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Chang-Sheng Ma,1,2,* Ya-Ping Ma,1,3,* Bo Han,1,2,* Wan-Li Duan,1 Shu-Chen Meng,1 Min Bai,1 Hao Dong,1 Li-Ying Zhang,1 Meng-Yuan Duan,1,2 Jing Liu,1 Ai-Jun Deng,2 Mao-Tao He1,2 1Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China; 3Department of Pathology, The 942Hospital of the People’s Liberation Army Joint Logistic Support Force, Yinchuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Tao He, Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China, Tel +86-18209617186, Fax +86-0536-3081201, Email hemaotao@sdsmu.edu.cn Ai-Jun Deng, Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China, Email dengaijun@hotmail.comPurpose: Ischemic stroke is a refractory disease wherein the reperfusion injury caused by sudden restoration of blood supply is the main cause of increased mortality and disability. However, current therapeutic strategies for the inflammatory response induced by cerebral ischemia-reperfusion (I/R) injury are unsatisfactory. This study aimed to develop a functional nanoparticle (MM/ANPs) comprising apelin-13 (APNs) encapsulated in macrophage membranes (MM) modified with distearoyl phosphatidylethanolamine-polyethylene glycol-RVG29 (DSPE-PEG-RVG29) to achieve targeted therapy against ischemic stroke.Methods: MM were extracted from RAW264.7. PLGA was dissolved in dichloromethane, while Apelin-13 was dissolved in water, and CY5.5 was dissolved in dichloromethane. The precipitate was washed twice with ultrapure water and then resuspended in 10 mL to obtain an aqueous solution of PLGA nanoparticles. Subsequently, the cell membrane was evenly dispersed homogeneously and mixed with PLGA-COOH at a mass ratio of 1:1 for the hybrid ultrasound. DSPE-PEG-RVG29 was added and incubated for 1 h to obtain MM/ANPs.Results: In this study, we developed a functional nanoparticle delivery system (MM/ANPs) that utilizes macrophage membranes coated with DSPE-PEG-RVG29 peptide to efficiently deliver Apelin-13 to inflammatory areas using ischemic stroke therapy. MM/ANPs effectively cross the blood-brain barrier and selectively accumulate in ischemic and inflamed areas. In a mouse I/R injury model, these nanoparticles significantly improved neurological scores and reduced infarct volume. Apelin-13 is gradually released from the MM/ANPs, inhibiting NLRP3 inflammasome assembly by enhancing sirtuin 3 (SIRT3) activity, which suppresses the inflammatory response and pyroptosis. The positive regulation of SIRT3 further inhibits the NLRP3-mediated inflammation, showing the clinical potential of these nanoparticles for ischemic stroke treatment. The biocompatibility and safety of MM/ANPs were confirmed through in vitro cytotoxicity tests, blood-brain barrier permeability tests, biosafety evaluations, and blood compatibility studies.Conclusion: MM/ANPs offer a highly promising approach to achieve ischemic stroke-targeted therapy inhibiting NLRP3 inflammasome-mediated pyroptosis. Keywords: apelin-13, cerebral ischemia-reperfusion injury, macrophage membrane, ischemic stroke therapy, pyroptosis

Menghan Yu,1 Xiaoshu Fu,1 Yanli Zhu,2 Miao Li,3 Min Wu,1 Entong Zhou,1 Hanwen Dong,1 Likun Wang,1 Ruoxi Wang,4 Fang Liu,2 Chunlai Jiang,1 Xiangwei Kong,5 Weiheng Su1,6 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2People’s Hospital of Jiangyuan District, Baishan, Jilin Province, People’s Republic of China; 3Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China; 4School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 5Changchun University of Science and Technology, Changchun, People’s Republic of China; 6Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Weiheng Su, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China, Email suweiheng@jlu.edu.cn Xiangwei Kong, Changchun University of Science and Technology, Changchun, People’s Republic of China, Email tenbpro@163.comPurpose: Tick-borne encephalitis virus (TBEV) infections result in severe central nervous system diseases in humans across Asia and Europe. In China, cases of tick-borne encephalitis are primarily caused by the Far East subtype of TBEV, which exhibits a distinct disease course compared to other extensively studied subtypes. However, there is limited knowledge regarding the nucleic acid and serological diagnostic characteristics of patients infected with the TBEV in China, which is the focus of investigation in the present study.Methods: This study established a TaqMan qPCR approach to detect TBEV RNA in the serum with optimal specificity, sensitivity, and precision. Using TaqMan qPCR and ELISA assay for TBEV IgM detection, serum samples from 63 hospitalized patients bitten by ticks in Northeast China were investigated for diagnostic characteristics.Results: Twenty-five patients were positive for viral RNA; nineteen patients were positive for IgM, and nine were positive for both viral RNA and IgM. Through comparative analysis, TBEV RNA copies were negatively correlated with the virus incubation period. IgM levels were positively correlated with the clinical symptom scores of patients. The severity of clinical symptoms and the length after the tick bite could be used to predict the IgM occurrence. Furthermore, IgM levels and viral RNA copies were not correlated in double-positive patients.Conclusion: Both nucleic acid and serological detection methods exhibited distinct windows for detecting TBEV infection, with some overlap, and were associated with specific correlated factors. This study provided novel insights into the diagnosis and course of TBEV-induced tick-borne encephalitis in China.Keywords: tick-borne encephalitis, TBE, tick-borne encephalitis virus, TBEV, TaqMan qPCR, IgM

