Objective To explore the role of DNAJC5B in immunotherapy for esophageal squamous cell carcinoma (ESCC). Methods Using the ESCC dataset from The Cancer Genome Atlas (TCGA) database, genes correlated with DNAJC5B expression were identified through Pearson correlation analysis. Subsequently, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Additionally, single-cell RNA sequencing (scRNA-seq) data were utilized to analyze the expression of DNAJC5B in different T-cell subsets. The prognostic value of DNAJC5B was evaluated using Kaplan-Meier survival curves, receiver operating characteristic curves, and Cox proportional hazards models. Results DNAJC5B was highly expressed in patients with advanced-stage ESCC, particularly in males. GO and KEGG analyses revealed a significant correlation between DNAJC5B expression and immune-related processes, such as the adaptive immune response and cell surface receptor signaling pathways. Single-cell analysis results indicated that DNAJC5B expression was positively correlated with immune function, with DNAJC5B predominantly accumulating in CD8+ T cells. Kaplan-Meier survival curves showed that the median survival time for patients with high DNAJC5B expression was 681 days, significantly shorter than the 1 361 days for patients with low expression (P<0.05). Furthermore, univariate and multivariate independent prognostic analyses demonstrated that DNAJC5B was an independent risk factor, with hazard ratios (HRs) of 3.577 and 4.114, respectively (both P<0.05). Conclusion DNAJC5B may play a crucial immunomodulatory role in ESCC, particularly in regulating CD8+ T-cell function and tumor immune escape. These findings support the potential of DNAJC5B as a biomarker for the treatment and prognostic assessment of ESCC.

Objective To investigate the composition ratios and trends of different etiologies after liver biopsy for patients with unexplained liver diseases.Methods A retrospective analysis was performed for the etiology of 960 patients with unexplained liver diseases who were hospitalized and underwent liver biopsy in The Third Affiliated Hospital of Sun Yat-Sen University from January 2011 to December 2020,and the etiologies were categorized by year and age group.The chi-square test was used for comparison of categorical data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups.Results There was a tendency of increase in the overall composition ratio of unexplained liver diseases over the past decade.The leading diagnosis after liver biopsy was autoimmune liver disease(AILD)in 306 patients(31.9%),followed by nonalcoholic fatty liver disease(NAFLD)in 95 patients(9.9%)and drug-induced liver disease(DILI)in 82 patients(8.5%),and there were still 320 patients with undetermined causes(33.3%).There were significant differences in sex ratio and median age distribution between the patients with different etiologies(sex ratio:χ2=155.36,P<0.001;median age distribution:H=182.48,P<0.001).AILD had been the leading etiology in 2011-2020,and there was a tendency of reduction in the composition ratio of AILD(χ2=24.40,P<0.001).NAFLD accounted for the highest proportion of 17.6%in the adolescent stage,while AILD accounted for the highest proportion of 17.8%,47.3%,and 56.3%,respectively,in the young,middle-aged,and elderly stages.Conclusion There is a tendency of increase in the composition ratio of unexplained liver diseases in patients undergoing liver biopsy,with AILD being the main disease diagnosed after liver biopsy,followed by NAFLD and DILI,but one-third of the patients still have an unclear etiological diagnosis.

AIM:To identify the expression characteristics of transfer RNA-derived small RNAs(tsRNAs)re-sponding to DNA damage in human hepatoblastoma HepG2 cells,and to investigate their potential functions.METHODS:Based on paired HepG2 cells and TP53 gene knockout HepG2 cells,we successfully constructed a DNA damage cellular model using adriamycin(ADR).Transcriptome analysis of small noncoding RNAs was performed to systematically identi-fy a set of tsRNAs responding to ADR and involved in p53 regulation.Functional enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Additionally,after silencing the expression of target tsRNA genes,the biological functions of these tsRNAs in HepG2 cells were initially confirmed through CCK-8 assay and plate colo-ny formation assay.RESULTS:DNA damage induced a set of tsRNAs involved in p53 regulation,among which tRF-5-1(tRF-5_tRNA-Gly-TCC-2-1)and tRF-i-1(tRF i_tRNA-Tyr-GTA-11-1)showed the most significant up-regulation in HepG2 cells(P<0.05).Silencing of either tRF-5-1 or tRF-i-1 gene inhibited the proliferative activity of HepG2 cells(P<0.05).CONCLUSION:A group of tsRNAs responding to DNA damage can be identified in HepG2 cell model,and tsRNAs can promote the proliferative activity of HepG2 cells,suggesting that tsRNAs may play an important role in the de-velopment and progression of liver malignancies.

