Objective:To investigate the relationship between plasma fluoride content, daily calcium intake and blood cell parameters in children and adolescents.Methods:This study was based on the National Health and Nutrition Examination Survey (NHANES) database of the United States from 2013 to 2016, with 3 684 children and adolescents aged 6 - 19 as the research subjects. Information on plasma fluoride content, daily calcium intake and blood cell parameters from the database were collected. Non-linear relationships between plasma fluoride content, daily calcium intake and blood cell parameters were analyzed using restricted cubic splines. If there was a non-linear relationship, the optimal inflection point was calculated using threshold/saturation effect analysis method. Subsequently, multiple linear regression models were used to analyze the associations among the three, and the modification effect of daily calcium intake (binary classification, stratified by median daily calcium intake) on the association between plasma fluoride content and blood cell parameters was analyzed.Results:There was no non-linear relationship between plasma fluoride content and white blood cell count, hemoglobin content and platelet count ( Pnon-linear > 0.05), but there was a non-linear relationship between plasma fluoride content and erythrocyte count and hematocrit ( Pnon-linear < 0.001). After adjusting for confounding factors, the optimal inflection points of the effects of plasma fluoride content on erythrocyte count and hematocrit were 0.54 and 0.31 μmol/L, respectively. There was no non-linear relationship between daily calcium intake and blood cell parameters ( Pnon-linear > 0.05). After adjusting for confounding factors, for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.49 × 10 9/L ( P = 0.009). There was a saturation effect in the association between plasma fluoride content, erythrocyte count and hematocrit: when plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.46 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 6.29% for every 1 μmol/L increase ( P = 0.006). The above associations were not statistically significant when plasma fluoride content was higher than the optimal inflection points ( P > 0.05). After stratification according to the median daily calcium intake, in the low-calcium group (daily calcium intake < 0.87 g), for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.77 × 10 9/L ( P = 0.001). When plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.41 × 10 12/L for every 1 μmol/L increase ( P = 0.002). When plasma fluoride content was ≥0.54 μmol/L, erythrocyte count decreased by 0.47 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When the plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 8.29% for every 1 μmol/L increase ( P = 0.011). The above associations were not statistically significant in the high-calcium group (daily calcium intake ≥0.87 g, P > 0.05). There was an interaction of daily calcium intake and plasma fluoride content on platelet count ( Pinteraction = 0.070), as demonstrated by an increase in platelet count of 12.68 × 10 9/L ( P = 0.013) in the low-calcium group and a decrease in platelet count of 9.05 × 10 9/L ( P = 0.035) in the high-calcium group for every 1 μmol/L increase in plasma fluoride content. Conclusions:The blood cell parameters of children and adolescents are closely related to plasma fluoride content, but not directly related to daily calcium intake. However, the correlation between plasma fluoride content and blood cell parameters varies among different calcium intake populations, and daily calcium intake can modify the association between plasma fluoride content and platelet count.

Mitochondrial and peroxisome fission deficiency-related encephalopathy caused by DNM1L gene mutation is a rare and fatal epileptic encephalopathy, with clinical phenotype and genetic heterogeneity. The acute stage is drug-resistant epilepsy with poor prognosis and serious neurological sequelae. A case of genetically confirmed encephalopathy related to mitochondrial and peroxisome fission defects is reported, the clinical data, treatment process are summarized, and the previous literature is reviewed to improve the understanding of the rare disease.

Myeloid neoplasms (MNs) belong to a group of hematological malignancies characterized by the abnormal biological functions of hematopoietic stem progenitor cells. The abnormal immune and hematopoietic microenvironment of patients with MN interact with malignant clonal hematopoietic stem cells, promoting the occurrence and development of their diseases. MN large granular lymphocyte proliferation (MN-LGLP) is a special and rare clinical phenomenon in this type of disease. Currently, research on this disease in domestic and international cohorts is limited. This study analyzes the clinical and laboratory characteristics of this type of patient and explores the impact of LGLP on the clinical characteristics and survival of patients with MN. Patients with MN-LGLP are prone to neutropenia and splenomegaly. The presence of LGLP is not a risk factor affecting the survival of patients with MN-LGLP. STAG, ASXL1, and TET2 are the most common accompanying gene mutations in MN-LGLP, and patients with MN-LGLP and STAG2 mutations have poor prognoses.