Guoqin Wang,1,&ast; Xiaoying Hu,1,&ast; Nan Ye,1 Xiaoyi Xu,1 Weiyi Guo,1 Lijun Sun,1 Hongrui Dong,1 Xiaoyi Zhao,2 Hong Cheng1 1Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Division of Nephrology, Affiliated Hospital of Chifeng University, Neimenggu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Cheng, Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Beijing, 100029, People’s Republic of China, Email drchengh@163.comPurpose: In recent years, the incidence of malignancy patients with membranous nephropathy (MN) has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Our study aims at elucidating the clinical and pathological characteristics of malignancy patients with MN, especially the expression patterns of MN-specific antigens in both kidney and tumor tissue.Patients and Methods: A retrospective analysis was performed to summarize the clinical and pathological data of MN patients with malignancy at Beijing Anzhen Hospital from January 1, 2012, to December 31, 2022, followed by a thorough review of relevant literature published between May 1, 2000 to May 1, 2023 and case aggregation.Results: 19 patients in our center’s MN cohort and 21 patients from literature review were diagnosed with malignancy either before or after being diagnosed with MN. Among them, 16 (40.0%) and 17 (42.5%) patients tested PLA2R-only and THSD7A-only positive in renal tissue, respectively. And 16 of 26 patients showed similar staining in tumor and kidney tissues. Compared to the idiopathic membranous nephropathy (IMN) patients at our center, patients with malignancy were older, had a lower estimated glomerular filtration rate, and had a lower rate of partial or complete response to treatment. Renal tissue from MN patients with concomitant malignancy was less frequently PLA2R-positive, more frequently THSD7A-positive, and more often glomerular IgG subclass IgG2 (P = 0.033) but less frequently IgG4 (P < 0.001).Conclusion: The clinical and pathological characteristics of MN patients with concomitant malignancy are different from those of IMN patients. Active screening for malignancy should be performed in non-PLA2R-positive elderly MN patients with a poor therapeutic response. Staining for MN target antigens in kidney and tumor tissues may be inconsistent, and the role of MN target antigens needs to be further explored.Keywords: malignancy, membranous nephropathy, PLA2R, THSD7A, NELL-1

Lang Liu,1,&ast; Binghua Zhang,1,&ast; Zhenwei Zhou,2 Jie Yang,1 Ailin Li,1 Yongji Wu,1 Zeyu Peng,1 Xiangyan Li,2 Zhonghua Liu,3 Xiangyang Leng,1 Changwei Zhao,4 Haisi Dong,2 Wenhai Zhao4 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Orthopaedics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 4Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haisi Dong, Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China, Tel/Fax +86 431-18604361976, Email adonghaisi@163.com Wenhai Zhao, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130021, People’s Republic of China, Tel/Fax +86 431-86177836, Email zwh9899@163.comBackground: Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata- Angelica Sinensis-Radix Achyranthis Bidentatae (RAR) has often been used in effective prescriptions for KOA as the main functional drug, but its underlying mechanism remains unclear. Therefore, network pharmacology and verification experiments were employed to investigate the impact and mode of action of RAR in the treatment of KOA.Methods: The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK‐8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments.Results: In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats.Conclusion: RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.Keywords: knee osteoarthritis, RAR, cartilage degeneration, network pharmacology, Mapk1

Keyang Li,1,&ast; Debao Li,2,&ast; Hongliang Dong,1 Dongmei Ren,2 Dandan Gong,1 Shubo Wang,1 Yang Li,1 Yuanyuan Wu,1 Jikang Yang,3 Wenjuan Yan,4 Yi Li4 1Department of Clinical Pharmacy, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 2Department of Clinical Laboratory, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 3Infectious Diseases Department, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 4Department of Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjuan Yan; Yi Li, Department of Clinical Laboratory, Henan Provincial People’s Hospital, Weiwu Road 7&num;, Jinshui District, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86 15225061830 ; +86 15939039006, Email yanwenjuan2008@126.com; liyilabmed@henu.edu.cnPurpose: Since the introduction of ceftazidime–avibactam (CZA) in the Chinese market, accumulating clinical evidence has substantiated its efficacy in the treatment of infections caused by carbapenem-resistant gram-negative bacteria (CR-GNB). Nevertheless, an ongoing debate persists concerning the choice between monotherapy and combination therapy when devising clinical anti-infection protocols.Patients and Methods: This retrospective, single-center observational study enrolled patients with CR-GNB infections who received CZA treatment between December 2019 and August 2023. The primary outcome assessed was 30-day mortality, and the secondary outcome measured was 14-day bacterial clearance. A multivariate Cox regression model was used to identify variables that were independently associated with 30-day mortality rate.Results: Eighty-three patients were enrolled in the study; of which, 45 received CZA monotherapy, whereas 38 received combination therapy. The overall 30-day mortality rate was 31.3%, and no significant difference was observed in the 30-day mortality rates between the CZA combination therapy and monotherapy groups (31.6% vs 31.1%, p=0.963). After adjustment by propensity score matching, the 30-day mortality rate was not significantly different between the two groups (28.6% vs 31.4%, p=0.794). Multivariate COX analysis revealed that age and SOFA score were independent predictors of 30-day mortality.Conclusion: Combination therapy with CZA and other antimicrobials was not found to have an advantage over monotherapy in reducing the 30-day mortality rate.Keywords: ceftazidime-avibactam, carbapenem-resistant gram-negative bacteria, combination therapy K. pneumoniae carbapenemase

Yue Wang,1 Jie Chen,1 Han Dong,2 Rui-Lin Ma,1 Ying Zou,3 Wei Wang,4 Qingmei Zheng,5 Ying Feng,6 Zhangyun Tan,7 Xiaoqin Zeng,8 Yinqing Zhao,7 Yan Deng,1 Yanfang Wang,1 Bei Gu,9 Aijun Sun1,10 1National Clinical Research Center for Obstetric & Gynecologic Diseases Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, 121000, People’s Republic of China; 3Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410008, People’s Republic of China; 4Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 5Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266500, People’s Republic of China; 6Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 7Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, Guangxi, 529100, People’s Republic of China; 8Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, 510000, People’s Republic of China; 9Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, People’s Republic of China; 10Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, 100010, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnBackground: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare.Methods: This is a multicenter cross-sectional survey. Participants’ basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0– 50 people/yr, 50– 200 people/yr, and > 200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis.Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50– 200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens.Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.Keywords: polycystic ovary syndrome, consultation number, lifelong learning, insulin resistance, obesity, hyperandrogenemia, metformin

