Aim Systematic evolution of ligands by exponential enrichment(SELEX)techniquewas employed to screen and identify nucleic acid aptamers that specifically bind to mouse atherosclerotic pathological tissues,aiming to pro-vide a research foundation for the development of molecular targets and diagnostic reagents for early atherosclerosis.Methods A single-stranded DNA(ssDNA)library with a capacity of 1015～1016 was constructed,which was then subjec-ted to binding-elution(negative selection)with normal mouse vascular tissue slices.The eluted library was subsequently bound to atherosclerotic tissue slices for binding-elution(positive selection).PCR was used to amplify the positive and negative screening products,and agarose gel electrophoresis was used to verify the amplified products.The ssDNA library after multiple rounds of selection was sequenced using T-A cloning and sequencing to obtain the primary structure of the nu-cleic acid aptamers,and the secondary structure was predicted using the Mfold online software.The selected nucleic acid aptamers were labeled with a FAM fluorescent group at the 5'-end and were bound to both positive and negative selection tissue slices,with fluorescence intensity observed under a fluorescence microscope.Image Pro Plus 6.0 was used to cal-culate the relative average fluorescence intensity to evaluate the binding specificity of nucleic acid aptamers.Results After 8 rounds of selection,agarose gel electrophoresis imaging showed PCR amplification products in the positive selection lanes,while no PCR amplification products were observed in the negative selection lanes,indicating the successful acquisi-tion of a nucleic acid aptamer library that specifically binds to atherosclerotic tissues.Five nucleic acid aptamers were i-dentified by T-A cloning and sequencing,and their predicted secondary structures all had stem-loop structures.Immuno-fluorescence staining verified that five nucleic acid aptamers had different degrees of binding with As blood vessels,and the quantitative results of the relative average fluorescence intensity showed that nucleic acid aptamer No.11 had the highest relative average fluorescence intensity value,which can be used as a candidate nucleic acid aptamer for subsequent re-search.Conclusion Specific nucleic acid aptamers that bind to atherosclerotic vesselswere successfully obtained,providing a research foundation for further screening of early molecular targets of Asand developing in vivo early diagnostic reagents.

Objective To develop a value evaluation index system for health management and logistics positions in pub-lic hospitals,providing a research tool for future performance evaluations and salary reform.Methods Literature review,focus group interviews,and the point-factor method were employed to establish an initial index pool.A public hospital in Guangzhou was selected as a case study.Delphi expert consultation was then utilized to refine and finalize the indicators for the evaluation system.Results For the two rounds of Delphi expert consultation,the response rates were 87.5％and 100.0％,with the expert authority coefficient of 0.812.The Kendall's W coordination coefficients were 0.796 and 0.624 for the first round,and 0.747 and 0.918 for the second,(all＜0.001).The coefficients of variation ranged from 0.157 to 0.265 for the first round and from 0.108 to 0.230 for the second round.Experts provided four suggestions,leading to the removal of one secondary indicator and modifications to the definitions of three others.Finally,the evaluation system consists of 4 primary indicators and 12 secondary indicators.Conclusion This system can provide a research tool and reference for the follow-up performance evaluation,improve the salary reform of public hospitals,and promote the high-quality development of public hospitals.

Objective:To screen the risk factors for non-complete procedural success of transvenous lead extraction(TLE),and to establish a prediction model based on the results and evaluate its predictive efficacy.Methods:A total of 1 029 patients who underwent TLE in Peking University People's Hospital from January 2014 to December 2020 were enrolled and divided into training set(n=720)and validation set(n=309)using the random number method.There were no statistically significant differences among the variables in the training set and the validation set.The training set was divided into the complete procedural success(CPS)group(n=664)and the non-CPS group(n=56).Univariate analysis was employed to screen the relevant indicators of non-CPS,followed by binary logistic regression analysis to identify the independent risk factors of non-CPS.Subsequently,a predictive model and nomogram were constructed.The receiver operating characteristic(ROC)curve analysis was applied to evaluate the ability of the model to distinguish non-CPS from TLE patients in the training set and validation set.The Hosmer-Lemeshow goodness-of-fit test was used to assess the consistency between the predicted risk and the actual risk of the model.Results:Univariate analysis showed that the relevant variables with P<0.1 including the age at the first implantation of the lead,the number of leads extracted,the oldest dwell time of lead extracted,the presence of abandoned leads,non-manual traction for lead extracted,the number of extracted leads>3,bilateral lead implantation,and the indications for TLE.The binary logistic regression analysis revealed that the presence of abandoned leads(OR=2.252,95%CI:1.111-4.564,P=0.024),the oldest dwell time of the extracted leads(OR=1.009,95%CI:1.005-1.012,P<0.001),and the number of extracted leads>3(OR=3.177,95%CI:1.306-7.733,P=0.011)were independent risk factors for non-CPS of TLE.ROC curve analysis revealed that the area under the ROC curve(AUC)of the training set was 0.80(95%CI:0.75-0.85,P<0.001).The AUC of the validation set was 0.81(95%CI:0.72-0.90,P<0.001).The Hosmer-Lemeshow goodness-of-fit test indicated that the P values of both the training set(P=0.089)and the validation set(P=0.136)were greater than 0.05.Conclusions:The presence of abandoned leads,the oldest dwell time of lead extracted,and the number of extracted leads>3 are independent risk factors for non-CPS in patients undergoing TLE.The nomogram model based on the above factors has satisfactory predictive ability.

