1.Mechanism of Huangqi Xiayuxue Decoction Against Hepatocellular Carcinoma via PI3K/Akt/FoxO Signaling Pathway
Xingru XING ; Yuanzhou SHI ; Jiawei WANG ; Di WU ; Yuyao ZHANG ; Yalin WU ; Du CHEN ; Zhen ZHANG ; Sha TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):131-141
ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology, animal experiments, and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 (CCK-8) assay was adopted to observe the effects of different volume fractions (5%, 10%, 15%, and 20%) of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2, MHCC-97H, Hepa1-6, and Huh-7 cells, and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma (5%, 10%, 15%, and 20%) on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-, medium-, and high-dose (4.63, 9.25, 18.5 g·kg-1) Huangqi Xiayuxue decoction and sorafenib (20 mg·kg-1) groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention, hematoxylin-eosin (HE) staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was employed to detect cell apoptosis. Immunohistochemistry (IHC) was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 (PI3K/Akt/FoxO1) signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology, among which tumor protein p53 (TP53), Akt1, and signal transducer and activator of transcription 3 (STAT3) were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation, as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group, all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2, MHCC-97H, Hepa1-6, and Huh-7 cells (P<0.01). The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma (P<0.01). Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume, promoted tumor cell apoptosis in the high-dose group, up-regulated the protein and mRNA levels of Bax and Caspase-3, down-regulated the protein and mRNA levels of Bcl-2, and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway (P<0.05, P<0.01). ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.
2.Mechanism of Huangqi Xiayuxue Decoction Against Hepatocellular Carcinoma via PI3K/Akt/FoxO Signaling Pathway
Xingru XING ; Yuanzhou SHI ; Jiawei WANG ; Di WU ; Yuyao ZHANG ; Yalin WU ; Du CHEN ; Zhen ZHANG ; Sha TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):131-141
ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology, animal experiments, and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 (CCK-8) assay was adopted to observe the effects of different volume fractions (5%, 10%, 15%, and 20%) of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2, MHCC-97H, Hepa1-6, and Huh-7 cells, and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma (5%, 10%, 15%, and 20%) on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-, medium-, and high-dose (4.63, 9.25, 18.5 g·kg-1) Huangqi Xiayuxue decoction and sorafenib (20 mg·kg-1) groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention, hematoxylin-eosin (HE) staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was employed to detect cell apoptosis. Immunohistochemistry (IHC) was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 (PI3K/Akt/FoxO1) signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology, among which tumor protein p53 (TP53), Akt1, and signal transducer and activator of transcription 3 (STAT3) were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation, as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group, all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2, MHCC-97H, Hepa1-6, and Huh-7 cells (P<0.01). The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma (P<0.01). Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume, promoted tumor cell apoptosis in the high-dose group, up-regulated the protein and mRNA levels of Bax and Caspase-3, down-regulated the protein and mRNA levels of Bcl-2, and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway (P<0.05, P<0.01). ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.
3.Evaluation of infectious disease outbreak investigation capabilities in grassroots Centers for Disease Control and Prevention in Zhejiang Province
WANG Zhen ; CHEN Ying ; XING Yuhang ; YIN Shujuan ; ZHANG Renjie ; LIU Biyao ; WANG Hongmei
Journal of Preventive Medicine 2026;38(3):316-320
Objective:
To investigate the infectious disease investigation and response capabilities of grassroots Centers for Disease Control and Prevention (CDC) in Zhejiang Province, so as to provide a reference for strengthening the development of CDC workforce.
Methods:
From May to June 2024, professional technical personnel engaged in or participating in on-site epidemiological investigation and response from 11 municipal-level CDC and 91 county-level CDC in Zhejiang Province were selected as survey participants. Data on sociodemographic information, outbreak response experience, and infectious disease investigation capabilities were collected using the National Questionnaire on the Current Status of Field Epidemiology Investigation Teams.
Results:
A total of 2 316 individuals were surveyed, including 459 from municipal-leve CDC (19.82%) and 1 857 from county-level CDC (80.18%). The cohort was predominantly female, aged 30-<40 years, with a bachelor's degree, specialized in public health and preventive medicine, holding intermediate professional titles, and having <10 years of work experience, accounting for 55.79%, 36.44%, 72.88%, 74.18%, 34.72%, and 53.76%, respectively. A relatively high proportion of participants had experience in on-site infectious disease response (81.39%), been members of field epidemiology investigation teams or emergency response teams responsible for field epidemiology investigation (81.17%), and had prior work experience in infectious disease-related departments (66.80%). In contrast, the proportion of those who had delivered academic presentations on field epidemiology investigations (4.15%) or contributed to the development of expert consensus documents, guidelines, or textbooks (8.51%). The total score for infectious disease investigation and response capabilities among field epidemiologists investigators in grassroots CDC in Zhejiang Province was 53.19±16.19, with dimension scores of 65.15±13.90 for personal comprehensive competence, 59.75±20.77 for outbreak investigation procedures, and 28.65±19.32 for essential epidemiological investigation skills.
