Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent cause of chronic liver disease worldwide, and its intricate pathogenesis presents challenges in the development of new drugs. As a common way of post-translational modification, acetylation regulates protein stability, enzyme activity, and subcellular localization, occurring extensively in MASLD-associated processes such as lipid metabolism, inflammatory response, and oxidative stress. In this paper, we comprehensively review the mechanism of acetylation in MASLD, analyze the expression levels of acetylases in liver tissues of MASLD patients from the gene expression omnibus (GEO), discuss the changes in relevant enzyme expression and mechanisms in animal models, and further explore the feasibility of targeting acetylation for MASLD treatment, in the hope of offering a new perspective for advancing drug discovery in the field of MASLD.

Objective To summarize the diagnosis and treatment of neuronal intranuclear inclusion disease （NIID） with peripheral neuropathy as the initial symptom in a Han Chinese family， and to improve the clinical awareness of this disease through a literature review. Methods A pedigree investigation was performed for a patient with NIID who was admitted to the outpatient service of Department of Neurology， Henan Provincial People’s Hospital， in January 2023， and the clinical and imaging features of the family members were summarized. Various techniques， such as second-generation whole-exome sequencing， third-generation whole-genome sequencing， and PCR capillary electrophoresis， were used for genetic analysis， and a family lineage map was plotted. A literature review was performed to summarize the features of cases with peripheral neuropathy as the initial symptom. Results There were 3 generations and 16 members in this family， among whom 5 had clinical manifestations， 8 underwent blood sampling， and 3 were found to have a GCC repeat expansion mutation in the 5' non-coding region of the NOTCH2NLC gene. The proband was aged 39 years， with the initial symptom of weakness in the extremities， and cranial MRI did not show the characteristic signal of NIID， while electromyography suggested multiple peripheral nerve injuries in the extremities. Genetic testing showed that the proband， his aunt， and his cousin all had a GGC repeat expansion mutation in the NOTCH2NLC gene， with a number of more than 60 repeats （154，144，and 148，respectively）. Conclusion In hereditary peripheral neuropathy， the possibility of NIID should be considered in case of negative results for common pathogenic genes. In addition， third-generation sequencing has a marked diagnostic value in repeat expansion mutation-related disorders.

Objective:To investigate the expression, prognostic value and mechanism of MCM10 in hepatocellular carcinoma (LIHC).Methods:The transcriptome and clinical data of hepatocellular carcinoma were obtained from The Cancer Genome Atlas database, and the rank sum test was used to analyze the expression level of MCM10 in tumor tissues and adjacent tissues. Cox regression analysis was used to analyze the relationship between MCM10 expression level and the survival prognosis of patients with hepatocellular carcinoma. Gene set enrichment analysis (GSEA) was utilized for pathway enrichment analysis between MCM10 high and low group gene expression profiles. The effect of MCM10 knockdown on the proliferation of HepG2 cells was determined by cell counting kit-8 (CCK-8) cell viability assay. The effect of MCM10 knockdown on the expression of G1/S-specific cyclin D1 was detected by Western blot.Results:The expression value of MCM10 in hepatocellular carcinoma was 0.709±0.595, and that in adjacent tissues was 0.077±0.094 ( P<0.0 001). Cox regression analysis showed that high expression of MCM10 was a risk factor and prognostic predictor of overall survival ( HR=1.32, 95% CI: 1.19~1.48) and disease-specific survival ( HR=1.40, 95% CI: 1.22~1.61) in LIHC. GSEA analysis showed that the differentially expressed genes were mainly enriched in cell cycle, p53 signaling pathway and positive regulation of G1-S phase transition, et al. CCK-8 assay showed that MCM10 knockdown could inhibit the proliferation of HepG2 cells. Western blot analysis further confirmed that knockdown of MCM10 expression inhibited the expression of cyclin D1 in HepG2 cells. Conclusions:MCM10 is a risk factor for the prognosis of patients with hepatocellular carcinoma, which can promote the proliferation of hepatoma cells through cyclin D1.

