Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Aim To systematically elucidate the molecular regulatory network of thermogenic function in brown adipose tissue(BAT)through multi-omics integrative analysis,to discover novel thermogenic regulatory genes and provide novel therapeutic targets for metabolic disorders.Methods A novel methodology for screening key genes regulating thermogenesis in BAT was constructed:First,differential expression analysis was performed on bulk RNA-seq data from murine BAT.Genes meeting the thresholds of ABS(log2FoldChange)＞1 and Padj＜0.05 were identified as differentially expressed genes.Intersectional analysis was then applied to obtain consensus upregulated and downregulated gene sets.Subsequently,scRNA-seq data of brown adipocytes were partitioned into high-expression group and low-expression group based on the expression levels of candidate genes.Differential analysis and gene set enrichment analysis(GSEA)were conducted between these groups to assess the correlation between candidate genes and thermogenic function.Finally,ex-perimental validation of selected candidate genes was performed using quantitative real-time PCR and Western blot.Results Bioinformatics analysis identified 65 thermogenesis-positive correlated genes and 7 thermogenesis-negative corre-lated genes.Subsequent quantitative PCR validation demonstrated that candidate genes Mfsd2a,Me1,Slc25a34,Pfkp,Ankrd9,Hsd17b12,Aldoa,Ctsz and Pcyt2 exhibited upregulation exceeding 5-fold,while Pid1 and Angpt1 showed down-regulation over 50％.All observed expression changes demonstrated statistical significance(P＜0.01)through rigorous hypothesis testing.These findings highlight the potential involvement of these genes in thermogenic regulation,warranting further functional investigations to elucidate their molecular mechanisms in energy metabolism pathways.Conclusions This study established a novel"computational screening → in silico knockout → experimental validation"paradigm for tar-get discovery,systematically unveiling the molecular network involved in BAT thermogenic regulation.This methodology is equally applicable for identifying key regulatory genes in other physiological or pathological processes.The study identi-fied 11 core genes that may play pivotal regulatory roles during BAT thermogenic activation,which could potentially offer novel pharmacological intervention targets to improve energy metabolism and treat obesity-related complications.

Aim To systematically elucidate the molecular regulatory network of thermogenic function in brown adipose tissue(BAT)through multi-omics integrative analysis,to discover novel thermogenic regulatory genes and provide novel therapeutic targets for metabolic disorders.Methods A novel methodology for screening key genes regulating thermogenesis in BAT was constructed:First,differential expression analysis was performed on bulk RNA-seq data from murine BAT.Genes meeting the thresholds of ABS(log2FoldChange)＞1 and Padj＜0.05 were identified as differentially expressed genes.Intersectional analysis was then applied to obtain consensus upregulated and downregulated gene sets.Subsequently,scRNA-seq data of brown adipocytes were partitioned into high-expression group and low-expression group based on the expression levels of candidate genes.Differential analysis and gene set enrichment analysis(GSEA)were conducted between these groups to assess the correlation between candidate genes and thermogenic function.Finally,ex-perimental validation of selected candidate genes was performed using quantitative real-time PCR and Western blot.Results Bioinformatics analysis identified 65 thermogenesis-positive correlated genes and 7 thermogenesis-negative corre-lated genes.Subsequent quantitative PCR validation demonstrated that candidate genes Mfsd2a,Me1,Slc25a34,Pfkp,Ankrd9,Hsd17b12,Aldoa,Ctsz and Pcyt2 exhibited upregulation exceeding 5-fold,while Pid1 and Angpt1 showed down-regulation over 50％.All observed expression changes demonstrated statistical significance(P＜0.01)through rigorous hypothesis testing.These findings highlight the potential involvement of these genes in thermogenic regulation,warranting further functional investigations to elucidate their molecular mechanisms in energy metabolism pathways.Conclusions This study established a novel"computational screening → in silico knockout → experimental validation"paradigm for tar-get discovery,systematically unveiling the molecular network involved in BAT thermogenic regulation.This methodology is equally applicable for identifying key regulatory genes in other physiological or pathological processes.The study identi-fied 11 core genes that may play pivotal regulatory roles during BAT thermogenic activation,which could potentially offer novel pharmacological intervention targets to improve energy metabolism and treat obesity-related complications.

