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Xiao Shen,1,* Linglin He,2,* Wanru Cai3 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wanru Cai, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, People’s Republic of China, Email caiwanru@aliyun.comAbstract: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a spectrum of common critical respiratory conditions characterized by damage and death of alveolar epithelial cells (AECs). Pyroptosis is a form of programmed cell death with inflammatory characteristics, and activation of pyroptosis markers has been observed in AECs of patients with ALI/ARDS. Lipopolysaccharides (LPS) possess strong pro-inflammatory effects and are a crucial pathological factor leading to ALI in patients and animals. In LPS-induced ALI models, AECs undergo pyroptosis. However, physiologically and pathologically relevant concentrations of LPS lead to minor effects on AEC cell viability and minimal induction of cytokine release in vitro and do not induce classical pyroptosis. Nevertheless, LPS can enter the cytoplasm directly and induce non-classical pyroptosis in AECs when assisted by extracellular vesicles from bacteria, HMGB1, and pathogens. In this review, we have explored the effects of LPS on AECs concerning inflammation, cell viability, and pyroptosis, analyzing key factors that influence LPS actions. Notably, we highlight the intricate response of AECs to LPS within the framework of ALI and ARDS, emphasizing the variable induction of pyroptosis. Despite the minimal effects of LPS on AEC viability and cytokine release in vitro, LPS can induce non-classical pyroptosis under specific conditions, presenting potential pathways for therapeutic intervention. Collectively, understanding these mechanisms is crucial for the development of targeted treatments that mitigate the inflammatory responses in ALI/ARDS, thereby enhancing patient outcomes in these severe respiratory conditions.Keywords: alveolar cell death, inflammatory response, programmed cell death, pathological impact, cytokine activation

Yongsheng Zhao,* Xianlei Xin,* Bin Wang, Lei He, Qinghua Zhao, Weizheng Ren Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weizheng Ren; Qinghua Zhao, Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of China, Email rwz301@163.com; zhaoqinghuabj@163.comPurpose: In this paper, we observed the use of contezolid in patients with complex intra-abdominal infections in the intensive care unit of the Hepatobiliary Surgery department at the Chinese PLA General Hospital.Patients and Methods: The study collected data on complex intra-abdominal infections patients who received the antibiotic contezolid between January 2022 and April 2023.Results: Contezolid was administered to 12 patients, including 8 with severe acute pancreatitis, 3 with intra-abdominal infections following abdominal surgery, and 1 with complicated intra-abdominal infection after trauma. Gram-positive bacteria, such as Enterococcus faecium, Enterococcus casseliflavus, Staphylococcus capitis, and Staphylococcus haemo-lytica, were detected in 11 patients. All patients who received contezolid had previously been treated with other anti-Gram-positive agents, including linezolid for 9 patients, teicoplanin for 6 patients, and vancomycin for 3 patients. The treatment with contezolid began 20.0 (15.0, 34.5) days after admission and lasted for 8.0 (6.0, 10.0) days. At the end of the treatment, the patients’ body temperature showed a significant decrease. After concomitant therapy, IL-6 levels decreased, and platelet count increased.Conclusion: Contezolid has shown potential in treating complex intra-abdominal infections caused by Gram-positive bacteria by reducing fever and inflammatory response.Keywords: intra-abdominal infection, contezolid, multiple drug-resistant bacteria, gram-positive bacteria

Guanxiong Liu,&ast; Duo Zhu,&ast; Quansheng He,&ast; Churen Zhou, Li He, Zhengran Li, Zaibo Jiang, Mingsheng Huang, Boyang Chang, Chun Wu Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Boyang Chang; Chun Wu, Email changby3@mail.sysu.edu.cn; wuch26@mail.sysu.edu.cnPurpose: This study aimed to assess the effectiveness and safety of combining hepatic arterial infusion chemotherapy (HAIC) with lenvatinib (LEN) and PD-1 inhibitors in treating arterioportal shunt (APS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT).Patients and Methods: Conducted retrospectively, the study enrolled 54 HCC patients with APS and PVTT treated with HAIC, LEN, and PD-1 inhibitors at our center between January 2021 and October 2023. APS improvement, APS recanalization, tumor response, PVTT response rate, overall survival (OS), intrahepatic progression-free survival (InPFS), and adverse events were evaluated.Results: APS improvement was observed in 42 patients (77.8%), with all improvement occurring within two treatment sessions. Complete APS occlusion was achieved in 40 patients (74.1%), and no recanalization occurred. The best objective response rate (ORR) and ORR after two HAIC sessions were 74.1% and 66.7%, respectively. The best PVTT response and PVTT response after two HAIC sessions were 98.1% and 94.4%, respectively. The median OS and InPFS were 10.0 months and 5.0 months, respectively. OS and InPFS were longer in patients with APS occlusion compared to those without (OS 12.1 vs 4.4 months, P< 0.001, InPFS 6.2 vs 2.3 months, P=0.049). ALBI grade, extrahepatic spread, APS disappearance were potential prognostic factors for OS, while APS grade and extrahepatic spread being independently associated with InPFS. No treatment-related mortality occurred.Conclusion: Combining HAIC with LEN and PD-1 inhibitors proves to be both effective and safe in managing APS in HCC with PVTT, potentially improving patient survival.Keywords: hepatocellular carcinoma, shunt, portal vein tumor thrombus, hepatic arterial infusion chemotherapy, combination therapy

Jingru Zhou,1 Yanjun Liu,2 Fang Yang,1 Meiling Jing,3 Xiaoli Zhong,1 Yanfen Wang,1 Yan Liu,1 Wenwen Ming,1 Huangyan Li,1 Tianxia Zhao,1 Lin He1 1Department of Nursing, Deyang People’s Hospital, Deyang, Sichuan, 618200, People’s Republic of China; 2Department of Infection, Mianzhu People’s Hospital, Mianzhu, Sichuan, 618000, People’s Republic of China; 3Department of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan, 610000, People’s Republic of ChinaCorrespondence: Lin He; Xiaoli Zhong, Email 2507148852@qq.com; 20943794@qq.comObjective: Sarcopenia is a common complication of COPD associated with an age-related reduction in skeletal muscle mass associated with decreased muscle strength and / or reduced mobility. The incidence of sarcopenia in patients with COPD is twice that of non-COPD patients and is associated with poor prognosis, this study aimed to investigate the influencing factors of sarcopenia in COPD patients.Methods: Selected studies from PubMed, Embase, Web of Science, Cochrane Library, Wanfang, Wanfang, CNKI, CBM, and Wanfang databases as of November 12023. Patients aged 18 were selected; data were then independently extracted by two reviewers using a standard data collection form.Results: In total, 17 articles reporting on 5408 patients were included. Age (OR = 1.083; 95% CI, 1.024– 1.145), ALB (OR = 0.752; 95% CI, 0.724– 0.780), BMI(OR = 0.701; 95% CI, 0.586– 0.838), smoking (OR = 1.859; 95% CI, 1.037– 3.334), diabetes (OR = 1.361; 95% CI, 1.095– 1.692), qi deficiency (OR = 9.883; 95% CI, 2.052, 47.593), GOLD C (OR =2.232; 95% CI, 1.866, 2.670) and GOLD D (OR = 2.195; 95% CI, 1.826– 2.637) were factors affecting muscle loss in COPD patients.Conclusion: Sarcopenia is more prevalent in patients with COPD. Age, body mass index, smoking, diabetes mellitus, qi deficiency, ALB, and GOLD grade were the contributing factors for sarcopenia in patients with chronic obstructive pulmonary disease. In the future, medical staff should not only pay attention to the early screening of sarcopenia in high-risk groups, but also provide relevant prevention information.Keywords: sarcopenia, chronic obstructive pulmonary disease, prevalence, risk factors, meta-analysis

Yuping Zhu,1 Xunfu Lai,1 Mengting Wang,2 Xin Tang,1 Tianyi Wan,3 Bin Li,1 Xiaoming Liu,1 Jialin Wu,1 Lei He,1 Yulin He1 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Radiology, Yichang Central People’s Hospital, Yichang, People’s Republic of China; 3Department of Radiology, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of ChinaCorrespondence: Yulin He, Department of Radiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 0791 8869 3802, Email ndyfy02171@ncu.edu.cnObjective: To separate the resting-state network of patients with dental pain using independent component analysis (ICA) and analyze abnormal changes in functional connectivity within as well as between the networks.Patients and Methods: Twenty-three patients with dental pain and 30 healthy controls participated in this study. We extracted the resting-state functional network components of both using ICA. Functional connectivity differences within 14 resting-state brain networks were analyzed at the voxel level. Directional interactions between networks were analyzed using Granger causality analysis. Subsequently, functional connectivity values and causal coefficients were assessed for correlations with clinical parameters.Results: Compared to healthy controls, we found enhanced functional connectivity in the left superior temporal gyrus of anterior protrusion network and the right Rolandic operculum of auditory network in patients with dental pain (p< 0.01 and cluster-level p< 0.05, Gaussian random field corrected). In contrast, functional connectivity of the right precuneus in the precuneus network was reduced, and were significantly as well as negatively correlated to those of the Visual Analogue Scale (r=− 4.93, p=0.017), Hamilton Anxiety Scale (r=− 0.46, p=0.027), and Hamilton Depression Scale (r=− 0.563, p< 0.01), using the Spearman correlation analysis. Regarding the causal relationship between resting-state brain networks, we found increased connectivity from the language network to the precuneus in patients with dental pain (p< 0.05, false discovery rate corrected). However, the increase in causal coefficients from the verbal network to the precuneus network was independent of clinical parameters.Conclusion: Patients with toothache exhibited abnormal functional changes in cognitive-emotion-related brain networks, such as the salience, auditory, and precuneus networks, thereby offering a new imaging basis for understanding central neural mechanisms in dental pain patients.Keywords: toothache, independent component analysis, resting-state networks, Granger causality

Xiaoyi Tang,1,2,&ast; Yijia Liu,1,2,&ast; Mengxin Zhao,3,&ast; Lei He,3 Jiahao Guo,3 Tian Wang,3 Wei Li,3 Jiaqi Zhao1 1Department of Ultrasound, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Ultrasound, the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai, 200003, People’s Republic of China; 3Department of Nanomedicine, Naval Medical University, Shanghai & School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Jiaqi Zhao, Email liwei@smmu.edu.cn; ultrasoundczzjq@163.comPurpose: This study aims to broaden the application of nano-contrast agents (NCAs) within the realm of the musculoskeletal system. It aims to introduce novel methods, strategies, and insights for the clinical management of ischemic muscle disorders, encompassing diagnosis, monitoring, evaluation, and therapeutic intervention.Methods: We developed a composite encapsulation technique employing O-carboxymethyl chitosan (OCMC) and liposome to encapsulate NCA-containing gold nanorods (GNRs) and perfluoropentane (PFP). This nanoscale contrast agent was thoroughly characterized for its basic physicochemical properties and performance. Its capabilities for in vivo and in vitro ultrasound imaging and photothermal imaging were authenticated, alongside a comprehensive biocompatibility assessment to ascertain its effects on microcirculatory perfusion in skeletal muscle using a murine model of hindlimb ischemia, and its potential to augment blood flow and facilitate recovery.Results: The engineered GNR@OCMC-liposome/PFP nanostructure exhibited an average size of 203.18± 1.49 nm, characterized by size uniformity, regular morphology, and a good biocompatibility profile. In vitro assessments revealed NCA’s potent photothermal response and its transformation into microbubbles (MBs) under near-infrared (NIR) irradiation, thereby enhancing ultrasonographic visibility. Animal studies demonstrated the nanostructure’s efficacy in photothermal imaging at ischemic loci in mouse hindlimbs, where NIR irradiation induced rapid temperature increases and significantly increased blood circulation.Conclusion: The dual-modal ultrasound/photothermal NCA, encapsulating GNR and PFP within a composite shell-core architecture, was synthesized successfully. It demonstrated exceptional stability, biocompatibility, and phase transition efficiency. Importantly, it facilitates the encapsulation of PFP, enabling both enhanced ultrasound imaging and photothermal imaging following NIR light exposure. This advancement provides a critical step towards the integrated diagnosis and treatment of ischemic muscle diseases, signifying a pivotal development in nanomedicine for musculoskeletal therapeutics.Keywords: ultrasonography, nanoscale contrast agent, nanotechnology, musculoskeletal ultrasound, photothermal imaging, microcirculatory perfusion

