JianHong Zuo

Metabolic reprogramming, particularly the Warburg effect, drives tumor progression not only by supplying energy but also by reshaping the epigenetic landscape through lysine lactylation. The present review summarizes the molecular organization of the lactylation regulatory network, highlighting two distinct writer mechanisms: i) A classical acyl-coenzyme A (acyl-CoA)-dependent pathway mediated by the MYST (MOZ, Ybf2/Sas3, Sas2 and Tip60) family; and ii) a recently described acyl-CoA-independent pathway driven by the metabolic sensors, alanyl-tRNA synthetases 1 and 2. The present review further explains how these ‘writers’, together with specific ‘erasers’ and ‘readers’, convert intracellular lactate accumulation into stable transcriptional programs that support immunosuppression, metabolic plasticity and therapeutic resistance. In addition, the current review discusses emerging therapeutic strategies targeting this axis, shifting from broad lactate metabolism inhibition towards more precise approaches that reduce the off-target toxicity of conventional epigenetic drugs. Finally, the present review outlines lactylation-associated gene signatures as potential biomarkers, providing a framework for the development of metabolic-epigenetic therapies.

Background Fibroblast growth factor18 (FGF18) is a synthetic growth factor that is associated with osteogenesis, chondrogenesis and articular cartilage repair. However, the exact mechanism is still unknown. In this work, we investigated the specific effects of FGF18 on chondrocyte differentiation and osteoarthritis (OA) development. Methods Recombinant FGF18 adenovirus (Ad-FGF18) was constructed to achieve instantaneous efficient expression. Chondrocyte progenitor cells were infected with Ad-FGF18 and subjected to chondrocyte differentiation. Alcian blue staining and chondrocyte differentiation markers’ qRT-PCR were used to evaluate the status of chondrocyte differentiation. Destabilization of the medial meniscus (DMM) surgery was used to construct the OA model. Ad-GFP or Ad-FGF18 was intra-articular injected once a week for 6 weeks. The knee joints were harvested for histological examination. Results FGF18 promoted chondrocyte differentiation by increasing the expression of Sox6, Col2 (Collagen type Ⅱ) and Acan (Aggrecan). In the knee joint of Ad-FGF18 intra-articular injected, there was little cartilage degradation, increased protein levels of COL2 and ACAN, and decreased protein levels of ADAMTS5 (a disintegrin and metallopeptidase with thrombospondin type 1 motif 5) and MMP13 (matrix metalloproteinase 13). Conclusions Our findings reveal that FGF18 promotes the differentiation of chondrocytes and protects articular cartilage from degradation during OA development. This finding provides a potential novel therapeutic approach for cartilage regeneration and treatment of osteoarthritis.

The research on targeted therapy of hypopharyngeal cancer is very scarce. The discovery of new targeted driver genes will promote the progress of hypopharyngeal cancer therapy to a great extent. In our research, whole-exome sequencing in 10 patients with hypopharyngeal cancer was performed to identify single nucleotide variations (SNVs) and insertions and deletions (INDELs). American College of Medical Genetics and Genomics (ACMG) guidelines were used to evaluate the pathogenicity of the selected variants. 8113 mutation sites in 5326 genes were identified after strict screening. We identified 72 pathogenic mutations in 53 genes according to the ACMG guidelines. Gene Ontology (GO) annotation and KEGG enrichment analysis show the effect of these genes on cancer. Protein–protein interaction (PPI) was analyzed by string online software. The validation results of the ualcan database showed that 22 of the 53 genes may be related to the poor prognosis of patients with hypopharyngeal cancer. RBM20 has the most significant correlation with hypopharyngeal cancer, and it is likely to be the driver gene of hypopharyngeal cancer. In conclusion, we found possible therapeutic targets for hypopharyngeal cancer, especially RBM20 and KMT2C. Our study provides a basis for the pathogenesis and targeted therapy of hypopharyngeal cancer.

