment adherence and cause LTFU. Being a primary breadwinner increases the risk for catastrophic household payments and LTFU.Keywords: household catastrophic costs, migration, loss to follow-up, Guizhou, MDR-TB

Tianxing Dai,1,2,&ast; Jing Li,3,&ast; Run-Bin Liang,1,&ast; Haoyuan Yu,2 Xu Lu,2 Guoying Wang1,2 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China; 2Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China; 3Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoying Wang, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, People’s Republic of China, Tel +86-20-83062703, Fax +86-20-83395651, Email wanggy3@126.comPurpose: Glycosylation has been demonstrated to be involved in tumorigenesis, progression, and immunoregulation, and to present specific profiles in different tumors. In this study, we aimed to explore the specific glycosylation-related gene (GRG) signature and its potential immunological roles and prognostic implications in hepatocellular carcinoma (HCC).Patients and Methods: The GRG expression profile was defined using the transcriptome data from The Cancer Genome Atlas and Gene Expression Omnibus. Univariate and the least absolute shrinkage and selection operator Cox analyses were performed to develop a GRG-based risk score model. A nomogram was subsequently established and validated. Its correlation with cancer immune microenvironment and drug susceptibility was further analyzed. The role and immunological correlation of ST6GALNAC4 were further experimentally validated at the tissue and cellular levels in HCC.Results: A total of 87 GRGs were identified to be significantly dysregulated in HCC, and a novel risk score model was constructed using eight critical GRGs, which demonstrated superior prognostic discrimination and predictive power in both training and validation groups. High risk scores in HCC patients were associated with lower OS. The model was also identified as an independent risk factor for HCC, and a novel nomogram was subsequently constructed and validated. Notably, significant correlations were found in risk scores with immune cells infiltration, tumor immunophenotyping, immune checkpoint genes’ expression, and sensitivities to multiple drugs. Furthermore, we validated in local HCC samples that ST6GALNAC4 was significantly upregulated and its knockdown significantly inhibited the tumor proliferation, migration and invasion ability and affected the expression of immune checkpoints on hepatoma cells.Conclusion: We identified a novel GRG-based model which showed significant prognostic and immunological correlations in HCC, and the oncogenic role of ST6GALNAC4 has been validated and may serve as a potential drug target.Keywords: hepatocellular carcinoma, glycosylation, ST6GALNAC4, gene signature, prognosis, immune checkpoint

Yaqi Wang,1,&ast; Shuang Yang,1,&ast; Suya Zhang,1,&ast; Xiaoyu Lu,2 Wenbing Ma1,2 1Department of Pharmacology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Biological Science and Bioengineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, 710049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenbing Ma, Department of Pharmacology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel/Fax +86-29-85323240, Email mawenbing@mail.xjtu.edu.cnBackground: The apolipoprotein E (ApoE) genetic variation may contribute to the development of Cerebral Infarction (CI). Serum lipid levels are known risk factors for CI, but the effect of the ApoE gene polymorphism on lipid metabolism remains unclear. This retrospective cohort study was designed to determine the role of ApoE genotypes in CI risk and the relationships between ApoE gene polymorphism and serum lipid levels among the population of northwest China.Patients and Methods: 517 CI patients and 517 non-CI controls were enrolled in the study. Polymerase chain reaction and hybridization were utilized to determine the ApoE gene polymorphisms.Results: The &epsiv;3/&epsiv;4 genotype and &epsiv;4 allele frequency were significantly higher in CI patients than in controls. When stratified by age and sex, statistically significant differences in the distribution and frequency of the &epsiv;3/&epsiv;4 genotype and &epsiv;4 allele were found between patients and controls. Compared to &epsiv;2 carriers, &epsiv;4 carriers had significantly lower ApoE levels and higher low-density lipoprotein cholesterol (LDL-C), ApoB and ApoB/ApoA-I levels in both two groups. Additionally, control participants with &epsiv;4 carriers had significantly higher levels of lipoprotein and total cholesterol (TC) levels than &epsiv;2 carriers, while CI patients with &epsiv;4 carriers had a significantly lower level of ApoA-I. After adjusting for other established risk factors, drinking, hypertension, lipoprotein, triglycerides (TG) and &epsiv;4 allele were significant independent risk factors for CI, which was shown to be associated with a nearly two-fold CI risk.Conclusion: This study demonstrated that &epsiv;4 allele is independent risk factors for CI among patients in Northwest China. ApoE polymorphism was associated with CI, which was partly mediated through blood lipids and may also be mediated through non-lipid pathways. These data might be of great clinical significance in individualized preventive and therapeutic strategies.Keywords: apolipoprotein E, cerebral infarction, gene polymorphism, Northwest China

