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Direct laser acceleration of electrons during a high-energy, picosecond laser interaction with an underdense plasma has been demonstrated to be substantially enhanced by controlling the laser focusing geometry. Experiments using the OMEGA EP facility measured electrons accelerated to maximum energies exceeding 120 times the ponderomotive energy under certain laser focusing, pulse energy, and plasma density conditions. Two-dimensional particle-in-cell simulations show that the laser focusing conditions alter the laser field evolution, channel fields generation, and electron oscillation, all of which contribute to the final electron energies. The optimal laser focusing condition occurs when the transverse oscillation amplitude of the accelerated electron in the channel fields matches the laser beam width, resulting in efficient energy gain. Through this observation, a simple model was developed to calculate the optimal laser focal spot size in more general conditions and is validated by experimental data.

Qizhi Diao,1 Yongpei Long,2 Fangyu Yang,3 Cuihui Nong,1 Huamiao Tang,1 Xiangmin Zhou,1 Guoqiang Zhu,4 Qiang Ding5 1Hainan Branch, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Sanya, People’s Republic of China; 2Department of Laboratory Medicine, The People’s Hospital of Jianyang City, Sichuan, People’s Republic of China; 3Department of Clinical Laboratory Medicine, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Chong Qing King Med Center for Clinical Laboratory Co., Ltd, Chongqing, People’s Republic of China; 5The Sixth People’s Hospital of Chongqing, Chongqing, People’s Republic of ChinaCorrespondence: Guoqiang Zhu; Qiang Ding, Email Guoqiangzhu01@163.com; yung10167086@126.comBackground and Objective: Inadequate risk assessment and a lack of risk monitoring are common deficiencies in clinical laboratory, and are also the main causes of biosafety incidents. Therefore, we summarized the experience of implementing adequate risk assessment and maintaining risk monitoring, and established a procedure for continuously improving biosafety management.Methods: Learning from our laboratory’s experience in implementing risk assessment, risk response, and risk monitoring before and during the COVID-19 epidemic, we summarized the procedures for fully identifying risks, accurately evaluating risks, maintaining risk monitoring, establishing and regular reviewing safety indicators. On this basis, we established a system for continuously improving biosafety management through risk monitoring and reviewing safety indicator.Results: We identified a total of 30 unacceptable risks prior to the COVID-19 pandemic, and developed and implemented appropriate risk control measures. After risk control, residual risks were acceptable, and no biosafety incidents have occurred. During the COVID-19 pandemic, after multiple risk monitoring, we identified ten new risks, three ineffective risk control measures, and multiple control measures for excessive protection. Then, we timely adjusted risk control measures to avoid laboratory personnel infection and excessive protection. Meanwhile, We established eight safety indicators and identified two improvement opportunities through regular reviews.Conclusion: Adequate risk identification and accurate risk assessment are particularly important for effectively controlling biosafety risks. Biosafety management should be continuously improved to deal with ineffective and excessive protection caused by various changes in experimental activities. Continuous improvement of biosafety management can be achieved through risk monitoring, regular review of safety indicators, and management reviews. This study will help laboratory managers to fully and accurately assess risks, as well as update risks and their control measures through risk monitoring, and the continuous improvement procedure established in the study has certain reference value for laboratories to effectively respond to emerging infectious diseases and avoid excessive protection.Keywords: risk assessment, risk monitoring, management review, continuous improvement, biosafety management

Jie Chi, Heng Tang, Fang Wang, Yuxuan Wang, Zhifeng Chen Department of Pharmacy, Tongling Municipal Hospital, Tongling, Anhui, People’s Republic of ChinaCorrespondence: Zhifeng Chen, Department of Pharmacy, Tongling Municipal Hospital, Tongling, Anhui, People’s Republic of China, Tel +8613856231378, Email 47986687@qq.comPurpose: During the COVID-19 pandemic, multifaceted non-pharmaceutical interventions have not only reduced the transmission of SARS-CoV2 but also affected the prevalence of other respiratory pathogens. With the lifting of many restrictions, a surge in cases of pneumonia in children has been reported in many hospitals in China. The study assessed the changes in pathogen and symptoms of children with community-acquired pneumonia (CAP) before and after the adjustments of prevention and control measures of epidemic and provided recommendations for CAP in children.Patients and methods: Children diagnosed with CAP were enrolled in the study from 2022 to 2023. A cross-sectional retrospective study was conducted in a general hospital. We analyzed the data about demographic data, clinical symptoms, pathogens, and medical treatments. The Chi-square and Mann–Whitney U-test were used to assess the statistical significance of groups.Results: We studied 1103 children, 339 in 2022 and 764 in 2023. Compared with children in 2022, more children were diagnosed with CAP in 2023 and these children had a higher body temperature and levels of CRP and PCT, which indicated these children got severe inflammation. The positive rate of the pathogen was also higher in 2023, especially the detective rate of Mycoplasma pneumoniae. The number of children infected with more than two pathogens was higher in 2023, especially those co-infected with the virus and M. Pneumoniae. Concerning the medicine therapy, the usage of β-lactam antibiotics, Macrolide antibiotics, and antiviral drugs kept rapid growth.Conclusion: After the adjustment of epidemic prevention and control policies in 2023, more children got CAP with severe clinical symptoms, and more antibiotics and antiviral drugs were used. Further study is needed to explore the reasons for the increase in children with CAP and to explore the rationality of treatment.Keywords: community-acquired pneumonia, children, post-pandemic, pathogen

