OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

Aim To investigate whether resveratrol (Resveratrol, Res) induces cardiomyocyte protection by increasing intracellular zinc ion and its possible signal mechanism. Methods H9c2 cells were routinely cultured and 2-deoxyglucose (2-DG) was used to establish an endoplasmic reticulum stress (ERS) model. The experiment was randomly divided into control group, 2-DG group, Res +2-DG group, TPEN + Res + 2-DG group and 3-MA + Res +2-DG group. Cell viability was detected by MTT and CCK-8; the expression levels of ERS molecular chaperone proteins glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94) and autophagy proteins LC3 II / I, p62 and p-AMPK were detected by Western blot; the expression of LC3 protein was measured by cellular immunofluorescence; the mitochondrial membrane potential (Aijjm) and the intracellular zinc ion level were measured by laser scanning confocal microscope. Results Compared with the control group, 2-DG reduced cell activity and resveratrol inhibited the changes caused by 2-DG, which was reversed by zinc chelator TPEN. 2-DG increased GRP78 and GRP94 expression and resveratrol inhibited the protein changes caused by 2-DG, which was reversed by TPEN. 2-DG increased the expression of LC3 II / I, p-AMPK and decreased the expression of p62, and resveratrol promoted the effect of 2-DG. 2-DG increased the fluorescence intensity of LC3, and resveratrol enhanced the effect of 2-DG, which was reversed by TPEN and 3-MA. 2-DG reduced the red fluorescence intensity of mitochondrial TMRE and green fluorescence intensity of intracellular zinc ions, and resveratrol inhibited these changes caused by 2-DG, which was also reversed by TPEN and 3-MA. The above differences were all statistically significant (P < 0. 05). Conclusion Resveratrol increases intracellular zinc to promote ERS-induced autophagy and prevent the mPTP opening in H9c2 cardiac cells.

Objective To evaluate the effect of the single-person hyperbaric chamber on hemodynamics of superior mesenteric artery in the personnel rushing to the extremely high altitude area.Methods Sixty healthy young male subjects who traveled by car from the plains(890 m above sea level)to a very high altitude area(5 130 m above sea level)were randomly divided into a control group,a low-flow oxygen therapy group and a hyperbaric oxygen group,with 20 cases in each group.After entering the plateau area,no intervention was made in the control group;in the low-flow oxygen therapy group,low-flow oxygen therapy was performed once a day by means of nasal oxygen cannula(oxygen flow rate of 2 L/min,60 min/times);in the hyperbaric oxygen group,hyperbaric oxygen therapy was carried out once a day in a single-person hyperbaric oxygen chamber(pressuri-zation pressure of 0.25 MPa,60 min/times).The subjects in the three groups had their peak systolic velocity(PSV),resistance index(RI),and pulsation index(PI)of the main trunks of the SMAs and their grade 1 and 2 branches measured and compared using color Doppler ultrasound diagnostic instruments on days 30,60,and 90,respectively,after acute entry to the plateau.SPSS 19.0 software was used for statistical analysis.Results There were no significant differences in PSV,RI and PI of SMA and its 1 st and 2nd grade branches between the 3 groups 30 days after entry(P＞0.05).Sixty days after entry,the control group had the values of PSV statistically higher than those of the other two groups(P＜0.05);there were no significant differences between the low-flow oxygen therapy group and the hyperbaric oxygen group in the values of PSV(P＞0.05);the three groups had no obvious differences in the values of RI and PI(P＞0.05).Ninety days after entry,the control group had the values of PSV,RI and PI all significantly higher than those of the other two groups(P＜0.05);the low-flow oxygen therapy group had the values of PSV statistically higher than those of the hyperbaric oxygen group(P＜0.05),while the values of RI and PI not significantly different from those of the hyperbaric oxygen group(P＞0.05).Conclusion Single-person hyperbaric oxygen chamber significantly improves the SMA blood flow changes due to oxygen partial pressure reduction in the plateau,and thus is of significance for preventing ischemic enteropathy of the personnel rushing to the plateau.[Chinese Medical Equipment Journal,2023,44(10):59-63]