Conclusions
The grassroots field epidemiology investigation teams in Zhejiang Province have developed a certain level of workforce capacity and outbreak response experience. However, they generally exhibit relatively short work tenures, limited academic outputs, and moderate-to-low proficiency in infectious disease investigation and management, particularly with notable gaps in critical field investigation skills. It is recommended to strengthen systematic training and practical exercises to enhance grassroots emergency response capabilities.
4.Laboratory Diagnosis and Molecular Epidemiological Characterization of the First Imported Case of Lassa Fever in China.
Yu Liang FENG ; Wei LI ; Ming Feng JIANG ; Hong Rong ZHONG ; Wei WU ; Lyu Bo TIAN ; Guo CHEN ; Zhen Hua CHEN ; Can LUO ; Rong Mei YUAN ; Xing Yu ZHOU ; Jian Dong LI ; Xiao Rong YANG ; Ming PAN
Biomedical and Environmental Sciences 2025;38(3):279-289
OBJECTIVE:
This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF.
METHODS:
Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus.
RESULTS:
LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response.
CONCLUSION
The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans
;
China/epidemiology*
;
Genome, Viral
;
Lassa Fever/virology*
;
Lassa virus/classification*
;
Molecular Epidemiology
;
Phylogeny
6.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
7.DWI and PWI in Differential Diagnosis Between Supratentorial Pilocytic Astrocytoma and WHO Grade 2 Pleomorphic Xanthoastrocytoma
Yaqing KANG ; Xiefeng YANG ; Xiaodan CHEN ; Zhen XING
Chinese Journal of Medical Imaging 2025;33(9):967-973,992
Purpose To investigate the differential diagnosis of diffusion-weighted imaging(DWI),perfusion-weighted imaging(PWI)and DWI combined with PWI in supratentorial pilocytic astrocytoma(PA)and WHO grade 2 pleomorphic xanthoastrocytoma(PXA).Materials and Methods The conventional MRI,DWI and PWI data of 23 cases of supratentorial PA and 11 cases of PXA(WHO grade 2)in the First Affiliated Hospital of Fujian Medical University from January 2010 to February 2022 were retrospectively analyzed.Supratentorial PA was further divided into lobar PA and non-lobar PA based on the lesion location.The basic data(gender,age,cystic degeneration,homogeneous enhancement,lesion size and meningeal involvement),minimum apparent diffusion coefficient,relative apparent diffusion coefficient and relative maximum cerebral blood volume were compared and analyzed between the two groups.Results The probability of leptomeningeal involvement in PXA(WHO grade 2)(36.3%)was higher than that in supratentorial PA(4.3%,P=0.029).Compared with supratentorial PA and lobar PA,PXA(WHO grade 2)had lower minimum apparent diffusion coefficient,relative apparent diffusion coefficient and higher relative maximum cerebral blood volume(t=-4.398-5.828,all P<0.05).The threshold value of minimum apparent diffusion coefficient to discriminate between supratentorial PA and PXA(WHO grade 2)was 1.09×10-3 mm2/s,and its sensitivity,specificity and area under the curve were 90.91%,83.33%and 0.947,respectively.When the differential diagnosis threshold of relative maximum cerebral blood volume was 1.79,its sensitivity,specificity and area under the curve were 90.00%,100.00%and 0.950,respectively.The area under the curve of DWI combined with PWI was 0.993,which did not significantly improve the diagnostic performance compared with DWI and PWI respectively(Z=1.371,0.928,both P>0.05).In subgroup analysis,the area under the curve of DWI combined with PWI in lobar PA and PXA(WHO grade 2)was 0.988,which did not improve the diagnostic performance compared with DWI and PWI respectively(Z=1.322,0.882,both P>0.05).Conclusion DWI and PWI are helpful in the differential diagnosis of PXA(WHO grade 2)from supratentorial PA and lobar PA,but combining DWI and PWI does not significantly improve the efficacy of differential diagnosis.
