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P16 gene hypermethylation and hepatocellular carcinoma:A systematic review and meta-analysis

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World Journal of Gastroenterology 2011年第25期17卷 3043-3048页

作者： jia-jie zang Feng Xie Jin-Fang Xu Ying-Yi Qin Rong-Xi Shen jia-Mei Yang jia He Department of Health Statistics Second Military Medical Univer-sity Shanghai 200433 China Department of Special Treatment and Liver Transplantation Eastern HepatobiliarySurgery Hospital Second Military Medical University Shanghai200438 China

AIM:To quantitatively investigate the effect of p16 hypermethylation on hepatocellular carcinoma (HCC) and hepatocirrhosis using a meta-analysis of available casecontrol studies.METHODS:Previous studies have primarily evaluated the incidence of p16 hypermethylation in HCC and corresponding control groups,and compared the incidence of p16 hypermethylation in tumor tissues,pericancer liver tissues,normal liver tissues and non-tumor liver tissues with that in other diseases.Data regarding publication information,study characteristics,and incidence of p16 hypermethylation in both groups were collected from these studies and summarized.RESULTS:Fifteen studies,including 744 cases of HCC and 645 non-tumor cases,were identified for meta-analysis.Statistically significant odds ratios (ORs) of p16 hypermethylation were obtained from tumor tissues and non-tumorous liver tissues of HCC patients (OR 7.04,95% CI:3.87%-12.78%,P < 0.0001),tumor tissues of HCC patients and healthy liver tissues of patients with other diseases (OR 12.17,95% CI:6.64%-22.31%,P < 0.0001),tumor tissues of HCC patients and liver tissues of patients with non-tumorous liver diseases (OR 6.82,95% CI:4.31%-10.79%,P < 0.0001),and cirrhotic liver tissues and non-cirrhotic liver tissues (OR 4.96,95% CI:1.45%-16.96%,P=0.01).The pooled analysis showed significantly increased ORs of p16 hypermethylation (OR 6.98,95% CI:4.64%-10.49%,P < 0.001) from HCC tissues and cirrhotic tissues.CONCLUSION:P16 hypermethylation induces the inactivation of p16 gene,plays an important role in hepatocarcinogenesis,and is associated with an increased risk of HCC and liver cirrhosis.

关键词：基因甲基化 P16 肝癌肿瘤组织评价系统肝脏疾病肝组织

A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma:Construction and analysis of a circRNA-mediated competing endogenous RNA network

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 272-287页

作者： Hai-Yan Zhang jia-jie Zhu Zong-Ming Liu Yu-Xuan Zhang jia-jia Chen Ke-Da Chen Zhejiang Chinese Medical University Hangzhou 310053China Shulan International Medical College Zhejiang Shuren UniversityHangzhou 310015China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.

关键词： Hepatocellular carcinoma circRNA-related ceRNA network Biomarker Least absolute shrinkage and selection operator Bioinformatics

Diophantine equations and Fermat's last theorem for multivariate(skew-)polynomials

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Applied Mathematics(A Journal of Chinese Universities) 2024年第1期39卷 159-173页

作者： PAN jie jia Yu-ming LI Fang School of Mathematical Sciences Zhejiang UniversityHangzhou 310058China Henan Experimental High School Zhengzhou 450003China

Fermat’s Last Theorem is a famous theorem in number theory which is diﬃcult to prove.However,it is known that the version of polynomials with one variable of Fermat’s Last Theorem over C can be proved very concisely.The aim of this paper is to study the similar problems about Fermat’s Last Theorem for multivariate(skew)-polynomials with any characteristic.

