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.

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: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.

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.

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.

Objective To study the value of high frequency sonography in diagnosis of peripheral nerve lipofibroma hamartoma.Methods The high frequency sonography images of seventeen patients with diagnosed peripheral nerve lipofibroma hamartoma were retrospective analyzed.The sonography features were compared with clinical surgery.Results The position and internal structure of nerve can be found by high frequency ultrasound,and which nerve fascicle,location and scope of lipofibroma hamartoma can be displayed clearly.The involved peripheral nerve was showed expansive growth.Because the hyperechoic fat tissue and hypoechoic nerve fibers alternated with one and another,the feature of high frequency sonography was lotus-like,there was no blood flow signal in nerve.Conclusions High frequency sonography is the preferred imaging method for diagnosis of lipofibroma hamartoma.

Objective To explore the curative effect of the treatment for minor-size tissue defect of forefoot by pedicle fibular side flap of the hallux.Methods The data of 12 patients with minor-size tissue defect of forefoot was retrospectively analyzed who were repaired with fibular side flap of the hallux from September 2003 to June 2012.There were 9 males and 3 females,with an average of 27 years (range,19-55 years).Among them,4 injured on the left,8 on the right side; 3 on the dorsal side and 9 on the plantar.There were 4 cases of traumatic wound,4 of tumor,2 of ulcer,and 2 of scar.Sizes of tissue defect were 1.3 cm×0.5 cm-2.5 cm×2.0 cm,the minimal flap size was 1.5 cm×0.8 cm,and the maximal flap size was 3.0 cm×1.5 cm.All flaps were elevated with fibular side artery and nerve of the hallux,and with width less than 1.5 cm,so wound of donor site could be sutured directly.The postoperative curative effect was assessed from five respects including flap healing,the sensation of the flaps,the flap appearance,the scar and weight-bearing walking.Results This kind of flap all survived successfully in the 12 cases,with satisfying cosmetic effect and sensory,without skin necrosis and blood vessel crisis.Nine patients were followed up for 3-96 months (average,12 months).The flaps were covered with soft and intact normal colored skin,no abrasion or wearing out happened and no subsequent reshaping was needed in the last follow-up.The minor-sized donor site wound could be sutured up directly.Since donor site was selected from non-weight-bearing area,walking and weight-bearing function of the patients were nearly unaffected at all.Sensory of the flaps were normal,with two-point discrimination ranging between 4-10 mm.Conclusion Due to the advantages of thinness,nerve nourishing,constant anatomical position and hidden position of donor site,anterograde fibular side flap of the hallux can be an ideal choice in repairing minor-size tissue defect of forefoot.