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Spatial Genetic Structure of Two HIV-I-resistant Polymorphisms (CCR2-64 Ⅰ and SDF1-3’A) Alleles in Population of shandong Province, China

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Biomedical and Environmental Sciences 2005年第4期18卷 241-253页

作者： FU-ZHONG XUE JIE-ZHEN WANG DAO-XIN MA GUO-RONG LI PING HU Department of Epidemiology and Biostatistics School of Public Health Shandong University Jinan 250012 ShandongChina Qilu Hospital Shandong University Jinan 250012 Shandong China Center for Disease Control and Prevention of shandong Province Jinan 250012 Shandong China

To explore the spatial genetic structure of two HIV-Ⅰ-resistant polymorphisms （CCR2-64 Ⅰ and SDF1-3＇A） alleles in the population of shandong Province, China. Methods Using the techniques of spatial stratified sampling and spatial statistics, the spatial genetic structure of the locus （CCR2-64 Ⅰ and SDF1-3＇A）, which was shown to be important co-receptor for HIV infection, was quantified from the populations of 36 sampled counties of shandong Province, and a total of 3147 and 3172 samples were taken for testing CCR2-64Ⅰ and SDF1-3＇A respectively from individuals without known history of HIV-Ⅰ infection and AIDS symptoms. Results There were significantly spatial genetic structures of the two alleles at different spatial distance classes on the scale of populations, but on the scale of individuals, no spatial structure was found in either the whole area of shandong Province or the area of each sampled county. Although the change of frequencies of the two alleles with geographic locations in shandong Province both showed gradual increase trends, their changing directions were inverse. The frequency of CCR2-64Ⅰallele gradually increased from the southwest to the northeast, while the frequency of SDF1-3＇A allele gradually increased from the northeast to the southwest. However the RH to AIDS of combined types of their different genotypes did not represent obvious geographic diversity on the whole area of the Province. Conclusion The frequency of allele usually has some spatial genetic structures or spatial autocorrelation with different spatial distance classes, but the genotypes of individuals have random distribution in the same geographic area. Evaluating spatial distribution of the genetic susceptibility of HIV （AIDS） to CCR2-64Ⅰand SDF1-3＇A alleles, should focus on the frequencies of combined genotypes of CCR2 and SDFI based on the two-locus genotypes of each individual rather than the frequencies of CCR2-641 and SDF1-3＇A alleles.

关键词： Spatial genetic structure Chemokine receptors HIV-Ⅰ Resistant polymorphism Relative hazard

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Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway

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Asian Journal of Andrology 2024年第1期26卷 57-66页

作者： Chang-Bo Zhao Wei-Bo Chen Wen-Zhen Wang Fang-Xin Gong Cui-Qin Fan Ye Li Tian Lan Wen-Jing Wang Ming-Zhen Yuan Department of Urology Shandong Provincial HospitalShandong UniversityJinan 250012China Department of Andrology Liaocheng People's HospitalShandong UniversityLiaocheng 252000China Department of Urology The Second Hospital of Shandong UniversityJinan 250012China Department of Physiology School of Basic Medical SciencesShandong UniversityJinan 250012China

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction(DMED)a challenging endeavor.Notable factors contributing to DMED include oxidative stress,nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)pathway activation,and apoptosis,while nitro-oleic acid(NO,-OA)has been shown to be beneficial in treating these aspects of this condition.We,herein,investigated the effects and possible mechanisms of NO,-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes.Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group.However,in response to 4 weeks of NO,-OA treatment,there was an improvement in erectile function.The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group.The expression of proapoptotic factors was increased,while that of antiapoptotic factors was decreased in the DMED group.Moreover,the cell morphology in the cavernous tissue of the DMED group also changed adversely.NO,-OA treatment significantly reversed all these changes observed in the DMED group.In conclusion,NO,-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress,activation of the NO/cGMP pathway,and a reduction in apoptosis.