Rui Jing,1 Hui Dong,1 Kun Huang,2 Zhong Liu,1 Ran Xue,1 Yiran Dong,1 Mei Jiao,3 Na Li,4 Yumei Guo,5 Yun Liu,6 Wenqian Zhang,1 Hongyun Sun1 1Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China; 2Tuberculosis Control Division, Licheng Center for Disease Control and Prevention, Jinan, People’s Republic of China; 3Department of Sexually Transmitted Diseases and AIDS Prevention and Control, Lixia Center for Disease Control and Prevention, Jinan, People’s Republic of China; 4Tuberculosis and Vector Control Division, Shizhong Center for Disease Control and Prevention, Jinan, People’s Republic of China; 5Department of Infectious Diseases and Endemic Disease Control, Huaiyin Center for Disease Control and Prevention, Jinan, People’s Republic of China; 6AIDS Prevention and Control Department, Tianqiao Center for Disease Control and Prevention, Jinan, People’s Republic of ChinaCorrespondence: Wenqian Zhang; Hongyun Sun, Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China, Tel +86 0531-81278897 ; +86 0531 81278873, Email wqzh618@gmail.com; jncdcxxtb@jn.shandong.cnPurpose: This study aimed to investigate awareness of tuberculosis control among post-treatment tuberculosis patients, in order to provide a basis for future preventive and control work in this population.Patients and Methods: A cross-sectional descriptive study was conducted on post-treatment patients with tuberculosis in seven districts of Jinan City between July 2021 and December 2022. A face-to-face or telephone interviews using structured questionnaires for the research subjects were conducted by data collectors. Analyses were carried out first for all subjects, and then separately for male and female subjects.Results: A total of 837 valid questionnaires were collected, of which 495 were males and 342 were females. The awareness rate of the core TB knowledge was 82.46%. The ≥ 65 year group in the total group (OR=0.43, 95% CI: (0.28, 0.68)), male (OR=0.47, 95% CI: (0.27, 0.83)) and female group (OR=0.40, 95% CI: (0.19, 0.86)) was lower than that of the control group. Educational level and monthly income are the main factors of TB cognition in total group. People with university or higher education (OR=2.05, 95% CI: (1.38, 3.05)) and with a monthly income of ≥ 6,000 (OR=1.89, 95% CI: (1.10, 3.25)) had a higher awareness rate. The group with current residence in the city was more aware than the reference group.Conclusion: In the future, the communication of the main transmission route, suspicious symptoms, and cure of TB needs to be strengthened for the post-treatment TB patients. The elderly, those with secondary school education or below, agricultural workers and low-income people are the groups with weak knowledge of TB, and they are also the groups that need to be focused on health education. The above information should be focused on the above groups of people in order to educate them in a way that is easily acceptable to them.Keywords: pulmonary tuberculosis, awareness rate, completed treatment patients, layered analysis

Abstract Quantum interference between reaction pathways around a conical intersection (CI) is an ultrasensitive probe of detailed chemical reaction dynamics. Yet, for the hydrogen exchange reaction, the difference between contributions of the two reaction pathways increases substantially as the energy decreases, making the experimental observation of interference features at low energy exceedingly challenging. We report in this paper a combined experimental and theoretical study on the H + HD → H2 + D reaction at the collision energy of 1.72 eV. Although the roaming insertion pathway constitutes only a small fraction (0.088%) of the overall contribution, angular oscillatory patterns arising from the interference of reaction pathways were clearly observed in the backward scattering direction, providing direct evidence of the geometric phase effect at an energy of 0.81 eV below the CI. Furthermore, theoretical analysis reveals that the backward interference patterns are mainly contributed by two distinct groups of partial waves (J ~ 10 and J ~ 19). The well-separated partial waves and the geometric phase collectively influence the quantum reaction dynamics.

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

Hao Dong,1,&ast; Rong Chen,2,&ast; Fang Xu,3,&ast; Fang Cheng4 1Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Rehabilitation Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Clinical Medical Laboratory Center, Taizhou People’s Hospital, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Gastroenterology, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Cheng, Department of Gastroenterology, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, No. 1 Yintan Road, Dongxihu District, Wuhan, 430023, Hubei Province, People’s Republic of China, Email 13886178189@163.comBackground and Aims: Cholelithiasis etiology intricately involves lipid metabolism. We sought to investigate the plausible causal link between genetically proxied lipid-lowering medications—specifically HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors—and cholelithiasis risk.Methods: Our study utilized two genetic instruments for exposure to lipid-lowering drugs. These instruments encompassed genetic variants linked to low-density lipoprotein (LDL) cholesterol within or in proximity to drug target genes, along with loci governing gene expression traits of these targets. Effect estimates were derived through Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) methods.Results: Higher HMGCR-mediated LDL cholesterol levels (IVW-MR, OR = 2.15, 95% CI = 1.58– 2.94; P = 0.000) and increased HMGCR expression (SMR, OR = 1.19, 95% CI = 1.04– 1.37; P = 0.014) are linked to elevated cholelithiasis risk, suggesting potential benefits of HMGCR inhibition. In contrast, higher PCSK9-mediated LDL cholesterol levels (IVW-MR, OR = 0.72, 95% CI = 0.56– 0.94; P = 0.015) and increased PCSK9 expression (SMR, OR = 0.90, 95% CI = 0.82– 0.99; P = 0.035) both correlate with lower cholelithiasis risk, indicating that PCSK9 inhibition may elevate this risk. Nevertheless, no substantial link emerged between NPC1L1-mediated LDL cholesterol or NPC1L1 expression and cholelithiasis in both IVW-MR and SMR analyses.Conclusion: This MR investigation affirms the causal link between the utilization of HMGCR inhibitors and a diminished risk of cholelithiasis. Additionally, it indicates a causal link between PCSK9 inhibitors use and increased cholelithiasis risk. However, no significant correlation was found between NPC1L1 inhibitors use and cholelithiasis risk.Keywords: cholelithiasis, lipid-lowering drugs, Mendelian randomization analysis, HMGCR inhibitors, PCSK9 inhibitors, NPC1L1 inhibitors

Han Wang,1,&ast; Jun-Jie Chen,2,&ast; Shu-Yi Yin,3,&ast; Xia Sheng,4 Hong-Xia Wang,5 Wan Yee Lau,6 Hui Dong,1 Wen-Ming Cong1 1Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3Department of Pathology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 4Department of Pathology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 5Department of Pathology, Jiading District Central Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, People’s Republic of China; 6Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China&ast;These authors contributed equally to this workCorrespondence: Hui Dong; Wen-Ming Cong, Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-021-81875191 ; +86-021-81875192, Email huidongwh@126.com; wmcong@smmu.edu.cnBackground: Microvascular invasion (MVI) is closely correlated with poor clinical outcomes in patients with hepatocellular carcinoma (HCC). A grading system of MVI is needed to assist in the management of HCC patient.Methods: Multicenter data of HCC patients who underwent liver resection with curative intent was analyzed. This grading system was established by detected number and distance from tumor boundary of MVI. Survival outcomes were compared among patients in each group. This system was verified by time-receiver operating characteristic curve, time-area under the curve, calibration curve, and decision curve analyses. Cox regression analysis was performed to study the associated factors of prognosis. Logistic analysis was used to study the predictive factors of MVI.Results: All patients were classified into 4 groups: M0: no MVI; M1: 1~5 proximal MVIs (≤ 1 cm from tumor boundary); M2a: > 5 proximal MVIs (≤ 1 cm from tumor boundary); M2b: ≥ 1 distal MVIs (> 1 cm from tumor boundary). The recurrence-free survival (RFS), overall survival (OS), and early RFS rates among all the individual groups were significantly different. Based on the number of proximal MVI (0~5 vs > 5), patients in the M2b group were further divided into two subgroups which also showed different prognosis. Multiple methods showed this grading system to be significantly better than the MVI two-tiered system in prognostic evaluation. Four multivariate models for RFS, OS, early RFS, late RFS, and a predictive model of MVI were then established and were shown to satisfactorily evaluate prognosis and have a great discriminatory power, respectively.Conclusion: This MVI grading system could precisely evaluate prognosis of HCC patients after liver resection with curative intent and it could be employed in routine pathological reports. The severity of MVI from both adjacent and distant from tumor boundary should be stated. A hypothesis about two occurrence modes of distal MVI was proposed. Keywords: hepatocellular carcinoma, microvascular invasion, hepatectomy, hepatic resection, pathology