Risk Factors of Urinary Pathogenic Bacteria Infection after Benign Prostatic Hyperplasia Surgery and Curative Effect Analysis of Shuangdong Capsule Intervention: Benign prostatic hyperplasia (BPH) is a common and frequently occurring disease in clinics, with the main manifestations including frequent micturition, urinary incontinence, dysuria, and endless urination. Transurethral resection of the prostate (TURP) is the main treatment for BPH, but some patients are prone to urinary tract infection after surgery, which affects the prognosis. Therefore, it is of great significance to study the pathogenic characteristics and risk factors of postoperative urinary-derived pathogenic bacteria infection in patients with BPH for the prevention and treatment of postoperative infection. In addition, the treatment of patients with this disease is also the focus of clinical attention. Long-term massive application of antibiotics can induce drug-resistant mutations of bacteria, so it is urgent to find an efficient and safe therapeutic scheme in clinics. However, traditional Chinese medicine (TCM) has a long history of treating urinary tract infections. Therefore, Shuangdong capsule, a traditional Chinese medicine preparation, was selected for the combined treatment in this study. The results showed that age, concomitant diabetes mellitus, and preoperative prophylactic application of antibiotics were the independent risk factors for postoperative urine-derived pathogenic infection in BPH patients. Clinical intervention for BPH patients with concomitant risk factors should be emphasized in clinical practice. The combined use of Shuangdong capsule and conventional western medicine can improve the clinical symptoms and inflammatory reactions of postoperative urine-derived pathogenic infection in BPH patients. Due to its exact curative effect and high safety, it is worthy of promotion. The clinical study registration number is M2022019.

Background: The genome map of hepatocellular carcinoma (HCC) is complex. In order to explore whether circulating tumor cell DNA (ctDNA) can be used as the basis for sequencing and use ctDNA to find tumor related biomarkers, we analyzed the mutant genes of ctDNA in patients with liver cancer by sequencing. Methods: We used next-generation targeted sequencing technology to identify mutations in patients with liver cancer. The ctDNA from 10 patients with hepatocellular carcinoma (including eight cases of primary hepatocellular carcinoma and two cases of secondary hepatocellular carcinoma) was sequenced. We used SAMtools to detect and screen single nucleotide polymorphisms (SNPs) and insertion deletion mutations (INDELs) and ANNOVAR to annotate the structure and function of the detected mutations. Screening of pathogenic and possible pathogenic genes was performed using American College of Medical Genetics and Genomics (ACMG) guidelines. GO analysis and KEGG analysis of pathogenic and possible pathogenic genes were performed using the DAVID database, and protein–protein interaction network analysis of pathogenic and possible pathogenic genes was performed using the STRING database. Then, the Kaplan–Meier plotter database, GEPIA database and HPA database were used to analyse the relationship between pathogenic and possible pathogenic genes and patients with liver cancer. Results: Targeted capture and deep sequencing of 560 cancer-related genes in 10 liver cancer ctDNA samples revealed 8,950 single nucleotide variation (SNV) mutations and 70 INDELS. The most commonly mutated gene was PDE4DIP, followed by SYNE1, KMT2C, PKHD1 and FN1. We compared these results to the COSMIC database and determined that ctDNA could be used for sequencing. According to the ACMG guidelines, we identified 54 pathogenic and possible pathogenic mutations in 39 genes in exons and splice regions of 10 HCC patients and performed GO analysis, KEGG analysis, and PPI network analysis. Through further analysis, four genes significantly related to the prognosis of liver cancer were identified. Conclusion: In this study, our findings indicate that ctDNA can be used for sequencing. Our results provide some molecular data for the mapping of genetic variation in Chinese patients with liver cancer, which enriches the understanding of HCC pathogenesis and provides new ideas for the diagnosis and prognosis of HCC patients.

