Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

Objective:To investigate the dose characteristics of the Zeiss INTRABEAM system in air and water, providing dose reference for electronic brachytherapy.Methods:A Monte Carlo program was used to establish a three-dimensional model of a miniature X-ray source vacuum drift tube and a 4 cm spherical applicator. The process of electron beam bombardment on a gold target to generate X-rays was simulated, and parameters such as photon fluence spectrum, percentage depth dose, and half-value layer were calculated. Additionally, the radial dose uniformity in water was measured.Results:The average energy of X-rays at 3 cm in air was 20.8 keV, with a half-value layer of 0.08 mm Al. Under the influence of the applicator, the spectrum becomes hardened, with axial and radial average energies of 28.7 and 29.0 keV, respectively. In water, the percentage depth dose (PDD) curve follows an inverse cubic decay with depth, indicating strong dose concentration and rapid fall-off in near-field irradiation. The radial dose uniformity in water exceeded 99.5%.Conclusions:The INTRABEAM device emits low-energy X-rays characterized by shallow penetration depth, and concentrated dose delivery. Its highly uniform dose distribution ensures comprehensive coverage of the target area, making it particularly suitable for treating superficial tumors and for intraoperative radiotherapy at close range.

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

Objectives:This study aims to explore the relationship between the pericoronary fat attenuation index(FAI)and triglyceride-glucose(TyG)index and atrial fibrillation recurrence after radiofrequency catheter ablation(RFCA)in patients with atrial fibrillation(AF).Methods:This retrospective study enrolled consecutive AF patients who underwent their first successful RFCA at the Affiliated Hospital of Xuzhou Medical University from 2019 to 2023.Pericoronary FAI was quantitatively measured,and the TyG index was calculated.Patients were divided into three groups according to the TyG index quartile:T1 group(TyG index<8.45,n=114);T2 group(8.45≤TyG index≤8.93,n=114);T3 group(TyG index>8.93,n=120).Linear regression was used to analyze the correlation between the TyG index and proximal FAI of three coronary arteries.Logistic regression was employed to explore the correlation between pericoronary FAI,TyG index,and AF recurrence post-RFCA,restrictive cubic splines(RCS)were plotted.Additive interaction and mediation analyses were used to explore the role of pericoronary FAI in the relationship between the TyG index and post-RFCA AF recurrence.Subgroup analysis was performed to explore the predictive value of the TyG index for postoperative recurrence in different patient subgroups.Results:A total of 348 patients were included.After adjusting for confounding factors using linear regression analysis,each unit increase in the TyG index was associated with a 5.389 HU increase in left circumfleex artery(LCX-FAI)(95%CI:3.874-6.904,P<0.001).During one-year follow-up,90 cases(25.86%)experienced AF recurrence.RCS analysis indicated that there was no significant nonlinear relationship between LCX-FAI,TyG index,and AF recurrence after RFCA(Pnon-linear=0.378,Pnon-linear=0.469).The recurrence rate of AF in patients with TyG index>9.08 and LCX-FAI>-83.65 HU was about 57.737 times higher than those with TyG index≤9.08 and LCX-FAI≤-83.65 HU(OR=57.737,95%CI:23.755-155.656,P<0.001).There was an additive interaction between the TyG index and LCX-FAI:relative excess risk due to interaction(RERI)was 50.901(95%CI:0.215-101.587),attributable proportion due to interaction(AP)was 0.882(95%CI:0.769-0.994),and the synergy index(S)was 9.713(95%CI:3.380-27.910).Mediation analysis indicated that LCX-FAI mediated 22%of the relationship between the TyG index and AF recurrence.Subgroup analysis revealed no multiplicative interaction between the type of atrial fibrillation and the TyG index in terms of AF recurrence risk(Pinteraction=0.562).Conclusions:In patients with atrial fibrillation,the TyG index is positively correlated with LCX-FAI,patients with TyG index>9.08 and LCX-FAI>-83.65 HU have significantly increased risk of AF recurrence after RFCA.LCX-FAI partially mediates the relationship between the TyG index and post-RFCA recurrence.Furthermore,the TyG index can effectively predict AF recurrence in both persistent and paroxysmal atrial fibrillation patients.

Objective:To investigate the dose characteristics of the Zeiss INTRABEAM system in air and water, providing dose reference for electronic brachytherapy.Methods:A Monte Carlo program was used to establish a three-dimensional model of a miniature X-ray source vacuum drift tube and a 4 cm spherical applicator. The process of electron beam bombardment on a gold target to generate X-rays was simulated, and parameters such as photon fluence spectrum, percentage depth dose, and half-value layer were calculated. Additionally, the radial dose uniformity in water was measured.Results:The average energy of X-rays at 3 cm in air was 20.8 keV, with a half-value layer of 0.08 mm Al. Under the influence of the applicator, the spectrum becomes hardened, with axial and radial average energies of 28.7 and 29.0 keV, respectively. In water, the percentage depth dose (PDD) curve follows an inverse cubic decay with depth, indicating strong dose concentration and rapid fall-off in near-field irradiation. The radial dose uniformity in water exceeded 99.5%.Conclusions:The INTRABEAM device emits low-energy X-rays characterized by shallow penetration depth, and concentrated dose delivery. Its highly uniform dose distribution ensures comprehensive coverage of the target area, making it particularly suitable for treating superficial tumors and for intraoperative radiotherapy at close range.

