Objective To compare the efficacy of modified radiofrequency ablation (RFA) combined with sclerosing agent injection and high stripping and ligation (HSL) combined with sclerosing agent injection in the treatment of great saphenous vein varicosity. Methods A total of 220 patients (252 affected limbs) who underwent surgery for great saphenous vein varicosity at Affiliated Hospital of Nantong University from May 2022 to March 2024 were selected. They were divided into RFA group (110 patients and 125 affected limbs treated with modified RFA combined with sclerosing agent injection) and HSL group (110 patients and 127 affected limbs treated with HSL combined with sclerosing agent injection) according to the surgical methods. The treatment effect, surgical time, bleeding during the surgery, time to get out of bed after surgery, and various postoperative complications were compared between the two groups. The pain level, disease severity, and the quality of life were measured using the visual analog scale (VAS), venous clinical severity score (VCSS) and chronic venous insufficiency questionnaire-14 item (CIVIQ-14), respectively. Results There was no statistically significant difference in the total effective rate between the two groups of patients, but the distribution of efficacy levels in the RFA group was better than that in the HSL group (P＝0.044). Compared with the HSL group, the RFA group had shorter surgery time, fewer incisions during surgery, less bleeding during the surgical process, shorter time to get out of bed after surgery（P＜0.01）, and a lower overall complication rate (P＝0.006). The RFA group had lower postoperative VAS, VCSS, and CIVIQ-14 scores than the HSL group 1 month after surgery (P＜0.01). During 6 months of postoperative follow-up, the recurrence rates were similar between the two groups. Conclusions Compared with HSL combined with sclerosing agent injection, the modified RFA combined with sclerosing agent injection for the great saphenous vein varicosity has the advantages of less trauma, faster recovery, fewer complications, better postoperative quality of life, and is worthy of clinical promotion and application.

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

BACKGROUND: Mild cognitive impairment (MCI) is common in atrial fibrillation (AF) patients and may develop earlier in those with multiple cardiovascular comorbidities, potentially impairing self-management and treatment adherence. This study aimed to characterize the prevalence and profile of MCI in AF patients, examine its associations with cardiovascular comorbidities, and assess how these comorbidities influence specific cognitive domains. METHODS: This cross-sectional study analyzed data from AF patients who underwent cognitive assessment between 2017 and 2021. Cognitive status was categorized as MCI or non-MCI based on the Montreal Cognitive Assessment. Associations between comorbidities and MCI were assessed by logistic regression, and cognitive domains were compared using the Mann-Whitney U test. RESULTS: Of 4136 AF patients (mean age: 64.7 ± 9.4 years, 64.7% male), 33.5% of patients had MCI. Among the AF patients, 31.2% of patients had coronary artery disease, 20.1% of patients had heart failure, and 18.1% of patients had hypertension. 88.7% of patients had left atrial enlargement, and 11.0% of patients had reduced left ventricular ejection fraction. Independent factors associated with higher MCI prevalence included older age (OR = 1.04, 95% CI: 1.03-1.05, P < 0.001), lower education level (OR = 1.51, 95% CI: 1.31-1.73, P < 0.001), hypertension (OR = 1.28, 95% CI: 1.07-1.52, P = 0.001), heart failure (OR = 1.24, 95% CI: 1.04-1.48, P = 0.020), and lower left ventricular ejection fraction (OR = 1.43, 95% CI: 1.04-1.98, P = 0.028). A higher CHA₂DS₂-VASc score (OR = 1.27, 95% CI: 1.22-1.33, P < 0.001; ≥ 2 points vs. < 2 points), and greater atherosclerotic cardiovascular disease burden (OR = 1.45, 95% CI: 1.02-2.08, P = 0.040; 2 types vs. 0 type) were linked to increased MCI risk. These above factors influenced various cognitive domains. CONCLUSIONS MCI is common in AF and closely associated with cardiovascular multimorbidity. Patients with multiple comorbidities are at higher risk, highlighting the importance of routine cognitive assessment to support self-management and integrated care.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective:To explore the clinical phenotype and genetic etiology for seven children with CHARGE syndrome (CS).Methods:Clinical data of 7 children with CS diagnosed between March 2020 and December 2022 at the Children′s Hospital Affiliated to Zhengzhou University were analyzed. Genomic DNA was extracted from peripheral blood samples from the children and their parents, and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliatedto Zhengzhou University (Ethics No. 2024-K-023).Results:The ages of the children had ranged from 1 day after birth to 12 years old, and all of them had shown growth retardation. The reasons for their admission had included postnatal breathing, swallowing and feeding difficulties in five cases. One child was found to have abnormal external genitalia in conjunct with hearing impairment, whilst another child had shown no secondary sexual characteristics during puberty. All of the children were found to harbor CHD7 gene variants, which included 3 nonsense variants, 2 frameshifting variants and 2 missense variants, i. e., c. 6292C>T (p.R2098*), c.2754G>A (p.W918*), c. 469C>T (p.R157*), c. 3308T>A (p.V1103D), c. 7111delC (p.Q2371Kfs), c. 6023delA (p.D2008Vfs) and c. 3565C>T (p.R1189C). All of the variants were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 3308T>A (p.V1103D) and c. 3565C>T (p.R1189C) variants were rated as likely pathogenic (PS2+ PM2_Supporting+ PP3), whilst the remainders were rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:There is strong clinical and genetic heterogeneity in CS. Early genetic testing may facilitate accurate diagnosis. The detection of novel variants has expanded the phenotypic spectrum of CS and the mutational spectrum of the CHD7 gene.