关键词： apoptosis diabetic mellitus erectile dysfunction nitro-oleic acid NO/cGMP pathway oxidative stress

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Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 35-42页

作者： Li-Li Miao Jing-Wen Wang Hui-Hui Liu Shuai Gao Yu-Chen Fan Kai Wang Department of Hepatology Qilu Hospital of Shandong UniversityJinan 250012China Experimental Center Shandong University of Traditional Chinese MedicineJinan 250355China Institute of Hepatology Shandong UniversityJinan 250012China

Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.

关键词： Hepatocellular carcinoma Glycine dehydrogenase DNA methylation Peripheral blood mononuclear cells

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Advances in the differentiation of pluripotent stem cells into vascular cells

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World Journal of Stem Cells 2024年第2期16卷 137-150页

作者： Yi-Chang Jiao Ying-Xin Wang Wen-Zhu Liu Jing-Wen Xu Yu-Ying Zhao Chuan-Zhu Yan Fu-Chen Liu Department of Neurology Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Mitochondrial Medicine Laboratory Qilu Hospital(Qingdao)of Shandong UniversityQingdao 266103Shandong ProvinceChina Brain Science Research Institute Shandong UniversityJinan 250012Shandong ProvinceChina

Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.

关键词： Induced pluripotent stem cell Blood vessels Vascular organoids Endothelial cells Smooth muscle cells Pericytes Tissue engineering vascular graft

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Outcomes of endoscopic sclerotherapy for jejunal varices at the site of choledochojejunostomy (with video): Three case reports

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World Journal of Gastroenterology 2024年第14期30卷 2059-2067页

作者： Jun Liu Peng Wang Li-Mei Wang Jing Guo Ning Zhong Department of Gastroenterology Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Hemorrhage associated with varices at the site of choledochojejunostomy is an unusual,difficult to treat,and often fatal manifestation of portal hypertension.So far,no treatment guidelines have been established.CASE SUMMARY We reported three patients with jejunal varices at the site of choledochojejun-ostomy managed by endoscopic sclerotherapy with lauromacrogol/α-butyl cyanoacrylate injection at our institution between June 2021 and August 2023.We reviewed all patient records,clinical presentation,endoscopic findings and treatment,outcomes and follow-up.Three patients who underwent pancre-aticoduodenectomy with a Whipple anastomosis were examined using conven-tional upper gastrointestinal endoscopy for suspected hemorrhage from the afferent jejunal loop.Varices with stigmata of recent hemorrhage or active he-morrhage were observed around the choledochojejunostomy site in all three patients.Endoscopic injection of lauromacrogol/α-butyl cyanoacrylate was carried out at jejunal varices for all three patients.The bleeding ceased and patency was observed for 26 and 2 months in two patients.In one patient with multiorgan failure and internal environment disturbance,rebleeding occurred 1 month after endoscopic sclerotherapy,and despite a second endoscopic sclero-therapy,repeated episodes of bleeding and multiorgan failure resulted in eventual death.CONCLUSION We conclude that endoscopic sclerotherapy with lauromacrogol/α-butyl cyanoac-rylate injection can be an easy,effective,safe and low-cost treatment option for jejunal varicose bleeding at the site of choledochojejunostomy.

关键词： Endoscopic sclerotherapy Jejunal varices Choledochojejunostomy Portal vein hypertension Case report

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Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation

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World Journal of Clinical Cases 2024年第15期12卷 2542-2550页

作者： Xian-Quan Cui Lu-Wei Zhang Peng Zhao Jing-Jing Feng Department of Organ Transplantation Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Department of Blood Purification Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND The number of patients undergoing solid organ transplantation has increased annually.However,infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants.Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4’’-O-isovaleryltransferase gene(ist)from streptomyces thermotoleran.Carrimycin has good antibacterial and antiviral effects.However,no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia(SP)after solid organ transplantation.AIM To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment.METHODS In March 2022,ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022.When the condition was critical and difficult to control with other drugs,carrimycin was administered.These ten patients'clinical features and treatment protocols were retrospectively analyzed,and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated.RESULTS All ten patients were included in the analysis.Regarding etiological agent detection,there were three cases of fungal pneumonia,two cases of bacterial pneumonia,two cases of Pneumocystis pneumonia,and three cases of mixed infections.After treatment with carrimycin,the disease in seven patients significantly improved,the course of the disease was significantly shortened,fever was quickly controlled,chest computed tomography was significantly improved,and oxygenation was significantly improved.Finally,the patients were discharged after curing.One patient died of acute respiratory distress syndrome,and two patients discontinued treatment.CONCLUSION Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation.Carrimycin may have anti

