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.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective Our previous studies established that microRNA (miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-Exos) alleviates acute lung injury (ALI). This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy. Methods Exosomes were isolated from hUC-MSCs. Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor. Hematoxylin-eosin staining evaluated inflammatory injury. Enzyme-linked immunosorbnent assay measured lipopolysaccharide (LPS),tumor necrosis factor-α,and interleukin-1β levels. qRT-PCR detected miR-451 and tuberous sclerosis complex 1 (TSC1) expressions. The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system. Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin (mTOR) pathway and autophagy. Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level. Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy. MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1. Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages. Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced. Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.

Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.

Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.

Objective:To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus (GEFS+ ).Methods:Three GEFS+ probands and their pedigree members presented at the Children′s Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects. Clinical data of the pedigrees were collected. Whole exome sequencing was carried out for the probands, and Sanger sequencing was used to verify the candidate variants.Results:Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus. His father, two aunts, grandmother, aunt grandmother, uncle grandfather, and paternal great-grandmother also had onset of febrile seizures at 1 ~ 2 years of age with remission before 6 years old. Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure. His mother, maternal uncle, and maternal grandmother also had febrile seizures before 5 ~ 6 years of age. Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus. His father and grandfather also had febrile seizures plus with remission at 7 ~ 8 years of age. Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A: c. 1613T>C variant, proband 2 had harbored a maternally derived heterozygous SCN1A: c. 2804A>G variant, and proband 3 had harbored a paternally derived heterozygous SCN1A: c. 1271T>C variant. All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (PM1+ PM2_Supporting+ PP1+ PP3+ PP4). Conclusion:The c. 1613T>C, c. 2804A>G and c. 1271T>C variants probably underlay the pathogenesis of GEFS+ in these pedigrees.

Objective:Preliminary explore the safety and efficacy of using only vitamin K antagonists without antiplatelet therapy after left ventricular assist devices (LVAD) implantation.Methods:This is a cohort study. Patients who underwent HeartCon LVAD implantation in TEDA International Cardiovascular Hospital from September 2020 to September 2022 were included. Oral warfarin sodium was given on postoperative days 1 to 2, with the target international standardized ratio (INR) of 2.0 to 2.5. Follow-up until September 2022, survival, INR level and occurrence of bleeding and thrombosis were recorded. Survival analysis was performed by the Kaplan-Meier method (censored for heart transplantation).Results:A total of 22 patients, including 16 male patients (72.7%), aged (51.0±13.3) years, were included. The duration of HeartCon LVAD support was (458±166) days and the INR during support was 2.28±0.26. One patient underwent the heart transplant at 307 d after implantation. One patient (4.5%) occured cardiac tamponade, two patients (9.1%) occured hemorrhagic stroke, five patients (22.7%) occured gastrointestinal bleeding, four patients (18.2%) occured gingival hemorrhage, two patients (9.1%) occured epistaxis, one patient (4.5%) occurred ischemic stroke, one patient (4.5%) occured pump thrombosis, and one patient (4.5%) occured aortic valve thrombosis. The survival rates were 100%, 95%, 95%, and 95% at 3 months, 6 months, 1 year, 2 years after implantation respectively.Conclusion:The single antithrombotic strategy using warfarin (target INR 2.0-2.5) without antiplatelet for patients with implantations of HeartCon type LVAD may be safe and effective.

Objective:To investigate the effects of anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata in repairing destructive wounds and rebuilding function of hands or feet.Methods:This study was a retrospective observational study. From January 2022 to March 2023, 16 patients with destructive wounds in hands or feet combined with extensor tendon defects who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital, including 12 males and 4 females, aged 3 to 63 years. The wounds were located on the hands in 12 cases and on the feet in 4 cases. The number of defective extensor tendon ranged one to five, and the length of the defect ranged from 2.5 to 6.0 cm. The wound area was 11.0 cm×5.5 cm to 29.0 cm×9.5 cm after debridement. The wounds were repaired with anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata, and the flap area was 12.0 cm×6.5 cm to 30.0 cm×11.0 cm. The fascia lata was used to repair the extensor tendon defects, and the harvesting area of fascia lata was 8.0 cm×3.0 cm to 12.0 cm×8.0 cm. The wounds in flap donor areas in 15 patients were sutured directly, and the wound in flap donor area in 1 patient was covered with medium-thickness skin graft from lower abdomen. The survival of flaps and the wound healing in donor and recipient areas of flaps were observed within 1 week after operation. The number of patients who underwent thinning and plastic surgery or tenolysis was recorded during postoperative follow-up. At the last follow-up, the recovery of sensory function of the transplanted flaps on hands or feet was evaluated, the efficacy of flap repair was evaluated according to the comprehensive flap evaluation scale, and the function of hands was evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association. The following two indexes were compared, including the measured total active motion of the injured fingers and the foot function assessed using Maryland foot function scale between before surgery and at the last follow-up.Results:Arterial crisis occurred in flaps in 2 patients after operation, and the flaps survived after timely exploration; the flaps in the rest patients survived well after operation. No obvious scar hyperplasia or ulceration was observed in donor and recipient areas of flaps after operation. All patients were followed up for 8 to 16 months, of which 6 patients underwent flap thinning and plastic surgery 6 to 7 months after operation, and 4 patients underwent tenolysis 3 to 6 months after operation. At the last follow-up, the recovery of sensory function of flaps reached S1 level in 5 cases and S2 level in 11 cases, and the two-point discrimination only had 1 point. The efficacy of flap repair scored 80 to 91, which were evaluated as excellent in 5 cases, good in 9 cases, and acceptable in 2 cases. The hand function was evaluated as excellent in 5 cases, good in 5 cases, and acceptable in 2 cases. The active extension function of the injured finger/toe was reconstructed successfully, and the total active motion of the injured finger was (225±22)° at the last follow-up, which was significantly higher than (117±20)° before surgery ( t=119.59, P<0.05); the foot function score was 86±7 at the last follow-up, which was significantly higher than 29±7 before surgery ( t=222.68, P<0.05), and the foot function was evaluated as excellent in 2 cases, good in 1 case, and acceptable in 1 case. Conclusions:The operation of harvesting the anterolateral femoral perforator flap pedicled with oblique branch of lateral circumflex femoral artery is relatively simple. After the wounds on hands or feet being repaired with the flaps, the appearance and function are good, with no obvious scar hyperplasia in donor and recipient areas of flaps. The fascia lata carried by the flap can repair the extensor tendon defect at the same time and improve the movement of the finger/toe.