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Ionic liquids as the effective technology for enhancing transdermal drug delivery: Design principles, roles, mechanisms, and future challenges

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 38-51页

作者： Xuejun Chen Ziqing Li Chunrong Yang Degong Yang department of Pharmacy Shantou University Medical CollegeShantou 515041China Guangdong Provincial Key Laboratory of infectious diseases and Molecular Immunopathology Shantou University Medical CollegeShantou 515041China

Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs;as novel solvents for improving the solubility of drugs in carriers;as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs;and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structure-activity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs.

关键词： Transdermal drug delivery system Ionic liquid Quantitative structure-activity relationship Intermolecular interaction

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Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1199-1208页

作者： Xinyi Yang Xu Zheng Yuqi Zhu Xiaying Zhao Jun Liu Jiangna Xun Songhua Yuan Jun Chen Hanyu Pan Jinlong Yang Jing Wang Zhimin Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Min Li Fei Peng Daru Lu Jianqing Xu Hongzhou Lu Shibo Jiang Ping Zhao Huanzhang Zhu State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology Ministry of EducationInstitute of GeneticsSchool of Life SciencesYiwu Research InstituteFudan UniversityShanghaiChina department of Microbiology Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Scientific Research Center Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina department of infectious diseases and Immunology Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Changzheng Hospital Naval Medical UniversityShanghaiChina Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghaiChina department of infectious diseases and Nursing Research Institution National Clinical Research Center for Infectious DiseasesThe Third People’s Hospital of ShenzhenShenzhenGuangdongChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)causes multi-organ damage,which includes hepatic dysfunction,as observed in over 50%of COVID-19 *** I converting enzyme(peptidyl-dipeptidase A)2(ACE2)is the primary receptor for SARS-CoV-2 entry into host cells,and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2,but at extremely low ***,we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into *** address this question,we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1(ASGR1)promoted SARS-CoV-2 pseudovirus infection of HeLa *** Huh-7 cells,simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus *** the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells,both of which barely expressed ACE2,SARSCoV-2 pseudovirus could successfully establish an ***,after treatment with ASGR1 antibody or siRNA targeting ASGR1,the infection rate significantly dropped,suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent *** confirmed that ASGR1 could interact with Spike protein,which depends on receptor binding domain(RBD)and N-terminal domain(NTD).Finally,we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal *** inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA,the infection efficiency of the live virus decreased ***,these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.

关键词： ACE2 infection glycoprotein

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A retrospective analysis of carbapenem-resistant Acinetobacter baumannii infections in critically ill patients:Experience at a tertiary-care teaching hospital ICU

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Journal of Intensive Medicine 2024年第2期4卷 181-186页

作者： Leyla Ferlicolak Neriman Defne Altintas Fugen Yoruk department of Internal Medicine Division of Intensive Care Unit Ankara University Faculty of MedicineAnkaraTurkey department of infectious diseases and Clinical Microbiology Ankara University Faculty of MedicineAnkaraTurkey

Background Acinetobacter baumannii is a clinically significant pathogen with a high incidence of multidrug resistance that is associated with life-threatening nosocomial ***,we aimed to provide an insight into the clinical characteristics and outcomes of a unique group of *** infections in which the isolates were resistant to carbapenems and most other antibiotic groups in a tertiary-care intensive care unit(ICU).Methods We performed a retrospective observational study in which records of patients hospitalized in the ICU between June 1,2021 and June 1,2023 were *** checked the clinical,laboratory,and microbiological records of all adult patients who had carbapenem-resistant ***(CRAB)*** antibiotic treatments and definitive antibiotic treatments after culture positivity and susceptibility test results were recorded.C-reactive protein(CRP)and procalcitonin levels and leukocyte counts were *** of ICU stay and 30-day mortality were defined as the outcome *** During the study period,57 patients were diagnosed with CRAB *** respiratory tract was the leading infection site(80.7%).In non-survivors,bloodstream infections(21.9%vs.4.0%P=0.05)and colistin-resistant(col-R)CRAB infections(43.8%vs.24.0%,P=0.12)were more common than in survivors,but these parameters were not statistically *** length of ICU stay was not different between survivors and ***,the rate of col-R among CRAB clinical isolates was 35.1%.The 30-day mortality in all patients with CRAB infection was 56.1%.Mortality in col-R CRAB and colistin-susceptible(col-S)CRAB infections was 70.0%and 48.6%,respectively(P=0.12).Prior carbapenem use was 56.1%.Prior colistin use before col-R and col-S CRAB infections was not significant(35.0%vs.27.0%,P=0.53).Conclusions Our study provides real-world data on highly resistant *** infections and shares the characteristics of infections with such resistant stra

