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CCS Chemistry 2024年第1期6卷 177-195页

作者： Lang Zhao Shao-Hua Zhuo Tian-Yang Wang Jun-Jun Wu Jing-Yun Su Wen-Hao Li Bo-Dou Zhang Yan-Mei Li Key Lab of Bioorganic Phosphorus Chemistry&Chemical Biology Department of ChemistryTsinghua UniversityBeijing 100084 Beijing Institute for Brain Disorders Beijing 100069 Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084

Cyclic dinucleotides(CDNs)are natural agonists of the stimulator of interferon genes(STING),which is an attractive immunotherapy target.Currently,CDNs and their derivatives are being investigated clinically.However,the poor bioavailability of exogenous CDNs has limited their application in immunotherapy.Although nanocarriers are widely used for cytosolic delivery of CDNs,their loading capacity is insufficient,and their complicated composition and purification process raises bio-compatibility concerns.Herein,we report a super-simplified CDN self-assembly strategy for carrier-free delivery of CDNs.In the presence of excess K^(+),CDNs form oligomers which further self-assemble with divalent metal ions(such as Mn^(2+))to form nanoparticles(NPs)in aqueous solution.We demonstrate that the self-assembled CDN NPs promote cellular uptake of CDNs and enhance tumor immunogenicity by remodeling the tumor microenvironment,inducing immunogenic tumor cell death and increasing tumorinfiltrating lymphocytes,which is conducive to the generation of tumor neoantigen-specific T-cell responses.We also demonstrate that the use of CDN NPs alone or in combination with immune checkpoint blockades inhibits tumor growth,highlighting the fact that CDN NPs are a potent platform for cancer immunotherapy.

关键词： cyclic dinucleotide STING carrierfree delivery tumor immunogenicity cancer immunotherapy

Risk factors for postpartum posttraumatic stress disorder after emergency admission

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World Journal of Emergency Medicine 2024年第2期15卷 121-125页

作者： Fengxia Du Jun Zha Yan Li Lichao Fang Shuyu Xia Youjia Yu Department of Obstetrics Suzhou Xiangcheng People’s HospitalSuzhou 215131China Department of Anesthesiology the Second Affiliated Hospital of Wannan Medical CollegeWuhu 241000China Department of Anesthesiology Suzhou Xiangcheng People’s HospitalSuzhou 215131China Department of Emergency and Intensive Care Unit Suzhou Xiangcheng People’s HospitalSuzhou 215131China

BACKGROUND:Postpartum posttraumatic stress disorder(PTSD)can occur in women who give birth after emergency admission.The identification of risk factors for this condition is crucial for developing effective preventive measures.This retrospective study aimed to explore the incidence and risk factors for postpartum PTSD in women who give birth after emergency admission.METHODS:Medical records of women who gave birth after emergency admission were collected between March 2021 and April 2023.The patients’general conditions and perinatal clinical indicators were recorded.The puerperae were divided into PTSD group and control group based on symptom occurrence at six weeks postpartum.Multivariate logistic regression analysis was performed to identify risk factors.RESULTS:A total of 276 puerperae were included,with a PTSD incidence of 20.3% at six weeks postpartum.Multivariate logistic regression analysis identified emergency cesarean section(odds ratio[OR]=2.102;95%confidence interval[CI]:1.114-3.966,P=0.022),admission to the emergency department after midnight(12:00 AM)(OR=2.245;95%CI:1.170-4.305,P<0.001),and cervical dilation(OR=3.203;95%CI:1.670–6.141,P=0.039)as independent risk factors for postpartum PTSD.Analgesia pump use(OR=0.500;95%CI:0.259–0.966,P=0.015)was found to be a protective factor against postpartum PTSD.CONCLUSION:Emergency cesarean section,admission to the emergency department after midnight,and cervical dilation were identified as independent risk factors for postpartum PTSD,while analgesic pump use was a protective factor.These findings provide insights for developing more effective preventive measures for women who give birth after emergency admission.