Objectives:This study aims to explore the relationship between the pericoronary fat attenuation index(FAI)and triglyceride-glucose(TyG)index and atrial fibrillation recurrence after radiofrequency catheter ablation(RFCA)in patients with atrial fibrillation(AF).Methods:This retrospective study enrolled consecutive AF patients who underwent their first successful RFCA at the Affiliated Hospital of Xuzhou Medical University from 2019 to 2023.Pericoronary FAI was quantitatively measured,and the TyG index was calculated.Patients were divided into three groups according to the TyG index quartile:T1 group(TyG index<8.45,n=114);T2 group(8.45≤TyG index≤8.93,n=114);T3 group(TyG index>8.93,n=120).Linear regression was used to analyze the correlation between the TyG index and proximal FAI of three coronary arteries.Logistic regression was employed to explore the correlation between pericoronary FAI,TyG index,and AF recurrence post-RFCA,restrictive cubic splines(RCS)were plotted.Additive interaction and mediation analyses were used to explore the role of pericoronary FAI in the relationship between the TyG index and post-RFCA AF recurrence.Subgroup analysis was performed to explore the predictive value of the TyG index for postoperative recurrence in different patient subgroups.Results:A total of 348 patients were included.After adjusting for confounding factors using linear regression analysis,each unit increase in the TyG index was associated with a 5.389 HU increase in left circumfleex artery(LCX-FAI)(95%CI:3.874-6.904,P<0.001).During one-year follow-up,90 cases(25.86%)experienced AF recurrence.RCS analysis indicated that there was no significant nonlinear relationship between LCX-FAI,TyG index,and AF recurrence after RFCA(Pnon-linear=0.378,Pnon-linear=0.469).The recurrence rate of AF in patients with TyG index>9.08 and LCX-FAI>-83.65 HU was about 57.737 times higher than those with TyG index≤9.08 and LCX-FAI≤-83.65 HU(OR=57.737,95%CI:23.755-155.656,P<0.001).There was an additive interaction between the TyG index and LCX-FAI:relative excess risk due to interaction(RERI)was 50.901(95%CI:0.215-101.587),attributable proportion due to interaction(AP)was 0.882(95%CI:0.769-0.994),and the synergy index(S)was 9.713(95%CI:3.380-27.910).Mediation analysis indicated that LCX-FAI mediated 22%of the relationship between the TyG index and AF recurrence.Subgroup analysis revealed no multiplicative interaction between the type of atrial fibrillation and the TyG index in terms of AF recurrence risk(Pinteraction=0.562).Conclusions:In patients with atrial fibrillation,the TyG index is positively correlated with LCX-FAI,patients with TyG index>9.08 and LCX-FAI>-83.65 HU have significantly increased risk of AF recurrence after RFCA.LCX-FAI partially mediates the relationship between the TyG index and post-RFCA recurrence.Furthermore,the TyG index can effectively predict AF recurrence in both persistent and paroxysmal atrial fibrillation patients.

Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

Objective:To investigate the distribution and primary drainage sites of the venous drainage system in the pedicled nasal septal mucosal flap, as well as to examine protective measures for the venous system of the nasal septal mucosal flap and its application in repairing the nasal skull base through the anatomical study of the nasal septum mucosal venous system in cadavers.Methods:Gross anatomy dissections were performed on 13 sides perfused fresh frozen cadaveric head specimens. The nasal septum mucosal flap was separated along the perichondrium and subperiosteum, then passed across the vomer, anterior wall of sphenoid sinus, clivus, and towards the anterior edge of vertical plate of palatine bone. Detailed documentation, including photographs, was made to record the morphology, distribution and drainage location of veins of the nasal septum mucosal flap and its pedicle, along with number of sphenopalatine veins. Furthermore, venous injuries resulting from obtaining a pedicled nasal septal mucosa flap were observed. From March 2023 to March 2024, a retrospective analysis was conducted on patients with nasopharyngeal lesions who underwent surgical repair using a modified pedicled nasal septum mucosal flap for venous system protection in the ENT institute and Department of Otorhinolaryngology at the Eye & ENT Hospital of Fudan University. The postoperative endoscopy was employed to assess the viability of the mucosal flap.Results:The veins of the nasal septum mucosa were primarily located in the posterior region, including the vomerine region, anterior wall of the sphenoid sinus, clivus region, and posterolateral wall of the nasal cavity, in a reticular pattern. Perforating veins draining into these bony structures could be observed, although their quantity and morphology varied. Notably, no prominent sphenopalatine veins were identified in 10 specimens examined, while 3 specimens exhibited sphenopalatine veins: one with a small single branch and two with venous bundles. Preservation of the nasal septal vein was possible when dissection was limited to the anterior edge of the wing of vomer. A wider range of dissection increased the risk of veinous injury. In cases where only vascular pedicles at the sphenopalatine foramen were preserved, three cadaveric head specimens retained intact sphenopalatine veins, while drainage veins were completely destroyed in ten other specimens. Fifteen patients with unilateral lesions (8 with recurrent nasopharyngeal carcinoma and 7 with nasopharyngeal radionecrosis) were included in this study. The postoperative reconstructions were carried out using contralateral pedicled nasal septal mucosal flaps. The average follow-up time was 7 months (ranging from 3 to 12 months), and all the nasal septal mucosal flaps survived.Conclusions:The primary location of the drainage vein within the nasal septum mucosa is situated in its posterior region, where it penetrates into adjacent bone structures. Very few sphenopalatine veins pass through the sphenopalatine foramen. Extensive dissection of the pedicled nasal septal mucosal flap may potentially impair the venous system and adversely affect flap survival rates, necessitating further clinical exploration.

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Objectives: . The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods: . The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. Results: . miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion . Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.