Yuqing Bu,1,&ast; Junye Wen,2,&ast; Fayan Wang,1,3 Shibo Dong,4 Liya He,1 Yang Li,1,5 Jinlong Liang,1,3 Hongzhen Zhang1,3,5 1Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 2Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 3Department of Medicine, Hebei North University, Zhangjiakou, Hebei Province, 075000, People’s Republic of China; 4Department of Imaging, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 5Department of Medicine, North China University of Science and Technology, Tangshan, Hebei Province, 063210, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhen Zhang, Email hongzhenzhang456@sohu.comAbstract: This study presents a case of dual primary liver cancer involving small cell neuroendocrine carcinoma and hepatocellular carcinoma. The 58-year-old Chinese male patient, who has a medical history of viral hepatitis B, presented with right upper abdominal pain persisting for one month. Imaging studies indicated the presence of multiple liver masses in segments V and VII–VIII, as well as a mass in the left lung. Subsequent hepatic biopsy performed on both segments confirmed the presence of hepatocellular carcinoma in segment V and small cell neuroendocrine carcinoma in segment VII–VIII. After undergoing one cycle of chemotherapy, the lung mass exhibited a reduction in size, while the liver masses showed an inadequate response. Subsequently, the patient underwent Transcatheter Arterial Chemoembolization (TACE) and Hepatic Artery Infusion Chemotherapy (HIAC), resulting in partial remission (PR). However, the patient was diagnosed with brain metastasis and subsequently treated with Sorafenib and Tirelizumab, a Programmed Death 1 (PD-1) immune checkpoint inhibitor. The efficacy evaluation indicated stability, and no severe adverse effects were observed at the time of writing. The patient’s survival time was 16 months.Keywords: synchronous tumor, liver tumor, primary tumor, small cell neuroendocrine carcinoma, hepatocellular carcinoma

Jing Wang,1,&ast; Lisha He,2,&ast; Zhiyan Jin,1,&ast; Guoguang Lu,1 Sufei Yu,1 Lingling Hu,1 Meidan Fang,1 Xiaxia Jin1 1Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Taizhou, Zhejiang Province, People’s Republic of China; 2Department of Ultrasound, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Taizhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meidan Fang; Xiaxia Jin, Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Taizhou, Zhejiang Province, People’s Republic of China, Tel +86 13586102337; +86 15967063239, Email fangmd@enzemed.com; jinxiax@enzemed.comObjective: To explore the early predictors and their predicting value of 28-day mortality in sepsis patients and to investigate the possible causes of death.Methods: 127 sepsis patients were included, including 79 cases in the survival group and 48 cases in the death group. The results of all patients on admission were recorded. After screening the risk factors of 28-day mortality, the receiver operating characteristic curve (ROC) was used to determine their predictive value for the 28-day mortality rate on admission, and the Kaplan-Meier curve was drawn to compare the 28-day mortality rate between groups. Finally, patients with cytokine and lymphocyte subsets results were included for investigating the possible causes of death through correlation analysis.Results: APACHE II (acute physiology and chronic health evaluation II), SOFA (Sequential Organ Failure Assessment) and red blood cell distribution width (RDW) were the risk factors for 28-day mortality in sepsis patients (OR: 1.130 vs.1.160 vs.1.530, P < 0.05). The area under the curve (AUC), sensitivity and specificity of APACHE II, SOFA and RDW in predicting the mortality rate at 28 days after admission in sepsis patients were 0.763 vs 0.806 vs 0.723, 79.2% vs 68.8% vs 75.0%, 65.8% vs 89.9% vs 68.4%. The combined predicted AUC was 0.873, the sensitivity was 89.6%, and the specificity was 82.3%. The Kaplan-Meier survival curve showed that the 28-day mortality rates of sepsis patients with APACHE II≥ 18.5, SOFA≥ 11.5 and RDW≥ 13.8 were 58.5%, 80.5% and 59.0%, respectively. In the death group, APACHE II was positively correlated with SOFA, IL-2, and IL-10, and RDW was positively correlated with PLT, TNF-α, CD3+ lymphocyte count, and CD8+ lymphocyte count.Conclusion: Sepsis patients with high APACHE II, SOFA and RDW levels at admission have an increased 28-day mortality rate. The elevation of these indicators in dead patients are related to immune dysfunction.Keywords: sepsis, APACHE II, SOFA, red blood cell distribution width, mortality, immune dysfunction

Xingping Zhou,1,&ast; Jinjin Luo,1,&ast; Xi Liang,1,2 Peng Li,1 Keke Ren,1 Dongyan Shi,1,2 Jiaojiao Xin,1,2 Jing Jiang,1,2 Jiaxian Chen,1 Lulu He,1 Hui Yang,1 Shiwen Ma,1 Bingqi Li,1 Jun Li1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel/Fax +86-571-87236425, Email lijun2009@zju.edu.cnBackground and Aim: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with high short-term mortality. Effective biomarkers are required for its early diagnosis and prognosis. This study aimed to determine the diagnostic and prognostic value of thrombomodulin (TM) in patients with HBV-ACLF.Methods: The expression of TM during disease progression was evaluated through transcriptomics analysis. The plasma TM concentrations of 393 subjects with HBV-ACLF (n=213), acute-on-chronic hepatic dysfunction (ACHD, n=50), liver cirrhosis (LC, n=50) or chronic hepatitis B (CHB, n=50), and normal controls (NC, n=30) from a prospective multicenter cohort, were measured to verify the diagnostic and prognostic significance of plasma TM for HBV-ACLF patients by enzyme-linked immunosorbent assay (ELISA).Results: TM mRNA was highly expressed in the HBV-ACLF group compared with the ACHD group (AUROC=0.710). High expression of TM predicted poor prognosis for HBV-ACLF patients at 28/90 days (AUROCs=0.823/0.788). Functional analysis showed that TM was significantly associated with complement activation and the inflammatory signaling pathway. External validation confirmed its high diagnostic accuracy for HBV-ACLF patients (AUROC=0.796). Plasma TM concentrations were correlated with organ failure, including coagulation and kidney failure. Plasma TM concentrations showed a potential prognostic value for 28-day mortality rates (AUROC=0.702). Risk stratification specifically identified HBV-ACLF patients with a high risk of death as having a plasma TM concentration of ≥ 8.4 ng/mL.Conclusion: This study reveals that the plasma TM can be a candidate biomarker for early diagnosis and prognosis of HBV-ACLF, and might play a vital role in coagulation and inflammation.Keywords: thrombomodulin, HBV-ACLF, biomarker, organ failure

Tian Zhang, Jiexin Wang, Yi Wang, Linxi He, Shangbin Lv, Yiran Wang, Weihong Li Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Weihong Li, Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, 610000, People’s Republic of China, Tel/Fax +8613882014290, Email lwh@cdutcm.edu.cnPurpose: Chronic inflammation is one of the key mechanisms of depression. Wenyang-Tianjin-Jie Decoction (WTJD) is an effective antidepressant found in the course of diagnosis and treatment, but the mechanism of therapeutic effect is not clear. The study aimed to evaluate the efficacy of WTJD in the kidney yang deficiency (KYD) type of depression rats and reveal its mechanisms.Materials and Methods: We selected forty 6-week-old male Sprague-Dawley rats for the study. We established a KYD [Phellodendron amurense Rupr (Huangbai) solution oral gavage and 4°C environments; 8 weeks] type of depression (chronic unpredictable mild stimulus; 6 weeks) rat model first. After successful modeling, we used WTJD or fluoxetine on rats for 3 weeks. Then we evaluated the depression and KYD behavior. Finally, we observed the expression of key inflammatory factors and proteins in peripheral blood and hippocampus, and further investigated the immune balance of Th17/Treg and Th1/Th2 cells and the activity of their main regulatory pathways JAK2/STAT3 and TLR4/TRAF6/NF-κB.Results: The imbalance of Th17/Treg and Th1/Th2 cells in rats were related to KYD and depressive symptoms. Through this study, we found that WTJD can inhibit the activity of JAK2/STAT3 and TLR4/TRAF6/NF-κB pathways, balance Th17/Treg and Th1/Th2 cell homeostasis, regulate the levels of inflammatory factors in the hippocampus and peripheral blood, and reverse KYD and depression.Conclusion: This study confirmed that WTJD had a reliable effect on depression rats with KYD, and its mechanism was to regulate the immune homeostasis of hippocampal T cells and related inflammatory factors to improve KYD and depression symptoms in rats.Keywords: depression, immune homeostasis, inflammation, traditional Chinese medicine, hippocampus

Lifang He,1,2 Jean Rizza A Dela Cruz3 1School of Nursing, XiangNan University, Chenzhou, 423000, People’s Republic of China; 2College of Nursing and Allied Health Sciences St.Paul University Manila, Manila, 1004, Philippines; 3Department of Nursing Olivarez College Tagaytay, Tagaytay City, 4120, PhilippinesCorrespondence: Jean Rizza A Dela Cruz, Department of Nursing Olivarez College Tagaytay, Tagaytay City, 4120, Philippines, Tel +639175507389, Email jeanrizza@icloud.comBackground: Newly graduated nurses with strong work readiness are more likely to smoothly transition from school to clinical settings. However, even before the pandemic, this transition from nursing graduate to clinical nurse was often challenging. Therefore, this study aims to investigate the impact of the initial wave of COVID-19 on the work readiness of nursing students.Methods: A convergent mixed-method design was employed. For the quantitative study, an online cross-sectional survey was conducted among 500 graduating nursing students from four Chinese public higher education institutions. The questionnaire comprises three parts: socio-demographic information, the Chinese version of the Work Readiness Scale for Graduate Nurse, and a questionnaire on the socio-behavioral impact of COVID-19 on the general population. In the qualitative study, a semi-structured interview was carried out with 8 students who took part in the survey. The results from both parts were integrated using the “Pillar Integration Process”.Results: The study identified six key pillars: “Graduating nursing students possess fundamental knowledge, skills, and a preparedness in terms of attitude and psychology”; “Specialist knowledge and skills and soft skills for transition from nursing students to clinical nurses need to be strengthened”; “The most obvious impact of COVID-19 on nursing students are the adoption of preventive measures and the limitations in study and daily life due to household confinement”; “Growth in both personal and professional awareness”; “Negative effects of fear and anxiety”; and “Negative effects of household confinement”.Conclusion: Graduating nursing students require additional preparation in specialized nursing knowledge, skills, and soft skills to make a successful transition from students to clinical nurses. It is important to acknowledge that the impact of COVID-19 on students’ work readiness has both positive and negative aspects. Therefore, whether during the pandemic or post-graduation, these students will benefit from increased support from universities and hospitals.Keywords: work readiness, COVID-19, nursing students, nursing education, mixed methods, pillar integration process

Min Zhao,1,&ast; Ming-Zhu Gao,1,&ast; Rong-yan Gu,1,&ast; Lei Luo,1 Song-rui Ding,1 Liang He,2 Yue Jia,3 Hong-ping Zhang,3 Hong-ying Yang,3 Gao-feng Li1 1Medical Administration Department, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, Yunnan, People’s Republic of China; 2Medical Laboratory Department, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, Yunnan, People’s Republic of China; 3Gynecological Department, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-ying Yang; Gao-feng Li, Email yanghy913@126.com; ligaofenghl@126.comBackground: Research on the risk factors for cervical cancer in Yunnan Province’s four characteristic ethnic groups (Han, Bai, Dai, and Hani) is lacking.Objective: To study the risk factors of cervical cancer in four ethnic women in Yunnan Province, and to provide evidence for its prevention.Methods: The cervical cancer patients of Han, Bai, Dai and Hani ethnic groups in Yunnan Province who were first diagnosed in the Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center) from January 2011 to December 2020 were selected as the research objects. The 1:1 matched case-control study method was used, and single factor and conditional logistic regression were used for statistical analysis.Results: HPV types 16, 18 and 58 are mostly related with cervical cancer, the younger the age of the last pregnancy, the more times of pregnancy, childbirth and abortion, especially the younger the first marriage age of Bai and Dai, are the risk factors of cervical cancer; the infection of genital tract bacteria, mycoplasma and chlamydia is closely related to the incidence of cervical cancer in four ethnicities. Multifactorial analysis showed that demographic characteristics and environment/behavior were not included in the influencing factors of cervical cancer; among Han, Bai, Dai and Hani ethnic minorities, contraception (OR=0.29, OR=0.03, OR=0.09, OR=0.16, P< 0.05) was positive factor, HPV infection (OR=64.77, OR=128.71, OR=71.89, OR=40.07, P< 0.01) was a causative factor of cervical cancer.Conclusion: Risk of high parity with cervical cancer could be due to a complex interplay of factors, it is very important to formulate prevention strategies and measures in line with the cervical cancer of Han, Bai, Dai and Hani ethnic groups women in Yunnan Province.Keywords: cervical cancer, risk factors, case-control study, Han, Bai, Dai and Hani ethnic minorities, Yunnan Province

Mengqi Wang,1,&ast; Shuting Lan,1,&ast; Wenqi Zhang,1,&ast; Qin Jin,2 Hua Du,3 Xiaomei Sun,1 Lijun He,1 Xiangyun Meng,1 Liya Su,1 Gang Liu1 1Key Laboratory of Medical Cell Biology, Department of Achievement Transformation, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Liu, Email 20190043@immu.edu.cnIntroduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations.Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells.Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway.Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.Keywords: copper, carbon quantum dots, breast cancer, oxidative stress, MAPK signaling pathway

