Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

Objective:To explore the molecular mechanism of a case with RhD-phenotype.Methods:A proband with RhD-phenotype who attended the clinic of the First Affiliated Hospital of Zhengzhou University on January 29, 2024 was selected as the study subject. Peripheral blood samples were collected from the proband (8 mL) and her close relatives (father, mother and brother; 3 mL each) for Rh phenotyping and irregular antibodies testing with gel card and test tube methods. Direct agglutination reaction and absorption-elution test were used to detect the c antigen on the red blood cells of the proband. PCR-sequence specific primers (PCR-SSP) typing and gene sequencing were used to determine the RHCE gene of the proband and her relatives. The origin of the proband′s variant was traced by pedigree analysis. Three-dimensional structural models of the wild-type RhCE*cE protein and the RhD-phenotype protein were constructed to predict the alterations of the RhD-phenotype protein caused by the variant. The procedures of this study were approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No.: 2023-KY-0870-003). Results:The red blood cells of the proband did not agglutinate with anti-C, anti-c, anti-E, and anti-e. The result of the serum irregular antibody test was negative. The results of direct agglutination reaction and absorption-elution test of the proband were both negative. Her Rh blood group was identified as RhD-. The results of the Rh blood grouping of her close relatives were normal. PCR-SSP detection showed that the RHCE genotypes of the proband and her close relatives were cE/cE and Ce/cE, respectively. Gene sequencing analysis showed that the RHCE genotypes of the proband and her close relatives were RHCE* cE (c.365C>A)/ RHCE* cE (c.365C>A) and RHCE* Ce/ RHCE* cE (c.365C>A), respectively. Pedigree analysis revealed that the variants in the proband were inherited from her father and mother, respectively. Homology modeling of RhCE*cE protein showed that the RhD-type peptide chain with a significantly shortened C-terminal was encoded by only 121 amino acid resides, which was 296 amino acid resides shorter compared to the wild-type RhCE*cE peptide chain encoded by 417 amino acid residues. Conclusion:Above results revealed the molecular biological mechanism of a RhD-phenotype. The c. 365C>A variant in the RHCE gene has rendered the RHCE* cE alleles invalid, which ultimately led to the RhD-phenotype.

Senile sarcopenia is an age-related geriatric syndrome characterized by a progressive decline in muscle mass, strength, and physical function, posing a significant threat to the health and quality of life of the elderly.In recent years, ultrasound technology has emerged as an important research tool in the evaluation of sarcopenia, owing to its advantages such as safety, convenience, and radiation-free nature.However, challenges remain in achieving parameter standardization, operational consistency, and clinical implementation.This review comprehensively summarizes recent domestic and international research advances in the application of multiparametric ultrasound technology for the diagnosis and evaluation of sarcopenia in the elderly.It also analyzes the practicality, advancements, and limitations of this technology while providing insights into future development trends, aiming to provide clinical research reference basis for the precise diagnosis and intervention strategies of sarcopenia.

As a third major discipline on par with internal medicine and surgery,interventional radiology is one of the key branches of modern medicine.The unique practicality and innovation of interventional radiology make it play an irreplaceable role in the diagnosis and treatment of diseases.In recent years,with the rapid development of technology and the updating of educational concepts,the teaching mode of interventional radiology is facing new challenges and opportunities.This article combines the clinical training methods adopted by interventional physicians in Europe and Germany,integrates imaging,anatomy and pathology teaching,strengthens the foundation,uses virtual reality(VR),augmented reality(AR)technology,and simulation training to enhance the practical ability of medical students.At the same time,with the help of online education platforms,the innovative methods and optimization strategies such as personalized learning program are implemented,which can greatly improve the teaching effectiveness of interventional radiology and provide useful references for teaching reform in this field.