Heng Wang,1,&ast; Tingting Gao,1,&ast; Ruijing Zhang,2,&ast; Jie Hu,1 Siqi Gao,1 Yuwen Wang,1 Xiaotong Qi,1 Yun Zhou,3 Guoping Zheng,1,4 Honglin Dong1 1Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Shanxi Provincial Integrated TCM and WM Hospital, Taiyuan, People’s Republic of China; 4Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia&ast;These authors contributed equally to this workCorrespondence: Honglin Dong, Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan City, Shanxi Province, 030001, People’s Republic of China, Email honglindong@sxmu.edu.cn Guoping Zheng, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia, Email guoping.zheng@sydney.edu.auBackground: Contrast-induced acute kidney injury (CI-AKI) is considered to be the third leading cause of hospital-acquired kidney injury. Current studies mostly suggest that contrast agents mainly harm renal tubular epithelial cells, but we hypothesized that the development of CI-AKI should be the result of the interaction of renal vascular and tubular injury.Methods: First we constructed a CI-AKI mouse model and verified the success of the model by pathological injury and serum creatinine level. Immunohistochemistry, protein quantification and qRT-PCR were used to detect the location and level of expression of neutrophil extracellular traps (NETs) in the kidney. Then, we blocked the in vivo accumulation of NETs using GSK484 and DNase I and detected the expression of NETs and the damage of glomerular and peritubular capillaries.Results: We first identified the presence of NETs in CI-AKI mice, and NETs were mainly accumulated in glomeruli and peritubular capillaries. The expression of NETs was positively correlated with the severity of CI-AKI kidney. After inhibition of NETs release or promotion of NETs degradation by drugs, renal vascular endothelial cell injury was reduced and renal pathological changes and creatinine levels were reversed in CI-AKI mice. In addition, inhibition of NETs reduced apoptosis and pyroptosis of renal cells and attenuated inflammation in vivo.Conclusion: These findings suggest that NETs are involved in the development of CI-AKI by damaging glomerular and peritubular capillary endothelial cells. This study will provide a new strategy for clinical prevention and treatment of CI-AKI.Keywords: contrast-induced acute kidney injury, neutrophils, neutrophil extracellular traps, glomeruli, peritubular capillaries

Xuan Wan,1,&ast; Yuting Fang,2,&ast; Jiangzhou Du,1 Shaoxi Cai,1 Hangming Dong1 1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China; 2BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoxi Cai; Hangming Dong, Email hxkc@smu.edu.cn; dhm@smu.edu.cnObjective: GW4869 is an exosomal inhibitor. It is necessary to delay the occurrence of gefitinib resistance during non-small-cell lung cancer (NSCLC) treatment. This study aimed to investigate the anti-tumor effects of GW4869 on epithelial-mesenchymal transition (EMT) and expression of extracellular heat shock protein 90α (eHSP90α) that contributes to acquired resisitance. Our study provides a new sight into the treatment of EGFR-mutated NSCLC.Materials and Methods: We performed western blotting to detect levels of EMT and eHSP90α. Wound healing and transwell assays were performed to evaluate the behavioral dynamics of EMT. A nude mouse model of HCC827 was established in vivo.Results: GW4869 inhibited the expression of eHSP90α, EMT, invasion and migration abilities of HCC827 and PC9. GW4869 enhanced sensitivity to gefitinib in BALB/c nude mice bearing tumors of HCC827.Conclusion: These studies suggest that GW4869 can inhibit EMT and extracellular HSP90α, providing new strategies for enhancing gefitinib sensitivity in NSCLC.Keywords: GW4869, EMT, gefitinib-sensitive NSCLC, eHSP90&#x03B1

Zhiqiang Shi,1 Yu Liu,1,2 Xiaodan Chang,3 Yuan Gao,4 Min Hao,1 Shuo Feng,1 Haoyu Dong1 1Department of Traditional Chinese Medicine Surgery, College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine Surgery, College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 3Department of Dermatology, Hohhot Second Hospital, Hohhot, People’s Republic of China; 4Department of Anorectal Diseases, Inner Mongolia Hospital of Traditional Chinese Medicine, Hohhot, People’s Republic of ChinaCorrespondence: Yu Liu, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot, Inner Mongolia, People’s Republic of China, Tel +86-153-3471-2606, Email 15074930848@163.comPurpose: This paper aims to investigate the effect of Tounong San (TNS), a well-known traditional Chinese medicine prescription for suppurative infections, on the immune function.Methods: A suppurative infection model was established by injecting Staphylococcus aureus into subcutaneous tissue on the backs of rats. The expressions of CD68, CD163, CD31 and MPO in abscess tissues, phagocytosis rate and reactive oxygen species (ROS) of neutrophils in blood, phagocytosis function of peritoneal macrophages, and proliferation of blood lymphocytes, expression of IL-1, IL-6, CH50, TNF-α, IFN-γ, IgG, IgM in serum were detected at different time points.Results: On the 3rd day of medication, fibrinogen wrapped around the abscesses was visible in TNS groups, with an increase in new blood vessels and the expression of a large number of macrophages and neutrophils. On the 6th day, the pus of TNS groups diminished, and the number of new blood vessels reached its peak. On the 9th day, the abscesses disappeared in TNS groups, fewer new blood vessels, macrophages, and neutrophils were expressed, and more fibrocytes appeared and filled the original pus cavities. On the 3rd and 9th day of medication, the phagocytic rates of neutrophils and macrophages were significantly improved in TNS group, and the ROS content of neutrophils was increased on the 9th day. TNS has no effect on lymphocyte proliferation in vitro, but it can regulate the secretion of IgG and IgM by lymphocytes. TNS increases the level of IL-1, decreases the levels of IL-6 and TNF-α, and regulates the expressions of IFN-γ and CH50 in two ways.Conclusion: TNS can form fibrinogen-wrapped pus to prevent bacterial infection from going deeper, and to improve the phagocytic function of phagocytes, the secretion of lymphocytes, and the defense function of the complement system. Therefore, it is a competitive drug for the treatment of suppurative diseases.Keywords: Tounong San, suppurative infection, immune function, pharmacological mechanism

