Facing the requirements of promoting the healthy China initiative and improving people's health, the "bone health program" was proposed in 2024. In-depth development of a traditional Chinese medicine(TCM) prevention and control system is of strategic significance to the implementation of the "bone health program". Focusing on osteoporosis(OP), a representative disease affecting people's bone health, this paper concludes that accelerating the research on the prevention and control of OP by TCM is conducive to enhancing the knowledge and awareness of OP among the public, and it is beneficial to revealing the evolutionary pattern of OP and improving the understanding and management of this disease. Additionally, it can provide an overall framework for and strengthen the systematicity and completeness of the research on the prevention and treatment of OP by TCM. Meanwhile, it can help to explore new research paradigms and optimize the existing research model, so as to promote innovative breakthroughs in the prevention and treatment of bone health-related diseases by TCM. Under the overall layout of the "bone health program", importance should be attached to the early prevention and the innovation of very early diagnosis and intervention of OP. Emphasis should be put on the discovery of the target network of disease and treatment mechanism for revealing the core pathogenesis of OP and the therapeutic mechanism of TCM. In addition to local lesions of the bone and its clinical outcomes, attention should be paid to the development of multiple metabolic complications. The fusion of advanced interdisciplinary technologies should be promoted for OP and its complications, and thus a research and development system based on clinical application scenarios and driven by big data can be built. The measures above will facilitate the progress in the prevention and treatment of OP and other bone diseases by TCM and provide new momentum for enriching and deepening the research connotation of the "bone health program".
Osteoporosis/therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; China ; Bone and Bones/drug effects*

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

Objective To establish a rapid,sensitive,and specific multiplex PCR detection method for the simultaneous detection of Cryptosporidium,Eimeria,and bovine parvovirus.Methods Specific primers targeting the SSU rRNA genes of Cryptosporidium and Eimeria,as well as the VP2 gene of bovine parvovirus were designed and the corresponding recombinant plasmid standards were constructed.To establish the multiplex PCR method,the reaction conditions were optimized using temperature gradient PCR and single-variable control methods.The sensitivity,specificity,reproducibility,and clinical application of the protocol were evaluated.Results The optimal annealing temperature was found to be 60.5℃,and the forward and reverse primer concentrations were determined to be 0.2 μmol/L for Eimeria,and 0.4 μmol/L for Cryptosporidium and bovine parvovirus.The assay demonstrated high sensitivity,with detection limits of 243,260,and 3 110 copies for the recombinant plasmid standards of Cryptosporidium,Eimeria,and bovine parvovirus,respectively.Specificity testing showed no cross-reactivity with ten common bovine pathogens,including Salmonella,bovine viral diarrhea virus,and bovine rotavirus.Consistent intra-and inter-batch results confirmed the strong reproducibility of the method.Clinical application to 81 diarrhea samples from various regions in the Ganzi Prefecture,Sichuan,revealed positivity rates of 18.52%(15/81)for Cryptosporidium,34.57%(28/81)for Eimeria,and 18.52%(15/81)forbovineparvovirus,withamixedinfectionrateof3.7%(3/81).Conclusions Themultiplex PCR method established in this study offers a reliable tool for differential diagnosis and epidemiological investigation of the three common diarrheal pathogens in yaks.

Objective To analyze the publication condition and development trends of global post-stroke fatigue(PSF)research from 2004 to 2024.Methods Relevant literature on PSF pub-lished between January 1,2004,and August 1,2024,were systematically searched and screened from WoSCC database.Visual analysis of publication volume,contributing countries,institutions,authors,and keywords in PSF research was conducted using CiteSpace software.Results A total of 373 articles were included in this study.The overall publication volume related to PSF exhibited an upward trend.The country,institution,and author with the highest number of publications were the United Kingdom,the University of Oslo,and LERDAL A,respectively.High-frequency keywords in-cluded quality of life,depression,fatigue severity scale,follow up,epidemiology,symptoms,associ-ations,and rehabilitation,while the emerging keywords were health care professionals,risk factors,and participation.Conclusion PSF-related research has demonstrated an overall upward trend.As-sessment and measurement protocols,rehabilitation treatment approaches,impacts on quality of life,and the intrinsic relationship with depression have emerged as research hotspots.Further exploration of precise and systematic assessment methods,along with the construction of scientific rehabilitation management programs and risk prediction models,will become the focal points of future research.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Objective:To explore the genetic basis of eighteen patients with tetrahydrobiopterin deficiency (BH4D) from Gansu Province.Methods:Eighteen patients diagnosed with BH4D at Gansu Provincial Maternal and Child Health Care Hospital from January 2018 to December 2021 were selected as the study subjects. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing.Results:All of the thirty-six alleles of the eighteen patients were successfully determined by molecular genetic testing. Sixteen patients were found to harbor variants of the PTS gene, and two had harbored variants of the QDPR gene. Ten variants were detected in the PTS gene, with the most common ones being c. 259C>T (34.38%) and c. 286G>A (15.63%). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 259C>T was classified as a pathogenic variant, whilst the c. 286G>A, c. 166G>A, c. 200C>T, c. 272A>G, c. 402A>C, c. 421G>T, c. 84-291A>G and c. 317C>T were classified as likely pathogenic variants. A novel c. 289_290insCTT variant was classified as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PP3+ PP4). The two variants (c.478C>T and c. 665C>T) detected in the QDPR gene were both classified as variants of uncertain significance (PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:Genetic testing has clarified the pathogenic variants in these BH4D patients, which has enabled timely and accurate clinical intervention and treatment, and provided a reference for genetic counseling and reproductive guidance for their families.

