OBJECTIVE: To investigate the genetic etiology of a fetus diagnosed with Mandibulofacial dysostosis with microcephaly (MFDM). METHODS: A fetus that underwent prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, on May 19, 2025 was selected for analysis. Results of fetal ultrasound findings, chromosomal karyotyping, copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) were collected. Sanger sequencing was performed for familial validation of the pathogenic variant. The Human Protein Atlas (HPA), STRING, and Simple ClinVar databases were queried to characterize the biological features of the candidate gene. Three-dimensional structures of the wild-type and variant proteins were modeled and analyzed, and the evolutionary conservation of the affected amino acid was assessed using UGENE. Prenatal phenotypes associated with EFTUD2 variants were summarized through a review of the literature. This study was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Ethics No.: 2025-KY-029-01). RESULTS: At 23⁺² weeks of gestation, ultrasound examination revealed bilateral microtia with low-set ears, mild micrognathia with a reduced mandibular-facial angle, a single umbilical artery, a slightly narrow aortic diameter, and trivial mitral regurgitation. Amniotic fluid karyotyping and CNV-seq showed no abnormalities. WES identified a de novo, previously unreported EFTUD2 variant, c.698dupA (p.V235Gfs*27), in the fetus. This frameshift variant is predicted to alter the structural integrity of the EFTUD2 protein. Literature review indicated that micrognathia and microtia or low-set ears are the most common sonographic features in fetuses with EFTUD2 variants, while secondary findings may include abnormal stomach bubble, cleft palate, single umbilical artery, gastrointestinal atresia, polyhydramnios, and reduced aortic diameter. CONCLUSION The EFTUD2: c.698dupA (p.V235Gfs*27) variant is likely the genetic cause underlying MFDM in this fetus.
Humans ; Mandibulofacial Dysostosis/diagnostic imaging* ; Microcephaly/diagnostic imaging* ; Female ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/chemistry* ; Peptide Elongation Factors/chemistry* ; Fetus ; DNA Copy Number Variations/genetics* ; Adult ; Ultrasonography, Prenatal

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

Objective: To explore the relative importance of different food attributes and levels in food decision making of school aged children, and to understand their meal preferences, so as to provide the evidence for formulating precise intervention strategies for dietary behaviours of school aged children. Methods: From May to June 2024, a total of 854 children aged 11 to 15 years old were selected from 2 middle schools (each school in urban and rural areas) in both Hubei Province and Anhui Province by stratified cluster random sampling method to conduct a D-optimal discrete choice experiment. The mixed Logit model was used to analyze children s preference for meal attributes and different levels, and to calculate the relative importance (RI) of attributes and willingness to pay (WTP) in meal choices. Results: The included five food attributes had statistical significance on meal choice of school aged children ( P <0.05). The relative importance of food attributes affecting the meal choices of school aged children in descending order were dining mode ( RI =31.26%), food varieties ( RI =30.56%), cooking method( RI =23.84%), taste( RI =8.06%) and price ( RI =6.27%). Among them, school aged children preferred home cooked meals ( β =0.74) (WTP=86.3 yuan),varied foods(grain/tubers+vegetables+fish, meat, eggs and beans) ( β =0.61) (WTP=71.9 yuan), fried/roasted cooking ( β =0.51) and spicy taste ( β =0.33).Price was negatively correlated with meal choices( β =-0.01) ( P <0.05). Based on residential area and body mass index (BMI), the stratified analysis showed that dining mode was highest in the relative importance for rural children with overweight and obese children ( RI =31.28%,34.17%), both of whom preferred home cooked meals ( β =0.76, 0.91), and meals containing fish, meat, eggs and beans with grain/tubers or grain/tubers and vegetables in terms of food choice (area: β =0.53, 0.53 ; BMI: β =0.55, 0.56) ( P <0.05). Conclusions School aged children have different preferences for different attributes of meals. The quality of school meals should be improved,the cost of buying healthy meals should be reduced,targeted family health education should be carried out,and healthy cooking methods should be advocated.