Objective To identify candidate compounds that activate thermogenesis during cold exposure by integrating the Library of Integrated Network-Based Cellular Signatures(LINCS)with RNA expression profiles specific to cold-induced thermogenesis.Methods Gene expression profiles of interscapular brown adipose tissue(BAT)and inguinal white adipose tissue(iWAT)were generated from 8-week-old C57BL/6J mice which were housed at 5 ℃ or room temperature(23 ℃)for 7 days.The gene expression signatures of the cold-induced BAT and iWAT were compared to the LINCS dataset to predict potential candidates for testing in a cold challenge model that was intended to assess thermogenesis activation.The pharmacological potential of the identified compounds was evaluated in a cold-exposed mouse model.The core body temperature and infrared thermal imaging were collected to monitor physiological responses during cold exposure.Additionally,hematoxylin and eosin(HE)staining was used to assess morphological changes of fat cells of BAT,iWAT,and epididymal white adipose tissue(eWAT).Results The transcriptomic signatures related to cold-induced thermogenesis were obtained and the top 20 candidate compounds were identified by comparison with the LINCS dataset.Mice treated with withaferin A(WA)during the cold challenge exhibited elevated rectal temperatures and smaller adipocyte sizes compared to controls.Conclusion Our drug repurposing strategy,which connects transcriptional profiles with LINCS data,identifies potential compounds.WA enhances thermogenesis and metabolic activity in adipose tissue,which helps maintain body temperature,and improves cold tolerance during exposure to low temperatures.

Objective To investigate the effects of insulin-like growth factor binding protein 7(IGFBP7)on the sensitivity of glioma cells to temozolomide(TMZ)and the related mechanism.Methods IGFBP7 mRNA expression levels in TMZ-sensitive(U87 TMZ-S,U251 TMZ-S)and TMZ-resistant(U87 TMZ-R,U251 TMZ-R)glioma cells were analyzed using RNA sequencing data from the gene expression omnibus(GEO)dataset GSE151680.TMZ-resistant U87 and U251 cell lines were established via stepwise dose escalation.IGFBP7 expressions in TMZ-R cells were detected by quantitative real-time PCR(qPCR)and Western blotting.IGFBP7 was stably knock-downed in TMZ-R cells while IGFBP7 was stably overexpressed in TMZ-S cells using lentiviral infection.Cell viability,migration,invasion and TMZ sensitivity were assessed using CCK-8 assay,apoptosis assay,wound healing assay,Transwell invasion assay and colony formation assay respectively.Cellular senescence was detected by β-galactosidase(SA-β-Gal)staining.The expression levels of senescence molecular markers cyclin-dependent kinase inhibitor 1(p21)and tumor protein p53(p53),as well as DNA damage marker γ-H2A histone family member X(γ-H2AX)were determined by Western blotting.The differences in mRNA expressions of IGFBP7 between glioma tissues and normal tissues as well as the correlations with the overall survival of glioma patients were analyzed using the cancer genome atlas(TCGA),Chinese Glioma Genome Atlas(CGGA),genotype-tissue expression(GTEx)database.Results Compared to normal glioma cells,IGFBP7 expressions were significantly elevated in TMZ-R glioma cells.Overexpression of IGFBP7 in TMZ-S glioma cells enhanced cell viability but suppressed apoptosis following TMZ treatment.The expressions of senescence-associated marker(p21,p53)and DNA damage marker(γ-H2AX)were upregulated in these cells.Notably,IGFBP7 expressions were significantly higher in glioma tissues than in normal tissues,and high IGFBP7 expressions were associated with poor prognosis in glioma patients.Conclusion Knockdown of IGFBP7 promotes TMZ-induced cell senescence and DNA damage,thereby enhancing the sensitivity of gliomas cells to TMZ.

