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Inhalation of taraxasterol loaded mixed micelles for the treatment of idiopathic pulmonary fibrosis

Chinese Chemical Letters 2024年第8期35卷 475-480页

作者： Tong Zhang Chao Sun Shubin Yang Zimin Cai Sifeng Zhu Wendian Liu Yun Luan Cheng Wang Key Laboratory of Marine Drugs Chinese Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China central Research Laboratory Department of General Surgerythe Second Hospital of Shandong UniversityJi’nan 250033China Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and TechnologyQingdao 266237China Orthopedics Dept.1 Rushan people’s hospitalRushan 264500China Department of Cardiology the Second Hospital of Shandong UniversityJi’nan 250033China

Idiopathic pulmonary fibrosis(IPF)is a chronic and fatal lung disease characterized by pulmonary inflam-mation,oxidative stress,and excessive extracellular matrix(ECM)*** anti-fibrotic drugs for IPF treatment in the clinic lack selectivity and demonstrate unsatisfactory efficacy,highlighting the urgent necessity for a novel therapeutic ***(TA),which has biological activities against lung injury induced by various factors,is a potential anti-IPF drug due to its anti-inflammatory,antiox-idant and lung-protective ***,the protective effect of TA on IPF has not been confirmed,and its clinical application is limited due to its poor aqueous *** this study,we demonstrated that TA could inhibit epithelial-mesenchymal transition(EMT)and migration of A549 cells by inhibiting the transforming growth factor-β1(TGF-β1)/Smad signaling *** improve the aqueous solubility and pulmonary administration performance of TA,we prepared TA loaded methoxy poly(ethylene glycol)-poly(d,l-lactide)(mPEG-PLA)/d-α-tocopheryl polyethylene glycol succinate(TPGS)mixed polymeric mi-celles(TA-PM).Then a MicroSprayer^(R) Aerosolizer was used to deliver TA-PM once every two days for three weeks to evaluate their therapeutic effects on bleomycin(BLM)-induced IPF *** results demonstrated that inhaled TA-PM significantly inhibited BLM-induced inflammation,oxidative stress and fibrosis in lung ***,TA-PM exhibited high pulmonary deposition and retention by pul-monary administration,along with a favorable safety ***,this study emphasizes the potential of inhaled TA-PM as a promising treatment for IPF,providing a new opportunity for their clinical appli-cation.

关键词： Taraxasterol Idiopathic pulmonary fibrosis Mixed polymeric micelles Pulmonary administration Bleomycin

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Celastrol inhibits inflammatory factors expression in glioblastoma

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Traditional Medicine Research 2024年第6期9卷 1-11页

作者： Na Qin Shu-Xian Yang Shi-Man Gao Ting Zhu Institute of Neuroregeneration&Neurorehabilitation Department of PathophysiologySchool of Basic MedicineQingdao UniversityQingdao 266071China Department of Pharmacy Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Women and Children’s hospital Qingdao UniversityQingdao 266034China

Background:Glioblastoma is one of the most common primary intracranial tumors of the central nervous system in *** chemotherapy is an important component of glioblastoma treatment,its effectiveness remains *** to multiple immunosuppressive mechanisms,glioblastoma immunotherapy has not been effective in treating many patients as a result of the clinical breakthroughs in the ***,the development of cancer immunotherapy relies on the understanding of how tumors interact with the immune system and the analysis of their molecular *** study identified the key interactions between immune cells in the glioma microenvironment using RNA microarrays and single-cell ***:First,we screened differentially expressed genes in tumor and control samples from GSE29796 and GSE50161 datasets using *** differentially expressed genes were used to perform enrichment analysis and construct protein-protein interaction topological analysis to analyze the interaction between *** single-cell RNA sequencing data from the GSE162631 database,we identified immune cell types within the glioblastoma microenvironment,and validated the hub gene expression in these *** addition,based on the GEPIA and TIMER databases,hub genes were investigated and compared with immune infiltration to determine differential ***,CellChat was used to visualize the gene expression distribution and cell-to-cell communication analysis of the proteins between different types of ***:We found that monocytes/macrophages may communicate with each other in the tumor microenvironment through MIF-(CD74+CXCR4)and MIF-(CD74+CD44).In addition,our study indicated that celastrol has the ability to inhibit inflammatory factors expression by MIF/CD74 signaling pathway in U87 ***:This study improved the effectiveness of cancer immunotherapy strategies and developed new ideas for immunotherapy that can be applied to gl

关键词： glioblastoma monocytes/macrophages single-cell RNA sequencing MIF/CD74 signaling pathway celastrol

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Automated detection of myopic maculopathy from color fundus photographs using deep convolutional neural networks

