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.

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 explore the current research situation,hotspots and development trend in the field of acupuncture and mox-ibustion intervention for post-stroke dysphagia(PSD). Methods The literature on acupuncture and moxibustion intervention for PSD was retrieved from CNKI,VIP and Wan-fang database from 1994 to December 31st,2023,and analyzed with VOSviewer and CiteSpace. Results A total of 1 816 articles were included,and the number of publications increased year by year,reaching a peak in 2021 with 180 articles.There were 274 core authors included in the literature,among which Cheng Hongliang,Zhou Hongfei and Feng Weixing were the authors with the highest publication volume.The First Affiliated Hos-pital of Tianjin University of Chinese Medicine was the most productive institution,and the connections between institutions were relatively scattered.The high-frequency keywords were swallowing dysfunction,stroke,acu-puncture and moxibustion therapy,as well as rehabilitation therapy,among which tongue triple acupuncture,elec-troacupuncture,nape acupuncture and scalp acupuncture were the most commonly used methods.In addition,acupuncture combined with rehabilitation training,electrical stimulation,or other methods for PSD and acupoint selection rules were also research hotspots.When evaluating the efficacy of acupuncture intervention for PSD,the focus gradually shifted from the effective rate to the use of videofluorographic swallowing study,water swal-lowing test,standardized swallowing assessment,surface electromyography and other indicators to evaluate the swallowing function and the severity of dysphagia. Conclusion Research on acupuncture and moxibustion interventions for PSD has developed rapidly,with hotspots in-cluding the selection of specific acupuncture and moxibustion techniques,the combination of acupuncture and moxibustion with other rehabilitation therapies,outcome indicators for acupuncture and moxibustion interven-tions in PSD,and the rules of acupoint selection.In the future,it is essential to strengthen academic exchanges and collaborations across institutions and regions.Greater emphasis should be placed on objective evaluation in-dicators of acupuncture and moxibustion therapies for improving the swallowing function in PSD patients,as well as on optimizing combinations of acupuncture and moxibustion with modern rehabilitation approaches,so as to better guide clinical practice.

Objective The prediction of RR intervals in hypertensive patients can help clinicians to analyze and warn patients'heart condition.Methods Using 8 patients'data as samples,the RR intervals of patients were predicted by long short-term memory network(LSTM)and gradient lift tree(XGBoost),and the prediction results of the two models were combined by the inverse variance method to overcome the disadvantage of single model prediction.Results Compared with the single model,the proposed combined model had a different degree of improvement in the prediction of RR intervals in 8 patients.Conclusion LSTM-XGBoost model provides a method for predicting RR intervals in hypertensive patients,which has potential clinical feasibility.

Objective To investigate the difference of electrocardiographic(ECG)features between total left main artery(LM)occlusion and subtotal occlusion,and analyze risk factors of in-hospital mortality.Methods A total of 94 patients with left main complete occlusion and 99 patients with subtotal occlusion were included.ECG characteristics,coronary angiography and other clinical data were compared,and factors of hospital death were analyzed.The receiver operating characteristics(ROC)curve was used to analyze the predictive value of ECG characteristics in hospital death risk in patients with LM occlusion.The relationship between ECG characteristics,shock and collateral circulation were analyzed in patients with LM occlusion.Results Compared with the subtotal occlusion group,patients with LM occlusion presented with more ST-segment elevation(STE)in Ⅰ,avL,V2-V5,more STE in avR and avL,more left anterior fascicular block+right bundle branch block,prolonged QRS duration,less STE in avR and less STE in avR+V1.The in-hospital mortality was 46.8%(44/94)in LM occlusion and 14.1%(14/99)in LM subtotal occlusion.STE in avR+avL predicted total LM occlusion with a specificity of 0.97,and left anterior branch+right bundle branch block predicted total LM occlusion with a specificity of 1.00.In patients with total LM occlusion,STE in Ⅰ,avL,V2-V5,prolongation of QRS duration,shock,no collateral circulation,STE in Ⅰ,avL,V2-V5 combined with left anterior fascicular block+right bundle branch block,and STE in Ⅰ,avL,V2-V5 combined with shock predicted in-hospital mortality,with the area under the curve of 0.716,0.619,0.766,0.688,0.572,0.785,respectively.The diagnostic specificity of STE in Ⅰ,avL,V2-V5 combined with shock was 0.82,and the sensitivity was 0.75.STE in Ⅰ,avL,V2-V5 combined with left anterior fascicular block+right bundle branch block predicted in-hospital death in LM occlusion with a specificity of 0.94.The proportion of shock was higher in patients with STE in Ⅰ,avL,V2-V5,left anterior fascicular block+right bundle branch block and collateral flow absence(P＜0.05).In patients with total occlusion,no collateral flow was observed in patients with STE in Ⅰ,avL,V2-V5.In patients with STE in avR(including avR+V1),82.4%of patients presented with right coronary collateral circulation supplying the left anterior descending coronary artery and left circumflex artery territory.In patients with STE in avR+avL,69.2%of patients presented with right coronary collateral circulation supplying left anterior descending coronary artery territory.Conclusion Total LM occlusion presents with different ECG features compared with subtotal occlusion.In LM total occlusion,the ECG features predict in-hospital mortality and are associated with different collateral circulation.