Objectives:To analyze the clinical characteristics,strategies,success and complication rates of lead extraction and re-implantation during the upgrade of cardiovascular implantable electronic devices(CIED)in non-infectious patients.Methods:This retrospective study collected and analyzed the baseline clinical data and surgical data of 66 non-infected patients who had their existing CIEDs(including cardiac pacemaker,implantable cardioverter defibrillator[ICD],cardiac resynchronization therapy pacemaker[CRT-P])upgraded to ICD or CRT-P or cardiac resynchronization therapy defibrillator(CRT-D)or subcutaneous implantable cardioverter defibrillator(S-ICD)in Peking University People's Hospital from March 2018 to March 2024.We analyzed the strategies of lead extraction and reimplantation as well as the operation success rate and complication rate.Results:Among the 66 patients,preoperative imaging revealed that 12 patients(18.2%)had severe stenosis/occlusion of the venous access route,with lead wear/perforation in 26 patients(39.4%).32 patients(48.5%)underwent transvenous lead extraction(TLE),of which all leads were removed in 27 patients(84.4%),and only non-functional leads were removed in 5 patients(15.6%).The success rate of the TLE procedure was 100%and no complication occurred.Among the 66 patients,functional leads retained and new leads were implanted on the same side in 28 patients(42.4%),all leads were removed and new leads were reimplanted on the opposite side in 22 patients(33.3%),only non-functional leads were removed and new leads were reimplanted on the same side in 5 patients(7.6%),all leads were removed and new leads were reimplanted on the same side in 5 patients(7.6%),and 6 patients(9.1%)had the leads abandoned and then were re-implanled.The success rate of the upgrade surgery was 100%,no complications were reported.Conclusions:When the existing CIEDs(including cardiac pacemaker,ICD,CRT-P)of non-infected patients are upgraded to ICD,CRT-P,CRT-D or S-ICD,lead extraction and reimplantation are safe and feasible,and reimplantation can be performed on the ipsilateral or contralateral side.

BACKGROUND:Sarcopenic obesity is a syndrome characterized by the loss of muscle mass and an increase in body fat,which increases the risk of metabolic diseases and physical disabilities in the elderly.Blood flow restriction training involves applying pressure to a body part during exercise to reduce blood flow,achieving the effects of high-intensity training with low-intensity exercise,making it suitable for the elderly and those with limited mobility.OBJECTIVE:To review and discuss the biological mechanisms,effectiveness,and limitations of blood flow restriction training in addressing sarcopenic obesity in the elderly,and to provide exercise prescription recommendations based on current evidence.METHODS:Literature published up to September 2024 was retrieved from major databases.English and Chinese search terms included"blood flow restriction training,KAATSU,elderly,sarcopenia,sarcopenic obesity,muscle,fat."A total of 66 articles were selected,organized,and analyzed.RESULTS AND CONCLUSION:This study explored the biological mechanisms of blood flow restriction training,including creating an ischemic-hypoxic environment,accumulating metabolites,activating potential signaling pathways,and promoting satellite cell proliferation.The effectiveness of blood flow restriction training in improving muscle strength,mass,and reducing body fat was evaluated,and its potential advantages and risks in the elderly population were discussed.It is recommended that elderly patients with sarcopenic obesity undergo blood flow restriction training combined with 20%-40%1 RM resistance training for three to four times per week.Starting from the first week,there are three sets of training with 30,15,and 15 repetitions respectively.From the second week,there are four sets with 30,15,15,and 15 repetitions respectively.The rest interval between each set is 30-60 seconds.The cuffwidth is 3-5 cm.The pressure of each set increases incrementally by 40%,60%,and 80%of the arterial occlusion pressure.The airbag pressure ranges from 80 to 240 mmHg.Future research is needed to further verify the long-term effects of blood flow restriction training,optimize the training protocol,and explore its application possibilities in different disease contexts.