关键词： Risk factors Posttraumatic stress disorder Emergency delivery

Engineered extracellular vesicles efficiently deliver CRISPR-Cas9 ribonucleoprotein(RNP)to inhibit herpes simplex virus1 infection in vitro and in vivo

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1362-1379页

作者： Yuanda Wan Liren Li Ruilin Chen Jiajia Han Qiyun Lei Zhipeng Chen Xiaodong Tang Wenyu Wu Shuwen Liu Xingang Yao NMPA Key Laboratory for Research and Evaluation of Drug Metabolism Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Center of Clinical Pharmacy Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Key Laboratory of Infectious Diseases Research in South China(Southern Medical University) Ministry of EducationGuangzhou 510515China

Extracellular vesicles(EVs)have recently emerged as a promising delivery platform for CRISPR/Cas9 ribonucleoproteins(RNPs),owing to their ability to minimize off-target effects and immune responses.However,enhancements are required to boost the efficiency and safety of Cas9 RNP enrichment within EVs.In response,we employed the Fc/Spa interaction system,in which the human Fc domain was fused to the intracellular domain of PTGFRN-Δ687 and anchored to the EV membrane.Simultaneously,the B domain of the Spa protein was fused to the C domain of cargos such as Cre or spCas9.Due to the robust interaction between Fc and Spa,this method enriched nearly twice the amount of cargo within the EVs.EVs loaded with spCas9 RNP targeting the HSV1 genome exhibited significant inhibition of viral replication in vitro and in vivo.Moreover,following neuron-targeting peptide RVG modification,the in vivo dosage in neural tissues substantially increased,contributing to the clearance of the HSV1 virus in neural tissues and exhibiting a lower off-target efficiency.These findings establish a robust platform for efficient EV-based SpCas9 delivery,offering potential therapeutic advantages for HSV1 infections and other neurological disorders.

关键词： Extracellular vesicles CRISPR/Cas9 Ribonucleoproteins PTGFRN Fc/Spa HSV1 Neuron-targeting delivery

Profile of Full-Term Births in Maternity Wards of Public Hospitals in Douala Cameroon

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Open Journal of Obstetrics and Gynecology 2024年第5期14卷 705-720页

作者： Henri Essome Merlin Boten Bounyom Astrid Ndolo Kondo Ingrid Doriane Ofakem Ilick Fulbert Mangala Nkwele Irène Cyrielle Edjoa Mboe Michel Roger Ekono Alphonse Ngalame Nyong Robert Tchounzou Moustapha Bilkissou Junie Ngaha Yaneu Marga Vanina Ngono Akam Gervais Mounchikpou Ngouhouo Grâce Tocki Toutou Théophile Nana Njamen Valère Mve Koh Pascal Foumane Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon Laquintinie Hospital Douala Cameroon Faculty of Health Sciences University of Bamenda Bamenda Cameroon Faculty of Health Sciences University of Buea Buea Cameroon Faculty of Medicine and Biomedical Sciences University of Yaound&#233 1 Yaound&#233 Cameroon Faculty of Medicine and Pharmaceutical Sciences of Sangmelima University of Ebolowa Ebolowa Cameroon

Introduction: Pregnancy as much as childbirth constitutes a risky situation, potentially fraught with sometimes dramatic complications: maternal death. Objective: We conducted this study with the aim of establishing the profile of those giving birth in our context with the aim to anticipate operationally in the future on morbidity but more on maternal deaths. Methodology: We conducted, using a structured questionnaire, a prospective descriptive study in representative maternity wards in the city of Douala;the study variables were socio-economic, anthropometric, obstetrical and clinical. Statistical analyses were carried out with CS Pro 7.3 and SPSS version 25.0 software. The Student, Chi-square and Fischer tests were used to compare the means of the variables and the percentages. Results: We recruited 305 births for our study. The average age of our births was 28.7 years ± 6.1 with an average height of 161.6 cm ± 5.06;an average body mass index at the start of pregnancy of 28.0 kilograms/square meter and 31.3 kilograms/square meter at delivery;the average weight gain was 8.4 g ± 5.37;an average gestation of 2.84±1.90;an average parity of 2.2 ± 2.1 with an average birth interval of 27.7 months ± 23.7. The average gestational age was 39.2 weeks ± 1.21 with pregnancy pathology dominated by malaria;85.9% began their prenatal follow-up before the 14th week of amenorrhea. Conclusion: The profile of childbirth in urban Cameroon does not seem potentially dystocic compared to that of the same regional and racial area.