Qichao Wu,&ast; Shuo Yuan,&ast; Lei Zang, Tianyi Wang, Xuanyu Lu, Aobo Wang, Fangda Si, Ning Fan, Peng Du Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zang, Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email zanglei@ccmu.edu.cnObjective: To investigate the correlation between postoperative imaging parameters and clinical outcomes in patients with foraminal stenosis (FS) and lateral recess stenosis (LRS) who underwent percutaneous endoscopic transforaminal decompression (PETD).Methods: The study included 104 eligible patients who underwent PETD, and the mean follow-up time was 2.4 years (range 2.2– 3.6 years). Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) scores, and the modified MacNab criteria were used to evaluate the clinical outcomes. The related parameters of the FS and LRS based on computed tomography and magnetic resonance imaging were measured before and after surgery. Correlations between the imaging parameters and clinical outcomes were investigated.Results: The proportion of excellent and good results following MacNab evaluation was 82.6%. In the treatment of LRS, VAS-back, VAS-leg, and ODI at the 2-year follow-up were negatively correlated with postoperative facet joint length based on computed tomography. In the treatment of FS, the above clinical results were positively correlated with the variation of foraminal width and nerve root-facet distance before and after surgery based on magnetic resonance imaging.Conclusion: PETD can achieve good clinical outcomes in the treatment of patients with LRS or FS. Postoperative facet joint length was negatively correlated with clinical outcomes of LRS patients. In FS patients, the variation in foraminal width and nerve root-facet distance before and after surgery were positively correlated with their clinical outcomes. These findings may help surgeons optimize treatment strategies and selection of surgical candidates.Keywords: lumbar spinal stenosis, clinical outcomes, percutaneous endoscopic transforaminal decompression, microsurgery, spinal endoscopy

Yubo Li,1– 4 Xiaoyan Ni,2– 4 Xinai Liu,1 Chun Yang,2– 4 Yi Wang,2,4 Xin Lu,2– 4 Changwu Zhou2– 4 1Department of MRI, Henan Provincial Hospital of Traditional Chinese Medicine (the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, People’s Republic of China; 2Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China; 4Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Xin Lu; Changwu Zhou, Shanghai Institute of Medical Imaging; Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 18702135336 ; +86 13912121145, Email luxcn@163.com; changwu83@163.comObjective: The prognostic value of the Liver Imaging Reporting and Data System (LI-RADS) 2018 in differentiating hepatocellular carcinoma (HCC) from other primary liver cancers (PLC) with cirrhosis is unclear. We aim to evaluate the value of LI-RADS 2018 with agent-enhanced MRI in the postoperative prognosis of PLC patients with cirrhosis.Methods: Between 2016 and 2021, 432 patients with cirrhosis and surgically proven single primary liver cancer were retrospectively evaluated. Two radiologists evaluated the preoperative MRI features independently and assigned each lesion a LI-RADS category. Overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated by using the Kaplan-Meier method, Log rank test, and Cox proportional hazards model.Results: The mean age of 432 patients (239 HCCs, 93 ICCs, and 100 cHCC-CCAs) was 57.27± 10.92 years. The LR-M category showed poorer OS and RFS than the LR-4 or LR-5 category did for all primary liver cancers (P < 0.001 for both), and so did HCCs with tumor size less than 30mm (P =0.003 and P =0.04, respectively). In the multivariable analysis, the LI-RADS category and tumor size > 30 mm had independent correlations with OS and RFS (all P < 0.05). Multivariable Cox analysis identified rim arterial phase hyperenhancement (APHE) as independent determinants of poor OS and RFS in primary liver cancers (all P < 0.05).Conclusion: The LI-RADS categories can predict the postsurgical prognosis of primary liver cancers independently.Keywords: hepatocellular carcinoma, magnetic resonance imaging, prognosis, liver cirrhosis