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale（VAS） of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from （8.89±3.31） on day 0 to （3.71±2.51） on day 14（P<0.001）, VAS score of nasal symptoms decreased from （24.86±7.40） on day 0 to （6.84±5.94） on day 14（P<0.001）, VAS score of rhinorrhoea decreased from （6.88±2.06） on day 0 to （1.91±1.81） on day 14（P<0.001）. Rhinoconjunctivitis quality of life questionnaire（RQLQ） score decreased from （94.63±33.35） on day 0 to （44.95±32.28） on day 14（P<0.001）. The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.
Male ; Female ; Humans ; Adult ; Rhinitis, Allergic, Seasonal/drug therapy* ; Nasal Sprays ; Quality of Life ; Administration, Intranasal ; Rhinorrhea ; Double-Blind Method ; Treatment Outcome ; Rhinitis, Allergic/drug therapy*

OBJECTIVE: To conduct clinical and genetic analysis of two male patients with atypical Rett syndrome. METHODS: Collection of clinical data in the two patients and these parents; whole exome sequencing (WES) was used to detect the potential variants, which were verified by Sanger sequencing. X chromosome inactivation (XCI) detection is performed in the Patient 1's mother to detect the allelic expression difference of the MECP2 gene. RESULTS: Patient 1, a 5-year and 10-month-old boy, had mental disorders and mild intellectual disability (ID) (IQ: 54), whose mother had ID. Patient 2 was a 9-month and 18-day-old male presented with recurrent infections, respiratory insufficiency, hypotonia and global developmental delay. WES indentified a hemizygous mutation, c.499C>T (p.R167W), in the MECP2 gene in patient 1, which was inherited from his mother. The inactivation of X chromosome is skewed, and the expression ratio of wild-type and mutant MECP2 is 100%:0. Patient 2 was found a de novo splicing mutation, c.62+2_62+3del in the MECP2 gene. They were both reported pathogenic variant related to Rett syndrome. c.499C>T (p.R167W) was defined as likely pathogenic (PS1+PM2+PP3) and c.62+2_62+3del was pathogenic (PVS1+PM2+PM6) based on American College of Medical Genetics and Genomics standards and guidelines. CONCLUSION Both the two patients were diagnosed with rare male Rett syndrome, which had atypical clinical manifestations and large difference. Above foundings have revealed novel phenotypes in Chinese male patients with Rett syndrome.
Craniosynostoses ; Female ; Genetic Testing ; Humans ; Intellectual Disability/genetics* ; Male ; Methyl-CpG-Binding Protein 2/genetics* ; Mutation ; Phenotype ; Rett Syndrome/genetics*

BACKGROUND: Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 ( MTHFD1 ) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. METHODS: A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF Cr ) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UF Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. RESULTS: In the high fluoride group, children's IQ scores decreased by 2.502 when the UF Cr level increased by 1.0 mg/L (β = -2.502, 95% confidence interval [CI]:-4.411, -0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group ( P   <  0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). CONCLUSION Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
Child ; Creatinine ; Cross-Sectional Studies ; Fluorides/urine* ; Formate-Tetrahydrofolate Ligase ; Humans ; Intelligence/genetics* ; Methylenetetrahydrofolate Dehydrogenase (NADP) ; Methylenetetrahydrofolate Reductase (NADPH2)

Objective:To investigate the relationship between cerebral small vessel disease and thyroid hormones in the elderly.Methods:A total of 314 subjects aged ≥60 years with records of head magnetic resonance image(MRI), serum thyroid function tests and physical examinations collected in the Department of Health Care Neurology of Beijing Hospital from May 2019 to November 2020 were consecutively included for this cross-sectional study.Participants were assigned into the cerebral small vessel disease group if their head MRI presentations met the following standards: the Fazekas score ≥3 points; the Fazekas score ≥2 points, with 1 cavity; new subcortical infarcts; or cerebral microhemorrhage.Differences in thyroid function were compared between the cerebrovascular disease group(n=129)and the group without cerebrovascular disease(control group, n=185).Results:A total of 314 subjects were enrolled, of whom 129 met the head MRI standards for cerebrovascular disease, and 185 who did not meet the standards entered the control group.Comparison of thyroid function found a statistically significant difference in FT3( t=3.270, P=0.001)between the two groups.As for the association of a specific type of cerebral small vessel disease with thyroid function, there was a statistically significant difference in the FT3 level between the lacunar infarction group and the non-lacunar infarction group( t=3.106, P=0.002)and between the cerebral microhemorrhage group and the non-cerebral microhemorrhage group( t=2.125, P=0.034). Groups with different Fazekas scores in white matter hyperintensity showed statistically significant differences in rT3( F=3.092, P=0.027), FT3( F=5.427, P=0.001)and FT4( F=2.646, P=0.049). After correction for hyperlipidemia, rT3 and FT4, it was found that age( OR=1.044, 95% CI: 1.022-1.067, P=0.000), hypertension( OR=0.533, 95% CI: 0.294-0.963, P=0.037)and FT3( OR=0.276, 95% CI: 0.159-0.478, P=0.000)were related to cerebral small vessel disease. Conclusions:FT3 levels at the lower end of the normal range are associated with cerebral small vessel disease in the elderly.