Objective To identify antibody specificity in an elderly patient with hydronephrosis accompanied by ureter-al stones and shock who had multiple antibodies.Methods Microcolumn gel method was used to screen unexpected anti-bodies of red blood cells and identify antibodies.Enzyme method and antibody absorption method were used to help judge the specificity of antibodies in patients.The ABO blood type,Rh blood type and MNS blood type of patient were determined by saline tube method.Results The patient′s blood types were O,CCDee,NNss,and a combination of anti-E,anti-c,anti-M and anti-S antibodies was detected.Conclusion Repeated blood transfusion may lead to the presence of one or more un-expected antibodies in patients.Patients with multiple or high-frequency antibodies may experience difficulties in identifica-tion and delayed blood use.

ObjectiveTo explore the mechanism of Jiawei Wendantang in preventing and treating diabetic atherosclerosis by observing the effect of this prescription on the nuclear factor-κB / NOD-like receptor protein 3（NF-κB/NLRP3） pathway and related inflammatory cytokines in rat model of diabetic atherosclerosis. MethodFifty-four SPF-grade rats were randomized into blank， model， atorvastatin （0.9 mg·kg^-1·d^-1）， and high-， medium-， low-dose （18.2， 9.1， 4.55 g·kg^-1·d^-1， respectively） Jiawei Wendantang groups. The rats in other groups except the blank group were modeled for diabetic atherosclerosis by intraperitoneal injection of streptozotocin and feeding with a high-sugar high-fat diet， and those in the blank group were injected with an equal dose of citric acid buffer and fed with a regular diet. The drug administration lasted for 4 weeks， and the blood glucose level in the tail vein was measured every 6 days. After the last administration， the rats were anesthetized for sample collection. Enzyme-linked immunosorbent assay was employed to measure the serum levels of interleukin-18 （IL-18）， C-reactive protein （CRP）， tumor necrosis factor-α （TNF-α）， and intercellular adhesion molecule-1 （ICAM-1）. Western blot was employed to determine the relative protein levels of NF-κB p65， NLRP3， and ICAM-1 in the abdominal aorta. Real-time quantitative polymerase chain reaction was employed to determine the mRNA levels of NLRP3 and interleukin-1β （IL-1β） in the abdominal aorta. The pathological changes in the thoracic aorta were observed by hematoxylin-eosin staining. ResultCompared with the blank group， the model group showed elevated levels of IL-18， CRP， TNF-α， and ICAM-1 in the serum and blood glucose （P<0.05， P<0.01）， up-regulated protein levels of NF-κB p65， NLRP3， and ICAM-1 （P<0.01）， and up-regulated mRNA levels of NLRP3 and IL-1β （P<0.05）. Compared with model group， Jiawei Wendantang lowered the levels of IL-18， CRP， TNF-α， ICAM-1 and blood glucose （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB p65， NLRP3， and ICAM-1 （P<0.01）， and down-regulated the mRNA levels of NLRP3 and IL-1β （P<0.05， P<0.01）. Moreover， Jiawei Wendantang alleviated the pathological injuries in the thoracic aorta. ConclusionJiawei Wendantang may modulate the NF-κB/NLRP3 signaling pathway to reduce the release and adhesion of inflammatory cytokines and regulate the blood glucose level to treat diabetic atherosclerosis.

Objective To investigate the predictive value of perfusion imaging parameters of multi-slice spiral computed tomography (MSCT) for the poor prognosis in patients with osteonecrosis of the femoral head (ONFH). Methods A total of 118 patients with ONFH who were treated in a hospital from May 2022 to May 2023 were selected as the research subjects. All patients received 3D printing guide plate assisted with curettage of necrotic focus combined with ceramic rod implantation. According to the one-year follow-up results, patients were divided into a good prognosis group (n＝94) and a poor prognosis group (n＝24). Baseline data and MSCT perfusion imaging parameters (mean transit time [MTT], blood flow [BF], blood volume [BV]) were compared between the two groups. The correlations of MTT, BF and BV with the severity and prognosis of ONFH were analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of MSCT perfusion imaging parameters for the prognosis of ONFH patients. Results There were significant differences in the necrosis site, necrosis volume and Association Research Circulation Osseous (ARCO) staging between the two groups (P＜0.05). The MTT was shorter, BF was less and BV was less in the poor prognosis group than those in the good prognosis group (P＜0.001). MTT, BF and BV were negatively correlated with necrosis volume and ARCO staging (P＜0.001). Decreased MTT, BF, and BV were independent risk factors for poor prognosis in ONFH patients (P＜0.001). The AUC of the combination of these three parameters for predicting poor prognosis was 0.918, which was significantly better than that of independent parameter (P＜0.05). Conclusions The parameters of MSCT perfusion imaging are closely related to the condition and prognosis of ONFH patients, and are help of predicting the prognosis of ONFH patients.

