Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.

Antimicrobial resistance poses a serious threat to human health and is the main cause for the increase in infection-related mortality.Rational and timely use of antimicrobial agents is crucial for improving the prognosis of infected patients,however,overdose and inappropriate use of antimicrobial agents can accelerate the acquisition of drug resistance of pathogenic microorganisms,promote the emergence of new resistance mechanisms,and ultimately lead to the emergence of"superbugs".Therefore,early identification of antimicrobial resistance is of significant im-portance for the rapid diagnosis and precise treatment of infectious diseases.With the development of molecular dia-gnostic techniques,third-generation sequencing(TGS)technique offers innovative solutions for detecting microbial resistance due to its advantages in long read length,easy operation,and rapid detection,significantly promoting ear-ly diagnosis and real-time monitoring of antimicrobial resistance.This review systematically summarizes the research progress of TGS in microbial resistance detection,analyzes its advantages and limitations in rapid detection of resis-tance in viruses,bacteria,and fungi,thus provides new perspectives for the early diagnosis and treatment of patho-genic microbial infections.

Antimicrobial resistance poses a serious threat to human health and is the main cause for the increase in infection-related mortality.Rational and timely use of antimicrobial agents is crucial for improving the prognosis of infected patients,however,overdose and inappropriate use of antimicrobial agents can accelerate the acquisition of drug resistance of pathogenic microorganisms,promote the emergence of new resistance mechanisms,and ultimately lead to the emergence of"superbugs".Therefore,early identification of antimicrobial resistance is of significant im-portance for the rapid diagnosis and precise treatment of infectious diseases.With the development of molecular dia-gnostic techniques,third-generation sequencing(TGS)technique offers innovative solutions for detecting microbial resistance due to its advantages in long read length,easy operation,and rapid detection,significantly promoting ear-ly diagnosis and real-time monitoring of antimicrobial resistance.This review systematically summarizes the research progress of TGS in microbial resistance detection,analyzes its advantages and limitations in rapid detection of resis-tance in viruses,bacteria,and fungi,thus provides new perspectives for the early diagnosis and treatment of patho-genic microbial infections.

Background and Aims:Patients with end-stage liver disease(ESLD)frequently experience persistent pruritus,which significantly impairs their quality of life.Although relief of pruritus after liver transplantation is often attributed to the normalization of bilirubin levels,the role of skin microbiota in developing pruritus remains unclear.This study aimed to investigate the dynamic changes in skin microbiota during the perioperative period of liver transplantation in ESLD patients and to explore their association with pruritic symptoms.Methods:Fifteen ESLD patients treated in the Third Xiangya Hospital between 2022 and 2023 were enrolled and skin swabs were collected from the anterior tibial region at three time points:before liver transplantation and on postoperative days 7 and 30.Skin samples from 15 age-matched healthy controls were collected at the same anatomical site.Microbial composition was analyzed using 16S rRNA sequencing.Meanwhile,pruritus severity was assessed using a visual analogue scale(VAS),and multiple serological indicators were measured to evaluate correlations between microbiota changes,pruritus severity,and liver function parameters.Results:Compared with healthy controls,ESLD patients exhibited significantly altered β-diversity in skin microbiota and an increased relative abundance of Staphylococcus(LDA>4),which was strongly correlated with VAS scores for pruritus(r=0.93,Padj=3.08×10?1?).On postoperative day 7,α-diversity decreased,and Staphylococcus abundance peaked,then gradually normalized by day 30 as pruritus improved.Further analysis revealed that Staphylococcus abundance was positively correlated with alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin,total bile acids,and international normalized ratio,and negatively correlated with albumin(all Padj<0.05).Notably,Staphylococcus levels were significantly higher in patients with moderate to severe pruritus(VAS score>5).Conclusion:ESLD patients demonstrate marked dysbiosis of the skin microbiota during the perioperative period of liver transplantation,characterized by an abnormal proliferation of Staphylococcus,which may contribute to the development and exacerbation of pruritus.Targeting the skin microbiome,particularly interventions against Staphylococcus,may offer a novel therapeutic strategy for alleviating pruritus in ESLD patients.