Objective:To compare and analyze the accuracy of the invasive glucose detecting device and the non-invasive glucose device(NeoGlu01)based on artificial intelligence(AI)algorithm in detecting peripheral blood glucose.Methods:A total of 96 diabetic voluntary patients were recruited from the community of Beijing district from December 2022 to March 2023.The Roche ACCU-CHECK? Guide invasive glucose device was used to detect the peripheral blood glucose of volunteers,and the NeoGlu 01 type of non-invasive glucose device was used to collect the signal of the finger,so as to obtain the blood glucose value that was calculated by AI algorithm at the same time.Pearson correlation analysis was adopted to analyze the detected blood glucose values of the two kinds of devices.Results:Both the peripheral blood glucose values of invasive glucose detecting device and the calculated AI values of NeoGlu01 type of non-invasive glucose device for 96 diabetic patients had favorable consistency with calibration value(R2=0.978,0.882,P<0.05),respectively.Both the detected values of peripheral blood glucose of invasive glucose detecting device and the calculated AI values of NeoGlu01 type of non-invasive glucose device were between 6.2 and 16.7 mmol/L for 96 diabetic patients,and the difference was no significant(P>0.05).Parkes error grid analysis,that referred to the values of peripheral blood glucose,indicated the two times of the results of the values of mean absolute relative difference(MARD)of total accuracy indicator of calculated AI value of non-invasive glucose device were respectively 11.05%and 11.44%,and both the accuracy rate and repeatability of that were favorable.Conclusion:The predictive blood glucose value of NeoGlu01 non-invasive blood glucose device has favorable consistency and accuracy with the detected value of invasive glucose detecting device in detecting peripheral blood glucose.

Objective:To investigate the effect of age on the occurrence of complicating pancreatitis(PEP)and its severity after endoscopic retrograde cholangiopancreatography(ERCP)for common bile duct stones.Methods:The clinical data of 512 patients with common bile duct stones undergoing ERCP from September 2014 to April 2018 were retrospectively analyzed.Of the patients,232 cases with age equal to or over 75 years were defined as observation group,and 280 cases with age below 75 years were served as control group.The main clinical variables and the incidence as well as the severity of PEP were compared between the two groups of patients.Results:In observation group,except the proportions of cases with concomitant geriatric conditions(hypertension,diabetes and coronary heart disease)were higher than those in control group(all P<0.05),all other general data showed no significant differences with control group(all P>0.05).There were no significant differences in terms of treatment success rate of ERCP,intraoperative variables and treatment procedures between the two groups of patients(all P>0.05).The incidence rates of postoperative bleeding and hyperamylasemia showed no significant differences between the two groups of patients(both P>0.05).In the entire group,the incidence rate of PEP was 10.94%(56/512),which in observation group was 6.47%(17/232),including 4.74%(11/232)mild,2.16%(5/232)moderate and 0.43%(1/232)severe PEP;in control group it was 13.93%(39/280),including 8.93%(25/280)mild,4.29%(12/280)moderate and 0.71%(2/280)severe PEP.The overall incidence rate of PEP in observation group was significantly lower than that in control group(P=0.017),and the incidence rate of each degree of PEP was lower than in control group,but all did not reach a significant difference(P=0.065,0.180,0.676).All complications in both groups of patients were alleviated after aggressive conservative treatment.Conclusion:Atrophy,fibrosis and exocrine hypofunction of the pancreas result from increase in age have a certain inhibitory effect on the occurrence of PEP,but have no obvious influence on the severity of PEP.However,this result still needs to be further assessed by big data from multiple centers.