关键词： Fermat's last theorem polynomial ring skew polynomial ring

Transforming Adolescent Smiles:Correcting Skeletal Mandibular Retrusion and Bimaxillary Protrusion with Clear Aligners

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Current Medical Science 2024年第3期44卷 657-666页

作者： Wen-jie FAN jia-qi ZHANG jia-qi ZHAN Li HU Li-li CHEN Department of Stomatology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China School of Stomatology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Wuhan National High Magnetic Field Center Wuhan430074China The Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People’s Hospital of Lianyungang Lianyungang222000China The First Affiliated Hospital of Kangda College of Nanjing Medical University/The First People’s Hospital of Lianyungang Lianyungang222000China

Maxillary protrusion combined with mandibular retraction is a highly prevalent but extremely complex maxillofacial deformity that can have a serious negative impact on patients’facial aesthetics and mental health.The traditional orthodontic treatment strategy often involves extracting 4 first premolars and conventional fixed techniques,combined with mini-implant screws,to retract the anterior teeth and improve facial protrusion.In recent years,an invisible orthodontic technique,without brackets,has become increasingly popular.However,while an invisible aligner has been used in some cases with reasonable results,there remain significant challenges in achieving a perfect outcome.This case report presents an adolescent patient with bimaxillary protrusion and mandibular retrognathia.Based on the characteristics of the invisible aligners and the growth characteristics of the adolescent’s teeth and jawbone,we designed precise three-dimensional tooth movement and corresponding resistance/over-correction for each tooth,while utilizing the patient’s jawbone growth potential to promote rapid development of the mandible,accurately and efficiently correcting bimaxillary protrusion and skeletal mandibular retrognathia.The patient’s facial aesthetics,especially the lateral morphology,have been greatly improved,and various aesthetic indicators have also shown significant changes,and to the patient’s great benefit,invasive mini-implant screws were not used during the treatment.This case highlights the advantages of using invisible aligners in adolescent maxillary protrusion combined with mandibular retraction patients.Furthermore,comprehensive and accurate design combined with good application of growth potential can also enable invisible orthodontic technology to achieve perfect treatment effects in tooth extractions,providing clinical guidance for orthodontists.

关键词： mandibular retrusion esthetic orthodontic treatment clear aligners growth potential

Climatic impacts induced by winter wheat irrigation over North China simulated by the nonhydrostatic RegCM4.7

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Advances in Climate Change Research 2024年第2期15卷 197-210页

作者： jia WU Zhen-Yu HAN Xue-jie GAO Zheng-jia LIU National Climate Centre China Meteorological AdministrationBeijing 100081China Key Laboratory for Climate Studies China Meteorological AdministrationBeijing 100081China Climate Change Research Center Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters Nanjing University of Information Science and TechnologyNanjing 210044China Institute of Geographic Sciences and Natural Resources Research Chinese Academy of SciencesBeijing 100101China

Quantification of the impact of winter wheat irrigation on the climate and the occurrence of extreme climatic events over North China is crucial for regional adaptation planning.Previous related studies mainly focused on the impact on surface processes;however,few focused on the effects of extreme events using high-resolution nonhydrostatic regional climate models.Here,the 9-km-resolution nonhydrostatic RegCM4.7 was coupled with a crop irrigation scheme and an updated winter wheat irrigation dataset to better simulate irrigation effects.Two experiments were conducted with and without winter wheat irrigation to isolate the effects of irrigation.Results showed that irrigation simulation reduces the model biases in temperature,precipitation,latent heat flux,soil moisture,sensitive heat flux,and top-layer soil moisture.Moreover,it also reduces the bias and increases the correlation with observations obtained in irrigated areas,especially in summer,indicating better representation of irrigation schemes.Winter wheat irrigation tends to cause substantial cooling of the local surface maximum,minimum,and mean air temperatures(by-1.68,-0.34,and-0.79℃,respectively)over irrigated areas of North China,with the largest changes observed in relation to maximum temperature.Additionally,precipitation is found to increase during spring and summer,which is strongly related to water vapor transport in the lower levels of the atmosphere.Further analyses indicated that the number of annual mean hot days decrease(-13.9 d),whereas the number of both comfort days(+10.2 d)and rainy days(days with total precipitation greater than 1 mm:+6.6 d)increase over irrigated areas,demonstrating beneficial feedback to human perception and agriculture.Fortunately,although the heat wave risk increases(number of annual mean heat wave days:+5.8 d),the impact is limited to small areas within irrigated region.Additionally,no notable change was found in terms of heavy rainfall events and precipitation intensity,which might be an undereastimation caused by th