Hui Tang,1 Xiurong Xing,1 Yingna Han,1 Daiquan Gao,2 Piu Chan,3 Shengfang Zhang,4 Huixin Xue4 1Department of Emergency Internal Medicine, Xuanwu Hospital of China Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology, Xuanwu Hospital of China Capital Medical University, Beijing, People’s Republic of China; 3Department of Neurobiology, Xuanwu Hospital of China Capital Medical University, Beijing, People’s Republic of China; 4School of Medicine, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Hui Tang, Department of Emergency Internal Medicine, Xuanwu Hospital of China Capital Medical University, No. 45 of Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-1083198280, Email tanghui_202186@21cn.comObjective: To investigate the clinical characteristics, risk factors and outcomes of brain-heart syndrome (BHS) in patients with acute cerebrovascular diseases (ACVDs).Methods: A retrospective analysis was conducted of 100 patients who were admitted to our hospital with ACVDs between January 2023 and December 2023. The demographic, clinical, laboratory and imaging data of the patients were collected, and the presence and severity of BHS were evaluated. The neurological and cardiac outcomes of the patients at discharge and at 12-month follow-up were also assessed.Results: Out of the 100 patients, 38% had BHS, classified as mild (18%), moderate (12%) and severe (8%). The most prevalent ACVDs were cerebral infarction (58%), cerebral haemorrhage (32%) and subarachnoid haemorrhage (10%). Cardiac complications included arrhythmia (26%), myocardial ischaemia (18%) and heart failure (10%). Patients with BHS had higher results for blood pressure, heart rate, white blood cell count, C-reactive protein, IL-6, D-dimer and troponin, more severe neurological deficits, higher mortality and poorer functional outcomes. Multivariable analysis identified age, hypertension, diabetes, coronary artery disease, prior cardiovascular events, cerebral haemorrhage, brainstem infarction and hypothalamic or insular lesions as independent risk factors for BHS.Conclusion: Brain-heart syndrome is a frequent, severe complication in patients with ACVD, linked with multiple risk factors and poor prognosis. Prompt diagnosis and treatment are crucial for improving patient outcomes.Keywords: brain-heart syndrome, acute cerebrovascular diseases, cerebral infarction, cerebral haemorrhage

Batch experiments were performed to investigate the removal of Cu2+ , Cl- , and 2,4-dichlorophe- noxyacetic acid (2,4-D) from aqueous solution using chitosan-modified bentonite. When the chi-tosan was loaded on the bentonite, the inter-layer space of the montmorillonite increased and the adsorption efficiency enhanced, as chitosan contains large numbers of -NH2 and -OH functional groups that could serve as coordination sites to bind heavy metals. In this study, the bentonite that was prepared through three procedures: Na2CO3 treatment, thermal treatment and compound treatment, was modified by chitosan. Experimental results demonstrated that the average removal rates of Cu2+ , Cl-, and 2,4-D effectively were 94.87 %, 86.19 % and 91.06 %, respectively.

Hui Tang,1,* Xiaoxia Ding,2,3,* Youming Huang,2 Danfeng Xu,2 Yibin Fan1,2 1Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 2Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 3Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yibin Fan, Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233030, People’s Republic of China, Tel +86 18806538451, Email fanyibin@hmc.edu.cnIntroduction: Vitiligo is an acquired skin pigmentation disorder, the cause of which is poorly understood. Researchers in this field are dedicated to exploring novel treatments for achieving re-pigmentation.Methods: Mice were randomly selected and divided into control, model, and model+laser groups. Evaluate the impact of different levels of carbon dioxide laser irradiation on tyrosinase activity, melanocyte viability, and melanin content.Results: In this study, it was found that the cell viability and melanin content were significantly enhanced in human melanocytes after treatment with different energy densities of fractional carbon dioxide laser. In addition, laser-treated vitiligo mouse models showed mild pathological changes.Discussion: Therefore, we believe that fractional carbon dioxide laser may be a potential adjunctive modality for treating vitiligo.Keywords: vitiligo, fractional carbon dioxide laser, melanocytes, melanogenesis, vitiligo mouse models

