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 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.

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.

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.

Hypertensive nephropathy is one of the common chronic kidney diseases in China,the morbidity and mortality are increasing year by year,which seriously endangers the physical and mental health of patients.Traditional Chinese medicine believes that human is an organic whole,the five viscera and six organs are closely related in physiology and pathology,based on the theory of"holistic concept",the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions.Therefore,based on the theory of"five viscera in one",this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver,heart,spleen,lung and kidney,aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.

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 compare the hemodynamic effects of anesthesia induction with remimazolam tosylate and etomidate in elderly frail patients.Methods This study was a single-center,prospective,randomized,single-blind trial.From January to April 2024,96 elderly frail patients undergoing elective surgery in Fuyang People's Hospital were recruited.After excluding 6 cases(3 refused to participate,1 had tracheal intubation time＞30 s,and 2 had missing data),90 patients were finally included.They were randomly divided into remimazolam tosylate group(intravenous injection of 0.2 mg/kg remimazolam tosylate for anesthesia induction,n=45)and etomidate group(intravenous injection of 0.3 mg/kg etomidate for anesthesia induction,n=45)by the random number table method.The area under the curve for mean arterial pressure(MAP)below or above baseline values(AUCMAP-and AUCMAP+),the heart rate(HR)below or above baseline values by 10％(AUCHR-and AUCHR+)within 10 minutes of anesthesia induction,the time to loss of consciousness,the time from the start of anesthesia induction to a bispectral index(BIS)＜60,the incidence of drug-related adverse reactions,the incidence of cardiovascular adverse events,and the usage of vasoactive drug administrations were compared between the two groups.Results Compared with the etomidate group,the AUCMAP-(145.10±35.75 vs.178.52±39.78)and AUCHR-[43.20(26.58,56.35)vs.54.99(43.01,65.85)]in remimazolam tosylate group were significantly reduced(P＜0.001,P=0.001).The time to loss of consciousness and the time from the start of anesthesia induction to BIS＜60 were prolonged(P＜0.001).The incidence of drug-related adverse reactions was significantly decreased(P＜0.05),and the number of norepinephrine administrations was significantly reduced(P＜0.05)in remimazolam tosylate group.However,there were no statistically significant differences in AUCMAP+,AUCHR+,the incidence of cardiovascular adverse events,and the usages of atropine,urapidil,and esmolol between the two groups(P＞0.05).Conclusion The use of remimazolam tosylate during anesthesia induction in elderly frail patients can provide more stable hemodynamic parameters and results in fewer adverse reactions than etomidate.