Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related...Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were evaluated.Patients were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB group.The median overall survival was not attained.The percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB group.Concurrent MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all patients.Conclusions:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.展开更多
In the present study,the nanofliud natural convection is investigated by the energy-conserving dissipative particle dynamics(eDPD)method,where the nanoparticles are considered at the single-particle level.The thermal ...In the present study,the nanofliud natural convection is investigated by the energy-conserving dissipative particle dynamics(eDPD)method,where the nanoparticles are considered at the single-particle level.The thermal expansion coefficientβand the viscosityμof the simulated system containing nanoparticles are calculated and found to be in close alignment with the previous simulation results.The single-particle hydrodynamics in e DPD enables simulations of nanofluid natural convection with higher Rayleigh numbers and greater nanoparticle volume fractions.Additionally,this approach is utilized to simulate the nanoparticle distribution during the enhanced heat transfer process in the nanofluid natural convection.The localized aggregation of nanoparticles enhances the heat transfer performance of the nanofluid under specific Rayleigh numbers and nanoparticles volume fractions.展开更多
Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear.We aimed...Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear.We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment.Methods:In the post-hoc analysis of a multicenter trial,na?ve CHB patients receiving 72-week entecavir treatment were enrolled.We evaluated the biochemical,viral and histopathological responses of these patients.The histopathological features of NASH were also evaluated,using paired liver biopsies at baseline and week 72.Results:A total of 1000 CHB patients were finally enrolled for analysis,with 18.2%of whom fulfilling the criteria of NASH.A total of 727 patients completed entecavir antiviral treatment and received the second biopsy.Serum HBe Ag loss,HBe Ag seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH(P>0.05).Among patients with NASH,the hepatic steatosis,ballooning,lobular inflammation scores and fibrosis stages all improved during follow-up(all P<0.001),46%(63/136)achieved NASH resolution.Patients with baseline body mass index(BMI)≥23 kg/m2(Asian criteria)[odds ratio(OR):0.414;95%confidence interval(95%CI):0.190-0.899;P=0.012]and weight gain(OR:0.187;95%CI:0.050-0.693;P=0.026)were less likely to have NASH resolution.Among patients without NASH at baseline,22(3.7%)developed NASH.Baseline BMI≥23 kg/m2(OR:12.506;95%CI:2.813-55.606;P=0.001)and weight gain(OR:5.126;95%CI:1.674-15.694;P=0.005)were predictors of incident NASH.Conclusions:Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB.The value of weight management in CHB patients during antiviral treatment deserves further evaluation.展开更多
The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful marketization.However,the in vivo distribution and release of siRNA still cannot be effect...The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful marketization.However,the in vivo distribution and release of siRNA still cannot be effectively monitored.In this study,based on the fluorescence resonance energy transfer(FRET)principle,a fluorescence dye Cy5-modified survivin siRNA was conjugated to nanogolds(Au-DR-siRNA),which were then wrapped with lipid nanoparticles(LNPs)for monitoring the release behaviour of siRNA in vivo.The results showed that once Au-DR-siRNA was released from the LNPs and cleaved by the Dicer enzyme to produce free siRNA in cells,the fluorescence of Cy5 would change from quenched state to activated state,showing the location and time of siRNA release.Besides,the LNPs showed a significant antitumor effect by silencing the survivin gene and a CT imaging function superior to iohexol by nanogolds.Therefore,this work provided not only an effective method for monitoring the pharmacokinetic behaviour of LNP-based siRNA,but also a siRNA delivery system for treating and diagnosing tumors.展开更多