Jingmou Yu,1,2 Xin Xie,2 Liangliang Wang,3 Wenbo Liu,4 Huifeng Xu,4 Xiangmei Lu,4 Xiaofan Li,4 Jin Ren,2,4 Weidong Li2,5 1Huzhou Key Laboratory of Medical and Environmental Applications Technologies, School of Life Sciences, Huzhou University, Huzhou, 313000, People’s Republic of China; 2Jiangxi Provincial Key Laboratory of System Biomedicine, Jiujiang University, Jiujiang, 332000, People’s Republic of China; 3Affiliated Hospital of Jiujiang University, Jiujiang, 332000, People’s Republic of China; 4School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang, 332000, People’s Republic of China; 5Jiujiang NO.1 People’s Hospital & Water of Life Hospital, Jiujiang, 332000, People’s Republic of ChinaCorrespondence: Jin Ren; Weidong Li, Email yanjiushengrj@126.com; 346880908@qq.comIntroduction: Metastasis is a major challenge in breast cancer therapy. The successful chemotherapy of breast cancer largely depends on the ability to block the metastatic process. Herein, we designed a dual-targeting and stimuli-responsive drug delivery system for targeted drug delivery against breast cancer metastasis.Methods: AS1411 aptamer-modified chondroitin sulfate A-ss-deoxycholic acid (ACSSD) was synthesized, and the unmodified CSSD was used as the control. Chemotherapeutic drug doxorubicin (DOX)-containing ACSSD (D-ACSSD) micelles were prepared by a dialysis method. The ACSSD conjugate was confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In vitro cellular uptake and cytotoxicity of D-ACSSD micelles were studied by confocal laser scanning microscopy (CLSM) and MTT assay in breast tumor cells. The inhibition capability of D-ACSSD micelles in cell migration and invasion was carried out in 4T1 cells. In vivo antitumor activity of DOX-containing micelles was investigated in metastatic 4T1-bearing Balb/c mice.Results: D-ACSSD and DOX-loaded CSSD (D-CSSD) micelles exhibited high drug encapsulation content and reduction-responsive characteristics. D-ACSSD micelles were spherical in shape. Compared with D-CSSD, D-ACSSD showed higher cellular uptake and more potent killing activity in 4T1 and MDA-MB-231 cells. Additionally, D-ACSSD exhibited stronger inhibitory effects on the invasion and migration of highly metastatic 4T1 cells than unmodified D-CSSD. Among the DOX-containing formulations, D-ACSSD micelles presented the most effective inhibition of tumor growth and lung metastasis in orthotopic 4T1-bearing mice in vivo. It also revealed that ACSSD micelles did not exhibit obvious systemic toxicity.Conclusion: The smart D-ACSSD micelles could be a promising delivery system for the therapy of metastatic breast cancer.Graphical Abstract: Keywords: metastasis, dual-targeting, breast cancer therapy, reduction-sensitive micelles, drug delivery

Sailing Chen,1,&ast; Dongyan Tian,1,&ast; Xuewei Yang,1,&ast; Qingqing Yin,1 Li Li,1 Yijing Lin,1 Shuangshuang Liu,1 Huiqian Chen,1 Mingyao Zhang,1 Jiajin Lin,2 Xiaosheng Lu,1 Ping Duan,1 Yijie Chen1,3,4 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Blood Transfusion, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Duan; Yijie Chen, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, 109 West Xueyuan Road, Wenzhou, 325027, People’s Republic of China, Tel +86 577-88002815, Fax +86-577-86689895, Email dppddpp@wmu.edu.cn; chenyijie@wmu.edu.cnPurpose: Poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with the membrane of red blood cells (RBC-NP) have been applied in various biomedical fields. Despite the well-documented great biocompatibility, the potential toxicity of RBC-NP on maternal mice or their developing fetuses during pregnancy, or juvenile mice post-birth, remains unclear, which warrants a systematic evaluation.Methods: We fabricate an RBC-NP with approximately 50 nm in diameter (RBC-NP-50). Upon RBC-NP-50, pregnant mice are intravenously injected with this nanoparticle either at a single high dose of 400 mg/kg (1HD) or a low dose of 200 mg/kg for 3 times (3LD). Afterwards, the biocompatible assessments are performed at 48 h after the final injection or 21 d post-birth/partum both on maternal and fetal/juvenile mice.Results: RBC-NP-50 is capable of accumulating in the placenta and then passing through the blood-fetal barrier (BFB) into the fetus. On 48 h after RBC-NP-50 exposure, no significant dose-dependent toxicity is observed in maternal mice including blood biochemistry, inflammatory factors, progesterone level, histological analysis, etc, whereas fetal brains reveal remarkable differentially expressed genes analyzed by transcriptome sequencing. On 21 d post-birth, those genes’ expression in juvenile mice is alleviated, along with negligible differences in behavioral evaluations including surface righting test, negative geotaxis test, cliff avoidance test, and olfactory orientation test.Conclusion: These results indicate that RBC-NP is considered to be generally safe and biocompatible both for maternal mice and fetus during pregnancy, and for the subsequent juvenile mice post-birth, although future studies will need to examine higher dosage or longer-term measurements.Keywords: erythrocyte membrane, pregnancy, fetus, biocompatibility, RNA sequencing