Wenwen Wang,1,&ast; Yuanyuan Peng,2,&ast; Keqiang Tang,3 Ziwei Zheng,1 Lan He,1 Shaoling Yang1 1Department of Ultrasound Medicine, Shanghai Eighth People’s Hospital, Shanghai, 200235, People’s Republic of China; 2Department of Imaging Medicine and Nuclear Medicine, Anhui University of Science and Technology, School of Medicine, Huainan, Anhui, 232001, People’s Republic of China; 3Department of Intensive Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital, Shanghai, 201619, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoling Yang, Department of Ultrasound Medicine, Shanghai Eighth People’s Hospital, Shanghai, 200235, People’s Republic of China, Tel +86-18930240812, Email drysl@163.comPurpose: This study aimed to assess the knowledge, attitudes and practices (KAP) among middle-aged and elderly population towards ultrasound screening for strokes.Patients and Methods: This web-based cross-sectional study was conducted between March, 2023, and May, 2023 at Shanghai Eighth People’s Hospital. A self-designed questionnaire was developed to collect demographic information of middle-aged and elderly population and assess their knowledge, attitudes and practices toward ultrasound screening for strokes.Results: A total of 552 participants enrolled in this study, among them 151 (27.36%) aged above 60 years old, 306 (55.43%) resided in rural area, 239 (43.30%) possessed educational attainment at the level of junior college, college or above. The mean knowledge, attitudes and practice scores were 5.53 ± 2.56, 40.22 ± 5.60 and 38.30 ± 7.38, respectively. Pearson’s analysis was performed to assess the relationship between knowledge, attitudes, and practices. It was shown that knowledge and attitudes were positively correlated (r = 0.544, P < 0.001), and knowledge and practices were also positively correlated (r = 0.404, P < 0.001). Additionally, there was a positive correlation between attitude and practice scores (r = 0.566, P < 0.001).Conclusion: The results of this study demonstrate that the middle-aged and elderly population exhibited insufficient knowledge, positive attitudes, and moderate practices towards ultrasound screening for strokes. There is a need to improve the understanding of stroke risk factors, symptoms, and emergency measures among this population.Keywords: knowledge, attitudes, practice, stroke, ultrasound imaging, middle-aged, elderly

Yunhong Ren,1,&ast; Yinhao Guo,2,&ast; Jing Tang,2 Ling He,1 Meiling Li,1 Xuemei Huang,1 Qin Lu,1 Baoxia Sun,1 Haixia Feng,1 Huan Liu,1 Juan Du,1 Jun Li1 1Mianyang Key Laboratory of Anesthesia and Neuroregulation, Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan, 621000, People’s Republic of China; 2Department of Anesthesiology, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li; Juan Du, Mianyang Key Laboratory of Anesthesia and Neuroregulation, Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan, People’s Republic of China, Email lj89199@163.com; 1151941061@qq.comPurpose: This study aimed to investigate the effects of different psychological personalities and pain catastrophizing levels on postoperative analgesia in patients undergoing cesarean section.Patients and Methods: Puerperas who underwent cesarean section at our hospital between January and August 2023 were recruited into the study and assessed using the Eysenck Personality Questionnaire-Revised Short Scale (EPQRSC) and Pain Catastrophizing Scale (PCS). Data on the numerical pain intensity at rest and during activity 24 h after surgery, number and dosage of analgesia pumps, and satisfaction with analgesia were recorded. According to the numerical pain score during activity 24 h post-operation, the patients were divided into the analgesia incomplete group (≥ 4) and control group (< 4). Univariate analysis, Spearman correlation analysis, and binary logistic regression analysis were used to evaluate the influence of personality characteristics and PCS on postoperative analgesia.Results: A total of 778 women were included in the study. The incidence of inadequate analgesia was 89.8%. The satisfaction rate of analgesia was 66.8%. Univariate analysis showed that extraversion; neuroticism; PCS; numbers of previous cesarean delivery; ASA; analgesic satisfaction; and 24-h analgesia pump compressions and dosage were associated with postoperative analgesia after cesarean section (P< 0.05). Using binary logistic regression analysis, the first cesarean section (odds ratio [OR]=0.056, 95% confidence interval [CI]=1.913– 19.174), the number of 24-h analgesic pump compressions (OR=8.464, 95% CI=0.356– 0.604), extraversion (OR=0.667, 95% CI=0.513– 0.866), neuroticism (OR=1.427, 95% CI=1.104– 1.844), and PCS (OR=7.718, 95% CI=0.657– 0.783) were factors affecting postoperative analgesia.Conclusion: The incidence of inadequate analgesia after a cesarean section was high (89.8% on the first day after surgery). Formulating accurate analgesia programs for women undergoing cesarean section with extraversion, neuroticism personality characteristics, and pain catastrophizing behaviors is necessary for improving their postoperative analgesia effects and satisfaction and promoting postpartum comfort.Keywords: aftercare, anesthetics, breast feeding, fear, personal satisfaction, postpartum depression

Chenkai Yang,1,&ast; Xiangqian Cao,1,&ast; Lei He,2,3,&ast; Cong Wu,2,&ast; Mengxin Zhao,2 Fei Duan,2 Zhiwen Qiu,2 Xiaodong Zhu,2 Yilin Yan,1 Shengzhou Li,1 Wei Li,2 Bing Shen1 1Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Nanomedicine & Shanghai Key Laboratory of Cell Engineering, Naval Medical University, Shanghai, People’s Republic of China; 3School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li, Department of Nanomedicine & Shanghai Key Laboratory of Cell Engineering, Naval Medical University, 800 Xiangyin Road, Yangpu District, Shanghai, 200433, People’s Republic of China, Tel +86 21 81871644, Fax +86 21 81870801, Email liwei_dds@163.com Bing Shen, Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 85 Wujin Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Tel/Fax +86 18017181979, Email urodrshenbing@shsmu.edu.cnIntroduction: Insufficient tumor permeability and inadequate nanoparticle retention continue to be significant limitations in the efficacy of anti-tumor drug therapy. Numerous studies have focused on enhancing tumor perfusion by improvement of tumor-induced endothelial leakage, often known as the enhanced permeability and retention (EPR) effect. However, these approaches have produced suboptimal therapeutic outcomes and have been associated with significant side effects. Therefore, in this study, we prepared tumor cell membrane-coated gold nanorods (GNR@TM) to enhance drug delivery in tumors through homogeneous targeting of tumor cell membranes and in situ real-time photo-controlled therapy.Methods: Here, we fabricated GNR@TM, and characterized it using various techniques including Ultraviolet-Visible (UV-Vis) spectrophotometer, particle size analysis, potential measurement, and transmission electron microscopy (TEM). The cellular uptake and cytotoxicity of GNR@TM were analyzed by flow cytometry, confocal laser scanning microscopy (CLSM), TEM, CCK8 assay and live/dead staining. Tissue drug distribution was determined by inductively coupled plasma mass spectrometry (ICP-MS) and immunofluorescence staining. Furthermore, to evaluate the therapeutic effect, mice bearing MB49 tumors were intravenously administered with GNR@TM. Subsequently, near-infrared (NIR) laser therapy was performed, and the mice’s tumor growth and body weight were monitored.Results: The tumor cell membrane coating endowed GNR@TM with extended circulation time in vivo and homotypic targeting to tumor, thereby enhancing the accumulation of GNR@TM within tumors. Upon 780 nm laser, GNR@TM exhibited excellent photothermal conversion capability, leading to increased tumor vascular leakage. This magnification of the EPR effect induced by NIR laser further increased the accumulation of GNR@TM at the tumor site, demonstrating strong antitumor effects in vivo.Conclusion: In this study, we successfully developed a NIR-triggered nanomedicine that increased drug accumulation in tumor through photo-controlled therapy and homotypic targeting of the tumor cell membrane. GNR@TM has been demonstrated effective suppression of tumor growth, excellent biocompatibility, and significant potential for clinical applications. Keywords: intratumor drug accumulation, photo-controlled therapy, homotypic targeting, tumor cell membrane, gold nanorods

Fan Zhang,&ast; Wei Li,&ast; Yingying Zhang, Dong Wang, Jing Li, Chengpeng Li, Liqun He Department of Cardiology, Intervention Cardiology Center, Wuhan No.1 Hospital, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liqun He, Department of Cardiology, Intervention Cardiology Center, Wuhan No.1 Hospital, No. 215, Zhongshan Avenue, Qiaokou District, Wuhan, 430022, People’s Republic of China, Tel/Fax +86-027-85332105, Email heliqundr@163.comPurpose: Acute coronary syndrome (ACS) is a common acute myocardial ischemia syndrome and is one of the death-related causes of cardiovascular diseases. Identifying biomarkers to indicate disease severity and predict the occurrence of major adverse cardiovascular events (MACE) would benefit the clinical prognosis of ACS. This study estimated the expression and significance of lncRNA TPRG1-AS1 in the onset and development of ACS, aiming to explore a novel biomarker for the diagnosis and prognosis of ACS.Patients and Methods: A total of 109 ACS patients and 66 patients who received coronary angiography and excluded ACS were enrolled in this study. TPRG1-AS1 in the serum of study subjects was analyzed by PCR. The significance of TPRG1-AS1 in screening ACS was evaluated by ROC analysis. The association of TPRG1-AS1 with the disease severity of ACS was assessed by Pearson correlation analysis with patients’ clinicopathological features. The potential of TPRG1-AS1 in predicting the occurrence of MACE was assessed by logistic regression analysis.Results: Significant upregulation of TPRG1-AS1 was observed in ACS patients, which served as a risk factor for ACS and distinguish between ACS patients and the normal group. TPRG1-AS1 was positively correlated with Gensini score, cys-C, cTnI, and NT-proBNP levels of ACS patients, which indicate severe development of ACS. Additionally, increasing serum TPRG1-AS1 was associated with the high incidence of MACE during patients’ hospitalization and was identified as a risk factor for MACE in ACS patients.Conclusion: Upregulated TPRG1-AS1 in ACS served as a diagnostic biomarker and predicted the severe development of patients.Keywords: cardiovascular disease, lncRNA, onset, inpatient MACE, severity

Yinghui Zhang,1 Yanhua Jin,1 Huan Wang,1 Long He,2 Yanning Zhang,1 Qi Liu,1 Yu Xin,1 Xueyu Li3 1Department of Nephrology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, People’s Republic of China; 2Organ Transplant Center, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, People’s Republic of China; 3Nursing Department, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Xueyu Li, Nursing Department, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, Liaoning Province, 110016, People’s Republic of China, Tel/Fax +18909882688, Email lxy_dr@163.com Yanning Zhang, Department of Nephrology, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, Liaoning Province, 110016, People’s Republic of China, Tel/Fax +18604105316, Email 18604105316@163.comPurpose: Chronic kidney disease (CKD) will become an end-stage renal disease (ESRD) at stage 5. Peritoneal dialysis (PD) is required for renal replacement therapy. This study aims to identify monocytes-related genes in peritoneal cells from long-term PD (LPD) patients and short-term PD (SPD) patients.Methods: Bulk RNA-seq data (GSE125498 dataset) and ScRNA-seq data (GSE130888) were downloaded to identify differentially expressed genes, monocytes-related genes, and monocytes marker genes in LPD patients. Immune infiltration was analyzed in the GSE125498 dataset. Core genes associated with monocytes changes were screened out, followed by functional analysis and expression validation using RT-PCR.Results: Monocytes are the most abundant immune cell in PD. The number of monocytes was remarkably decreased in LPD compared with SPD. A total of 16 up-regulated core genes negatively correlated with the abundance of monocytes were obtained in LPD. The expression of 16 core genes was lower in monocyte clusters than that in other cell clusters. In addition, LCK, CD3G, CD3E, CD3D, and LAT were involved in the signaling pathways of Th1 and Th2 cell differentiation, T cell receptor signaling pathway, and Th17 cell differentiation. CD2 was involved in hematopoietic cell lineage signaling pathway.Conclusion: Identification of monocytes related-genes and related signaling pathways could be helpful in understanding the molecular mechanism of monocytes changes during PD.Keywords: long-term peritoneal dialysis, short-term peritoneal dialysis, monocytes, peritoneal cells, single-cell sequencing, signaling pathway