目的系统评价NICU临终新生儿父母决策参与体验的质性研究。方法检索数据库PubMed、Web of Science、Embase、CINAHL、Cochrane Library、Sinomed、中国知网、万方和维普数据库关于NICU临终新生儿父母决策参与体验的质性研究,检索时限为...目的系统评价NICU临终新生儿父母决策参与体验的质性研究。方法检索数据库PubMed、Web of Science、Embase、CINAHL、Cochrane Library、Sinomed、中国知网、万方和维普数据库关于NICU临终新生儿父母决策参与体验的质性研究,检索时限为建库至2023年8月。文献质量评价采用澳大利亚乔安娜布里格斯研究所质性研究质量评价标准,采用汇集性Meta整合方法对文献进行归纳。结果共纳入13篇文献,提炼出33个结果,归纳为12个新类别,合成4个整合结果:临终新生儿父母决策参与倾向、临终新生儿父母决策角色体验、临终新生儿父母决策中的障碍、临终新生儿父母决策中的需求。结论NICU临终新生儿父母面临艰难的决策选择,医护人员需与父母共同确定其在决策中的理想角色,制定个性化的沟通内容,社会、医院以及家庭需创造支持性的社会心理环境,给予父母信息及情感支持,提高临终新生儿父母在决策中的应对力。展开更多
Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attem...Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.展开更多
Product selectivity and reaction pathway are highly dependent on surface structure of heterogeneous catalysts.For vapor-phase hydrogenation of dimethyl oxalate(DMO),"EG route"(DMO→methyl glycolate(MG)ethyle...Product selectivity and reaction pathway are highly dependent on surface structure of heterogeneous catalysts.For vapor-phase hydrogenation of dimethyl oxalate(DMO),"EG route"(DMO→methyl glycolate(MG)ethylene glycol(EG)→ethanol(ET))and"MA route"(DMO→MG→methyl acetate(MA))were proposed over traditional Cu based catalysts and Mo-based or Fe-based catalysts,respectively.Herein,tunable yield of ET(93.7%)and MA(72.1%)were obtained through different reaction routes over WO_(x) modified Cu/SiO_(2) catalysts,and the corresponding reaction route was further proved by kinetic study and in-situ DRIFTS technology.Mechanistic studies demonstrated that H_(2) activation ability,acid density and Cu-WO_(x) interaction on the catalysts were tuned by regulating the surface W density,which resulted in the different reaction pathway and product selectivity.What's more,high yield of MA produced from DMO hydrogenation was firstly reported with the H_(2) pressure as low as 0.5 MPa.展开更多
Background:Head and neck squamous cell carcinoma(HNSCC)is a prevalent form of cancer globally,with chemoresistance posing a major challenge in treatment outcomes.The efficacy of the commonly used chemotherapeutic agent...Background:Head and neck squamous cell carcinoma(HNSCC)is a prevalent form of cancer globally,with chemoresistance posing a major challenge in treatment outcomes.The efficacy of the commonly used chemotherapeutic agent,cisplatin,is diminished in patients with poor prognoses.Methods:Various bioinformatics databases were utilized to examine Carboxylesterase 1(CES1)gene expression,clinicopathologic features,patient survival analysis,and gene function.An organoid model of HNSCC was established,along with the induction of drug-resistant HNSCC in the organoid model.CES1 expression was assessed using qRT-PCR and Western Blot,and differential markers were identified through transcriptome sequencing.Knockdown and overexpression models of CES1 were created in SCC-9 and patient-derived organoid(PDO)cells using shRNA and lentivirus to investigate the tumor biology and cisplatin resistance associated with CES1.Results:Research in bioinformatics has uncovered a strong correlation between the expression level of CES1 and the prognosis of HNSCC.The data suggests a significant link between CES1 expression and tobacco smoking.RNA-sequencing revealed a notable increase in CES1 expression in HNSCC-PDOcis-R cells compared to the parental PDO cells.Subsequently,we performed in vitro studies by HNSCC-PDO and SCC-9 and found that CES1-overexpressing cells exhibited reduced sensitivity to cisplatin and stronger tumor malignant biological behavior compared with CES1-knockdown cells.Conclusion:The observed association between CES1 expression and tobacco smoking implies a potential influence of smoking on the efficacy of cisplatin-based chemotherapy in HNSCC through the regulation of CES1 expression.展开更多