The importance of structural variants(SVs)for human phenotypes and diseases is now recognized.Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed,few benchmarking procedures are available to confidently assess their performances in biological and clinical research.To facilitate the validation and application of these SV detection approaches,we established an Asian reference material by characterizing the genome of an Epstein-Barr virus(EBV)-immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls.We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers,including 109x Pacific Biosciences(PacBio)continuous long reads(CLRs),22 x PacBio circular consensus sequencing(CCS)reads,104x Oxford Nanopore Technologies(ONT)long reads,and 114×Bionano optical mapping plat-form,and one de novo assembly-based SV caller using CCS reads.A total of 544 randomly selected SVs were validated by PCR amplification and Sanger sequencing,demonstrating the robustness of our SV calls.Combining trio-binning-based haplotype assemblies,we established an SV benchmark for identifying false negatives and false positives by constructing the continuous high-confidence regions(CHCRs),which covered 1.46 gigabase pairs(Gb)and 6882 SVs supported by at least one diploid haplotype assembly.Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology,disease,and clinical research.

BACKGROUND:Monoaxial pedicle screws are not conducive to the instal ation during percutaneous pedicle screw technique, but it has better mechanical conductivity and stability than polyaxial pedicle screws. How to select and use these two kinds of screws in the clinic to exert their advantages and to further elevate efficacy has become a subject worthy of reflection. OBJECTIVE:To compare the clinical efficacy of percutaneous pedicle screw placement for thoracolumbar fracture using monoaxial and polyaxial pedicle screws at different placement selections. METHODS:A total of 46 cases of thoracolumbar fracture without neurological symptoms underwent minimal y invasive percutaneous pedicle screw fixation. 25 patients (monoaxial screw group) were treated with monoaxial pedicle screws and the other 21 ones (polyaxial screw group) with polyaxial pedicle screws. Kyphotic angle, correction rate, correction loss rate and height of injury vertebrae were compared before and after fixation in both groups. The therapeutic effects of monoaxial and polyaxial percutaneous pedicle screw fixation in the treatment of thoracolumbar fractures were evaluated. RESULTS AND CONCLUSION:(1) Fixation time, blood loss, complication and hospital stay were not significantly different in both groups (P>0.05). (2) Kyphotic angle and height of the fractured vertebra body were significantly different between the two groups (P<0.05). (3) The restoration of anterior height of injured vertebrae, kyphotic angle and correction rate were better in the monoaxial screw group than in the polyaxial screw group after treatment (P<0.05). The correction loss rate was significantly better in the monoaxial screw group than in the polyaxial screw group during last fol ow-up (P<0.05). However, there was no significant difference in the posterior height of injured vertebraeafter fixation (P>0.05). (4) These findings indicate that compared with the polyaxial percutaneous pedicle screw fixation, the monoaxial pedicle screw may be preferable in percutaneous pedicle screw fixation for thoracolumbar fractures, has more satisfactory fracture distraction reduction, and has less postoperative correction loss rate.

Objective To investigate epidermal growth factor receptor(EGFR)gene T790M mutation in plasmatic ctDNA samples from 171 patients with non-small cell lung cancer and analyze the relationship between EGFR T790M mutation and the clinical factors. Methods The EGFR T790M mutation was detected in 171 cases by super amplification refractory mutation system(Super ARMS)in this paper. Rusults The EGFR gene T790M mutation was identified in 7.60%(13/171)plasmatic ctDNA samples which mostly came from patients withⅢb~Ⅳstages of lung cancer. The EGFR T790M mutation rate was identified in 2.05%(3/146)plasmatic samples of pa-tients who did not received treatment of EGFR-TKIs,which was lower than 40.00%(10/25,P<0.05)plasmatic samples of patients who received treatment of first generational EGFR-TKIs. The EGFR T790M mutation rate was identified in 75.00%(3/4) and 60.00%(6/10) plasmatic samples of patients who have received TKI for 6 to 10 months and more than 10 months,which was higher than 9.10%(1/11,P < 0.05)plasmatic samples of patients who have received TKIs for less than 6 months. Conclusions This article demonstrated that EGFRT790M muta-tion was more common in lately NSCLC patients who have received TKIs treatmentover 6 months,meanwhile the EGFR T790M mutation dynamical detective technology will effectively guide the clinic treatment.