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Current medical Science 2024年第2期44卷 426-434页

作者： Bi-xin XI Si-ying LIU Yu-ting XU De-dong ZHANG Qun HU Ai-guo LIU Department of Pediatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene *** disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional *** this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese ***:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype *** compound heterozygous variants of the GPI gene,c.174C>A(***58Lys)and c.1538G>T(***513Leu),were identified using whole-exome and Sanger *** AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI ***:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and *** study identified novel compound heterozygous variants associated with GPI *** pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino ***:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.

关键词： glucose-6-phosphate isomerase deficiency whole-exome sequencing compound heterozygous variants genetic characterization hydrogen bond

Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia

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当代医学科学（英文） 2024年第4期44卷 799-808页

作者： Tong-yuan LIU Xing FU Ying YANG Jia GU Min XIAO Deng-ju LI Department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:The metabolic reprogramming of acute myeloid leukemia(AML)cells is a compensatory adaptation to meet energy requirements for rapid *** study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML ***:SKM-1 cells(an AML cell line)were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide(BPTES,a glutaminase inhibitor)or *** viability was detected by Cell Counting Kit-8(CCK-8)assay,and cell apoptosis and reactive oxygen species(ROS)by flow *** blotting was conducted to examine the levels of apoptotic proteins,including cleaved caspase-3 and poly(ADP-ribose)polymerase(PARP).Moreover,the human long noncoding RNA(lncRNA)microarray was used to analyze gene expression after glutamine deprivation,and results were confirmed with quantitative RT-PCR(qRT-PCR).The expression of metallothionein 2A(MT2A)was suppressed using *** growth and apoptosis were further detected by CCK-8 assay and flow cytometry,respectively,in cells with MT2A ***:Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 *** lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine ***2A knockdown increased apoptosis,while proliferation was not affected in SKM-1 *** addition,metformin inhibited cell growth and induced apoptosis in SKM-1 *** glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to ***,the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 ***:Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

关键词： acute myeloid leukemia glutamine metallothionein metformin

Therapeutic Effectiveness of Leukocyte-and Platelet-rich Fibrin for Diabetic Foot Ulcers:A Retrospective Study

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Current medical Science 2024年第3期44卷 568-577页

作者： Fen WANG Xiao-ling ZHANG Jing ZHANG Song GONG Jing TAO Hui XIANG Xiao-qing FU Xu-na BIAN Xue-feng YU An-hui XU Cheng-la YI Shi-ying SHAO Department of Endocrinology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Branch of National Clinical Research Center for Metabolic Diseases Wuhan430030China Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Trauma Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Diabetic foot ulcer(DFU)is one of the most serious complications of ***-and platelet-rich fibrin(L-PRF)is a second-generation autologous platelet-rich *** study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical *** Patients with DFU who received L-PRF treatment and standard of care(SOC)from 2018 to 2019 in tongji hospital were *** clinical information including patient characteristics,wound evaluation(area,severity,infection,blood supply),SOC of DFU,and images of ulcers was retrospectively extracted and analyzed.L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction(PVR)greater than 80%.Therapeutic effectiveness,including overall PVR and the overall and weekly healing rates,was *** Totally,26 patients with DFU were enrolled,and they had an ulcer duration of 47.0(35.0,72.3)*** severity and infection of ulcers varied,as indicated by the Site,Ischemia,Neuropathy,Bacterial Infection,and Depth(SINBAD)scores of 2–6,Wagner grades of 1–4,and the Perfusion,Extent,Depth,Infection and Sensation(PEDIS)scores of 2–*** initial ulcer volume before L-PRF treatment was 4.94(1.50,13.83)cm3,and the final ulcer volume was 0.35(0.03,1.76)*** median number of L-PRF doses was 3(2,5).A total of 11 patients achieved complete epithelialization after the fifth week of treatment,and 19 patients achieved at least an 80%volume reduction after the seventh *** overall wound-healing rate was 1.47(0.63,3.29)cm3/week,and the healing rate was faster in the first 2 weeks than in the remaining *** treatment did not change the percentage of complete epithelialization or healing *** Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index,SINBAD score,or Wagner grade,indicating that this method is appropriate for D

关键词： diabetic foot ulcer autologous platelet-rich plasma leukocyte-and platelet-rich fibrin standard of care percentage volume reduction

Histological Features of Uterine Myometrial Dysfunction:Possible Involvement of Localized Inflammation

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Current medical Science 2024年第3期44卷 633-641页