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Eye and Vision 2024年第4期10卷 11-22页

作者： Jun Li Lilong Wang Yan Gao Qianqian Liang Lingzhi Chen Xiaolei Sun Huaqiang Yang Zhongfang Zhao Lina Meng Shuyue Xue Qing Du zhichun Zhang Chuanfeng LV Haifeng Xu Zhen Guo Guotong Xie Lixin Xie qingdao Eye hospital of Shandong First Medical University 5 Yanerdao RoadQingdao 266071China State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyShandong Eye InstituteShandong First Medical University&Shandong Academy of Medical SciencesQingdao 266071China Ping An Healthcare Technology 9F Building BPingAn IFCNo.1-3 Xinyuan South RoadBejing 100027China Shandong Eye hospital of Shandong First Medical University Jinan 250021China Rongcheng Eye hospital Weihai 264200China hospital of PLA Navy Qingdao 266071China Qilu hospital of Shandong University(qingdao) Qingdao 266035China Ping An Healthcare and Technology Company Limited hanghai 200030China ping An International Smart City Technology Company Limited Shenzhen 518000China.

Background:Myopic maculopathy(MM)has become a major cause of visual impairment and blindness worldwide,especially in East Asian *** learning approaches such as deep convolutional neural networks(DCNN)have been successfully applied to identify some common retinal diseases and show great potential for the intelligent analysis of *** study aimed to build a reliable approach for automated detection of MM from retinal fundus images using DCNN ***:A dual-stream DCNN(DCNN-DS)model that perceives features from both original images and corresponding processed images by color histogram distribution optimization method was designed for classification of no MM,tessellated fundus(TF),and pathologic myopia(PM).A total of 36,515 gradable images from four hospitals were used for DCNN model development,and 14,986 gradable images from the other two hospitals for external *** also compared the performance of the DCNN-DS model and four ophthalmologists on 3000 randomly sampledfundus ***:The DCNN-DS model achieved sensitivities of 93.3%and 91.0%,specificities of 99.6%and 98.7%,areas under the receiver operating characteristic curves(AUCs)of 0.998 and 0.994 for detecting PM,whereas sensitivities of 98.8%and 92.8%,specificities of 95.6%and 94.1%,AUCs of 0.986 and 0.970 for detecting TF in two external testing *** the sampled testing dataset,the sensitivities of four ophthalmologists ranged from 88.3%to 95.8%and 81.1%to 89.1%,and the specificities ranged from 95.9%to 99.2%and 77.8%to 97.3%for detecting PM and TF,***,the DCNN-DS model achieved sensitivities of 90.8%and 97.9%and specificities of 99.1%and 94.0%for detecting PMand T,***:The proposed DCNN-DS approach demonstrated reliable performance with high sensitivity,specificity,and AUC to classify different MM levels on fundus photographs sourced from *** can help identify MM automatically among the large myopic groups and show great potenti

关键词： Myopic maculopathy Tessellated fundus Pathologic myopia Deep convolutional neural network Color fundus image

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Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion

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World Journal of Diabetes 2024年第6期15卷 1340-1352页

作者： Zi-Tian Liu Guang-Wei Yang Xiang Zhao Shuo-Hui Dong Yang Jiao Zheng Ge Ao Yu Xi-Qiang Zhang Xin-Zhen Xu Zhi-Qiang Cheng Xiang Zhang Ke-Xin Wang Department of General Surgery Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Department of General Surgery Shandong University of Qilu Hospital(Qingdao)Qingdao 266000Shandong ProvinceChina

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not *** To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat *** DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat *** adipose tissue was weighed and observed under *** inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose ***-sequencing was utilized to evaluate gene expression alterations *** hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the *** resistance was evaluated by *** After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue *** cell volume in both visceral adipose tissue(VAT)and SAT *** to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic *** circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT *** experiment showed that GH stimulated adiponectin secretion and improve insulin *** GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.

关键词： Growth hormone Insulin resistance Bariatric surgery Adipose tissue Adiponectin

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Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

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Traditional Medicine Research 2024年第2期9卷 52-65页

作者： Yu-Ming Wang Hong-Wei Tao Feng-Chan Wang Ping Han Na Liu Guo-Jing Zhao Hai-Bo Hu Xue-Chao Lu College of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Respiratory and Critical Care Medicine Qingdao Hospital of Traditional Chinese Medicine(Qingdao Hiser hospital)Qingdao 266000China.