Objective:To clarify the genetic diagnosis of two children with ring chromosome 18 and explore their mechanisms and clinical phenotypes.Methods:Two patients treated at the Children′s Hospital of Henan Province respectively in June 2022 and March 2023 were selected as the study subjects. Genetic testing and diagnosis were carried out through copy number variation sequencing (CNV-seq), G-banded chromosomal karyotyping, and whole exome sequencing (WES). This study was approved by the Children′s Hospital of Henan Province (Ethics No. 2023-K-075).Results:Child 1 had mainly manifested developmental delay, white matter hypoplasia, type 1 diabetes mellitus, and micropenis. He was found to have a chromosomal karyotype of 46, XY, r(18)(p11.21q22.1)[40]/46, XY[7], and CNV-seq results showed that he has a 14.86 Mb deletion at 18p11.21p11.32 and a 14.02 Mb deletion at 18q22.1q23. Child 2 had peculiar facial features, delayed white matter myelination, developmental delay, atrial septal defect, severe sensorineural deafness, and congenital laryngeal stridor. He was found to have a chromosomal karyotype of 46, XY, r(18)(p11.2q23). CNV-seq result proved that he had a 14.86 Mb deletion at 18p11.21p11.32 and a 20.74 Mb deletion at 18q21.32q23. WES has failed to detect single nucleotide variants (SNVs) in either child, but revealed a large segmental deletion at chromosome 18 in both of them.Conclusion:Both children were diagnosed with ring chromosome 18 syndrome. The different size of the deletional fragments in the 18q region and mosaicism of ring chromosome 18 in child 1 may underlay the variation in their clinical phenotypes. The type 1 diabetes mellitus and micropenis noted in both children are novel features for ring chromosome 18 syndrome.

Objective:To construct and prepare recombinant virus strains chimeric with human metapneumovirus (HMPV) antigenic epitopes.Methods:Recombinant influenza virus vectors which chimeric with different HMPV antigenic epitopes were rescued by reverse genetics using eight-plasmid system. The recombinant influenza virus strain used the internal genes of A/PR/8/34 (PB1, PB2, PA, NP, NS, M, HA, and NA) as a backbone, with concomitant genetic modifications to insert the B-cell epitopes of HMPV into the HA gene, and the CTL+ Th cell epitopes of HMPV into the NA gene. Preparation of recombinant influenza virus strains using reverse genetics in a " 7+ 1" model. The recombinant virus strains were evaluated by measuring hemagglutinin (HA) titers, half tissue culture infectious dose (TCID 50) and growth curves. Sequencing analysis was conducted to verify whether the rescued viruses carried the chimeric HMPV epitopes. Results:The epitopes of HMPV were inserted into the influenza virus genome and two recombinant influenza virus strains were rescued successfully, named as FLU/HMPV/B and FLU/HMPV/CTL+ Th. HA titers of the recombinant strains were both 2 7, their TCID 50 were 10 5.2/ml and 10 5.0/ml, respectively. After cultured for three passages in chick embryo, these two recombinant strains could proliferate steadily. Whole genome sequencing verified that the FLU/HMPV/B carried the B-cell epitopes of HMPV, the FLU/HMPV/CTL+ Th carried the CTL and Th cell epitopes of HMPV. Growth curve tests also verified that the recombinant strains could proliferate steadily in eggs. Conclusions:Two recombinant influenza virus vector strains carrying the B cell, CTL and Th epitopes of HMPV were rescued successfully. The result of the recombinant virus strains in terms of growth characteristics as well as genetic stability indicate that they meet the requirements for proceeding to the next step of animal experiments. The immunogenicity and immunoprotective effect will be further evaluated by mouse experiments. Ultimately new ideas for the realization of " one vaccine for two uses" or " one vaccine formultiple uses", as well as a new strategy for the development of HMPV vaccine will be proposed.