Abstract Neurodegenerative diseases include Alzheimer′s disease, Parkinson′s disease, Huntington′s disease, amyotrophic lateral sclerosis, and other disease. There are many causes of neurodegenerative diseases, and the pathogenesis is not entirely clear. Currently, most scholars believe that the occurrence of diseases is closely related to mitochondria. Mitochondrial quality control includes the production, fusion, division, and clearance of mitochondria. Abnormal mitochondrial quality control affects the function of neurons and nerve fibers, leading to the occurrence of neurodegenerative diseases. The author elaborates on the relationship between mitochondria and the pathogenesis of neurodegenerative diseases, providing a basis for the treatment of neurodegenerative diseases.

Objective:To investigate whether hysteroscopic transcervical resection of septum (TCRS) prior to in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) can improve cumulative live birth rates in patients with uterine septum. Methods:A retrospective cohort study was conducted to analyze data from 244 patients with partial uterine septum who underwent IVF/ICSI at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University between January 2016 and August 2022. The patients were divided into a surgical group ( n=171) and a non-surgical group ( n=73) based on whether TCRS was performed prior to IVF/ICSI. The clinical outcomes of IVF/ICSI in the two groups were analyzed, with the primary observation indicator being the cumulative live birth rate. Cox regression analysis was employed to identify determinants. Results:The age of patients in the operated group [(31.20±3.80) years] was younger than that in the non-operated group [(32.92±5.34) years, P=0.005], and the basal antral follicle count [17.0 (11.0, 24.0)] was higher than that in the non-operated group [14.0 (8.0, 21.5), P=0.039]. There were no significant differences in other baseline data (all P>0.05). The cumulative pregnancy rate [79.53% (136/171)] and the cumulative live birth rate [60.23% (103/171)] in the operated group during the 24-month follow-up period were significantly higher than those in the non-operated group [65.75% (48/73), P=0.022; 45.21% (33/73), P=0.030]. Compared with the operated group [296.0 (260.0, 430.0) d], the duration from the start of ovarian stimulation to the first live birth was significantly prolonged in the non-operated group [379.0 (329.5, 471.5) d, P<0.001]. Adjusted Cox-regression analysis showed that whether or not surgery was performed ( HR=1.683, 95% CI: 1.116-2.539, P=0.013) and the basal antral follicle count ( HR=1.032, 95% CI: 1.000-1.065, P=0.048) were independent factors affecting cumulative live birth rate. Conclusion:Performing TCRS before IVF/ICSI can improve cumulative live birth rates of patients with uterine septum.