Xin Jiang,&ast; Lijie Gao,&ast; Jian Wang, Jiajia Bao, Jinghuan Fang, Li He Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinghuan Fang; Li He, Department of Neurology, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, Sichuan Province, 610041, People’s Republic of China, Email jinghuan_fang@126.com; heli2003new@126.comBackground: Blood pressure variation and collateral status have been reported to be associated with clinical outcome in patients with acute ischemic stroke who received endovascular treatment; however, the relationship between blood pressure variation within 72 hours after EVT and clinical outcome in different collateral status remains unclear.Methods: Acute ischemic stroke patients due to large vessel occlusion with EVT were retrospectively enrolled. We classified participants into poor collateral (ASITN/SIR grade < 2) and good collateral subgroups (ASITN/SIR grade ≥ 2). The primary outcome was unfavorable neurological outcome defined as a 3-month modified Rankin Scale (mRS) score ≥ 2. The interactive effect was tested to determine the influence of collateral status on the association between BP variation and clinical outcome.Results: A total of 545 patients were included. The poor collateral subgroup was detected in 198 patients with an average age of 70.2 years. The association between BP variation and primary outcome did not differ under different collateral status (P for interaction > 0.05). However, the association between the mean and coefficient of variation (CV) values of DBP and 3-month mortality was significantly discrepant under different collateral status (P for interaction < 0.05). In the good collateral subgroup, higher mean DBP was associated with a lower risk of 3-month mortality (OR 0.95, 95% CI 0.91– 1, P = 0.033) compared with the poor subgroup (OR 1.04, 95% CI 0.97– 1.1, P = 0.286). In addition, a higher CV of DBP was associated with a higher risk of 3-month mortality (OR 1.24, 95% CI 1.13– 1.36, P < 0.01) compared with poor status (OR 1.08, 95% CI 0.94– 1.23, P=0.275).Conclusion: For patients who received EVT with good collateral status, increased CV of DBP was significantly associated with higher 3-month mortality, while higher mean DBP within 72 h after EVT was associated with a decrease in 3-month mortality.Keywords: acute ischemic stroke, blood pressure variability, clinical outcome, collateral status, endovascular treatment

Xiaohang Chen,1,2 Shuaiqi Ji,1,2 Yuxiang Yan,1 Shuoqi Lin,1,2 Lianghang He,1,2 Xiaoyu Huang,2 Lin Chang,2 Dali Zheng,1 Youguang Lu1,2 1Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Youguang Lu; Dali Zheng, Email fjlyg63@fjmu.edu.cn; dalizheng@fjmu.edu.cnAbstract: Tumors are the second-most common disease in the world, killing people at an alarming rate. As issues with drug resistance, lack of targeting, and severe side effects are revealed, there is a growing demand for precision-targeted drug delivery systems. Plant-derived nanovesicles (PDNVs), which arecomposed of proteins, lipids, RNA, and metabolites, are widely distributed and readily accessible. The potential for anti-proliferative, pro-apoptotic, and drug-resistant-reversing effects on tumor cells, as well as the ability to alter the tumor microenvironment (TME) by modulating tumor-specific immune cells, make PDNVs promising anti-tumor therapeutics. With a lipid bilayer structure that allows drug loading and a transmembrane capacity readily endocytosed by cells, PDNVs are also expected to become a new drug delivery platform. Exogenous modifications of PDNVs enhance their circulating stability, tumor targeting ability, high cell endocytosis rate, and controlled-release capacity. In this review, we summarize PDNVs’ natural antitumor activity, as well as engineered PDNVs as efficient precision-targeted drug delivery tools that enhance therapeutic effects. Additionally, we discuss critical considerations related to the issues raised in this area, which will encourage researchers to improve PDNVs as better anti-tumor therapeutics for clinic applications.Graphical Abstract: Keywords: plant-derived nanovesicles, cancer therapy, natural bioactivity, drug delivery platform, engineered EVs, targeted precision therapy

Jialun Peng,1,&ast; Qilong Zhai,1,&ast; Jinzheng Li,1 Xingyu Chen,1 Hongyu Wu,1 Tao Zhong,1 Gangyi Tang,2 Dajun Yu,2 Lixian He,2 Jinxu Li2 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Department of General Surgery, Wushan County People’s Hospital of Chongqing, Chongqing, 404700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinzheng Li; Gangyi Tang, Tel +86 138 9600 6584 ; +86 159 2387 3984, Fax +86 023 6369 3000, Email 303234@hospital.cqmu.edu.cn; 604267374@qq.comAbstract: Liver abscesses caused by Clostridium perfringens are rare but rapidly fatal. In only a few days, patients progress from liver abscess to sepsis, intravascular hemolysis, multiple organ failure, and even death. These abscesses often occur in patients after trauma or surgery or in those with immunodeficiency. Because patients only show non-specific symptoms such as fever and abdominal pain in the early stage, they can easily be misdiagnosed and miss the therapeutic window, resulting in a poor prognosis. The diagnosis of Clostridium perfringens liver abscess mainly depends on computed tomography (CT), needle aspiration, and/or blood culture. After diagnosis, treatments such as antibiotic therapy, surgical abscess drainage, blood transfusion as needed, and correction of metabolic disturbances must be immediately administered to prevent severe complications. Here, we present two cases of liver abscess due to Clostridium perfringens infection. Both patients initially presented only with fever, abdominal pain, and jaundice, symptoms that were easily confused with cholangitis caused by cholelithiasis. The patients then progressed rapidly and, despite receiving antimicrobial and multimodal sepsis treatment, both eventually died of multiple organ dysfunction syndrome. Clinicians should be on high alert for Clostridium perfringens liver abscesses disguised as biliary disease. Early diagnosis and treatment with the appropriate antibiotics and surgery are fundamental for the survival of the affected patients.Keywords: intravascular hemolysis, biliary diseases, diagnosis, treatment

Lian He,1 Yusai Xie,2 Yusong Qiu,1 Yong Zhang1 1Department of Pathology, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang, Liaoning, 110042, People’s Republic of China; 2Laboratory of Basic Medicine, General Hospital of Northern Theatre Command, Shenyang, Liaoning, 110016, People’s Republic of ChinaCorrespondence: Yusai Xie, Laboratory of Basic Medicine, General Hospital of Northern Theatre Command, Shenyang, Liaoning, 110016, People’s Republic of China, Email ysxie@cmu.edu.cn Yong Zhang, Department of Pathology, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang, Liaoning, 110042, People’s Republic of China, Email zhycmu@163.comPurpose: ZPR1 is a zinc finger-containing protein that plays a crucial role in neurodegenerative diseases, lipid metabolism disorders, and non-alcoholic fatty liver disease. However, the expression pattern, prognostic value, and treatment response of ZPR1 in pan-cancer and hepatocellular carcinoma (HCC) remain unclear.Patients and Methods: Pan-cancer expression profiles and relevant clinical data were acquired from UCSC Xena platform. Pan-cancer expression, epigenetic profile, and clinical correlation analysis for ZPR1 were performed. We next explored the prognostic significance and potential biological functions of ZPR1 in HCC. Furthermore, the relationship between ZPR1 and immune infiltration and treatment response was investigated. Finally, quantitative immunohistochemistry (IHC) analysis was applied to assess the correlation of ZPR1 expression and immune microenvironment in HCC tissues using Qupath software.Results: ZPR1 was differentially expressed in most tumor types and significantly up-regulated in HCC. ZPR1 showed hypo-methylated status in most tumors. Pan-cancer correlation analysis indicated that ZPR1 was closely associated with clinicopathological factors and TMB, MSI, and stemness index in HCC. High ZPR1 expression could be an independent risk factor for adverse prognosis in HCC. ZPR1 correlated with immune cell infiltration and therapeutic response. Finally, IHC results suggested that ZPR1 correlated with CD4, CD56, CD68, and PD-L1 expression and is a promising pathological diagnostic marker in HCC.Conclusion: Immune infiltrate-associated ZPR1 could be considered a novel negative prognostic biomarker for therapeutic response in HCC.Keywords: hepatocellular carcinoma, ZPR1, prognosis, digital pathology, pan-cancer

Weiqin Cheng,1 Ling He,1 Hechuan Luo,1 Yan Jiang,2 Chengbing Tan,2 Xiao Fan1 1Department of Radiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, People’s Republic of China; 2Department of Neurology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, People’s Republic of ChinaCorrespondence: Xiao Fan, Department of Radiology, Children’s Hospital of Chongqing Medical University, No. 136 Zhongshan Er Road, Yuzhong District, Chongqing, 400014, People’s Republic of China, Tel +86 13637907710, Email fanxiao@cqmu.edu.cnObjective: To investigate and summarize the magnetic resonance imaging (MRI) manifestations of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children.Methods: We retrospectively analyzed data from 17 pediatric patients with autoimmune GFAP astrocytopathy confirmed by the detection of GFAP autoantibodies in cerebrospinal fluid in our single-center. Furthermore, we reviewed current literature and summarized previous findings on the MRI characteristics of this disease in children.Results: In these 17 patients, the clinical manifestations and results of CSF analysis were suggestive of autoimmune disorder, with a good improvement. The lesions on MRI were most commonly located in the bilateral basal ganglia (70.6%), thalamus (64.7%), cerebral white matter (29.4%). 93.3% of the cerebral lesions were relatively scattered and small, 80% of the spinal lesions presented as longitudinally extensive ones. Both periventricular radial linear (PVRL) (53.8%) and punctate or linear enhancement in basal ganglia and thalamus (53.8%) were commonly observed, followed by the leptomeningeal enhancement (46.2% in the brain and 62.5% in the spinal cord). We then included 55 pediatric patients with MRI data from current literature in our analysis (n = 72, 44 males). Our results revealed similar MRI findings but the enhancement pattern between our series and previously published cases, that is, leptomeningeal enhancement in the brain 46.2% vs 31.4%, in spinal cord 62.5% vs 18.4%, and PVRL enhancement 53.8% vs 11.2%. There were no detailed reports on punctate or linear enhancement.Conclusion: The MRI characteristics of autoimmune GFAP astrocytopathy in children could be suggestive. Scattered and small lesions (especially punctate or linear) in the bilateral thalamus, basal ganglia, and white matter, as well as longitudinally extensive spinal cord lesions (if present), with punctate, PVRL and leptomeningeal enhancement might be a distinct indication for the early diagnosis of this disorder.Keywords: glial fibrillary acidic protein, GFAP, astrocytopathy, autoimmune, magnetic resonance imaging, children

Tian Tian,1,&ast; Mei-Jun Guan,1,&ast; Li-Juan Liu,1 Xiao-Qiu Su,1 Hui Wang,2 Li He1 1Department of Gynecology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2Department of Gynecological Day Surgery, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li He, Department of Gynecology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 1617 of Riyue Anenue, Qingyang District, Chengdu, 611731, People’s Republic of China, Tel +86 13881782966, Email helihlop0@126.comObjective: To discuss the impact of the “information platform + self-care model” on the health status of discharged patients following vaginal natural orifice transluminal endoscopic surgery (vNOTES).Methods: Patients underwent vNOTES at a tertiary specialized women’s and children’s hospital in Chengdu. They were randomly assigned to one of two groups—the intervention group (29 patients) and the control group (29 patients). The control group received standard education after discharge, while the intervention group received guidance based on an “information platform + self-care model” on discharge; a questionnaire survey was conducted for both groups one month after discharge.Results: The quality of life score in the intervention group was higher than that in the control group, and the difference was statistically significant (P < 0.05); the scores of the intervention group on dimensions such as vitality, general health perceptions, physical role functioning, social role functioning, emotional role functioning, and mental health, except for physical functioning (Z = 0.034, P = 0.973) and bodily pain (Z = 1.470, P = 0.141), were higher than those in the control group one month after discharge, and the difference was statistically significant (P

Xue Ke,1 Li He,2 Jia-Feng Zheng,1 Yong-Hong Lin,1 Fang Wang1 1Department of Reproductive Medicine, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Gynecology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of ChinaCorrespondence: Fang Wang, Department of Reproductive Medicine, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Email wangfcd2022@163.comPurpose: Ectopic pregnancy (EP) is rare among patients having received tubal ligation; in these cases, a fertilized ovum is implanted in the proximal tube stump. Distal tubal EP cases in patients having undergone ipsilateral tubal ligation and who have relatively intact contralateral adnexa are extremely rare. Here, we report a case of pregnancy in the distal stump of the ipsilateral fallopian tube following fallopian tubal isthmus ligation.Case Presentation: A 28-year-old woman was admitted after having experienced lower abdominal pain for 10 days and amenorrhea for 1 week and receiving a transvaginal color ultrasonography finding of a heterogeneous echo (2.1 × 1.2 × 1.4 cm) near the left ovary. The patient had a medical history of transvaginal left tubal ligation under single-port laparoscopy for a left hydrosalpinx. Postoperatively, the patient had undergone in vitro fertilization for assisted reproduction. After ovum retrieval, whole-embryo cryopreservation had been performed due to the ovarian hyperstimulation syndrome trend. This pregnancy was natural after embryo cryopreservation. After the patient was admitted, laparoscopic exploration revealed an elevated ampulla in the distal stump of the left fallopian tube. Left salpingectomy with removal of the ectopic pregnancy in the distal remnant tube was performed under the guidance of transvaginal single-port laparoscopy. Serum β-human chorionic gonadotropin levels gradually decreased. Thereafter, the patient underwent two cycles of frozen embryo transfer, both of which resulted in chemical pregnancies.Conclusion: This case suggests that gynecologists should pay attention to the possibility of fallopian tube ectopic pregnancy in the distal tubal segment post-tubal ligation.Keywords: distal stump, ectopic pregnancy, tubal ligation, unilateral salpingectomy, in vitro fertilization

