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Long-term tadalafil once daily in Chinese men with erectile dysfunction:a 2-year final analysis of a post-marketing,multicenter,randomized,open-label trial

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Asian Journal of andrology 2024年第3期26卷 282-287页

作者： Hui Jiang Lian-Ming Zhao Su Yan Ji-Hong Liu Zhao-Hui Zhu Jin-Dan Luo Yu-Tian Dai Fu-Biao Li Hao-Cheng Lin Zhi-Chao Zhang Department of Urology Peking University First HospitalBeijing 100000China Department of Urology Peking University Third HospitalBeijing 100191China Department of Urology Peking Union Medical College HospitalBeijing 100730China Department of Urology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Urology Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Urology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Departmentof andrology Nanjing Drum Tower HospitalNanjing 210008China Department of andrology The First Hospital of Jilin UniversityChangchun 130021China andrology center Department of UrologyPeking University First HospitalBeijing 100034China

The long-term safety and effectiveness of once-daily tadalafil is crucial,but limited data are available in Chinese patients witherectile dysfunction(ED).In this post-marketing,multicenter,randomized,open-label trial with 2-year follow-up,635 ED caseswere randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months,of whom 580 continued once-daily tadalafil 5 mg for21 ***-emergent adverse events in the 12-month and 24-month period were similar,with the most common beingviral upper respiratory tract infection,upper respiratory tract infection,and *** improvement from baseline inthe International Index of Erectile Function-Erectile Function(IIEF-EF)score was detected at month 12(least squares mean[LSM]change:7.9,95%confidence interval[CI]:7.5–8.4,P<0.001)and was maintained to month 24(LSM change:8.6,95%CI:8.1–9.0,P<0.001).The proportions of patients regaining normal erectile function(IIEF-EF score≥26)were 43.7%and 48.0%at months 12 and 24,*** Assessment Questionnaire results showed improved erection function in 97.5%ofpatients and improved ability to engage in sexual activity in 95.9%of patients at month 12;these values were 96.1%and 95.0%at month 24,*** quality of sexual life score based on the Sexual Life Quality Questionnaire(SLQQ)was increased by52.2%at month 12 and by 55.3%at month 24(both P<0.001).The treatment satisfaction score determined by SLQQ(mean±standard deviation)was 62.4±21.0 at month 12 versus 65.9±20.2 at month ***-year daily application of tadalafil 5mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

关键词： clinical trial erectile dysfunction long-term safety once-daily dosing tadalafil

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Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation

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Chinese Journal of Integrative Medicine 2024年第7期30卷 600-607页

作者： XU Ben ZHANG Jia-en YE Lin YUAN Chang-wei Department of Urology Peking University First Hospital and Institute of UrologyPeking UniversityNational Urological Cancer CenterBeijing100034China

Objective To explore the molecular mechanism by which curcumin affects renal interstitial fibrosis(RIF)progression by regulating ADAM metallopeptidase with thrombospondin type 1 motif 18(ADAMTS18)*** NRK-49F cells RIF model were induced with transforming growth factorβ1(TGF-β1).Effects of different concentrations of curcumin(0,10,20,and 30μmol/L)on cell proliferation,cell cycle,cell apoptosis as well as cyclin D1 expression were analyzed by cell counting kit-8,flow cytometry and Western blot,***18 methylation levels were determined by methylation-specific polymerase chain ***18,fibronectin(FN),type I collagen(Col-I)and alpha-smooth muscle actin(α-SMA)mRNA and protein expressions were analyzed by real-time PCR(RT-PCR)and Western blot,***,cells were treated with 50 mmol/L 5-aza-2′-deoxycytidine(5-aza-dC,demethylation agent)for 72 *** of curcumin on extracellular matrix(ECM)deposition was evaluated by immunochemical staining and Western ***-49F cells were transfected with ADAMTS18 small interfering RNA and grouped into a normal control,ADAMTS18-knock-out(KO),and ADAMTS18-KO+30μmol/L curcumin groups,and whether curcumin can reverse the effect of ADAMTS18 knockdown on RIF was *** Compared with the control group,TGF-β1 significantly inhibited the proliferation of NRK-49F cells,blocked the G1/G0 phase,promoted cell apoptosis and inhibited cyclin D1 expression(P<0.01).Among the different concentrations of curcumin,30μmol/L curcumin significantly reversed these processes(P<0.01).Immunochemical staining and Western blot results showed that curcumin significantly inhibited the deposition of FN,Col-I andα-SMA(P<0.01).Curcumin and 5-zaz-dC had synergistic effects,promoting ADAMTS18 expression,removing ADAMTS18 methylation,and reducing ECM ***18 knockdown promoted ECM accumulation,and curcumin reversed this process(P<0.01).Conclusion TGF-β1-induced fibrosis in NRK-49F ***

