Background: The genus Atractylodes, native to East Asia, encompasses several species that serve as sources for the widely used traditional Chinese medicines Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma. However, the international trade arouses concern regarding potential confusion and misidentification of Atractylodes species. Objective: A comprehensive understanding of the chemical diversity is crucial for ensuring the quality and exploring the potential variations in medicinal efficacy of Atractylodes. Methods: The GC-MS/MS-based metabolomics and multivariate statistical analysis identified 589 differentially accumulated metabolites across 5 Atractylodes species. Results: A total of 150 metabolites were predicted as potential chemical markers for species differentiation and quality assessment of Atractylodes. According to the metabolic profiles, the species of Atractylodes can be roughly classified into three categories: A. lancea and A. coreana with the volatile oil components being mainly atractylodin and β-eudesmol; A. macrocephala with the biomarker being atractylon; and A. japonica and A. carlinoides lying between the two categories above. Conclusions: Metabolomic results indicated that the metabolic profiles of A. carlinoides and A. macrocephala were similar and distinct from those of the other three species. Sesquiterpenoids were the main chemical components in the rhizome of A. carlinoides, which indicated the potential medicinal value of this plant.

Background: The genus Atractylodes, native to East Asia, encompasses several species that serve as sources for the widely used traditional Chinese medicines Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma. However, the international trade arouses concern regarding potential confusion and misidentification of Atractylodes species. Objective: A comprehensive understanding of the chemical diversity is crucial for ensuring the quality and exploring the potential variations in medicinal efficacy of Atractylodes. Methods: The GC-MS/MS-based metabolomics and multivariate statistical analysis identified 589 differentially accumulated metabolites across 5 Atractylodes species. Results: A total of 150 metabolites were predicted as potential chemical markers for species differentiation and quality assessment of Atractylodes. According to the metabolic profiles, the species of Atractylodes can be roughly classified into three categories: A. lancea and A. coreana with the volatile oil components being mainly atractylodin and β-eudesmol; A. macrocephala with the biomarker being atractylon; and A. japonica and A. carlinoides lying between the two categories above. Conclusions: Metabolomic results indicated that the metabolic profiles of A. carlinoides and A. macrocephala were similar and distinct from those of the other three species. Sesquiterpenoids were the main chemical components in the rhizome of A. carlinoides, which indicated the potential medicinal value of this plant.

Background: The genus Atractylodes, native to East Asia, encompasses several species that serve as sources for the widely used traditional Chinese medicines Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma. However, the international trade arouses concern regarding potential confusion and misidentification of Atractylodes species. Objective: A comprehensive understanding of the chemical diversity is crucial for ensuring the quality and exploring the potential variations in medicinal efficacy of Atractylodes. Methods: The GC-MS/MS-based metabolomics and multivariate statistical analysis identified 589 differentially accumulated metabolites across 5 Atractylodes species. Results: A total of 150 metabolites were predicted as potential chemical markers for species differentiation and quality assessment of Atractylodes. According to the metabolic profiles, the species of Atractylodes can be roughly classified into three categories: A. lancea and A. coreana with the volatile oil components being mainly atractylodin and β-eudesmol; A. macrocephala with the biomarker being atractylon; and A. japonica and A. carlinoides lying between the two categories above. Conclusions: Metabolomic results indicated that the metabolic profiles of A. carlinoides and A. macrocephala were similar and distinct from those of the other three species. Sesquiterpenoids were the main chemical components in the rhizome of A. carlinoides, which indicated the potential medicinal value of this plant.