Objective To explore the clinical efficacy of two procedures in thoracoscopic anterior mediastinal tumor resection. Methods A retrospective study was conducted on patients who underwent thoracoscopic anterior mediastinal tumor resection at the Department of Thoracic Surgery, the 910th Hospital of Joint Logistics Support Force from October 2016 to January 2024. Patients were divided into two groups according to the surgical approach: a modified approach group (bilateral intercostal ports+two subcostal ports) and a classic subxiphoid approach group (one subxiphoid port+two subcostal ports). Perioperative data and postoperative improvement of myasthenia gravis (MG) subgroup were compared between the two groups. Results A total of 55 patients were included, including 27 males and 28 females with a mean age of (49.4±15.1) years. There were 23 patients in the modified approach group and 32 patients in the classic subxiphoid approach group. The modified approach group had shorter operation time [(129.0±20.5) min vs. (148.9±16.7) min, P<0.001], less intraoperative blood loss [(63.0±16.6) mL vs. (75.0±10.8) mL, P<0.001], shorter postoperative drainage tube removal time [(3.1±0.4) d vs. (3.9±0.6) d, P<0.001] and shorter postoperative hospital stay [(4.2±0.4) d vs. (5.0±0.6) d, P<0.001), and lower proportion of intraoperative cardiac dysfunction [4 (17.4%) vs. 14 (43.8%), P=0.040]. There was no statistical difference in maximum diameter of tumor resected [(4.5±1.7) cm vs. (4.0±0.9) cm, P=0.193] and postoperative drainage volume [(396.4±121.5) mL vs. (399.9±161.3) mL, P=0.932]. There was 1 patient of perioperative collateral injury in the modified approach group (pericardial injury), and 6 patients in the classic subxiphoid approach group (1 patient of diaphragm injury, 1 patient of liver contusion, 4 patients of pericardial injury). There was no statistical difference in pain scores at 24 h, 48 h and 72 h after surgery (P>0.05). The postoperative improvement of MG symptoms in the modified approach group was better than that in the classic subxiphoid approach group at 1 year after surgery (complete stable remission rate: 77.8% vs. 50.0%; effective rate: 100.0% vs. 91.6%). No conversion to open chest surgery occurred in either group, and there were no postoperative rehospitalizations or deaths related to surgery within 30 days after surgery in both groups. Conclusion The modified approach is safe and controllable with more open surgical field and more reliable complete resection range than the classic subxiphoid approach group.

Objective:To explore the clinical phenotype and genetic variant in a Chinese pedigree affected with Hunter syndrome and create immortalized cell lines for the affected pedigree members.Methods:A pedigree of six members who had visited Xi′an Children′s Hospital in July 2022 was selected as the study subject. Clinical data was collected. Whole exome sequencing was carried out for the pedigree members. Candidate variant was verified by Sanger sequencing. In addition, peripheral B lymphocytes were transfected with Epstein-Barr virus to create immortalized cell lines, which were then subjected to enzyme activity analysis.Results:The patient, a five-year-and-seven-month-old boy, had exhibited stiff limbs and enlarged joints. He had developed hernia, scaphocephaly, and barrel chest from 3 months of age. His uncle also had stiff limbs, poor hearing, blindness, and right oblique inguinal hernia. Above features had resembled those of Hunter syndrome. Genetic testing revealed that both the child and his uncle had harbored an IDS (NM_000202.8): c. 823G>A (p.D275N) variant, which was unreported previously. Bioinformatic analysis indicated that the D275 to be a highly conserved site, and the D275N variant may affect the stability of the protein′s spatial conformation, thereby decrease the catalytic activity of the enzyme. The successfully constructed immortalized lymphoblastoid cell lines for the child and his parents showed increased volume, irregular shape, burr structure and cluster growth. And the value of IDS activity of the patient′s immortalized lymphoblastoid cells was below the limit of detection. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS3+ PM2_Supporting+ PM5+ PP1+ PP3). Conclusion:Above finding has enriched the phenotypic and mutational spectra of Hunter syndrome, and provided a basis for the genetic counseling for this pedigree. The creation of immortalized cell lines has offered a model for further investigation of the impact of variant on the function of IDS and development of targeted drugs.