关键词： renal fibrosis curcumin Chinese medicine ADAMTS18 methylation modification

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Voluntary wheel running ameliorated the deleterious effects of high-fat diet on glucose metabolism,gut microbiota and microbial-associated metabolites

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Food Science and Human Wellness 2024年第3期13卷 1672-1684页

作者： Ling Zhang Wenyu Zou Yongyan Hu Honghua Wu Ying Gao Junqing Zhang Jia Zheng Department of Endocrinology Peking University First HospitalBeijing 100034China Laboratory Animal Facility Peking University First HospitalBeijing 100034China

Exercise training is critical for the early prevention and treatment of obesity and diabetes ***,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and *** showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia *** profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis *** conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose *** further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.

关键词： High-fat diet Voluntary wheel running Gut microbiota Metabolomics Glucose metabolism

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Effect of perioperative chemotherapy on resection of isolated pulmonary metastases from colorectal cancer:A single center experience

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3457-3470页

作者： Zhao Gao Xuan Jin Ying-Chao Wu Shi-Jie Zhang Shi-Kai Wu Xin Wang Department of Medical Oncology Peking University First HospitalBeijing 10000China Department of General Surgery Peking University First HospitalBeijing 10000China Department of Thoracic Surgery Peking University First HospitalBeijing 10000China

BACKGROUND Numerous studies have assessed surgical resection as a standard treatment option for patients with colorectal cancer(CRC)and resectable pulmonary metastases(PM).However,the role of perioperative chemotherapy after complete resection of isolated PM from patients with CRC patients remains *** hypothesize that perioperative chemotherapy does not provide significant survival benefits for patients undergoing resection of PM from *** To determine whether perioperative chemotherapy affects survival after radical resection of isolated PM from *** We retrospectively collected demographic,clinical,and pathologic data on patients who underwent radical surgery for isolated PM from *** survival(CSS)and disease-free survival were calculated using Kaplan-Meier ***-group differences were compared using the log-rank *** multivariate analysis,Cox regression was utilized when *** This study included 120 patients with a median age of 61.6 *** 5-year CSS rate was 78.2%,with 36.7% experiencing *** resection for isolated PM resulted in a 5-year CSS rate of 50.0% for second *** chemotherapy(P=0.079)did not enhance survival *** associated with improved survival included fewer metastatic lesions[hazard ratio(HR):2.51,P=0.045],longer disease-free intervals(HR:0.35,P=0.016),and wedge lung resections(HR:0.42,P=0.035).Multiple PM predicted higher recurrence risk(HR:2.22,P=0.022).The log-rank test showed no significant difference in CSS between single and repeated metastasectomy(P=0.92).CONCLUSION Perioperative chemotherapy shows no survival benefit post-PM resection in ***-free intervals and fewer metastatic lesions predict better *** metastasectomy is warranted for eligible patients.

关键词： Pulmonary metastasis Colorectal cancer Perioperative chemotherapy Survival Repeated pulmonary metastasectomy

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ERβ-activated LINC01018 promotes endometriosis development by regulating the CDC25C/CDK1/CyclinB1 pathway

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Journal of Genetics and Genomics 2024年第6期51卷 617-629页

作者： Ruihui Lu Jingwen Zhu Xin Li Cheng Zeng Yan Huang Chao Peng Yingfang Zhou Qing Xue Department of Obstetrics and Gynecology Peking University First HospitalBeijing 100034China

Endometriosis refers to as an estrogen-dependent *** receptorβ(ERB),the main estrogen receptor subtype which is encoded by the estrogen receptor 2(ESR2)gene,can mediate the action of estrogen in *** selective estrogen receptor modulators can target the ERβ,they are not specific due to the wide distribution of ERβ.Recently,long noncoding RNAs have been implicated in ***,we aim to explore and validate the downstream regulatory mechanism of ERβ,and to investigate the potential role of long intergenic noncoding RNA 1018(LINC01018)as a nonhormonal treatment for *** study demonstrates that the expression levels of ESR2 and LINCo1018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between the ESR2 and LINCo1018 ***,ERβdirectly binds to an estrogen response element located in the LINCO1018 promoter region and activates LINC01018 ***,ERβcan regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in *** with these findings,the knockdown of LINC01018 inhibits endometriotic lesion proliferation in *** summary,our study demonstrates that the ERβ/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.