Background and Aims:Chronic skin ulcers are a significant disease affecting patients'daily lives and psychological well-being.Abnormalities in the cells and extracellular matrix within the tissue may disrupt the balance of the microenvironment,hindering the normal skin repair process and leading to delayed healing of the ulcer.There is currently a lack of research on the mechanisms underlying the development of chronic ulcers and their diagnostic biomarkers.Single-cell sequencing,a newly developed high-throughput sequencing method in recent years,uses gene sequencing at the single-cell resolution to precisely reveal disease mechanisms and has been applied in various diseases.This study used single-cell transcriptome sequencing(scRNA-Seq)to investigate the cellular heterogeneity in chronic skin ulcer tissue to elucidate the potential molecular mechanisms behind delayed healing and provide new insights for clinical treatment.Methods:The scRNA-Seq technology was used to compare the differences in cell subpopulations and gene expression between chronic ulcer tissue and normal skin tissue.Single cells were sorted using a microfluidic platform,and cDNA libraries were constructed for subsequent differential gene analysis and functional enrichment analysis.Results:scRNA-Seq analysis revealed significant immune-metabolic remodeling features in chronic ulcer tissue:the number of B cells,monocytes,and macrophages in ulcer tissue increased by 2.1 to 3.5 times compared to the normal tissue control.This was accompanied by widespread activation of collagen synthesis genes(COL1A1/COL3A1)and synergistic suppression of immune regulators(e.g.,granzyme family GZMA/GZMB/H).Cross-cell subpopulation functional network analysis showed that hypoxia response mediated by the HIF-1 signaling pathway and PI3K/Akt pathway abnormalities formed a positive feedback loop,exacerbating the imbalance in the secretion of inflammatory factors(CXCL3/8,TGFBI)and compensatory upregulation of mitochondrial oxidative phosphorylation.Conclusion:Chronic skin ulcers exhibit significant differences in cellular heterogeneity and gene expression,suggesting that chronic ulcers are not simply tissue defects but a complex pathological process dominated by chronic inflammation and immune dysregulation.The coordinated dysregulation of multiple cell subpopulations in the ulcer microenvironment,along with persistent inflammatory responses and metabolic abnormalities,is interconnected through the HIF-1/TNF/MAPK pathway network.Downregulation of granzyme gene family members and abnormal histone modifications may contribute to immune clearance defects,providing a theoretical basis for developing novel therapies targeting epigenetic regulation or mitochondrial function.

Background and Aims:Patients with end-stage liver disease(ESLD)frequently experience persistent pruritus,which significantly impairs their quality of life.Although relief of pruritus after liver transplantation is often attributed to the normalization of bilirubin levels,the role of skin microbiota in developing pruritus remains unclear.This study aimed to investigate the dynamic changes in skin microbiota during the perioperative period of liver transplantation in ESLD patients and to explore their association with pruritic symptoms.Methods:Fifteen ESLD patients treated in the Third Xiangya Hospital between 2022 and 2023 were enrolled and skin swabs were collected from the anterior tibial region at three time points:before liver transplantation and on postoperative days 7 and 30.Skin samples from 15 age-matched healthy controls were collected at the same anatomical site.Microbial composition was analyzed using 16S rRNA sequencing.Meanwhile,pruritus severity was assessed using a visual analogue scale(VAS),and multiple serological indicators were measured to evaluate correlations between microbiota changes,pruritus severity,and liver function parameters.Results:Compared with healthy controls,ESLD patients exhibited significantly altered β-diversity in skin microbiota and an increased relative abundance of Staphylococcus(LDA>4),which was strongly correlated with VAS scores for pruritus(r=0.93,Padj=3.08×10?1?).On postoperative day 7,α-diversity decreased,and Staphylococcus abundance peaked,then gradually normalized by day 30 as pruritus improved.Further analysis revealed that Staphylococcus abundance was positively correlated with alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin,total bile acids,and international normalized ratio,and negatively correlated with albumin(all Padj<0.05).Notably,Staphylococcus levels were significantly higher in patients with moderate to severe pruritus(VAS score>5).Conclusion:ESLD patients demonstrate marked dysbiosis of the skin microbiota during the perioperative period of liver transplantation,characterized by an abnormal proliferation of Staphylococcus,which may contribute to the development and exacerbation of pruritus.Targeting the skin microbiome,particularly interventions against Staphylococcus,may offer a novel therapeutic strategy for alleviating pruritus in ESLD patients.