Abstract Breastfeeding has an irreplaceable effect on the growth and development of premature infants and the reduction of complications during hospitalization. In recent years, with the opening of China′s birth policy, the incidence of premature babies has increased, and the corresponding complications have also gradually increased. Breast milk not only carries a rich supply of nutrients, including rich proteins, lipids, sugars to support the normal growth and development of infants, but also contains a large number of immunoglobulins, hormones and other bioactive substances to promote the improvement of body immune function and the development of nervous system. In recent years, many studies have been carried out on the current situation of breast milk operation in breast milk bank, the collection and influencing factors of breast milk, the strategies of breast milk enrichment and its effects on the growth and development of premature infants and complications. Therefore, breast-feeding and intensive breast-feeding can effectively promote the growth and development of premature infants, and reduce the occurrence of complications.

OBJECTIVE: To explore the molecular mechanism of a case with RhD-- phenotype. METHODS: A proband with RhD-- phenotype who attended the clinic of the First Affiliated Hospital of Zhengzhou University on January 29, 2024 was selected as the study subject. Peripheral blood samples were collected from the proband (8 mL) and her close relatives (father, mother and brother; 3 mL each) for Rh phenotyping and irregular antibodies testing with gel card and test tube methods. Direct agglutination reaction and absorption-elution test were used to detect the c antigen on the red blood cells of the proband. PCR-sequence specific primers (PCR-SSP) typing and gene sequencing were used to determine the RHCE gene of the proband and her relatives. The origin of the proband's variant was traced by pedigree analysis. Three-dimensional structural models of the wild-type RhCE*cE protein and the RhD-- phenotype protein were constructed to predict the alterations of the RhD-- phenotype protein caused by the variant. The procedures of this study were approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No.: 2023-KY-0870-003). RESULTS: The red blood cells of the proband did not agglutinate with anti-C, anti-c, anti-E, and anti-e. The result of the serum irregular antibody test was negative. The results of direct agglutination reaction and absorption-elution test of the proband were both negative. Her Rh blood group was identified as RhD--. The results of the Rh blood grouping of her close relatives were normal. PCR-SSP detection showed that the RHCE genotypes of the proband and her close relatives were cE/cE and Ce/cE, respectively. Gene sequencing analysis showed that the RHCE genotypes of the proband and her close relatives were RHCE*cE (c.365C>A)/RHCE*cE (c.365C>A) and RHCE*Ce/RHCE*cE (c.365C>A), respectively. Pedigree analysis revealed that the variants in the proband were inherited from her father and mother, respectively. Homology modeling of RhCE*cE protein showed that the RhD-- type peptide chain with a significantly shortened C-terminal was encoded by only 121 amino acid resides, which was 296 amino acid resides shorter compared to the wild-type RhCE*cE peptide chain encoded by 417 amino acid residues. CONCLUSION Above results revealed the molecular biological mechanism of a RhD-- phenotype. The c.365C>A variant in the RHCE gene has rendered the RHCE*cE alleles invalid, which ultimately led to the RhD-- phenotype.
Humans ; Rh-Hr Blood-Group System/chemistry* ; Female ; Phenotype ; Male ; Alleles ; Pedigree ; Base Sequence ; Molecular Sequence Data ; Adult

[Objective] To study the molecular biological mechanism for a case of ABO blood group B subtype, and perform three-dimensional modeling of the mutant enzyme. [Methods] The ABO phenotype was identified by the tube method and microcolumn gel method; the ABO gene of the proband was detected by sequence-specific primer polymerase chain reaction (PCR-SSP), and the exon 6 and 7 of the ABO gene were sequenced and analyzed. Homologous modeling of Bw.03 glycosyltransferase (GT) was carried out by Modeller and analyzed by PyMOL2.5.0 software. [Results] The weakening B antigen was detected in the proband sample by forward typing, and anti-B antibody was detected by reverse typing. PCR-SSP detection showed B, O gene, and the sequencing results showed c.721 C>T mutation in exon 7 of the B gene, resulting in p. Arg 241 Trp. Compared with the wild type, the structure of Bw.03GT was partially changed, and the intermolecular force analysis showed that the original three hydrogen bonds at 241 position disappeared. [Conclusion] Blood group molecular biology examination is helpful for the accurate identification of ambiguous blood group. Homologous modeling more intuitively shows the key site for the weakening of Bw.03 GT activity. The intermolecular force analysis can explain the root cause of enzyme activity weakening.

