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| 1 | Evaluation and reflection on claudin 18.2 targeting therapy in advanced gastric cancer显示文摘Claudin 18.2(CLDN18.2)is a tight-junction protein.CLDN18.2-targeting strategy has cut a striking figure in CLDN18.2 positive patients with advanced gastric cancer.Zolbetuximab,the CLDN18.2 antibody,obtained a better clinical benefit in patients compared with the controlled.In phase II trials,combination treatment of epirubicin,oxaliplatin and capecitabine(EOX)+zolbetuximab achieved the optimal effects of overall survival which extended to 13.2 months with tolerable safety events,indicating its greater potential playing the second promising target in gastric cancer.This review will reveal the definitive clinical benefit CLDN18.2-targeting therapies have achieved and update the highlighting development(like chimeric antigen receptor T-cell immunotherapy)to CLDN18.2 positive patients.We then focus on 10 questions arisen from recent progress and anticipate to provide a future perspective for novel cancer treatment. | Jianwei Zhang Ruilan Dong Lin Shen | 2020 | Chinese Journal of Cancer Research2020，32，2： | 13 |
| 2 | Influenza A Virus(H1N1) Infection Induces Glycolysis to Facilitate Viral Replication显示文摘Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus(H1N1), a single-stranded, negative-sense RNA virus with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues and in human lung epithelial(A549) cells. In detail, the expression of hexokinase 2(HK2), the first enzyme in glycolysis, was upregulated in H1N1-infected A549 cells,and the expression of pyruvate kinase M2(PKM2) and pyruvate dehydrogenase kinase 3(PDK3) was upregulated in H1N1-infected mouse lung tissues. Pharmacologically inhibiting the glycolytic pathway or targeting hypoxia-inducible factor 1(HIF-1), the central transcriptional factor critical for glycolysis, significantly reduced H1N1 replication, revealing a requirement for glycolysis during H1N1 infection. In addition, pharmacologically enhancing the glycolytic pathway further promoted H1N1 replication. Furthermore, the change of H1N1 replication upon glycolysis inhibition or enhancement was independent of interferon signaling. Taken together, these findings suggest that influenza A virus induces the glycolytic pathway and thus facilitates efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat influenza A virus infection in the future. | Lehao Ren Wanju Zhang Jing Zhang Jiaxiang Zhang Huiying Zhang Yong Zhu Xiaoxiao Meng Zhigang Yi Ruilan Wang | 2021 | Virologica Sinica2021，36，6： | 3 |
| 3 | Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylationmediated mitophagy显示文摘Parkin,an E3 ubiquitin ligase,plays a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy.Accumulating evidence suggests that the acetylation modification of the key mitophagy machinery influences mitophagy level,but the underlying mechanism is poorly understood.Here,our study demonstrated that inhibition of histone deacetylase(HDAC)by treatment of HDACis activates mitophagy through mediating Parkin acetylation,leading to inhibition of cervical cancer cell proliferation.Bioinformatics analysis shows that Parkin expression is inversely correlated with HDAC2 expression in human cervical cancer,indicating the low acetylation level of Parkin.Using mass spectrometry,Parkin is identified to interact with two upstream molecules,acetylase acetyl-Co A acetyltransferase 1(ACAT1)and deacetylase HDAC2.Under treatment of suberoylanilide hydroxamic acid(SAHA),Parkin is acetylated at lysine residues 129,220 and 349,located in different domains of Parkin protein.In in vitro experiments,combined mutation of Parkin largely attenuate the interaction of Parkin with PTEN induced putative kinase 1(PINK1)and the function of Parkin in mitophagy induction and tumor suppression.In tumor xenografts,the expression of mutant Parkin impairs the tumor suppressive effect of Parkin and decreases the anticancer activity of SAHA.Our results reveal an acetylation-dependent regulatory mechanism governing Parkin in mitophagy and cervical carcinogenesis,which offers a new mitophagy modulation strategy for cancer therapy. | Xin Sun Yuhan Shu Guiqin Ye Caixia Wu Mengting Xu Ruilan Gao Dongsheng Huang Jianbin Zhang | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 3 |
