ObjectiveTo screen for and validate key differentially expressed proteins in serum of patients with metabolic dysfunction‑associated fatty liver disease （MAFLD）， and to provide a basis for identifying diagnostic biomarkers and developing intervention strategies for this disease. MethodsA total of 20 patients who were diagnosed with MAFLD in the third affiliated hospital of Chengdu University of Traditional Chinese Medicine from December 2024 to January 2025 were enrolled as MAFLD group， and 20 healthy controls were enrolled as HC group. Demographic data and serum biochemical parameters were collected from both groups. Data-independent acquisition （DIA） quantitative proteomics was used to measure the relative expression levels of serum proteins， and related methods were used to obtain significantly differentially expressed proteins， including the gene ontology functional enrichment analysis， the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis， protein-protein interaction （PPI） network， Hub node interaction， and weighted gene co-expression network analysis （WGCNA）. Rats were given a high-fat diet to establish a model of MAFLD， and randomly assigned to the control group and model group. Serum biochemical parameters and inflammatory factors were measured， liver histopathological changes were observed， and the protein expression levels of MER proto-oncogene tyrosine kinase （MERTK） and matrix metalloproteinase-9 （MMP-9） in liver tissue were verified. The independent-samples t test was used for comparison of normally distributed continuous data between groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or data with heterogeneity of variance between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsCompared with the HC group， the MAFLD group had significant increases in the serum levels of aspartate aminotransferase （t=-7.348， P<0.05）， alanine aminotransferase （Z=5.088， P<0.05）， alkaline phosphatase （t=-3.943， P<0.05）， triglyceride （Z=2.070， P<0.05）， and high-density lipoprotein cholesterol （t=3.867， P<0.05）. A total of 3 559 proteins were identified by DIA serum proteomics， among which 160 differentially expressed proteins were mainly enriched in pathways including metabolic disorders， immune inflammatory response， and extracellular matrix remodeling. The PPI network and the Hub node analysis showed that serpin family E member 1， MMP-9， and intercellular cell adhesion molecule-1 were core regulatory proteins. WGCNA showed that the MEyellow module was significantly positively correlated with MAFLD phenotype （cor=0.55， P<0.001）， which was functionally enriched in the efferocytosis pathway. MERTK （P<0.001） and MMP-9 （P<0.001） showed the most significant differential expression in this module. A rat model of MAFLD was successfully established using a high-fat diet， and compared with the control group， the model group had enlarged， yellowish， and greasy liver and disordered structure of hepatic lobules， hepatocyte fatty degeneration， and inflammatory cell infiltration based on HE staining， as well as massive lipid droplet deposition based on oil red O staining， while no obvious fibrous cords were observed in Masson staining. Compared with the control group， the model group had significant increases in the serum levels of aspartate aminotransferase （t=-5.148， P<0.05）， alanine aminotransferase （t=-5.663， P<0.05）， total bilirubin （t=-13.061， P<0.05）， triglyceride （Z=-2.722， P<0.05）， total cholesterol （t=3.588， P<0.05）， and tumor necrosis factor-α （t=-16.741， P<0.05）， as well as significant increases in the protein expression levels of MERTK （t=-11.448， P<0.001） and MMP-9 （t=-10.875， P<0.001） in liver tissue. ConclusionMMP-9 and MERTK are abnormally expressed in MAFLD and may be used as potential diagnostic biomarkers for this disease.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)followed by hepatic arterial infusion chemotherapy(HAIC)combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July,2020 and June,2023.23 of the patients received TACE combined with HAIC and TKI(TACE+HAIC+TKI group)and 47 received TACE combined with HAIC,PD-1 inhibitors and TKI(TACE+HAIC+PD-1+TKI group).The clinical characteristics,laboratory test results,efficacy,outcomes and adverse events of the patients were compared between the two groups.Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates(ORR;60.87%vs 36.17%,P=0.031),comparable disease control rates(95.65%vs 93.62%,P=0.068),and different median progression-free survival(PFS)time(10.2 vs 11.8 months,P=0.003)and median overall survival(OS)time(15.7 vs 19.5 months,P=0.035).After propensity score matching(PSM),the median PFS and OS time of the two groups was 10.1 vs 14.5 months(P=0.024)and 14.2 vs 21.2 months(P=0.221),respectively.The 1-year PFS rates of the 2 groups were 24.0%vs 52.2%,and the 1-,2-and 3-year OS rates were 72.3%vs 93.1%,23.9%vs 63.8%,and 23.9%vs 36.5%,respectively.The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group(21.28%vs 0,P=0.025),but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups.Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)followed by hepatic arterial infusion chemotherapy(HAIC)combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July,2020 and June,2023.23 of the patients received TACE combined with HAIC and TKI(TACE+HAIC+TKI group)and 47 received TACE combined with HAIC,PD-1 inhibitors and TKI(TACE+HAIC+PD-1+TKI group).The clinical characteristics,laboratory test results,efficacy,outcomes and adverse events of the patients were compared between the two groups.Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates(ORR;60.87%vs 36.17%,P=0.031),comparable disease control rates(95.65%vs 93.62%,P=0.068),and different median progression-free survival(PFS)time(10.2 vs 11.8 months,P=0.003)and median overall survival(OS)time(15.7 vs 19.5 months,P=0.035).After propensity score matching(PSM),the median PFS and OS time of the two groups was 10.1 vs 14.5 months(P=0.024)and 14.2 vs 21.2 months(P=0.221),respectively.The 1-year PFS rates of the 2 groups were 24.0%vs 52.2%,and the 1-,2-and 3-year OS rates were 72.3%vs 93.1%,23.9%vs 63.8%,and 23.9%vs 36.5%,respectively.The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group(21.28%vs 0,P=0.025),but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups.Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.
Humans ; Pregnancy ; Female ; Lupus Erythematosus, Systemic/pathology* ; Signal Transduction ; N-Acetylneuraminic Acid/metabolism* ; Immunoglobulin G ; Dendritic Cells/pathology*