BACKGROUND Postmenopausal osteoporosis(PMOP)is the most common form of primary osteoporosis among women,and the associated pain often drives patients to seek clinical intervention.Numerous studies have highlighted the...BACKGROUND Postmenopausal osteoporosis(PMOP)is the most common form of primary osteoporosis among women,and the associated pain often drives patients to seek clinical intervention.Numerous studies have highlighted the unique clinical benefits of exercise therapy(ET)in alleviating PMOP-related pain.However,bibliometric analyses examining collaboration,development trends,and research frontiers in the field of ET for PMOP pain remain scarce.AIM To explore the research trends in ET for pain treatment in PMOP patients over the past decade.METHODS All scholarly works were meticulously sourced from the Science Citation Index-Expanded within the prominent Web of Science Core Collection.Utilizing the capabilities of CiteSpace 6.2.R5,we conducted a thorough analysis of publications,authors,frequently cited scholars,contributing nations,institutions,journals of significant citation,comprehensive references,and pivotal keywords.Additionally,our examination explored keyword cooccurrences,detailed timelines,and periods of heightened citation activity.This comprehensive search,from 2014 through 2023,was completed within a single day,on October 11,2023.RESULTS In total,2914 articles were ultimately included in the analysis.There was a rapid increase in annual publication output in 2015,followed by stable growth in subsequent years.Boninger,Michael L,is the most prolific author,whereas Ware JE has the most citations.The United States’global influence is significant,surpassing all other nations.The University of California System and Harvard University are the most influential academic institutions.J Bone Joint Surg Am is the most influential journal in this field.“Spinal cord injury”is the keyword that has garnered the most attention from researchers.The developmental pattern in this field is characterized by interdisciplinary fusion,with different disciplines converging to drive progress.CONCLUSION The academic development of the field of ET for pain in PMOP has matured and stabilized.Clinical management and rehabilitation strategies,along with the mechanisms underlying the relationship between ET and bone resorption analgesia,continue to be the current and future focal points of research in this field.展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 62375202)Natural Science Foundation of Tianjin (Grant No. 23JCYBJC00950)+2 种基金Tianjin Health Science and Technology Project Key Discipline Special (Grant No. TJWJ2022XK034)Tianjin Key Medical Discipline (Specialty) Construction Project (Grant No.TJYXZDXK-059B)Research Project in Key Areas of TCM in 2024 (Grant No. 2024022)
文摘Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were evaluated.Patients were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB group.The median overall survival was not attained.The percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB group.Concurrent MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all patients.Conclusions:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.
基金Project supported by the National Natural Science Foundation of China(Nos.11872283 and 2002212)the Sailing Program of Shanghai,China(No.20YF1432800)。
文摘In the present study,the nanofliud natural convection is investigated by the energy-conserving dissipative particle dynamics(eDPD)method,where the nanoparticles are considered at the single-particle level.The thermal expansion coefficientβand the viscosityμof the simulated system containing nanoparticles are calculated and found to be in close alignment with the previous simulation results.The single-particle hydrodynamics in e DPD enables simulations of nanofluid natural convection with higher Rayleigh numbers and greater nanoparticle volume fractions.Additionally,this approach is utilized to simulate the nanoparticle distribution during the enhanced heat transfer process in the nanofluid natural convection.The localized aggregation of nanoparticles enhances the heat transfer performance of the nanofluid under specific Rayleigh numbers and nanoparticles volume fractions.