| 4 | A cohort study of adolescents with depression in China:tracking multidimensional outcomes and early biomarkers for intervention显示文摘Background Depression in adolescents is recognised as a global public health concern,but little is known about the trajectory of its clinical symptoms and pathogenesis.Understanding the nature of adolescents with depression and identifying earlybiomarkers can facilitatepersonalised intervention andreducediseaseburden.Aims To track multidimensional outcomes of adolescents with depression and develop objective biomarkers for diagnosis,as well as response to treatment,prognosis and guidance for early identification and intervention.Methods This is a multidimensional cohort study on the Symptomatic trajectory and Biomarkers of Early Adolescent Depression(sBEAD).We planned to recruit more than 1000 adolescents with depression and 300 healthy controls within 5 years.Multidimensional clinical presentations and objective indicators are collected at baseline,weeks 4,8,12 and 24,and years 1,2,3,4 and 5.Conclusions To the best of our knowledge,this is the first longitudinal cohort study that examines multidimensional clinical manifestations and multilevel objective markers in Chinese adolescents with depression.This study aims at providing early individualised interventions for young,depressed patients to reduce the burden of disease. | Xiaofei Zhang Yanling Zhou Jiaqi Sun Ruilan Yang Jianshan Chen Xiaofang Cheng Zezhi Li Xinlei Chen Chanjuan Yang Xinhong Zhu Liping Cao | 2022 | General Psychiatry2022，35，4： | 2 |
| 5 | Nitric Oxide Enhances Angiogenesis via the Synthesis of Vascular Endothelial Growth Factor and cGMP After Stroke in the Rat显示文摘 | RUILAN ZHANG LEI WANG LI ZHANG | 2003 | Circ Res2003，92，： | 1 |
| 6 | Combination therapy of stroke in rats with a nitric oxide donor and human bone marrow stromal cells enhances angiogenesis and neurogenesis显示文摘 | Jie Chen Yi Li Ruilan Zhang | 2004 | Brain Research2004，1005，2： | 1 |
| 7 | Effects of a selective CDI 1b/CD18 antagonist and recombinant human tissue plasminagen activator treatmenl alone and in combination in a rat embolic model of stroke显示文摘 | Zhang Li Zhang Zhenggang Zbang Ruilan | 2003 | Stroke2003，34，7： | 1 |
| 8 | Effects of a selective CD11b/CD18 antagonist and recombinant human tissue plasminogen activator treatment alone and in combination in a rat embolic model of stroke显示文摘 | Zhang Li Zhang Zhenggang Zhang Ruilan | 2003 | Stroke2003，34，7： | 1 |
| 9 | Periodic-phase-diagram similarity method for weak signal detection显示文摘The periodic-phase-diagram similarity method is proposed to identify the frequency of weak harmonic signals.The key technology is to find a set of optimal coefficients for Duffing system,which leads to the periodic motion under the influence of weak signal and strong noise.Introducing the phase diagram similarity,the influences of strong noise on the similarity of periodic phase diagram are discussed.The principle of highest similarity of periodic phase diagram with the same frequency is detected by discussing the persistence of similarity of periodic motion phase diagram under the strong noise and the periodic-phase-diagram similarity method is constructed.The weak signals of early fault and strong noise are input into Duffing system to obtain the identified system.The stochastic subharmonic Melnikov method is extended to obtain the conditions of the optimal coefficients for the identified system.Based on the results,the constructed frequency conversion harmonic weak signals are considered to form a datum periodic system.With the change of frequency in the datum periodic system,the phase diagram similarity of the two constructed systems can be calculated.Based on the periodic-phase-diagram similarity method,the frequency of weak harmonic signals can be identified by the principle of highest similarity of periodic phase diagram with the same frequency.The results of numerical simulation and the early fault diagnosis results of actual bearings verify the feasibility of the periodic-phase-diagram similarity method.The accuracy of the detection effect is 97%,and the minimum signal-to-noise ratio is−80.71 dB. | Ruilan Tian Yangkun Zhang Shaopu Yang Kai Yuan Qiang Xue Quanrong Ren | 2021 | International Journal of Mechanical System Dynamics2021，1，2： | 0 |
