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Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation

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Journal of Integrative Medicine 2024年第2期22卷 188-198页

作者： Meng Li Yang Zhou Hui Zhu Lie-ming xu jian Ping Institute of Liver Diseases Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Preventive Treatment Center Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437 China Department of Gastroenterology Suzhou Traditional Chinese Medicine HospitalSuzhou 215000Jiangsu ProvinceChina Shanghai Key Laboratory of Traditional Chinese Medicine Shanghai 201203China Key Laboratory of Liver and Kidney Diseases(Ministry of Education) Shanghai 201203China

Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related proteins.Real-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 phosphorylation.This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in chol

关键词： Liver cirrhosis biliary Long non-coding RNA H19 Danhongqing formula Cholangiocyte Hepatic stellate cells STAT3 transcription factor

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Ultrahigh spatiotemporal resolution beam signal reconstruction with bunch phase compensation

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Nuclear Science and Techniques 2024年第5期35卷 99-108页

作者： You-ming Deng Yong-Bin Leng Xing-Yi xu jian Chen Yi-Mei Zhou Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201800China University of the Chinese Academy of Sciences Beijing 100049China Shanghai Synchrotron Radiation Facility Chinese Academy of SciencesShanghai 201204China University of Science and Technology of China Hefei 230026China Shanghai Advanced Research Institute Chinese Academy of SciencesShanghai 201204China

Various electromagnetic signals are excited by the beam in the acceleration and beam-diagnostic elements of a particle accelerator.It is important to obtain time-domain waveforms of these signals with high temporal resolution for research,such as the study of beam–cavity interactions and bunch-by-bunch parameter measurements.Therefore,a signal reconstruction algorithm with ultrahigh spatiotemporal resolution and bunch phase compensation based on equivalent sampling is proposed in this paper.Compared with traditional equivalent sampling,the use of phase compensation and setting the bunch signal zero-crossing point as the time reference can construct a more accurate reconstructed signal.The basic principles of the method,simulation,and experimental comparison are also introduced.Based on the beam test platform of the Shanghai Synchrotron Radiation Facility(SSRF)and the method of experimental verification,the factors that affect the reconstructed signal quality are analyzed and discussed,including the depth of the sampled data,quantization noise of analog-to-digital converter,beam transverse oscillation,and longitudinal oscillation.The results of the beam experiments show that under the user operation conditions of the SSRF,a beam excitation signal with an amplitude uncertainty of 2%can be reconstructed.

关键词： Turn-by-turn bunch phase compensation technique Equivalent sampling Signal reconstruction algorithm Ultrahigh spatiotemporal resolution SSRF

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Evidence-based practices in sustainable travel behavior intervention: A knowledge graph-based systematic review

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Journal of Traffic and Transportation Engineering(English Edition) 2024年第2期11卷 293-311页

作者： jian Li Chenjie xu Key Laboratory of Road and Traffic Engineering of the Ministry of Education College of Transportation EngineeringTongji UniversityShanghai 201804China

Sustainable travel behavior intervention is an essential strategy to promote the development of urban transportation.The interventions offer personalized strategies based on certain scenario and participants to promote its effectiveness over hard travel restrictions.However,personalized strategies may also bring about difficulties to identify the actual effect of the measures.Furthermore,based on current practice,to make full use of travel behavior interventions,it is necessary to construct a unified methodological evidencebased framework to assess the reliability and effectiveness of travel behavior intervention studies.In response to these issues,we applied evidence-based knowledge graph to the field of sustainable travel behavior interventions to help decision supporters design sustainable travel behavior interventions wisely and in turn avoid excessive use of hard travel restrictions.We introduced concept of evidence-based practice to conduct a systematic analysis concerning reliability and validity of current full volume empirical studies by dimensions of scenarios,types of interventions and targets.In addition,we took advantage of high extensivity and integrability of knowledge graph to organize evidence-based related elements.Result of the systematic analysis shows that in terms of reliability of evidence,school intervention is the best scenario,knowledge incentive is the best intervention type and promoting public transit and walking proportion are the best targets.Oppositely,the reliability of interventions in workplace,belonging to reward and threat along with aiming at changing travel patterns generally and lowering travel carbon emission need to be enhanced.From the study,various research prospects are raised to promote evidence quality in the field of travel behavior intervention implementation.As a pioneer study,our research contributes to the field of urban transportation in introducing concepts of evidence-based practice and enabling optimization and extension of our achievement via the usage of k

