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

Objective To establish atopic dermatitis(AD)-like models in BALB/c mice using three chemical inducers,calcipotriol(MC903),2,4-dinitrochlorobenzene(DNCB),and oxazolone(OXA),and to explore the occurrence of ferroptosis in the different models.Methods Healthy 7-week-old female BALB/c mice were divided randomly into eight groups(n=8 mice per group)based on the induction site(ear/dorsal skin)and inducer:ear/dorsal control groups,MC903 ear/dorsal model groups,DNCB ear/dorsal model groups,and OXA ear/dorsal model groups.Models were established by topical application of the respective agents at specified concentrations.Mice in the MC903 ear/dorsal groups underwent continuous induction for 14 d.Mice in the DNCB and OXA ear/dorsal groups were sensitized for 3 consecutive days,4 days after the sensitization was completedand then challenged 12 times on day 8 and every other day for up to day 30.Skin lesions were observed and skin thickness was measured.Plasma levels of reactive oxygen species(ROS),interleukin(IL)-4,interferon(IFN)-γ,and malondialdehyde(MDA)were detected,the skin was examined by histopathological staining and ultrastructural observation,and expression levels of ferroptosis-related proteins(glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1),long-chain-fatty-acid-CoA ligase 4(ACSL4),transferrin receptor 1(TfR1))were detected by Western Blot.Results Compared with each control mice,all model mice exhibited obvious redness,swelling,scratching,desquamation,and rough thickening of the skin,and skin thickness was significantly increased(P＜0.01).ROS,IFN-γ,IL-4,and MDA levels were elevated to varying extents(P＜0.05)and histopathological features,including epidermal hyperplasia,keratinocyte degeneration,dermal vascular congestion,and immune cell infiltration,were detected in model mice.Transmission electron microscopy also revealed mitochondrial membrane rupture,increased density,and cristae reduction.Expression levels of ferroptosis markers were dysregulated,including significantly decreased GPX4/FTH1(P＜0.05)and increased ACSL4/TfR1 expression(P＜0.05).Conclusions All three chemicals successfully induced AD-like phenotypes in BALB/c mice through site-specific applications.Ferroptosis is involved in the pathological process of AD,but heterogeneity exists among inducers and modeling sites.

Objective To establish atopic dermatitis(AD)-like models in BALB/c mice using three chemical inducers,calcipotriol(MC903),2,4-dinitrochlorobenzene(DNCB),and oxazolone(OXA),and to explore the occurrence of ferroptosis in the different models.Methods Healthy 7-week-old female BALB/c mice were divided randomly into eight groups(n=8 mice per group)based on the induction site(ear/dorsal skin)and inducer:ear/dorsal control groups,MC903 ear/dorsal model groups,DNCB ear/dorsal model groups,and OXA ear/dorsal model groups.Models were established by topical application of the respective agents at specified concentrations.Mice in the MC903 ear/dorsal groups underwent continuous induction for 14 d.Mice in the DNCB and OXA ear/dorsal groups were sensitized for 3 consecutive days,4 days after the sensitization was completedand then challenged 12 times on day 8 and every other day for up to day 30.Skin lesions were observed and skin thickness was measured.Plasma levels of reactive oxygen species(ROS),interleukin(IL)-4,interferon(IFN)-γ,and malondialdehyde(MDA)were detected,the skin was examined by histopathological staining and ultrastructural observation,and expression levels of ferroptosis-related proteins(glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1),long-chain-fatty-acid-CoA ligase 4(ACSL4),transferrin receptor 1(TfR1))were detected by Western Blot.Results Compared with each control mice,all model mice exhibited obvious redness,swelling,scratching,desquamation,and rough thickening of the skin,and skin thickness was significantly increased(P＜0.01).ROS,IFN-γ,IL-4,and MDA levels were elevated to varying extents(P＜0.05)and histopathological features,including epidermal hyperplasia,keratinocyte degeneration,dermal vascular congestion,and immune cell infiltration,were detected in model mice.Transmission electron microscopy also revealed mitochondrial membrane rupture,increased density,and cristae reduction.Expression levels of ferroptosis markers were dysregulated,including significantly decreased GPX4/FTH1(P＜0.05)and increased ACSL4/TfR1 expression(P＜0.05).Conclusions All three chemicals successfully induced AD-like phenotypes in BALB/c mice through site-specific applications.Ferroptosis is involved in the pathological process of AD,but heterogeneity exists among inducers and modeling sites.

Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at increased risk of acute lung injury. However, it is still not clear whether this increased risk is related to the usage of renin-angiotensin system (RAS) blockers. We collected medical records of coronavirus disease 2019 (COVID-19) patients from the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China), and evaluated the potential impact of an angiotensin II receptor blocker (ARB) on the clinical outcomes of COVID-19 patients with hypertension. A total of 30 hypertensive COVID-19 patients were enrolled, of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received. Compared with the non-ARB group, patients in the ARB group had a lower proportion of severe cases and intensive care unit (ICU) admission as well as shortened length of hospital stay, and manifested favorable results in most of the laboratory testing. Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course. No significant difference in the time of seroconversion or antibody levels was observed between the two groups. The median levels of soluble angiotensin-converting enzyme 2 (sACE2) in serum and urine samples were similar in both groups, and there were no significant correlations between serum sACE2 and biomarkers of disease severity. Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport, bicarbonate transport, and blood coagulation. Our results suggest that ARB usage is not associated with aggravation of COVID-19. These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.
Aged ; Aged, 80 and over ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme 2/blood* ; Antibodies, Viral/blood* ; Antihypertensive Agents/therapeutic use* ; Biomarkers ; COVID-19/complications* ; China ; Female ; Humans ; Hypertension/drug therapy* ; Intensive Care Units ; Length of Stay ; Male ; Middle Aged ; Retrospective Studies ; Transcriptome ; Viral Load

Objective To explore the molecular epidemiological characteristics of norovirus isolated from the patients with acute gastroenteritis in Zhejiang province during 2016.Methods The stool samples and clinical data of 1 308 patients with acute gastroenteritis were collected from January to December in 2016.The type Ⅰ and Ⅱ of norovirus in stool samples were detected by one-step double real-time RT-PCR.Some of the positive specimens were selected by stratified sampling and amplified by conventional RT-PCR,and the PCR products were sequenced for genotype identification and phylogenetic analysis.Results Among the samples studied the positive rate of norovirus was 10.55％ (138/1 308) in which 12 cases were GⅠ genotype,118 cases were G Ⅱ genotype and 8 cases were mixed infection of G Ⅰ/G Ⅱ genotypes.The positive rate of norovirus in different age groups decreased with the increased age of patients,and became the lowest in the patient group of more than or equal to 60 years old.There was no significant difference for the positive rates of norovirus in different genders.Norovirus infection was distributed throughout all the year with the peak value of positive rate (37.50％) in December.The sequence analysis demonstrated that G Ⅱ.4 and G Ⅱ.17 genotypes were the prevalent strains of G Ⅱ genotypes with proportions of 40.91％ (18/44) and 34.09％ (15/44),while GⅠ.6 genotype was the prevalent strain of GⅠ genotypes.Conclusion Norovirus should be the important pathogen causing acute gastroenteritis in Zhejiang province during 2016.G Ⅱ.4 and G Ⅱ.17 of norovirus may be the predominant epidemic genotypes.

