Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Objective To investigate the therapeutic mechanism of Dingkun Dan(DKD)in polycystic ovary syndrome(PCOS)by examining the effects of microRNA-30d-5p on ovarian granulosa cells(GCs).Methods A PCOS rat model was established using dehydroepiandrosterone(DHEA).Normal rat GCs and PCOS rat GCs were cultured in vitro and divided into four groups:blank control group,model group,low-dose DKD group,and high-dose DKD group.After grouping,GCs viability was assessed using the methyl thiazolyl tetrazolium(MTT)assay,GCs apoptosis was analyzed by flow cytometry,and the gene expression of transforming growth factor β1(TGF-β1),Smad2,Smad3,and microRNA-30d-5p in GCs was measured by real-time polymerase chain reaction(RT-PCR),protein expression of TGF-β1,Smad2,and Smad3 in GCs was detected by Western Blot.Results Compared with the blank control group,the model group exhibited significantly decreased GCs viability,increased GCs apoptosis,upregulated mRNA and protein expression of TGF-β1,Smad2,and Smad3,and downregulated microRNA-30d-5p expression,the differences were statistically significant(P＜0.01).Compared with the model group,both low-and high-dose DKD groups showed increased GCs viability,reduced GCs apoptosis,downregulated mRNA and protein levels of TGF-β1 Smad2 and Smad3,elevated microRNA-30d-5p expression,and the differences were statistically significant(P＜0.05 or P＜0.01).Conclusion DKD promotes GCs proliferation by targeting Smad2 via microRNA-30d-5p,suggesting a potential therapeutic role in PCOS-related ovulatory dysfunction.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Objective To establish a method for rapid detection of tramadol in urine by liquid-liquid extraction（LLE）-surface-enhanced Raman spectroscopy （SERS）. Methods Tramadol was extracted from urine with chloroform∶isopropyl alcohol （9∶1） extractant and detected in urine samples by enhanced Raman spectroscopy （wavelength 785 nm）. Results The quantitative curve of tramadol was Y=204.35 X−465.62, r=0.9952, and the linear range was 1-100 μg/ml. The detection limit of tramadol by this method （S/N=3） was 0.53 μg/ml. The sensitivity of SERS was higher than that of conventional methods, and it had reasonable reproducibility. Conclusion This method is simple, efficient and economical, and can be used for qualitative and quantitative analysis of tramadol personalized medicine.

Objective To explore the effect of esketamine combined with butorphanol on hemodynamics in painless gastroenteroscopy for elderly patients with obesity and the anesthetic efficacy and safety of this combined anesthesia regimen.Methods The subjects of this study,124 elderly patients with obesity who received painless gastroenteroscopy from January 2022 to March 2024,were randomly divided into two groups,each with 62 cases.Both groups were administrated with propofol 1.50 mg/kg for anesthesia induction.The observation group was given esketamine 0.20 mg/kg combined with butorphanol 10 μg/kg intravenously prior to propofol injection,while the control group was given saline of the same volume as esketamine combined with butorphanol 10 μg/kg intravenously before propofol injection.Vital signs indicators[mean arterial pressure(MAP),heart rate(HR),and percutaneous arterial oxygen saturation(SpO2)]were compared between the two groups at the time of entry(T0),immediately after anesthesia induction(T1),immediately after gastroscopy placement(T2),immediately upon completion of gastroscopy(T3),immediately after colonoscopy insertion(T4),and immediately upon completion of colonoscopy examination(T5).The anesthesia effect was evaluated for the two groups during painless gastroenteroscopy examination.The duration of gastroenteroscopy and propofol dosage were compared between the two groups as well.Visual analogue scale(VAS)score was used to evaluate the postoperative pain level for patients from the two groups 1,2,3,and 4 h after surgery.Intraoperative and postoperative adverse reactions in two groups were recorded.Results The MAP at T3,T4,and T5 time points in observation group were lower than that at T0 time point,the HR at T4 and T5 time point in observation group was lower than that at T0 time point,the differences were statistically significant(P＜0.05),there was no significant difference in SpO2 at each time point in observation group(P＞0.05).While the MAP,HR,and SpO2 at T1,T2,T3,T4,and T5 time points in control group were significantly lower than those at T0 time points,the differences were statistically significant(P＜0.05).The MAP,HR,and SpO2 at T1,T2,T3,T4,and T5 time points in control group were lower than those in observation group,the differences were statistically significant(P＜0.05).The excellent and good rate of anesthesia in observation group was better than that in control group,the difference was statistically significant(P＜0.05).The propofol dosage in observation group was less than that in control group,the recovery time in observation group was shorter than that in control group,the differences were statistically