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Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis

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Science China Life Sciences 2025年第1期68卷 103-115页

作者： Xizi Luo Nan Zhang Yuntao Liu Beibei Du Xuan Wang Tianxu Zhao Bingqiang Liu Shishun Zhao Jiazhang Qiu Guoqing Wang State Key Laboratory for Diagnosis and treatment of Severe Zoonotic Infectious Diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Basic MedicineJilin University State Key Laboratory for Diagnosis and treatment of Severe Zoonotic Infectious Diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Veterinary MedicineJilin University College of Mathematics Jilin University Bioinformatic Lab School of MathematicsShandong University department of Cardiology China-Japan Union HospitalJilin University

The coronavirus disease 2019（COVID-19） outbreak caused by the severe acute respiratory syndrome coronavirus-2（SARS-CoV-2） developed into a global health emergency. Systemic microthrombus caused by SARS-CoV-2 infection is a common complication in patients with COVID-19. Cardiac microthrombosis as a complication of SARS-CoV-2 infection is the primary cause of cardiac injury and death in patietns with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors,patients who died during the hypercoagulable period of characteristic coagulation abnormality（CAC）, and patients who died during the fibrinolytic period of CAC. We collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.

关键词： SARS-CoV-2 cardiac microthrombosis immune hyperactivation cell competition

Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

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Neural Regeneration Research 2025年第10期20卷 2838-2854页

作者： Lu Guan Mengting Qiu Na Li Zhengxiang Zhou Ru Ye Liyan Zhong Yashuang Xu Junhui Ren Yi Liang Xiaomei Shao Jianqiao Fang Junfan Fang Junying Du department of Neurobiology and Acupuncture Research Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Key Laboratory for Research of Acupuncture treatment and Transformation of Emotional Diseases Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Fuchun Community Health Service Center of Fuyang District HangzhouZhejiang ProvinceChina

pain is often comorbid with emotional disorders such as anxiety and *** of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid *** review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain *** understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these ***,the mechanisms that regulate gamma-aminobutyric acidergic systems remain *** is also unclear as to whether the mechanisms are presynaptic or *** exploration of the complexities of this system may reveal new pathways for research and drug development.

关键词： anterior cingulate cortex anxiety chronic pain circuit communication comorbidity depression gamma-aminobutyric acidergic neurons parvalbumin neurons synaptic transmission

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

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Neural Regeneration Research 2025年第2期20卷 378-393页

作者： Jingxiang Zhang Xia Sheng Quanju Ding Yujun Wang Jiwei Zhao Jingfa Zhang department of Ophthalmology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina department of Urology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of MedicineShanghaiChina National Clinical Research Center for Eye Diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghaiChina

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular *** causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular *** pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely ***,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential *** current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/*** review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

关键词： choroidal neovascularization epithelial-mesenchymal transition mesenchymal transition myofibroblast neovascular age-related macular degeneration submacular fibrosis subretinal fibrosis therapeutic targets transforming growth factor-β vascular endothelial growth factor

Effect of Preemptive Ketamine Administration on Postoperative Visceral pain after Gynecological Laparoscopic Surgery

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2016年第4期36卷 584-587页

作者：林洪启贾东林 department of Anesthesiology the People's Hospital of Henan Province department of pain treatment Peking University Third Hospital

The pain following gynecological laparoscopic surgery is less intense than that following open surgery; however, patients often experience visceral pain after the former surgery. The aim of this study was to determine the effects of preemptive ketamine on visceral pain in patients undergoing gynecological laparoscopic surgery. Ninety patients undergoing gynecological laparoscopic surgery were randomly assigned to one of three groups. Group 1 received placebo. Group 2 was intravenously injected with preincisional saline and local infiltration with 20 m L ropivacaine（4 mg/m L） at the end of surgery. Group 3 was intravenously injected with preincisional ketamine（0.3 mg/kg） and local infiltration with 20 m L ropivacaine（4 mg/m L） at the end of surgery. A standard anesthetic was used for all patients, and meperidine was used for postoperative analgesia. The visual analogue scale（VAS） scores for incisional and visceral pain at 2, 6, 12, and 24 h, cumulative analgesic consumption and time until first analgesic medication request, and adverse effects were recorded postoperatively. The VAS scores of visceral pain in group 3 were significantly lower than those in group 2 and group 1 at 2 h and 6 h postoperatively（P〈0.05 and P〈0.01, respectively）. At 2 h and 6 h, the VAS scores of incisional pain did not differ significantly between groups 2 and 3, but they were significantly lower than those in group 1（P〈0.01）. Groups 1 and 2 did not show any differences in visceral pain scores at 2 h and 6 h postoperatively. Moreover, the three groups showed no statistically significant differences in visceral and incisional pain scores at 12 h and 24 h postoperatively. The consumption of analgesics was significantly greater in group 1 than in groups 2 and 3, and the time to first request for analgesics was significantly longer in groups 2 and 3 than in group 1, with no statistically significant difference between groups 2 and 3. However, the three groups showed no significant difference in