关键词： Mortality Colistin-resi stant Gram-negative bacteria MDR Intensive care unit

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Sm-like 5 knockdown inhibits proliferation and promotes apoptosis of colon cancer cells by upregulating p53,CDKN1A and TNFRSF10B

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2716-2726页

作者： Cai-Jing Mo Xiao-Yuan Deng Ru-Lan Ma Kun Zhu Lei Shi Kang Li department of Surgical Oncology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina department of infectious diseases The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina

BACKGROUND The role of Sm-like 5(LSM5)in colon cancer has not been *** this study,we investigated the role of LSM5 in progression of colon cancer and the potential underlying mechanism *** To determine the role of LSM5 in the progression of colon cancer and the potential underlying mechanism *** The Gene Expression Profiling Interactive Analysis database and the Human Protein Atlas website were used for LSM5 expression analysis and prognosis ***-time quantitative polymerase chain reaction and Western blotting were utilized to detect the expression of mRNAs and proteins.A lentivirus targeting LSM5 was constructed and transfected into colon cancer cells to silence LSM5 *** and apoptosis assays were also conducted to evaluate the growth of the colon cancer *** GeneChip assay and bioinformatics analysis were performed to identify the potential underlying mechanism of LSM5 in colon *** LSM5 was highly expressed in tumor tissue and colon cancer cells.A high expression level of LSM5 was related to poor prognosis in patients with colon *** of LSM5 suppressed proliferation and promoted apoptosis in colon cancer *** of LSM5 also facilitates the expression of p53,cyclin-dependent kinase inhibitor 1A(CDKN1A)and tumor necrosis factor receptor superfamily 10B(TNFRSF10B).The inhibitory effect of LSM5 knockdown on the growth of colon cancer cells was associated with the upregulation of p53,CDKN1A and *** LSM5 knockdown inhibited the proliferation and facilitated the apoptosis of colon cancer cells by upregulating p53,CDKN1A and TNFRSF10B.

关键词： Sm-like 5 Colon cancer Proliferation Apoptosis Knockdown

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Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 398-413页

作者： Juan-Juan Shi Yi-Kai Wang Mu-Qi Wang Jiang Deng Ning Gao Mei Li Ya-Ping Li Xin Zhang Xiao-Li Jia Xiong-Tao Liu Shuang-Suo Dang Wen-Jun Wang department of infectious diseases The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi'an 710004Shaanxi ProvinceChina department of Operating Room The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi'an 710004Shaanxi ProvinceChina

BACKGROUND Prohibitin 1(PHB1)has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed,and it participates in a variety of essential cellular functions,including apoptosis,cell cycle regulation,prolifera-tion,and *** evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma(HCC).However,the role of PHB1 in HCC is *** To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in *** HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria;then,PHB1 levels in the sera and liver tissues of these participates were determined using ELISA,RT-PCR,and *** HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA(shRNA-PHB1)for 24-72 *** prolif-eration was analysed with an MTT *** cycle progression and apoptosis were analysed using flow cytometry(FACS).The mRNA and protein expression levels of the cell cycle-related molecules p21,Cyclin A2,Cyclin E1,and CDK2 and the cell apoptosis-related molecules cytochrome C(Cyt C),p53,Bcl-2,Bax,caspase 3,and caspase 9 were measured by real-time PCR and Western blot,*** Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals,and decreased PHB1 was positively correlated with low differentiation,TNM stage III-IV,and alpha-fetoprotein≥400μg/*** of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent *** revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced *** proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compar