基金supported by grants from the National Major Special Project for the Prevention and Treatment of Major Infectious Diseases:AIDS and viral hepatitis(2013ZX10005002,2018ZX10725506)the National Key Research and Development Program(2017YFC0908903)。
文摘Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear.We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment.Methods:In the post-hoc analysis of a multicenter trial,na?ve CHB patients receiving 72-week entecavir treatment were enrolled.We evaluated the biochemical,viral and histopathological responses of these patients.The histopathological features of NASH were also evaluated,using paired liver biopsies at baseline and week 72.Results:A total of 1000 CHB patients were finally enrolled for analysis,with 18.2%of whom fulfilling the criteria of NASH.A total of 727 patients completed entecavir antiviral treatment and received the second biopsy.Serum HBe Ag loss,HBe Ag seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH(P>0.05).Among patients with NASH,the hepatic steatosis,ballooning,lobular inflammation scores and fibrosis stages all improved during follow-up(all P<0.001),46%(63/136)achieved NASH resolution.Patients with baseline body mass index(BMI)≥23 kg/m2(Asian criteria)[odds ratio(OR):0.414;95%confidence interval(95%CI):0.190-0.899;P=0.012]and weight gain(OR:0.187;95%CI:0.050-0.693;P=0.026)were less likely to have NASH resolution.Among patients without NASH at baseline,22(3.7%)developed NASH.Baseline BMI≥23 kg/m2(OR:12.506;95%CI:2.813-55.606;P=0.001)and weight gain(OR:5.126;95%CI:1.674-15.694;P=0.005)were predictors of incident NASH.Conclusions:Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB.The value of weight management in CHB patients during antiviral treatment deserves further evaluation.
基金by the National Natural Science Foundation of China(81872812,82073800)the China Postdoctoral Science Fundation(2021TQ0111,2021M691040).
文摘The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful marketization.However,the in vivo distribution and release of siRNA still cannot be effectively monitored.In this study,based on the fluorescence resonance energy transfer(FRET)principle,a fluorescence dye Cy5-modified survivin siRNA was conjugated to nanogolds(Au-DR-siRNA),which were then wrapped with lipid nanoparticles(LNPs)for monitoring the release behaviour of siRNA in vivo.The results showed that once Au-DR-siRNA was released from the LNPs and cleaved by the Dicer enzyme to produce free siRNA in cells,the fluorescence of Cy5 would change from quenched state to activated state,showing the location and time of siRNA release.Besides,the LNPs showed a significant antitumor effect by silencing the survivin gene and a CT imaging function superior to iohexol by nanogolds.Therefore,this work provided not only an effective method for monitoring the pharmacokinetic behaviour of LNP-based siRNA,but also a siRNA delivery system for treating and diagnosing tumors.
文摘目的系统评价NICU临终新生儿父母决策参与体验的质性研究。方法检索数据库PubMed、Web of Science、Embase、CINAHL、Cochrane Library、Sinomed、中国知网、万方和维普数据库关于NICU临终新生儿父母决策参与体验的质性研究,检索时限为建库至2023年8月。文献质量评价采用澳大利亚乔安娜布里格斯研究所质性研究质量评价标准,采用汇集性Meta整合方法对文献进行归纳。结果共纳入13篇文献,提炼出33个结果,归纳为12个新类别,合成4个整合结果:临终新生儿父母决策参与倾向、临终新生儿父母决策角色体验、临终新生儿父母决策中的障碍、临终新生儿父母决策中的需求。结论NICU临终新生儿父母面临艰难的决策选择,医护人员需与父母共同确定其在决策中的理想角色,制定个性化的沟通内容,社会、医院以及家庭需创造支持性的社会心理环境,给予父母信息及情感支持,提高临终新生儿父母在决策中的应对力。
基金This work was supported by grants from National Natural Science Foundation of China(81830078,82071868,32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+2 种基金Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Shanghai Key Laboratory of Orthopedic Implant(No.KFKT202206).
文摘Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.
基金supported by National Natural Science Foundation of China (No.22102147 and 22002151)State Key Laboratory of Chemical Engineering (No.SKL-ChE-22A02)+2 种基金Zhejiang Provincial Natural Science Foundation of China under Grant No.LQ21B030009the Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDA29050300)Qinchuang Yuan high-level innovation and entrepreneurship talents implementing project (No.QCYRCXM-2022-177)。
文摘Product selectivity and reaction pathway are highly dependent on surface structure of heterogeneous catalysts.For vapor-phase hydrogenation of dimethyl oxalate(DMO),"EG route"(DMO→methyl glycolate(MG)ethylene glycol(EG)→ethanol(ET))and"MA route"(DMO→MG→methyl acetate(MA))were proposed over traditional Cu based catalysts and Mo-based or Fe-based catalysts,respectively.Herein,tunable yield of ET(93.7%)and MA(72.1%)were obtained through different reaction routes over WO_(x) modified Cu/SiO_(2) catalysts,and the corresponding reaction route was further proved by kinetic study and in-situ DRIFTS technology.Mechanistic studies demonstrated that H_(2) activation ability,acid density and Cu-WO_(x) interaction on the catalysts were tuned by regulating the surface W density,which resulted in the different reaction pathway and product selectivity.What's more,high yield of MA produced from DMO hydrogenation was firstly reported with the H_(2) pressure as low as 0.5 MPa.