Objectives:To study the clinical significance of time to positive (TTP) of blood culture for neonatal sepsis.Methods:From August 2016 to June 2019, a retrospective study was conducted in patients with positive blood cultures admitted to the Neonatology Department of our hospital. The patients were assigned into different groups according to the species of pathogen, types of neonatal sepsis and the samples contaminated or not. TTP of different groups were analyzed.Results:A total of 307 cases with positive blood cultures were identified from 10 035 cases with blood culture specimens. Among the 307 cases, 162 were contaminated (the contaminated group) and 145 (1.4%) were diagnosed of neonatal sepsis (the pathogenic group). The proportion of TTP <24 h, 24~<48 h, 48~<72 h and ≥72 h in the 145 sepsis cases were 90.3% (131/145), 7.6% (11/145), 1.4% (2/145) and 0.7% (1/145), respectively. The median TTP was 9.0 h in early-onset sepsis (EOS) group and 11.5 h in late-onset sepsis (LOS) group. The median TTP of the contaminated group was 24.5 (19.9, 30.5)h, which was longer than 11.1 (8.1,16.2)h of the pathogenic group ( P<0.05). The median TTP of Gram (+) group was 14.0 (9.4,18.8)h, which was longer than 9.6 (7.5,11.3)h of Gram (-) group ( P<0.05). The median TTP of fungi group was 32.5 (25.5, 39.0) h, which was longer than 10.6 (8.1, 15.5)h of bacteria group ( P<0.05). Conclusions:Different pathogens has different TTP for neonatal sepsis. If blood culture maintains negative for more than 72 h, empiric use of antibiotics may be discontinued for patients of suspected sepsis without specific clinical manifestations or other lab results.

Objective To study the risk factors of acute bilirubin encephalopathy (ABE) in neonates with severe hyperbilirubinemia (total serum bilirubin ≥ 427.5 μmol/L).Method Clinical information of neonates with severe hyperbilirubinemia admitted to the Neonatal Department of Baoan Maternal and Child Health Hospital in Shenzhen from December 2013 to October 2017 were collected.The enrolled cases were grouped as ABE and the control group (without ABE).The risk factors for ABE were compared between the two groups and the Logistic regression analysis was used to evaluate the independent risk factor.Result A total of 104 neonates were recruited.There were 32 cases in the ABE group and 72 cases in the control group.The level of total serum bilirubin and indirect bilirubin,the ratio of total bilirubin/albumin,the incidence of glucose-6-phosphate dehydrogenase deficiency and metabolic acidosis and sepsis,the rate of using traditional Chinese medicine and the failure of treatment in other hospitals and non-resident population were all significantly higher in the ABE group than the control (P ＜ 0.05).Logistic regression analysis showed that total serum bilirubin (OR =1.013,95％ CI 1.007 ～ 1.020) and sepsis (OR =6.343,95％ CI 1.801 ～22.338) were the independent risk factors for ABE.Conclusion The severe hyperbilirubinemia infants,particularly with sepsis,are at higher risk of developing acute bilirubin encephalopathy.

