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.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Objective:To compare the efficacy of subfascial and extrafascial anterior quadratus lumborum block (AQLB).Methods:This study included two trials. TrialⅠ This trail was a retrospective study. The images of patients undergoing abdominal CT examination from January to December 2023 were retrospectively analyzed in the picture archiving and communication system of the Affiliated Hospital of Jiangsu University. One hundred adult patients with no musculoskeletal disorders or history of thoracolumbar surgery were randomly selected, and the anatomical relation between the quadratus lumbar muscle (QLM) and psoas major muscle (PMM) at the L 4 level was observed. Trial Ⅱ This trail was a prospective study. Twenty American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ male patients, aged 18-65 yr, with a body mass index of 18-25 kg/m 2, who underwent elective unilateral AQLB lower abdominal surgery in Affiliated Hospital of Jiangsu University from January to February 2024, were included and divided into subfascial group and extrafascial group using computer-generated random numbers, with 10 cases per group (5 cases on the left and 5 cases on the right side each). AQLB was performed using 0.375% ropivacaine 30 ml: the injection point for subfascial group was located between the fascia of the QLM and the anterior layer of the thoracolumbar fascia at the L 4 level, while the injection point for extrafascial group was located underneath the fascia of the PMM at the L 4 level. The blocked side of the body was divided into 15 regions using the anatomical landmarks on the body surface. The positive rates of skin sensory block and sensory disappearance of dermatomes in each region were assessed by cold stimulation at 40 min after block. The modified Bromage score was used to evaluate the lower limb motor block at 40 min after block and 1 h after surgery. Results:PartⅠ At the L 4 level, the overlapping of the bilateral QLM and PMM only occurred in 1 patient (1%), the overlapping only appearing on the left side occurred in 1 patient (1%), and the PMM and QLM in the remaining 98 patients (98%) were separated. Part Ⅱ The positive rates in 3, 5, 6 and 8 regions and the sensory disappearance rates of T 7 to T 12 dermatomes were significantly higher in subfascial group than in extrafascial group ( P<0.05). One patient in extrafascial group had a modified Bromage score of 1 on the block side at 40 min after block, and both groups scored 0 at the other time points. Conclusions:QLM and PMM are separated at the L 4 level in most patients. Subfascial AQLB is more effective than extrafascial AQLB in blocking the middle-lower region of the abdominal wall and has no motor block.

Objective:To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly.Methods:A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis.Results:In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene.Conclusions:CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.

Inherited retinal diseases (IRDs) are the major cause of refractory blinding eye diseases, and gene replacement therapy has already made preliminary progress in the treatment of IRDs. For IRDs that cannot be treated by gene replacement therapy, gene editing provides an alternative therapeutic method. Strategies like disruption of pathogenic variants with or without gene augmentation therapy and precise repair of pathogenic variants can be applied for IRDs with various inheritance patterns and pathogenic variants. In animal models of retinitis pigmentosa, Usher syndrome, Leber congenital amaurosis, cone rod cell dystrophy, and other disorders, CRISPR/Cas9, base editing, and prime editing showed the potential to edit pathogenic variations in vivo, indicating a promising future for gene editing therapy of IRDs.