关键词： Evidence-based decision-making Evidence assessment Knowledge graph Travel behavior intervention Sustainable travel

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Strategies for the development and approval of COVID-19 vaccines and therapeutics in the post-pandemic period

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Signal Transduction and Targeted Therapy 2024年第1期9卷 19-35页

作者： Danyi Ao xuemei He jian Liu Li xu State Key Laboratory of Biotherapy West China HospitalSichuan University610041 SichuanPeople’s Republic of China

The spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in significant casualties and put immense strain on public health systems worldwide,leading to economic recession and social unrest.In response,various prevention and control strategies have been implemented globally,including vaccine and drug development and the promotion of preventive measures.Implementing these strategies has effectively curbed the transmission of the virus,reduced infection rates,and gradually restored normal social and economic activities.However,the mutations of SARS-CoV-2 have led to inevitable infections and reinfections,and the number of deaths continues to rise.Therefore,there is still a need to improve existing prevention and control strategies,mainly focusing on developing novel vaccines and drugs,expediting medical authorization processes,and keeping epidemic surveillance.These measures are crucial to combat the Coronavirus disease(COVID-19)pandemic and achieve sustained,long-term prevention,management,and disease control.Here,we summarized the characteristics of existing COVID-19 vaccines and drugs and suggested potential future directions for their development.Furthermore,we discussed the COVID-19-related policies implemented over the past years and presented some strategies for the future.

关键词： prevention sustained approval

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Tislelizumab in previously treated, locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

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Chinese Journal of Cancer Research 2024年第3期36卷 257-276页

作者： jian Li Ye xu Aimin Zang Yunong Gao Quanli Gao Yanqiao Zhang Dong Wang jianming xu Ying Yuan Haiping jiang Jieer Ying Chunmei Shi Yanhong Deng Jing Wang Tianshu Liu Yi Huang Xiaoping Qian Yueyin Pan Ying Cheng Sheng Hu Jin Wang Mengyue Shi Ke Wang Han Hu Lin Shen Department of Medical Oncology the First Affiliated Hospital Zhejiang University School of Medicine Department of Medical Oncology Cancer Hospital of the University of Chinese Academy of Sciences Department of Medical Oncology Fujian Medical University Union Hospital Department of Oncology the Sixth Affiliated Hospital Sun Yat-sen University Department of Medical Oncology Hunan Cancer Hospital Department of Medical Oncology Zhongshan HospitalFudan University Department of Immunotherapy Hubei Cancer Hospital Department of Medical Oncology the Affiliated Hospital of Nanjing University Medical School Department of Medical Oncology Anhui Provincial Hospital Department of Medical Oncology Jilin Cancer Hospital State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Department of Gastrointestinal Oncology Peking University Cancer Hospital&Institute Department of Medical Oncology Hubei Cancer Hospital Clinical Development BeiGene(Shanghai)Co. Ltd. Biostatistics BeiGene(Beijing)Co. Ltd. Department of Oncology Fudan University Shanghai Cancer Center Department of Medical Oncology Affiliated Hospital of Hebei University Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gynecology Peking University Cancer Hospital&Institute Department of Immunotherapy Henan Cancer Hospital Department of Gastrointestinal Oncology Affiliated Cancer Hospital of Harbin Medical University Department of Gastrointestinal Oncology Chongqing University Cancer Hospital Department of Gastrointestinal Oncology the Fifth Medical Center Chinese PLA General Hospital Department of Medical Oncology the Second Affiliated Hospital Zhejiang University School of Medicine

Objective: The open-label, phase Ⅱ RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody) as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR) tumors.Methods: Adults with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled. Patients received tislelizumab 200 mg intravenously every 3 weeks. Objective response rate(ORR; primary endpoint), duration of response(DoR), and progression-free survival(PFS) were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results: Eighty patients were enrolled and treated; 75(93.8%) patients had measurable disease at baseline. Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79; 98.8%). At primary analysis(data cutoff July 8, 2021; median follow-up 15.2 months), overall ORR [46.7%; 95% confidence interval(95% CI), 35.1-58.6; one-sided P<0.0001] and ORR across tumor-specific subgroups [colorectal(n=46):39.1%(95% CI, 25.1–54.6); gastric/gastroesophageal junction(n=9): 55.6%(95% CI, 21.2-86.3); others(n=20):60.0%(95% CI, 36.1-80.9)] were significantly greater with tislelizumab vs. a prespecified historical control ORR of 10%; five(6.7%) patients had complete responses. Median DoR, PFS, and overall survival were not reached with long-term follow-up(data cutoff December 5, 2022; median follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events(TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs.Conclusions: Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