8.The Functions and Mechanisms of tRNA Methylation Modifications in Cell Cycle Regulation
Chinese Journal of Biochemistry and Molecular Biology 2025;41(8):1127-1136
tRNA is one of the RNA molecules with the most diverse post-transcriptional modifications.It not only functions as an adaptor molecule transporting amino acids during translation but also relies on its extensive post-transcriptional modifications to regulate gene expression,thereby influencing numerous bio-logical processes.These modifications are dynamically regulated by tRNA methyltransferases and demeth-ylases,which collaboratively maintain a balance-the former catalyze methyl group addition,while the latter remove methyl groups,ensuring reversible control.Mutations or dysregulation of these enzymes are closely associated with tumorigenesis and other diseases,constituting a major research focus.They pro-mote tumor progression through two distinct pathways:cytoplasmic tRNA(ctRNA)methylation enhances the translation of oncogenes,whereas mitochondrial tRNA(mtRNA)methylation optimizes mitochondrial protein synthesis to reprogram energy metabolism.From the dual dimensions of"enzyme supply"and"energy provision",tRNA methylation establishes a material foundation for tumor cell growth and directly contributes to cell cycle dysregulation.The cell cycle,an orderly process governing cell division,is tight-ly controlled by checkpoint proteins to guarantee accurate genetic information transmission.Notably,ab-errant cell cycle activation is not only a hallmark of cancer but also a pivotal therapeutic target.tRNA methyltransferases and demethylases exert multidimensional control over both cell cycle progression and metabolic adaptation.Elucidating the mechanisms underlying tRNA modification mediated cell cycle reg-ulation will not only accelerate the discovery of novel therapeutic targets but may also overcome the con-straints of conventional cell cycle targeted therapies.Within this context,we systematically review the molecular mechanisms by which tRNA methylation-modifying enzymes regulate the cell cycle,with an emphasis on their translational potential.
9.Application and development direction of finite element method in biomechanical analysis of thoracolumbar fractures of the spine
Kai HE ; Wenhua XING ; Feng LI ; Shengxiang LIU ; Xianming BAI ; Chen ZHOU ; Xu GAO ; Yu QIAO ; Qiang HE ; Zhiyu GAO ; Zhen GUO ; Aruhan BAO ; Chade LI
Chinese Journal of Tissue Engineering Research 2025;29(15):3244-3252
BACKGROUND:The highest incidence of spinal fracture is in the thoracolumbar segment,and its symptoms are back pain,posterior convexity deformity,activity limitation,or with spinal cord nerve injury causing lower limb pain,numbness,and even paraplegia and other complications.The finite element method is a digital computer modeling technique,which can simulate the physical model and carry out force analysis realistically.OBJECTIVE:To review the application of finite element method in thoracolumbar spine fractures.METHODS:We searched the Chinese and English literature databases PubMed,Web of Science,and CNKI for relevant literature on the application of the finite element analysis method in spinal thoracolumbar fracture published before March 2024.The search terms in Chinese and English were:finite element analysis methods,biomechanical phenomena,stress analysis,thoracolumbar fractures,spinal fractures.Finally,55 papers were included.RESULTS AND CONCLUSION:(1)The exploration of thoracolumbar fractures caused by different etiologies(osteoporotic,traumatic,and pathological)through the finite element method is conducive to a deeper understanding of the biomechanics of various types of thoracolumbar fractures,and to improve the individualized and fine-tuned treatment of thoracolumbar fractures.(2)The finite element analysis of a single sample or a small number of samples has the chance,and a larger number of samples are required for the future finite element analysis to reduce the chance caused by the sample.(3)The rigid structure of bones alone cannot meet the biomechanical working conditions of the integrity of the physical object,and future finite element models need to incorporate all the structures of the physical object(e.g.,soft tissues,such as muscles and ligaments)as far as possible.(4)The finite element method has been used in more studies on osteoporotic and traumatic thoracolumbar spine fractures,which will need to be more in-depth in the future,and less in the field of pathologic thoracolumbar fractures,which has a wider scope for future research.
10.Genetic profiling and intervention strategies for phenylketonuria in Gansu, China: an analysis of 1 159 cases.
Chuan ZHANG ; Pei ZHANG ; Bing-Bo ZHOU ; Xing WANG ; Lei ZHENG ; Xiu-Jing LI ; Jin-Xian GUO ; Pi-Liang CHEN ; Ling HUI ; Zhen-Qiang DA ; You-Sheng YAN
Chinese Journal of Contemporary Pediatrics 2025;27(7):808-814
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
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Phenylketonurias/epidemiology*
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Female
;
Male
;
Retrospective Studies
;
Phenylalanine Hydroxylase/genetics*
;
Mutation
;
Child, Preschool
;
China/epidemiology*
;
Child
;
Infant


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