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

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

Objective This study aimed to investigate natural infection of rodents with Ehrlichia and Neoehrlichia at major Chinese land-border ports along the"Belt and Road".Methods In 2022,rodents were monitored in 10 ports in northern and southern China and identified based on diagnostic morphological characteristics.The 16S rRNA genes of Ehrlichia and Neoehrlichia were detected by PCR using universal primers from rodent samples and phylogenetic analysis was performed based on the sequences of the detected positive pathogens.Results A total of 356 rodents were sampled,including 2 orders,5 families,15 genera,and 20 species.Predominantly,73,61,56,and 58 were Meriones unguiculatus(20.51%),Rattus norvegicus(17.13%),Apodemus agrarius(15.73%),and Microtus gregalis(16.29%).Only one Microtus fortis from Suifenghe Port was infected with Ehrlichia sp.Moreover,12 rodents were infected with Neoehrlichia spp.(overall positivity rate:3.37%).Conclusions Natural infections with Ehrlichia spp.and Neoehrlichia spp.were demonstrated in rodents at important Chinese land-border ports.The positivity rate of Neoehrlichia spp.was high in some ports,indicating that surveillance for ticks and their prevention and control measures should be intensified in these regions.

Objective To study the damage effect of high-voltage electric shock on skin based on metabolomics,analyze its metabolic differences,and explore its injury mechanism.Methods A total of 16 SPF C57BL/6J male mice were divided into the electric shock group(head skin received electric shock treatment)and control group(head skin received electric shock acoustic-optical stimulation),and the skin appearance after treatment of mice in the two groups was observed.The histopathological changes caused by electric shock were analyzed by HE staining,EVG staining and Masson staining.GC-MS and LC-MS metabonomics were used to analyze the changes of skin metabolism spectrum and tissue metabolites after electric shock exposure,and the differential metabolites were analyzed.The obtained differential metabolites were combined and KEGG enrichment analysis was conducted.Results After high-voltage electric shock,the skin of mice could be damaged to the dermis,and the epidermis was partially thickened,lifted and separated.The structure of skin appendages in the dermis was destroyed,with a large number of inflammatory cells infiltrating and obvious swelling,accompanied by congestion,which led to severe skin inflammatory reaction and impaired skin barrier function.Metabonomics analysis suggested that the metabolites changed after electric shock exposure.KEGG enrichment analysis showed that electric shock significantly affected the central carbon metabolism pathway of cancer,pentose phosphate pathway,purine metabolism,glycine,serine and threonine metabolism processes,amino acid tRNA biosynthesis mechanism,glycerophospholipid metabolism pathway,pyrimidine metabolism pattern,glycolysis/gluconeogenesis,alanine metabolism process,glucagon signal pathway and so on.Conclusion High voltage electric shock can cause deep skin damage,disturb its energy metabolism and amino acid metabolism,and seriously interfere with its antioxidant and DNA repair system functions.

Objective To study the damage effect of high-voltage electric shock on skin based on metabolomics,analyze its metabolic differences,and explore its injury mechanism.Methods A total of 16 SPF C57BL/6J male mice were divided into the electric shock group(head skin received electric shock treatment)and control group(head skin received electric shock acoustic-optical stimulation),and the skin appearance after treatment of mice in the two groups was observed.The histopathological changes caused by electric shock were analyzed by HE staining,EVG staining and Masson staining.GC-MS and LC-MS metabonomics were used to analyze the changes of skin metabolism spectrum and tissue metabolites after electric shock exposure,and the differential metabolites were analyzed.The obtained differential metabolites were combined and KEGG enrichment analysis was conducted.Results After high-voltage electric shock,the skin of mice could be damaged to the dermis,and the epidermis was partially thickened,lifted and separated.The structure of skin appendages in the dermis was destroyed,with a large number of inflammatory cells infiltrating and obvious swelling,accompanied by congestion,which led to severe skin inflammatory reaction and impaired skin barrier function.Metabonomics analysis suggested that the metabolites changed after electric shock exposure.KEGG enrichment analysis showed that electric shock significantly affected the central carbon metabolism pathway of cancer,pentose phosphate pathway,purine metabolism,glycine,serine and threonine metabolism processes,amino acid tRNA biosynthesis mechanism,glycerophospholipid metabolism pathway,pyrimidine metabolism pattern,glycolysis/gluconeogenesis,alanine metabolism process,glucagon signal pathway and so on.Conclusion High voltage electric shock can cause deep skin damage,disturb its energy metabolism and amino acid metabolism,and seriously interfere with its antioxidant and DNA repair system functions.