| 10 | Efficient development strategies for large ultra-deep structural gas fields in China显示文摘Through analyzing the development of large ultra-deep structural gas fields in China,strategies for the efficient development of such gas fields are proposed based on their geological characteristics and production performance.According to matrix properties,fracture development degree and configuration between matrix and fractures,the reservoirs are classified into three types:single porosity single permeability system,dual porosity dual permeability system,and dual porosity single permeability system.These three types of gas reservoirs show remarkable differences in different scales of permeability,the ratio of dynamic reserves to volumetric reserves and water invasion risk.It is pointed out that the key factors affecting development efficiency of these gas fields are determination of production scale and rapid identification of water invasion.Figuring out the characteristics of the gas fields and working out pertinent technical policies are the keys to achieve efficient development.The specific strategies include reinforcing early production appraisal before full scale production by deploying high precision development seismic survey,deploying development appraisal wells in batches and scale production test to get a clear understanding on the structure,reservoir type,distribution pattern of gas and water,and recoverable reserves,controlling production construction pace to ensure enough evaluation time and accurate evaluation results in the early stage,in line with the development program made according to the recoverable reserves,working out proper development strategies,optimizing pattern and proration of wells based on water invasion risk and gas supply capacity of matrix,and reinforcing research and development of key technologies. | LI Xizhe GUO Zhenhua HU Yong LUO Ruilan SU Yunhe SUN Hedong LIU Xiaohua WAN Yujin ZHANG Yongzhong LI Lei | 2018 | Petroleum Exploration and Development2018，45，1： | 0 |
| 11 | Efficacy and safety of awake prone positioning in the treatment of non-intubated spontaneously breathing patients with COVID-19-related acute respiratory failure:A systematic review and meta-analysis显示文摘Background Since the beginning of the coronavirus disease 2019(COVID-19)pandemic,prone positioning has been widely applied for non-intubated,spontaneously breathing patients.However,the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear.We aimed to systematically analyze the outcomes associated with awake prone positioning(APP).Methods We conducted a systematic literature search of PubMed/MEDLINE,Cochrane Library,Embase,and Web of Science from January 1,2020,to June 3,2022.This study included adult patients with acute respiratory failure caused by COVID-19.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines were followed,and the study quality was assessed using the Cochrane risk-of-bias tool.The primary outcome was the reported cumulative intubation risk across randomized controlled trials(RCTs),and the effect estimates were calculated as risk ratios(RRs;95%confidence interval[CI]).Results A total of 495 studies were identified,of which 10 fulfilled the selection criteria,and 2294 patients were included.In comparison to supine positioning,APP significantly reduced the need for intubation in the overall population(RR=0.84,95%CI:0.74–0.95).The two groups showed no significant differences in the incidence of adverse events(RR=1.16,95%CI:0.48–2.76).The meta-analysis revealed no difference in mortality between the groups(RR=0.93,95%CI:0.77–1.11).Conclusions APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19.However,it did not significantly reduce mortality in comparison to usual care without prone positioning. | Jingjing Wang Daonan Chen Puyu Deng Chenchen Zhang Xue Zhan Hui Lv Hui Xie Dechang Chen Ruilan Wang | 2023 | Journal of Intensive Medicine2023，3，4： | 0 |
| 12 | Dynamic crushing behavior and energy absorption of hybrid auxetic metamaterial inspired by Islamic motif art显示文摘Auxetic honeycomb structures are promising metamaterials with outstanding mechanical properties,and can be potentially used in energy absorption applications.In this study,a novel modified re-entrant hybrid auxetic metamaterial inspired by Islamic motif art is designed by integrating four-pointed double re-entrant motifs with symmetric semi-hexagonal unit cells to achieve a high energy absorption capacity(EAC).Theoretical analyses and numerical simulations are performed to examine the dynamic crushing behavior of the four-pointed double re-entrant combined structure(FDRCS).The developed finite element models(FEMs)are validated by the experiments under quasi-static compression.The deformation mode and stress-strain curves are further studied under low,medium,and high crushing velocities.The theoretically predicted plateau stress of the