关键词： Prohibitin 1 Hepatocellular carcinoma cells Apoptosis Cell cycle Mitochondrial pathway

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Enhanced homing of mesenchymal stem cells for in situ niche remodeling and bone regeneration

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Nano Research 2024年第8期17卷 7449-7460页

作者： Yin Yuan Lijun Chen Jing Yang Sining Zhou Yangxin Fang Qi Zhang Ning Zhang Yifei Li Li Yuan Fan Jia Shuo Ni Charlie Xiang State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Biology The David H.Koch Institute for Integrative Cancer Research at MITMassachusetts Institute of TechnologyCambridgeMA 02139USA Research Units of infectious disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China Innovative Precision Medicine(IPM)Group Hangzhou 311215China MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of CardiologySir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China department of Cancer Immunology and Virology Dana-Farber Cancer InstituteBostonMA 02215USADepartment of ImmunologyHarvard Medical SchoolBoston MA 02115USA department of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200233China

Mesenchymal stem cells(MSCs)transplantation is a promising strategy for osteoporosis ***,limited sources and poor tissue-homing efficiency limit their clinical *** this study,we isolated a kind of MSCs from women’s menstrual blood(MenSCs)noninvasively and established a novel MSCs bone marrow-targeted delivery system by utilizing waterin-oil-in-water droplet *** were encapsulated withinβ-cyclodextrin-functionalized alginate microcapsules loaded with zoledronates,which has a high affinity for *** this delivery system,MenSCs could be preferentially delivered to the bone marrow tissues via intravenous infusion,and restored bone mass by remodeling the bone marrow niche in situ in ovariectomized mouse ***,scRNA-seq analysis demonstrated that those MenSCs homed to the bone marrow recruited CD4^(+)FOXP3^(+)natural regulatory T(nT_(reg))cells by secreting *** recruited nTreg promoted CD8^(+)T cells to secret Wnt family member 10B(WNT10B),activating the Wnt signaling in osteoblasts and thus promoting bone formation in situ in the bone *** study reveals a promising application of MenSCs in postmenopausal osteoporosis treatment and highlights the clinical value of MenSCs by encouraging women to reserve autologous MenSCs before menopause to prevent and alleviate postmenopausal osteoporosis.

关键词： mesenchymal stem cells microfluidics bone marrow homing stem cell niche postmenopausal osteoporosis

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Complementary and alternative medicine on cognitive defects and neuroinflammation after sepsis

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Journal of Traditional Chinese Medicine 2024年第2期44卷 408-416页

作者： LI Zhenxuan WANG Xuerui Luis Ulloa Ayman Youssef BAI Yunjing XU Xiaolong LIU Qingquan department of infectious diseases Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on infectious diseases Beijing 100010China Infection immunity laboratory Beijing Institute of Traditional Chinese MedicineBeijing 100010China Clinical College of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Center for Perioperative Organ Protection Department of AnesthesiologyDuke University Medical CenterDurhamNorth Carolina 27710USA

Sepsis-associated encephalopathy(SAE)is a common manifestation of sepsis,ranging from mild confusion and delirium to severe cognitive impairment and deep *** is associated with higher mortality and long-term outcomes,particularly substantial declines in cognitive *** mechanisms of SAE probably include neuroinflammation that is mediated by systemic inflammation and ischemic lesions in the brain,a disrupted blood–brain barrier,oxidative stress,neurotransmitter dysfunction,and severe microglial *** evidence suggests that complementary and alternative medicine,especially Traditional Chinese Medicine(TCM),is favorable in alleviating cognitive decline after ***,we summarized the studies of traditional herbal remedies,TCM formulas and acupuncture therapy in animal models of neurological dysfunctions after sepsis in recent decades and reviewed their potential mechanisms.