Objective:To analyze the clinical characteristics of a child with Congenital disorder of glycosylation due to compound heterozygous variants of COG6 gene ( COG6-CDG). Methods:A child who was admitted to Xi′an Children′s Hospital on January 10, 2023 was selected as the study subject. Clinical data were collected. Pathogenic variants were analyzed by whole exome sequencing, and candidate variants were verified by Sanger sequencing, in vitro experiments and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Xi′an Children′s Hospital (No. 20230101). Results:The child, a 1-month-8-day-old male, was admitted for diarrhea and weight loss for one month. He had presented with cholestasis, diarrhea, facial dysmorphism, poor response, bilateral Simian crease, and brain atrophy. After discharge, he had continued to have high fever, feeding difficulty, and deceased finally. Whole exome sequencing results showed that he had harbored compound heterozygous variants of the COG6 gene, namely c. 807delT (p.F269Lfs*37) and c. 1746+ 1G>C (p.Gly565_Met582del). Sanger sequencing verified that the variants were inherited from his father and mother, respectively. In vitro experiments verified that the c. 1746+ 1G>C variant could affect the mRNA splicing and produce a truncated protein, whilst the c. 807delT variant could significantly reduce gene expression at both mRNA and protein levels. Based on the guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP), the variants were classified as pathogenic (PVS1+ PM3+ PM2_Supporting) and likely pathogenic (PVS1+ PM2_Supporting), respectively. Conclusion:The c. 807delT (p.F269Lfs*37) and c. 1746+ 1G>C (p.Gly565_Met582del) compound heterozygous variants of the COG6 gene probably underlay the pathogenesis of this child. Above finding has enriched the mutational spectrum of COG6-CDG and provided a basis for the genetic counseling for this family.

Objective:To analyze the gene variants of a patient affected with Duchenne/Becker muscular dystrophy in a pedigree and further explore the genotype-phenotype correlation for providing basis for family genetic counseling.Methods:The clinical features and family history of family members were collected.Multiplex ligation-dependent probe amplification(MLPA)was utilized to detect copy number variation of target genes.The pathogenic variations were ana-lyzed by whole exome sequencing(WES).The suspected gene variations were verified by Sanger sequencing.For the splice site mutations,mini-gene was constructed and expressed in vitro to detect the number of transcript and cDNA se-quence.Results:The proband of this family is a male,with no obvious involvement of the lower limbs.Laboratory tests showed an elevated level of creatine kinase(CK)in peripheral blood(700-1600 U/L),and electromyography showed myogenic damage.MLPA did not detect pathogenic exon copy number variation in dystrophin(DMD)gene.Genetic testing showed the proband carried a maternal hemizygotic splicing variation of DMD gene(NM_004006.2):c.2622+2T＞C.An in vitro mini-gene splicing assay confirmed that this splicing mutation could affect RNA splicing.According to clinical features and genetic testing results,the proband was speculated first proof of Duchenne/Becker muscular dys-trophy(DMD/BMD)caused by DMD gene mutation.Conclusion:This study identified the pathogenic variation of a proband with DMD/BMD of DMD gene,which enriched the variation spectrum of DMD/BMD in China.It was con-firmed that the splicing variation of the DMD gene c.2622+2T＞C can produce multiple transcripts leading to different functional impairments,and based on the specificity of temporal and spatial expression,it corresponded to the mild clin-ical manifestations of the patient,providing some reference value for the correlation between genotype and phenotype.