Yongpeng Huang, Hui Tang, Xiangyan Meng, Dongxin Liu, Yanli Liu, Bo Chen, Zhiyun Zou State Key Laboratory of NBC Protection for Civilian, Beijing, People’s Republic of ChinaCorrespondence: Bo Chen; Zhiyun Zou, Email NBC_BoChen@163.com; zouzhiyun65@163.comIntroduction: Nanoparticles have the advantages of improving the solubility of poorly water-soluble drugs, facilitating the drug across biological barriers, and reducing macrophage phagocytosis in pulmonary drug delivery. However, nanoparticles have a small aerodynamic particle size, which makes it difficult to achieve optimal deposition when delivered directly to the lungs. Therefore, delivering nanoparticles to the lungs effectively has become a popular research topic.Methods: Nanoaggregate microparticles were used as a pulmonary drug delivery strategy for the improvement of the bioavailability of cyclosporine A (CsA). The nanoaggregate microparticles were prepared with polyvinyl pyrrolidone (PVP) as the excipient by combining the anti-solvent method and spray drying process. The physicochemical properties, aerodynamic properties, in vivo pharmacokinetics and inhalation toxicity of nanoaggregate microparticles were systematically evaluated.Results: The optimal nanoparticles exhibited mainly spherical shapes with the particle size and zeta potential of 180.52 nm and − 19.8 mV. The nanoaggregate microparticles exhibited irregular shapes with the particle sizes of less than 1.6 μm and drug loading (DL) values higher than 70%. Formulation NM-2 as the optimal nanoaggregate microparticles was suitable for pulmonary drug delivery and probably deposited in the bronchiole and alveolar region, with FPF and MMAD values of 89.62% and 1.74 μm. In addition, inhaled NM-2 had Cmax and AUC0-∞ values approximately 1.7-fold and 1.8-fold higher than oral cyclosporine soft capsules (Neoral®). The inhalation toxicity study suggested that pulmonary delivery of NM-2 did not result in lung function damage, inflammatory responses, or tissue lesions.Conclusion: The novel nanoaggregate microparticles for pulmonary drug delivery could effectively enhance the relative bioavailability of CsA and had great potential for clinical application. Keywords: pulmonary drug delivery, dry powder inhalers, nanoaggregate microparticles, aerosol performance, pharmacodynamic study, inhalation toxicity

Wei Xiao,1 Yanqiong Liu,2 Hua Tang,3 Qin Xie,2 Yanlan Luo,2 Tao Mei1 1Department of Neurosurgical Care Unit, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, People’s Republic of China; 2Cardiovascular Medicine Department, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, People’s Republic of China; 3Neurosurgery Department, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, People’s Republic of ChinaCorrespondence: Tao Mei, Email yilan1008@sina.comBackground: Intracerebral hemorrhage (ICH) affects up to 1% of chronic oral anticoagulation (OAC) users per year. This study explored the knowledge, attitude and practice (KAP) towards ICH prevention among patients taking OACs.Methods: This multicenter cross-sectional survey was conducted at 4 hospitals from February to May 2023, and a self-administered questionnaire was developed to assess KAP toward ICH prevention among patients taking OACs. Structural equation modeling was used to assess the relationship between KAP.Results: A total of 536 valid questionnaires (67.25%) were analyzed, from 43.8% participants on Warfarin, 40.5% on Rivaroxaban and 15.7% on Dabigatran. The average knowledge, attitudes and practice scores were 9.22, 24.11, and 28.01 out of 16, 35 and 40, respectively. Participants who received Rivaroxaban had lower knowledge scores but higher attitude and practice store compared to those who received Warfarin or Dabigatran (all p < 0.001). According to Structure Equation Modeling, attitude had direct positive effect on practice (β = 0.694 [0.603– 0.804], p = 0.012), while knowledge had direct negative effect on attitude (β = − 2.077 [− 2.507– 1.651], p = 0.013), as well as negative effect on practice, both direct (β = − 0.450[− 0.689– 2.03], p=0.012), and indirect (β = − 1.441 [− 1.928– 1.192], p = 0.004).Conclusion: Patients taking OACs showed insufficient knowledge, negative attitude and proactive practice regarding ICH; practice scores were affected by age, type of anticoagulation medication, and attitude rather than knowledge.Keywords: cerebral hemorrhage, anticoagulants, warfarin, dabigatran, rivaroxaban, knowledge, attitude, practice

Liang Ruan,1,2 Shuailei Xu,1,2 Yuhan Qin,2 Huihong Tang,1,2 Xudong Li,1,2 Gaoliang Yan,2 Dong Wang,2 Chengchun Tang,2 Yong Qiao2 1School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Chengchun Tang; Yong Qiao, Department of Cardiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, People’s Republic of China, Email tangchengchun@hotmail.com; jinyong8866@163.comPurpose: Red blood cell distribution width to albumin ratio (RAR) is a novel inflammatory biomarker that independently predicts adverse cardiovascular events and acute kidney injury. This study aimed to assess the predictive value of RAR for cardio-renal syndrome type I (CRS-I) risk in acute myocardial infarction (AMI) patients.Patients and methods: This study retrospectively enrolled 551 patients who were definitively diagnosed as AMI between October 2021 and October 2022 at the Affiliated Zhongda Hospital of Southeast University. Participants were divided into two and four groups based on the occurrence of CRS-I and the quartiles of RAR, respectively. Demographic data, laboratory findings, coronary angiography data, and drug utilization were compared among the groups. Logistic regression and receiver operating characteristic curve (ROC) analysis were performed to identify independent risk factors for CRS-I and evaluated the predictive value of RAR for CRS-I.Results: Among the cohort of 551 patients, 103 (18.7%) developed CRS-I. Patients with CRS-I exhibited significantly elevated RAR levels compared to those without the condition, and the incidence of CRS-I correlated with escalating RAR. Univariate and multivariate logistic regression analyses identified RAR as an independent risk factor for CRS-I. ROC curves analysis demonstrated that RAR alone predicted CRS-I with an area under the curve (AUC) of 0.683 (95% CI=0.642– 0.741), which was superior to the traditional inflammatory marker C-reactive protein (CRP). Adding the variable RAR to the model for predicting the risk of CRS-I further improved the predictive value of the model from 0.808 (95% CI=0.781– 0.834) to 0.825 (95% CI=0.799– 0.850).Conclusion: RAR is an independent risk factor for CRS-I, and high levels of RAR are associated with an increased incidence of CRS-I in patients with AMI. RAR emerges as a valuable and readily accessible inflammatory biomarker that may play a pivotal role in risk stratification in clinical practice.Keywords: acute myocardial infarction, cardio-renal syndrome type I, red blood cell distribution width to albumin ratio, inflammatory