significant(P＜0.05).There were no significant differences in duration of gastroenteroscopy examination,postanesthesia care unit(PACU)stay and leave hospital time between the two groups(P＞0.05).1,2,3,and 4 h postoperative pain VAS scores in observation group were less than those in control group,the differences were statistically significant(P＜0.05).The incidence of respiratory depression was 3.23％,which was significantly lower than 19.35％in control group,the incidence of hypotension was 4.84％,which was significantly lower than 25.81％in control group,the incidence of bradycardia was 0.00％,which was significantly lower than 17.74％in control group,the incidence of nausea and vomiting was 1.61％,which was significantly lower than 12.90％in control group,the differences were statistically significant(P＜0.05).There were no significant differences in the incidence of tachycardia,coughing,body movement,and dizziness between the two groups(P＞0.05).Conclusion Application of esketamine combined with butorphanol in painless gastroenteroscopy for elderly patients with obesity can effectively improve sedative and analgesic effects,stabilize hemodynamics,and reduce adverse reactions.It is worthy clinical application.

Objective To explore the effect of esketamine combined with butorphanol on hemodynamics in painless gastroenteroscopy for elderly patients with obesity and the anesthetic efficacy and safety of this combined anesthesia regimen.Methods The subjects of this study,124 elderly patients with obesity who received painless gastroenteroscopy from January 2022 to March 2024,were randomly divided into two groups,each with 62 cases.Both groups were administrated with propofol 1.50 mg/kg for anesthesia induction.The observation group was given esketamine 0.20 mg/kg combined with butorphanol 10 μg/kg intravenously prior to propofol injection,while the control group was given saline of the same volume as esketamine combined with butorphanol 10 μg/kg intravenously before propofol injection.Vital signs indicators[mean arterial pressure(MAP),heart rate(HR),and percutaneous arterial oxygen saturation(SpO2)]were compared between the two groups at the time of entry(T0),immediately after anesthesia induction(T1),immediately after gastroscopy placement(T2),immediately upon completion of gastroscopy(T3),immediately after colonoscopy insertion(T4),and immediately upon completion of colonoscopy examination(T5).The anesthesia effect was evaluated for the two groups during painless gastroenteroscopy examination.The duration of gastroenteroscopy and propofol dosage were compared between the two groups as well.Visual analogue scale(VAS)score was used to evaluate the postoperative pain level for patients from the two groups 1,2,3,and 4 h after surgery.Intraoperative and postoperative adverse reactions in two groups were recorded.Results The MAP at T3,T4,and T5 time points in observation group were lower than that at T0 time point,the HR at T4 and T5 time point in observation group was lower than that at T0 time point,the differences were statistically significant(P＜0.05),there was no significant difference in SpO2 at each time point in observation group(P＞0.05).While the MAP,HR,and SpO2 at T1,T2,T3,T4,and T5 time points in control group were significantly lower than those at T0 time points,the differences were statistically significant(P＜0.05).The MAP,HR,and SpO2 at T1,T2,T3,T4,and T5 time points in control group were lower than those in observation group,the differences were statistically significant(P＜0.05).The excellent and good rate of anesthesia in observation group was better than that in control group,the difference was statistically significant(P＜0.05).The propofol dosage in observation group was less than that in control group,the recovery time in observation group was shorter than that in control group,the differences were statistically significant(P＜0.05).There were no significant differences in duration of gastroenteroscopy examination,postanesthesia care unit(PACU)stay and leave hospital time between the two groups(P＞0.05).1,2,3,and 4 h postoperative pain VAS scores in observation group were less than those in control group,the differences were statistically significant(P＜0.05).The incidence of respiratory depression was 3.23％,which was significantly lower than 19.35％in control group,the incidence of hypotension was 4.84％,which was significantly lower than 25.81％in control group,the incidence of bradycardia was 0.00％,which was significantly lower than 17.74％in control group,the incidence of nausea and vomiting was 1.61％,which was significantly lower than 12.90％in control group,the differences were statistically significant(P＜0.05).There were no significant differences in the incidence of tachycardia,coughing,body movement,and dizziness between the two groups(P＞0.05).Conclusion Application of esketamine combined with butorphanol in painless gastroenteroscopy for elderly patients with obesity can effectively improve sedative and analgesic effects,stabilize hemodynamics,and reduce adverse reactions.It is worthy clinical application.