Background and Aims:Chronic skin ulcers are a significant disease affecting patients'daily lives and psychological well-being.Abnormalities in the cells and extracellular matrix within the tissue may disrupt the balance of the microenvironment,hindering the normal skin repair process and leading to delayed healing of the ulcer.There is currently a lack of research on the mechanisms underlying the development of chronic ulcers and their diagnostic biomarkers.Single-cell sequencing,a newly developed high-throughput sequencing method in recent years,uses gene sequencing at the single-cell resolution to precisely reveal disease mechanisms and has been applied in various diseases.This study used single-cell transcriptome sequencing(scRNA-Seq)to investigate the cellular heterogeneity in chronic skin ulcer tissue to elucidate the potential molecular mechanisms behind delayed healing and provide new insights for clinical treatment.Methods:The scRNA-Seq technology was used to compare the differences in cell subpopulations and gene expression between chronic ulcer tissue and normal skin tissue.Single cells were sorted using a microfluidic platform,and cDNA libraries were constructed for subsequent differential gene analysis and functional enrichment analysis.Results:scRNA-Seq analysis revealed significant immune-metabolic remodeling features in chronic ulcer tissue:the number of B cells,monocytes,and macrophages in ulcer tissue increased by 2.1 to 3.5 times compared to the normal tissue control.This was accompanied by widespread activation of collagen synthesis genes(COL1A1/COL3A1)and synergistic suppression of immune regulators(e.g.,granzyme family GZMA/GZMB/H).Cross-cell subpopulation functional network analysis showed that hypoxia response mediated by the HIF-1 signaling pathway and PI3K/Akt pathway abnormalities formed a positive feedback loop,exacerbating the imbalance in the secretion of inflammatory factors(CXCL3/8,TGFBI)and compensatory upregulation of mitochondrial oxidative phosphorylation.Conclusion:Chronic skin ulcers exhibit significant differences in cellular heterogeneity and gene expression,suggesting that chronic ulcers are not simply tissue defects but a complex pathological process dominated by chronic inflammation and immune dysregulation.The coordinated dysregulation of multiple cell subpopulations in the ulcer microenvironment,along with persistent inflammatory responses and metabolic abnormalities,is interconnected through the HIF-1/TNF/MAPK pathway network.Downregulation of granzyme gene family members and abnormal histone modifications may contribute to immune clearance defects,providing a theoretical basis for developing novel therapies targeting epigenetic regulation or mitochondrial function.

To investigate the drug-resistance mutations and treatment of hospitalized children with Mycoplasma pneumoniae pneumonia (MPP) in Hunan Province. Children with pneumonia, who were hospitalized in the pediatric ward of the Second Xiangya Hospital of Central South University from January 1, 2023, to December 31, 2023, were enrolled in this study, and their clinical data was also collected. The targeted next-generation sequencing (tNGS) was used to detect Mycoplasma pneumoniae (MP) infection and drug-resistance mutations, and the drug-resistance and treatment in children with MPP were also analyzed. A total of 125 children with pneumonia were involved in this study, including 70 children in the MPP group and 55 children in the bacterial pneumonia group. The results showed that there were 41 boys and 29 girls with an average age of (6.50±3.45) years, with the most common group being the school-age group (age≥6 years). The clinical symptoms were characterized by fever and cough. Laboratory examination showed that the white blood cell and neutrophil counts in the MPP group were lower than those in the bacterial pneumonia group, while the lymphocyte ratio and hemoglobin levels in the MPP group were higher than those in the bacterial pneumonia group, with statistically significant differences (all P<0.05). Twelve children (17.14%) in the MPP group had severe pneumonia, and all children with severe pneumonia had 23Sr RNA A2063G and/or A2064G mutations. The tNGS detected 60 cases of MPP resistance gene mutations, including 59 cases (98.33%) of A2063G mutation in 23Sr RNA and one case (1.67%) of A2064G mutation in 23Sr RNA. There was a significant difference in the positive rate of drug-resistance mutations among patients of different age groups (χ 2=7.991, P=0.021). A total of 63 children (90.00%) with MPP were treated according to the results of drug-resistance mutations, and seven children (70.00%) with MPP without drug-resistance mutations were treated according to the tNGS results. In children with the drug resistance of MPP, 46 cases (95.83%) of non-severe pneumonia and 10 cases (83.33%) of severe pneumonia were treated according to the tNGS results. All patients had a good prognosis, with no deaths reported and a median hospital stay M ( Q1, Q3) of 9 (7, 11) days. In conclusion, MPP is more common in children aged≥6 years old in Hunan Province, and the detection of drug-resistant mutations includes A2063G and A2064G, with A2063G being the main one. The positive rate of drug-resistant mutations is related to age.