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and *** clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains ***:In this study,a monocrotaline-induced PAH rat model was established and treated with *** therapeutic effects of MFJT on PAH rat model were *** pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried *** key targets identified from network pharmacology were ***:Results showed significant therapeutic effects of MFJT on PAH rat *** of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular *** docking showed that the key components were well docked with the core *** experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

关键词： Mufangji tang pulmonary arterial hypertension apoptosis inflammatory response oxidative stress vascular remodeling

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Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

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Bone Research 2024年第2期12卷 334-348页

作者： Ziqian Xiang Pengfei Zhang Chunwang Jia Rongkun Xu Dingren Cao Zhaoning Xu Tingting Lu Jingwei Liu Xiaoxiong Wang Cheng Qiu Wenyang Fu Weiwei Li Lei Cheng Qiang Yang Shiqing Feng Lianlei Wang Yunpeng Zhao Xinyu Liu Department of Orthopaedics Qilu Hospital of Shandong UniversityJinan 250012China University of Health and Rehabilitation Sciences Qingdao 226000China Xiangya School of Medicine Central South UniversityChangsha 410013China School of Nursing and Rehabilitation Shandong UniversityJinan 250012China Department of Pediatrics Cangzhou Central HospitalCangzhou 061011China Department of Pediatric Surgery Qilu Hospital of Shandong UniversityJinan 250012China Department of Pathology Qilu Hospital of Shandong UniversityJinan 250012China Department of Spine Surgery Tianjin HospitalTianjin UniversityTianjin 30021China The Second hospital of Shandong University Cheeloo College of MedicineShandong UniversityJinan 250012China

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be ***,Piezo1 channel was identified as a key iron transporter in response to mechanical ***1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron ***,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical ***,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

关键词： stress overload channel

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Special electromyographic features in a child with paramyotonia congenita: A case report and review of literature

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World Journal of Clinical Cases 2024年第3期12卷 587-595页

作者： Hui Yi Chen-Xiang Liu Shu-Xin Ye Yu-Lin Liu Department of Neuroelectrophysiology Qilu Children’s Hospital of Shandong UniversityJinan 250000Shandong ProvinceChina Department of Neuroelectrophysiology University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital)Qingdao 266000Shandong ProvinceChina

BACKGROUND Paramyotonia congenita(PMC)stands as a rare sodium channelopaty of skeletal muscle,initially identified by *** identification of PMC often relies on electromyography(EMG),a diagnostic *** child’s needle EMG unveiled trains of myotonic discharges with notably giant amplitudes,alongside irregular wave trains of myotonic *** distinctive observation had not surfaced in earlier *** SUMMARY We report the case of a 3-year-old female child with PMC,who exhibited la-ryngeal stridor,muffled speech,myotonia from ***,exposure to cool water,crying,and physical activity exacerbated the myotonia,which was relieved in warmth,yet never *** myotonia was observable in bilateral *** symptoms remained unchanged after potassium-rich food consumption like *** periodic paralysis was *** magnetic resonance imaging yielded normal *** potassium remained within normal range,while creatine kinase showed slight ***-wide genetic testing pinpointed a heterozygous mutation on chromosome SCN4A:c.3917G>A(p.G1306E).After a six-month mexiletine regimen,symptoms *** In this case revealed the two types of myotonic discharges,and had not been documented in other *** underscore two distinctive features:Giant-amplitude potentials and irregular waves.

关键词： Paramyotonia congenita Channelopathy Electromyography Child Case report

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Effectiveness of colonoscopy,immune fecal occult blood testing,and risk-graded screening strategies in colorectal cancer screening

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2270-2280页

作者： Ming Xu Jing-Yi Yang Tao Meng Department of Colorectal Surgery Qilu Hospital(Qingdao)Cheeloo College of MedicineQingdao 266000Shandong ProvinceChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Colorectal cancer(CRC)is one of the most common malignant tumors,and early screening is crucial to improving the survival rate of *** combination of colonoscopy and immune fecal occult blood detection has garnered significant attention as a novel method for CRC *** and fecal occult blood tests,when combined,can improve screening accuracy and early detection rates,thereby facilitating early intervention and ***,certain risks and costs accompany it,making the establishment of a risk classification model crucial for accurate classification and management of screened *** To evaluate the feasibility and effectiveness of colonoscopy,immune fecal occult blood test(FIT),and risk-graded screening strategies in CRC *** Based on the randomized controlled trial of CRC screening in the population conducted by our hospital May 2020 to May 2023,participants who met the requirements were randomly assigned to a colonoscopy group,an FIT group,or a graded screening group at a ratio of 1:2:2(after risk assessment,the high-risk group received colonoscopy,the low-risk group received an FIT test,and the FITpositive group received colonoscopy).The three groups received CRC screening with different protocols,among which the colonoscopy group only received baseline screening,and the FIT group and the graded screening group received annual follow-up screening based on baseline *** primary outcome was the detection rate of advanced tumors,including CRC and advanced *** population participation rate,advanced tumor detection rate,and colonoscopy load of the three screening programs were *** A total of 19373 subjects who met the inclusion and exclusion criteria were enrolled,including 8082 males(41.7%)and 11291 females(58.3%).The mean age was 60.05±6.5 *** them,3883 patients were enrolled in the colonoscopy group,7793 in the FIT group,and 7697 in the graded screening *** rounds

