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Hypoglycemic activities of flowers of Xanthoceras sorbifolia and identification of anti-oxidant components by off-line UPLC-QTOF-MS/MS-free radical scavenging detection

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Chinese Herbal Medicines 2024年第1期16卷 151-161页

作者： Xiajing Xu Yongli Guo Menglin Chen Ning Li Yi Sun Shumeng Ren jiao xiao Dongmei Wang xiaoqiu Liu Yingni Pan School of Chinese Materia Medica Key Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang CityShenyang Pharmaceutical UniversityShenyang 110016China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

Objective: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities.Methods: The AlCl3colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti-oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C18column(2.0 mm × 150 mm, 5 μm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase(PDB ID: 2CDU) by molecular docking.Results: Combined with the results of activity screening in vitro, the anti-oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatographymass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory profile.Conclusion: The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin.

关键词： anti-hyperglycemic activity anti-oxidant flowers of Xanthoceras sorbifolia Bunge NADPH oxidase off-line UPLC-QTOF-MS/MS-free radical scavenging

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New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： xiao-Peng Duan Bao-Dong Qin xiao-Dong jiao Ke Liu Zhan Wang Yuan-Sheng Zang Department of Medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each other.Due to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol framework.In recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities.Despite the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains limited.The majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial designs.Therefore,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision medicine.Meanwhile,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

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Development and validation of a nomogram model for predicting the risk of pre-hospital delay in patients with acute myocardial infarction

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World Journal of Cardiology 2024年第2期16卷 80-91页

作者： jiao-Yu Cao Li-Xiang Zhang xiao-Juan Zhou Department of Cardiology The First Affiliated Hospital of USTCDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina

BACKGROUND Acute myocardial infarction(AMI)is a severe cardiovascular disease caused by the blockage of coronary arteries that leads to ischemic necrosis of the myocardium.Timely medical contact is critical for successful AMI treatment,and delays increase the risk of death for patients.Pre-hospital delay time(PDT)is a significant challenge for reducing treatment times,as identifying high-risk patients with AMI remains difficult.This study aims to construct a risk prediction model to identify high-risk patients and develop targeted strategies for effective and prompt care,ultimately reducing PDT and improving treatment outcomes.AIM To construct a nomogram model for forecasting pre-hospital delay(PHD)likelihood in patients with AMI and to assess the precision of the nomogram model in predicting PHD risk.METHODS A retrospective cohort design was employed to investigate predictive factors for PHD in patients with AMI diagnosed between January 2022 and September 2022.The study included 252 patients,with 180 randomly assigned to the development group and the remaining 72 to the validation group in a 7:3 ratio.Independent risk factors influencing PHD were identified in the development group,leading to the establishment of a nomogram model for predicting PHD in patients with AMI.The model's predictive performance was evaluated using the receiver operating characteristic curve in both the development and validation groups.RESULTS Independent risk factors for PHD in patients with AMI included living alone,hyperlipidemia,age,diabetes mellitus,and digestive system diseases(P<0.05).A characteristic curve analysis indicated area under the receiver operating characteristic curve values of 0.787(95%confidence interval:0.716–0.858)and 0.770(95%confidence interval:0.660-0.879)in the development and validation groups,respectively,demonstrating the model's good discriminatory ability.The Hosmer–Lemeshow goodness-of-fit test revealed no statistically significant disparity between the anticipated and observed incidence of PHD in both

关键词： Pre-hospital delay Acute myocardial infarction Risk prediction Nomogram

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Buckling Properties of Water-Drop-Shaped Pressure Hulls with Various Shape Indices Under Hydrostatic External Pressure

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China Ocean Engineering 2024年第1期38卷 1-17页

作者： DING xiao-de ZHANG Jian WANG Fang jiao Hui-feng WANG Ming-lu School of Mechanical Engineering Jiangsu University of Science and TechnologyZhenjiang 212003China Shanghai Engineering Research Center of Marine Renewable Energy College of Engineering Science and Technol-ogyShanghai Ocean UniversityShanghai 201306China China Ship Scientific Research Center Wuxi 214082China

