Objective To study the in vitro expression of three phenylalanine hydroxylase(PAH)mutants(p.R243Q,p.R241C,and p.Y356X)and determine their pathogenicity.Methods Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein.Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells.Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants,and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay.Results Bioinformatics analysis predicted that all three mutants were pathogenic.The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control(P>0.05),while the mRNA expression level of the p.Y356X mutant significantly decreased(P<0.05).The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control(P<0.05).The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control(P<0.05),while there was no significant difference between the p.R243Q mutant and the wild type control(P>0.05).Conclusions p.R243Q,p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells,with p.R241C and p.Y356X mutants also affecting the function of PAH protein.These three PAH mutants are to be pathogenic.[Chinese Journal of Contemporary Pediatrics,2024,26(2):188-193]

Objective To investigate the effect of chemokine CXC ligand 9(CXCL9)on cognitive function impairment in patients with breast cancer brain metastases undergoing whole-brain radiotherapy(WBRT)using bioinformatics methods.Methods The mRNA of breast cancer brain metastases datasets GSE43837 and GSE12276 and Alzheimer's disease(AD)dataset GSE161199 were screened and downloaded from GEO database.Limma method and Venn diagrams were used to identify common differentially expressed genes(DEGs),and protein-protein interaction and functional prediction through GeneMANIA website assays were performed.A total of 42 patients with breast cancer brain metastases who first visited the Department of Radiotherapy at the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were selected.Patients were divided into normal cognitive function group and cognitive function impairment group based on cognitive status.Enzyme-linked immunosorbent assay(ELISA)was employed to detect serum CXCL9 levels one week before and three months after radiotherapy.The mini-mental state examination(MMSE)was used to assess patients'cognitive function.Results The DEGs from datasets GSE43837 and GSE12276 included PKP1,POLDIP2,SPAG5,ALDOC,PTPRZ1,PKIA,TLCD1,CPE,PMP22 and CXCL9.The DEGs from GSE161199 included RPS16,CD79A,LYPD3,RPL28,HBG2,RPL23AP7,TRNR,CXCL9.Venn diagram showed that CXCL9 was a common DEG between breast cancer brain metastasis and AD.Functional enrichment analysis indicated that CXCL9 was involved in cellular responses to chemokines,negative regulation of immune system processes,negative regulation of vascular morphogenesis,Toll-like receptor signaling pathway,nucleotide oligomerization domain(NOD)-like receptor signaling pathway,and JAK-STAT signaling pathway.Before radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 61.9%and 38.1%,respectively,with a statistically significant difference in MMSE scores[(24.53±2.19)vs.(28.89±1.36),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had a significantly increased number of brain metastases and significantly lower Karnofsky performance status(KPS)scores and serum CXCL9 levels(P＜0.05).Three months after radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 47.6%and 52.4%,respectively,with a statistically significant difference in MMSE scores[(25.16±1.98)vs.(28.18±1.08),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had significantly lower CXCL9 levels(P=0.003).In patients with normal cognitive function,CXCL9 levels were remarkably lower after radiotherapy compared to those before radiotherapy(P=0.009).Conclusions Patients with cognitive function impairment had significantly lower CXCL9 levels than those with normal cognitive function,and whole-brain radiotherapy may be related to a certain degree of reduction in CXCL9 levels.

Objective: To investigate the infection sources and the transmission chains of three outbreaks caused by 2019-nCoV Omicron variant possibly spread through cross-border logistics in Beijing. Methods: Epidemiological investigation and big data were used to identify the exposure points of the cases. Close contacts were traced from the exposure points, and the cases' and environmental samples were collected for nucleic acid tests. Positive samples were analyzed by gene sequencing. Results: The Omicron variant causing 3 outbreaks in Beijing from January to April, 2022 belonged to BA.1, BA.1.1 and BA.2. The outbreaks lasted for 8, 12 and 8 days respectively, and 6, 42 and 32 cases infected with 2019-nCoV were reported respectively. International mail might be the infection source for 1 outbreak, and imported clothes might be the infection sources for another 2 outbreaks. The interval between the shipment start time of the imported goods and the infection time of the index case was 3-4 days. The mean incubation period (Q₁, Q₃) was 3 (2,4) days and the mean serial interval (Q₁, Q₃) was 3 (2,4)days. Conclusions: The 3 outbreaks highlighted the risk of infection by Omicron variant from international logistics-related imported goods at normal temperature. Omicron variant has stronger transmissibility, indicating that rapid epidemiological investigation and strict management are needed.
Humans ; Beijing ; SARS-CoV-2 ; COVID-19 ; Disease Outbreaks ; China/epidemiology*