Objective:To investigate the effect of age on the occurrence of complicating pancreatitis(PEP)and its severity after endoscopic retrograde cholangiopancreatography(ERCP)for common bile duct stones.Methods:The clinical data of 512 patients with common bile duct stones undergoing ERCP from September 2014 to April 2018 were retrospectively analyzed.Of the patients,232 cases with age equal to or over 75 years were defined as observation group,and 280 cases with age below 75 years were served as control group.The main clinical variables and the incidence as well as the severity of PEP were compared between the two groups of patients.Results:In observation group,except the proportions of cases with concomitant geriatric conditions(hypertension,diabetes and coronary heart disease)were higher than those in control group(all P<0.05),all other general data showed no significant differences with control group(all P>0.05).There were no significant differences in terms of treatment success rate of ERCP,intraoperative variables and treatment procedures between the two groups of patients(all P>0.05).The incidence rates of postoperative bleeding and hyperamylasemia showed no significant differences between the two groups of patients(both P>0.05).In the entire group,the incidence rate of PEP was 10.94%(56/512),which in observation group was 6.47%(17/232),including 4.74%(11/232)mild,2.16%(5/232)moderate and 0.43%(1/232)severe PEP;in control group it was 13.93%(39/280),including 8.93%(25/280)mild,4.29%(12/280)moderate and 0.71%(2/280)severe PEP.The overall incidence rate of PEP in observation group was significantly lower than that in control group(P=0.017),and the incidence rate of each degree of PEP was lower than in control group,but all did not reach a significant difference(P=0.065,0.180,0.676).All complications in both groups of patients were alleviated after aggressive conservative treatment.Conclusion:Atrophy,fibrosis and exocrine hypofunction of the pancreas result from increase in age have a certain inhibitory effect on the occurrence of PEP,but have no obvious influence on the severity of PEP.However,this result still needs to be further assessed by big data from multiple centers.

Objective To investigate the effect of X-ray assisted nasal catheter extractor on nose biliary oronasal conversion. Methods A total of 892 patients,receiving endoscopic nasal biliary drainage in Affiliated Zhongshan Hospital of Dalian University from January 2014 to December 2015, were randomly divided into experiment group and control group. X-ray assisted nasal catheter extractor was used in the experiment group,and guide wire was used in the control group. The mean extracting number and operation time, the total success rate, one-time success rate, response to stimulation and the incidence of complications were compared between the two groups. Results There were 457 cases in the experiment group. The mean extracting number was 1.08±0.32,the mean operation time was 1.07±0.29 min,the total success rate was 100.00%(457/457)and one-time success rate was 93.65%(428/457). The stimulation degree score was 1.27±0.50 with 348 cases of mild response,96 cases of moderate response and 13 cases of severe response. The rate of adverse reaction was 15.54%(71/457)with 50 cases of nausea, 18 cases of vomiting and 3 cases of mucosal bleeding. There were 435 cases in control group. The mean extracting number was 1.68±0.61,the mean operation time was 1.75±0.53 min, the total success rate was 75.63%(329/435)and one-time success rate was 38.16%(166/435). The stimulation degree score was 1.59 ±0.62 with 210 cases of mild response,194 cases of moderate response and 31 cases of severe response. The rate of adverse reaction was 35.86%(156/435)with 87 cases of nausea,36 cases of vomiting,27 cases of mucosal bleeding,and 6 cases of nasal duct prolapsed for vomiting. There were significant differences in the mean extracting number, mean operation time, stimulation degree score and the adverse reaction rate between the two groups(all P<0.001). The total success rate and one-time success rate in the experiment group were higher than those in the control group(all P<0.001).Conclusion X-ray assisted nasal catheter extractor can improve the success rate of operation,shorten the operation time,reduce the stimulation degree and the rate of adverse reactions in nose biliary oronasal conversion.

The clinical data of 7 patients who underwent the treatment of gradual and persistent balloon dilatation (GPBD) by percutaneous transhepatic cholangiography (PTC)for traumatic biliary stricture in Zhongshan Hospital Affiliated to Dalian University were analyzed retrospectively.Balloon catheters were successfully implanted in 5 cases by PTC,and with the help of ERCP in 2 PTC failed cases.There was no bleeding,acute pancreatitis and other complications.Two balloon catheters were damaged and displaced,respectively.All the biliary strictures were relieved.No biliary sludge was attached on the surface of the balloon and in the bile duct.Bile duct mucosa had congestion edema and cellulose attachment.There was no biliary stricture recurrence in the follow-up of 5 to 27 months.This study showed GPBD by PTC was a simple,safe and effective method for treating traumatic biliary strictures.