关键词： Colorectal tumor Immune fecal occult blood testing Colonoscopy Hierarchical screening Risk assessment

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Analysis of lymph node metastasis and survival prognosis in early gastric cancer patients: A retrospective study

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1637-1646页

作者： Dong-Yuan Liu Jin-Jin Hu Yong-Quan Zhou Ai-Rong Tan Department of General Surgery The 971st Hospital of Chinese People's Liberation ArmyQingdao 266071Shandong ProvinceChina Department of Chest Surgery Feicheng People's HospitalFeicheng 271600Shandong ProvinceChina Department of Gastrointestinal Surgery Zhongshan Hospital of Fudan UniversityShanghai 200032China Department of Oncology Qingdao Municipal HospitalQingdao 266000Shandong ProvinceChina

BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been *** retrospectively analyzing the clinical data of EGC patients,we can better under-stand the status of lymph node metastasis and its impact on survival and *** To evaluate the prognosis of EGC patients and the factors that affect lymph node METHODS The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort *** were 561 males and 450 *** mean age was 58±11 *** patient underwent radical *** status of lymph node metastasis in each group was determined according to the pathological examination results of surgical *** outcomes were as follows:(1)Lymph node metastasis in EGC patients;(2)Analysis of influencing factors of lymph node metastasis in EGC;and(3)Analysis of prognostic factors in patients with *** distributed measurement data are expressed as mean±SD,and a t test was used for comparisons between *** data are expressed as absolute numbers or percentages,and the chi-square test was used for comparisons between *** data were compared using a nonparametric rank sum test.A log-rank test and a logistic regression model were used for univariate analysis.A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate *** Kaplan-Meier method was used to calculate the survival rate and construct survival curves.A log-rank test was used for survival *** Analysis of influencing factors of lymph node metastasis in *** results of the multifactor analysis showed that tumor length and diameter,tumor site,tumor invasion depth,vascular thrombus,and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC(odds ratios=1.80,1.49,2.6

关键词： Gastric neoplasms Lymph node metastasis Prognosis Influencing factor Retrospective study

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Bone destruction of orbital wall in idiopathic orbital inflammatory pseudotumor:does it always imply malignancy?

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International Journal of Ophthalmology(English edition) 2024年第9期17卷 1681-1688页

作者： Qi-Han Guo Xuan Zhang An-Qi Huang Ben-Tao Yang Rui Liu Nan Wang Liang-Yuan Xu Jian-Min Ma Department of Ophthalmology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China The Affiliated Tai’an City central hospital of qingdao University Tai’an 271000Shandong ProvinceChina Department of Pathology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Radiology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China

AIM:To assess the clinical presentations and outcomes of idiopathic orbital inflammatory pseudotumor(IOIP)patients with orbital wall bone destruction(OWBD)and to propose an expanded classification system that includes bone ***:The study retrospectively reviewed clinical presentations,imaging findings,treatment modalities,and outcomes of six patients diagnosed histopathologically with IOIP and OWBD at the Beijing Tongren hospital,Capital Medical University between October 2018 and June ***:Over two years,6(10%)of 60 IOIP patients at our hospital exhibited OWBD,but this may overrepresent severe *** cohort consisted of three men and three women,aged 17 to 60y(mean 35.5±16.1y).Presenting symptoms included proptosis,eyelid swelling,decreased visual acuity with pain,and palpable *** revealed multiple anatomical structures involved with the medial wall being the most common site of bone *** examination showed classic type in five patients and sclerosing type in one *** patients underwent surgical resection followed by methylprednisolone ***-up(mean 30.3±3.1mo)indicated three patients had no recurrence,while others had varying degrees of symptom persistence or ***:IOIP with bone destruction is a rare but significant subtype that mimics malignancy,leading to potential diagnostic and therapeutic *** findings suggest that complete surgical resection combined with adjunctive glucocorticoid therapy can yield favorable ***,larger-scale studies are needed to further optimize therapeutic approaches.

关键词： idiopathic orbital inflammatory pseudotumor bone destruction orbital disease

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