Objective: The purpose of this article is to translate and adapt the Trans Woman Voice Questionnaire (TWVQ) into the simplified Chinese version (TWVQ-SC), and to evaluate its reliability and validity. Methods: Authorized by the author of the TWVQ,the TWVQ-SC was developed through translation, back translation,and cross-cultural adaptation.The TWVQ-SC contained 30 items capturing personal perception of vocal function, psychosocial impact of voice, and degree of limitation in social participation. Subjects included 279 trans women in the experimental group, 128 cis women in the control group, and 89 trans women in the retest group. The Cronbach α and the item total correlation coefficient (ITC) were calculated to examine the internal consistency. The intraclass correlation coefficient (ICC) was chosen to examine the test-retest reliability. Regarding validity, the expert judgment method was utilized to examine the content validity. Factor analysis and Spearman's rank correlation coefficient were used to examine the construct validity, and the discriminant validity was examined by the rank sum test of the total scores of the cisgender and transgender subjects. Results: The Cronbach's α of TWVQ-SC is 0.97 and the ITC of 30 items range from 0.40 to 0.86. The ICC is 0.84. The four principal components' cumulative contribution is 65.12%. The Spearman rank correlation coefficient to VHI-10 is 0.85 (P<0.01). The total score of the TWVQ scale in the transgender female group is significantly higher than that in the cisgender female group (U=1 580,P<0.01). Conclusion: TWVQ-SC demonstrates good reliability and validity and therefore can be used clinically as a self-assessment tool for transgender women to evaluate their own voice.
Humans ; Female ; Reproducibility of Results ; Translations ; Surveys and Questionnaires ; Language ; China

Objective:To explore the predictive value of amplitude integrated electroencephalography(aEEG)in the neurological prognosis of children with neonatal bacterial meningitis(NBM).Methods:The clinical data and aEEG results from 148 children diagnosed with NBM who completed aEEG examinations in the Department of Neonatology at Kunming Children′s Hospital from January 2018 to December 2019 were retrospectively analyzed.According to whether aEEG is abnormal, the children were divided into aEEG abnormal group and aEEG non-abnormal group.According to the degree of aEEG abnormality, children with aEEG abnormality were divided into aEEG mild abnormal group and aEEG severe abnormal group.The abnormal rate and abnormal characteristics of aEEG were analyzed; The clinical data of two groups were compared.Results:(1)Among the 148 children with NBM, 49 children had abnormal aEEG, 99 children had no abnormality, and the aEEG abnormal rate was 33.1%.The abnormal aEEG was manifested as delayed sleep-wake cycle maturation in 39 (26.3%) cases, abnormal discharge in eight (5.4%) cases, and abnormal background activity in one (0.6%) case.(2)The proportion of children with convulsive seizures and refractory NBM in aEEG abnormal group were significantly higher than those in aEEG non-abnormal group ( P<0.05). In the routine and biochemical abnormal indexes of cerebrospinal fluid, the proportion of protein >3 g/L, cerebrospinal fluid leukocyte>500×10 6/L, cerebrospinal fluid glucose<1.5 mmol/L, positive cerebrospinal fluid culture, positive blood and cerebrospinal fluid culture, abnormal head MRI in aEEG abnormal group significantly increased ( P<0.05); While there was no significant difference regarding blood routine leukocyte abnormality, CRP increase, and positive blood culture ratio between two groups ( P>0.05). (3) 148 cases of NBM children were followed up to 15 months old, 119 (80.4%) cases completed the follow-up, the loss rate was 19.6%, three cases died, and 11 cases had psychomotor retardation.Compared with the children with abnormal aEEG, the prognosis of children with NBM was significantly different, the Spearman rank correlation coefficient r was 0.315 ( P<0.05). COX regression was used to analyze the predictive value of each index for adverse outcomes. Abnormal aEEG was an independent risk factor for adverse outcomes in children with NBM ( OR=7.452, 95% CI 1.605-34.591, P<0.05). Conclusion:The aEEG monitoring of children with NBM, if abnormal, may indicate severe NBM, which is likely to be transformed into refractory NBM or has a poor prognosis.