The water-drop-shaped pressure hull has a good streamline,which has good application prospect in the underwater observatory.Therefore,this study conducted analytical,experimental and numerical investigation of the buckling properties of water-drop-shaped pressure hulls under hydrostatic pressure.A water-drop experiment was conducted to design water-drop-shaped pressure hulls with various shape indices.The critical loads for the water-drop-shaped pressure hulls were resolved by using Mushtari’s formula.Several numerical simulations including linear buckling analysis and nonlinear buckling analysis including eigenmode imperfections were performed.The results indicated that the critical loads resolved by Mushtari's formula were in good agreement with the linear buckling loads from the numerical simulations.This formula can be extended to estimate the buckling capacity of water-drop-shaped pressure hulls.In addition,three groups of pressure hulls were fabricated by using stereolithography,a rapid prototyping technique.Subsequently,three groups of the pressure hulls were subjected to ultrasonic measurements,optical scanning,hydrostatic testing and numerical analysis.The experimental results were consistent with the numerical results.The results indicate that the sharp end of the water-drop-shaped pressure hulls exhibited instability compared with the blunt end.This paper provides a new solution to the limitations of experimental studies on the water-drop-shaped pressure hulls as well as a new configuration and evaluation method for underwater observatories.

关键词： buckling pressure hull water drop underwater observatory

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Oleuropein alleviates sepsis-induced acute lung injury via the AMPK/Nrf-2/HO-1 signaling

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Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 187-198页

作者： Shan-Hu Wang Yang-Yang Wu xiao-jiao Xia Department of Pediatrics The Second Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325027China

Objective:To explore the effect of oleuropein on sepsis-induced acute lung injury(ALI)in vitro and in vivo and investigate the underlying mechanism.Methods:In an lipopolysaccharide(LPS)-mediated cell model of sepsis-induced ALI and a cecal ligation and puncture-induced mouse model of septic ALI,CCK-8 assay and flow cytometry analysis were used to detect cell activity and apoptosis.ELISA and relevant assay kits were used to measure the levels of inflammatory cytokines and oxidative stress,respectively.Western blot was applied to determine the expression of apoptosis-and AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor-2(Nrf-2)/heme oxygenase-1(HO-1)signaling-associated proteins.JC-1 staining,adenosine triphosphate(ATP)assay kit,and MitoSOX Red assays were performed to detect mitochondrial membrane potential,ATP content,and mitochondrial ROS formation,respectively.Moreover,lung injury was evaluated by measuring lung morphological alternations,lung wet-to-dry ratio,myeloperoxidase content,and total protein concentration.Results:Oleuropein reduced inflammatory reaction,oxidative damage,and apoptosis,and ameliorated mitochondrial dysfunction in LPS-exposed BEAS-2B cells and mice with septic ALI.Besides,oleuropein activated the AMPK/Nrf-2/HO-1 signaling pathway.However,these effects of oleuropein were abrogated by an AMPK inhibitor compound C.Conclusions:Oleuropein can protect against sepsis-induced ALI in vitro and in vivo by activating the AMPK/Nrf-2/HO-1 signaling,which might be a potential therapeutic agent for the treatment of sepsis-induced ALI.