Huaqiao Tang,1,&ast; Liying Dong,1,&ast; Xue Xia,1,&ast; Xinling Chen,1 Meichen Ren,1 Gang Shu,1 Hualin Fu,1 Juchun Lin,1 Ling Zhao,1 Li Zhang,2 Guoqiang Cheng,2 Xianxiang Wang,3 Wei Zhang1 1College of Veterinary, Sichuan Agricultural University, Chengdu, 611130, People’s Republic of China; 2Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610041, People’s Republic of China; 3College of Science, Sichuan Agricultural University, Chengdu, 611130, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Zhang, Email Zhangwei26510c@126.comIntroduction: Chrysin has a wide range of biological activities, but its poor bioavailability greatly limits its use. Here, we attempted to prepare casein (cas)-based nanoparticles to promote the biotransfer of chrysin, which demonstrated better bioavailability and anti-infection activity compared to free chrysin.Methods: Cas-based chrysin nanoparticles were prepared and characterized, and most of the preparation process was optimized. Then, the in vitro and in vivo release characteristics were studied, and anti-pulmonary infection activity was evaluated.Results: The constructed chrysin-cas nanoparticles exhibited nearly spherical morphology with particle size and ζ potential of 225.3 nm and − 33 mV, respectively. These nanoparticles showed high encapsulation efficiency and drug-loading capacity of 79.84% ± 1.81% and 11.56% ± 0.28%, respectively. In vitro release studies highlighted a significant improvement in the release profile of the chrysin-cas nanoparticles (CCPs). In vivo experiments revealed that the relative oral bioavailability of CCPs was approximately 2.01 times higher than that of the free chrysin suspension. Further investigations indicated that CCPs effectively attenuated pulmonary infections caused by Acinetobacter baumannii by mitigating oxidative stress and reducing pro-inflammatory cytokines levels, and the efficacy was better than that of the free chrysin suspension.Conclusion: The findings underscore the advantageous bioavailability of CCPs and their protective effects against pulmonary infections. Such advancements position CCPs as a promising pharmaceutical agent and candidate for future therapeutic drug innovations.Keywords: chrysin, nanoparticles, Acinetobacter baumannii, casein

Han Chen,1,2 Jianhao Li,1,2 Dan Cao,1,2 Hong Tang1,2 1Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China; 2Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Hong Tang, Email tanghong6198@wchscu.cnBackground: The progression of hepatocellular carcinoma (HCC) is related to macrophage polarization (MP). Our aim was to identify genes associated with MP in HCC patients and develop a prognostic model based on these genes.Results: We successfully developed a prognostic model consisting of six MP-related genes (SCN4A, EBF3, ADGRB2, HOXD9, CLEC1B, and MSC) to calculate the risk score for each patient. Patients were then classified into high- and low-risk groups based on their median risk score. The performance of the MP-related prognostic model was evaluated using Kaplan-Meier and ROC curves, which yielded favorable results. Additionally, the nomogram demonstrated good clinical effectiveness and displayed consistent survival predictions with actual observations. Gene Set Enrichment Analysis (GSEA) revealed enrichment of pathways related to KRAS signaling downregulation, the G2M checkpoint, and E2F targets in the high-risk group. Conversely, pathways associated with fatty acid metabolism, xenobiotic metabolism, bile acid metabolism, and adipogenesis were enriched in the low-risk group. The risk score positively correlated with the number of invasion-related genes. Immune checkpoint expression differed significantly between the two groups. Patients in the high-risk group exhibited increased sensitivity to mitomycin C, cisplatin, gemcitabine, rapamycin, and paclitaxel, while those in the low-risk group showed heightened sensitivity to doxorubicin. These findings suggest that the high-risk group may have more invasive HCC with greater susceptibility to specific drugs. IHC staining revealed higher expression levels of SCN4A in HCC tissues. Furthermore, experiments conducted on HepG2 cells demonstrated that supernatants from cells with reduced SCN4A expression promoted M2 macrophage polarization marker, CD163 in THP-1 cells. Reduced SCN4A expression induced HCC-related genes, while increased SCN4A expression reduced their expression in HepG2 cells.Conclusion: The MP-related prognostic model comprising six MPRGs can effectively predict HCC prognosis, infer invasiveness, and guide drug therapy. SCN4A is identified as a suppressor gene in HCC.Keywords: hepatocellular carcinoma, macrophage polarization-related genes, tumor microenvironment, prognosis, SCN4A