作者： Sheng-lan ZHU Hui-ting ZHANG Yuan-yuan DU Yi JIANG Shao-shuai WANG Wen-cheng DING Ling FENG National Clinical Research Center for Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum ***(LPS)has been widely used to induce inflammation in animal ***,this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium,as well as the potential underlying molecular mechanisms *** In vivo,an animal model was established by intraperitoneal injection of 300μg/kg LPS in rats on gestational day ***-eosin(H&E)staining and Masson staining were employed to determine morphological changes in the rat uterine smooth ***-linked immunosorbent assay(ELISA)was used to detect inflammatory ***,tissue fluorescence,and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4(TLR4)and the nuclear factor kappa-B(NF-κB)signaling *** vitro,human uterine smooth muscle cells(HUtSMCs)were exposed to 2μg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated *** In this study,LPS induced uterine myometrial dysfunction in rats,leading to a disorganized arrangement,a significant increase in collagen fiber deposition,and widespread infiltration of inflammatory *** both in vivo animal models and in vitro HUtSMCs,LPS elevated IL-6,IL-1β,and TNF-αlevels while concurrently suppressing the expression of connexin 43(Cx43)and oxytocin receptor(OXTR).Mechanistically,the LPS-treated group exhibited TLR4 activation,and the phosphorylation levels of p65 and IκBαwere notably *** LPS triggered the TLR4/NF-κB signaling pathway,inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony.

关键词： lipopolysaccharide inflammatory response TLR4 NF-κB myometrium

Therapeutic cancer vaccines:advancements,challenges,and prospects

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Signal Transduction and Targeted Therapy 2024年第1期9卷 150-172页

作者： Ting Fan Mingna Zhang Jingxian Yang Zhounan Zhu Wanlu Cao Chunyan Dong Department of Oncology East Hospital Affiliated to Tongji UniversityTongji University School of MedicineShanghaiChina Postgraduate Training Base Shanghai East HospitalJinzhou Medical UniversityShanghai 200120China

With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies,cancer immunotherapy has undergone a profound transformation over the past ***,therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens,including tumor-associated antigens and tumor-specific *** objective was to amplify and diversify the intrinsic repertoire of tumor-specific T ***,the complete realization of these capabilities remains an ongoing ***,we provide an overview of the current landscape of cancer vaccines in this *** range of antigen selection,antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine ***,this review addresses the current status of clinical trials and discusses their strategies,focusing on tumor-specific immunogenicity and anti-tumor efficacy ***,current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges,including tumor immune microenvironment suppression,optimal candidate identification,immune response evaluation,and vaccine manufacturing ***,the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.

关键词： breakthrough approval overcome

A Prediction Model for Detecting Dysthyroid Optic Neuropathy Based on Clinical Factors and Imaging Markers of the Optic Nerve and Cerebrospinal Fluid in the Optic Nerve Sheath

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当代医学科学（英文） 2024年第4期44卷 827-832页

作者： Hong-yu WU Ban LUO Gang YUAN Qiu-xia WANG Ping LIU Ya-li ZHAO Lin-han ZHAI Wen-zhi LV Jing ZHANG Lang CHEN Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Ophthalmology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Endocrinology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of medical Imaging Guangdong Second Provincial General HospitalGuangzhou 510317China Department of Radiology Sir Run Run Shaw Hospital Affiliated with the School of Medicine of Zhejiang UniversityHangzhou 310000China Department of Artificial Intelligence Julei Technology CompanyWuhan 430030China

Objective:This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve ***:This retrospective study included patients with thyroid-associated ophthalmopathy(TAO)without DON and patients with TAO accompanied by DON at our *** imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and,together with clinical factors,were screened by Least absolute shrinkage and selection ***,we constructed a prediction model using multivariate logistic *** accuracy of the model was verified using receiver operating characteristic curve ***:In total,80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our *** variables(optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath)were found to be independent predictive factors and were included in the prediction *** the development cohort,the mean area under the curve(AUC)was 0.994,with a sensitivity of 0.944,specificity of 0.967,and accuracy of ***,in the validation cohort,the AUC was 0.960,the sensitivity was 0.889,the specificity was 0.893,and the accuracy was ***:A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath,serving as a noninvasive potential tool to predict DON.

关键词： dysthyroid optic neuropathy magnetic resonance imaging optic nerve optic nerve subarachnoid space water-fat sequence

Annexin A1 in the nervous and ocular systems

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Neural Regeneration Research 2024年第3期19卷 591-597页

作者： Aijia Wang Hong Zhang Xing Li Yin Zhao Department of Ophthalmology 2Department of AnesthesiologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

The therapeutic potential of Annexin A1,an important member of the Annexin superfamily,has become evident in results of experiments with multiple human systems and animal *** anti-inflammatory and pro-resolving effects of Annexin A1 are characteristic of pathologies involving the nervous *** this review,we initially describe the expression sites of Annexin A1,then outline the mechanisms by which Annexin A1 maintains the neurological homeostasis through either formyl peptide receptor 2 or other molecular approaches;and,finally,we discuss the neuroregenerative potential qualities of Annexin *** eye and the nervous system are anatomically and functionally connected,but the association between visual system pathogenesis,especially in the retina,and Annexin A1 alterations has not been well ***,we explain the beneficial effects of Annexin A1 for ocular diseases,especially for retinal diseases and glaucoma on the basis of published findings,and we explore present and future delivery strategies for Annexin A1 to the retina.