关键词： preemptive analgesia ketamine gynecological laparoscopic surgery visceral pain

Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells accelerate tooth extraction socket healing through the jaw vascular unit

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Science China Life Sciences 2025年

作者： Ruyu Wang Tianxiao Wang Ziyu Chen Jiandong Jiang Yifei Du Hua Yuan Yongchu Pan Yuli Wang department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine Nanjing Medical University department of Stomatology Chongzhou People's Hospital Medical Basic Research Innovation Centre for Cardiovascular and Cerebrovascular Diseases Ministry of Education International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical University Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College department of Orthodontic The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine Nanjing Medical University

Delayed tooth extraction socket(TES) healing can cause failure of subsequent oral implantation and increase socioeconomic burden on patients. Excessive amounts of M1 macrophages, apoptotic neutrophils(ANs), and neutrophil extracellular traps(NETs) impair alveolar bone regeneration during TES healing. In the present study, we first discovered that conditioned medium(CM) collected from berberine-treated human bone marrow mesenchymal stem cells(BBR-HB-CM) accelerated TES healing. BBR-HB-CM contained bioactive materials that promoted the polarization of macrophages from M1 to M2, impeded the formation of ANs and NETs, and modulated M2 macrophage efferocytosis in vivo and in vitro. Mechanistically, BBR-HB-CM promoted bone formation by inhibiting macrophage-myofibroblast transition and reprogrammed macrophage polarization through p85/AKT/mTOR pathway-dependent autophagy. The 3-methyladenine abolished the therapeutic effects of BBR-HB-CM. Further studies revealed that BBR-HB-CM accelerated TES healing in rats with type 2 diabetes mellitus. Overall, our results demonstrated that BBR-HB-CM had high potential to promote rapid TES healing.

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Synergistically S/N self-doped biochar as a green bifunctional cathode catalyst in electrochemical degradation of organic pollutant

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Green Energy & Environment 2025年第1期10卷 214-230页

作者： Xuechun Wang Huizhong Wu Jiana Jing Ge Song Xuyang Zhang Minghua Zhou Raf Dewil Key Laboratory of Pollution Process and Environmental Criteria Ministry of EducationCollege of Environmental Science and EngineeringNankai UniversityTianjin300350China Tianjin Key Laboratory of Environmental Technology for Complex Trans-Media Pollution Nankai UniversityTianjin300350China Tianjin Advanced Water treatment Technology International Joint Research Center College of Environmental Science and EngineeringNankai UniversityTianjin300350China department of Chemical Engineering KU LeuvenJ.De Nayerlaan 5Sint-Katelijne-Waver B2860Belgium

Biomass-derived heteroatom self-doped cathode catalysts has attracted considerable interest for electrochemical advanced oxidation processes(EAOPs)due to its high performance and sustainable ***,we illustrated the morphological fates of waste leaf-derived graphitic carbon(WLGC)produced from waste ginkgo leaves via pyrolysis temperature regulation and used as bifunctional cathode catalyst for simultaneous H_(2)O_(2) electrochemical generation and organic pollutant degradation,discovering S/N-self-doping shown to facilitate a synergistic effect on reactive oxygen species(ROS)*** the optimum temperature of 800℃,the WLGC exhibited a H_(2)O_(2) selectivity of 94.2%and tetracycline removal of 99.3%within 60 *** functional theory calculations and in-situ Fourier transformed infrared spectroscopy verified that graphitic N was the critical site for H_(2)O_(2) *** pyridinic N and thiophene S were the main active sites responsible for_OH generation,N vacancies were the active sites to produce ^(1)O_(2) from *** performance of the novel cathode for tetracycline degradation remains well under a wide pH range(3–11),maintaining excellent stability in 10 *** is also industrially applicable,achieving satisfactory performance treating in real water *** system facilitates both radical and non-radical degradation,offering valuable advances in the preparation of cost-effective and sustainable electrocatalysts and hold strong potentials in metal-free EAOPs for organic pollutant degradation.