Huaming Xu,1 Chunhui Lin,2,3 Hao Tang,4 Rongrong Li,2,3 Zhaoxin Xia,2,3 Yi Zhu,3 Zhen Liu,2,3 Jilu Shen2,3 1The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, People’s Republic of China; 2The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Anhui Public Health Clinical Center, Hefei, People’s Republic of China; 4The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Jilu Shen, Tel +86 151 5515 2963, Email shenjilu@ahmu.edu.cn; 1464675852@qq.comIntroduction: As the last line of defense for clinical treatment, Carbapenem antibiotics are increasingly challenged by multi-drug resistant bacteria containing carbapenemases. The rapid spread of these multidrug-resistant bacteria is the greatest threat to severe global health problems.Methods: To solve the problem of rapid transmission of this multidrug-resistant bacteria, we have developed a rapid detection technology using CRPSPR-Cas12a gene editing based on multiple Recombinase polymerase amplification. This technical method can directly isolate the genes of carbapenemase-containing bacteria from samples, with a relatively short detection time of 30 minutes. The instrument used for the detection is relatively inexpensive. Only a water bath can complete the entire experiment of Recombinase polymerase amplification and trans cleavage. This reaction requires no lid during the entire process while reducing a large amount of aerosol pollution.Results: The detection sensitivity of this method is 1.5 CFU/mL, and the specificity is 100%.Discussion: This multi-scene detection method is suitable for screening populations in wild low-resource environments and large-scale indoor crowds. It can be widely used in hospital infection control and prevention and to provide theoretical insights for clinical diagnosis and treatment.

Zhongxiang Liu,1,&ast; Shuhua Han,2,&ast; Yuhong Luo,3,&ast; Zhangyan Zhao,4 Lingyu Ni,5 Linlin Chai,6 Haicheng Tang4 1Department of Pulmonary and Critical Care Medicine, the Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, the First Affiliated Hospital of Jiangsu Vocational College of Medicine, Yancheng, 224000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 3College of Life Science and Technology, Guangxi University, Nanning, 530004, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People’s Republic of China; 5China School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210046, People’s Republic of China; 6Department of Pathology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, The First Affiliated Hospital of Jiangsu Vocational College of Medicine, Yancheng, 224000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Chai, Department of Pathology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, People’s Republic of China, Email chailinlin0924@163.com Haicheng Tang, Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901, Caolang Road, Jinshan District, Shanghai, 201508, People’s Republic of China, Email thc822@163.comBackground: PERP, a member of the peripheral myelin protein gene family, is a new therapeutic target in cancer. The relationships between PERP and immune cell infiltration in lung cancer have not been studied. Therefore, the role of PERP in the tumour microenvironment (TME) of lung cancer needs to be further explored.Methods: In this study, we explored the association between PERP expression and clinical characteristics by analysing data from the TCGA database. Cox regression and Kaplan‒Meier methods were used to investigate the relationship between the expression of PERP and overall survival in patients with lung adenocarcinoma (LUAD). The relationship between PERP expression and the degree of infiltration of specific immune cell subsets in LUAD was evaluated using the TIMER database and GEPIA. We also performed GO enrichment analysis and KEGG enrichment analysis to reveal genes coexpressed with PERP using the Coexpedia database. Finally, we verified the expression and function of PERP in LUAD tissues and the A549 cell line by RT‒PCR, Western blot, CCK-8, IHC, and wound healing assays. The mouse model was used to study the in vivo effects of PERP.Results: According to our results, PERP expression was significantly higher in LUAD tissues and associated with the clinical characteristics of the disease. Survival was independently associated with PERP in LUAD patients. We further verified that PERP might regulate B-cell infiltration in LUAD to affect the prognosis of LUAD. To identify PERP-related signalling pathways in LUAD, we performed a genome-aggregation analysis (GSEA) between low and high PERP expression datasets. LUAD cells express higher levels of PERP than paracarcinoma cells, and PERP inhibits the proliferation and metastasis of A549 cells through apoptosis.Conclusion: PERP may affect the prognosis of lung adenocarcinoma by inhibiting apoptosis and is associated with immune cell infiltration.Keywords: PERP, lung adenocarcinoma, apoptosis, prognosis

Mi Qi, Yajuan Cheng, Ke Liu, Jingxing Cai, Tianyu Liu, Xiaoying Wu, Huili Tang, He Huang, Qinbiao Chen, Xiaoguang Zhou The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Mi Qi; Xiaoguang Zhou, Tel +86-13510794978 ; +86-18818780760, Email qimi@mail.sysu.edu.cn; gzzhouxg@163.comPurpose: Ischemic stroke is a high-incidence disease that threatens human well-being. The potent neuroprotective effects render reactive oxygen species (ROS) scavengers potential agents for acute ischemic stroke therapy. Challenges such as inadequate permeability across the blood-brain barrier (BBB), limited half-life, and adverse effects hinder the widespread utilization of small molecule and inorganic ROS scavengers. Thus, there is an urgent demand for efficacious neuroprotective agents targeting ischemic stroke. Our study discovered the superoxide dismutase (SOD)-mimetic activity of recombinant human heavy chain ferritin (rHF) nanoparticles expressed from Escherichia coli (E. coli). Subsequent investigations delved into the ROS-scavenging proficiency of rHF within neural cells, its therapeutic efficacy against ischemic stroke, and the elucidation of its neuroprotective mechanisms.Methods: rHF protein nanoparticles were expressed in E. coli and purified via size-exclusion chromatography. The superoxide anion (•O2−) scavenging SOD-mimetic activity of rHF nanoparticles was measured using a SOD detection kit. The ROS scavenging ability and protection effects against oxidative damage of rHF nanoparticles were studied in H2O2-induced PC12 cells. Therapeutic effects and neuroprotective mechanisms of rHF against ischemic stroke were investigated with transient middle cerebral artery occlusion (MCAO) reperfusion mice model.Results: rHF nanoparticles can eliminate excessive ROS in nerve cells and alleviate oxidative damage. The results of animal experiments demonstrated that rHF nanoparticles passed across BBB, reduced infarct areas in brain tissue, and lowered the neurological deficit score of ischemia-reperfusion model mice. Additionally, rHF nanoparticles mitigated neuronal apoptosis and ferroptosis, suppressed microglial activation, maintained oxygen homeostasis, and exhibited negligible organ toxicity.Conclusion: rHF nanoparticle could be developed as a new ROS scavenger for nerve cells and has therapeutic potential as a drug for cerebral ischemia-reperfusion injury. Keywords: human heavy chain ferritin, ROS scavenger, ischemic stroke, SOD-mimetic, neuroprotection

