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

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 investigate the clinical application of ceftazidime/avibactam(CAZ/AVI)in lung trans-plant recipients with pulmonary infection caused by carbapenem-resistant Gram-negative bacilli(CRGNB),and ana-lyze the factors affecting the prognosis.Methods Lung transplant recipients who had CRGNB pulmonary infection and were treated with CAZ/AVI were included in the analysis.Based on 14-day clinical response,14-day microbial response,and 30-day survival status,the recipients were divided into a clinical response group and a clinical failure group,a microbial response group and a microbial failure group,as well as a survival group and a death group,re-spectively.Univariate analysis was conducted on various data from the two groups.Factors affecting therapeutic ef-ficacy and survival were included in a binary logistic regression model.Independent risk factors for CAZ/AVI anti-infective efficacy and all-cause mortality outcomes were analyzed.Results A total of 43 recipients were included.After 14-day anti-infective treatment,32 recipients(74.42％)achieved clinical response,and 30 recipients(69.77％)achieved microbial response.34 recipients(79.07％)survived 30 days after CAZ/AVI treatment.The Charlson comorbidity index(CCI),proportion of renal dysfunction,and incidence of shock in recipients in the clini-cal response group were all lower than those in the clinical failure group(P＜0.05),while the serum albumin(ALB)level was higher(P＜0.05).The incidence of shock in recipients in the microbial response group was lower than that in the microbial failure group(P＜0.05).CCI,proportion of renal dysfunction,and incidence of shock in recipients in the survival group were all lower than those in the death group(all P＜0.05),while ALB level was higher during treatment period(P＜0.05).Multivariate analysis of 14-day clinical response and 30-day survival showed that higher CCI was an independent risk factor affecting 14-day clinical response of recipients(OR=2.22,95％CI:1.07-4.63),while lower ALB levels(OR=0.72,95％CI:0.54-0.98)and higher CCI(OR=5.27,95％CI:1.18-23.58)were independent risk factors for 30-day all-cause mortality in recipients with pulmonary in-fection after lung transplant.Conclusion CAZ/AVI may be an effective drug for treating pulmonary infection caused by CRGNB in lung transplant recipients.Higher CCI is an independent risk factor for 14-day clinical failure in recipients after CAZ/AVI treatment.Lower ALB level and higher CCI are independent risk factors for increased 30-day mortality in recipients.

Renal leiomyosarcoma is an extraordinarily rare malignant neoplasm，accounting for less than 1% of all renal malignancies. The prevention and management of postoperative thrombotic and hemorrhagic complications are pivotal in improving patient outcomes. We presented a case of a 62-year-old female with a giant right renal leiomyosarcoma（FNCLCC grade 3）who underwent preoperative arterial embolization followed by radical nephrectomy. On postoperative day 4，the patient developed deep vein thrombosis of the lower extremities. During subsequent anticoagulation therapy，she experienced a life-threatening complication of subcapsular hepatic hematoma. Discontinuing anticoagulation，bed rest，active blood transfusion，and antibiotic prophylaxis for infection being used as conservative treatment，the patient demonstrated significant clinical improvement and discharged after full recovery.

Objective:To explore the clinical effects of sequential treatment of extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defects by free transplantation of anterolateral thigh perforator flap combined with bone transport.Methods:This study was a retrospective observational study. From April 2020 to January 2024, 8 patients with extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defects who met the inclusion criteria were admitted to Beijing Dawanglu Emergency Rescue Hospital. Among them, there were 6 males and 2 females, aged 17 to 58 years. After debridement, the area was 17 cm×8 cm to 30 cm×12 cm, and the length of tibial defect was 9 to 12 cm. Stage Ⅰ surgery was performed by free transplantation of anterolateral thigh perforator flap to repair the extensive skin and soft tissue injuries of the lower leg and using autologous skin graft from the thigh to repair the remaining wound. Stage Ⅱ surgery was performed after wound healing, the external fixation bracket was removed and replaced with an Orthofix unilateral external fixation lengthening frame (hereinafter referred to as external fixation lengthening frame) to transport the proximal tibial osteotomy for repairing the large segmental bone defects. The intraoperative arteriovenous anastomosis and the blood supply of the flap during stage Ⅰ surgery were documented, along with the survival status of the flap/skin graft in the donor and recipient areas postoperatively, and the wound healing time in the recipient area. The time required for bone transport completion, the duration of external fixation retention, and the occurrence of complications during this period were recorded after stage Ⅱ surgery. During follow-up, the occurrence of adverse events in the recipient area was recorded. At the final follow-up, fracture healing of the affected limb was evaluated according to the Paley score, and limb function was observed.Results:In 2 patients, the descending branch of the lateral circumflex femoral artery and the accompanying vein were end-to-end anastomosed with the proximal anterior tibial or posterior tibial artery and vein for antegrade blood supply and antegrade reflux; in 2 patients, the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal anterior tibial artery for retrograde blood supply, and the accompanying vein of the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the proximal anterior tibial vein for antegrade reflux; in 3 patients, the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal posterior tibial artery for retrograde blood supply, and the accompanying vein of the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal posterior tibial vein for retrograde reflux; one patient underwent repair of the injury in the affected lower leg using a free cross-leg vascular pedicle flap from the healthy limb. The flaps/skin grafts in the donor and recipient areas of all 8 patients survived, and the wound healing time in recipient area was 14 to 30 days. The bone transport duration of the patients in this group was 93 to 125 days, and the external fixation lengthening frame was continuously retained for 7 to 14 months after the bone transport was stopped; during the bone transport period, 1 patient had pin tract infection, which was controlled after dressing change and enhanced nursing. During the follow-up, there was no ulceration of the wound surface in recipient area, and no osteomyelitis or fracture developed in the affected limb. At the last follow-up, the bone healing evaluation was all excellent; the walking posture and function of the affected limb were basically normal.Conclusions:The application of free transplantation of anterolateral thigh perforator flap combined with bone transport in the sequential treatment of extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defecst can achieve wound healing and functional reconstruction of bone defects, and has great clinical application value.