Bai-Wen Zhang,1 Hao Dong,1 Zhe Wu,1 Xi Jiang,2 Wei Zou3 1Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China; 2Jinzhou Medical University, Jinzhou, 121001, People’s Republic of China; 3The Third Department of Acupuncture and Moxibustion, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of ChinaCorrespondence: Wei Zou, The Third Department of Acupuncture and Moxibustion, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China, Tel +86 0451-82161746, Email weizouzw@126.comAbstract: Neuralgia is a frequently occurring condition that causes chronic pain and burdens both patients and their families. Earlier research indicated that anti-inflammatory treatment, which was primarily utilized to address conditions like neuralgia, resulted in positive outcomes. However, recent years have witnessed the emergence of various novel mechanisms associated with pain-related disorders. This review provides a concise overview of the inflammatory mechanisms involved in neuralgia. It also examines recent advancements in research, exploring the influence of ion channels and synaptic proteins on neuralgia and its complications. Additionally, the interactions between these mechanisms are discussed with the aim of suggesting innovative therapeutic approaches and research directions for the management of neuralgia.Keywords: neuralgia, inflammatory mechanisms, innovative therapeutic approaches

Lu Zhang, Yan Yan, Ru Liao, Haiyan Dong Department of Pharmacy, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaCorrespondence: Haiyan Dong, Department of Pharmacy, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Tel/Fax +86-29-85323508, Email batistuta28@126.comBackground: Linezolid-induced thrombocytopenia incidence varies considerably. Linezolid-related thrombocytopenia in patients has received few studies which have investigated risk factors including platelet parameters except for platelet counts. The study aims to analyze the effect of platelet parameters, including mean platelet volume and platelet large cell ratio, on linezolid-related thrombocytopenia in patients.Methods: The effect of platelet parameters on linezolid-related thrombocytopenia was identified by univariate and multivariate logistic regressions. A Kaplan–Meier survival analysis was carried out to compare the survival of patients who developed linezolid-related thrombocytopenia with patients who did not.Results: Thrombocytopenia occurred at a rate of 41.5% (66/159) after linezolid therapy in hospitalized patients. Platelet parameters, including the difference in mean platelet volume (MPV/fL=0.08 (− 1.2– 0.9)vs-0.5 (− 1.5– 0.3), (OR, 0.459; P = 0.001), the difference in platelet large cell ratio (PLCR/fL=0.9 (− 5.1– 6.2)vs-3.8 (− 8.6– 2.4), (OR, 1.156; P = 0.001), baseline platelet counts (OR, 0.995; P = 0.006) and duration of linezolid therapy≥ 10d (OR, 1.346; P = 0.007), were significantly associated with linezolid-related thrombocytopenia in hospitalized patients. In addition, other risk factors which also are associated with linezolid-related thrombocytopenia include baseline red blood cells, co-medication with parecoxib and co-medication with caspofungin. Accumulated in-hospital mortality of patients with thrombocytopenia was significantly higher than that of patients without thrombocytopenia during linezolid treatment (19.7% vs 8.6%, P = 0.003).Conclusion: The difference in mean platelet volume, the difference in large platelet ratio, baseline platelet counts and duration of linezolid therapy≥ 10d significantly affected the development of linezolid-related thrombocytopenia in hospitalized patients.Keywords: linezolid, platelet parameters, thrombocytopenia, risk factors

Peng Shan,1,2 Hang Dong,1,2 Shilan Li3 1Department of Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, People’s Republic of China; 2Core Unit of National Clinical Research Center for Laboratory Medicine, Hefei, Anhui, 230036, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, People’s Republic of ChinaCorrespondence: Shilan Li, Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, People’s Republic of China, Tel +86-0551-62284147, Email shilanli980@sina.comAbstract: Acute basophilic leukemia (ABL) arising from chronic myeloid leukemia (CML) with abundant mast cells (MCs), coexisting with a complex karyotype is rare. Here, we report an 81-year-old man admitted to our hospital with a history of ABL. He was diagnosed with CML in the chronic phase in January 2018, and Imatinib was used at a daily dose of 400mg. Then, transformation to ABL with abundant MCs in the bone marrow and complex karyotypes including 48,XY, trisomy 8 (+8), isochromosome 17(q10) [i(17)(q10)], and derivative chromosome 22 t(9;22) [der(22)t(9;22)] were discovered simultaneously in January 2022. In conclusion, the increased number of MCs in our case is a reminder that they might play an important role in the prognosis of CML and trigger the development of complex karyotypes. Moreover, this is the first case report of ABL arising from CML with abundant MCs, coexisting with 48,XY, +8, i(17)(q10), and der(22)t(9;22), during Imatinib treatment. Further studies are needed to better characterize this rare condition.Keywords: CML, TKIs, MCs, ABL, complex karyotype

