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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 86-102页

作者： Xiaoling Fu Yutong Song Xianquan Feng Zhihong Liu Wenhao Gao Hongtao Song Qian Zhang School of Pharmacy Fujian Medical UniversityFuzhou 350108China fuzong clinical medical college of fujian medical university Fuzhou 350025China First school of clinical medicine Nanjing Medical UniversityNanjing 211166China

Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)treatment.MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 phenotype.Furthermore,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis model.Moreover,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment effects.Overall,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

关键词： Polydopamine Thermosensitive liposomes Photothermal therapy Oxygen generation Rheumatoid arthritis

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 1-7页

作者： Feng-Mei Wang Peng Mo Xue Yan Xin-Yue Lin Zhi-Chao Fu Department of Obstetrics and Gynecology Fuzong Clinical Medical College(900th Hospital)Fujian Medical UniversityFuzhou 350025Fujian ProvinceChina Department of Obstetrics and Gynecology Dongfang HospitalXiamen UniversityFuzhou 350025Fujian ProvinceChina Department of Radiotherapy Fuzong Clinical Medical College(900th Hospital)Fujian Medical UniversityFuzhou 350025Fujian ProvinceChina Department of Radiotherapy Dongfang HospitalXiamen UniversityFuzhou 350025Fujian ProvinceChina

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

关键词： Esophageal carcinoma Locally advanced Radiotherapy Immunotherapy

B-cell lymphoma-2 phosphorylation at Ser70 site-related autophagy mediates puerarin-inhibited the apoptosis of MC3T3-E1 cells during osteoblastogenesis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 27-34页

作者： LI Xi LIN Xiangquan CHEN Dongdong LIU Hui the Third clinical medical college Fujian Medical University Department of Orthopedics Fuzhou Second HospitalFuzhou 350007China

OBJECTIVE:To explore the relationship between autophagy and apoptosis regulated by puerarin during osteoblastogenesis.METHODS:In this study,the effects of puerarin on the autophagic activity and apoptosis level of osteoblast precursors(MC3T3-E1 cells)was observed.Subsequently,the roles of puerarin on B-cell lymphoma-2(Bcl-2)phosphorylation at different sites in osteoblast precursors were observed.The effect of puerarin on the interaction between Bcl-2 and autophagy regulatory molecule or pro-apoptotic molecule was also investigated using Co-immunoprecipitation assays.In addition,the effect of puerarin on mitochondrial membrane potential of osteoblast precursors was also identified by mitochondrial membrane potential fluorescence probe assays.RESULTS:Our results showed that puerarin can promote the autophagic activity and apoptosis level of MC3T3-E1cells.In addition,puerarin promoted Bcl-2phosphorylation at Ser70 site,and the dissociation of Bcl-2-Beclin1 complex.Moreover,puerarin could enhance the binding of Bcl-2-Bcl-2-Associated X(Bax)complex in MC3T3-E1 cells.Furthermore,puerarin increased the mitochondrial membrane potential of MC3T3-E1 cells.CONCLUSIONS:Therefore,puerarin promotes Beclin1into autophagy flux through Bcl-2 phosphorylation at Ser70,thereby enhancing autophagy of osteoblast precursors,which mediates its anti-apoptotic role during osteoblastogenesis.Furthermore,the dissociation of Bcl-2-Beclin1 complex is conducive to the binding of Bcl-2-Bax complex,which resists the apoptosis of osteoblast precursors via the increased mitochondrial membrane potential.

关键词： puerarin osteoblasts autophagy apoptosis lymphoma B-cell

Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

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Neural Regeneration Research 2024年第7期19卷 1541-1547页

作者： Xingyong Chen Nannan Yao Yanguang Mao Dongyun Xiao Yiyi Huang Xu Zhang Yinzhou Wang Department of Neurology Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology Cangzhou Central HospitalCangzhouHebei ProvinceChina fujian Academy of medical Science FuzhouFujian ProvinceChina Key Testing Laboratory of fujian Province FuzhouFujian ProvinceChina

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

关键词： blood-brain barrier CYP1B1 oxidative stress oxygen glucose deprivation/reoxygenation tight junction vascular endothelial cells Wnt/β-catenin pathway β-catenin

Advances in the treatment of IgA nephropathy with biological agents

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Chronic Diseases and Translational Medicine 2024年第1期10卷 1-11页

作者： Yongze Zhuang Hailing Lu Junxia Li Department of Nephrology 900 Hospital of the Joint Logistics TeamPLAFuzhou General Clinical Medical CollegeFujian Medical UniversityFuzhouFujianChina