Xiangyu Li,&ast; Shixin Zhang,&ast; Miaomiao Zhang, Ge Li, Bo Yang, Xinyue Lu, Lesheng Teng, Youxin Li, Fengying Sun School of Life Sciences, Jilin University, Changchun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengying Sun, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, Jilin, 130012, People’s Republic of China, Tel/Fax +86-431-85155320, Email sunfengying@jlu.edu.cnPurpose: Effective therapy for rheumatoid arthritis (RA) keeps a challenge due to the complex pathogenesis of RA. It is not enough to completely inhibit the process of RA with any single therapy method. The purpose of the research is to compensate for the insufficiency of monotherapy using multiple treatment regimens with different mechanisms.Material and Methods: In this study, we developed a new method to synthesize mesoporous silica nanoparticles hybridized with photosensitizer PCPDTBT (HNs). Branched polyethyleneimine-folic acid (PEI-FA) could be coated on the surface of HNs through electrostatic interactions. It simultaneously blocked the hypoxia-activated prodrug tirapazamine loaded into the mesopores and binded with Mcl-1 siRNA (siMcl-1) that interfered with the expression of the anti-apoptotic protein Mcl-1. Released from the co-delivery nanoparticles (PFHNs/TM) Tirapazamine and siMcl-1 upon exposure to acidic conditions of endosomes/lysosomes in activated macrophages. Under NIR irradiation, photothermal therapy and photodynamic therapy derived from PCPDTBT, hypoxia-activated chemotherapy derived from tirapazamine, and RNAi derived from siMcl-1 were used for the combined treatment for RA by killing activated macrophages. PEI-FA-coated PFHNs/TM exhibited activated macrophage-targeting characteristics, thereby enhancing the in vitro and in vivo NIR-induced combined treatment of RA.Results: The prepared PFHNs/TM have high blood compatibility (far below 5% of hemolysis) and ideal in vitro phototherapy effect while controlling the TPZ release and binding siMcl-1. We prove that PEI-FA-coated PFHNs/TM not only protect the bound siRNA but also are selectively uptaked by activated macrophages through FA receptor-ligand-mediated endocytosis, and effectively silence the target anti-apoptotic protein by siMcl-1 transfection. In vivo, PFHNs/TM have also been revealed to be selectively enriched at the inflammatory site of RA, exhibiting NIR-induced anti-RA efficacy.Conclusion: Overall, these FA-functionalized, pH-responsive PFHNs/TM represent a promising platform for the co-delivery of chemical drugs and nucleic acids for the treatment of RA cooperating with NIR-induced phototherapy.Graphical Abstract: Keywords: rheumatoid arthritis, nano-delivery system, phototherapy, hypoxia-activated chemotherapy, RNA interference

Yao Cheng,1 Xinfeng Lu,2 Feixia Zhao,3 Guoqiang Sun1 1Obstetrics Department, Maternal and Child Health Hospital of Hubei Province, Wuhan, People’s Republic of China; 2Medical Record Department, Maternal and Child Health Hospital of Hubei Province, Wuhan, People’s Republic of China; 3Medical College of Wuhan University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Guoqiang Sun, Obstetrics Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuluo Road No. 745, Hongshan District, Wuhan, 430070, People’s Republic of China, Tel +86-15972153596, Email sunguoqiang@hbfy.comPurpose: In order to gain more knowledge on the risk of gestational diabetes mellitus (GDM), and to provide evidence for clinical guidance on the optimum level of serum folic acid and vitamin B12, this study aimed to clarify the relationship between serum folic acid and vitamin B12 and the risk of GDM.Patients and Methods: This retrospective case−control study was conducted based on the clinical information system of the Maternal and Child Health Hospital of Hubei Province. Clinical data including maternal socio-demographical characteristics, serum folic acid, and vitamin B12 were collected. Logistic regression analyses and restricted cubic splines were performed to examine the impact of serum folic acid and vitamin B12 on the risk of GDM.Results: Significantly elevated risks of GDM were observed in groups with high serum folic acid concentration (OR = 1.84, 95% CI: 1.07− 3.16), and in low vitamin B12 concentration (OR = 2.14, 95% CI: 1.26− 3.65). After stratified by age, the increased risk of GDM was still noticed in a low level of vitamin B12 among mothers aged < 30 years (OR = 4.76, 95% CI: 1.45− 15.61). In mothers with pre−pregnancy BMI < 24, elevated risk of GDM was significantly associated with a high folic acid (OR = 2.09, 95% CI: 1.11− 3.93) or a low vitamin B12 concentration (OR = 2.24, 95% CI: 1.22− 4.14). Moreover, the risk of GDM was on the decline with the increased level of folic acid in the beginning, and it started to manifest an upward trend when the serum folic acid reached 19.02 ng/mL.Conclusion: This study demonstrated that serum folic acid excess or vitamin B12 deficiency could contribute to the increased risk of GDM, and revealed the potential side effect of serum folic acid overdose. As serum folic acid and vitamin B12 tests are widely applied in clinical practice, this finding could help clinicians to evaluate maternal risk from a new perspective.Keywords: gestational diabetes mellitus, folic acid, vitamin B12, age, BMI