关键词： Biomarkers DNA mismatch repair immune checkpoint inhibitors microsatellite instability phase II clinical trials programmed cell death 1 receptor

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T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 819-832页

作者： Hui-Da Zheng Qiao-Yi Huang Qi-ming Huang Xiao-Ting Ke Kai Ye Shu Lin jian-Hua xu Department of Gastrointestinal Surgery The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Gynaecology and Obstetrics The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Computed Tomography/Magnetic Resonance Imaging The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Centre of Neurological and Metabolic Research The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Group of Neuroendocrinology Garvan Institute of Medical ResearchSydneyNSW 2010Australia

BACKGROUND The study on predicting the differentiation grade of colorectal cancer(CRC)based on magnetic resonance imaging(MRI)has not been reported yet.Developing a non-invasive model to predict the differentiation grade of CRC is of great value.AIM To develop and validate machine learning-based models for predicting the differ-entiation grade of CRC based on T2-weighted images(T2WI).METHODS We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023.Patients were randomly assigned to a training cohort(n=220)or a validation cohort(n=95)at a 7:3 ratio.Lesions were delineated layer by layer on high-resolution T2WI.Least absolute shrinkage and selection operator regression was applied to screen for radiomic features.Radiomics and clinical models were constructed using the multilayer perceptron(MLP)algorithm.These radiomic features and clinically relevant variables(selected based on a significance level of P<0.05 in the training set)were used to construct radiomics-clinical models.The performance of the three models(clinical,radiomic,and radiomic-clinical model)were evaluated using the area under the curve(AUC),calibration curve and decision curve analysis(DCA).RESULTS After feature selection,eight radiomic features were retained from the initial 1781 features to construct the radiomic model.Eight different classifiers,including logistic regression,support vector machine,k-nearest neighbours,random forest,extreme trees,extreme gradient boosting,light gradient boosting machine,and MLP,were used to construct the model,with MLP demonstrating the best diagnostic performance.The AUC of the radiomic-clinical model was 0.862(95%CI:0.796-0.927)in the training cohort and 0.761(95%CI:0.635-0.887)in the validation cohort.The AUC for the radiomic model was 0.796(95%CI:0.723-0.869)in the training cohort and 0.735(95%CI:0.604-0.866)in the validation cohort.The clinical model achieved an AUC of 0.751(95%CI:0.661-0.842)in the training cohort and

关键词： Radiomics Colorectal cancer Differentiation grade Machine learning T2-weighted imaging

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Advances in the application of hydrogel-based scaffolds for tendon repair

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Genes & Diseases 2024年第4期11卷 296-313页

作者： Renqiang Chen Fanglin Chen Kenian Chen jian xu Department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China Department of Orthopedics The Fourth Affiliated Hospital of Guangxi Medical UniversityLiuzhou Guangxi 545005China

Tendon injuries often lead to joint dysfunction due to the limited self-regeneration capacity of tendons.Repairing tendons is a major challenge for surgeons and imposes a signif-icant financial burden on society.Therefore,there is an urgent need to develop effective stra-tegies for repairing injured tendons.Tendon tissue engineering using hydrogels has emerged as a promising approach that has attracted considerable interest.Hydrogels possess excellent biocompatibility and biodegradability,enabling them to create an extracellular matrix-like growth environment for cells.They can also serve as a carrier for cells or other substances to accelerate tendon repair.In the past decade,numerous studies have made significant prog-ress in the preparation of hydrogel scaffolds for tendon healing.This review aims to provide an overview of recent research on the materials of hydrogel-based scaffolds used for tendon tis-sue engineering and discusses the delivery systems based on them.

关键词： Application Hydrogel-based Repairscaffolds Review Tendon injury Tissue engineering

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High-Performance Recyclable Furan-based Epoxy Resin and Its Carbon Fiber Composites with Dense Hydrogen Bonding

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Chinese Journal of Polymer Science 2024年第1期42卷 73-86,I0008页

作者： Chang-Bo Zhao Lu-Kun Feng Hui Xie ming-Liang Wang Bing Guo Zhi-Yong xue Cai-Zhen Zhu jian xu Advanced Materials Research Institute North China Electric Power UniversityBejing 102206China Institute of Low-Dimensional Materials Genome Initiative College of Chemistry and Environmental EngineeringShenzhen UniversityShenzhen 518060China Chengdu Institute of Organic Chemistry Chinese Academy of SciencesChengdu 610041China School of Science and Shenzhen Key Laboratory of Flexible Printed Electronics Technology and Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive ApplicationHarbin Institute of TechnologyShenzhen 518055China