To investigate the drug-resistance mutations and treatment of hospitalized children with Mycoplasma pneumoniae pneumonia (MPP) in Hunan Province. Children with pneumonia, who were hospitalized in the pediatric ward of the Second Xiangya Hospital of Central South University from January 1, 2023, to December 31, 2023, were enrolled in this study, and their clinical data was also collected. The targeted next-generation sequencing (tNGS) was used to detect Mycoplasma pneumoniae (MP) infection and drug-resistance mutations, and the drug-resistance and treatment in children with MPP were also analyzed. A total of 125 children with pneumonia were involved in this study, including 70 children in the MPP group and 55 children in the bacterial pneumonia group. The results showed that there were 41 boys and 29 girls with an average age of (6.50±3.45) years, with the most common group being the school-age group (age≥6 years). The clinical symptoms were characterized by fever and cough. Laboratory examination showed that the white blood cell and neutrophil counts in the MPP group were lower than those in the bacterial pneumonia group, while the lymphocyte ratio and hemoglobin levels in the MPP group were higher than those in the bacterial pneumonia group, with statistically significant differences (all P<0.05). Twelve children (17.14%) in the MPP group had severe pneumonia, and all children with severe pneumonia had 23Sr RNA A2063G and/or A2064G mutations. The tNGS detected 60 cases of MPP resistance gene mutations, including 59 cases (98.33%) of A2063G mutation in 23Sr RNA and one case (1.67%) of A2064G mutation in 23Sr RNA. There was a significant difference in the positive rate of drug-resistance mutations among patients of different age groups (χ 2=7.991, P=0.021). A total of 63 children (90.00%) with MPP were treated according to the results of drug-resistance mutations, and seven children (70.00%) with MPP without drug-resistance mutations were treated according to the tNGS results. In children with the drug resistance of MPP, 46 cases (95.83%) of non-severe pneumonia and 10 cases (83.33%) of severe pneumonia were treated according to the tNGS results. All patients had a good prognosis, with no deaths reported and a median hospital stay M ( Q1, Q3) of 9 (7, 11) days. In conclusion, MPP is more common in children aged≥6 years old in Hunan Province, and the detection of drug-resistant mutations includes A2063G and A2064G, with A2063G being the main one. The positive rate of drug-resistant mutations is related to age.

Objective:To investigate the effect of plasma-derived exosomes on the function of human venous endothelial cells in normal and rheumatoid arthritis patients.Methods:The plasma of healthy controls and rheumatoid arthritis patients was collected, and the surface protein markers were identified by transmission electron microscopy (TEM) and NTA. The effects of exosomes on endothelial cell proliferation and migration and invasion were detected by CCK8, cell scratch, Transwell chamber experiments; real time polymerase chain reaction (RT-PCR). The changes of cell secretion hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) content were detected. The comparison between the two groups was performed by t test. Results:The double concave disc-like cystic vesicles were observed by transmission electron microscopy, nanoparticle tracking analysis (NTA) showed that the diameter was about 50-150 nm. Western blotting showed that the relative molecular weights of flotillin1 and CD81, on the surface of plasma exosomes were 47 000 and 26 000, respectively. Endothelial cell activity decreased with the increase of exosomes concentration, but the difference between the two groups was not significant( t=1.86, P>0.05). Compared with normal human con-exo, ra-exo significantly inhibited endothelial cell migration [(2.24±0.23) vs (1.46±0.13), t=6.60, P<0.05], reduced invasive capacity [(0.673±0.030) vs (0.827±0.030), t=8.11, P<0.05] in patients with rheumatoid arthritis. In addition, the ability to secrete HIF-1a, VEGF cytokines was decreased significantly, the difference was statistically significant [(0.706±0.020) vs (0.908±0.040), t=10.10, P<0.05; (0.692±0.010) vs (0.841±0.020), t=14.90, P<0.05]. Conclusion:The exosomes from plasma may play an important role in RA and vascular injury.