关键词： Carrimycin Organ transplantation Severe pneumonia Immunosuppressant Infection Antiviral drugs

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KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer’s disease

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World Journal of Psychiatry 2024年第3期14卷 445-455页

作者： Qun-Shan Lu Lin Ma Wen-Jing Jiang Xing-Bang Wang Mei Lu Department of Geriatric Medicine Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of Cardiovascular Proteomics of shandong Province Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and

关键词： Alzheimer's disease Diabetes Insulin resistance KAT7 Dual-specificity tyrosine phosphorylation-regulated kinase-1A HMGN1

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Association between prolactin/testosterone ratio and breast cancer in Chinese women

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Chinese Medical Journal 2024年第3期137卷 368-370页

作者： Qian Cai Xiaohan Tian Yuyi Tang Han Cong Jie Liu Song Zhao Rong Ma Jianli Wang Jiang Zhu Department of Geriatric Medicine Qilu Hospital of Shandong UniversityJinanShandong 250012China Key Laboratory of Cardiovascular Proteomics of shandong Province Qilu Hospital of Shandong UniversityJinanShandong 250012China Department of Pharmacology School of Basic Medical SciencesShandong UniversityJinanShandong 250012China Department of Breast Surgery General SurgeryQilu Hospital of Shandong UniversityJinanShandong 250012China Department of Thyroid and Breast Surgery Guangdong Second Provincial General HospitalGuangzhouGuangdong 510310China Department of Toxicology and Cancer Biology Collage of MedicineUniversity of KentuckyLexingtonKY 40536USA Department of Immunology School of Basic Medical ScienceShandong UniversityJinanShandong 250012China Department of Gynaecology and Obstetrics Qilu Hospital of Shandong UniversityJinanShandong 250012China

To the Editor:Breast cancer is a prevalent malignant tumor and ranks as the second leading cause of cancer-related deaths globally.^([1])The breast is the target organ of some endocrine hormones,which regulate its growth and development.Aside from estrogen and progesterone,the relationship among prolactin,androgen,and breast cancer has recently garnered increasing attention.

关键词： breast cancer prolactin

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Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment

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World Journal of Diabetes 2024年第4期15卷 735-757页

作者： Jing Gao Ying Zou Xiao-Yu Lv Li Chen Xin-Guo Hou Department of Endocrinology Qilu Hospital of Shandong UniversityCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina Institute of Endocrine and Metabolic Diseases Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of Endocrine and Metabolic Diseases Shandong Province Medicine&HealthJinan 250012Shandong ProvinceChina Department of Endocrinology Jinan Clinical Research Center for Endocrine and Metabolic DiseaseJinan 250012Shandong ProvinceChina

BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes

关键词： Bioinformatics analysis Type 2 diabetes mellitus Cognitive impairment Hippocampus Immune Microglia

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Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy:a meta-analysis

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World Journal of Emergency Medicine 2024年第3期15卷 181-189页

作者： Zeyu Yang Huiruo Liu Dazhou Lu Shengchuan Cao Feng Xu Chuanbao Li Department of Emergency Medicine Qilu Hospital of Shandong UniversityJinan 250012China shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityChest Pain CenterQilu Hospital of Shandong UniversityJinan 250012China Key Laboratory of Emergency and Critical Care Medicine of shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinan 250012China shandong Key Laboratory:Magnetic Field-free Medicine&Functional Imaging(MF) Qilu Hospital of Shandong UniversityJinan 250012China National Medical Products Administration(NMPA)Key Laboratory for Clinical Research and Evaluation of Innovative Drug Qilu Hospital of Shandong UniversityJinan 250012China

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

关键词： Acute coronary syndrome High-dose Glucose-insulin-potassium treatment Reperfusion therapy Meta-analysis

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