Hongchuan Liu,1 Huaihuai Dong,2 Liangjun Guo,3 Yongsheng Jin,2 Lihong Liu1 1Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2School of Pharmacy, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Department of Drug and Equipment, The 72st Group Army Hospital of PLA, Huzhou, 313000, People’s Republic of ChinaCorrespondence: Yongsheng Jin, School of Pharmacy, Naval Medical University, No. 325 of Guohe Street, Yangpu District, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 21 8187 1227, Email ysjinsmmu@163.com Lihong Liu, Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, No. 8 of Gongti South Street, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel/Fax +86 10 85231786, Email hongllh@126.comBackground: The synergistic effect of dihydromyricetin (DHM) and fluconazole (FLC) can improve the killing effect of FLC-resistant Candida albicans in vitro and in vivo. However, it is not clear whether DHM affects the pharmacokinetic characteristics of FLC.Methods: In this study, 12 Sprague–Dawley (SD) rats were randomly divided into two groups as follows: (1) an FLC group in which rats were administered FLC only (42 mg/kg orally); (2) an FLC with the combined administration of DHM group, in which rats received an equivalent FLC dose immediately following the administration of DHM (100 mg/kg). Blood samples were collected from the ocular choroid vein of rats and converted into plasma. The concentrations of FLC in the rat plasma were then determined by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS), and the related pharmacokinetic parameters were analysed. The initial mobile phase included 0.1% acetonitrile and water with gradient elution. Multiple reaction monitoring modes of m/z 307.2→ 220.1 for FLC, and m/z 237.1→ 194.2 for carbamazepine, were utilised to conduct quantitative analysis.Results: The calibration curve of FLC in rat plasma demonstrated good linearity in the range of 0.1– 30 μg/mL (r > 0.99), and the lower limit of quantification was 0.1 μg/mL. Moreover, the intra- and inter-day precision relative standard deviation of FLC was less than 9.09% and 6.51%, respectively. There were no significant differences in the pharmacokinetic parameters between the two groups.Conclusion: The results showed that DHM administration did not significantly alter FLC pharmacokinetics in SD rat plasma.Keywords: HPLC-MS/MS, dihydromyricetin, fluconazole, pharmacokinetic

Bingqing Zhang,&ast; Qiang Li,&ast; Qinglin Xu, Baochao Li, Heng Dong, Yongbin Mou Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongbin Mou; Heng Dong, Nanjing Stomatological Hospital, Medical School of Nanjing University, &num;30 Zhongyang Road, Nanjing, 210008, People’s Republic of China, Email yongbinmou@nju.edu.cn; dongheng90@smail.nju.edu.cnBackground: Inflammatory bowel disease (IBD) is closely related to higher intracellular oxidative stress. Therefore, developing a novel method to scavenge the harmful reactive oxygen species (ROS) and alleviate colon inflammation to treat IBD is a promising strategy.Methods: CeO2@PDA-PEG (CeO2@PP) were synthesized by modifying ceria (CeO2) nanorods with polydopamine (PDA) and polyethylene glycol (PEG). The ROS scavenging ability of CeO2@PP was detected by using flow cytometry and confocal laser scanning microscope (CLSM). The anti-inflammatory ability of CeO2@PP was determined in vitro by treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The biocompatibility of CeO2@PP was evaluated in vivo and in vitro. Moreover, the therapeutic effects of CeO2@PP in vivo were estimated in a dextran sulfate sodium salt (DSS)-induced colitis mouse model.Results: Physicochemical property results demonstrated that PDA and PEG modification endowed CeO2 nanorods with excellent dispersibility and colloidal stability. CeO2@PP maintained superior enzyme-like activity, including superoxide dismutase (SOD) and catalase (CAT), indicating antioxidant ability. Moreover, in vitro results showed that CeO2@PP with PDA promotes LPS-induced RAW 264.7 macrophages into M2-type polarization. In addition, in vitro and in vivo results showed that CeO2@PP have great biocompatibility and biosafety. Animal experiments have shown that CeO2@PP have excellent anti-inflammatory effects against DSS-induced colitis and effectively alleviated intestinal mucosal injury.Conclusion: The nanoplatform CeO2@PP possessed excellent antioxidant and anti-inflammatory properties for scavenging ROS and modulating macrophage polarization, which is beneficial for efficient colitis therapy.Graphical Abstract: Keywords: ceria, PDA, nanozyme, antioxidation, anti-inflammation, macrophage polarization, colitis

Bingyan Yu,1,2,&ast; Xiangming Hu,2,&ast; Jieliang Liu,2 Zhiqiang Nie,3 Ci Ren Luo Bu,4 Guang Li,2 Yingling Zhou,2 Haojian Dong2,4 1School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Cardiology, Hypertension Research Laboratory, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4Nyingchi People’s Hospital, Nyingchi, Tibet, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haojian Dong, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China, Tel +862083827812, Fax +862083827812, Email donghaojian@gdph.org.cnPurpose: Lipoprotein(a) (Lp[a]) is well-known as a residual risk factor for coronary artery disease (CAD). However, the different adverse effects of Lp(a) about CAD in patients with or without type 2 diabetes mellitus (T2DM) are unclear. This study aimed to investigate the Lp(a) thresholds for CAD diagnosis in T2DM and non-T2DM patients, and further compare the Lp(a) alarm values along with optimal low-density lipoprotein cholesterol (LDL-C) level.Methods: This retrospective study consecutively enrolled patients with suspected CAD who underwent coronary angiography in Guangdong Provincial People’s Hospital between September 2014 and July 2015. A logistic regression model was established to explore the association of Lp(a) and CAD in patients. Restricted cubic splines were used to compare the threshold values of Lp(a) for CAD in patients with and without T2DM, and further in optimal LDL-C level situation.Results: There were 1522 patients enrolled finally. After multivariable adjustment, Lp(a) was an independent risk factor for CAD in patients with T2DM (odds ratio [OR]: 1.98, 95% CI]: 1.12– 3.49, p = 0.019) and without T2DM (OR: 3.42, 95% CI: 2.36– 4.95, p < 0.001). In the whole population, the Lp(a) threshold of CAD was 155, while 145 mg/L for T2DM and 162 mg/L for non-T2DM ones, respectively. In patients with LDL-C< 1.8 mmol/l, the alarm value of Lp(a) was even lower in T2DM than non-T2DM patients (155 vs 174 mg/L).Conclusion: Lp(a) was a significant residual risk for CAD in patients whether with T2DM or not. And Lp(a) had a lower alarm value in T2DM patients, especially in optimal LDL-C level.Keywords: lipoprotein(a), coronary artery disease, type 2 diabetes mellitus, low-density lipoprotein cholesterol