关键词： Profile delivery Term Malaria Douala

Determinants and Outcomes of Pregnancies among Booked versus Unbooked Patients in a Tertiary Hospital South East, Nigeria

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Open Journal of Obstetrics and Gynecology 2024年第1期14卷 144-161页

作者： Chijioke S. Anyigor-Ogah John O. Egede Chijioke O. Ogeh Chika C. Agunanne Alphosus I. Ozioko Chinyere C. Duru Department of Family Medicine Alex Ekwueme Federal University Teaching Hospital Abakaliki Ebonyi State Nigeria Department of Obstetrics and Gynaecology Alex Ekwueme Federal University Teaching Hospital Abakaliki Ebonyi State Nigeria Department of Paediatrics Alex Ekwueme Federal University Teaching Hospital Abakaliki Ebonyi State Nigeria

Background: Inadequate antenatal care, both in coverage and standard, has been linked with poor pregnancy outcomes. In a resource poor setting, home delivery is considered very cheap, but the possible outcome of such pregnancies has been a subject of interest. This study evaluated the association of booking status with pregnancy outcomes. Objectives: To examine the factors that influence booking and impact of the booking status on pregnancy outcomes. Methods: This was a hospital-based prospective cohort study of 240 (120 booked and 120 un-booked) pregnant mothers selected through systematic random sampling. The study was carried out at the Department of Obstetrics and Gynaecology, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Nigeria. Chi-square test, t-test and logistic regression were used for analysis. Results: The mean age of the participants was 30.39 ± 5.05 years and 29.05 ± 6.36 years respectively for the booked and unbooked. Marital status (OR = 6.35, 95% CI = 1.24 - 32.59), educational status (OR = 36.40, 95% CI = 5.26-152.83), place of residence (OR = 0.15, 95% CI = 0.06 - 0.41), partner’s support (OR = 0.05, 95% CI = 0.01 - 0.37), family support (OR = 0.03, 95% CI = 0.01 - 0.13), mode of delivery (OR = 0.23, 95% CI = 0.12 - 0.46), APGAR score in first minute (OR = 6.02, 95% CI = 2.45 - 14.83) and NBICU admission (OR = 3.75, 95% CI = 1.67 - 8.43) were associated with booked status. However, being unmarried, nulliparity/grandmultiparity, low level of education, blue colar jobs, low income, rural dwelling and poor partner and poor family support were associated with the unbooked. The booked parturients had a better perinatal outcome compared the unbooked. Conclusion/Recommendation: There was high prevalence of operative deliveries, perinatal morbidity and mortality among the unbooked mothers. Girl child education, employment and poverty alleviation would improve antenatal care utilization.

关键词： Socio-Demographic Characteristics Booking Status Antenatal delivery

A micelle-based stage-by-stage impelled system for efficient doxorubicin delivery

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Bioactive Materials 2023年第7期25卷 783-795页

作者： Sunfan Li Fangzhou Li Dong Wan Zuqin Chen Jie Pan Xing-Jie Liang School of Chemical Engineering and Technology Tiangong UniversityTianjin300387PR China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaNo.11First North RoadZhongguancunBeijing100190PR China University of Chinese Academy of Sciences Beijing100049PR China Medical School of Chinese PLA No.28 Fuxing RoadBeijing100853PR China Department of Radiology The First Medical CentreChinese PLA General HospitalBeijingPR China Department of Radiology Chinese PAP Guangxi Corps HospitalNanningGuangxiPR China

Chemotherapy remains the mainstay of cancer treatment,benefiting millions of patients each year,but the side effects of chemotherapy drugs severely limit their clinical use.Doxorubicin(DOX)can cause various side effects such as heart damage and treatment-related tumors.The effective use of active and passive targeting will improve the clinical application of DOX.Here,TPGS3350 and bioactive peptides were utilized to construct a micelle-based stage-by-stage impelled efficient system(missiles)for DOX delivery(DOX missiles).By taking advantage of the EPR effect,DOX missiles are efficiently enriched at the tumor site.After being cleaved by matrix metalloproteinase2(MMP2),the peptide(VRGD)targets tumor cells to facilitate uptake of the missiles by the tumor cells via receptor-mediated endocytosis.The intracellular activated caspase-3-catalyzed explosion of DOX missiles further enables efficient tumor killing.This study provides an efficient approach for DOX delivery and toxicity reduction.