Objective To explore pathogen spectrum constitution of acute diarrhea in outpatient and emergency of Zhejiang Province, and provide basis for treatment, prevention and control of the disease. Methods During January 2009 to December 2014, we selected seven sentinel hospitals in different regions of Zhejiang, monitored and researched on pathogen spectrum in patients with acute diarrhea from outpatient and emergency. We recorded patients' personal basic information, the main symptoms and signs, and collected stool samples (5 g). Eight kinds of bacteria (Vibrio cholerae, Shigella spp., Salmonella spp., Diarrheagenic E. coli, Vibrio parahaemolyticus, Aeromonas hydrophila, Yersinia enterocolitica and Plesiomonas shigelloides) and five kinds of viruses (Rotavirus, Norovirus, Sappovirus, Astrovirus and Adenovirus) were detected. Chi-square test and Fisher's exact probability method were used to compare different characteristics of patients with single bacterial infection, single virus infection and multiple infection (bacteria-bacteria, bacteria-viruses, virus-virus). Results During 2009 to 2014, 9 364 fecal
samples from acute diarrhea patients were collected and tested, among which 3 500 cases were tested positive, with total positive rate of 37.38%. Positive rates of bacteria and viruses were 13.14%(1 230 cases) and 20.75%(1 943 cases), respectively. Mixed infection positive rate of multiple pathogens was 3.49%(327 cases). Positive rate of Vibrio parahaemolyticus (5.96%, 558 cases) was the highest among bacterial pathogens, followed by pathogenic Escherichia coli (3.86%, 361 cases). Viruses were mainly Norovirus (10.73%, 1 005 cases) and rotavirus (8.35%, 782 cases). A big difference existed in diarrheogenic pathogen spectrum between patients less than 15 years old and patients equal or older than 15 years old. Pathogens for patients less than 15 years old were mainly virus, with the positive rate of 32.69%(1 014 cases). However, the positive rate of bacteria was 16.86% (1 056 cases) in patients equal or older than 15 years old. Single bacterial infection was highest in age group of 25-34 years old (18.62%, 302 cases) , single virus infection was highest in age group of 1-4 years old (41.12%, 435 cases) , and mixed infections of multiple pathogens were mainly existed in age group of 1-4 years old (7.37%, 78 cases) . Pathogen positive rate were increasing year by year. Pathogen positive rate of patients with acute diarrhea has obvious seasonality, with single bacterial infection being highest during July to September and single virus infection being highest during December to March. Pathogen spectrum of outpatient and emergency patients with acute diarrhea in Zhejiang Province changed a little from 2009 to 2014, mainly rotavirus (22.34% (782/3 500)), norovirus (28.71%(1 005/3 500)), vibrio parahaemolyticus (15.92%(558/3 500)) and Escherichia coli (10.31%(361/3 500)). However, pathogen spectrums in different years owned different features. Conclusion Common pathogens in outpatient and emergency patients with acute diarrhea in Zhejiang Province were tested with significant seasonal epidemic law. The composition of pathogenic spectrum was variant in different age group. Constitutes of major pathogen spectrum in different years differed a little.

Objective To explore pathogen spectrum constitution of acute diarrhea in outpatient and emergency of Zhejiang Province, and provide basis for treatment, prevention and control of the disease. Methods During January 2009 to December 2014, we selected seven sentinel hospitals in different regions of Zhejiang, monitored and researched on pathogen spectrum in patients with acute diarrhea from outpatient and emergency. We recorded patients' personal basic information, the main symptoms and signs, and collected stool samples (5 g). Eight kinds of bacteria (Vibrio cholerae, Shigella spp., Salmonella spp., Diarrheagenic E. coli, Vibrio parahaemolyticus, Aeromonas hydrophila, Yersinia enterocolitica and Plesiomonas shigelloides) and five kinds of viruses (Rotavirus, Norovirus, Sappovirus, Astrovirus and Adenovirus) were detected. Chi-square test and Fisher's exact probability method were used to compare different characteristics of patients with single bacterial infection, single virus infection and multiple infection (bacteria-bacteria, bacteria-viruses, virus-virus). Results During 2009 to 2014, 9 364 fecal
samples from acute diarrhea patients were collected and tested, among which 3 500 cases were tested positive, with total positive rate of 37.38%. Positive rates of bacteria and viruses were 13.14%(1 230 cases) and 20.75%(1 943 cases), respectively. Mixed infection positive rate of multiple pathogens was 3.49%(327 cases). Positive rate of Vibrio parahaemolyticus (5.96%, 558 cases) was the highest among bacterial pathogens, followed by pathogenic Escherichia coli (3.86%, 361 cases). Viruses were mainly Norovirus (10.73%, 1 005 cases) and rotavirus (8.35%, 782 cases). A big difference existed in diarrheogenic pathogen spectrum between patients less than 15 years old and patients equal or older than 15 years old. Pathogens for patients less than 15 years old were mainly virus, with the positive rate of 32.69%(1 014 cases). However, the positive rate of bacteria was 16.86% (1 056 cases) in patients equal or older than 15 years old. Single bacterial infection was highest in age group of 25-34 years old (18.62%, 302 cases) , single virus infection was highest in age group of 1-4 years old (41.12%, 435 cases) , and mixed infections of multiple pathogens were mainly existed in age group of 1-4 years old (7.37%, 78 cases) . Pathogen positive rate were increasing year by year. Pathogen positive rate of patients with acute diarrhea has obvious seasonality, with single bacterial infection being highest during July to September and single virus infection being highest during December to March. Pathogen spectrum of outpatient and emergency patients with acute diarrhea in Zhejiang Province changed a little from 2009 to 2014, mainly rotavirus (22.34% (782/3 500)), norovirus (28.71%(1 005/3 500)), vibrio parahaemolyticus (15.92%(558/3 500)) and Escherichia coli (10.31%(361/3 500)). However, pathogen spectrums in different years owned different features. Conclusion Common pathogens in outpatient and emergency patients with acute diarrhea in Zhejiang Province were tested with significant seasonal epidemic law. The composition of pathogenic spectrum was variant in different age group. Constitutes of major pathogen spectrum in different years differed a little.