Guixuan Wang,1,2 Danyang Zou,2 Xinying Lu,2 Xin Gu,2 Yuanyuan Cheng,2 Tengfei Qi,2 Yanchun Cheng,2 Junjun Yu,2 Meiping Ye,2 Pingyu Zhou1,2 1Shanghai Skin Disease Clinical College of Anhui Medical University, Shanghai Skin Disease Hospital, Shanghai, People’s Republic of China; 2STD Institute, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Pingyu Zhou, Shanghai Skin Disease Clinical College of Anhui Medical University, Shanghai Skin Disease Hospital, 1278 Bao’de Road, Shanghai, 200443, People’s Republic of China, Tel +86-18017336631, Email zpyls@yahoo.comBackground: The gut microbiota plays an important role in the development of neurological disorders such as Parkinson’s disease and Alzheimer’s disease. However, studies on the gut microbiota of patients with neurosyphilis (NS) were rarely reported.Methods: In this study, we collected fecal samples from 62 syphilis patients, including 39 with NS and 23 with non-NS. Among the NS patients, 18 were general paresis (GP). The white blood cell counts, protein concentrations, and Venereal Disease Research Laboratory test positive rates of cerebrospinal fluid from patients in NS or GP group were significantly higher than those from patients in non-NS group. 16S ribosomal RNA sequencing results revealed that the alpha and beta diversities of the gut microbiota were similar between NS and non-NS patients or GP and non-NS patients.Results: Linear discriminant analysis with effect size (LEfSe) analysis showed that some taxa, such as Coprobacter, were increased in both NS group and GP group, compared with non-NS group. Besides, the clade of Akkermansia was also overrepresented in GP Patients. Meanwhile, some taxa such as Clostridia_UCG-014 and SC-I-84 were underrepresented in NS patients. The abundances of class Bacilli and genus Alloprevotella were decreased in GP patients. Among them, the abundances of some taxa such as Coprobacter and Akkermansia have been reported to be associated with other neuropsychiatric disorders.Conclusion: Our findings suggest that the alternation of the gut microbiota in NS patients may contribute to the course of NS, which will deepen our understanding of NS.Keywords: syphilis, neurosyphilis, general paresis, gut microbiota, 16S ribosomal RNA sequencing