ALDH1B1 predicts poor survival for locally advanced nasopharyngeal carcinoma patients Tao Zhu, Jun-Yan He, Yan-Ping Liu, Kun Deng, Jian-Hong Zuo, Xiao-Hong Ai

Background: The Genome map of hepatocellular carcinoma (HCC) is complex. We used the next generation of targeted sequencing technology to decipher the mutations in patients with liver cancerMethods: The circulating tumor cell DNA (ctDNA) of 10 patients with hepatocellular carcinoma (Including 8 cases of primary hepatocellular carcinoma and 2 cases of metastatic hepatocellular carcinoma) were sequenced. We used SAMtools to detect and screen single nucleotide polymorphism (SNP) and insertion deletion (INDEL) mutations, and ANNOVAR to annotate the structure and function of the detected mutations.Results: Targeted capture and deep sequencing of 560 cancer-related genes in 10 liver cancer ctDNA samples showed 8950 single nucleotide variations (SNVS) mutations and 70 INDELS. The most common mutation gene was PDE4DIP, followed by SYNE1, KMT2C, PKHD1 and FN1. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, we authenticated 54 pathogenic and possible pathogenic mutations in 39 genes in exons and splice regions of 10 patients with HCC.Conclusion: Our research provides the gene mutation map of Chinese hepatocarcinoma patients, and enriches the understanding of the pathogenesis of HCC.

Background: Whole-exome sequencing has been used in many cancer research, but it is rarely used in Hypopharyngeal carcinoma. In our research, we performed whole-exome sequencing of DNA from 10 tumor tissue specimens from patients with hypopharyngeal cancer rather than targeted sequencing of specific genes.Methods: Whole-exome sequencing in 10 patients with hypopharyngeal carcinoma was performed to identify single nucleotide variations (SNVs) and insertions and deletions (INDELs). American College of Medical Genetics and Genomics (ACMG) guidelines were used to evaluate the pathogenicity of the selected variants. Gene Ontology (GO) and pathway enrichment were used to analyze the function and effect of mutated genes. Protein protein interaction (PPI) was analyzed by string online software.Results: 8113 mutation sites in 5326 genes were identified after strict screening. MEGF8, ITPR1, DYSF, DNAH10, CUL7, MYH14, LRP1, ASTN1, TTN, ASH1L, MYH11, KMT2C were mutated in more than 6 patients. We identified 72 pathogenic or potentially pathogenic mutations in 53 genes according to the ACMG guidelines. GO annotation and KEGG enrichment analysis show the possible effect of these pathogenic genes on cancer. Conclusion: We identified novel mutations in patients with hypopharyngeal cancer, and provided a foundation for future research on the pathogenesis of hypopharyngeal carcinoma and targeted treatment of hypopharyngeal carcinoma.

Purpose As a common head and neck tumor, laryngeal cancer has attracted heightened attention for its treatment and prognosis. Surgery and radiotherapy were mainly therapeutic approaches in laryngeal cancer, and intensity-modulated radiotherapy (IMRT) was a precision treatment way in radiotherapy. However, the therapeutic effect of surgery plus IMRT in laryngeal cancer was rarely reported. This study aims to determine the effect of IMRT on the treatment of patients with laryngeal cancer. Methods A total of 125 patients with laryngeal cancer were collected and retrospectively analyzed based on their clinical data and follow-up results. These patients had a clear treatment plan for surgery and intensity-modulated radiotherapy. Results Smoking, lymph node metastasis, TNM staging and therapeutic approaches could affect the survival of patients with laryngeal cancer. It was shown that the laryngeal function retention rate in the simple IMRT group was significantly higher than the simple surgery group and surgery plus IMRT group. The 5-year survival rate of surgery plus IMRT, simple surgery and simple IMRT were 82.86%, 53.85% and 43.33%, respectively. The locoregional recurrences rate of surgery plus IMRT, simple surgery and simple IMRT were 14.29%, 34.62% and 43.33%. Conclusion Surgery plus IMRT was a feasible and efficacious treatment technique for patients with laryngeal cancer, which effectively prolong the survival time of patients.