关键词： Doxorubicin delivery Peptide Missiles Chemotherapy

Gold nanoparticle-assisted delivery of brain-derived neurotrophic factor to cerebral organoids

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Nano Research 2022年第4期15卷 3099-3105页

作者： Sung Bum Park Hye-Jin Cho Sang Rin Moon Kyoung Jin Choi Won Hoon Jung Ki Young Kim Byumseok Koh Therapeutics and Biotechnology Division Korea Research Institute of Chemical Technology141 Gajeong-roYuseong-guDaejeon 34114Republic of Korea Chemical Platform Technology Division Korea Research Institute of Chemical Technology141 Gajeong-roYuseong-guDaejeon 34114Republic of Korea

Gold nanoparticle(AuNP)-assisted delivery of proteins/drugs to cells or in vivo systems has long been studied.However,their interaction with in vivo mimicking organoids is still largely unknown.Here,we conjugated brain-derived neurotropic factor(BDNF)to the AuNP surface and monitored how AuNP-BDNF interacts with cerebral organoids.Data suggest that AuNP-BDNF can successfully enter cerebral organoids and can be found up to 15.21μm inside cerebral organoids.AuNP-BDNF does not induce significant cytotoxicity to cerebral organoids at concentrations up to 2 nM and increases the expression of 75 genes compared to control cerebral organoids.These data suggest the successful delivery of BDNF through AuNP-BDNF conjugation in cerebral organoids,and the conjugation can affect its differentiation.

关键词： gold nanoparticles cerebral organoids delivery penetration differentiation viability

Gestational diabetes mellitus:The optimal time of delivery

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World Journal of Diabetes 2023年第3期14卷 179-187页

作者： Xuan Li Teng-Teng Li Rui-Xian Tian Jia-Jia Fei Xing-Xing Wang Hui-Hui Yu Zong-Zhi Yin Department of Obstetrics and Gynecology The First Affiliated Hospital of Anhui Medical UniversityHefei 230022Anhui ProvinceChina NHC Key Laboratory of the Study of Abnormal Gametes and the Reproductive Tract Anhui Medical UniversityHefei 230022Anhui ProvinceChina Key Laboratory of Population Health Across Life Cycle Anhui Medical UniversityHefei 230022Anhui ProvinceChina

Gestational diabetes mellitus(GDM)is a common pregnancy complication strongly associated with poor maternal-fetal outcomes.Its incidence and prevalence have been increasing in recent years.Women with GDM typically give birth through either vaginal delivery or cesarean section,and the maternal-fetal outcomes are related to several factors such as cervical level,fetal lung maturity,the level of glycemic control still present,and the mode of treatment for the condition.We categorized women with GDM based on the latter two factors.GDM that is managed without medication when it is responsive to nutrition-and exercise-based therapy is considered diet-and exercise-controlled GDM,or class A1 GDM,and GDM managed with medication to achieve adequate glycemic control is considered class A2 GDM.The remaining cases in which neither medical nor nutritional treatment can control glucose levels or patients who do not control their blood sugar are categorized as class A3 GDM.We investigated the optimal time of delivery for women with GDM according to the classification of the condition.This review aimed to address the benefits and harms of giving birth at different weeks of gestation for women with different classes of GDM and attempted to provide an analytical framework and clearer advice on the optimal time for labor.

关键词： Diabetes Glucose Pregnancy delivery Optimal time Maternal-fetal outcomes

Engineered nucleus-free mesenchymal stem cells (MSCs) for the targeted delivery of therapeutics to disease site

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Genes & Diseases 2023年第2期10卷 310-312,I0001页

作者： Zander Schwartz Piao Zhao Annie Wang Guozhi Zhao Wei Zeng Yonghui Wang Hue H. Luu Rex C. Haydon Tong-Chuan He Russell R. Reid Jason Strelzow School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Specialized therapeutic delivery, or use of pharmaceuticals and other biomaterials to target specific parts of the body or diseased tissue, has long been sought as an ideal way of treating human diseases. A recent article published in Nature Biomedical Engineering revealed an innovative strategy to engineer nucleus-free human mesenchymal stem cells (MSCs) for targeted delivery of therapeutics to disease site.1 MSCs have emerged as promising vehicles of therapeutic delivery.2,3 MSCs are undifferentiated pluripotent stem cells derived from areas such as bone marrow and adipose tissue.4,5 MSCs are sought after for their chemotaxis, or ability to home towards a chemical stimulus, and capacity for modification with elements such as chemoattractant receptors and adhesion molecules.1 These properties allow for site-specific and minimally-invasive therapeutic administration and treatment.

关键词： targeted delivery sought

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大手携小手

英语角 2024年第14期 48-51页

作者：无中福会少年宫

delivery intheFuture Soon,when we shop online,we might receive(收到)things the same day.Because there will be robots delivering(运输)them.作者:滕子印。

关键词： online delivery deliver