Objective: To reveal the molecular basis of the cisAB (p. Met266Leu) glycosyltransferase by studying a proband with cisAB subtype and his family. Methods: A male newborn was selected as the research subject. Tube methods were used to identify ABO blood types of the proband and his family members. PCR-SSP detection, ABO gene sequencing, and cloning analysis were performed on the proband and some family members. The inheritance pattern of the subtype gene in the family was determined through pedigree analysis. Homology modeling was used to analyze the impact of amino acid variations on the structure of the transferase, and molecular docking was used to demonstrate the bifunctional activity of the transferase and the donor-receptor binding conformation. Results: Serological tests showed that the proband and his father had enhanced anti-H agglutination, and the grandmother had a forward and reverse discrepancy. Sequencing of the proband revealed heterozygous variations of c. 297A>G, c. 526C>G, c. 657C>T, c. 703G>A, c. 803G>C, and c. 930G>A compared with A1. 01 (compared with B. 01, lacking the c. 796C>A variation, namely harboring the c. 796A>C variation) and c. 261delG. Combined with cloning analysis, the proband's genotype was determined to be ABO cisAB (c. 796A>C)/ABO O. 01. 01, the father's genotype was ABO cisAB (c. 796A>C)/ABO O. 01. 02, and the grandmother's genotype was ABO cisAB (c. 796A>C)/ABO B102. Pedigree analysis indicated that the cisAB allele in this newborn was inherited from his father and grandmother rather than a natural mutation. Homology modeling showed that the side chain orientation and intermolecular forces of Leu266 in the cisAB (p. Met266Leu) transferase changed, and molecular docking demonstrated that the "binding pocket" of the active center of the variant enzyme could accommodate both UDP-GalNAc and UDP-Gal, indicating that the cisAB enzyme structure has bifunctional activity. Conclusion: The bifunctional activity of this cisAB (p. Met266Leu) enzyme is related to the nucleotide variation of c. 796A>C, and molecular docking indicates that the enzyme has dual affinity for A/B sugar donors.

Objective: To delineate the epidemiologic profile of rifampicin resistant pulmonary tuberculosis (RR-PTB) among students in Chongqing, so as to provide evidence for effectively controlling RR-PTB outbreaks in schools. Methods: Individual level surveillance records of 395 student RR-PTB cases reported from 2015 to 2024 were extracted from the China Information System for Disease Control and Prevention. The Joinpoint regression analysis was employed to quantify temporal trends in the registration rate of student RR-PTB cases, and the comparison of RR-PTB registration rates with different demographic characteristics and different regions was performed using Chi-square test. Results: From 2015 to 2024, a total of 395 student RR-PTB cases were identified, with the registration rate ranged from 0.07 per 100 000 to 1.47 per 100 000, showed a fluctuating upward trend ( AAPC= 35.22%, t =4.13, P <0.01). A turning point was detected in 2017, rates rose during 2015-2017 (APC=295.23%， t =4.62， P < 0.01 ) and plateaued thereafter (APC=-0.47%， t =-0.12， P =0.91). The proportion of RR-PTB cases occurring among students increased both among all RR-PTB cases (1.54% in 2015, 7.48% in 2024) and all student pulmonary tuberculosis cases (0.20% in 2015, 7.17% in 2024), with significant linear trends ( χ 2 trend =33.55,159.98, both P <0.01). The majority of cases were enrolled in senior high school (50.38%), classified as retreatment (53.92%), of Han ethnicity (75.95%), and diagnosed with multidrug resistant tuberculosis(53.16%). There were significant differences in the composition of different ethnicity, registration category and resistance pattern between different years( χ 2=23.47, 17.23, 59.64，all P <0.05). The South-Eastern Wuling Mountainous Region exhibited the highest notification rate (3.96 per 100 000), whereas the western region had the lowest rate ( 0.47 per 100 000). County level jurisdictions reported higher rates than district level ones (2.16 per 100 000 vs 0.63 per 100 000 ). Statistically significant differences were observed in the RR-PTB reported rates among students across different districts and counties( χ 2=418.05,167.05,both P <0.01). Conclusions From 2015 to 2024, the registration rate of detected student RR-PTB cases in Chongqing showed an increasing trend. Students have become one of the key populations for drug resistant TB prevention and control. Intensified health education and active case finding should be implemented to enhance proactive surveillance capabilities.

OBJECTIVE To analyze the results of speech-evoked auditory brainstem response(s-ABR)tests in patients with presbycusis and explore the mechanisms of speech coding in these patients.METHODS Thirty patients with presbycusis(presbycusis group),30 elderly individuals with normal hearing(elderly normal group),and 30 young adults with normal hearing(young control group)were recruited.The s-ABR was elicited using a 40 ms duration complex speech stimulus/da/,and the characteristics of s-ABR were analyzed in each group.RESULTS The latencies of waves V and A in the presbycusis group were significantly prolonged compared to both the elderly normal group and the young control group(P<0.05).However,there was no statistically significant difference in the latencies of waves between the elderly normal group and the young control group(P>0.05).The amplitude of wave A and the slope of the V-A complex wave in the presbycusis group were significantly lower than those in the young control group(P<0.05),while no statistically significant differences were observed in the amplitudes of other waves.CONCLUSION The characteristics of s-ABR in patients with presbycusis suggest that these patients have poor synchronization in response to stimulus timing and deficiencies in coding high-frequency and rapidly changing auditory information,which may be one of the mechanisms underlying the decline in speech abilities in patients with presbycusis.