Objective To investigate the effect of Kaixinsan(KXS,a traditional Chinese medicine formula)for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.Methods Forty female BALB/c mice were randomized equally into control group,model group,and low-and high-dose KXS treatment groups,and in the latter 3 groups,mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage.Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test,and the changes in serum levels of depression-related factors were examined.RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS.The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.Results KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models.RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress,lipid metabolism and iron ion binding in the prefrontal cortex.Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice.In SH-SY5Y cells,both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.Conclusion KXS alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

Objective To explore the changes of metabonomics in blood of mice after high-voltage electric shock,then screen out the significantly changed differential metabolites and metabolic pathways.Methods The head of C57BL/6J mice was subjected to high-voltage electric shock(electric shock group)or exposed to acoustic and optical stimulation of high-voltage electric(control group),then the whole blood from mice were collected to separate serum.The dual platform combined metabonomic analysis based on gas chromatography-mass spectrometer(GC-MS)and liquid chromatography-mass spectrometer(LC-MS)was performed and orthogonal partial least squares discriminant analysis(OPLS-DA)was used to screen the differential metabolites and related metabolic pathways.Results A total of 415 differential metabolites were screened out in metabonomics in blood of mice after high-voltage electric shock,including 187 up-regulated and 228 down-regulated metabolites.These differentially metabolites were significantly enriched in metabolic pathways including central carbon metabolism in cancer,glucagon signaling pathway,etc.Conclusion By establishing the model of high-voltage electrical injury on experimental mice,this study reveals the significant change of metabolite content and metabolic pathway in blood by high-voltage electrical injury.Which provides a basis for the damage of blood metabolic activity by high-voltage electrical injury,and suggests the potential harm of high-voltage electrical injury to blood metabolic activity in the whole body.

Objective To investigate the effect of Kaixinsan(KXS,a traditional Chinese medicine formula)for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.Methods Forty female BALB/c mice were randomized equally into control group,model group,and low-and high-dose KXS treatment groups,and in the latter 3 groups,mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage.Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test,and the changes in serum levels of depression-related factors were examined.RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS.The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.Results KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models.RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress,lipid metabolism and iron ion binding in the prefrontal cortex.Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice.In SH-SY5Y cells,both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.Conclusion KXS alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.
Humans ; Aged ; Aged, 80 and over ; C-Reactive Protein/analysis* ; Frailty/epidemiology* ; Cohort Studies ; Cross-Sectional Studies ; China/epidemiology*

BACKGROUND:For patients with rheumatoid arthritis and Kümmel ’s disease, how to effectively control back pain, to recover patient’s locomotor activity and to avoid a vicious cycle of disuse osteoporosis is a key therapeutic target. Kyphoplasty is a recently developed new technology of minimal y invasive spine surgery. Few reports concerned the kyphoplasty for rheumatoid arthritis and Kümmel ’s disease. OBJECTIVE:To assess the clinical outcome of bone cement kyphoplasty for the treatment of Kümmel ’s disease combined with rheumatoid arthritis. METHODS:From June 2012 to July 2013, 11 female patients at the age of 65.4±5.1 years with Kümmel ’s disease combined with rheumatoid arthritis, who suffered from severe back pain, were treated with bone cement vertebroplasty. Back pain and imaging indexes were compared and observed before surgery and during fol ow-up. Imaging indexes contained preoperative and postoperative anterior height of vertebral body after fractures, the ratio of anterior height to posterior height of the vertebral body, and local kyphosis angle (Cobb method). RESULTS AND CONCLUSION:No patients were lost to fol ow up. 11 patients were fol owed up for 6 to 12 months. Significant differences in fol ow-up and preoperative Visual Analogue Scale scores, anterior height of vertebral body after fractures, the ratio of anterior height to posterior height of the vertebral body, and local kyphosis angle were detected (P<0.05). Two patients experienced bone cement leakage. No severe complications appeared such as pulmonary embolism or neurological dysfunction. These data confirmed that bone cement vertebroplasty for rheumatoid arthritis combined with Kümmel ’s disease can effectively lessen back pain, partial y restore the height of vertebral body after fracture, rebuild spinal stabilization, reduce local kyphosis, and is a safe effective repair method.