关键词： Annexin A1(ANXA1) glaucoma nervous system neuroprotection neuroregeneration ocular disease retina

Predictors of Adverse Pregnancy Outcomes Following Traumatic Injuries

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Current medical Science 2024年第3期44卷 642-647页

作者： Wan-rong LU Ping WU Gong SONG Mei-qi GU Zhe XU Li HE National Clinical Research Center for Gynecology and Obstetrics Cancer Biology Research CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Traumatic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective After traumatic injury in pregnant women,providing timely and appropriate management for high-risk patients is crucial for both pregnant women and *** study aimed to identify risk factors that predict adverse pregnancy outcomes after traumatic *** A retrospective cohort study including 317 pregnant patients who experienced trauma was *** collected data included general demographics,injury mechanisms and adverse pregnancy *** were divided into two subgroups based on the absence or presence of trauma-related adverse pregnancy *** and multivariate logistic regressions were conducted to estimate the associations between clinical variables and adverse pregnancy *** A total of 41(12.93%)patients experienced adverse pregnancy outcomes within the first 24 h *** study revealed that age>35 years(OR=14.995,95%CI:5.024–44.755,P<0.001),third trimester trauma(OR=3.878,95%CI:1.343–11.204,P=0.012),abdominal pain(OR=3.032,95%CI:1.221–7.527,P=0.017),vaginal bleeding(OR=3.226,95%CI:1.093–9.523,P=0.034),positive scan in focused assessment with sonography for trauma(FAST)positive(OR=8.496,95%CI:2.825–25.555,P<0.001),9≤injury severity score(ISS)<16(OR=3.039,95%CI:1.046–8.835,P=0.041)and ISS≥16(OR=5.553,95%CI:1.387–22.225,P=0.015)increased the probability of posttraumatic adverse pregnancy *** age,gestational age at delivery,vaginal bleeding and positive FAST results were risk factors for abnormal *** Advanced maternal age,third trimester,and positive FAST results should alert multidisciplinary trauma teams to closely monitor patients to prevent adverse pregnancy outcomes.

关键词： adverse pregnancy outcomes predictive factors abnormal delivery trauma

Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats

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Current medical Science 2024年第2期44卷 355-368页

作者： Shao-ze JING Shu-han YANG Yun-kun QU Hai-hu HAO Hua WU Department of Orthopedics Third Hospital of Shanxi Medical UniversityShanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalTaiyuan 030032China Department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Osteoarthritis(OA)is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local *** study aimed to investigate the anti-OA effect of scutellarein(SCU),a single-unit flavonoid compound obtained from Scutellaria barbata ***,in ***:The extracted rat chondrocytes were treated with SCU and IL-1β.The chondrocytes were divided into control group,IL-1βgroup,IL-1β+SCU 50µmol/L group,and IL-1β+SCU 100µmol/L *** of rat chondrocytes was observed by toluidine blue and safranin O ***-8 method was used to detect the cytotoxicity of ***,qRT-PCR,Western blotting,immunofluorescence,SAβ-gal staining,flow cytometry,and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1β***,anterior cruciate ligament transection(ACL-T)was used to establish a rat OA *** changes were detected by safranin O/fast green,hematoxylin-eosin(HE)staining,and ***:SCU protected cartilage and exhibited anti-inflammatory effects via multiple ***,it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its *** addition,SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase(NF-κB/MAPK)pathway,thereby reducing inflammatory cytokine production in the joint ***,SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes,further highlighting its potential role in OA *** vivo experiments revealed that SCU(at a dose of 50 mg/kg)administered for 2 months could significantly delay the progression of cartilage damage,which was reflected in a lower Osteoarthritis Research Society International(OARSI)score,and reduced expression of matrix metalloproteinase 13(MMP13)in ***:SCU is effective in the therapeutic management of OA and could serve as a potential candidate f

关键词： scutellarein osteoarthritis apoptosis mitogen-activated protein kinase(MAPK) nuclear factor kappa-B(NF-κB)

Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease

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World Journal of Gastroenterology 2024年第25期30卷 3132-3139页

作者： Di Wang Bing-Yan Zhou Lei Xiang Xu-Yong Chen Jie-Xiong Feng Department of Pediatric Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030Hubei ProvinceChina

In this editorial,we comment on the article by Chen et *** dysfunction-associated fatty liver disease(MAFLD)is a global public health burden whose incidence has risen concurrently with overweight and *** its detri-mental health impact,early identification of at-risk individuals is *** diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy,imaging,or blood biomarkers,and one of the following conditions:Overweight/obesity,type 2 diabetes mellitus,or metabolic ***,in large-scale epidemiological studies,liver biopsies are not *** application of techniques such as ultrasonography,computed tomography,magnetic resonance imaging,and magnetic resonance spectroscopy is restricted by their limited sensitivity,low effectiveness,high costs,and need for specialized *** biomarkers offer several advantages,particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are *** of cumulative effects of excess high-normal blood alanine aminotrans-ferase(ALT)levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging ***,investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring,enabling timely inter-vention and management and improving patient outcomes.

关键词： Nonalcoholic fatty liver disease Metabolic dysfunction-associated fatty liver disease Alanine aminotransferase Screening Risk marker