Zhicong Liu,1,&ast; Pengtao Song,2,&ast; Lingyan Zhou,1 Dongxiang Ji,1 Hui Shen,1 Hui Dong,1 Xueren Feng1 1Department of Respiratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People’s Republic of China; 2Department of Pathology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Dong; Xueren Feng, Department of Respiratory Medicine, Huzhou Centre Hospital, Affiliated Centre Hospital Huzhou University, Huzhou, People’s Republic of China, Email 1150861366@qq.com; fxr9301006@163.comBackground: Lung cancer remains the leading cause of cancer-related mortality. Studies have revealed that a combination of crizotinib and EGFR tyrosine kinase inhibitors (TKIs) could be an effective treatment option for patients with sensitizing EGFR mutations and de novo or acquired MET amplification. Until now, there have been few reports of the response in patients harboring three mutations.Case Presentation: A patient was diagnosed with advanced lung adenocarcinoma harboring EGFR Del19, L858R mutation and METex14. She received osimertinib, and repeated imaging revealed further tumor progression. Sixty-six days later, combined treatment with osimertinib and crizotinib was initiated. Unfortunately, the patient succumbed to death at home after 17 days.Conclusion: This report firstly provided a lung adenocarcinoma patient with two common EGFR mutations (Del19 and L858R) and METex14. Our case raises a reminder about the tolerance and safety of combination therapy, especially in older peoples.Keywords: lung adenocarcinoma, compound mutations, osimertinib, crizotinib, combination therapy, case report

Hang Dong, Meng Gao, Lu Lu, Rong Gui, Yunfeng Fu Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yunfeng Fu, Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha, Hunan, 410013, People’s Republic of China, Email fuyunfeng@csu.edu.cnIntroduction: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with a poor prognosis. Current single-agent checkpoint therapy has limited effectiveness in TNBC patients. In this study, we developed doxorubicin-loaded platelet decoys (PD@Dox) for chemotherapy and induction of tumor immunogenic cell death (ICD). By combining PD-1 antibody, PD@Dox has the potential to enhance tumor therapy through chemoimmunotherapy in vivo.Methods: Platelet decoys were prepared using 0.1% Triton X-100 and co-incubated with doxorubicin to obtain PD@Dox. Characterization of PDs and PD@Dox was performed using electron microscopy and flow cytometry. We evaluated the properties of PD@Dox to retain platelets through sodium dodecyl sulfate-polyacrylamide gel electrophoresis, flow cytometry, and thromboelastometry. In vitro experiments assessed drug-loading capacity, release kinetics, and the enhanced antitumor activity of PD@Dox. The mechanism of PD@Dox was investigated through cell viability assays, apoptosis assays, Western blot analysis, and immunofluorescence staining. In vivo studies were performed using a TNBC tumor-bearing mouse model to assess the anticancer effects.Results: Electron microscopic observations confirmed that platelet decoys and PD@Dox exhibited a round shape similar to normal platelets. Platelet decoys demonstrated superior drug uptake and loading capacity compared to platelets. Importantly, PD@Dox retained the ability to recognize and bind tumor cells. The released doxorubicin induced ICD, resulting in the release of tumor antigens and damage-related molecular patterns that recruit dendritic cells and activate antitumor immunity. Notably, the combination of PD@Dox and immune checkpoint blockade therapy using PD-1 antibody achieved significant therapeutic efficacy by blocking tumor immune escape and promoting ICD-induced T cell activation.Conclusion: Our results suggest that PD@Dox, in combination with immune checkpoint blockade therapy, holds promise as a potential strategy for TNBC treatment.Keywords: drug delivery, doxorubicin, immunogenic cell death, immune checkpoint blockade therapy

Pineapple mealybug, Dysmicoccus brevipes (Hemiptera: Pseudococcidae), is a significant pest in pineapple production and a key trade barrier. We explored the potential use of ethyl formate (EF) as a methyl bromide alternative for the postharvest fumigation of D. brevipes in imported pineapples. When treated at 8 °C for 4 h, EF fumigation was effective against D. brevipes with LCt99, the lethal concentration × time product of EF necessary to achieve 99% mortality of D. brevipes nymphs and adults at 64.2 and 134.8 g h/m3, respectively. Sorption trials conducted with 70 g/m3 EF for 4 h at 8 °C using 7.5, 15 and 30% pineapple loading ratios (w/v) indicated that loading ratio lower than 30% is necessary to achieve the LCt99 values required to control D. brevipes. In a scaled up trial using 1 m3 chamber, EF fumigation with 70 g/m3 for 4 h at 8 °C with 20% pineapple loading ratio (w/v) resulted in a complete control of D. brevipes treated. There were no significant differences in hue values, sugar contents, firmness, and weight loss between EF-treated and untreated pineapples. Our results suggest that EF is a promising alternative to methyl bromide fumigation for the postharvest phytosanitary disinfection of D. brevipes in pineapples.

We investigate the current-phase relations of Al/InAs-quantum well planar Josephson junctions fabricated using nanowire shadowing technique. Based on several experiments, we conclude that the junctions exhibit an unusually large second-order Josephson harmonic, the $\sin(2\varphi)$ term. First, superconducting quantum interference devices (dc-SQUIDs) show half-periodic oscillations, tunable by gate voltages as well as magnetic flux. Second, Josephson junction devices exhibit kinks near half-flux quantum in supercurrent diffraction patterns. Third, half-integer Shapiro steps are present in the junctions. Similar phenomena are observed in Sn/InAs quantum well devices. We perform data fitting to a numerical model with a two-component current phase relation. Analysis including a loop inductance suggests that the sign of the second harmonic term is negative. The microscopic origins of the observed effect remain to be understood. We consider alternative explanations which can account for some but not all of the evidence.

