ObjectiveType 2 diabetes mellitus (T2DM) often causes severe hepatic metabolic complications, dominated by metabolic associated fatty liver disease (MAFLD). Persistent hepatic steatosis and oxidative stress further trigger steatohepatitis and progressive liver damage, increasing the mortality risk of diabetic patients. Aerobic exercise effectively improves hepatic lipid metabolism and antioxidant capacity, but poor patient adherence restricts its long-term clinical application. Mitochondrial-derived mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a key peptide regulating insulin sensitivity and hepatic redox homeostasis. This study aimed to explore the protective mechanism of MOTS-c against T2DM-related liver injury and its combined beneficial effect with aerobic exercise via the NRF2/PPARγ signaling axis. This study aimed to investigate whether MOTS-c cooperates with aerobic exercise to alleviate T2DM-associated hepatic oxidative stress and metabolic dysfunction by activating the NRF2/PPARγ axis, and to clarify the molecular and transcriptomic characteristics of their combined intervention. MethodsStable MOTS-c overexpression and knockdown HepG2 cell lines were constructed using lentiviral transfection. An oleic acid-induced cellular lipid accumulation model and NRF2-knockout cell model were applied to verify the NRF2-dependent mechanism ofMOTS-c. Intracellular lipid deposition, triglyceride levels, antioxidant enzyme activities, and the expression of NRF2/PPARγ pathway-related genes and proteins were detected. In vivo, a T2DM rat model with obvious hepatic steatosis was established via a high-fat and high-sucrose diet combined with streptozotocin injection. Model rats received aerobic exercise, MOTS-c intraperitoneal injection, or combined intervention. We detected systemic glycolipid metabolic indicators, hepatic histopathological changes, and the expression of core proteins in the hepatic NRF2/PPARγ axis. Hepatic transcriptomic sequencing was performed to screen differentially expressed genes (DEGs) and enrich key pathways co-regulated by MOTS-c and aerobic exercise. ResultsCellular results showed that MOTS-c overexpression significantly reduced oleic acid-induced lipid deposition, enhanced antioxidant enzyme activity, and upregulated NRF2 and PPARγ expression. Conversely, MOTS-c knockdown aggravated hepatic lipid accumulation and oxidative damage and inhibited NRF2/PPARγ pathway activation. NRF2 knockout completely eliminated the protective effects of MOTS-c on lipid metabolism and redox balance, confirming its NRF2-dependent regulatory mechanism. In T2DM rats, both MOTS-c supplementation and aerobic exercise effectively improved insulin resistance, corrected glycolipid metabolic disorders, and alleviated hepatic steatosis, while consistently activating the hepatic NRF2/PPARγ axis. Compared with single intervention, the combined treatment showed a better improvement trend in hepatic metabolic and oxidative injury, without definitive synergistic effects. Transcriptomic analysis revealed that the co-regulated DEGs of MOTS-c and aerobic exercise were primarily enriched in lipid metabolism and PPAR signaling pathways, with multiple antioxidant and lipid-regulating genes significantly modulated by combined intervention. ConclusionMOTS-c exhibits obvious exercise-mimetic hepatoprotective effects in T2DM. It activates the hepatic NRF2/PPARγ axis to strengthen antioxidant defense, stabilize lipid metabolism, and relieve T2DM-associated hepatic steatosis and oxidative damage. Furthermore, MOTS-c produces additive beneficial effects with aerobic exercise, showing a superior intervention trend on diabetic liver dysfunction. This study identifies the NRF2/PPARγ axis as the core mechanism of MOTS-c-regulated hepatic protection, elucidates the transcriptomic basis of combined intervention, and provides a reliable theoretical basis and potential therapeutic target for clinical intervention in T2DM-complicated MAFLD.

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Acute kidney injury (AKI) is one of the common critical illnesses characterized by a higher incidence, poor prognosis and limited effective therapeutics in clinical practice. Early diagnosis, etiologic differentiation and prognostic evaluation are crucial for improving outcomes and key components of integrated AKI management. However, the lack of ideal markers and intervention targets poses significant challenges in these aspects. Klotho, a protein predominantly synthesizes and secretes by renal tubular epithelial cells, has been shown to exert various protective effects on the kidney. Recent evidence suggests that abnormal Klotho levels are implicated in the pathogenesis and development of AKI, and hold promise for application in early diagnosis, etiologic recognition, and prognostic evaluation of AKI. Additionally, administration of exogenous Klotho protein or upregulation of endogenous Klotho expression has demonstrated preventive and therapeutic efficacy against AKI caused by a variety of etiologies. This paper reviewed the alterations in Klotho levels during AKI and evaluated its potential role in enhancing the integrated diagnosis and treatment of AKI.