Hang Yin,1,&ast; Xia Zhang,2,&ast; Manjie Zhang,1 Hong Tang,1 Chunxia Zhang,1 Jia Li1 1Oncology Department, The First Affiliated Hospital of Dalian Medical University, Dalian, 116000, People’s Republic of China; 2Oncology Department, Dalian Fifth People’s Hospital, Dalian, 116000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia Li; Chunxia Zhang, The First Affiliated Hospital of Dalian Medical University, Dalian, 116000, People’s Republic of China, Email lijia_211@hotmail.com; qm1210@hotmail.comAbstract: Currently, lung cancer remains one of the deadliest cancers, with a very high mortality rate, accounting for approximately 18% of all cancer-related deaths. Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancer deaths. In particular, elderly patients generally have poor tolerance to chemotherapy or cannot tolerate chemotherapy. This case analysis focuses on an elderly patient with non-small cell lung cancer stage IV. The patient was an 86-year-old female with poor nutritional status and low body weight (27 kg) and could not tolerate platinum-based dual-drug first-line chemotherapy. This patient had tumour cells in alveolar lavage fluid without conditions examined for pd-l1 expression. However, the efficacy of previous first-line immunotherapy was positive, and the patient and his family members agreed to apply it, so there was no contraindication to apply anlotinib + pembrolizumab. Results were reviewed after two cycles, and CR was used to evaluate the efficacy. After four cycles, the efficacy was evaluated as complete remission (CR), the patient developed immune-related side effects, immunotherapy was suspended, and maintenance therapy with anlotinib was used. The most recent review was in 2023-6-9, and PET/CT indicated that the patient had sustained CR. In general, this case provides support for the successful possibility of a treatment strategy for elderly patients with poor physical fitness who cannot tolerate platinum-based doublet chemotherapy and who have driver gene-negative squamous cell lung cancer (PS> 0-1).Keywords: pembrolizumab, immune checkpoint inhibitors, non-small cell lung cancer, case report, anlotinib

Pan Lei,1,2 Wanying Shen,2 Huijuan Tang,2 Li You,2 Guoyi Chen,2 Yijun Tang,1 Wei Lu3 1Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China; 2Hubei Hongshan Laboratory, College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, People’s Republic of China; 3Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of ChinaCorrespondence: Yijun Tang, Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China, Email tyj_799@taihehospital.com Wei Lu, Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China, Email luwei0903@taihehospital.comPurpose: Adagrasib is a selective and reversible inhibitor of KRAS G12C, which significantly delays the progression of solid tumors. However, the absorption, distribution, metabolism, and excretion of adagrasib in vivo are unclear. This study explores the absorption and distribution of adagrasib in vivo.Methods: An ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method was established for the determination of adagrasib in the rat plasma and tissue. Sprague-Dawley rats were intravenous administrated (5 mg/kg) and oral administrated (30 mg/kg) with adagrasib, and the plasma concentration of adagrasib was determined. After single oral administration of adagrasib (30 mg/kg), the heart, liver, spleen, lung, kidney, intestine, and pancreas were excised. The organs were homogenized with saline solution, and the concentration of adagrasib in tissues was determined.Results: The intra- and inter-day accuracy were from 84.90% to 113.47%, and the precision was within ± 15%. The matrix effect and recovery were within ± 15%. The maximum plasma concentration (Cmax) of adagrasib was 677.45 ± 58.72 ng/mL. The elimination half-life time (t1/2) was 3.50 ± 0.21 h after oral administration and 2.08 ± 0.54 h after intravenous administration. The oral bioavailability was 50.72%. The highest concentrations of adagrasib in liver was 5047.80 ± 676.48 ng/g at 2 h after administration, and it was still detectable at 24 hours after administration.Conclusion: Adagrasib was slowly absorbed and cleared rapidly, and it was also widely distributed in vivo. This study provides a potential reference for adagrasib in clinical studies.Keywords: adagrasib, UPLC-MS/MS, pharmacokinetics, tissue distribution