基金supported by the National Natural Science Foundation of China(No.82160386)the Guangxi Natural Science Foundation of China(No.2024GXNSFDA010032,2023GXNSFAA026189).
文摘Background:Head and neck squamous cell carcinoma(HNSCC)is a prevalent form of cancer globally,with chemoresistance posing a major challenge in treatment outcomes.The efficacy of the commonly used chemotherapeutic agent,cisplatin,is diminished in patients with poor prognoses.Methods:Various bioinformatics databases were utilized to examine Carboxylesterase 1(CES1)gene expression,clinicopathologic features,patient survival analysis,and gene function.An organoid model of HNSCC was established,along with the induction of drug-resistant HNSCC in the organoid model.CES1 expression was assessed using qRT-PCR and Western Blot,and differential markers were identified through transcriptome sequencing.Knockdown and overexpression models of CES1 were created in SCC-9 and patient-derived organoid(PDO)cells using shRNA and lentivirus to investigate the tumor biology and cisplatin resistance associated with CES1.Results:Research in bioinformatics has uncovered a strong correlation between the expression level of CES1 and the prognosis of HNSCC.The data suggests a significant link between CES1 expression and tobacco smoking.RNA-sequencing revealed a notable increase in CES1 expression in HNSCC-PDOcis-R cells compared to the parental PDO cells.Subsequently,we performed in vitro studies by HNSCC-PDO and SCC-9 and found that CES1-overexpressing cells exhibited reduced sensitivity to cisplatin and stronger tumor malignant biological behavior compared with CES1-knockdown cells.Conclusion:The observed association between CES1 expression and tobacco smoking implies a potential influence of smoking on the efficacy of cisplatin-based chemotherapy in HNSCC through the regulation of CES1 expression.
文摘BACKGROUND Postmenopausal osteoporosis(PMOP)is the most common form of primary osteoporosis among women,and the associated pain often drives patients to seek clinical intervention.Numerous studies have highlighted the unique clinical benefits of exercise therapy(ET)in alleviating PMOP-related pain.However,bibliometric analyses examining collaboration,development trends,and research frontiers in the field of ET for PMOP pain remain scarce.AIM To explore the research trends in ET for pain treatment in PMOP patients over the past decade.METHODS All scholarly works were meticulously sourced from the Science Citation Index-Expanded within the prominent Web of Science Core Collection.Utilizing the capabilities of CiteSpace 6.2.R5,we conducted a thorough analysis of publications,authors,frequently cited scholars,contributing nations,institutions,journals of significant citation,comprehensive references,and pivotal keywords.Additionally,our examination explored keyword cooccurrences,detailed timelines,and periods of heightened citation activity.This comprehensive search,from 2014 through 2023,was completed within a single day,on October 11,2023.RESULTS In total,2914 articles were ultimately included in the analysis.There was a rapid increase in annual publication output in 2015,followed by stable growth in subsequent years.Boninger,Michael L,is the most prolific author,whereas Ware JE has the most citations.The United States’global influence is significant,surpassing all other nations.The University of California System and Harvard University are the most influential academic institutions.J Bone Joint Surg Am is the most influential journal in this field.“Spinal cord injury”is the keyword that has garnered the most attention from researchers.The developmental pattern in this field is characterized by interdisciplinary fusion,with different disciplines converging to drive progress.CONCLUSION The academic development of the field of ET for pain in PMOP has matured and stabilized.Clinical management and rehabilitation strategies,along with the mechanisms underlying the relationship between ET and bone resorption analgesia,continue to be the current and future focal points of research in this field.