Objective:To screen the risk factors for non-complete procedural success of transvenous lead extraction(TLE),and to establish a prediction model based on the results and evaluate its predictive efficacy.Methods:A total of 1 029 patients who underwent TLE in Peking University People's Hospital from January 2014 to December 2020 were enrolled and divided into training set(n=720)and validation set(n=309)using the random number method.There were no statistically significant differences among the variables in the training set and the validation set.The training set was divided into the complete procedural success(CPS)group(n=664)and the non-CPS group(n=56).Univariate analysis was employed to screen the relevant indicators of non-CPS,followed by binary logistic regression analysis to identify the independent risk factors of non-CPS.Subsequently,a predictive model and nomogram were constructed.The receiver operating characteristic(ROC)curve analysis was applied to evaluate the ability of the model to distinguish non-CPS from TLE patients in the training set and validation set.The Hosmer-Lemeshow goodness-of-fit test was used to assess the consistency between the predicted risk and the actual risk of the model.Results:Univariate analysis showed that the relevant variables with P<0.1 including the age at the first implantation of the lead,the number of leads extracted,the oldest dwell time of lead extracted,the presence of abandoned leads,non-manual traction for lead extracted,the number of extracted leads>3,bilateral lead implantation,and the indications for TLE.The binary logistic regression analysis revealed that the presence of abandoned leads(OR=2.252,95%CI:1.111-4.564,P=0.024),the oldest dwell time of the extracted leads(OR=1.009,95%CI:1.005-1.012,P<0.001),and the number of extracted leads>3(OR=3.177,95%CI:1.306-7.733,P=0.011)were independent risk factors for non-CPS of TLE.ROC curve analysis revealed that the area under the ROC curve(AUC)of the training set was 0.80(95%CI:0.75-0.85,P<0.001).The AUC of the validation set was 0.81(95%CI:0.72-0.90,P<0.001).The Hosmer-Lemeshow goodness-of-fit test indicated that the P values of both the training set(P=0.089)and the validation set(P=0.136)were greater than 0.05.Conclusions:The presence of abandoned leads,the oldest dwell time of lead extracted,and the number of extracted leads>3 are independent risk factors for non-CPS in patients undergoing TLE.The nomogram model based on the above factors has satisfactory predictive ability.

Aim Systematic evolution of ligands by exponential enrichment(SELEX)techniquewas employed to screen and identify nucleic acid aptamers that specifically bind to mouse atherosclerotic pathological tissues,aiming to pro-vide a research foundation for the development of molecular targets and diagnostic reagents for early atherosclerosis.Methods A single-stranded DNA(ssDNA)library with a capacity of 1015～1016 was constructed,which was then subjec-ted to binding-elution(negative selection)with normal mouse vascular tissue slices.The eluted library was subsequently bound to atherosclerotic tissue slices for binding-elution(positive selection).PCR was used to amplify the positive and negative screening products,and agarose gel electrophoresis was used to verify the amplified products.The ssDNA library after multiple rounds of selection was sequenced using T-A cloning and sequencing to obtain the primary structure of the nu-cleic acid aptamers,and the secondary structure was predicted using the Mfold online software.The selected nucleic acid aptamers were labeled with a FAM fluorescent group at the 5'-end and were bound to both positive and negative selection tissue slices,with fluorescence intensity observed under a fluorescence microscope.Image Pro Plus 6.0 was used to cal-culate the relative average fluorescence intensity to evaluate the binding specificity of nucleic acid aptamers.Results After 8 rounds of selection,agarose gel electrophoresis imaging showed PCR amplification products in the positive selection lanes,while no PCR amplification products were observed in the negative selection lanes,indicating the successful acquisi-tion of a nucleic acid aptamer library that specifically binds to atherosclerotic tissues.Five nucleic acid aptamers were i-dentified by T-A cloning and sequencing,and their predicted secondary structures all had stem-loop structures.Immuno-fluorescence staining verified that five nucleic acid aptamers had different degrees of binding with As blood vessels,and the quantitative results of the relative average fluorescence intensity showed that nucleic acid aptamer No.11 had the highest relative average fluorescence intensity value,which can be used as a candidate nucleic acid aptamer for subsequent re-search.Conclusion Specific nucleic acid aptamers that bind to atherosclerotic vesselswere successfully obtained,providing a research foundation for further screening of early molecular targets of Asand developing in vivo early diagnostic reagents.