Huili Tang, Xueqing Wu, Jiamei Feng, Qingqian Gao, Shijun Shao, Wenchao Qu, Lu Xie, Jiaye Sun Department of Breast, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Xueqing Wu, Department of Breast, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 185 Pu ‘an Road, Huangpu District, Shanghai, People’s Republic of China, Tel + 86-13817792022, Fax + 86-200021, Email snow_zi@hotmail.comPurpose: To determine the risk factors, clinical characteristics, and prognosis of adolescent non-puerperal mastitis patients.Patients and methods: A retrospective analysis was conducted on 10 cases of NPM in adolescents who underwent surgical treatment at Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from August 2021 to August 2023. We analyze the patient’s general information, clinical characteristics, related medical history, laboratory indicators, breast magnetic resonance imaging examination, postoperative pathology, prognosis, etc.Results: The clinical manifestations of NPM in adolescents mainly included redness, swelling and pain in the breasts, congenital nipple retraction, and extensive lesion range. Inflammatory markers and prolactin were elevated. Magnetic resonance imaging showed circular enhancement with abscess formation as the main type. All patients underwent surgical treatment with a fast recovery time after surgery. No recurrence was observed during follow-up and the postoperative breast appearance was satisfactory. Multivariate Logistic regression analysis indicated that congenital nipple retraction, elevated prolactin levels and trauma were independent risk factors for adolescents non-puerperal mastitis.Conclusion: Adolescent non-puerperal mastitis is a rare and unique type. Summarizing its main risk factors, clinical characteristics, and prognosis provides a basis for further research.Keywords: adolescents, non-puerperal mastitis, risk factors, clinical characteristics, prognosis

Yongting Wang,1 Yunxia Lan,2 Tiantian Jia,1 Mengdan Ma,1 Chunxu Liu,1 Hao Tang1 1Cardiac Surgery Intensive Care Unit, The Affiliated Chest Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Nursing, The Affiliated Chest Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Yunxia Lan, Department of Nursing, The Affiliated Chest Hospital of Zhengzhou University, No. 1 Weiwu Road, Zhengzhou, 450008, People’s Republic of China, Tel/Fax +86 371 6566 2695, Email lanyunxia@126.comPurpose: To construct a training program for ICU nurses to manage artificial airway gasbags to prevent ventilator-associated pneumonia (VAP) and explore its application in ICU nurses.Methods: From January to March 2023, 17 experts were consulted using the Delphi method to construct the draft of the training program. 52 ICU nurses were selected from a third-level, first-class hospital in Henan Province. They received training using the program for 4 weeks. The training effects were evaluated by examining the theoretical knowledge, testing operation skills, and the ICU medical staff gasbag management knowledge-attitude-behavior questionnaire before and one week after the training in April 2023.Results: The coefficients of expert authority for the two round inquiries were 0.816 and 0.837, respectively. The coordination coefficient of expert opinions ranges from 0.2 to 0.3. The final training program for ICU nurses on managing artificial airway gasbags to prevent VAP was constructed and included 4 primary indicators, 25 secondary indicators, 47 tertiary indicators. After the training by the program, the scores of the ICU nurses’ theoretical knowledge (before, 73.73 ± 8.54 VS after, 88.31 ± 6.29; t = 11.017, P< 0.001) and technical operation (before, 75.29 ± 7.48 VS after, 86.92 ± 4.72; t = 8.986, P< 0.001) were significantly increased. The total scores of the ICU nurses’ knowledge-attitude-behavior on gasbag management (before, 76.67 ± 10.68 VS after, 109.04 ± 9.87; t = 19.916, P< 0.001) were also significantly increased compared to the performance before training.Conclusion: The training program for ICU nurses on managing artificial airway gasbags to prevent VAP based on the Miller pyramid model is scientific and practical and can enhance the knowledge-attitude-behavior level of ICU nurses. This training program constructed in this study can be recommended and applied after further verification for the ICU nurses to manage the artificial airway gasbags in order to reducing the occurrence of the VAP in the clinical practice.Keywords: nursing management, evaluation and assessment, Miller pyramid model, airway management, intensive care

Han Chen,1,2 Dan Cao,1,2 Ning Han,1,2 Mingming Zhang,1,2 Wei Jiang,1,2 Xin Wang,1,2 Qinmin Zeng,1,2 Hong Tang1,2 1Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Hong Tang, Email tanghong6198@wchscu.cnIntroduction: Hepatocellular carcinoma (HCC) is a solid tumor with a rich blood supply, and anti-angiogenesis has important clinical significance. Hepatitis B Virus-Encoded MicroRNA 3 (HBV-miR-3) has recently been reported to be involved in HCC development. In this study, we aim to elucidate the role of HBV-miR-3 in promoting HBV-related HCC angiogenesis through Factor Inhibiting Hypoxia-inducible factor 1 (FIH-1).Results: By analyzing HBV-related HCC tissue samples, we found that high expression of HBV-miR-3 was associated with poor overall survival and HBV-miR-3 expression was significantly correlated with VEGFR2 and FIH-1 expressions. In vitro, HBV-miR-3 agomir repressed FIH-1 expression and promoted HIF-1α/VEGFA signaling activation in HepG2 cells, resulting in increased HUVEC lumen formation in HepG2-HUVEC co-culture model. Conversely, HBV-miR-3 antagomir induced FIH-1 expression and inhibited HIF-1α/VEGFA signaling activation in HepG2.2.15 cells, resulting in decreased HUVEC lumen formation in HepG2.2.15-HUVEC co-culture model. The effect of HBV-miR-3 to HCC angiogenesis was also confirmed by a mouse tumor bearing model. We also confirmed that HBV-miR-3 repressed FIH-1 expression via targeting the 3’-UTR of FIH-1 mRNA by luciferase activity assay.Conclusion: HBV-miR-3 was related to HCC patients’ overall survival and it promoted angiogenesis by repressing FIH-1 expression. HBV-miR-3 may be a new marker for predicting prognosis and a novel target for anti-angiogenic treatment of HBV-related HCC. Keywords: HBV-miR-3, FIH-1, HBV-related HCC, angiogenesis