Objective To investigate the composition ratios and trends of different etiologies after liver biopsy for patients with unexplained liver diseases.Methods A retrospective analysis was performed for the etiology of 960 patients with unexplained liver diseases who were hospitalized and underwent liver biopsy in The Third Affiliated Hospital of Sun Yat-Sen University from January 2011 to December 2020,and the etiologies were categorized by year and age group.The chi-square test was used for comparison of categorical data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups.Results There was a tendency of increase in the overall composition ratio of unexplained liver diseases over the past decade.The leading diagnosis after liver biopsy was autoimmune liver disease(AILD)in 306 patients(31.9%),followed by nonalcoholic fatty liver disease(NAFLD)in 95 patients(9.9%)and drug-induced liver disease(DILI)in 82 patients(8.5%),and there were still 320 patients with undetermined causes(33.3%).There were significant differences in sex ratio and median age distribution between the patients with different etiologies(sex ratio:χ2=155.36,P<0.001;median age distribution:H=182.48,P<0.001).AILD had been the leading etiology in 2011-2020,and there was a tendency of reduction in the composition ratio of AILD(χ2=24.40,P<0.001).NAFLD accounted for the highest proportion of 17.6%in the adolescent stage,while AILD accounted for the highest proportion of 17.8%,47.3%,and 56.3%,respectively,in the young,middle-aged,and elderly stages.Conclusion There is a tendency of increase in the composition ratio of unexplained liver diseases in patients undergoing liver biopsy,with AILD being the main disease diagnosed after liver biopsy,followed by NAFLD and DILI,but one-third of the patients still have an unclear etiological diagnosis.

AIM:To identify the expression characteristics of transfer RNA-derived small RNAs(tsRNAs)re-sponding to DNA damage in human hepatoblastoma HepG2 cells,and to investigate their potential functions.METHODS:Based on paired HepG2 cells and TP53 gene knockout HepG2 cells,we successfully constructed a DNA damage cellular model using adriamycin(ADR).Transcriptome analysis of small noncoding RNAs was performed to systematically identi-fy a set of tsRNAs responding to ADR and involved in p53 regulation.Functional enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Additionally,after silencing the expression of target tsRNA genes,the biological functions of these tsRNAs in HepG2 cells were initially confirmed through CCK-8 assay and plate colo-ny formation assay.RESULTS:DNA damage induced a set of tsRNAs involved in p53 regulation,among which tRF-5-1(tRF-5_tRNA-Gly-TCC-2-1)and tRF-i-1(tRF i_tRNA-Tyr-GTA-11-1)showed the most significant up-regulation in HepG2 cells(P<0.05).Silencing of either tRF-5-1 or tRF-i-1 gene inhibited the proliferative activity of HepG2 cells(P<0.05).CONCLUSION:A group of tsRNAs responding to DNA damage can be identified in HepG2 cell model,and tsRNAs can promote the proliferative activity of HepG2 cells,suggesting that tsRNAs may play an important role in the de-velopment and progression of liver malignancies.

With the increasing life expectancy and lifestyle changes of patients with chronic hepatitis B (CHB), the significance of comorbidities of chronic non-communicable diseases (NCDs) in disease progression and health prognosis of CHB patients is gaining prominence. This study aims to explore the association between CHB and NCDs comorbidities, focusing on the impact of common metabolism-related diseases, such as metabolic syndrome and diabetes, on the health outcomes of CHB patients. We also summarize studies on integrating the management of comorbidities in CHB patients and provide relevant recommendations for effective management. The findings of this study serve as a foundation for understanding the clinical characteristics and prevalence trends, reducing the disease burden of comorbidities among CHB patients, and establishing a comprehensive and coordinated management system for comorbidities.