Objective To rvaluate the therapeutic efficacy of balloon-dilatation covered stents in the treatment of renal artery stenosis(RAS).Methods The clinical data of 30 patients with RAS,who received intravascular ultrasonography(IVUS)-guided LifeStream balloon-dilatation covered stent implantation at the Affiliated Central Hospital of Dalian University of Technology(Dalian Municipal Central Hospital)of China from August 2022 to December 2023,were retrospectively analyzed.The various parameters of the lumen and the stent were measured,and the performance of the stent was evaluated.Results The minimum original blood vessel diameter below the base of the stenotic segment plaque was 5.40(5.17,5.80)mm and the maximum blood vessel diameter was 6.20(5.80,6.93)mm,which became 6.00(5.80,6.00)mm and 7.90(6.00,8.00)mm respectively after stent release,the differences were statistically significant(both P＜0.05).Before stent release the luminal eccentricity index was(14.72±9.37)％,which was(1.54±9.16)％after stent release,the difference was statistically significant P＜0.05).The instant stent symmetry after stent release was(82.69±14.61)％,and the stent expansion factor was(99.81±10.70)％.Ideal narrow coverage rate was obtained.During operation,poor stent adhesion occurred in 2 patients and renal artery rupture with bleeding occurred in one patient,which were solved after immediate re-expansion treatment.Spearman's correlation analysis showed that stent symmetry,stent expansion factor,and stent eccentricity index did not linearly correlate with the lumen cross-sectional area stenosis rate and the plaque eccentricity index(all P＞0.05).Conclusion For the treatment of RAS,the LifeStream balloon-dilatation covered stent is clinically safe,feasible,and effective with satisfactory immediate clinical outcomes.

This article summarizesd Professor Li Zhigang's experience in treating limb dysfunction after acute disseminated encephalomyelitis(ADEM)by acupuncture.Prof.Li respected the classical theory of Chinese medicine,which is to seek the root cause of the disease,clarified the disease mechanism of"deficiency of Yangming leads to longitudinal tendons and unfavorable belt veins",and followed the principle of"treating flaccidity syndrome only by taking advantage of Yangming",and combined with the morbidity characteristics of ADEM that occurs in children,emphasized the important influence of regulating the root of innate and acquired in the treatment of the disease.The importance of regulating the essence of congenital and acquired constitution in the treatment of this disease was emphasized,taking into account the importance of regulating the mind and spirit.The main acupoints of Yangming Stomach Meridian,Large Intestine Meridian,Spleen Meridian,and Governor Vessel,together with the five main points of the lower limbs and the main points of water-inducing,all together play the role of tonifying the middle energizer,benefiting the essence and filling in the marrow,and strengthening the muscles and bones.

Objective:To investigate the awareness of medical staff on pharmacovigilance and the current situation of the construction of pharmacovigilance system in medical institutions.Methods:A self-designed questionnaire was sent to medical institutions in China through Professional Committee on Pharmacovigilance Research, China Society for Drug Regulation in the form of Wechat, and medical staff participated voluntarily. The contents of the questionnaire included 23 questions in 4 dimensions, including the basic information of the respondents, their understanding of the concept and regulations of pharmacovigilance, the management of pharmacovigilance, and the reporting and feedback of adverse drug reactions(ADRs)/events in their medical institutions. The survey time was from August 18, 2023 to October 18, 2023. The data from the questionnaire were analyzed descriptively.Results:The collected questionnaires were from medical institutions in 31 provinces, autonomous regions, and municipalities directly under the central government, with a total of over 100 questionnaires collected in each region. A total of 10 991 medical staff participated in the survey, including 5 504 pharmacists, 2 120 doctors, and 3 367 nurses. Among them, 10 131 (92.18%) respondents had heard of pharmacovigilance, 4 511 (41.04%) had participated in pharmacovigilance-related works, 9 368 respondents (86.41%) answered that the ADRs monitoring and management system had been established in medical institutions where they worked, 8 186 respondents (75.51%) answered that leading group for pharmacovigilance (including ADRs monitoring) had been set up in the medical institutions where they worked, 8 605 respondents (79.37%) answered that the pharmacovigilance works was managed by special personnel in the institutions where they worked, 7 859 (72.49%) answered that there were liaison officers in the clinical departments where they worked, 6 043 (55.74%) answered that the individuals would be rewarded for reporting ADRs, 4 809 (44.36%) answered that pharmacovigilance had been included in the daily works and assessment indicators of the departments, and 5 351 (49.36%) answered that reports of ADRs were reviewed by special personnel. Active reporting by medical staff was the main collection channel of ADRs, 3 391 (31.28%) answered they had actively captured ADRs from the hospital information system, and 7 728 (71.28%) answered they had reported ADRs through the hospital information system, 10 061 (92.81%) answered that the monitoring results of ADRs would be regularly fed back in the hospitals where they worked, and 6 239 (57.55%) answered that regular training on pharmacovigilance for all medical staff would be provided in the institutions where they worked.Conclusions:Medical staff have generally heard of pharmacovigilance and are aware of the national pharmacovigilance system, but they still have insufficient understanding of the concept and regulations of pharmacovigilance. The degree of participating in pharmacovigilance works of medical staff in different regions are different. The monitoring and management of ADRs could be paid attention to in the most medical institutions, but the degree of improvement of pharmacovigilance system in different levels of medical institutions is different.