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree with recurrent Joubert syndrome with negative results by whole-exome sequencing in the prior proband. METHODS: Chinese pedigree which opted elective abortion at the Women and Children's Hospital Affiliated to Chongqing Medical University in December 2024 was selected as the study subject. Whole-genome sequencing was carried out on fetal tissue after termination of pregnancy. Candidate variants were validated by Sanger sequencing and interpreted, while non-coding variant was analyzed using in silico prediction tools. RNA sequencing and cDNA sequencing were conducted on fetal brain tissue. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.2024YL045-02). RESULTS: Both the fetus and the affected child were found to harbor compound heterozygous variants of the CEP290 gene, namely c.7341dup (p.Leu2448fs*8) (pathogenic, maternally inherited) and c.1523-408G>A (likely pathogenic, paternally inherited). Both in silico analysis and fetal brain RNA sequencing confirmed aberrant RNA splicing caused by the intronic variant. CONCLUSION This case has highlighted the value of combining whole-genome sequencing with RNA functional validation. Above results not only enriched the spectrum of CEP290 gene mutations but also underscored its diagnostic value in resolving complex prenatal cases, providing critical clues for the prenatal diagnosis and recurrence risk assessment in genetic counseling.
Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Antigens, Neoplasm/genetics* ; Cell Cycle Proteins/genetics* ; Cerebellum/abnormalities* ; Cytoskeletal Proteins/genetics* ; Eye Abnormalities/genetics* ; Introns/genetics* ; Kidney Diseases, Cystic/diagnosis* ; Pedigree ; Retina/abnormalities* ; Sequence Analysis, RNA/methods* ; Whole Genome Sequencing/methods* ; Child

OBJECTIVE: To explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification. METHODS: A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). RESULTS: The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband's father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+PM2_Supporting+PP2+PP3+PP4). CONCLUSION The heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c.728C>T variant of the TUBB8 gene, oocyte donation may be considered.
Humans ; Female ; Adult ; Mutation, Missense ; Oocytes/metabolism* ; Heterozygote ; Tubulin/genetics* ; Infertility, Female/genetics* ; High-Throughput Nucleotide Sequencing ; Pedigree

OBJECTIVE: To investigate the clinical phenotype and genetic etiology of a patient with primary infertility accompanied by Oocyte maturation defect (OOMD). METHODS: A 24-year-old female patient who visited the Reproductive Medicine Center of Gansu Provincial Maternity and Child Care Hospital in April 2024 was selected as the study subject. Whole-exome sequencing (WES) was performed on the proband and her husband. Candidate gene variants were validated in the family using Sanger sequencing, and compound heterozygous variants were confirmed through vector construction. Candidate variants were classified for pathogenicity according to the "Standards and Guidelines for the Interpretation of Sequence Variants" established by the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Hospital [Ethics No.: (2023) GSFYLS(78)]. RESULTS: The proband, a 24-year-old female, had been unable to conceive for four years without contraception after marriage. She had undergone two ovarian stimulation cycles using the antagonist protocol and the PPOS protocol, respectively. A total of 74 oocytes were retrieved, with all showing OOMD and some oocytes exhibiting abnormal morphology and poor quality. WES results revealed two heterozygous missense variants in exons 14 and 16 of the PATL2 gene: c.1127G>A (p.R376Q) and c.1388C>G (p.A463G). Family validation results indicated that the missense variant in exon 14 was inherited from the proband's father, while the variant in exon 16 was de novo. CONCLUSION The compound heterozygous variants of the PATL2 gene probably underlay the OOMD and infertility in this proband. Further analysis based on the variant sites and protein structures is needed to determine whether PATL2 gene variants can fully affect oocyte development, thereby providing a personalized treatment plan for the proband.
Female ; Humans ; Young Adult ; Exome Sequencing ; Infertility, Female/genetics* ; Oocytes/metabolism* ; Pedigree ; Phenotype

ObjectiveTo analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022. MethodsBlood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics. ResultsAmong the 1 023 newly reported HIV-infected patients receiving ART, the median age （P₂₅，P₇₅） was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL^-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL^-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC [14.8% (4/27)], CRF08_BC [14.8% (4/27)] and subtype C [14.8% (4/27)]. ConclusionDuring the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.

Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses. Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann-Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes. Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy. Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.