Objective:To explore the genetic basis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency (OTCD) and MECP2 duplication syndrome.Methods:A proband who was admitted to the Neonatal Intensive Care Unit of Gansu Provincial Maternal and Child Health Care Hospital on December 19, 2017 was selected as the study subject. High-throughput sequencing and multiplex ligation-dependent probe amplification (MLPA) were carried out for her pedigree, and short tandem repeat-based linkage analysis and chromosome copy number variation sequencing (CNV-seq) were used for the prenatal diagnosis.Results:The proband, a 3-day-old female, was found to harbor heterozygous deletion of exons 7-9 of the OTC gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PVS1+ PM2_Supporting+ PP4). The proband was diagnosed with OTCD, which was in keeping with her acute encephalopathy and metabolic abnormalities (manifesting as hyperammonemia, decreased blood citrulline, and increased urine orotic acid). Prenatal diagnosis was carried out for the subsequent pregnancy. The fetus did not harbor the exons 7-9 deletion of the OTC gene, but was found to carry a duplication in Xq28 region (which encompassed the whole region of MECP2 duplication syndrome) and was positive for the SRY sequence. The same duplication was also found in the proband and her mother. Considering the possible existence of X-chromosome inactivation, the proband was diagnosed with two X-linked recessive disorders including OTCD and MECP2 duplication syndrome, and the fetus was determined as a male affected with the MECP2 duplication syndrome. Conclusion:Discoveries of the pathogenic variants underlying the OTCD and MECP2 duplication syndrome have enabled clinical intervention, treatment, genetic counseling and prenatal diagnosis for this pedigree.

Objective:To explore the genetic basis for a patient with unexplained developmental delay and special facial features.Methods:A male patient admitted to the Maternal and Child Health Care Hospital of Gansu Province on May 27, 2021 due to infertility was selected as the study subject. Clinical data of the patient was collected, and genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing.Results:The patient was found to harbor a 2.54 Mb deletion in 1p36.33p36.32 and a heterozygous c. 1123G>C (p.E375Q) variant of the CHD3 gene, neither of which was detected in his parents. Conclusion:The patient was diagnosed with Snijders Blok-Campeau syndrome in conjunct with 1p36 deletion syndrome, which has enabled genetic counseling for his family.

Objective:To explore the genetic basis for a patient with autosomal dominant retinitis pigmentosa (RP).Methods:A male patient with RP treated at Gansu Provincial Maternal and Child Health Care Hospital in September 2019 was selected as the study subject. Clinical data was collected. Peripheral blood samples of the patient and his parents were subjected to whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The patient, a 29-year-old male, developed night blindness, amblyopia, visual field defects and optic disc abnormalities since childhood. Gene sequencing revealed that he has harbored a heterozygous c. 942G>C (p.Lys314Asn) variant of the IMPDH1 gene, which was inherited from his mother, whilst his father was of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 942G>C variant was predicted as likely pathogenic (PM1+ PM2_Supporting+ PP3+ PP1). Conclusion:The c. 942G>C (p.Lys314Asn) variant in the IMPDH1 gene probably underlay the RP in this patient.

Objective:To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency (CACTD).Methods:Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis.Results:Both children were males and had manifested mainly with hypoglycemia. Trio-WES and Sanger sequencing showed that child 1 had harbored compound heterozygous variants of the SLC25A20 gene, namely c. 49G>C (p.Gly17Arg) and c. 106-2A>G, which were inherited from his father and mother, respectively. Child 2 had harbored homozygous c. 199-10T>G variants of the SLC25A20 gene, which were inherited from both of his parents. Among these, the c. 106-2A>G and c. 49G>C variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 49G>C (p.Gly17Arg), c. 106-2A>G, and c. 199-10T>G variants were classified as likely pathogenic (PM2_supporting+ PP3+ PM3_strong+ PP4), pathogenic (PVS1+ PM2_supporting+ PM5+ PP3), and pathogenic (PVS1+ PM2_supporting+ PP3+ PP5), respectively. Conclusion:Combined with their clinical phenotype and genetic analysis, both children were diagnosed with CACTD. Above finding has provided a basis for their treatment as well as genetic counseling and prenatal diagnosis for their families.