Immunoglobulin A nephropathy(IgAN)is the most common primary glomerular disease,and the“four-hit”theory represents its currently accepted pathogenic mechanism.Mucosal immunity triggered by infections in the respiratory tract,intestines,or other areas leads to antigen presentation,T cell stimulation,B cell maturation,and the production of IgA-producing plasma cells.The proteins B-lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL)are involved in this process,and alternative complement and lectin pathway activation are also part of the pathogenic mechanism.Kidney Disease Improving Global Outcomes guidelines indicate that a specific effective treatment for IgAN is lacking,with renin-angiotensin-aldosterone system inhibitors being the primary therapy.Recent research shows that biological agents can significantly reduce proteinuria,stabilize the estimated glomerular filtration rate,and reverse some pathological changes,such as endocapillary proliferation and crescent formation.There are four main categories of biological agents used to treat IgA nephropathy,specifically anti-CD20 monoclonal antibodies,anti-BLyS or APRIL monoclonal antibodies,monoclonal antibodies targeting both BLyS and APRIL(telitacicept and atacicept),and monoclonal antibodies inhibiting complement system activation(narsoplimab and eculizumab).However,further research on the dosages,treatment duration,long-term efficacy,and safety of these biological agents is required.

关键词： anti-CD20 monoclonal antibodies APRIL biological agents BLyS complement IgAnephropathy

Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 687-698页

作者： Juan Lin Zhu-Feng Chen Guo-Dong Guo Xin Chen Shengli clinical medical college Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina Department of Pathology Fujian Provincial HospitalFuzhou 350001Fujian ProvinceChina Department of Internal Medicine Fujian Provincial HospitalFuzhou 350001Fujian ProvinceChina

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,respectively.However,the clinical importance of the special combined AB and PAS stain is unclear.AIM To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient prognosis.METHODS Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed quantitatively.Immuno-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed simultaneously.The cancer-specific survival(CSS)rate was estimated via Kaplan-Meier analysis.Cox proportional hazards models were used for univariate and multivariate survival analyses.RESULTS Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the PAS.Cox multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor prognosis.CONCLUSION A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric SRCC.PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

关键词： Alcian blue Periodic acid-Schiff Prognosis Gastric Signet ring cell carcinoma

Meibomian glands segmentation in infrared images with limited annotation

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 401-407页

作者： Jia-Wen Lin Ling-Jie Lin Feng Lu Tai-Chen Lai Jing Zou Lin-Ling Guo Zhi-Ming Lin Li Li college of Computer and Data Science Fuzhou UniversityFuzhou 350108Fujian ProvinceChina fujian Provincial Key Laboratory of Networking Computing and Intelligent Information Processing Fuzhou UniversityFuzhou 350108Fujian ProvinceChina Shengli clinical medical college of fujian medical university Fuzhou 350001Fujian ProvinceChina Department of Ophthalmology Fujian Provincial Hospital South BranchFujian Provincial HospitalFuzhou 350001Fujian ProvinceChina

●AIM:To investigate a pioneering framework for the segmentation of meibomian glands(MGs),using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis.●METHODS:Totally 203 infrared meibomian images from 138 patients with dry eye disease,accompanied by corresponding annotations,were gathered for the study.A rectified scribble-supervised gland segmentation(RSSGS)model,incorporating temporal ensemble prediction,uncertainty estimation,and a transformation equivariance constraint,was introduced to address constraints imposed by limited supervision information inherent in scribble annotations.The viability and efficacy of the proposed model were assessed based on accuracy,intersection over union(IoU),and dice coefficient.●RESULTS:Using manual labels as the gold standard,RSSGS demonstrated outcomes with an accuracy of 93.54%,a dice coefficient of 78.02%,and an IoU of 64.18%.Notably,these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%,2.06%,and 2.69%,respectively.Furthermore,despite achieving a substantial 80%reduction in annotation costs,it only lags behind fully annotated methods by 0.72%,1.51%,and 2.04%.●CONCLUSION:An innovative automatic segmentation model is developed for MGs in infrared eyelid images,using scribble annotation for training.This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs.It holds substantial utility for calculating clinical parameters,thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

关键词： infrared meibomian glands images meibomian gland dysfunction meibomian glands segmentation weak supervision scribbled annotation

Abnormal function of EPHA2/p.R957P mutant in congenital cataract

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1007-1017页

作者： Jing-Jin Zhang Zong-Fu Cao Bi-Ting Zhou Ju-Hua Yang Zhong Li Shuang Lin Xiao-Le Chen Nan-Wen Zhang Qin Ye Xu Ma Yi-Hua Zhu Department of Ophthalmology the First Affiliated Hospital of Fujian Medical UniversityFujian Institute of OphthalmologyFujian Provincial Clinical Medical Research Center of Eye Diseases and OptometryFuzhou 350005Fujian ProvinceChina Department of Ophthalmology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhou 350005Fujian ProvinceChina Chinese Academy of medical Sciences&Peking Union medical college Beijing 100000China National Human Genetic Resources Center National Research Institute for Family PlanningBeijing 100081China Department of Bioengineering and Biopharmaceutics School of PharmacyFujian Medical UniversityFuzhou 350004Fujian ProvinceChina

AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited.Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery.The pathogenicity of the variant was evaluated by the guidelines of American college of medical Genetics and InterVar software.Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2(EPHA2).Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins.The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting assay,respectively.The cell migration was analyzed by wound healing assay.Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo.RESULTS:A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif(SAM)domain of EPHA2.Functional studies demonstrated the variant’s impact:reduced EPHA2 protein expression,altered subcellular localization,and disrupted interactions with other lens membrane proteins.This mutant notably enhanced human lens epithelial cell migration,and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast(DIC)optics.CONCLUSION:Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

关键词： congenital cataract EPHA2 missense variant function analysis

Perinatal outcomes of re-recurrent gestational diabetes mellitus and their prognostic factors:A retrospective cohort study in China

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Chinese medical Journal 2024年第4期137卷 499-501页

作者： Xia Xu Yanni Guo Tingting Liao Huale Zhang Rumeng Jiang Shuyao Huang Jianying Yan Department of Obstetrics and Gynecology Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian 350001China

To the Editor:Gestational diabetes mellitus(GDM)is a pathologic condition in which glucose intolerance and insulin resistance develop to different degrees during pregnancy.Women with GDM have higher odds of adverse maternal and fetal outcomes.Patients with a history of GDM were at a significantly increased risk for recurrence of GDM in subsequent pregnancies.Our previous and some other studies found an increased incidence of adverse perinatal outcomes in pregnant with recurrent GDM.^([1])So far,women with a prior history of GDM are not recommended to refrain from subsequent pregnancy in light of the limited available data.What about those women with a history of recurrent GDM?Should women with recurrent GDM be recommended to avoid further pregnancy?Currently,studies on perinatal outcomes of women with re-recurrent GDM and their prognostic factors are very rare.Therefore,this retrospective cohort study was performed to explore perinatal outcomes of pregnant woman with re-recurrent GDM and their prognostic factors.

关键词： mellitus pregnancy diabetes

Associations between the use of red yeast rice preparations and adverse health outcomes:An umbrella review of meta-analyses of randomized controlled trials

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Journal of Integrative Medicine 2024年第2期22卷 126-136页

作者： Zhen-yu Ma Shu-ping Yang Ying Li Tian-tian Xu Ya-lin Yang Hui-yong Yang Heng-bing Li Le-jin Zhou Yong Diao Su-yun Li School of Medicine Huaqiao UniversityQuanzhou 362021Fujian ProvinceChina college of Traditional Chinese Medicine Shandong University of Traditional Chinese MedicineJinan 250355Shandong ProvinceChina Second clinical medical college Nanjing Medical UniversityNanjing 211166Jiangsu ProvinceChina

Background:Red yeast rice(RYR),a natural lipid-lowering agent,is widely used in clinical practice.However,the existing meta-analyses concerning the safety of RYR preparations have yielded inconsistent results,and the credibility of the evidence has not been quantified.Objective:This study was designed to evaluate the existing evidence and offer a comprehensive understanding of the associations between the use of RYR preparations and various adverse health outcomes.Search strategy:Seven literature databases were searched from inception to May 5,2023,using medical subject headings and free-text terms(e.g.,“red yeast rice,”“Xuezhikang,”and“Zhibitai”).Inclusion criteria:Meta-analyses that investigated and quantitatively estimated associations between the use of RYR preparations and adverse health outcomes were included in this study.Data extraction and analysis:Two researchers independently extracted data using a standardized data collection table;any disagreements were resolved by consulting a third researcher.Based on the participant,intervention,comparator and outcome(PICO)framework in each eligible meta-analysis,a series of unique associations between the use of RYR preparations and adverse health outcomes were determined.The associations’effect estimates were re-evaluated using random-effect models.Results:Fifteen meta-analyses,comprising 186(164 unique)randomized controlled trials,were identified.Based on A Mea Surement Tool to Assess Systematic Reviews version 2,3(20%)and 12(80%)of these meta-analyses had low and critically low confidence,respectively.A total of 61 unique associations between the use of RYR preparations and adverse health outcomes were extracted from eligible metaanalyses.Based on the random-effect models,10(16.4%)associations indicated a significant protective effect of RYR preparations against adverse health outcomes,while 5(8.2%)indicated an increased risk of adverse health outcomes related to uric acid,alanine transaminase and aspartate transaminase levels.The other 46(75.4%)associations s

关键词： Red yeast rice Safety Adverse health outcomes Umbrella review Meta-analysis Systematic review