Objective: To evaluate the impact of primary percutaneous coronary intervention (PPCI) with pre-operative intra-aortic balloon pump (P-IABP) implantation on short and long term prognosis in octogenarian patients of ST-segment elevation myocardial infarction (STEMI). Methods: We performed aretrospectively study in octogenarian STEMI patients treated in our hospital from 2004-01 to 2014-08. The patients were divided into 2 groups: P-IABP group,n=24 and PPCI group,n=73 including 12 patients who received rescue IABP (R-IABP) because of intra- or post-procedural hemodynamic collapse as a subgroup.Major end point events included 1 month and 1-, 2-year post-operative death; major adverse cardiac and cerebral events (MACCE) included 1 month post-operative cardiac shock, new or worsening heart failure (HF), re-infarction and stroke. The predictors causing different endpoint events were identiifed by Cox proportional hazard model analysis. Results: 1 month and 1-, 2-year post-operative death were similar between 2 groups (8.3% vs 16.4%), (16.7% vs 24.7%), (25.0% vs 30.1%) respectively; MACCE incidence was also similar (20.8% vs 30.1%), allP>0.05. Death rates between P-IABP group and R-IABP subgroup were similar at different time points,P>0.05; while MACCE incidence in P-IABP group was lower than R-IABP subgroup (20.8% vs 66.7%),P=0.005 and it was mainly presented by reduced HF occurrence (8.3% vs 41.7%),P=0.003. Coxproportional hazard model analysis indicated that post-operative TIMI lfow<3 grade was the independent predictor for 1 month death (HR=4.79, 95% CI1.59-14.39,P=0.005), complicating diseases as chronic obstructive pulmonary disease, kidney impairment and anemiawere themain independent predictors for 2-year death (HR=3.0, 95% CI 1.37-6.56,P=0.006). Conclusion: PPCI and P-IABP had no signiifcant differencefor short and long term survivalin octogenarianSTEMIpatients. Compared with R-IABP, P-IABP patients had the lower MACC Eincidence at 1 month post-operation .

Objective Our retrospective study was aimed to analyze the clinical significance of microsurgical clipping and intravascular embolization in patients with intracranial aneurysm (IA).Methods Clinical data of 86 patients with IA received treatment at our hospital from February 2010 to November 2014 was retrospectively analyzed.Patients were divided into two groups according to the treatment method, IE group (intravascular embolization,43 cases)and MC group (microsurgical clipping,43 cases).The general information,treatment effect, hospitalization expenses and time and the rate of complication of the patients between two groups were compared.Results There was no sta-tistical difference in general information between two groups (P >0.05).The cure rate of patients in IE group was obviously better than that in MC group (P <0.01).The hospitalization expenses in IE group was lower than that in MC group,and the hospitalization time was shorter than that in MC group,all the differences had statistical significance (P <0.01).The rate of complication in IE group was obviously lower than that in MC group (P <0.01).Conclusion The clinical effect of intravascular embolization was significantly better than microsurgical clipping,which is worth promoting in clinic.

Objective: To make long-term comparison of drug-eluting stent (DES) implantation betweenleft internal mammary artery (LIMA) graft and native vessel in patients with previous coronary artery bypass grafting (CABG).
Methods: A total of 151 patients with anterior wall ischemia because of previous CABG induced LIMA graft lesion who received percutaneous coronary intervention (PCI) in our hospital from 2004-07 to 2012-12 were retrospectively studied. The clinical, coronaryangiography (CAG) and follow-up conditions for DES implantation were analyzed;according to the target vessel, the patients were divided into 2 groups:LIMA group, n=40 and Native vessel (NV) group, which meant all segments of left main to left anterior descending arteries, n=111. Primary end points included target lesion revascularization (TLR), target lesion failure (TLF) as cardiac death, target vessel related non-fatal MI with the composition of TLR and major adverse cardiovascular events (MACE).
Results:The median follow-up time was 30 (10-100) months. The rates of TLR and TLF were similar between 2 groups:(15.0%vs 11.7%, log-rank P=0.65) and (17.5%vs 13.5%, log-rank P=0.63). MACE occurrence in LIMA group was higher than NV group (35.0%vs 18.0%, log-rank P=0.043) which was mainly presented by new non-target vessel revascularization as right coronary artery, left circumlfex and saphenous vein graft(17.5%vs 4.5%, log-rank P=0.014). Cox multivariate analysis indicated that target lesion stent length was the only independent predictor for both TLR (HR=1.03, 95%CI1.00-1.06, P=0.01) and TLF (HR=1.03, 95%CI1.00-1.05, P=0.02);whereas, LIMA-PCI was the only independent predictor for MACE occurrence (HR=3.09, 95%CI1.28-7.60, P=0.012).
Conclusion: The chances of TLR and TLF were similar inpatients with previous CABG by either LIMA or NV, while MACE occurrence was higher in LIMA patients which should be further investigated.

microRNAs combined with specific mRNAs are 19-25 nucleotide-long small-molecule RNA that mediate sequence-dependent post-transcriptional gene expression.Accumulating evidences indicate that microRNAs target critical signal transduction molecules of immune system,and involve in regulation of immune tolerance.Recently,microRNAs have been a potential biomarker,and are widely useded in diagnosis and prognosis of cancer,infectious disease,autoimmune disease,and transplantation.If we can further identify regulatory mechanism of microRNAs and their target genes,which makes possible the successful induction of immune tolerance and exert a huge push on organ transplantation.