Tingting Li,1,2 Wenjing Han,1,2 Xinlu Yang,1 Yu Wang,1 Li Peng,1 Lingwei He,1 Lianjia Hu,1 Jiayuan Liu,1 Min Xia,1 Sheng Wang1,2 1Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Department of Anesthesiology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Sheng Wang, Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17 Lujiang Road, Luyang District, Hefei, Anhui Province, People’s Republic of China, Tel +86 191 5600 7726, Email iamsheng2020@ustc.edu.cnPurpose: This study aimed to explore the effects of different injection rates of propofol on postoperative cognition in elderly patients undergoing laparoscopic inguinal hernia repair.Methods: A total of 180 elderly patients who planned to undergo laparoscopic inguinal hernia repair were randomly divided into three groups: slow injection of propofol (VS-Group, 30 mg kg− 1 h− 1); medium injection of propofol (VM-Group, 100 mg kg− 1 h− 1) or fast injection of propofol (VF-Group, 300 mg kg− 1 h− 1). Propofol was induced by microinfusion pump, and the depth of anesthesia was monitored by bispectral index (BIS). Propofol and remifentanil were continuously infused during anesthesia maintenance and adjusted according to BIS. The primary outcome was the use of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to measure the incidence of postoperative cognitive decline (POCD) in elderly patients on the first and seventh postoperative day. Secondary outcomes included induced dose of propofol, incidence of burst suppression and maximum electroencephalographic (EEG) effect of propofol (BIS-min) during induction.Results: The incidence of POCD on the first and seventh day postoperatively was similar among the three groups (P > 0.05). However, with the increase of propofol injection rate, induced dose of propofol, incidence of burst suppression and BIS-min during induction, the number of patients requiring vasoactive agents were significantly increased (P < 0.001). Multivariate regression analysis showed that the brief duration of burst suppression during induction did not affect the occurrence of POCD, while age and duration of hospitalization were risk factors for POCD.Conclusion: For elderly patients undergoing laparoscopic inguinal hernia repair, lowering the injection rate of propofol (such as 30 mg kg− 1 h− 1) cannot decrease the incidence of early POCD, but reduces induction dose of propofol and use of vasoactive drugs, making the patient’s hemodynamics more stable.Keywords: propofol, injection rate, bispectral index, burst suppression, elderly, postoperative cognitive decline

Lei Guo,1,&ast; Xiangzhao Xu,2,&ast; Rui Qin,1 Yongqiang Shi,1 Wei Xue,3 Ling He,3 Shuqin Ma,3 Yi Chen1 1Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Anesthesiology, The People’s Hospital of Nanchuan, Chongqing, People’s Republic of China; 3Department of Obstetrics, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Chen, Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, 804S Shengli Street, Yinchuan, Ningxia, 750004, People’s Republic of China, Tel +86-951-6743252, Email czzyxgp@163.comBackground: Norepinephrine and phenylephrine are widely used for obstetric anesthesia. Our central objective was to determine the ED (effective dose) 90 and potency ratio of prophylactic norepinephrine and phenylephrine boluses for preventing postspinal anesthesia hypotension during cesarean section.Methods: Patients scheduled for elective cesarean section (n = 80) were randomly allocated to receive prophylactic norepinephrine (NE) or phenylephrine (PE) boluses immediately after induction of spinal anesthesia. An initial dose of NE (3 μg) and PE (37.5 μg) was given to the first patient, and an up-and-down sequential allocation method was used to determine the next dose level according to the responses (the effectiveness for preventing postspinal anesthesia hypotension [defined as SBP < 80% of baseline value]). Primary outcomes were ED90 and the potency ratio of prophylactic norepinephrine and phenylephrine boluses. Secondary outcomes were the incidence of postspinal anesthesia hypotension, severe postspinal anesthesia hypotension, nausea, vomiting, bradycardia, hypertension, umbilical artery blood gas values, and Apgar scores.Results: The ED90 values for prophylactic norepinephrine and phenylephrine boluses were 8.0 μg (95% CI 7.1– 11.0 μg) and 90.9 μg (95% CI 82.0– 123.9 μg), respectively. The estimated relative potency ratio was 11.4:1. The incidence of bradycardia was lower in the NE group (2.5% vs 20%, P = 0.034). Other outcomes were comparable between the two groups.Conclusion: An 8-μg prophylactic bolus of norepinephrine and a 90-μg prophylactic bolus of phenylephrine can effectively prevent postspinal anesthesia hypotension in patients during cesarean section.Keywords: cesarean section, norepinephrine, phenylephrine, postspinal anesthesia hypotension

Wenjun Zhu,&ast; Yaping Tian,&ast; Lin Xiang, Linna Cao, Lirong He Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lirong He, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 18170905103, Fax +86 0791 86311242, Email hlr_ndefy@163.comAbstract: One of the most pressing emerging issues in bacterial resistance is multidrug-resistant Klebsiella pneumoniae. The treatment of K. pneumoniae infections is often problematic because of the lack of available therapeutic options, leading to negative effects on morbidity, mortality, and healthcare-associated costs. Carrimycin is a macrolide antibiotic with good antibacterial effects. In this study, we report a patient diagnosed with multidrug-resistant K. pneumoniae infection who was treated with carrimycin. The patient presented with cough, expectoration, dyspnea, and severe hypoxemia requiring noninvasive ventilation. We successively used a variety of antibiotics, including meropenem, tigecycline, and polymyxin, with unsatisfactory results. Finally, we used carrimycin, and the patient’s condition improved, resulting in hospital discharge. Therefore, for patients with multidrug-resistant K. pneumoniae infection that does not respond to conventional anti-infective treatments, carrimycin can be considered a treatment option.Keywords: carrimycin, Klebsiella pneumoniae, multidrug-resistant

Lihua Huang,1,&ast; Zhanpeng Lu,2,&ast; Xiaoqing Zhou,3 Liuliu He,1 Xiaoyan You,1 Chunmei Chen,1 Chunsheng Zou1 1Department of Clinical Laboratory, The Second Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 2Department of Critical Care,The Eighth Affiliated Hospital of Sun Yat sen University, Shenzhen, People’s Republic of China; 3General Surgery Department, The Second Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua Huang, Department of Clinical Laboratory, The Second Affiliated Hospital of Gannan Medical University, 331 Yingbin Dadao, Xinfeng County, Ganzhou, Jiangxi Province, People’s Republic of China, Tel +86 18970771329, Email huanglihua2022@163.comPurpose: In the anaerobic metabolic pathway, lactate dehydrogenase (LDH) plays an important role in hypoxia, inflammation, and cell damage, making it a potential biomarker for the progression of chronic obstructive pulmonary disease (COPD). We aimed to examine the relationship between LDH levels and all-cause mortality in participants with COPD.Patients and Methods: Data of participants in the US National Health and Nutrition Examination Surveys (NHANES) 2007– 2012 aged ≥ 20 years who underwent spirometry tests were examined, and follow-up mortality data were obtained. According to serum LDH levels, participants with COPD were divided into five groups (59– 111, 112– 123, 124– 135, 136– 150, and 151– 344 U/L). To evaluate whether LDH levels were independently associated with COPD mortality, we used multivariate Cox regression analysis and smooth curve fitting.Results: We included 1320 subjects, 64 with stage III or IV COPD and 541 with stage II COPD. Over a median follow-up of 9.7 years (IQR: 7.8, 11.2), 252 of the 1320 subjects died. The mean LDH level was 132.5 U/L (standard deviation [SD], 27.0). A U-shaped relationship was observed between LDH levels and all-cause mortality. Below and above the inflection point, which was approximately 110 U/L, we found different slopes for the correlation between LDH and all-cause mortality of patients with COPD. Below the threshold, per 1-standard deviation (1SD) increase in LDH resulted in a 68% reduced risk of all-cause mortality (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.13– 0.81, P=0.016); conversely, above the threshold, per 1SD increase in LDH accelerated the risk of all-cause mortality (HR 1.23, 95% CI: 1.08– 1.41, P= 0.002).Conclusion: Using the nationally representative NHANES data, we found a U-shaped association between LDH level and all-cause mortality in participants with COPD. An optimal LDH level of approximately 110 U/L was associated with the lowest risk of all-cause mortality.Keywords: lactate dehydrogenase, pulmonary disease, chronic obstructive, nutrition surveys, nonlinear, threshold

Yan Cao,1 Yingjie Su,2 Cuirong Guo,2 Liudang He,2 Ning Ding2 1Department of Emergency Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, People’s Republic of China; 2Department of Emergency Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Ning Ding, Department of Emergency Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, No. 161 Shaoshan South Road, Changsha, Hunan, 410004, People’s Republic of China, Tel +86731-8566-7935, Email doctordingning@sina.com; doctordingning@163.comObjective: This study aimed to explore the relationship between albumin level with short- and long-term outcomes in sepsis patients admitted in the intensive care unit (ICU) based on a large public database to provide clinical evidence for physicians to make individualized plans of albumin supplementation.Methods: Sepsis patients admitted in the ICU in MIMIC-IV were included. Different models were performed to investigate the relationships between albumin and mortalities of 28-day, 60-day, 180-day and 1-year. Smooth fitting curves were performed.Results: A total of 5357 sepsis patients were included. Mortalities of 28-day, 60-day, 180-day and 1-year were 29.29% (n = 1569), 33.92% (n = 1817), 36.70% (n = 1966) and 37.71% (n = 2020). In the fully adjusted model (adjusted for all potential confounders), with each 1g/dL increment in albumin level, the risk of mortality in 28-day, 60-day, 180-day and 1-year decreased by 39% (OR = 0.61, 95% CI: 0.54– 0.69), 34% (OR = 0.66, 95% CI: 0.59– 0.73), 33% (OR = 0.67, 95% CI: 0.60– 0.75), and 32% (OR = 0.68, 95% CI: 0.61– 0.76), respectively. The non-linear negative relationships between albumin and clinical outcomes were confirmed by smooth fitting curves. The turning point of albumin level was 2.6g/dL for short- and long-term clinical outcomes. When albumin level ≤ 2.6g/dL, with each 1g/dL increment in albumin level, the risk of mortality in 28-day, 60-day, 180-day and 1-year decreased by 59% (OR = 0.41, 95% CI: 0.32– 0.52), 62% (OR = 0.38, 95% CI: 0.30– 0.48), 65% (OR = 0.35, 95% CI: 0.28– 0.45), and 62% (OR = 0.38, 95% CI: 0.29– 0.48), respectively.Conclusion: Albumin level was associated with short- and long-term outcomes in sepsis. Albumin supplementation might be beneficial for septic patients with serum albumin< 2.6g/dL.Keywords: albumin, mortality, inflammation, sepsis, MIMIC-IV

Simin Yang,1,&ast; Lihua He,2,&ast; Ke Li,3,&ast; Xiaoyu Yu,1 Lijun Ni,1 Liang Hu,1 Jian Guo,1 Ewelina Biskup,4,5 Lunxian Tang,3 Wenjuan Wu1 1Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Hospital Infection Management, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Emergency Intensive Care Unit, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Department of Basic and Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 5Department of Internal Medicine, University Hospital of Basel, Basel, Switzerland&ast;These authors contributed equally to this workCorrespondence: Lunxian Tang; Wenjuan Wu, Tel +86-15921155750 ; +86-13386057159, Email 456tlx@163.com; wwj1210@126.comPurpose: To investigate whether rapid active molecular screening and infection prevention and control (IPC) interventions can reduce colonization or infection with carbapenem-resistant Enterobacterales (CRE) in a general emergency intensive care unit (EICU) without enough single-room isolation.Methods: The study was designed as a before-and-after quasi-experiment. Before the experimental period, the ward was rescheduled and the staff were trained. From May 2018 to April 2021, active screening was performed by seminested real-time fluorescent polymerase chain reaction (PCR) detection with rectal swabs from all patients on admission to the EICU, and the results were reported in 1 hour. Other IPC interventions including hand hygiene, contact precautions, patient isolation, environmental disinfection, environment surveillance, monitoring, auditing and feedback were conducted under strict supervision. The patients’ clinical characteristics were collected simultaneously.Results: In this 3-year study, 630 patients were enrolled and 19.84% of the patients were initially colonized or infected with CRE as shown by active molecular screening. The average drug resistance ratio to carbapenem shown by clinical culture detection of Klebsiella pneumoniae (KPN) before the study was performed was 71.43% in EICU. The drug resistance ratio decreased significantly from 75%, 66.67% to 46.67% in the next 3 years (p< 0.05) during which active screening and IPC interventions were strictly executed. While the ratio gaps between EICU and the whole hospital were narrowed from 22.81%, 21.11% to 4.64%. Patients with invasive devices, skin barrier damage, and the recent use of antibiotics on admission were found to have a higher risk of being colonized or infected with CRE (p< 0.05).Conclusion: Active rapid molecular screening and other IPC interventions may significantly reduce CRE nosocomial infections even in wards without enough single-room isolation. The key to reduce the spread of CRE in the EICU is the strict execution of IPC interventions by all medical staff and healthcare workers.Keywords: carbapenem-resistant, Enterobacterales, active screening, infection prevention and control intervention, emergency intensive care unit, nosocomial infection