Objective:To evaluate the efficacy and safety of endoscopic ultrasound-guided selective varices devascularization (EUS-SVD) for the treatment of esophagogastric varices.Methods:A total of 43 cases of liver cirrhosis with esophageal and gastric varices at the First Affiliated Hospital of Anhui Medical University from February to December 2021 were included in a retrospective cohort study. The cases were divided into two treatment groups based on endoscopic treatment: EUS-SVD group ( n=22) and conventional endoscopic sclerosant injection group (conventional gastroscopy group, n=21). The doses of sclerosants and tissue glue, effective rate of esophageal varice treatment within 2 months after surgery, rebleeding rate within 3 months after surgery, and adverse reactions were compared. Results:The differences in terms of mean patient age, gender composition, etiology of liver cirrhosis, Child-Pugh classification of liver function, classification of esophageal varices, composition of endoscopic treatment indications, and mean maximum diameter of gastric varices were not statistically significant between the two groups ( P>0.05), indicating the comparability of baseline data. Perforating veins outside the gastric wall of gastric varices could be detected during the procedure in the EUS-SVD group, and disappearance of gastric varices after injection treatment could be determined, while these two indicators could not be detected in the conventional gastroscopy group. The amounts of sclerosing agents and tissue adhesives used in the EUS-SVD group were 7.54±3.10 mL and 1.30±0.57 mL, respectively, while the corresponding amounts in the conventional gastroscopy group were 7.57±3.50 mL ( t=0.026, P=0.980) and 1.38±0.67 mL ( t=-0.452, P=0.654), respectively. The effective treatment rate for esophageal varice within 2 months after surgery was 63.6% (14/22) in the EUS-SVD group and 52.4% (11/21) in the conventional gastroscopy group, but the difference was not statistically significant ( χ2=0.559, P=0.455). The rebleeding rate within 3 months after surgery was 4.5% (1/22) in the EUS-SVD group, significantly lower than the rate of 33.3% (7/21) in the conventional gastroscopy group ( P=0.021). Neither group experienced events of ectopic embolism or death. There was no statistically significant difference between the two groups in terms of postoperative pain, fever, nausea and vomiting, or rebleeding rate within 72 hours after surgery ( P>0.05). The incidence of gastric fundus ulcers was 9.1% (2/22) in the EUS-SVD group, significantly lower than the rate of 42.9% (9/21) in the conventional gastroscopy group ( χ2=6.435, P=0.011). Conclusion:EUS-SVD treatment for esophagogastric varices is safe and effective. It can clearly display the deep-seated intramural vessels of the gastric wall, measure the diameter of the blood vessels, accurately inject tissue glue, occlude the varicose veins and perforating vessels, and reduce the occurrence of postoperative ulcers and rebleeding.

Objective:To compare the accuracy of endoscopy and endoscopic ultrasonography (EUS) combined with Indian ink marking in locating injection sites for gastric varices, and to explore the influence of the features of gastric varices under endoscopy on the injection sites.Methods:Consecutive patients with gastric varices scheduled for EUS-guided glue injection therapy at the First Affiliated Hospital of Anhui Medical University from August 2021 to October 2022 were perspectively included. Firstly, gastric varices were assessed under endoscopy, where the size of the veins were estimated while the injection site was preliminarily judged during the procedure. Then EUS was used to identify perforating feeding veins and mark injection sites with Indian ink. After tissue adhesive was injected into identified varices, the change of varices after injection was observed and the marking was identified under endoscopy again. The clarity of the markinges was confirmed and the consistency between EUS-guided Indian ink mark and that under endoscopy was compared. Patients were divided into anastomosis group and non-anastomosis group based on marking consistency to investigate the effect of gastric varices features on the location of injection sites under endoscopy. Treatment efficacy and postoperative adverse events were counted.Results:Finally, 34 patients were included and all of them underwent successful marking under EUS guidance without complications. A total of 40 marker sites were clearly visible with Indian ink staining under endoscopy. The difference in distribution between the anastomotic group and non-anastomotic group marker points between EUS and endoscopy was statistically significant ( χ2=9.103, P=0.003). Vascular occlusion rate was 100.00% (40/40). There were 13 adverse events after operation, mainly fever, abdominal pain and nausea, and no serious adverse events such as allergy and ectopic embolization occurred. There was significant difference between the blood vessel diameter of the anastomotic group (10.84±4.02 mm) and that of the non-anastomotic group (8.80±1.61 mm, t=1.870, P=0.031). The percentage of raised vessels in the anastomotic group was 88.00% (22/25), higher than that in the non-anastomotic group [53.33% (8/15)], and the difference was statistically significant ( χ2=6.009, P=0.024). Conclusion:Accuracy in positioning under endoscopy is influenced by variceal diameter and bulge shape, being less precise in varices with smaller diameters and less pronounced bulges.

Objective:To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children.Methods:Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis.Results:Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G?>?A accounted for 37.5% (6/16), c.1456T?>?G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin ( t ?=?5.539, P ??0.05) and age of onset ( t ?=?0.3611, P ?>?0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T?>?G homozygous mutations had the highest serum bilirubin levels. Conclusion:The common pathogenic variants of the UGT1A1 gene sequence are c.1456T?>?G, c.211G?>?A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.