In situ wetting-drying cycles significantly and repeatedly influence the soil water content in the active zone but not in the steady zone. To investigate effects of in situ wetting-drying cycles on the mechanical behaviour of intact loess, a series of pressure plate tests was carried out with an intact loess sampled from the active and steady zones. Results show that the specimens from the steady zone have higher yield stresses at given suctions and a larger inclination of normalized loading collapse (LC) curve than the specimens from the active zone. As evidenced by the scanning electron microscopy results, the clay particles accumulating around the contacts between silt particles are widely observed in the former specimens but not in the latter specimens. The distribution of clay particles in the former specimens results in a stabilized skeleton with mechanical properties sensitive to suction variations. On the other hand, the maximum collapse potential of the specimen from the steady zone is 37% larger than that of the specimen from the active zone, mainly because of the larger inclination of normalized LC curve owned by the former specimen. Key words: intact loess, compression, collapse, in situ wetting-drying cycles. Les cycles de mouillage-sechage in situ influencent de maniere significative et repetitive la teneur en eau du sol dans la zone active, mais pas dans la zone stable. Pour etudier les effets des cycles de mouillage-sechage in situ sur le comportement mecanique du loess intact, une serie d'essais sur plaque de pression a ete realisee avec un loess intact echantillonne dans les zones actives et stables. Les resultats montrent que les specimens de la zone stable ont des contraintes d'elasticite plus elevees a des suctions donnees et une plus grande inclinaison de la courbe d'effondrement normalisee (LC) que les specimens de la zone active. Comme le montrent les resultats de la microscopie electronique a balayage, les particules d'argile qui s'accumulent autour des contacts entre les particules de limon sont largement observees dans les premiers specimens, mais pas dans les seconds. La repartition des particules d'argile dans les anciens specimens donne lieu a un squelette stabilise dont les proprietes mecaniques sont sensibles aux variations de la succion. D'autre part, le potentiel d'effondrement maximal de l'eprouvette de la zone stable est 37 % plus eleve que celui de l'eprouvette de la zone active, principalement en raison de la plus grande inclinaison de la courbe LC normalisee appartenant a la premiere eprouvette. [Traduit par la Redaction] Mots-cles: loess intact, compression, effondrement, cycles de mouillage-sechage in situ., 1. Introduction Loess is distributed over vast arid and semiarid regions in the People's Republic of China and many other countries (Munoz-Castelblanco et al. 2012; Ng et al. 2018). Active [...]

Large superelastic deformation in ferroelastic-ferroelectrics (FMs) is a complex phenomenon involving multiple mechanisms operating simultaneously. Understanding how these mechanisms contribute corporately is critical to apply this useful property to the intrinsically brittle FMs, which can therefore display both excellent functional and mechanical performance. Here, we have directly observed and quantitatively analyzed in situ in a transmission electron microscope the three main mechanisms of twinning domain, phase transformation and mobile point defect contributing to extremely large superelastic deformation in single-crystal BaTiO3 (5.0% strain) and Pb(Mg1/3Nb2/3)O3-PbTiO3 (10.1% strain). Our results reveal the hierarchical origin of large recoverable strain in “brittle” FMs.

Zhihong Lu,1,&ast; Ailin Luo,2,&ast; Su Min,3,&ast; Hailong Dong,1 Qiuju Xiong,3 Xinhua Li,2 Qingzhu Deng,2 Tingting Liu,1 Xue Yang,1 Chen Li,4 Qingchuan Zhao,5 Lize Xiong1,6 1Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Department of Anaesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Anaesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Medical Statistics, Fourth Military Medical University, Xi’an, People’s Republic of China; 5Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, People’s Republic of China; 6Translational Research Institute of Brain and Brain-Like Intelligence and Department of Anesthesiology, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Lu; Lize Xiong, Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Changle West Road127, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel +86-29-84775337 ; Tel +86-29-84772126, Email deerlu23@163.com; xlzmzk@163.comPurpose: The aim of this study was to evaluate the efficacy of transcutaneous electrical acupoint stimulation (TEAS) in improving bowel function and thus shortening hospital stay after laparoscopic colon surgery within the ERAS pathway.Patients and Methods: From November 2016 to March 2018, 100 patients who underwent elective colon surgery were enrolled and 94 finished study (n = 47 for each) in three university hospitals. Patients in the TEAS group received TEAS 30 min before surgery and once a day for 3 days after surgery, while those in the Control Group received no stimulation. Primary outcome was the time to discharge.Results: Compared with standardized postoperative care, TEAS resulted in a shorter time to first flatus (P=0.03) and time to first defecation (P=0.03), as well as a reduction in the length of hospital stay (P=0.02). Median patient-controlled analgesia (PCA) deliveries and PCA attempts at 24h, 48h and 72h after surgery were less in the TEAS group (P< 0.01). No evidence of significant advantages in postoperative pain intensity, nausea, vomiting, sleeping quality and expenses was found in the TEAS group.Conclusion: Perioperative TEAS further shortens the time to meet discharge criteria after laparoscopic colon surgery in patients under ERAS strategy.Keywords: transcutaneous electrical acupoint stimulation, colon surgery, laparoscopy, ERAS

Mengzhu Hou,1,&ast; Nan Chen,2,&ast; Lili Dong,3,&ast; Yulian Fang,1 Rui Pan,2 Wei Wang,1 Lu Wang,1 Jing Ning,3 Hanquan Dong3 1Tianjin Pediatric Research Institute, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China; 2Department of Clinical Lab, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China; 3Department of Respiratory, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Ning; Hanquan Dong, Department of Respiratory, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), No. 238 Longyan Road, Beichen District, Tianjin, 300134, People’s Republic of China, Tel +86 13752230008 ; +86 13820476506, Email jingning2022@126.com; mifits@sina.comPurpose: The data on pediatrics with Multidrug-Resistant (MDR) Klebsiella pneumoniae infections are scarce. This study aims to investigate the molecular epidemiology of MDR Klebsiella pneumoniae, detect the mechanism of drug resistance, and determine the clinical risk factors for carbapenem-resistant Klebsiella pneumonia (CRKP) bloodstream infections (BSIs) in a children’s hospital.Methods: A total of 62 strains were collected from Tianjin Children’s Hospital. Carba NP and polymerase chain reactions (PCR) were performed to detect MDR mechanisms. Multilocus sequence typing (MLST) was used for analyzing strain homology. Clinical data were collected and logistic regression was used for BSI risk factors.Results: ST11 was the principal ST among the CRKP isolates clinically, accounting for 56.45% (35/62); there were also 57.14% (20/35) ST11 CRKP strains co-carrying blaNDM-5 and blaKPC-2, which were resistant to most of the tested antibiotics, being susceptible only to cotrimoxazole and tigecycline. The clinical data showed that 72.73% (40/55) of children with CRKP infection had serious underlying diseases; 20.00% (11/55) patients developed BSIs with the potential to cause multiple organ failure, shock and death. The logistic regression showed that the risk of BSIs caused by CRKP strain infections in children with hematological malignancies after chemotherapy was 7 times that of other children (95%Cl: 1.298– 45.415, P=0.025).Conclusion: ST11 was the prevalent clone in our hospital. The emergence of ST11 CRKP co-carrying blaNDM-5 and blaKPC-2 should be a cause for alarm as they were resistant to most of the tested antibiotics. CRKP strain infections are mainly occurring in young immunocompromised patients and the chemotherapy for hematological malignancies is an independent risk factor for BSIs.Keywords: carbapenem-resistantKlebsiella pneumonia, blaKPC-2, blaNDM-5, ST11, children, bloodstream infection