Xiaoxu Li,1,&ast; Shifang Zhuang,2,&ast; Lin He,2 Shanmei Wang,3 Ming Zhao,1 Xiaodong Lyu4 1Department of Neurosurgery, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China; 2Genskey Medical Technology Co., Ltd, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodong Lyu, Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, 127 Dongming Road, Zhengzhou, 450000, People’s Republic of China, Tel/Fax +8613523417973, Email zlyyxiaodonglyu1268@zzu.edu.cnAbstract: Nocardia brain abscess is relatively rare and generally occurs in immunodeficient patients. Here, we present the first case of brain abscess due to Nocardia brevicatena in an immunocompetent patient, with unknown origin. In this case, a 49-year-old man was admitted to our hospital with limb twitching and complained of a history of intermittent headache. He was diagnosed with brain abscess through brain imaging and cured after craniotomy for abscess excision and targeted antibiotic treatment. Surgical specimens were sent for further detection. The causative organism was identified by weak acid-fast staining, culture and metagenomic next-generation sequencing (mNGS). We hope this case could provide a reference for incoming patients as well as their clinical management.Keywords: brain abscess, Nocardia brevicatena, non-immunocompromised, mNGS, surgical treatment

Jinghan Zhang,1 Fei Yan,2 Wei Zhang,1 Lei He,1 Yi Li,3 Shuai Zheng,1 Yuanyuan Wang,4 Tengfei Yu,1 Lijuan Du,1 Yuanyuan Shen,5 Wen He1 1Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Center for Cell and Gene Circuit Design, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 3Department of Radiology, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 4Department of Ultrasound, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 5National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Bio Medical Engineering, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of ChinaCorrespondence: Yuanyuan Shen; Wen He, Email shenyy@szu.edu.cn; hewen@bjtth.orgBackground: Focused ultrasound (FUS) combined with microbubbles (MBs) has emerged as a potential approach for opening the blood–brain barrier (BBB) for delivering drugs into the brain. However, MBs range in size of microns and thus can hardly extravasate into the brain parenchyma. Recently, growing attention has been paid to gas vesicles (GVs), which are genetically encoded gas-filled nanostructures with protein shells, due to their potential for extravascular targeting in ultrasound imaging and therapy. However, the use of GVs as agents for BBB opening has not yet been investigated.Methods: In this study, GVs were extracted and purified from Halobacterium NRC-1. Ultrasound imaging performance of GVs was assessed in vitro and in vivo. Then, FUS/GVs-mediated BBB opening for small molecular Evans blue or large molecular liposome delivery across the BBB was examined.Results: The results showed a good contrast performance of GVs for brain perfusion ultrasound imaging in vivo. At the acoustic negative pressure of 1.5 MPa, FUS/GVs opened the BBB safely, and effectively enhanced Evans blue and 200-nm liposome delivery into the brain parenchyma.Conclusion: Our study suggests that biosynthetic GVs hold great potential to serve as local BBB-opening agents in the development of new targeted drug delivery strategies for central nervous system disorders.Keywords: gas vesicles, blood–brain barrier, focused ultrasound, drug delivery, nanoparticles

Qingjuan Zuo,1,2 Guorui Zhang,1,3 Lili He,2 Sai Ma,4 Huijuan Ma,5 Jianlong Zhai,6 Zhongli Wang,7 Tingting Zhang,2 Yan Wang,2 Yifang Guo1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Cardiology, the Third Hospital of Shijiazhuang City Affiliated to Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Internal Medicine, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 5Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 6Department of Cardiology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 7Department of Physical Examination Center, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yifang Guo, Department of Geriatric Cardiology, Hebei General Hospital, No. 348, Heping West Road, Xinhua District, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel +86-15100189182, Email guoyifang@hotmail.comPurpose: To investigate the effect of canagliflozin (20 mg/kg) on hepatic steatosis and atherosclerosis, and further to explore its possible mechanism.Methods: Blood glucose, blood lipid, oxidative stress response and inflammatory cytokines were examined by intraperitoneal glucose tolerance test and ELISA assay. HE and Oil Red O staining were used to estimate the extent of hepatic steatosis and atherosclerosis. RNA-seq and qRT-PCR were used to further investigate the potential mechanism. The effects of canagliflozin on autophagy were detected using transmission electron microscopy and Western blotting. The endothelial function-related markers were determined by qRT-PCR.Results: Canagliflozin notably alleviated the elevation in blood glucose and insulin resistance in western diet-fed ApoE-/- mice. In ApoE-/-+Cana group, ApoE-/- mice had lower levels of TG, TC, LDL-C, TNF-α, IL-6, IL-1β, and MCP-1. HE and Oil Red O staining presented that canagliflozin restrained the atherosclerotic plaque development and lipid accumulation. RNA-seq showed that 87 DEGs were relevant to improvement of hepatic steatosis and atherosclerosis by canagliflozin. Among them, CPS1, ASS1, ASL, ARG1, MATLA, GLS2, GOT1, SREBP1, Plin5, Retreg1, and C/EBPβ were verified. KEGG enrichment analysis indicated that DEGs were mainly involved in amino acid metabolism. Besides, we observed that canagliflozin reduced the contents of aspartic acid and citrulline in liver. Western blotting showed that ASS1 and p-AMPK/AMPK was remarkably elevated after administration of canagliflozin. Correspondingly, canagliflozin down-regulated SREBP1, FAS, ACC1, HMGCR, p-mTOR/m-TOR, p-ULK1/ULK1 and p62, but up-regulated CPT1, Beclin 1 and LC3 II/LC3I. TEM showed that canagliflozin reduced the number of lipid droplets and increased the autophagosomes. Moreover, we found that canagliflozin elevated the aortic endothelial function-associated markers including ASS1, ASL and eNOS.Conclusion: Canagliflozin may attenuate hepatic steatosis by improving lipid metabolism, enhancing autophagy, and reducing inflammatory response through ASS1/AMPK pathway. Besides, canagliflozin further effectively improves the aortic endothelial function, thereby suppressing atherosclerosis development.Keywords: canagliflozin, hepatic steatosis, atherosclerosis, RNA-seq, dyslipidemia, inflammatory response, autophagy

Dongyue Ren,1 Lin He,2 Xiaoling Pang1 1Department of Emergency, the Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Good Clinical Practice Institution, the Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Xiaoling Pang, Department of Emergency, the Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan East Road, Huanggu District, Shenyang, 110032, People’s Republic of China, Tel +86-18900913992, Email xlpang@cmu.edu.cnObjective: This study aimed to investigate the association of CLTA-4 gene polymorphism with Type 1 and 2 diabetes mellitus (DM) (T1DM and T2DM) in the Han population of northern China.Methods: A total of 234 Chinese Han DM patients and 187 non-diabetic subjects were included in the study. Two gene polymorphisms of the CLTA-4, including CTLA-4+49A/G (rs231775) and CTLA4-318C/T (rs5742909), were studied using polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) analysis. Chi-square analysis and Student’s t-test were performed to determine the distribution of the gene polymorphism and alleles at the locus of CTLA4-318C/T and CTLA4+49A/G among T1DM and T2DM patients with or without diabetic ketosis (DK), diabetic nephropathy (DN) or autoantibodies (Ab).Results: Our results indicated that the distribution frequencies of genotypes and alleles at the CTLA-4+49A/G and CTLA4-318C/T loci of T1DM patients were not significantly different from those of the controls. However, the distribution frequencies of genotypes and alleles at the CTLA-4+49A/G loci of T2DM patients were significantly different from the controls (P=0.024 for genotypes and P=0.004 for A and G alleles). Besides, the A and G alleles at the CTLA4-318C/T loci of T2DM DK+ patients showed significantly different distribution frequencies compared to those of the T2DM DK patients (P=0.001).Conclusion: Our data suggest that the gene polymorphisms of CTLA-4, including CTLA-4+49A/G and CTLA4-318C/T, are important predictors of DM. CTLA-4 may be a susceptibility gene for T2DM. Patients with T2DM carrying the T allele at the CTLA4-318 C/T locus are more predisposed to diabetic ketosis.Keywords: diabetes mellitus, gene polymorphism, CTLA-4, diabetic ketosis, diabetic nephropathy, autoantibodies

Po-Yi Paul Su,1 Lingyi Zhang,1,2 Liangliang He,1,3 Na Zhao,1 Zhonghui Guan1 1Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, USA; 2Department of Anesthesiology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Pain Management, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zhonghui Guan, Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, USA, Tel +415.885.7246, Fax +415.885.7575, Email zhonghui.guan@ucsf.eduAbstract: Chronic pain remains a public health problem and contributes to the ongoing opioid epidemic. Current pain management therapies still leave many patients with poorly controlled pain, thus new or improved treatments are desperately needed. One major challenge in pain research is the translation of preclinical findings into effective clinical practice. The local neuroimmune interface plays an important role in the initiation and maintenance of chronic pain and is therefore a promising target for novel therapeutic development. Neurons interface with immune and immunocompetent cells in many distinct microenvironments along the nociceptive circuitry. The local neuroimmune interface can modulate the activity and property of the neurons to affect peripheral and central sensitization. In this review, we highlight a specific subset of many neuroimmune interfaces. In the central nervous system, we examine the interface between neurons and microglia, astrocytes, and T lymphocytes. In the periphery, we profile the interface between neurons in the dorsal root ganglion with T lymphocytes, satellite glial cells, and macrophages. To bridge the gap between preclinical research and clinical practice, we review the preclinical studies of each neuroimmune interface, discuss current clinical treatments in pain medicine that may exert its action at the neuroimmune interface, and highlight opportunities for future clinical research efforts.Keywords: neuroimmune, chronic pain, glial cells, macrophage, T-cells

Xiao Fan,1 Qi Li,2 Tingsong Li,3 Xiaoyan He,4 Chuan Feng,1 Bin Qin,1 Ye Xu,1 Ling He1 1Department of Radiology, the Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 2Department of Radiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Neurology, the Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 4Center for Clinical Molecular Medicine, the Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of ChinaCorrespondence: Ling He, Department of Radiology, the Children’s Hospital of Chongqing Medical University, No. 136 Zhongshan Er Road, Yuzhong District, Chongqing, People’s Republic of China, Tel +86 13983399138, Email doctorheling@yeah.netBackground: Studies suggested that myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are an isolated group of diseases that are different from multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). The proportion of individuals with MOGAD is higher among children. However, limited data are available on autoimmune antibodies and neuroimaging features in children with MOGAD.Methods: This study retrospectively reviewed 42 children with MOGAD. The clinical, neuroradiological, and cerebrospinal fluid data were compared according to courses and radiological results.Results: Of the 42 patients, 28 suffered a monophasic course and 14 had a relapsing course. During the follow-up magnetic resonance imaging (MRI), 21 patients had a well-resolved brain condition and another 21 patients showed slight improvement with marked residuals. Most patients with relapse had cortical lesions and a leukodystrophy-like MRI pattern (all p < 0.05). Children with poor radiological outcomes have confluent and hazy lesions that involve both cortexes, white matter lesion of > 2 cm, and a leukodystrophy-like pattern, as well as cerebral lesions with T1 hypointensity or enhancement and spinal lesions (all p < 0.05). The multivariable logistic regression analysis used the aforementioned differential features and showed cerebral enhancement and a leukodystrophy-like pattern as the most effective variations associated with poor radiological outcomes of MOGAD with an area under the curve of 0.875.Conclusion: MOGAD in children have some radiological features suggestive of clinical courses and radiological outcomes. A good understanding of these differential features can help to give early warnings of disease recurrence or poor radiological improvement and develop subsequent therapeutic strategies.Keywords: myelin oligodendrocyte glycoprotein, encephalomyelitis, magnetic resonance imaging, demyelination, central nervous system

Jing Wen,1,2 Liu He,1 Xin Du,1 Chang-Sheng Ma1 1Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital; National Clinical Research Center for Cardiovascular Diseases, Beijing, People’s Republic of China; 2Department of Geriatrics, Beijing Fengtai Hospital, Beijing, People’s Republic of ChinaCorrespondence: Chang-Sheng Ma; Xin Du, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Beijing Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-10-84005363, Fax +86-10-84005361, Email chshma@vip.sina.com; duxinheart@sina.comBackground: It is uncertain whether the effect of hyperglycemia on mortality among patients with acute coronary syndrome (ACS) could be adjusted by other modifiable risk factors. Greater body mass index (BMI) might enhance the effect of fasting blood glucose (FPG) on cardiovascular mortality in patients with ACS.Methods: We retrospectively enrolled patients admitted for ACS from 2008 to 2017 in Beijing and divided them into three BMI groups (normal weight ≤ 25 kg/m2, overweight 25– 29.9 kg/m2, obese ≥ 30 kg/m2). The relationships between the blood glucose levels and all-cause or cardiovascular mortalities and their heterogeneities across the groups were analyzed using Cox regression models.Results: A total of 8,086 patients were enrolled, with 746 all-cause and 496 cardiovascular mortalities recorded during the follow-up period. Each 1 mmol/L increase in FPG was associated with an increased risk of all-cause mortality across all groups (adjusted hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.02– 1.09 for normal weight patients; adjusted HR: 1.09, 95% CI: 1.05– 1.13 for overweight patients; adjusted HR: 1.12, 95% CI: 1.03– 1.22 for obese patients), and was associated with an increased risk of cardiovascular mortality among overweight (adjusted HR: 1.10, 95% CI: 1.05– 1.14) and obese patients (adjusted HR: 1.15, 95% CI: 1.04– 1.26), which was greater (p for heterogeneity = 0.006) than the association in the normal weight group (adjusted HR: 1.03, 95% CI: 0.99– 1.08). Similar results were found among 2,537 patients with ACS diagnosed with diabetes.Conclusion: Greater BMI enhances the effect of FPG on cardiovascular mortality among patients with ACS.Keywords: acute coronary syndrome, mortality, fasting plasma glucose, body mass index