Iokfai Cheang,1,2,&ast; Xu Zhu,1,&ast; Xinyi Lu,1 Xin Yue,1 Yuan Tang,1 Rongrong Gao,1 Shengen Liao,1 Wenming Yao,1 Yanli Zhou,1 Haifeng Zhang,1,3 Kai-Hang Yiu,2,4 Xinli Li1 1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China; 2Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, 999077, People’s Republic of China; 3Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, People’s Republic of China; 4Division of Cardiology, Department of Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Li, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China, Tel +86 13611573111, Email xinli3267@njmu.edu.cn Kai-Hang Yiu, Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, 999077, People’s Republic of China, Tel +852 22553633, Fax +852 28186304, Email khkyiu@hku.hkBackground: Inflammation is one of the major pathways in the progression of hypertension (HTN), and the related inflammatory markers have demonstrated certain predictive values. The current study aimed to integrate these markers to construct an inflammatory prognostic scoring (IPS) system and to assess the prognostic values of IPS in patients with HTN.Methods: A total of 9846 adult participants with HTN from NHANES 1999– 2010 were enrolled and followed up. Demographic characteristics and the related laboratory results for the 12 inflammatory markers were collected. LASSO-COX regression, Kaplan–Meier, restricted cubic spline COX regression (RCS), receiver operator characteristic curve (ROC), and random survival forests (RSF) analysis were applied to explore the values of individual and IPS parameters.Results: At the census date of follow-up, 2387 (24.2%) were identified as all-cause deaths and 484 (4.9%) as cardiovascular deaths. All inflammatory markers showed certain prognostic values. Then, based on the LAASO analysis, LDH, ALP, LYM, NLR, MLR, SIRI, and RDW were included in the construction of the IPS system. The higher IPS had significantly worse long-term prognosis in Kaplan–Meier analysis (p log-rank < 0.001). Also, IPS remained an independent prognosticator compared to the lowest quartile (All p for trend < 0.001), and the ROC showed satisfactory values in the long-term prognosis of both cardiovascular and all-cause mortality. RCS further showed a linear association of IPS with cardiovascular mortality and all-cause mortality (p for non-linearity > 0.05). Two different algorithms of RSF, variable importance and minimal depth, to evaluate the prognostic importance showed that IPS was the best in survival prediction.Conclusion: Our results highlight that a higher IPS (system integrating the inflammatory markers) was associated with the increased risk of cardiovascular and all-cause mortality in patients with HTN, suggesting that IPS is a useful method for risk stratification in HTN.Keywords: hypertension, HTN, inflammation, inflammatory prognostic scoring system, prognosis, random survival forest

In southern China, the staple food rice (Oryza sativa) field is commonly rotated with brown mustard Brassica juncea. Root-knot nematodes (RKNs) are a major threat to rice production. From 2019 to 2021, B. juncea in 56 fields from 26 counties in Guangxi Province were observed with symptoms of leaf yellowing, stunting, and several hook-shaped galls on the roots. Females and egg masses of Meloidogyne sp. were found within the galls. The females, males, and second-stage juveniles (J2s) were collected, and identified with morphological and molecular characteristics and female perineal patterns. Brassica juncea was transplanted in pots and a pathogenicity test was conducted to confirm the species as Meloidogyne graminicola. In China, this is the first record of a natural infection of mustard with M. graminicola, and this finding has great importance for Chinese mustard production, since this nematode may damage mustard plants and become an additional problem for this crop.

Yanxia Han,1,&ast; Zhenyun Wu,1,&ast; Qian Zhao,1 Bo Jiang,2 Xiaolang Miao,2 Xiangmin Lu,2 Hongying Qian,1 Meie Niu1 1Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2School of Nursing, Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meie Niu, Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, 188th, Shizi Street, Suzhou, 215006, People’s Republic of China, Tel +86 13812671786, Email meniu_123@163.comPurpose: Anthropometric indices are simple indicators of patient nutritional status. However, the association between these indices and skeletal-muscle atrophy in patients with stable chronic obstructive pulmonary disease (COPD) has not been fully investigated. In this study, we evaluated this association.Patients and Methods: We recruited 123 outpatients with stable COPD from a general hospital in China from 2020 to 2021. We recorded their demographic characteristics, including age, sex, course of illness, dyspnea score, body mass index (BMI), force expiratory volume in 1 second (FEV1), forced vital capacity (FVC), smoking status, and severity grading. In addition, patients’ anthropometric indices, including fat-free mass index (FFMI) and appendicular skeletal-muscle mass index (ASMI), were measured using a body composition analyzer, and measurements were taken of the triceps skinfold (TSF), midarm circumference (MAC), and calf circumference (CC). We drew and analyzed a receiver operating characteristic (ROC) curve to identify the best intercept point value for the assessment of skeletal-muscle atrophy.Results: The TSF, MAC, CC, FFMI, and ASMI of COPD patients were 1.08 ± 0.44 cm, 26.39 ± 2.92 cm, 34.5 ± 3.06 cm, 17.49 ± 1.86 kg/m2, and 8.17 ± 0.90 kg/m2, respectively. These anthropometric indices had a significant positive correlation with skeletal-muscle mass (correlation values, 0.481– 0.820). CC was strongly correlated with both FFMI and ASMI. The ROC curve showed an area-under-the-curve (AUC) value of 0.873– 0.959.Conclusion: Anthropometric indices were correlated with skeletal-muscle mass. CC showed the best diagnostic value in COPD patients, suggesting its effectiveness as a simple method for assessing skeletal-muscle atrophy and identifying patients with a noticeable reduction in muscle mass. Such patients require early, multidisciplinary intervention.Keywords: fat-free mass, skeletal-muscle mass, chronic obstructive pulmonary disease, anthropometric index, muscle atrophy