Objective To investigate the satisfaction degree among medical interns with the effect of infectious diseases online teaching.Methods A questionnaire survey was conducted among 172 interns from a 5-year clinical medicine program who were doing internship with infectious diseases in the Third Affiliated Hospital of Sun Yat-Sen University in the spring and fall semesters of 2022.The survey aimed to investigate the advantages and disadvantages of online teaching for medical interns com-pared with traditional offline teaching.Results In terms of the advantages,online internship online teaching saved commuting time among 95.4％(164/172)of the students,enhanced self-management ability among 41.9％(72/172)of the students,en-riched teaching elements among 71.5％(123/172),promoted reviewing and consolidation of clinical knowledge among 38.4％(66/172)of the students.As regarding the disadvantages,online internship decreased clinical situational experience among 83.7％(144/172)students,reduced teaching-student interactions among 76.2％(131/172)of the students,decreased learn-ing efficiency among 51.7％(89/172)of the students and lowered quality of learning among 59.3％(102/172)of the students due to frequent network inefficiency.For prospection,37.8％(65/172)of the students expressed their wish to resume the tradi-tional offline teaching model continue and 57.6％(99/172)of them suggested that the combination of online and offline teaching mode should be adopt.Conclusion The inevitability and possibility of online internship of infectious diseases are gradually in-creasing.Compared with offline internships in infectious disease,students welcome a hybrid model of internships that combines online and offline models.

After implantation, complex and highly specialized molecular events render functionally distinct organ formation, whereas how the epigenome shapes organ-specific development remains to be fully elucidated. Here, nano-hmC-Seal, RNA bisulfite sequencing (RNA-BisSeq), and RNA sequencing (RNA-Seq) were performed, and the first multilayer landscapes of DNA 5-hydroxymethylcytosine (5hmC) and RNA 5-methylcytosine (m⁵C) epigenomes were obtained in the heart, kidney, liver, and lung of the human foetuses at 13-28 weeks with 123 samples in total. We identified 70,091 and 503 organ- and stage-specific differentially hydroxymethylated regions (DhMRs) and m⁵C-modified mRNAs, respectively. The key transcription factors (TFs), T-box transcription factor 20 (TBX20), paired box 8 (PAX8), krueppel-like factor 1 (KLF1), transcription factor 21 (TCF21), and CCAAT enhancer binding protein beta (CEBPB), specifically contribute to the formation of distinct organs at different stages. Additionally, 5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes. Our integrated studies reveal a putative essential link between DNA modification and RNA methylation, and illustrate the epigenetic maps during human foetal organogenesis, which provide a foundation for for an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.
Humans ; DNA Methylation ; RNA ; Epigenesis, Genetic ; DNA/genetics* ; Basic Helix-Loop-Helix Transcription Factors/genetics*

OBJECTIVES: Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied, but there is a lack of effective strategies and drugs for the treatment of tumor metastases. Here, we describe a functional product based on a combination of compounds, which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases, improving anti-cancer treatment, and enhancing immunity and antioxidant capacity. Our designed combination, named MVBL, consists of four inexpensive compounds: L-selenium-methylselenocysteine (MSC), D-‍α‍-tocopheryl succinic acid (VES), β‍-carotene (β‍-Ca), and L-lysine (Lys). METHODS: The effects of MVBL on cell viability, cell cycle, cell apoptosis, cell migration, cell invasion, reactive oxygen species (ROS), and paclitaxel (PTX)-combined treatment were studied in vitro. The inhibition of tumor metastasis, antioxidation, and immune enhancement capacity of MVBL were determined in vivo. RESULTS: MVBL exhibited higher toxicity to tumor cells than to normal cells. It did not significantly affect the cell cycle of cancer cells, but increased their apoptosis. Wound healing, adhesion, and transwell assays showed that MVBL significantly inhibited tumor cell migration, adhesion, and invasion. MVBL sensitized MDA-MB-231 breast cancer cells to PTX, indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs. In mice, experimental data showed that MVBL inhibited tumor metastasis, prolonged their survival time, and enhanced their antioxidant capacity and immune function. CONCLUSIONS This study revealed the roles of MVBL in improving immunity and antioxidation, preventing tumor growth, and inhibiting metastasis in vitro and in vivo. MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.
Mice ; Animals ; beta Carotene ; Lysine/pharmacology* ; Antioxidants/pharmacology* ; Quality of Life ; Paclitaxel/pharmacology* ; Apoptosis ; alpha-Tocopherol ; Succinates/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Neoplasms

Animals ; Antlers ; Exosomes ; Mesenchymal Stem Cells ; Osteoarthritis/therapy*