Fei Peng,1 Jing Liu,1,2 Yujun Zhang,1,2 Guoyan Zhao,1,2 Deying Gong,1,2 Liu He,1,2 Wensheng Zhang,1,2 Feng Qiu1,2 1Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Feng Qiu; Wensheng Zhang, Email fengqiu@scu.edu.cn; zhang_ws@scu.edu.cnIntroduction: Ropivacaine as a conventional local anesthetic has been used more and more frequently in the treatment of postoperative pain, but its analgesic effect can only last for several hours. In order to fulfill the clinic requirement for long-term analgesia, a long-acting ropivacaine nanocrystal formulation was fabricated through the interaction between ropivacaine and a self-assembling peptide.Methods: Transmission electron microscopy, dynamic light scattering, circular dichroism and fluorescence spectrometry were used to examine the structural changes caused by the interaction between ropivacaine and the peptide. Scanning electron microscopy, dynamic light scattering, Fourier transform infrared spectrometry, X-ray diffraction and optical microscopy were used to characterize the ropivacaine-peptide nanocrystal. In vitro drug release and pharmacokinetics study were conducted to evaluate the slow-release profile of the nanocrystal formulation. A rodent cutaneous trunci muscle reflex model was used to evaluate the nociceptive blockade effects, and histological analysis was used to evaluate the local toxicity. A rodent plantar incisional pain model was used to evaluate the analgesic effect.Results: Soluble ropivacaine monomers interacted with the Q11 peptide through π-π stacking and remolded its self-assembling structure, leading to the formation of drug/peptide nanoparticles which could be mineralized to form drug/peptide nanocrystals by adjusting the pH. Under physiological condition, the nanocrystals could release free ropivacaine slowly. As evaluated in rodent models, the anesthetic and analgesic effects of this formulation were significantly extended without causing toxicity.Conclusion: Based on the interaction between ropivacaine and Q11, a controllable biomineralization process could be induced to obtain homogeneous nanocrystals, which could be used as an injectable long-acting analgesic formulation. This crystallization strategy utilizing the peptide-drug interaction also provided a promising pathway to fabricate long-acting formulations for many other small molecular drugs.Keywords: self-assembling peptide, nanocrystal, local anesthetics, π-π stacking, slow release, long-acting analgesia

Mark W Hooper,1 Liang He2 1MedCryst Therapeutics Ltd, Centre for Innovation & Enterprise, Oxford University Begbroke Science Park, Oxford, OX5 1PF, UK; 2PharmHe, Chertsey, UKCorrespondence: Mark W Hooper, MedCryst Therapeutics Ltd, Centre for Innovation & Enterprise, Oxford University Begbroke Science Park, Oxford, OX5 1PF, UK, Tel +44 7468 902851, Email mark@medcryst.comPurpose: Gout is caused by crystals of monosodium urate (MSU) in the joints. Topical nonsteroidal anti-inflammatory drug products (NSAIDs) are often the first-choice immediate treatment. This study examined the effect of commercially available and newly developed transdermal NSAID products on the solubility of MSU in a physiologically relevant system, alongside the efficacy of transdermal NSAID delivery.Materials and Methods: Drug permeability of 7 commercially available topical NSAID products, alongside 3 newly developed “Gout Buster” products, was evaluated in vitro using pig’s ear skin in Franz diffusion cells. The standard Franz cell experimental protocol was adapted to include assessment of MSU solubility in phosphate buffered saline for each product. Some materials were also tested via direct solubility studies.Results: The amount of drug delivered transdermally varied significantly between different formulations, with the best ibuprofen delivery being ∼ 5 times higher than the lowest, and best diclofenac delivery being ∼ 3.5 times higher than the lowest. Changes in formulations and the drug concentration in the product both affected the amount of drug delivered. Overall ibuprofen permeation was higher than diclofenac. The commercially available products showed little or no effect on the MSU solubility (99– 103% vs control). The Gout Buster products showed significant improvement in the MSU solubility after permeation through skin (120– 126%). Increased sodium levels reduced the solubility of MSU in direct solubility studies.Conclusion: In these trials, the Gout Buster products showed significantly improved permeation of both ibuprofen and diclofenac over the commercial products at similar drug concentrations, and showed significant improvement for MSU solubility. Increased sodium levels reduced the solubility of MSU and could cause more crystallisation in vivo. Therefore, topical NSAID products with the Gout Buster formulation may have the best likelihood of both reducing inflammation and helping re-dissolve the MSU crystals that cause gout.Keywords: Franz-cell experiments, nonsteroidal anti-inflammatory drug, in vitro study, Gout Buster

Shuo Wang,1 Biyu Lei,1 E Zhang,2 Puyang Gong,1 Jian Gu,1 Lili He,1 Lu Han,1 Zhixiang Yuan1 1College of Pharmacy, Southwest Minzu University, Chengdu, 610041, Sichuan, People’s Republic of China; 2Department of Basic Sciences, Officers College of People’s Armed Police, Chengdu, Sichuan, 610213, People’s Republic of ChinaCorrespondence: Zhixiang Yuan; Lu Han, Email zhixiang-yuan@hotmail.com; lunahan@swun.edu.cnAbstract: Inflammation is a beneficial and physiological process, but there are a number of inflammatory diseases which have detrimental effects on the body. In addition, the drugs used to treat inflammation have toxic side effects when used over a long period of time. Mesenchymal stem cells (MSCs) are pluripotent stem cells that can be isolated from a variety of tissues and can be differentiate into diverse cell types under appropriate conditions. They also exhibit noteworthy anti-inflammatory properties, providing new options for the treatment of inflammatory diseases. The therapeutic potential of MSCs is currently being investigated for various inflammatory diseases, such as kidney injury, lung injury, osteoarthritis (OA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). MSCs can perform multiple functions, including immunomodulation, homing, and differentiation, to enable damaged tissues to form a balanced inflammatory and regenerative microenvironment under severe inflammatory conditions. In addition, accumulated evidence indicates that exosomes from extracellular vesicles of MSCs (MSC-Exos) play an extraordinary role, mainly by transferring their components to recipient cells. In this review, we summarize the mechanism and clinical trials of MSCs and MSC-Exos in various inflammatory diseases in detail, with a view to contributing to the treatment of MSCs and MSC-Exos in inflammatory diseases.Keywords: mesenchymal stem cells, exosome, inflammatory diseases, clinic data, drug delivery, targeted therapy

Quangang Yuan,1,&ast; Jiang Guo,2,&ast; Long He,1 Qiulin Chen,1 Xianhong Zou,1 Siming Yang,1 Zhenyang Zhang1 1Department of Urology, Chongqing Hechuan Hongren Hospital, Chongqing, 401520, People’s Republic of China; 2Department of Urology, Anyue People’s Hospital of Ziyang City, Ziyang City, Sichuan Province, 642300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenyang Zhang, Tel/Fax +86 23-67710675, Email urinaryzhang@163.comObjective: To investigate the risk factors, pathogen distribution, and drug resistance of systemic inflammatory response syndrome (SIRS) after holmium laser ureteroscopic lithotripsy for impacted ureteral calculi (HLULIUC).Patients and Methods: The clinical data of 293 patients with HLULIUC in our hospital from October 2017 to February 2021 were retrospectively collected, including age, BMI, stone size, operation time, urine routine, urine culture, basic illness, complete blood count, liver and kidney function, etc. Patients were divided into SIRS and non-SIRS groups according to whether they had SIRS or not. Then the differences in clinical data, blood and urine bacterial culture results, and drug resistance between the two groups were analyzed.Results: The incidence of SIRS after HLULIUC was 17.75%. Logistic regression analysis showed that the risk factors of SIRS after HLULIUC include ureteral calculi≥ 1cm (OR=2.839, 95% CI=1.341– 5.647, P=0.021), long operation time (OR=4.534, 95% CI=2.597– 12.751, P=0.017), diabetes mellitus (OR=3.137, 95% CI=1.142– 7.319, P=0.012), increased preoperative C-reactive protein (OR=1.864, 95% CI=1.05– 4.347, P=0.032), and positive urine leukocytes (OR=3.514, 95% CI=1.7237– 9.734, P=0.007) and culture (OR=6.034, 95% CI=3.097– 15.751, P< 0.001) before operation. The main pathogens causing SIRS after HLULIUC were Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa. The pathogenic bacteria are sensitive to drugs including piperacillin/tazobactam, meropenem, tigecycline, teicoplanin, vancomycin, and imipenem. The resistance rates to quinolones (such as levofloxacin) and to the second- and third-generations of cephalosporins were as high as 52.94%– 90.19%.Conclusion: Ureteral calculi≥ 1cm, long operation time, diabetes, increased C-reactive protein, and preoperative positive urine leukocytes and culture are independent risk factors of SIRS after HLULIUC. Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa are the main pathogenic bacteria for SIRS after HLULIUC. The pathogenic bacteria are sensitive to drugs, including piperacillin/tazobactam, meropenem, tigecycline, teicoplanin, vancomycin, and imipenem.Keywords: impacted ureteral calculi, holmium laser ureteroscopic lithotripsy, systemic inflammatory response syndrome, risk factors, drug resistance, sensitivity

Mengqian Ge,1 Jinghui zhang,2 Simiao Chen,2 Yanfen Huang,2 Weiyan Chen,3 Lan He,1 Yuyan Zhang2 1The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of ChinaCorrespondence: Yuyan Zhang, Email yannoo7376@sina.comAbstract: Alzheimer’s disease (AD) is a neurodegenerative disease associated with senile plaques (SP) and neurofibrillary tangles (NFTs) in the brain. With aging of the population, AD has become the most common form of dementia. However, the mechanisms leading to AD are still under investigation, and there are currently no specific drugs for its treatment. Therefore, further study on the pathogenesis of AD to develop new drugs for AD treatment remains a top priority. Several studies have suggested that intracellular calcium homeostasis is dysregulated in AD, and this has been implicated in the deposition of amyloid β (Aβ), hyperphosphorylation of tau protein, abnormal synaptic plasticity, and apoptosis, all of which are involved in the occurrence and development of AD. In addition, some based on pathways linking calcium homeostasis and AD have achieved results in AD treatment. This review comprehensively explores the relationship between calcium homeostasis and the pathogenesis of AD to provide a theoretical basis for the future exploration of AD and the development of novel therapeutic drugs.Keywords: calcium homeostasis, Aβ, tau, apoptosis, synaptic plasticity, therapy

Ye Hong,1 Ping Duan,2 Lang He,3 Qing Li,1 Yueyun Chen,1 Peipei Wang,1 Yang Fu,1 Ting Liu,1 Zhenyu Ding1 1Department of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China; 2Department of Oncology, Cheng Du First People’s Hospital, Chengdu, People’s Republic of China; 3Department of Oncology, The Fifth People’s Hospital Affiliated to Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Zhenyu Ding, Department of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People’s Republic of China, Tel +86 28 8542 2562, Fax +86 28 8516 4059, Email dingzhenyu@scu.edu.cnBackground and Purpose: Leptomeningeal metastases (LM) is the end-event of lung cancer and the prognosis is dismal. Few studies explored the prognostic performance of systematic immunological levels in lung cancer patients with LM. Our study aimed to explore the possible relationship between the prognosis of LM and systematic immunological level and other clinical characteristics.Methods: This retrospective, multi-institutional, observational study was conducted in 4 tertiary centers in China. Patients were screened from January 2009 to May 2019. Patients with radiographically or histologically confirmed LM were enrolled. The data of systematic immunological level and other clinical characteristics of each patient were extracted and statistically analyzed to establish a prognostic model based on statistical analysis results. The predictive accuracy and discriminative capability of the model were evaluated by the calibration curve and concordance index (C-index).Results: A total of 109 patients were enrolled in the study. Patients with adenocarcinoma, tumors harboring EGFR mutation, at their age of 50– 59, with either bone, brain, or lung metastases, were enriched in this cohort. The median overall survival (OS) was 20.4 months (95% CI: 15.2– 25.6). Cox univariate and multivariate analysis revealed better PS (0– 1), no distant lymph nodes metastasis (DLNM), simultaneous diagnosis of lung cancer and leptomeningeal metastasis (SDLL), and lower neutrophil to lymphocyte ratio (NLR), were associated with better OS. Based on these independent prognostic variables, a prognostic nomogram model with a C-index for OS prediction of 0.71, was constructed. The actual probability of survival at 1-, 2- and 3-year showed good concordance with the prediction curve of our nomogram.Conclusion: The systematic immunological level was an independent prognostic factor of lung cancer patients with LM. The prognostic model based on statistical analysis had a good ability to predict the OS of patients.Keywords: leptomeningeal metastases, lung cancer, prognosis, survival, nomogram model

Numerous high-accuracy neural networks for object detection have been proposed in recent years. Creating a specific training dataset seems to be the main obstacle in putting them into practice. This paper aims to overcome this obstacle and proposes an automatic dataset creation method. This method first extracts objects from the source images and then combines them as synthetic images. These synthetic images are annotated automatically using the data flow in the process and can be used directly for training. To the best of our knowledge, this is the first automatic dataset creation method for object detection tasks. In addition, the adaptive object extraction method and created natural synthetic images make the proposed method maintain strong adaptation and generalization ability. To validate the feasibility, a dataset that includes 44 categories of objects is created for the object detection task in a vending supermarket. Under the strictest metric $AP_{75} $ , both the trained EfficientDet and YOLOv4 achieve higher than 95% in accuracy on the common difficulty testing set and higher than 90% in accuracy on the high difficulty testing set.