关键词： sepsis-associated encephalopathy cognitive dysfunction complementary therapies neuroinflammatory diseases medicine Chinese traditional review

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Endogenous retrovirus activation: potential for immunology and clinical applications

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National Science Review 2024年第4期11卷 21-23页

作者： Jundan Yu Peishan Qiu Jingwen Ai Bo Liu Guan-Zhu Han Fan Zhu Wenhong Zhang Jie Cui department of infectious diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response National Medical Center for Infectious Diseases Huashan Hospital Shanghai Medical College Fudan University CAS Key Laboratory of Molecular Virology &Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai Huashen Institute of Microbes and Infections College of Life Sciences Nanjing Normal University State Key Laboratory of Virology and department of Medical Microbiology School of Basic Medical SciencesWuhan University The Institute of Infection and Health Research Fudan University Key Laboratory of Medical Molecular Virology(MOE/MOH) Shanghai Medical CollegeFudan University Laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology Center

Endogenous retroviruses (ERVs), the remnants of ancient retrovirus infections, constitute approximately 8% of the human genome and play important roles in human evolution, development,and diseases. Multiple drugs, such as DNA methyltransferase inhibitors and lysine-specific histone demethylase 1inhibitors, reactivate ERVs, induce viral mimicry and trigger innate immune responses to enhance tumor immunogenicity.

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Predictors of portal vein thrombosis after splenectomy in patients with cirrhosis

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World Journal of Hepatology 2024年第2期16卷 241-250页

作者： Ting Li Li-Li Wang Ya-Ping Li Jian Gan Xi-Sheng Wei Xiao-Rong Mao Jun-Feng Li department of infectious diseases The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710000Shaanxi ProvinceChina department of Radiology First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina department of Gastroenterology Yantai Affiliated Hospital of Binzhou Medical UniversityYantai 264100Shandong ProvinceChina department of infectious diseases The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND Portal vein thrombosis(PVT)is a commonthsn complication after splenectomy in patients with ***,the predictors of postoperative PVT are not *** To investigate the predictors of PVT after splenectomy in patient with *** A total of 45 patients with cirrhosis who underwent splenectomy were consecutively enrolled from January 2017 to December *** incidence of PVT at 1 months,3 months,and 12 months after splenectomy in patients with cirrhosis was *** hematological indicators,biochemical and coagulation parameters,and imaging features were recorded at baseline and at each observation *** univariable,multivariable,receiver operating characteristic curve and timedependent curve analyses were *** The cumulative incidence of PVT was 40.0%,46.6%,and 48.9%at 1 months,3 months,and 12 months after *** analysis showed that portal vein diameter(PVD)≥14.5 mm and monthsdel end-stage liver disease(MELD)score>10 were independent predictors of PVT at 1 months,3 months,and 12 months after splenectomy(P10(P10 were independent predictors of PVT at 1 months,3 months,and 12 months after splenectomy in patient with cirrhosis.

关键词： Cirrhosis Splenectomy Portal vein thrombosis Predictors

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Left atrial appendage occluder detachment treated with transthoracic ultrasound combined with digital subtraction angiography guided catcher:A case report

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World Journal of Clinical Cases 2024年第6期12卷 1157-1162页

作者： Kai Yu Yun-Hua Mei department of Ultrasound Wuhan Dongxihu District People's HospitaWuhan 430400Hubei ProvinceChina department of infectious diseases Wuhan Dongxihu District People's HospitalWuhan 430400Hubei ProvinceChina

BACKGROUND There are very few cases of cardiac occluder detachment,and it is rare to completely remove the occluder using interventional methods without undergoing thoracotomy surgery after *** case innovatively used ultrasound guidance combined with digital subtraction angiography(DSA)to completely remove the occluder,accumulating some *** SUMMARY The patient underwent left atrial appendage occlusion surgery in our hospital due to atrial *** the surgery,the occluder fell off and became free in the left ventricle,which is very *** innovatively used ultrasound guidance,combined with DSA,and interventional surgery to successfully capture the free occluder using a catcher,completely remove it,and then re implant a new left atrial appendage *** the surgery,the patient recovered very *** The size selection of the occluder is slightly conservative,and the shape of the left atrial appendage opening is irregular.

关键词： Left atrial appendage occluder Detachment Ultrasound combined with digital subtraction angiography Interventional operation Successfully captured Case report

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