关键词： Biochar S and N self-doping H_(2)O_(2)production In-situ FTIR Metal-free electrochemical advanced oxidation processes

Intranasal ketamine for the treatment of patients with acute pain in the emergency department

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World Journal of Emergency Medicine 2016年第1期7卷 19-24页

作者： Roshana Shrestha Samita Pant Ashis Shrestha Kabita Hada Batajoo Rashmi Thapa Sumana Vaidya department of General Practice and Emergency Medicine Manmohan Medical College and Teaching Hospital department of General Practice and Emergency Medicine Patan Academy of Health Sciences department of General Practice and Emergency Medicine KIST Medical College Hospital department of General Practice and Emergency Medicine KMC Medical College Hospital

BACKGROUND:pain in the emergency department(ED)is common but *** objective of this study was to examine the efficacy and safety of intranasal(IN)ketamine used as an analgesic for patients with acute injury with moderate to severe ***:This study was a cross sectional,observational study of patients more than 8 years old experiencing moderate to severe pain[visual analog score(VAS)>50 mm].The initial dose of IN ketamine was 0.7 mg/kg with an additional dose of 0.3 mg/kg if VAS was more than 50 mm after *** scores and vital signs were recorded at 0,15,30 and 60 ***-effects,sedation level and patient's satisfaction were also *** primary outcome was the number of patients achieving≥20 mm reductions in VAS at 15 *** secondary outcome measures were median reduction in VAS at 15,30 and 60 minutes,changes of vital signs,adverse events,satisfaction of patients,and need for additional ***:Thirty-four patients with a median age of 29.5 years(IQR 17.5–38)were enrolled,and they had an initial median VAS of 80 mm(IQR 67–90).The VAS decreased more than 20 mm at15 minutes in 27(80%)*** reduction of VAS from baseline to 40 mm(IQR 20–40),20 mm(IQR 14–20)and 20 mm(IQR 10–20)respectively at 15,30 and 60 minutes(Ppain in an overcrowded and resource limited ED.

关键词： Analgesia Intranasal Ketamine pain Visual analog score

MicroRNAs as potential diagnostic biomarkers for bipolar disorder

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Neural Regeneration Research 2025年第6期20卷 1681-1695页

作者： Bridget Martinez Philip V.Peplow department of Pharmacology University of Nevada-RenoRenoNVUSA department of Medicine University of Nevada-RenoRenoNVUSA department of Anatomy University of OtagoDunedinNew Zealand

Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed i

关键词： biomarker bipolar disorder blood leukocytes blood plasma blood plasma extracellular vesicles/exosomes blood serum brain tissue brain tissue extracellular vesicles/exosomes lymphoblastoid cell lines microRNA neural progenitor cells whole blood

Imperative for long-term management and surveillance in Kawasaki disease

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World Journal of Clinical Cases 2025年第4期13卷 61-63页

作者： Yan Pan Fu-Yong Jiao department of Pediatrics The First Affiliated Hospital of Yangtze UniversityJingzhou 434000Hubei ProvinceChina Shaanxi Kawasaki Disease Diagnosis and treatment Center Children’s HospitalShaanxi Provincial People’s Hospital of Xi’an Jiaotong UniversityXi’an 710000Shaanxi ProvinceChina

Kawasaki disease(KD)is a significant pediatric vasculitis known for its potential to cause severe coronary artery *** the effectiveness of initial treatments,such as intravenous immunoglobulin,KD patients can experience long-term cardiovascular issues,as evidenced by a recent case report of an adult who suffered a ST-segment elevation myocardial infarction due to previous KD in the World Journal of Clinical *** editorial emphasizes the critical need for long-term management and regular surveillance to prevent such *** drawing on recent research and case studies,we advocate for a structured approach to follow-up care that includes routine cardiac evaluations and preventive measures.

关键词： Kawasaki disease Long-term management Coronary artery aneurysm Surveillance Preventive care