【Objective】 To explore the risk factors for the production of anti-HLA antibodies in patients with hematological diseases before hematopoietic stemcell transplantation. 【Methods】 The results and clinical data of 1 008 patients with hematological diseases in our hospital who underwent anti-HLA antibody testing were collected by using Luminex technology platform before transplantation from 2016 to 2018 for statistical analysis. 【Results】 The total positive rate of anti-HLA antibodies in 1 008 patients was 24.08%. Multivariate analysis showed that independent risk factors associated with the production of anti-HLA antibodies included age≥30 years old(P=0.046, OR1.467, 95%CI1.007-2.136), time from disease diagnosis to antibody testing≥41 days(P=0.000, OR1.830, 95%CI1.306-2.565), initial platelet count<20×10⁹/L(P=0.020, OR1.543, 95%CI1.072-2.220), prior pregnancy(P=0.000, OR5.187, 95%CI3.689-7.293), transfusions before admission(P=0.001, OR1.762, 95%CI1.257-2.470)and total platelet transfusion volumes after admission≥30 U(P=0.000, OR2.352, 95%CI1.638-3.376). Age ≥30 years old(P=0.023, OR=1.839, 95%CI1.088-3.108)and prior pregnancy(P=0.042, OR=5.258, 95%CI1.062-26.038)are associated with the production of anti-HLA class Ⅰ and class Ⅱ antibodies, respectively. The time from disease diagnosis to antibody testing≥41 days(P=0.000, OR=2.873, 95%CI1.612-5.119), initial platelet count<20×10⁹/L(P=0.008, OR=2.164, 95%CI1.225-3.822), prior pregnancy(P=0.002, OR=6.734, 95%CI1.993-22.751), transfusions before admission(P=0.001, OR=2.746, 95%CI1.531-4.925)and total platelet transfusion volumes after admission>30 U(P=0.006, OR=3.459, 95%CI1.416-8.451)are associated with the production of anti-HLA class Ⅰ and Ⅱ antibodies. 【Conclusion】 Older age, longer course of disease, lower PLT count, history of pregnancy and blood transfusion, and higher total amount of PLT transfusion are risk factors which affect the production of anti-HLA antibodies.Therefore, it is advisable to test for anti-HLA antibodies according to the situation before transplantation, which is of great value in guiding donor selection, monitoring antibody changes and improving transplant prognosis.

Objective To systematically evaluate and analyze the qualitative research on the experience of maintenance hemodialysis patients,so as to provide references for the implementation of exercise interventions in maintenance hemodialysis patients.Methods We searched databases including PubMed,Embase,Web of Science,Cochrane Library,PsycINFO,CINAHL,CBM,CNKI,WanFang Database and VIP from inception to September 30,2022,to collect qualitative studies about exercise experience of maintenance hemodialysis patients.The quality of included studies was evaluated according to JBI Critical Appraisal Tool for qualitative studies in Australia.The results were integrated by integrating methods.Results A total of 14 studies were included.47 completed findings were grouped according to their similarities to form 12 categories.These categories resulted in 4 synthesized findings.Integration results 1:recognizing the positive effects and potential risks of intradialytic exercise.Integration results 2:barriers and facilitators of intradialytic exercise.Integration results 3:needs of intradialytic exercise.Integration results 4:exercise experience on non-dialysis day.Conclusion The experience and needs of maintenance hemodialysis patients should be considered to ensure patient compliance and continuity when exercise programs were designed.