The emerging biomass-based epoxy vitrimers hold great potential to fulfill the requirements for sustainable development of society.Since the existence of dynamic chemical bonds in vitrimers often reduces both the thermal and mechanical properties of epoxy resins, it is challenging to produce recyclable epoxy vitrimers with both excellent mechanical properties and good thermal stability. Herein, a monomer 4-(((5-(hydroxymethyl)furan-2-yl)methylene)amino)phenol(FCN) containing furan ring with potential to form high density of hydrogen bonding among repeating units is designed and copolymerized with glycerol triglycidyl ether to yield epoxy resin(FCN-GTE), which intrinsically has dual hydrogen bond networks, dynamic imine structure and resultant high performance. Importantly, as compared to the BPA-GTE, the FCN-GTE exhibits significantly improved mechanical properties owing to the increased density of hydrogen bond network and physical crosslinking interaction. Furthermore, density functional theory(DFT) calculation and in situ FTIR analysis is conducted to decipher the formation mechanism of hydrogen bond network. In addition, the FCN-GTE possesses superior UV shielding, chemical degradation, and recyclability because of the existence of abundant imine bonds. Notably, the FCN-GTE-based carbon fiber composites could be completely recycled in an amine solution.This study provides a facile strategy for synthesizing recyclable biomass-based high-performance epoxy vitrimers and carbon fiber composites.

关键词： Furan Hydrogen bond network Dynamic Schiff base Carbon fiber composites Recycling

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Giant vascular malformations invading the skull:A case report

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World Journal of Clinical Cases 2024年第16期12卷 2869-2875页

作者： ming-Chen Xie Fu-xu Wang jian xu Department of Neurosurgery The Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina

BACKGROUND Vascular malformations(VMs)arise as a result of errors in the process of angiogenesis and are usually present at birth,but may not become apparent until after birth.However,giant VMs of the head and face are uncommon,with few reported cases,and the prognosis for their surgical intervention is unclear.CASE SUMMARY A 12-year-old girl was admitted to the hospital with findings of an enlarged right temporal scalp.After admission,computed tomography(CT)angiography of cerebral ateries showed a right occlusal gap and a right temporal artery venous malformation.Furthermore,cerebral angiography showed a right temporal lobe VM with multiple vessels supplying blood.The patient underwent surgery to remove the malformed vessels and the eroded skull.Two hours after the surgery,the patient's right pupil was dilated,and an urgent CT scan of the skull showed a right subdural haematoma under the incision,which was urgently removed by a second operation.After surgery,we gave continuous antibiotic anti-infection treatment,and the patient recovered well and was discharged two weeks later.CONCLUSION Surgical removal of giant haemangiomas is risky and adequate preoperative(including interventional embolisation)and intraoperative preparations should be made.

关键词： Giant vascular malformation Early intervention Surgical intervention Interventional embolization Case report

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Persymmetric adaptive polarimetric detection of subspace range-spread targets in compound Gaussian sea clutter

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Journal of Systems Engineering and Electronics 2024年第1期35卷 31-42页

作者： xu Shuwen HAO Yifan WANG Zhuo xuE jian National Key Laboratory of Radar Signal Processing Xidian UniversityXi’an 710071China Xi’an Electronic Engineering Research Institute Xi’an 710100China Beijing Institute of Radio Measurement Beijing 100039China School of Communications and Information Engineering Xi’an University of Posts and TelecommunicationsXi’an 710121China

This paper focuses on the adaptive detection of range and Doppler dual-spread targets in non-homogeneous and nonGaussian sea clutter.The sea clutter from two polarimetric channels is modeled as a compound-Gaussian model with different parameters,and the target is modeled as a subspace rangespread target model.The persymmetric structure is used to model the clutter covariance matrix,in order to reduce the reliance on secondary data of the designed detectors.Three adaptive polarimetric persymmetric detectors are designed based on the generalized likelihood ratio test(GLRT),Rao test,and Wald test.All the proposed detectors have constant falsealarm rate property with respect to the clutter texture,the speckle covariance matrix.Experimental results on simulated and measured data show that three adaptive detectors outperform the competitors in different clutter environments,and the proposed GLRT detector has the best detection performance under different parameters.

关键词： sea clutter adaptive polarimetric detection compound Gaussian model subspace range-spread target persymmetric structure

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