Purpose To investigate the significance of procedural arteriography in interventional embolization of adrenal metastasis, due to the fact that it is usually difficult to seek feeding arteries in the treatment of adrenal metastasis using interventional embolization. Materials and Methods Eighteen patients with adrenal metastasis were treated with procedural arteriography and interventional embolization therapy, the source and number of feeding arteries was retrospectively analyzed. Results The total success rate of procedural arteriography was 95.5%. The abnormal feeding arteries which were discovered by procedural arteriography accounted for 29.0%. The number of feeding arteries was two, which were mainly derived from inferior suprarenal artery and superior suprarenal arteries. Conclusion The source of feeding arteries of adrenal metastasis is abundant and the variability is obvious, thus procedural arteriography should be used to the greatest extent during operation of digital subtraction angiography to avoid omission of feeding arteries.

Objective To observe the curative effect of pure 1 25 I treatment to non-small cell lung cancer combined obstructive pneumonia.Methods 28 cases with non-small cell lung cancer combined obstructive pneumonia were enrolled.Treatment planning system was used to calculate the dosage of tumor and make up the therapeutic plan.CT-guided radiation treatment of particle im-plantation was then conducted.Follow-up was done to evaluate the curative effect one to two months after treatment.Results The total effective rate of therapeutic evaluation was 89.3%.Clinical symptoms including chest distress,hard breathing and fever were ameliorated remarkedly.Life quality score of appetite and fatigue was also improved.White blood cell reduced significantly in blood routine examination.Conclusion There is a definite curative effect of pure 1 25 I treatment to non-small cell lung cancer combined ob-structive pneumonia.

Objective To compare the 2 methods of the flow cytometry and the microcolumn gel agglutination assay for testing anti-ABO Ig G antibody.Methods The flow cytometry and the microcolumn gel agglutination assay were adopted to detect the an-ti-ABO IgG antibody in the O blood type pregnant women(experimental group)and the A/B blood type pregnant women (control group).The difference in the positive rates between the experimental and control groups and the correlation between these two methods were analysed.The different titers of samples were selected for detection on different days to compare their reproducibili-ty.Results 300 samples from the experimental goup and 300 samples from the control group were collected.The detection results of 2 methods showed that the positive rates of the experimental group was significantly higher than that of the control group with statistical difference(P <0.05).The correlation coefficients(rs )between these two methods were 0.694.The coefficient of variation in the flow cytometry was smaller than that in the microcolumn gel agglutination assay(P <0.05).Conclusion ABO blood type in-compatibility is more common in O type pregnant women.The flow cytometry and the microcolumn gel agglutination assay possess good correlation.The reproducibility of the flow cytometry is better than that of microcolumn gel agglutination assay.