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 compare the clinical effects between sutureless bridge intrascleral fixation and ciliary sul-cus suture suspension of intraocular lens(IOL)1 year postoperatively.Methods In this retrospective study,14 patients(14 eyes)who underwent sutureless bridge intrascleral IOL fixation in the No.988 Hospital of Joint Logistic Support Force of PLA from March 2019 to January 2022 were taken as the intrascleral fixation group and 15 patients(15 eyes)who under-went IOL ciliary sulcus suture suspension in the same period were taken as the suture suspension group.During the 1-year follow-up,the preoperative and postoperative uncorrected visual acuity(UCVA),best corrected visual acuity(BCVA)(logMAR),spherical equivalent(SE),endothelial cell count(ECC),intraocular pressure(IOP)and IOL position were compared between the two groups.Results At 1,6 and 12 months postoperatively,the UCVA in both groups significant-ly increased compared with those before surgery(all P＜0.05),and UCVA in the intrascleral fixation group were better than those in the suture suspension group at all postoperative time points(F=4.560,6.411 and5.373;all P＜0.05).At 1,6 and 12 months postoperatively,there was no significant difference in BCVA in both groups compared with those before surgery(all P＞0.05),but BCVA in the intrascleral fixation group were better than those in the suture suspension group at all postoperative time points(F=6.170,6.957 and 10.624;all P＜0.05).After surgery,eyes in the intrascleral fixation group showed hyperopia drift,while eyes in the suture suspension group showed myopia drift.At 1,6 and 12 months post-operatively,the SE of the intrascleral fixation group were(0.59±0.30)D,(0.57±0.27)D and(0.64±0.29)D,respec-tively,and those of the suture suspension group were(-0.75±0.44)D,(-0.72±0.42)D and(-1.12±0.64)D,re-spectively.At 6 months postoperatively,the ECC of both groups were significantly lower than those before surgery(t=8.579 and 21.929;both P＜0.001).The IOP in both groups were within the normal range preoperatively and stable during the follow-up.The IOL were centrally located without obvious decentration or tilt during the follow-up.In addition,there were no vitreous and retinal complications.Conclusion Both sutureless bridge intrascleral IOL fixation and IOL ciliary sulcus suture suspension can obtain a favorable prognosis of visual acuity with refractive shift,while sutureless bridge in-trascleral fixation shows better clinical outcomes.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Objective To develop an intelligent horizontal rotating cell culture device with high modularity,easy operation,easy disinfection,low cost and high stability.Methods The cell culture device consisted of a rotating culture module,a dirve module,a control module and control software,with the shells of all the modules being manufactured by 3D printing.The rotating culture module was composed of a tubular electrospun scaffold,a cell culture chamber,a magnetic coupling rotor and polypropylene pipeline;the drive module was made up of a N20 reduction motor and a magnetic coupling rotor;the control module included an ESP-8266 chip and a printed circuit board;the control software was developed with Blinker IoT platform and C++language.The device was used to culture human intrahepatic bile duct epithelial cells to verify its effects.Results Light microscopy and scanning electron microscopy images showed that a uniform and continuous cell layer was formed on the surface of the tubular electrospun scaffold.Conclusion The intelligent horizontal rotating cell culture device achieves uniform growth of cells on the inner surface of tubular electrospun scaffolds,and can be used as an effective platform for cell culture on tubular scaffolds.[Chinese Medical Equipment Journal,2024,45(9):41-45]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective CT scans combined with Mimics software were used to measure femoral offset(FO),rotation center height(RCH)and lower leg length discrepancy(LLD)following total hip arthroplasty(THA),and the relationship between FO,RCH and LLD after THA is discussed.Methods Retrospective analysis was performed on 40 patients with unilateral THA who met standard cases from October 2020 to June 2022.There were 21 males and 19 females,18 patients on the left side and 22 patients on the right side,aged range from 30 to 81 years old,with an average age of(58.90±14.13)years old,BMI ranged from 17.3 to 31.5 kg·m-2withan average of(25.3±3.4)kg·m-2.There were 30 cases of femoral head necrosis(Ficattype Ⅳ),2 cases of hip osteoarthritis(Tonnis type Ⅲ),2 cases of developmental hip dislocation combined with end-stage osteoarthritis(Crowe type Ⅲ),and 6 cases of femoral neck fracture(Garden type Ⅳ).Three-dimensional CT reconstruction of pelvis was taken preoperative and postoperative,and three-dimensional reconstruction model was established after processing by Mimics software.FO,RCH and LLD were measured on the model.The criteria for FO reconstruction were as follows:postoperative bi-lateral FO difference less than 5 mm;the standard for equal length of both lower limbs was as follows:postoperative LLD differ-ence less than 5 mm.Results Bilateral FO difference was positively correlated with LLD(r=0.744,P＜0.00l).Chi-square test was performed between the FO reconstructed group and the non-reconstructed eccentricity group:The results showed that the i-sometric ratio of lower limbs in the FO reconstructed group was significantly higher than that in the FO reconstructed group(x2=6.320,P=0.012).The bilateral RCH difference was significantly negatively correlated with LLD(r=-0.877,P＜0.001).There is a linear relationship between bilateral FO difference and bilateral RCH difference and postoperative LLD,and the lin-ear regression equation is satisfied:postoperative LLD=0.038x-0.099y+0.257(x:postoperative bilateral FO difference,y:post-operative bilateral RCH difference;Unit:cm),F=77.993,R2=0.808,P=0.009.Conclusion After THA,LLD increased with the increase of FO and decreased with the increase of RCH.The effect of lower limb isometric length can be obtained more easily by reconstruction of FO.There is a linear relationship between the bilateral FO difference and the bilateral RCH difference after THA and LLD,and the regression equation can provide a theoretical reference forjudging LLD.

Rheumatoid arthritis(RA)is a type of chronic autoimmune disease with unknown etiology and inflammatory syno-vitis.The occurrence and development of RA are closely related to intestinal mucosal immunity.Imbalance of intestinal flora,impaired intestinal barrier integrity,production of local autoantibodies and changes of immune cells in the lamina propria are all potential risks of RA.We explored the relationship between intestinal mucosal immunity and RA(gut-joint axis)in detail,with respect to provide novel thought and theoretical basis for the treatment of RA.

Exosomes represent a class of nanoscale extracellular vesicles that facilitate the exchange of genetic information among various cells.Alzheimer's disease(AD)stands as a progressive neurodegenerative disorder characterized by its subtle and advan-cing onset,representing the foremost form of dementia lacking effective therapeutic interventions.Notably,investigations have illuminated the involvement of exosomes in the pathogenesis of AD,attributing diagnostic and therapeutic significance to their role,particularly concerning exosomal microRNAs(miRNA).The miRNAs carried by exosomes serve as potential biomarkers for AD,while also exhibiting potential benefits in ameliorating cognitive dysfunction in individuals afflicted by AD.This article aims to comprehensively review the origins of exosomes(encom-passing both mesenchymal cell-derived exosomes and brain-de-rived exosomes)and their potential as therapeutic agents targe-ting AD.