FDRCS under different crushing velocities is consistent with the numerical simulation results.The crushing stress and the EAC of the FDRCS are influenced by the geometric parameters and crushing velocities.The FDRCS exhibits a negative Poisson's ratio(NPR),owing to the four-point re-entrant structure(RES).Moreover,the specific energy absorption(SEA)of these structures is higher than that of nonauxetic hexagonal and auxetic re-entrant structures,owing to the generation of more plastic hinges that dissipate more energy during dynamic crushing. | Ruilan TIAN Huaitong GUAN Xuhao LU Xiaolong ZHANG Huanan HAO Wenjie FENG Guanglei ZHANG | 2023 | Applied Mathematics and Mechanics(English Edition)2023，44，3： | 0 |
| 13 | HIF-1αpromotes virus replication and cytokine storm in H1N1 virus-induced severe pneumonia through cellular metabolic reprogramming显示文摘The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine storm.However,the specific mechanisms triggering virus replication and cytokine storm are still not fully elucidated.Here,we identified hypoxia inducible factor-1α(HIF-1α)as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial cells.Specifically,HIF-1αprotein expression is upregulated after H1N1 infection.Deficiency of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in vivo.In addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in vitro.Mechanistically,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and lactate.Inhibition of glycolysis significantly suppresses viral replication and inflammatory responses.Further analysis revealed that H1N1-induced HIF-1αcan promote the expression of hexokinase 2(HK2),the key enzyme of glycolysis,and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate,which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/βproduction.In conclusion,this study demonstrated that the upregulation of HIF-1αby H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2,providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection. | Xiaoxiao Meng Yong Zhu Wenyu Yang Jiaxiang Zhang Wei Jin Rui Tian Zhengfeng Yang Ruilan Wang | 2024 | Virologica Sinica2024，39，1： | 0 |
| 14 | Correlation between clinical course and radiographic development on CT scan in patients with COVID-19显示文摘Background:To analyze the correlation between clinical course and radiographic development on computed tomography(CT)in patients with confirmed coronavirus disease 2019(COVID-19)and to provide more evidence for treatment.Methods:This retrospective,observational,cohort study enrolled 49 patients with Reverse transcription-polymerase chain reaction(RT-PCR)-confirmed COVID-19,which included 30 patients admitted to the intensive care unit(ICU)of Wuhan Third Hospital and 19 patients either admitted to or receiving telemedicine consultation from Shanghai General Hospital,Shanghai Xuhui Dahua Hospital,and hospitals in other provinces.CT scans were performed in all enrolled patients and the radiographic features including simple ground-glass opacities(GGOs),GGO with interlobular septal thickening,consolidations with GGO,and consolidations only were monitored by repeating the CT.The progression of these radiographic features was analyzed in combination with their clinical staging and the time interval between onset of symptoms to CT.Results:Based on illness severity,the 49 patients were classified into four stages:mild(n=6),moderate(n=12),severe(n=16),and critically ill(n=15).The CT findings were classified into three phases:early(n=5),progres-sion(n=39),and recovery(n=5).Among the 49 patients,9 had bilateral diffuse GGO or diffuse consolidations(white lungs)and were counted as 18 lesions.Three patients had no abnormal findings on initial CT,but their repeat CT showed new lesions.In all,we identified 892 lesions including simple GGO,GGO with interlobular septal thickening,consolidations with GGO,and consolidations only.Conclusions:Most patients had pulmonary lesions on the posterior,inferior,and peripheral lung fields on CT.The development of GGO with interlobular septal thickening,GGO with consolidations,and consolidations only happened mainly between day 8 and 14.The emergence of consolidations may suggest the progression to the severe phase of the illness,whereas simple consolidations or“white lung”may suggest a critically ill phase. | Yun Xie Luyu Yang Hui Dong Song Cao Wenkai Zhang Qiong Chen Baoliang Jin Zhiguo Zhou Jun Liu Zhiyan He Ruilan Wang | 2021 | Journal of Intensive Medicine2021，1，1： | 0 |
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