Interarterial subtype of coronary artery with anomalous aortic origin is a rare and congenital cardiovascular malformation,manifested by chest pain and syncope after exertion or activity,which can lead to decreased cardiac contractility,myocardial infarction,and even sudden death.Here we report a case of an adolescent patient,who presented with chest pain during activity accompanied by syncope and lost consciousness.Initially diagnosed with acute myocardial infarction,the patient was subsequently diagnosed as interarterial subtype of a coronary artery originating from anomalous aorta after echocardiography,coronary angiography,coronary CT angiography examinations.After anomalous coronary artery correction and coronary angioplasty,the paitent recovered well.

Objective:To investigate the predictive value of differential distribution of peripheral lymphocyte subsets before and after the first 131I treatment on the therapeutic response to 131I treatment in patients with papillary thyroid cancer (PTC). Methods:A retrospective study was conducted on 46 PTC patients (16 males, 30 females, age 20-77 years) who underwent total thyroidectomy and received 131I treatment between January 2021 and August 2021 in First Hospital of Shanxi Medical University. Peripheral blood lymphocyte subsets (T, B, CD4 + T, CD8 + T, natural killer (NK), helper T (Th)1, Th2, Th17, and regulatory T (Treg) cells) were measured 1-2 d before and 30 d after 131I treatment. Based on serological and imaging evidence, therapeutic response at 6-12 months post- 131I therapy was categorized as either excellent response (ER) or non-excellent response (NER). Differences of preablative stimulated thyroglobulin (psTg) and clinical baseline characteristics between two groups were assessed by using independent-sample t test, paired t test, or Mann-Whitney U test. Predictive value of lymphocyte subsets before and after 131I treatment for therapeutic response was assessed through logistic regression analysis, ROC curve analysis, and decision curve analysis (DCA). Results:In ER group ( n=33) and NER group ( n=13), most lymphocyte subsets showed different degrees of reduction 30 d after 131I treatment compared to before 131I treatment, such as T, B, CD4 + T and Th1 cells in ER group, as well as T, B, CD4 + T, Th1, Th2, Th17, and Treg cells in NER group ( t values: 2.41-9.57, all P<0.05). Before 131I treatment, NER group had significantly higher levels of psTg, Th2, Th17, and Treg cells compared to the ER group ( t values: from -3.32 to -2.48, U=29.00, all P<0.05). After 131I treatment, most of lymphocyte subsets in NER group (T, B, CD4 + T, CD8 + T, Th1 and Treg cells) showed higher trend than those in ER group but without statistical significances ( t values: from -1.12 to -0.06, all P>0.05). Th2 cells before 131I treatment (odds ratio ( OR)=25.00, 95% CI: 1.36-459.10, P=0.030) was identified as a risk factor for NER. ROC curve analysis indicated that AUCs of psTg and Th2 cells for predicting therapeutic response were 0.932 and 0.790, respectively, which was 0.958 for the combined psTg and Th2 cells. DCA showed that within the threshold probability range of 10%-60%, the curves for psTg, Th2 cells, and the combined psTg and Th2 cells were all higher than the extreme curve, suggesting good effect. Conclusions:Most lymphocyte subsets decrease to varying degrees, and NER group shows a significant decrease 30 d after 131I treatment. Th2 cells may be a risk factor for poor response to 131I treatment, providing a certain value in predicting the therapeutic response to 131I treatment.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To observe the effect of combined acupuncture and medication on hyperarousal state and serum copeptin(CPT)in patients with chronic insomnia(CI),and to explore its possible mechanism of action.Methods:A total of 70 CI patients meeting the inclusion criteria were divided into an observation group and a control group by the random number table method,with 35 cases in each group.The control group was given estazolam tablets before bedtime,1 mg/time,once a day.The observation group was treated with additional Yi Nao An Shen acupuncture therapy(acupuncture for benefiting the brain and tranquillization)on the basis of the medication treatment,4 times a week.After 4 weeks of treatment,the Pittsburgh sleep quality index(PSQI)score,insomnia severity index(ISI)score,pre-sleep arousal scale(PSAS)score,hyperarousal scale(HAS)score,and the change in serum CPT level were compared between the two groups.Results:During the study,there were 2 dropout cases in the observation group and 1 dropout case in the control group.After treatment,the PSQI,ISI,PSAS,and HAS scores and the serum CPT level in both groups decreased compared with the same group before treatment,and the intra-group differences were statistically significant(P<0.05).After treatment,changes in each above scale score and the serum CPT level in the observation group were much more significant and were statistically different from those in the control group(P<0.05).Conclusion:Acupuncture plus medication can improve sleep quality,reduce the degree of insomnia,and regulate hyperarousal state in patients with CI,and its mechanism of action may be related to the down-regulation of serum CPT level.