Over 40% of high-risk prostate cancer patients experience biochemical recurrence after radical prostatectomy. Salvage radiotherapy is the main therapeutic intervention for those with biochemical recurrence. To balance survival and quality of life, individual considerations are needed for the population benefiting from salvage radiotherapy, timing, whether to combine with androgen deprivation therapy, target volume, dose fractionation patterns, and adverse reactions. Currently, prostate-specific antigen related parameters are mainly used in clinics to guide salvage radiotherapy. In the future, the application of new functional molecular imaging technologies and genomic analysis of tissues, combined with traditional clinical and pathological parameters, could better assist clinical decision-making.

Objective:To explore the molecular mechanism of a case with RhD-phenotype.Methods:A proband with RhD-phenotype who attended the clinic of the First Affiliated Hospital of Zhengzhou University on January 29, 2024 was selected as the study subject. Peripheral blood samples were collected from the proband (8 mL) and her close relatives (father, mother and brother; 3 mL each) for Rh phenotyping and irregular antibodies testing with gel card and test tube methods. Direct agglutination reaction and absorption-elution test were used to detect the c antigen on the red blood cells of the proband. PCR-sequence specific primers (PCR-SSP) typing and gene sequencing were used to determine the RHCE gene of the proband and her relatives. The origin of the proband′s variant was traced by pedigree analysis. Three-dimensional structural models of the wild-type RhCE*cE protein and the RhD-phenotype protein were constructed to predict the alterations of the RhD-phenotype protein caused by the variant. The procedures of this study were approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No.: 2023-KY-0870-003). Results:The red blood cells of the proband did not agglutinate with anti-C, anti-c, anti-E, and anti-e. The result of the serum irregular antibody test was negative. The results of direct agglutination reaction and absorption-elution test of the proband were both negative. Her Rh blood group was identified as RhD-. The results of the Rh blood grouping of her close relatives were normal. PCR-SSP detection showed that the RHCE genotypes of the proband and her close relatives were cE/cE and Ce/cE, respectively. Gene sequencing analysis showed that the RHCE genotypes of the proband and her close relatives were RHCE* cE (c.365C>A)/ RHCE* cE (c.365C>A) and RHCE* Ce/ RHCE* cE (c.365C>A), respectively. Pedigree analysis revealed that the variants in the proband were inherited from her father and mother, respectively. Homology modeling of RhCE*cE protein showed that the RhD-type peptide chain with a significantly shortened C-terminal was encoded by only 121 amino acid resides, which was 296 amino acid resides shorter compared to the wild-type RhCE*cE peptide chain encoded by 417 amino acid residues. Conclusion:Above results revealed the molecular biological mechanism of a RhD-phenotype. The c. 365C>A variant in the RHCE gene has rendered the RHCE* cE alleles invalid, which ultimately led to the RhD-phenotype.

Senile sarcopenia is an age-related geriatric syndrome characterized by a progressive decline in muscle mass, strength, and physical function, posing a significant threat to the health and quality of life of the elderly.In recent years, ultrasound technology has emerged as an important research tool in the evaluation of sarcopenia, owing to its advantages such as safety, convenience, and radiation-free nature.However, challenges remain in achieving parameter standardization, operational consistency, and clinical implementation.This review comprehensively summarizes recent domestic and international research advances in the application of multiparametric ultrasound technology for the diagnosis and evaluation of sarcopenia in the elderly.It also analyzes the practicality, advancements, and limitations of this technology while providing insights into future development trends, aiming to provide clinical research reference basis for the precise diagnosis and intervention strategies of sarcopenia.