Objective: To investigate the epidemiological characteristics and the transmission chain of a family clustering of COVID-19 cases caused by severe acute respiratory 2019-nCoV Delta variant in Changping district of Beijing. Methods: Epidemiological investigation was conducted and big data were used to reveal the exposure history of the cases. Close contacts were screened according to the investigation results, and human and environmental samples were collected for nucleic acid tests. Positive samples were analyzed by gene sequencing. Results: On November 1, 2021, a total of 5 COVID-19 cases caused by 2019-nCoV Delta variant were reported in a family detected through active screening. The infection source was a person in the same designated isolation hotel where the first case of the family cluster was isolated from 22 to 27, October. The first case was possibly infected through aerosol particles in the ventilation duct system of the isolation hotel. After the isolation discharge on October 27, and the first case caused secondary infections of four family members while living together from October 27 to November 1, 2021. Conclusion: 2019-nCoV Delta variant is prone to cause family cluster, and close attention needs to be paid to virus transmission through ventilation duct system in isolation hotels.
Aerosols ; COVID-19 ; Epidemics ; Humans ; SARS-CoV-2

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ² test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia/epidemiology* ; Blood Transfusion ; Female ; Gastrointestinal Neoplasms/surgery* ; Humans ; Length of Stay ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective: To investigate the source and the transmission chain of a cold-chain product associated COVID-19 epidemic caused by 2019-nCoV Delta variant in Beijing. Methods: Epidemiological investigation were used to verify the exposure points of the cases. Close contacts were traced from the exposure points, and human and environmental samples were collected for nucleic acid tests. Positive samples were analyzed by gene sequencing. Results: A total of 112 cases of COVID-19 were reported in the epidemic from January 18 to February 6, 2022 in Beijing. Except for 1 case was uncertain, there were epidemiological links among 111 cases. The source of infection was the packages of imported cold-chain products from Southeast Asia, which were harvested and stored in a local cold-storage in January 2021, and packaged and sent to the cold-storage A in A district in June 2021, and then sold in batches in cold-storage B in B district from January 2022. The first case was infected in the handling of positive frozen products, and then 77 cases occurred due to working, eating and living together with the index case in the cold-storage B, cold-storage C and restaurant D. Besides the cold-storage B, C and the restaurant D, there were 16 sub-transmission chains, resulting in additional 35 cases. Conclusion: The epidemic indicated that the risk of 2019-nCoV infection from imported cold-chain products contaminated by package and highlighted the importance to strengthen the management of cold-chain industry in future.
Beijing/epidemiology* ; COVID-19/epidemiology* ; Epidemics ; Humans ; SARS-CoV-2

Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.
Adult ; Aged ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; Tinnitus/epidemiology*

Objective::Based on gene array technology, gene set enrichment analysis (GSEA) and immune infiltration analysis were performed on chip data of intracranial aneurysm (IA) mRNA expression profile, in order to provide theoretical basis for understanding the formation mechanism of IA. Method::The GSE75436 raw data were obtained from the gene expression omnibus (GEO). GSEA of biological process (BP) in gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) signaling pathways were analyzed for gene expression profile by R software. The CIBERSORT deconvolution method was used to analyze the infiltration ratio of 22 types of immune cells in the expression profile. And COREMINE database was used to predict traditional Chinese medicines (TCMs), which were significant correlation with the enrichment result. Result::The GSEA results showed that the changes in gene expression of IA samples mainly involved in the regulation of cytokines, activation and differentiation of leukocyte, inflammatory immune response and other processes. The infiltration matrix analysis of immune cells showed that mast cells resting and neutrophils were significantly reduced in IA samples. The comparison of paired samples showed that mast cells and natural killer cells (NK cells) were significantly activated in the IA samples of the same individual, while neutrophils and T cells CD4 naive were significantly reduced. Through COREMINE prediction, it was found that Stephaniae Tetrandrae Radix was correlated with the activation of granulocytes, Sapindi Mukorossi Semen and Pistaciae Chinensis Cortex were correlated with the activation of neutrophils, Trichosanthis Semen, Paeoniae Radix Alba and Ligustri Lucidi Fructus were correlated with the cytotoxicity mediated by NK cells. Conclusion::Activation of mast cells and NK cells are closely associated with the occurrence and development of IA. The inflammatory immune processes and pathways such as nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway and cytotoxicity mediated by NK cells may be important factors in the pathogenesis of IA, and TCMs such as Stephaniae Tetrandrae Radix may be the potential molecular drug sources.