Objective:To confirm the potential etiological factors of congenital aortic stenosis(AS)by genetic analysis on prenatal diagnostic results of the fetus with AS.Methods:Amniocentesis for chromosomal G-band karyotyping combinated with single nucleotide polymorphism array(SNP-array)analysis was conducted on the amniotic fluid collected from a 25-week pregnant woman diagnosed as"fetus AS";chromosome karyotyping was also performed on the peripheral blood of the fetal parents.Results:The fetal karyotype analysis showed a chimeric Y-chromosome isobaric double-adherent granules.The SNP-array analysis results revealed a 11.2 Mb duplication in the Yp11.31q11.21 region and a 14.8 Mb deletion in the Yq11.21q11.23 region.Both the parents presented a normal karyotype,suggesting it was a newfound mutation.After extensive genetic counseling,the pregnant woman and her family chose to terminate the pregnancy locally.Conclusion:The chromosomal karyotype of the chimeric Y-chromosome isobaric double-adherent granules may be a contributing factor to the AS phenotype in the male fetus.The combined use of chromosomal karyotyping and SNP-array analysis on the amniotic cells is instrumental in the early diagnosis of the disease.

Objective:To investigate the differences in glucose homeostasis and amino acid metabolism between patients with new-onset T2DM with qi-yin deficiency syndrome and those with spleen deficiency and phlegm-dampness syndrome.Methods:This study was a cross-sectional and cohort study. From January 2021 to December 2022, 136 T2DM inpatients were selected from the Department of Metabolic Diseases of Shanxi Traditional Chinese Medicine Hospital, and 18 patients were screened to meet the inclusion criteria of new-onset T2DM, and were identified as qi-yin deficiency syndrome and sspleen deficiency and phlegm-dampness syndrome, and were included in corresponding qi-yin and deficiency group and spleen deficiency and phlegm-dampness group, with 9 cases in each group. All patients wore a dynamic blood glucose monitoring system to calculate the 24-h mean standard deviation of blood glucose (SDBG), the coefficient of variation of blood glucose (GLU cv), the maximum value of blood glucose (GLU max), the minimum value of blood glucose (GLU min), the maximum amplitude of glucose fluctuation (LAGE), the average amplitude of glucose fluctuation (MAGE), and the proportion of time within the target range of blood glucose (TIR). Blood specimens were retained for amino acid metabolism testing to screen for differential metabolites and metabolic pathways in the 2 groups of syndromes. Results:Patients in the spleen deficiency and phlegm-dampness group had mAlb [27.61 (13.60,40.45) mg/L vs. 5.10 (1.95, 9.70) mg/L, Z=-2.34], GLU-0 h [(14.83±4.79) mmol/L vs. (9.72±2.35) mmol/L, t=2.87], GLU-1 h [(24.40±5.23) mmol/L vs. (17.71±2.68) mmol/L, t=3.42], GLU-2 h [(25.17±4.43) mmol/L vs. (19.69±3.11) mmol/L, t=3.03], HOMA2-IR [1.83 (1.46, 3.19) vs. 1.14 (0.90, 1.35), Z=-2.14] were higher than those in the qi-yin deficiency syndrome ( P<0.05), GLU cv [16.86 (13.58, 26.20)% vs. 28.30 (23.17, 40.87)%, Z=-2.08] was lower than that of the qi-yin deficiency syndrome ( P<0.05) and had severe blood glucose fluctuations. Screening of 2 groups of differential metabolites identified threonine, alanine, and glutamine as potential metabolic markers for T2DM with qi-yin deficiency versus spleen deficiency and phlegm-dampness. Analysis of the 2 groups of differential metabolite pathways for different TCM syndromes revealed that Aminoacyl-tRNA biosynthesis was the most significantly enriched pathway. Conclusion:Patients with T2DM spleen deficiency and phlegm dampness syndrome had worse insulin function and glucose homeostasis than those with qi-yin deficiency syndrome; differences in amino acid metabolism were important influences on the development of the 2 types of the syndromes, namely, spleen deficiency and phlegm dampness syndrome versus qi-yin deficiency syndrome; and Aminoacyl-tRNA biosynthesis participates in the development of early diabetes mellitus, which plays a key role in the pathogenesis of T2DM.