Malonylation is an important post-translational modification of proteins.In this work,a comprehensive malonylation proteomics study on hepatocellular carcinoma(HCC)tumorous and non-tumorous tissues using antibody enrichment combined with high performance liquid chromatography-mass spectrometry for discovery of early diagnostic biomarkers or potential new drug targets of HCC was performed.A total of 1299 malonylated peptides containing 1064 malonylated sites were identified from HCC tissues,corresponding to 511 malonylated proteins.Quantitative results showed that 56 and 80 malonylated proteins were up-regulated and down-regulated in HCC tissues,including 60 and 101 malonylated sites,respectively.Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis showed that these differentially modified proteins were involved in various important pathways such as metabolic pathways,fatty acid degradation,and glycolysis/gluconeogenesis.As a key enzyme in glycolysis/gluconeogenesis,phosphoenolpyruvate carboxykinase 1(PCK1)was malonylated at lysine 244(K244)and the malonylation was only detected in HCC tumorous tissues.More importantly,the K244 site served as a binding site for Mn2+and highly conserved across different species.Therefore,it could speculate that the malonylation of K244 would affect its activity and played a role in liver cancer by affecting its binding with Mn2+,which requied further verification through site mutation experiments.Western blot analysis by malonylation pan antibody showed that the malonylation level reduced markedly in HCC tumorous tissues compared with adjacent non-tumorous tissues,which was consistent with mass spectrometry data.In addition,the proliferation and invasion of PLC/PRF/5 cell was significantly inhibited and protein malonylation level was increased obviously when treated with sodium malonate.All the evidence indicated that protein malonylation played an important role in HCC pathogenesis,and its molecular mechanism deserved further investigation.Furthermore,the 136 differentially malonylated proteins provided rich source of candidate targets for further research on HCC pathogenesis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Objective:To provide novel genetic biomarkers for the diagnosis and treatment of sepsis,bioinformatics analysis was used to screen differentially expressed genes and identify Hub genes in sepsis.Methods:Gene Expression Omnibus(GEO)database was used to retrieve gene expression datasets of sepsis and screen for differentially expressed genes(DEGs).Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were used to clarify the molecular mechanism of DEGs,and Hub genes were screened.Results:A total of 361 DEGs were identified,including 163 up-regulated genes and 198 down-regulated genes.Enrichment analysis revealed that these DEGs were primarily involved in antigen processing and presentation,T cell biology,cell adhesion molecules,and T cell receptor signaling pathways.CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1 were determined as optimal diagnostic biomarkers for sepsis.Conclusions:This study elucidated 10 Hub genes(CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1)as potential biomarkers for the diagnosis and treatment of sepsis.However,since the the generalizability of these Hub genes in patients with sepsis remains unvalidated,further experimental verification is still needed in the future.

Objective:To investigate the relationship between serum soluble thrombomodulin(sTM),soluble interleukin-2 receptor(sIL-2R)and short-term prognosis in patients with acute exacerbation chronic obstructive pulmonary disease(AECOPD)combine with type Ⅱ respiratory failure(RF).Methods:251 patients with AECOPD combine with type Ⅱ RF who were admitted to our hospital from April 2021 to April 2024 were selected,the serum sTM and sIL-2R levels of all patients were detected,and the prognosis of 10 d after admission of patients was counted,patients were divided into death group(n=40)and survival group(n=211)according to different prognosis.Influencing factors were analyzed by multivariate logistic regression analysis,predictive value was analyzed by receiver operating characteristic(ROC)curve.Results:Serum sTM and sIL-2R levels in death group were higher than those in survival group(P＜0.05).long course of chronic obstructive pulmonary disease(COPD)and severe RF,high sTM and high sIL-2R were risk factors for death of 10 d after admission of patients with AECOPD combine with type Ⅱ RF(P＜0.05).The area under the curve(AUC)of serum sTM and sIL-2R detection in predicting death of 10 d after admission of patients with AECOPD combine with type Ⅱ RF was 0.801 and 0.810,respectively,the AUC of joint detection of serum sTM and sIL-2R was 0.859,which was higher than that of each index alone.Conclusion:Serum sTM and sIL-2R levels in patients with AECOPD combine with type Ⅱ RF are significantly increase,which are relate to the occurrence of poor prognosis of 10 d after admission,serum sTM and sIL-2R are expect to be used as auxiliary predictive markers for short-term prognosis of patients with AECOPD combine with type Ⅱ RF,and long course of COPD and severe RF,APACHE Ⅱ score are the influencing factors of poor prognosis in patients with AECOPD combine with type Ⅱ RF.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