关键词： Estrogen receptorβ Long intergenic noncoding RNA 1018 (LINC01018) Endometriosis Cell cycle Proliferation

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When Glanzmann thrombasthenia encounters antithrombin defi ciency: how do we balance the risk and benefi t of antithrombotic therapy?

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World Journal of Emergency Medicine 2024年第1期15卷 67-69页

作者： Yu Wang Zhihao Liu Haoyu Weng Jianping Li Department of Endocrinology Peking University First HospitalBeijing 100034China Department of Cardiology Peking University First HospitalBeijing 100034China Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education Health Science CenterPeking UniversityBeijing 100034China

Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and *** this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic *** is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous ***,we describe a rare case of GT and antithrombin deficiency coexisting in a single *** was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).

关键词： thrombin throm bleeding

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Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin

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Science China(Life Sciences) 2024年第6期67卷 1226-1241页

作者： Zhengyang Guo Jiaqi Huang Xiao Huo Chen Huang Xiaotong Yu Yan Sun Yanfang Li Tianhui He Hongyan Guo Jianling Yang Lixiang Xue Cancer center of peking university Third hospital Beijing 100191China center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China peking university Third hospital Cancer center Department of Radiation OncologyPeking University Third HospitalBeijing 100191China Department of Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China

Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed *** ovarian cancer,multiple metabolic enzymes of lipid metabolism are abnormally expressed,resulting in metabolism *** a characteristic pathway in polyunsaturated fatty acid(PUFA)metabolism,arachidonic acid(AA)metabolism is disturbed in ovarian ***,we established a 10-gene signature model to evaluate the prognostic risk of PUFA-related *** 10-gene signature has strong robustness and can play a stable predictive role in datasets of various platforms(TCGA,ICGC,and GSE17260).The high association between the risk subgroups and clinical characteristics indicated a good performance of the *** data further indicated that the high expression of LTA4H was positively correlated with poor prognosis in ovarian *** of LTA4H enhanced sensitivity to Cisplatin and modified the characteristics of immune cell infiltration in ovarian ***,our results indicate that CCL5 was involved in the aberrant metabolism of the AA/LTA4H axis,which contributes to the reduction of tumor-infiltrating CD8+T cells and immune escape in ovarian *** findings provide new insights into the prognosis and potential target of LTA4H/CCL5 in treating ovarian cancer.

关键词： ovarian cancer polyunsaturated fatty acids prognostic risk model LTA4H tumor immunity CCL5

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^(18)F-FDG PET/CT findings of paratesticular alveolar rhabdomyosarcoma

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Cancer Innovation 2024年第2期3卷 68-71页

作者： Xueqi Chen Jiayin Shou Shanshi Li Yan Fan Jianhua Zhang Department of Nuclear Medicine Peking University First HospitalBeijingChina Department of Radiation Oncology Peking University First HospitalBeijingChina

Rhabdomyosarcoma(RMS)originates from primitive mesenchymal cells and is the most common soft tissue tumor in childhood.^(18)F-fluoro-deoxyglucose(^(18)F-FDG)positron emission tomography(PET)/computed tomography(CT)has been reported to be valuable in RMS staging and risk *** RMS is a relatively uncommon form of RMS,most of which are of the embryonal histologic *** alveolar RMS is associated with aggressive behavior,high metastatic potential,and poor *** the best of our knowledge,^(18)F-FDG PET/CT imaging findings of paratesticular alveolar RMS have never been ***,we report on a 16-year-old boy's rare paratesticular alveolar RMS with multiple metastases and its findings on^(18)F-FDG PET/*** case also demonstrates the potential value of^(18)F-FDG PET/CT in RMS staging and treatment decisions,and may aid in the differential diagnosis.