Objective:To explore the risk factors for malnutrition after a traumatic brain injury and to construct a model which usefully predicts that risk.Methods:This was a retrospective study of 374 patients with a craniocerebral injury for whom the relevant clinical data were available. Based on their nutritional status, they were stratified into a malnutrition group ( n=220) and a control group ( n=154). Univariate and multivariate logistic regressions were evaluated seeking to identify the independent risk factors associated with malnutrition, and a prediction model was constructed based on the results. The model′s discrimination ability and accuracy were assessed using a receiver operating characteristics (ROC) curve. Results:A total of 220 patients (58.8%) developed malnutrition. Multifactorial logistic regression analysis showed that the independent risk factors for malnutrition were: age ≥60 years, pulmonary infection, dysphagia, cognitive impairment, a GCS score ≤8, or a Barthel index ≤40. In the ROC curve analysis, the area under the curve quantifying the model′s ability to predict malnutrition was 0.924 (95% CI: 0.896, 0.951), with a sensitivity of 0.868 and a specificity of 0.857, indicating its good prediction performance. Conclusions:Age ≥60 years, pulmonary infection, dysphagia, cognitive impairment, a GCS score ≤8 or a Barthel index ≤40 are independent predictors of malnutrition after a traumatic brain injury. The prediction model constructed based on those risk factors has demonstrated useful predictive power for malnutrition.

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.

Lipidomics is an emerging discipline that systematically studies the various types, functions, and metabolic pathways of lipids within living organisms. This field compares changes in diseases or drug impact, identifying biomarkers and molecular mechanisms present in lipid metabolic networks across different physiological or pathological states. Through employing analytical chemistry within the realm of lipidomics, researchers analyze traditional Chinese medicine (TCM). This analysis aids in uncovering potential mechanisms for treating diverse physiopathological conditions, assessing drug efficacy, understanding mechanisms of action and toxicity, and generating innovative ideas for disease prevention and treatment. This manuscript assesses recent literature, summarizing existing lipidomics technologies and their applications in TCM research. It delineates the efficacy, mechanisms, and toxicity research related to lipidomics in Chinese medicine. Additionally, it explores the utilization of lipidomics in quality control research for Chinese medicine, aiming to expand the application of lipidomics within this field. Ultimately, this initiative seeks to foster the integration of traditional medicine theory with modern science and technology, promoting an organic fusion between the two domains.

Lipidomics is an emerging discipline that systematically studies the various types,functions,and metabolic pathways of lipids within living organisms.This field compares changes in diseases or drug impact,identifying biomarkers and molecular mechanisms present in lipid metabolic networks across different physiological or pathological states.Through employing analytical chemistry within the realm of lipidomics,researchers analyze traditional Chinese medicine(TCM).This analysis aids in uncovering potential mechanisms for treating diverse physiopathological conditions,assessing drug efficacy,un-derstanding mechanisms of action and toxicity,and generating innovative ideas for disease prevention and treatment.This manuscript assesses recent literature,summarizing existing lipidomics technologies and their applications in TCM research.It delineates the efficacy,mechanisms,and toxicity research related to lipidomics in Chinese medicine.Additionally,it explores the utilization of lipidomics in quality control research for Chinese medicine,aiming to expand the application of lipidomics within this field.Ultimately,this initiative seeks to foster the integration of traditional medicine theory with modern science and technology,promoting an organic fusion between the two domains.

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

Viruses,as important biological agents influencing human health and social development,have played a key role in the spread of epidemics and the evolution of diseases since ancient times.Upon infecting hosts,viruses often trigger a series of com-plex responses,including innate and adaptive immunity,inflammatory responses and pathological damage.Despite advances in mod-ern antiviral drugs development,chemical drugs typically rely on a single molecular target within the viral life cycle,making them highly susceptible to the emergence of drug resistance and the induction of systemic toxic side effects.In contrast,traditional Chi-nese medicines(TCMs),posing the distinctive advantage of multi-component,multi-target,and multi-pathway,have exerted a pivotal role in viral prevention and viral treatment.In recent years,fresh herbs have gained increasing attention for their ability to preserve intact bioactive components.Fresh herb-derived nanovesicles possess excellent biocompatibility,targeting and cross-species regula-tory capabilities.These fresh herb-derived nanovesicles can effectively encapsulate and deliver a variety of antiviral components,demonstrating significant potential in antiviral immunomodulation,inflammation control and viral-induced pathologies.This review systematically sorts out the mechanisms of viral infection,and summarizes the advantages of fresh herbs,and the application pros-pects of fresh herb-derived nanovesicles in antiviral therapy.Furthermore,it focuses on summarizing the research progress of fresh herb-derived nanovesicles in the field of antiviral therapy,with the aim of providing insights and references for the development of fresh herb-derived nanovesicles-based antiviral strategies,as well as offering novel approaches and perspectives for the clinical treat-ment of viral diseases.