关键词： AMPK/Nrf-2/HO-1 signaling Inflammatory response Lung damage Mitochondrial dysfunction Oleuropein Oxidative stress Sepsis

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RNA m6A dynamic modification mediated by nucleuslocalized FTO is involved in follicular reserve

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Zoological Research 2024年第2期45卷 415-428页

作者： jiao-Na Zhang Rui-Ting Wang Francesca-Gioia Klinger Shun-Feng Cheng Wei Shen xiao-Feng Sun College of Life Sciences Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of ShandongQingdao Agricultural UniversityQingdaoShandong 266109China Department of Biomedicine and Prevention University of Rome Tor VergataRome 00133Italy

In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers.The fat-mass and obesity-associated protein(FTO)catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes.Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles,with an inverse relationship observed for m6A levels and nuclear-localized FTO expression.Application of Fto small interfering RNA(si RNA)altered the expression of genes related to cell proliferation,hormone regulation,and cell chemotaxis,and affected RNA alternative splicing.Overexpression of the full-length Fto gene led to changes in m6A levels,alternative splicing of Cdk5,cell proliferation,cell cycle progression,and proportion of primordial follicles.Conversely,overexpression of Fto lacking a nuclear localization signal(NLS)did not significantly alter m6A levels or primordial follicle assembly.These findings suggest that FTO,localized in the nucleus but not in the cytoplasm,regulates RNA m6A demethylation and plays a role in cell proliferation,cell cycle progression,and primordial follicle assembly.These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.

关键词： m6A FTO Ovary Primordial follicle assembly Alternative splicing

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Bilateral iridocorneal endothelial syndrome-Chandler’s syndrome:a case report and literature review

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 773-776页

作者： xiao-Hua Pan Yu-Fei Tao Ming-Min Yang xiao-Li Shen jiao Si Ming Li Ning Fan Shenzhen Eye Hospital Jinan UniversityShenzhen 518040Guangdong ProvinceChina

Dear Editor,I ridocorneal endothelial syndrome(ICE)is a rare ocular disease first proposed by Eagle et al[1]in 1979.It is mainly characterized by corneal endothelial abnormalities,accompanied by iris atrophy,iris pigmented nodules and peripheral anterior synechiae.ICE syndrome is typically unilateral,and classified into three clinical variants based on the changes of the cornea and iris,including progressive iris atrophy,Chandler’s syndrome,and Cogan-Reese syndrome.

关键词： corneal atrophy clinical

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A near-infrared fluorescent probe for visualizing transformation pathway of Cys/Hcy and H2S and its applications in living system

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Chinese Chemical Letters 2024年第5期35卷 296-301页

作者： Yudi Cheng xiao Wang jiao Chen Zihan Zhang Jiadong Ou Mengyao She Fulin Chen Jianli Li Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education Xi’an Key Laboratory of Functional Supramolecular Structure and MaterialsCollege of Chemistry&Materials ScienceNorthwest UniversityXi’an 710127China Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationBiomedicine Key Laboratory of Shaanxi ProvinceLab of Tissue Engineeringthe College of Life SciencesFaculty of Life Science&MedicineNorthwest UniversityXi’an 710069China

Sulfydryl-contained(-SH)substances including hydrogen sulfide(H_(2)S),cysteine(Cys),homocysteine(Hcy)and glutathione(GSH)play crucial roles in living systems,and their variations are closely associated with various diseases.Herein,we developed a near-infrared intramolecular charge transfer(ICT)based fluorescent probe Y-NBD,achieving detection of Cys/Hcy and H_(2)S with different fluorescent signals(green-red for Cys/Hcy,red for H_(2)S),large Stokes shifts(∼100/105nm or 191 nm)and high signal-background-ratio,but not responding to GSH.Y-NBD was successfully applied to image exogenous/endogenous Cys/Hcy and H_(2)S in various living cancer cells(HeLa,A549,and HepG2)and in zebrafish.It not only visualized the transformation pathway of several thiols in HepG2 cells but also verified that the intestine is the main site for the activation and metabolism of Y-NBD in zebrafish,as well as realized to evaluate the degree of drug-induced liver injury.This work provides a promising tool for imaging Cys/Hcy and H_(2)S in living systems and shows great potency in evaluating drug-induced liver injury and its treatment.