关键词： Nonhydrostatic regional climate model Irrigation effect Extreme events North China

NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2400-2410页

作者： Bo Hu jiaping Zhang jie Huang Bairu Luo Xiansi Zeng Jinjing jia Department of Pathology and Municipal Key-Innovative Discipline of Molecular Diagnostics Jiaxing Hospital of Traditional Chinese MedicineJiaxing UniversityJiaxingZhejiang ProvinceChina Research Center of Neuroscience Jiaxing University Medical CollegeJiaxingZhejiang ProvinceChina Department of Clinical Pathology Jiaxing University Master Degree Cultivation BaseZhejiang Chinese Medical UniversityJiaxingZhejiang ProvinceChina

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.

关键词： Alzheimer’s disease caspase-1 GSDMD inflammasome neuroinflammation NLRP1 NLRP3 pyroptosis therapeutic strategies

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

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Military Medical Research 2024年第1期11卷 80-97页

作者： Qian-Yun Guo jia-Qi Yang Xun-Xun Feng Yu-jie Zhou Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease Beijing Institute of Heart Lung and Blood Vessel DiseaseClinical Center for Coronary Heart DiseaseDepartment of CardiologyBeijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

关键词： Heart regeneration Cardiac disease Therapeutics Signaling mechanisms

Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

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Military Medical Research 2024年第1期11卷 1-18页

作者： Zi-Sen Zhang Yi-Yan Liu Shuang-Shuang He Dai-Qin Bao Hong-Chen Wang jie Zhang Xiao-Yong Peng jia-Tao zang Yu Zhu Yue Wu Qing-Hui Li Tao Li Liang-Ming Liu State Key Laboratory of Trauma Burns and Combined InjuryDepartment of Shock and TransfusionResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reacti

关键词： Pericyte Vascular reactivity Vascular permeability Cx43 Microvesicle

Transcriptomic analysis identifies the neuropeptide cortistatin (CORT) as an inhibitor of temozolomide (TMZ) resistance by suppressing the NF-kB-MGMT signaling axis in human glioma

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Genes & Diseases 2024年第3期11卷 385-399页

作者： Zongze He Bo Peng Qi Wang jie Tian Ping Liu jie Feng Yiwei Liao Longyi Chen Ping jia jian Tang Department of Neurosurgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Rehabilitation Medicine Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Glioma is a common tumor originating in the brain that has a high mortality rate.Temozolomide(TMZ)is the first-line treatment for high-grade gliomas.However,a large pro-portion of gliomas are resistant to TMZ,posing a great challenge to their treatment.In the study,the specific functions and mechanism(s)by which cortistatin(CORT)regulates TMZ resis-tance and glioma progression were evaluated.The decreased expression of CoRT was detected in glioma tissues,and highly expressed CORT was associated with a better survival rate in pa-tients with glioma.CORT overexpression notably decreased the capacity of glioma cells to pro-liferate and migrate in vitro and to form tumors in vivo.CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT,p21,and Puma expression.Importantly,CORT overexpression reduced the resistance of gliomas to TMZ in vivo.CORT expression Was negatively correlated with MGMT expression in both glioma tissues and cells,and it was found that CORT inhibited NF-kB pathway activation in glioma cells,thereby inhibiting MGMT expression.In conclusion,CORT regulates glioma cell growth,migration,apoptosis,and TMZ resistance by weakening the activity of NF-kB/p65 and thereby regulating MGMT expression.The CORT/NF-kB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ.Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells,independent of its effects on TMZ resistance,providing evidence of novel therapeutic targets for glioma that should be evaluated infurther studies.

关键词： Cortistatin Glioma MGMT NF-kB pathway Temozolomide