关键词： ^(18)F-FDG paratesticular alveolar rhabdomyosarcoma PET/CT

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Effect of tubastatin A on NLRP3 inflammasome activation in macrophages under hypoxia/ reoxygenation conditions

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World Journal of Emergency Medicine 2024年第4期15卷 289-296页

作者： Hao Li Chang Liu Ying Cui Panpan Chang Wei Chong Department of Emergency Medicine the First Hospital of China Medical UniversityShenyang 110001China Trauma Medicine center Peking University People's HospitalBeijing 100871China Key Laboratory of Trauma and Neural Regeneration Peking UniversityBeijing 100871China National center for Trauma Medicine of China Beijing 100871China

BACKGROUND:There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock(HS).The aim of this study was to explore the potential of the histone deacetylase 6(HDAC6)-specific inhibitor tubastatin A(TubA)to suppress nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation in macrophages under hypoxia/reoxygenation(H/R)***:The viability of RAW264.7 cells subjected to H/R after treatment with different concentrations of TubA was assessed using a cell-counting kit-8(CCK8)***,2.5μmol/L TubA was used with RAW264.7 cells under H/R ***264.7 cells were divided into three groups,namely the control,H/R,and TubA *** levels of reactive oxygen species(ROS)in the cells were detected using fluorescence *** protein expression of HDAC6,heat shock protein 90(Hsp90),inducible nitric oxide synthase(iNOS),NLRP3,gasdermin-D(GSDMD),Caspase-1,GSDMD-N,and Caspase-1 p20 was detected by western *** levels of interleukin-1β(IL-1β)and IL-18 in the supernatants were detected using enzyme-linked immunosorbent assay(ELISA).RESULTS:HDAC6,Hsp90,and iNOS expression levels were significantly higher(P<0.01)in the H/R group than in the control group,but lower in the TubA group than in the H/R group(P<0.05).When comparing the H/R group to the control group,ROS levels were significantly higher(P<0.01),but significantly reduced in the TubA group(P<0.05).The H/R group had higher NLRP3,GSDMD,Caspase-1,GSDMD-N,and Caspase-1 p20 expression levels than the control group(P<0.05),however,the TubA group had significantly lower expression levels than the H/R group(P<0.05).IL-1βand IL-18 levels in the supernatants were significantly higher in the H/R group compared to the control group(P<0.01),but significantly lower in the TubA group compared to the H/R group(P<0.01).CONCLUSION:TubA inhibited the expression of HDAC6,Hsp90,and iNOS in macrophages

关键词： Hemorrhagic shock Hypoxia/reoxygenation Macrophage NLRP3 Tubastatin A

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PACS gene family-related neurological diseases: limited genotypes and diverse phenotypes

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World Journal of Pediatrics 2024年第1期20卷 82-91页

作者： Han Zhang Kai Gao Shuang Wang Yue-Hua Zhang Zhi-Xian Yang Ye Wu Yu-Wu Jiang Department of Pediatrics Peking University First Hospital.No.1 Xi'an Men StreetWest DistrictBeijing 100034China Bejing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases BeijingChina Children Epilepsy center Peking University First HospitalBeijingChina Key Laboratory for Neuroscience Ministry of Education/National Health and Family Planning CommissionPeking UniversityBeijingChina center of Epilepsy Beijing Institute for Brain DisordersBeijingChina

Background The PACS gene family has been demonstrated to be related to intracellular vesicular *** phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy,intellectual disability/developmental delay,and malformations,such as facial *** We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation *** information obtained from these patients was analyzed along with that obtained from previously reported *** With the inclusion of the newly diagnosed cases in this study,103 cases with PACS gene family-related neurological diseases were reported,of which 43 were PACS2-related cases and the remaining were PACSI-related *** patients had seizures,which have been reported to be effectively controlled by several types of anti-seizure medications(ASMs).The most efficacious and frequently prescribed ASMs included sodium valproate(43.3%,13/30),oxcarbazepine/carbamazepine(26.7%,8/30),and levetiracetam(20%,6/30).Almost all patients had intellectual disability/developmental *** most common pathogenic missense variants were PACSI ***203Trp and PACS2 *** addition,we report a patient carrying a likely pathogenic copy number variation(CNV)(de novo heterozygous deletion of chr14:105821380-106107443,286 kilobase,destroyed part of the furin-binding region domain and the protein structure after it)with more severe and refractory late-onset *** The clinical phenotypes of the different PACS heterozygous missense variants were *** pathogenic variant sites of PACSI and PACS2 were quite limited but located in different regions.A CNV destroying part of the PACS2 gene might also be *** findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family.

关键词： Developmental delay Epilepsy Intellectual disability PACSI PACS2

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