Li He,1,&ast; Zhi Fu,2,&ast; Menglong Wang,2 Xin Wang,1 Lu Wang,1 Guangming Li,2 Dongdong Lin2 1Department of Intensive Care Unit, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangming Li; Dongdong LinDepartment of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of ChinaTel +86 10 83997733; Tel/Fax +86 10 83997733Email gm_drli@163.com; dongdlin01@163.comObjective: To evaluate and explore the effectiveness of the new prevention and control measures for the donor-derived infection (DDI) associated with CRO after liver transplantation.Methods: The data of 120 organ donors and recipients from January 2018 to May 2020 were retrospectively analyzed at The Liver Transplantation Center of Beijing Youan Hospital, Capital Medical University, to investigate the epidemiological status of CRO in donors. The cases were divided into two groups. The implemented group was treated according to the execution of a clustered CRO prevention and control measure based on active screening combined with early initiation of prophylactic/therapeutic administration of antibiotics. The effectiveness of the prevention and control measures was evaluated by comparing the length of postoperative ICU stay, total postoperative length of hospital stay, duration of ventilator use, duration of restricted antibiotics use, the incidence of DDI, incidence and composition distribution of DDI-related CRO, and incidence of severe DDI-relevant adverse events between the two groups.Results: There was a high detection rate of 39.32% (105 strains) of drug-resistant bacteria in the donors. Fifty-six strains of CRO were detected. Participants in group B, which implemented the new prevention and control measures, were transferred out of the ICU sooner (P = 0.023), used fewer restrictive antibiotics (P = 0.003), and were discharged more quickly (P = 0.013) than those in group A. Postoperative DDI incidences (P = 0.113) and severe DDI-related adverse events were not statistically different between the two groups (P = 0.062). CR-Kp-related DDI was less common in group B (P = 0.021).Conclusion: The situation of donor-derived drug-resistant bacterial infections remains critical. The clustered prevention and control measures for CRO based on active screening combined with early initiation of prophylactic/therapeutic application of antibiotics would be beneficial.Keywords: organ donation, liver transplantation, drug-resistant bacteria, epidemiology, carbapenem-resistant Enterobacteriaceae, active screening, novel β-lactamase inhibitors

Ruolan Li,&ast; Feng Lu,&ast; Xue Sun, Liying He, HuXinyue Duan, Wei Peng, ChunJie Wu State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Peng; ChunJie Wu Tel/Fax +86-28-61801001Email pengwei@cdutcm.edu.cn; wucjcdtcm@163.comPurpose: Hydroxy-α-sanshool (HAS) improves cognitive dysfunction, but its structural instability has limited its clinical application. The present study was conducted to investigate the optimal formulation of hydroxy-α-sanshool liposomes (HAS-LPs) and its effect on ameliorating learning and memory disorders in an Alzheimer’s disease (AD) model.Methods: In this study, HAS was prepared as HAS-LP using a thin film dispersion method. After selecting the optimal preparation conditions, HAS-LP was characterized using transmission electron microscopy (TEM) and by measuring the zeta potential, particle size, and in vitro drug release. Next, evaluated the effect of HAS-LP on the rat nasal mucosa and then applied it to AD mice. By performing behaviour experiments, pathological test and related pharmacokinetic parameters, we explored its effect on attenuating learning and memory impairment in mice.Results: When the mass ratio of HAS:cholesterol:soybean lecithin was 1:4:16 and 15 mL of ultrapure water were added, the highest encapsulation efficiency and drug loading were obtained. HAS-LP had a particle size of 181.77 nm, a polydispersity index of 0.207 and a zeta potential of − 53.8 mV, and it remained stable at 25 °C for 1 week and 4 °C for 8 weeks. Moreover, HAS-LP exhibited slow drug release and was highly consistent with the Higuchi release model. HAS-LP was not significantly toxic to the nasal mucosa and effectively alleviated D-galactose-induced learning memory deficits and protected mouse hippocampal neuronal cells. HAS-LP was highly enriched in plasma and brain tissue after administration via the nasal route and obtained some ability to target the brain.Conclusion: HAS encapsulated in soybean lecithin and cholesterol was successfully developed, suggesting that treatment with the nanoparticles might reverse some AD symptoms. Therefore, these nanoparticles might be used as promising new candidates for the delivery of HAS to treat AD.Keywords: hydroxy-α-sanshool, intranasal liposome, Alzheimer’s disease

Cong Su,1,&ast; Ting Wu,2,&ast; Bao Meng,2 Chengcheng Yue,2 Yating Sun,2 Lingling He,2 Tingting Bian,2 Yanyan Liu,3,4 Ying Huang,5 Yanhu Lan,4 Jiabin Li2– 4,6 1Department of Infection Management, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Anhui Center for Surveillance of Bacterial Resistance, Hefei, People’s Republic of China; 4Institute of Bacterial Resistance, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 6Department of Infectious Diseases, The Chaohu Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiabin LiDepartment of Infectious Diseases, The First Affiliated Hospital and the Chaohu Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, People’s Republic of ChinaEmail lijiabin@ahmu.edu.cnYanhu LanInstitute of Bacterial Resistance, Anhui Medical University, Jixi Road 218, Hefei, 230022, People’s Republic of ChinaEmail zixinhu@163.comBackground: Klebsiella pneumoniae (K. pneumoniae) causes community-acquired and hospital-acquired pneumonia. The mortality rates of invasive infections caused by hypervirulent K. pneumoniae (HvKP) are extremely high. However, the microbiological characteristics and clinical manifestations of K. pneumoniae in AnHui province still remain unclear.Purpose: To show the high prevalence of HvKP infections regarding clinical characteristics and antimicrobial resistance in Anhui province.Patients and Methods: A retrospective analysis was conducted to study the clinical data of 115 strains of K. pneumoniae from July 2019 to March 2020 in The First Affiliated Hospital of AnHui Medical University. The virulence genes, capsular types, carbapenemase genes, and molecular subtypes of these hypervirulent isolates were detected.Results: Overall, 59.1% (68/115) cases were HvKP infections, mainly from the department of intensive care unit (ICU, n=14, 20.6%) and the department of respiratory and critical care (n=13, 19.1%). K2 was the most prevalent capsular serotype (n=26), followed by K1 (n=21). The results of MLST identification of 68 strains showed that ST23 (n=15, 22.1%) was the most common type of ST, followed by ST11 and ST65 (n=12, 17.6%), ST86 (n=9, 13.2%), and ST412 (n=6, 8.8%). Among 68 hvKP strains, 12 isolates were carbapenem resistant, and all except two harboured KPC.Conclusion: The high incidence of carbapenemase producing HvKP in the Anhui province, especially the higher mortality of HvKP, should be paid more attention. Meanwhile, epidemiological surveillance and clinical treatment strategies should be continuously determined and implemented.Keywords: Klebsiella pneumoniae, virulence genes, capsular types, antimicrobial resistance

Wenjun Wang, Lirong He, Chao Ouyang, Chong Chen, Xiaofeng Xu, Xiaoqun Ye Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of ChinaCorrespondence: Xiaoqun YeDepartment of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel +86-13870807068Fax +86-7916300507Email 511201663@qq.comBackground: Obstructive sleep apnea (OSA) is associated with an increased risk of lung cancer. This study aimed to identify key common genes in OSA and lung cancer and explore their prognostic value in lung cancer.Materials and Methods: Transcriptome data of OSA and lung cancer were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database, respectively. Genes associated with OSA and lung cancer were screened by weighted gene co-expression network analysis (WGCNA). Univariate and multivariate Cox regression algorithms were applied to identify key genes and construct the risk score model. Receiver operating characteristic (ROC) curves and a nomogram were performed to evaluate the prognostic value of the risk score. The screened key genes and their roles in prognosis were validated by GEO (GSE30219) analysis.Results: A total of 104 common genes were screened in OSA and lung cancer by WGCNA. Modulator of apoptosis 1 (MOAP1), chromobox 7 (CBX7), platelet-derived growth factor subunit B (PDGFB), and mitogen-activated protein kinase 3 (MAP2K3) were identified as key genes by univariate and then multivariate Cox regression analyses. The risk score model was constructed on the basis of four gene signatures. ROC curves and the nomogram showed that the risk score had a high accuracy in predicting the survival of patients with lung cancer. In addition, the result of multivariate Cox regression analysis indicated that the risk score was an independent prognostic factor in lung cancer.Conclusion: This study constructed a unique model for predicting the prognosis of lung cancer patients on the basis of four genes common to OSA and lung cancer. These genes may also serve as candidate genes to improve our knowledge about the underlying mechanism of OSA that leads to an increased risk of lung cancer at the genetic level.Keywords: lung cancer, obstructive sleep apnea, OSA, weighted gene co-expression network analysis, WGCNA, lung cancer prognosis

Hongmei Zhong,1– 4 Guilin Zeng,2– 4 Lang He2– 4 1Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan Province, People’s Republic of China; 2Department of Oncology, The Fifth People’s Hospital of Chengdu, Chengdu, 611130, Sichuan Province, People’s Republic of China; 3The Fifth People’s Hospital Affiliated to Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, Sichuan Province, People’s Republic of China; 4Chengdu Cancer Prevention and Treatment Institute, Chengdu, 611130, Sichuan Province, People’s Republic of ChinaCorrespondence: Lang HeDepartment of Oncology, The Fifth People’s Hospital of Chengdu, The Fifth People’s Hospital Affiliated to Chengdu University of Traditional Chinese Medicine, Chengdu Cancer Prevention and Treatment Institute, Chengdu, 611130, Sichuan Province, People’s Republic of ChinaTel +86 15182457840Email czyhelang@163.comBackground: Long noncoding RNA (LncRNA) has been shown to mediate the development of human malignancies. However, data on its role in breast cancer remains scant. We aimed to evaluate the prognostic potential of lncRNAs in breast cancer.Methods: We downloaded data on breast cancer patients from The Cancer Genome Atlas (TCGA) database. Tissues were obtained from The Fifth People’s Hospital of Chengdu. We then used the DESeq2 package to profile the expression of the lncRNAs between the patients and normal samples. Besides, we performed prognosis and survival analysis using survival tools in R package. We then assayed the role of the differentially expressed lncRNAs, AC012213.3 (ENSG00000266289), in cancer cell lines. Quantitative real-time PCR and Western blot analysis were performed to evaluate the expression of the gene in the cell lines and then assessed its role in the progression of breast cancer using cell proliferation (CCK8 and colony formation assays), migration, invasion (transwell and wound-healing assays) and apoptotic (flow cytometry) assays.Results: Our data showed high expression of lncRNA AC012213.3 in breast cancer tissues and cell lines. The high expression of the AC012213.3 was associated with the worse prognosis and clinical features. Besides, in vitro assays demonstrated that downregulation of AC012213.3 suppresses the proliferation and invasion of breast cancer cells. Further analysis showed that RAD54B is a downstream AC012213.3 target gene and was upregulated in breast cancer. Interestingly, RAD54B expression was associated with shorter survival in breast cancer. In addition, AC012213.3 was shown to facilitate breast cancer progression through the RAD54B/PI3K/AKT axis.Conclusion: Taken together, our data demonstrated that lncRNA AC012213.3 is upregulated in breast cancer and could enhance breast cancer progression through RAD54B/PI3K/AKT axis.Keywords: lncRNA, AC012213.3, breast cancer, PI3K