Objective:To investigate the characteristics of cell subsets in rheumatoid arthritis patients complicated with interstitial lung disease (RA-ILD).Methods:The clinical data of 344 patients with RA admitted to the Affiliated Hospital of Nantong University from June 2022 to November 2023 were analyzed. The patients were categorized into two groups based on the diagnostic criteria of ILD: 120 cases in the RA associated with ILD group (RA-ILD group) were included and 224 cases in the RA without ILD group (RA group), the clinical characteristics were compared between the RA-ILD group and the RA group. The influence factors of RA-ILD were analyzed by univariate and multivariate logistic regression.Results:Compared with RA patients, RA-ILD patients were more common in males, with older age, longer course of disease, and higher smoking rate ( P<0.05). The high titer anti-cyclic citrullinated peptide (CCP) antibody, white blood cells, neutrophil, neutrophil to lymphocyte count ratio, aspartate aminotr-ansferase(AST), creatinine (Cr) and lactate dehydrogenase (LDH) levels in RA-ILD patients were higher than those in RA patients. The triglyceride level was lower than that of RA patients ( P<0.05). The percentage of total T cells in peripheral blood lymphocyte subsets in RA-ILD patients [68.65%(62.22%, 76.78%)] was lower than that in RA patients [71.88%(65.83%, 78.39%)] ( Z=-2.26, P=0.024). The percentage of CD4 +T cells [40.2% (32.10%, 45.23%)] was lower than that of RA patients [46.5% (39.74%, 53.19%)] ( Z=-6.29, P<0.001). CD4 +T cell count [486.50 (324.25, 636.75)cells/μl] was lower than that of RA patients [564.50 (438.25, 752.00)cells/μl] ( Z=-4.50, P<0.001). CD4 +/CD8 + levels [1.86 (1.26, 2.18)] were lower than those of RA patients [2.03 (1.40, 2.94)] ( Z=-2.79, P=0.005). B cell count [127.00 (78.00, 207.25)cells/μl] was lower than that of RA patients [163.50 (91.25, 231.50)cells/μl] ( Z=-2.11, P=0.035), The percentage of NK cells in peripheral blood lymphocyte subsets in RA-ILD patients [19.72%(13.14%, 25.83%)] was higher than that in RA patients [12.55% (8.23%, 17.80%)] ( Z=6.13, P<0.001). NK cell count [182.50 (109.00, 293.75)cells/μl] was higher than that of RA patients [156.00 (89.00, 194.75)cells/μl] ( Z=3.17, P=0.002). The percentage of CD8 +T cells [25.10 %(18.74%, 29.86%)] was higher than that of RA patients [22.27% (17.32%, 29.21%)] ( Z=2.00, P=0.046). Imaging types of RA-ILD patients showed that usual interstitial pneumonia (UIP) was more common, followed by non-specific interstitial pneumonia (NSIP). CD8 + T cell count and percentage expression level in UIP were higher than NSIP, and CD4 +/CD8 + expression level was lower than NSIP ( P<0.05). Multivariate logistic regression analysis of indicators with statistical differences were male gender [ OR(95% CI)=2.888 (1.556, 5.360), P=0.001], age [ OR(95% CI)=1.065 (1.033, 1.098), P<0.001], disease duration [ OR(95% CI)=1.004 (1.001, 1.007), P=0.013], high titer anti-CCP antibody [ OR(95% CI)=2.764 (1.214, 6.292), P=0.015], LDH [ OR(95% CI)=1.006 (1.002, 1.009), P=0.001], CD4 +T cell percentage [ OR(95% CI)=0.964 (0.929, 1.000), P=0.049], CD4 +T cell count [ OR(95% CI)=0.998 (0.996, 1.000), P=0.011] and NK cell count [ OR(95% CI)=1.004 (1.001, 1.007), P=0.003]. These indicators were correlated factors for RA-ILD. Conclusion:Male patients with older age, history of smoking and a long disease course are more likely to develop ILD. Male gender with older, long disease course, high titer anti-CCP antibody, increased LDH and NK cell count, CD4 +T cell percentage and decreased CD4 +T cell count are correlation factors for RA-ILD, which may help RA patients to recognize ILD early.

The 2025 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) was convened, which examined the emerging nexus between climate change and allergic diseases, underscoring its profound impact on human health. This article synthesizes novel research findings presented at the conference, with a focused review of advancements in therapeutic strategies, preventive approaches, and clinical management paradigms within the field of food allergy.

Objective:To investigate whether hysteroscopic transcervical resection of septum (TCRS) prior to in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) can improve cumulative live birth rates in patients with uterine septum. Methods:A retrospective cohort study was conducted to analyze data from 244 patients with partial uterine septum who underwent IVF/ICSI at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University between January 2016 and August 2022. The patients were divided into a surgical group ( n=171) and a non-surgical group ( n=73) based on whether TCRS was performed prior to IVF/ICSI. The clinical outcomes of IVF/ICSI in the two groups were analyzed, with the primary observation indicator being the cumulative live birth rate. Cox regression analysis was employed to identify determinants. Results:The age of patients in the operated group [(31.20±3.80) years] was younger than that in the non-operated group [(32.92±5.34) years, P=0.005], and the basal antral follicle count [17.0 (11.0, 24.0)] was higher than that in the non-operated group [14.0 (8.0, 21.5), P=0.039]. There were no significant differences in other baseline data (all P>0.05). The cumulative pregnancy rate [79.53% (136/171)] and the cumulative live birth rate [60.23% (103/171)] in the operated group during the 24-month follow-up period were significantly higher than those in the non-operated group [65.75% (48/73), P=0.022; 45.21% (33/73), P=0.030]. Compared with the operated group [296.0 (260.0, 430.0) d], the duration from the start of ovarian stimulation to the first live birth was significantly prolonged in the non-operated group [379.0 (329.5, 471.5) d, P<0.001]. Adjusted Cox-regression analysis showed that whether or not surgery was performed ( HR=1.683, 95% CI: 1.116-2.539, P=0.013) and the basal antral follicle count ( HR=1.032, 95% CI: 1.000-1.065, P=0.048) were independent factors affecting cumulative live birth rate. Conclusion:Performing TCRS before IVF/ICSI can improve cumulative live birth rates of patients with uterine septum.