Objective:To analyze the influential factors of hypoalbuminemia in patients with preeclampsia and observe the pregnancy outcomes.Methods:The clinical data of 237 pregnant women with preeclampsia who received treatment in The Sixth Affiliated Hospital of Guangzhou Medical University (Qingyuan People's Hospital) from July 2018 to December 2020 were retrospectively collected and analyzed. These patients were divided into hypoproteinemia (observation group) and no hypoproteinemia (control group) groups according to whether they had hypoproteinemia. The general situation, clinical data, and adverse maternal and infant outcomes were statistically analyzed. Risk factors of hypoalbuminemia were analyzed using a logistic regression model. The predictive efficacy was evaluated using the receiver operating characteristic curve.Results:There were no significant differences in general data between the two groups (all P > 0.05). Multivariate analysis showed that D-dimer ( OR = 1.25, P = 0.004), 24-hour urinary protein ( OR = 1.29, P < 0.001), and total bile acid ( OR = 1.08, P = 0.010) were the independent risk factors for hypoproteinemia in preeclampsia. The predictive efficacy of these three indicators (area under the receiver operating characteristic curve = 0.855, P < 0.001) was greater than that of a single indicator. The incidences of adverse maternal and infant outcomes including placental abruption (9.4%, P = 0.019), liver and kidney dysfunction (34.4%, P < 0.001), pleural and ascitic fluid (28.1%, P = 0.001), fetal intrauterine growth restriction (50.0%, P = 0.001), fundus lesions (6.2%, P = 0.018), HELLP syndrome (9.4%, P = 0.019), mild neonatal asphyxia (15.6%, P = 0.022), severe asphyxia (6.2%, P = 0.049), metabolic acidosis (12.5%, P = 0.001), intrauterine infection (12.5%, P = 0.004), and neonatal hospitalization for more than 20 days (37.5%, P < 0.001) were greater in the observation group compared with the control group. There were no significant differences in postpartum hemorrhage, eclampsia, respiratory distress syndrome, fetal loss, and neonatal death between the two groups (all P > 0.05). Conclusion:D-dimer, 24-hour urinary protein, and total bile acid are independent risk factors for hypoproteinemia in preeclampsia. Patients with preeclampsia complicated by hypoproteinemia have a high risk of adverse maternal and infant outcomes.

Objective To explore the association between lipid profiles and left ventricular hypertrophy in a Chinese general population. Methods We conducted a retrospective observational study to investigate the relationship between lipid markers [including triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL-cholesterol, apolipoprotein A-I, apolipoprotein B, lipoprotein[a], and composite lipid profiles] and left ventricular hypertrophy. A total of 309,400 participants of two populations (one from Beijing and another from nationwide) who underwent physical examinations at different health management centers between 2009 and 2018 in China were included in the cross-sectional study. 7,475 participants who had multiple physical examinations and initially did not have left ventricular hypertrophy constituted a longitudinal cohort to analyze the association between lipid markers and the new-onset of left ventricular hypertrophy. Left ventricular hypertrophy was measured by echocardiography and defined as an end-diastolic thickness of the interventricular septum or left ventricle posterior wall > 11 mm. The Logistic regression model was used in the cross-sectional study. Cox model and Cox model with restricted cubic splines were used in the longitudinal cohort. Results In the cross-sectional study, for participants in the highest tertile of each lipid marker compared to the respective lowest, triglycerides [odds ratio (OR): 1.250, 95％CI: 1.060 to 1.474], HDL-cholesterol (OR: 0.780, 95％CI: 0.662 to 0.918), and lipoprotein(a) (OR: 1.311, 95％CI: 1.115 to 1.541) had an association with left ventricular hypertrophy. In the longitudinal cohort, for participants in the highest tertile of each lipid marker at the baseline compared to the respective lowest, triglycerides [hazard ratio (HR): 3.277, 95％CI: 1.720 to 6.244], HDL-cholesterol (HR: 0.516, 95％CI: 0.283 to 0.940), non-HDL-cholesterol (HR: 2.309, 95％CI: 1.296 to 4.112), apolipoprotein B (HR: 2.244, 95％CI: 1.251 to 4.032) showed an association with new-onset left ventricular hypertrophy. In the Cox model with forward stepwise selection, triglycerides were the only lipid markers entered into the final model. Conclusion Lipids levels, especially triglycerides, are associated with left ventricular hypertrophy. Controlling triglycerides level potentiate to be a strategy in harnessing cardiac remodeling but deserve to be further investigated.

Objective:To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus.Methods:Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children′s Medical Center and Qingyuan People′s Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal.Results:Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses.Conclusions:Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.