关键词： Fluorescent probe Near-infrared Hydrogen sulfide Cysteine/homocysteine Large Stokes shift Dicyanoisophorone Drug-induced liver injury

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Single-incision laparoscopic transabdominal preperitoneal repair in the treatment of adult female patients with inguinal hernia

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 49-58页

作者： xiao-Jun Zhu Jing-Yi jiao Hui-Min Xue Peng Chen Chang-Fu Qin Peng Wang Department of General Surgery The Affiliated Hospital of Nantong UniversityNantong 226001Jiangsu ProvinceChina Medical School Nantong UniversityNantong 226001Jiangsu ProvinceChina Department of Hernia and Abdominal Wall Surgery Peking University People's HospitalBeijing 100044China

BACKGROUND Women have a 3%lifetime chance of developing an inguinal hernia,which is not as common in men.Due to its cosmetic benefits,single-incision laparoscopic transabdominal preperitoneal(SIL-TAPP)inguinal hernia repair is becoming in-creasingly popular in the management of inguinal hernia in women.However,there are no studies comparing the safety and applicability of SIL-TAPP repair with conventional laparoscopic transabdominal preperitoneal(CL-TAPP)inguinal hernia repair for the treatment of inguinal hernia in women.AIM To compare the outcomes of SIL-TAPP and CL-TAPP repair in adult female patients with inguinal hernia and to estimate the safety and applicability of SIL-TAPP repair in adult female inguinal hernia patients.METHODS We retrospectively compared the clinical information and follow-up data of fe-male inguinal hernia patients who underwent SIL-TAPP inguinal hernia repair and those who underwent CL-TAPP inguinal hernia repair at the Affiliated Hos-pital of Nantong University from February 2018 to December 2020 and assessed the long-term and short-term outcomes of both cohorts.RESULTS This study included 123 patients,with 71 undergoing SIL-TAPP repair and 52 un-dergoing CL-TAPP repair.The two cohorts of patients and inguinal hernia charac-teristics were similar,with no statistically meaningful difference.The rate of intraoperative inferior epigastric vessel injury was lower in patients in the SIL-TAPP cohort(0,0%)than in patients in the CL-TAPP cohort(4,7.7%)and was significantly different(P<0.05).In addition,the median[interquartile range(IQR)]total hospitalization costs were significantly lower in patients in the SIL-TAPP cohort[$3287(3218-3325)]than in patients in the CL-TAPP cohort[$3511(3491-3599)].Postoperatively,the occurrence rate of trocar site hernia was lower in the SIL-TAPP cohort(0,0%)than in the CL-TAPP cohort(4,7.7%),and the median(IQR)cosmetic score was significantly higher in the SIL-TAPP cohort[10(10-10)]than in the CL-TAPP cohort[9(9-10)].CONCLUSION SIL-TAPP repair did not increas

关键词： Single-incision Groin hernia Female Inguinal hernia Laparoscopic transabdominal preperitoneal inguinal hernia repair

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Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice

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Chinese Journal of Integrative Medicine 2024年第7期30卷 608-615页

作者： WEI Ya-ru HOU Yun-long YIN Yu-jie LI Zhen LIU Yi HAN Ning-xin WANG Zi-xuan LIU Lu WANG xiao-qi HAO Yuan-jie MA Kun GU jiao-jiao JIA Zhen-hua Graduate School Hebei University of Chinese Medicine Shijiazhuang Yiling Pharmaceutical New Drug Evaluation Center Hebei Institute of Integrated Traditional and Western Medicine National Key Laboratory for Innovation and Transformation of Luobing Theory Department of Cardiology Hebei Yiling Hospital Graduate School Hebei Medical University

Objective: To investigate the potential role of Tongxinluo(TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI) in mice. Methods: A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups(n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril(BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition(EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1(CD31), α-smoth muscle actin(α-SMA), phosphatidylinositol-3-kinase(PI3K) and phospho protein kinase B(p-AKT) were assessed using Western blot. Results: TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT(P0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL. Conclusion: TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

关键词： myocardial fibrosis endothelial mesenchymal transition myocardial ischemia-reperfusion injury phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway

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