TAFRO syndrome is an idiopathic systemic inflammatory disease that overlaps with idiopathic multicentric Castleman disease (iMCD). The clinical features of TAFRO syndrome include thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis/renal insufficiency (R) and organomegaly (O). The paper reports a special clinical subtype of iMCD—TAFRO syndrome in a patient, manifested as multiple-system involvement including serous effusion (ascites), fever, thrombocytopenia, anemia, multiple lymphadenopathies, pancreatitis and renal insufficiency. Bone marrow biopsy pathology showed active bone marrow hyperplasia. Renal biopsy revealed renal thrombotic microangiopathy, acute renal tubular interstitial injury combined with chronic lesions. Lymph node biopsy demonstrated lymphoproliferative lesions consistent with Castleman disease (hyaline vascular type). Following diagnosis, glucocorticoids, tacrolimus, rituximab and lenalidomide were administered, resulting in significant symptomatic improvement: ascites disappeared, and urinary findings, erythrocyte counts, renal function and hematological indexes normalized. The paper describes the patient's clinical manifestations, diagnosis and treatment process, and prognosis, and reviews relevant literature, to improve clinicians' understanding of this rare disease.

OBJECTIVE To investigate the current status of cleaning and disinfection of medical bedding items in public medical institutions of Liangshan ethnic minority area and analyze the risk of infections so as to provide ba-ses for optimizing the infection control strategies in the ethnic minority area.METHODS On the basis of question-naire survey,onsite sampling method and bacterial isolation and identification technique,a cross-sectional survey was conducted for the current status of cleaning and disinfection of medical bedding items in 15 different grades of public medical institutions of Liangshan ethnic minority area by stratified random sampling method from Sep.2021 to Sep.2023.RESULTS A total of 66 valid questionnaire were recycled,and 540 bedding item samples were col-lected.Totally 93.33％of the medical institutions relied on laundries for centralized cleaning of the medical bed-ding items.The implementation rates of management items such as policy formulation(100.00％)and pre-job training were remarkably higher in the tertiary hospitals than in the secondary and primary hospitals(allP＜0.05).There were no significant differences in the qualified rates of surveillance of microbiological indexes for the medical bedding items among the medical institutions,the qualified rate of surveillance of microbiological inde-xes was highest(71.30％)in the general hospitals and was lowest(61.11％)in the infectious diseases specialized hospital.The qualified rate of surveillance of microbiological indexes was lowest(3.33％)in pediatrics department or internal medicine department,and it raised most remarkably(80.00％)after the disinfection,and there was significant difference(x2=36.274,P＜0.001).CONCLUSIONS The current status of disinfection of the medical bedding items is not optimistic in the medical institutions of Liangshan ethnic minority area.There are the prob-lems such as imperfect system,insufficient equipment and absence of personnel training.It is necessary to com-plete the execution and supervision system for cleaning and disinfection standards,increase the cleaning facilities,promote the use of antibacterial textile and bring in smart management system so as to improve the cleaning and disinfection quality and reduce the risk of hospital-associated infections.

Objective To analyze the monitoring of healthcare-associated infection(HAI)in the intensive care unit(ICU)over the past 12 years based on Joinpoint regression model,and evaluate the trend changes and relevant fac-tors of HAI incidence.Methods ICU patients in a tertiary first-class hospital from January 2012 to December 2023 were selected and performed prospective monitoring.Trend changes of HAI incidence and the correlation with con-sumption of hand hygiene products as well as HAI management measures were analyzed.Results From 2012 to 2023,6 929 ICU patients were included in the monitoring,543 patients had 655 episodes of HAI,with incidence and case incidence of HAI being 7.84％ and 9.45％,respectively.The average severity of the disease was 3.62,and the adjusted HAI incidence was 2.17％.The daily incidence of ventilator-associated pneumonia(VAP),cathe-ter-associated urinary tract infection(CAUTI),and central line-associated bloodstream infection(CLABSI)were 6.19‰,3.45‰,and 1.23‰,respectively.The consumption of hand hygiene products was 122.98 mL/bed-day.The compliance rate and correct rate of hand hygiene were 90.63％and 90.46％,respectively.From 2012 to 2023,incidence of HAI(51.29％vs 4.39％),case incidence of HAI(72.41％vs 4.94％),the adjusted incidence of HAI(15.98％vs 1.04％),daily incidence of VAP(22.50‰ vs 4.33‰),daily incidence of CAUTI(14.23‰ vs 1.64‰),and daily incidence of CLABSI(10.60‰ vs 0.20‰)all decreased significantly(all P＜0.05).Both con-sumption of hand hygiene products(75.16 mL/bed-day vs 147.35 mL/bed-day)and correct rate of hand hygiene(85.00％vs 90.28％)increased significantly(both P＜0.05).A total of 1 946 pathogens were detected,with an increase in the proportion of Staphylococcus aureus(1.30％ vs 9.57％)and a decrease in the proportion of fungi(11.04％vs 1.74％).The daily consumption of hand hygiene products negatively correlated with the incidence of HAI,the case incidence of HAI,as well as the daily incidence of CAUTI and CLABSI(all P＜0.05).Incorpora-ting HAI real-time monitoring system and HAI management into performance assessment could decrease HAI-rela-ted incidence(P＜0.05).Conclusion HAI-related incidence presents a downward trend.Scientific and comprehen-sive HAI prevention and control management measures such as healthcare workers'hand hygiene management,on-line HAI real-time monitoring system,and incorporating HAI management into performance assessment can de-crease HAI-related incidence and promote the improvement of medical quality.