Xinni Pan,1 Yi Lu,2 Shanshan Fan,1 Hao Tang,2 Haisong Tan,3 Cheng Cao,2 Yingsheng Cheng,1 Yanlei Liu2 1Department of Radiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Instrument Science and Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Urology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Yingsheng Cheng, Department of Radiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200235, People’s Republic of China, Tel +86-021-38297858, Email chengyingsheng@hotmail.com Yanlei Liu, Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People’s Republic of China, Tel +86-18721788078, Email liuyanlei@sjtu.edu.cnBackground: Radiotherapy is one of the main clinical methods for the treatment of malignant tumors at present. However, its application is limited by the radiation resistance of some tumor cells and the irradiation damage to the surrounding normal tissues, and the limitation of radiotherapy dose also affects the therapeutic effect. Therefore, developing diagnostic and therapeutic agents with imaging and radiosensitizing functions is urgently needed to improve the accuracy and efficacy of radiotherapy.Materials and Strategy: Herein, we synthesized multifunctional nanotheranostic FRNPs nanoparticles based on gold nanocages (GNCs) and MnO2 for magnetic resonance (MR)/photoacoustic (PA) imaging and combined photothermal, radiosensitive and chemical therapy. A programmed therapy strategy based on FRNPs is proposed. First, photothermal therapy is applied to ablate large tumors and increase the sensitivity of the tumor tissue to radiotherapy, then X-ray radiation is performed to further reduce the tumor size, and finally chemotherapeutic agents are used to eliminate smaller residual tumors and distant metastases.Results: As revealed by fluorescence, MR and PA imaging, FRNPs achieved efficient aggregation and retention at tumor sites of mice after intravenous injection. In vivo studies have shown that the programmed treatment of FRNPs-injected nude mice which were exposed to X-ray after 808 laser irradiation achieved the greatest inhibition of tumor growth compared with other treatment groups. Moreover, no obvious systemic toxicity was observed in all groups of mice, indicating the good biocompatibility of FRNPs and the safety of the treatment scheme.Conclusion: To sum up, our work not only showed a new radiosensitizer, but also provided a promising theranostic strategy for cancer treatment.Keywords: gold nanoparticles, MnO2, radiosensitizing, multimodal imaging, cancer therapy

Moving toward exascale computing, the size of data stored and accessed by applications is ever increasing. However, traditional disk-based storage has not seen improvements that keep up with the explosion of data volume or the speed of processors. Multiple levels of non-volatile storage devices are being added to handle bursty I/O, however, moving data across the storage hierarchy can take longer than the data generation or analysis. Asynchronous I/O can reduce the impact of I/O latency as it allows applications to schedule I/O early and to check their status later. I/O is thus overlapped with application communication or computation or both, effectively hiding some or all of the I/O latency. POSIX and MPI-I/O provide asynchronous read and write operations, but lack the support for non-data operations such as file open and close. Users also have to manually manage data dependencies and use low-level byte offsets, which requires significant effort and expertise to adopt. In this article, we present an asynchronous I/O framework that supports all types of I/O operations, manages data dependencies transparently and automatically, provides implicit and explicit modes for application flexibility, and error information retrieval. We implemented these techniques in HDF5. Our evaluation of several benchmarks and application workloads demonstrates it effectiveness on hiding the I/O cost from the application.

The Cori system at NERSC has two computepartitions with different CPU architectures: a 2,004 nodeHaswell partition and a 9,688 node KNL partition, whichranked as the 5th most powerful and fastest supercomputeron the November 2016 Top 500 list. The compute partitionsshare a common storage configuration, and understanding theIO performance gap between them is important, impactingnot only to NERSC/LBNL users and other national labs, butalso to the relevant hardware vendors and software developers.In this paper, we have analyzed performance of single coreand single node IO comprehensively on the Haswell and KNLpartitions, and have discovered the major bottlenecks, whichinclude CPU frequencies and memory copy performance. Wehave also extended our performance tests to multi-node IOand revealed the IO cost difference caused by network latency,buffer size, and communication cost. Overall, we have developeda strong understanding of the IO gap between Haswell and KNLnodes and the lessons learned from this exploration will guideus in designing optimal IO solutions in many-core era.

Popular parallel I/O libraries, such as HDF5, provide tuning parameters to obtain superior performance. However, the selection of effective parameters on production systems is complex due to the interdependence of I/O software and file system layers. Hence, application developers typically use the default parameters and often experience poor I/O performance. This work conducts a benchmarking-based analysis on the HDF5 behaviors with a wide variety of I/O patterns to extract performance characteristics under the production workload. To make the analysis well controlled, we exercise I/O benchmarks on POSIX-IO, MPI-IO, and HDF5 using the same I/O patterns and in the same jobs. To address high performance variability in production environments, we repeat the benchmarks across I/O patterns, storage devices, and time intervals. Based on the results, we identified consistent HDF5 behaviors that appropriate configurations and operations on dataset layout and file-metadata placement can improve performance significantly. We apply our findings and evaluate the tuned I/O library on two supercomputers: Summit and Cori. The results show that our tuned parameters can achieve more than 10× I/O performance speedup than that with default parameters on both systems, suggesting the effectiveness, stability, and generality of our solution.