OBJECTIVE: To investigate the expression and clinical significance of interleukin-10 (IL-10) and interleukin-15 (IL-15) in patients with multiple myeloma (MM). METHODS: Eighty newly diagnosed MM patients in Department of Hematology in Nanyang First People's Hospital from September 2020 to January 2023 were selected as observation group, and 80 healthy people in our hospital were selected as control group. The expression of IL-10 and IL-15 of the two groups were detected, and survival analysis was conducted for the MM patients. RESULTS: The levels of IL-10 and IL-15 in the observation group before treatment were significantly higher than those in the control group (both P <0.05). The levels of IL-10 and IL-15 in different DS stage had significant differences in MM patients (both P <0.05). The levels of IL-10 and IL-15 in stage II and stage III had no significant differences, which were both significantly higher than those in stage I (both P <0.05). The levels of IL-10 and IL-15 in sCR+CR group after treatment were significantly lower than those before treatment (both P <0.05). The levels of IL-10 and IL-15 in VGPR+PR group after treatment were also significantly lower than those before treatment (both P <0.05), but higher than those in the sCR+CR group (both P <0.05). The progression-free survival (PFS) and overall survival (OS) of patients with IL-10>22.01 pg/ml were significantly shorter than those with IL-10≤22.01 pg/ml (both P <0.001). The PFS and OS of patients with IL-15>48.56 pg/ml were also shorter than those with IL-15≤48.56 pg/ml (both P <0.05). CONCLUSIONS The levels of IL-10 and IL-15 in MM patients are closely related to efficacy and prognosis, and both decreased after treatment. The more reduction, the better effect. Patients with IL-10 and IL-15 below the threshold have longer median PFS and OS.
Humans ; Interleukin-10/metabolism* ; Multiple Myeloma/metabolism* ; Interleukin-15/metabolism* ; Prognosis ; Female ; Male ; Middle Aged ; Clinical Relevance

OBJECTIVE: To detect the expression of methyltransferase-like 7B ( METTL7B) in bone marrow specimens of patients with acute myeloid leukemia (AML), and to analyze its influence and significance on clinical diagnosis, treatment, and prognosis of AML patients. METHODS: Bone marrow specimens from 60 newly diagnosed AML patients were collected as the observation group, and bone marrow specimens from 20 iron-deficiency anemia (IDA) patients were collected as the control group. Clinical and pathological data of AML patients were also collected. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the expression of METTL7B in AML patients and IDA patients. Statistical analyses were performed to investigate the relationship between the expression level of METTL7B and clinical-pathological characteristics in AML patients, as well as the impact of METTL7B expression level on efficacy. Kaplan-Meier method was used to analyze the effect of METTL7B expression level on the overall survival time (OS) in AML patients. Meanwhile, a Cox proportional hazards regression model was constructed to identify the factors potentially affecting the prognosis of AML patients. RESULTS: Compared with the control group, the expression level of METTL7B was significantly upregulated in AML patients (P < 0.05). Compared with the low-expression group of METTL7B, the high-expression group had a higher proportion of patients with high white blood cell (WBC) count, poor prognosis, and ineffective treatment, and the differences were statistically significant (P < 0.05). The OS of patients in the high-expression group of METTL7B was significantly shorter than that in the low-expression group (P < 0.05). Multivariate Cox regression analysis showed that high WBC count, poor prognosis in prognosis stratification, and high expression of METTL7B were independent risk factors for the prognosis of AML patients (P < 0.05). CONCLUSION METTL7B is highly expressed in AML patients, and patients with high METTL7B expression exhibit shorter survival and poor prognosis. METTL7B is expected to serve as a new indicator for evaluating the prognosis of AML patients and may develop into a potential target for targeted treatment of AML in the future.
Humans ; Leukemia, Myeloid, Acute/metabolism* ; Prognosis ; Methyltransferases/metabolism* ; Male ; Female ; Middle Aged ; Adult ; Proportional Hazards Models

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies